Robotic-assisted Versus Conventional Laparoscopic Hysterectomy for Benign Gynecological Conditions: A Systematic Review and Meta-analysis.

Background: Minimally invasive gynecologic surgery is safe and feasible procedure for benign gynaecological conditions with less morbidity. Objective: To determine the best approach in benign gynecology and establish superiority of robotic over conventional laparoscopic hysterectomy in terms of safety and effectiveness. Methods: Search strategy: Electronic databases: MEDLINE, Embase, CENTRAL (the Registry of Controlled Clinical Studies of the Cochrane Collaboration), Google scholar, Pubmed and Scopus were searched from 2010-2022. Selection criteria: All randomized controlled trials and quasi-randomised trials which compared robotic versus conventional laparoscopic hysterectomy were included to conduct this systematic review and meta-analysis to investigate compared to traditional approaches. Results: Only five RCTs (326 patients in total) comparing robotic and conventional laparoscopic hysterectomy were included after a comprehensive literature search. Results of our analysis showed no clear benefit in any of the two techniques in operating time, estimated blood loss, length of hospital stay and overall complications. Conclusion: This systematic review suggests no statistical difference in surgical and patient outcomes between robotic and conventional laparoscopic hysterectomy relating to OT, EBL, LOHS, overall complications, and survival.

Minimally invasive autopsy in the evaluation of fetal malformations and stillbirths: A feasibility study.

BACKGROUND: Minimally invasive autopsy (MIA) using post-mortem magnetic resonance imaging with ancillary investigations is reported as accurate as conventional autopsy. This study assesses MIA's feasibility and accuracy compared to conventional autopsy. METHOD: MIA and/or conventional autopsy were performed on malformed fetuses (14-20 weeks gestation) and stillbirths (>20 weeks gestation), with/without malformation. Concordance in diagnostic accuracy (95% confidence interval [CI]) and agreement (Kappa coefficient [k]) were assessed in malformed cases where both MIA and autopsy were conducted. RESULTS: We enrolled 200 cases, including 100 malformed fetuses (<20 weeks) and 100 stillbirths (with/without malformations). Concordance of 97.3% was observed between MIA and autopsy in 156 malformed cases. The overall diagnostic accuracy of MIA was 96.04%. CONCLUSION: While conventional autopsy remains the gold standard, MIA is feasible in tertiary care settings. It can be considered a potential alternative for post-mortem assessment, particularly in settings with limited facility of conventional autopsy and parental refusal.

Cervical Cancer Screening Coverage at Tertiary Care Institutes Across India.

OBJECTIVES: The 70% screening coverage target proposed in the global cervical cancer elimination strategy is not achieved even at tertiary centres in India. A situational analysis was done to assess the currently existing facilities and barriers in tertiary care institutes. METHODS: This cross sectional multicentric study was conducted from August to September 2021 in six tertiary care institutes across India. Women aged 30-49 years attending outpatient services (OPD) were invited for cervical screening. Women and health care professionals (HCPs) were administered structured questionnaires to assess knowledge, attitude and practices regarding cervical cancer screening services. RESULTS: Out of 6709 eligible women who attended OPD, 1666 (24.8%; range:19-57%) received screening. Availability of screening kits was limited to 10-25 Pap/HPV tests per day. Visual inspection with acetic acid (VIA) and HPV testing were offered only at certain centres. Colposcopy and treatment facilities were optimal at all centres. Knowledge, attitude and practices were analysed for 1800 women: 45.7% had heard of cervical cancer, 78.0% did not know that it is preventable, 75.8% never heard about screening. Common symptoms correctly identified included postmenopausal bleeding (4.8%), postcoital bleeding (5.7%), intermenstrual bleeding (5.8%) and vaginal discharge (12.4%). Risk factors were identified by minority: poor menstrual hygiene (6.6%), oral contraceptive pill use (6.4%), multiparity (4.4%), and HPV infection (3.0%). Out of 21, mean total knowledge score (MTKS) was 2.07± 2.67. Out of 317 HCPs, 96.5% knew that cervical cancer is caused by HPV infection, is preceded by premalignant stage, and that it is preventable by screening and treatment (80.1%). Knowledge about screening modalities was present in 87.4% for cytology, 75.1% for VIA, 68.8% for HPV test. MTKS of HCPs was 20.88±6.61 out of 32. CONCLUSION: Even at tertiary centres, limited availability of HPV tests, reluctance to implement VIA and lack of awareness among women remain the major barriers.

