Predictors and Outcomes of Oral Anticoagulant Deprescribing in Geriatric Inpatients With Atrial Fibrillation: A Retrospective Multicenter Cohort Study.

OBJECTIVE: To investigate prevalence and predictors of oral anticoagulant therapy (OAT) deprescribing in older inpatients with atrial fibrillation (AF), and its association with 1-year incidence of major clinical outcomes. DESIGN: Multicenter retrospective cohort study. SETTING AND PARTICIPANTS: Inpatients aged ≥75 years with known AF on OAT at admission discharged from 3 Italian acute geriatric wards between January 2014 and July 2018. METHODS: Data from a routine Comprehensive Geriatric Assessment (CGA), along with OAT status at discharge were recorded. One-year incidence of all-cause death, stroke or systemic embolism (SSE), and major and clinically relevant nonmajor bleeding (MB/CRNMB) were retrieved from administrative databases. Associations were explored through multilevel analysis. RESULTS: Among 1578 patients (median age 86 years, 56.3% female), OAT deprescription (341 patients, 21.6%) was associated with bleeding risk, functional dependence and cognitive impairment, and inversely, with previous SSE and chronic AF. Incidences of death, SSE, and MB/CRNMB were 56.6%, 1.5%, and 4.1%, respectively, in OAT-deprescribed patients, and 37.6%, 2.9%, and 4.9%, respectively, in OAT-continued patients, without significant differences between groups. OAT deprescription was associated with all-cause mortality [adjusted odds ratio (aOR) 1.41, 95% CI 1.68-1.85], along with older age, comorbidity burden, cognitive impairment, and functional dependence, but with neither SSE nor MB/CRNMB incidence, as opposed to being alive and free from SSE and MB/CNRMB, respectively (aOR 0.68, 95% CI 0.25-1.82, and aOR 0.95 95% CI 0.49-1.85, respectively). Conversely, OAT deprescription was associated with higher odds of being dead than alive both in patients free from SSE and in those free from MB/CRNMB. CONCLUSIONS AND IMPLICATIONS: CGA-based OAT deprescribing is common in acute geriatric wards and is not associated with increased SSE. The net clinical benefit of OAT in geriatric patients is strongly related with the competing risk of death, suggesting that functional and cognitive status, as well as residual life expectancy, should be considered in clinical decision making in this population.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

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.

Video-assisted thoracic surgery or thoracotomy for lung cancer surgery in obese patients? An analysis of the European Society of Thoracic Surgeons database.

OBJECTIVES: There is a lack of evidence on whether perioperative outcomes differ in obese patients after video-assisted thoracic surgery (VATS) or open lobectomy. We queried the European Society of Thoracic Surgeons database to assess morbidity and postoperative length of hospital stay in obese patients submitted to VATS and open pulmonary lobectomy for non-small-cell lung cancer. METHODS: We collected all consecutive patients from 2007 to 2021 submitted to lobectomy through VATS or thoracotomy with a body mass index greater than or equal to 30. An intention-to-treat analysis was carried out. Primary outcomes were morbidity rate, mortality and postoperative length of stay (LOS). Differences in outcomes were assessed through univariable, multivariable-adjusted and propensity score-matched analysis. RESULTS: Out of a total of 78 018 patients submitted to lung lobectomy, 13 999 cases (17.9%) were considered in the analysis, including 5562 VATS lobectomies and 8437 thoracotomy lobectomies. The VATS group showed a lower complication rate (23.2% vs 30.2%, P < 0.001), mortality (0.8% vs 1.5%, P < 0.001) and postoperative LOS (median 5 vs 7 days, P < 0.001). After propensity score matching, the VATS approach confirmed a lower complication rate (24.7% vs 29.7%, P = 0.002) and postoperative LOS (median 5 vs 7 days, P < 0.001). Moreover, these results were consistently observed when analyzing the severe obese subgroup (body mass index 35-39.9) and morbid obese subgroup (body mass index ≥40). CONCLUSIONS: In obese patients with non-small cell lung cancer, VATS lobectomy was found to be associated with improved postoperative outcomes than open lobectomy. Consequently, it should be considered the approach of choice for the Obese population.

