Determinants of polycystic ovary syndrome: A matched case-control study.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a multifaceted endocrine disorder of women of reproductive age with a multifactorial aetiology. Despite much research, there is still inconclusive data on the impact of dietary, lifestyle and socio-economic factors on PCOS aetiology. Thus, the present study explored the association of PCOS with diet, eating behaviour, other lifestyle and socio-economic factors. METHODS: A matched-pair case-control study was conducted on 150 women with PCOS and 150 healthy controls. Information on diet, eating behaviour and physical activity, and also anthropometric and socio-economic data were collected through standard questionnaires. The adjusted odds ratios (AmOR) were calculated and reported using conditional multivariable logistic regression. RESULTS: The results showed low education level (AmOR = 8.44; 95% confidence interval [CI] = 1.63-43.68), high sugar consumption (AmOR = 11.61; 95% CI = 2.05-65.72) along with higher body mass index (BMI) and inactivity to be significantly associated with PCOS. Also, a significant protective effect was found for cognitive dietary restraint (AmOR = 0.79; 95% CI = 0.66-0.93), crude fibre (AmOR = 0.61; 95% CI = 0.45-0.82) and protein intake. CONCLUSIONS: Low education status may contribute to higher receptiveness to choosing unhealthy diets and lifestyles, resulting in adiposity and an increased risk of PCOS.

Pattern of Medical Device Adverse Events in a Tertiary Care Hospital in Northern India: An Ambispective Study.

BACKGROUND: Knowledge about the pattern of adverse events caused by medical devices (MDs) is limited in India. We aimed to assess the pattern of MD adverse events (MDAEs) in a tertiary hospital in Northern India. MATERIALS AND METHODS: This descriptive study was conducted ambispectively at various clinical departments of PGIMER, Chandigarh. We followed the guidelines edged by the Materiovigilance Program of India (MvPI) to conduct this study. The prospective study (PS) was done from January to December 2020, with a concurrent retrospective study (RS) proceeding to 3 years to learn more about the reporting culture, demographics, notification status, risk class of defective devices, and the type of adverse events. RESULTS: We received 224 MDAE in the PS and identified 413 MDAE in the RS. Reporting of adverse events to the national MvPI was negligible in the RS. In the PS, nurses reported the majority of MDAEs (65%), followed by doctors (30%). The occurrence of MDAE was higher in males (PS; 52%, RS; 57%) and age groups between 21 and 30 years (PS; 19.1%, RS; 23.2%) in both studies. MDAEs were frequent in low- to moderate-risk devices (class B: 66%) in the PS, while it was documented only for high-risk devices (class C: 51% and class D: 49%) in the RS. Most of the serious adverse events (SAEs) were reported among moderate to high-risk devices, and an increased frequency of SAE (60.4%) was observed among nonnotified MDs. The overall incidence of near-miss events was 14%. CONCLUSION: Knowledge of MDAEs and reporting of defective devices to regulatory authorities is essential to prevent further incidence. Adverse events caused by MDs are ubiquitous irrespective of their risk classification, notification status, and patient demographic factors. Accelerated reporting of MDAE by all cadre of healthcare professionals is urgently required to safeguard the health of Indians.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

Immunogenicity and safety of a new quadrivalent HPV vaccine in girls and boys aged 9-14 years versus an established quadrivalent HPV vaccine in women aged 15-26 years in India: a randomised, active-controlled, multicentre, phase 2/3 trial.

