Bangladesh Medical Research Council Bulletin (Vol. 51, No. 03, 2025)

Women are unique having unique health issues. They have female exclusive diseases and diseases that are common for both sexes but with different implications. Over the past five decades, the understanding of women’s health has expanded from a narrow focus on reproduction to a holistic appreciation of women’s health across the life course. Bangladesh, like many low- and middle-income countries, has made great progress in saving mothers’ lives, but women’s other health needs remain largely neglected. The Global Burden of Disease 2021 reveals that women in Bangladesh now live longer but spend more years in poor health, largely due to unaddressed gynaecological and chronic conditions.1 ¹

The Bangladesh Paradox

Bangladesh exemplifies both progress and neglect in women’s health. The country’s success in reducing the maternal mortality ratio from 322 to 196 per 100,000 live births between 2001 and 2016 reflects decades of targeted investment ^2-4 Over the past three decades, the rate of disability-adjusted life years (DALYs) due to maternal disorders among women aged 15–49 has decreased (1508 Vs 449 per 100,000 female population) 3.4 times, while the reduction for benign gynecological disorders in the same age group has been 1.5 times (1034 Vs 676 per 100,000 female population).

Female-exclusive disease burden: a silent epidemic

The 2021 GBD data show that female-exclusive diseases account for 831,217 DALYs in Bangladesh—nearly seven times higher than the 118,866 DALYs from male-exclusive diseases. ^13,14 Similar to the global and LMICs scenario (15.8 million and 12.5 million), in Bangladesh, other gynecological conditions account for the highest (270,287) disability-adjusted life years (DALYs), which is almost one-third of the total DALYs due to female-exclusive diseases (Figure 1). These are not fatal illnesses— but they erode quality of life, productivity and dignity. ¹ Cervical cancer alone claims 193,425 years of life lost (YLLs)—more than triple the male YLLs from prostate cancer (61,060) ¹

Beyond reproduction: chronic conditions shaping women’s lives

Among the top 20 causes of disease burden, Bangladeshi women experience disproportionate DALYs than males from low-back pain, depressive disorders, diabetes, diarrhoeal diseases, and musculoskeletal conditions, patterns similar to global trends but with far higher intensity.

The female-to-male DALY-rate ratio for these conditions increased from 1·4 to 1·7 per 100 000 population over the last 30 years. These numbers translate into daily suffering of women, which is seldom captured in routine reporting or addressed in policy frameworks.

Structural and systemic gaps

Despite Bangladesh’s commitment to universal health coverage, the health system remains skewed toward obstetric emergencies, neglecting non-maternal women’s health. In Bangladesh, where about half of the 171 million population are women, one female doctor serves 7,644 women compared with one male doctor for every 4,573 men (5). Tertiary hospitals in Bangladesh serve both sexes or focus on children, leaving women’s specific health needs largely overlooked. There have been multiple structured registers (antenatal care register, postnatal care register, emergency obstetric and newborn care register, delivery register, OT register) allocated to record information of obstetric patients in different service delivery points of public health facilities, whereas it is nonexistent of gynaecological services.

Keywords:Women’s health, Gynecological disorders, Sex-specific disease burden, Disability-adjusted life years (DALYs), Chronic conditions, Bangladesh

Abstract

Background:Coronary Artery Disease (CAD) is a leading cause of morbidity and mortality globally, with its rising prevalence, especially in South Asia. Dyslipidemia is a well-established risk factor for CAD. Recent research has focused on novel lipid indices like atherogenic Index (AI), atherogenic index of plasma (AIP), lipoprotein combine index (LCI), castelli risk index- I (CRI-I) & castelli risk index-II (CRI-II). These are calculated simply from fasting lipid profile components and they can act as potential predictors of CAD severity. Therefore, these lipid indices offer more comprehensive assessment of atherogenic risk and CAD severity compared to individual lipid components.

