Pregnancy after sexuality preserving cystectomy with urinary diversion for bladder cancer. case report and review of the literature

Background: Radical cystectomy for bladder cancer represents a high demolitive surgical procedure with a significative impact on quality of life. Sexuality preserving techniques have been proposed in order to improve functional outcomes. Although sex-sparing techniques would provide women with the chance of having pregnancy, experience is still limited when malignant conditions are considered. We report the outcomes of pregnancy and delivery in a 43-year-old woman with a Padua ileal orthotopic neobladder after robot-assisted sexuality preserving cystectomy for muscle-invasive urothelial bladder cancer performed four years earlier, at age 39. Case presentation: Since pregnancy was confirmed, the patient had been under close urological and gynecological observation. Hydronephrosis and voiding-relating complications were reported and treated by inserting a nephrostomy tubes and indwelling bladder catheter. At the time of delivery, elective caesarian section was performed without complications. Conclusions: Sexuality preserving cystectomy could be an option in selected and highly motivated young patients with diagnosis of bladder cancer. A multidisciplinary team of experts included gynecologists, urologists, radiologists, anesthesiologists and neonatologists is required for the optimal management of pregnancy and peripartum care in women with urinary diversion

Low cancer yield in pi-rads 3 upgraded to 4 by dynamic contrast-enhanced mri. is it time to reconsider scoring categorization

Objectives: To evaluate MRI diagnostic performance in detecting clinically significant prostate cancer (csPCa) in peripheral-zone PI-RADS 4 lesions, comparing those with clearly restricted diffusion (DWI-score 4), and those with equivocal diffusion pattern (DWI-score 3) and positive dynamic contrast-enhanced (DCE) MRI. Methods: This observational prospective study enrolled 389 men referred to MRI and, if positive (PI-RADS 3 with PSA-density [PSAD] ≥ 0.15 ng/mL/mL, 4 and 5), to MRI-directed biopsy. Lesions with DWI-score 3 and positive DCE were classified as "PI-RADS 3up," instead of PI-RADS 4. Univariable and multivariable analyses were implemented to determine features correlated to csPCa detection. Results: Prevalence of csPCa was 14.5% and 53.3% in PI-RADS categories 3up and 4, respectively (p < 0.001). MRI showed a sensitivity of 100.0%, specificity 40.9%, PPV 46.5%, NPV 100.0%, and accuracy 60.9% for csPCa detection. Modifying the threshold to consider MRI positive and to indicate biopsy (same as previously described, but PI-RADS 3up only when associated with elevated PSAD), the sensitivity changed to 93.9%, specificity 57.2%, PPV 53.0%, NPV 94.8%, and accuracy 69.7%. Age (p < 0.001), PSAD (p < 0.001), positive DWI (p < 0.001), and PI-RADS score (p = 0.04) resulted in independent predictors of csPCa. Conclusions: Most cases of PI-RADS 3up were false-positives, suggesting that upgrading peripheral lesions with DWI-score 3 to PI-RADS 4 because of positive DCE has a detrimental effect on MRI accuracy, decreasing the true prevalence of csPCa in the PI-RADS 4 category. PI-RADS 3up should not be upgraded and directed to biopsy only if associated with increased PSAD. Key points: • As per PI-RADS v2.1 recommendations, in case of a peripheral zone lesion with equivocal diffusion-weighted imaging (DWI score 3), but positive dynamic contrast-enhanced (DCE) MRI, the overall PI-RADS score should be upgraded to 4. • The current PI-RADS recommendation of upgrading PI-RADS 3 lesions of the peripheral zone to PI-RADS 4 because of positive DCE decreased clinically significant prostate cancer detection rate in our series. • According to our results, the most accurate threshold for setting indication to prostate biopsy is PI-RADS 3 or PI-RADS 3 with positive DCE both associated with increased PSA density

Qualitative assessment of contrast-enhanced ultrasound in differentiating clear cell renal cell carcinoma and oncocytoma

