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1
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Boudreaux J. Transfusion management in thalassemia. Ann N Y Acad Sci 2023; 1527:42-48. [PMID: 37531552 DOI: 10.1111/nyas.15049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2023]
Abstract
This review describes the current challenges and recommendations in the transfusion management of thalassemia patients. In addition, it reviews the components of blood safety and blood product modification in special populations. Adverse transfusion reactions are described as are some of the newer technologies being utilized to reduce potential transfusion-associated pathogens. Lastly, research in blood storage and in manufactured blood is briefly described.
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Affiliation(s)
- Jeanne Boudreaux
- Aflac Cancer & Blood Disorders Center, Emory University, Atlanta, Georgia, USA
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2
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Abstract
Conventional therapy for severe thalassemia includes regular red cell transfusions and iron chelation therapy to prevent and treat complications of iron overload. Iron chelation is very effective when appropriately used, but inadequate iron chelation therapy continues to contribute to preventable morbidity and mortality in transfusion-dependent thalassemia. Factors that contribute to suboptimal iron chelation include poor adherence, variable pharmacokinetics, chelator adverse effects, and difficulties with precise monitoring of response. The regular assessment of adherence, adverse effects, and iron burden with appropriate treatment adjustments is necessary to optimize patient outcomes.
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Affiliation(s)
- Janet L Kwiatkowski
- Division of Hematology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, 3501 Civic Center Boulevard, Clinical Hub Building, Room 13547, Philadelphia, PA 19104, USA.
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3
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Gehrer CM, Hoffmann A, Hilbe R, Grubwieser P, Mitterstiller AM, Talasz H, Fang FC, Meyron-Holtz EG, Atkinson SH, Weiss G, Nairz M. Availability of Ferritin-Bound Iron to Enterobacteriaceae. Int J Mol Sci 2022; 23:13087. [PMID: 36361875 PMCID: PMC9657528 DOI: 10.3390/ijms232113087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 10/18/2022] [Accepted: 10/20/2022] [Indexed: 11/10/2023] Open
Abstract
The sequestration of iron in case of infection, termed nutritional immunity, is an established strategy of host defense. However, the interaction between pathogens and the mammalian iron storage protein ferritin is hitherto not completely understood. To better characterize the function of ferritin in Gram-negative infections, we incubated iron-starved cultures of Salmonella Typhimurium and knockout mutant strains defective for major iron uptake pathways or Escherichia coli with horse spleen ferritin or ionic iron as the sole iron source. Additionally, we added bovine superoxide dismutase and protease inhibitors to the growth medium to assess the effect of superoxide and bacterial proteases, respectively, on Salmonella proliferation and reductive iron release. Compared to free ionic iron, ferritin-bound iron was less available to Salmonella, but was still sufficient to significantly enhance the growth of the bacteria. In the absence of various iron acquisition genes, the availability of ferritin iron further decreased. Supplementation with superoxide dismutase significantly reduced the growth of the ΔentC knockout strain with holoferritin as the sole iron source in comparison with ionic ferrous iron. In contrast, this difference was not observed in the wildtype strain, suggesting that superoxide dismutase undermines bacterial iron uptake from ferritin by siderophore-independent mechanisms. Ferritin seems to diminish iron availability for bacteria in comparison to ionic iron, and its iron sequestering effect could possibly be enhanced by host superoxide dismutase activity.
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Affiliation(s)
- Clemens M. Gehrer
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Alexander Hoffmann
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Richard Hilbe
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Philipp Grubwieser
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Anna-Maria Mitterstiller
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Heribert Talasz
- Biocenter, Institute of Medical Biochemistry, Medical Universitiy of Innsbruck, 6020 Innsbruck, Austria
| | - Ferric C. Fang
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195-7110, USA
- Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195-7735, USA
| | - Esther G. Meyron-Holtz
- Laboratory of Molecular Nutrition, Faculty of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel
| | - Sarah H. Atkinson
- Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine Research Coast, KEMRI-Wellcome Trust Research Programme, Kilifi 80108, Kenya
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LG, UK
- Department of Paediatrics, University of Oxford, Oxford OX3 9DU, UK
| | - Günter Weiss
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
- Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, 6020 Innsbruck, Austria
| | - Manfred Nairz
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Medical University of Innsbruck, 6020 Innsbruck, Austria
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Teng TZJ, Thong XR, Lau KY, Balasubramaniam S, Shelat VG. Acute appendicitis-advances and controversies. World J Gastrointest Surg 2021; 13:1293-1314. [PMID: 34950421 PMCID: PMC8649565 DOI: 10.4240/wjgs.v13.i11.1293] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/24/2021] [Accepted: 09/29/2021] [Indexed: 02/06/2023] Open
Abstract
Being one of the most common causes of the acute abdomen, acute appendicitis (AA) forms the bread and butter of any general surgeon's practice. With the recent advancements in AA's management, much controversy in diagnostic algorithms, possible differential diagnoses, and weighing the management options has been generated, with no absolute consensus in the literature. Since Alvarado described his eponymous clinical scoring system in 1986 to stratify AA risk, there has been a burgeoning of additional scores for guiding downstream management and mortality assessment. Furthermore, advancing literature on the role of antibiotics, variations in appendicectomy, and its adjuncts have expanded the surgeon's repertoire of management options. Owing to the varied presentation, diagnostic tools, and management of AA have also been proposed in special groups such as pregnant patients, the elderly, and the immunocompromised. This article seeks to raise the critical debates about what is currently known about the above aspects of AA and explore the latest controversies in the field. Considering the ever-evolving coronavirus disease 2019 situation worldwide, we also discuss the pandemic's repercussions on patients and how surgeons' practices have evolved in the context of AA.
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Affiliation(s)
- Thomas Zheng Jie Teng
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Department of Undergraduate Medicine, Lee Kong Chian School of Medicine, Singapore 308232, Singapore
| | - Xuan Rong Thong
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Department of Undergraduate Medicine, Lee Kong Chian School of Medicine, Singapore 308232, Singapore
| | - Kai Yuan Lau
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Department of Undergraduate Medicine, Lee Kong Chian School of Medicine, Singapore 308232, Singapore
| | | | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Department of Undergraduate Medicine, Lee Kong Chian School of Medicine, Singapore 308232, Singapore
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Saliba AN, Atoui A, Labban M, Hamade H, Bou-Fakhredin R, Mufarrij A, Taher AT. Thalassemia in the emergency department: special considerations for a rare disease. Ann Hematol 2020; 99:1967-1977. [PMID: 32621178 PMCID: PMC7333588 DOI: 10.1007/s00277-020-04164-6] [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: 06/04/2020] [Accepted: 06/29/2020] [Indexed: 01/19/2023]
Abstract
Thalassemia is characterized by a defect in the synthesis of one or more of the globin subunits of hemoglobin. This defect results in imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. With advances in diagnosis, treatment, and transfusion support, the prognosis of patients with thalassemia has improved over the past few decades. An increasing number of patients with thalassemia is living with long-term complications, including cardiomyopathy, chronic liver disease, endocrinopathy, and infections. In this paper, we review common complications that bring the patient with thalassemia to urgent or emergent medical attention. We also discuss the aspects of emergency care that are most relevant while caring for the patient with thalassemia in the emergency department.