BACKGROUND: To meet global cervical cancer elimination efforts, a wider range of affordable and accessible vaccines against human papillomavirus (HPV) are needed. We aimed to evaluate the immunogenicity and safety of a quadrivalent HPV vaccine (targeting HPV types 6, 11, 16, and 18), developed and manufactured by the Serum Institute of India (SIIPL). Here we report outcomes in the 9-14 years cohort. METHODS: This randomised, active-controlled, phase 2/3 trial was conducted at 12 tertiary care hospitals across India. Healthy participants aged 9-14 years or 15-26 years with no history of HPV vaccination were eligible for enrolment. Female participants were randomly assigned (1:1) with an interactive web response system, by use of a central computer-generated schedule and block randomisation (block sizes of 2, 4, 6, and 8), to receive the SIIPL quadrivalent HPV vaccine (Cervavac; SIIPL, Pune, India) or the comparator quadrivalent HPV vaccine (Gardasil; Merck Sharp & Dohme, Harleem, the Netherlands). Participants, investigators, laboratory technicians, and sponsors were masked to treatment allocation of female participants. Male participants were given the SIIPL quadrivalent HPV vaccine in an open-label manner. Study vaccines were administered intramuscularly with a two-dose schedule (at day 0 and 6 months) in the cohort aged 9-14 years, and with a three-dose schedule (at day 0, month 2, and month 6) in the cohort aged 15-26-years. Immunogenicity was assessed 30 days after the last dose by use of multiplexed ELISA. The primary outcome was the non-inferiority of immune response in terms of the geometric mean titre (GMT) of antibodies against HPV types 6, 11, 16, and 18 generated by the SIIPL quadrivalent HPV vaccine in girls and boys (aged 9-14 years) compared with the GMT generated by the comparator quadrivalent HPV vaccine in women aged 15-26 years at month 7 in the modified per-protocol population (ie, all participants who received all doses of study vaccines per assigned treatment group and had both day 0 and 1-month immunogenicity measurements after the last dose following protocol-defined window periods with no major protocol deviations). Non-inferiority was established if the lower bound of the 98·75% CI of the GMT ratio was 0·67 or higher. The co-primary outcome of occurrence of solicited adverse events (within 7 days of each dose) and unsolicited adverse events (up to 30 days after the last dose) was assessed in all participants who were enrolled and received at least one dose of study vaccine. The trial is registered with the Clinical Trials Registry - India (CTRI/2018/06/014601), and long-term follow-up is ongoing. FINDINGS: Between Sept 20, 2018, and Feb 9, 2021, 2341 individuals were screened, of whom 2307 eligible individuals were enrolled and vaccinated: 1107 (738 girls and 369 boys) in the cohort aged 9-14 years and 1200 (819 women and 381 men) in the cohort aged 15-26 years. No race or ethnicity data were collected. 350 girls and 349 boys in the SIIPL quadrivalent HPV vaccine group and 338 women in the comparator vaccine group were included in the modified per-protocol population for the primary endpoint analysis. The median follow-up for the analyses was 221 days (IQR 215-231) for girls and 222 days (217-230) for boys in the SIIPL quadrivalent HPV vaccine group, 223 days (216-232) for girls in the comparator vaccine group, and 222 days (216-230) for women in the comparator vaccine group. GMT ratios were non-inferior in girls and boys receiving the SIIPL quadrivalent HPV vaccine compared with women receiving the comparator vaccine: GMT ratios for girls were 1·97 (98·75% CI 1·67-2·32) for HPV type 6, 1·63 (1·38-1·91) for HPV type 11, 1·90 (1·60-2·25) for HPV type 16, and 2·16 (1·79-2·61) for HPV type 18. For boys the GMT ratios were 1·86 (1·57-2·21) for HPV type 6, 1·46 (1·23-1·73) for HPV type 11, 1·62 (1·36-1·94) for HPV type 16, and 1·80 (1·48-2·18) for HPV type 18. The safety population comprised all 1107 participants (369 girls and 369 boys in the SIIPL quadrivalent HPV vaccine group, and 369 girls in the comparator group). Solicited adverse events occurred in 176 (48%) of 369 girls and 124 (34%) of 369 boys in the SIIPL vaccine group and 179 (49%) of 369 girls in the comparator vaccine group. No grade 3-4 solicited adverse events occurred within 7 days of each dose. Unsolicited adverse events occurred in 143 (39%) girls and 147 (40%) boys in the SIIPL vaccine group, and 143 (39%) girls in the comparator vaccine group. The most common grade 3 unsolicited adverse event was dengue fever, in one (<1%) girl in the SIIPL vaccine group and three (1%) girls in the comparator group. There were no grade 4 or 5 adverse events. Serious adverse events occurred in three (1%) girls and three (1%) boys in the SIIPL vaccine group, and five (1%) girls in the comparator vaccine group. No vaccine-related serious adverse events were reported. There were no treatment-related deaths. INTERPRETATION: We observed a non-inferior immune response with the SIIPL quadrivalent HPV vaccine in girls and boys aged 9-14 years and an acceptable safety profile compared with the comparator vaccine. These findings support extrapolation of efficacy from the comparator vaccine to the SIIPL quadrivalent HPV vaccine in the younger population. The availability of the SIIPL quadrivalent HPV vaccine could help meet the global demand for HPV vaccines, and boost coverage for both girls and boys globally. FUNDING: Biotechnology Industry Research Assistance Council, Department of Biotechnology (DBT), Government of India, and Serum Institute of India.

Pregnancy in Eisenmenger syndrome: a case series from a tertiary care hospital of Northern India.

