Acetazolamide as an Adjunctive Diuretic Therapy for Patients with Acute Decompensated Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent evidence suggests that acetazolamide may be beneficial as an adjunctive diuretic therapy in patients with acute decompensated heart failure (HF). We aim to pool all the studies conducted until now and provide updated evidence regarding the role of acetazolamide as adjunctive diuretic in patients with acute decompensated HF. METHODS: PubMed/Medline, Cochrane Library, and Scopus were searched from inception until July 2023, for randomized and nonrandomized studies evaluating acetazolamide as add-on diuretic in patients with acute decompensated HF. Data about natriuresis, urine output, decongestion, and the clinical signs of congestion were extracted, pooled, and analyzed. Data were pooled using a random effects model. Results were presented as risk ratios (RRs), odds ratios (ORs), or weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Certainty of evidence was assessed using the grading of recommendation, assessment, development, and evaluation (GRADE) approach. A P value of < 0.05 was considered significant in all cases. RESULTS: A total of 5 studies (n = 684 patients) were included with a median follow-up time of 3 months. Pooled analysis demonstrated significantly increased natriuresis (MD 55.07, 95% CI 35.1-77.04, P < 0.00001; I2 = 54%; moderate certainty), urine output (MD 1.04, 95% CI 0.10-1.97, P = 0.03; I2 = 79%; moderate certainty) and decongestion [odds ratio (OR) 1.62, 95% CI 1.14-2.31, P = 0.007; I2 = 0%; high certainty] in the acetazolamide group, as compared with controls. There was no significant difference in ascites (RR 0.56, 95% CI 0.23-1.36, P = 0.20; I2 = 0%; low certainty), edema (RR 1.02, 95% CI 0.52-2.0, P = 0.95; I2 = 45%; very low certainty), raised jugular venous pressure (JVP) (RR 0.86, 95% CI 0.63-1.17, P = 0.35; I2 = 0%; low certainty), and pulmonary rales (RR 0.82, 95% CI 0.44-1.51, P = 0.52; I2 = 25%; low certainty) between the two groups. CONCLUSIONS: Acetazolamide as an adjunctive diuretic significantly improves global surrogate endpoints for decongestion therapy but not all individual signs and symptoms of volume overload. SYSTEMATIC REVIEW REGISTRATION: This systematic review was prospectively registered on the PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ), registration number CRD498330.

Gender-based differences in primary percutaneous coronary intervention in patients with myocardial infarction from a developing country: A retrospective cohort study.

Introduction: Limited data exists about gender's impact on differences in risk factors and outcomes in our setting. Therefore, we sought to ascertain sex-related differences in patients with AMI in our setting. Material and methods: This retrospective study analyzed data from 247 myocardial infarction patients hospitalized in a tertiary care hospital, between March and October 2020. After hospital admission, all patients underwent ECG, myocardial enzymes, troponin and other biochemical tests followed by primary PCI. Results: Patients were divided in two groups male (n = 153, mean age 55.2 ± 11.0 years) and female (n = 94, mean age 58.4 ± 12.7 years). The prevalence of smoking was higher in males than females (22.8% vs. 3.1%, p < 0.01) and so was history of three-vessel disease (3VD; 18.9% vs. 7.4%, p = 0.013). History of myocardial infarction was lower in females than males (13.8% vs. 24.8%, p = 0.03) however the age did not vary significantly between the two groups (p = 0.21). Serum creatinine (sCr) levels (1.0 ± 0.77 µmol/L vs. 1.2 ± 0.73 µmol/L, p = 0.28) and body mass index (28.4 ± 5.3 vs 27.4 ± 4.8, p = 0.45) were lower in females as compared to males, however not statistically significant. The incidence of major adverse events, severe arrhythmia and in-hospital outcomes showed no significant difference (p > 0.05) between the two groups. Post-op TIMI score and average length of hospital stay were not statistically different either (3.29 ± 2.9 vs. 2.6 ± 1.7, p = 0.726). Conclusion: Our study shows that females have a comparable age of onset of major cardiovascular events as that of males. Post-PCI clinical outcomes and in-hospital stay had no significant differences between the two groups.

The clinical course, biochemical markers, and clinical outcomes of COVID-19 positive patients from the third wave in Pakistan: A retrospective cohort study.