Pediatric Adrenocortical Neoplasms: A Study Comparing Three Histopathological Scoring Systems.

Adrenocortical neoplasms are rare in childhood. Their histopathological categorization into benign and malignant is often challenging, impacting further management. While the AFIP/Wieneke scoring system is widely used for the prognostic classification of these tumors, it has limitations. Few other tumor scoring systems have evolved over the past few years. These have been validated in adults but not yet in pediatric patients. We evaluated a cohort of pediatric adrenocortical neoplasms to assess the applicability of AFIP/Wieneke criteria and the recently introduced Helsinki score and reticulin algorithm in predicting clinical outcomes. A tumor was considered 'clinically aggressive' in the presence of any of the following: metastases, recurrence, progressive disease, or death due to disease. Cases without any such event were considered 'clinically good'. Event-free survival time was the duration from the date of clinical presentation to any post-operative adverse event. For overall survival analysis, the endpoint was either the last follow-up or death due to disease.Using ROC curve analysis, the obtained cut-off Helsinki score of 24 could stratify the cases into two prognostically relevant groups. Survival analysis showed significant differences in the event-free and overall survival of these two groups of patients, validating the proposed cut-off. None of the three histopathological scoring systems could predict an unfavorable outcome with 100% accuracy. All showed a sensitivity of ≥ 80%, with the reticulin algorithm achieving 100% sensitivity. The specificity and accuracy of the AFIP/Wieneke criteria were the lowest (62.5% and 73.08%, respectively). While the Helsinki score (at the cut-off score of 24) and the reticulin algorithm had similar accuracy rates (80.77%, and 80%, respectively), the specificity of the former was higher (81.25%) than the latter (68.75%). A separate analysis revealed that the Ki-67 index at a cut-off of 18% had a sensitivity of 80% and a specificity of 81.25% for predicting an unfavorable outcome.

Characteristics of Gut Microbiome After Traumatic Brain Injury.

BACKGROUND: Preclinical studies have reported significant changes in the gut microbiome after traumatic brain injury (TBI). We hypothesized that TBI induces the growth of Proteobacteria in the human gut. Our primary outcome was to study the profile of the human fecal microbiome after TBI and the secondary outcome was to identify colonization with colistin-resistant and multidrug-resistant pathogens. METHODS: Consecutive patients with moderate-severe TBI admitted to the neurotrauma-intensive care unit within 48 hours of injury were enrolled into this observational study. Samples from rectal swabs obtained on days 0, 3, and 7 after admission were assessed for microbial growth and antibiotic resistance. Demographic data and variables such as hypotension, blood transfusion, surgery, start of nasogastric feeding, use of antibiotics, length of hospital stay and mortality were noted. RESULTS: One hundred one patients were enrolled into this study; 57 (56.4%) underwent surgery, 80 (79.2%) required blood transfusion, 15 (14.9%) had an episode of hypotension, 37 (36.6%) received enteral feed within the first 3 days, and 79 (78.2%) received antibiotics. Rectal microbiological samples were collected from 101, 95, and 85 patients on days 0, 3, and 7, respectively. All organisms isolated at the 3 time-points belonged to the Proteobacteria phylum, with Enterobacteriaceae forming the largest group. Colistin-resistant organisms were found in 17 (16.8%) of 101 patients and multidrug-resistant organisms in 25 (64.1%) of the 39 patients in whom isolates were tested against the entire panel of antimicrobials. CONCLUSION: TBI is associated with widespread colonization with Proteobacteria as early as 48 hours after injury. Colonization with colistin and multidrug-resistant organisms highlights the importance of the judicious use of antibiotics.

Serum Matrix Metalloproteinase 7 as a Diagnostic and Prognostic Biomarker for Extrahepatic Biliary Atresia.

