The state of circulation of the parenchyma of the kidney with unilateral lesion and its correction in the perioperative period

The aim of this work is to improve the results of complex treatment of patients with unilateral renal injury through the dynamic determination of renal blood flow disorders and its reasonable correction in the perioperative period. Based on the experimental study on 120 white Wistar rats in conditions of stable restriction of blood supply to the kidney parenchyma, acute disturbance of urodynamics, or their combination was reduced blood flow of the parenchyma of the injured kidney in proportion to the degree of pathological process, which occurs in the waveforms with maximum detection on the 3rd and 7th – 10th days. These disorders occur most clearly during the first 14 days, followed by stabilization of the process after 1 month. Adaptive-compensatory changes in the blood flow of the opposite kidney give a positive effect, starting from the 14th day, and lasting until the 4th month. Based on a clinical study using ultrasound Doppler and radioisotope studies, 108 patients with unilateral kidney damage were found to have impaired blood flow not only in the affected kidney but also in the opposite. A method of medical correction of disturbed blood flow during the perioperative period was developed and implemented, which allows to improve its quality by 7.8%

The role of lead in the ethiopathenesis of male fertility reduction

The problem of preserving and strengthening of the reproductive health of the population in conditions of the industrial regions is becoming one of the key. In the pathogenesis of male fertility, an important role belongs to the level of lead in biosubstrates, which is 1,2-2,1 times higher in industrial cities as compared to the normative level. Therewith, fertilizing properties of the ejaculate of the fertile men living in the industrial region comply with WHO standards, while in the infertile group various forms of pathology was revealed

La nycturie: un problème sous-estimé

La nycturie est une affection caractérisée par la nécessité de se réveiller ≥ 1 fois au cours de la nuit pour vider la vessie (pour uriner). Bien que la nycturie soit une affection multifactorielle qui peut coexister avec d'autres symptômes des voies urinaires inférieures, le facteur causal le plus courant est une production d’urine élévée pendant la nuit. La polyurie nocturne c’est une dominance de la diurèse nocturne par rapport à la diurèse diurne. Il est calculé à travers l'indice nocturne, qui ne doit pas dépasser 20 % dans la catégorie jusqu'à 60 ans et 33 % dans la catégorie 60 ans et plus

Analyse des patients subissant une cystectomie radicale: une expérience monocentrique

Pertinence. Le cancer de la vessie est le 7ème cancer le plus souvent diagnostiqué chez les hommes. Le taux d'incidence standardisé mondial (pour 100 000 habitants / an) est de 9 pour les hommes et de 2,2 pour les femmes (en Ukraine celui-ci est de 13,7 et 2,0 respectivement). Matériaux et méthodes de l’étude. Une analyse rétrospective de 73 cas de patients ayant subi une cystectomie radicale de 2018 jusqu’au mois de mai 2020 sur la base du département d'urologie №2 de l’Hôpital régional I.I. Mechnikov de Dnipro

Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial

Background The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma. Methods In the ongoing, randomised, open-label, phase 3 KEYNOTE-426 study, adults (≥18 years old) with treatmentnaive, advanced renal cell carcinoma with clear cell histology were enrolled in 129 sites (hospitals and cancer centres) across 16 countries. Patients were randomly assigned (1:1) to receive 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles plus 5 mg axitinib orally twice daily or 50 mg sunitinib monotherapy orally once daily for 4 weeks per 6-week cycle. Randomisation was done using an interactive voice response system or integrated web response system, and was stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk status and geographical region. Primary endpoints were overall survival and progression-free survival in the intentionto-treat population. Since the primary endpoints were met at the first interim analysis, updated data are reported with nominal p values. This study is registered with ClinicalTrials.gov, NCT02853331. Findings Between Oct 24, 2016, and Jan 24, 2018, 861 patients were randomly assigned to receive pembrolizumab plus axitinib (n=432) or sunitinib monotherapy (n=429). With a median follow-up of 30·6 months (IQR 27·2–34·2), continued clinical benefit was observed with pembrolizumab plus axitinib over sunitinib in terms of overall survival (median not reached with pembrolizumab and axitinib vs 35·7 months [95% CI 33·3–not reached] with sunitinib); hazard ratio [HR] 0·68 [95% CI 0·55–0·85], p=0·0003) and progression-free survival (median 15·4 months [12·7–18·9] vs 11·1 months [9·1–12·5]; 0·71 [0·60–0·84], p<0·0001). The most frequent (≥10% patients in either group) treatmentrelated grade 3 or worse adverse events were hypertension (95 [22%] of 429 patients in the pembrolizumab plus axitinib group vs 84 [20%] of 425 patients in the sunitinib group), alanine aminotransferase increase (54 [13%] vs 11 [3%]), and diarrhoea (46 [11%] vs 23 [5%]). No new treatment-related deaths were reported since the first interim analysis. Interpretation With extended study follow-up, results from KEYNOTE-426 show that pembrolizumab plus axitinib continues to have superior clinical outcomes over sunitinib. These results continue to support the first-line treatment with pembrolizumab plus axitinib as the standard of care of advanced renal cell carcinoma

Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426

https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.450

Pembrolizumab plus axitinib versus sunitinib as first-line therapy for advanced renal cell carcinoma (RCC): Updated analysis of KEYNOTE-426

The randomized, open-label, phase 3 KEYNOTE-426 study (NCT02853331) demonstrated that pembrolizumab (pembro) + axitinib (axi) significantly improved OS, PFS, and ORR vs sunitinib as first-line therapy for advanced RCC (aRCC) at the first pre-planned interim analysis (minimum study follow-up of 7 mo). Updated analyses are presented here

RESTORE-IMI 1: A Multicenter, Randomized, Doubleblind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections

Background. The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections. Methods. Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilatorassociated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenemnonsusceptible (but colistin- and imipenem/relebactam-susceptible) pathogens were randomized 2:1 to 5–21 days imipenem/ relebactam or colistin+imipenem. Primary endpoint: favorable overall response (defined by relevant endpoints for each infection type) in the modified microbiologic intent-to-treat (mMITT) population (qualifying baseline pathogen and ≥1 dose study treatment). Secondary endpoints: clinical response, all-cause mortality, and treatment-emergent nephrotoxicity. Safety analyses included patients with ≥1 dose study treatment. Results. Thirty-one patients received imipenem/relebactam and 16 colistin+imipenem. Among mITT patients (n = 21 imipenem/relebactam, n = 10 colistin+imipenem), 29% had Acute Physiology and Chronic Health Evaluation II scores >15, 23% had creatinine clearance <60 mL/min, and 35% were aged ≥65 years. Qualifying baseline pathogens: Pseudomonas aeruginosa (77%), Klebsiella spp. (16%), other Enterobacteriaceae (6%). Favorable overall response was observed in 71% imipenem/relebactam and 70% colistin+imipenem patients (90% confidence interval [CI] for difference, –27.5, 21.4), day 28 favorable clinical response in 71% and 40% (90% CI, 1.3, 51.5), and 28-day mortality in 10% and 30% (90% CI, –46.4, 6.7), respectively. Serious adverse events (AEs) occurred in 10% of imipenem/relebactam and 31% of colistin+imipenem patients, drug-related AEs in 16% and 31% (no drugrelated deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively. Conclusions. Imipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infection