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Affiliation(s)
- Antoine N Saliba
- Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Ali Atoui
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Mohamad Labban
- Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Hani Hamade
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Rayan Bou-Fakhredin
- Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Afif Mufarrij
- Department of Emergency Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ali T Taher
- Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
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Invasive Yersiniosis in a Pediatric Patient With β-Thalassemia Major: Acute Decompensation After Rapid Blood Transfusion. Pediatr Emerg Care 2019; 35:e118-e120. [PMID: 31219970 DOI: 10.1097/pec.0000000000001873] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Yersinia enterocolitica infection, or yersiniosis, is a common cause of gastroenteritis in developing nations, but the disease is less common in the developed world. Yersiniosis typically presents as a self-limited gastroenteritis in an immunocompetent patient and rarely progresses to the more fulminant disseminated form. Certain patient populations are at greater risk of disseminated disease, and providers caring for these patients should have heightened suspicion for invasive disease. Patients dependent on serial transfusion therapy, such as those with inherited hemoglobinopathies, often have chronically elevated serum iron levels. These patients are at increased risk of fulminant yersiniosis due to the bacteria's siderophilic nature. Yersinia infection can be devastating in these patients, and early intervention with empiric antibiotics combined with targeted resuscitation can be essential in their care. The following case illustrates the utility for heightened surveillance, early intervention, and guided resuscitation in the management of this at-risk population.
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Demosthenous C, Vlachaki E, Apostolou C, Eleftheriou P, Kotsiafti A, Vetsiou E, Mandala E, Perifanis V, Sarafidis P. Beta-thalassemia: renal complications and mechanisms: a narrative review. ACTA ACUST UNITED AC 2019; 24:426-438. [PMID: 30947625 DOI: 10.1080/16078454.2019.1599096] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVES Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease. METHODS A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease. RESULTS Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators. DISCUSSION AND CONCLUSION Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.
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Affiliation(s)
- Christos Demosthenous
- a Department of Hematology and HCT Unit , General Hospital of Thessaloniki "George Papanicolaou" , Thessaloniki , Greece
| | - Efthymia Vlachaki
- b Adults Thalassemia Unit, Second Department of Internal Medicine , Aristotle University, Hippokration Hospital , Thessaloniki , Greece
| | - Chrysa Apostolou
- b Adults Thalassemia Unit, Second Department of Internal Medicine , Aristotle University, Hippokration Hospital , Thessaloniki , Greece
| | - Perla Eleftheriou
- c Department of Haematology , University College London , London , UK
| | - Aggeliki Kotsiafti
- b Adults Thalassemia Unit, Second Department of Internal Medicine , Aristotle University, Hippokration Hospital , Thessaloniki , Greece
| | - Evangelia Vetsiou
- b Adults Thalassemia Unit, Second Department of Internal Medicine , Aristotle University, Hippokration Hospital , Thessaloniki , Greece
| | - Evdokia Mandala
- d Fourth Department of Internal Medicine , Aristotle University, Hippokration Hospital , Thessaloniki , Greece
| | - Vassilios Perifanis
- e First Propedeutic Department of Internal Medicine , Aristotle University, AHEPA General Hospital of Thessaloniki , Thessaloniki , Greece
| | - Pantelis Sarafidis
- f Department of Nephrology , Hippokration Hospital, Aristotle University of Thessaloniki , Thessaloniki , Greece
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8
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Perillo M, Becker-Weidman D, Bezuidenhout AF, Siewert B, Eisenberg RL. Infections of the Gastrointestinal Tract. Semin Roentgenol 2017; 52:63-72. [PMID: 28606310 DOI: 10.1053/j.ro.2017.04.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Michele Perillo
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA
| | | | | | - B Siewert
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA.
| | - Ronald L Eisenberg
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA
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9
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Furlan L, Graziadei G, Colombo G, Forzenigo LV, Solbiati M. K. pneumoniae liver abscess following deferoxamine subcutaneous self-injection. Am J Hematol 2017; 92:480-481. [PMID: 28188653 DOI: 10.1002/ajh.24675] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 01/31/2017] [Accepted: 02/03/2017] [Indexed: 12/29/2022]
Affiliation(s)
- Ludovico Furlan
- Dipartimento di Medicina Interna e Specializzazioni Mediche, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
- Dipartimento di Scienze Cliniche e di ComunitàUniversità degli Studi di MilanoMilano Italy
| | - Giovanna Graziadei
- Centro Anemie Congenite, Dipartimento di Medicina Interna e Specializzazioni MedicheFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoMilano Italy
| | - Giulia Colombo
- Dipartimento di Medicina Interna e Specializzazioni Mediche, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
- Dipartimento di Scienze Cliniche e di ComunitàUniversità degli Studi di MilanoMilano Italy
| | - Laura Virginia Forzenigo
- Dipartimento di RadiologiaFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoMilano Italy
| | - Monica Solbiati
- Dipartimento di Medicina Interna e Specializzazioni Mediche, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy
- Dipartimento di Scienze Cliniche e di ComunitàUniversità degli Studi di MilanoMilano Italy
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10
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Botzenhardt S, Li N, Chan EW, Sing CW, Wong ICK, Neubert A. Safety profiles of iron chelators in young patients with haemoglobinopathies. Eur J Haematol 2017; 98:198-217. [PMID: 27893170 DOI: 10.1111/ejh.12833] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND This review describes the safety of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX) and combined therapy in young patients less than 25 yr of age with haemoglobinopathies. METHODS Searches in electronic literature databases were performed. Studies reporting adverse events associated with iron chelation therapy were included. Study and reporting quality was assessed using AHRQ Risk of Bias Assessment Tool and McMaster Quality Assessment Scale of Harms. Prospective clinical studies were pooled in a random-effects meta-analysis of proportions. RESULTS Safety data of 2040 patients from 34 studies were included. Ninety-two case reports of 246 patients were identified. DFX (937 patients) and DFP (667 patients) possess the largest published safety evidence. Fewer studies on combination regimens are available. Increased transaminases were seen in all regimens (3.9-31.3%) and gastrointestinal disorders with DFP and DFX (3.7-18.4% and 5.8-18.8%, respectively). Therapy discontinuations due to adverse events were low (0-4.1%). Reporting quality was selective and poor in most of the studies. CONCLUSION Iron chelation therapy is generally safe in young patients, and published data correspond to summary of product characteristics. Each iron chelation regimen has its specific safety risks. DFO seems not to be associated with serious adverse effects in recommended doses. In DFP and DFX, rare, but serious, adverse reactions can occur. Data on combined therapy are scarce, but it seems equally safe compared to monotherapy.