Background: Differentiation of neonatal cholestasis into neonatal hepatitis (NH) and extrahepatic biliary atresia (EHBA) is essential to formulate the treatment plan; promptness is indispensable for optimal outcomes. The clinical and nonoperative algorithms lack precision; the gold standard investigations (liver biopsy or per-operative cholangiogram) are invasive. There is a need for a noninvasive test which is both, sensitive and specific and has a high likelihood ratio. Aim: To study the (diagnostic) role of matrix metalloproteinase 7 (MMP-7) as a serum biomarker to differentiate between EHBA and NH and evaluate the prognostic significance in EHBA based on its correlation with liver histopathology and serological predictors of liver fibrosis - Aspartate-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4). Materials and Methods: This was a prospective study conducted upon patients of neonatal cholestasis presenting with acholic stools (n = 46) with equal number of controls (n = 45) with no liver pathology. Observational parametric included disease-specific workup and serum MMP-7 levels (all participants); liver biopsyl and APRI-FIB-4 (EHBA). Results: (Diagnostic) Serum MMP-7 levels were significantly elevated in EHBA (n = 25; 28 ng/mL) as compared to those in NH (n = 21; 1.88 ng/mL) and normal infants (n = 45; 1.2 ng/mL) (P < 0.001 for both). Serum cutoff at 4.99 ng/mL differentiated EHBA-NH with a high sensitivity (96%), specificity (90.5%), and a negative predictive value (95%), with the number needed to misdiagnose being 23. (Prognostic) Inflammatory activity and fibrosis-stage on liver histopathology (METAVIR-and-Ishak scores) correlated with MMP-7 levels. APRI and FIB-4 scores also depicted a strong correlation with each other, age of the patient, and liver fibrosis. Conclusions: MMP-7 has a diagnostic value in differentiating EHBA from NH and may also be used as a prognostic biomarker in the follow-up of these patients. MMP-7 levels in controls may be used as a baseline for future studies.

Adrenocortical Neoplasms in Children: Treatment and Outcomes.

Background: Adrenocortical tumors are rare tumors in children with a paucity of outcome data, especially in a resource-challenged setting. Materials and Methods: A retrospective study was conducted to evaluate the presentation, management, and outcomes of children with adrenocortical tumors who presented to our institute from January 1992 to December 2019. Results: During the study period, 28 children were included. Adenoma was present in nine children and the remaining 19 children had adrenocortical carcinoma. The median age of presentation was 48 months. Nearly half of the children with carcinomas presented with a mass compared to only 10% adenomas (P = 0.049). Virilization was present in 60% of the patients and in most cases was associated with Cushingoid features. Three children (15.7%) had metastasis at presentation. All children underwent surgical excision with a spill in 6 and gross residue in two patients. Recurrence was observed in five patients after a mean duration of 11.8 months. The 4-year overall survival and event-free survival were 100% in patients with adenomas compared to 75% and 44%, respectively, in carcinoma. Children who underwent complete surgical excision without any spill had a relatively favorable outcome. Conclusion: Adrenocortical tumors are uncommon tumors in children. Adenomas have a favorable outcome. There was no disease-free survival in incompletely resected or metastatic tumors. Tumor spill may also have an adverse outcome in completely resected tumors.

Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial).

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).

Cervical Cancer Screening and Associated Barriers among Women in India: A Generalized Structural Equation Modeling Approach.

Exploring the barriers and facilitators of cervical cancer screening (CCS) is essential to reduce the incidence and mortality, particularly in low and middle-income countries. The present study investigates the direct, indirect, and total effects of the barriers and facilitators on CCS in India through the generalized structural equation modeling using data from women files of the fourth round of the National Family Health Survey (NFHS-4). Generalized structural equation models were used to quantify the hypothetical pathway via fitting a series of regression equations. Age, body mass index, religion, years of schooling, awareness of sexually transmitted infection, contraception use, lifetime number of sex partners, number of children, and wealth index were shown to have significant direct effects on the CCS. Older women had 1.16 times the odds of getting screened for cervical cancer as compared to their younger counterpart. The odds of CCS among the women in richest wealth quintile is 2.50 times compared to the poorest. Those who are aware of STIs have 1.39 times the odds of getting screened for cervical cancer. Wealth index, years of schooling, and religion have a substantial indirect and total impact on the CCS. The findings will aid in policy formulations for enhancing the CCS in India.

Role of shear wave elastography as an adjunct to axillary ultrasonography in predicting nodal metastasis in breast cancer patients with suspicious nodes.