Background: We aimed to assess whether clear cell renal cell carcinoma (ccRCC) can be differentiated from renal oncocytoma (RO) on a contrast-enhanced ultrasound (CEUS). Methods: Between January 2021 and October 2022, we retrospectively queried and analyzed our prospectively maintained dataset. Renal mass features were scrutinized with conventional ultrasound imaging (CUS) and CEUS. All lesions were confirmed by histopathologic diagnoses after nephron-sparing surgery (NSS). A multivariable analysis was performed to identify the potential predictors of ccRCC. The area under the curve (AUC) was depicted in order to assess the diagnostic accuracy of the multivariable model. Results: A total of 126 renal masses, including 103 (81.7%) ccRCC and 23 (18.3%) RO, matched our inclusion criteria. Among these two groups, we found significant differences in terms of enhancement (homogeneous vs. heterogeneous) (p < 0.001), wash-in (fast vs. synchronous/slow) (p = 0.004), wash-out (fast vs. synchronous/slow) (p = 0.001), and rim-like enhancement (p < 0.001). On the multivariate logistic regression, heterogeneous enhancement (OR: 19.37; p = <0.001) and rim-like enhancement (OR: 3.73; p = 0.049) were independent predictors of ccRCC. Finally, these two variables had an AUC of 82.5% and 75.3%, respectively. Conclusions: Diagnostic imaging for presurgical planning is crucial in the choice of either conservative or radical management. CEUS, with its unique features, revealed its usefulness in differentiating ccRCC from RO

Comparison of Perioperative, Functional, and Oncologic Outcomes of Open vs. Robot-Assisted Off-Clamp Partial Nephrectomy: A Propensity Scored Match Analysis

Off-clamp partial nephrectomy represents one of the latest developments in nephronsparing surgery, with the goal of preserving renal function and reducing ischemia time. The aim of this study was to evaluate and compare the functional, oncologic, and perioperative outcomes between off-clamp robot-assisted partial nephrectomy (off-C RAPN) and off-clamp open partial nephrectomy (off-C OPN) through a propensity score-matched (PSM) analysis. A 1:1 PSM analysis was used to balance variables potentially affecting postoperative outcomes. To report surgical quality, 1 year trifecta was used. Univariable Cox regression analysis was performed to identify predictors of trifecta achievement. The Kaplan–Meier method was used to compare cancer-specific survival (CSS), overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS) probabilities between groups. Overall, 542 patients were included. After PSM analysis, two homogeneous cohorts of 147 patients were obtained. The off-C RAPN cohort experienced shorter length of stay (LoS) (3.4 days vs. 5.4 days; p < 0.001), increased likelihoods of achieving 1 year trifecta (89.8% vs. 80.3%; p = 0.03), lower postoperative Clavien–Dindo ≤ 2 complications (1.3% vs. 18.3%, p < 0.001), and lower postoperative transfusion rates (3.4% vs. 12.2%, p = 0.008). At univariable analysis, the surgical approach (off-C RAPN vs. off-C OPN, OR 2.22, 95% CI 1.09–4.46, p = 0.02) was the only predictor of 1 year trifecta achievement. At Kaplan–Meier analysis, no differences were observed between the two groups in terms of OS (log-rank p = 0.451), CSS (log-rank p = 0.476), DFS (log-rank p = 0.678), and MFS (log-rank p = 0.226). Comparing RAPN and OPN in a purely off-clamp scenario, the minimally invasive approach proved to be a feasible and safe surgical approach, with a significantly lower LoS and minor rate of postoperative complications and transfusions as a result of improved surgical quality expressed by higher 1 year trifecta achievement

Reversal of gastrointestinal carcinoma-induced immunosuppression and induction of antitumoural immunity by a combination of cyclophosphamide and gene transfer of IL-12