Objective: To evaluate the association of calculated lipid indices with severity of CAD and to assess their role as diagnostic biomarker for detection of coronary artery disease severity (assessed by SYNTAX score).

Methods:This cross-sectional study was conducted at Sir Salimullah Medical College (SSMC) from March 2024 to February 2025. Total 218 patients (age 18- 70 years) with CAD were purposively selected as study subjects from the Cardiology department of Sir Salimullah Medical College Mitford Hospital (SSMCMH) and National Institute of Cardiovascular Diseases (NICVD), Dhaka. The demographic, clinical, and biochemical data were collected. Fasting lipid profile was measured in every patient and lipid indices were calculated using the values of lipid profile components. For all patients coronary angiogram were done, SYNTAX score were calculated to assess CAD severity. All (218) subjects were divided into three groups according to their SYNTAX score; mild CAD (low risk, SYNTAX Score 0 - 22), moderate CAD (intermediate risk; SYNTAX Score 23 - 32) and severe CAD (high risk; SYNTAX Score of > > 32). The associations of lipid indices with CAD severity was analyzed by unpaired t-test, spearman rank correlation coefficient test and logistic regression test. To evaluate the diagnostic performance of lipid indices for detection of CAD severity, their cutoff points were determined by Youden Index. Using those cutoff points diagnostic performance of lipid indices were evaluated by ROC (receiver operator characteristic) curve analysis, AUC (area under curve) and performance tests (sensitivity, specificity, positive predictive value, negative predictive value, accuracy). Statistical significance was set at p≤0.05.

Results: Unpaired t-test, Spearman rank correlation coefficient test, logistic regression analysis revealed positive correlation and association of calculated lipid indices with the CAD severity. The CRI-II had the highest (0.647) area under the curve (AUC), and AIP had lowest (0.606) AUC. As predictors of CAD severity AI, and CRI-I showed 68.8% sensitivity, 54.8% specificity, 86.43% PPV, 29.48% NPV, 66.05% accuracy with cutoff point 3.0 and 4.0 respectively. AIP and LCI showed 71.6% sensitivity, 52.4% specificity, 86.3% PPV, 30.55% NPV, 67.89% accuracy with cutoff point 0.13 for both. CRI-II showed 62.5% sensitivity, 59.5% specificity, 86.61% PPV, 27.47% NPV, 61.93% accuracy with cutoff point 4.0

Conclusion: The calculated lipid indices were found to be positively associated with CAD severity and positively correlated with SYNTAX score. The diagnostic performance of calculated lipid indices for detection of CAD severity was not satisfactory because their AUC, sensitivity and specificity were not promising.

Keywords: Coronary Artery Disease (CAD), Atherogenic Index (AI), Atherogenic Index of Plasma (AIP), Lipoprotein Combine Index (LCI), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II), SYNTAX Score (SS)

Abstract

Background:Gestational Diabetes Mellitus (GDM) is a common metabolic complication of pregnancy characterized by glucose intolerance and insulin resistance. Early detection and management of GDM are critical to prevent adverse maternal and foetal outcomes. Cystatin C; traditionally known as a renal marker, has recently been implicated in metabolic dysfunctions such as insulin resistance and hyperglycaemia.

Objective: This study aimed to evaluate the association of high serum Cystatin C with glycaemic parameters and insulin resistance in pregnant women with GDM.

Methods: This case-control study was conducted at Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) General Hospital, Dhaka, from March 2024 to February 2025. Total 160 pregnant women between 24–28 weeks of gestation were enrolled; including 80 diagnosed GDM (cases) and 80 age and gestational week matched healthy pregnant women (controls). Selection was done using convenient and purposive sampling. GDM was diagnosed based on the American diabetes association (ADA) 2023 criteria. Clinical, anthropometric, and biochemical parameters, including fasting plasma glucose, 2-hour post-load plasma glucose, serum insulin, HOMA-IR, and serum Cystatin C, were measured. Data were analysed using SPSS version 26, with p < 0.05 considered statistically significant.

