This study investigated the safety and efficacy of the HyperQure™ extravascular renal denervation (RDN) system in a swine model of mild hypertension. Ten female pigs were fed a 3% salt diet to induce hypertension and underwent either extravascular RDN using the HyperQure™ RDN system (n = 7) or a sham procedure (n = 3). Blood pressure (BP) was continuously monitored using implanted transmitters, and safety assessments were conducted via computed tomography angiography (CTA) at 28 days post-procedure. The primary endpoint was the change in systolic blood pressure (SBP) at four weeks, while secondary endpoints included changes in diastolic BP (DBP), mean arterial pressure (MAP), and histological evaluation of renal nerve and artery integrity. At four weeks, SBP decreased by 11.8 ± 5.2 mmHg in the RDN group compared to an increase of 6.4 ± 4.2 mmHg in controls, resulting in a mean difference of 18.2 mmHg (p < .05). Similar improvements were observed in DBP and MAP, with mean differences of 15.4 and 16.2 mmHg, respectively (both p < .05). CTA revealed no significant renal artery or intraperitoneal organ injury. Histological analysis confirmed effective nerve ablation, as evidenced by reduced tyrosine hydroxylase staining, without intimal damage. No postoperative complications were observed during the 28-day study period. These findings demonstrate the safety and efficacy of the HyperQure™ extravascular RDN system in reducing BP, providing a promising alternative for patients with resistant hypertension or those ineligible for intravascular RDN. Further clinical trials are warranted to validate these results.

Cryptosporidium parvum is a protozoan parasite that causes severe diarrheal illness in children and each year nearly 50,000 children under age 5 die due to the disease. Despite tremendous research efforts, there remains a lack of effective therapies and vaccines. Novel inhibitors against N-myristoyltransferase of C. parvum (CpNMT) are potential starting points towards the development of effective therapies. In quest of promising selective CpNMT inhibitors, structure guided modifications of compound 1 (2-chloro-5-(ethyl-phenyl-sulfamoyl)-N-[2-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide) were performed. The resulting compounds were evaluated for selective inhibition of CpNMT over the host enzyme HsNMT1. Compounds 11e and 11f exhibited good inhibition, with IC50 values of 2.5 and 2.8 μM, respectively. While 11e was slightly more selective towards CpNMT over HsNMT1 (∼5-fold), compound 11f showed >40-fold selectivity, validating our structure-based design approaches. Compounds 11e and 11f were also found to be efficacious against C. parvum growth, with EC50 values of 6.9 and 16.4 μM, respectively.

Mitigation measures against infectious aerosols are desperately needed. We aimed to: 1) compare germicidal ultraviolet radiation (GUV) at 254 nm (254-GUVUpper-Room) and 222 nm (222-GUVWhole-Room) with portable high efficiency particulate air (HEPA) filters to inactivate/remove airborne bacteriophage ϕX174, 2) measure the effect of air mixing on the effectiveness of 254-GUVUpper-Room, and 3) determine the relative susceptibility of ϕX174, SARS-CoV-2, and Influenza A(H3N2) to GUV (254 nm, 222 nm). A nebulizer generated ϕX174 laden aerosols in an occupied clinical room (sealed-low flow). Mitigation devices (3 commercial GUV devices, HEPA-470m3/hr-class H13 filter) were compared by counterbalanced experimental design with negative (no mitigation) control. Viral inactivation was determined by air sampling (SartoriusMD8 and Gilair5). Environmental physical properties (airflow, particle matter, GUV irradiance, temperature and humidity) were also characterized. The effect of improving air mixing on the efficacy of 254-GUVUpper-Room devices was systematically explored by adding fans. The relative susceptibility of SARS-CoV-2, Influenza A(H3N2) and ϕX174 were assessed by exposure to 254 nm and 222 nm wavelength radiation in a 82 L chamber. 254-GUVUpper-Room with highest irradiance (Philips UV-C WL345W) resulted in highest calculated equivalent air changes per hour (eACH) of 8.18 ± 0.74 (hr-1). This increased to 19.20 ± 2.45 (hr-1) with the addition of 2 fans. HEPA filtration achieved 11.10 ± 1.25 (hr-1). For 254 nm GUV rank order (most-to-least) of susceptibility was SARS-CoV-2, ϕX174, Influenza A(H3N2), and for 222 nm GUV SARS-CoV-2, Influenza A(H3N2), ϕX174. GUV effectively inactivates virus laden aerosol in poorly ventilated clinical environments. Efficacy is improved by increasing airflow. HEPA performance is superior to GUV under low flow conditions.

Estimates of chronic hepatitis B virus (HBV) prevalence and critically the amount of infection that is undiagnosed or unlinked to care are uncertain-even in countries like UK where vertical transmission and overall prevalence are very low. In the absence of country of birth data, we aim to estimate HBV prevalence through combining public health surveillance data on antenatally screened women by ethnic group and multipliers generated from non-antenatally screened populations by ethnic group with English population denominators. Of 714,287 women aged 16-49 years with ethnic group data tested as part of antenatal care between 2015 and 2021, 4174 (0.6%) were HBsAg-positive; 94% in people of ethnic groups other than White British. Of 1,447,467 people tested for HBsAg with ethnic group data from other testing sources (primary and secondary care excluding occupational health and renal services), 27,628 (1.9%) were HBsAg-positive; 87% in people of ethnic groups other than White British. We estimate that the overall number and prevalence of people with chronic hepatitis B in England is 268,767 (95% CI: 227,896-314,044) and 0.58% (95% CI: 0.50-0.68). Approximately two-thirds were male, one-third female, and 68% were aged under 50. We estimate that over 83% of HBV infections are in people of ethnic groups other than White British, with 23% in people from Black ethnic groups, 21% from other White ethnic groups and 19% in Asian ethnic groups. These estimates are the first step towards establishing whether England can meet World Health Organisation targets to eliminate HBV as a public health problem-using methods that can also be used by other countries.