Background: Third wave of COVID-19 has affected several countries. Case fatality rates from first and second waves are expected to be surpassed by the current wave due to various variant transmissions. This study was aimed to compare and contrast the significant clinical markers between survivors and non-survivors during the third wave of COVID-19 to assess severity and prognosis. Methods: It includes all the patients who were diagnosed with COVID-19 polymerase chain reaction (PCR) during the third wave, and were monitored for their disease course and outcomes. A total of 209 patients were included in the analysis via non-probability consecutive sampling method. Results: The median age was higher in non-surviving patients (p = 0.010). Majority of deaths occurred in intensive care patients (p < 0.001) and those with diabetes (p = 0.032) and hypertension (p = 0.003). Fever was the most predominant symptom in all patients (78.9%), dyspnea was common among expired individuals (p = 0.043) while recovered patients were more likely to be asymptomatic (p = 0.044). Gastrointestinal symptoms were not found marked during this wave. Being on ventilator has higher mortality (p < 0.001). Predominant radiological findings were interstitial patches or infiltrate (43.7%). Multivariable analysis showed hypertension (p = 0.042), BiPAP/CPAP (p < 0.001), being on ventilator (p = 0.004), and ARDS (p < 0.001) was associated with poor survival while patchy interstitial infiltrates on X-ray had good survival probability (p = 0.032). On Kaplan-Meier survival analysis, hypertension (p = 0.003), BiPAP/CPAP (p = 0.008), ventilator (p = 0.025), ICU stay (p = 0.001), high-grade fever (p = 0.001), and ARDS (p < 0.001) had reduced cumulative survival. Conclusion: Certain biochemical markers were more predictive of disease severity in the third-wave than the preceding waves.

Psychological Distress, Anxiety, Family Violence, Suicidality, and Wellbeing in Pakistan During the COVID-19 Lockdown: A Cross-Sectional Study.

Background and Objectives: The purpose of this study was to draw the attention toward the implications of COVID-19 and the related restrictions imposed worldwide especially in Pakistan. The primary objective was to highlight the levels of psychological distress, anxiety, family violence, suicidality, and well-being due to COVID-19 and the secondary objective was to associate it to social demographic factors. Materials and Methods: It is designed as a cross-sectional study by employing an online questionnaire in the English language and obtaining responses using a snowball sampling technique. We used three validated measures including Kessler Psychological Distress Scale (K10), Generalized Anxiety Disorder (GAD-7) index and World Health Organization Well-Being Index (WHO-5). Results: A sample of 420 participants was recruited from across Pakistan, with most participants were females (79%), students (89.8%) and belonging to Punjab (54%). Nearly one-fourth of the participants (23.8%) scored above the minimum value set for moderate or high psychological distress (K10 > 12). There was a higher prevalence of distress among females and resident of province Punjab. The majority of individuals reported that they were living with their family (94.5%) and more than half (52.6%) were neutral regarding their satisfaction with their living conditions. 40.5% believed that the lockdown has had a negative impact on their mental health. 31.4% have reported that they themselves have experienced abuse from a family member. 48.6% scored high on the GAD-7 scale and low wellbeing score was found among 80.2%. Students were found to be more vulnerable to mental illness and anxiety. Conclusion: With the lockdown restrictions, psychosocial distress has become prevalent in Pakistan.

COVID-19-associated Coagulopathy and Thromboembolism: Determination of Their Patterns and Risk Factors as Predictors of Mortality Among Severe COVID-19 Patients.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is associated with Coagulopathy (CAC) and Venous Thromboembolism (VTE). These are well-reported complications of COVID-19 infection. Earlier publications have shown that CAC and thromboembolism are predictors of mortality among COVID-19 patients with severe disease. MATERIALS AND METHODS: A prospective study was conducted in the Intensive Care Unit (ICU) where all confirmed COVID-19 patients were enrolled and followed until death or ICU discharge. CAC, VTE, along with all comorbidities, were recorded. Predictors of mortality were determined by univariate and multivariate regression. RESULTS: Among 261 patients with COVID-19, 48.3% survived and 51.7% died. CAC was present in 53.2% and 76.3% of the survivors and non-survivors, respectively (p<0.001); 89 patients (31.4%) had VTE (p=0.36) and 11 patients (4.2%) had arterial thrombosis (p=0.76) among survivors and nonsurvivors. Age between 71-80 years (p=0.009), male gender (p=0.045), CAC (p<0.001), comorbidities like chronic kidney disease (CKD, p=0.013), chronic obstructive pulmonary disease (COPD, p=0.001) and asthma (p=0.046), were significant predictors of mortality. CONCLUSION: A severe complication of COVID-19 is CAC, such as sepsis-induced coagulopathy, overt disseminated-coagulopathy and VTE. Old age, various comorbidities (e.g., COPD, CKD, or asthma), CAC, VTE (pulmonary embolism) and coagulation parameters with critical severity score (D-dimers, platelets, prothrombin time) and the SOFA (Sequential Organ Failure Assessment) score were significant predictors of mortality among COVID-19 patients.

