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Background: takotsubo syndrome (TTS) is an acute heart failure syndrome characterized by a relevant comorbid background, including chronic obstructive pulmonary disease (COPD). However, TTS patients with COPD are still not well characterized., Aim: to describe the clinical characteristics and outcomes of patients with TTS and COPD., Methods: n = 440 TTS patients were dichotomized according to the presence of COPD. Endpoint of the study were in-hospital complications (composite of death, major arrhythmias, cardiogenic shock and acute pulmonary edema), TTS recurrence and long-term mortality at follow-up., Results: mean age of the population was 72±11, 10 % males. COPD prevalence was 16 % (n = 69). On subgroup analysis, patients with COPD were more likely smokers (41 % vs 13 %, p < 0.001), with higher rates of dyspnea and physical triggers at presentation (52 % vs 18 %, p < 0.001 and 52 % vs 32 %, p = 0.001 respectively) and lower left ventricular ejection fraction (36 % vs 39 %, p = 0.035) In-hospital complications were more common in patients with COPD (26 % vs 13 %, p = 0.006), driven by higher rates of acute pulmonary edema (19 % vs 6 %, p < 0.001) and cardiogenic shock (10 % vs 4 %, p = 0.023). At multivariable logistic regression analysis, COPD was independently associated with in-hospital complications occurrence (Odds Ratio 2.10, 95 % CI 1.09-4.05; p = 0.027). At univariable Cox regression analysis COPD was associated with TTS recurrence (Hazard Ratio (HR 9.82, 95 % CI 3.2-30.12; p < 0.001)), at multivariable Cox regression analysis with long-term mortality (HR 2.97, 95 % CI 1.44-6.12; p = 0.003)., Conclusion: COPD marks a vulnerable TTS phenotype including higher risk of in-hospital complications, long-term recurrence and mortality., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: In our study, we aimed to test the efficacy and safety of Trans-Perineal Laser Ablation of the prostate (TPLA®) in the surgical treatment of high-risk Benign Prostatic Obstruction (BPO) patients., Methods: We defined a high-risk BPO patient as an elderly man affected by severe comorbidities, among which coagulation issues due to pre-existent medications or diseases. From October 2020 to June 2022, we prospectively enrolled high-risk patients affected by a moderate to severe and/or complicated BPO condition. The analysis of the efficacy of the Trans-Perineal Laser Ablation was defined as the primary endpoint of the study. Secondary endpoints were post-operative surgical complications and patient-reported quality of life., Results: Globally, 40 consecutive patients were enrolled. Median (IQR) age was 80 (72.5-84) years. Median Charlson Comorbidity Index was 6 (5-7). Median prostate volume was 38 (30.5-73) cc. In all cases, a TPLA® procedure was performed under local anesthesia, and patients being discharged within the same day of the procedure. A progressive reduction of median prostate volumes was reported at 3 and 6 months post-operatively, compared to baseline [38 (30.5-73) vs 35 (26-49) vs 34 (28-49) cc, p < 0.001]. Median International Prostate Symptom Score (IPSS) improved accordingly [25 (19-30) vs 10.5 (7.5-13) vs 8 (6-11.5), p < 0.001]. A permanent bladder catheter was successfully removed in 13 out of 23 (56.5%) cases. Within 90 days from surgery, 19 (47.5%) patients experienced at least one surgical complication. According to the Clavien-Dindo classification, complications were classified as grade I in 16 (40%) cases, grade II in 9 (22.5%), and grade III in 1 (2.5%). We did not observe any grade IV or V complications., Conclusions: The Trans-Perineal Laser Ablation of the Prostate is a feasible, safe, and effective Minimally Invasive Surgical Technique, when offered to elderly, high-risk patients affected by severe Benign Prostatic Obstruction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: More than 10% of patients with negative clinical metastatic status (cN0M0) on conventional imaging for prostate cancer (PCa) harbor lymph node involvement (pN+) at final pathology following radical prostatectomy (RP) and lymphadenectomy. Our aim was to assess outcomes of initial observation for cN0M0 pN+ PCa and identify prognostic factors that may help in clinical decision-making., Methods: We performed a retrospective multicenter study of patients with cN0M0 PCa on conventional imaging (computed tomography and/or magnetic resonance imaging, and a bone scan) who were found to have pN+ disease at RP between 2000 and 2021. Biochemical recurrence (BCR) and systemic progression/recurrence were the primary outcomes. Kaplan-Meier curves and Cox proportional hazards model were used for survival and multivariate analysis., Key Findings and Limitations: A total of 469 men were included in this retrospective multicenter trial. Median prostate-specific antigen (PSA) was 10.1 ng/ml (interquartile range [IQR] 6.6-18.0). Among these patients, 56% had grade group ≥4, 53.7% had stage ≥pT3b, 42.6% had positive margins, and 19.6% had PSA persistence. The median number of positive nodes and of nodes removed were 1 (IQR 1-3) and 20 (14-28), respectively. At median follow-up of 41 mo, 48.5% experienced BCR. The 5-yr BCR-free survival rate was 31.7% (95% confidence interval [CI] 26.33-37.1%). Salvage treatments were needed in 211 patients and included radiotherapy (RT; n  = 53), RT + androgen deprivation therapy (ADT; n  = 88), ADT alone ( n  = 68), and salvage lymphadenectomy ( n  = 2). The 5-yr estimated survival rates were 66.3% (95% CI 60.4-72.1) for metastasis-free survival, 97.7% (95% CI 95.5-99.8%) for cancer-specific survival, and 95.3% (95% CI 92.4-98.1%) for overall survival. On multivariable analysis, PSA persistence was an independent predictor of BCR (odds ratio [OR] 51.8, 95% CI 12.2-219.2), exit from observation (OR 8.5, 95% CI 4.4-16.5), and systemic progression (OR 3.0, 95% CI 1.771-4.971)., Conclusions: Initial observation in the management of pN+ cN0M0 PCa is feasible and has excellent survival rates in the intermediate term. Patients with worse disease features, especially PSA persistence, have a higher likelihood of recurrence and progression and may be candidates for more aggressive upfront management., Patient Summary: We investigated the value of initial observation for men with prostate cancer with negative scan findings for metastasis who were then found to have positive lymph nodes after surgery to remove the prostate. Our results show that initial observation is a good option for patients with less aggressive prostate cancer features., (© 2024 Published by Elsevier B.V. on behalf of European Association of Urology.)

