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Hopewell S, Srikesavan C, Evans A, Er F, Rangan A, Preece J, Francis A, Massa MS, Feldmann M, Lamb S, Nanchahal J. Anti-TNF (adalimumab) injection for the treatment of pain-predominant early-stage frozen shoulder: the Anti-Freaze-Feasibility randomised controlled trial. BMJ Open 2024; 14:e078273. [PMID: 38692727 PMCID: PMC11086567 DOI: 10.1136/bmjopen-2023-078273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 03/01/2024] [Indexed: 05/03/2024] Open
Abstract
OBJECTIVE The Anti-Freaze-F (AFF) trial assessed the feasibility of conducting a definitive trial to determine whether intra-articular injection of adalimumab can reduce pain and improve function in people with pain-predominant early-stage frozen shoulder. DESIGN Multicentre, randomised feasibility trial, with embedded qualitative study. SETTING Four UK National Health Service (NHS) musculoskeletal and related physiotherapy services. PARTICIPANTS Adults ≥18 years with new episode of shoulder pain attributable to early-stage frozen shoulder. INTERVENTIONS Participants were randomised (centralised computer generated 1:1 allocation) to either ultrasound-guided intra-articular injection of: (1) adalimumab (160 mg) or (2) placebo (saline (0.9% sodium chloride)). Participants and outcome assessors were blinded to treatment allocation. Second injection of allocated treatment (adalimumab 80 mg) or equivalent placebo was administered 2-3 weeks later. PRIMARY FEASIBILITY OBJECTIVES: (1) Ability to screen and identify participants; (2) willingness of eligible participants to consent and be randomised; (3) practicalities of delivering the intervention; (4) SD of the Shoulder Pain and Disability Index (SPADI) score and attrition rate at 3 months. RESULTS Between 31 May 2022 and 7 February 2023, 156 patients were screened of whom 39 (25%) were eligible. The main reasons for ineligibility were other shoulder disorder (38.5%; n=45/117) or no longer in pain-predominant frozen shoulder (33.3%; n=39/117). Of the 39 eligible patients, nine (23.1%) consented to be randomised (adalimumab n=4; placebo n=5). The main reason patients declined was because they preferred receiving steroid injection (n=13). All participants received treatment as allocated. The mean time from randomisation to first injection was 12.3 (adalimumab) and 7.2 days (placebo). Completion rates for patient-reported and clinician-assessed outcomes were 100%. CONCLUSION This study demonstrated that current NHS musculoskeletal physiotherapy settings yielded only small numbers of participants, too few to make a trial viable. This was because many patients had passed the early stage of frozen shoulder or had already formulated a preference for treatment. TRIAL REGISTRATION NUMBER ISRCTN 27075727, EudraCT 2021-03509-23, ClinicalTrials.gov NCT05299242 (REC 21/NE/0214).
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Affiliation(s)
- Sally Hopewell
- Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Cynthia Srikesavan
- Centre for Rehabilitation Research in Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
- College of Medicine and Health, University of Exeter, Exeter, UK
| | - Alison Evans
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Fema Er
- Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Amar Rangan
- South Tees Hospitals NHS Foundation Trust, The James Cook University Hospital, Middlesbrough, UK
- Department of Health Sciences, University of York, York, UK
| | - Jane Preece
- Patient and Public Involvement Representative, Kidderminster, UK
| | - Anne Francis
- Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - M Sofia Massa
- Oxford Clinical Trials Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Marc Feldmann
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Sarah Lamb
- College of Medicine and Health, University of Exeter, Exeter, UK
| | - Jagdeep Nanchahal
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
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Faust TF, Castañeda PG. Arthrofibrosis of the knee in pediatric orthopedic surgery. ACTA ORTOPEDICA MEXICANA 2024; 38:179-187. [PMID: 38862148 DOI: 10.35366/115813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2024]
Abstract
Arthrofibrosis is a challenging complication associated with knee injuries in both children and adults. While much is known about managing arthrofibrosis in adults, it is necessary to understand its unique aspects and management strategies in the pediatric population. This paper provides an overview of arthrofibrosis in pediatric orthopedic surgery, focusing on its causes, implications, classifications, and management. This paper is a comprehensive review of the literature and existing research on arthrofibrosis in pediatric patients. Arthrofibrosis is characterized by excessive collagen production and adhesions, leading to restricted joint motion and pain. It is associated with an immune response and fibrosis within and around the joint. Arthrofibrosis can result from various knee injuries in pediatric patients, including tibial spine fractures, ACL and PCL injuries, and extra-articular procedures. Technical factors at the time of surgery play a role in the development of motion loss and should be addressed to minimize complications. Preventing arthrofibrosis through early physical therapy is recommended. Non-operative management, including dynamic splinting and serial casting, has shown some benefits. New pharmacologic approaches to lysis of adhesions have shown promise. Surgical interventions, consisting of arthroscopic lysis of adhesions (LOA) and manipulation under anesthesia (MUA), can significantly improve motion and functional outcomes. Arthrofibrosis poses unique challenges in pediatric patients, demanding a nuanced approach that includes prevention, early intervention with non-operative means, and improvements in surgical techniques. Modern pharmacological interventions offer promise for the future. Customized interventions and research focused on pediatric patients are critical for optimal outcomes.
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Affiliation(s)
- T F Faust
- Department of Research, Alabama College of Osteopathic Medicine. Alabama, USA
| | - P G Castañeda
- Baylor School of Medicine, Department of Pediatric Orthopedic Surgery, Texas Children's Hospital. USA
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Brindisino F, Venturin D, Bartoli M, Caselli S, Pellicciari L, Poser A. Psychometric properties of the Disability of Arm Shoulder and Hand (DASH) in subjects with frozen shoulder: a reliability and validity study. BMC Musculoskelet Disord 2024; 25:260. [PMID: 38566086 PMCID: PMC10986124 DOI: 10.1186/s12891-024-07371-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 03/20/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Frozen Shoulder (FS) is a painful condition characterized by severe pain and progressive restriction of shoulder movement, leading to functional impairment and reduced quality of life. While different Patient Reported Outcome Measurements (PROMs) tools exist for assessing shoulder diseases, few specific PROMs are validated for FS patients. PURPOSE This study aims to assess the psychometric properties of the Disability of Arm, Shoulder, and Hand (DASH) questionnaire in FS patients. METHODS One hundred and twenty-four subjects (mean ± SD age = 55.4 ± 7.9 years; 55.6% female) diagnosed with FS were included and completed the DASH questionnaire, the Numerical Pain Rating Scale (NPRS), the Shoulder Pain and Disability Index (SPADI), and the Short-Form Health Survey 36 (SF-36). Floor or ceiling effects were investigated. Structural validity was analysed through a unidimensional Confirmatory Factor Analysis (CFA), internal consistency through Cronbach's alpha, test-retest reliability through the Intraclass Correlation coefficient (ICC), measurement error through the Standard Error of Measurement (SEM), and the Minimum Detectable Change (MDC), and construct validity through the hypothesis testing with the correlation with the other outcome measures used. RESULTS No floor or ceiling effects were observed. CFA confirmed a one-factor structure after addressing local item dependency (Root Mean Square Error of Approximation = 0.055; Standardized Root Mean Square Residual = 0.077; Comparative Fit Index = 0.970; Tucker-Lewis Index = 0.968). Cronbach's alpha was high (= 0.951), and test-retest reliability was excellent (ICC = 0.999; 95% CI: 0.998-1.000). SEM was equal to 0.5 points, and MDC to 1.5 points. Construct validity was considered satisfactory as 80% of the a-priori hypotheses were met. CONCLUSION The DASH questionnaire demonstrated good psychometric properties in FS patients, supporting its use as a valuable tool for assessing the impact of FS in clinical and research settings.
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Affiliation(s)
- Fabrizio Brindisino
- Department of Medicine and Health Science "Vincenzo Tiberio", University of Molise c/o Cardarelli Hospital, C/da Tappino, Campobasso, 86100, Italy
| | - Davide Venturin
- Department of Medicine and Health Science "Vincenzo Tiberio", University of Molise c/o Cardarelli Hospital, C/da Tappino, Campobasso, 86100, Italy
| | - Matteo Bartoli
- Physiotherapy private practice KinesiLab, via Marcantonio Colonna 88, Marino, Italy
| | - Serena Caselli
- Unità Operativa di Medicina Riabilitativa, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy
| | - Leonardo Pellicciari
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Via Altura, 3, Bologna, I-40139, Italy.
| | - Antonio Poser
- Physiotherapy private practice Kinè, Kinè s.r.l, Viale della Quercia 2/B,, Treviso, Italy
- University of Siena, c/o via Banchi di Sotto, 55, Siena, Italy
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Ng MTH, Borst R, Gacaferi H, Davidson S, Ackerman JE, Johnson PA, Machado CC, Reekie I, Attar M, Windell D, Kurowska-Stolarska M, MacDonald L, Alivernini S, Garvilles M, Jansen K, Bhalla A, Lee A, Charlesworth J, Chowdhury R, Klenerman P, Powell K, Hackstein CP, Furniss D, Rees J, Gilroy D, Coles M, Carr AJ, Sansom SN, Buckley CD, Dakin SG. A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution. Nat Commun 2024; 15:1394. [PMID: 38374174 PMCID: PMC10876649 DOI: 10.1038/s41467-024-45341-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 01/19/2024] [Indexed: 02/21/2024] Open
Abstract
Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.
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Affiliation(s)
| | | | | | | | | | | | - Caio C Machado
- University of Oxford, Oxford, UK
- University of Sao Paulo, Sao Paulo, Brazil
| | | | | | | | | | - Lucy MacDonald
- Research into Inflammatory Arthritis Centre Versus Arthritis (RACE), University of Glasgow, Glasgow, UK
| | - Stefano Alivernini
- Fondazione Policlinico Universitario Agostino Gemelli - IRCCS, Rome, Italy
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Riesmeijer SA, Kamali Z, Ng M, Drichel D, Piersma B, Becker K, Layton TB, Nanchahal J, Nothnagel M, Vaez A, Hennies HC, Werker PMN, Furniss D, Nolte IM. A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren's disease. Nat Commun 2024; 15:199. [PMID: 38172110 PMCID: PMC10764787 DOI: 10.1038/s41467-023-44451-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 12/13/2023] [Indexed: 01/05/2024] Open
Abstract
Dupuytren's disease (DD) is a highly heritable fibrotic disorder of the hand with incompletely understood etiology. A number of genetic loci, including Wnt signaling members, have been previously identified. Our overall aim was to identify novel genetic loci, to prioritize genes within the loci for functional studies, and to assess genetic correlation with associated disorders. We performed a meta-analysis of six DD genome-wide association studies from three European countries and extensive bioinformatic follow-up analyses. Leveraging 11,320 cases and 47,023 controls, we identified 85 genome-wide significant single nucleotide polymorphisms in 56 loci, of which 11 were novel, explaining 13.3-38.1% of disease variance. Gene prioritization implicated the Hedgehog and Notch signaling pathways. We also identified a significant genetic correlation with frozen shoulder. The pathways identified highlight the potential for new therapeutic targets and provide a basis for additional mechanistic studies for a common disorder that can severely impact hand function.
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Affiliation(s)
- Sophie A Riesmeijer
- University of Groningen, University Medical Center Groningen, Department of Plastic Surgery, Groningen, The Netherlands.
