Lung Protective Mechanical Ventilation in Severe Acute Brain Injured Patients: A Multicenter, Randomized Clinical Trial (PROLABI).

BACKGROUND: Lung protective strategies using low tidal volumes and moderate positive end expiratory pressures (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in acutely brain-injured patients due to concerns about carbon dioxide control and effect of PEEP on cerebral hemodynamic. METHODS: In this multicenter, open-label, controlled clinical trial 190 adult acute brain injured patients were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency and ARDS at day 28. Neurological outcome was assessed at intensive care unit discharge by Oxford Handicap Scale and at six months by Glasgow Outcome Scale. FINDINGS: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (RR 1.35; 95%CI 1.03-1.79; p=0.025). Mortality was 28.9% and 15.1% (RR 1.91; 95%CI 1.06-3.42; p=0.02), ventilator dependency was 42.3% and 27.9% (RR 1.52; 95%CI 1.01-2.28; p=0.039), and incidence of ARDS was 30.8% and 22.1% (RR 1.39; 95%CI 0.85-2.27; p=0.179) respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. INTERPRETATION: In acutely brain-injured patients without ARDS a lung-protective ventilatory strategy as compared to a conventional strategy did not reduce mortality, percentage of patients weaned from mechanical ventilation, incidence of ARDS and was not beneficial in terms of neurological outcomes. Due to the early termination, these preliminary results require confirmation in larger trials. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT01690819.

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.

Coronavirus disease 2019 and first-trimester spontaneous abortion: a case-control study of 225 pregnant patients.

BACKGROUND: The disease caused by the severe acute respiratory syndrome coronavirus 2 was named coronavirus disease 2019 and classified as a global public health emergency. The evidence related to the impact of coronavirus disease 2019 on pregnancy is limited to the second and third trimester of pregnancy, whereas data on the first trimester are scant. Many viral infections can be harmful to the fetus during the first trimester of pregnancy, and whether severe acute respiratory syndrome coronavirus 2 is one of them is still unknown. OBJECTIVE: With this study, we evaluated severe acute respiratory syndrome coronavirus 2 infection as a risk factor for early pregnancy loss in the first trimester of pregnancy. Furthermore, coronavirus disease 2019 course in the first trimester was assessed. STUDY DESIGN: Between February 22 and May 21, 2020, we conducted a case-control study at S. Anna Hospital, Turin, among pregnant women in their first trimester, paired for last menstruation. The cumulative incidence of coronavirus disease 2019 was compared between women with spontaneous abortion (case group, n=100) and those with ongoing pregnancy (control group, n=125). Current or past infection was determined by the detection of severe acute respiratory syndrome coronavirus 2 from nasopharyngeal swab and severe acute respiratory syndrome coronavirus 2 immunoglobulin G and immunoglobulin M antibodies in a blood sample. Patient demographics, coronavirus disease 2019-related symptoms, and the main risk factors for abortion were collected. RESULTS: Of 225 women, 23 (10.2%) had a positive test result for coronavirus disease 2019. There was no difference in the cumulative incidence of coronavirus disease 2019 between the cases (11/100, 11%) and the controls (12/125, 9.6%) (P=.73). Logistic regression analysis confirmed that coronavirus disease 2019 was not an independent predictor of early pregnancy loss (odds ratio, 1.28; confidence interval, 0.53-3.08). Coronavirus disease 2019-related symptoms in the first trimester were fever, anosmia, ageusia, cough, arthralgia, and diarrhea; no cases of pneumonia or hospital admission owing to coronavirus disease 2019-related symptoms were recorded. No difference in the incidence of symptoms was noted between the 2 groups. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during the first trimester of pregnancy does not seem to predispose to early pregnancy loss; its cumulative incidence did not differ between women with spontaneous abortion and women with ongoing pregnancy. Coronavirus disease 2019 appears to have a favorable maternal course at the beginning of pregnancy, consistent with what has been observed during the second and third trimesters.