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Affiliation(s)
- Sebastian Botzenhardt
- Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Niya Li
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, University of Hong Kong, Hong Kong, China.,Clinical Trials Center, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China
| | - Esther W Chan
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, University of Hong Kong, Hong Kong, China
| | - Chor Wing Sing
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, University of Hong Kong, Hong Kong, China
| | - Ian C K Wong
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, University of Hong Kong, Hong Kong, China.,Research Department of Practice & Policy, University College London School of Pharmacy, London, UK
| | - Antje Neubert
- Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
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11
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Kato H, Sasaki S, Sekiya N. Primary cellulitis and cutaneous abscess caused by Yersinia enterocolitica in an immunocompetent host: A case report and literature review. Medicine (Baltimore) 2016; 95:e3988. [PMID: 27368001 PMCID: PMC4937915 DOI: 10.1097/md.0000000000003988] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Primary extraintestinal complications caused by Yersinia enterocolitica are extremely rare, especially in the form of skin and soft-tissue manifestations, and little is known about their clinical characteristics and treatments. We presented our case and reviewed past cases of primary skin and soft-tissue infections caused by Y enterocolitica. We report a case of primary cellulitis and cutaneous abscess caused by Y enterocolitica in an immunocompetent 70-year-old woman with keratodermia tylodes palmaris progressiva. She presented to an outpatient clinic with redness, swelling, and pain of the left ring finger and left upper arm without fever or gastrointestinal symptoms 3 days before admission. One day later, ulceration of the skin with exposed bone of the proximal interphalangeal joint of the left ring finger developed, and cefditoren pivoxil was described. However, she was admitted to our hospital due to deterioration of symptoms involving the left finger and upper arm. Cefazolin was initiated on admission, then changed to sulbactam/ampicillin and vancomycin with debridement of the left ring finger and drainage of the left upper arm abscess. Wound culture grew Y enterocolitica serotype O:8 and methicillin-sensitive Staphylococcus aureus. Blood cultures were negative and osteomyelitis was ruled out. Vancomycin was switched to ciprofloxacin, then skin and soft-tissue manifestations showed clear improvement within a few days. The patient received 14 days of ciprofloxacin and oral amoxicillin/clavulanate and has since shown no recurrence. We reviewed 12 cases of primary skin and soft-tissue infections caused by Y enterocolitica from the literature. In several past cases, portal entry involved failure of the skin barrier on distal body parts. Thereafter, infection might have spread to the regional lymph nodes from the ruptured skin. Y enterocolitica is typically resistant to aminopenicillins and narrow-spectrum cephalosporins. In most cases, these inefficient antibiotic agents were initially prescribed, but patient conditions rapidly improved after implementing appropriate therapy and drainage. In addition, primary skin and soft-tissue infections occurred even in patients lacking risk factors. Physicians should consider the rare differential diagnosis of Y enterocolitica infection when seeing patients with deteriorating skin lesions under standard treatment, even if the patient is immunocompetent.
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Affiliation(s)
- Hirofumi Kato
- Department of Clinical Laboratory, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
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12
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Borgna-Pignatti C, Marsella M. Iron Chelation in Thalassemia Major. Clin Ther 2015; 37:2866-77. [PMID: 26519233 DOI: 10.1016/j.clinthera.2015.10.001] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 10/01/2015] [Accepted: 10/02/2015] [Indexed: 01/19/2023]
Abstract
PURPOSE Iron chelation has improved survival and quality of life of patients with thalassemia major. there are currently 3 commercially available iron-chelating drugs with different pharmacokinetic and pharmacodynamic activity. The choice of adequate chelation treatment should be tailored to patient needs and based on up-to-date scientific evidence. METHODS A review of the most recent literature was performed. FINDINGS The ability of the chelators to bind the redox active component of iron, labile plasma iron, is crucial for protecting the cells. Chelation therapy should be guided by magnetic resonance imaging that permits the tailoring of therapy according to the needs of the patient because different chelators preferentially clear iron from different sites. Normal levels of body iron seem to decrease the need for hormonal and cardiac therapy. IMPLICATIONS The 3 chelators currently available have different benefits, different safety profiles, and different acceptance on the part of the patients. Good-quality, well-designed, randomized, long-term clinical trials continue to be needed.
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Affiliation(s)
| | - Maria Marsella
- Pediatrics and Adolescentology Unit, Maternal and Child Health Department, "G. Rummo" Hospital, Benevento, Italy
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13
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Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases. Mediterr J Hematol Infect Dis 2015; 7:e2015057. [PMID: 26543526 PMCID: PMC4621170 DOI: 10.4084/mjhid.2015.057] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 10/03/2015] [Indexed: 01/19/2023] Open
Abstract
Splenectomy, while often necessary in otherwise healthy patients after major trauma, finds its primary indication for patients with underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infections found in splenectomized patients are due to Gram-negative (G-) bacteria. The underlying disease is the most important factor in determining the frequency and severity of infections. So, splenectomy for malignant diseases has the major risk of infections.
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Chakraborty A, Komatsu K, Roberts M, Collins J, Beggs J, Turabelidze G, Safranek T, Maillard JM, Bell LJ, Young D, Marsden-Haug N, Klos RF, Dworkin MS. The descriptive epidemiology of yersiniosis: a multistate study, 2005-2011. Public Health Rep 2015; 130:269-77. [PMID: 25931631 DOI: 10.1177/003335491513000314] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES Yersiniosis, a foodborne infection of zoonotic origin caused by the bacteria Yersinia enterocolitica and Yersinia pseudotuberculosis, is a reportable disease in 38 states. Both sporadic and foodborne outbreaks of yersiniosis have been reported in the U.S., with annual occurrence of an estimated 98,000 episodes of illness, 533 hospitalizations, and 29 deaths. We analyzed surveillance data from nine non-FoodNet-participating U.S. states during the period 2005-2011 to describe the epidemiology of this disease. METHODS As part of a passive surveillance system, laboratory-confirmed cases of yersiniosis were reported to state health departments in Arizona, Illinois, Michigan, Missouri, Nebraska, North Carolina, South Carolina, Washington, and Wisconsin. We calculated overall, age-, and race-specific annual incidence rates per 100,000 population using 2010 Census data as the denominator. We used Poisson regression to examine seasonal variation and annual incidence trends by race, age group, and overall. RESULTS The average annual incidence of yersiniosis was 0.16 cases per 100,000 population during 2005-2011. We observed a statistically significant decreasing annual trend of yersiniosis incidence among African Americans <5 years of age (p<0.01), whereas white people aged 19-64 years (p=0.08) and Hispanic people (p=0.05) had an overall increasing annual incidence of yersiniosis. We observed higher incidence during October-December (p<0.01) and January-March (p=0.03) quarters among African Americans, whereas white people had a higher incidence during April-June (p=0.05). CONCLUSION This multistate analysis revealed differences in the epidemiology of yersiniosis by race/ethnicity that may be useful for future research and prevention efforts. While this study was consistent with the FoodNet report in recognizing the high and declining incidence among African American children and winter seasonality among African Americans, our study also identified April-June seasonality among the white population.
