COVID-19 and vitamin D (Co-VIVID study): a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Vitamin D levels have been reported to be associated with COVID-19 susceptibility, severity, and mortality events. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the use of vitamin D intervention on COVID-19 outcomes. AREAS COVERED: Literature search was conducted using PubMed, Cochrane library, and ClinicalTrials.gov databases. We included RCTs reporting the use of vitamin D intervention to control/placebo group in COVID-19. The study was registered at PROSPERO: CRD42021271461. EXPERT OPINION: A total of 6 RCTs with 551 COVID-19 patients were included. The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z = 2.33, p = 0.02, I2 = 48%). The rates of RT-CR positivity were significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = 0.46, 95% CI 0.24 to 0.89, Z = 2.31, p = 0.02, I2 = 0%). Conclusively, COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events, and RT-PCR positivity.

Maternal adropin levels in patients with gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Adropin is a regulatory protein with potential implications in energy homeostasis, glucose regulation, and insulin resistance. AIM: The aim of this meta-analysis was to compare the maternal serum/plasma adropin levels between gestational diabetes mellitus (GDM) patients and non-GDM controls. METHODS: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. A one-study leave-out sensitivity analysis and trimester-wise subgroup analysis were performed. RESULTS: A total of eight observations were included in this meta-analysis. The results based on random-effects meta-analysis indicated that adropin levels were significantly increased in GDM patients as compared to non-GDM controls (SMD = 2.41, 95% CI = 0.52-4.29, p= .01). The sensitivity analysis indicated that no single study had significantly influenced the overall outcome. CONCLUSIONS: The results indicate that maternal serum/plasma adropin concentrations were significantly higher in GDM patients as compared to non-GDM controls suggesting the potential associations of adropin in GDM. Despite this, further studies are needed to investigate the mechanistic, diagnostic and prognostic roles of trimester-wise adropin levels in GDM and associated fetal outcomes.

Effect of metformin intervention on circulating irisin levels in polycystic ovary syndrome: a systematic review and collaborative meta-analysis.

BACKGROUND: Irisin is an adipo-myokine with potential implications in metabolic disorders such as polycystic ovary syndrome (PCOS). Despite of a strong evidence showing increased irisin level in PCOS, there is no conclusive evidence on the effect of metformin intervention on circulatory irisin in PCOS. AIM: The aim of this meta-analysis was to compare the circulatory (serum/plasma) irisin levels before and after metformin intervention in subjects with PCOS. METHODS: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. A one-study leave-out sensitivity analysis was conducted to validate the overall obtained results. RESULTS: A total of five observations were included in this meta-analysis. The results based on random effects meta-analysis indicated that irisin levels were significantly decreased after metformin intervention as compared to the baseline pretreatment levels in PCOS (SMD: -1.00, 95% CI: -1.60 to -0.41, Z: 3.29, p = .001). The sensitivity analysis leaving-out a particular observation at a time and repeating the meta-analysis validated the robustness of the overall finding suggesting the significant effect of metformin treatment on irisin levels in PCOS. CONCLUSION: Circulating irisin levels were significantly decreased upon metformin intervention in PCOS patients. The higher pretreatment irisin levels in PCOS may recede once the altered metabolic state is restored upon metformin intervention. Well-designed randomized trials with large sample sizes are warranted to further substantiate the reported evidence reported and to establish the possible mechanisms.

Phase 2 non-randomised trial of secondary cytoreduction and hyperthermic intraperitoneal chemotherapy in recurrent platinum-sensitive ovarian cancer.

BACKGROUND: The role of secondary cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) is not clearly defined in recurrent platinum-sensitive ovarian cancer (PSOC). There is a paucity of studies on secondary cytoreduction with HIPEC in PSOC from developing countries like India. This study was done to assess the feasibility and safety of secondary cytoreduction and HIPEC in recurrent PSOC. METHODS: This was a prospective, non-randomised, open-label, phase 2 trial of secondary cytoreduction and HIPEC (Cisplatin 75 mg/m2 43°C over 60 minutes) in patients with recurrent platinum-sensitive epithelial carcinoma of ovary/fallopian tube/peritoneum done in a tertiary cancer centre from February 2016 to August 2019. The primary outcome was to assess the overall survival (OS) and the secondary outcomes were to assess the progression-free survival (PFS) and toxicity. RESULTS: Twenty-seven patients were screened and among them, 15 patients were included in this analysis with a median follow-up of 25 months. The mean cancer antigen (CA) 125 at the time of recurrence was 149 U/mL (range: 10-2,030 U/mL) and the median platinum-free interval was 21 months. The perioperative chemotherapy used was paclitaxel + carboplatin 53.3% (8/15), liposomal doxorubicin + carboplatin 40% (6/15) and none 6.5% (1/15). The median Peritoneal Carcinomatosis Index score was 8 (range: 3-25). The Clavien Dindo score was I, II and III in 6.7%, 26.7% and 13.3% patients, respectively. Recurrence was radiological and biochemical in 60% (9/15) and 7% (1/15), respectively. The most common site of recurrence was intra-abdominal (peritoneal). The median PFS and OS were 15 months (range: 0-34) and 26 months (range: 23-29), respectively. The grade 3 or 4 toxicity was 40%. CONCLUSION: Secondary cytoreduction with HIPEC is feasible and safe in recurrent PSOC. Conclusive evidence that secondary cytoreduction with HIPEC is essential awaits the results from ongoing randomised controlled trials.

