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Abstract Background The Life-Space Assessment (LSA) is an instrument that measures mobility in older adults as they reach different areas, defined as life-spaces extending from home to beyond towns or regions. The purpose of the study was to develop the Hindi version of the LSA (LSA- H) and to investigate the validity and reliability of the Hindi version as well as its cultural adaptation. Methods A cross-sectional study of two hundred forty-five older adults participated in the study from four different study practice areas. Following forward backwards translation, the LSA-H was developed, and the scores were correlated with those of the Activities-Specific Balance Confidence Scale Hindi (ABC- H), the Physical Health Subscale of the WHO-BREF Questionnaire and the Geriatric Depression Scale: Short Form Hindi (GDS-SFH) to test the criterion and concurrent validity. Results The mean score and standard deviation of the LSA-H questionnaire were 56.53 ± 35.99, those of the Physical Health Subscale of the WHO-BREF instrument were 18.54 ± 7.87, those of the GDS-SFH questionnaire were 6.95 ± 4.21 and those of the ABC- H questionnaire were 54.40 ± 28.96. The Pearson correlation coefficient (r) between the LSA-H score and ABC-H score was 0.707 (p value

Background and objectives: Intermittent androgen deprivation therapy (iADT) may result in measurable improvements in quality of life over continuous ADT in patients with advanced prostate cancer (aPC). Here, we studied time to castration and testosterone recovery in real-world patients with aPC undergoing iADT with relugolix. Methods and design: Eligibility criteria for this retrospective study were histologically confirmed through the diagnosis of aPC and initiation of iADT with relugolix. Primary endpoints were time to castrate level of testosterone after relugolix initiation and time to recovery to noncastrate levels after relugolix discontinuation. Results: Overall, 25 patients with aPC were treated with iADT and with relugolix. Median time to serum testosterone 50 ng/dL was 1.4 months [range 0.83–6.57 months] from holding treatment with relugolix. Conclusion: iADT with relugolix is associated with a rapid time to testosterone suppression and recovery. These results may guide patients’ counseling and monitoring of serum testosterone and PSA levels in patients wishing to pursue iADT for aPC.

Several life-prolonging therapies with diverse mechanisms of action (MoA) are available for the treatment of metastatic hormone-sensitive/castration-resistant prostate cancer, with many patients requiring multiple lines of therapy. Nevertheless, treatment optimization to further delay disease progression and improve overall survival remains an unmet need. Despite the number of agents with differing MoAs approved for advanced prostate cancer, many patients receive only one or two life-prolonging therapies. One strategy for enhancing the benefit of treatment for this aggressive disease is combining therapies with different MoAs (treatment intensification) early in the disease course, which may be more effective than administering therapies sequentially, yet still allow for subsequent sequential use of individual therapies to optimize patient outcomes. In this narrative review we discuss the rationale for combining 223radium dichloride (223Ra; an alpha-emitting radionuclide) with enzalutamide (an androgen receptor inhibitor) for treatment intensification, including their differing MoAs, their individual efficacy in this setting, and their largely non-overlapping tolerability profiles. We also summarize the preclinical and clinical data available for this combination to date, including interim safety data from the phase 3 EORTC 1333/PEACE III study which highlight the low fracture risk of 223Ra plus enzalutamide when administered concomitantly with bone health agents. Relevant data were sourced from clinical studies published by the authors and via searches of PubMed, clinical trial registries and congress abstracts.

Background: Research from India studying individuals at high risk of psychosis is deemed necessary. The Prevention through Risk Identification, Management, and Education (PRIME) Screen-Revised (PS-R) is a commonly used tool to screen individuals at high risk of psychosis. We aimed to translate PS-R into Telugu and assess the linguistic equivalence, reliability (internal consistency), and factor structure of the PS-R, administered in a community youth sample. Methodology: PS-R was translated to Telugu by the standard “forward-translation-back-translation” method, and linguistic equivalence was assessed in 20 bilingual youth by Haccoun’s technique. Data for assessing reliability and factor structure were collected using a community-based household study conducted in the Yadadri Bhuvanagiri district of Telangana. Two villages from a rural area, Bommalaramaram, and two wards from an urban area, Bhongir, were chosen. Data from 613 (387 rural and 226 urban) youth aged 15–24 years were included in the analysis. Spearman–Brown coefficient was calculated as a measure of split-half reliability. An exploratory factor analysis was conducted to measure its factor structure. Results: Linguistic equivalence was statistically confirmed using inter-version correlation coefficients. Spearman–Brown reliability coefficient was 0.774. Principal component analysis showed that 12 scale items were significantly loaded by 3 latent factors with eigenvalues of 3.105, 1.223, and 1.08, respectively. Factor solution showed that 6, 3, and 2 items correlated with the three factors, respectively. Conclusions: We conclude that the Telugu version of the PS-R is fairly reliable and valid for screening individuals at high risk for psychosis among community youth. The three factors represent “positive symptoms of schizophrenia and distress,” “positive schizotypy,” and “apophenia and magical foretelling.”

Abstract Background Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. Methods We will carry out this trial with our team’s established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. Discussion Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

Thromboembolic events (TE) are a common complication in patients with metastatic renal cell carcinoma (mRCC) and are associated with poorer clinical outcomes. However, the incidence of TE and clinical and genomic characteristics of patients with mRCC who develop this complication are poorly understood. Herein, we describe the incidence and clinical features of patients with mRCC with or without TE at our institution, and examine their association with the underlying genomic and transcriptomic characteristics of the tumor. This retrospective study included all consecutive cases of mRCC seen at our institution. A CLIA-certified lab performed tumor genomics and transcriptomics. Patients were classified based on the presence of a TE within the first year of diagnosis. Three hundred and seventy patients with mRCC were included in the study. TE was seen in 11% (42) of the patients. Patients with favorable International mRCC Database Consortium (IMDC) risk were less likely to develop a TE. In contrast, patients receiving combination treatment with a tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor were more likely to develop a TE. No difference in overall survival among patients with or without TE was observed (52 vs. 55 months; HR 0.85, 95% CI 0.5574–1.293, p = 0.24). The most upregulated pathways in mRCC with TEs versus those without were the xenobiotic metabolism and mTORC1 signaling pathways. Our findings suggest potential biomarkers that, after external validation, could be used to better select patients who would benefit from prophylactic anticoagulation.

Millets have been the staple food in many parts of the world, but in recent times they have been losing ground because of the increased use of processed foods and grains, such as wheat and rice. India has been the granary of millets due to the largest production and export of Indian millets globally. The very nature of millets being drought-resistant, small seeded grass, which can be grown in arid conditions, with less water and less farming intensive, makes it a great choice for ecological agriculture and sustainable source of food for combating hunger in the rapidly changing global climate and constructing climate-resistant agri-food systems. The various health benefits of millets make them an excellent choice for patients with celiac disease, type 2 diabetes mellitus, ischemic heart disease, dyslipidemia, obesity, etc.

