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This large multicenter study of 37 magnetic resonance imaging scanners aimed at characterizing, for the first time, spatial profiles of inaccuracy (namely, Δ-profiles) in apparent diffusion coefficient (ADC) values with varying acquisition plan orientation and diffusion weighting gradient direction, using a statistical approach exploiting unsupervised clustering analysis.&#xD;A diffusion-weighted imaging (DWI) protocol (b-value: 0-200-400-600-800-1000 s/mm 2 ) with different combinations of acquisition plan orientation (axial/sagittal/coronal) and diffusion weighting gradient direction (anterior-posterior/left-right/feet-head) was acquired on a standard water phantom. For each acquisition setup, Δ-profiles along the 3 main orthogonal directions were characterized by fitting data with a second order polynomial function ( ar 2 + br + c ) . Moreover, for each Δ-profile, the maximum minus minimum of the fitting function ( δ max ) was calculated. &#xD;The parameters a , b , c , and δ max showed some significant variations between scanner systems by different manufacturers or with different static magnetic field strengths, as well as between different acquisition/estimation setups. Unsupervised clustering analysis showed two evident clusters with significantly different values of parameter a ( p < 0.0001), which can be grouped by acquisition protocol/Δ-profile direction but not scanner system.&#xD;The results of ∆-profiles confirm an appreciable inter-scanner variability in ADC measurement and corroborate the importance of guarantying the reliability of ADC estimations in clinical or research studies, considering for each scanner system the specific acquisition sequence in terms of acquisition plan orientation and diffusion weighting gradient direction., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Aims: While factors associated with adverse events are well elucidated in setting of isolated left ventricular dysfunction, clinical and imaging-based prognosticators of adverse outcomes are lacking in context of biventricular dysfunction. The purpose of this study was to establish role of clinical variables in prognosis of biventricular heart failure (HF), as assessed by cardiac magnetic resonance imaging., Methods: Study cohort consisted of 840 patients enrolled in DERIVATE registry with coexisting CMR-derived right ventricular (RV) and left ventricular (LV) dysfunction, as defined by RV and LV ejection fractions ≤45 % and ≤ 50 %, respectively. The primary objective was to identify factors associated with adverse long-term outcomes, defined as composite of all-cause death and HF hospitalizations (DHFH). Kaplan-Meir curves were plotted for survival analysis. Cox proportional hazard models were constructed to estimate adjusted hazard ratios (aHRs) and associated 95 % confidence intervals for clinical variables and their correlation with adverse events., Results: Mean age was 61.0 years; 83.1 % were male, 26.6 % had diabetes mellitus (DM), and 45.9 % had non-ischemic cardiomyopathy. At median follow-up of 2 years, DHFH occurred in 32.5 % of the cohort. Kaplan-Meir analysis showed higher rate of DHFH in patients with DM (35.2 % vs. 22.6 %, p < 0.001). Multivariate Cox regression analysis showed that DM was independently associated with DHFH (aHR 1.61 [95 % CI: 1.15-2.25]; p = 0.003). Importantly, ACE-inhibitor/ARB usage in patients with DM was associated with significant reduction in DHFH (aHR 0.53 [95 % CI: 0.31-0.90]; p = 0.02)., Conclusion: In patients with biventricular HF, DM was a strong predictor of DHFH, with ACE-inhibitor/ARB usage having cardioprotective effect., Competing Interests: Declaration of competing interest Subhi J. Al’Aref is supported by NIH: National Institutes of Health, USA 2R01 HL12766105 & 1R21 EB030654 and receives royalty fees from Elsevier. Carlo De Cecco received grant from Siemens. Gianluca Pontone received institutional fees by General Electric, Bracco, Heartflow, Medtronic, Bayer, Bhoeringher. Juerg Schwitter received research support by Bayer Healthcare Switzerland. U. Joseph Schoepf received grant by Astellas, Bayer, General Electric, and Siemens Healthcare, personal fees by Guerbet, speaking honorarium by Heartflow. Akos Varga-Szemes received grant from Siemens Healthcare and personal fees from Elucid Bioimaging. The other authors have no conficts of interestes relevant to this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale: Lung-protective strategies using low Vt and moderate positive end-expiratory pressure (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in patients with acute brain injuries because of concerns about carbon dioxide control and the effect of PEEP on cerebral hemodynamics. Objectives: To test the hypothesis that ventilation with lower VT and higher PEEP compared to conventional ventilation would improve clinical outcomes in patients with acute brain injury. Methods: In this multicenter, open-label, controlled clinical trial, 190 adult patients with acute brain injury 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 acute respiratory distress syndrome (ARDS) at Day 28. Neurological outcome was assessed at ICU discharge by the Oxford Handicap Scale and at 6 months by the Glasgow Outcome Scale. Measurements and Main Results: 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% (relative risk [RR], 1.35; 95% confidence interval [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. Conclusions: In patients with acute brain injury without ARDS, a lung-protective ventilatory strategy, as compared with a conventional strategy, did not reduce mortality, percentage of patients weaned from mechanical ventilation, or incidence of ARDS and was not beneficial in terms of neurological outcomes. Because of the early termination, these preliminary results require confirmation in larger trials. Clinical trial registered with www.clinicaltrials.gov (NCT01690819).