- University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
| | - Zoha Kamali
- University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands
- Department of bioinformatics, School of Advanced Medical Technologies, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Michael Ng
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Dmitriy Drichel
- Cologne Center for Genomics, University of Cologne, Cologne, Germany
- Faculty of Medicine and the Cologne University Hospital, Cologne, Germany
| | - Bram Piersma
- University of Groningen, Groningen, The Netherlands
| | - Kerstin Becker
- Cologne Center for Genomics, University of Cologne, Cologne, Germany
| | | | | | - Michael Nothnagel
- Cologne Center for Genomics, University of Cologne, Cologne, Germany
- Faculty of Medicine and the Cologne University Hospital, Cologne, Germany
| | - Ahmad Vaez
- University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands
- Department of bioinformatics, School of Advanced Medical Technologies, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hans Christian Hennies
- Faculty of Medicine and the Cologne University Hospital, Cologne, Germany
- Department of Biological Sciences, University of Huddersfield, Huddersfield, UK
| | - Paul M N Werker
- University of Groningen, University Medical Center Groningen, Department of Plastic Surgery, Groningen, The Netherlands
| | - Dominic Furniss
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science, Botnar Research Centre, University of Oxford, Oxford, UK
| | - Ilja M Nolte
- University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands
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Ramos MS, Pasqualini I, Surace PA, Molloy RM, Deren ME, Piuzzi NS. Arthrofibrosis After Total Knee Arthroplasty: A Critical Analysis Review. JBJS Rev 2023; 11:01874474-202312000-00001. [PMID: 38079496 DOI: 10.2106/jbjs.rvw.23.00140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
» Arthrofibrosis after total knee arthroplasty (TKA) is the new formation of excessive scar tissue that results in limited ROM, pain, and functional deficits.» The diagnosis of arthrofibrosis is based on the patient's history, clinical examination, absence of alternative diagnoses from diagnostic testing, and operative findings. Imaging is helpful in ruling out specific causes of stiffness after TKA. A biopsy is not indicated, and no biomarkers of arthrofibrosis exist.» Arthrofibrosis pathophysiology is multifactorial and related to aberrant activation and proliferation of myofibroblasts that primarily deposit type I collagen in response to a proinflammatory environment. Transforming growth factor-beta signaling is the best established pathway involved in arthrofibrosis after TKA.» Management includes both nonoperative and operative modalities. Physical therapy is most used while revision arthroplasty is typically reserved as a last resort. Additional investigation into specific pathophysiologic mechanisms can better inform targeted therapeutics.
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Affiliation(s)
- Michael S Ramos
- Department of Orthopaedic Surgery, Orthopaedic and Rheumatologic Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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Maasarani S, Wee CE, Lee CD, Khalid SI, Layon S, Noland SS. Surgical Trigger Finger Release Is Associated With New-Onset Dupuytren Contracture in the Short-Term Postoperative Period: A Matched Analysis. Hand (N Y) 2023; 18:1080-1088. [PMID: 35253506 PMCID: PMC10798206 DOI: 10.1177/15589447221077375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND This article compares the rates and time-to-development of new-onset Dupuytren disease in patients with trigger finger treated by steroid injection, surgical release, or both. METHODS PearlDiver's Mariner 30 database was queried to identify patients with trigger finger between January 2010 and June 2019. One-to-one exact matching based on baseline patient demographics allowed us to create 4 identical groups defined by the type of trigger finger intervention received. RESULTS The matched population analyzed in this study consisted of 85 944 patients who were equally represented in the steroid injection cohort (n = 21 486, 25.00%), surgical release cohort (n = 21 486, 25.00%), steroids prior to surgery cohort (n = 21 486, 25.00%), and no intervention (control) cohort (n = 21 486, 25.00%). A new Dupuytren diagnosis after trigger finger treatment occurred in 1 in 128 patients overall, 1 in 156 patients treated with steroid injection, and 1 in 126 patients treated with surgical release. Trigger fingers treated by steroid injection only had the lowest rates of Dupuytren disease overall (n = 137, 0.64%, P = .0424) and treatment with fasciectomy (n = 14, 0.07%, P < .0005). In all, 171 patients in the surgery cohort developed Dupuytren disease 1 year after undergoing surgical trigger finger release. Furthermore, this cohort had the highest rates of fasciectomy (n = 55, 0.26%, P < .0005) and the lowest rates of no intervention (n = 103, 0.48%, P = .0471). Trigger fingers managed by surgical release developed Dupuytren disease (mean, 56.11 days; SD, 80.93 days, log-rank P = .02) and underwent fasciectomy (mean, 49.74 days; SD, 62.27 days; log-rank P < .0005) more quickly than all other cohorts. CONCLUSIONS Patients solely undergoing surgical release of their trigger finger had significantly higher odds and expedited rate of developing new-onset Dupuytren disease overall and undergoing subsequent treatment by fasciectomy compared with trigger fingers managed by other interventions.
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Affiliation(s)
| | | | | | | | - Sarah Layon
- University of Minnesota Medical School, Minneapolis, USA
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Ouyang Y, Chen S, Tu Y, Wan T, Fan H, Sun G. Exploring the potential relationship between frozen shoulder and Dupuytren's disease through bioinformatics analysis and machine learning. Front Immunol 2023; 14:1230027. [PMID: 37720213 PMCID: PMC10500125 DOI: 10.3389/fimmu.2023.1230027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 08/02/2023] [Indexed: 09/19/2023] Open
Abstract
Background Frozen shoulder (FS) and Dupuytren's disease (DD) are two closely related diseases, but the mechanism of their interaction is unknown. Our study sought to elucidate the molecular mechanism of these two diseases through shared gene and protein interactions. Methods GSE75152 and GSE140731 data were downloaded from the Gene Expression Omnibus (GEO) database, and shared genes between FS and DD were selected by using R packages. Then, we used Cytoscape software and the STRING database to produce a protein-protein interaction (PPI) network. Important interaction networks and hub genes were selected through MCODE and cytoHubba algorithms. To explore the potential mechanisms of the development of the two diseases, the hub genes were further enriched by GO and KEGG analyses. We predicted the transcription factors (TFs) of hub genes with Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST). Moreover, we identified candidate genes for FS with DD with cytoHubba and machine learning algorithms. Finally, we analyzed the role of immunocyte infiltration in FS and constructed the relationship between candidate genes and immunocytes in FS. Results We identified a total of 321 shared genes. The results of GO and KEGG enrichment of shared genes showed that extracellular matrix and collagen fibril tissue play a certain role in the occurrence and development of disease. According to the importance of genes, we constructed the key PPI network of shared genes and the top 15 hub genes for FS with DD. Then, we predicted that five TFs are related to the hub genes and are highly expressed in the FS group. Machine learning results show that the candidate genes POSTN and COL11A1 may be key for FS with DD. Finally, immune cell infiltration revealed the disorder of immunocytes in FS patients, and expression of candidate genes can affect immunocyte infiltration. Conclusion We identified a PPI network, 15 hub genes, and two immune-related candidate genes (POSTN and COL11A1) using bioinformatics analysis and machine learning algorithms. These genes have the potential to serve as diagnostic genes for FS in DD patients. Furthermore, our study reveals disorder of immunocytes in FS.
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Affiliation(s)
- Yulong Ouyang
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Shuilin Chen
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yuanqing Tu
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Ting Wan
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Hao Fan
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Guicai Sun
- Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Feusi O, Fleischmann T, Waschkies C, Pape HC, Werner CM, Tiziani S. Vitamin C as a Potential Prophylactic Measure Against Frozen Shoulder in an In Vivo Shoulder Contracture Animal Model. Am J Sports Med 2023; 51:2041-2049. [PMID: 37249131 PMCID: PMC10315865 DOI: 10.1177/03635465231172192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 03/17/2023] [Indexed: 05/31/2023]
Abstract
BACKGROUND Frozen shoulder is a common, painful, and movement-restricting condition. Although primary frozen shoulder is idiopathic, secondary frozen shoulder can occur after trauma or surgery. Prophylactic and therapeutic options are often unsatisfactory. Vitamin C (ascorbic acid) is a potent physiological antioxidant and likely inhibits the activation of nuclear factor κB, which plays a decisive role in inflammatory reactions. HYPOTHESIS Because of its anti-inflammatory effects, vitamin C may be valuable in the prevention of secondary frozen shoulder. STUDY DESIGN Controlled laboratory study. METHODS An in vivo shoulder contracture model was conducted by fixation of the right proximal limb of Sprague-Dawley rats. A treatment group (n = 8) receiving vitamin C orally was compared with a control group (n = 9) without vitamin C. The primary outcome was capsular thickness at the shoulder joint measured on magnetic resonance imaging (MRI) examination. Further histological examination was performed but was not statistically analyzed because of variability of the cutting plane through the glenoid. RESULTS Vitamin C treatment resulted in less thickening of the axillary fold of the operated shoulder at 2 of the 3 locations measured on MRI compared with untreated controls (insertion to the glenoid, P = .074; insertion to the humerus, P = .006; middle of the axillary recess, P = .008). The observed structural changes in histological examination corroborated the significant changes obtained from the MRI measurements. CONCLUSION Prophylactic vitamin C seemed to reduce the thickening of the axillary recess in secondary frozen shoulder in this preclinical study. CLINICAL RELEVANCE Vitamin C may be helpful as a noninvasive therapeutic measure to prevent secondary frozen shoulder (eg, within the context of surgery in the shoulder region or immobilization) or to treat primary frozen shoulder at an early stage. Further studies are required to evaluate the effect of this treatment in humans and the necessary dosage in humans.
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Affiliation(s)
- Oscar Feusi
- Department of Trauma, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Thea Fleischmann
- Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Conny Waschkies
- Division of Surgical Research, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Hans-Christoph Pape
- Department of Trauma, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Clément M.L. Werner
- Department of Trauma, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Simon Tiziani
- Department of Trauma, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Hopewell S, Kenealy N, Knight R, Rangan A, Dutton S, Srikesavan C, Feldmann M, Lamb S, Nanchahal J. Anti-TNF (adalimumab) injection for the treatment of adults with frozen shoulder during the pain predominant stage protocol for a multi-centre, randomised, double blind, parallel group, feasibility trial. NIHR OPEN RESEARCH 2023; 2:28. [PMID: 37881307 PMCID: PMC10593336 DOI: 10.3310/nihropenres.13275.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 04/18/2023] [Indexed: 10/27/2023]
Abstract
Objectives The Anti-Freaze-F trial will assess the feasibility of conducting a large randomised controlled trial to assess whether intra-articular injection of anti-TNF (adalimumab) can reduce pain and improve function in people with pain predominant early stage frozen shoulder. Methods and analysis We are conducting a multi-centre, randomised feasibility study, with an embedded qualitative sub-study. We will recruit adults ≥18 years with a new episode of shoulder pain attributable to early stage frozen shoulder, recruited from at least five UK NHS musculoskeletal and related physiotherapy services. Participants (n=84) will be randomised (centralised computer generated 1:1 allocation) to receive either: 1) intra-articular injection of anti-TNF (adalimumab 160mg) or 2) placebo injection (saline [0.9% sodium chloride]), both under ultrasound guidance. A second injection of the allocated treatment (adalimumab 80mg) or equivalent volume of placebo will be administered 2-3 weeks later. All participants will receive a physiotherapy advice leaflet providing education and advice about frozen shoulder and pain management. The primary feasibility objectives are: 1) the ability to screen and identify potential participants with pain predominant early stage frozen shoulder; 2) willingness of eligible participants to consent and be randomised to intervention; 3) practicalities of delivering the intervention, including time to first injection and number of participants receiving second injection; 4) standard deviation of the Shoulder Pain and Disability Index (SPADI) score and attrition rate at 3 months (i.e. 12 weeks) post-randomisation in order to estimate the sample size for a definitive trial. We will also assess follow up rates and viability of patient-reported outcome measures and range of shoulder motion for a definitive trial. Research Ethics Committee approval (REC 21/NE/0214). Trial registration number ISRCTN 27075727; EudraCT number: 2021-003509-23; ClinicalTrials.gov NCT05299242.
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Affiliation(s)
- Sally Hopewell
- Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Nicola Kenealy
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Ruth Knight
- Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Amar Rangan
- James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK
- Hull York Medical School and Department of Health Sciences, University of York, York, UK
| | - Susan Dutton
- Oxford Clinical Trials Research Unit / Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Cynthia Srikesavan
- Centre for Rehabilitation Research in Oxford, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Marc Feldmann
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
| | - Sarah Lamb
- College of Medicine and Health, University of Exeter, Exeter, UK
| | - Jagdeep Nanchahal
- Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
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11
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Alghamdi A, Alyami AH, Althaqafi RMM, Alzeyadi A, Alrubaei FS, Alyami AA, Singer MS, Saati AA, Alotaibi WT, Alsharif MO. Cytokines' Role in the Pathogenesis and Their Targeting for the Prevention of Frozen Shoulder: A Narrative Review. Cureus 2023; 15:e36070. [PMID: 37056530 PMCID: PMC10092900 DOI: 10.7759/cureus.36070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2023] [Indexed: 03/14/2023] Open
Abstract
Frozen shoulder (FS) is a common name for shoulder movement limitation with different degrees of shoulder rigidity and pain. It is characterized by varying developmental courses, different levels of shoulder movement limitation, and background ambiguity due to the multiplicity of its causative factors. Systemic inflammatory cytokines monitoring and restraining is easy to apply, fast to conduct, and needs lower costs compared to invasive methods for frozen shoulder stage evaluation and early controlling of its progress to the stage that necessitates surgical intervention. The aim of this review was to assess the recent findings concerning the role of cytokines in FS pathogenesis and the possibility of preventing or controlling their progress through targeting these cytokines by the new drugs candidates, such as hyaluronan (HA), botulinum toxin type A (BoNT A), Tetrandrine, tumor necrosis factor-stimulated gene-6 (TSG-6), and cannabidiol. Searching the PubMed site, we encountered out of 1608 records, from which 16 original studies were included for the quantitative construction of this systematic review screening of the recent studies to investigate the different FS pathogenic pathways. Most of the scenarios are centered around the inflammatory and fibrotic process triggered by synovial and capsular fibroblast stimulation. This mechanism depends mainly on alarmins cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), with the stimulation of interleukin-1 α (IL-1α), interleukin-1 β (IL-1β), tumor necrosis alpha (TNF-α), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in a joint capsule. Different pathways of transforming growth factor- β (TGF-β) stimulation, resulting in overexpression of the fibrotic factors as tenascin C (TNC), fibronectin 1, collagen I (COL 1) and collagen III (COL III), and matrix metalloproteinases (MMPs) in the capsular or synovial/capsular fibroblasts. The overall investigation of these studies led us to conclude that the new drug candidates proved their efficiency in controlling the common pathogenesis of the inflammatory and fibrotic pathways of frozen shoulder and therefore represent a prospect for easy and early controlling and efficiently treating this serious disease.