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Affiliation(s)
- Apurba Chakraborty
- University of Illinois at Chicago School of Public Health, Division of Epidemiology and Biostatistics, Chicago, IL
| | | | | | - Jim Collins
- Michigan Department of Community Health, Lansing, MI
| | | | | | - Tom Safranek
- Nebraska Department of Health and Human Services, Lincoln, NE
| | | | - Linda J Bell
- South Carolina Department of Health and Environmental Control, Columbia, SC
| | - David Young
- South Carolina Department of Health and Environmental Control, Columbia, SC
| | - Nicola Marsden-Haug
- Washington State Department of Health, Communicable Disease Epidemiology, Shoreline, WA
| | - Rachel F Klos
- Wisconsin Department of Health Services, Madison, WI
| | - Mark S Dworkin
- University of Illinois at Chicago School of Public Health, Division of Epidemiology and Biostatistics, Chicago, IL
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15
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Abstract
Salmonella, Shigella, and Yersinia cause a well-characterized spectrum of disease in humans, ranging from asymptomatic carriage to hemorrhagic colitis and fatal typhoidal fever. These pathogens are responsible for millions of cases of food-borne illness in the United States each year, with substantial costs measured in hospitalizations and lost productivity. In the developing world, illness caused by these pathogens is not only more prevalent but also associated with a greater case-fatality rate. Classic methods for identification rely on selective media and serology, but newer methods based on mass spectrometry and polymerase chain reaction show great promise for routine clinical testing.
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16
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Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R, Hoffman TM, Kiernan MS, Lerakis S, Piga A, Porter JB, Walker JM, Wood J. Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. Circulation 2013; 128:281-308. [PMID: 23775258 DOI: 10.1161/cir.0b013e31829b2be6] [Citation(s) in RCA: 285] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non-cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.
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17
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Wong KK, Fistek M, Watkins RR. Community-acquired pneumonia caused by Yersinia enterocolitica in an immunocompetent patient. J Med Microbiol 2012; 62:650-651. [PMID: 23242642 DOI: 10.1099/jmm.0.053488-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Most cases of Yersinia enterocolitica manifest with symptoms of enterocolitis, such as diarrhoea, fever and abdominal pain. Y. enterocolitica is a very rare cause of pneumonia, and usually occurs in immunocompromised patients. We report a case of community-acquired pneumonia (CAP) caused by Y. enterocolitica in an elderly patient who did not develop symptoms of enterocolitis. This aetiology should be considered in patients with CAP who do not respond to initial empirical therapy.
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Affiliation(s)
- Ken Koon Wong
- Department of Internal Medicine, Akron General Medical Center, Akron, OH 44302, USA
| | - Michael Fistek
- Department of Internal Medicine, Akron General Medical Center, Akron, OH 44302, USA
| | - Richard R Watkins
- Department of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH 44272, USA.,Division of Infectious Diseases, Akron General Medical Center, Akron, OH 44302, USA
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18
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Berdoukas V, Farmaki K, Carson S, Wood J, Coates T. Treating thalassemia major-related iron overload: the role of deferiprone. J Blood Med 2012; 3:119-29. [PMID: 23112580 PMCID: PMC3480237 DOI: 10.2147/jbm.s27400] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Over the last 20 years, management for thalassemia major has improved to the point where we predict that patients’ life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow specific organ assessment of the degree of iron overload, and improvement in the treatment of hepatitis. In October 2011, the Food and Drug Administration licensed deferiprone, further increasing the available choices for iron chelation in the US. The ability to prescribe any of the three chelators as well as their combinations has led to more effective reduction of total body iron. The ability to determine the amount of iron in the liver and heart by magnetic resonance imaging allows the prescription of the most appropriate chelation regime for patients and to reconsider what our aims with respect to total body iron should be. Recent evidence from Europe has shown that by normalizing iron stores not only are new morbidities prevented but also reversal of many complications such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance, and type 2 diabetes can occur, improving survival and patients’ quality of life. The most effective way to achieve normal iron stores seems to be with the combination of deferoxamine and deferiprone. Furthermore, outcomes should continue to improve in the future. Starting relative intensive chelation in younger children may prevent short stature and abnormal pubertal maturation as well as other iron-related morbidities. Also, further information should become available on the use of other combinations in chelation treatment, some of which have been used only in a very limited fashion to date. All these advances in management require absolute cooperation and understanding of parents, children, and, subsequently, the patients themselves. Only with such cooperation can normal long-term survival be achieved, as adherence to treatment is now likely the primary barrier to longevity.
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Affiliation(s)
- Vasilios Berdoukas
- Division of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, CA, USA
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19
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Bhandari S, Galanello R. Renal aspects of thalassaemia a changing paradigm. Eur J Haematol 2012; 89:187-97. [DOI: 10.1111/j.1600-0609.2012.01819.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/05/2012] [Indexed: 01/19/2023]
Affiliation(s)
- Sunil Bhandari
- Department of Renal Medicine; Hull & East Yorkshire Hospitals NHS Trust & Hull York Medical School; East Yorkshire; UK
| | - Renzo Galanello
- Clinica Pediatrica, Ospedale Regionale Microcitemie ASL8; Università degli Studi di Cagliari; Cagliari; Italy
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20
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Pfeiffer ML, DuPont HL, Ochoa TJ. The patient presenting with acute dysentery--a systematic review. J Infect 2012; 64:374-86. [PMID: 22266388 DOI: 10.1016/j.jinf.2012.01.006] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2011] [Revised: 01/05/2012] [Accepted: 01/09/2012] [Indexed: 12/29/2022]
Abstract
OBJECTIVES The etiologies, clinical presentations and diagnosis of acute pathogen-specific dysentery in children and adults in industrialized and developing regions is described to help develop recommendations for therapy. METHODS We conducted a systematic review of literature published between January 2000 and June 2011 to determine the frequency of occurrence of pathogen-specific dysentery. RESULTS Shigella, Salmonella, and Campylobacter remain the most frequent bacterial causes of dysentery worldwide. Shiga toxin-producing Escherichia coli (STEC) is potentially important in industrialized countries. Entamoeba histolytica must be considered in the developing world, particularly in rural or periurban areas. Clinicians should use epidemiological clues and knowledge of endemicity to suspect Vibrio spp., Aeromonas spp., Plesiomonas spp., Yersinia enterocolitica, Clostridium difficile, Cytomegalovirus or Schistosoma mansoni in cases presenting with dysentery. A single fecal sample studied for etiologic agents is the customary way to make an etiologic diagnosis. CONCLUSIONS While a majority of dysenteric cases will not have an identifiable agent causing the illness, when an etiologic organism is identified, other than STEC, each has a specific recommended form of therapy, which is provided in this review.
