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.

The Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Urosepsis-Associated Delirium.

Introduction Urosepsis is a systemic, dysregulated, inflammatory reaction to a urinary tract infection and can have severe effects on all systems, which can often lead to multi-organ failure and death. Sepsis-associated delirium is a common complication in critically ill patients, contributing to adverse outcomes and prolonged hospital stays. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential biomarker for sepsis severity and prognosis. Material and methods Our study investigates the utility of NLR in the diagnostic strategies for urosepsis-associated delirium in a cohort of 76 patients with sepsis and septic shock admitted to the Intensive Care Unit (ICU). We performed a single-centre retrospective observational study in the Craiova Clinical Emergency Hospital between June and October 2023. Results Patients with urological conditions that were diagnosed with urosepsis included 76 patients. These patients were clustered as follows: a group with delirium (37 patients, 48.7%) and another group without delirium (39 patients, 51.3%). Complete blood count parameters were obtained upon admission, and delirium was assessed using standardized diagnostic criteria. We identified a strong significant positive correlation between elevated NLR values on ICU admission and the development of delirium during hospitalization in urosepsis patients. Receiver operating characteristic (ROC) analysis showed similar diagnostic performance for NLR score. Conclusions The findings suggest that NLR may serve as a valuable biomarker for early detection, risk stratification, and guiding therapeutic interventions in urosepsis-associated delirium, thus improving outcomes in critically ill patients.

Transperineal Prostate Biopsy Targeted by Magnetic Resonance Imaging Cognitive Fusion.

Prostate cancer is among the most frequently diagnosed cancers and a leading cause of cancer-related death in men. Currently, the most reliable and widely used imaging test for prostate cancer diagnosis is multiparametric pelvic magnetic resonance imaging (mpMRI). Modern biopsy techniques are based on the computerised merging of ultrasound and MRI images to provide better vision during the biopsy procedure (Fusion Biopsy). However, the method is expensive due to high equipment cost. Cognitive fusion of ultrasound and MRI images has recently emerged as a cheaper and easier alternative to computerised fusion. The aim of this prospective study is to perform an in-patient comparison of the systematic prostate biopsy procedure (SB) vs. cognitive fusion (CF) guided prostate biopsy method in terms of safety, ease of use, cancer detection rate and clinically significant cancer detection. We enrolled 103 patients with suspected prostate cancer that were biopsy naive, with PSA > 4 ng/dL and PIRADS score of 3, 4 or 5. All patients received a transperineal standard 12-18 cores systematic biopsy (SB) and a four-cores targeted cognitive fusion (CF) biopsy. Following the prostate biopsy, 68% of the patients were diagnosed with prostate cancer (70/103 patients). SB diagnosis rate was 62% while CF biopsy was slightly better with a 66% rate. There was a significant 20% increase in clinically significant prostate cancer detection rate for the CF compared to SB (p < 0.05) and a significant prostate cancer risk upgrade from the low to the intermediate risk category (13%, p = 0.041). Transperineal cognitive fusion targeted prostate biopsy is a straightforward biopsy method that is easy to perform and is a safe alternative to standard systematic biopsy with improved significant cancer detection accuracy. A combined targeted and systematic approach should be used for the best diagnostic results.

VEGF Immunoexpression in Prostate Adenocarcinoma.

Angiogenesis is a basic biomolecular mechanism for tumor progression, the vascular endothelial growth factor (VEGF) being one of the main enhancers of this complex process. In this study, we analyzed VEGF-A immunoexpression in 61 prostate adenocarcinomas (PAs), related to the prognostic parameters of the lesions. VEGF scores were higher in PAs that associated serum PSA values above 20ng/ml, in tumors with pure complex or mixed growth patterns, as well as in high-grade and advanced lesions. The results obtained indicate the involvement of VEGF in prostate angiogenesis and the usefulness of the maker for the identification of aggressive lesions.

Analysis of Prostate Adenocarcinoma Histopathological Types in Relation to Tumor Grade.

