Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. Adding perioperative immunotherapy may improve outcomes. METHODS: In this phase 3, open-label, randomized trial, we assigned, in a 1:1 ratio, cisplatin-eligible patients with muscle-invasive bladder cancer to receive neoadjuvant durvalumab plus gemcitabine-cisplatin every 3 weeks for four cycles, followed by radical cystectomy and adjuvant durvalumab every 4 weeks for eight cycles (durvalumab group), or to receive neoadjuvant gemcitabine-cisplatin followed by radical cystectomy alone (comparison group). Event-free survival was one of two primary end points. Overall survival was the key secondary end point. RESULTS: In total, 533 patients were assigned to the durvalumab group and 530 to the comparison group. The estimated event-free survival at 24 months was 67.8% (95% confidence interval [CI], 63.6 to 71.7) in the durvalumab group and 59.8% (95% CI, 55.4 to 64.0) in the comparison group (hazard ratio for progression, recurrence, not undergoing radical cystectomy, or death from any cause, 0.68; 95% CI, 0.56 to 0.82; P<0.001 by stratified log-rank test). The estimated overall survival at 24 months was 82.2% (95% CI, 78.7 to 85.2) in the durvalumab group and 75.2% (95% CI, 71.3 to 78.8) in the comparison group (hazard ratio for death, 0.75; 95% CI, 0.59 to 0.93; P = 0.01 by stratified log-rank test). Treatment-related adverse events of grade 3 or 4 in severity occurred in 40.6% of the patients in the durvalumab group and in 40.9% of those in the comparison group; treatment-related adverse events leading to death occurred in 0.6% in each group. Radical cystectomy was performed in 88.0% of the patients in the durvalumab group and in 83.2% of those in the comparison group. CONCLUSIONS: Perioperative durvalumab plus neoadjuvant chemotherapy led to significant improvements in event-free survival and overall survival as compared with neoadjuvant chemotherapy alone. (Funded by AstraZeneca; NIAGARA ClinicalTrials.gov number, NCT03732677; EudraCT number, 2018-001811-59.).

A comprehensive review on the treatment of pesticide-contaminated wastewater with special emphasis on organophosphate pesticides using constructed wetlands.

Pesticides pose a significant threat to aquatic ecosystems due to their persistent nature and adverse effects on biota. The increased detection of pesticides in various water bodies has prompted research into their toxicological impacts and potential remediation strategies. However, addressing this issue requires the establishment of robust regulatory frameworks to determine safe thresholds for pesticide concentrations in water and the development of effective treatment methods. This assessment underscores the complex ecological risks associated with organophosphate pesticides (OPPs) and emphasizes the urgent need for strategic management and regulatory measures. This study presents a detailed examination of the global prevalence of OPPs and their potential adverse effects on aquatic and human life. A comprehensive risk assessment identifies azinphos-methyl, chlorpyrifos, and profenfos as posing considerable ecological hazard to fathead minnow, daphnia magna, and T. pyriformis. Additionally, this review explores the potential efficacy of constructed wetlands (CWs) as a sustainable approach for mitigating wastewater contamination by diverse pesticide compounds. Furthermore, the review assess the effectiveness of CWs for treating wastewater contaminated with pesticides by critically analyzing the removal mechanism and key factors. The study suggests that the optimal pH range for CWs is 6-8, with higher temperatures promoting microbial breakdown and lower temperatures enhancing pollutant removal through adsorption and sedimentation. The importance of wetland vegetation in promoting sorption, absorption, and degradation processes is emphasized. The study emphasizes the importance of hydraulic retention time (HRT) in designing, operating, and maintaining CWs for pesticide-contaminated water treatment. The removal efficiency of CWs ranges from 38% to 100%, depending on factors like pesticide type, substrate materials, reactor setup, and operating conditions.

Clinical Validation of Mathematically Derived Early Tumor Dynamics for Solid Tumors in Response to Durvalumab.