BACKGROUND: Despite advances in medical care, we still come across pregnancy in Eisenmenger syndrome. Eisenmenger syndrome represents the severe end of the spectrum for disease in pulmonary artery hypertension associated with CHD. Due to very high maternal and perinatal morbidity and mortality, pregnancy is contraindicated among these women. Current guidelines also recommend that the women who become pregnant should opt for early termination of pregnancy. Here, we present a case series of 11 women of Eisenmenger syndrome and their pregnancy outcome. METHODS: It was a retrospective analysis of 12 pregnancies among 11 women with Eisenmenger syndrome who were managed in a tertiary care referral centre of Northern India. RESULTS: The mean age of these women was 28 ± 4 years (range 22 to 36 years). Almost 80% of them (9/11) were diagnosed with Eisenmenger syndrome during pregnancy. The commonest cardiac lesion was Ventricular Septal defect (54.5%) followed by Atrial Septal defect (27.3%) and Patent Ductus arteriosus (9.1%). Only three women opted for medical termination of pregnancy, rest eight continued the pregnancy or presented late. Pregnancy complications found include pre-eclampsia (50%), abruption (22%), and fetal growth retardation (62.5%). There were three maternal deaths (mortality rate 27%) in postpartum period. CONCLUSION: This case series highlights the delay in diagnosis and treatment of CHD despite improvement in medical care. Women with Eisenmenger syndrome require effective contraception, preconceptional counselling, early termination of pregnancy, and multidisciplinary care.

Usage of postpartum intrauterine contraceptive device (postpartum-IUD) after an increase in the institutional delivery rate in India: time to re-visit the effect of timing of counselling on its acceptance.

PURPOSE: While increase in institutional deliveries brings an opportunity to counsel women for postpartum family planning (PPFP), its uptake remains low. Reasons for poor acceptance of postpartum intrauterine contraceptive device (postpartum-IUD), and its relation with the timing of counselling need to be investigated. METHODS: Women attending the antenatal clinic, reporting in labour, and within 48 h of delivery respectively were invited to participate. Eligible women were asked about awareness and choice for PPFP. After counselling, acceptance for PPFP was compared with the baseline. Acceptance and continuation of postpartum-IUD were compared between women counselled in the antenatal, intrapartum, and postpartum periods. RESULTS: Only 23% of 360 women were aware of postpartum-IUD. After counselling, acceptance for PPFP increased from 14% to 97% and for postpartum-IUD, from 0.5% to 33.9%. Acceptance of postpartum-IUD among women counselled in the antenatal, intrapartum and postpartum period was 45%, 35% and 21.7% respectively. Acceptance was higher among the antenatal-counselling group than the postpartum-counselling group (OR 0.45; CI 0.22-0.94; p = 0.03). CONCLUSION: Counselling, irrespective of its timing, improves acceptance for PPFP. Acceptance and continuation of postpartum-IUD are higher following counselling in antenatal period. All eligible women should be counselled irrespective of 'when' they approach the facility.

Acceptance for postpartum-IUD is maximum when women are counselled in the antenatal period. With a surge in institutional deliveries, the opportunity to counsel women in the intrapartum and postpartum period should not be missed as this also increases acceptance for PPFP and postpartum-IUD.

Clinical profile and outcomes of Scrub typhus in pregnant women presenting to a tertiary care hospital of North India.

Scrub typhus, caused by Orientia tsutsugamushi, is a re-emerging endemic zoonosis in the Asia Pacific region. It is a febrile condition ranging in severity from mild to severe, with fatality rates as high as 30%. The present study aims towards analysing the clinical profile and pregnancy outcomes in 27 cases of scrub typhus admitted to a tertiary care centre in North India. The medical records of 27 pregnant women who had scrub typhus were analysed. The IgM ELISA was used to look for IgM antibodies to Orientia tsutsugamushi in the patient's serum sample. An optical density of more than or equal to 0.468 was considered as positive. Majority of the pregnant females delivered healthy and live babies. However, poor foetal outcomes were observed in four (14.8%) cases with intrauterine deaths occurring in two (7.4%) cases and still birth in one (3.7%) case, while one (3.7%) patient had spontaneous abortion. Maternal mortality was reported in one patient (3.7%) due to a delay in diagnosis. In endemic settings, a strong index of suspicion for scrub typhus is necessary in pregnant females presenting with fever. The key to reducing morbidity in both the mother and foetus is early diagnosis and treatment.Impact StatementWhat is already known on this subject? Scrub typhus is a febrile condition ranging in severity from mild to severe, with 30% mortality in untreated patients.What do the results of this study add? Majority of the pregnant females delivered healthy and live babies. However, poor foetal outcomes were observed in four (14.8%) cases with intrauterine deaths occurring in two (7.4%) cases and still birth in one (3.7%) case, while one (3.7%) patient had spontaneous abortion. Maternal mortality was reported in one patient (3.7%) due to a delay in diagnosis.What are the implications of these findings for clinical practice and/or further research? In endemic settings, a strong index of suspicion for scrub typhus is necessary for pregnant females presenting with fever. The key to reducing morbidity in both the mother and foetus is early diagnosis and treatment.