OBJECTIVE: To evaluate the role of shear wave elastography (SWE) of suspicious axillary lymph nodes and its combination with B-mode USG in predicting nodal metastasis in breast cancer patients. METHODS: Prospective observational study was performed from June 2018 to August 2020 on breast cancer patients with suspicious axillary nodes on USG. B-mode features (cortical thickness, effacement of fatty hilum, non-hilar blood flow and round shape) and SWE parameters (Emax, Emin, Emean and ESD) of the node with the thickest cortex were evaluated. Diagnostic performances of USG, SWE and their combination were estimated using pathological status of the node on biopsy as the gold standard. RESULTS: Of the 54 patients evaluated, optimal elasticity maps were obtained in 49 nodes of 49 patients (mean age, 46.3 ± 12.1 years; 48/49 (98%) females). On biopsy, 38 nodes (77.6%) had metastasis, while 11 (22.4%) had reactive hyperplasia. Emax, Emin, Emean and ESD of both cortex and hilum were significantly higher in metastatic than reactive nodes. Emax (cortex) ≥14.9 kPa had the best diagnostic performance (sensitivity, 73.7%; specificity, 81.8%). Cortical thickness ≥6.7 mm had the best diagnostic performance among B-mode features (sensitivity, 89.5%; specificity, 72.7%). Combining cortical thickness with effacement of fatty hilum and/or non-hilar blood flow yielded sensitivity of 89.5% and specificity of 90.9%. Addition of Emax (cortex) to cortical thickness and combination of ≥2 B-mode features increased their specificities to 90.9 and 100%, respectively. CONCLUSIONS: Metastatic axillary nodes are stiffer than reactive nodes on SWE in breast cancer patients. Emax (cortex) has the best diagnostic performance in differentiating between reactive hyperplasia and nodal metastasis. Combination of Emax (cortex) and cortical thickness increases the specificity for diagnosing metastasis, especially in nodes showing only cortical thickening. ADVANCES IN KNOWLEDGE: Combination of SWE and B-mode USG is highly specific for differentiating metastasis from reactive hyperplasia in suspicious nodes of breast carcinoma patients, especially in nodes with only cortical thickening.

Impact of COVID-19 pandemic on pediatric cardiac services in India.

BACKGROUND: COVID-19 pandemic has disrupted pediatric cardiac services across the globe. Limited data are available on the impact of COVID.19 on pediatric cardiac care in India. AIMS: The aims are to study the impact of COVID-19 pandemic on the care of children with heart disease in India in terms of number of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries. SETTINGS AND DESIGN: This is a retrospective, multicentric, observational study. METHODS: We collected monthly data on the number and characteristics of outpatient visits, hospitalizations, catheter-based interventions, and cardiac surgeries and major hospital statistics, over a period of 5 months (April to August 2020), which coincided with the first wave of COVID-19 pandemic in India and compared it with data from the corresponding months in 2019. RESULTS: The outpatient visits across the 24 participating pediatric cardiac centers decreased by 74.5% in 2020 (n = 13,878) as compared to the corresponding period in 2019 (n = 54,213). The reduction in the number of hospitalizations, cardiac surgeries, and catheterization procedures was 66.8%, 73.0%, and 74.3%, respectively. The reduction in hospitalization was relatively less pronounced among neonates as compared to infants/children (47.6% vs. 70.1% reduction) and for emergency surgeries as compared to elective indications (27.8% vs. 79.2%). The overall in-hospital mortality was higher in 2020 (8.1%) as compared to 2019 (4.8%), with a higher postoperative mortality (9.1% vs. 4.3%). CONCLUSIONS: The current COVID-19 pandemic significantly impacted the delivery of pediatric cardiac care across India with two-third reduction in hospitalizations and cardiac surgeries. In an already resource-constrained environment, the impact of such a massive reduction in the number of surgeries could be significant over the coming years. These findings may prove useful in formulating strategy to manage subsequent waves of ongoing COVID-19 pandemic.

Outcome of COVID-19-positive children with heart disease and grown-ups with congenital heart disease: A multicentric study from India.