PURPOSE: Early prediction of response to immunotherapy may help guide patient management by identifying resistance to treatment and allowing adaptation of therapies. This analysis evaluated a mathematical model of response to immunotherapy that provides patient-specific prediction of outcome using the initial change in tumor size/burden from baseline to the first follow-up visit on standard imaging scans. METHODS: We applied the model to 600 patients with advanced solid tumors who received durvalumab in Study 1108, a phase I/II trial, and compared outcome prediction performance versus size-based criteria with RECIST version 1.1 best overall response (BOR), baseline circulating tumor (ct)DNA level, and other clinical/pathologic predictors of immunotherapy response. RESULTS: In multiple solid tumors, the mathematical parameter representing net tumor growth rate at the first on-treatment computed tomography (CT) scan assessed around 6 weeks after starting durvalumab (α1) had a concordance index to predict overall survival (OS) of 0.66-0.77 on multivariate analyses. This measurement of early tumor dynamics significantly improved multivariate OS models that included standard RECIST v1.1 criteria, baseline ctDNA levels, and other clinical/pathologic factors in predicting OS. Furthermore, α1 was assessed consistently at the first on-treatment CT scan, whereas all traditional RECIST BOR groups were confirmed only after this time. CONCLUSION: These results support further exploring α1 as an integral biomarker of response to immunotherapy. This biomarker may be predictive of further benefit and can be assessed before RECIST response groups can be assigned, potentially providing an opportunity to personalize oncologic management.

The potential and pitfalls of using a large language model such as ChatGPT, GPT-4, or LLaMA as a clinical assistant.

OBJECTIVES: This study aims to evaluate the utility of large language models (LLMs) in healthcare, focusing on their applications in enhancing patient care through improved diagnostic, decision-making processes, and as ancillary tools for healthcare professionals. MATERIALS AND METHODS: We evaluated ChatGPT, GPT-4, and LLaMA in identifying patients with specific diseases using gold-labeled Electronic Health Records (EHRs) from the MIMIC-III database, covering three prevalent diseases-Chronic Obstructive Pulmonary Disease (COPD), Chronic Kidney Disease (CKD)-along with the rare condition, Primary Biliary Cirrhosis (PBC), and the hard-to-diagnose condition Cancer Cachexia. RESULTS: In patient identification, GPT-4 had near similar or better performance compared to the corresponding disease-specific Machine Learning models (F1-score ≥ 85%) on COPD, CKD, and PBC. GPT-4 excelled in the PBC use case, achieving a 4.23% higher F1-score compared to disease-specific "Traditional Machine Learning" models. ChatGPT and LLaMA3 demonstrated lower performance than GPT-4 across all diseases and almost all metrics. Few-shot prompts also help ChatGPT, GPT-4, and LLaMA3 achieve higher precision and specificity but lower sensitivity and Negative Predictive Value. DISCUSSION: The study highlights the potential and limitations of LLMs in healthcare. Issues with errors, explanatory limitations and ethical concerns like data privacy and model transparency suggest that these models would be supplementary tools in clinical settings. Future studies should improve training datasets and model designs for LLMs to gain better utility in healthcare. CONCLUSION: The study shows that LLMs have the potential to assist clinicians for tasks such as patient identification but false positives and false negatives must be mitigated before LLMs are adequate for real-world clinical assistance.

Simultaneous ammonia and organics degradation from municipal landfill leachate by electrochemical oxidation.

The two primary issues for wide implementation of the electrochemical oxidation of wastewater are the significant cost of electrode and high energy consumption. On the other side, conventional biological processes and membrane technology have several drawbacks for recalcitrant landfill leachate (LL) treatment. To address these issues, graphite/PbO2 anode was used to treat medium to mature age (biodegradability index, 5-day biochemical oxygen demand/chemical oxygen demand: 0.25) LL. To reduce the cost of the oxidation process and maximize the efficiency, operating conditions were optimized. The optimum parameter values were obtained as 24.7 mA cm-2, 180 ± 3 rpm, and 1.9 cm of current density, stirring rate, and electrode gap, respectively. Dissolved organic carbon (DOC), chemical oxygen demand (COD), and ammonia-N removal efficiencies of 55 ± 1.4%, 81 ± 1.9%, and 56 ± 3% were obtained after 8 h of degradation at optimum conditions. The decrease in aromatic substances and ultraviolet (UV) quenching materials were evaluated by UV-Visible spectroscopy and Specific UV absorbance. The conversion of aromatic compounds into simpler molecule compounds was also verified by Fourier-transform infrared spectroscopy analysis. The lab-scale anode synthesis cost was evaluated as 0.42 USD.