Atypical Presentation of Fibrodysplasia Ossificans Progressiva: A Case Report and Review of Literature.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by widespread areas of abnormal bone formation in muscles, ligaments, tendons and joint capsules. Typically, the symptoms begin in the first decade of life with episodes of painful inflammatory soft tissue swellings. Gradually, there occurs restriction of motion at various joints, severely limiting the activities of daily living and the quality of life of such patients by the third decade of life. There is no definite cure available for the disease and the current treatment options target symptomatic and palliative management. We describe the case of a 10-year-old child who presented to our institute with a severe disability of upper limbs due to joint contractures along with several bony masses at various locations of the body but without having any prior complaints of painful soft tissue lesions or the characteristic flare-ups of the disease ever. Identification of typical soft tissue ossified masses in the specific anatomic pattern, along with the presence of short and malformed great toes helped us in reaching the diagnosis. Surgical procedures including biopsies should be strictly avoided in such patients to prevent triggering the development of more lesions, which occurred in our patient after inadvertent removal of the first swelling by an orthopaedic specialist.

High Expression of Three-Gene Signature Improves Prediction of Relapse-Free Survival in Estrogen Receptor-Positive and Node-Positive Breast Tumors.

The objective of the present study was to validate prognostic gene signature for estrogen receptor alpha-positive (ER03B1+) and lymph node (+) breast cancer for improved selection of patients for adjuvant therapy. In our previous study, we identified a group of seven genes (GATA3, NTN4, SLC7A8, ENPP1, MLPH, LAMB2, and PLAT) that show elevated messenger RNA (mRNA) expression levels in ERα (+) breast cancer patient samples. The prognostic values of these genes were evaluated using gene expression data from three public data sets of breast cancer patients (n = 395). Analysis of ERα (+) breast cancer cohort (n = 195) showed high expression of GATA3, NTN4, and MLPH genes significantly associated with longer relapse-free survival (RFS). Next cohort of ERα (+) and node (+) samples (n = 109) revealed high mRNA expression of GATA3, SLC7A8, and MLPH significantly associated with longer RFS. Multivariate analysis of combined three-gene signature for ERα (+) cohort, and ERα (+) and node (+) cohorts showed better hazard ratio than individual genes. The validated three-gene signature sets for ERα (+) cohort, and ERα (+) and node (+) cohort may have potential clinical utility since they demonstrated predictive and prognostic ability in three independent public data sets.

A review of global cancer burden: trends, challenges, strategies, and a role for surgeons.

Cancer is one of the leading causes of death worldwide. The global cancer burden (GCB) is expected to rise significantly and will disproportionately affect the less developed world (LDW). The aim of this review is to analyze the trends in GCB and describe the types, estimates, and causes of new cancer cases. The challenges and strategies associated with tackling this rising GCB are described in which surgeons can play a vital role.

A survey of the educational environment for oncologists as perceived by surgical oncology professionals in India.

BACKGROUND: The current educational environment may need enhancement to tackle the rising cancer burden in India. The aim of this study was to conduct a survey of Surgical Oncologists to identify their perceptions of the current state of Oncology education in India. METHODS: An Institutional Review Board approved questionnaire was developed to target the audience of the 2009 annual meeting of the Indian Association of Surgical Oncology in India. The survey collected demographic information and asked respondents to provide their opinions about Oncology education in India. RESULTS: A total of 205 out of 408 attendee's participated in the survey with a 42.7% response rate. The majority of respondents felt that Oncology education was poor to fair during medical school (75%), residency (56%) and for practicing physicians (71%). The majority of participants also felt that the quality of continuing medical education was poor and that minimal emphasis was placed on evidence based medicine. CONCLUSIONS: The results of our survey demonstrate that the majority of respondents feel that the current educational environment for Oncology in India should be enhanced. The study identified perceptions of several gaps and needs, which can be the targets for implementing measures to enhance the training of Oncology professionals.

Identification of gene expression signature in estrogen receptor positive breast carcinoma.

A significant group of patient with estrogen receptor (ER) α positive breast tumors fails to appreciably respond to endocrine therapy. An increased understanding of the molecular basis of estrogen-mediated signal transduction and resultant gene expression may lead to novel strategies for treating breast cancer. In this study, we sought to identify the dysregulated genes in breast tumors related to ERα status. Microarray analyses of 31 tumor samples showed 108 genes differentially expressed in ERα (+) and ERα (-) primary breast tumors. Further analyses of gene lists indicated that a significant number of dysregulated genes were involved in mRNA transcription and cellular differentiation. The majority of these genes were found to have promoter-binding sites for E74-like factor 5 (ELF5; 54.6% genes), E2F transcription factor 1 (E2F1; 22.2% genes), and nuclear transcription factor Y alpha (NFYA; 32.4% genes). Six candidate genes (NTN4, SLC7A8, MLPH, ENPP1, LAMB2, and PLAT) with differential expression were selected for further validation studies using RT-qPCR (76 clinical specimen) and immunohistochemistry (48 clinical specimen). Our studies indicate significant over-expression of all the six genes in ERα (+) breast tumors as compared to ERα (-) breast tumors. In vitro studies using T-47D breast cancer cell line confirmed the estrogen dependant expression of four of the above six genes (SLC7A8, ENPP1, LAMB2, and PLAT). Collectively, our study provides further insights into the molecular basis of estrogen-dependent breast cancer and identifies "candidate biomarkers" that could be useful for predicting endocrine responsiveness.