Reproductive and Obstetric Outcomes Following a Natural Cycle vs. Artificial Endometrial Preparation for Frozen-Thawed Embryo Transfer: A Retrospective Cohort Study.

Background: The proportion of frozen embryo transfer cycles has consistently grown in recent decades. Some adverse obstetric outcomes after frozen embryo transfer could possibly be explained by different approaches in endometrial preparation. The aim of the present study was to investigate reproductive and obstetric outcomes after frozen embryo transfer, comparing different endometrial preparation strategies. Methods: This retrospective study included 317 frozen embryo transfer cycles, of which 239 had a natural or modified natural cycle and 78 underwent artificial endometrial preparation. After excluding late abortion and twin pregnancies, the outcomes of 103 pregnancies were analyzed, 75 of which were achieved after a natural cycle/modified natural cycle, and 28 were achieved after an artificial cycle. Results: The overall clinical pregnancy rate/embryo transfer was 39.7%, the miscarriage rate was 10.1%, and the live birth rate/embryo transfer was 32.8%, without significant differences in reproductive outcomes between natural/modified cycle and artificial cycle groups. The risks of pregnancy-induced hypertension and abnormal placental insertion were significantly increased in pregnancies achieved after the artificial preparation of the endometrium (p = 0.0327 and =0.0191, respectively). Conclusions: Our study encourages the use of a natural cycle or modified natural cycle for endometrial preparation for frozen embryo transfer in order to ensure the presence of a corpus luteum able to orchestrate maternal adaptation to pregnancy.

Effectiveness of mid-regional pro-adrenomedullin, compared to other biomarkers (including lymphocyte subpopulations and immunoglobulins), as a prognostic biomarker in COVID-19 critically ill patients: New evidence from a 15-month observational prospective study.

Background: Mid-regional pro-adrenomedullin (MR-proADM), an endothelium-related peptide, is a predictor of death and multi-organ failure in respiratory infections and sepsis and seems to be effective in identifying COVID-19 severe forms. The study aims to evaluate the effectiveness of MR-proADM in comparison to routine inflammatory biomarkers, lymphocyte subpopulations, and immunoglobulin (Ig) at an intensive care unit (ICU) admission and over time in predicting mortality in patients with severe COVID-19. Methods: All adult patients with COVID-19 pneumonia admitted between March 2020 and June 2021 in the ICUs of a university hospital in Italy were enrolled. MR-proADM, lymphocyte subpopulations, Ig, and routine laboratory tests were measured within 48 h and on days 3 and 7. The log-rank test was used to compare survival curves with MR-proADM cutoff value of >1.5 nmol/L. Predictive ability was compared using the area under the curve (AUC) and 95% confidence interval (CI) of different receiver-operating characteristic curves. Results: A total of 209 patients, with high clinical severity [SOFA 7, IQR 4-9; SAPS II 52, IQR 41-59; median viral pneumonia mortality score (MuLBSTA)-11, IQR 9-13] were enrolled. ICU and overall mortality were 55.5 and 60.8%, respectively. Procalcitonin, lactate dehydrogenase, D-dimer, the N-terminal prohormone of brain natriuretic peptide, myoglobin, troponin, neutrophil count, lymphocyte count, and natural killer lymphocyte count were significantly different between survivors and non-survivors, while lymphocyte subpopulations and Ig were not different in the two groups. MR-proADM was significantly higher in non-survivors (1.17 ± 0.73 vs. 2.31 ± 2.63, p < 0.0001). A value of >1.5 nmol/L was an independent risk factor for mortality at day 28 [odds ratio of 1.9 (95% CI: 1.220-3.060)] after adjusting for age, lactate at admission, SOFA, MuLBSTA, superinfections, cardiovascular disease, and respiratory disease. On days 3 and 7 of the ICU stay, the MR-proADM trend evaluated within 48 h of admission maintained a correlation with mortality (p < 0.0001). Compared to all other biomarkers considered, the MR-proADM value within 48 h had the best accuracy in predicting mortality at day 28 [AUC = 0.695 (95% CI: 0.624-0.759)]. Conclusion: MR-proADM seems to be the best biomarker for the stratification of mortality risk in critically ill patients with COVID-19. The Ig levels and lymphocyte subpopulations (except for natural killers) seem not to be correlated with mortality. Larger, multicentric studies are needed to confirm these findings.