Introduction: The preservation of the bladder neck during robot-assisted radical prostatectomy (RARP) could improve urinary continence recovery and limit the risk of positive surgical margins (PSMs). We refined our lateral approach to the bladder neck technique and compared its outcomes with those of the standard anterior approach., Material and Methods: From a retrospective analysis of 599 consecutive RARPs, 171 patients treated with the lateral and 171 patients treated with the anterior approach were pair-matched 1:1 on the basis of age, grade, and pathological stage. We described our surgical technique and compared the two approaches in terms of basal PSMs, recovery of urinary continence, and complications., Results: As compared to the anterior approach, the lateral approach had shorter operative times and comparable rates of basal PSMs and postoperative complications. The rates of urinary continence after one, three, and 12 months were comparable between the two groups and were generally higher in localized disease. At regression analysis, predictors of urinary incontinence were only age, pathological stage T3b, ISUP grade 5 and nerve-sparing surgery., Conclusions: The lateral approach leads to an anatomical dissection of the bladder neck without increasing the risk of PSMs. However, no significant benefits in terms of continence recovery were demonstrated over the standard anterior approach.

Context: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP., Evidence Synthesis: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis., Evidence Acquisition: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05)., Conclusions: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited., Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis., Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023., Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months., Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters., Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months., Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Background: PSA density and an elevated PI-RADS score are among the strongest predictors of prostate cancer (PCa) in a fusion biopsy. Positive family history, hypertension, diabetes, and obesity have also been associated with the risk of developing PCa. We aim to identify predictors of the prostate cancer detection rate (CDR) in a series of patients undergoing a fusion biopsy., Methods: We retrospectively evaluated 736 consecutive patients who underwent an elastic fusion biopsy from 2020 to 2022. Targeted biopsies (2-4 cores per MRI target) were followed by systematic mapping (10-12 cores). Clinically significant PCa (csPCa) was defined as ISUP score ≥ 2. Uni- and multi-variable logistic regression analyses were performed to identify predictors of CDR among age, body mass index (BMI), hypertension, diabetes, positive family history, PSA, a positive digital rectal examination (DRE), PSA density ≥ 0.15, previous negative biopsy status, PI-RADS score, and size of MRI lesion., Results: The median patients' age was 71 years, and median PSA was 6.6 ng/mL. A total of 20% of patients had a positive digital rectal examination. Suspicious lesions in mpMRI were scored as 3, 4, and 5 in 14.9%, 55.0%, and 17.5% of cases, respectively. The CDR was 63.2% for all cancers and 58.7% for csPCa. Only age (OR 1.04, p < 0.001), a positive DRE (OR 1.75, p = 0.04), PSA density (OR 2.68, p < 0.001), and elevated PI-RADS score (OR 4.02, p = 0.003) were significant predictors of the CDR in the multivariable analysis for overall PCa. The same associations were found for csPCa. The size of an MRI lesion was associated with the CDR only in uni-variable analysis (OR 1.07, p < 0.001). BMI, hypertension, diabetes, and a positive family history were not predictors of PCa., Conclusions: In a series of patients selected for a fusion biopsy, positive family history, hypertension, diabetes, or BMI are not predictors of PCa detection. PSA-density and PI-RADS score are confirmed to be strong predictors of the CDR.