A prospective randomized trial comparing corifollitropin-α late-start (day 4) versus standard administration (day 2) in expected poor, normal, and high responders undergoing controlled ovarian stimulation for IVF.

OBJECTIVE: To assess whether corifollitropin-α (CFα) late-start administration (day 4) and standard administration (day 2) can obtain similar oocyte yield and live birth rate. STUDY DESIGN: A randomized controlled trial. SETTING: University Hospital IVF Unit. PATIENTS: One hundred thirteen women undergoing IVF. INTERVENTIONS: Patients distributed in three subgroups (expected poor, normal, or high responders to FSH) were randomized into two treatment arms: (a) CFα late-start: CFα on day 4 + GnRH antagonist from day 8 + (when needed) recFSH from day 11; (b) CFα standard start: CFα on day 2 + GnRH antagonist from day 6 + (when needed) recFSH from day 9. IVF or ICSI was performed as indicated. RESULTS: Considering the whole study group, the late-start regimen obtained comparable oocyte yield (8.9 ± 5.6 vs. 8.8 ± 6.2; p = n.s.), cPR/started cycle (25% vs. 31.6%, p = n.s.), and cumulative live birth rate (LBR)/ovum pickup (OPU) (29.2% vs. 37.7%, p = n.s.) than the standard regimen. The outcome of the two regimens was comparable in the two subgroups of high and normal responders. Differently, in poor responders, oocyte yield was similar, but LBR/OPU was significantly lower with late-start CFα administration that caused 40% cancellation rate due to monofollicular response. ROC curves showed that the threshold AMH levels associated with cycle cancellation were 0.6 ng/ml for late-start regimen and 0.2 ng/ml for standard regimen. CONCLUSION: CFα may be administered on either day 2 or day 4 to patients with expected high or normal response to FSH without compromising oocyte yield and/or live birth rate. Differently, late-start administration is not advisable for expected poor responders with AMH ≤ 0.6 ng/ml. TRIAL REGISTRATION: NCT03816670.

Correction to: A prospective randomized trial comparing corifollitropin-α late-start (day 4) versus standard administration (day 2) in expected poor, normal, and high responders undergoing controlled ovarian stimulation for IVF.

The original article unfortunately has a missing acknowledgement.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer: Morbidity and Functional Outcomes from a Large Multicenter Series of Open versus Robotic Approaches.

PURPOSE: Salvage radical prostatectomy has historically yielded a poor functional outcome and a high complication rate. However, recent reports of robotic salvage radical prostatectomy have demonstrated improved results. In this study we assessed salvage radical prostatectomy functional outcomes and complications when comparing robotic and open approaches. MATERIALS AND METHODS: We retrospectively collected data on salvage radical prostatectomy for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers from 2000 to 2016. The Clavien-Dindo classification was applied to classify complications. Complications and functional outcomes were evaluated by univariable and multivariable analysis. RESULTS: We included 395 salvage radical prostatectomies, of which 186 were open and 209 were robotic. Robotic salvage radical prostatectomy yielded lower blood loss and a shorter hospital stay (each p <0.0001). No significant difference emerged in the incidence of major and overall complications (10.1%, p=0.16, and 34.9%, p=0.67), including an overall low risk of rectal injury and fistula (1.58% and 2.02%, respectively). However, anastomotic stricture was more frequent for open salvage radical prostatectomy (16.57% vs 7.66%, p <0.01). Overall 24.6% of patients had had severe incontinence, defined as 3 or more pads per day, for 12 or 6 months. On multivariable analysis robotic salvage radical prostatectomy was an independent predictor of continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature of the study and the absence of a standardized surgical technique. CONCLUSIONS: In this contemporary series to our knowledge salvage radical prostatectomy showed a low risk of major complications and better functional outcomes than previously reported. Robotic salvage radical prostatectomy may reduce anastomotic stricture, blood loss and hospital stay, and improve continence outcomes.

The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015".