Objective: Patients with TNM T1a cervical cancer have excellent prognosis; however, the risk for recurrence remains an issue of concern and management guidelines are based on limited data. Here we performed subgroup analysis of the Surveillance in Cervical Cancer (SCCAN) consortium with the objective of defining the prognosis of T1a cervical cancer patients., Methods: SCCAN was an international, multicentric, retrospective cohort study of patients with cervical cancer undergoing surgical treatment in tertiary centers. Inclusion criteria included: histologically confirmed cervical cancer treated between 2007 and 2016; TNM T1a; primary surgical management; and at least 1-year of follow-up data availability. Exclusion criteria included treatment with primary chemo-radiation, and missing treatment-related or clinical data., Results: Out of 975 patients included, 554 (57 %) were T1a1 and 421 (43 %) T1a2. The majority had squamous-cell carcinoma (78 %). 79 patients (8.1 %) had lymphovascular space invasion (LVSI). 455 patients (47 %) underwent radical hysterectomy/ parametrectomy. Laparoscopic and open surgery was performed in 401 (41 %) and in 361 (37 %) patients, respectively. Adjuvant treatment was administered to 56 patients (5.7 %). Assessment of lymph nodes (LN) was performed in 524 patients (54 %), with LN involvement found in 15 (2.9 %). There were 40 (4.1 %) recurrences, occurring at a median of 26 months (4-106), out of which 33 (82.5 %) occurred in pelvis. Among T1a1 cases, there were 10 recurrences (2.0 %) if LVSI was negative, and 3 recurrences (6.7 %) if LVSI was positive. Among T1a2 cases, there were 23 recurrences (6.7 %) if LVSI was negative, and 4 recurrences (5.1 %) if LVSI was positive. There were 3 recurrences in the LN+ group (recurrence rate 20 %)., Conclusions: The risk of recurrence in T1a cervical cancer was 4.1 % corresponding to the rates seen in patients with FIGO 1B cancer in recently published prospective trials. LN involvement represents a risk factor for disease recurrence. Our results indicate that stage T1a cervical cancer, apart from T1a1 LVSI negative disease, should follow the same principles in the management as that of FIGO stage 1B cancer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest for this research publication., (Copyright © 2024. Published by Elsevier Inc.)