Introduction: Androgen deprivation therapy (ADT) is the key of medical treatment for advanced prostate cancer (PCa), especially in elderly patients. However, the adherence of ADT prescription to current guidelines is not optimal and must be balanced against possible side effects. Aim of this study was to evaluate the prescriptive appropriateness of ADT and ADT-related adverse events in a referral center for PCa., Methods: Five hundred fifty six patients who received an outpatient prescription for ADT from 2014 to 2018 were retrospectively identified from an administrative database. Only standard ADT was considered, including GnRH agonists, GnRH antagonists, and antiandrogens. Prescriptive appropriateness was defined according to the last European Association of Urology (EAU) guidelines. Our cohort was stratified according to age categories and patient follow-up was updated., Results: Four hundred twenty five patients were available for analysis. Mean age was 80 years; 96.3% of our patients fell in the "elderly" category. There was a predominance of GnRH agonists over the antagonists (84.9% vs 13%). 15.5% of ADTs did not have an appropriate indication according to guidelines. Patient compliance to ADT was evaluated as good in 372 (87.5%) cases. ADT-related complications were detected in 166 (39%) patients: bone, cardiovascular, and other complications were reported in 7.3%, 8.9%, and 19% of patients. Progression of disease was noted in 165 (38.8%) cases during ADT. At last follow-up, 124 (30.1%) patients were deceased., Conclusions: In a referral center, most ADT prescriptions followed EAU guidelines, but a non-negligible proportion still did not fall within these indications, exposing patients to unnecessary side effects. Compliance to ADT was generally good with a predominant use of GnRH agonists. Tolerance to ADT was fair, even if standardized reports were lacking.

Salvage radical prostatectomy after primary radiotherapy (sRP) is considered a challenging procedure. We highlight the complications of sRP and detail critical surgical steps to help prevent them. A nonsystematic literature review in PubMed using the term "salvage radical prostatectomy" was performed on December 1, 2021. Salvage robot-assisted RP (sRARP) cases and imaging materials were used to create an educational video providing practical examples. Owing to radiation-induced changes in the prostate and surrounding tissues after radiotherapy, sRP is typically more challenging than primary RP. Among its critical steps are incision of the endopelvic fascia, bladder neck dissection with attempts at sparing the neck, development of posterior planes between the prostate and rectum, and dissection of the prostatic apex. Complication rates are significant, in particular for bladder neck contracture (0-16%) and anastomotic leakage (10-33%). Rectal injury is now rare (<2%) but still feared; careful adherence to surgical principles is required to avoid this complication. Functional outcomes are nonoptimal, with a high risk of urinary incontinence (severe incontinence in ∼25% of men). sRARP is a challenging urological procedure and should be performed by experienced surgeons. Thorough knowledge of the surgical anatomy and a meticulous technique for the most difficult surgical steps are crucial to minimise complications and to improve patient outcomes., Patient Summary: In patients with prostate cancer, removal of the prostate because of cancer recurrence after primary treatment with radiotherapy can be difficult because of radiation-induced tissue damage. This challenging procedure should be performed by experienced surgeons to minimise the risk of complications., (© 2022 The Authors.)