Placenta as a site of HEV replication and inflammatory cytokines modulating the immunopathogenesis of HEV in pregnant women.

Viral hepatitis E is an under-estimated clinical entity with high mortality (20%-30%), especially in the third trimester of pregnancy. As complications due to hepatitis E virus (HEV) in pregnancy is much greater, it is hypothesized that HEV may cross the placenta and replicate in placental tissues even weeks after clearance from the blood, and cytokines may play a role in the immunopathogenesis of HEV in pregnancy. A total of 12 pregnant women with features of acute viral hepatitis/acute liver failure and positive for either HEV-immunoglobulin M (IgM)/HEV-RNA and 30 pregnant women negative for HEV RNA/IgM/immunoglobulin G were enrolled as study subjects and healthy controls, respectively. Following delivery, 5 ml blood was collected from the mother for HEV-RNA. Replicative RNA and viral load in placental tissue were detected through Real-Time PCR. Placental tissues from the maternal/fetal sides were stained for HEV antigen using HEV-open reading frame-2 antibody by immunohistochemistry (IHC) and for histopathological changes by haematoxylin and eosin. Plasma samples were tested for interleukin (IL)-1ß and IL-18 cytokine levels using Duo-R&D ELISA kit, whereas peripheral blood mononuclear cells were used to study the inflammasomes and IL-1ß and IL-18 cytokine genes expression.Of the 10 HEV RNA-positive sera, 9 had HEV RNA either in the maternal/fetal side of the placenta with the mean viral load of 137.4 IU/ml. Of the 10 HEV RNA-positive pregnant women, stillbirth in two and fetal and maternal death in one case was reported. IHC revealed strong brownish cytoplasmic staining (HEV antigen) in cytotrophoblasts and syncytiotrophoblast cells in positive samples. The maternal/fetal side of the infected placenta showed irregular intervillous fibrin deposition as well as tissue necrosis. The mean levels of IL-1ß and IL-18 cytokines in serum of infected subjects were significantly higher than the healthy controls (17.31 ± 4.462 vs. 8.85 ± 4.36 pg/ml; p < 0.0001*** and 2275 ± 536.9 vs. 1085 ± 531.7 pg/ml; p < 0.0001***), respectively. Detecting replicative HEV RNA and HEV antigen in placental tissues indicated the extra-hepatic replication of HEV. Furthermore, placental tissue necrosis and significant rise of cytokine levels in HEV-infected pregnant women might be contributing to the HEV pathogenesis in pregnancy.

Efficacy of multi-strain probiotic along with dietary and lifestyle modifications on polycystic ovary syndrome: a randomised, double-blind placebo-controlled study.

PURPOSE: Effect of multi-strain probiotic along with dietary and lifestyle modifications in the management of polycystic ovary syndrome (PCOS) has rarely been reported. We thus aimed to investigate the effect of multi-strain probiotic (Lactobacillus acidophilus UBLA-34, L. rhamnosus UBLR-58, L. reuteri UBLRu-87 (each of 2 billion colony forming units (CFU)); L. plantarum UBLP-40, L. casei UBLC-42, L. fermentum UBLF-31, Bifidobacterium bifidum UBBB-55 (each of 1 billion CFU) and fructo-oligosaccharides (100 mg)) and dietary and lifestyle modifications on restoration of menstrual regularity, weight reduction, metabolic and hormonal profile in women with PCOS. METHODS: A 104 participants (age 18-40 years) were randomly allocated to receive probiotic or placebo capsules for 6 months. Baseline and end line assessment were performed for menstrual cycle regularity, ultrasonography scan for ovaries, total testosterone, dehydroepiandrosterone (DHEAS), insulin, luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, fasting blood sugar (FBS), homeostatic model assessment-insulin resistance (HOMA-IR), weight reduction, waist-/hip circumference (WC, HC), waist to hip ratio (WHR), and body mass index (BMI). Plasma lipopolysaccharide and effect of intervention on quality of life was investigated. Diet and exercise were controlled during the trial. RESULTS: Probiotic supplement along with dietary and lifestyle modifications significantly regularised menstrual cycle (p 0.023), improved levels of total testosterone (p 0.043), WC (p 0.030), WHR (p 0.027) and menstrual domain of quality of life (p 0.034) as compared to placebo. No adverse events related to study were reported. CONCLUSION: Multi-strain probiotic along with dietary and lifestyle modifications were effective in the management of PCOS. TRIAL REGISTRATION: CTRI: CTRI/2016/07/007086, dated 13 July 2016.

