Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial.

Importance: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. Objective: To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. Design, Setting, and Participants: Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region. Interventions: Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment. Main Outcomes and Measures: Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated. Results: Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam. Conclusions and Relevance: Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage. Trial Registration: clinicaltrials.gov Identifier: NCT02166476.

Stereomorphology of the peripheral zone of the human prostate.

OBJECTIVE: Introduction: The human prostate gland is a complex organ that consists of two main components - glandular and non-glandular. The first of them represents a compound of components of different origin, structure, location, and complexity of spatial organization. Their stereomorphology and microanatomical interrelations remain understudied for a number of reasons. The aim: The objective of the research was to study the stereomorphological features of the glandular component of the peripheral zone of the prostate in view of its zonal structure concept. PATIENTS AND METHODS: Materials and methods: The material for the study was the glandular zone of the human prostate, which corresponds to the peripheral zone of the prostate according to the classification (Mc.Neal J.E., 1988). The following methods were used in the study: histological (4 mkm thick paraffin sections), microscopic (light microscopy using the Olympus BX-41 microscope), stereomorphological (obtaining waxed model reconstructions based on graphic ones). The study was conducted on 10 isolated prostate preparations (10 series of 50 preparations in each) taken from the deceased men without changes in the organ under investigation. The prostate gland was fixed in a 10% solution of buffered formalin, followed by obtaining serial plane-parallel sections and staining with hematoxylin and eosin according to the conventional technique. RESULTS: Results and conclusions: The ducts of the glands of the peripheral zone of the human prostate normally have recurrent luminal dilatations, which, like the multi-cavity terminal portions, can serve as a place for depositing a secret. The ducts of the peripheral zone glands, with the exception of the main duct, visually differ little in diameter. Their walls and walls of intra-acinar cavities are lined with homologous epithelial cells. Therefore, there is no clear morphological boundary between the transfer of the terminal portion to the duct and from one excretory duct to the other.

Management of the patients with blunt renal trauma: 20 years of clinical experience.

OBJECTIVE: Introduction: Blunt renal trauma (BRT) is a dangerous medical condition. The aim: Analysis of effectiveness of conservative and expectant treatment tactics under ultrasound and CT monitoring in patients with blunt renal trauma (BRT). PATIENTS AND METHODS: Materials and methods: The results of treatment of 81 patients with BRT during 20 years (1998-2017) were analyzed. Amount of men was 58 (71.6%), women - 23 (28.4%). Grade I trauma was seen in 37.0% of cases, grade II - in 25.9%, grade III - in 11.1%, grade IV - in 16.1% and grade V - in 9.9% of observations. RESULTS: Review: Conservative tactics was effective in 67.9% of observations. In 11.1% of cases treatment was accompanied with percutaneous drainage of liquid perirenal hematoma and urohematomas (in 2 cases with formation of perirenal abscess). Indications for surgical treatment (in 21.0% of observations) were progressing perirenal hematoma, unstable hemodynamics, inefficiency of hemorrhage stop with conservative treatment. In 9 cases, the kidney was sutured. Eight patients with multiple ruptures of the kidney, damage of the kidney vessels, massive bleeding underwent nephrectomy. CONCLUSION: Conclusions: Achievements in visualization and therapeutic technologies can avoid and, at severe trauma, reduce the surgical treatment rates in BRT. In the presence of urohematomas with the formation of perinephral abscess and development of sepsis, the method of choice is percutaneous drainage. Indications for surgical treatment are multiple parenchymal lacerations with damage of the segmental vessels and vessels of the renal hilum when the hemorrhage stop is ineffective by conservative or noninvasive methods.