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract infections, especially in infants and the elderly. Developing an RSV vaccine that promotes a robust mucosal immune response is necessary to successfully prevent viral transmission and the development of severe disease. We previously reported that crosslinked carbon dots (CCD) may be an excellent adjuvant candidate for intranasal (IN) protein subunit vaccines. Considering the strong immunogenicity of RSV prefused F protein (preF), we prepared an IN RSV vaccine composed of the CCD adjuvant and the preF protein as antigen (CCD/preF) and evaluated the induced antigen-specific humoral and cellular immunity. We found that IN immunization with the CCD/preF vaccine elicited strong serum IgG responses and mucosal immunity, including secreted IgA antibodies, tissue-resident memory T (TRM) cells, and antigen-specific B cells, which lasted for at least 1 year. In addition, a combination of intramuscular and IN immunization with CCD/preF vaccine induced stronger systemic and mucosal immunity. Together, this study proved the high immunogenicity of the CCD/preF vaccines and supported the university of the mucosal CCD adjuvant, supporting further development of the CCD/preF vaccine in larger animal models and clinical studies.

The Komfo Anokye Teaching Hospital (KATH) in Ghana serves a population of over 5.4 million people. The number of operating rooms creates a bottleneck to accessing surgical care. In a previously published paper, the plastic surgery department at KATH sought to utilize a wide-awake local anesthesia no tourniquet (WALANT) technique to perform hand surgery as a solution to improving surgical capacity. This technique, popularized by Donald H. Lalonde, was first utilized in February 2017 at KATH. We aim to provide an update on the utilization of this procedure room created almost a decade ago.

Surgeries from January 1, 2023, to December 31, 2023, were included in this study. Procedures were categorized into elective versus emergent, and information regarding the cost of procedures for the patient was analyzed.

In 2023, a total of 500 surgeries were performed in the WALANT procedure room, with an average of 42 surgeries performed monthly. This represents a 40% increase in surgical volume compared to 2017. The plastic surgery team performed a total of 188 hand surgeries and 249 nonhand reconstructive surgeries. The procedure room has also garnered increased utilization from general surgery and orthopedic surgery, with an 86.4% increase in utilization from 2017. Prices remain comparable to prices in 2017 and remain more cost-effective compared to the same procedure done under general anesthesia in the main operating room. A total cost savings for patients of ₵578,816.30 was achieved for the 2023 year.

This local anesthesia technique and subsequent procedure room were born out of a necessity to increase surgical capacity at a major tertiary center in Ghana. Over the past 7 years, it has proven to be increasingly productive while remaining cost-effective for both patients and the hospital system alike. The transformation of a storage room into this procedure room shows how easily replicable this setup can be throughout other hospital systems. Finally, WALANT is an accepted practice in many parts of the world, and is easily learned. This model is thus a sustainable and practical solution to the surgical capacity problems facing overburdened medical systems in developing countries.

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n = 12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity (CVR) in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.

Acute lung injury (ALI) is a life-threatening complication of influenza A virus (IAV) infection, characterized by high morbidity and mortality. Recent studies have implicated ferroptosis, a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, in the pathogenesis of IAV-induced ALI. However, the underlying mechanisms and key regulators of IAV-induced ferroptosis remain largely unknown. In this study, we found that IAV infection induces predominant ferroptosis in alveolar and bronchial epithelial cells, contributing to tissue damage and the development of acute lung injury. Treatment with the ferroptosis inhibitor ferrostatin-1 improved survival, mitigated weight loss, and alleviated lung injury in IAV-infected mice. Mechanistically, IAV-induced ferroptosis was associated with excess lipid peroxidation, nitrative stress, and disrupted iron metabolism. Targeted lipidomic analysis revealed that phospholipid peroxidation is a crucial mechanism in IAV-induced ferroptosis. Importantly, we identified indoleamine 2,3-dioxygenase 1 (IDO1) as a key regulator of IAV-induced ferroptosis. IDO1 knockdown inhibited IAV-induced cell death, and reduced intracellular reactive oxygen species, peroxynitrite, and inducible nitric oxide synthase expression. Furthermore, pharmacological inhibition of IDO1 with 1-methyl-tryptophan improved ALI phenotype in IAV-infected mice. These findings highlight the critical role of ferroptosis in IAV-induced ALI pathogenesis and identify IDO1 as a potential therapeutic target for the treatment of this life-threatening condition.

Postpartum depression (PPD) is a significant public health concern; however, its association with congenital anomalies (CAs) remains understudied. This study investigated the relationship between CAs and PPD risk and identified persistent patterns of PPD among mothers of infants with and without CAs.

We analysed data from 86,464 mother-child pairs in the Japan Environment and Children's Study. PPD was assessed using the Edinburgh Postnatal Depression Scale at 1 and 6 months postpartum. Bayesian multiple log-binomial regression was used to examine associations between CAs and PPD.

The risk ratios (RRs) of PPD were higher in the CAs group than in the Non-CAs group at 1 month (RR = 1.06, 95% credible interval [CrI] = [1.00, 1.12]) and 6 months (RR = 1.11, 95% CrI = [1.04, 1.18]) postpartum. Four PPD patterns were identified: persistent, recovered, late-onset and resilient. Mothers of neonates with CAs on both late-onset (median OR = 1.13, 95% CrI = [1.02, 1.25]) and persistent patterns (median OR = 1.13, 95% CrI = [1.03, 1.24]) tended to have positive associations with CAs compared with the resilient group.

Reliance on self-reported PPD measures may introduce bias and lack of differentiation between types and severities of CAs, while the study's focus on mothers alone without including fathers may not capture the full spectrum of parental mental health impacts.

This study suggests that mothers of neonates with CAs have a significantly increased risk of PPD, which persists up to 6 months after delivery.

With advances in technology, early computed tomography (CT) scanning is advocated for trauma patients. However, the benefits of early CT scanning remain unclear. Thus, we examined whether time elapsed from hospital arrival to CT acquisition is associated with the prognoses of severe trauma patients.

We utilized the Japan Trauma Data Bank, a nationwide database. Patients directly transferred from the trauma scene were included. Severe trauma patients, defined as those with Injury Severity Scores (ISS) greater than 15, were enrolled. We excluded patients with cardiac arrest on hospital arrival, ISS of 75, missing data on timing of CT, inappropriate CT time, and elapsed time from hospital arrival to CT scan longer than or equal to 60 min, as well as those who required damage control surgery and those who died within 24 h. Patients were divided into six groups based on elapsed time to CT acquisition (0-9, 10-19, 20-29, 30-39, 40-49, 50-59 min.). The primary outcome was in-hospital mortality, and the secondary outcome was amount of transfusion, including red blood cells, fresh frozen plasma, and platelets.