Prostate adenocarcinomas are some of the most common malignancies diagnosed in men, and the evaluation of tumor growth patterns is the basis for establishing the aggressiveness of the lesions. The study included 283 cases of prostate adenocarcinomas for which histopathological type and tumor grade were analyzed. The results indicated the association of ductal, sarcomatoid and signet ring-like cell types with aggressive growth patterns and high scores, atrophic and pseudohyperplastic types with mild growth patterns and low scores, foamy gland type presented intermediate growth patterns/scores, while conventional and colloid types had variable aspects. The grading systems used may be considered consistent with the histological types of prostate adenocarcinomas.

The role of androgen receptors in vascular and cell proliferation of the prostate adenocarcinomas.

Prostate adenocarcinoma (PA) is by incidence and prognosis a unique model for investigating the biomolecular mechanisms involved in tumor progression. In this study, we analyzed the immunoexpression of androgen receptor (AR), cluster of differentiation 105 (CD105) and Ki67 for 61 cases of PA, in relation to the main clinicopathological parameters of the lesions. The AR scores, CD105 microvessel density (MVD) and Ki67 proliferation index (PI) were significantly higher in patients with serum prostate-specific antigen (PSA) above 20 ng∕mL, in ductal, colloid and sarcomatoid types of PA, in growth patterns 4-5 or mixed, respectively in the case of high-grade advanced stage tumors, with perineural and vascular invasion, as well as in groups with a reserved prognosis. The results obtained, reflected in the positive linear correlation of AR, CD105 and Ki67 expression, indicate synchronous endocrine, angiogenic and proliferative mechanisms involved in tumor progression, which can be used to optimize the targeted tumor therapy.

Immunoexpression of transcription factors in urothelial bladder carcinomas.

Transcription factors play a central role in the epithelial-mesenchymal transition (EMT), which is one of the biomolecular mechanisms involved in the progression of urothelial carcinomas of the bladder (UCB). In this study, we analyzed the immunoexpression of Twist 1, Snail, Slug and ß-catenin in relation to histopathological prognostic parameters of UCB. The obtained results indicated the association of Snail and ß-catenin expression with low grade and early stage of UCB, as well as the association of Twist 1 and Slug expression with high grade and advanced stage lesions. The specific or sequential action of transcription factors in the bladder tumoral EMT may be useful for identifying the aggressive lesions.

Improved diagnosis and long-term recurrence rate reduction for non-muscle-invasive bladder cancer patients undergoing fluorescent hexylaminolevulinate photodynamic diagnosis.

BACKGROUND: Bladder cancer (BC) currently accounts for 5% of all malignancies and the most common tumor of the urinary tract. Diagnosis of bladder cancer is based on urine cytology and white-light cystoscopy (WLC) performed for patients with suspected bladder mass and÷or hematuria. Recent studies suggest that using the fluorescence photodynamic diagnosis (PDD) significantly improves diagnostic sensitivity with a positive influence upon the recurrence rate of bladder cancer. OBJECTIVE: To evaluate the diagnostic efficiency and long-term influence upon the tumor recurrence rate for patients with non-muscle-invasive bladder cancer (NMIBC) undergoing hexaminolevulinate PDD compared to standard WLC. PATIENTS, MATERIALS AND METHODS: Between 2009 and 2011, 113 primary NMIBC patients were enrolled in our prospective study and randomized in two parallel groups: 57 patients in the study group (PDD) and 56 patients in the control group (WLC). All patients had primary Ta÷T1 NMIBC with good life expectancy and no significant bladder outlet obstruction [postvoid residual urine volume (PVR) <100 mL]. RESULTS: Fluorescence cystoscopy examination identified 26.3% more tumors than the conventional examination (p=0.034) in the PDD group. Tumor recurrence rate analysis proved a significant reduction by up to 20% after five years of follow-up by using PDD [hazard ratio (HR) 0.566, 95% confidence interval (CI) 0.343-0.936; p=0.0267]. CONCLUSIONS: The use of PDD for patients with NMIBC results in a significant 26% diagnostic sensitivity improvement as well as superior patient prognosis and quality of life following conservative treatment by reducing the tumor recurrence rate with up to 20% after five years of follow-up.