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21
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Abstract
Although seen less frequently than acetaminophen or salicylate poisoning, acute iron poisoning remains a dangerous threat, particularly to pediatric patients. Multiple factors-including legal and manufacturing practices-have changed the landscape of iron poisoning over the decades. Despite these changes, diagnosis and management of iron poisoning have minimally evolved, and the current evidence for iron poisoning is yet based principally on case series, expert consensus, animal studies, and adult volunteer studies. This review article describes in detail the epidemiology of acute iron poisoning as it relates to the pediatric patient, as well as the historical and current array of literature on diagnosis and management.
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22
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Kwiatkowski JL. Management of transfusional iron overload - differential properties and efficacy of iron chelating agents. J Blood Med 2011; 2:135-49. [PMID: 22287873 PMCID: PMC3262345 DOI: 10.2147/jbm.s13065] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Indexed: 01/19/2023] Open
Abstract
Regular red cell transfusion therapy ameliorates disease-related morbidity and can be lifesaving in patients with various hematological disorders. Transfusion therapy, however, causes progressive iron loading, which, if untreated, results in endocrinopathies, cardiac arrhythmias and congestive heart failure, hepatic fibrosis, and premature death. Iron chelation therapy is used to prevent iron loading, remove excess accumulated iron, detoxify iron, and reverse some of the iron-related complications. Three chelators have undergone extensive testing to date: deferoxamine, deferasirox, and deferiprone (although the latter drug is not currently licensed for use in North America where it is available only through compassionate use programs and research protocols). These chelators differ in their modes of administration, pharmacokinetics, efficacy with regard to organ-specific iron removal, and adverse-effect profiles. These differential properties influence acceptability, tolerability and adherence to therapy, and, ultimately, the effectiveness of treatment. Chelation therapy, therefore, must be individualized, taking into account patient preferences, toxicities, ongoing transfusional iron intake, and the degree of cardiac and hepatic iron loading.
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Affiliation(s)
- Janet L Kwiatkowski
- The Children's Hospital of Philadelphia, Division of Hematology and University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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23
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Berdoukas V, Farmaki K, Wood JC, Coates T. Iron chelation in thalassemia: time to reconsider our comfort zones. Expert Rev Hematol 2011; 4:17-26. [PMID: 21322775 DOI: 10.1586/ehm.10.74] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Over the last 20 years, the management of thalassemia major has improved to the point where we predict that the patients' life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow organ-specific assessment of the degree of iron overload and improvement in the treatment of hepatitis. The ability to prescribe any of the three chelators, as well as their combinations, has led to a more effective reduction of the total body iron. The ability to determine the amount of iron in the liver and heart by MRI has allowed the prescription of the most appropriate chelation regime for the patient and has allowed the reconsideration of 'the comfort zones'. Thus, normalizing iron stores not only prevents new morbidities but also reverses many complications, such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance and Type 2 diabetes, therefore improving survival and patients' quality of life. Furthermore, outcomes should continue to improve in the future. Starting relatively intensive chelation in younger children may prevent short stature and abnormal pubertal maturation, as well as other iron-related morbidities. In addition, further information should become available on the use of other combinations in chelation treatment, some of which have only been used in a very limited fashion so far. New safe oral chelators may also become available that may offer additional ease of use. All these advances in management do require absolute cooperation and understanding on behalf of children's parents and subsequently the adult themself. Only with such cooperation can normal long-term survival be achieved as it is likely that adherence to treatment is the primary barrier to longevity.
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Affiliation(s)
- Vasilios Berdoukas
- The Division of Hematology/Oncology, The Children's Hospital of Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027-6016, USA.
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24
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Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus: an important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis 2011; 15:e157-e166. [PMID: 21177133 DOI: 10.1016/j.ijid.2010.11.003] [Citation(s) in RCA: 198] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2010] [Revised: 10/28/2010] [Accepted: 11/09/2010] [Indexed: 02/05/2023] Open
Abstract
Vibrio vulnificus is a halophilic Gram-negative bacillus found worldwide in warm coastal waters. The pathogen has the ability to cause primary sepsis in certain high-risk populations, including patients with chronic liver disease, immunodeficiency, iron storage disorders, end-stage renal disease, and diabetes mellitus. Most reported cases of primary sepsis in the USA are associated with the ingestion of raw or undercooked oysters harvested from the Gulf Coast. The mortality rate for patients with severe sepsis is high, exceeding 50% in most reported series. Other clinical presentations include wound infection and gastroenteritis. Mild to moderate wound infection and gastroenteritis may occur in patients without obvious risk factors. Severe wound infection is often characterized by necrotizing skin and soft-tissue infection, including fasciitis and gangrene. V. vulnificus possesses several virulence factors, including the ability to evade destruction by stomach acid, capsular polysaccharide, lipopolysaccharide, cytotoxins, pili, and flagellum. The preferred antimicrobial therapy is doxycycline in combination with ceftazidime and surgery for necrotizing soft-tissue infection.
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Affiliation(s)
- Michael A Horseman
- Department of Pharmacy Practice, College of Pharmacy, Texas A&M Health Sciences Center, Kingsville, Texas, USA.
