Correlation of the Geriatric Assessment with Overall Survival in Older Patients with Cancer.

AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS: This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS: Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION: The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.

Pharmacology and toxicology of xylazine: quid novum?

The current opioid overdose crisis is characterized by the presence of unknown psychoactive adulterants. Xylazine is an alpha-2 receptor agonist that is not approved for human use but is commonly used in veterinary medicine due to its sedative and muscle-relaxant properties. Cases of human intoxication due to accidental or voluntary use have been reported since the 1980s. However, reports of adulteration of illicit opioids (heroin and illicit fentanyl) with xylazine have been increasing all over Western countries. In humans, xylazine causes respiratory depression, bradycardia, and hypotension-posing individuals, using xylazine-adulterated opioids. We present a narrative review of the latest intoxication cases related to xylazine, to bring awareness to readers and also to help pathologists to detect and deal with xylazine cases.

Hybrid descriptors-conjoint indices: a case study on imidazole-thiourea containing glutaminyl cyclase inhibitors for design of novel anti-Alzheimer's candidates.

Clinical studies show that the pyroglutamate alteration of amyloid-ß (Aß) catalysed by metalloenzyme glutaminyl cyclase results in the formation of the more neurotoxic pGlu-Aß, and inhibition of glutaminyl cyclase can bring down the load of pGlu-Aß in the brain and reduces Alzheimer's disease pathology with improvement in cognition. The present study involves the identification of activity-modulating structural features of 188 inhibitors of glutaminyl cyclase under the influence of index of ideality of correlation (IIC) and correlation intensity index (CII) as prediction parameters. The QSAR models developed employing IIC and CII were found to be statistically better and had better predictability than the models developed without them. The best model (split 4) showed r2 values of 0.8155 and 0.8218 for calibration and validation sets, respectively. The structural features classified from QSAR models were used to design some new glutaminyl cyclase inhibitors. Among the designed ligands, ligand 5 possesses the highest pIC50 value (6.30) as well as binding affinity (-6.2 kcal/mol) and creates hydrogen bonds with TRP 329, π-alkyl interactions with ILE 303 and TYR 299, π-π stacking interaction with PHE 325 and interactions with ZN 391. All novel designed ligands have better pIC50 values and binding affinities.

Study Protocol of the Bladder Adjuvant RadioTherapy (BART) Trial: A Randomised Phase III Trial of Adjuvant Radiotherapy Following Cystectomy in Bladder Cancer.

AIMS: To assess the efficacy and safety of adjuvant radiotherapy in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy. MATERIALS AND METHODS: The BART (Bladder Adjuvant RadioTherapy) trial is an ongoing multicentric, randomised, phase III trial comparing the efficacy and safety of adjuvant radiotherapy versus observation in patients with high-risk MIBC. The key eligibility criteria include ≥pT3, node-positive (pN+), positive margins and/or nodal yield <10, or, neoadjuvant chemotherapy for cT3/T4/N+ disease. In total, 153 patients will be accrued and randomised, in a 1:1 ratio, to either observation (standard arm) or adjuvant radiotherapy (test arm) following surgery and chemotherapy. Stratification parameters include nodal status (N+ versus N0) and chemotherapy (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy). For patients in the test arm, adjuvant radiotherapy to cystectomy bed and pelvic nodes is planned with intensity-modulated radiotherapy to a dose of 50.4 Gy in 28 fractions using daily image guidance. All patients will follow-up with 3-monthly clinical review and urine cytology for 2 years and subsequently 6 monthly until 5 years, with contrast-enhanced computed tomography abdomen pelvis 6 monthly for 2 years and annually until 5 years. Physician-scored toxicity using Common Terminology Criteria for Adverse Events version 5.0 and patient-reported quality of life using the Functional Assessment of Cancer Therapy - Colorectal questionnaire is recorded pre-treatment and at follow-up. ENDPOINTS AND STATISTICS: The primary endpoint is 2-year locoregional recurrence-free survival. The sample size calculation was based on the estimated improvement in 2-year locoregional recurrence-free survival from 70% in the standard arm to 85% in the test arm (hazard ratio 0.45) using 80% statistical power and a two-sided alpha error of 0.05. Secondary endpoints include disease-free survival, overall survival, acute and late toxicity, patterns of failure and quality of life. CONCLUSION: The BART trial aims to evaluate whether contemporary radiotherapy after standard-of-care surgery and chemotherapy reduces pelvic recurrences safely and also potentially affects survival in high-risk MIBC.