Background: Vulvodynia (VVD) is a debilitating chronic vulvar pain significantly affecting patients' quality of life. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and complex illness characterized by an unpleasant sensation related to the filling of the bladder and it strongly impacts patients' lives. The exact mechanisms of the two syndromes remain unknown, but there is an overlap between suspected pathophysiologies., Objective: To present an overview of the current research on the association between VVD and IC/BPS., Search Strategy: A systematic search of three electronic databases was conducted. Studies examining the correlation between VVD and IC/BPS with male and female patients aged over 18 years were included., Selection Criteria: Studies assessing the coexistence of VVD and IC/BPS were included. Reviews, letters to the editor, conference abstracts, book chapters, guidelines, Cochrane reviews, and expert opinions were excluded., Data Collection and Analysis: Two reviewers screened the studies for eligibility. Eligible studies were screened for quality., Main Results: A total of 13 studies were included in the final review. Among them, 11 presented a positive association between the two syndromes. The studies highlighted that VVD and IC/BPS share common comorbidities and possibly etiopathogenic pathways., Conclusion: VVD and IC/BPS are both complex and multifactorial syndromes. This review highlights an association between them, but additional studies on the topic should be conducted for a more precise conclusion., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: A study analyzing perioperative outcomes related to a sudden switch from 3D to 2D-4K technology for laparoscopic sacral colpopexy by expert pelvic surgeons: are we addicted to technology?, Material and Methods: After a sudden transition from 3D to 2D-4K laparoscopic technology, a total of 115 consecutive pelvic prolapse patients who underwent sacral colpopexy from June 2020 to September 2021 were retrospectively assessed from our database. Perioperative parameters, operative times (OT), and intraoperative difficulty scales were assessed. One-year follow-ups were analyzed for the study. Primary endpoints were OT; secondary endpoint was the evaluation of complications linked to this procedure., Results: We found statistical differences in OT and intraoperative difficulty scales between medians of the last 3D procedures and the first ten 2D-4K surgeries, without differences between operators. Only after more than 20 surgeries, we observed no significant differences between 3D and 2D-4K sacral colpopexy. We observed no statistical differences in terms of anatomic failure, PGI-I, and intra-postoperative complications., Conclusion: The transition of urogynecology from an exclusive vaginal approach to 2D-3D-4K laparoscopy significantly increased the level of technology necessary for surgical treatment of prolapse. This could, as a result, lead to pelvic surgeons becoming increasingly dependent on technology.

Inotuzumab ozogamicin (InO) is a CD22-directed antibody conjugated with calicheamicin. The phase IB of the ITCC-059 trial tested InO combined with chemotherapy in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Relapsed /refractory CD22+ BCP-ALL pediatric patients were enrolled. The primary objective was to establish the recommended phase II dose (RP2D). Secondary objectives included preliminary efficacy and tolerability. InO was combined with 1.5 mg/m2 of vincristine (days 3, 10, 17, 24), 20 mg/m2 of dexamethasone (2 5-day blocks, then amended), and intrathecal therapy. A rolling-6 design was used testing InO from 0.8 to 1.8 mg/m2/cycle. Between May 2020 and April 2022, 30 patients were treated, and 29 were evaluable for dose limiting toxicities (DLT). At 1.1 mg/m2/cycle, two of four patients had DLT (liver toxicity). InO was de-escalated to 0.8 mg/m2/cycle (N=6) without DLT while awaiting a protocol amendment to reduce dexamethasone dose to 10 mg/m2. Post amendment, InO was re-escalated to 1.1 mg/m2/cycle (N=6, 1 DLT), then to 1.4 mg/m2/ cycle (N=3, no DLT), and finally to 1.8 mg/m2/cycle (N=7, 1 DLT). Three additional patients were treated in an expansion cohort. The pooled response rate was 80% (24/30; 95% confidence interval [CI]: 61.4-92.3) and, among responders, 66.7% achieved minimal residual disease negativity. The RP2D of InO combined with vincristine, dexamethasone and intrathecal therapy was declared at 1.8 mg/m2/cycle (1.5 mg/m2/cycle after remission) in a fractioned schedule. This combination showed a response rate similar to the single agent cohorts of this trial, with liver toxicity issues at the initial higher dexamethasone dose (clinicaltrials gov. Identifier: NTR5736).