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12
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Dyer BP, Rathod-Mistry T, Burton C, van der Windt D, Bucknall M. Diabetes as a risk factor for the onset of frozen shoulder: a systematic review and meta-analysis. BMJ Open 2023; 13:e062377. [PMID: 36599641 PMCID: PMC9815013 DOI: 10.1136/bmjopen-2022-062377] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVE Summarise longitudinal observational studies to determine whether diabetes (types 1 and 2) is a risk factor for frozen shoulder. DESIGN Systematic review and meta-analysis. DATA SOURCES MEDLINE, Embase, AMED, PsycINFO, Web of Science Core Collection, CINAHL, Epistemonikos, Trip, PEDro, OpenGrey and The Grey Literature Report were searched on January 2019 and updated in June 2021. Reference screening and emailing professional contacts were also used. ELIGIBILITY CRITERIA Longitudinal observational studies that estimated the association between diabetes and developing frozen shoulder. DATA EXTRACTION AND SYNTHESIS Data extraction was completed by one reviewer and independently checked by another using a predefined extraction sheet. Risk of bias was judged using the Quality In Prognosis Studies tool. For studies providing sufficient data, random-effects meta-analysis was used to derive summary estimates of the association between diabetes and the onset of frozen shoulder. RESULTS A meta-analysis of six case-control studies including 5388 people estimated the odds of developing frozen shoulder for people with diabetes to be 3.69 (95% CI 2.99 to 4.56) times the odds for people without diabetes. Two cohort studies were identified, both suggesting diabetes was associated with frozen shoulder, with HRs of 1.32 (95% CI 1.22 to 1.42) and 1.67 (95% CI 1.46 to 1.91). Risk of bias was judged as high in seven studies and moderate in one study. CONCLUSION People with diabetes are more likely to develop frozen shoulder. Risk of unmeasured confounding was the main limitation of this systematic review. High-quality studies are needed to confirm the strength of, and understand reasons for, the association. PROSPERO REGISTRATION NUMBER CRD42019122963.
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Affiliation(s)
- Brett Paul Dyer
- Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Newcastle-under-Lyme, UK
| | - Trishna Rathod-Mistry
- Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Newcastle-under-Lyme, UK
| | - Claire Burton
- Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Newcastle-under-Lyme, UK
| | - Danielle van der Windt
- Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Newcastle-under-Lyme, UK
| | - Milica Bucknall
- Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Newcastle-under-Lyme, UK
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13
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Fares MY, Koa J, Abboud J. Assessment of Therapeutic Clinical Trials for Adhesive Capsulitis of the Shoulder. JSES Int 2023. [DOI: 10.1016/j.jseint.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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14
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Kulm S, Langhans MT, Shen TS, Kolin DA, Elemento O, Rodeo SA. Genome-Wide Association Study of Adhesive Capsulitis Suggests Significant Genetic Risk Factors. J Bone Joint Surg Am 2022; 104:1869-1876. [PMID: 36223477 DOI: 10.2106/jbjs.21.01407] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Adhesive capsulitis of the shoulder involves loss of passive range of motion with associated pain and can develop spontaneously, with no obvious injury or inciting event. The pathomechanism of this disorder remains to be elucidated, but known risk factors for adhesive capsulitis include diabetes, female sex, and thyroid dysfunction. Additionally, transcriptional profiling and pedigree analyses have suggested a role for genetics. Identification of elements of genetic risk for adhesive capsulitis using population-based techniques can provide the basis for guiding both the personalized treatment of patients based on their genetic profiles and the development of new treatments by identification of the pathomechanism. METHODS A genome-wide association study (GWAS) was conducted using the U.K. Biobank (a collection of approximately 500,000 patients with genetic data and associated ICD-10 [International Classification of Diseases, 10th Revision] codes), comparing 2,142 patients with the ICD-10 code for adhesive capsulitis (M750) to those without. Separate GWASs were conducted controlling for 2 of the known risk factors of adhesive capsulitis-hypothyroidism and diabetes. Logistic regression analysis was conducted controlling for factors including sex, thyroid dysfunction, diabetes, shoulder dislocation, smoking, and genetics. RESULTS Three loci of significance were identified: rs34315830 (in WNT7B; odds ratio [OR] = 1.28; 95% confidence interval [CI], 1.22 to 1.39), rs2965196 (in MAU2; OR = 1.67; 95% CI, 1.39 to 2.00), and rs1912256 (in POU1F1; OR = 1.22; 95% CI, 1.14 to 1.31). These loci retained significance when controlling for thyroid dysfunction and diabetes. The OR for total genetic risk was 5.81 (95% CI, 4.08 to 8.31), compared with 1.70 (95% CI, 1.18 to 2.36) for hypothyroidism and 4.23 (95% CI, 2.32 to 7.05) for diabetes. CONCLUSIONS The total genetic risk associated with adhesive capsulitis was significant and similar to the risks associated with hypothyroidism and diabetes. Identification of WNT7B, POU1F1, and MAU2 implicates the Wnt pathway and cell proliferation response in the pathomechanism of adhesive capsulitis. LEVEL OF EVIDENCE Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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15
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Eberlin CT, Kucharik MP, Cherian NJ, Meek WM, McInnis KC, Martin SD. Adhesive Capsulitis of the Hip: A Case Presentation and Review. Orthop Rev (Pavia) 2022; 14:37679. [DOI: 10.52965/001c.37679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
There remains a paucity of literature addressing adhesive capsulitis of the hip (ACH), making the diagnosis and treatment a continued challenge for healthcare providers. ACH encompasses restricted hip range-of-motion and pain that progresses through analogous Stages (1-4) to adhesive capsulitis of the shoulder. We report a case presentation of a middle-aged man that illustrates the significance of certain patient factors and provide a review of current literature to aid in the diagnostic evaluation and treatment for addressing ACH. Initial conservative treatment of ACH includes the appropriate management of associated comorbidities, oral and/or injectable pharmacologics, and physical therapy. While frequently resolving with time, refractory cases of ACH may require more aggressive approaches including pressure dilation, manipulation under anesthesia, synovectomy, capsular release and, for select patients, total hip arthroplasty. Given the limited available literature addressing ACH, healthcare providers may be forced to rely on a small number of published case reports and outdated review articles to guide their diagnostic evaluation and treatment approaches. Thus, this case presentation and review provides an updated approach to better diagnose and manage patients with ACH.
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Affiliation(s)
| | | | | | - Wendy M Meek
- Massachusetts General Hospital - Mass General Brigham
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16
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Abstract
Frozen shoulder is a common debilitating disorder characterized by shoulder pain and progressive loss of shoulder movement. Frozen shoulder is frequently associated with other systemic conditions or occurs following periods of immobilization, and has a protracted clinical course, which can be frustrating for patients as well as health-care professionals. Frozen shoulder is characterized by fibroproliferative tissue fibrosis, whereby fibroblasts, producing predominantly type I and type III collagen, transform into myofibroblasts (a smooth muscle phenotype), which is accompanied by inflammation, neoangiogenesis and neoinnervation, resulting in shoulder capsular fibrotic contractures and the associated clinical stiffness. Diagnosis is heavily based on physical examination and can be difficult depending on the stage of disease or if concomitant shoulder pathology is present. Management consists of physiotherapy, therapeutic modalities such as steroid injections, anti-inflammatory medications, hydrodilation and surgical interventions; however, their effectiveness remains unclear. Facilitating translational science should aid in development of novel therapies to improve outcomes among individuals with this debilitating condition.
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17
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Schiltz M, Beeckmans N, Gillard B, DE Baere T, Hatem SM. Randomized controlled trial of suprascapular nerve blocks for subacute adhesive capsulitis. Eur J Phys Rehabil Med 2022; 58:630-637. [PMID: 35575454 PMCID: PMC9987327 DOI: 10.23736/s1973-9087.22.07410-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Shoulder pain and loss of function remain a therapeutic challenge in adhesive capsulitis. Suprascapular nerve blocks, a common treatment in adhesive capsulitis, are considered a safe and effective method for the resolution of pain and restoration of shoulder range of motion (ROM). To our knowledge, no data are available on the use of suprascapular nerve blocks in adhesive capsulitis in the subacute phase. AIM The aim of this study was to compare the efficacy of ultrasound-guided suprascapular nerve blocks versus saline injections for treating adhesive capsulitis in the subacute phase. DESIGN Randomized double-blinded controlled trial; level of evidence 2. SETTING Out-patient consultation of Physical and Rehabilitation Medicine in a general hospital. POPULATION Thirty-five patients with subacute adhesive capsulitis. METHODS Patients were randomly allocated to receive either 3 successive (1-week interval) ultrasound-guided suprascapular nerve blocks with ropivacaine 5 mL 2 mg/mL (intervention group) or ultrasound-guided injections of 5 mL sterile saline solution (NaCl 0.9%) (control group), at the floor of the suprascapular fossa. Primary outcome was shoulder function assessed by the Constant-Murley Score. Secondary outcomes were shoulder ROM and shoulder pain intensity. Assessments were performed before each injection and 4 weeks after the last injection. RESULTS A significant increase of Constant-Murley Score (P<0.001), increase of shoulder ROM (all directions: P<0.011) and decrease of pain (P<0.001), were observed over time in both study groups. However, no significant differences were observed between the intervention and the control group. CONCLUSIONS Three successive suprascapular nerve blocks did not provide a better outcome than saline injections on shoulder function, ROM, and pain in subacute adhesive capsulitis. These negative findings warrant some considerations on the natural history of adhesive capsulitis, as well as timing, type, and placebo effects of injections. CLINICAL REHABILITATION IMPACT The current place of suprascapular nerve blocks in the treatment strategy of adhesive capsulitis needs to be rediscussed.
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Affiliation(s)
- Marc Schiltz
- Department of Physical and Rehabilitation Medicine, UZ Brussel, Brussels, Belgium - .,Department of Physical and Rehabilitation Medicine, Clinique St-Jean, Brussels, Belgium -
| | - Nele Beeckmans
- Department of Physical Medicine and Rehabilitation, Regional Hospital RZ Tienen, Tienen, Belgium
| | - Bruno Gillard
- Department of Physical and Rehabilitation Medicine, Clinique St-Jean, Brussels, Belgium
| | - Tom DE Baere
- Department of Orthopedic Surgery, CHIREC Hospital, Brussels, Belgium
| | - Samar M Hatem
- Department of Physical and Rehabilitation Medicine, UZ Brussel, Brussels, Belgium.,Department of Physical and Rehabilitation Medicine, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.,STIMULUS Consortium, Vrije Universiteit Brussel, Brussels, Belgium
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18
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Willmore EG, Millar NL, van der Windt D. Post-surgical physiotherapy in frozen shoulder: A review. Shoulder Elbow 2022; 14:438-451. [PMID: 35846406 PMCID: PMC9284307 DOI: 10.1177/1758573220965870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 11/17/2022]
Abstract
Despite its prevalence, the optimal management of frozen shoulder is unclear. A range of conservative measures are often undertaken with varying degrees of success. In cases of severe and persistent symptoms, release procedures which could include any combination of manipulation under anaesthetic, arthroscopic capsular release or hydrodilatation are frequently offered, none of which has been shown to offer superior outcome over the others. When surgical release is performed a period of rehabilitation is normally recommended but no best practice guidelines exist resulting in considerable variations in practice which may or may not directly affect patient outcome. During this narrative review, we hypothesise that these differing responses to treatment (both conservative and surgical options) are potentially the result of different causal mechanisms for frozen shoulder and may also suggest that post-release rehabilitation may need to take this into account.