Long-term hepatic and cardiac health in patients diagnosed with Sheehan's syndrome.

PURPOSE: Sheehan's syndrome (SS) is characterised by chronic pituitary insufficiency following a vascular insult to the pituitary in the peripartum period. There is a lack of substantial evidence on the long-term hepatic and cardiac consequences in these patients, following hormone replacement. METHODS: Patients with a diagnosis of SS were recruited for the study. Detailed clinico-biochemical and radiological evaluation were performed in all patients (n = 60). Hepatic and cardiac complications were assessed using fibroscan and echocardiography (2D speckle-tracking) respectively, in a subset of patients (n = 29) as well as age-and BMI-matched controls (n = 26). Controlled attenuation parameter (for steatosis) and liver stiffness measurement (for fibrosis) were used to define non-alcoholic fatty liver disease (NAFLD). Diastolic cardiac function was evaluated using standard criteria and systolic function by ejection fraction and global longitudinal strain (GLS). RESULTS: The mean age of the cohort was 42.7 ± 11.6 years. Multiple (≥ 2) hormone deficiencies were present in 68.8% of patients, with hypothyroidism (91.4%), hypocortisolism (88.3%), and growth hormone (GH) deficiency (85.7%) being the most common. At a mean follow-up of 9.8 ± 6.8 years, NAFLD was present in 63% of patients, with 51% having severe steatosis, which was predicted by the presence of GH deficiency and higher body mass index. Though the ejection fraction was similar, increased left ventricular GLS (18.8 vs. 7.7%) was present in a significantly higher number of patients versus controls. CONCLUSION: NAFLD, especially severe hepatic steatosis, is highly prevalent in SS. Subclinical cardiac systolic dysfunction (impaired GLS) is also more common, but of mild intensity.

Cervical cytology in the detection of uterine clear cell carcinoma: Diagnostic predictors from a case-control study.

INTRODUCTION: Uterine clear cell adenocarcinoma (CCC) is a rare, aggressive malignancy with poor prognosis. The present study aimed to identify and describe its characteristic morphological features in cervical cytology. METHODS: This was a 3-year retrospective case-control study. Cases included cervical samples of histopathologically proven endometrial and cervical CCC. Controls included cervical samples of histopathologically proven endometrial serous carcinoma (n = 15), endometrioid adenocarcinoma (n = 20), and endocervical adenocarcinoma (n = 15). Twenty-eight cytomorphological features were evaluated; the strength of association was determined by odds ratio (OR) and Cramer's V, and the diagnostic accuracy of statistically significant features was assessed. RESULTS: Cases consisted of histopathologically proven 25 (34.7%) endometrial and 13 (18.0%) cervical CCC. Corresponding cervical samples were available for a total of 14 (36.8%) patients, of which 13 (92.8%) were positive for epithelial cell abnormality. On univariate analysis, three cytomorphological variables were significant predictors of uterine CCC: presence of dense cytoplasm (OR = 88; V = 0.72), deep nuclear membrane irregularities (OR = 17.5; V = 0.55), and coarse chromatin (OR = 21.3; V = 0.46). Dense cytoplasm had the highest positive predictive value (92%) and high specificity (97.8%), whereas coarse chromatin had the highest sensitivity (92.3%) and negative predictive value (96.7%). CONCLUSIONS: The presence of dense cytoplasm and deep nuclear membrane irregularities in the tumour cells were strong predictors, and coarse chromatin a moderate predictor, of uterine CCC compared to its close cytological mimics.

Facility-based stillbirth surveillance review and response: an initiative towards reducing stillbirths in a tertiary care hospital of India.

OBJECTIVES: India has the highest number of stillbirths in the world in 2019, with an estimated stillbirth rate of 13.9 per 1,000 births. Towards better identification and documentation, a stillbirth surveillance pilot was initiated with the World Health Organization Southeast Asia collaboration in Northern India in 2014. This study aimed to assess whether stillbirth surveillance is feasible and whether this approach provides sufficient information to develop strategies for prevention. METHODS: This study followed the framework provided in "WHO Making Every Baby Count" in which mortality audit is conducted in six steps; (1) identifying cases; (2) collecting information; (3) analysis; (4) recommending solutions; (5) implementing solutions; and (6) evaluation. RESULTS: A total of 5,284 births were examined between December 2018 and November 2019; 266 stillbirths were identified, giving a stillbirth rate of 50.6 per 1,000 births in a tertiary care referral hospital of northern India. Out of 266 stillbirths, 223 cases were reviewed and recommendations were formulated to strengthen obstetric triage, implementing fetal growth charts, strengthen the existing referral system and improve the communication skills of health care providers for better compliance with clinical practice guidelines. CONCLUSIONS: Conducting stillbirth surveillance review and the response of cases in low-middle income countries setting is feasible. As countries progress towards ending preventable mortality, this has the potential to serve as a key process in improving evidence-based and context-specific planning and preventive strategies towards improving the quality of care.

