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Radio-induced apoptosis is mediated by the activation of tumor protein p53, Bax and caspases. The purpose of this study was to investigate the early activation of this pathway in men receiving in vivo irradiation immediately before radical prostatectomy for locally advanced prostate cancer. We also investigated cell proliferation index (Ki-67), proto-oncogene (p53) and anti-apoptotic protein (Bcl-2) levels as potential predictive factors. We selected a homogeneous sample of 20 patients with locally advanced prostate cancer and candidate to radical prostatectomy. To assess the apoptotic pathways, Bax, is studied through immunofluorescence assay, before and after 12 Gy single dose intraoperative radiotherapy (IORT) to the prostate, on bioptic samples and on surgical specimens. Moreover, before and after IORT, Bcl-2, p53, and Ki-67 were also detected through immunohistochemistry. A count of positive Bax spots for immunofluorescence was performed on tumor cells, prostatic intraepithelial neoplasia (PIN), and healthy tissue areas before and after IORT. We also analyzed Caspases 3 and 9 expressions after IORT. Before IORT, Bcl-2 mean value in neoplastic cells was 2.23% ± 1.95, mean Ki-67 in neoplastic area was 4.5% ± 3.8, and p53 was 22.5% ± 6.8. After IORT, Bcl-2 mean value in neoplastic cells was 8.85 ± 8.92%, Ki-67 in neoplastic area was 7.8 ± 6.09%, and p53 was 24.9 ± 26.4%. After the irradiation, healthy areas expressed significantly lower levels of Bax (2.81 ± 1.69%) with respect to neoplastic cells (p < 0.0001), while in PIN areas, Bax positive cells were significantly more present than in neoplastic areas (p = 0.0001). At statistical analysis, it was observed that cancer cells with Ki-67 ≥ 8% had a trend toward greater expression of Bax (p = 0.0641). We observed an increase of Bcl-2 expression after IORT in neoplastic areas (p = 0.0041). Biopsy specimens with p53 ≥ 18% and Ki-67 ≥ 8% had worse post-operative staging with extracapsular invasion (p = 0.04 for both parameters) and nodal positivity (p = 0.04 for p53 and p = 0.0001 at pathology for ki-67). No correlation between IORT and Caspases activation was noted. In conclusion, after 12 Gy IORT, Bax was overexpressed in tumor and PIN cells. Pre-operative Ki-67 and p53 definition could be used in future studies to predict patients with worse pathological stage, while Bcl-2 activation after IORT might be a predictive factor for loco-regional failure.

PurposeTo explore the role of vacuum assisted closure (VAC) therapy versus conventional dressings in the Fournier’s gangrene wound therapy.Patients and MethodsThis is a retrospective multi-institutional cohort study. Data of 92 patients from nine centers between 2007 and 2018 were retrospectively analyzed. After surgery, patient having a local or a disseminated FG were managed with VAC therapy or with conventional dressings. The 10-weeks wound closure cumulative rate and OS were analyzed.ResultsOf the 92 patients, 62 (67.4%) showed local and 30 (32.6%) a disseminated FG. After surgery, 19 patients (20.7%) with local and 14 (15.2%) with disseminated FG underwent to VAC therapy; 43 (46.7%) with local and 16 (17.4%) with disseminated FG were treated using conventional dressings. The multivariable logistic regression analysis demonstrated that the VAC in patients with disseminated FG led to a higher cumulative rate of wound closure than patients treated with no-VAC (OR = 6.5; 95% CI 1.1–37.4, p = 0.036). The Kaplan–Meier survival curves for the OS showed a significant difference between no-VAC patients with local and disseminated FG (OS rate at 90 days 0.90, 95% CI 0.71–0.97 vs 0.55, 95% CI 0.24–0.78, respectively; p = 0.039). Cox regression confirmed that no-VAC patients with disseminated FG showed the lowest OS (hazard ratio adjusted for sex and age HR = 3.4, 95% CI 1.1–10.4; p = 0.033).ConclusionsIn this large cohort study, VAC therapy in patients with disseminated FG may offer an advantage in terms of 10-weeks wound closure cumulative rate and OS at 90 days after initial surgery.

