Muhammad Samsoor Zarak

Axicabtagene ciloleucel (axi-cel) is an effective chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) large B-cell lymphoma (LBCL). However, controlling cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) without compromising therapeutic efficacy remains a difficult challenge. In July 2020, our center adopted a toxicity management protocol modified from cohort 4 of the registrational ZUMA-1 trial, with earlier steroid use and incorporation of anakinra. To evaluate this change, we conducted a retrospective analysis of patients receiving axi-cel for R/R LBCL in the third-line setting from January 2018 through April 2023. The outcomes of interest were toxicity incidence/duration, treatment response, CAR-T expansion, and drug/health care utilization. Of the 195 identified patients, the postchange cohort (n = 103) had higher rates of anakinra (22% vs 5%) and steroid use (88% vs 71%) use than the comparator cohort (n = 92), without increases in cumulative steroid dose. Overall CRS and ICANS rates were similar, with directionally lower severe (grade 3+) ICANS rates in the postchange cohort. A significant reduction in CRS and ICANS duration was observed with the new protocol (adjusted estimate, ˗0.93 days [95% confidence interval (CI), ˗1.67 to ˗0.19] and ˗2.49 days [95% CI, ˗4.96 to ˗0.03], respectively). Day 7 CAR-T expansion was lower in the postchange cohort, possibly due to earlier steroid use. However, efficacy outcomes, intensive care unit admission rates, and hospitalization length were similar between the cohorts. This study supports earlier intervention for CAR-T toxicities and establishes anakinra as a safe and effective alternative toxicity management drug to tocilizumab.

Atrial fibrillation (AFib) is a common dysrhythmia and a risk factor for stroke and heart failure. Early detection and treatment are key to avoiding complications (especially in sustained AFib). Here, we systematically review the potential of wearable smartwatches (WSWs) to screen for AFib. A literature search was conducted, and only those validation studies were shortlisted where the screening ability of WSWs was compared with EKG, and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and Kappa statistic were provided. Twelve studies were included with a combined sample size of 1,075,088. Most validation measures of WSWs were above 90% and comparable with KardiaBand by AliveCor (KB), which is an FDA-approved device to detect AFib. WSWs have the potential to reliably and continuously screen for AFib and detect it in a timely manner. The inconclusive results produced by WSWs are a significant problem. Once the inconclusive results are rectified, WSWs may be used for widespread screening of AFib in those people who are at high risk of developing AFib.

The combined toxicity of amlodipine and metformin is a rarely reported phenomenon in the literature. The management varies depending on the clinical status of the patient. We present a case that was managed successfully with the early initiation of hemodialysis.

Background Cardiac sarcomas are rare and aggressive tumors with little known about the demographics, genetics, or treatment outcomes. Objectives The objectives of this study were to characterize the demographics, treatment modality, and survival associated with cardiac sarcomas and evaluate the potential for mutation-directed therapies. Methods All cases from 2000 to 2018 of cardiac sarcoma were extracted from the SEER database. Genomic comparison utilized The Cancer Genome Atlas (TCGA) database, as well as reviews and re-analysis of past applicable genomic studies. Results Cardiac sarcomas occurred most often in White patients, compared with national census data cardiac sarcomas occurred at a significantly higher rate in Asians. The majority of cases were undifferentiated (61.7%) and without distant metastases (71%). Surgery was the most common primary treatment modality and offered survival benefit (HR 0.391 (p = 0.001) that was most pronounced and sustained as compared to patients who received chemotherapy (HR 0.423 (p = 0.001) or radiation (HR 0.826 (p = 0.241) monotherapy. There was no difference in survival when stratified by race or sex; however, younger patients (< 50) had better survival. Genomics data on histologically undifferentiated cardiac sarcomas revealed a significant number were likely poorly differentiated pulmonary intimal sarcomas and angiosarcomas. Conclusions Cardiac sarcoma is a rare disease with surgery continuing to be a cornerstone of therapy followed by traditional chemotherapy. Case studies have indicated the potential for therapies directed to specific genetic aberrations to improve survival for these patients and utilization of next-generation sequencing (NGS) will help improve both classification and these therapies for cardiac sarcoma patients. Graphical abstract