Massive transfusion protocol: Need of the hour - A tertiary care centre experience.

Background and Aims: Massive transfusion (MT) in critically ill patients during major volume losses can lead to serious adverse outcomes. Studies have reported that rampant red cell infusion for maintaining perfusion support has had detrimental effects on patients' short- and long-term survival rates. Evidence-based studies quote the importance of maintaining blood product ratio during massive hemorrhage and ensuring good outcomes with the least morbidity and mortality. Material and Methods: It is an observational study to compare the ratio of usage of blood products and their role in the outcome of MT cases. Results: A total of 70 patients (29 females and 41 males) who received MT were included in the study. There was no fixed ratio of packed red blood cells (PRBC) to blood components for patients with massive hemorrhage. The average ratio of PRBC: fresh frozen plasma (FFP):platelet concentrate (PC) was 1:0.9:0.6. However, blood component therapy with PRBC: FFP ratio between 1 and 2 was associated with a significant rise in post-acute phase hemoglobin value (P value = 0.018). Conclusion: Appropriate blood component therapy during the acute bleeding phase in massively transfused patients can further decrease the transfusion demand and transfusion-related complications. There is a need to adhere to the MT protocol for the clinical areas requiring MT in the developing world too.

Cytomorphological features of cervical small cell neuroendocrine carcinoma in SurePath™ liquid-based cervical samples.

Small cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare, highly aggressive tumour with poor prognosis and high propensity for distant metastases. The cytological features of SCNEC have rarely been described in cervical samples, and to the best of our knowledge, there are no previous reports using SurePath™ liquid-based cytology. In the present report we present the cytomorphological features of histopathologically confirmed cases of cervical SCNEC in SurePath preparations. On cytological examination, all three cases demonstrated variable numbers of tumour cells, ranging from a few dispersed cells and tiny micro-biopsies to large aggregates of small tumour cells with a high nucleus-to-cytoplasmic ratio, stippled chromatin, inconspicuous nucleoli, and scant cytoplasm. Immunocytochemistry for CD56 on the cervical preparation confirmed the diagnosis in one case. The presence of small tumour cells with characteristic stippled/salt-and-pepper type nuclear chromatin were the most consistent cytological features in these cases. Knowledge of these characteristic cytological features can help in suggesting a diagnosis of SCNEC in cervical samples which can then be confirmed by immunocytochemistry.

Ultrasound-guided fine needle aspiration of ovarian masses: Assessment of diagnostic accuracy and risk stratification using a categorical reporting system.

INTRODUCTION: The present study was undertaken to assess the accuracy of fine needle aspiration cytology (FNAC) and cell-block immunocytochemistry, and to estimate the risk of malignancy, using a categorical reporting system, in the diagnosis of ovarian masses. METHODS: This was a 5-year retrospective study of FNAs of ovarian masses. The cytological diagnoses were categorised as inadequate, non-neoplastic, benign neoplasms, indeterminate for malignancy, suspicious for malignancy and malignant neoplasms. The cytology was correlated with the corresponding histopathology to assess the diagnostic accuracy and risk of malignancy associated with each diagnostic category. RESULTS: Of a total of 66 703 FNAs performed during the study period, 580 (0.9%) were performed on ovarian masses. Of these, 40 (6.9%) were reported as non-neoplastic; 76 (13.1%) as benign neoplasms; 14 (2.4%) as indeterminate for malignancy, 48 (8.3%) as suspicious for malignancy, 337 (58.1%) as malignant neoplasms and 65 (11.2%) as inadequate for interpretation. Immunocytochemistry (ICC) was performed on 99 (17%) aspirates. Subsequent histopathology was available in 208 (35.8%) cases. On cyto-histopathological correlation, 183 (88%) were concordant and 25 (12%) were discordant. The overall sensitivity, specificity, positive and negative predictive values and diagnostic accuracy for diagnosing ovarian malignancy were 88.4%, 85.7%, 96.8%, 60.0% and 88% respectively. Risk of malignancy for each category was 80%, 0%, 4.5%, 66.7%, 88.5% and 98.5% respectively. CONCLUSIONS: Ultrasound-guided FNAC has high specificity and diagnostic accuracy for preoperative diagnosis of ovarian malignancies and hence is a valid diagnostic procedure in certain clinical situations. Reporting using a categorical system imparts uniformity and also provides the clinicians with an associated risk of malignancy to guide further management.