BackgroundAim of this study was to evaluate and compare perioperative outcomes of transperitoneal (TP) and retroperitoneal (TR) approaches in a multi-institutional cohort of minimally invasive partial nephrectomy (MI-PN).Material and methodsAll consecutive patients undergone MI-PN for clinical T1 renal tumors at 26 Italian centers (RECORd2 project) between 01/2013 and 12/2016 were evaluated, collecting the pre-, intra-, and postoperative data. The patients were then stratified according to the surgical approach, TP or RP. A 1:1 propensity score (PS) matching was performed to obtain homogeneous cohorts, considering the age, gender, baseline eGFR, surgical indication, clinical diameter, and PADUA score.Results1669 patients treated with MI-PN were included in the study, 1256 and 413 undergoing TP and RP, respectively. After 1:1 PS matching according to the surgical access, 413 patients were selected from TP group to be compared with the 413 RP patients. Concerning intraoperative variables, no differences were found between the two groups in terms of surgical approach (lap/robot), extirpative technique (enucleation vs standard PN), hilar clamping, and ischemia time. Conversely, the TP group recorded a shorter median operative time in comparison with the RP group (115 vs 150 min), with a higher occurrence of intraoperative overall, 21 (5.0%) vs 9 (2.1%); p = 0.03, and surgical complications, 18 (4.3%) vs 7 (1.7%); p = 0.04. Concerning postoperative variables, the two groups resulted comparable in terms of complications, positive surgical margins and renal function, even if the RP group recorded a shorter median drainage duration and hospital length of stay (3 vs 2 for both variables), p < 0.0001.ConclusionsThe results of this study suggest that both TP and RP are feasible approaches when performing MI-PN, irrespectively from tumor location or surgical complexity. Notwithstanding longer operative times, RP seems to have a slighter intraoperative complication rate with earlier postoperative recovery when compared with TP.

Google DeepMind has developed a system called the Habermas Machine in honour of Jürgen Habermas and his theory of deliberation. The system seeks to facilitate deliberation and assist individuals in finding common ground on controversial issues. This system, based on large language models, has been tested on groups in the United Kingdom, engaging more than 5,700 participants divided into groups. The study reported that participants preferred the AI-mediated group statements, considering them clearer, more informative and less biased than those generated by human facilitators. In light of Habermas’s discourse theory and theory of deliberation in general, this paper aims to briefly raise some constructive remarks on this machine developed by DeepMind. Artificial intelligence can effectively be beneficial for deliberation. However, an artificial intelligence generator of consensus might bring about some theoretical and practical issues, concerning the very nature of the agreement, moral inclusivity and, more broadly, its implicit rationality. Rather than being just theoretical, these issues involve the concrete future relationship between practical autonomy and artificial intelligence.

ObjectivesSystemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by multiorgan involvement. Osteoporosis and fragility fractures, particularly vertebral fractures, are significant, yet often underestimated, comorbidities in patients with SLE. This study aims to evaluate the prevalence of vertebral fractures and their associations with demographic, disease-related and therapy-related factors in patients with SLE.MethodsWe conducted a monocentric, cross-sectional study to systematically evaluate bone health using dual-energy X-ray absorptiometry and vertebral fracture assessment (VFA). Associations between vertebral fractures and clinical, laboratory variables were investigated with logistic and linear regressions.ResultsOne hundred and six patients with SLE were included. The overall prevalence of radiographic vertebral fractures was 21.7%, whereas clinical vertebral fractures were reported in 14.2% of patients. New, previously not diagnosed, radiographic vertebral fractures were detected in 14.2% of all patients with SLE at screening with VFA. Older age, longer disease duration, cumulative glucocorticoid (GC) dose and lower bone mineral density were significantly associated with vertebral fractures. Cumulative GC dose had the strongest association with vertebral fractures. We also found a positive association between the number of vertebral fractures on VFA and cumulative GC dose (β 0.025, p=0.025).ConclusionsOur findings underscore the importance of actively screening for vertebral fractures in patients with SLE, especially those on long-term GC therapy, to prevent underdiagnosis, mitigate the risk of further skeletal damage and facilitate the timely initiation of targeted antiosteoporotic treatments when indicated.Trial registration numberNCT05590390.

Background The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery. Methods We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1–4, N0–1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups. Results We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups. Conclusions We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials.

Emerging evidence indicates that reactivation of BK polyomavirus (BKPyV) in the kidney and urothelial tract of kidney transplant recipients (KTRs) may be associated with cancer in these sites. In this retrospective study of a single center cohort of KTRs (n = 1307), 10 clear cell renal cell carcinomas and 5 urinary bladder carcinomas were analyzed from 15 KTRs for the presence of BKPyV infection through immunohistochemistry and fluorescent in situ hybridization (FISH). Three of these patients had already exhibited biopsy-proven polyomavirus-associated nephropathies (PyVAN). Although the presence of BKPyV large-T antigen was evident in the urothelium from a kidney removed soon after PyVAN diagnosis, it was undetectable in all the formalin-fixed and paraffin-embedded (FFPE) blocks obtained from the 10 kidney tumors. By contrast, large-T antigen (LT) labeling of tumor cells was detected in two out of five bladder carcinomas. Lastly, the proportion of BKPyV DNA-FISH-positive bladder carcinoma nuclei was much lower than that of LT-positive cells. Taken together, our findings further strengthen the association between BKPyV reactivation and cancer development in KTRs, especially bladder carcinoma.