BACKGROUND: Outcome data of children with heart disease who acquired COVID-19 infection are limited. AIMS: We sought to analyze outcome data and identify risk factors associated with mortality in children with heart disease and grown-ups with congenital heart disease (GUCH) who had a laboratory-confirmed COVID-19 infection. SETTINGS AND DESIGN: This is a retrospective, multicentric, observational study. MATERIALS AND METHODS: The study included children with heart disease and GUCH population, who presented with either symptomatic or asymptomatic COVID-19 infection to any of the participating centers. COVID-19-negative patients admitted to these centers constituted the control group. RESULTS: From 24 pediatric cardiac centers across India, we included 94 patients with a median age of 12.5 (interquartile range 3-96) months and 49 (52.1%) patients were males. Majority (83 patients, 88.3%) were children. One-third of the patients (n = 31, 33.0%) had acyanotic congenital heart disease, and 41.5% (n = 39) were cyanotic, with > 80% of the patients being unoperated. Only 30 (31.9%) patients were symptomatic for COVID-19 infection, while the rest were incidentally detected positive on screening. A total of 13 patients died (case fatality rate: 13.8%). The in-hospital mortality rate among hospitalized patients was significantly higher among COVID-19-positive cases (13 of 48; 27.1%) as compared to COVID-negative admissions (9.2%) during the study period (P < 0.001). On multivariate analysis, the independent predictors of mortality among COVID-19-positive cases were severity of illness at admission (odds ratio [OR]: 535.7, 95% confidence interval [CI]: 6.9-41,605, P = 0.005) and lower socioeconomic class (OR: 29.5, 95% CI: 1.1-814.7, P = 0.046). CONCLUSIONS: Children with heart disease are at a higher risk of death when they acquire COVID-19 infection. Systematic preventive measures and management strategies are needed for improving the outcomes.

Axillary ultrasonography combined with pre-operative wire localisation of clipped node in nodal restaging after neoadjuvant chemotherapy in node positive breast cancer patients: a pilot study.

OBJECTIVE: To evaluate the role of axillary ultrasonography (axUS) and ultrasound-guided pre-operative wire localisation of pre-treatment positive clipped node (CN) for prediction of nodal response to neoadjuvant chemotherapy (NACT) in node positive breast carcinoma patients. METHODS AND MATERIALS: A prospective study was conducted between June 2018 and August 2020 after Ethics Committee approval. Breast carcinoma patients (cT1-cT4b) with palpable axillary nodes (cN1-cN3) and suitable for NACT were recruited after written informed consent. Single, most suspicious node was biopsied and clipped. Nodal response to NACT was assessed on axUS. Wire localisation of CN was performed prior to axillary lymph node dissection (ALND). Diagnostic performances of axUS and CN excision were assessed. RESULTS: Of the 69 patients evaluated, 32 patients (mean age, 43.5 ± 11.8 years; females, 31/32 [97%]; pre-menopausal, 18/32 [56.3%]) with metastatic nodes who received NACT were included. Nodal pathological complete response rate was 34.4% (11/32) overall and 70% (7/10) in patients with ≤2 suspicious nodes on pre-NACT axUS. False-negative rates (FNRs) of axUS and CN excision were 4.8% and 28.6% respectively. Combination of post-NACT axUS and CN excision had an FNR of 4.8% overall and 0% in patients with ≤2 suspicious nodes on pre-NACT axUS. CONCLUSION: Combination of AxUS and ultrasound-guided wire localisation of pre-treatment positive CN has high diagnostic accuracy for nodal restaging after NACT in node positive breast cancer patients. ADVANCES IN KNOWLEDGE: Addition of axUS assessment to wire localisation of CN reduces its FNR for detecting residual metastasis after NACT.

Intraobserver and interobserver variations in cortical transit time measurement in children with pelviureteric junction obstruction.

Cortical transit time (CTT) has recently been shown to be a useful parameter in the management of children with pelviureteric junction obstruction (PUJO). The aim of this study was to assess intraobserver and interobserver variations in the qualitative and quantitative assessment of CTT in children with PUJO. A retrospective study was performed, and 99mTc-MAG3 renogram images of all children with PUJO performed from January 2016 to December 2017 were retrieved. The images were assessed by three observers at two different time points. CTT was qualified as delayed if CTT was more than 3 min else; it was noted as normal. The intraobserver and interobserver variations in the results of the CTT of the normal kidney and affected kidney both before and after surgery were studied. The kappa statistic was used to compare the interobserver variation of qualitative interpretation of CTT. The Bland-Altman plot was used to evaluate the intraobserver and interobserver variations of the quantitative interpretation of CTT. A total of 57 99mTc-MAG3 renal scintigraphies were evaluated. Overall, 114 renal units were evaluated with 51 normal renal units and 63 renal units with PUJO. Of these, 63 renal units with PUJO, 31 renal units had been operated upon, whereas the remaining 32 renal units had no intervention at the time of the study. The kappa statistic in the normal, affected operated, and affected unoperated kidneys was interpreted as almost perfect, substantial to almost perfect, and moderate to substantial level of agreement, respectively. The Bland-Altman plot revealed a large mean difference and wide 95% limits of agreement in affected kidneys (both operated and unoperated). The study concludes that the qualitative CTT interpretation in the affected renal unit which is most commonly used in recent studies is a reliable and reproducible parameter in children with PUJO. The quantitative measurement had wide inter- and intraobserver variation for clinical use.