A randomized controlled trial comparing the efficacy, tolerability, and cost of oral iron preparations in iron-deficiency anemia in pregnancy.

OBJECTIVE: To evaluate the efficacy, tolerability, and cost of four commonly prescribed oral iron preparations: ferrous sulfate (FS), ferrous fumarate (FF), ferrous ascorbate (FA), and carbonyl iron (CI) in the treatment of iron-deficiency anemia (IDA) in pregnant women. METHODS: It was a prospective, randomized, open-label, blinded endpoint (PROBE) design with four parallel active control groups: FS, FF, FA, CI. The primary outcome was the proportion of participants becoming non-anemic (Hb ≥ 11 g%) at the end of the study period. The secondary outcomes were the proportion of participants achieving normal red blood corpuscular indices such as mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration; the proportion of participants achieving normal iron indices such as serum iron, serum ferritin, total iron-binding capacity, and transferrin saturation; and comparison of incidence of any adverse events between treatment groups and comparison of costs of individual drug therapy between treatment groups. RESULTS: One hundred and twenty patients were randomized to four different groups (n = 30). The results of the present study show that all the four iron salts at the dose of 200 mg elemental iron per day were equally effective in improving hemoglobin concentration and other hematological parameters. The adverse effects were more common in the FF group (56.7%). The pharmacoeconomic analysis showed that all the drugs are equally cost-effective. CONCLUSION: To conclude from the results of the present study, it can be said that FS, FF, FA, and CI are equally effective in treating IDA and they can be prescribed interchangeably.

Maternal and fetal outcomes of dengue fever in pregnancy: a large prospective and descriptive observational study.

PURPOSE: The primary objective of the study was to assess maternal and fetal outcomes of pregnancies affected with dengue fever. METHODS: This was a prospective, observational and descriptive study carried out over a period of 1 year. 216 pregnant women with fever were screened. Of these, 44 women tested positive for dengue (non-structural protein antigen 1 or dengue IgM antibodies in the sera). The clinical and laboratory characteristics of women with dengue were recorded. Maternal outcomes, pregnancy outcomes and fetal outcomes were studied. RESULTS: Mean period of gestation was 31.89 ± 7.31 weeks. Thrombocytopenia was seen in 23 (52.3%) women. Of 40 women, 10 (25%) developed post-partum haemorrhage. The incidence of maternal systemic complications was high: eight (18.2%) women developed acute kidney injury and two (4.5%) required haemodialysis support; eight (18.2%) women developed ARDS and seven (15.9%) women required ventilatory support; four (9.1%) women developed acute liver failure. 18 (40.9%) women had evidence of shock. Seven (15.9%) women died and another seven (15.9%) were classified as WHO maternal near-miss cases. Two (4.5%) pregnancies suffered from miscarriages, four (9%) from still births and two (4.5%) from neonatal deaths. Preterm babies were delivered in 15 (34.1%) and low birth weight babies in 13 (29.5%). CONCLUSIONS: Dengue in pregnancy adversely affects maternal and fetal outcomes with high maternal mortality of 15.9%. Prematurity and postpartum haemorrhage are significant risks to mother and baby. Vector control strategies should be implemented with vigour in affected areas.

Classifying stillbirths in a tertiary care hospital of India: International Classification of Disease-perinatal Mortality (ICD-PM) versus cause of death-associated condition (CODAC) system.