Role of C- reactive proteins and liver function tests in assessing the severity of dengue fever.

OBJECTIVE: To determine whether C-reactive protein and liver function tests can serve as severity markers for dengue fever. METHODS: The cross-sectional study was conducted in 2015-16 in Karachi and comprised patients with dengue fever visiting a tertiary care hospital. World Health Organisation classifications 1997 and 2009 were used to categorise patients according to clinical signs and symptoms. Receiver Operating Characteristics curve was used to determine discriminative ability and optimum cut-off value of biochemical markers. Comparisons were done through one-way analysis of variance using SPSS 17. RESULTS: Of the 218 patients, 133(61%) were males and 85(39%) were females. The overall mean age was 35.07±15.96 years. Levels of C-reactive protein and total bilirubin were significantly higher for dengue haemorrhagic fever compared to dengue fever; dengue shock syndrome compared to dengue fever; dengue shock syndrome compared to dengue haemorrhagic fever; and dengue shock syndrome compared to dengue fever / dengue haemorrhagic fever (p<0.05 each). Levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly higher for dengue shock syndrome compared to dengue fever; dengue shock syndrome compared to dengue haemorrhagic fever; and dengue shock syndrome compared to dengue fever / dengue haemorrhagic fever (p<0.05 each). Levels of C-reactive protein, total bilirubin, alanine aminotransferase and alkaline phosphatise in patients with severe dengue were significantly higher compared to non-severe dengue. CONCLUSIONS: C-reactive protein and liver function tests were found to be effective biochemical markers in assessing dengue fever severity.

Frequency of Hyperthermia in Acute Ischemic Stroke Patients Visiting a Tertiary Care Hospital.

OBJECTIVE: To determine the frequency of hyperthermia in acute ischemic stroke patients visiting a tertiary care hospital in a developing country. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: Medical Wards of Civil Hospital, Karachi, from January to June 2013. METHODOLOGY: Patients aged ≥18 years of either gender with acute ischemic stroke presenting within 24 hours of onset of symptoms were included. Written informed consent was obtained from all participants as well as approval of ethical review committee of the institute. Axillary temperature by mercury thermometer was monitored at the time of admission and after every 6 hours for 3 days. The data was analyzed using SPSS version 17.0 (SPSS Inc., IL, Chicago, USA). RESULTS: Atotal of 106 patients of ischemic stroke were included. The mean age of enrolled participants was 60.1 ±9.5 years. Among these, 61 (57.5%) were males and 45 (42.5%) females. Among all patients, 51.9% presented with loss of consciousness, 30.2% with slurred speech, 77.4% with limb weakness, and 9.4% with decrease vision. Atotal of 17 (16%) patients with ischemic stroke developed hyperthermia. When the prevalence of hyperthermia was stratified according to age, among patients of < 60 years of age, 26% developed hyperthermia compared to 7.1% in patients of ≥60 years of age (p=0.008). On gender stratification, among male patients, 14.8% developed hyperthermia compared to 17.8% in female patients (p=0.43). CONCLUSION: It is concluded from this study that the frequency of hyperthermia in ischemic stroke was 16% and it should be looked for as it has significant impact on the outcome. The hyperthermia was significantly more common in younger adults as compared to older adults. However, gender had no influence on the prevalence rate of hyperthermia.

The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies.

Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objective of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 µM compared to that of the standard drug, prednisolone <1.5 µM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 µM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 µM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 µg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P<0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 µM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases.

End Stage Renal Disease: Seroprevalence of Hepatitises B and C along with Associated Aetiology and Risk Factors in Children.

Background. End Stage Renal Disease (ESRD) normally requires dialysis or transplantation for survival. Since ESRD patients are on long term dialysis, infections such as Hepatitis B (HBV) and Hepatitis C (HCV) are commonly reported. Methods. This was a retrospective study carried out at a government hospital during a 12-month period from January 2013 to December 2013. The data was collected using a predesigned pro forma to note the etiology, gender, age, and HBsAg and anti-HCV test result of each patient. Results. 444 children suffering from ESRD were included in our analysis. The mean age of sample was 12.7 ± 4.1 years. Sixty percent (n = 262) of the children were boys. The most common etiology of ESRD was kidney stones (n = 44, 29.3%). HBV was positive in 11 children (2.5%) while HCV was positive in 13 (2.9%). Conclusion. This study asserts the need for carrying out further work to confirm these findings and expand our recommendations. It is imperative to reliably determine the burden of HBV and HCV disease and to determine the aetiology of their spread especially in children with ESRD.

Synthesis of diethyl 4-substituted-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates as a new series of inhibitors against yeast α-glucosidase.

1,4-Dihydropyridine-3,5-dicarboxylate derivatives (1-25) were synthesized in high yields via Hantzsch reaction and evaluated for their α-glucosidase inhibitory activity. Compounds 1, 2, 6-8, 11, 13-15, and 23-25 showed a potent inhibitory activity against yeast α-glucosidase with IC50 values in the range of 35.0-273.7 µM, when compared with the standard drug acarbose (IC50 = 937 ± 1.60 µM). Their structures were characterized by different spectroscopic techniques. The kinetics, selectivity, and toxicity studies on these compounds were also carried out. The kinetic studies on most active compounds 14 and 25 determined their modes of inhibition and dissociation constants Ki. Compound 14 was found to be a non-competitive inhibitor with Ki = 25.0 ± 0.06, while compound 25 was identified as a competitive inhibitor with Ki = 66.0 ± 0.07 µM.

Variation in admission rates of acute coronary syndrome patients in coronary care unit according to different seasons.

OBJECTIVE: Environmental stresses, especially extreme cold and hot weathers, have tendency to have more admissions for acute coronary syndromes. Due to scarcity of local data, we studied the variation in patient admission rates with acute coronary syndrome according to different seasons. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Coronary Care Unit, Civil Hospital and Pakistan Steel Hospital, Karachi, from January 2011 to December 2011. METHODOLOGY: The study group comprised consecutive patients with acute coronary syndrome (unstable angina, Non ST-Elevation Myocardial Infarction (NSTEMI), ST-Elevation Myocardial Infarction (STEMI) admitted to the coronary care unit. Patients with stable angina and valvular heart disease were excluded. Data was analyzed for admission according to different seasons, (winter, spring, summer and autumn). RESULTS: The mean age of the 428 cases was 48.5 ± 10.4 years (range 27 to 73 years). Among the study group, 261 (61%) and 167 (39%) cases were male and female respectively. ST-elevation myocardial infarction, non ST-elevation myocardial infarction and unstable angina were present in 206 (48%), 128 (30%) and 94 (22%) respectively. Among the 428 patients, 184 (43%) cases had hypertension, 133 (31%) cases were smokers, 103 (24%) cases had dyslipidemia and diabetes mellitus and 08 (2%) cases had history of premature coronary artery disease. The number of patients admissions with acute coronary syndrome tended to change with sudden change in season. It increased in Winter 158 (36.9%) and Summer 130 (30.3%) in comparison to Spring 80 (18.69%) and Autumn 60 (14.02%) season. CONCLUSION: It was found variation in admission rates of acute coronary syndrome patients according to different seasons. The number of admissions not only increased in the cold season (winter) but also in hot season (summer) with sudden changes in temperature.

Synthesis and Biological Potential Assessment of 2-Substituted Quinazolin-4(3H)-ones as Inhibitors of Phosphodiesterase-I and Carbonic Anhydrase-II.