Appropriateness and complications of androgen deprivation therapy for prostate cancer: Can we do better? A retrospective observational analysis from a referral center.

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.

Occurrence of secondary insults during endovascular treatment of acute ischemic stroke and impact on outcome: the SIR-STROKE prospective observational study.

BACKGROUND: Neurological outcome after endovascular treatment (EVT) of acute ischemic stroke (AIS) may depend on both patient-specific and procedural factors. We hypothesized that altered systemic homeostasis might be frequent and affect outcome in these patients. The aim of this study was to analyze secondary insults during EVT of AIS and its association with outcome and anesthesiologic regimen. METHODS: This was a single-center prospective observational study on patients undergoing EVT for AIS under local anesthesia (LA), conscious sedation (CS), or general anesthesia (GA). Altered systemic parameters were recorded and quantified as secondary insults. The primary endpoint was to evaluate number, duration, and severity of secondary insults during EVT. Secondary endpoints were to analyze association of insults with modified Rankin Scale at 90 days and anesthesiologic regimen. RESULTS AND CONCLUSIONS: One hundred twenty patients were enrolled. Overall, 78% of patients experienced at least one episode of hypotension, 21% hypertension, 54% hypoxemia, 16% bradycardia, and 13% tachycardia. In patients monitored with capnometry, 70% experienced hypocapnia and 21% hypercapnia. LA was selected in 24 patients, CS in 84, and GA in 12. Hypotension insult was more frequent during GA than LA and CS (p = 0.0307), but intraprocedural blood pressure variation was higher during CS (p = 0.0357). Hypoxemia was more frequent during CS (p = 0.0087). Proportion of hypotension duration was higher in unfavorable outcome but secondary insults did not remain in the final model of multivariable analysis. Secondary insults occurred frequently during EVT for AIS but the main predictors of outcome were age, NIHSS at admission, and prompt and successful recanalization.

The effect of peripheral regional analgesia in thoracic surgery: a systematic review and a meta-analysis of randomized-controlled trials.

BACKGROUND: Several peripheral regional anaesthesia (RA) techniques are commonly used in thoracic surgery even in the absence of precise indications regarding their effectiveness on postoperative pain management. OBJECTIVE: This systematic review and meta-analysis aims to describe and evaluate the relative effectiveness of different peripheral regional blocks and systemic analgesia in the context of video-assisted thoracoscopic surgery (VATS) or thoracotomy. DESIGN: Systematic review of randomized controlled clinical trials (RCTs) with meta-analyses. DATA SOURCES: We searched PubMed and Embase for all RCTs comparing the 24 hour morphine equivalents (MMEs) consumption following peripheral regional blocks and systemic analgesia (SA). ELIGIBILITY CRITERIA: We selected only RCTs including adult participants undergoing thoracic surgery, including esophagectomy and reporting on postoperative pain outcomes including 24 hour MMEs consumption. RESULTS: Among the 28 randomized studies including adult participants undergoing thoracic surgery and reporting on 24 hour opioid consumption, 11 reporting a comparison of individual blocks with systemic analgesia were meta-analyzed. RA was effective for almost all peripheral blocks. Regarding intercostal block, its antalgic effect was not well evaluated SMD -1.57 (CI -3.88, 0.73). RA in VATS was more effective in reducing MMEs than thoracotomy SMD -1.10 (CI -1.78, -0.41). CONCLUSIONS: RA is a useful choice in thoracic surgery. However, it is still not possible to determine the most appropriate block in the individual surgical settings to be performed due to RCTs paucity.

Single-Dose St. Thomas Versus Custodiol® Cardioplegia for Right Mini-thoracotomy Mitral Valve Surgery.