Of the registered trauma cases, 13,802 cases were included in this study. The crude proportion of in-hospital mortality in the 0-9 min. group was the highest (15.4% [138/898]) compared to other groups. Compared to the 0-9 min. group, multivariable logistic regression analysis revealed that the earlier elapsed time to CT acquisition did not contribute to the improved rate of in-hospital mortality (10-19 min.; OR 0.84, 95% CI 0.64-1.09, p = 0.19, 20-29 min.; OR 0.89, 95% CI 0.69-1.16, p = 0.39, 30-39 min.: OR 0.88, 95% CI 0.67-1.16, p = 0.36, 40-49 min.: OR 0.92, 95% CI 0.67-1.26, p = 0.60, 50-59 min.: OR 1.03, 95% CI 0.73-1.46, p = 0.85). Transfusion amounts did not differ between groups.

Early CT scanning after hospital arrival did not contribute to improved in-hospital mortality or reduce the transfusion amount for severe trauma patients.

A liver abscess can be due to several different microbiological aetiologies. While pyogenic liver abscess is most frequently encountered, amoebic liver abscess and hydatid cyst caused by the parasites, Entamoeba histolytica and Echinococcus granulosus, respectively, should be considered whenever there is epidemiological exposure. As parasitic infections are now rarely seen in clinical practice in developed countries with improvement in sanitation, lack of clinical experience in managing amoebic liver abscesses and overlapping clinical and imaging features between amoebic and pyogenic liver abscesses may lead to delay in diagnosis. In particular, although amoebic liver abscesses respond well to treatment if diagnosed early, they can progress and rupture with high mortality if treatment is delayed. Hence, early diagnosis and prompt initiation of antimicrobials are crucial to prevent complications and death. This case report highlights a case of a very large 21 cm ALA in a young lady to illustrate the challenges faced during diagnostic evaluation.

Hemorrhagic shock and reperfusion (HSR) is the main cause of death following trauma. Cognitive impairment may persist after successful resuscitation from hemorrhagic shock, but the mechanisms remain elusive. This study demonstrated the presence of ferroptosis in an in vitro model of oxygen-glucose deprivation and reoxygenation (OGD/R) in HT22 neurons, and also in a murine model of HSR using 3-month-old C57BL/6 mice. The ferroptosis induced by OGD/R was characterized by transmission electron microscopy, the localization of FTH1 and TFR1 in HT22 cells. However, neuronal ferroptosis was prevented by suppressing AMPK through siRNA transfection or AMPK inhibitor pretreatment (compound C) in vitro. There was a consistent increase in Nrf2 with ROS accumulation, iron deposition, and lipid peroxidation in the hippocampal neurons and tissues. Nrf2 knockdown or overexpression significantly modulated OGD/R induced-ferroptosis. Activating ferroptosis by erastin (a ferroptosis inducer) or inhibiting it by ferrostatin-1 (a ferroptosis inhibitor) respectively enhanced or mitigated cognitive deficits as well as the ferroptosis-related changes induced by HSR. In addition to the improved cognition, single-nucleus transcriptome analysis of ipsilateral hippocampi from Nrf2-/- mice demonstrated the broad decrease of ferroptosis in neuronal cell clusters. LAMA2 and DAG1 were dominantly elevated and co-localized in the hippocampal CA3 region of Nrf2-/- mice by fluorescence in situ hybridization. The activation of astrocytes was significantly attenuated after Nrf2 knockout, associated with the increases of laminin-dystroglycan during astrocyte-neuron crosstalk. Thus, data from this study proposes a novel explanation, namely laminin-dystroglycan interactions during astrocytes-neurons crosstalk stimulating AMPK and Nrf2 induced neuronal ferroptosis, for the development of cognitive impairment after HSR.

Organ function depends on the three-dimensional integrity of the extracellular matrix (ECM). The structure resulting from the location and association of ECM components is a central regulator of cell behavior, but a dearth of matrix-specific analysis keeps it unresolved. Here, we deploy a high-resolution, 3D ECM mapping method and design a machine-learning powered pipeline to detect and characterize ECM architecture during health and disease. We deploy these tools in the human lung, an organ heavily dependent on ECM structure that can host diseases with different histopathologies. We analyzed segments from healthy, emphysema, usual interstitial pneumonia, sarcoidosis, and COVID-19 patients, and produced a remodeling signature per disease and a health/disease probability map from which we inferred the architecture of healthy and diseased ECM. Our methods demonstrate that exaggerated matrix deposition, or fibrosis, is not a single phenomenon, but a series of disease-specific alterations. STATEMENT OF SIGNIFICANCE: The extracellular matrix, or ECM, is the foremost biomaterial. It shapes and supports all tissues while regulating all cells. ECM structure is intricate, yet precise: each organ, at every stage, has a specific ECM structure. During disease, tissues suffer from structural changes that accelerate and perpetuate illness by dysregulating cells. Both healthy and diseased ECM structures are of great biomedical importance, but surprisingly, they have not been mapped in detail. Here, we present a method that combines tissue engineering with machine learning to reveal, map and analyze ECM structures, applied it to pulmonary diseases that kill millions every year. This method can bring objectivity and a higher degree of confidence into the diagnosis of pulmonary disease. In addition the amount of tissue needed for a firm diagnosis may be much smaller than required for manual microscopy evaluation.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known correlate of protection. Previously, several broadly reactive, high-affinity anti-RSV G human monoclonal antibodies were isolated from RSV-exposed individuals and were shown to be protective in vitro and in vivo. Here, we determined the structures of three of these antibodies in complex with RSV G and defined distinct conformational epitopes comprised of highly conserved RSV G residues. Binding competition and structural studies demonstrated that this highly conserved region displays two non-overlapping antigenic sites. Analyses of anti-RSV G antibody sequences reveal that antigenic site flexibility may promote the elicitation of diverse antibody germlines. Together, these findings provide a foundation for next-generation RSV prophylactics, and they expand concepts in vaccine design for the elicitation of germline lineage-diverse, broadly reactive, high-affinity antibodies.