Purpose: To assess differences in referral and pathologic outcomes for uro-oncology cases prior to and during the COVID pandemic, comparing clinical and pathological data of cancer surgeries performed at an academic referral center between 2019 and 2020., Methods: We collected data of 880 prostate biopsies, 393 robot-assisted radical prostatectomies (RARP) for prostate cancer (PCa), 767 trans-urethral resections of bladder tumor (TURB) and 134 radical cystectomies (RC) for bladder cancer (BCa), 29 radical nephro-ureterectomies (RNU) for upper tract urothelial carcinoma, 130 partial nephrectomies (PN) and 12 radical nephrectomies (RN) for renal cancer, and 41 orchifunicolectomies for testicular cancer. Data of patients treated in 2019 (before COVID-19 pandemic) were compared to patients treated in 2020 (during pandemic)., Results: No significant decline in uro-oncological surgical activity was seen between 2019 and 2020. No significant increase in time between diagnosis and surgery was observed for all considered cancers. No differences in terms of main pathologic features were observed in patients undergoing RARP, TURB, RNU, RN/PN, or orchifunicolectomy. A higher proportion of ISUP grade 3 and 4 PCa were diagnosed in 2020 at biopsy (p = 0.001), but this did not translate into worse pathological grade/stage at RARP. In 2020, more advanced disease features were seen after RC, including lymph node involvement (p = 0.01) and non-organ confined disease (p = 0.02)., Conclusion: Neither decline in uro-oncologic activity nor delay between diagnosis and treatment was observed at our institution during the first year of COVID-19 pandemic. No significant worsening of cancer disease features was found in 2020 except for muscle-invasive BCa., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To evaluate the performance of urinary fibrinogen β-chain (FBC) - either alone or associated with urinary tyrosine-phosphorylated proteins (UPY) - as bladder cancer (BCa) diagnostic biomarker., Materials & Methods: 164 subjects were tested., Results: Significantly different FBC and UPY levels were found between BCa patients and controls, as well as between low-grade and high-grade cancers. The diagnostic accuracy was 0.84 for FBC and 0.87 for UPY. The combination of FBC and UPY improved the accuracy to 0.91. The addition of clinical variables (age, gender, and smoking habit) to FBC and UPY into a model for BCa prediction significantly improved the accuracy to 0.99. The combination of FBC and UPY adjusted for clinical variables associates with the highest sensitivity and good specificity., Conclusion: Urinary FBC and UPY could be used as biomarkers for BCa diagnosis., Competing Interests: Financial & competing interests disclosure This study was supported by the CRT Foundation Grant (Italy) Progetti Ordinari 2015, Cod. ROL 46644 to G Giribaldi and P Gontero. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2021 The Authors.)

Ischemic heart disease still represents a large burden on individuals and health care resources worldwide. By conventions, it is equated with atherosclerotic plaque due to flow-limiting obstruction in large-medium sized coronary arteries. However, clinical, angiographic and autoptic findings suggest a multifaceted pathophysiology for ischemic heart disease and just some cases are caused by severe or complicated atherosclerotic plaques. Currently there is no well-defined assessment of ischemic heart disease pathophysiology that satisfies all the observations and sometimes the underlying mechanism to everyday ischemic heart disease ward cases is misleading. In order to better examine this complicated disease and to provide future perspectives, it is important to know and analyze the pathophysiological mechanisms that underline it, because ischemic heart disease is not always determined by atherosclerotic plaque complication. Therefore, in order to have a more complete comprehension of ischemic heart disease we propose an overview of the available pathophysiological paradigms, from plaque activation to microvascular dysfunction.

Hypertension and aging are characterized by vascular remodelling and stiffness as well as endothelial dysfunction. Endothelial function declines with age, since aging is associated with senescence of the endothelium due to increased rate of apoptosis and reduced regenerative capacity of the endothelium. Different phenotypes of hypertension have been described in younger and adult subjects with hypertension. In younger patients, functional and structural alterations of resistance arteries occur as the earliest vascular alterations which have prognostic significance and may contribute to stiffness of large arteries through wave reflection. In individuals above age of 50 years as well as in subjects with long-lasting elevated blood pressure, vascular changes occur predominantly in conduit arteries which become stiffer. Activation of renin-angiotensin-aldosterone and endothelin systems plays a key role in endothelial dysfunction, vascular remodelling, and aging by inducing reactive oxygen species production, and promoting inflammation and cell growth., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Aim: Dysphagia is a known complication in Pompe Disease (PD), a severe metabolic myopathy due to alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) with alglucosidase alfa is the only approved therapy for PD. Presently no data are available on the effects of ERT on dysphagia in PD patients. The aim of this work is to evaluate the course of this complication in a 6 years old boy affected by PD after treatment with ERT., Methods: Dysphagia was assessed by Videofluoroscopic Swallowing Study (VFSS) at baseline, before the start of ERT and after 36 months of therapy. We used the Dysphagia Severity Rating Scale (DSS) to define the severity grade of dysphagia., Results: VFSS performed at baseline revealed complete incoordination of oral stage swallowing which was classified as a grade 1 dysphagia according to DSS. After 36 months of treatment VFSS revealed normal swallowing, classified as grade 0 by DSS., Conclusion: Our results suggest that ERT is effective in improving dysphagia. VFSS may be a useful tool to investigate and monitor swallowing disorders in patients affected by PD.