Results: The mean BMI was significantly higher in the GDM group (28.97 ± 3.75 kg/m²) compared to controls (27.97 ± 4.04 kg/m², p < 0.002). Fasting plasma glucose (5.92 ± 2.14 mmol/L vs. 4.41 ± 0.40 mmol/L, p < 0.001), 2-hour post load plasma glucose (9.03 ± 2.92 mmol/L vs. 6.53 ± 1.02 mmol/L, p = 0.041), and HOMA-IR (5.87 ± 3.94 vs. 3.99 ± 1.78, p < 0.001) were significantly elevated in the GDM group. Serum insulin was higher among cases but not statistically significant (p = 0.38). Serum Cystatin C level was significantly elevated in the GDM group (0.932 ± 0.23 mg/L vs. 0.734 ± 0.11 mg/L, p < 0.001). The high level (>0.80 mg/dl) serum Cystatin C was strongly associated with GDM (OR 9.0; 95% CI, 5.0 to 16.3, p < 0.001). Cystatin C was positively correlated with fasting plasma glucose (r = 0.321, p < 0.05); 2-hour post load plasma glucose (r = 0.303, p < 0.05) and HOMA-IR (r = 0.323, p < 0.05). Correlations of Cystatin C with serum insulin (r = 0.121, p > 0.05) and BMI (r = 0.150, p > 0.05) were positive but not statistically significant.

Conclusion: High serum Cystatin C levels exhibit strong, positive, and statistically significant association with the presence of GDM and a positive correlation was found with glycaemic parameters and insulin resistance. So, woman with elevated Cystatin C suggest a higher risk of developing GDM.

Keywords: Gestational Diabetes Mellitus, Cystatin C, Insulin Resistance, HOMA-IR, Glycaemic Parameters, Pregnancy, Biomarker

Effectiveness of HPV E6/E7 mRNA Test to Triage Primary Screen Positive Women in Cervical Cancer Screening

Abstract

Background: Marked advancements in molecular technology and better understanding of the natural history of Human Papillomavirus (HPV) have significantly contributed to the introduction of molecular biomarkers in cervical cancer screening in recent years. The detection of highly sensitive HPV DNA and the highly specific HPV E6/E7 mRNA are now widely utilized in developed countries for cervical cancer screening. Among these, the HPV E6/E7 mRNA test is considered more specific for identifying precancerous cervical lesions.

Objective: To evaluate the effectiveness of the HPV E6/E7 mRNA test as a triage tool for screening of cervical cancer in primary screen positive women by VIA (visual inspection with acetic acid) or Pap smear (cytology) or HPV DNA test.

Methods: This cross-sectional observational study was conducted in the colposcopy clinic of the National Centre for Cervical & Breast Cancer Screening & Training, Bangladesh Medical University (BMU) in collaboration with the Department of Virology, BMU, Dhaka, Bangladesh, from October 2023 to September 2024. This study included 150 women by consecutive sampling who tested positive on any primary cervical cancer screening method (VIA/Cytology/HPV DNA) and were referred to the colposcopy clinic of BMU. After collecting cervical sample from each enrolled subject, colposcopy and colposcopy directed biopsy was performed. HPV E6/E7 mRNA test was performed on cervical sample in virology department of BMU. Presence of E6/E7 mRNA predicts the precancerous & early invasive lesion. Colposcopy reported normal or precancerous lesion (CIN 1, 2, 3). Finally, histopathology on biopsy material confirmed it as normal (e.g cervicitis) or precancerous (CIN 1, 2, 3) or cancerous (e.g invasive carcinoma or carcinoma in situ). All data were processed and analysed using 26 version of SPSS. Diagnostic efficacy of HPV E6/E7 mRNA and colposcopy for detection of pre-cancerous/cancerous cervical lesion were calculated taking histopathology as gold standard.