A number of classification system are available to classify stillbirths, but there remains a lack of a uniform global system of classification. This study evaluated the feasibility of the ICD-PM classification system and COD-AC to classify the stillbirths and to discuss the interpretation of "the newer" classification system (ICD-PM) over the COD-AC system. Over a period of one year, out of 5776 total births 314 were stillborns with a stillbirth rate of 54 per 1000 total births. As per ICD PM Classification System, 69.1% of stillbirths were ante partum and rest intrapartum. The associated maternal conditions at the time of foetal death were also classified into five groups and maximum mothers (44.3%) were grouped under M4-medical/surgical disorders. According to COD-AC system of classification 90% of cases were assigned the cause of death, rest 10% remained unexplained. The ICD-PM and CODAC classification both seem to be feasible but ICD-PM clearly defines the time of foetal death and correlates feto-maternal dyad together.IMPACT STATEMENTWhat is already known on this subject? Classifying stillbirths is crucial to recognise the actual cause of foetal death and to gather the relevant information for planning the preventive strategies especially in low middle-income countries (LMICs) which contribute to 98% of total global burden of 2.6 million stillbirths annually. In literature CODAC system was found most suitable for low middle-income countries. In 2016, WHO proposed a newer system, i.e., ICD-PM: WHO application of ICD-10 to deaths during the perinatal period.What do the results of this study add? With ICD-PM classification stillbirths were categorised more clearly in different groups and feto-maternal condition were linked together along with both intrapartum and ante partum stillbirth which can help to set the priorities and future planning for prevention. The proportion of unexplained stillbirth has also reduced significantly compared to CODAC system.What are the implications of these findings for clinical practice and/or further research? CD-PM system of classification seems feasible and would facilitate the uniform and consistent stillbirth data even from LMICs for global comparison although more number of studies are needed for conclusion. The system has been changed to ICD-PM in our institute.

To compare the optimal cytoreduction rate in advanced epithelial ovarian cancer stage III/IV after 3 versus 6 cycles of neoadjuvant chemotherapy.

This study aimed to compare the impact of 3 versus 6 cycles of neoadjuvant chemotherapy (NACT) on the optimal cytoreduction in patients of advanced ovarian malignancy during interval debulking surgery (IDS). Thirty patients with advanced-stage IIIc/IV epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer were randomly allocated to receive 6 cycles in the late IDS group versus 3 cycles in early IDS before undergoing interval debulking surgery. A higher percentage of patients achieved optimal cytoreduction in the late IDS group compared to the early IDS group (60 versus 23%) which was statistically significant (p = .010). Giving 6 cycles of NACT before surgery increased the odd of optimal cytoreduction by 10 than giving 3 cycles of NACT which was statistically significant (p = 0.046) Thus, we conclude that administering 6 cycles of neoadjuvant chemotherapy before debulking surgery helps in achieving optimal cytoreduction in a higher number of patients with lesser surgical morbidity.IMPACT STATEMENTWhat is already known on the subject? Currently, there are no established criteria that would help to determine the number of chemotherapy cycles before debulking surgery in patients with advanced ovarian malignancy.What do the results of this study add? Administering 6 cycles of neoadjuvant chemotherapy before debulking surgery helps in achieving optimal cytoreduction in a higher number of patients with lesser surgical morbidity in cases of advanced epithelial ovarian cancer.What are the implications of these findings for clinical practice and/or further research? We conclude that late interval debulking may be used as a treatment option in the advanced stage IIIc/stage IV. However, the findings need to be studied in a larger study group with a longer follow up period.

Human papillomavirus 16 infection alters the Toll-like receptors and downstream signaling cascade: A plausible early event in cervical squamous cell carcinoma development.

OBJECTIVE: Toll-like receptors constitute an important component of innate immune mechanism. HPV is a known etiological factor of cervical cancer and is known to interfere with the expression of TLRs and downstream signaling pathway. It remains poorly understood whether HPV modulates the expression of TLRs. Hence, understanding HPV mediated immune alterations might aid in identifying novel therapeutic targets. The aim was to study the relative gene expression of TLRs & downstream signaling pathway in cervical carcinoma. METHODS: Cervical squamous cell carcinoma (CSCC) and normal cervical tissues were obtained. Subsequent to HPV genotyping, mRNA expression profiling using PCR Array was performed. Protein expression of relevant genes with western blot was studied. Levels of cytokines in cervicovaginal washes were estimated using a Luminex multiplex platform. RESULTS: All cases of cervical cancer were HR-HPV positive and predominant subtype was HPV16 (71.1%). Significant TLR4 upregulation and TLR2,7 downregulation were observed in HR-HPV infected cervix. TLR4,7 demonstrated low expression in CSCC. Molecules from cancer allied pathways; RELA, AKT, CDKN2A, and MDM2 demonstrated upregulation in CSCC. Protein expression data corroborated with gene expression profile. A diminished level of Th1 cytokines TNF-α, IFN-É£, IL-17, and IL-12 was observed in CSCC. Significantly increased levels of IL-1ß, IL-6 and IL-2 were detected in HR-HPV infected cervix. Kaplan Meier curve demonstrated high TLR4 and low TLR7 expression was associated with poor prognosis. CONCLUSION: The study demonstrates the HPV mediated dampening of the innate immune response in CSCC and provides support for exploring potential TLR2, 7 agonists as an adjunct therapy in CSCC patients.