Background: Prostate Cancer (PCa) is the sixth leading cause of cancer death in men, worldwide. Incidence of prostate cancer in India is on the rise. Most studies suggest that obesity has a positive correlation with a higher risk of developing high-grade PCa and dying of PCa. Central obesity and related biochemical alterations in terms of hyperinsulinemia and dyslipidemia are associated with severity of prostate cancer in terms of high Gleason score. Materials & Methods: Central obesity was assessed using anthropometric measurements including waist hip ratio (WHR) and body mass index (BMI). Serum PSA, testosterone, and insulin levels were estimated. Serum levels of triglycerides (TG), cholesterol, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), high-density lipoprotein (HDL) were also measured. Standard staging procedures were followed and for histopathological evaluation of PCa, Gleason grading was done on core biopsy tissue. Results: In the present population-based study, persons with high Gleason score had significantly higher WHR supporting that central obesity may predispose to high-grade prostate cancer. Study has shown a significant relationship between high Gleason score and cholesterol, TG, VLDL, and low HDL levels; however no significant relation was found with LDL levels. Testosterone is a key prostate growth factor although PCa presents at an age when testosterone levels are declining. Conclusion: In this study, there was no significant difference in testosterone levels in patients with high and low Gleason scores. Keywords: Prostate, Cancer, High grade, Low grade

The recent rise in telemedicine, notably during the COVID-19 pandemic, highlights the potential of integrating artificial intelligence tools in healthcare. This study assessed the effectiveness of ChatGPT versus medical oncologists in the telemedicine-based management of metastatic prostate cancer. In this retrospective study, 102 patients who met inclusion criteria were analyzed to compare the competencies of ChatGPT and oncologists in telemedicine consultations. ChatGPT’s role in pre-charting and determining the need for in-person consultations was evaluated. The primary outcome was the concordance between ChatGPT and oncologists in treatment decisions. Results showed a moderate concordance (Cohen’s Kappa = 0.43, p < 0.001). The number of diagnoses made by both parties was not significantly different (median number of diagnoses: 5 vs. 5, p = 0.12). In conclusion, ChatGPT exhibited moderate agreement with oncologists in management via telemedicine, indicating the need for further research to explore its healthcare applications.

Background: Community-based screening is one of the key preventive strategies to tackle the ever-rising burden of non-communicable diseases (NCDs) under the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS). Objective: The current study was aimed to build capacity among frontline health workers (FHWs) in screening for cardiovascular diseases (CVDs) under NPCDCS in the selected districts of Bihar state. Methodology: This was an implementation study with follow-up components, conducted among 75 FHWs [14 auxiliary nurse midwives (ANMs) and 61 accredited social health activists (ASHAs)] from 15 primary healthcare facilities across four districts of Bihar state from October 2019 to September 2021. The selected FHWs were initially trained on NPCDCS for a day, including pre- and post-training knowledge assessment. Then, supportive supervision (SS) visits using a predesigned questionnaire were done. Results: The pre- and post-training mean knowledge scores of the FHWs were 12.9 and 22.1, respectively, with an overall effect size of 2.5. During SS visits, only 20.0% of the visited primary healthcare facilities had all the required logistics to conduct weekly NCD screening clinics for CVDs. Considering different measurements and operative skill proficiencies of FHWs, waist circumference skills (41.7% for ANMs and 50.8% for ASHAs), followed by blood pressure (BP) (41.7%) and random blood sugar (RBS) measurement (25.0%), were found to be the most deficient skills (among ANMs). Moreover, the quality of initial and follow-up home visits was found to be satisfactory for only 54.1% of the ASHAs. The reported barriers of NCD screening were reported to be non-cooperation, unawareness among community dwellers, lack of knowledge and skill of FHWs, logistic constraints and delayed honorarium credit. Conclusion: One-day training on NCDs for FHWs was quite effective. However, for translating all the desired skills for CVD screening into action, periodic training needs assessment, and SS of FHWs might be fruitful.

Introduction: Many plans and policy changes about health outcomes have evolved, but none of them have ever given a definite shape to the postgraduate (PG) curriculum so as to make it more intensive and integrative, which needs to be so structured and tailored that it is more patient, community centric, and less knowledge based. Objectives: The objective of this study was to identify the gap in existing curriculum in learning of health policy and program among PGs of community medicine and recommend a structured model for the same. Materials and Methods: A qualitative study (grounded theory approach) with all PGs of community medicine in one teaching institute in South India (8 PG students) was taken up. Results: PGs felt that they never had any day-to-day update. They wanted to understand the working pattern and ground reality of policy and program which was unavailable to them. People who came to postgraduation after being medical officers felt that the monitoring and evaluation done by inexperienced MD Community Medicine students was never accepted by state public health because they did not understand the implementation problems and so could not rightly critically evaluate the programmatic challenges. Conclusion: With the shift in medical education patterns and expectations of residents, it becomes important to justify the need of developing a structured based curriculum, more so for policy and programs, which will make them capable enough by polishing their managerial and financial skill set. The evaluation technique should focus more on practical aspects on field instead of their theory examination.

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg (n = 111) or placebo (n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42–1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21–0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13–0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44–1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

Objective:Ureteral stents are usually removed after 2-4 weeks. Classically rigid cystoscope was used for stent removal along with retrieval forceps. A flexible cystoscope is an excellent alternative to a rigid cystoscope to reduce discomfort. In this study we compared semirigid ureteroscope with a flexible cystoscope for retrieving stents.Materials and Methods:It was a prospective randomized clinical trial including 100 patients. All patients were divided into two groups: Group A: Patients undergoing Double J stent (DJS) removal using a flexible cystoscope. Group B: Patients undergoing DJS removal using a semirigid ureteroscope. Outcome parameters compared in both groups were pain during and after the procedure, operative time, and operative difficulty.Results:There were 70 males and 30 females in the study. Mean visual analogue scores (VAS) for pain during the procedure in groups A and group B were 5.2±1.4 and 5.82±1.8 (p=0.057) and after the procedure were 1.95 and 2.25 in group A and group B, respectively (p=0.253). Mean VAS scores for pain during the procedure in males in groups A and B were 5.2±1.6 and 5.9±1.7, respectively (p=0.080). The mean operative times in groups A and group B were 4.9 and 4.2 min, respectively (p=0.076). VAS scores for operative difficulty overall were 3.6±1.1 and 2.9±1.2 (p=0.058), while in males were 3.7±1.0 and 2.8±1.3 (p=0.002) for groups A and B, respectively.Conclusion:Ureteral stents removal by semirigid ureteroscope is a good alternative as it is readily available, with the same degree of discomfort as flexible cystoscopes. They are inexpensive and easier to operate than flexible scopes.