Immunotherapy-based strategies for gastrointestinal carcinomas (GIC) have been exploited so far, but these approaches have to face strong mechanisms of immune escape induced by tumours. We previously demonstrated that sub-therapeutic doses of an adenovirus expressing IL-12 genes (AdIL-12) mediated a potent antitumour effect against subcutaneous (s.c.) colorectal carcinomas (CRC) in mice pre-treated with low doses of cyclophosphamide (Cy). In our study we used this combination to assess its impact on the immunosuppressive microenvironment. In s.c. CRC model we demonstrated that non-responder mice failed to decrease Tregs in tumour, spleen and peripheral blood. Reconstitution of Tregs into tumour-bearing mice treated with combined therapy abolished the antitumoural effect. In addition, Cy + AdIL-12 modified Tregs functionality by inhibiting the in vitro secretion of IL-10 and TGF-β and their ability to inhibit dendritic cells activation. Combined treatment decreased the number of myeloid-derived suppressor cells (MDSCs) in comparison to non-treated mice and, interestingly, administration of Tregs restored splenic MDSCs population. Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer. Finally, we evaluated the combination on disseminated CRC and pancreatic carcinoma (PC). Cy + AdIL-12 were able to eradicate liver metastatic CRC (47%) and PC tumour nodules (40%) and to prolong animal survival. The results of this study support the hypothesis that Cy + AdIL-12 might be a valid immunotherapeutic strategy for advanced GIC.Fil: Malvicini, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Ingolotti, Mariana. Universidad Austral; ArgentinaFil: Piccioni, Flavia Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Bayo Fina, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Atorrasagasti, María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Aquino, Jorge Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; ArgentinaFil: Espinoza, Jaime A.. Universidad Adolfo Ibañez; Chile. Universidad de La Frontera; ChileFil: Gidekel, Manuel. Universidad Adolfo Ibañez; ChileFil: Scharovsky, Olga Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Matar, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Medicas. Instituto de Genetica Experimental; ArgentinaFil: Mazzolini Rizzo, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral; Argentin

Relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine up to four months post administration in individuals aged 80 years or more in Italy. A retrospective matched cohort study

Several countries started a 2nd booster COVID-19 vaccination campaign targeting the elderly population, but evidence around its effectiveness is still scarce. This study aims to estimate the relative effectiveness of a 2nd booster dose of COVID-19 mRNA vaccine in the population aged &gt;= 80 years in Italy, during predominant circulation of the Omicron BA.2 and BA.5 subvariants. We linked routine data from the national vaccination registry and the COVID-19 surveillance system. On each day between 11 April and 6 August 2022, we matched 1:1, according to several demographic and clinical characteristics, individuals who received the 2nd booster vaccine dose with individuals who received the 1st booster vaccine dose at least 120 days earlier. We used the Kaplan-Meier method to compare the risks of SARS-CoV-2 infection and severe COVID-19 (hospitalisation or death) between the two groups, calculating the relative vaccine effectiveness (RVE) as (1 - risk ratio)X100. Based on the analysis of 831,555 matched pairs, we found that a 2nd booster dose of mRNA vaccine, 14-118 days post administration, was moderately effective in preventing SARS-CoV-2 infection compared to a 1st booster dose administered at least 120 days earlier [14.3 %, 95 % confidence interval (CI): 2.2-20.2]. RVE decreased from 28.5 % (95 % CI: 24.7-32.1) in the time-interval 14-28 days to 7.6 % (95 % CI: -14.1 to 18.3) in the time-interval 56-118 days. However, RVE against severe COVID19 was higher (34.0 %, 95 % CI: 23.4-42.7), decreasing from 43.2 % (95 % CI: 30.6-54.9) to 27.2 % (95 % CI: 8.3-42.9) over the same time span. Although RVE against SARS-CoV-2 infection was much reduced 2-4 months after a 2nd booster dose, RVE against severe COVID-19 was about 30 %, even during prevalent circulation of the Omicron BA.5 subvariant. The cost-benefit of a 3rd booster dose for the elderly people who received the 2nd booster dose at least four months earlier should be carefully evaluated

Effectiveness of mRNA vaccines and waning of protection against SARS-CoV-2 infection and severe covid-19 during predominant circulation of the delta variant in Italy. Retrospective cohort study