Results: The majority of participants were aged 30–39 years (45.3%) and multiparous (87.3%). Colposcopy revealed cervical intraepithelial neoplasia 1 (CIN I) in 60% of cases, while histopathology showed chronic cervicitis (54.67%) and CIN I (30.67%) as the most common findings. HPV E6/E7 mRNA was overexpressed in 15% of cases. Among E6/E7 mRNA-positive patients, 78.3% had biopsy-confirmed precancerous and cancerous lesions, compared to 39.37% in the mRNA-negative group. The E6/E7 mRNA test showed high specificity (93.9%), high PPV (78.3%) and overall accuracy 63.3% for detecting precancerous and early invasive lesions, with low sensitivity of 26.5%. Colposcopy showed higher sensitivity (94.12%) but very low specificity (8.54%) and low accuracy (47.33%). Compared to colposcopy, the E6/E7 mRNA test provided more reliable diagnostic accuracy (63.3% vs 47.33%) for detecting precancerous and early invasive lesions of cervix.

Conclusion: The findings obtained from the study emphasize the importance of integrating HPV E6/E7 mRNA molecular testing into routine cervical cancer screening programs as a triage test due to its high specificity, PPV and accuracy compared to colposcopy for identifying clinically significant precancerous and early invasive lesions of cervix. Therefore, the HPV E6/E7 mRNA test may serve as an effective triage tool before doing colposcopy for identifying clinically significant precancerous cervical lesions and contributing to the prevention of cervical cancer. Thus it also can minimize colposcopy referral and over treatment.

Keywords: HPV E6/E7 mRNA, Screening, Triage, Cervical Cancer, CIN

Phenotypic and Genotypic Detection of Efflux Pump in Meropenem-Resistant Pseudomonas aeruginosa Among Burn Patients

Abstract

Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa in burn wounds is becoming a difficult issue worldwide. The recent emergence of meropenem-resistant MDR Pseudomonas aeruginosa poses a serious threat to public health. The activity of the MDR efflux pump is a key mechanism contributing to meropenem resistance.

Objective: The study aims to detect efflux pump phenotypically and genotypically in meropenem-resistant MDR Pseudomonas aeruginosa among burn wound patients.

Methods: A total of 120 laboratory isolates of Pseudomonas species from burn wounds were collected from the patients of National Institute of Burn and Plastic Surgery, Dhaka. The automated VITEK® 2 Compact system in the department of microbiology and immunology at Bangladesh Medical University (BMU) was used to identify Pseudomonas aeruginosa. Antimicrobial susceptibility testing and identification of MDR Pseudomonas aeruginosa were conducted by using the Kirby-Bauer disk diffusion technique. Out of 120 laboratory isolates of Pseudomonas species, Pseudomonas aeruginosa accounted for the majority of these isolates (109, 90.8%), followed by Pseudomonas fluorescens (6, 5%) and Pseudomonas putida (5, 4.17%). Among 109 Pseudomonas aeruginosa, 92 (84.4%) were multidrug resistant (MDR). Among 92 MDR cases, 78 (84.8%) were meropenem-resistant Pseudomonas aeruginosa. Finally, 78 meropenem-resistant Pseudomonas aeruginosa among all MDR were selected as study subjects. Efflux pump that causes meropenem resistance was identified both phenotypically and genotypically. Ethidium bromide cartwheel (EtBr-CW) approach was used for phenotypic identification and efflux pump genes (MexAB-OprM) detection by conventional polymerase chain reaction (PCR) was used for genotypic identification of efflux pump.

