Favipiravir for treating COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19. OBJECTIVES: To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023. SELECTION CRITERIA: We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.

Therapeutic mammoplasty: a "wise" oncoplastic choice-lessons from the largest single-center cohort from Asia.

Introduction: The majority of breast cancer patients from India usually present with advanced disease, limiting the scope of breast conservation surgery. Therapeutic mammoplasty (TM), an oncoplastic technique that permits larger excisions, is quite promising in such a scenario and well suited to breast cancer in medium-to-large-sized breasts with ptosis and in some cases of large or multifocal/multicentric tumors. Here, we describe our TM cohort of 205 (194 malignant and 11 benign) patients from 2012 to 2019 treated at a single surgeon center in India, the largest Asian dataset for TM. Methods: All patients underwent treatment after careful discussions by a multidisciplinary tumor board and patient counseling. We report the clinicopathological profiles and surgical, oncological, cosmetic, and patient-related outcomes with different TM procedures. Results: The median age of breast cancer patients was 49 years; that of benign disease patients was 41 years. The breast cancer cohort underwent simple (n = 84), complex (n = 71), or extreme (n = 44) TM surgeries. All resection margins were analyzed through intra-operative frozen-section assessment with stringent rad-path analysis protocols. The margin positivity rate was found to be 1.4%. A majority of the cohort was observed to have pT1-pT2 tumors, and the median resection volume was 180 cc. Low post-operative complication rates and good-to-excellent cosmetic scores were observed. The median follow-up was 39 months. We observed 2.07% local and 5.7% distal recurrences, and disease-specific mortality was 3.1%. At median follow-up, the overall survival was observed to be 95.9%, and disease-free survival was found to be 92.2%. The patient-reported outcome measures (PROMs) showed good-to-excellent scores for all types of TMs across BREAST-Q domains. Conclusion: We conclude that in India, a country where women present with large and locally advanced tumors, TM safely expands the indications for breast conservation surgery. Our results show oncological and cosmetic outcomes at acceptable levels. Most importantly, PROM scores suggest improved overall wellbeing and better satisfaction with the quality of life. For patients with macromastia, this technique not only focuses on cancer but also improves self-image and reduces associated physical discomfort often overlooked by women in the Indian setting. The popularization of this procedure will enable Indian patients with breast cancer to receive the benefits of breast conservation.

Evaluation of Remdesivir to the outcomes of hospitalized patients with COVID-19 infection in a tertiary-care hospital in southern India.

INTRODUCTION: Remdesivir was the only antiviral used in the treatment of COVID-19 in the first wave of the COVID-19 pandemic, following the adaptive COVID-19 treatment trial-1 interim analysis report. However, its use in moderate to critical hospitalized COVID-19 patients continues to be controversial. METHODOLOGY: In a cohort of 1,531 moderate to critical COVID-19 patients, we retrospectively performed a nested case-control study where 515 patients on Remdesivir were compared to 411 patients with no Remdesivir. Cases and controls were matched for age, sex and severity. The primary outcome was in-hospital mortality and secondary outcomes were duration of hospital stay, need for intensive care unit (ICU), progression to oxygen therapy, progression to non-invasive ventilation, progression to mechanical ventilation, and duration of ventilation. RESULTS: Mean age of the cohort was 57.05 + 13.5 years. 75.92% were males. Overall, in-hospital mortality was 22.46% (n = 208). There was no statistically significant difference in all-cause mortality among cases and controls (20.78% vs. 24.57%, p = 0.17). Progression to non-invasive ventilation was lower in the Remdesivir group (13.6% vs 23.7%, p < 0.001), however progression to mechanical ventilation was higher in the Remdesivir group (11.3% vs 2.7%, p value < 0.001*). In a subgroup analysis of critically ill patients, the use of Remdesivir lowered mortality (OR 0.32 95% CI: 0.13 - 0.75). CONCLUSIONS: Remdesivir did not decrease the in-hospital mortality in moderate to severe COVID-19 but decreased progression to non-invasive ventilation. Its mortality benefit in critically ill patients needs further evaluation. Remdesivir may be useful if given early in the treatment of patients with moderate COVID-19.

Proceedings of the 3rd Indian Cancer Genome Atlas Conference 2022: Biobanking to Omics: Collecting the Global Experience.