Strategies for safe management of hospital wastewater during the COVID-19 pandemic.

Management of hospital wastewater is a challenging task, particularly during the situations like coronavirus 2019 (COVID-19) pandemic. The hospital effluent streams are likely to contain many known and unknown contaminants including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with a variety of pollutants arising from pharmaceuticals, life-style chemicals, drugs, radioactive species, and human excreta from the patients. The effluents are a mixed bag of contaminants with some of them capable of infecting through contact. Hence, it is essential to identify appropriate treatment strategies for hospital waste streams. In this work, various pollutants emerging in the context of COVID-19 are examined. A methodical review is conducted on the occurrence and disinfection methods of SARS-CoV-2 in wastewater. An emphasis is given to the necessity of addressing the challenges of handling hospital effluents dynamically involved during the pandemic scenario to ensure human and environmental safety. A comparative evaluation of disinfection strategies makes it evident that the non-contact methods like ultraviolet irradiation, hydrogen peroxide vapor, and preventive approaches such as the usage of antimicrobial surface coating offer promise in reducing the chance of disease transmission. These methods are also highly efficient in comparison with other strategies. Chemical disinfection strategies such as chlorination may lead to further disinfection byproducts, complicating the treatment processes. An overall analysis of various disinfection methods is presented here, including developing methods such as membrane technologies, highlighting the merits and demerits of each of these processes. Finally, the wastewater surveillance adopted during the COVID-19 outbreak is discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-023-04803-1.

Patient-reported Quality of Life following Stereotactic Body Radiation Therapy for Primary Kidney Cancer - Results from a Prospective Cohort Study.

AIMS: We report on the first prospective series of patient-reported quality of life (QoL) following stereotactic body radiation therapy (SBRT) for primary kidney cancer. MATERIALS AND METHODS: Patients were treated on a multi-institutional prospective cohort study with 30-42 Gy SBRT in three or five fractions. QoL assessments were carried out using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-15 Palliative (EORTC-QLQ-C15-PAL), the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FACT FKSI-19) and the EuroQol-5D-3L tools at baseline, 1 week, and 1, 3 and 6 months post-treatment. QoL over time was analysed using linear mixed modelling, pairwise and anchor-based analyses. RESULTS: Twenty-eight patients were included. No significant reduction in any QoL metric was observed on repeated measures. However, a trend to reduced EORTC global QoL and fatigue was observed at 1 week, with improvement over time in other symptom scores such as pain, appetite and nausea. On pairwise analysis, there were statistically significant reductions in global QoL at 1 week (with subsequent recovery) and dyspnoea at 6 months post-SBRT. Trends to improved pain, appetite and nausea were observed following SBRT. Less than half of patients reported stable or better EORTC global QoL at 1 week. For all other QoL and symptom scales, most patients had reported stable or better scores at all times, with a slight proportional improvement in emotional functioning, nausea, fatigue, pain and appetite, and a slight worsening of physical functioning and dyspnoea over time. CONCLUSIONS: SBRT results in well-preserved QoL in the weeks to months following treatment for primary kidney cancer.

Application of Hereditary Renal Cell Carcinoma Risk Criteria to a Large Prospective Database.