Summary: Background: Metastatic renal cell carcinoma (mRCC) is a heterogenous disease with poor 5-year overall survival (OS) at 14%. Patients with mRCC to endocrine organs historically have prolonged OS. Pancreatic metastases are uncommon overall, with mRCC being the most common etiology of pancreatic metastases. In this study, we report the long-term outcomes of patients with mRCC to the pancreas in two separate cohorts. Methods: We performed a multicenter, international retrospective cohort study of patients with mRCC to the pancreas at 15 academic centers. Cohort 1 included 91 patients with oligometastatic disease to the pancreas. Cohort 2 included 229 patients with multiples organ sites of metastases including the pancreas. The primary endpoint for Cohorts 1 and 2 was median OS from time of metastatic disease in the pancreas until death or last follow up. Findings: In Cohort 1, the median OS (mOS) was 121 months with a median follow up time of 42 months. Patients who underwent surgical resection of oligometastatic disease had mOS of 100 months with a median follow-up time of 52.5 months. The mOS for patients treated with systemic therapy was not reached. In Cohort 2, the mOS was 90.77 months. Patients treated with first-line (1L) VEGFR therapy had mOS of 90.77 months; patients treated with IL immunotherapy (IO) had mOS of 92 months; patients on 1L combination VEGFR/IO had mOS of 74.9 months. Interpretations: This is the largest retrospective cohort of mRCC involving the pancreas. We confirmed the previously reported long-term outcomes in patients with oligometastatic pancreas disease and demonstrated prolonged survival in patients with multiple RCC metastases that included the pancreas. In this retrospective study with heterogeneous population treated over 2 decades, mOS was similar when stratified by first-line therapy. Future research will be needed to determine whether mRCC patients with pancreatic metastases require a different initial treatment strategy. Funding: Statistical analyses for this study were supported in part by the University of Colorado Cancer Center Support Grant from the NIH/NCI, P30CA046934-30.

Since the onset of the COVID-19 Pandemic, various public health measures have been in focus, viz. social distancing, hand hygiene, use of masks, screening of patients for COVID-19 symptoms, development of quarantine and isolation facilities, and public health surveillance. Most of these relate to the principles of prevention, early case detection, and primary care. In the ongoing fight against COVID-19, community medicine (CM) professionals are involved at various positions and have been leading from the front in a variety of activities, be it screening, patient care, surveillance, orientation and training of front line workers, community engagement, evidence generation through research, and development of guidelines. However, their engagement in policymaking has still been limited. The government should work more closely with CM professionals in order to stem the tide of COVID-19 or any such public health emergencies in the future by shifting the focus to preventive and promotive interventions. CM professionals should take a more proactive approach in getting involved in policymaking and demonstrate leadership through their actions to lead the national, state, and district-level public health teams through collaboration across disciplines and sectors. This will help bring the leadership of public health in India in the right hands for optimum population health and appropriate and timely health emergency response.

There has been substantial evolution in the treatment of metastatic renal cell carcinoma with notable changes in the first-line setting. Currently, doublet combination therapy with either two immune checkpoint inhibitors or a combination of an immune checkpoint and tyrosine kinase inhibitor is considered the standard of care. The doublet combination therapies have demonstrated significantly improved clinical outcomes. A recently conducted trial (COSMIC-313) showed superior efficacy with a triplet combination of cabozantinib, nivolumab, and ipilimumab when compared to a placebo, nivolumab, and ipilimumab but at the cost of additional toxicity. Many other combination treatments, such as pembrolizumab plus lenvatinib plus belzutifan (NCT04976634), are being investigated, possibly leading to more options in the first-line setting in the future.

The tumor suppressor gene PTEN is the second most commonly deleted gene in cancer. Such deletions often include portions of the chromosome 10q23 locus beyond the bounds of PTEN itself, which frequently disrupts adjacent genes. Coincidental loss of PTEN-adjacent genes might impose vulnerabilities that could either affect patient outcome basally or be exploited therapeutically. Here, we describe how the loss of ATAD1, which is adjacent to and frequently co-deleted with PTEN, predisposes cancer cells to apoptosis triggered by proteasome dysfunction and correlates with improved survival in cancer patients. ATAD1 directly and specifically extracts the pro-apoptotic protein BIM from mitochondria to inactivate it. Cultured cells and mouse xenografts lacking ATAD1 are hypersensitive to clinically used proteasome inhibitors, which activate BIM and trigger apoptosis. This work furthers our understanding of mitochondrial protein homeostasis and could lead to new therapeutic options for the hundreds of thousands of cancer patients who have tumors with chromosome 10q23 deletion.

BRCA1-mutated prostate cancer has been shown to be less responsive to poly (ADP-ribose) polymerase (PARP) inhibitors as compared to BRCA2-mutated prostate cancer. The reason for this differential response is not clear. We hypothesized this differential sensitivity to PARP inhibitors may be explained by distinct genomic landscapes of BRCA1 versus BRCA2 co-segregating genes. In a large dataset of 7,707 men with advanced prostate cancer undergoing comprehensive genomic profiling (CGP) of cell-free DNA (cfDNA), 614 men harbored BRCA1 and/or BRCA2 alterations. Differences in the genomic landscape of co-segregating genes was investigated by Fisher’s exact test and probabilistic graphical models (PGMs). Results demonstrated that BRCA1 was significantly associated with six other genes, while BRCA2 was not significantly associated with any gene. These findings suggest BRCA2 may be the main driver mutation, while BRCA1 mutations tend to co-segregate with mutations in other molecular pathways contributing to prostate cancer progression. These hypothesis-generating data may explain the differential response to PARP inhibition and guide towards the development of combinatorial drug regimens in those with BRCA1 mutation.

