Gender-specific outcomes in immune checkpoint inhibitor therapy for advanced or metastatic urothelial cancer: a systematic review and meta-analysis.

PURPOSE To analyze gender-specific differences in survival parameters in advanced or metastatic urothelial cancer patients undergoing immune checkpoint inhibition. METHODS The primary aim of this systematic review and meta-analysis was to evaluate gender-specific differences in disease-free (DFS), progression-free (PFS), cancer-specific survival (CSS), event-free survival (EFS), overall survival (OS) and objective response rate (ORR). The sources MEDLINE, Embase and Cochrane Library were systematically searched from January 2010 to June 2022. No restrictions were made concerning language, study region or publication type. A comparison of gender-specific differences in survival parameters was performed using a random-effects meta-analysis. A risk of bias assessment was done using the ROBINS-I tool. RESULTS Five studies were included. In a random-effect meta-analysis of the studies, PCD4989g and IMvigor 211 with both using atezolizumab, females were more likely to have better objective response rate (ORR) than men (OR 2.24; 95% CI 1.20-4.16; p = 0.0110). In addition, females had a comparable median OS to men (MD 1.16; 95% CI - 3.15-5.46; p = 0.598). In summary, comparing all results, a tendency was seen toward better response rates and survival parameters in female patients. The risk of bias assessment yielded an overall low risk of bias. CONCLUSIONS There is a tendency toward better outcomes in women for immunotherapy in advanced or metastatic urothelial cancer, but only for the antibody atezolizumab women have a significantly better ORR. Unfortunately, many studies fail to report gender-specific outcomes. Therefore, further research is essential when aiming for individualized medicine. This research should address immunological confounders

Problematizando Experiências de Vítimas de Violências: Indagações e Análises

Título Problematizando experiências de vítimas de violência: indagações e análises. Autor Thiago Sandrini Mansur RESUMO Em geral, as reflexões sobre as pessoas que sofrem algum tipo de violência foram, por muito tempo, negligenciadas pelas sociedades em todo o mundo. Isso se torna ainda mais enfático no que diz respeito aos segmentos menos favorecidos da sociedade, sobretudo com relação àqueles que estão confinados em estabelecimentos de internação. No Brasil, este cenário foi se modificando lentamente ao longo do século XX, ganhando novos contornos por meio das experiências dos movimentos de defesa dos direitos humanos, sobretudo, a partir do período de contestação à ditadura militar. Num período mais recente de nossa história, o surgimento de centros de apoio às vítimas de violência pode ser considerado como uma maneira de colocar em análise as diversas formas de manifestação da violência, embora tais estabelecimentos não sejam os únicos, nem os primeiros a fazer isso. Os centros de apoio se tornaram locais não somente para que as vítimas de violência recebessem atendimento, mas, sobretudo, para que se incitasse a luta pela responsabilização de seus algozes e a criação de novos paradigmas para uma cultura de paz e não-violência. Tendo em vista este cenário, objetivou-se problematizar as experiências de pessoas que foram atingidas pela violência, residentes na Região Metropolitana da Grande Vitória e que buscaram apoio em um desses centros de atendimento. Problematizar uma experiência significa se perguntar como um conjunto de práticas discursivas e não discursivas que antes era aceito em uma sociedade sem questionamentos e tido como familiar e natural se torna um motivo de preocupação, incitando discussões, polemizando debates, suscitando mudanças de comportamento e instigando novos hábitos. Para alcançar tal propósito, foram realizadas atividades em grupo, nas quais se problematizou as experiências de mães que tiveram seus filhos violentados por agentes do Estado, quando em cumprimento de medida sócio-educativa de privação de liberdade. Também foram feitas entrevistas de restituição nas quais as mães puderam avaliar as experiências em grupo, bem como discutir os resultados e as conclusões da pesquisa. O objetivo dessas atividades foi compreender que práticas discursivas e não-discursivas sobre (e de) vítimas de violência se atualizam através de falas, ações, sentimentos e pensamentos. A que supostas verdades remetem? Que relações de saber-poder fazem funcionar? Como a experiência de estar em grupo coloca em questão certos modos de ser das vítimas? Em primeiro lugar, evidenciou-se que as pessoas participantes da pesquisa eram, em sua grande maioria, pobres, afro-descendentes, moradores de periferia e com baixa escolaridade, justamente o perfil típico das pessoas atingidas pela violência. Os resultados e as discussões levaram à conclusão de que muitas das pessoas atingidas pela violência, bem como seus familiares, embora sob esse forte impacto, apostaram e ainda apostam em afirmar a vida, ao invés de se colocarem no lugar de resignação, que muitas vezes é destinado às vítimas. Percebeu-se que conhecer e compartilhar as experiências dessas pessoas pode contribuir para a discussão acadêmica do problema e para a transformação de alguns dos efeitos deletérios da violência. Atualmente, quando falamos em vítimas de violência, imediatamente nos surgem imagens de indivíduos passivos e inertes que padecem na dor pelo resto de suas vidas. Tais imagens estão atreladas a uma visão intimista da realidade (SENNET, 1998), na qual se pensam as experiências como vivências individuais e particulares de cada um. Sendo assim, aquilo que uma pessoa vive diria respeito apenas a ela mesma e a mais ninguém. A existência dos centros de apoio às vítimas de violência delimita a constituição de espaços em que essas experiências podem ser problematizadas em suas verdades instituídas. Entendemos que problematizar uma experiência é evidenciar seu caráter de produção histórica e social. Isto significa dizer que aquilo que denominamos vítima de violência apresenta-se como uma forma circunstancial e provisória, ou seja, não-natural. Palavras-chave: Violência; Vítima; Experiência