Oxidative treatment of micropollutants present in wastewater: A special emphasis on transformation products, their toxicity, detection, and field-scale investigations.

Micropollutants have become ubiquitous in aqueous environments due to the increased use of pharmaceuticals, personal care products, pesticides, and other compounds. In this review, the removal of micropollutants from aqueous matrices using various advanced oxidation processes (AOPs), such as photocatalysis, electrocatalysis, sulfate radical-based AOPs, ozonation, and Fenton-based processes has been comprehensively discussed. Most of the compounds were successfully degraded with an efficiency of more than 90%, resulting in the formation of transformation products (TPs). In this respect, degradation pathways with multiple mechanisms, including decarboxylation, hydroxylation, and halogenation, have been illustrated. Various techniques for the analysis of micropollutants and their TPs have been discussed. Additionally, the ecotoxicity posed by these TPs was determined using the toxicity estimation software tool (T.E.S.T.). Finally, the performance and cost-effectiveness of the AOPs at the pilot scale have been reviewed. The current review will help in understanding the treatment efficacy of different AOPs, degradation pathways, and ecotoxicity of TPs so formed.

Insights into the performance of binary heterojunction photocatalysts for degradation of refractory pollutants.

The uncontrolled discharge of industry- and consumer-derived micropollutants and synthetic contaminants into freshwater bodies represents a severe threat to human health and aquatic ecosystem. Inexpensive and highly efficient wastewater treatment methods are, therefore, urgently required to eliminate such non-biodegradable, recalcitrant, and toxic organic pollutants. In this context, advanced oxidation processes, particularly heterogenous photocatalysis, have received enormous attention over the past few decades. Among the different classes of photocatalysts explored by the scientific community, heterojunction photocatalysts, in general, and binary heterojunction photocatalysts, in particular, have shown tremendous promise, attributed to their many distinct advantages. As such, the present review highlights the application of diverse array of binary heterojunction photocatalysts for eliminating water-borne contaminants. Specifically, a bibliometric analysis has been conducted to identify the ongoing research trend and future prospects of heterojunction photocatalysts. It appears that metal oxide/metal oxide-based heterojunctions have superior thermal and mechanical stability compared to other heterojunction photocatalysts. In contrast, metal oxide/non-metal semiconductor-based heterojunctions are extremely effective in pollutant degradation without significant leaching of metal ions. The review concludes by proposing novel strategic research guidelines in order to make further advances in this rapidly evolving cross-disciplinary field of topical interest.

Combination of advanced biological systems and photocatalysis for the treatment of real hospital wastewater spiked with carbamazepine: A pilot-scale study.

Over the past few decades, the increase in dependency on healthcare facilities has led to the generation of large quantities of hospital wastewater (HWW) rich in chemical oxygen demand (COD), total suspended solids (TSS), ammonia, recalcitrant pharmaceutically active compounds (PhACs), and other disease-causing microorganisms. Conventional treatment methods often cannot effectively remove the PhACs present in wastewater. Hence, hybrid processes comprising of biological treatment and advanced oxidation processes have been used recently to treat complex wastewater. The current study explores the performance of pilot-scale treatment of real HWW (3000 L/d) spiked with carbamazepine (CBZ) using combinations of moving and stationary bed bio-reactor-sedimentation tank (MBSST), aerated horizontal flow constructed wetland (AHFCW), and photocatalysis. The combination of MBSST and AHFCW could remove 85% COD, 93% TSS, 99% ammonia, and 30% CBZ. However, when the effluent of the AHFCW was subjected to photocatalysis, an enhanced CBZ removal of around 85% was observed. Furthermore, the intermediate products (IPs) formed after the photocatalysis was also less toxic than the IPs formed during the biological processes. The results of this study indicated that the developed pilot-scale treatment unit supplemented with photocatalysis could be used effectively to treat HWW.

Visible Light-Assisted Degradation of Sulfamethoxazole on 2D/0D Sulfur-Doped Bi2O3/MnO2 Z-Scheme Heterojunction Immobilized Photocatalysts.