The association of Candida and antifungal therapy with pro-inflammatory cytokines in oral leukoplakia.

OBJECTIVES: To study the association of Candida and antifungal therapy with pro-inflammatory cytokines (PIC) in oral leukoplakia (OL). MATERIALS AND METHODS: A prospective observational study where immunocompetent adult subjects with OL (30 homogenous (HL), 30 non-homogenous (NHL)) and 30 age and sex-matched healthy controls (C) with no predisposing factors for oral Candida infection were recruited. Sterile cotton swabs and ophthalmic sponges were used to sample the lesion surface in OL and buccal mucosa in C, for direct microscopy and culture for Candida and to determine levels of PIC (IL-6, IL-8. IL-17, TNF-α) by ELISA, respectively. Sampling for PIC was repeated at same sites in OL, 2 weeks after antifungal therapy. RESULTS: Candida was associated with 55.3% of NHL, 23.3% of HL and 13.3% of C. The oral secretary levels of PIC were raised in NHL as compared to HL and C. The levels of IL-6, IL-8, TNF-α (p<0.001) and IL-17 (p<0.01) were significantly raised in Candida positive NHL while IL-6 (p<0.05) and TNF-α (p<0.01) were significantly raised in Candida positive HL before antifungal treatment. After antifungal treatment, there was significant reduction in PIC in Candida positive NHL and HL. CONCLUSIONS: Candida infection contributes to the inflammatory milieu in Candida associated OL which increases the risk of carcinogenesis. Antifungal therapy reduces the PIC in Candida associated OL. CLINICAL RELEVANCE: Identification and elimination of predisposing factors for Candida infection, like cessation of harmful habits, maintenance of oral/denture hygiene, surveillance for Candida and antifungal therapy at intervals, are recommended in OL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04712929.

Therapeutic implications of candida phenotypes, virulence factors and antifungal sensitivity in Oral leukoplakia.

OBJECTIVES: To determine the association of Candida phenotypes, virulence factors, antifungal sensitivity and clinical response to Fluconazole in Oral leukoplakia (OL). METHODS: Sterile swabs were obtained from oral lesions in immunocompetent subjects [30 Homogenous (HOL), 31 Non- Homogenous (NHOL] and normal buccal mucosa in 30 age and sex-matched healthy controls (C). Candida phenotypes, virulence factors (Secreted Aspartyl Proteinase (SAP), Phospholipase (PL), Biofilm formation (BF) and antifungal sensitivity were determined. Clinical features (Size, Erythema, thickness, oral burning sensation (VAS scores) before and after Fluconazole therapy in OL were recorded by two calibrated observers. RESULTS: Candida was associated with OL (p â€‹< â€‹0.01). Candida albicans was the most common phenotype sensitive to Fluconazole. SAP, PL and BF activity was significantly high in NHOL. Strong positive correlation was seen between SAP, and PL activity and pre-treatment VAS scores in NHOL. There was significant reduction in VAS scores, size of lesion [HOL (p â€‹< â€‹0.001) NHOL (p â€‹< â€‹0.05)], erythematous areas (67.8%) in NHOL and thickness of lesions (42.6%) in both types OL after Fluconazole therapy with substantial inter-observer agreement. Non albicans candida (NAC) species had similar virulence profiles but resistant to Fluconazole and showed minimal clinical improvement. CONCLUSIONS: Virulence activity of Candida in OL increases severity of lesions. Fluconazole is effective against virulent Candida albicans, causes clinical improvement and down-staging from high -risk NHOL to low-risk HOL which can reduce risk of malignant transformation. Detection of highly virulent NAC infection and antifungal sensitivity is recommended in OL recalcitrant to Fluconazole therapy.

Spirometry-based prevalence of chronic obstructive pulmonary disease & associated factors among community-dwelling rural elderly.