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Affiliation(s)
- Elaine G Willmore
- Therapy Department, Gloucestershire
Hospitals NHS Foundation Trust, Cheltenham, UK
| | - Neal L Millar
- Institute of Infection, Immunity and
Inflammation, College of Medicine, Veterinary and Life Sciences, University of
Glasgow, Glasgow, UK
| | - Daniëlle van der Windt
- School for Primary, Community and Social
Care, Centre for Prognosis Research, Primary Centre, Versus Arthritis, Keele
University, Staffordshire, UK
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19
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Van Nuffel M, Poelmans A, Kellens S, Vandenneucker H, Degreef I. The prevalence of frozen shoulder in patients with limited Dupuytren disease. Acta Orthop Belg 2022; 88:387-391. [DOI: 10.52628/88.2.9933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Evidence from the literature suggests an association between Dupuytren disease and frozen shoulder syndrome, both clinically and histologically. An increased tendency for fibrotic healing after repetitive microtrauma could be an underlying mechanism. However, it remains unclear how strong this associa- tion is and if only mild signs of Dupuytren disease would also increase the risk of frozen shoulder. In 61 patients, we examined the hands for signs of Dupuytren disease and the shoulders for pain and limited motion. We found a 21,7% prevalence of frozen shoulder syndrome in patients with signs of Dupuytren disease versus 13,9% in those without. The other way around, in patients with frozen shoulder syndrome the prevalence of Dupuytren disease was 50% versus 36.7% in those without frozen shoulder syndrome. These differences were not statistically significant, contrary to similar research in the literature. However, methodological issues, especially the choice of control group, may explain the differences between our findings and previous studies. We conclude that the clinical association between Dupuytren disease may not be so strong as previously thought, especially in patients with only limited signs of the disease.
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20
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VAN Nuffel M, Vandenneucker H, Kellens S, Rumes N, Degreef I. The Impact of Dupuytren Disease on Recovery of Motion at the Knee after Total Knee Arthroplasty. J Hand Surg Asian Pac Vol 2022; 27:320-325. [PMID: 35404210 DOI: 10.1142/s242483552250028x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Background: Arthrofibrosis is a complication of total knee arthroplasty (TKA) that can lead to poor outcome. Idiopathic arthrofibrosis and Dupuytren disease (DD) have similar histological appearance. The aim of this study is to determine the influence of DD on the recovery of motion after TKAy. Methods: Patients older than 50 who underwent a TKA for primary osteoarthritis were examined 1 year later for the presence of DD. They were divided into two groups based on the presence or absence of DD. The groups were compared to each other with regard to arc of motion (AOM) of the operated knee at 6 weeks and 1 year; the need for additional measures to improve the AOM, and the effect of obesity [body mass index (BMI) > 30]. Results: The study included 61 patients of which 25 (41%) had DD. There was no difference in AOM at 6 weeks or 1 year between the two groups. Patients in the DD group required a greater number of additional measures to improve AOM. Also, non-obese patients (BMI < 30) in the DD group had lower AOM at 1 year. Conclusions: Patients in the DD group needed additional physiotherapy or manipulation under anaesthesia (MUA) to achieve the same AOM. This might indicate a possible connection between DD and post-operative stiffness of the knee. Identifying patients with DD in the pre-operative period may help recognise patients who may have difficulty in regaining AOM after TKA. Level of Evidence: Level III (Therapeutic).
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Affiliation(s)
- Maarten VAN Nuffel
- Department of Medical Sciences, KU Leuven-University of Leuven, Leuven, Belgium; Department of Orthopaedic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Hilde Vandenneucker
- Department of Medical Sciences, KU Leuven-University of Leuven, Leuven, Belgium; Department of Orthopaedic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Sebastiaan Kellens
- Department of Medical Sciences, KU Leuven-University of Leuven, Leuven, Belgium; Department of Anesthesiology, University Hospitals Leuven, Leuven, Belgium
| | - Nanou Rumes
- Department of Medical Sciences, KU Leuven-University of Leuven, Leuven, Belgium; Department of Orthopaedic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Ilse Degreef
- Department of Medical Sciences, KU Leuven-University of Leuven, Leuven, Belgium; Department of Orthopaedic Surgery, University Hospitals Leuven, Leuven, Belgium
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21
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King WV, Hebron C. Frozen shoulder: living with uncertainty and being in "no-man's land". Physiother Theory Pract 2022; 39:979-993. [PMID: 35164645 DOI: 10.1080/09593985.2022.2032512] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND Frozen Shoulder (FS) is a painful debilitating condition that is a significant burden to those experiencing it and healthcare systems. Despite research investigating the pathogenesis and effective treatment for the condition, there is a paucity of research exploring how having frozen shoulder is lived through and meaningful to persons experiencing it. OBJECTIVE To explore how living with Frozen Shoulder is experienced and meaningful. METHODS A qualitative research study design using hermeneutic phenomenology methodology was used. In-depth unstructured interviews were conducted with six purposively recruited participants. Interpretive Phenomenological methods were used to analyze the data forming emergent, superordinate and master themes to qualitatively expose the meaningful aspects of living through FS. FINDINGS Five Master themes were identified: 1) "Dropping me to my knees," an incredible pain experience; 2) The struggle for normality; 3) An emotional change of self; 4) The challenges of the healthcare journey; and 5) Coping and adapting. The overarching 'binding theme' was Frozen Shoulder: Living with uncertainty and being in "no-man's land." CONCLUSIONS This study illuminated the struggle to maintain a normal life while living with the significant pain, physical restriction, sleep loss and disability experienced by persons with Frozen Shoulder. Attempts to cope and adapt were impeded by the challenges of the healthcare journey. The uncertainty of these experiences was conveyed as being in "no man's land" an expression that reflected the existential crisis and impact on persons' sense of self.
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Affiliation(s)
- William V King
- Bognor War Memorial Hospital, Sussex Community NHS Foundation Trust, Bognor Regis, UK
| | - Clair Hebron
- School of Sport and Health Sciences, Brighton University, Eastbourne, UK
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22
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Nanostring-Based Identification of the Gene Expression Profile in Trigger Finger Samples. Healthcare (Basel) 2021; 9:healthcare9111592. [PMID: 34828637 PMCID: PMC8619339 DOI: 10.3390/healthcare9111592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 10/26/2021] [Accepted: 11/05/2021] [Indexed: 11/17/2022] Open
Abstract
Trigger finger is a common yet vastly understudied fibroproliferative hand pathology, severely affecting patients' quality of life. Consistent trauma due to inadequate positioning within the afflicted finger's tendon/pulley system leads to cellular dysregulation and eventual fibrosis. While the genetic characteristics of the fibrotic tissue in the trigger finger have been studied, the pathways that govern the initiation and propagation of fibrosis are still unknown. The complete gene expression profile of the trigger finger has never been explored. Our study has used the Nanostring nCounter gene expression assay to investigate the molecular signaling involved in trigger finger pathogenesis. We collected samples from patients undergoing trigger finger (n = 4) release surgery and compared the gene expression to carpal tunnel tissue (n = 4). Nanostring nCounter analysis identified 165 genes that were differentially regulated; 145 of these genes were upregulated, whereas 20 genes were downregulated. We found that several collagen genes were significantly upregulated, and a regulatory matrix metalloproteinase (MMP), MMP-3, was downregulated. Bioinformatic analysis revealed that several known signaling pathways were dysregulated, such as the TGF-β1 and Wnt signaling pathways. We also found several novel signaling pathways (e.g., PI3K, MAPK, JAK-STAT, and Notch) differentially regulated in trigger finger. The outcome of our study helps in understanding the molecular signaling pathway involved in the pathogenesis of the trigger finger.
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23
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Almadani YH, Vorstenbosch J, Efanov JI, Xu L. Dupuytren's Disease: An Outcomes-Focused Update. Semin Plast Surg 2021; 35:216-222. [PMID: 34526871 DOI: 10.1055/s-0041-1731631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Dupuytren's disease (DD) remains a common fibroproliferative condition with significant sequelae and impact on patient's lives. The etiology of DD is poorly understood, and genetic predisposition is thought to be a strongly associated factor. Despite remarkable strides in improving our molecular understanding of DD, clinical treatment options have not yet overcome the frequently encountered challenge of recurrence. Recurrence rates continue to shape the prognosis of this fibrotic condition. In this outcomes-focused article, the various treatment modalities are reviewed. This further emphasizes the importance of patient education and providing them with the information to make informed decisions about their treatment.
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Affiliation(s)
- Yasser H Almadani
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Joshua Vorstenbosch
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
| | - Johnny Ionut Efanov
- Division of Plastic and Reconstructive Surgery, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada
| | - Liqin Xu
- Division of Plastic and Reconstructive Surgery, McGill University Health Centre, Montreal, Quebec, Canada
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24
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Marker L, Schjerling P, Mackey AL, Hansen T, Jakobsen J, Kjær M, Krogsgaard MR. Collagens in primary frozen shoulder: expression of collagen mRNA isoforms in the different phases of the disease. Rheumatology (Oxford) 2021; 60:3879-3887. [PMID: 33347577 DOI: 10.1093/rheumatology/keaa802] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 09/24/2020] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES Primary frozen shoulder (pFS) has three phases that differ in clinical presentation. It is characterized by contracture of the joint capsule. We hypothesized that there is a general upregulation of collagens in pFS, and that this is highest in the first phase of the disease. The aims of this study were to investigate the expression of various collagens and degradation of collagens in patients with primary pFS and relate this to the three phases of the condition. METHODS From twenty-six patients with pFS and eight control patients with subacromial impingement, biopsies were obtained during shoulder arthroscopy from the middle glenohumeral ligament and the anterior capsule, and mRNA levels for collagens, MMP-2 and -14 and TGF-β1, - β2 and -β3 in the tissue were analysed using real-time PCR. RESULTS Genes for collagens type I, III, IV, V, VI and XIV, were activated in pFS, and the total mRNA for all collagens was increased (P < 0.05). This upregulation was independent of disease phases in pFS. In addition, MMP-2, MMP-14, TGF-β1 and TGF-β3 were upregulated in all phases of the disease. CONCLUSION There is a general upregulation and an increased degradation of collagens in pFS in all three phases of the disease. This indicates a constantly increased turnover of the fibrotic tissue in the capsule from pFS. The difference in clinical presentation of pFS observed in the three phases of the disease is not primarily a result of variations in collagen production.
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Affiliation(s)
- Line Marker
- Section for Sports Traumatology M51, Department of Orthopaedic Surgery M, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Peter Schjerling
- Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg and Frederiksberg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, Copenhagen, Denmark
| | - Abigail L Mackey
- Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg and Frederiksberg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, Copenhagen, Denmark.,Xlab, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Hansen
- Section for Sports Traumatology M51, Department of Orthopaedic Surgery M, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Jens Jakobsen
- Section for Sports Traumatology M51, Department of Orthopaedic Surgery M, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Michael Kjær
- Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg and Frederiksberg Hospital, Center for Healthy Aging, Faculty of Health and Medical Sciences, Copenhagen, Denmark
| | - Michael R Krogsgaard
- Section for Sports Traumatology M51, Department of Orthopaedic Surgery M, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
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25
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Ibrahim IO, Nazarian A, Rodriguez EK. Clinical Management of Arthrofibrosis: State of the Art and Therapeutic Outlook. JBJS Rev 2021; 8:e1900223. [PMID: 32618740 DOI: 10.2106/jbjs.rvw.19.00223] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
* Arthrofibrosis is a pathologic condition that is characterized by excessive periarticular scar-tissue formation. Arthrofibrosis may occur secondary to injury, surgical trauma, hemarthrosis, or infection, or it may occur idiopathically.* The pathogenesis of arthrofibrosis is incompletely understood but involves the dysregulation of normal reparative pathways, with transforming growth factor-beta (TGF-[beta]) as a principal mediator.* Current treatment options for arthrofibrosis primarily involve physiotherapy, operative manipulation, and surgical debridement, all with imperfect results.* Currently, there are no pharmacologic treatment options for arthrofibrosis. This has prompted increased investigational interest in the development of antifibrotic intra-articular therapies.