BACKROUND: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium. AIM: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients. METHODS: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment). RESULTS: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia. DISCUSSION: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents. CONCLUSION: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence.

Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study.

BACKGROUND: Neuroinflammation has been proposed as a possible mechanism of brain damage after traumatic brain injury (TBI), but no consensus has been reached on the most relevant molecules. Furthermore, secondary insults occurring after TBI contribute to worsen neurological outcome in addition to the primary injury. We hypothesized that after TBI, a specific pattern of cytokines is related to secondary insults and outcome. METHODS: A prospective observational clinical study was performed. Secondary insults by computerized multimodality monitoring system and systemic value of different cytokines were collected and analysed in the first week after intensive care unit admission. Neurological outcome was assessed at 6 months (GOSe). Multivariate projection technique was applied to analyse major sources of variation and collinearity within the cytokines dataset without a priori selecting potential relevant molecules. RESULTS: Twenty-nine severe traumatic brain injury patients undergoing intracranial pressure monitoring were studied. In this pilot study, we demonstrated that after TBI, patients who suffered of prolonged and severe secondary brain damage are characterised by a specific pattern of cytokines. Patients evolving to brain death exhibited higher levels of inflammatory mediators compared to both patients with favorable and unfavorable neurological outcome at 6 months. Raised ICP and low cerebral perfusion pressure occurred in 21 % of good monitoring time. Furthermore, the principal components selected by multivariate projection technique were powerful predictors of neurological outcome. CONCLUSIONS: The multivariate projection method represents a valuable methodology to study neuroinflammation pattern occurring after secondary brain damage in severe TBI patients, overcoming multiple putative interactions between mediators and avoiding any subjective selection of relevant molecules.

Extracorporeal Co2 removal in hypercapnic patients at risk of noninvasive ventilation failure: a matched cohort study with historical control.

OBJECTIVES: To assess efficacy and safety of noninvasive ventilation-plus-extracorporeal Co2 removal in comparison to noninvasive ventilation-only to prevent endotracheal intubation patients with acute hypercapnic respiratory failure at risk of failing noninvasive ventilation. DESIGN: Matched cohort study with historical control. SETTING: Two academic Italian ICUs. PATIENTS: Patients treated with noninvasive ventilation for acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease (May 2011 to November 2013). INTERVENTIONS: Extracorporeal CO2 removal was added to noninvasive ventilation when noninvasive ventilation was at risk of failure (arterial pH ≤ 7.30 with arterial PCO2 > 20% of baseline, and respiratory rate ≥ 30 breaths/min or use of accessory muscles/paradoxical abdominal movements). The noninvasive ventilation-only group was created applying the genetic matching technique (GenMatch) on a dataset including patients enrolled in two previous studies. Exclusion criteria for both groups were mean arterial pressure less than 60 mm Hg, contraindications to anticoagulation, body weight greater than 120 kg, contraindication to continuation of active treatment, and failure to obtain consent. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was the cumulative prevalence of endotracheal intubation. Twenty-five patients were included in the noninvasive ventilation-plus-extracorporeal CO2 removal group. The GenMatch identified 21 patients for the noninvasive ventilation-only group. Risk of being intubated was three times higher in patients treated with noninvasive ventilation-only than in patients treated with noninvasive ventilation-plus-extracorporeal CO2 removal (hazard ratio, 0.27; 95% CI, 0.07-0.98; p = 0.047). Intubation rate in noninvasive ventilation-plus-extracorporeal CO2 removal was 12% (95% CI, 2.5-31.2) and in noninvasive ventilation-only was 33% (95% CI, 14.6-57.0), but the difference was not statistically different (p = 0.1495). Thirteen patients (52%) experienced adverse events related to extracorporeal CO2 removal. Bleeding episodes were observed in three patients, and one patient experienced vein perforation. Malfunctioning of the system caused all other adverse events. CONCLUSIONS: These data provide the rationale for future randomized clinical trials that are required to validate extracorporeal CO2 removal in patients with hypercapnic respiratory failure and respiratory acidosis nonresponsive to noninvasive ventilation.