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25
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Chan GCF, Chan S, Ho PL, Ha SY. Effects of chelators (deferoxamine, deferiprone and deferasirox) on the growth of Klebsiella pneumoniae and Aeromonas hydrophila isolated from transfusion-dependent thalassemia patients. Hemoglobin 2010; 33:352-60. [PMID: 19814682 DOI: 10.3109/03630260903211888] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Infections are among the leading causes of death for thalassemia major patients. The known predisposing factors of infection include prior splenectomy, iron overload and use of iron chelator such as deferoxamine (DFO). While encapsulated organisms frequently found in splenectomized patients were readily controlled by prophylactic vaccination and vigilant antibiotic treatment, ferrophilic organisms such as Yersinia and Klebsiella remain common pathogens in thalassemic patients. Yersinia infections are more prevalent in temperate regions and Klebsiella infections are commonly found in tropical and subtropical areas. While the use of DFO further aggravates the risk of Yersinia infection, oral chelators such as deferiprone (L1) do not enhance the growth of Yersinia in vitro or in vivo. We found that the growth of Klebsiella was marginally enhanced by DFO in vitro when compared to Yersinia. Such an unfavorable effect was not found in either L1 or deferasirox (DFRA) in vitro. The growth of Aeromonas was not affected by the presence of all three forms of chelators. Therefore, we suggest that factors other than DFO may account for the increased prevalence of Klebsiella and Aeromonas infection in Asian thalassemic patients.
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Affiliation(s)
- Godfrey Chi-Fung Chan
- Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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26
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27
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Antonopoulos P, Constantinidis F, Charalampopoulos G, Dalamarinis K, Karanicas I, Kokkini G. An emergency diagnostic dilemma: a case of Yersinia enterocolitica colitis mimicking acute appendicitis in a beta-thalassemia major patient: the role of CT and literature review. Emerg Radiol 2007; 15:123-6. [PMID: 17619918 DOI: 10.1007/s10140-007-0643-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2007] [Accepted: 06/01/2007] [Indexed: 12/29/2022]
Abstract
The role of computed tomography (CT) scanning in a case of Yersinia enterocolitica (YE) enteritis mimicking acute appendicitis in a 34-year-old female patient with beta-thalassemia major is presented. Although the abdominal CT findings on admittance were indicative of acute appendicitis (enlargement of the appendix and thickening of its wall), making appendectomy a likely treatment option, a second CT scan 3 days later was diagnostic for infectious colitis (bowel wall thickening, ulcerations of the colonic mucosa, and fat stranding), and an unnecessary appendectomy was thus avoided. The diagnosis of YE colitis was later confirmed by serology tests.
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Affiliation(s)
- Petros Antonopoulos
- Department of Computed Tomography, 1st IKA, Sismanoglio General Hospital, Sismanogliou 1 Maroussi, 15126, Athens, Greece.
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28
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Rahav G, Volach V, Shapiro M, Rund D, Rachmilewitz EA, Goldfarb A. Severe infections in thalassaemic patients: prevalence and predisposing factors. Br J Haematol 2006; 133:667-74. [PMID: 16704445 DOI: 10.1111/j.1365-2141.2006.06082.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
The incidence of infections among patients with thalassaemia and the role of risk factors for infection are uncertain. We studied the occurrence of infections necessitating hospitalisation in 92 homozygous beta-thalassaemia patients who had been followed longitudinally for decades, and investigated the role of potential risk factors for these infections. Pneumonia accounted for 26% of the infections and fever of unknown origin for 14%. Staphylococcus aureus was the major pathogen possibly related to injections associated with intensive chelation with deferoxamine. There was a significant increase in the rate of infection over time, notably after 15 years. Splenectomy correlated with the incidence of infection (P < 0.001) without being confounded by other variables and with highest frequencies of infections present after 10 years. A direct correlation between iron overload and infection was evident only before the initiation of iron-chelating treatment (P < 0.01). Following initiation of deferoxamine, paradoxically, the infection rate increased (P = 0.046). The combination of splenectomy and deferoxamine treatment was associated with the highest adjusted infection rate. Parathyroid dysfunction and glucose-6-phosphate dehydrogenase deficiency were significantly associated with infection (P = 0.02 and P = 0.04 respectively). The infection rate in thalassaemia is affected mainly by the duration of the disease and is increased by splenectomy and, in the long term, by treatment with deferoxamine.
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Affiliation(s)
- Galia Rahav
- Department of Clinical Microbiology and Infectious Diseases, Hadassah Medical Centre and School of Medicine, The Hebrew University, Ein-Kerem, Jerusalem, Israel.
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29
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Adachi JA, Barriga J, Ericsson CD. Bacterial gut infections. Curr Opin Infect Dis 2006; 12:459-66. [PMID: 17035812 DOI: 10.1097/00001432-199910000-00008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Infections of the bowel as a result of bacterial enteropathogens are one of the most common medical problems. The use of novel molecular biology techniques and the recent development of new antimicrobial drugs and vaccines are helping us to identify, understand, treat and prevent these infections.
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Affiliation(s)
- J A Adachi
- Department of Internal Medicine, Division of Infectious Diseases, University of Texas-Houston Medical School, Houston, TX 77030, USA
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30
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Abstract
Infections are major complications and constitute the second most common cause of mortality and a main cause of morbidity in patients with thalassaemia, a group of genetic disorders of haemoglobin synthesis characterised by a disturbance of globin chain production. Thalassaemias are among the most common genetic disorders in the world. Predisposing factors for infections in thalassaemic patients include severe anaemia, iron overload, splenectomy, and a range of immune abnormalities. Major causative organisms of bacterial infections in thalassaemic patients are Klebsiella spp in Asia and Yersinia enterocolitica in western countries. Transfusion-associated viral infections (especially hepatitis C) can lead to liver cirrhosis and hepatocellular carcinoma. A unique and challenging infection detected in Asian patients is pythiosis, caused by a fungus-like organism, the mortality rate of which is very high. Because the prognosis for thalassaemia has much improved, with many patients surviving to the fifth decade of life in developed countries, it is mandatory to reduce mortality by recognising and presumptively treating infections in these patients as quickly as possible.
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Affiliation(s)
- Sandro Vento
- Section of Infectious Diseases, Department of Pathology, University of Verona, Verona, Italy.
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31
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Grigull L, Linderkamp C, Sander A, Schmid H, Mutschler U, Welte K, Beilken A. Multiple spleen and liver abscesses due to Yersinia enterocolitica septicemia in a child with congenital sideroblastic anemia. J Pediatr Hematol Oncol 2005; 27:624-6. [PMID: 16282898 DOI: 10.1097/01.mph.0000188630.03392.12] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
In patients with iron overload, opportunistic infections are an underestimated risk. Yersinia enterocolitica is a rare organism to be isolated in this setting. The authors report a case of disseminated Y. enterocolitica sepsis in a 5-year-old boy with sideroblastic anemia. Ultrasound examination revealed massive ascites, a pseudo-appendicitis, and hypoechogenic lesions corresponding to abscess formations in the liver and spleen. The initial antibiotic therapy consisted of cefotaxime, gentamicin, and metronidazole, but only treatment with ciprofloxacin and meropenem led to defervescence and clinical stabilization. The risk of developing uncommon infections in patients with iron overload should be acknowledged by all physicians, and the relevance of ultrasound examination is emphasized. In this case, only a detailed history revealed that several days before the onset of diarrhea, the child was feeding a deer; this is how infection was probably acquired.