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Affiliation(s)
- Ishaq O Ibrahim
- Harvard Combined Orthopaedic Residency Program, Massachusetts General Hospital, Boston, Massachusetts
| | - Ara Nazarian
- Harvard Medical School Orthopedic Trauma Initiative, Boston, Massachusetts.,Center for Advanced Orthopaedic Studies (A.N.), and Orthopaedic Trauma Service (E.K.R.), Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts.,Department of Orthopaedic Surgery, Yerevan State Medical University, Yerevan, Armenia
| | - Edward K Rodriguez
- Harvard Medical School Orthopedic Trauma Initiative, Boston, Massachusetts.,Center for Advanced Orthopaedic Studies (A.N.), and Orthopaedic Trauma Service (E.K.R.), Carl J. Shapiro Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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26
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Lesevic M, Awowale JT, Moran TE, Diduch DR, Brockmeier SF, Werner BC. Immediate Pain Relief at Time of Corticosteroid Injection for Idiopathic Adhesive Capsulitis as a Predictor of Eventual Outcomes. Orthop J Sports Med 2021; 9:23259671211019353. [PMID: 34345633 PMCID: PMC8283233 DOI: 10.1177/23259671211019353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 02/18/2021] [Indexed: 11/16/2022] Open
Abstract
Background Corticosteroid injection and physical therapy remain the mainstay of treatment for idiopathic adhesive capsulitis of the shoulder; however, a certain percentage of patients will not improve using these interventions and will require manipulation under anesthesia (MUA) and/or lysis of adhesions (LOA). Purpose To evaluate whether the immediate pain reduction after fluoroscopic-guided, mixed anesthetic-corticosteroid injection for idiopathic adhesive capsulitis is related to the eventual need for LOA/MUA or a repeat glenohumeral steroid injection. Study Design Case-control study; Level of evidence, 3. Methods This single-institution study involved patients undergoing fluoroscopic glenohumeral corticosteroid injection for a diagnosis of idiopathic adhesive capsulitis between 2010 and 2017. Included were patients with a minimum of 1-year postinjection follow-up and visual analog scale (VAS) pain scores from immediately before and after the injection. The primary analysis was the relationship between patients with an immediate change in VAS score after injection and those who underwent LOA/MUA. A repeat glenohumeral injection was also evaluated as an outcome. Receiver operator characteristic curves and a multivariate binomial logistic regression analysis were performed. Results Overall, 739 shoulders in 728 patients (mean age, 52.6 years; 68% women) were included, of which 38 (5.1%) underwent LOA/MUA and 209 (28%) underwent repeat injections. The immediate change in the VAS score was not significantly associated with the eventual need for LOA/MUA. Preinjection VAS and immediate postinjection VAS scores were not significant predictors of eventual LOA/MUA or subsequent injection. For all 3 predictors, the area under the receiver operator characteristic curve classified them as extremely poor discriminators. Conclusion The immediate pain response to a fluoroscopic-guided glenohumeral injection for idiopathic shoulder adhesive capsulitis was not predictive of the eventual need for LOA/MUA or subsequent injection. Patients can be counseled that even if their initial pain response to an injection is poor, they still have an excellent chance of avoiding surgery, as the overall rate of LOA/MUA was low (5.1%).
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Affiliation(s)
- Milos Lesevic
- University of Virginia, Department of Orthopaedic Surgery, Charlottesville, Virginia USA
| | - John T Awowale
- University of Virginia, Department of Orthopaedic Surgery, Charlottesville, Virginia USA
| | - Thomas E Moran
- University of Virginia, Department of Orthopaedic Surgery, Charlottesville, Virginia USA
| | - David R Diduch
- University of Virginia, Department of Orthopaedic Surgery, Charlottesville, Virginia USA
| | - Stephen F Brockmeier
- University of Virginia, Department of Orthopaedic Surgery, Charlottesville, Virginia USA
| | - Brian C Werner
- University of Virginia, Department of Orthopaedic Surgery, Charlottesville, Virginia USA
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27
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Gonga-Cavé BC, Pena Diaz AM, O'Gorman DB. Biomimetic analyses of interactions between macrophages and palmar fascia myofibroblasts derived from Dupuytren's disease reveal distinct inflammatory cytokine responses. Wound Repair Regen 2021; 29:627-636. [PMID: 34212454 DOI: 10.1111/wrr.12928] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/16/2021] [Accepted: 04/28/2021] [Indexed: 12/31/2022]
Abstract
Dupuytren's disease (DD) is a common and heritable fibrosis of the hand. It is characterized by the shortening and thickening of the palmar fascia into myofibroblastic nodules that can progress to palmar-digital contractures and permanent loss of dexterity. Molecular analyses of DD tissues and the presence of inflammatory cell infiltrates suggest a pathogenesis initiated by a proinflammatory fascial milieu that promotes myofibroblast activation and palmar fascia contractures. However, the relative contributions of vascular and/or tissue derived immune system cells and cytokine-sensitive stromal myofibroblasts to the development of this proinflammatory microenvironment are poorly understood. To gain insights into this process, we have developed and tested a collagen-based 3D tissue biomimetic co-culture system to assess paracrine interactions between THP-1-derived pro-inflammatory macrophages and primary human palmar fascia myofibroblasts (PFMs). We observed significant and reproducible impacts of collagen-adherent macrophage and PFM co-cultures on the cytokine gene expression profiles of these cells compared to their respective monocultures, and significant changes to the resulting cytokine milieu in their shared culture media, notably TNF and IL-6. Our findings are consistent with central roles for PFMs in cytokine production and immunoregulation of the pro-inflammatory milieu hypothesized to promote DD development.
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Affiliation(s)
- Brianna C Gonga-Cavé
- Department of Biochemistry, University of Western Ontario, London, Ontario, Canada
| | - Ana Maria Pena Diaz
- Roth McFarlane Hand and Upper Limb Centre, Lawson Health Research Institute, London, Ontario, Canada
| | - David B O'Gorman
- Department of Biochemistry, University of Western Ontario, London, Ontario, Canada.,Department of Surgery, University of Western Ontario, London, Ontario, Canada.,Roth McFarlane Hand and Upper Limb Centre, Lawson Health Research Institute, London, Ontario, Canada
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28
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Green HD, Jones A, Evans JP, Wood AR, Beaumont RN, Tyrrell J, Frayling TM, Smith C, Weedon MN. A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor. PLoS Genet 2021; 17:e1009577. [PMID: 34111113 PMCID: PMC8191964 DOI: 10.1371/journal.pgen.1009577] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 05/04/2021] [Indexed: 11/19/2022] Open
Abstract
Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16-1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren's disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02-1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren's disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.
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Affiliation(s)
- Harry D. Green
- Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
| | - Alistair Jones
- Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital, Exeter, United Kingdom
| | - Jonathan P. Evans
- Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital, Exeter, United Kingdom
| | - Andrew R. Wood
- Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
| | - Robin N. Beaumont
- Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
| | - Jessica Tyrrell
- Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
| | - Timothy M. Frayling
- Genetics of Complex Traits, University of Exeter Medical School, Exeter, United Kingdom
| | - Christopher Smith
- Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital, Exeter, United Kingdom
| | - Michael N. Weedon
- Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital, Exeter, United Kingdom
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29
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Wang JY, Liaw CK, Huang CC, Liou TH, Lin HW, Huang SW. Hyperlipidemia Is a Risk Factor of Adhesive Capsulitis: Real-World Evidence Using the Taiwanese National Health Insurance Research Database. Orthop J Sports Med 2021; 9:2325967120986808. [PMID: 33869642 PMCID: PMC8024456 DOI: 10.1177/2325967120986808] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 09/30/2020] [Indexed: 11/17/2022] Open
Abstract
Background: Patients with adhesive capsulitis are evaluated for pain and progressive contracture of the glenohumeral joint. Whether endocrine, immune, or inflammatory processes are involved in its definite pathogenesis is still under debate. Some cross-sectional studies with a small sample size have noted that hyperlipidemia is a possible risk factor for frozen shoulders. Purpose/Hypothesis: The purpose was to conduct a longitudinal population-based study to investigate the risk of adhesive capsulitis among patients with hyperlipidemia. It was hypothesized that patients with hyperlipidemia would have a higher risk of adhesive capsulitis and that the use of statin drugs could reduce the rate. Study Design: Cohort study; Level of evidence, 3. Methods: Using data from the National Health Insurance Research Database (NHIRD) of Taiwan, the authors obtained the records of patients with hyperlipidemia who received a diagnosis between 2004 and 2005 and were followed up until the end of 2010. The control cohort comprised age- and sex-matched patients without hyperlipidemia. Propensity score matching was performed for the other comorbidities. A Cox multivariate proportional hazards model was applied to analyze the risk factors of adhesive capsulitis. The hazard ratio (HR) and adjusted HR were estimated between the study and control cohorts after adjustment for confounders. The effects of statin use on adhesive capsulitis risk were also analyzed. Results: The NHIRD records of 28,748 patients and 114,992 propensity score–matched controls were evaluated. A higher incidence rate of adhesive capsulitis was revealed in the hyperlipidemia cohort, with a crude HR of 1.70 (95% CI, 1.61-1.79; P < .001) and adjusted HR of 1.50 (95% CI, 1.41-1.59; P < .001). Patients with hyperlipidemia who used a statin still had higher crude and adjusted HRs compared with controls. Statin use did not exert protective effects on patients with hyperlipidemia. Conclusion: Patients with hyperlipidemia had a 1.5-fold higher risk of adhesive capsulitis than did healthy controls. Statin use did not provide protection against adhesive capsulitis in patients with hyperlipidemia.
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Affiliation(s)
- Jr-Yi Wang
- Department of Orthopedic Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City.,Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei
| | - Chen-Kun Liaw
- Department of Orthopedic Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City.,Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei
| | - Chi-Chang Huang
- Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan
| | - Tsan-Hon Liou
- Department of Physical Medicine and Rehabilitation, Shuang Ho Hospital, Taipei Medical University, Taipei.,Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University
| | - Hui-Wen Lin
- Department of Mathematics, Soochow University, Taipei.,ICF Research Center, Shuang Ho Hospital, Taipei Medical University, Taipei
| | - Shih-Wei Huang
- Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan.,Department of Physical Medicine and Rehabilitation, Shuang Ho Hospital, Taipei Medical University, Taipei.,Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University
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30
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Jump CM, Duke K, Malik RA, Charalambous CP. Frozen Shoulder: A Systematic Review of Cellular, Molecular, and Metabolic Findings. JBJS Rev 2021; 9:e19.00153. [PMID: 33512972 DOI: 10.2106/jbjs.rvw.19.00153] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND Frozen shoulder is a common, poorly understood condition affecting the shoulder joint, with poor long-term outcomes in some in relation to pain and mobility. Understanding the pathophysiology of frozen shoulder at a cellular level and a molecular level may help in the development of novel treatments. The aim of this study was to perform a systematic review of studies examining the cellular, molecular, and metabolic findings in frozen shoulder. METHODS A literature search was conducted using Embase, CINAHL (Cumulative Index of Nursing and Allied Health Literature), and PubMed using relevant terms. Studies were included if they assessed cellular, molecular, or metabolic alterations in tissue or blood samples of patients with frozen shoulder. RESULTS Of 4,794 studies identified, 25 were included for analysis. Histological findings included nonspecific chronic inflammation and the proliferation of fibroblasts, adipocytes, and blood vessels. Molecular studies showed increased pro-inflammatory mediators, reduced matrix metalloproteinases (MMPs), and increased activity of factors promoting fibroblast activation and nerve growth. Metabolic alterations included an increase in blood lipids. CONCLUSIONS Frozen shoulder is thought to occur after a primary insult to the shoulder triggers a complex cascade and upregulation of growth factors and cytokines with an increased turnover of the extracellular matrix, activation of myofibroblasts with deposition of collagen, and reduced matrix degradation. The presence of a background pro-inflammatory state (e.g., patients with diabetes or hyperlipidemia) may exacerbate these abnormalities. Further work assessing patients in early stages of the disease and comparing the inflammatory or fibrogenic characteristics of the shoulder capsule with those of the other joints may help to determine the initiating factors and to explain the predisposition of the shoulder to stiffness. CLINICAL RELEVANCE Our findings may form the basis for identifying new targets for the clinical management of frozen shoulder.