Results: Out of 109 Pseudomonas aeruginosa isolates, majority (92, 84.4%) of Pseudomonas aeruginosa were multidrug-resistant (MDR) where majority (78, 84.8%) showed resistance to meropenem. Among meropenem-resistant Pseudomonas aeruginosa (78), efflux pump was detected both genotypically and phenotypically in 52 (66.7%) cases and only genotypically in 05 (6.4%) cases. Therefore, in 57 (73.1%) cases efflux pump was detected genotypically through detection of efflux pump gene. Among the different efflux pump genes, Mex A gene was found in 52 cases, Mex B gene in 57 cases, Opr M gene in 19 cases, both Mex A and Mex B genes in 51 cases and Mex A, Mex B, Opr M genes together in 19 cases.

Conclusion: The majority of Pseudomonas aeruginosa were multidrug resistant (MDR) and showed resistance to meropenem. Efflux pump genes (MexA, MexB, OprM) were found in good number of the patients.

Keywords: Efflux pump, Meropenem, Multidrug resistant P. aeruginosa

Diagnostic Performance of Frozen Section in Detecting Myometrial Invasion and Cervical Extension in Endometrial Carcinoma

Abstract

Background: Low-risk endometrial cancer is treated with total hysterectomy and bilateral salphingo-oophorectomy. High-risk patients need detailed surgical staging including lymphadenectomy. An accurate preoperative work up and assessment of high-risk features during surgery is essential. So, an intraoperative frozen section is important for guiding surgical decisions by checking for myometrial invasion and cervical extension.

Objective: To assess the diagnostic performance of frozen section in detecting myometrial invasion and cervical extension in endometrial carcinoma.

Methods: This cross-sectional study was conducted at the Department of gynecological oncology at Bangladesh Medical University, Dhaka, from December 2022 to December 2023. We included 31 patients with histopathologically confirmed endometrial cancer (by fractional or diagnostic curettage) who underwent surgery. During surgery, frozen section of resected uterus was done and sent to pathology department to comment for deep myometrial invasion (≥50%) and the presence of cervical involvement within one hour. Later on, histopathology was done on the resected uterus. Finally, frozen section report was compared with final histopathology findings.

Results: The mean age of participants was 56.3 years, ranging from 35 to 70. Most were postmenopausal (83.9%) and nearly two-thirds had low parity. Common health issues included obesity (38.7%), diabetes, and hypertension (45.2%). To detect deep myometrial invasion compared to histopathology, the frozen section showed sensitivity 90.0%, specificity 95.2%, and overall accuracy 93.5%. To detect cervical extension compared to histopathology, the frozen section showed sensitivity 77.8%, specificity 95.5%, and accuracy 90.3%, with few false positive and negative results.

Conclusion: Frozen section is a reliable intraoperative method for evaluating myometrial invasion and cervical extension in endometrial cancer. It offers surgeons valuable real-time information, helping to guide surgical staging and treatment plans, for better patient outcomes.

Keywords: Endometrial cancer, frozen section, cervical extension, myometrial invasion

Association of Triglyceride-Glucose Index with the Severity (Assessed by SYNTAX Score) of Coronary Artery Disease in Patients with Acute Coronary Syndrome

Abstract

Background: Acute Coronary Syndrome (ACS) is a significant manifestation of coronary artery disease (CAD). Severity of CAD is determined by SYNTAX score based on coronary angiogram which is an invasive procedure. A noninvasive evaluation of CAD severity by Triglyceride-Glucose (TyG) index before coronary angiogram might help with risk assessment and selection of treatment strategy.

Objective: To evaluate the association of Triglyceride-Glucose (TyG) index with severity of CAD determined by SYNTAX score in patients with ACS.