Primary bladder adenocarcinoma: Case report with long-term follow-up

Primary Bladder Adenocarcinoma is a rare malignancy that has been observed in a heterogeneous patient population.This case report presents a 51 year old female with muscle-invasive primary bladder adenocarcinoma diagnosed in 2008. After transurethral resection and cystectomy with ileum neobladder adjuvant radiochemotherapy was administered. Two years later, a symptomatic fistula between neobladder and ileoileal anastomosis was excised, resulting in urinary incontinency. In 2016, the patient shows no signs of disease relapse but suffers from reduction of bladder capacity.This case report presents classical symptoms of adenocarcinoma of the bladder and a possible treatment regimen with associated side effects. Keywords: Adenocarcinoma, Urinary bladder, Urinary diversion, Urinary fistula, Oncolog

Radiomic Features and Machine Learning for the Discrimination of Renal Tumor Histological Subtypes: A Pragmatic Study Using Clinical-Routine Computed Tomography

This study evaluates the diagnostic performance of radiomic features and machine learning algorithms for renal tumor subtype assessment in venous computed tomography (CT) studies from clinical routine. Patients undergoing surgical resection and histopathological assessment of renal tumors at a tertiary referral center between 2012 and 2019 were included. Preoperative venous-phase CTs from multiple referring imaging centers were segmented, and standardized radiomic features extracted. After preprocessing, class imbalance handling, and feature selection, machine learning algorithms were used to predict renal tumor subtypes using 10-fold cross validation, assessed as multiclass area under the curve (AUC). In total, n = 201 patients were included (73.7% male; mean age 66 ± 11 years), with n = 131 clear cell renal cell carcinomas (ccRCC), n = 29 papillary RCC, n = 11 chromophobe RCC, n = 16 oncocytomas, and n = 14 angiomyolipomas (AML). An extreme gradient boosting algorithm demonstrated the highest accuracy (multiclass area under the curve (AUC) = 0.72). The worst discrimination was evident for oncocytomas vs. AML and oncocytomas vs. chromophobe RCC (AUC = 0.55 and AUC = 0.45, respectively). In sensitivity analyses excluding oncocytomas, a random forest algorithm showed the highest accuracy, with multiclass AUC = 0.78. Radiomic feature analyses from venous-phase CT acquired in clinical practice with subsequent machine learning can discriminate renal tumor subtypes with moderate accuracy. The classification of oncocytomas seems to be the most complex with the lowest accuracy

Primary renal sarcomas: imaging features and discrimination from non-sarcoma renal tumors