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Affiliation(s)
- Christopher M Jump
- Department of Orthopaedics, Blackpool Victoria Hospital, Blackpool, United Kingdom
| | - Kathryn Duke
- Department of Orthopaedics, Blackpool Victoria Hospital, Blackpool, United Kingdom
| | | | - Charalambos P Charalambous
- Department of Orthopaedics, Blackpool Victoria Hospital, Blackpool, United Kingdom.,School of Medicine, University of Central Lancashire, Preston, United Kingdom
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31
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Gacaferi H, Kolk A, Visser CPJ. Arthroscopic bursectomy less effective in the degenerative shoulder with chronic subacromial pain. JSES Int 2020; 5:220-227. [PMID: 33681841 PMCID: PMC7910744 DOI: 10.1016/j.jseint.2020.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
Background Varying results after surgery in patients with subacromial pain syndrome (SAPS) have raised the question on whether there is a subgroup of patients that can benefit from surgery. Therefore, we aimed to identify preoperative and peroperative factors associated with a favorable patient-reported outcome after arthroscopic bursectomy in patients with SAPS. Methods Patients with chronic SAPS who underwent arthroscopic bursectomy after failed conservative management were included (n = 94). Patients were evaluated at the baseline, and 2 weeks, 8 weeks, 6 months, and 1 year after surgery. The primary outcome was the Western Ontario Rotator Cuff index (WORC) score one year after surgery. The secondary outcome measure was a visual analog scale for pain. Mixed model analyses were used to identify prognostic factors. Results The mean WORC (mean difference 39%, 95% confidence interval (CI) 32.8-45.3, P < .001) and visual analog scale pain scores (mean difference 41 mm points, 95% CI 3.37-4.88, P < .001) significantly improved one year after surgery. Nineteen patients (20%) developed a postoperative frozen shoulder. A longer duration of preoperative complaints and the peroperative identification of degenerative glenoid cartilage were associated with significantly worse WORC scores, with -0.086% per month (95% CI -0.156 to -0.016, P = .016) and -20% (95% CI -39.4 to -1.26, P = .037), respectively. Conclusion We identified demographic and clinical factors that predict the course after arthroscopic subacromial bursectomy. We found that arthroscopic bursectomy is less effective in patients with SAPS with a degenerative shoulder. This finding suggests that an improved treatment effect of arthroscopic subacromial bursectomy can be expected in patients with chronic SAPS if intra-articular pathologies such as glenohumeral osteoarthritis are sufficiently excluded.
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Affiliation(s)
- Hamez Gacaferi
- Department of Orthopedics, Alrijne Hospital, Leiden, the Netherlands.,Department of Orthopedics, Leiden University Medical Center (LUMC), Leiden, the Netherlands
| | - Arjen Kolk
- Department of Orthopedics, Leiden University Medical Center (LUMC), Leiden, the Netherlands
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32
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Park HB, Gwark JY, Kam M, Jung J. Association between fasting glucose levels and adhesive capsulitis in a normoglycemic population: a case-control study. J Shoulder Elbow Surg 2020; 29:2240-2247. [PMID: 32713668 DOI: 10.1016/j.jse.2020.03.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 03/14/2020] [Accepted: 03/20/2020] [Indexed: 02/01/2023]
Abstract
BACKGROUND Hyperglycemia is the most commonly cited risk factor for adhesive capsulitis. However, no study has established whether fasting glucose levels within the normoglycemic range are associated with idiopathic adhesive capsulitis (IAC). This study hypothesized that increments of fasting glucose levels within the normoglycemic range would be linked to IAC. This study investigated any association between normoglycemic fasting glucose levels and IAC. METHODS This case-control study comprised a group of 151 patients with IAC without intrinsic shoulder lesions, extrinsic causes, or known metabolic risk factors such as diabetes, dyslipidemia, and thyroid dysfunction. The control group comprised 453 age- and sex-matched persons seeking general check-ups at the authors' health promotion center during the same period as the case group. Control subjects had normal shoulder function, no previous diagnosis of adhesive capsulitis or of metabolic disease, and no history of trauma or of shoulder surgery. The studied variables were body mass index, serum lipid profiles, thyroid hormone levels, fasting glucose levels, glycosylated hemoglobin A1c, and high-sensitivity C-reactive protein. Fasting glucose levels were studied as scale data and categorical data (<85, 85-89, 90-94, and 95-99 mg/dL). Multivariable conditional logistic regression analysis evaluated the matched sets of subjects. Odds ratios and 95% confidence intervals were determined for various potentially associated factors. RESULTS Fasting glucose level, hypercholesterolemia, and high-sensitivity C-reactive protein were significantly associated with IAC (P ≤ .030). Fasting glucose levels in the <85 mg/dL quartile were significantly negatively associated with IAC (P ≤ .001). In contrast, fasting glucose levels in the 90-94 mg/dL quartile or higher were significantly positively associated with IAC (P ≤ .034). CONCLUSION IAC is positively associated with fasting glucose levels of 90-99 mg/dL, which are currently considered normoglycemic.
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Affiliation(s)
- Hyung Bin Park
- Department of Orthopaedic Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea; Gyeongsang Institute of Health Sciences, Gyeongsang National University, Jinju, Republic of Korea.
| | - Ji-Yong Gwark
- Department of Orthopaedic Surgery, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Mincheol Kam
- Department of Orthopaedic Surgery, Himchan Hospital, Changwon, Republic of Korea
| | - Jaehoon Jung
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
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Andronic O, Ernstbrunner L, Jüngel A, Wieser K, Bouaicha S. Biomarkers associated with idiopathic frozen shoulder: a systematic review. Connect Tissue Res 2020; 61:509-516. [PMID: 31340682 DOI: 10.1080/03008207.2019.1648445] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Background: The pathophysiology of idiopathic frozen shoulder (FS) remains poorly described. There is a lack of differentiation between idiopathic and secondary cause. The aim of this systematic review was to summarize the evidence regarding the pathophysiology of idiopathic FS on a molecular level and emphasize the clinical relevance. Methods: A database search of Medline, EMBASE and Cochrane Central Register of Controlled Trials from inception to April 2018 was performed. Participants who underwent previous injections or surgeries were excluded. A thorough selection and quality assessment process using the Cochrane Risk of Bias assessment tool and the Joanna Briggs Institute Critical Appraisal Checklist was conducted by two reviewers independently. Results: A total of 15 studies analyzing 333 study subjects were included. Twelve studies evaluated capsular tissue and three studies investigated blood samples. The tissue samples revealed increased expression of various inflammatory cytokines including interleukins, cyclooxygenase and tumor necrosis factor. Several types of acid-sensing ion channels (ASIC1 and ASIC3) were associated with disturbed neurogenesis and melatonin-regulated pain mechanism. The blood samples showed prevalence of specific interleukin and metalloproteinase genotypes. A decreased matrix metalloproteinase/tissue inhibitor of metalloproteinase ratio was found both in tissue and blood. Conclusion: The findings indicate an abnormal local neurogenesis with possible regulation through melatonin. The disturbance in remodeling of the extracellular matrix and in collagen translation, together with a persistent inflammation and an impaired healing, all interact in the process that leads to persistent fibrosis. There is global fibroplasia with localized anterior capsule contracture.
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Affiliation(s)
- Octavian Andronic
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich , Zurich, Switzerland
| | - Lukas Ernstbrunner
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich , Zurich, Switzerland
| | - Astrid Jüngel
- Center of Experimental Rheumatology, University Clinic of Rheumatology, Balgrist Campus , Zürich, Switzerland
| | - Karl Wieser
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich , Zurich, Switzerland
| | - Samy Bouaicha
- Department of Orthopaedics, Balgrist University Hospital, University of Zurich , Zurich, Switzerland
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34
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Fernández Martínez AM, Baldi S, Alonso-Burgos A, López R, Vallejo-Pascual ME, Cuesta Marcos MT, Romero Alonso D, Rodríguez Prieto J, Mauriz JL. Mid-Term Results of Transcatheter Arterial Embolization for Adhesive Capsulitis Resistant to Conservative Treatment. Cardiovasc Intervent Radiol 2020; 44:443-451. [PMID: 33135118 DOI: 10.1007/s00270-020-02682-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 10/07/2020] [Indexed: 11/25/2022]
Abstract
PURPOSE To evaluate the mid-term clinical outcomes of transcatheter arterial embolization (TAE) for adhesive capsulitis (AC) resistant to medical treatments. MATERIALS AND METHODS This is a prospective analysis performed between February 2016 and February 2020. Inclusion criteria for TAE were shoulder pain, restriction of movement and no response to conservative treatment for at least 3 months. Demographic variables, risk factors, technical aspects, adverse events, changes by visual analogue scale (VAS) for pain and physical examination before and after TAE were assessed. RESULTS This study included 40 patients with AC (35 women and 5 men; mean age 50 ± 9 years old). Abnormal vessels were observed in 31/40 (77.5%) procedures. As embolic agent, imipenem/cilastatin was used. The mean follow-up was 21.2 ± 10.5 months. Significant differences were obtained in terms of pain reduction before and 6 months after TAE with the median visual analogue scale (VAS) of 8 vs. 0.5, P = 0.0001. Substantial differences were found regarding mobility in flexion and abduction before and 6 months after embolization, respectively (79.5° ± 18.5° vs. 133° ± 24.5°, P = 0.0001; 72.4° ± 18.8° vs. 129.7° ± 27.9°, P = 0.0001). No complications occurred. Complete recovery was obtained in 37/40 (92.5%) patients and partial recovery in 2/40 (5%). No clinical recurrence appeared. CONCLUSIONS Clinical results of transcatheter arterial embolization with imipenem/cilastatin are effective and stable in the mid-term follow-up for patients presenting with AC resistant to conservative treatments.
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Affiliation(s)
| | - Sebastián Baldi
- Interventional Radiology, Universitary Hospital of León, León, Spain
| | | | - Roberto López
- Physical Chemistry Area, Faculty of Biology and Environmental Sciences, University of León, León, Spain
| | | | | | | | | | - Jose Luis Mauriz
- Institute of Biomedicine (IBIOMED), University of León, León, Spain
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Frozen shoulder: overview of clinical presentation and review of the current evidence base for management strategies. Future Sci OA 2020; 6:FSO647. [PMID: 33312703 PMCID: PMC7720362 DOI: 10.2144/fsoa-2020-0145] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Adhesive capsulitis of the shoulder (ACS) is a condition with significant clinical and economic implications. The etiology of adhesive capsulitis is not clearly understood and there remains lack of consensus in clinical management for this condition. It can occur as a primary idiopathic condition or secondary to medical conditions or trauma. The hallmarks of ACS are pain and stiffness, caused by formation of adhesive or scar tissue in the glenohumeral joint. Management strategies vary depending on stage of presentation, patient factors and clinician preferences, and can range from conservative options to surgical intervention. The aim of this review is to summarize the pathophysiology and clinical presentation of ACS and to discuss the evidence base for various management strategies employed today. Frozen shoulder (FS) is a relatively common condition characterized by pain and stiffness of the shoulder joint. The exact cause of primary FS is unknown and in some patients the condition can persist for several years. Treatment strategies vary depending on stage of presentation, patient factors and clinician preferences. This review gives a summary of the clinical presentation of FS and an overview of the current evidence for both surgical and conservative treatment options for the condition.
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36
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Breckenridge JD, McAuley JH, Ginn KA. Motor Imagery Performance and Tactile Spatial Acuity: Are They Altered in People with Frozen Shoulder? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17207464. [PMID: 33066655 PMCID: PMC7602509 DOI: 10.3390/ijerph17207464] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 10/09/2020] [Accepted: 10/11/2020] [Indexed: 12/24/2022]
Abstract
Frozen shoulder (adhesive capsulitis) is a severe chronic pain condition that is not well understood and current treatment is suboptimal. In several other chronic pain conditions motor imagery and tactile acuity deficits are present, which are thought to represent associated neuroplastic changes. The aims of this study were to determine if motor imagery performance assessed by the left/right judgement task, and tactile acuity assessed by two-point discrimination, are altered in people with unilateral frozen shoulder. In this cross-sectional, prospective study eighteen adults diagnosed with frozen shoulder in a physiotherapy clinic setting completed a left/right judgement task, response times (RT) and accuracy for the left/right judgement task were determined. Next, tactile acuity over both shoulders was assessed with a novel, force-standardised two-point discrimination test. Results corresponding to the affected side were compared to the pain free shoulder; Left/right judgement task: mean RT (SD) corresponding to the affected shoulder was significantly slower than RT for the healthy shoulder (p = 0.031). There was no side-to-side difference in accuracy (p > 0.05). Neither RT nor accuracy was related to pain/disability scores or duration of symptoms (p > 0.05). Two-point discrimination: mean two-point discrimination threshold of the affected shoulder was significantly larger than the contralateral healthy shoulder (p < 0.001). Two-point discrimination threshold was not related to pain/disability scores or pain duration (p > 0.05); One explanation for these findings is altered sensorimotor processing and/or disrupted sensorimotor cortex representations of the affected shoulder. A case then exists for the use of treatments aimed at reversing these changes, training the brain to reduce chronic shoulder pain.