OBJECTIVE: Custodiol® and St. Thomas cardioplegia are widely employed in mini-thoracotomy mitral valve (MV) operations. One-dose of the former provides 3 h of myocardial protection. Conversely, St. Thomas solution is usually reinfused every 30 min and safety of single delivery is unknown. We aimed to compare single-shot St. Thomas versus Custodiol® cardioplegia. METHODS: Primary endpoint of the prospective observational study was cardiac troponin T level at different post-operative time-points. Propensity-weighted treatment served to adjust for confounding factors. RESULTS: Thirty-nine patients receiving St. Thomas were compared with 25 patients receiving Custodiol® cardioplegia; cross-clamping always exceeded 45 min. No differences were found in postoperative markers of myocardial injury. Ventricular fibrillation at the resumption of electric activity was more frequent following Custodiol® cardioplegia (P = .01). CONCLUSION: Effective myocardial protection exceeding 1 h of ischemic arrest can be achieved with a single-dose St. Thomas cardioplegia in selected patients undergoing right mini-thoracotomy MV surgery.

The Diagnostic Relevance of ß-D-Glucan for Candidemia within Internal Medicine Wards.

Candidemia diagnosis is based on the combination of clinical, microbiological and laboratory data. We aimed to evaluate performances and accuracy of (1,3)-ß-D-glucan (BDG) at various cut-offs in internal medicine patients. An observational retrospective−prospective study was performed. Patients with at least two determinations of BDG and paired, associated blood cultures within ±48 h were considered. A total of 140 patients were included: 26 with Candida spp. blood-stream infections (BSI) and 114 without candidemia. Patients with candidemia were older and had higher BDG values, need of parenteral nutrition, higher colonization by Candida in more than one site, presence of percutaneous gastrostomy and higher Candida or Charlson scores. BDG maintained the best compromise between sensitivity, specificity and optimal negative predictive value was 150 pg/mL. BDG values at cut-off of 150 pg/mL increase the strength of association between BDG and development of candidemia (Odds Ratio­OR 5.58; CI 2.48−12.53 vs. OR 1.06; CI 1.003−1.008). Analyzing BDG > 150 pg/mL along with Candida score > 2 and Charlson score > 4, the strength of the association amongst BDG, clinical scores and development of candidemia is increased. The overall clinical evaluation with the help of scores that consider BDG values > 150 pg/mL, Candida score > 2 and Charlson score > 4 in combination seems to predict better the need of antifungal empiric treatment.

Focal High-Intensity Focused Ultrasound vs. Active Surveillance for ISUP Grade 1 Prostate Cancer: Medium-Term Results of a Matched-Pair Comparison.

INTRODUCTION/BACKGROUND: Only 1 randomized controlled trial has compared focal therapy and active surveillance (AS) for the low-risk prostate cancer (PCa). We investigated whether focal HIFU (fHIFU) yields oncologic advantages over AS for low-risk PCa. MATERIALS AND METHODS: We included 2 non-randomized prospective series of 132 (fHIFU) and 421 (AS) consecutive patients diagnosed with ISUP 1 PCa between 2008 and 2018. A matched pair analysis was performed to decrease potential bias. Study main outcomes were freedom from radical treatment (RT) or androgen-deprivation therapy (ADT), treatment-free survival (TFS), time to metastasis, and overall survival (OS). RESULTS: Median fHIFU follow-up was 50 months (interquartile range, 29-84 months). Among matched variables, no major differences were recorded except for AS having more suspicious digital rectal examination findings (P = .0074) and recent enrollment year (P = .0005). Five-year intervention-free survival from RT or ADT was higher for the fHIFU cohort (67.4% vs. 53.8%; P = .0158). Time to treatment was approximately 10 months shorter for AS than for fHIFU (time to RT, P = .0363; time to RT or ADT, P = .0156; time to any treatment, P = .0319). No differences were found in any-TFS (fHIFU, 61.4% vs. AS, 53.8%; P = .2635), OS (fHIFU, 97% vs. AS, 97%; P = .9237), or metastasis (n = 0 in fHIFU and n = 2 in AS; P = .4981). Major complications (≥ Clavien 3) were rare (n = 4), although 36.4% of men experienced complications. No relevant changes were noted in continence (P = .3949). CONCLUSION: At a 4-year median follow-up, fHIFU for mainly low-risk PCa (ISUP grade 1) is safe, may decrease the need for radical treatment or ADT and may allow longer time to treatment compared to AS. Nonetheless, no advantages are seen in PCa progression and/or death (OS).

