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Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed sequela of acute pulmonary embolism with varied clinical presentation causing significant morbidity among the affected population. There exist important differences in the occurrence, clinical features and diagnosis of CTEPH between men and women, with women carrying a greater predisposition for the disease. Ongoing studies have also pointed out variations among men and women, in the treatment offered and long-term outcomes including mortality. This focused review article highlights important sex-associated differences in multiple aspects of CTEPH including its epidemiology, clinical features, diagnosis, treatment and outcomes as reported in current literature and highlights the need for future research to facilitate a clearer understanding of these differences. Plain Language Summary Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease where blood clots remain stuck in the lungs after a previous clotting episode which leads to high blood pressure in the lung arteries. One interesting aspect is that CTEPH affects men and women differently. Women show different symptoms and may have better survival rates than men, especially if they receive surgery to remove the clots. The reasons for these differences are not fully understood. Diagnosing CTEPH is challenging because its symptoms are similar to other heart and lung conditions, which can cause treatment delays. It is important to consider referring patients with possible CTEPH to specialists early for accurate diagnosis and treatment. Developing new treatments and collecting data will help improve care for these patients. Article highlights Epidemiology Higher prevalence and higher odds of developing Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in women. Older age at diagnosis in women. Clinical features Women reported more symptoms at presentation including chest pain, dizziness. Poorer performance on 6 minute walk test and worse World Health Organization (WHO) functional class in women. No significant difference in pulmonary artery pressures between men and women. Treatment Lower frequency of Pulmonary Endarterectomy (PEA) noted in women. Probability of women receiving PEA decreased with advancing age, a trend not seen in men. Higher proportion of women received medical management alone compared with men. Rates of Balloon Pulmonary Angioplasty (BPA) same across both sexes. Outcomes Without treatment, both women and men with CTEPH typically have a life expectancy of less than three years. Most studies suggest no major differences in long term survival after PEA. Women had lower all-cause mortality in non-operated patients. [ABSTRACT FROM AUTHOR]

The IL-6–gp130–STAT3 signaling axis is a major regulator of inflammation. Activating mutations in the gene encoding gp130 and germline gain-of-function mutations in STAT3 (STAT3GOF) are associated with multi-organ autoimmunity, severe morbidity, and adverse prognosis. To dissect crucial cellular subsets and disease biology involved in activated gp130 signaling, the gp130-JAK-STAT3 axis was constitutively activated using a transgene, L-gp130, specifically targeted to T cells. Activating gp130 signaling in T cells in vivo resulted in fatal, early onset, multi-organ autoimmunity in mice that resembled human STAT3GOF disease. Female mice had more rapid disease progression than male mice. On a cellular level, gp130 signaling induced the activation and effector cell differentiation of T cells, promoted the expansion of T helper type 17 (TH17) cells, and impaired the activity of regulatory T cells. Transcriptomic profiling of CD4+ and CD8+ T cells from these mice revealed commonly dysregulated genes and a gene signature that, when applied to human transcriptomic data, improved the segregation of patients with transcriptionally diverse STAT3GOF mutations from healthy controls. The findings demonstrate that increased gp130-STAT3 signaling leads to TH17-driven autoimmunity that phenotypically resembles human STAT3GOF disease. Editor's summary: Gain-of-function mutations in the transcription activator STAT3 cause an autoimmune disease called STAT3GOF syndrome. A challenging feature of this syndrome is the phenotypic heterogeneity of the individual STAT3 mutations. By manipulating an upstream activator instead of STAT3 itself, Baumgartner et al. developed a mouse model that recapitulated more aspects of the disease. Mice with constitutive activation of the cytokine receptor subunit gp130 in T cells developed fatal, multi-organ inflammation with changes in T cell profiles and gene expression that were similar to those in patients with STAT3GOF autoimmunity, suggesting that this model may be useful for investigating the disease and exploring therapeutic options. —Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR]

Background: Asymmetry of abdominal muscles is a potential cause for lowback pain. Most studies assume the rotational strength towards non dominant side to be more but no studies have been conducted to objectively measure the asymmetry. In subjects with spinal deformity like scoliosis which has a rotational component to it, it can be presumed that there could be asymmetry between the oblique force couplehowever this study aims to find out whether this asymmetry exists in normal healthy individuals. By using manual muscle testing for assess- ing oblique muscle strength only gross asymmetry can be detected. Therefore there is a need for more objective measure to detect subtle discrepancies within strength of both sides. Objective: The objective of this study is to measure the strength of external and internal oblique on both side using handheld dynamometer and to compare the strength on both sides. Methodology:30 healthy young individuals in the age group of 18-30 years were selected to participate in the study. All subjects were right hand dominant.External oblique and internal oblique muscle strength was mea- sured in KGs using a Jamartypeofhydraulichandhelddynamometer. Results: There was a significant difference between the strength of external obliques on right and left side with strength on right side being more whereas there was no significant difference between strength of internal oblique between right and left side. [ABSTRACT FROM AUTHOR]

AbstractRepurposing therapeutic agents with existing clinical data is a common strategy for developing radiation countermeasures. IEPA (imidazolyl ethanamide pentandioic acid) is an orally bioavailable small molecule pseudopeptide with myeloprotective properties, a good clinical safety profile, and stable chemical characteristics facilitating stockpiling. Here, we evaluated IEPA’s radiomitigative efficacy in the hematopoietic subsyndrome of acute radiation syndrome (H-ARS) using total-body irradiation (TBI) models in C57BL/6J mice and WAG/RijCmcr rats, applying various posology schemes and introducing syringe feeding of the IEPA formulation in the pudding. Additionally, we assessed IEPA in the delayed effects of acute radiation exposure (DEARE) model after partial-body irradiation (PBI) in WAG/RijCmcr rats. Endpoints included survival, body weight, hematology, and pulmonary parameters, depending on the model. Results from mouse and rat TBI models demonstrated survival improvements with repeated IEPA dosing at 10 mg/kg, with the largest benefits observed in the bi-daily (BID) treatment over the 30-day ARS phase in female rats. Survival across PBI-DEARE subsyndromes was comparable between IEPA and vehicle groups, though IEPA improved pulmonary parameters in female rats during the lung-DEARE phase. Sex-related differences in response to irradiation and IEPA were noted, with females showing a survival advantage. IEPA treatment is compatible with Neulasta® (Pegfilgrastim; PEG-G-CSF); adequately powered studies are needed to confirm the trend toward improved survival over standard care alone. IEPA is a promising development candidate as a medical countermeasure against the effects of acute radiation syndrome. Further confirmatory studies in small and large animal models should validate the robustness and translatability of preliminary rodent data on IEPA’s radiomitigative efficacy. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs), substance use, depressive symptoms, and HIV outcomes in people living with HIV (PLWHIV) have not been comprehensively investigated within a single study., Aim: The aim of this study was to investigate the prevalence and association of ACEs, substance use, depressive symptoms and human immunodeficiency virus (HIV) outcomes in PLWHIV accessing HIV care during the coronavirus disease 2019 (COVID-19) pandemic., Setting: District hospital HIV clinic in South Africa., Methods: A total of 196 PLWHIV completed a socio-demographic and clinical questionnaire; an adapted World Health Organization (WHO) Alcohol, Smoking and Substance Involvement Screening Test; WHO ACEs International Questionnaire, and Patient Health Questionnaire., Results: The most common ACEs were having one or no parent, parental separation or divorce ( n = 131, 66.8%), exposure to collective ( n = 57, 29.1%) and community violence ( n = 55, 28.1%), with 40.3% ( n = 79) experiencing ≥ 3 ACEs. The most commonly used substances were alcohol ( n = 34, 17.3%), tobacco ( n = 33, 16.8%), and cannabis ( n =13, 6.6%). The prevalence of depressive symptoms was 19.4% ( n = 38). Linear regression analyses indicated greater alcohol (adj β = 2.84, p < 0.01), tobacco (adj β = 3.64, p < 0.01) and cannabis use risk scores (adj β = 2.39, p < 0.01) were associated with ≥ 3 ACEs. Logistic regression indicated depressive risk (adjusted odds ratio [OR] = 9.39, 95% confidence interval [CI] 4.78-23.51) was associated with ≥ 3 ACEs., Conclusion: A high prevalence of ACEs, substance use and depressive symptoms exists among PLWHIV, along with an association between cumulative ACEs and both substance use and depressive symptoms., Contribution: Enhanced screening and management services are recommended to address this triple burden in PLWHIV., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2024. The Authors.)