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Affiliation(s)
- John D. Breckenridge
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney 2006, Australia;
- The Clinical Research Institute, Sydney 2145, Australia
- Correspondence: ; Tel.: +61-2-9672-3511
| | - James H. McAuley
- Neuroscience Research Australia (NeuRA), Hospital Rd, Randwick 2013, Australia;
- School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney 2033, Australia
| | - Karen A. Ginn
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney 2006, Australia;
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Picard S, Vasilevski D, Fagherazzi G. Distribution of Highly Prevalent Musculoskeletal Disorders and Their Association With Diabetes Complications in a Population of 140 Individuals With Type 1 Diabetes: A Retrospective Study in a French Diabetes Center. Clin Diabetes 2020; 38:181-187. [PMID: 32327891 PMCID: PMC7164982 DOI: 10.2337/cd19-0062] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Although they are usually not considered to be diabetes complications, musculoskeletal disorders (MSKDs) are common in individuals with type 1 or type 2 diabetes and can strongly interfere with daily diabetes care, especially in people using diabetes technologies. The authors of this retrospective study in a population of 140 patients with type 1 diabetes report the distribution of subtypes of MSKDs and speculate about the mechanisms involved. The authors emphasize the need for multidisciplinary care involving not only the diabetes care team but also orthopedic surgeons. This report should lead to large, prospective studies to increase knowledge about these under-studied complications.
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Affiliation(s)
- Sylvie Picard
- Endocrinology and Diabetes, Point Medical, Dijon, France
| | | | - Guy Fagherazzi
- National Institute of Health and Medical Research (INSERM U1018), Center for Research in Epidemiology and Population Health, Paris South–Paris Saclay University, Gustave Roussy Institute, Villejuif, France
- Luxembourg Institute of Health, Strassen, Luxembourg
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Jain M, Tripathy PR, Manik R, Tripathy S, Behera B, Barman A. Short term effect of yoga asana - An adjunct therapy to conventional treatment in frozen shoulder. J Ayurveda Integr Med 2020; 11:101-105. [PMID: 30878219 PMCID: PMC7329720 DOI: 10.1016/j.jaim.2018.12.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/29/2018] [Accepted: 12/26/2018] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The available treatments for frozen shoulder yield variable results. Physical therapy and analgesics are considered as the first-line treatment for this disorder, but the effects are not uniform. There is some evidence to support that alternative medicine may have a role in its management. OBJECTIVE(S) This study was designed to examine the short-term effects of yoga therapy in patients with frozen shoulder of mild to moderate severity. MATERIALS AND METHODS A prospective randomized controlled trial was conducted on patients with frozen shoulder between 30 and 60 years of age. They were divided into two groups: yoga (Y) and control (NY). A set of Asana exercises called "Standing Group of Asana" was practiced by the yoga group in addition to the conventional therapy as received by the control group. The patients were reviewed at 1, 2 and 4 weeks. The pain and functional assessment were done at baseline and at each review using the Shoulder Pain and Disability Index (SPADI). RESULTS There were 16 male and 20 female participants in the Y group, and 15 males and 21 females in the NY group. There was no statistically significant difference in age, sex, and pre-treatment SPADI score between the groups. At the end of the four weeks, the SPADI pain scores in the Y and NY group were 20.47 and 20.14, respectively (p = 0.666). The SPADI disability scores in the Y and NY group were 20.4 and 19.7, respectively (p = 0.599). Overall SPADI scores were 40.67 and 40.03 in the Y and NY group, respectively (p = 0.736). Both groups had a significant reduction in SPADI pain and disability scores. However, there was no significant difference between the groups in terms of SPADI scores. CONCLUSION The effect of the Standing Group of Asana has no added advantage relative to standard frozen shoulder treatment when practiced for one month.
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Affiliation(s)
- Mantu Jain
- Department of Orthopedics, AIIMS, Bhubaneswar, 751019, India.
| | | | - Rajesh Manik
- Yoga Instructor, Department of AYUSH, AIIMS, Bhubaneswar, 751019, India
| | - Sujit Tripathy
- Department of Orthopedics, AIIMS, Bhubaneswar, 751019, India
| | - Binod Behera
- Department of Community Medicine, AIIMS, Bhubaneswar, 751019, India
| | - Apurba Barman
- Department of Physical Medicine & Rehabilitation, AIIMS, Bhubaneswar, 751019, India
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Karahan N, Ozdemir G, Kolukısa D, Duman S, Arslanoğlu F, Çetin M. Can Collagenase Be Used in the Treatment of Adhesive Capsulitis? Med Princ Pract 2020; 29:174-180. [PMID: 31480049 PMCID: PMC7098315 DOI: 10.1159/000503086] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 09/03/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The objective of this study was to evaluate the efficacy of subacromial injections of collagenase and corticosteroid in rats with experimentally induced adhesive capsulitis. METHOD Thirty adult Wistar albino male rats were distributed into 3 groups of 10 rats each after stabilization of their shoulders for 3 weeks: the first group received a single dose of 0.002 mg (0.25 mL) subacromial collagenase; the second group received a single dose of 1.60 mg (0.25 mL) subacromial steroid, and the third group received a single dose of 0.25 mL subacromial saline solution. One week later, we investigated shoulder range of motions, collagen content of the shoulder, and joint cartilage structure. RESULTS There was no statistically significant difference in the cartilage damage between the groups (p > 0.05). Fibrosis measurements were significantly lower in the collagenase group than in the steroid and saline groups. There was no significant difference in fibrosis between the steroid and saline groups (p > 0.05). Abduction measurements were significantly higher in the collagenase group than in the steroid and saline groups (p < 0.001). No significant difference in the abduction measurements was observed between the saline and steroid groups (p > 0.05). CONCLUSION We observed that subacromial injections of collagenase Clostridium histolyticum effectively treated adhesive capsulitis. The results suggest that this treatment could be considered for use in patients with an intact rotator cuff.
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Affiliation(s)
- Nazım Karahan
- Department of Orthopaedics and Traumatology, Corlu State Hospital, Tekirdağ, Turkey,
| | - Güzelali Ozdemir
- Department of Orthopaedics and Traumatology, Ankara Numune Education and Research Hospital, Ankara, Turkey
| | - Duygu Kolukısa
- Department of Pathology, Mersin City Hospital, Mersin, Turkey
| | - Serda Duman
- Department of Orthopaedics and Traumatology, Diyarbakir Selahattin Eyyubi State Hospital, Diyarbakır, Turkey
| | - Fatih Arslanoğlu
- Department of Orthopaedics and Traumatology, Istanbul Medipol Universitesi, Istanbul, Turkey
| | - Mehmet Çetin
- Department of Orthopaedics and Traumatology, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey
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Pogorzelski J, Imhoff AB, Degenhardt H, Siebenlist S. [Primary (idiopathic) shoulder stiffness : Definition, disease progression, epidemiology and etiology]. Unfallchirurg 2019; 122:917-924. [PMID: 31396647 DOI: 10.1007/s00113-019-0703-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Shoulder stiffness is characterized by restriction of the active and passive movement of the glenohumeral joint. The stiffness is ultimately caused by fibrosis and the resulting contracture of the glenohumeral joint capsule and its ligaments; however, the term stiff shoulder is only a descriptive umbrella term that must be further defined as the course of the disease and the recommended treatment are decisively influenced by the cause of the shoulder stiffness. Primary shoulder stiffness, also known as idiopathic shoulder stiffness or "frozen shoulder", must be distinguished from various forms of secondary shoulder stiffness and often occurs in three stages, which can all last for several months to years: the initial "freezing phase", followed by a "frozen phase" and finally a "thawing phase". Although primary shoulder stiffness is a frequent pathological alteration with an prevalence of 2-5% in the general population, the exact etiology remains largely unknown; however, there is consensus throughout the literature that certain systemic pathologies, such as diabetes mellitus are associated with a higher incidence of primary shoulder stiffness.
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Affiliation(s)
- Jonas Pogorzelski
- Abteilung und Poliklinik für Sportorthopädie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland.
| | - Andreas B Imhoff
- Abteilung und Poliklinik für Sportorthopädie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland
| | - Hannes Degenhardt
- Abteilung und Poliklinik für Sportorthopädie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland
| | - Sebastian Siebenlist
- Abteilung und Poliklinik für Sportorthopädie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Deutschland
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Kraal T, Beimers L, The B, Sierevelt I, van den Bekerom M, Eygendaal D. Manipulation under anaesthesia for frozen shoulders: outdated technique or well-established quick fix? EFORT Open Rev 2019; 4:98-109. [PMID: 30993011 PMCID: PMC6440298 DOI: 10.1302/2058-5241.4.180044] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Manipulation under anaesthesia (MUA) for frozen shoulder (FS) leads to a considerable increase in range of motion and Oxford shoulder score, a significant reduction in pain and around 85% satisfaction.A clearly defined indication for MUA in FS patients cannot be extracted from this review or the available literature. The associating criteria before proceeding to MUA vary widely.All but one study in this review lacked a control group without intervention. Therefore, firm conclusions about the role of MUA in the treatment of FS cannot be drawn from the current literature.An overall complication rate of 0.4% was found and a re-intervention rate of 14%, although most of the included papers were not designed to monitor complications.The following criteria before proceeding to MUA are proposed: a patient unable to cope with a stiff and painful shoulder; clinical signs of a stage 2 idiopathic FS; lessening pain in relation to stage 1; external rotation < 50% compared to contralateral shoulder joint; a minimal duration of symptoms of three months; and failure to respond to an intra-articular corticosteroid infiltration. Cite this article: EFORT Open Rev 2019;4:98-109. DOI: 10.1302/2058-5241.4.180044.
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Affiliation(s)
- Tim Kraal
- Department of Orthopaedic Surgery, Amphia Hospital, The Netherlands
| | - Lijkele Beimers
- Department of Orthopaedic Surgery, Slotervaart Center of Orthopedic Research & Education (SCORE), The Netherlands
| | - Bertram The
- Department of Orthopaedic Surgery, OLVG Hospital, The Netherlands
| | - Inger Sierevelt
- Department of Orthopaedic Surgery, Slotervaart Center of Orthopedic Research & Education (SCORE), The Netherlands
| | | | - Denise Eygendaal
- Department of Orthopaedic Surgery, Amphia Hospital, The Netherlands
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Picard S, Vasilevski D, Fagherazzi G. Musculoskeletal disorders in patients with type 1 diabetes: An understudied group of diabetes complications that deserves further investigation. DIABETES & METABOLISM 2019; 46:177-178. [PMID: 30711648 DOI: 10.1016/j.diabet.2019.01.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 01/23/2019] [Indexed: 11/19/2022]
Affiliation(s)
- S Picard
- Endocrinology and Diabetes, Point Medical, Dijon, France.
| | - D Vasilevski
- Foot and Hand Surgery, Point Medical, Dijon, France
| | - G Fagherazzi
- Inserm U1018, Centre for Research in Epidemiology and Population Health (CESP), Paris South, Paris Saclay University, Gustave-Roussy Institute, Villejuif, France
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Morris G, Jacobson JA, Kalume Brigido M, Gaetke-Udager K, Yablon CM, Dong Q. Ultrasound Features of Palmar Fibromatosis or Dupuytren Contracture. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:387-392. [PMID: 30027660 DOI: 10.1002/jum.14699] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 04/25/2018] [Accepted: 04/30/2018] [Indexed: 06/08/2023]
Abstract
OBJECTIVES To retrospectively characterize the ultrasound appearance of palmar fibromatosis in patients with a surgical or clinical diagnosis of palmar fibromatosis. METHODS A search of ultrasound reports from 2005 to 2015 and a subsequent search of medical records were performed to identify patients with a surgical or clinical diagnosis of palmar fibromatosis. The ultrasound images were retrospectively reviewed to record the lesion location, size, echogenicity, compressibility, hyperemia, and calcification. RESULTS A total of 36 patients were identified (average age, 60 years; 61% male), yielding a total of 55 palmar fibromatosis lesions, of which 2%, 7%, 29%, 36%, 20%, and 5% were located at the first, second, third, fourth, and fifth digits and between the fourth and fifth digits, respectively. The lesions were located directly superficial to the flexor tendons in 93% with their epicenters at the distal metacarpal in 89%. Average lesion dimensions were 13.1 mm in length, 6.8 mm in width, and 2.5 mm in depth. On ultrasound images, the lesions were characteristically hypoechoic (98%) and noncompressible (95%). Atypical features included calcification (2%), compressibility (5%), hyperemia on color Doppler images (6%), epicenters at the metacarpophalangeal joint (7%) or proximal phalanx (4%), and location superficial but lateral to the flexor tendons (7%). CONCLUSIONS Palmar fibromatosis most commonly appears hypoechoic and is located directly superficial to the flexor tendons with an epicenter at the distal metacarpal, most commonly the fourth digit. However, the epicenter location may be at the distal metacarpal and proximal phalanx of other digits, adjacent to the flexor tendons, with possible hyperemia and calcification.