This is a retrospective, multicentric study, aimed to describe the real-life application of fertility preservation methods during treatment in female lymphoma patients, aged 18-40 years old, diagnosed between Oct 1st/2010 and May 31st/2018. Among 414 women included, median age was 28 years old, histologies were: HL 74%, PMBCL 13%, DLBCL 10%, others 3%. First line treatments were: ABVD in 295 (71%), R-CHOP like in 102 (25%), higher intensity regimens in 17 (4%) cases. Fertility preservation strategies were: GnRHa in 315 (78%), Oral Contraceptive in 41 (10%), oocytes and ovarian tissue cryopreservation in 55 and 42 patients, respectively. After therapy, we observed a restored regular period in 293 (70%) and premature ovarian failure (POF) in 33 (8%), Furthermore we recorded 43 pregnancies, all spontaneous with 5 years median follow-up. Median age at diagnosis and number of lines of treatment correlate with higher rate of amenorrhea, risk of POF and menopause ( p  < 0.001).

Background: In recent years there have been significant advances in the diagnosis, management and treatment of intracranial aneurysms (IAs) in Italy. Changes in prevalence of several epigenetic risk factors in the population as well as in environmental factors may have influenced the epidemiological burden of this disease. No long-term, population-based study about the incidence of treated ruptured IAs (rIAs) in Italy has yet been reported in literature., Methods: A long-term (January 2015December 2020), nationwide epidemiology study was performed by using discharge data collected by the Italian National Agency for Regional Healthcare Services with a particular focus on the treatment incidence of rIAs. A sub-analysis per macro-areas (north, center, and south and islands) was also performed, including the data about regional healthcare systems organization. The prevalence of common epigenetic and environmental risk factors has been also assessed., Results: Over 6 years, the mean incidence of rIAs treatment was 2.7x100,000 per year (SD±0.1; range: 2.6-2.9). In 2020, there was a significant north-south decreasing gradient in incidence (north vs. center vs. south and islands: 3.4 vs. 2.4 vs. 1.8x100,000/year; all P<0.001). There were no meaningful differences between macro-areas in terms of access to emergency care and number of neurosurgical wards per population. The rate of unruptured IAs (uIAs) treatment did not show a correlation to that of ruptured ones. Minor regional differences were retrieved for high-risk hypertension as well as for alcohol abuse prevalence. Air pollutants and temperature charts showed a north-south gradient similar to that of the incidence in the treated rIAs., Conclusions: The mean incidence of treated rIAs was stable over the 2015-2020 period in Italy. A north-south decreasing gradient in rIAs treatment incidence was reported. Neither the Regional healthcare organizations nor the rate of uIAs treatment were significant factors explaining the regional differences in the incidence of rIAs treatment. Minor differences in epigenetic and environmental risk factors may be synergistically involved.

The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6 th edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients' population. A panel of experts belonging to the Hematopoietic Cell Transplant and Infectious Disease Working Group (WG) of Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) developed a consensus to define the best practices in prevention, diagnosis, and management of HC in pediatric HCT setting., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Identifying markers associated with adverse events after acute myocarditis (AM) is relevant to plan follow-up. We assessed the prognostic performance of previously described cardiac magnetic resonance imaging (CMRI) markers and their combination: septal late gadolinium enhancement (LGE) localization and left ventricular ejection fraction (LVEF) < 50 % on baseline CMRI versus complicated clinical presentation (CCP: the presence of sustained ventricular tachycardia, or LVEF<50 % on the first echocardiogram or fulminant presentation)., Methods: We retrospectively assessed 248 AM patients (median age of 34 years, 87.1 % male) from 6 hospitals with onset of cardiac symptoms<30 days, increased troponin, and CMRI/histology consistent with myocarditis to identify those at risk of major cardiac events (cardiac death, heart transplantation, aborted sudden cardiac death, sustained ventricular tachycardia, or heart failure hospitalization)., Results: Thirteen patients (5.2 %) experienced at least one major cardiac event after a median follow-up of 4.7 years with a significant hazard ratio of 35.8 for CCP vs. 9.2 for septal LGE vs. 12.4 for LVEF<50 % on baseline CMRI (p = 0.001). CCP had the best c-index to identify patients with events: 0.836 vs. 0.786 for septal LGE and 0.762 for LVEF<50 %, while the combination of CCP plus LVEF<50 % or septal LGE has