A library of twenty-five derivatives of 2-substituted quinazolin-4(3H)-ones 1-25 was synthesized and evaluated against phosphodiesterase-I (PDE) and carbonic anhydrase-II (CA). Compounds 17 (IC50 = 210.7 ± 2.62 µM), 16 (IC50 = 301.6 ± 1.18 µM), and 13 (IC50 = 458.13 ± 3.60 µM), selectively exhibited PDE inhibition while compounds 22 (IC50 = 61.33 ± 2.38 µM), 1 (IC50 = 108.30 ± 0.93 µM), and 21 (IC50 = 191.93 ± 2.72 µM), discriminatingly exhibited CA inhibition as compared to standards EDTA (IC50 = 277.69 ± 2.52 µM) and acetazolamide (IC50 = 0.12 ± 0.03 µM), for PDE and CA inhibitions, respectively. However, compound 15 was found to be active against both enzymes with the IC50 values 344.33 ± 4.32 µM and 20.94 ± 0.58 µM, for PDE and CA inhibitions, respectively. Remaining compounds were found to be inactive against both the enzymes. Structure-activity relationship studies are discussed herein.

Frequency and risk factors associated with hypomagnesaemia in hypokalemic type-2 diabetic patients.

OBJECTIVE: To determine the frequency and factors associated with hypomagnesaemia in hypokalemic type-2 diabetic patients presenting at Civil Hospital, Karachi. STUDY DESIGN: A cross-sectional study. PLACE AND DURATION OF STUDY: Department of Medicine and Diabetic Clinic of Civil Hospital and Dow Medical College, Karachi, from November 2010 to May 2011. METHODOLOGY: A total of 358 adult type-2 diabetics with hypokalemia were selected for this study. With aseptic measures, venous blood was collected for serum magnesium, potassium, HDLc, LDLc Triglyceride (TGs) and glycosylated hemoglobin (HbA1c) from each subject after an overnight fasting and was analyzed on Roche Hitachi 820 Photo Spectrometry. The data was analyzed on SPSS version 17 to determine the factors associated with hypomagnesaemia like duration of diabetes, Body Mass Index (BMI), diabetic nephropathy, HDLc, LDLc Triglyceride (TGs) and glycosylated hemoglobin (HbA1c) level. RESULTS: Mean age of study population was 55.62 ± 9.9 years. Most of them (n=228, 63.7%) were males. Out of the 358 subjects, 198 (55.3%) had hypomagnesaemia. There was significant association between hypomagnesaemia with duration of diabetes, Body Mass Index (BMI), diabetic nephropathy, HDLc, LDLc Triglyceride (TGs) and glycosylated hemoglobin (HbA1c) level. CONCLUSION: Hypomagnesaemia is very common in type-2 diabetic hypokalemic patients. Therefore, it should be routinely sought by the clinicians. Early recognition and subsequent treatment of hypomagnesaemia may help in better glycemic control, may delay the chronic complications and decrease the mortality in diabetic hypokalemic patients.

Frequency of hyper-homocysteinaemia in ischaemic stroke patients of Karachi.

OBJECTIVE: To find out the frequency of hyper-homocysteinaemia in ischaemic stroke patients and its relation with other risk factors. METHODS: The cross-sectional study based on convenience sampling was conducted at the Civil Hospital, Karachi, from May to July 2012. It comprised ischaemic stroke patients selected from the Out Patient Department and Emergency Department. An overnight 8-hour fasting venous blood sample (4 ml in ethylenediamminetetraacetate) was drawn for analysis. Rest of the data was collected through a structured proforma and was analysed using SPSS 17.0. RESULTS: The mean age of the 96 patients in the study was 64.9 ± 10.9 years (range: 40-85). Overall, 56 (58.3%) cases had hyper-homocysteinemia.The frequency was significantly high in the age 60-79 age group (p < 0.007). CONCLUSION: Hyper-homocysteinaemia, a modifiable risk factor, is associated with a high number of ischaemic stroke patients. Hence, steps should be taken to minimise this risk factor by screening and early intervention.

Bilobed gallbladder.

We report a rare case of duplication anomaly of gallbladder in a female aged 17 years, who presented with right hypochondrial pain for 3 months. Ultrasound findings suggested multiple stones in gallbladder and per-operatively she was found to have bilobed gallbladder. This case emphasizes the need for complete removal of both gallbladders during initial surgery, as a failure of this may result in recurrence of symptoms and stones and a need for re-exploration.

Desmoid tumour of lower abdomen.

A desmoid tumour is slow growing fibromatosis with aggressive infiltration of adjacent tissue and extremely unusual systemic metastases. We report on a female patient aged 25 years who had a mass in lower abdomen for 2 years. There was no previous history of any surgical intervention. Preoperative evaluation included ultrasound and computed tomography. Patient underwent primary resection with wide margins. Histology revealed a desmoid tumour.