Background: COVID-19 vaccination is one of the pivotal key tools against the ongoing pandemic, but its acceptance relies on efficacy and safety data among various populations, including patients with cancers. However, there is limited data on seroconversion rates, efficacy, and safety of the COVID-19 vaccine in patients with cancer. Breakthrough infections after vaccination have also been reported, which could further strengthen the refusal behavior of specific populations to be immunized. Our objective was to investigate the efficacy and safety of COVID-19 vaccination in real-world patients with advanced genitourinary cancers. Methods and results: A retrospective study of the 738 patients with advanced metastatic genitourinary malignancy was conducted at our genitourinary oncology clinic from October 2020 to September 2021, out of which 462 patients (62.6%) were vaccinated. During the study period, two vaccinated, and six unvaccinated patients tested positive for SARS-CoV-2 (breakthrough infection rate: 0.4% vs. 2.2%, p = 0.027). Vaccine protection against infection was 81.8% (95% CI: 0.04–0.98). One vaccinated and 4 unvaccinated patients were hospitalized due to COVID-19 (0.2% vs. 1.4%, p = 0.048). Vaccine effectiveness in preventing hospitalization was 85.7% (95% CI: 0.02–1.33). Within one month of vaccination, 1.5% of patients (n = 7) had emergency visits, 0.8% (n = 4) were hospitalized for any reason, and of these, 3 (0.6%) experienced a delay in the receipt of their cancer therapy. Conclusion: In our hypothesis-generating data among patients with advanced genitourinary cancers, COVID-19 vaccination was efficacious and safe and was rarely associated with treatment disruptions. These data should help improve the acceptance of the COVID-19 vaccine in the general population and patients with cancer. The vaccine effectiveness in our patients is comparable with existing published data without cancer.

Abstract Background Disulfiram and metals inactivate key oncoproteins resulting in anti-neoplastic activity. The goal of this study was to determine the maximum tolerated dose of copper when administered with disulfiram in patients with advanced solid tumors and liver involvement. Methods Disulfiram 250 mg was administered daily in 28-day cycles. Four doses of copper gluconate were tested (2, 4, 6, and 8 mg of elemental copper) in a standard 3 + 3 dose escalation design. Patients were evaluated for dose limiting toxicities and response. Protein S-glutathionylation was evaluated as a pharmacodynamic marker. Results Twenty-one patients were enrolled and 16 patients were evaluable for dose limiting toxicities. Among the 21 patients, there was a median of 4 lines of prior chemotherapy. Five Grade 3 toxicities were observed (anorexia, elevated aspartate aminotransferase or AST, elevated alkaline phosphatase, fever, and fatigue). Response data was available for 15 patients. Four patients had stable disease with the longest duration of disease control being 116 days. The median duration of treatment for evaluable patients was 55 days (range 28–124). Reasons for discontinuation included functional decline, disease progression, and disease-associated death. Increased S-glutathionylation of serum proteins was observed with treatment. Conclusion Disulfiram 250 mg daily with copper gluconate (8 mg of elemental copper) was well-tolerated in patients with solid tumors involving the liver and was not associated with dose limiting toxicities. While temporary disease stabilization was noted in some patients, no objective responses were observed. Treatment was associated with an increase in S-glutathionylation suggesting that this combination could exert a suppressive effect on cellular growth and protein function. Trial registration NCT00742911 , first posted 28/08/2008.

Abstract Niclosamide has preclinical activity against a wide range of cancers. In prostate cancer, it inhibits androgen receptor variant 7 and synergizes with abiraterone. The approved niclosamide formulation has poor oral bioavailability. The primary objective of this phase Ib trial was to identify a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of a novel reformulated orally-bioavailable niclosamide/PDMX1001 in combination with abiraterone and prednisone in men with castration-resistant prostate cancer (CRPC). Eligible patients had progressing CRPC, adequate end-organ function, and no prior treatment with abiraterone or ketoconazole. Patients were treated with escalating doses of niclosamide/PDMX1001 and standard doses of abiraterone and prednisone. Peak and trough niclosamide plasma levels were measured. Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and Prostate Cancer Working Group 2 criteria were used to evaluate toxicities and responses. Nine patients with metastatic CRPC were accrued, with no dose-limiting toxicities observed at all dose levels. The recommended Phase II dose of niclosamide/PDMX1001 was 1200 mg orally (PO) three times daily plus abiraterone 1000 mg PO once daily and prednisone 5 mg PO twice daily. Trough and peak niclosamide concentrations exceeded the therapeutic threshold of > 0.2 µM. The combination was well tolerated with most frequent adverse effects of diarrhea. Five out of eight evaluable patients achieved a PSA response; two achieved undetectable PSA and radiographic response. A novel niclosamide/PDMX1001 reformulation achieved targeted plasma levels when combined with abiraterone and prednisone, and was well tolerated. Further study of niclosamide/PDMX1001 with this combination is warranted.

Introduction: AIIMS Delhi developed an online platform Mortality in India established through Verbal Autopsies, which ultimately provides data on the cause of death in the country. AIIMS Patna being one of the partner institutions in this initiative of AIIMS Delhi, thus, conducted a 2-day workshop of Registrar General of India supervisors with the objective to strengthen the knowledge of participants and improve their practices on writing a good narrative during verbal autopsy (VA) using a key symptom list. Materials and Methods: A total of 32 participants attended the 2-day workshop at the Department of Community and Family Medicine, AIIMS Patna, in January 2019. A pretest questionnaire was administered before the start of the workshop and to test the improvement in knowledge of participants after attending the workshop, the same questionnaire was again administered as a posttest at the end of the workshop. Feedback of participants was also collected on a predesigned semi-structured questionnaire. The collected responses were entered in MS Excel 2010. Descriptive and inferential statistics were calculated using SPSS version 16.0 software. Results: There was a statistically significant improvement (P < 0.001) in the mean posttest score (8.6 ± 1.2) as compared to the mean pretest score (6.1 ± 2.8). Maximum participants, i.e., 15 (46.8%), reported that filling VA forms in a narrative way was the most useful part of the workshop. All the participants, i.e., 32 (100%), strongly agreed that the workshop was appropriately organized, content of the training was relevant, they were encouraged to actively participate, and adequate material was provided. Conclusion: Further intensive workshop with more field training and refresher training at regular intervals is expected in future.

Objective: Covid19 has emerged as a greatest threat of the decade worldwide. At present there is no certain treatment for treating coronavirus diseases, while some antiviral drugs (Remdesivir , Lopinavir and Ritonavir) are under investigation. Many countries including India have adopted the convalescent plasma therapy in the treatment of moderate to severely ill patients. Despite the treatment being given ,there are no such evidences on the utility and efficacy of convalescent plasma.Hence this study tries to find out the impact on the discharge status from hospital of the patients receiving the very therapy. Design: Systematic review and meta analysis. Setting: An extensive search was made, following PRISMA guidelines on online databases such as Pubmed, Google scholar and Science direct.Studies those fulfilled the inclusion and exclusion criteria ,were included and reviewed and analyzed for a common outcome(discharge status). Participants: A total of 6 eligible studies were analyzed qualitatively and quantitatively which included three case control, two case series and one case report. Results: The overall pooled discharge rate from the above studies was 75.7% after the CP therapy. When analyzed for relative risk , it showed CP therapy having a lower risk of staying in hospital (not getting discharged) when compared to Standard therapy ,overall RR (relative risk) being 0.946. Conclusion: Our study shows that there is always a higher rate of discharge and low risk of prolonged hospital stay in those patients who receive plasma therapy. CP therapy being a low cost and easy to administer therapy with very less adverse events, requires more focus on further research as it has a potential to become an ideal effective treatment option for COVID-19.