The cadherin switch assessment in the epithelial-mesenchymal transition of urothelial bladder carcinomas.

INTRODUCTION: The epithelial-mesenchymal transition (EMT) process is a complex molecular mechanism that is involved in the acquisition of an aggressive, invasive and metastatic phenotype by carcinomas. The cadherin switch consists in the alteration of E-cadherin and N-cadherin expression and is specific for the EMT process. MATERIALS AND METHODS: This study included 35 cases of primitive urothelial carcinomas investigated in relation with clinicopathological prognostic parameters and expression of E- and N-cadherins in the advancing edge and intratumoral compartments. RESULTS: In both compartments, the immunoexpression of E-cadherin decreased, while that of N-cadherin increased in high grade, deeply invasive, or those cases with lymph node metastases and advanced stages carcinomas, with a negative linear correlation observed between their expression percentage values. In this study, it was observed the presence of cadherin switch in urothelial carcinomas, the variation of the two proteins' immunostaining patterns being higher at the advancing edge. The presence of N-cadherin in intratumoral compartment designated it as actively involved in EMT process. CONCLUSIONS: The analysis of cadherins switch can be used to identify superficial urothelial carcinoma with invasion and metastasis potential.

Paratesticular liposarcoma of the spermatic cord: a case report and review of the literature.

Spermatic cord liposarcoma is a rare medical condition and liposarcomas are most commonly found in the retroperitoneum, in the extremities and less often in the head and the neck area. The spermatic cord is a rare site of origin, accounting for about 3-7% of all liposarcomas. We report a case of liposarcoma of spermatic cord. A 62-year-old male patient presented with a painless right inguinal mass. MRI (magnetic resonance imaging) showed a fatty mass in the right inguinoscrotal region, and was interpreted as an inguinal hernia containing omentum protruding into scrotum. The mass was removed with right testis and spermatic cord. The surgical margins were negative. Histopathological examination and immunohistochemistry revealed a well-differentiated liposarcoma. In this article, we discuss the clinical behavior of the spermatic cord liposarcoma and currently recommended treatment of the spermatic cord liposarcoma by reviewing the literature. In conclusion, spermatic cord liposarcoma are rare neoplasm that present as firm, slow-growing palpable paratesticular masses and the surgical treatment should include a wide resection around the inguinal canal, with removal of the spermatic cord and the surrounding soft tissue deep to the internal inguinal ring.

Retroperitoneal ancient schwannoma - case presentation.

Retroperitoneal ancient schwannomas are rare tumors, more usually found in the head, neck and flexor surfaces of the extremities. Ancient schwannomas are a subtype of classic schwannomas with a predominance of degenerative changes, calcifications, hemosiderin deposition, interstitial fibrosis and vascular hyaline degeneration. A 33-year-old male was referred on our hospital with a painful mass in left iliac fossa. The patient underwent surgery and intra-operatively the cystic encapsulated mass was found to be retroperitoneal, between the left psoas major muscle and left iliac muscle. On microscopic examination, we found the presence of Schwann cells in regions with high and low cellularity (Antoni A and B areas) and S100 protein immunohistochemical examination was intensely positive, being consistent with the diagnosis of schwannoma. Complete excision is the only method of the surgical treatment; schwannomas are not sensitive to radiotherapy and chemotherapy. Some authors consider that a complete excision of the tumor, while others believe that enucleated or partial excision of the tumor is sufficient. The prognosis is good, and the most common complication is recurrence, possibly by incomplete excision of it being reported in 5-10% of cases. In conclusion, retroperitoneal schwannomas is usually identified incidentally on tomographic images. Diagnosis is based on histopathological examination after surgery and immunohistochemical examination.