AIMS: To evaluate the clinical impact of the Canadian criteria for identifying patients and families at risk for hereditary renal cell carcinoma (RCC). MATERIALS AND METHODS: The Canadian hereditary RCC risk criteria were applied to patients from 16 centres in the Canadian Kidney Cancer information system (CKCis) prospective database. The primary end point was the proportion of patients who met at least one criterion. RESULTS: Between January 2011 and May 2017, 8388 patients were entered in the database; 291 had inadequate risk data; 2827 (35%) met at least one criterion for genetic testing (at-risk population). Most (83%) met just one criterion. The criterion of non-clear cell histology contributed the largest proportion of at-risk patients (59%), followed by age ≤ 45 years (28%). Sixty-one patients had documentation of genetic testing, with 56 being classified at-risk (2% of at-risk). Twenty patients (35%) of the patients at risk and tested for hereditary RCC were found to harbour a germline mutation. CONCLUSIONS: Application of the Canadian hereditary RCC risk criteria to a large prospective database resulted in 35% of patients being identified at risk for hereditary RCC who could qualify for genetic testing. However, the true incidence of hereditary RCC in this population is unknown as most patients did not have documented genetic testing carried out and, thus, the sensitivity and specificity of the criteria cannot be determined. The low proportion of at-risk patients who underwent genetic testing is disappointing and highlights that there may be gaps in reporting, knowledge and/or barriers in access to genetic testing.

Renal cell carcinoma in the Canadian Indigenous population.

Background: Diagnosis and treatment of renal cell carcinoma (rcc) might be different in Indigenous Canadians than in non-Indigenous Canadians. In this cohort study, we compared rcc presentation and treatments in Indigenous and non-Indigenous Canadians. Methods: Patients registered in the Canadian Kidney Cancer Information System treated at 16 institutions between 2011 and 2018 were included. Baseline patient, tumour, and treatment characteristics were compared between Indigenous and non-Indigenous Canadians. The primary objective was to determine if differences in rcc stage at diagnosis were evident between the groups. The secondary objective was to determine if treatments and outcomes were different between the groups. Results: During the study period, 105 of the 4529 registered patients self-identified as Indigenous. Those patients were significantly younger at the time of clinical diagnosis (57.9 ± 11.3 years vs. 62.0 ± 12.1 years, p = 0.0006) and had a family history prevalence of rcc that was double the prevalence in the non-Indigenous patients (14% vs. 7%, p = 0.004). Clinical stage at diagnosis was similar in the two groups (p = 0.61). The disease was metastatic at presentation in 11 Indigenous Canadians (10%) and in 355 non-Indigenous Canadians (8%). Comorbid conditions that could affect the management of rcc-such as obesity, renal disease, diabetes mellitus, and smoking-were more common in Indigenous Canadians (p < 0.05). Indigenous Canadians experienced a lower rate of active surveillance (p = 0.01). Treatments and median time to treatments were similar in the two groups. Conclusions: Compared with their non-Indigenous counterparts, Indigenous Canadian patients with rcc are diagnosed at an earlier age and at a similar clinical stage. Despite higher baseline comorbid conditions, clinical outcomes are not worse for Indigenous Canadians than for non-Indigenous Canadians.

Obesity risk factors in American Indians and Alaska Natives: a systematic review.

OBJECTIVES: We systematically reviewed the literature on risk factors for obesity in American Indians (AIs) and Alaska Natives (ANs) of all ages. STUDY DESIGN: We searched titles and abstracts in PubMed with combinations of the following terms: obesity, body mass index (BMI), American Indian, Alaska Native, and Native American. METHODS: We limited our review to articles that provided an empirically testable claim about a variable associated with obesity, measured obesity as a dependent variable, and provided data specific to AI/ANs. RESULTS: Our final sample included 31 articles; 20 examined AI/AN youth (<18 years), and 11 examined AI/AN adults (≥18 years). Risk factors for obesity varied by age. In infants, low birth weight, early termination of breastfeeding, and high maternal BMI, and maternal diabetes increased the risk of childhood obesity. In children and adolescents, parental obesity, sedentary behaviors, and limited access to fruits and vegetables were associated with obesity. In adulthood, sedentary behaviors, diets high in fats and carbohydrates, stress, verbal abuse in childhood, and the belief that health cannot be controlled were associated with obesity. CONCLUSIONS: Extant studies have three limitations: they do not apply a life course perspective, they lack nationally representative data and have limited knowledge of the resilience, resistance and resourcefulness of AI/ANs. Future studies that avoid these shortcomings are needed to inform interventions to reduce the prevalence of obesity in AI/ANs across the life course.

