Long-Term Cardiovascular Diseases of Heatstroke: A Delayed Pathophysiology Outcome.

Heatstroke, defined as an elevated core body temperature above 40°C accompanied by altered mental status (e.g., confusion, disorientation, seizure and coma), is the most severe and life-threatening condition in the spectrum of heat-related illnesses. Heatstroke patients may present with multi-organ dysfunction, but with rapid cooling and organ failure management, a full recovery often occurs within weeks. Long-term impairment is rare, with neurological impairment occurring most frequently. Despite an abundance of research on the persistent neurological and hepatic impairments, our knowledge of the long-term cardiovascular events in patients with heatstroke history is poor. We wondered whether heatstroke leads to cardiovascular diseases long after full recovery. Using Pubmed, Web of Science and Scopus, we gathered cohort studies looking at cardiovascular disease incidence or mortality as an outcome, including heatstroke animal studies. Based on the available literature, we found that a history of heatstroke is associated with an increased risk of cardiovascular diseases, including ischemic heart disease, heart failure and atrial fibrillation. Delayed metabolic disturbances occurring in exertional heatstroke mice are linked to the formation of atherosclerosis and the development of heart failure. These processes provide potential pathophysiological pathways leading to ischemic heart disease and heart failure in heatstroke patients. Our findings may massively impact our understanding of heatstroke recovery and the follow up of heatstroke patients. Therefore larger, more adequately powered cohort studies with cardiovascular disease as an outcome, in tandem with animal studies examining the underlying pathophysiology, are required to confirm or reject these findings and answer the proposed questions

Role of Smoking in the Pathogenesis of Multiple Sclerosis: A Review Article.

Multiple sclerosis (MS) is a complex and unpredictable neurological condition. It is the most commonly seen autoimmune disorder. The incidence of disease and its prevalence are growing worldwide. Early identification of the disease and accurate diagnosis is important to prevent further complications and disability. The etiology remains unclear, and it is believed that complex gene-environment interactions play an essential role. Genetic predisposition only describes a portion of the disease risk, whereas lifestyle and environmental factors are significant contributors. Smoking was identified as an important risk factor for MS. The main objectives of this review were to examine the underlying mechanisms of immune dysregulation in the development of MS, explore the association between smoking and MS, and identify other genetic and environmental factors that alter the risk of developing the disease. We searched PubMed for articles relevant to the study topic published between 2000 and 2020 using the search terms "multiple sclerosis," "cigarette smoking," "risk factors," and, "epigenetics." Studies reveal a marked association between smoking and the risk of MS. Unlike genetic risk factors, many lifestyles and environmental factors can be adjusted, with potential for prevention, particularly for people at the highest risk, such as families of individuals with MS

Outcomes with chimeric antigen receptor t-cell therapy in relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis

BackgroundWe conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).MethodsWe performed a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.ResultsWe analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively.ConclusionCAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion

Hearing loss: an unusual presentation of neurobrucellosis: a case report

Abstract Introduction Brucellosis is a zoonotic disease, caused by a Gram-negative coccobacillus of Brucella genus, transmitted to humans by animals, especially cattle. It rarely involves the nervous system (neurobrucellosis); only a few cases present with hearing loss. We report a case of neurobrucellosis, that presented with bilateral sensorineural hearing loss and mild to moderate persistent headache. To the best of our knowledge, this is the first well-documented case from Nepal. Case presentation The patient was a 40-year-old Asian male shepherd from the western mountainous region of Nepal who came to the emergency department of Manipal Teaching Hospital, Pokhara in May, 2018 and did a follow-up for 6 months. He presented with high-grade fever, profuse sweating, headache, myalgia, and bilateral sensorineural hearing loss. His history of consuming raw milk of cattle, symptoms including persistent mild to moderate headache, bilateral hearing loss, and serological findings were suggestive of neurobrucellosis. Following treatment, the symptoms improved, including the complete recovery of hearing loss. Conclusion Hearing loss may be the manifestation of neurobrucellosis. Physicians should know about such presentations in brucella endemic areas

Table_1_Outcomes with mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in adults: A systematic review and meta-analysis.docx

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various hematologic disorders. Alternative donor strategies such as mismatched unrelated donors (MMUD) offer the option of HSCT to patients lacking a human leukocyte antigen (HLA)-matched donor. We conducted a systematic review and meta-analysis to evaluate outcomes after MMUD-HSCT.MethodsA literature search was performed on PubMed, Cochrane Library, and ClinicalTrials.gov from the inception date through April 6, 2022. After screening 2477 manuscripts, 19 studies were included. Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.ResultsA total of 3336 patients from 19 studies were included. The median age was 52.1 years, and 53% of recipients were males. The graft source was bone marrow in 19% and peripheral blood stem cells in 81% of recipients. The median time to transplant from hematologic diagnosis was 10 (1-247) months. Hematologic diagnoses included myeloid (82.9%), lymphoid (41.1%), and other disorders (3%). The reduced intensity and myeloablative conditioning were used in 65.6% and 32% of recipients, respectively. In-vivo T-cell depletion was performed in 56.7% of the patients. Most patients had one (87.9%) or two (11.4%) antigen HLA-mismatch. The pooled 1-year overall survival (OS) was 63.9% (95% CI 0.57-0.71, n=1426/2706), and the pooled 3-year OS was 42.1% (95% CI 0.34.2-0.50, n=907/2355). The pooled progression-free survival was 46.6% (95% CI 0.39-0.55, n=1295/3253) after a median follow-up of 1.8 (range 1-6) years. The pooled relapse rate was 26.8% (95% CI 0.22-0.32, n=972/3253) after a median follow-up of 2.25 (1-3) years. The pooled incidence of acute (grade II-IV) graft-versus-host disease (GVHD) and chronic GVHD was 36.4% (95% CI 0.31-0.42, n=1131/3030) and 41.2% (95% CI 0.35-0.48, n=1337/3228), respectively. The pooled non-relapse mortality was 22.6% (95% CI 0.17-0.29, n=888/3196) after a median follow-up of 2.6 (1-5) years.ConclusionMMUD-HSCT has demonstrated favorable outcomes with an acceptable toxicity profile. It represents a promising option in patients lacking an HLA-matched or haploidentical donor and may expand HSCT access to underrepresented racial and ethnic populations.</p