Methods: This cross-sectional study was done in the department of Biochemistry of Sir Salimullah Medical College from March 2024 to February 2025. A total 224 patients with ACS undergoing coronary angiography were enrolled as study subjects by purposive sampling. TyG index was calculated from fasting plasma glucose and fasting serum triglycerides level. Subjects were grouped according to the tertile of TyG index into tertile 1 (T1), tertile 2 (T2) and tertile 3 (T3). A SYNTAX score of ≤22 was considered as not severe and a SYNTAX score of >22 was considered as severe CAD. Severity of CAD was compared among different tertile groups by chi-square test. Association of high TyG index with severity of CAD was determined by odds ratio (OR). The correlation of TyG index with severity of CAD was determined by Pearson’s correlation coefficient test. The cut-off point of TyG index was determined by Youden’s Index. The diagnostic role of TyG index for detection of severe CAD was determined by Receiver operator characteristic (ROC) curve, the area under (AUC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. P-value ≤0.05 was considered statistically significant.

Results: Among 224 subjects divided into TyG index tertiles, the highest tertile (T3) was strongly associated with a high SYNTAX score (>22), and subjects with high TyG index (>8.47) were found to have 37.83 times more risk to have severe CAD (OR=37.83, CI:17.06–84.0). The TyG index showed a significant positive correlation with the SYNTAX score (r=0.880, p<0.001). Receiver operating characteristics (ROC) curve analysis of TyG index (cut-off point 8.47) for predicting severe CAD showed the area under curve (AUC) to be 0.99, sensitivity 76.5%, specificity 92.0%, PPV 88.0%, NPV 83.5% and accuracy 85.0%.

Conclusion: High TyG index was associated with increased severity of coronary artery disease in ACS patients. High TyG index was a good predictor of severe CAD with high sensitivity, specificity, diagnostic accuracy and AUC.

Keywords: Coronary Artery Disease, Acute Coronary Syndrome, Triglyceride-Glucose Index, SYNTAX score

Cardiac Rehabilitation for Heart Failure Patients: A Narrative Review

Abstract

Heart failure (HF) affects millions globally, and family caregivers play a vital role in supporting HF patients through cardiac rehabilitation (CR). These caregivers help with medication management, physical activity, and emotional support, contributing significantly to patient outcomes. However, the impact of caregiving on family members’ health and well-being is understudied. This review aims to evaluate the effects of family caregiver involvement on cardiovascular outcomes, quality of life, and mental well-being for HF patients.

A narrative review was conducted by analyzing studies on family caregivers in CR for HF patients, using databases such as PubMed, Google Scholar, and Embase. Family caregivers’ involvement is associated with improved cardiovascular outcomes, exercise capacity, and mental well-being in HF patients, but they also face emotional and physical burdens. Supporting caregivers is essential for optimizing CR programs.

Keywords: Heart failure, Family caregivers, Cardiac rehabilitation

Pseudohypoparathyroidism Type 1a with Hypocalcemia in a 25-Year-Old Woman: A Case Report of Delayed Presentation

Abstract

Pseudohypoparathyroidism (PHP) is a rare endocrine disorder caused by end-organ resistance to parathyroid hormone (PTH), resulting in hypocalcemia and hyperphosphatemia despite elevated PTH levels. PHP type 1a is associated with Albright hereditary osteodystrophy (AHO) features such as brachydactyly, short stature, and a round face. Usually these group of patients present in early childhood. In this case report, we found a 25-year-old female with fatigue and muscle cramps. She had short stature (101 cm), brachydactyly, a round face, and a positive knuckle dimple sign. Investigations revealed hypocalcemia (5.6 mg/dL), hyperphosphatemia (2 mmol/L), normal magnesium and albumin levels, and elevated PTH (70.1 pg/mL). Radiographs revealed shortened fourth and fifth metacarpals. Genetic and cAMP testing were unavailable. Treatment with oral calcium carbonate (1.5 g/day) and calcitriol (0.5 mcg/day) normalized calcium and resolved symptoms within one month. In low-resource settings, recognition of the AHO phenotype with basic biochemical evidence can enable timely PHP diagnosis. Early calcium and vitamin D therapy is essential to prevent complications.

Keywords: Pseudohypoparathyroidism, Albright hereditary osteodystrophy, Brachydactyly, Hyperphosphatemia, Elevated PTH, Hypocalcemia