Efficacy of Allopurinol in Improving Endothelial Dysfunction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear. AIMS: We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients. CONCLUSION: While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation.

Empathy levels among undergraduate medical students in Karachi, Pakistan: a cross-sectional study.

Empathy is a concept native to the field of medicine. However, over the course of medical school, empathy levels are expected to decline. The aim of this study was to assess the empathy levels among medical students in relation to their year of study and specialties of choice in the future. Materials and methods: A cross-sectional study was conducted to assess empathy levels among students from medical colleges in Karachi, Pakistan, using an online survey. The total duration of the study was 2 months. The authors analyzed the data using SPSS version 20. Results: A total of 463 undergraduate medical students participated in this survey. The overall mean empathy score was 101.9±16.3 with 104.6±14.1 for females, which was significantly higher than the male participants. The highest empathy levels were demonstrated in fourth-year medical students with a mean empathy score of 104.1±16.3, whereas, the lowest empathy levels were found in second-year medical students with a mean empathy score of 99.8±9.4. Study participants considering emergency medicine, neurology, obstetrics/gynecology, and oncology as their specialty of choice demonstrated the highest empathy levels followed by pediatrics and internal medicine. Conclusion: On average, there was a female preponderance in empathy levels among undergraduate medical students. Empathy levels among fourth-year students involved in clinical practice were greater as compared to students in their initial years of study. Further investigations are required to validate the findings of this study.

Knowledge, attitude, and perceptions about cancer genetic testing in clinical practice in Karachi, Pakistan.

Healthcare professionals (HCP) play an important role in the practical application of genetic screening tests but often feel inadequately prepared for cancer genetic testing (CGT) in clinical care. As the complexity of gene-related malignancies increases, it demands HCPs' preparedness to cater to patients' needs. Therefore, the aim of our study is to assess the knowledge, attitude, and practices of HCPs in Pakistan regarding the application of cancer genetics. Our cross-sectional survey was conducted from April 2022 to June 2022 amongst HCPs at a private and a governmental institution in Karachi, Pakistan. Non-probability random convenience sampling was used to select the population; however. non-clinical HCPs, as well as Interns, were excluded from our study. A total of 210 HCPs, 56.7% (119) bearing an experience of over 5 years of clinical experience, were included in this study. Most respondents from both hospitals deemed their knowledge inadequate, with only 2% (2) and 1.8% (2) being extremely knowledgeable, respectively. 68.6% (144) HCPs displayed a positive attitude towards CGT, with 55.2% (116) participants perceiving CGT in a positive light. As compared to the private sector, significantly more HCPs in the public sector dedicated ≥ 5 h/week for CME (P = 0.006), and were better prepared to counsel patients (P = 0.021) and interpret results concerning CGT (P = 0.020). Additionally, screening tests for specific cancer types were popularly considered a worthwhile avenue of investment to improve the current state of CGT in our healthcare system [47.6% (N = 100)]. Demonstrating a lack of knowledge among Pakistani doctors, our results call upon the need for additional training concerning CGT in both the public and private sectors alike. Understanding specific gaps in knowledge may further help enhance post-graduate training programs and eventually lead to effective incorporation of CGT into our healthcare setting.

Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by multilineage cytopenia in the absence of mixed donor chimerism (<95% donor), relapse, or severe graft-versus-host disease (GVHD). We present a systemic review and meta-analysis aimed at assessing the outcomes with CD34-selected stem cell boost (SCB) for PGF in adult allo-HSCT recipients. We screened a total of 1753 records identified from 4 databases (PubMed, Embase, Cochrane, and ClinicalTrials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "hematological malignancies," "hematopoietic stem cell transplantation," "CD34 antigen(s)," "graft failure," and "poor graft function," from the date of inception to January 2021. After excluding review, duplicate, and nonrelevant articles, we included 7 studies reporting outcomes following administration of CD34-selected SCB for PGF after allo-HSCT, including hematologic complete response (CR) and overall response rate (ORR), GVHD, and overall survival (OS). Quality evaluation was done using the National Institutes of Health quality assessment tool. Pooled analysis was done using the R 'meta' package, and proportions with 95% confidence intervals (CIs) were computed. The inter-study variance was calculated using the Der Simonian-Laird estimator. We identified 209 patients who received CD34-selected SCB for PGF after allo-HSCT. The median age was 49 years (range, 18 to 69 years), and 61% were men. Primary graft sources included peripheral blood stem cells (72%) and bone marrow (28%). Donor types were matched sibling (37%), matched unrelated (36%), mismatched unrelated (22%), and haploidentical donors (5%). The median time from allo-HSCT to SCB was 138 days (range, 113 to 450 days). The median SCB dose was 3.45 × 106 CD34 cells/kg (range, 3.1 to 4.9 × 106 cells/kg). CR and ORR were 72% (95% CI, 63% to 79%; I2 = 26%) and 80% (95% CI, 74% to 85%; I2 = 0%), respectively. After a median follow-up of 42 months (range, 30 to 77 months), the actuarial survival rate was 54% (95% CI, 47% to 61%; I2 = 0%). OS ranged from 80% at 1 year to 40% at 9 years. The incidences of acute and chronic GVHD after SCB were 17% (95% CI, 13% to 23%; I2 = 0%) and 18% (95% CI, 8% to 34%; I2 = 76%), respectively. Nonrelapse mortality was reported in 42 patients, with a pooled rate of 27% (95% CI, 17% to 40; I2 = 59%), and death due to relapse was reported in 25 patients, with a pooled rate of 17% (95% CI, 11% to 23%; I2 = 0%). Our data show that CD34-selected SCB improves outcomes after PGF post allo-HSCT with an acceptable toxicity profile. The literature lacks high-quality randomized evidence, and there remains an unmet need for prospective studies to address the optimal dosing and manipulation of SCB. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Protective role of peroxiredoxin-4 in heart failure.

Recently, we have read with great interest the article published by Ibarrola et al. (Clin. Sci. (Lond.) (2018) 132, 1471-1485), which used proteomics and immunodetection methods to show that Galectin-3 (Gal-3) down-regulated the antioxidant peroxiredoxin-4 (Prx-4) in cardiac fibroblasts. Authors concluded that 'antioxidant activity of Prx-4 had been identified as a protein down-regulated by Gal-3. Moreover, Gal-3 induced a decrease in total antioxidant capacity which resulted in a consequent increase in peroxide levels and oxidative stress markers in cardiac fibroblasts.' We would like to point out some results stated in the article that need further investigation and more detailed discussion to clarify certain factors involved in the protective role of Prx-4 in heart failure.

Frequency of Hypocalcaemia following Total Thyroidectomy.

BACKGROUND & OBJECTIVE: Patients who undergo Total thyroidectomy are at higher risk for postoperative hypocalcaemia, which can lead to significant short and long term morbidity. The aim of this study was to determine the frequency of postoperative hypocalcaemia undergoing Total thyroidectomy. METHODS: A total of 854 patients who underwent Total thyroidectomy and completion thyroidectomy between January 2003 to December 2016 at Endocrine Surgical unit, Jinnah Postgraduate Medical Centre, Karachi, were included in this retrospective study. Data were obtained for demographics, preoperative diagnosis, postoperative calcium levels, extent of surgery and final surgical pathology. RESULTS: A total of 854 patients underwent Total thyroidectomy. Of these 87.58% (n=748) were malignant and 12.41% (n=106) were benign. Among the malignant and benign patients, 47.3% (n=404) underwent Total thyroidectomy and 52.69% (n=450) underwent completion thyroidectomy. Overall incidence of transient hypocalcaemia was 7% (n=60) and that of permanent hypocalcaemia was 0.11% (n= 1). CONCLUSION: Hypocalcaemia is one of major concern following total- thyroidectomy. Meticulous surgical techniques, identification and preservation of vascularity of parathyroid glands are essential in preventing postoperative hypocalcaemia following total thyroidectomy.