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Affiliation(s)
- Gregory Morris
- Department of Radiology, University of Michigan, Ann Arbor, Michigan USA
| | - Jon A Jacobson
- Department of Radiology, University of Michigan, Ann Arbor, Michigan USA
| | | | - Kara Gaetke-Udager
- Department of Radiology, University of Michigan, Ann Arbor, Michigan USA
| | - Corrie M Yablon
- Department of Radiology, University of Michigan, Ann Arbor, Michigan USA
| | - Qian Dong
- Department of Radiology, University of Michigan, Ann Arbor, Michigan USA
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Abstract
Dupuytren disease (DD) is a benign, fibroproliferative disease of unknown cause. The disease predominantly affects the palms of the hands, causing permanent digital contracture of affected digits. DD is a late-onset disease and is often progressive, irreversible, and bilateral. The disease has a significant impact on the health care economy. The mainstay of treatment of DD is surgical excision of diseased palmar fascia. There is evidence of genetic susceptibility. This article introduces the epidemiology of DD and examines the Dupuytren diathesis to highlight the importance of identifying clinical severity in relation to patient counseling and recurrence risk following treatment.
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Affiliation(s)
- Sandip Hindocha
- Plastic Surgery & Laser Centre, Bedford Hospital NHS Trust, Reception J, Kempston Road, Bedford MK429DJ, UK.
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45
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Shoulder adhesive capsulitis: epidemiology and predictors of surgery. J Shoulder Elbow Surg 2018; 27:1437-1443. [PMID: 29807717 DOI: 10.1016/j.jse.2018.04.004] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 03/27/2018] [Accepted: 04/09/2018] [Indexed: 02/01/2023]
Abstract
BACKGROUND Adhesive capsulitis is characterized by a gradual, painful loss of shoulder motion. This study evaluated patient variables significantly associated with developing adhesive capsulitis compared with a sex-matched control group without adhesive capsulitis. We also sought to determine those factors associated with adhesive capsulitis patients requiring surgical intervention. METHODS All patients presenting to our hospital with adhesive capsulitis between 2004 and 2014 were identified. Demographic characteristics were collected, and a sex-matched control group was randomly generated from the electronic medical record and used for comparison. Patients who underwent surgical intervention for adhesive capsulitis were also identified, and factors associated with surgical intervention were identified with logistic regression analysis. RESULTS Included were 2190 adhesive capsulitis patients with a normal age distribution of 56.4 ± 13.1 years. Most were classified as overweight (30.7%) or obese (27.0%). Compared with controls, adhesive capsulitis patients were more likely to be younger (<50 vs. ≥50 years; odds ratio [OR], 0.69; P < .001), obese (OR, 1.26; P < .001), black/African American (OR, 1.71; P < .001), Hispanic/Latino (OR, 4.85; P < .001), or diabetic (OR, 1.12; P < .001) and less likely to have hypertension (OR, 0.93; P = .006). Overall, 361 subsequently underwent surgical intervention. Older patients, racial minorities, and government-sponsored/uninsured patients were significantly less likely to have surgery for adhesive capsulitis (P < .01), whereas workers' compensation patients were 8 times more likely to receive surgery compared with privately insured patients (P < .001). CONCLUSIONS Obesity and diabetes were significantly associated with adhesive capsulitis and should be considered modifiable patient factors. Additionally, younger patients and racial minorities were also significantly more likely to be diagnosed with adhesive capsulitis. Younger, white, and workers' compensation patients were more likely to receive surgery, whereas patients with government-sponsored or no insurance status were more likely to receive nonoperative treatment.
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Prodromidis AD, Charalambous CP. Is There a Genetic Predisposition to Frozen Shoulder?: A Systematic Review and Meta-Analysis. JBJS Rev 2018; 4:01874474-201602000-00004. [PMID: 27490134 DOI: 10.2106/jbjs.rvw.o.00007] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
BACKGROUND Frozen shoulder is a common disorder that leads to substantial functional loss for patients by impairing activities of daily living. It also adversely affects patients and society by impairing the ability to work. Its pathogenesis is not fully understood. The aim of the present study was to perform a systematic review and meta-analysis to assess the evidence suggesting a genetic link to frozen shoulder. METHODS A literature search of MEDLINE, EMBASE, and CINAHL databases using relevant keywords revealed 5506 studies. After appropriate screening of titles, abstracts, and full studies, seven studies were analyzed. RESULTS Three studies investigated rates of frozen shoulder among relatives. One study (n = 1828 twin pairs) showed an 11.6% prevalence in twin pairs and demonstrated a heritability of 42% for frozen shoulder after adjusting for age. A second study (n = 273) showed that 20% of patients with frozen shoulder had a positive family history involving a first-degree relative. The relative risk of frozen shoulder was 4:1 when all patients with frozen shoulder were compared with a control population. A third study (n = 87) showed that 29% of patients with frozen shoulder had a first-degree relative with frozen shoulder. Two studies evaluated racial predilection for frozen shoulder. One study (n = 50) reported a substantially higher number of white patients (76%) with frozen shoulder than black patients (24%). A second study (n = 87) showed that being born or having parents or grandparents born in the British Isles were risk factors for frozen shoulder. Four immunological studies investigated human leukocyte antigen (HLA)-B27 as a risk factor for frozen shoulder. Meta-analysis of two of these studies with clearly defined controls showed significantly higher rates of HLA-B27 positivity in patients with frozen shoulder as compared with controls (p < 0.001). CONCLUSION The limited evidence points toward a genetic link to frozen shoulder. We used family history and racial predilection as markers for genetic association, both of which indicated the presence of a genetic predisposition to frozen shoulder. However, as there is a lack of unbiased genetic approaches, there is an opportunity for genome-wide association studies to address definitively the molecular genetics of frozen shoulder. Such studies may eventually lead to a better understanding of the pathogenesis of frozen shoulder and the development of novel therapeutic interventions. LEVEL OF EVIDENCE Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Apostolos D Prodromidis
- Orthopaedic Department, Blackpool Victoria Hospital, Blackpool, UK.,School of Medicine and Dentistry, University of Central Lancashire, Preston, UK
| | - Charalambos P Charalambous
- Orthopaedic Department, Blackpool Victoria Hospital, Blackpool, UK.,School of Medicine and Dentistry, University of Central Lancashire, Preston, UK.,Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
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Cucchi D, Marmotti A, De Giorgi S, Costa A, D'Apolito R, Conca M, Russo A, Saccomanno MF, de Girolamo L. Risk Factors for Shoulder Stiffness: Current Concepts. JOINTS 2017; 5:217-223. [PMID: 29270559 PMCID: PMC5738468 DOI: 10.1055/s-0037-1608951] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Shoulder stiffness is a condition of painful restriction of the glenohumeral range of motion. Numerous risk factors for primary and postoperative shoulder stiffness have been described. This article summarizes the known aspects of the pathophysiology of shoulder stiffness, with special attention to elements of molecular biology and genetics, which could influence the risk of developing shoulder stiffness. Furthermore, the role of hormonal and metabolic factors, medical disorders, drugs, and of other published risk factors for primary and postoperative shoulder stiffness is reviewed and discussed. Finally, aspects related to shoulder surgery and postoperative rehabilitation protocols, which could influence the development of postoperative stiffness are presented.
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Affiliation(s)
- Davide Cucchi
- Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.,Department of Orthopaedics and Trauma Surgery, University of Bonn, Bonn, Germany
| | | | - Silvana De Giorgi
- Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Bari, Italy
| | - Alberto Costa
- Departemnt of Orthopaedics and Traumatology, Orlandi Hospital, Bussolengo, Verona, Italy
| | - Rocco D'Apolito
- Department of Orthopaedics, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy
| | - Marco Conca
- UO Ortopedia Clinica San Carlo, Paderno Dugnano, Milan, Italy
| | - Alessandro Russo
- Laboratorio di Biomeccanica e Innovazione Tecnologica-Clinica II, Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Maristella F Saccomanno
- Department of Orthopaedics, Catholic University, "A. Gemelli" University Hospital, Rome, Italy
| | - Laura de Girolamo
- Laboratorio di Biotecnologie applicate all'Ortopedia, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
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Abstract
Frozen shoulder causes significant functional disability and pain in a population group constituted by patients who are often middle-aged and working. Frozen shoulder remains poorly understood. The available literature is limited and often prone to bias. A rapid, non-surgical and cost-effective treatment that reduces pain and restores function is an attractive option. Hydrodilatation is a potential first-line treatment of frozen shoulder in secondary care. Cite this article: EFORT Open Rev 2017;2:462–468. DOI: 10.1302/2058-5241.2.160061
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Affiliation(s)
- S Rymaruk
- University Hospital of South Manchester NHS Foundation Trust, UK
| | - C Peach
- University Hospital of South Manchester NHS Foundation Trust, UK
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50
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Inayat F, Ali NS, Shahid H, Younus F. Prevalence and Determinants of Frozen Shoulder in Patients with Diabetes: A Single Center Experience from Pakistan. Cureus 2017; 9:e1544. [PMID: 29018641 PMCID: PMC5630460 DOI: 10.7759/cureus.1544] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Introduction Frozen shoulder (FS) or adhesive capsulitis is a constellation of symptoms like pain, stiffness, and/or functional deficit at the glenohumeral joint. It is one of the musculoskeletal complications in patients with diabetes that can be particularly debilitating. The aim of this study is to estimate the prevalence of FS and to compare the determinants of this disease in a population with diabetes from Lahore, Pakistan. Materials and Methods We carried out this cross-sectional study on a systematically randomized sample of 80 patients with diabetes. It included 38 males and 42 females from 2,964 patients registered at the Diabetes Management Center, Services Hospital Lahore, Pakistan. The study was conducted in the months of April, May, and June 2017. A structured questionnaire was designed and the responses of patients were recorded at the clinic after informed verbal and written consent. The questionnaire outlined the key factors that can lead to a higher frequency of FS in patients with diabetes. Results Thirty-three of the total 80 respondents included in the study were diagnosed with FS. The estimated prevalence of FS in diabetics from this data was 41.3% in Lahore, which is an urban area of Pakistan with a population of more than seven million. Female sex, insulin dependence, uncontrolled blood glucose levels, and a positive family history were associated with a significantly higher prevalence of FS. In our study, most patients with FS were in Stage 1 of the disease and had unilateral involvement. Conclusion The present study shows that the prevalence of FS is higher in patients with diabetes residing in Lahore than in comparable foreign populations with diabetes. It can be attributed to socioeconomic status, lack of awareness, a higher threshold for diagnosis, and/or poor glycemic control. Mass awareness campaigns, especially for female patients with diabetes, are required to be initiated to create awareness about the disease and to facilitate early diagnosis and appropriate management. In-depth and multicenter studies are needed to further explore the association between FS and diabetes.
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Affiliation(s)
- Faisal Inayat
- Department of Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York City, NY, USA
| | - Nouman Safdar Ali
- Department of Medicine, Jinnah Hospital, Allama Iqbal Medical College, Lahore, Pakistan
| | - Haroon Shahid
- Department of Radiology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan
| | - Fariha Younus
- Department of Medicine Unit 4, Services Hospital, Services Institute of Medical Sciences, Lahore, Pakistan
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