Objectives To layout mHealth (mobile health) applications operating in India with the facility of either online doctor consultation or offline doctor appointment booking. Methods A cross-sectional, observational and web-based study was conducted. We searched the Google Play Store with the search strategy “health apps in India”. In the results, 250 applications (apps) appeared. Out of 250 apps, finally, 22 apps were found to be providing online doctor consultation and/or doctor appointment booking-related services. Results Among the selected mHealth apps operating in India and providing doctor consultation-related services online/offline, Practo, mfine, DocsApp, 1mg, Netmeds, Lybrate, MediBuddy, and Medlife were found to be the eight most popular ones with over a million downloads and on average four-plus user rating out of five. Practo, mfine, and Lybrate offer doctor consultation through chat, audio, and video calling. Netmeds and DocsApp offer doctor consultation through both chat and audio call. 1mg offers free chat consultation, while MediBuddy and Medlife offer audio call consultation only. Considering booking doctor appointments for offline consultation, Practo, mfine, 1mg, and Lybrate only offer this facility among the eight most popular selected mHealth apps. Conclusions mHealth apps providing doctor consultation are gaining popularity in India, and they have enormous potential in the country. The government should make enabling policies to facilitate and popularise mHealth apps.

Objective: To investigate the risk factors and protective measures of COVID-19 among policemen in an eastern state of India. Methods: This case-control study was conducted in Bihar, located in the eastern part of India. In total, 6 confirmed COVID-19 cases (the case group) and 11 negative contacts of these cases (the control group) of Bihar Military Police participated in the study. Results: All subjects were male with a median age of 51 (range: 23-60) years. Among these 6 confirmed cases, 5 cases were asymptomatic. One third (33.3%) of the case group and the majority (90.9%) of the control group reported maintenance of physical distance of at least 1 meter with others all the time, which was significantly different (P=0.028). There was no other statistically significant difference between the case group and the control group. Conclusions: Physical distancing is the most effective public health measure to control contagious diseases like COVID-19, especially in the absence of an effective vaccine in police settings.

Background: COVID-19 is an ongoing largest public health emergency of the 21st century. India is effectively controlling the pandemic by taking bold and stringent steps right from the beginning of the pandemic. This article aimed to formulate a multipronged strategy to combat the COVID-19 pandemic in India. Method: We have gone through websites of World Health Organization, Centers for Disease Control and Prevention, Indian Council of Medical Research, and Ministry of Health and Family Welfare of Government of India to avail updated information on COVID-19. Result: We found that there may be three pillars of this COVID-19 pandemic management, namely public health measures, diagnostic and testing, and hospital and health care. These pillars should be aimed to achieve three primary goals, namely containment, capacity building, and recovery. For India, gradual relaxation in lockdown with social distancing and personal and environmental hygiene measures must be the more suitable exit plan.

Context: One of the major obstacles in treating TB is the patient's nonadherence to the treatment regimen resulting in prolonged disease transmission and development of resistance to anti-TB drugs. An individual's mental health affects his/her adaptation to the disease. Mental health issues and TB both are inextricably connected and research into this area will provide an opportunity to develop a more holistic model of TB treatment and prevention. Aims: The aim of this study is to investigate the prevalence of mental health issues in patients with TB and its influence on individual perception of well-being with an emphasis on psychopathology as a major obstacle to treatment adherence. Research into this area will provide an opportunity to develop a more holistic model of TB treatment and prevention. Settings and Design: Primary data were collected with the help of ASHA workers, and primary survey-based study was designed. Methods and Material: A total of 249 diagnosed Tuberculosis cases were included in the study. A digitalized version of the PGIHQN-1 questionnaire was made and used to separate the psychiatric population from the normal group. Asha workers were trained to use the digital version on tablets. Statistical Analysis Used: Using Microsoft Excel, Graphic Tables, and corelation were done using SPSS Statistics. Results: Mental health issues were found in diagnosed TB cases, which required further evaluations. Along with mental health issues, limited resources, gender, limited education, lack of proper knowledge about the disease, having responsibilities (Marital status), locality were found to be the important factors that complicate TB outcomes, hence should be taken into consideration while imparting psychological interventions. Conclusion: Mental health issues complicate TB outcome and hence need to be properly addressed, and thorough psychoeducation, psychological first aid (listen, protect, connect, model& teach), and timely intervention in the form of proper diagnosis and specific treatment and rehabilitation are needed.

Background: Posterior Urethral Valves (PUV) are the most common cause of congenital LUT obstruction in males. Biomarkers of glomerular or tubular injury may be of particular value in predicting the need for surgical intervention or in tracing progression of chronic kidney disease. Measurement of biomarker in urine is relatively easy. Aim: To evaluate the changes in values of urinary Transforming Growth Factor Beta 1(TGF-B1) and Monocyte Chemotactic Protein (MCP-1) before and after valve ablation and its prognostic value in Posterior urethral valve. Material and Method: This prospective study was conducted from September 2016 to August 2018. The study group included 20 consecutive male babies with the diagnosis of PUV treated and followed up versus equal numbers of age matched control without any renal or urinary tract disease. Pre-operative urine samples were collected in Operative room. Cystoscopy and valve ablation was done. Follow up was done clinically by urinary stream and radiologically with VCUG. Follow-up was planned at 1 month, 3 months and 6 months following cystoscopic valve ablation. All collected urine samples were centrifuged at 10,000 rpm for 20 minutes. Supernatant was collected and two divided aliquots were stored at -200c to be thawed on the day of assay. Optical density of each well was recorded at 450 nm and 540 nm A p-value of

Background: Monitoring of a program is a continuous assessment of certain key indicators of it through periodic reports. The efficiency of a health program is assessed by comparing its achievements with the expectations. Methods: The study was conducted based on the annual TB report of India for the year 2018 in order to monitor (Revised National Tuberculosis Control Program) RNTCP performance in the Bihar State and its various districts. Results: Case notification rate of various districts Bihar was far below the national average of 138 per lakh. Considering treatment initiation, the performance of various districts of Bihar were less than national figures (79.0%). In newly diagnosed TB cases, the treatment success rate of Bihar was 73%. This performance was more compared to Uttar Pradesh (66.0%) but less compared to Jharkhand (92.0%), West Bengal (88.0%), and national data (79.5%). Considering human resources, the total human resources in the states of Bihar (61.9%) and Jharkhand (58.3%) were similar. However, in Bihar, there was a vast shortage of ground-level staff [i.e. (senior treatment supervisor) STS, (senior TB lab supervisor) STLS, (public-private mix) PPM Co-ordinator, and (TB health visitor) TBHV)]. Conclusion: It was found that Bihar was one of the less performing states in RNTCP with a vast shortage of ground-level staff and low overall treatment success rate compared to its neighboring states. Stringent monitoring and evaluation in every step of the program implementation should be done in order to improve RNTCP performance in Bihar.

Introduction: Data from several sources revealed that huge incongruity persists in nutritional status across the states in India. Thus, this study was undertaken to generate a nutritional index, so that these disparities could be quantified and comparison be done. Materials and Methods: A nutritional index for 21 major states of India has been constructed on the basis of eight important nutrition-related indicators. The scaled value of each indicator for all the states was calculated. Each indicator was assigned an arbitrary weight (Wi) on the basis of its impact on nutritional status. On the basis of the scaled value and weight given to the particular indicator, a composite-weighted index was thus calculated. Results: States were ranked on their nutritional status as per the final composite score they attained. Out of 21 major states, Kerala took the top position followed by Jammu and Kashmir and Himachal Pradesh on the 2nd and 3rd position, respectively, while Uttar Pradesh got the lowest rank followed by Bihar and Jharkhand on the 2nd and 3rd lowest positions. Conclusion: Our study concludes that not taking an account of the burden of malnutrition when disbursing funds leads to ineffective implementation of various nutritional programs. Integrated Child Development Services has already been brought in mission mode under Poshan Abhiyan. Other determinants, i.e., illiteracy, poor sanitation, diseases, and infections, should also be considered and addressed through nutritional programs.

We combined observations of ocean surface winds from Indian SCATterometer SATellite-1 (SCATSAT-1) with a background wind field from a numerical weather prediction (NWP) model available at National Centre for Medium-Range Weather Forecast (NCMRWF) to generate a 6-hourly gridded hybrid wind product. A distinctive feature of the study is to produce a global gridded wind field from SCATSAT-1 scatterometer passes with spatio-temporal data gaps at regular synoptic hours relevant for forcing models and other NWP studies. We are following the concept from the modern particle filter technique, which does not represent the model probability density function (PDF) as Gaussian. We generated the 6-hourly hybrid winds for 2018 and validated them using the wind speed from daily gridded level-4 SCATSAT-1 winds (L4AW), Cross Calibrated Multi-Platform (CCMP) dataset and global buoy data from National Data Buoy Centre (NDBC). The results suggest the potential of the technique to produce scatterometer winds at the desired temporal frequency with significantly less noise and bias along the swath. The study shows that the generated hybrid winds are of prime quality compared with the already existing daily products available from Indian Space Research Organization (ISRO).

This study aimed to do a situation analysis of Telangana and systematically map the research done in the area of fluorosis and its health risks. Identify existing gaps in the available literature and unsheathe the challenges and threats in the progress so far among the people living in fluorine-contaminated zones in India. After weighing our research question, we adopted an iterative process for our search strategy by including electronic databases. A quality check was performed and guided as per the Preferred Reporting Items for Systematic reviews and Meta-Analyses–scoping review (SCR) for SCRs which included details of the study type, setting, bias, funding, etc. It was found that out of the 15 studies summed up, most of them (>95%) had been conducted in South India. Nearly 27% of the studies were trials or experimental studies, 20% were studies involving groundwater sample testing, and few were in vitro studies. Nearly 26% were conducted on animals to see for interventions. With a total of 12,382 habitat affections, we found that Rajasthan had the highest fluoride habitation. There was a need to focus more on the seemingly less important. Many programs in India focus on risk assessment and healthy behavior. Although population affection as depicted by the Indian data statistics from the department of drinking water and sanitation show values as low as 0.01% affection for a few endemic states, they scale up to include and paralyze the lives of a lot many people in the 1.3 billion nations. At a cost, where these lives can be saved from living in suffering, what we need is mere pro-activeness, being responsible, integrating methods to tackle, using local methods to prevent, adequate nutrition, and rehabilitation.

Background: Poly (ADP-ribose) polymerase (PARP) inhibitors are approved for patients with metastatic castration-resistant prostate cancer harboring deleterious or suspected deleterious BRCA1 and/or 2 mutations. Identifying patients with prostate cancer harboring these mutations may be challenging. Circulating cell-free DNA (cfDNA) provides an avenue for an easier detection of these mutations. Herein, we aimed to evaluate the concordance of BRCA mutations in the tumor tissue and cfDNA in patients with metastatic prostate cancer in the real-world setting. Methods: Somatic genomic profiling results were obtained from a clinical cohort of patients at our institution who had at least two samples tested. One of the samples needed to be from either primary or metastatic tissue. Concordance was adjusted to not include mutation types that the cfDNA platforms were not designed to detect. Results: The presence or absence of mutations in the BRCA gene was assessed in a total of 589 samples, including 327 cfDNA samples, from 260 patients with metastatic prostate cancer. The median time between the first test and any subsequent test was 22.8 (0.0–232) months. BRCA mutation was present in the patient’s original prostate tissue in 23 samples (3.9%) of patients. The adjusted concordance between prostate tumor tissue and cfDNA was 97.9% [95% CI, 95.3–99.1%]. The adjusted concordance between metastatic samples and cfDNA was 93.5% [95% CI, 86.4–97.3%]. Of the patients who had a BRCA mutation detected in their prostate tissue, there was a 70% probability of detecting a BRCA mutation in the patient’s cfDNA as well. For patients who did not have a detectable BRCA mutation in their primary prostate tissue, the probability of detecting a subsequent one later in the disease course was less than 0.9%. Conclusion: There is a high level of concordance between tissue and blood for BRCA mutations. Testing cfDNA can provide reliable information on BRCA mutational status and is a viable alternative to solid tissue sequencing when unavailable. The development of a new BRCA mutation later in the disease course is a rare event.