Background & objectives: Chronic obstructive pulmonary disease (COPD) is a major public health problem in India. Its magnitude is particularly high among the elderly. Old age and comorbidity may lead to misdiagnosis and under treatment of this condition. COPD is not curable; however, various forms of treatment can help control symptoms and improve the quality of life. Most of the earlier studies lacked uniformity in definitions, designs, methodology and reporting techniques. Studies based on spirometry are only a few. Understanding the current prevalence and associated factors of COPD is important for planning control strategies. Hence, this study was conducted to determine the prevalence of COPD and associated factors among the elderly. Methods: In this community-based study among 449 elderly persons in a rural area, information regarding socio-demographic details, selected health conditions and exposure to risk factors was recorded. The assessment of airway obstruction was done by using a portable spirometer (MIR Spirolab). The diagnosis of COPD was based on the GOLD criteria. The association of COPD with sociodemographic and other variables was analysed by the multivariate logistic regression. Results: Acceptable spirometry findings were available for 392 (87.3%) participants. The prevalence of COPD was 42.9 per cent (95% confidence interval 37.9-47.7%). The prevalence was 54.5 per cent among men and 33.4 per cent among women. Smoking, higher age group and low body mass index were significantly associated with COPD. Interpretation & conclusions: The prevalence of COPD was found to be high among the rural elderly in this study. Interventions aimed at cessation of smoking and preparedness of health systems for diagnosis and management of COPD are hence required.

Clinico-pathological and molecular characterization of diffuse midline gliomas: is there a prognostic significance?

PURPOSE: H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages. METHODS: One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed. RESULTS: DMGs comprised 5.3% of all gliomas with 49.2% H3K27M mutant and 50.8% wild types. Majority (75.68%) of pediatric and 38.20% of adults were H3K27M mutant (p = 0.0001). Amongst H3K27M mutants, brainstem (46.43%) was the commonest location in pediatric and thalamus (61.76%) in adults. H3K27M mutation was mutually exclusive with IDH mutation in 93.55%, while p53, ATRX mutation were seen in 56.4% and 30.6% cases respectively. Software-based immunohistochemistry evaluation (H-scoring) showed 99.2% concordance with sequencing for H3K27M mutation. Radiologically, no significant difference in contrast enhancement was seen between mutant and wild types (p = 0.05). The difference in overall survival (OS) was not significant in mutant versus wild types, with age or location. Tumor resection independently and on correlation with H3K27M did not influence OS (p = 0.51 and p = 0.47). Adjuvant therapy impacted survival significantly in adults (p = 0.0009), however, not in pediatric cases (p = 0.06). CONCLUSIONS: The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.

Indian experience of AUS/FLUS diagnosis: is it different from rest of Asia and the West?-A systematic review and meta-analysis.

BACKGROUND: Atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is the most heterogeneous subcategory of the Bethesda system for thyroid cytopathology with laid down permissible limits of frequency and risk of malignancy (ROM). Due to differences in thyroid clinical practice worldwide, variations have been found in frequency, resection rates (RR) and ROM. Therefore, this systematic review and meta-analysis of AUS/FLUS across different regions was conducted and comparison of data from India was done with the rest of Asia and the West. METHODS: We searched PubMed and Google search engines from January 2009-Dec 2019 using terms "AUS Thyroid" and "FLUS Thyroid". Meta-analysis was performed using DerSimonian-Laird method and 95% confidence intervals were calculated using random effects model. Independent samples t-test was used to compare frequency, RR, and ROM of AUS/FLUS between India, rest of Asia and the West. RESULTS: Out of 15,000 studies on internet, 60 (18 Indian, 12 Asian and 30 Western) were included. Total aspirates were 201,657; 14,279 Indian, 62,448 Asian, 124,930 Western. Pooled estimates were: frequency 7.3% (6.3-8.3%), RR 41.9% (37.4-46.6%), ROM 33.3% (26.8-39.9%). Pooled prevalence of rate did not vary significantly across the three regions. Pooled prevalence of RR was highest in India (52.9%) and lowest in rest of Asia (26.5%); of ROM was highest in Asia (45.9%), lowest in the West (26.3%) (P<0.01). Statistical analysis demonstrated publication bias, limited to Indian and Western studies. Papillary thyroid carcinoma was the most common surgical diagnosis (87.9%; 1,082/1,231). CONCLUSIONS: This meta-analysis showed differences in thyroid clinical practice followed in India, rest of Asia and the West. Although pooled prevalence of rate of AUS/FLUS was similar across the three, pooled RR and ROM varied. AUS/FLUS nodules were more frequently resected in Indian and Western studies than in rest of Asia. ROM was higher than recommended values in all three areas, being intermediate for India.