The SAFE Pilot Trial-SAlvage Focal Irreversible Electroporation-For Recurrent Localized Prostate Cancer: Rationale and Study Protocol.

Introduction: Currently, the majority of prostate cancer (PCa) recurrences after non-surgical first-line treatment are managed with androgen-deprivation therapy (ADT). Salvage radical prostatectomy (sRP) is a curative alternative to ADT but yields significant morbidity. Preliminary evidence from focal salvage treatments shows similar oncological control but lower morbidity compared to sRP. Among available ablative focal energies, irreversible electroporation (IRE) is a treatment modality that proved promising, especially in treating apical lesions, where PCa most often recurs. Our aim is to test the safety of salvage IRE for recurrent PCa. Methods: We performed a single-arm pilot feasibility study (IDEAL stage 2a): SAFE, SAlvage Focal irreversible Electroporation for recurrent localized PCa. Twenty patients with biopsy-proven PCa recurrence after primary non-surgical (radiation or ablation) treatment were included. All men will undergo mpMRI ± targeted biopsies, pre-operative PSMA-PET staging before inclusion and sIRE. Outcomes will be evaluated through internationally validated questionnaires and morbidity scales. All men will undergo a control biopsy at one year. Results: Primary objectives were the evaluation of the safety of sIRE (and patients' quality of life) after treatment. Secondary objectives were the evaluation of functional outcomes, namely, continence and erectile function changes and evaluation of short-term oncological efficacy. Conclusions: SAFE is the second pilot study to evaluate sIRE and the first one performed according to the most recent diagnostic and staging imaging standards. sIRE may provide a curative option for recurrent PCa together with lower comorbidities compared to sRP.

Effectiveness of an Active and Continuous Surveillance Program for Intensive Care Units Infections Based on the EPIC III (Extended Prevalence of Infection in Intensive Care) Approach.

We evaluated the effectiveness of the Extended Prevalence of Infection in Intensive Care (EPIC) III data collection protocol as an active surveillance tool in the eight Intensive Care Units (ICUs) of the Intensive and Critical Care Department of the University Hospital of Turin. A total of 435 patients were included in a six-day study over 72 ICU beds. 42% had at least one infection: 69% at one site, 26% at two sites and 5% at three or more sites. ICU-acquired infections were the most common (64%), followed by hospital-associated infections (22%) and community-acquired (20%), considering that each patient may have developed more than one infection type. 72% of patients were receiving at least one antibiotic: 48% for prophylaxis and 52% for treatment. Mortality, the length of ICU and hospital stays were 13%, 14 and 29 days, respectively, being all estimated to be significantly different in patients without and with infection (8% vs. 20%; 4 vs. 20 and 11 vs. 50 (p < 0.001). Our data confirm a high prevalence of infections, sepsis and the use of antimicrobials. The repeated punctual prevalence survey seems an effective method to carry out the surveillance of infections and the use of antimicrobials in the ICU. The use of the European Centre for Disease Prevention and Control (ECDC) definitions and the EPIC III protocol seems strategic to allow comparisons with national and international contexts.

Magnetic Resonance Imaging for Cerebral Micro-embolizations During Minimally Invasive Mitral Valve Surgery.