On January 13th and 14th 2022, the Center for Translational Cancer Research organized the virtual third Indian Cancer Genome Atlas (ICGA) Conference 2022 "Biobanking to Omics - Collecting the Global Experience." This conference was planned as the steppingstone to help ICGA understand the road ahead and the probable roadblocks in its preparatory phase as ICGA begins to streamline the tumor tissue biobanking and multi-omics efforts in the Indian subcontinent. The first day of the conference was dedicated to updates on the current status of ICGA, the future prospect, and the global understanding of multi-omics efforts. The key highlights included two keynote speeches by Dr Wui Jin Koh, Senior Vice President and Chief Medical Office, National Comprehensive Cancer Network, and by Dr Christina Curtis, Associate Professor, Stanford University School of Medicine. The first day ended with an intriguing panel discussion on "ICGA updates and Future Steps." The second day focused on biobanking practices across the globe and several aspects of biobank setup such as infrastructure, maintenance, quality control, patient consent, and lessons learned from established biobanking setups. The talk by Rosita Kammler, Head, Translational Research Coordination, International Breast Cancer Study Group, Switzerland, and Ruhul Amin, Director, Bangladesh Medical Research Council were the key highlights. The second day also ended with an engaging panel discussion on "Tumor tissue biobanking - national and international perspectives." Overall, the conference was well received and had good attendance from national and international students, researchers, and faculty from academia as well as industry.

Zinc transporter LIV1: A promising cell surface target for triple negative breast cancer.

Breast cancer is one of the leading causes contributing to the global cancer burden. The triple negative breast cancer (TNBC) molecular subtype accounts for the most aggressive type. Despite progression in therapeutic options and prognosis in breast cancer treatment options, there remains a high rate of distant relapse. With advancements in understanding the role of zinc and zinc carriers in the prognosis and treatment of the disease, the scope of precision treatment/targeted therapy has been expanded. Zinc levels and zinc transporters play a vital role in maintaining cellular homeostasis, tumor surveillance, apoptosis, and immune function. This review focuses on the zinc transporter, LIV1, as an essential target for breast cancer prognosis and emerging treatment options. Previous studies give an insight into the role of LIV1 in fulfilling the most important hallmarks of cancer such as apoptosis, metastasis, invasion, and evading the immune system. Normal tissue expression of LIV1 is limited. Higher expression of LIV1 has been linked to Epithelial-Mesenchymal Transition, histological grade of cancer, and early node metastasis. LIV1 was found to be one of the attractive targets in the therapeutic hunt for TNBCs. TNBCs are an immunogenic breast cancer subtype. As zinc transporters are known to serve as the metabolic gatekeepers of immune cells, this review bridges tumor infiltrating lymphocytes, TNBC and LIV1. In addition, the suitability of LIV1 as an antibody-drug conjugate (Seattle genetics [SGN]-LIV1A) target in TNBC, represents a promising strategy for patients. Early clinical trial results reveal that this novel agent reduces tumor burden by inducing mitotic arrest, immunomodulation, and immunogenic cell death, warranting further investigation of SGN-LIV1A in combination with immuno-oncology agents. Priming the patient's immune response in combination with SGN-LIV1A could eventually change the landscape for the TNBC patient population.

Prediction of land use/cover change in the Bharathapuzha river basin, India using geospatial techniques.

The Bharathapuzha river basin, once endowed with dense vegetation and abundant water, has been experiencing acute water shortage and extreme climatic conditions in recent times. To understand the influence of human interventions on the natural environmental conditions, including the problems mentioned above, it is essential to critically examine the changes in land use/cover over these years. The objective of this study is to assess land use/cover change in the Bharathapuzha river basin, Kerala during the period 1990-2017 using LANDSAT series satellite images. The dynamics of land use/cover change were quantified and mapped using geospatial techniques. The multi-temporal LANDSAT images were classified by supervised maximum likelihood method to generate the corresponding land use/cover maps; changes in land use/cover in the river basin were subsequently detected by the post-classification technique. Results of the study revealed a drastic change in land use/cover in the period 1990-2017; the primary causes of this were deforestation and urbanization. The near- and long-term future land use/cover maps of the basin for 2020 and 2035 were generated from the historically retrieved land use/cover change pattern. Multi-Layer Perceptron Neural Network and Markov chain techniques were used to generate future land use/cover maps. These maps reveal that the predominant land use/cover class in the basin will be barren land and about 46.13% of the existing (in 2017) dense vegetation will diminish by 2035. The efficiency of sustainable watershed management activities in the river basin can be improved based on the critical observations from this study.