Retrieving the spent photocatalysts from the reaction system is always a challenging task. Therefore, the present work is focused on immobilizing sulfur-doped-Bi2O3/MnO2 (S-BOMO) heterojunction photocatalysts over different support matrices and evaluating their performance for the removal of sulfamethoxazole (SMX) in water under visible light. Our findings revealed S-BOMO coated clay beads (S-BOMO CCB) achieving more than 86% (240 min) SMX degradation ∼3, ∼1.3, and ∼2 times higher compared to S-BOMO coated on the different substrates, including glass beads, floating stones, and polymer material substrates, respectively. Mott-Schottky measurements confirmed the construction of the Z-scheme heterojunction involving MnO2 and 2S-Bi2O3. This Z-scheme mechanism, along with its narrow band gap of 1.58 eV, resulted in a rapid spatial transfer of the photogenerated charge carriers between the semiconductors and is believed to enhance the overall photocatalytic activity of the nanocomposite. Radical trapping and electron paramagnetic resonance results clearly established the active role of hydroxyl radicals and hydrogen peroxide in the degradation of SMX. Further, the 2S-BOMO CCB demonstrated excellent stability and photocatalytic activity over multiple runs. According to the sensitivity analysis and the results of anion effect experiments, phosphate and sulfate ions exhibit a significant impact on sulfamethoxazole degradation. Toxicity analysis revealed that 2S-BOMO CCB and sulfamethoxazole degradation byproducts were apparently innocuous. Additionally, the practical applicability of 2S-BOMO CCB was examined in various real water matrices, with the degradation efficiency followed the order: tap water < groundwater < surface water < hospital wastewater < municipal wastewater < pharmaceutical industry wastewater. The economic assessment revealed the reduction in the overall cost of the immobilized 2S-BOMO following the recovery process. Overall, the findings of this work provided critical insights into the synthesis and performance of incredibly effective and stable immobilized photocatalysts for the degradation of pharmaceutical pollutants.

The Impacts and Changes Related to the Cancer Drug Resistance Mechanism.

BACKGROUND: Cancer drug resistance remains a difficult barrier to effective treatment, necessitating a thorough understanding of its multi-layered mechanism. OBJECTIVE: This study aims to comprehensively explore the diverse mechanisms of cancer drug resistance, assess the evolution of resistance detection methods, and identify strategies for overcoming this challenge. The evolution of resistance detection methods and identification strategies for overcoming the challenge. METHODS: A comprehensive literature review was conducted to analyze intrinsic and acquired drug resistance mechanisms, including altered drug efflux, reduced uptake, inactivation, target mutations, signaling pathway changes, apoptotic defects, and cellular plasticity. The evolution of mutation detection techniques, encompassing clinical predictions, experimental approaches, and computational methods, was investigated. Strategies to enhance drug efficacy, modify pharmacokinetics, optimizoptimizee binding modes, and explore alternate protein folding states were examined. RESULTS: The study comprehensively overviews the intricate mechanisms contributing to cancer drug resistance. It outlines the progression of mutation detection methods and underscores the importance of interdisciplinary approaches. Strategies to overcome drug resistance challenges, such as modulating ATP-binding cassette transporters and developing multidrug resistance inhibitors, are discussed. The study underscores the critical need for continued research to enhance cancer treatment efficacy. CONCLUSION: This study provides valuable insights into the complexity of cancer drug resistance mechanisms, highlights evolving detection methods, and offers potential strategies to enhance treatment outcomes.

Life cycle assessment of municipal solid waste generated from hilly cities in India - A case study.

Improper disposal of waste poses a grave environmental threat, contributing to pollution of air, water, and soil. It is necessary to address this issue in order to mitigate the adverse effects of solid waste on both the environment and public health. In many developing nations, municipal authorities of bigger cities are enduring significant challenges in proper management of waste. The present study evaluates the impacts of various waste management alternative scenarios for environmental impacts for the selected study locations using Life Cycle Assessment (LCA) methodology. The methodology comprised of five different scenarios of waste management including an existing baseline scenario. In this context, the environmental impact categories analyzed were Global Warming potential (GWP), Acidification potential (AP), Eutrophication potential (EP) and Human Toxicity potential (HTP). The results indicated that amongst all the proposed scenarios, Scenario 1 and 4 exhibited the maximum and minimum environmental impacts respectively. The study revealed that least greenhouse gas emissions, acidification potential, eutrophication potential and human toxicity potential were comparatively lesser for scenario 4 varying from 5.65 to 11.36 kg CO2eq t-1; 1.24-3.345 kg SO2eq t-1, EP 0.19-0.68 kg PO4eq t-1, and 0.35-4.22 kg 1,4-DBeq t-1 respectively. Further, a sensitivity analysis was also performed to evaluate the influence of recycling rate of valuable resources in all the considered scenarios. The sensitivity analysis indicated an inversely proportional relation between change in recycling rate and total environmental burdens.