Myocardial infarction with non-obstructive coronary arteries (MINOCA) refers to the occurrence of myocardial infarction symptoms and signs despite angiographic findings showing normal or near-normal coronary arteries. Unlike the more commonly recognized myocardial infarction with coronary artery disease (MICAD), MINOCA often has a better prognosis; however, it is not without risk, as it is associated with increased mortality. We present a 72-year-old female who presented to the hospital with acute chest pain. Following a thorough diagnostic workup, including laboratory tests, left heart catheterization, and cardiac imaging, she was diagnosed with MINOCA. This case report provides a comprehensive review of the pathophysiological mechanisms underlying MINOCA, such as plaque disruption without significant stenosis, microvascular dysfunction, coronary artery spasm, coronary thrombosis or embolism, and spontaneous coronary artery dissection. Additionally, we explore the associated risk factors, highlighting the unconventional risk factors. MINOCA represents a diverse clinical condition with various causes and complex pathophysiology. The variability underscores the necessity for further research to deepen our understanding of this condition. Enhanced knowledge will lead to better diagnostic and treatment strategies, ultimately improving patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Borkowski et al.)

Objective: Previous randomized prospective trials have demonstrated the effectiveness of transcatheter tissue plasminogen activator (tPA) thrombolysis in treating acute limb ischemia (ALI) compared to conventional surgery. These pivotal trials have also highlighted contraindications for these procedures. Given recent advancements in techniques and technology, our aim is to reassess the relevance of these contraindications in contemporary practice., Methods: A retrospective chart analysis was performed utilizing the inpatient medical records of consecutive individuals who underwent tPA treatment for acute limb ischemia (ALI) from September 2016 to April 2022. Inclusion criteria encompassed patients aged 18 and above displaying clinical symptoms and imaging evidence of ALI within 14 days. All patients received tPA with suction thrombectomy following the fast-track thrombolysis protocol. In cases where a persistent thrombus or stenosis was detected, catheter-directed thrombolysis was considered overnight, and patients underwent angiography and reassessment in the operating room subsequently., Results: Patients were classified into two groups based on the STILE trial's established contraindications for endovascular treatment in acute limb ischemia (ALI). If a patient had any of these contraindications, they were placed in the contraindicated group. This resulted in 24 patients (32%) in the contraindicated group and 52 patients (68%) in the non-contraindicated group. No statistically significant demographic variations were observed between these groups. Contraindications in our study included uncontrolled hypertension (12/24, 50%), recent invasive procedures (7/27, 29%), history of cerebrovascular accident (CVA) within 6 months (3/24, 12%), and intracranial malformation/neoplasms (2/24, 8%). Three patients within the non-contraindicated group experienced bleeding complications: two with puncture site bleeds and one with nasal bleeding. In contrast, one patient in the contraindicated group had transient postoperative hematuria. There were no significant differences in bleeding complications observed between the two groups ( p = .771). Additionally, no amputations were observed within our population., Conclusions: In light of our study results and advancements in endovascular therapies, we can now safely and efficiently treat patients who were previously considered contraindicated for such treatments. It is essential to individualize treatments and carefully balance the risks and benefits of endovascular versus open surgical revascularization for these patients. Additionally, we believe that the nearly 30-year-old guidelines for endovascular therapies need to be revisited and updated to align with modern technology., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cardiovascular diseases (CVDs) are the leading cause of death globally. Their prevalence and mortality rates continue to rise. This narrative review explores well-known risk factors for CVDs such as dyslipidemia, hypertension, diabetes, obesity, and smoking, and their prevalence among different racial and ethnic groups. In addition, we expand the discussion to include the impact of socioeconomic status (SES) on cardiovascular outcomes. The data demonstrate that non-Hispanic Black and Hispanic populations not only exhibit higher rates of hypertension, obesity, diabetes, and smoking but also face systemic barriers linked to lower SES, which worsen their cardiovascular outcomes. These barriers include a lack of education, lower income, higher rates of unemployment, and poor living conditions. Beyond these commonly studied factors, these groups also suffer from higher levels of food and housing insecurity and a lack of adequate insurance coverage, all of which contribute to poorer health. Additionally, there is a higher prevalence of mental health disorders, such as depression and anxiety, among these populations. This further compounds the risks and adverse outcomes associated with CVDs. It is essential to conduct further research into how SES and race influence cardiovascular health and to refine risk assessment methods. Concentrating on these aspects would make it possible to create interventions designed to meet the needs of diverse communities and strategies that could potentially reduce morbidity and mortality from CVD across populations. Moreover, this review advocates for integrating comprehensive socioeconomic data into cardiovascular health strategies, which is crucial for developing effective public health initiatives., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Borkowski et al.)