Correction: Tailoring of optical properties of fluorescein using green synthesized gold nanoparticles.

Correction for 'Tailoring of optical properties of fluorescein using green synthesized gold nanoparticles' by Jisha John et al., Phys. Chem. Chem. Phys., 2015, 17, 15813-15821.

Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab.

The incidence of cytomegalovirus (CMV) reactivation/disease after autologous stem cell transplant (ASCT) is much lower than that after allogeneic stem cell transplantation. With the recent use of rituximab during cancer chemotherapy or conditioning regimens prior to transplantation, there has been an increasing concern of opportunistic infections including CMV. In the present study, we reviewed the patients undergoing ASCT from December 2007 to December 2013 to identify those developing CMV reactivation/disease. Out of the 978 patients who underwent ASCT at the Karmanos Cancer Institute, 239 patients were tested for symptomatic CMV reactivation based on clinical suspicion. Of the tested patients, 7/239 (2.9 %) were documented to have CMV reactivation within 90 days of ASCT. The median time to develop CMV viremia was 32 days from transplantation. Of the 239 patients tested, CMV viremia was detected in 3 out of 72 patients who received rituximab as compared to 4 out of 167 patients who did not. Three of these seven viremic patients were treated with anti-viral drugs; viremia resolved in all patients at a median of 24 days. Three patients were found to develop other bacterial and/or fungal infections following CMV viremia. Two of the seven patients died during 1-year follow-up, due to primary disease progression or Candida sepsis. None of the patients developed proven tissue-invasive CMV disease. The study did not evaluate the incidence of asymptomatic CMV infection/reactivation. Despite prior publications based on limited data, rituximab does not appear to contribute to an increased frequency of symptomatic CMV reactivation following ASCT.

Tailoring of optical properties of fluorescein using green synthesized gold nanoparticles.

Dye-nanoparticle mixtures hold great promise in biological as well as photonics applications due to their capability to tailor the emission behavior of dye by tuning the nanoparticles parameters. However, as compared to the well-defined dye-nanoparticle distance, studies lack the understanding of homogenous mixtures of dye and nanoparticles. In this work, we investigate the influence of shape and concentration of gold nanoparticles prepared via green synthesis on the optical properties of fluorescein dye in a dye-nanoparticle mixture. We have investigated the radiative path of deexcitation using steady state fluorescence and the non-radiative path is probed using a laser based dual-beam thermal lens technique. The energy transfer efficiency as well as dye-nanoparticle distance is studied using both techniques. Furthermore, we have explored the influence of nanoparticles parameters on the fluorescence quantum yield of fluorescein using the thermal lens technique. The studies indicate that spherical nanoparticles are efficient quenchers while star shaped nanoparticles can probe larger dye-NP distances. The tailoring of dye properties by tuning nanoparticle parameters can be utilized in diverse areas including bioimaging, solar cells, and sensors.

Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies.

BACKGROUND: Diabetes and vitamin D deficiency are global epidemics. Researchers have long been exploring the role of potentially modifiable factors to manage type 2 diabetes. We conducted a systematic review of prospective studies and randomized controlled trials that involved vitamin D supplementation and specifically intended to study glycemic outcomes related to type 2 diabetes. METHODS: Two authors independently searched Medline and PubMed for longitudinal studies that had assessed the effect of vitamin D supplements on glycemic control, insulin resistance and beta-cell dysfunction in patients with diabetes. RESULTS: Seventeen randomized control trials and seven longitudinal studies with a minimum follow-up of one month were included. Results of the various short-term studies (follow up ≤ 3 months) suggested that vitamin D supplementation had a positive impact on glycemic control and metabolic parameters such as insulin resistance and beta cell dysfunction. However, the evidence was weak due to the low methodological quality of the studies. There was no significant effect on HbA1c, beta cell function and insulin resistance in the long-term studies (follow up > 3 months). There existed heterogeneity in the methodology of the studies, inclusion criteria, mode of supplementation of vitamin D and the duration of follow up. CONCLUSIONS: Current evidence based on randomized controlled trials and longitudinal studies do not support the notion that vitamin D supplementation can improve hyperglycemia, beta cell secretion or insulin sensitivity in patients with type 2 diabetes. Large-scale trials with proper study design, optimal vitamin D supplementation and longer follow up need to be conducted.