Synergistic mechanisms for the superior sorptive removal of aquatic pollutants via functionalized biochar-clay composite.

This study investigated the successful synthesis of functionalized algal biochar-clay composite (FBKC). Subsequently, the sorption performance of FBKC towards norfloxacin (NFX) antibiotic and crystal violet dye (CVD) from water was extensively assessed in both batch and continuous flow systems. A series of characterization techniques were carried out for FBKC and the utilized precursors, indicating that the surface area of FBKC was increased thirty-fold with a well-developed pore structure compared to the original precursors. FBKC demonstrated a maximum sorption capacity of 192.80 and 281.24 mg/g for NFX and CVD, respectively. The suited fitting of the experimental data to Freundlich and Clark models suggested multi-layer sorption of NFX/CVD molecules. The mechanistic studies of NFX/CVD sorption onto FBKC unveiled multiple mechanisms, including π-π interaction, hydrogen bonding, electrostatic attraction, and surface/pore filling effect. The estimated cost of 5.72 €/kg and superior sorption capacity makes FBKC an efficient low-cost sorbent for emergent water pollutants.

Development of microbial fuel cell integrated constructed wetland (CMFC) for removal of paracetamol and diclofenac in hospital wastewater.

Hospital wastewater management has become a significant concern across the globe due to the presence of pharmaceutically active compounds (PhACs) and other toxic substances, which can potentially disrupt ecosystems. The presence of recalcitrant PhACs in hospital wastewater increases the difficulty level for conventional wastewater treatment systems. Furthermore, incorporating advanced oxidation-based treatment systems increase capital and operation costs. To reduce treatment costs, low-cost innovative technology, i.e., composite constructed wetland and microbial fuel cell system (CMFC), has been developed for higher treatment efficiency of PhACs in hospital wastewater along with simultaneous bioelectricity generation as an additional outcome. In this study, influencing operating parameters, such as initial chemical oxygen demand (COD), electrode spacing, and substrate-to-water-depth ratio, were optimized for two plant species: water hyacinth (WH) and duckweed (DW). The optimized systems were run in batch and continuous mode for WH-CMFC and DW-CMFC to treat synthetic hospital wastewater with paracetamol and diclofenac, and the bioelectricity generation was monitored. DW-CMFC system depicted better treatment efficiency and voltage generation as compared to WH-CMFC. In continuous mode, the DW-CMFC system exhibited a removal of 95.3% COD, 97.1% paracetamol, and 87.5% diclofenac. WH-CMFC and DW-CMFC achieved power densities of around 21.26 mW/m2 and 42.93 mW/m2, respectively. The fate of PhACs during and after treatment and toxicity analysis of the transformation products formed were also carried out. Higher bio-electricity generation and efficient wastewater treatment of the DW-CMFC make it a sustainable option for hospital wastewater management.

The spatio-temporal dynamics of suspended sediment sources based on a novel indexing approach combining Bayesian geochemical fingerprinting with physically-based modelling.

Applications of sediment source fingerprinting continue to increase globally as the need for information to support improved management of the sediment problem persists. In our novel research, a Bayesian fingerprinting approach using MixSIAR was used with geochemical signatures, both without and with informative priors based on particle size and slope. The source estimates were compared with a newly proposed Source Sensitivity Index (SSI) and outputs from the INVEST-SDR model. MixSIAR results with informative priors indicated that agricultural and barren lands are the principal sediment sources (contributing ∼5-85% and ∼5-80% respectively during two sampling periods i.e. 2018-2019 and 2021-2022) with forests being less important. The SSI spatial maps (using % clay and slope as informative priors) showed >78% agreement with the spatial map derived using the INVEST-SDR model in terms of sub-catchment prioritization for spatial sediment source contributions. This study demonstrates the benefits of combining geochemical sediment source fingerprinting with SSI indices in larger catchments where the spatial prioritization of soil and water conservation is both challenging but warranted.

6q13q14.3 Microdeletion Syndrome with Severe Hypotonia and Facial Dysmorphism: Genotype-Phenotype Correlation.