The role of aortic clamping techniques on the occurrence of neurological complications after right mini-thoracotomy mitral valve surgery is still debated. Brain injuries can occur also as silent cerebral micro-embolizations (SCM), which have been linked to significant deficits in physical and cognitive functions. Aims of this study are to evaluate the overall rate of SCM and to compare endoaortic clamp (EAC) with trans-thoracic clamp (TTC). Patients enrolled underwent a pre-operative, a post-operative, and a follow-up MRI. Forty-three patients were enrolled; EAC was adopted in 21 patients, TTC in 22 patients. Post-operative SCM were reported in 12 cases (27.9%). No differences between the 2 groups were highlighted (23.8% SCM in the EAC group versus 31.8% in the TTC). MRI analysis showed post-operative SCM in nearly 30% of selected patients after right mini-thoracotomy mitral valve surgery. Subgroup analysis on different types of aortic clamping showed comparable results. CLINICAL RELEVANCE: The rate of SCM reported in the present study on patients undergoing minimally invasive MVS and RAP is consistent with data in the literature on patients undergoing cardiac surgery through median sternotomy and antegrade arterial perfusion. Moreover, no differences were reported between EAC and TTC: both the aortic clamping techniques are safe, and the choice of the surgical setting to adopt can be really done according to the patient's characteristics.

Long-term Outcomes of Focal Cryotherapy for Low- to Intermediate-risk Prostate Cancer: Results and Matched Pair Analysis with Active Surveillance.

BACKGROUND: To date, only one trial compared focal therapy and active surveillance (AS) for low-risk prostate cancer (PCa). In addition, long-term outcomes of focal cryotherapy (FC) are lacking. OBJECTIVE: Our aim was to evaluate long-term outcomes of FC and compare them with AS. DESIGN, SETTING, AND PARTICIPANTS: We included two prospective series of 121 (FC) and 459 (AS) consecutive patients (2008-2018) for low- to intermediate-risk PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Study outcomes were radical therapy-free or androgen deprivation therapy (ADT)-free, any treatment-free, metastasis-free, and overall survival. A matched pair analysis was performed using seven covariates. RESULTS AND LIMITATIONS: The median FC follow-up was 85 mo (interquartile range 58-104); 92 (76%) men had International Society of Urological Pathology (ISUP) grade 1. Among matched variables, no significant differences were present except for cT stage and year of entry (both p < 0.01). Ten-year radical therapy-free or ADT-free, any treatment-free, metastasis-free, and overall survival were 51%, 40.2%, 93.9%, and 97%, respectively for FC. No differences were noted with AS (all p > 0.05), with the exception of time to radical therapy, time to radical therapy and ADT, and time to any treatment, all being shorter for AS (all p < 0.01). Freedom from radical treatment or ADT was higher for FC (AS 10 yr 39.3%; p = 0.04). Complications were relatively rare (26.5%) and mainly of low grade (Clavien >2, n = 3); three men developed incontinence (p = 0.0814), while both International Index of Erectile Function 5 and International Prostate Symptom Score scores increased (p = 0.0287 and p = 0.0165, respectively). Limitations include absence of randomization. CONCLUSIONS: At an early long-term follow-up, FC in the context of mainly low-risk PCa is safe and increases time to radical therapy but does not provide meaningful oncological advantages compared with AS. PATIENT SUMMARY: We compared focal cryotherapy with active surveillance mainly for low-risk prostate cancer. Focal cryotherapy, despite having fewer complications, did not yield meaningful advantages over active surveillance at 10 yr. Active surveillance should be preferred to focal cryotherapy for these patients.

Combination of urinary fibrinogen ß-chain and tyrosine-phosphorylated proteins for the detection of bladder cancer.

AIM: To evaluate the performance of urinary fibrinogen ß-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.

Carbapenemase-Producing Klebsiella pneumoniae Colonization and Infection in Solid Organ Transplant Recipients: A Single-Center, Retrospective Study.

Carbapenemase-KPC producing Klebsiella pneumoniae (CP-Kp) infection represents a serious threat to solid organ transplant (SOT). All patients admitted between 1 May 2011 and 31 August 2014 undergoing SOT were included in the retrospective study. The primary outcomes included a description of the association of enteric colonization and invasive infections by CP-Kp with one-year mortality. Secondary outcomes were the study of risk factors for colonization and invasive infections by CP-Kp. Results: A total of 5.4% (45/828) of SOT recipients had at least one positive rectal swab for CP-Kp, with most (88.9%) occurring after transplantation. 4.5% (35/828) of patients developed a CP-Kp-related invasive infection, with 68.6% (24/35) being previously colonized. The 1-year mortality was 31.1% in patients with enteric colonization with CP-Kp and, it was 51.4% among patients with CP-Kp-related invasive infections. At univariate analysis, colonization, invasive infections, sepsis, severe sepsis, and septic shock were significantly associated with 1-year mortality. At multivariate analysis, only invasive infections and the combination of sepsis, severe sepsis, or septic shock were significantly associated with 1-year mortality, whereas gastrointestinal colonization was significantly associated with survival. In this population, the 1-year mortality was significantly associated with invasive infections; otherwise, gastrointestinal colonization was not associated with increased 1-year mortality.