Background: Salivary gland neoplasms are uncommon in both pediatric and adult populations. Mucoepidermoid carcinoma (MEC) is one of the most common salivary gland tumors and usually presents with atypical clinical features. This study sought to evaluate the demographic and clinical factors affecting outcomes in adults and pediatric populations with MEC that could be used to risk stratification for treatment selection and clinical trial enrollment. Methods: Data on 4507 MEC patients were extracted from the Surveillance Epidemiology and End Result (SEER) database (2000–2018). Patients aged ≤ 18 years were classified into the pediatric population, and those older than 18 years were placed in the adult group. Kaplan–Meier survival curves were created to analyze survival probabilities for various independent factors. Results: The pediatric population comprised 3.7% of the entire cohort, with a predominance of females (51.5%), while the adult population constituted 96.3% of the cohort, with a predominance of female patients (52.2%). Caucasians were the predominant race overall (75.3%), while more African Americans were seen in the pediatric group. In tumor size of p < 0.05). Surgical resection was the most common treatment option (53.9%), making up 63.6% of the pediatric and 53.5% of the adult groups. A combination of surgical resection and radiation was used in 29.8% of the entire cohort while a combination of surgical resection, radiation, and chemotherapy made up only 3.2%. The pediatric group had a lower overall mortality rate (5.5%) than the adult group (28.6%). Females had a higher 5-year survival rate in comparison to males (86.5%, and 73.7%, respectively). Surgical resection led to a more prolonged overall survival and 5-year cancer-specific survival (98.4% (C.I, 93.7–99.6) in the pediatric group and 88.8% (C.I, 87.5–90.0) in the adult group), respectively. Metastasis to the lung, bone, brain, and/or liver was found to have significantly lower survival rates. Multivariate analysis demonstrated that adults (hazard ratio [HR] = 7.4), Asian or Pacific Islander (HR = 0.5), male (HR = 0.8), poorly differentiated histology (HR = 3.8), undifferentiated histology (HR = 4.5), regional spread (HR = 2.1), and distant spread (HR = 3.2) were associated with increased mortality (p < 0.05). Conclusions: Mucoepidermoid carcinoma of the salivary glands primarily affects Whites and is more aggressive in adults than in the pediatric population. Even with surgical resection, the overall survival is poor in the adult population as compared to its pediatric counterparts. Advanced age, larger tumor size, male sex, and lymph node invasion are associated with increased mortality.

The objective of the study was to observe the association of villous atrophy with anti-tissue transglutaminase levels in the identified subjects that met our addressed inclusion criteria. A case series study was conducted among 40 patients presenting with dyspepsia along with signs and symptoms of celiac disease at the Bolan Medical Complex Hospital, Quetta over a period of five months from 25/5/17 to 25/10/17. The patients were referred to undergo tissue transglutaminase antibody serum test. The positive ones underwent biopsies to assess pathological entities including villous atrophy, blunting (focal or total), crypts, Intestinal layers and the number of Intraepithelial lymphocytes. The results collected were analyzed by using IBM SPSS version 20 (IBM Corp., Armonk, NY). There was a weak, negative correlation between tTGA and focal villous blunting (r = -0.345, p = 0.029) showing that high levels of tTGA are associated with lower risk of focal villous blunting. Correlation of tTGA and total villous blunting was a weak positive correlation (r = 0.282, p = 0.07) showing that high levels of tTGA are associated with increased risk of total villous blunting. There was a weak, negative correlation between tTGG and focal villous blunting (r = 0.409, p = 0.009) showing that high levels of tTGG are associated with a greater risk of focal villous blunting (p < 0.01) while tTGG and total villous blunting was a weak negative correlation (r = -0.330, p = 0.03) showing that high levels of tTGG are associated with lower risk of total villous blunting. The study concludes by providing evidence of the absence of tissue transglutaminase antibodies in patients with histology-proven celiac disease. It implies that serology tests may be negative in some of the patients with typical chronic symptoms. Therefore, in such cases, histopathology may be conclusive in defining the status of celiac disease.

Background Vitamin D is a vital micronutrient and plays a vital role in defining the bone mineral density of an individual. There are many factors that regulate the levels of vitamin D in our body. The deficiency in vitamin D leads to various complications, with the most important one weakening of bones. Adolescence defines the degree of bone mineral density, which reduces with the growing age in a gradual fashion. Methods The study was a cross-sectional study conducted in Zarghoon town, Quetta, Pakistan. A sample size of 142 was taken from urban and rural areas. Participants were adolescent girls falling in the age bracket of 13-18 years. The circulating level of 25-hydroxy vitamin D was assessed using the ELISA (enzyme-linked immunosorbent assay) technique. Data were analyzed with SPSS Version 20 (IBM Corp.). Results Overall, vitamin D deficiency was 32.4%, and 9.9 % of girls were found to be severely deficient, where the highest proportion belonged to urban samples. The prevalence rate of vitamin D insufficiency was 39.4%. The urban population had a higher prevalence of low levels of vitamin D. In urban respondents, 49.1% had an insufficient vitamin D level, 33.3% had a deficient vitamin D level, and 17.5% had a severely deficient vitamin D level. In rural respondents, 47.1% had normal vitamin D levels, 32.9% had insufficient vitamin D levels, 15.3% were deficient, and 4.7% were severely deficient. Conclusion It was concluded that vitamin D deficiency has a high prevalence among adolescent girls of school age. Additionally, it is more prevalent in urban areas than in rural areas.

Background: COVID-19 cases are exponentially surging around the globe. At the time of study, Pakistan had 7,993 cases and 159 deaths. Out of these positive cases, 432 cases were from Baluchistan. Baluchistan being the South western province of Pakistan; is the basin of the first contact of the virus in Pakistan.Methods: A retrospective study was conducted where data was included from the very first tested case up till 19th April 2020. A total data of 432 patients were acquired and analyzed using SPSS version 20. Results: The proportion of males was 308 (71.3%), belonging to the middle age group 21-30 years (23.4%, n=101). Contrary to popular belief, 60.6% (n=262) of these cases had been infected by local spread, while only 28.9% (n=125) were pilgrims (Zaireen) returning from Iran. Moreover, 146 (33.8%) cases have been reported in just the last five days of acquired data. Quetta and Loralai have displayed the highest COVID-19 attack rate of 14 among all the other districts. Furthermore, the mortality rate was 1.15% and all cases were of age above 40 years.Conclusions: There has been a rapid surge in several cases in Baluchistan, as portrayed herein. While this study depicts a fair picture of the COVID-19 demographic trend, the study has clear indications for the provincial, local spread that have been realized by this data along with a spike in cases in the last few days, which is maybe due to non-compliance to physical distancing rules.

Effective risk stratification is integral to the management of acute coronary syndromes. The Thrombolysis in Myocardial Infarction (TIMI) risk score for ST-segment elevation myocardial infarction (STEMI) is based on eight high-risk parameters that can be used at the bedside for risk stratification of patients presenting with STEMI. This study was designed to determine the frequency of cardiac complications of anterior wall STEMI assessed on TIMI risk score and to compare the rate of cardiac complications according to the TIMI score. An observational case series study was conducted in the Department of Cardiology at Sandeman Provincial Hospital in Quetta, Pakistan. The study duration was six months, from September 22, 2016 to March 23, 2017. A total of 369 patients were selected who had anterior wall myocardial infarction and received thrombolytic therapy, according to the inclusion and exclusion criteria. The TIMI score was calculated by proforma at the time of admission. Patients were divided into three groups: low-risk, moderate-risk, and high-risk TIMI groups. The frequency of complications of anterior wall myocardial infarction at the time of discharge was compared among these groups. The study included 285 male patients (77.2%) and 84 (22.8%) female patients. A total of 174 (47.2%) patients were smokers, 79 (21.4%) were obese, and 93 (25.2%) had hyperlipidemia. Of the 369 patients, 205 (55.6%) were included in the low-risk group, 150 (40.7%) in the moderate-risk group, and 14 (3.8%) in the high-risk group. Post-myocardial infarction arrhythmias were noted in 33 (16.09%) patients in the low-risk group and six (4%) patients in the moderate-risk group. Left ventricular dysfunction was noted in 158 (77.07%) patients in the low-risk group, 78 (52%) patients in the moderate-risk group, and seven (50%) patients in the high-risk group. Cardiogenic shock occurred in seven (3.41%) patients in the low-risk group, 47 (31.33%) patients in the moderate-risk group, and 0 (0%) patient in the high-risk group. Death occurred in seven (3.41%) patients in the low-risk group, 19 (12.66%) patients in the moderate-risk group, and seven (50%) patients in the high-risk group. TIMI scoring provides a better assessment in terms of complications caused by STEMI. The complications include the mechanical and electrophysiology of the heart.