Controlled Ovarian Stimulation with recombinant-FSH plus recombinant-LH vs. human Menopausal Gonadotropin based on the number of retrieved oocytes: results from a routine clinical practice in a real-life population.

BACKGROUND: The association of recombinant FSH (rFSH) plus recombinant LH (rLH) is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its efficacy has, to date, not yet been compared to that of human Menopausal Gonadotropin (hMG), the FSH + LH activity-containing urinary drug. METHODS: Eight hundred forty-eight (848) IVF patients classified as expected "poor" or "normal" responders according to antral follicle count (AFC) and basal (day 3) FSH were treated with rFSH + rLH (2:1 ratio, n = 398, Group A) or hMG (n = 450, Group B). Data were collected under real-life practice circumstances and the pregnancy rate with fresh embryos was calculated by stratifying patients according to the number of retrieved oocytes (1-2, 3-4, 5-6, 7-8, >8). RESULTS: Overall, the pregnancy rate in both groups progressively improved according to the number of oocytes retrieved. When comparing patients within the same subgroup of oocyte yield, Group A and B showed a comparable outcome up to the reported highest yield (>8). When more than 8 oocytes were available, Group A had a significantly better pregnancy rate outcome. Patients' characteristics did not significantly differ between the two groups and the better outcome in the best responding patients in Group A was confirmed by a multivariable logistic regression analysis, that showed that both the use of rFSH + rLH and the total number of retrieved oocytes increased the probability of pregnancy with odd ratio (OR) of 1.628 and 1.083, respectively. CONCLUSIONS: When comparing patients with the same number of retrieved oocytes under real-life circumstances, the association of rFSH + rLH results in a significantly higher pregnancy rate than hMG when more than 8 oocytes are retrieved. The reason(s) for this are unknown, but a more favorable effect on oocyte quality and/or endometrial receptivity could be involved.

Radiofrequency ablation of thoracic tumours: lessons learned with ablation of 100 lesions.

PURPOSE: Our aim was to analyse the results of our first 100 radiofrequency ablation (RFA) procedures, of primary (nonsmall-cell lung cancers, NSCLC) and secondary (MTS) lung cancers to assess what lessons could be learned from our experience. MATERIALS AND METHODS: We analysed 100 lesions (mean size 23 mm) in 81 patients (25 NSCLC/56 MTS). On the basis of the clinical-radiological evolution, we analysed complete ablation (CA) versus partial ablation (PA) at the first computed tomography (CT) scan and during the follow-up (mean 23 months), time to progression (TTP) and survival. Possible predictive factors for local effectiveness and survival were sought. RESULTS: At the first CT scan CA was obtained in 88 %; the difference between the mean diameter of lesions achieving CA and PA was significant (20 versus 38 mm; p = 0.0001). A threshold of 30 mm (p = 0.0030) and the histological type (NSCLC 75 %/MTS 94 %; p = 0.0305) were also predictive of CA. A total of 18.4 % of the CA recurred (average TTP 19 months). Survival at 1, 2 and 3 years was 84.5, 65.4 and 51.5 %, respectively. The predictors of survival at 3 years were the coexistence of other MTS (p = 0.0422) and a diameter <20 mm (p = 0.0323), but not the local effectiveness of RFA. CONCLUSION: RFA for thoracic malignancies is accurate for lesions up to 30 mm, especially if metastatic; survival is more closely related to staging factors than to the local effectiveness of RFA.

Radiofrequency thermal ablation (RFA) of hepatic metastases (METS) from breast cancer (BC): an adjunctive tool in the multimodal treatment of advanced disease.

