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Chronic inflammation influences the tumor immune microenvironment (TIME) in high-grade serous ovarian cancer (HGSOC). Specifically, cyclooxygenase-2 (COX-2) overexpression promotes cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) expression. Notably, elevated COX-2 levels in the TIME have been associated with reduced response to anti-CTLA-4 immunotherapy. However, the precise impact of COX-2, encoded by PTGS2 , on the immune profile remains unknown. To address this, we performed an integrated bioinformatics analysis using data from the HGSOC cohorts (TCGA-OV, n = 368; Australian cohort AOCS, n = 80; GSE26193, n = 62; and GSE30161, n = 45). Employing Gene Set Variation Analysis (GSVA), MIXTURE and Ecotyper cell deconvolution algorithms, we concluded that COX-2 was linked to immune cell ecosystems associated with shorter survival, cell dysfunction and lower NK cell effector cytotoxicity capacity. Next, we validated these results by characterizing circulating NK cells from HGSOC patients through flow cytometry and cytotoxic assays while undergoing COX-2 and CTLA-4 blockade. The blockade of COX-2 improved the cytotoxic capacity of NK cells against HGSOC cell lines. Our findings underscore the relevance of COX-2 in shaping the TIME and suggest its potential as a prognostic indicator and therapeutic target. Increased COX-2 expression may hamper the effectivity of immunotherapies that require NK cell effector function. These results provide a foundation for experimental validation and clinical trials investigating combined therapies targeting COX-2 and CTLA-4 in HGSOC.

Unlabelled: In a previous study, we showed our experience in a group of 54 patients with a high risk of urolithiasis recurrence, who were subjected to a complete metabolic evaluation., Aim: To report the evolution of these patients after 5 years of follow-up., Patients and Methods: All patients underwent a general management of urolithiasis plus specific treatments for underlying metabolic disorders. Each patient had an annual medical assessment including a clinical examination, urinalysis and imaging studies (non-enhanced computed tomography scan, ultrasonography and plain abdominal Rx rays). In every case, the underlying metabolic disorder, treatment adherence, stones on imaging studies and symptomatology were evaluated. Adherence of general and specific measures were evaluated subjectively. Failure of secondary prevention was defined as the recurrence of clinical or imaging urolithiasis (increase of the number of lithiasis) despite a correct treatment of the metabolic disorders., Results: Twenty nine patients completed the follow-up. Mean age was 45 years old. Nineteen patients (65%) had only one metabolic disorder, three patients (10%) two disorders, one patient (3%) four disorders, and six patients (21%) a normal metabolic study. The median of follow-up was 54 months (45-60). During that period, twenty-three patients (79%) kept the treatment as it was indicated. In this subgroup, 21 had no clinical or imaging recurrence of urolithiasis during follow-up (91%). Total adherence to treatment and follow-up was 42% (23/54) of the initial group of patients., Conclusions: A complete metabolic study allows to identify patients with a high risk of urolithiasis recurrence, enabling a specific treatment of the metabolic disorder. Our experience shows that 75% (21/29) of patients remain free of recurrence at five years of follow-up.

Purpose: To compare the efficacy of ureteroscopy and extracorporeal shock wave lithotripsy (ESWL) in treating distal ureteral calculi and evaluate the best treatment alternative for this disease., Material and Methods: A total of 104 patients with distal ureteral calculi requiring surgical intervention were enrolled and observed in a prospective follow-up. For ESWL, a Modulix SLX Storz lithotriptor was used and for ureteroscopy, a Storz 33 cm semi-rigid ureteroscope with a diameter of 7,5 to 9,5 french and a 6-degree optic. Out of the patient total, 54 patients underwent ESWL and 50 underwent ureteroscopy. 62 patients were men and 42 women; mean age in the ESWL group was 49.72, and in the ureteroscopy group, 52,16. Mean calculus size for ESWL was 8.29 mm and 8,96 mm for ureteroscopy. A P< .05 was considered statistically significant., Results: Mean procedure time for ESWL was 55 minutes in men and 45 minutes in women. For ureteroscopy, procedure time was 80 minutes for men and 55 minutes for women. For ESWL, the mean hospital stay was 4.8 hours (same-day discharge for all patients). Mean hospital stay for ureteroscopy patients was 22 hours. 7% of ESWL patients experienced complications compared with 7.9% of those undergoing ureteroscopy. At the 30-day follow up, 74.3% of ESWL patients were stone free, while 92,3% of the ureteroscopy patients were stone free (P< .05)., Conclusions: Based on the results of this study, ureteroscopy is a better method for treating distal ureteral calculi because of its stone free rates and because the difference in complication rates was not significant.

Introduction: Urolithiasis is a metabolic disorder with a tendency to relapse. The aim of this study was to assess the prevalence of metabolic abnormalities in patients at high risk and the impact of sex and age., Materials and Methods: Descriptive study of 54 patients (37 men and 17 women), with lithiasic pathology at high risk of recurrence. The metabolic study included the measurement of calcemia, uricemia, fosfemia, parathormone, calciuria/24 h, uricosuria/24 h, fosfaturia/24 h, oxalaturia/24 h, citraturia/24 h and creatinine/24 h. The values obtained were corrected according to weight and creatinine. The test used for statistical analysis was t-student (STATA 7.0). It was considered significant p<0.05., Results: In 64,8% (35/54) of the cases a metabolic abnormality was observed and in 27,7% (15/54) there was 2 or more alterations present. The metabolic disorders most frequently observed were hypercalciuria (15/54) 27,7%, hypocitraturia (15/54) 27,7%, hyperuricemia (8/54) 14,8%. and hyperoxaluria (8/54) 14,8%. There was no significant difference in age or sex between the groups with and without metabolic abnormality., Conclusions: Most patients with recurrent lithiasic pathology or at high-risk display one or more metabolic disorders, being hypercalciuria and hypocitraturia the most frecuently encountered. In this study, there was no difference between sexes in most of the metabolic disorders, nor in its age distribution. These results demonstrate the need for metabolic studies in high-risk patients, since there are tools that allow therapeutic medical management of metabolic disorders and thus reduce the recurrence of lithiasis.

We present the clinical and laboratory features of 2 patients with B prolymphocytic leukemia. Both are females of the fifth and seventh decade of life. One had the classical clinical picture of massive splenomegaly and a high white cell count, with characteristic prolymphocytes, and the other was asymptomatic, with a low white cell count. The cells were positive to B cell lineage reagents with strong surface immunoglobuline (Ig) and unreactive to T cell antibodies. Analysis of Ig genes at the DNA level demonstrated that both cases had heavy-chain gene rearrangements, confirming the B-cell origin. These are the first patients of prolymphocytic leukemia described in Chile.