Objectives: To estimate the effectiveness of mRNA vaccines against SARS-CoV-2 infection and severe covid-19 at different time after vaccination. Design: Retrospective cohort study. Setting: Italy, 27 December 2020 to 7 November 2021. Participants: 33 250 344 people aged ≥16 years who received a first dose of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine and did not have a previous diagnosis of SARS-CoV-2 infection. Main outcome measures: SARS-CoV-2 infection and severe covid-19 (admission to hospital or death). Data were divided by weekly time intervals after vaccination. Incidence rate ratios at different time intervals were estimated by multilevel negative binomial models with robust variance estimator. Sex, age group, brand of vaccine, priority risk category, and regional weekly incidence in the general population were included as covariates. Geographic region was included as a random effect. Adjusted vaccine effectiveness was calculated as (1-IRR)×100, where IRR=incidence rate ratio, with the time interval 0-14 days after the first dose of vaccine as the reference. Results: During the epidemic phase when the delta variant was the predominant strain of the SARS-CoV-2 virus, vaccine effectiveness against SARS-CoV-2 infection significantly decreased (P&lt;0.001) from 82% (95% confidence interval 80% to 84%) at 3-4 weeks after the second dose of vaccine to 33% (27% to 39%) at 27-30 weeks after the second dose. In the same time intervals, vaccine effectiveness against severe covid-19 also decreased (P&lt;0.001), although to a lesser extent, from 96% (95% to 97%) to 80% (76% to 83%). High risk people (vaccine effectiveness -6%, -28% to 12%), those aged ≥80 years (11%, -15% to 31%), and those aged 60-79 years (2%, -11% to 14%) did not seem to be protected against infection at 27-30 weeks after the second dose of vaccine. Conclusions: The results support the vaccination campaigns targeting high risk people, those aged ≥60 years, and healthcare workers to receive a booster dose of vaccine six months after the primary vaccination cycle. The results also suggest that timing the booster dose earlier than six months after the primary vaccination cycle and extending the offer of the booster dose to the wider eligible population might be warranted

Impatto della vaccinazione e della pregressa diagnosi sul rischio di infezione e di malattia severa associata a SARS-CoV-2. Un’analisi dei casi diagnosticati nel mese di ottobre 2022

In Italia, l’epidemia di infezioni da SARS-CoV-2 nel corso del 2022 è stata influenzata dalla predominanza della variante Omicron, caratterizzata da alta trasmissibilità, e dalla progressiva eliminazione di quasi tutte le misure non farmacologiche di prevenzione. La combinazione di questi due elementi ha determinato una notevole circolazione virale di SARS-CoV-2 con oltre 24,5 milioni di casi da inizio epidemia. Dato l’alto numero di persone che ha superato almeno una infezione da SARS-CoV-2 e l’alta copertura vaccinale nella popolazione è necessario stimare il ruolo protettivo dell’immunità associata sia al vaccino che all’infezione pregressa nel prevenire l’infezione e la malattia severa da COVID-19. Il presente rapporto fornisce una stima del rischio di infezione e di malattia grave, per il mese di ottobre 2022, sulla base della vaccinazione e della precedente infezione. La massima protezione contro la diagnosi di infezione da SARS-CoV-2 e la malattia severa si realizza attraverso una immunità ibrida (l’effetto combinato della vaccinazione e della pregressa infezione) mentre livelli di rischio più alto si riscontrano sempre tra le persone non vaccinate e senza una precedente diagnosi di infezione. A parità di fascia di età e di pregressa infezione, si osserva una tendenza alla riduzione del rischio di malattia severa associata alla vaccinazione, in particolare se recente

Impact of sex and gender on the efficacy of antiplatelet therapy: the female perspective

Ischemic heart disease is the single leading cause of death and a significant cause of morbidity among women in industrialized countries. Current guidelines recommend antiplatelet therapy as the main cornerstone for the prevention and treatment of cardiovascular disease. Unfortunately, evidence is emerging that the response to antiplatelet drugs differs according to sex, although the biological basis for this gender disparity is unknown. In order to explain the epidemiological data showing a more severe clinical expression of cardiovascular disease in addition to adverse outcomes despite optimal pharmacological and interventional approaches in women compared to men, differences in platelet reactivity related to sex and gender are currently under investigation. In this report, we review available data from clinical trials of antiplatelet drugs administered for primary and secondary prevention, focusing on the underenrollment of female subjects in interventional randomized studies and weak community awareness of the impact of cardiovascular disease on life expectancy in women. Based on our findings, the development of real gender-oriented evidence-based guidelines for antiplatelet use in the setting of cardiovascular disease is urgently required