Is there a role for adjuvant therapy after surgery in "high risk for recurrence" kidney cancer? An update on current concepts.

Background: Although surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting. In this paper, we provide a narrative review of the progress in this field, and we summarize the results from recent adjuvant trials that have been completed. Methods: A literature search was conducted. The primary search strategy at the medline, Cochrane reviews, and http://ClinicalTrials.gov/databases included the keywords "adjuvant therapy," "renal cell carcinoma," and "targeted therapy or/and immunotherapy." Conclusions: Data from the s-trac study indicated that, in the "highest risk for recurrence" patient population, disease-free survival was increased with the use of adjuvant sunitinib compared with placebo. The assure trial showed no benefit for adjuvant sunitinib or sorafenib in the "intermediate- to high-risk" patient population. The ariser (adjuvant girentuximab) and protect (adjuvant pazopanib) trials indicated no survival benefit, but subgroup analyses in both trials recommended further investigation. The inconsistency in some of the current results can be attributed to a variety of factors pertaining to the lack of standardization across the trials. Nevertheless, patients in the "high risk of recurrence" category after surgery for their disease would benefit from a discussion about the potential benefits of adjuvant treatment and enrolment in ongoing adjuvant trials.

Anastomosing hemangioma of the kidney: radiologic and pathologic distinctions of a kidney cancer mimic.

Anastomosing hemangioma (ah) is a rare subtype of primary vascular tumour that can, clinically and radiologically, present similarly to malignant renal tumours such as renal cell carcinoma (rcc) and angiosarcoma. Rarely seen in the genitourinary system, the ah we report here occurred in a 40-year-old male patient diagnosed initially with rcc based on imaging and successfully treated by laparoscopic left radical nephrectomy, with adrenal sparing and perihilar lymph node dissection. The pathologic diagnosis of ah can be challenging on small biopsy specimens; we therefore opine that it is appropriate to excise these lesions to facilitate diagnosis and definitively exclude common renal cancers. However, in this review, we describe some radiologic and pathologic distinctions between ah and malignant tumours.

Use of targeted therapy in patients with metastatic renal cell carcinoma: clinical and economic impact in a Canadian real-life setting.

Introduction: Outside of randomized controlled clinical trials, the understanding of the effectiveness and costs associated with targeted therapies for metastatic renal cell carcinoma (mrcc) is limited in Canada. The purpose of the present study was to use real-world prospective data to assess the effectiveness and cost of targeted therapies for patients with mrcc. Methods: The Canadian Kidney Cancer Information System, a pan-Canadian database, was used to identify prospectively collected data relating to patients with mrcc. First- and subsequent-line time to treatment termination (ttt) was determined from therapy initiation time (sunitinib or pazopanib) to discontinuation of therapy. Kaplan-Meier survival curves were used to estimate the unadjusted and adjusted overall survival (os) by treatment. Unit treatment cost was used to estimate the cost by line of treatment and the total cost of therapy for the management of patients with mrcc. Results: The study included 475 patients receiving sunitinib or pazopanib in the first-line setting. Patients were treated mostly with sunitinib (81%); 19% of patients were treated with pazopanib. The median ttt in the first line was 7.7 months for patients receiving sunitinib and 4.6 months for those receiving pazopanib (p < 0.001). The adjusted os was 32 months with sunitinib and 21 months with pazopanib (hazard ratio: 1.61; p < 0.01). The total median cost of first- and second-line treatments was $56,476 (interquartile range: $23,738-$130,447) for patients in the sunitinib group and $46,251 (interquartile range: $28,167-$91,394) for those in the pazopanib group. Conclusions: For the two therapies, os differed significantly, with a higher median os being observed in the sunitinib group. The cost of treatment was higher in the sunitinib group, which is to be expected with longer survival.