ABSTRACT Background and Aims This study evaluated the impact of major elective surgery on performance status, defined as functional and cognitive status, in older adults 3 months postoperatively. Secondary endpoints included assessing the need for domiciliary care, rehospitalization, or institutionalization, and evaluating associations with anesthesia type. Methods In this observational prospective cohort study, 169 patients aged ≥ 70 underwent major elective surgery between May 2020 and June 2023; 150 had complete information at 3‐months (T3). Decline in performance status, either functional or cognitive, was defined as a ≥ 10‐point worsening in the Barthel Index (BI) or death, or a ≥ 3‐point decline in Mini‐Mental State Examination (MMSE), all measured 3 months after surgery. Results Mean (SD) age was 77 (5) years, with a mean (SD) Charlson Comorbidity Index (CCI) of 7 (2). Most surgeries (133, 79%) were performed for oncologic indications. Baseline median [IQR] BI was 100 [100‐100], and MMSE was 27 [25–28]. At T3, 44 (29%) patients showed a ≥ 10‐point BI decline (p < 0.001) and 7 died, while 14% exhibited a ≥ 3‐point MMSE decrease. Domiciliary care was required in 14 (9%) patients, while 26 (17%) were institutionalized. Fifty‐five (37%) patients reported health sequelae within 3 months post‐surgery. Multivariable regression analysis associated higher CCI and post‐discharge health issues with BI decline or death, but not with MMSE. Domiciliary care needs or rehospitalization was linked to elevated CCI and laparotomic approach. Conclusion Major elective surgery may compromise functional status in nearly one‐third of older patients, especially those with high comorbidity and post‐discharge sequelae. Cognitive decline was less prevalent, and the need for domiciliary or institutional care was relatively low. Trial Registration: URL: https://register.clinicaltrials.gov/prs/beta/studies/S000CLIN00000033/recordSummary; Clinicaltrials.gov identifier: NCT05594277.

Objective To review our method of perform needle biopsies of renal masses. Methods We analysed 150 consecutive imaging-guided percutaneous biopsies. The pathological diagnosis was verified on clinical outcome in 129 cases (40 surgical resection, 53 thermal ablation, two medical treatment and 34 watchful waiting). Twenty-six patients underwent fine-needle aspiration biopsy (FNAB), 45 core-needle biopsy (CB) and 58 FNAB + CB. After review by two expert pathologists, cumulative accuracy of all FNAB (84) and all CB (103) was calculated. The rate of complications and mass management other than surgery was estimated. Results The final diagnosis was malignancy in 97 cases (benign mass in 32). FNAB correctly diagnosed 64/84 masses (76.2%), CB 96/103 (93.2%). Of 58 masses submitted for both FNAB and CB, CB provided a 22.5% accuracy improvement. Major and minor complications occurred in 0% and 5.3%. Renal biopsy altered clinical management in 89/129 cases (68.9%), in terms of choosing therapeutic options other than surgery. Conclusion CB is more accurate than FNAB and should be preferred in renal mass biopsy. FNAB may precede CB when an expert pathologist can immediately evaluate the samples. Renal biopsy influences renal mass management.

Background: seasonal influenza in nursing homes is a major public health concern, since in EU 43,000 long term care (LTC) facilities host an estimated 2.9 million elderly residents. Despite specific vaccination campaigns, many outbreaks in such institutions are occasionally reported. We explored the dynamics of seasonal influenza starting from real data collected from a nursing home located in Italy and a mathematical model. Our aim was to identify the best vaccination strategy to minimize cases (and subsequent complications) among the guests. Materials and methods: after producing the contact matrices with surveys of both the health care workers (HCW) and the guests, we developed a mathematical model of the disease. The model consists of a classical SEIR part describing the spreading of the influenza in the general population and a stochastic agent based model that formalizes the dynamics of the disease inside the institution. After a model fit of a baseline scenario, we explored the impact of varying the HCW and guests parameters (vaccine uptake and vaccine efficacy) on the guest attack rates (AR) of the nursing home. Results: the aggregate AR of influenza like illness in the nursing home was 36.4% (ward1 = 56%, ward2 = 33.3%, ward3 = 31.7%, ward4 = 34.5%). The model fit to data returned a probability of infection of the causal contact of 0.3 and of the shift change contact of 0.2. We noticed no decreasing or increasing AR trend when varying the HCW vaccine uptake and efficacy parameters, whereas the increase in both guests vaccine efficacy and uptake parameter was accompanied by a slight decrease in AR of all the wards of the LTC facility. Conclusion: from our findings we can conclude that a nursing home is still an environment at high risk of influenza transmission but the shift change room and the handover situation carry no higher relative risk. Therefore, additional preventive measures in this circumstance may be unnecessary. In a closed environment such as a LTC facility, the vaccination of guests, rather than HCWs, may still represent the cornerstone of an effective preventive strategy. Finally, we think that the extensive inclusion of real life data into mathematical models is promising and may represent a starting point for further applications of this methodology.