Background: Length of hospital stay (LOS) for a disease is a vital estimate for healthcare logistics planning. The study aimed to illustrate the effect of factors elicited on arrival on LOS of the COVID-19 patients. Materials and Methods: It was a retrospective, record based, unmatched, case control study using hospital records of 334 COVID-19 patients admitted in an East Indian tertiary healthcare facility during May to October 2020. Discharge from the hospital (cases/survivors) was considered as an event while death (control/non-survivors) as right censoring in the case-control survival analysis using cox proportional hazard model. Results: Overall, we found the median LOS for the survivors to be 8 days [interquartile range (IQR): 7-10 days] while the same for the non-survivors was 6 days [IQR: 2-11 days]. In the multivariable cox-proportional hazard model; travel distance (>16 km) [adjusted hazard ratio (aHR): 0.69, 95% CI: (0.50-0.95)], mode of transport to the hospital (ambulance) [aHR: 0.62, 95% CI: (0.45-0.85)], breathlessness (yes) [aHR: 0.56, 95% CI: (0.40-0.77)], number of co-morbidities (1-2) [aHR: 0.66, 95% CI: (0.47-0.93)] (≥3) [aHR: 0.16, 95% CI: (0.04-0.65)], COPD/asthma (yes) [ [aHR: 0.11, 95% CI: (0.01-0.79)], DBP (

Mutations in the promoter of the human Telomerase Reverse Transcriptase (hTERT) gene are common and associated with its elevated expression in bladder cancer, melanoma, and glioblastoma. Though these mutations and TERT overexpression are associated with aggressive disease and poor outcome, an incomplete understanding of mutant TERT regulation limits treatment options directed at this gene. Herein, we unravel a signaling pathway that leads to upregulated hTERT expression resulting from the −124 bp promoter mutation, the most frequent variant across human cancer. We employed engineered bladder cancer cells that harbor a GFP insertion at the TSS region on −124 hTERT promoter for high-content screening drug discovery using a focused library of ~800 kinase inhibitors. Studies using in vitro and in vivo models prioritized AST-487, an inhibitor of the wild-type, and mutant RET (rearranged during transfection) proto-oncogene as a novel drug inhibitor of both wild-type and mutant promoter-driven hTERT expression. We also identified the RET kinase pathway, targeted by AST-487, as a novel regulator of mutant hTERT promoter-driven transcription in bladder cancer cells. Collectively, our work provides new potential precision medicine approaches for cancer patients with upregulated hTERT expression, perhaps, especially those harboring mutations in both the RET gene and the hTERT promoter, such as in thyroid cancer.

BackgroundIn 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016.MethodsEight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS.ResultsComplete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019.ConclusionThrough effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets.

Background: There has been a growing interest in ivermectin ever since it was reported to have an in-vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This trial was conducted to test the efficacy of ivermectin in mild and moderate coronavirus disease 19 (COVID-19). Methods: A double blind, parallel, randomised, placebo-controlled trial conducted among adult COVID-19 patients with mild to moderate disease severity on admission in a COVID dedicated tertiary healthcare of eastern India. Enrolment was done between 1st August and 31st October 2020. On day 1 and 2 post enrolment, patients in the intervention arm received ivermectin 12 mg while the patients in the non-interventional arm received placebo tablets. Results: About one-fourth (23.6%) of the patients in the intervention arm and one-third (31.6%) in the placebo arm were tested reverse transcriptase polymerase chain reaction (RTPCR) negative for SARS-CoV-2 on 6th day. Although this difference was found to be statistically insignificant [rate ratio (RR): 0.8; 95% confidence interval (CI): 0.4-1.4; p=0.348]. All patients in the ivermectin group were successfully discharged. In comparison the same for the placebo group was observed to be 93%. This difference was found to be statistically significant (RR: 1.1; 95% CI; 1.0-1.2; p=0.045). Conclusions: Inclusion of ivermectin in treatment regimen of mild to moderate COVID-19 patients could not be said with certainty based on our study results as it had shown only marginal benefit in successful discharge from the hospital with no other observed benefits.

Near infra red spectroscopy (NIRS) is a noninvasive diagnostic tool for measuring regional oxygen saturation (rSO2). Cerebral oxygenation measured with NIRS is used to corroborate mixed venous oxygenation and hence considered an indicator of tissue perfusion. We describe NIRS guiding an anatomical variation leading to inadequate cerebral circulation or any impairment in cerebral oxygen delivery during Blalock Taussig shunt.

Abstract Background Water, Sanitation, and Hygiene (WASH) practices may affect the growth and nutritional status among adolescents. Therefore, this paper assesses WASH practices and its association with nutritional status among adolescent girls. Methods As a part of an intervention programme, this study is based on baseline cross-sectional data. It was conducted between May 2016–April 2017 in three Indian states (Bihar, Odisha, and Chhattisgarh). From a sample of 6352 adolescent girls, information on WASH practices, accessibility to health services and anthropometric measurements (height, weight and mid upper arm circumference (MUAC)) was collected. Descriptive statistics were used to examine WASH practices, and nutritional status among adolescent girls. Determinants of open defecation and menstrual hygiene were assessed using logistic regression. Association between WASH and nutritional status of adolescent girls was determined using linear regression. Results Findings showed 82% of the adolescent girls were practicing open defecation and 76% were not using sanitary napkins. Significant predictors of open defecation and non use of sanitary napkin during menstruation were non Hindu households, households with poorer wealth, non availability of water within household premise, non visit to Anganwadi Centre, and non attendance in Kishori group meetings. One-third of adolescent girls were stunted, 17% were thin and 20% had MUAC

Abstract Background Prognostic scoring systems are used to estimate the risk of mortality from metastatic renal cell carcinoma (mRCC). Outcomes from different therapies may vary within each risk group. These survival algorithms have been applied to assess outcomes in patients receiving T-cell checkpoint inhibitory immunotherapy and tyrosine kinase inhibitor therapy, but have not been applied extensively to patients receiving high dose interleukin-2 (HD IL-2) immunotherapy. Methods Survival of 810 mRCC patients treated from 2006 to 2017 with high dose IL-2 (aldesleukin) and enrolled in the PROCLAIMSM registry data base was assessed utilizing the International Metastatic RCC Database Consortium (IMDC) risk criteria. Median follow-up is 23.4 months (mo.) (range 0.2–124 mo.). Subgroup evaluations were performed by separating patients by prior or no prior therapy, IL-2 alone, or therapy subsequent to IL-2. Some patients were in two groups. We will focus on the 356 patients who received IL-2 alone, and evaluate outcome by risk factor categories. Results Among the 810 patients, 721 were treatment-naïve (89%) and 59% were intermediate risk. Overall, of the 249 patients with favorable risk, the median overall survival (OS) is 63.3 mo. and the 2-year OS is 77.6%. Of 480 patients with intermediate risk, median OS is 42.4 mo., 2-year OS 68.2%, and of 81 patients with poor risk, median OS 14 mo., 2-year OS 40.4%. Among those who received IL-2 alone (356 patients), median OS is 64.5, 57.6, and 14 months for favorable, intermediate and poor risk categories respectively. Two year survival among those treated only with HD IL-2 is 73.4, 63.7 and 39.8%, for favorable, intermediate and poor risk categories respectively. Conclusions Among mRCC patients treated with HD IL-2, all risk groups have median and 2-year survival consistent with recent reports of checkpoint or targeted therapies for mRCC. Favorable and intermediate risk (by IMDC) patients treated with HD IL-2 have longer OS compared with poor risk patients, with most durable OS observed in favorable risk patients. Favorable risk patients treated with HD IL-2 alone have a 2-year OS of 74%. These data continue to support a recommendation for HD IL-2 for patients with mRCC who meet eligibility criteria. Trial registration PROCLAIM, NCT01415167 was registered with ClinicalTrials.gov on August 11, 2011, and initiated for retrospective data collection until 2006, and prospective data collection ongoing since 2011.