Chronic Kidney Disease (CKD) represents a significant global health challenge, with Indonesia experiencing the highest surge in End-Stage Kidney Disease (ESKD) prevalence over the past decade. Kidney registries are essential for reporting health outcomes, evaluating healthcare services, advocating for policy change, and informing health infrastructure development. Survival rates in ESKD patients undergoing hemodialysis (HD) are a critical outcome measure. However, there is a lack of survival analysis data for ESKD patients receiving HD in Indonesia.

This study aims to assess the one-year survival rate of ESKD patients undergoing HD in Indonesia, while examining risk factors associated with survival, including age, gender, CKD etiology, and dialysis adequacy.

This analytical observational study employed a retrospective cohort design, utilizing patient data from Indonesia Renal Registry between 2016 and 2019. Kaplan-Meier survival curves were generated, and Log rank test was applied to assess the significance of survival differences across subgroups based on age, gender, CKD etiology, and dialysis adequacy.

A total of 122,449 ESKD patients on HD were analyzed, with a mean age of 52 years; majority (55.5%) were male, and hypertensive kidney disease was the leading cause of CKD (43.7%). The overall one-year survival rate was 91.5% (95% CI: 91.3-91.6). Survival decreased significantly with advancing age (p < 0.01), and female patients exhibited lower survival rates compared to males (p < 0.01). Patients with diabetic nephropathy had the lowest survival rate among CKD etiologies (p < 0.01). Dialysis adequacy, assessed in 11,633 patients, revealed that 69.2% had a Kt/V below 1.8. Those with inadequate dialysis had significantly lower survival rates (p=0.00015).

The one-year survival rate for ESKD patients undergoing HD in Indonesia is 91.5%. Increased age, female, diabetic nephropathy as the underlying CKD etiology, and inadequate dialysis adequacy are associated with reduced survival rates.

Among critically ill patients, chronic obstructive pulmonary disease (COPD) is an independent risk factor for death. Recently, biomarkers such as neutrophil-lymphocyte ratio (NLR) and albumin (ALB) have been used to predict the prognosis in patients with COPD. However, the association between NLR/ALB and all-cause mortality in critically ill COPD patients remains unclear. This study aims to explore the association between the NLR/ALB and prognosis in critically ill patients with COPD.

Data was sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Primary outcome was 28-day all-cause mortality, with secondary outcomes being in-hospital and 90-day all-cause mortality. The area under the receiver operating characteristic curve (AUROC) was calculated to compare prognostic accuracy of NLR, NLR/ALB, PLR, SII and MLR variables. After identifying the most predictive factor, KM survival curves, Cox models and subgroup analyses were used to examine NLR/ALB's relationship with mortality in critically ill COPD patients. Additionally, patients with COPD from the National Health and Nutrition Examination Survey data (1999-2018) was used with Cox regression to investigate NLR/ALB's correlation with all-cause mortality in COPD patients.

1916 critically ill COPD patients from MIMIC IV, divided into quartiles by NLR/ALB levels: Q1 (NLR/ALB<1.108), Q2 (2.095>NLR/ALB≥1.108), Q3 (4.221>NLR/ALB≥2.095), Q4 (NLR/ALB≥4.221). In multivariate Cox regression, Q4 vs Q1: 28-day mortality HR=2.27 (95% CI: 1.63-3.16); 90-day mortality HR=2.06 (95% CI: 1.56-2.71); in-hospital mortality HR=1.93 (95% CI: 1.35-2.77); P<0.001. Subgroup analyses showed that the correlation between NLR/ALB and 28-day mortality was stable Additionally, we recruited 2,003 COPD patients from the NHANES that found NLR/ALB also correlated with all-cause mortality in COPD (In multivariate Cox regression: Q4 vs Q1 hR=1.92 (95% CI: 1.45-2.55, P<0.001)).

Elevated NLR/ALB levels are associated with increased all-cause mortality in critically ill patients with COPD.

This study evaluates the impact of using a Clinical Decision Support System software in the form of a computer-guided consultation (CGC) when conducting Chronic Obstructive Pulmonary Disease (COPD) reviews in primary care. 5221 patients on the COPD register underwent CGC review with 21.1% found not to have COPD. Previously unrecognised cardiac disease was highlighted by the CGC in 7% of confirmed COPD cases. CGC review resulted in the number of patients possessing a self-management plan rising from 62-85%. 13% were found to have sub-optimal inhaler technique during CGC review with the CGC prompting correction in all cases. Only 26% of patients identified by the CGC as appropriate for Pulmonary Rehabilitation (PR) referral had previously attended a PR program. The integration of technology in the form of clinical decision support system software results in greater implementation of guideline-level care representing a scalable solution when performing COPD reviews.

Hypertensive heart disease (HTN-HD) meaningfully contributes to hypertension morbidity and mortality. Initially established as an adaptive response, HTN-HD progresses toward worsening of left ventricule (LV) function and heart failure (HF). Hypertensive stress elevates sympathetic nervous system (SNS) activity, a negative clinical predictor, and expands macrophages. How they interact in the compensatory phase of HTN-HD is unclear. We report that LV pressure overload recruited a brainstem neural circuit to enhance splenic SNS and induce placental growth factor (PlGF) secretion. During hypertensive stress, PlGF drove the proliferation of self-renewing cardiac resident macrophages (RMs) expressing its receptor neuropilin-1 (NRP1). Inhibition of the splenic neuroimmune axis or ablation of NRP1 in RM hindered the adaptive response to hypertensive stress, leading to HF. In humans, circulating PlGF correlated with cardiac hypertrophy, and failing hearts expressed NRP1 in RMs. Here, we discovered a multiorgan response driving a neural reflex to expand cardiac NRP1+ RM and counteract HF.

The prevalence of anemia in patients with community-acquired pneumonia (CAP) has been well described. However, few studies have explored its association with short-term and long-term mortality risk in CAP patients.

We aimed to investigate the associations between hemoglobin concentrations at baseline and 14-day and 1-year mortality risk in a CAP population with a large sample size. Our data originated from the Dryad database, including a dataset from the study "Incidence rate of community-acquired pneumonia in adults: a population-based prospective active surveillance study in 3 cities in South America." A total of 1463 study samples with follow-up data from the dataset were enrolled for our analysis.