PURPOSE: The study was done to analyse the results of a series of radiofrequency ablation (RFA) procedures performed on hepatic metastases (METS) from breast cancer in order to evaluate the clinical impact of this therapy. MATERIALS AND METHODS: We analysed 45 patients (mean age 55 years) with 87 METS (mean size 23 mm), in terms of adverse events (AE), complete ablation (CA) at initial follow-up assessment and during the subsequent follow-up (mean 30 months), time to progression, and survival. The correlation between local effectiveness and METS size was investigated. Possible predictors of 3-year survival, including the local effectiveness of RFA (complete ablation maintained at 1-year versus treatment failure) were analysed. RESULTS: Nine AE occurred (two major complications, 2.3 %). CA at initial follow-up was obtained in 90 %; 19.7 % CA relapsed, with a time to progression of 8 months. The difference between the mean diameter of maintained CA (22 mm) and that of the treatment failures (30 mm) was highly significant (p = 0.0005), as was the 30 mm threshold (p = 0.0062). Overall survival at 1-3 years was 90, 58 and 44 %. At univariate analysis, the local effectiveness of RFA did not reach statistical significance. CONCLUSION: RFA of hepatic METS from breast cancer has high local effectiveness in tumours up to 30 mm, but it is not relevant in determining survival.

Outcomes and Impact of Pre-ECMO Clinical Course in Severe COVID-19-Related ARDS Treated with VV-ECMO: Data from an Italian Referral ECMO Center.

Background: The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe the cohort of C-ARDS patients treated with VV-ECMO at our ECMO center, focusing on factors that may affect in-hospital mortality and describing the time course of lung mechanics to assess prognosis. Methods: We performed a prospective observational study in the intensive care unit at the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021. Indications and management of ECMO followed the Extracorporeal Life Support Organization (ELSO) guidelines. Results: The 60-day in-hospital mortality was particularly high (85.4%). Non-survivor patients were more frequently treated with non-invasive ventilatory support and steroids before ECMO (95.1% vs. 57.1%, p = 0.018 and 73.2% vs. 28.6%, p = 0.033, respectively), while hypertension was the only pre-ECMO factor independently associated with in-hospital mortality (HR: 2.06, 95%CI: 1.06-4.00). High rates of bleeding (85.4%) and superinfections (91.7%) were recorded during ECMO, likely affecting the overall length of ECMO (18 days, IQR: 10-24) and the hospital stay (32 days, IQR: 24-47). Static lung compliance was lower in non-survivors (p = 0.031) and differed over time (p = 0.049), decreasing by 48% compared to initial values in non-survivors. Conclusions: Our data suggest the importance of considering NIS among the common ECMO eligibility criteria and changes in lung compliance during ECMO as a prognostic marker.

Surgical Treatment for Isolated Tricuspid Valve Disease: A Less Invasive Approach for Better Outcomes.

Background. Severe tricuspid valve (TV) disease has a strong association with right ventricle dysfunction, heart failure and mortality. Nevertheless, surgical indications for isolated TV disease are still uncommon. The purpose of this study is to analyze outcomes of patients undergoing minimally invasive isolated TV surgery (ITVS). Methods. Data of patients undergoing right mini-thoracotomy ITVS were prospectively collected. A subgroup analysis was performed on late referral patients. Five-year survival was assessed using the Kaplan-Meier survival estimate. Results. Eighty-one consecutive patients were enrolled; late referral was recorded in 8 out of 81 (9.9%). No cases of major vascular complications nor of stroke were reported. A 30-day mortality was reported in one patient (1.2%). Five-year Kaplan-Meier survival analysis revealed a significant difference between late referral patients and the control group (p = 0.01); late referral and Euroscore II were found to be significantly associated with reduced mid-term survival (p = 0.005 and p = 0.01, respectively). Conclusions. To date, perioperative mortality in patients undergoing ITVS is still consistently high, even in high-volume, high-experienced centres, and this accounts for the low rate of referral. Results from our report show that, with proper multidisciplinary management, appropriate pre-operative screening, and allocation to the safest approach, ITVS may offer better results than expected.

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.