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Affiliation(s)
- Lorenz Grigull
- Medizinische Hochschule Hannover, Department of Paediatric Haematology and Oncology, Hannover, Germany.
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32
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Wang SC, Lin KH, Chern JPS, Lu MY, Jou ST, Lin DT, Lin KS. Severe bacterial infection in transfusion-dependent patients with thalassemia major. Clin Infect Dis 2003; 37:984-8. [PMID: 13130412 DOI: 10.1086/378062] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2003] [Accepted: 06/05/2003] [Indexed: 12/29/2022] Open
Abstract
The incidence and clinical spectrum of severe bacterial infection were studied in 89 patients with thalassemia major that was diagnosed between January 1971 and March 2002. There were 20 patients with 24 episodes of severe bacterial infection, resulting in an incidence of 1.6 infections per 100 patient-years. The clinical spectrum included liver abscess (6 cases), septicemia (6 cases), soft-tissue infection (2 cases), osteomyelitis (2 cases), corneal ulcer (1 case), enteritis (1 case), and abscesses of the lung, kidney, intra-abdominal region, retropharynx, gums, and buttocks (1 case each). The leading causal microorganisms were gram-negative bacilli, especially Klebsiella pneumoniae (10 of 20 isolates). Other responsible pathogens were Pseudomonas aeruginosa (2/20), Vibrio vulnificus (2/20), Acinetobacter baumanii (1/20), Streptococcus intermidius (1/20), Yersinia enterocolitica (1/20), Staphylococcus aureus (1/20), Escherichia coli (1/20), and Salmonella species (1/20). Splenectomy and delays in the start of iron-chelating therapy were 2 independent risk factors.
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Affiliation(s)
- Shih-Chung Wang
- Department of Pediatrics, Chang-Hua Christian Hospital, Chang-Hua, Taiwan
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Chung BHY, Ha SY, Chan GCF, Chiang A, Lee TL, Ho HK, Lee CY, Luk CW, Lau YL. Klebsiella infection in patients with thalassemia. Clin Infect Dis 2003; 36:575-9. [PMID: 12594637 DOI: 10.1086/367656] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2002] [Accepted: 11/15/2002] [Indexed: 12/29/2022] Open
Abstract
Klebsiella infection has previously been reported in a few patients with transfusion-dependent thalassemia. The incidence and clinical spectrum of this infection in our cohort of patients were reviewed retrospectively. Among 160 patients observed for 12 years, there were 15 episodes of Klebsiella infection that occurred in 12 patients (7.5%), resulting in an incidence of 0.78 infections per 100 patient-years. The clinical spectrum included sinusitis (4 cases), intracranial infection (5 cases), septicemia (4 cases), and abscesses of the liver, lung, kidney, and parotid gland (1 case each). Three patients had recurrent infections involving different sites, 2 (16%) died of fulminant septicemia, and 3 (25%) had significant permanent neurological deficits. The antibiotic susceptibility pattern for the isolates was similar to the pattern for isolates recovered in the community. With regard to predisposing factors, iron overload and liver function derangement were found to be significant on univariate analysis (P=.046 and P=.049, respectively) but insignificant on multivariate analysis. Klebsiella infection was a serious and frequently encountered complication in our patients with transfusion-dependent thalassemia, resulting in high mortality and morbidity rates.
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Affiliation(s)
- B H Y Chung
- Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China
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Wiener E. Impaired phagocyte antibacterial effector functions in beta-thalassemia: a likely factor in the increased susceptibility to bacterial infections. Hematology 2003; 8:35-40. [PMID: 12623425 DOI: 10.1080/1024533031000081414] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Bacterial diseases are serious complications of beta-thalassemia syndromes but the mechanisms underlying the increased susceptibility to these infections are not fully understood. Factors which are likely to be involved are anemia, splenectomy, iron-overload and alterations in innate/adaptive immune responses. There is substantial evidence that a defect in innate effector functions of phagocytes (neutrophils, monocytes/macrophages) plays an important role in the weakened resistance to pathogenic bacteria and is at least in part due to iron overload. There is substantial evidence of an iron-related defect in bacterial phagocytosis by neutrophils. Moreover, reduced chemotaxis by these phagocytes has been repeatedly demonstrated. Similarly, an impairment of monocyte bacterial phagocytosis and generation of anti-bacterial compounds have recently been delineated but any relation to iron overload needs to be established. Additional mechanisms of defective innate immune responses such as altered expression of pathogen recognising receptors and function seem possible and have to be explored. Further insight into innate phagocyte effector functions in beta-thalassemia is essential for understanding the increased susceptibility to bacterial infections and their management.
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Affiliation(s)
- Edith Wiener
- Departmentof Haematology, Imperial College Faculty of Medicine, Hammersmith Hospital, London, UK.
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Lesic B, Foulon J, Carniel E. Comparison of the effects of deferiprone versus deferoxamine on growth and virulence of Yersinia enterocolitica. Antimicrob Agents Chemother 2002; 46:1741-5. [PMID: 12019084 PMCID: PMC127255 DOI: 10.1128/aac.46.6.1741-1745.2002] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Deferoxamine, a drug used to treat patients with iron overload, has the capacity to promote systemic Y. enterocolitica infections in humans. The aim of this study was to determine whether deferiprone, the only orally active alternative treatment, has the same potential. When Y. enterocolitica IP864 was grown in an iron-poor chemically defined medium, addition of deferoxamine promoted its growth, while various concentrations of deferiprone did not display this activity. Similarly, on iron-poor agar plates, various Y. enterocolitica strains were able to grow around paper disks impregnated with deferoxamine in a dose-dependent manner, while no growth was observed around the deferiprone disks. In a mouse experimental model of infection, the 50% lethal dose (LD(50)) of strain IP864 was decreased by more than 5 log units in mice pretreated with deferoxamine, while a deferiprone pretreatment did not affect it. Therefore, in contrast to deferoxamine, deferiprone does not enhance growth of pathogenic Y. enterocolitica in vitro and does not have the potential to promote Y. enterocolitica septicemia in a mouse model of infection. Deferiprone may thus represent a useful alternative iron-chelation therapy during invasive Y. enterocolitica infections.
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Affiliation(s)
- Biliana Lesic
- Laboratoire des Yersinia, Institut Pasteur, 75724 Paris Cedex 15, France
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Hansen MG, Pearl G, Levy M. Intussusception due to Yersinia enterocolitica enterocolitis in a patient with beta-thalassemia. Arch Pathol Lab Med 2001; 125:1486-8. [PMID: 11698009 DOI: 10.5858/2001-125-1486-idtyee] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Patients who are homozygous for thalassemia major are at risk for Yersinia enterocolitica infections. We present a case of a 4-year-old child with intussusception of the terminal ileum whose past medical history was significant for beta-thalassemia. His monthly blood transfusions for this condition may have put him at risk for Y enterocolitica enterocolitis. The pathogenesis of this disease relates to the role of iron as an essential growth factor for Yersinia, and this patient's transfusions left him in an iron-overloaded state, despite treatment with Desferal. Our patient's unusual presentation of intussusception was secondary to the mass effect caused by lymphoid hyperplasia, specifically hypertrophied Peyer's patches in the ileum caused by Y enterocolitica infection. To our knowledge, this is the first such case of intussusception caused by Yersinia to be reported.
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Affiliation(s)
- M G Hansen
- Department of Pathology, Orlando Regional Medical Center, 1414 South Orange Ave, Orlando, FL 32806, USA.
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Kanj SS, Araj GF, Taher A, Reller LB. Campylobacter fetus pericarditis in a patient with beta-thalassemia: case report and review of the literature. Clin Microbiol Infect 2001; 7:510-3. [PMID: 11678937 DOI: 10.1046/j.1198-743x.2001.00300.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
A case of pericardial effusion due to Campylobacter fetus in a patient with thalassemia is presented. The patient failed to respond to ceftriaxone and clarithromycin despite in vitro susceptibility, but improved after pericardiectomy and ampicillin. Pericarditis due to C. fetus has rarely been reported. A high index of suspicion is essential to recognise this organism, because of its special microbiological characteristics.
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Affiliation(s)
- S S Kanj
- Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut, PO Box 113-6044, Beirut, Lebanon.
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Abstract
With increased recognition of the profound morbidity of sickle cell disease and with growing evidence of the efficacy of transfusion therapy in prevention and treatment of sickle cell complications, most patients now receive intermittent transfusion therapy. The purpose of this report is to review blood component therapy and Its risks for sickle cell patients. Packed red cells are the preferred blood component. Leukocyte-reduced units should be standard because of their beneficial effects in reducing alloimmunization, transfusion reactions, platelet refractoriness, and infection transmission. The use of washed, frozen, or Irradiated units is limited to specific problems. Sickle trait-positive units function normally, but because of difficulties with calculating hemoglobin S percentages and leukocyte filters, they are not routinely used. Transfusion-acquired infections have shown a marked decrease but still present a major risk. Viral hepatitis transmission is currently low, but at least 10% of adult sickle cell patients are hepatitis C positive, and they often have liver damage. Although bacterial infections are rare, they account for 16% of transfusion-related fatalities. Patients who are iron overloaded are particularly vulnerable to Yersina enterocolitica. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. However, preventive phenotypic matching for common antigens can minimize alloimmunization; limited matching for at least E, C, and K has become the standard of care. Recently, more patients are being identified who have developed red cell autoantibodies, which can mask alloantibodies and occasionally are hemolytic. Careful laboratory evaluation of all cases is essential. Transfusions also may trigger sickle cell events, including pain crises, stroke, and acute pulmonary deterioration. In part, these are induced by blood viscosity and increased blood pressure. Diuretic therapy and close monitoring of transfusion volume and vital signs can minimize these events. In summary, transfusion therapy carries risks, but the routine use of leukocyte-reduced, phenotypically matched units in conjunction with close monitoring of patients can make transfusion therapy safer.
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Affiliation(s)
- E P Vichinsky
- Department of Pediatrics, University of California, San Francisco, USA
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Prati D. Benefits and Complications of Regular Blood Transfusion in Patients with Beta-Thalassaemia major. Vox Sang 2000. [DOI: 10.1046/j.1423-0410.2000.7930129.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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Cunningham-Rundles S, Giardina PJ, Grady RW, Califano C, McKenzie P, De Sousa M. Effect of transfusional iron overload on immune response. J Infect Dis 2000; 182 Suppl 1:S115-21. [PMID: 10944493 DOI: 10.1086/315919] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Increased susceptibility to infectious disease is observed in persons with transfusion-dependent thalassemia and iron overload who experience increased exposure to pathogens and chronic immune stimulation. An abnormal low CD8(+) T (LT8) immune phenotype defines a subgroup of patients. The CD8(+) T cell immunophenotype is stable despite continued blood transfusion and is independent of age. CD8(+) T cells, but not CD4(+) T cells, were modulated during intravenous chelation with deferoxamine. Return to characteristic pretreatment levels of CD8 was observed in both the low and the normal groups, suggesting the possibility of a set point. Proliferative response to mitogens and antigens was increased by chelation. Because CD8(+) T cells are important in immune response to infectious disease, these studies suggest that intrinsic CD8(+) T cell subset differences may be a critical factor in determining susceptibility to infection independent of transfusional iron overload or alloantigen exposure.
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Affiliation(s)
- S Cunningham-Rundles
- Immunology, Division of Hematology/Oncology, Dept. of Pediatrics, New York-Presbyterian Hospital Cornell University Medical Center, New York, New York 10021, USA.
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Peterson LR, Thomson RB. Use of the clinical microbiology laboratory for the diagnosis and management of infectious diseases related to the oral cavity. Infect Dis Clin North Am 1999; 13:775-95. [PMID: 10579108 PMCID: PMC7135049 DOI: 10.1016/s0891-5520(05)70108-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Our knowledge regarding the pathogenesis of infections relative to the oral cavity is rapidly expanding, similar to our overall understanding of how infectious diseases impact our daily lives. The complexity of the flora within the oral cavity is quite unique and often makes diagnosis difficult; however, it is becoming more apparent that accurate diagnostic testing is important from the standpoint of focusing appropriate therapy on pathogens within this crucial body site, and avoiding overuse of antimicrobial agents in settings of infection where they have no demonstrated benefit. New diagnostic methods are being developed to detect pathogens and rapidly delineate resistance patterns. Many will be based on new genetic assays, but they must be cost effective, sensitive, and specific. Another growing challenge is to provide adequate lab support to outpatient offices and clinics, without compromising the specimen culture or turnaround times. So many patients are being seen away from hospital laboratories that we need ways to diagnose sinusitis, pharyngitis, abscess, and other infections of the oral cavity without killing the anaerobes and other significant facultative bacteria, and without ruining the direct stains by overgrowth or inflammatory cell degradation during specimen transport. These results need to be available quickly enough to give useful information for office diagnosis in order to effect therapy. To optimize both diagnosis and treatment, a key to the future will be better communication between the clinical practitioner and laboratory, with an increasing emphasis on training expertise in medical microbiology and infectious diseases.
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Affiliation(s)
- L R Peterson
- Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA.
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