Practice Patterns and Outcomes for Pemetrexed Plus Platinum Doublet as Neoadjuvant Chemotherapy in Adenocarcinomas of Lung: Looking Beyond the Usual Paradigm.

AIMS: Neoadjuvant chemotherapy (NACT) is the standard of care in non-small cell lung cancers (NSCLC) with locally advanced N2 disease. There is a scarcity of data for the pemetrexed-platinum regimen as NACT. Also, apart from N2 disease, the role of NACT in locally advanced NSCLCs for tumour downstaging is unclear. MATERIALS AND METHODS: Non-metastatic adenocarcinomas of lung treated with pemetrexed-platinum-based NACT were analysed. The patients with locoregionally advanced N2 disease and those who were borderline candidates for upfront definitive treatment were planned for NACT after discussion in a multidisciplinary clinic. In total, four cycles of 3-weekly pemetrexed and platinum were delivered in the combined neoadjuvant and adjuvant setting. A response assessment was carried out using RECIST criteria. Progression-free (PFS) and overall survival were calculated using the Kaplan-Meier method. RESULTS: Of 114 patients, 96 evaluable patients received NACT with pemetrexed-platinum. The most common indication for NACT was N2 disease at baseline (46.8%). The objective response rate was 36.4% (95% confidence interval 22-52%), including two complete and 32 partial responses, whereas 12.5% of patients had progressive disease on NACT. The median PFS was 14 months (95% confidence interval 10.7-17.3) and the median overall survival was 22 months (95% confidence interval 15.6-28.4) at a median follow-up of 16 months. There was a significant improvement in the overall survival of patients undergoing definitive therapy versus no definitive therapy (median overall survival 25 months [95% confidence interval 19.6-30.4] versus 12 months [95% confidence interval 3.2-20.7], respectively; P = 0.015, hazard ratio 0.56 [95% confidence interval 0.3-0.9]). Among patients who could not undergo definitive chemoradiation upfront due to dosimetric constraints (n = 34), 24 (70.6%) patients finally underwent definitive therapy after NACT. CONCLUSIONS: Pemetrexed-platinum-based NACT seems to be an effective option and many borderline cases, where upfront definitive therapy is not feasible, may become amenable to the same after incorporation of NACT.

Clinical presentation, management, and outcomes in the Indian Heart Rhythm Society-Atrial Fibrillation (IHRS-AF) registry.

AIM: A national atrial fibrillation (AF) registry was conducted under the aegis of the Indian Heart Rhythm Society (IHRS), to capture epidemiological data-type of AF, clinical presentation and comorbidities, current treatment practices, and 1-year follow-up outcomes. METHODS: A total of 1537 patients were enrolled from 24 sites in India in the IHRS-AF registry from July 2011 to August 2012. Their baseline characteristics and follow-up data were recorded in case report forms and subsequently analyzed. RESULTS: The average age of Indian AF patients was 54.7 years. There was a marginal female preponderance - 51.5% females and 48.5% males. At baseline, 20.4% had paroxysmal AF; 33% had persistent AF; 35.1% had permanent AF and 11% had first AF episode. At one-year follow-up, 45.6% patients had permanent AF. Rheumatic valvular heart disease (RHD) was present in 47.6% of patients. Hypertension, heart failure, coronary artery disease, and diabetes were seen in 31.4%, 18.7%, 16.2%, and 16.1%, respectively. Rate control was the strategy used in 75.2% patients, digoxin and beta-blockers being the most frequently prescribed rate-control drugs. Oral anticoagulation (OAC) drugs were used in 70% of patients. The annual mortality was 6.5%, hospitalization 8%, and incidence of stroke 1%. CONCLUSIONS: In India, AF patients are younger and RHD is still the most frequent etiology. Almost two-third of the patients have persistent/permanent AF. At one-year follow-up, there is a significant mortality and morbidity in AF patients in India.

Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: a network meta-analysis.

Essentials Despite trial data, guidelines have not endorsed direct oral Xa inhibitors above other options. We provide profiles of venous thromboembolism and hemorrhage risk for 12 options. Direct oral Xa inhibitors had a favorable profile compared with low-molecular-weight heparin. Other options did not have favorable profiles compared with low-molecular-weight heparin. SUMMARY: Background There are numerous trials and several meta-analyses comparing venous thromboembolism (VTE) prophylaxis options after total hip and knee replacement (THR and TKR). None have included simultaneous comparison of new with older options. Objective To measure simultaneously the relative risk of VTE and hemorrhage for 12 prophylaxis options. Methods We abstracted VTE and hemorrhage information from randomized controlled trials published between January 1990 and June 2016 comparing 12 prophylaxis options. We then constructed networks to compute the relative risk for each option, relative to once-daily dosing with low-molecular-weight heparin (LMWH) Low. Results Main: Relative to LMWH Low, direct oral Xa inhibitors had the lowest risk of total deep vein thrombosis (DVT)-asymptomatic and symptomatic- (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.35-0.57), translating to 53-139 fewer DVTs per 1000 patients. Vitamin K antagonists (VKAs) titrated to International Normalized Ratio [INR] 2-3 predicted 56% more DVT events (OR, 1.56; 95% CI, 1.14-2.14). Aspirin performed similarly (OR, 0.80; 95% CI, 0.34-1.86), although small numbers prohibit firm conclusions. Direct oral Xa inhibitors did not lead to significantly more bleeding (OR, 1.21; 95% CI, 0.79-1.90). Secondary: Relative to LMWH Low, direct oral Xa inhibitors prevented 4-fold more symptomatic DVTs (OR, 0.25; 95% CI, 0.13-0.47). Conclusions Relative to LMWH Low, direct oral Xa inhibitors had a more favorable profile of VTE and hemorrhage risk, whereas VKAs had a less favorable profile. The profile of other agents was not more or less favorable. Clinicians should consider these profiles when selecting prophylaxis options.

Should sputum-negative presumptive TB patients be actively followed to identify missing cases in India?

Setting: Sputum smear microscopy, the primary diagnostic tool used for diagnosis of tuberculosis (TB) in India's Revised National TB Control Programme (RNTCP), has low sensitivity, resulting in a significant number of TB cases reported as sputum-negative. As the revised guidelines pose challenges in implementation, sputum-negative presumptive TB (SNPT) patients are subjected to 2 weeks of antibiotics, followed by chest X-ray (CXR), resulting in significant loss to care among these cases. Objective: To determine whether reducing delays in CXR would yield additional TB cases and reduce initial loss to follow-up for diagnosis among SNPT cases. Methods: In an ongoing intervention in five districts of Maharashtra, SNPT patients were offered upfront CXR. Results: Of 119 male and 116 female SNPT patients with a mean age of 45 years who were tested by CXR, 32 (14%) were reported with CXR suggestive of TB. Administering upfront CXR in SNPT patients yielded twice as many additional cases, doubling the proportion of cases detected among all those tested as against administering CXR 2 weeks after smear examination. Conclusion: Our interventional study showed that the yield of TB cases was significantly greater when upfront CXR examination was undertaken without waiting for a 2-week antibiotic trial.