Observation With or Without Subsequent Salvage Therapy for Pathologically Node-positive Prostate Cancer With Negative Conventional Imaging: Results From a Large Multicenter Cohort.

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.

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.

Accuracy of plateau pressure and stress index to identify injurious ventilation in patients with acute respiratory distress syndrome.

BACKGROUND: Guidelines suggest a plateau pressure (PPLAT) of 30 cm H(2)O or less for patients with acute respiratory distress syndrome, but ventilation may still be injurious despite adhering to this guideline. The shape of the curve plotting airway pressure versus time (STRESS INDEX) may identify injurious ventilation. The authors assessed accuracy of PPLAT and STRESS INDEX to identify morphological indexes of injurious ventilation. METHODS: Indexes of lung aeration (computerized tomography) associated with injurious ventilation were used as a "reference standard." Threshold values of PPLAT and STRESS INDEX were determined assessing the receiver-operating characteristics ("training set," N = 30). Accuracy of these values was assessed in a second group of patients ("validation set," N = 20). PPLAT and STRESS INDEX were partitioned between respiratory system (Pplat,Rs and STRESS INDEX,RS) and lung (PPLAT,L and STRESS INDEX,L; esophageal pressure; "physiological set," N = 50). RESULTS: Sensitivity and specificity of PPLAT of greater than 30 cm H(2)O were 0.06 (95% CI, 0.002-0.30) and 1.0 (95% CI, 0.87-1.00). PPLAT of greater than 25 cm H(2)O and a STRESS INDEX of greater than 1.05 best identified morphological markers of injurious ventilation. Sensitivity and specificity of these values were 0.75 (95% CI, 0.35-0.97) and 0.75 (95% CI, 0.43-0.95) for PPLAT greater than 25 cm H(2)O versus 0.88 (95% CI, 0.47-1.00) and 0.50 (95% CI, 0.21-0.79) for STRESS INDEX greater than 1.05. Pplat,Rs did not correlate with PPLAT,L (R(2) = 0.0099); STRESS INDEX,RS and STRESS INDEX,L were correlated (R(2) = 0.762). CONCLUSIONS: The best threshold values for discriminating morphological indexes associated with injurious ventilation were Pplat,Rs greater than 25 cm H(2)O and STRESS INDEX,RS greater than 1.05. Although a substantial discrepancy between Pplat,Rs and PPLAT,L occurs, STRESS INDEX,RS reflects STRESS INDEX,L.

The influence of gender on the epidemiology of and outcome from severe sepsis.

INTRODUCTION: The impact of gender on outcome in critically ill patients is unclear. We investigated the influence of gender on the epidemiology of severe sepsis and associated morbidity and mortality in a large cohort of ICU patients in the region of Piedmont in Italy. METHODS: This was a post-hoc analysis of data from a prospective, multicenter, observational study in which all patients admitted to one of 24 participating medical and/or surgical ICUs between 3 April 2006 and 29 September 2006 were included. RESULTS: Of the 3,902 patients included in the study, 63.5% were male. Female patients were significantly older than male patients (66±16 years vs. 63±16 years, P<0.001). Female patients were less likely to have severe sepsis and septic shock on admission to the ICU and to develop these syndromes during the ICU stay. ICU mortality was similar in men and women in the whole cohort (20.1% vs. 19.8%, P=0.834), but in patients with severe sepsis was significantly greater in women than in men (63.5% vs. 46.4%, P=0.007). In multivariate logistic regression analysis with ICU outcome as the dependent variable, female gender was independently associated with a higher risk of ICU death in patients with severe sepsis (odds ratio=2.33, 95% confidence interval=1.23 to 4.39, P=0.009) but not in the whole cohort (odds ratio=1.07, 95% confidence interval=0.87 to 1.34). CONCLUSION: In this large regional Italian cohort of ICU patients, there were more male than female admissions. The prevalence of severe sepsis was lower in women than in men, but female gender was independently associated with a higher risk of death in the ICU for patients with severe sepsis.

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.