Extracorporeal carbon dioxide removal for treatment of exacerbated chronic obstructive pulmonary disease (ORION): study protocol for a randomised controlled trial.

BACKGROUND: Hypercapnic exacerbations are severe complications of chronic obstructive pulmonary disease (COPD), characterized by negative impact on prognosis, quality of life and healthcare costs. The present standard of care for acute exacerbations of COPD is non-invasive ventilation; when it fails, the use of invasive mechanical ventilation is inevitable, but is associated with extremely poor prognosis. Extracorporeal circuits designed to remove CO2 (ECCO2R) may enhance the efficacy of NIV to remove CO2 and avoid the worsening of respiratory acidosis, which inevitably leads to failure of non-invasive ventilation. Although the use of ECCO2R for acute exacerbations of COPD is steadily increasing, solid evidence on its efficacy and safety is scarce, thus the need for a randomized controlled trial. METHODS: multicenter randomized controlled unblinded clinical trial including 284 (142 per arm) patients with acute hypercapnic respiratory failure caused by exacerbation of COPD, requiring respiratory support with NIV. The primary outcome is event free survival at 28 days, a composite outcome defined by survival in absence of prolonged mechanical ventilation, severe hypoxemia, septic shock and second episode of COPD exacerbation. Secondary outcomes are incidence of endotracheal intubation and tracheostomy, intensive care and hospital length-of-stay and 90-day mortality. DISCUSSION: Acute exacerbations of COPD represent a significant burden in terms of prognosis, quality of life and healthcare costs. Lack definite evidence despite increasing use of ECCO2R justifies a randomized trial to evaluate whether patients with acute hypercapnic acidosis not responsive to NIV should undergo invasive mechanical ventilation (with all serious related risks) or be treated with ECCO2R to avoid invasive ventilation but be exposed to possible adverse events of ECCO2R. Owing to its pragmatic nature, sample size and composite primary outcome, this trial aims at providing valuable answers to relevant questions for clinical treatment of acute exacerbations of COPD. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04582799 . Registered 12 October 2020, .

Endo-Aortic vs. Trans-Thoracic Clamping in Right Mini-Thoracotomy Mitral Valve Surgery: Outcome on Myocardial Protection.

Background: Perfusion strategies and aortic clamping techniques for right mini-thoracotomy mitral valve (MV) surgery have evolved over time and remarkable short- and long-term results have been reported. However, some concerns have raised about the adequacy of myocardial protection during the minimally invasive approach, particularly with the endo-aortic clamp (EAC). Aim of this study was to compare the efficacy, in terms of myocardial preservation, of the EAC with the trans-thoracic aortic clamp (TTC) in patients undergoing right mini-thoracotomy MV surgery. Methods: A single center, prospective observational study was performed on patients undergoing right mini-thoracotomy MV surgery with retrograde arterial perfusion and EAC or TTC. A propensity matched analysis was performed to compare the two groups. Primary outcome was the comparison between cardiac troponin T levels measured at different time-points after surgery. Results: Eighty EAC patients were compared with 37 TTC patients. No cases of myocardial infarction or low cardiac-output syndrome were overall reported. No differences were recorded in terms of stroke, peri-operative mortality, and in the release of myocardial markers, lactates levels and need for inotropic support at different time-points after surgery. CK-MB peak levels were significantly lower in the EAC group. Conclusion: Despite concerns arising about the EAC, this prospective study shows equivalence in terms of myocardial preservation of the EAC compared with the TTC in patients undergoing right mini-thoracotomy MV surgery.