Hypotonia is a symptom of diminished tone of skeletal muscle and can be nongenetic or a part of genetic syndrome. Hypotonia, developmental delay, and facial dysmorphism are nonspecific findings observed in many genetic syndromes mostly in chromosomal microdeletion and duplication. Here we report a case with severe hypotonia and facial dysmorphism, diagnosed with deletion at 6q13q14.3 by array comparative genomic hybridization (CGH) at very early age. Recent genetic diagnostic technologies such as array CGH may enable clinicians to diagnose chromosomal abnormalities earlier and provide appropriate medical management.

Sustainable functionalized smectitic clay-based nano hydrated zirconium oxides for enhanced levofloxacin sorption from aqueous medium.

In this study, the functionalized smectitic clay (SC)-based nanoscale hydrated zirconium oxide (ZrO-SC) was successfully synthesized and utilized for the adsorptive removal of levofloxacin (LVN) from an aqueous medium. The synthesized ZrO-SC and its precursors (SC and hydrated zirconium oxide (ZrO(OH)2)) were extensively characterized using various analytical methods to get insight into their physicochemical properties. The results of stability investigation confirmed that ZrO-SC composite is chemically stable in strongly acidic medium. The surface measurements revealed that ZrO impregnation to SC resulted in an increased surface area (six-fold higher than SC). The maximum sorption capacity of ZrO-SC for LVN was 356.98 and 68.87 mg g-1 during batch and continuous flow mode studies, respectively. The mechanistic studies of LVN sorption onto ZrO-SC revealed that various sorption mechanisms, such as interlayer complexation, π-π interaction, electrostatic interaction, and surface complexation were involved. The kinetic studies of ZrO-SC in the continuous-flow mode indicated the better applicability of Thomas model. However, the good fitting of Clark model suggested the multi-layer sorption of LVN. The cost estimation of the studied sorbents was also assessed. The obtained results indicate that ZrO-SC is capable of removing LVN and other emergent pollutants from water at a reasonable cost.

Health profile of people living in the Gare Palma mining area of Tamnar block, Raigarh, Chhattisgarh, India.

Introduction: A community-based health survey was conducted in Tamnar block, Raigarh district of Chhattisgarh, India. Methodology: A total of 909 individuals (adults) were selected from 909 households from 33 sampled villages from March 2019 to February 2020. All individuals were clinically examined, and observations were recorded. Results: Among adults older than 18 years, hypertension was observed in 21.7%. Type II diabetes was observed in only 4.0% of individuals. Tuberculosis was seen in 23 (2.5%) individuals. Discussion: Common morbidities were similar in tribal and non-tribal communities living in the same area. For communicable diseases, being male, having nutritional deficiencies, and smoking were independent risk factors. For non-communicable diseases, the independent significant risk factors identified were being male, an altered body mass index, disturbed sleep, smoking, and nutritional deficiencies.

A critical assessment of SARS-CoV-2 in aqueous environment: Existence, detection, survival, wastewater-based surveillance, inactivation methods, and effective management of COVID-19.

In early January 2020, the causal agent of unspecified pneumonia cases detected in China and elsewhere was identified as a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was the major cause of the COVID-19 outbreak. Later, the World Health Organization (WHO) proclaimed the COVID-19 pandemic a worldwide public health emergency on January 30, 2020. Since then, many studies have been published on this topic. In the present study, bibliometric analysis has been performed to analyze the research hotspots of the coronavirus. Coronavirus transmission, detection methods, potential risks of infection, and effective management practices have been discussed in the present review. Identification and quantification of SARS-CoV-2 viral loads in various water matrices have been reviewed. It was observed that the viral shedding through urine and feces of COVID-19-infected patients might be a primary mode of SARS-CoV-2 transmission in water and wastewater. In this context, the present review highlights wastewater-based epidemiology (WBE)/sewage surveillance, which can be utilized as an effective tool for tracking the transmission of COVID-19. This review also emphasizes the role of different disinfection techniques, such as chlorination, ultraviolet irradiation, and ozonation, for the inactivation of coronavirus. In addition, the application of computational modeling methods has been discussed for the effective management of COVID-19.

Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab.

PURPOSE: Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. PATIENTS AND METHODS: Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. RESULTS: Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. CONCLUSION: Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.