Objectives To assess imaging features of primary renal sarcomas in order to better discriminate them from non-sarcoma renal tumors. Methods Adult patients diagnosed with renal sarcomas from 1995 to 2018 were included from 11 European tertiary referral centers (Germany, Belgium, Turkey). Renal sarcomas were 1:4 compared to patients with non-sarcoma renal tumors. CT/MRI findings were assessed using 21 predefined imaging features. A random forest model was trained to predict renal sarcoma vs. non-sarcoma renal tumors based on demographics and imaging features. Results n = 34 renal sarcomas were included and compared to n = 136 non-sarcoma renal tumors. Renal sarcomas manifested in younger patients (median 55 vs. 67 years, p < 0.01) and were more complex (high RENAL score complexity 79.4% vs. 25.7%, p < 0.01). Renal sarcomas were larger (median diameter 108 vs. 43 mm, p < 0.01) with irregular shape and ill-defined margins, and more frequently demonstrated invasion of the renal vein or inferior vena cava, tumor necrosis, direct invasion of adjacent organs, and contact to renal artery or vein, compared to non-sarcoma renal tumors (p < 0.05, each). The random forest algorithm yielded a median AUC = 93.8% to predict renal sarcoma histology, with sensitivity, specificity, and positive predictive value of 90.4%, 76.5%, and 93.9%, respectively. Tumor diameter and RENAL score were the most relevant imaging features for renal sarcoma identification. Conclusion Renal sarcomas are rare tumors commonly manifesting as large masses in young patients. A random forest model using demographics and imaging features shows good diagnostic accuracy for discrimination of renal sarcomas from non-sarcoma renal tumors, which might aid in clinical decision-making

Cystatin C predicts renal function impairment after partial or radical tumor nephrectomy

Purpose: To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function. Methods: From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m2). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation. Results: Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10–20), rates of eGFR < 60 ml/min/1.73m2 were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m2 in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m2. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2–1.3 mg/dl, when graphically depicted vs. postoperative CysC values (‘creatinine blind area’). Conclusion: Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting

Cartilage calcification of the ankle joint is associated with osteoarthritis in the general population

Abstract Background Cartilage calcification (CC) is associated with osteoarthritis (OA) in weight-bearing joints, such as the hip and the knee. However, little is known about the impact of CC and degeneration on other weight-bearing joints, especially as it relates to the occurrence of OA in the ankles. The goal of this study is to analyse the prevalence of ankle joint cartilage calcification (AJ CC) and to determine its correlation with factors such as histological OA grade, age and BMI in the general population. Methods CC of the distal tibia and talus in 160 ankle joints obtained from 80 donors (mean age 62.4 years, 34 females, 46 males) was qualitatively and quantitatively analysed using high-resolution digital contact radiography (DCR). Correlations with factors, such as the joint’s histological OA grade (OARSI score), donor’s age and BMI, were investigated. Results The prevalence of AJ CC was 51.3% (95% CI [0.40, 0.63]), independent of gender (p = 0.18) and/or the joint’s side (p = 0.82). CC of the distal tibia was detected in 35.0% (28/80) (95% CI [0.25, 0.47]) and talar CC in 47.5% (38/80) (95% CI [0.36, 0.59]) of all cases. Significant correlations were noted between the mean amount of tibial and talar CC (r = 0.59, p = 0.002), as well as between the mean amount of CC observed in one ankle joint with that of the contralateral side (r = 0.52, p = 0.02). Furthermore, although the amount of AJ CC observed in the distal tibia and talus correlated with the histological OA-grade of the joint (r = 0.70, p < 0.001 and r = 0.72, p < 0.001, respectively), no such correlation was seen in the general population with relation to age (p = 0.32 and p = 0.49) or BMI (p = 0.51 and p = 0.87). Conclusion The prevalence of AJ CC in the general population is much higher than expected. The relationship between the amount of AJ CC and OA, independent of the donors’ age and BMI, indicates that CC may play a causative role in the development of OA in ankles

Can remote ischemic preconditioning counteract the renal functional deterioration attributable to partial nephrectomy under warm ischemia? Results of an animal study

Background To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. Methods Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. Results IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). Conclusion RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels