Antibacterial Activity of the Essential Oil of Piper tuberculatum Jacq. Fruits against Multidrug-Resistant Strains: Inhibition of Efflux Pumps and ß-Lactamase.

Antimicrobial resistance has become a growing public health concern in recent decades, demanding a search for new effective treatments. Therefore, this study aimed to elucidate the phytochemical composition and evaluate the antibacterial activity of the essential oil obtained from the fruits of Piper tuberculatum Jacq. (EOPT) against strains carrying different mechanisms of antibiotic resistance. Phytochemical analysis was performed using gas chromatography-mass spectrometry (GC/MS). The antibacterial activity of EOPT and its ability to inhibit antibiotic resistance was evaluated through the broth microdilution method. The GC-MS analysis identified 99.59% of the constituents, with ß-pinene (31.51%), α-pinene (28.38%), and ß-cis-ocimene (20.22%) being identified as major constituents. The minimum inhibitory concentration (MIC) of EOPT was determined to assess its antibacterial activity against multidrug-resistant strains of Staphylococcus aureus (IS-58, 1199B, K2068, and K4100). The compound showed a MIC of ≥ 1024 µg/mL, suggesting a lack of intrinsic antibacterial activity. However, when the EOPT was associated with antibiotics and EtBr, a significant decrease in antibiotic resistance was observed, indicating the modulation of efflux pump activity. This evidence was corroborated with the observation of increased fluorescent light emission by the bacterial strains, indicating the involvement of the NorA and MepA efflux pumps. Additionally, the significant potentiation of ampicillin activity against the S. aureus strain K4414 suggests the ß-lactamase inhibitory activity of EOPT. These results suggest that the essential oil from P. tuberculatum fruits has antibiotic-enhancing properties, with a mechanism involving the inhibition of efflux pumps and ß-lactamase in MDR S. aureus strains. These findings provide new perspectives on the potential use of EOPT against antibiotic resistance and highlight the importance of Piper species as sources of bioactive compounds with promising therapeutic activities against MDR bacteria. Nevertheless, further preclinical (in vivo) studies remain necessary to confirm these in vitro-observed results.

Neutrophil-to-lymphocyte ratio as a predictor of overall survival and cancer advancement in patients undergoing radical cystectomy for bladder cancer.

Introduction: Neutrophil-to-lymphocyte ratio (NLR) has proven to be promising as a prognostic factor in many malignancies. We investigated the prognostic significance of NLR in patients undergoing radical cystectomy (RC) for bladder cancer (BC). Material and methods: We retrospectively evaluated the data of 134 consecutive patients with BC who underwent RC between 2011 and 2017 at a single center. Overall survival (OS) was assessed using the Kaplan-Meier method and compared between NLR subpopulations using the log-rank test. Univariate and multivariate Cox proportional hazard models were used to identify the variables affecting OS. Results: At a median follow-up of 2.2 years, high NLR (>2.7) correlated with worse a survival outcome (p = 0.0345 in log-rank test), higher tumor stage (p = 0.0047), and higher frequency of positive lymph nodes (p = 0.0285). The univariate model showed that a high NLR (p = 0.038528), advanced pathological tumor stage (p = 0.000763), lymph node involvement (p = 0.013384), a high grade of cancer (p = 0.015611), lymphovascular invasion (LVI) (p = 0.001530), positive margins (p = 0.000890) and ureterocutaneostomy as urinary diversion (p = 0.038854) had a negative impact on OS. Tumor extending beyond the submucosa (>pT1) (hazard ratio 2.161, confidence interval 1058-4411, p = 0.0345) and lymphatic infiltration (hazard ratio 1.599, confidence interval 1028-2482, p = 0.037) have been recognized as independent risk factors of poor prognosis in multivariate Cox regression analysis. Conclusions: In our cohort, an elevated NLR is associated with worse OS and adverse histopathological findings. Consequently, the NLR is an easily acquired biomarker, which may be useful in pretreatment patient risk stratification.

Preoperative Neutrophil-lymphocyte Ratio as a Predictor of Overall Survival in Patients with Localized Renal Cell Carcinoma.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR), as an indicator of the systemic inflammatory response, predicts adverse outcomes in many malignancies. We investigated its prognostic significance in patients with non-metastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated data of 196 consecutive non-metastatic RCC patients who underwent radical or partial nephrectomy between 2010 and 2012 at a single center. Overall survival (OS) was assessed using the Kaplan-Meier method and compared using the log-rank test. We applied univariate and multivariate Cox regression models to evaluate the prognostic value of dichotomized NLR for OS.   Results: At a median follow up of 68 months, high NLR (? 2,69) correlated with worse survival outcome (P = .006 in log-rank test) and higher tumor stage (P = .035). Univariate and multivariate analysis identified elevated NLR (P = .039), as well as age (P = .002), high Fuhrmann grade (P = .002) and high pathologic T stage (P < .001), as significantly associated with overall survival. CONCLUSION: In our cohort, an elevated neutrophil-to-lymphocyte ratio is significantly associated with worse OS on univariate and multivariate analysis. Consequently, the NLR is an easily acquired biomarker, which may be useful in pretreatment patient risk stratification.

Partial cystectomy in a 76 year old patient suffering from small cell carcinoma of the urinary bladder.

Small cell carcinomas of the urinary bladder originating from the neuroendocrine cells are extremely rare. We present a case of a 76-year-old patient with small cell carcinoma of the urinary bladder. The patient had hematuria and cystoscopy revealed a tumor located in a urinary bladder diverticulum. Partial resection of the bladder wall with diverticulectomy was performed. Microscopic examination established the diagnosis of neuroendocrine carcinoma, which was confirmed by immunohistochemistry. Three-month follow-up showed no recurrent disease. Patient refused further chemotherapy and radiotherapy.