Impact of a quality programme on overindication of surgeries for endometriosis and cholecystectomies.

Approximately 45% of patients receive medical services with minimal or no benefit (low-value care). In addition to the increasing costs to the health system, performing invasive procedures without an indication poses a potentially preventable risk to patient safety. This study aimed to determine whether a managed quality improvement programme could prevent cholecystectomy and surgery for endometriosis treatment with minimal or no benefit to patients.This before-and-after study was conducted at a private hospital in São Paulo, Brazil, which has a main medical remuneration model of fee for service. All patients who underwent cholecystectomy or surgery for endometriosis between 1 August 2020 and 31 May 2021 were evaluated.The intervention consisted of allowing the performance of procedures that met previously defined criteria or for which the indications were validated by a board of experts.A total of 430 patients were included in this analysis. The programme prevented the unnecessary performance of 13% of cholecystectomies (p=0.0001) and 22.2% (p=0.0006) of surgeries for the treatment of endometriosis. This resulted in an estimated annual cost reduction to the health system of US$466 094.93.In a hospital with a private practice and fee-for-service medical remuneration, the definition of clear criteria for indicating surgery and the analysis of cases that did not meet these criteria by a board of reputable experts at the institution resulted in a statistically significant reduction in low-value cholecystectomies and endometriosis surgeries.

Portuguese version of the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP): psychometric validation and prospective application for early functional outcomes at a single institution.

BACKGROUND: The Expanded Prostate Index Composite for Clinical Practice (EPIC-CP) is a short version of the original EPIC, developed to facilitate the instrument's use in routine care. This study aimed to validate the EPIC-CP Portuguese version, and evaluate its role in presenting early functional outcomes of surgically treated prostate cancer patients at a Latin American referral center. METHODS: The EPIC-CP was self-administered prospectively and individually by all localized prostate cancer patients, before and after robotic-assisted radical prostatectomy, from March 2017 to June 2018 at a single institution. For validation, we used the Cronbach's alpha coefficient to evaluate internal consistency. The EPIC-CP domains were compared before surgery, and 6 months and 12 months after surgery. Statistical analyses were performed using the student's t test, and Wilcoxon and Friedman tests, with p values < 0.05 considered significant. RESULTS: One hundred and fifty two patients answered the EPIC-CP. The patients had a median age of 62.7 (± 8.5) years and prostate specific antigen level of 6.3 (± 4.6) ng/ml. The Cronbach's alpha varied from 0.75 to 0.77 for all domains with good internal consistency, except for the "vitality/hormonal" domain, which had a score of 0.35. The domain evolution for the preoperative and 6-month postoperative groups revealed that the domains related to urinary continence and bowel worsened, and were increased during the first 6 months; however, this variation had no obvious clinical implications, and the irritative symptoms improved. Regarding the sexual domain, the scores worsened, and also increased over the first 6 months. The results of the confirmatory factor analysis were robust, with an explained variance of 0.951 and covariance of 0.929. CONCLUSIONS: The Portuguese version of the EPIC-CP is a reliable and valid questionnaire for postoperative patients, and very useful to improve the knowledge of the early functional outcomes of men treated for prostate cancer.

Bradykinin inhibits hepatic gluconeogenesis in obese mice.

The kallikrein-kinin system (KKS) has been previously linked to glucose homeostasis. In isolated muscle or fat cells, acute bradykinin (BK) stimulation was shown to improve insulin action and increase glucose uptake by promoting glucose transporter 4 translocation to plasma membrane. However, the role for BK in the pathophysiology of obesity and type 2 diabetes remains largely unknown. To address this, we generated genetically obese mice (ob/ob) lacking the BK B2 receptor (obB2KO). Despite similar body weight or fat accumulation, obB2KO mice showed increased fasting glycemia (162.3 ± 28.2 mg/dl vs 85.3 ± 13.3 mg/dl), hyperinsulinemia (7.71 ± 1.75 ng/ml vs 4.09 ± 0.51 ng/ml) and impaired glucose tolerance when compared with ob/ob control mice (obWT), indicating insulin resistance and impaired glucose homeostasis. This was corroborated by increased glucose production in response to a pyruvate challenge. Increased gluconeogenesis was accompanied by increased hepatic mRNA expression of forkhead box protein O1 (FoxO1, four-fold), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase (PEPCK, three-fold) and glucose-6-phosphatase (eight-fold). FoxO1 nuclear exclusion was also impaired, as the obB2KO mice showed increased levels of this transcription factor in the nucleus fraction of liver homogenates during random feeding. Intraportal injection of BK in lean mice was able to decrease the hepatic mRNA expression of FoxO1 and PEPCK. In conclusion, BK modulates glucose homeostasis by affecting hepatic glucose production in obWT. These results point to a protective role of the KKS in the pathophysiology of type 2 diabetes mellitus.

Altered glucose homeostasis and hepatic function in obese mice deficient for both kinin receptor genes.

The Kallikrein-Kinin System (KKS) has been implicated in several aspects of metabolism, including the regulation of glucose homeostasis and adiposity. Kinins and des-Arg-kinins are the major effectors of this system and promote their effects by binding to two different receptors, the kinin B2 and B1 receptors, respectively. To understand the influence of the KKS on the pathophysiology of obesity and type 2 diabetes (T2DM), we generated an animal model deficient for both kinin receptor genes and leptin (obB1B2KO). Six-month-old obB1B2KO mice showed increased blood glucose levels. Isolated islets of the transgenic animals were more responsive to glucose stimulation releasing greater amounts of insulin, mainly in 3-month-old mice, which was corroborated by elevated serum C-peptide concentrations. Furthermore, they presented hepatomegaly, pronounced steatosis, and increased levels of circulating transaminases. This mouse also demonstrated exacerbated gluconeogenesis during the pyruvate challenge test. The hepatic abnormalities were accompanied by changes in the gene expression of factors linked to glucose and lipid metabolisms in the liver. Thus, we conclude that kinin receptors are important for modulation of insulin secretion and for the preservation of normal glucose levels and hepatic functions in obese mice, suggesting a protective role of the KKS regarding complications associated with obesity and T2DM.

Soluble H-Y antigen and the search for molecules controlling sex determination in mammals

Recentemente demonstrou-se que a linhagem celular TM-4, derivada de células de Sertoli isoladas do testículo de camundongos imaturos BALB/c, secreta o antígeno H-Y. Essa evidência vem em apoio à hipótese de que o antígeno H-Y é o indutor do testículo em mamíferos. A disponibilidade de uma fonte de antígeno H-Y solúvel permitiu-nos desenvolver um imunoensaio sensível para a determinaçäo do antígeno H-Y em pacientes intersexuados. No entanto, a pesquisa de moléculas que controlam a determinaçäo do sexo em mamíferos (e em outros vertebrados) permanece um campo controvertido. O uso de sondas moleculares para o cromossomo Y, em conjunto com testes sorológicos, poderá permitir evidências mais conclusivas num futuro próximo