During the follow-up period of 3 years, the 14-day risk and 1-year mortality risk were 206 (14.08%) and 401 (27.41%), respectively, among these CAP patients. Curve analysis indicated a strong U-shaped relationship between blood hemoglobin concentrations and 14-day mortality (r = -0.191, P < .001) and 1-year mortality (r = -0.220, P < .001). The blood hemoglobin level with the lowest point of mortality risk was 14.5 g/dL, suggesting that an increased hemoglobin concentration contributed to reduced 14-day and 1-year mortality risk in CAP patients when hemoglobin does not exceed 14.5 g/dL even if it is within the normal clinical range. In addition, we also observed significant associations of hemoglobin with 14-day mortality risk (odds ratio [OR] = 0.817; 95% CI, 0.742-0.899 P < .001) and 1-year mortality risk (OR = 0.834; 95% CI, 0.773-0.900; P < .001), but only in participants without risk factors for health care-associated pneumonia (HCAP) rather than in participants with risk factors for HCAP.

The greatest discovery is that our findings indicated a significant U-shaped relationship between hemoglobin levels and 14-day and 1-year mortality risk in CAP patients. However, a significant relationship was only discovered in subjects without risk factors for HCAP. More evidence is needed to support this finding.

Parasites have a severe impact on animal and human health. Parasites like worms, ticks, mites, fleas, biting flies, mosquitoes, and pathogenic protozoa affect humans and their pets as well as their livestock globally, both in terms of severity and numbers. Parasitic infections are a global phenomenon, and they can be associated with severe or mild symptoms but represent a continuous risk of severe diseases for animals and humans. Therefore, effective treatment options and the prevention of infection are key for the wellbeing of pets, livestock, and humans, including the reduction of zoonotic risk of infection. The effective control of parasites in animals can greatly improve their quality of life and is also beneficial for humans; this is threatened by drug-resistant parasite populations. Today's key areas for improvement of parasite control are as follows: a) convenience of prevention and treatment, b) effectiveness against drug-resistant parasites, c) availability and reduced costs of treatment, and d) control measurements that are environmentally friendly.

Little is known about the association between chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) in people with established CVD. Knowing if COPD is associated with a higher risk of cardiovascular events would guide appropriate secondary prevention.

To examine the risk of COPD on major adverse cardiac events (MACEs, acute myocardial infarction, stroke and cardiovascular death) in a complete real-world population of a large province, with known CVD.

We conducted a retrospective population cohort study using health administration, medication, laboratory, electronic medical record and other data from Ontario, Canada. All people with a history of CVD with and without physician-diagnosed COPD as of 2008 were followed until 2016 and cardiac risk factors, sociodemographic factors, comorbidities and other factors were compared. Sequential cause-specific hazard models adjusting for these factors determined the risk of MACE in people with COPD.

Of 496 056 individuals with CVD in Ontario on 1 January 2008, 69 161 (13.9%) had COPD. MACE occurred more frequently among those with CVD (45.3 per 1000 person-years) and COPD compared with those with CVD alone (28.6 per 1000 person-years) (HR 1.24, 95% CI 1.21-1.26) after adjustment for cardiac risk factors, comorbidities, socioeconomic status and other factors. People with COPD were less likely to receive preventive CVD medications or see a cardiologist.

In a large, real-world population of people with established CVD, COPD was associated with a higher rate of cardiovascular events but a lower rate of preventive therapy. Strategies are needed to improve secondary CVD prevention in the COPD population.

In China, coronary heart disease (CHD) is a significant public health issue affecting the population's health. Evidence suggests that outdoor PM2.5 is a crucial environmental risk factor for CHD mortality. This study aims to provide scientific evidence for the prevention and treatment of CHD by analyzing the trend of CHD mortality attributed to outdoor PM2.5 in China from 1994 to 2019.

Data were obtained from the Global Burden of Disease Study (GBD) 2019. CHD mortality attributed to outdoor PM2.5 in China from 1994 to 2019 was extracted from the GBD Data tool. We used an age-period-cohort (APC) model based on the intrinsic estimator (IE) algorithm to decompose the age, period, and cohort effects related to CHD mortality attributed to outdoor PM2.5.

From 1994 to 2019, the crude mortality rates (CMRs) and age-standardized mortality rates (ASMRs) of CHD attributed to outdoor PM2.5 in China showed an overall upward trend. The APC model analysis showed that the relative risk of CHD mortality attributed to outdoor PM2.5 increased exponentially with age, reaching 89.284 (95% CI: 48.669, 163.793) in the 90-95 age group. The period effect increased monotonically, with a relative risk of 3.699 (95% CI: 3.639, 3.760) in 2019. The cohort effect decreased monotonically, with the lowest relative risk of CHD mortality attributed to outdoor PM2.5 in residents born between 1990 and 1994, at 0.135 (95% CI: 0.031, 0.588).

The older adult, a high-risk population, should receive more attention. In the future, continuous efforts should be made to strengthen environmental air pollution control and implement targeted health interventions to reduce the impact of outdoor PM2.5 on CHD mortality.

Soil and water pollution represent significant threats to global health, ecosystems, and biodiversity. Healthy soils underpin terrestrial ecosystems, supporting food production, biodiversity, water retention, and carbon sequestration. However, soil degradation jeopardizes the health of 3.2 billion people, while over 2 billion live in water-stressed regions. Pollution of soil, air, and water is a leading environmental cause of disease, contributing to over 9 million premature deaths annually. Soil contamination stems from heavy metals, synthetic chemicals, pesticides, and plastics, driven by industrial activity, agriculture, and waste mismanagement. These pollutants induce oxidative stress, inflammation, and hormonal disruption, significantly increasing risks for non-communicable diseases (NCDs) such as cardiovascular disease (CVD). Emerging contaminants like micro- and nanoplastics amplify health risks through cellular damage, oxidative stress, and cardiovascular dysfunction. Urbanization and climate change exacerbate soil degradation through deforestation, overfertilization, and pollution, further threatening ecosystem sustainability and human health. Mitigation efforts, such as reducing chemical exposure, adopting sustainable land-use practices, and advancing urban planning, have shown promise in lowering pollution-related health impacts. Public health initiatives, stricter pollution controls, and lifestyle interventions, including antioxidant-rich diets, can also mitigate risks. Pollution remains preventable, as demonstrated by high-income nations implementing cost-effective solutions. Policies like the European Commission's Zero-Pollution Vision aim to reduce pollution to safe levels by 2050, promoting sustainable ecosystems and public health. Addressing soil pollution is critical to combating the global burden of NCDs, particularly CVDs, and fostering a healthier environment for future generations.

This systematic review aimed to explore any demographic, biological and behavioural characteristics of men who have sex with men (MSM) with diarrhoeagenic E.coli.

We searched MEDLINE, EMBASE, and CINAHL for manuscripts published to March 2024. One author screened manuscript abstracts; two authors independently conducted a full text review. We only included primary data on gastrointestinal E.coli in MSM. Risk of bias was assessed independently by two authors using the Joanna Briggs Institute tools. This review was registered on PROSPERO(CRD42023455321).

Eleven manuscripts (cross-sectional studies (n = 8), case-series (n = 1), case-control study (n = 1), longitudinal study (n = 1)) from Europe (n = 7) Australia (n = 2), USA (n = 2) including 983 MSM with gastrointestinal E.coli published between 2014-2023 were included in this review. Demographic factors (living with HIV, using HIV-PrEP, using dating apps and working as airline crew, group sex, non-regular (casual) sexual partners); behavioural factors (non-regular sexual partners, non-condom use, oro-anal sex, penile-anal sex, use of sex toys, insertive and receptive fisting, scat play); and infection factors (co-infection with Chlamydia trachomatis including LGV, Neisseria gonorrhoeae, Treponema pallidum, hepatitis C, other enteric pathogens [Shigella spp. Giardia duodenalis, Entamoeba histolytica, hepatitis A and intestinal spirochaetosis]) were observed in MSM with E. coli. Antimicrobial resistance (extended spectrum beta-lactamase and quinolone resistance) was described in MSM with E.coli.

We have highlighted demographic, behavioral and infection factors observed in MSM with E.coli suggesting sexual transmissibility. These data provide insight for future clinical guidelines, public health control strategies and research.

Globally, solid biofuels (SB) have been widely used for household cooking and energy production for decades due to electricity shortages and socio-economic barriers to adopting renewable energy alternatives. This has detrimental effects on air quality, human health, and climate through trace gas and aerosol emissions. Despite numerous studies, the long-term consequences of SB emissions remain poorly understood. Here, we use the Community Earth System Model and the Community Emissions Data System emission inventory to investigate the SB emission impacts on air quality and human health for 2000-2019. Global SB emission increased the ambient PM2.5 (particulate matter with aerodynamic diameters≤ 2.5 μm) and ozone (O3) concentrations up to 23.61 μ g /m3 and 13.69 ppbv, with significant effects found in India, China, and the Rest of Asia (ROA). Our study estimates total annual premature deaths (APDs) associated with global SB-attributable PM2.5 and O3 exposure as 1.11 million [95% confidence interval (95% CI): 1.00-1.22 million] in 2000 up to 1.43 million (95% CI: 1.30-1.56 million) in 2019. China's SB emissions and associated APDs have reduced substantially, whereas India and ROA had a major leap in both estimates in 2019 compared to 2000. China's progress in cutting residential SB emissions accounts for its improvements. Our study urges the reduction of SB usage and emissions to potentially improve overall air quality and human health conditions, especially in highly populated, low- and middle-income countries, where the poor air quality and associated health burden attributable to SB emissions are estimated to be higher.

This study aims to assess whether preoperative hematoma reconstruction and precise volume calculation can improve the hematoma evacuation rate in patients with spontaneous intracerebral hemorrhage(sICH) undergoing stereotactic aspiration (SA).

A retrospective analysis was conducted on patients with sICH who underwent SA from January 2021 to December 2023. Patients were divided into 2 groups based on the use of 3D Slicer for preoperative hematoma reconstruction and volume calculation. Propensity score matching (PSM) was applied to adjust for baseline differences between groups. Statistical analysis was performed to compare hematoma evacuation rate and residual hematoma volume.

After PSM, the 3D Slicer group achieved a higher mean evacuation rate (70.9%) compared with the non-3D Slicer group (53.1%), with a median residual hematoma volume of 7.4 mL versus 15.3 mL, respectively.

Preoperative hematoma reconstruction and volume calculation using 3D Slicer in patients with sICH undergoing SA significantly improves hematoma evacuation rate and reduces residual hematoma volume.

Atherosclerosis is a systemic multifocal disease which most commonly involves branching points of the large and medium-sized arteries. The carotid intima-media thickness (c-IMT) is an established marker for increased cardiovascular risk and cerebrovascular disease. In this study, we aimed to establish the role of femoral intima-media thickness (FIMT) in predicting cardiovascular risk in angiographically confirmed patients of coronary artery disease (CAD) when compared with apparently healthy patients (having normal coronary angiogram).

A total of 114 consecutive patients presented at our institute with symptoms of CAD who underwent coronary angiogram were included in the study. After the coronary angiogram, patients were divided into three groups, group A having normal coronary angiogram, group B having CAD with a synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score of more than 22, and group C having CAD with a SYNTAX score of 22 or less. The Doppler ultrasound of the bilateral femoral artery in each patient was done 1 day before a coronary angiogram and FIMT was recorded.

There was a significant difference (p-value -  < 0.001) found in the mean FIMT in patients with normal coronaries (mean FIMT - 0.49 ± 0.05) and patients having CAD (mean FIMT - 0.73 ± 0.17). The area under the receiver operating characteristic (ROC) curve of mean FIMT in predicting abnormal coronaries was 0.903 (95%CI 0.847-0.958, p < 0.001).

The FIMT has a strong correlation with coronary artery disease. With the help of this non-invasive tool, we can diagnose subclinical atherosclerosis and it may contribute to the prevention of CAD and its severe manifestations.

Background: Peripheral artery disease (PAD) and chronic obstructive pulmonary disease (COPD) are inflammatory diseases. These two entities often co-exist, but little is known about the prevalence of this phenomenon in patients with PAD. The objectives of this prospective cross-sectional study were to determine the prevalence of COPD in patients with PAD and to assess the frequency of COPD underdiagnosis in this group of patients. Patients and methods: Consecutive patients admitted to angiology department were evaluated. Measurements of ankle-brachial and toe-brachial index as well as peripheral arteriography were performed in all participants to confirm PAD. In tobacco smokers with PAD spirometry was performed to identified patients with COPD. Clinical information was obtained from the patients on the basis of questionnaires. Results: Eighty-eight out of 300 consecutive patients were included and assessed. COPD was diagnosed in 33 (37.5%) hospitalized smokers with PAD. COPD has not previously been diagnosed in 28 (84.8%) patients who met the criteria of the disease. Conclusions: There was high prevalence of COPD among tobacco smokers hospitalized in the angiology department. Most of them had never had spirometry performed before. The underdiagnosis rate is relatively high; therefore, all patients with PAD who smoke tobacco should have a spirometry performed, as a screening for COPD.

The first objective of this study was to quantify the impact and disability weight (DW) of frequent diseases or syndromes of preweaning dairy calves using the perceptions of producers and veterinarians. The second objective was to compare the opinions of producers and veterinarians regarding the impact and DW of dairy calves' frequent diseases and syndromes. A survey was conducted to obtain demographic information and opinions of 39 dairy producers and 52 veterinarians on the impact of frequent disease and syndromes on calf health. Most of the producers (97.4%, 38/39) were clients of the ambulatory clinic at the Faculté de Médecine Vétérinaire de l'Université de Montréal in Saint-Hyacinthe, Québec, Canada. They were actively engaged in calf research projects. Québec veterinarians were contacted via email through their association. Additionally, veterinarians from the bovine ambulatory clinic and the bovine veterinary hospital at the Faculté de Médecine Vétérinaire de l'Université de Montréal were contacted directly via email. A visual analog scale, represented by a horizontal line ranging from 0 (no impact) to 10 (maximum impact; i.e., death or euthanasia), was used to estimate the impact of 9 frequent diseases or syndromes (diarrhea, dystocia, inadequate transfer of passive immunity, fracture, wound or abscess, arthritis, respiratory disease, umbilical infection, and congenital defect) on calf health following previously reported methods (using the most probable, and range of the perceived impact for each participant and disease). The DW values were obtained by converting the impact values to a probability density in a scale from 0 to 1 using BetaPERT methodology, a type of data distribution model. Average impact and DW were quantified for each frequent disease and syndrome. Average impact differed statistically across different diseases and syndromes. The highest average impacts were obtained for the presence of a fracture (6.49/10), arthritis (6.22/10), and congenital defects (6.03/10), whereas the lowest impact was observed for the presence of a wound or abscess (3.42/10). The opinions of producers and veterinarians were similar for most of the selected diseases and syndromes; however, statistical differences were observed for arthritis (producers = 5.13 vs. veterinarians = 6.88), umbilical infection (producers = 3.65 vs. veterinarians = 4.74), and dystocia (producers = 3.87 vs. veterinarians = 4.58). A strong correlation coefficient (0.72) was observed between the observed ranks of diseases and syndromes of producers and veterinarians. In conclusion, we quantified how frequent diseases and syndromes affect calf health. Producers and veterinarians mostly agreed on their impact. Estimating DW is a crucial first step in creating a health measure for dairy calves. Similar to humans, this metric will be important for health comparative analysis for producers, veterinarians, and industry.

Emergency room (ER) physicians must deal with patients with clinically suspected symptoms, such as dyspnea, cough, and increased sputum production, on the frontlines of medical care if patients present with severe chronic obstructive pulmonary disease (COPD). This study aims to investigate the longitudinal tendencies of COPD-related ER visits.

A total of 360,313 patients were included in this study. The COPD-related ER visit rates between 2001 and 2015 were categorized using the International Classification of Disease (ICD) codes (496). The effects of age, period, and cohort on COPD-related ER visit rates were determined using an age-period-cohort (APC) model.

Age was associated with a high risk of COPD in the pediatric and older populations. A significant increase was observed in the period effect, from 2001 to 2015. The cohort effect tended to oscillate from 1918 to 1973, and was reversed in the latest cohort. Furthermore, the COPD-related ER visit rate increased between 2001 and 2015 in both men and women.

Age, period, and cohort were observed to increase COPD visit rates. The APC model can be used to determine trends in COPD-related ER visits.

-To investigate if age-related macular degeneration (AMD) predicts risk of all-cause and cardiovascular disease (CVD) mortality in a high CVD risk cohort.

- Prospective cohort study PARTICIPANTS: - 1545 adult participants who presented to a tertiary Australian hospital for evaluation of acute coronary syndrome were included in this study.

- Participants were evaluated for acute coronary syndrome using coronary angiography. Participants were concurrently examined for AMD from mydriatic fundus photographs which were graded using the Wisconsin grading system into categories of any AMD, early AMD and late AMD. Coronary artery disease (CAD) was graded from coronary angiograms using the Gensini score. Mortality data were obtained 9 years after baseline examination through data linkage with the Australian National Death Index. Hazard ratios (HR) were obtained using Cox regression analysis.

All-cause and CVD mortality data were obtained through data linkage with the Australian National Death Index. Death rates through June 2018 were compared by demographics and potential confounders.

- Any AMD was identified in 107 (6.9%) participants, including those with early (n=86) and late AMD (n=21). Over 9 years of follow-up, 234 (15.1%) participants had died, including 174 (11.3%) participants from fatal CVD events. After controlling for age, sex, body mass index , total cholesterol, smoking status, history of diabetes, hypertension, myocardial infarction, stroke and macrovascular CAD severity using the Gensini score, there was an increased rate of all-cause mortality for those with any AMD (hazard ratio [HR] 2.37, [95% CI: 1.54-3.64]), early AMD (HR 2.42 [1.48-3.94]) and late AMD (HR 2.25 [1.08-4.71]). Any AMD (HR 2.62, [1.61-4.26]) and early AMD (HR 2.61 [1.50-4.64]) were also associated with a greater likelihood of CVD mortality. Late AMD was not associated with CVD mortality.

- In individuals with high CVD risk, presence of AMD at any stage independently predicted increased all-cause mortality. Meanwhile, any and early AMD increased risk of CVD mortality. Although mechanisms are unclear, this potentially reflects shared pathways between AMD and CVD.

To estimate the prevalence of Chronic Obstructive Pulmonary Disease (COPD) among non-smoking Sri Lanka adults as part of a larger study which assessed the burden of obstructive lung disease (BOLD) in Sri Lanka.

The prevalence of COPD among non-smokers was 5.3%, with mild to moderate disease. Among spirometry-diagnosed COPD patients, a higher proportion was females and above age 40. Use of biomass (Odds Ratio (OR) = 1.339, 95% Confidence Interval (CI) 1.070-1.821), exposure to passive smoking (OR = 2.376, 95% CI 1.557-3.397) and female sex (OR = 1.353, 95% CI 0.992-1.648) significantly increased the odds of developing COPD and/or related symptoms. Having a chimney, reduced the risk of COPD and/or related symptoms by 29% when cooking with biomass/kerosene.

Severe injuries and some pathologies associated with massive bleeding, such as maternal hemorrhage, gastrointestinal and perioperative bleeding, and rupture of an aneurysm, often lead to major blood loss and the development of hemorrhagic shock. A sharp decrease in circulating blood volume triggers a vicious cycle of vasoconstriction and coagulopathy leading to ischemia of all internal organs and, in severe decompensated states, ischemia of the brain and heart. The basis of tissue damage and dysfunction in hemorrhagic shock is an interruption in the supply of oxygen and substrates for energy production to the cells, making the mitochondria a source and target of oxidative stress and proapoptotic signaling. Based on these mechanisms, different strategies are proposed to treat the multiple organ failure that occurs in shock. The main direction of such treatment is to provide the cells with a sufficient amount of substrates that utilize oxidative phosphorylation at different stages and increase the efficiency of energy production by the mitochondria. These strategies include restoring the efficiency of mitochondrial complexes, for example, by restoring the nicotinamide adenine dinucleotide (NAD) pool. Another direction is approaches to minimize oxidative stress as well as apoptosis, which are primarily dependent on the mitochondria. There are also a number of other methods to reduce mitochondrial dysfunction and improve the quality of the mitochondrial population. In this review, we consider such strategies for the treatment of hemorrhagic shock and show the promise of therapeutic approaches aimed at restoring the bioenergetic functions of the cell and protecting mitochondria.

Monitoring the evolving global and regional burden of kidney cancer attributable to high BMI is vital for informing prevention and healthcare policies. This study aimed to evaluate historical trends in the global and regional burden of kidney cancer attributable to high BMI from 1990 to 2021 and to predict future trends through 2036 for individuals aged 20 years and older. We conducted a retrospective analysis using the Global Burden of Disease 2021 database. We analyzed data on mortality and disability-adjusted life years (DALYs) linked to kidney cancer from high BMI. Stratifications included sociodemographic index (SDI), region, sex, and age. Temporal trends were assessed using joinpoint regression models, while the relationship between SDI and regional burden was examined. Projections were generated using Bayesian age-period-cohort models. In 2021, high BMI contributed to 19.86% of global kidney cancer deaths (0.032 million) and 19.00% of DALYs (0.782 million), representing an increase since 1990. Globally, age-standardized mortality rate and age-standardized disability rate have declined in recent years. However, rates have risen in developing regions such as South Asia and East Asia. Projections indicate stable global rates with slight fluctuations through 2036. The global kidney cancer burden attributable to high BMI shows signs of decline but continues to rise in some developing regions. Addressing this disparity requires strengthening obesity prevention and control strategies tailored to regional needs.

Proactive palliative interventions can improve symptom control and quality of life in individuals with chronic obstructive pulmonary disease (COPD); however, they are often underutilised. This study aimed to develop and validate a prediction model to identify women with COPD in their last year of life to facilitate timely palliative care referrals and interventions.

Data from 1236 women diagnosed with COPD from the 1921-1926 Australian Longitudinal Study on Women's Health cohort, linked to administrative health records, were analysed. We employed Lasso regression and multivariable logistic regression to select predictors. To assess the predictive performance of the model, we used the area under the receiver operating characteristic (AUROC) curve, calibration plot, and calibration metrics. The Youden index was used to establish the optimal cutoff point for risk classification. The clinical utility of the model was evaluated using decision curve analysis (DCA).

The final model to predict 1-year all-cause mortality included six predictors: smoking status, body mass index, needing regular assistance with daily activities, number of supplied medications, duration of illness, and number of hospital admissions. The model performed well, with AUROC of 0.82 (95% CI: 0.80-0.85) and showed excellent calibration. Using a cutoff of 56.6% predicted risk, the model achieved a sensitivity of 72.3%, specificity of 77.7%, and accuracy of 75.0%. The DCA indicated that the model provided a greater net benefit for clinical decision-making.

Our prediction model for identifying women with COPD who may benefit from palliative care has shown robust predictive performance and can be easily applied, but requires external validation.

Preserved ratio impaired spirometry (PRISm) is defined as forced expiratory volume in one second (FEV1)/forced vital capacity (FVC)≥0.70 and FEV1<80% predicted. Previous studies have shown that individuals with PRISm may develop airflow obstruction and have an increased mortality risk. However, studies with long-term follow-up are lacking, and this topic has not been evaluated in the general population. We explored the all-cause mortality risk of individuals with PRISm in a large sample of the general population.

We used data from the National Health and Nutrition Examination Survey III and 2007-2012. Participants aged 20-79 years at baseline and who underwent spirometry were included. Normal spirometry was defined as a prebronchodilator FEV1/FVC≥0.70 and FEV1≥80% predicted. We used Cox proportional hazards regression models to compare all-cause mortality between the groups. We performed sensitivity analyses stratified by the lower limit of normal definition of spirometry criteria. Subgroup analyses by sex, age, smoking status, race, body mass index, level of education, poverty-to-income ratio, respiratory symptoms, and comorbidities were performed in participants with the different spirometry classifications.

Overall, 24,691 participants were included, with a median follow-up time of 25.7 years. Of these, 19,969 had normal spirometry and 1,452 had PRISm. PRISm was associated with a high all-cause mortality risk (unadjusted hazard ratio [HR]=2.47, 95% confidence interval [CI]: 2.25-2.71, P<0.001; adjusted HR=1.69, 95% CI: 1.54-1.86, P<0.001) compared with normal spirometry. Sensitivity analyses and subgroup analyses showed a similar increased all-cause mortality risk in PRISm.

Our finding revealed that PRISm was significantly associated with increased risk of all-cause mortality in the general population compared with normal spirometry. Further research is needed to explore the intervention effect of PRISm.