Contexte : La microscopie de frottis de crachats, le premier outil utilisé dans le diagnostic de la TB dans le programme national TB révisé d'Inde (RNTCP), a une faible sensibilité, ce qui aboutit à un nombre significatif de cas de TB rapportés comme étant à frottis négatif. Comme la mise en œuvre des directives révisées reste un défi, les patients présumés TB à frottis négatif (SNPT) sont soumis à 2 semaines d'antibiotiques suivis par une radiographie pulmonaire (CXR), d'où un nombre significative de cas de SNPT perdus de vue.Objectif : Déterminer si la réduction du délai de CXR aboutit à détecter des cas de TB supplémentaires et réduit les pertes de vue initiales parmi les cas de SNPT.Méthodes : Dans le cadre d'une intervention en cours dans cinq districts de Maharashtra, on a offert aux cas de SNPT une CXR immédiate.Résultats : Un total de 119 hommes et 116 femmes, patients SNPT, d'âge moyen 45 ans, ont eu une CXR. Parmi ces 235 patients, 32 (14%) ont eu une CXR suggestive de TB. Le recours immédiat à une CXR chez les patients présumées TB à frottis négatif a produit deux fois plus de cas supplémentaires et doublé la proportion de cas détectés parmi les patients ayant bénéficié d'une CXR immédiate par rapport à ceux l'ayant eue 2 semaines après la microscopie de frottis.Conclusion : Notre étude d'intervention a montré que la détection de cas de TB était significativement plus importante en faisant une CXR immédiate sans attendre les 2 semaines de traitement d'essai par antibiotiques.

Marco de referencia: La baciloscopia del esputo es el principal instrumento utilizado en el diagnóstico de la tuberculosis (TB) en el marco del Programa Revisado de Control de la Tuberculosis de la India (RNTCP) y ofrece una baja sensibilidad, con lo cual un gran número de casos de TB se notifican con baciloscopia negativa. Dadas las dificultades de aplicación de una revisión reciente de las directrices, en los pacientes con presunción clínica de TB y un resultado negativo de la baciloscopia se administran antibióticos de amplio espectro durante 2 semanas seguidos de una radiografía de tórax (CXR), con la consiguiente pérdida de la atención de muchos de los pacientes con baciloscopia negativa.Objetivo: Determinar si el hecho de acortar la demora en la realización de la CXR mejora el rendimiento diagnóstico de casos de TB y disminuye las pérdidas iniciales durante el seguimiento de los casos con baciloscopia negativa.Método: En el marco de una intervención en curso en cinco distritos de Maharashtra, se propuso a los pacientes con presunción clínica de TB y baciloscopia negativa practicar de inmediato la CXR.Resultados: Se practicó la CXR en pacientes con presunción de TB pulmonar y baciloscopia negativa; participaron 119 pacientes de sexo masculino y 116 de sexo femenino, con una edad promedio de 45 años. De estas 235 personas, en 32 casos el informe de la CXR refería imágenes indicativas de TB (14%). La práctica inmediata de la CXR en los pacientes con presunción clínica de TB que reciben un resultado negativo de la baciloscopia aportó el doble de casos adicionales y duplicó así la proporción de casos detectados en todas las personas examinadas, en comparación con la CXR practicada 2 semanas después de la baciloscopia.Conclusión: El presente estudio de intervención reveló un aumento considerable del rendimiento diagnóstico de casos de TB cuando se practica la CXR de inmediato, en lugar de esperar el resultado de una antibioterapia de prueba de 2 semanas.

Transforming the Perioperative Treatment Paradigm in Non-Metastatic RCC-A Possible Path Forward.

In 2017, there is no adjuvant systemic therapy proven to increase overall survival in non-metastatic renal cell carcinoma (RCC). The anti-PD-1 antibody nivolumab improves overall survival in metastatic treatment refractory RCC and is generally tolerable. Mouse solid tumor models have revealed a benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivolumab in RCC patients have shown preliminary feasibility and safety with no surgical delays or complications. The recently opened PROSPER RCC trial (A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients with Localized Renal Cell Carcinoma Undergoing Nephrectomy; EA8143) will examine if the addition of perioperative nivolumab to radical or partial nephrectomy can improve clinical outcomes in patients with high risk localized and locally advanced RCC. With the goal of increasing cure and recurrence-free survival (RFS) rates in non-metastatic RCC, we are executing a three-pronged, multidisciplinary approach of presurgical priming with nivolumab followed by resection and adjuvant PD-1 blockade. We plan to enroll 766 patients with clinical stage ≥T2 or node positive M0 RCC of any histology in this global, randomized, unblinded, phase 3 National Clinical Trials Network study. The investigational arm will receive two doses of nivolumab 240 mg IV prior to surgery followed by adjuvant nivolumab for 9 months. The control arm will undergo the current standard of care: surgical resection followed by observation. Patients are stratified by clinical T stage, node positivity, and histology. The trial is powered to detect a 14.4% absolute benefit in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 years (HR = 0.70). The study is also powered to detect a significant overall survival benefit (HR 0.67). Key safety, feasibility, and quality of life endpoints are incorporated. PROSPER RCC exemplifies team science with a host of planned correlative work to investigate the impact of the baseline immune milieu and changes after neoadjuvant priming on clinical outcomes.

Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of low-risk upper tract urothelial carcinoma.

INTRODUCTION: The conservative management of upper tract urothelial carcinoma (UTUC) has historically been offered to patients with imperative indications. The recent International Consultation on Urologic Diseases (ICUD) publication on UTUC stratified treatment allocations based on high- and low-risk groups. This report updates the conservative management of the low-risk group. METHODS: The ICUD for low-risk UTUC working group performed a thorough review of the literature with an assessment of the level of evidence and grade of recommendation for a variety of published studies in this disease space. We update these publications and provide a summary of that original report. RESULTS: There are no prospective randomized controlled studies to support surgical management guidelines. A risk-stratified approach based on clinical, endoscopic, and biopsy assessment allows selection of patients who could benefit from kidney-preserving procedures with oncological outcomes potentially similar to radical nephroureterectomy with bladder cuff excision, with the added benefit of renal function preservation. These treatments are aided by the development of high-definition flexible digital URS, multi-biopsies with the aid of access sheaths and other tools, and promising developments in the use of adjuvant topical therapy. CONCLUSIONS: Recent developments in imaging, minimally invasive techniques, multimodality approaches, and adjuvant topical regimens and bladder cancer prevention raise the hope for improved risk stratification and may greatly improve the endoscopic treatment for low-risk UTUC.

Pattern of socio-economic and health aspects among TB patients and controls.

BACKGROUND: Socio-economic and health-related factors have a significant impact on tuberculosis (TB) incidence among population residing in resource-scare settings. OBJECTIVE: To evaluate the pattern of socio-economic and health-related factors among TB patients and control in Delhi, India. METHODS: The present cross-sectional study was performed among 893 TB patients (or cases) and 333 healthy disease-free controls. The data for the present study was obtained from several district TB centres in north, west and south Delhi. The collected data was edited, coded and statistical analysed with the help of SPSS 20.0 version. RESULTS: Illiteracy and primary education were significant risk factors being associated with a TB. Rented housing condition had an odds ratio (OR) of 1.4 (95% confidence interval [CI]: 1.09-1.89) compared to owned housing condition. 3-5 individuals per room were 3 times more likely to be associated with a case of TB (95% CI: 2.49-4.41). Migrant individuals were 13 times more likely to be associated with a case of TB (95% CI: 8.77-19.78) in comparison to settled population. Daily consumption of non-vegetarian food also significantly contributed to case of TB with an OR of 3.4 (95% CI: 2.51-4.72). Loss of appetite and family TB served as significant health-related factors associated with TB risk. CONCLUSION: Lower educational status, rented household, individuals per room (as a measure of overcrowding) and migratory status served as prominent risk factors for TB disease. Preference and frequency of non-vegetarian food being consumed, night sweating, weight loss, loss of appetite, earlier TB and family TB were principle health-related risk factors associated with TB disease.