Introduction: Immunization is one of the most cost-effective measures in public health to date, preventing at an approximately 2 to 3 million fatalities in young children every year. As per recent World Health Organisation (WHO) bulletin, these lifesaving vaccines have been successfully averted around 20 million premature deaths and 500 million disease cases. Inspite of this progress the routine vaccine coverage is slow to rise as challenges still live for the underserved, inaccessible and vulnerable children. It is therefore essential to evaluate the coverage of immunization at periodic intervals and to take the required measures to enhance the vaccination status in the State Bihar. Aims and Objective: This study aims to find out the vaccination coverage in different Blocks of study area. Material and Methods: The study was community based cross sectional study which was conducted between January to March 2019 in the selected villages of 59 low performing blocks of Bihar. The study subjects were all the children aged 12-23 month old from selected low performing blocks of the Bihar. Results-Corrected FIC of the study was 90.85%. Close to nine percent (8.8%) children thou have started vaccination could not able to complete it. Rest of the beneficiaries are completely left out. The most common reason for incomplete immunization was unavailability of child on the day of vaccination followed by sickness of the child. Conclusion: The overall Immunization coverage of Bihar is less than the National Immunization coverage as per NFHS-4. This study shows higher rate of immunization as far as Corrected Immunization Coverage is concerned.

There is a growing body of evidence related to the importance of body composition in cancer survivorship. Current evidence exclusive to the metastatic prostate cancer setting is limited, yet sheds light on the importance of body composition to reduce risk of mortality and disease progression in this patient population. In our commentary we present the current state of evidence related to body composition and metastatic prostate cancer survival among metastatic castration-resistant and castration-sensitive prostate cancer patients among varying treatment modalities. Additionally, we discuss the proposed biological mechanisms that may underpin how favorable changes in body composition may be helpful for survivorship, and review promising lifestyle strategies that can be implemented as part of survivorship care to improve body composition in this patient population.

Metastatic bladder cancer has poor overall survival. Though systemic therapies have shown to improve overall survival, real-world studies have shown that more than half of the patients do not receive any systemic therapy, while only around 15–20% receive second-line therapy. Even in patients receiving systemic therapies a disproportionately higher use of carboplatin is observed in the first line despite proven superior effectiveness of cisplatin. Reasons for these observations include moderate effectiveness and relatively toxicity of platinum-based chemotherapy regimens, concerns with performance status and co-morbidities in this predominantly older patient population, communications barriers, lack of social support, and access to affordable healthcare. Herein we discuss potential ways to overcome these challenges which include (1) preventing/delaying metastatic disease by maximizing the receipt of neoadjuvant cisplatin-based therapy, and development of better tolerated and more effective neoadjuvant and adjuvant therapies, (2) use of avelumab maintenance therapy after 4–6 cycles of platinum-based chemotherapy to overcome attrition of patients from first to second-line therapy, (3) advancing effective and well-tolerated systemic therapies such as enfortumab vedotin, and erdafitinib to the first-line metastatic setting or even to the localized setting, (4) further development of effective and well-tolerated therapies like sacituzumab govitecan, a novel antibody-drug conjugate and (5) improving affordability and accessibility to systemic therapy agents.

H+/K+-ATPase (Proton Pump) is responsible for acid production from parietal cells of stomach. Acid-related disorders are caused by uncontrolled activity of proton pumps. Inhibition of these proton pumps has been shown to be effective in the treatment of GERD (Gastro-oesophageal reflux disease). Our aim was to investigate the effective proton pump inhibitor and prediction of the best analogues. Quantitative Structure Activity Relationship (QSAR) was performed on two sets of molecules, i.e., on tert-Butyl1, 5- bis(4-(benzo[d]isothiazol-3-yl)piperazin-1-yl)-1,5-dioxopentan-2-ylcarbamte urea/thio-urea derivatives and schiff base of quinazolinone derivatives. Biological activity for H+/K+-ATPase inhibition was found to be significantly correlated with polarizability and surface tension (ST) for the first set of analogues and with polar surface area (PSA), polarizability and hydrophobic constant for the second set of analogues, indicating the involvement of strong electronic interaction between the molecule and the receptor. Based on the correlations obtained from the schiff’s base derivatives by the QSAR model, new H+/K+-ATPase inhibitors were predicted. Based on the generated QSAR Model, a series of new compounds were designed. Afterwards, these compounds were docked with the protein and their ADME properties were evaluated. Toxicity of these new analogues was also predicted. The QSAR studies were not performed on both sets of analogues previously. Present study predicts more potent, less toxic, easily synthesisable leadcompounds.

Cancers with mutations in BRCA2 have defective DNA repair capacity which is potentially targetable with poly-ADP(ribose) polymera se (PARP) inhibitors such as olaparib and rucaparib. However, the development of a secondary mutation that restores BRCA2 function is a well-documented mechanism of resistance to PARP inhibitors. Here, we present a case report of a man with metastatic castration-resistant prostate cancer with a germline BRCA2 frameshift mutation. Treatment with olaparib resulted in an initial response but was followed by progression. Cell-free DNA testing after progression revealed the presence of polyclonal BRCA2 mutations that were estimated to restore it into the correct reading frame. We describe his treatment course and genetic testing results and then discuss the biological mechanisms driving this mechanism of resistance.

To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3–12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4–7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.

Background CD73–adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5′-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR; ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response.Methods Patients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative (CS=0), CD73low or CD73high (< and ≥median CS, respectively). Multivariable Cox regression analysis compared disease-free survival (DFS) and overall survival (OS) between CD73 expression groups. In the TCGA dataset, samples were categorized as low, intermediate and high NT5E, ENTPD1 and ADORA2A gene expression groups. Gene expression signatures for infiltrating immune cells, angiogenesis, myeloid inflammation, and effector T-cell response were compared between NT5E, ENTPD1 and ADORA2A expression groups.Results Among the 138 patients eligible for inclusion, ‘any’ CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73high tumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negative group (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, high NT5E expression was associated with significantly worse 5-year OS (p=0.008). NT5E and ENTPD1 expression correlated with higher regulatory T cell (Treg) signature, while ADORA2A expression was associated with increased Treg and angiogenesis signatures.Conclusions High CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73–adenosine pathway in RCC.