the highest c-index of 0.866. All 3 markers had high negative predictive value (NPV) of ≥0.98., Conclusions: Major cardiac events after an AM are relatively low, and CCP, septal LGE, and LVEF<50 % are significantly associated with events. These markers have especially high NPV to identify patients without events after an AM. These observations can help clinicians to monitor the patients after an AM., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Electrolyte imbalances are common in patients with heart failure. Several studies have shown that a low serum chloride level is associated with adverse outcomes in hospitalized patients with acute heart failure and in outpatients with chronic heart failure. We performed a systematic review and meta-analysis to assess the association of hypochloremia with all-cause mortality in patients with heart failure., Methods: Data search was conducted from inception through 1 February 2023, using the following MeSH terms: ('chloride' OR 'hypochloremia') AND 'heart failure'. Studies evaluating the association between serum chloride and all-cause mortality in patients with heart failure were included. The predefined primary outcome was all-cause mortality. Pooled hazard ratios and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effects model; fixed-effects model and leave-one-out sensitivity analyses were also performed., Results: A total of 15 studies, involving 25 848 patients, were included. The prevalence of hypochloremia ranged from 8.6 to 31.5%. Follow-up time ranged from 6 to 67 months. Hypochloremia as a categorical variable was associated with an increased risk of all-cause mortality [hazard ratio 1.56; 95% confidence interval (CI) 1.38-1.75; P  < 0.001]. As a continuous variable, serum chloride was associated with all-cause mortality (hazard ratio per mmol/l decrease in serum chloride: 1.06; 95% CI 1.05-1.07; P  < 0.001). Results were confirmed by using several sensitivity analyses., Conclusion: Hypochloremia exhibits a significant prognostic value in patients with heart failure. Serum chloride can be used as an effective tool for risk stratifying in patients with heart failure., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Introduction: Cerebral infarction from delayed cerebral ischemia (DCI) is a leading cause of poor neurological outcome after aneurysmal subarachnoid hemorrhage (aSAH). We performed an international clinical practice survey to identify monitoring and management strategies for cerebral vasospasm associated with DCI in aSAH patients requiring intensive care unit admission., Methods: The survey questionnaire was available on the European Society of Intensive Care Medicine (May 2021-June 2022) and Neurocritical Care Society (April - June 2022) websites following endorsement by these societies., Results: There were 292 respondents from 240 centers in 38 countries. In conscious aSAH patients or those able to tolerate an interruption of sedation, neurological examination was the most frequently used diagnostic modality to detect delayed neurological deficits related to DCI caused by cerebral vasospasm (278 respondents, 95.2%), while in unconscious patients transcranial Doppler/cerebral ultrasound was most frequently used modality (200, 68.5%). Computed tomography angiography was mostly used to confirm the presence of vasospasm as a cause of DCI. Nimodipine was administered for DCI prophylaxis by the majority of the respondents (257, 88%), mostly by an enteral route (206, 71.3%). If there was a significant reduction in arterial blood pressure after nimodipine administration, a vasopressor was added and nimodipine dosage unchanged (131, 45.6%) or reduced (122, 42.5%). Induced hypertension was used by 244 (85%) respondents as first-line management of DCI related to vasospasm; 168 (59.6%) respondents used an intra-arterial procedure as second-line therapy., Conclusions: This survey demonstrated variability in monitoring and management strategies for DCI related to vasospasm after aSAH. These findings may be helpful in promoting educational programs and future research., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Autosomal dominant Kabuki syndrome (KS) is a rare multiple congenital anomalies/neurodevelopmental disorder caused by heterozygous inactivating variants or structural rearrangements of the lysine-specific methyltransferase 2D (KMT2D) gene. While it is often recognizable due to a distinctive gestalt, the disorder is clinically variable, and a phenotypic scoring system has been introduced to help clinicians to reach a clinical diagnosis. The phenotype, however, can be less pronounced in some patients, including those carrying postzygotic mutations. The full spectrum of pathogenic variation in KMT2D has not fully been characterized, which may hamper the clinical classification of a portion of these variants. DNA methylation (DNAm) profiling has successfully been used as a tool to classify variants in genes associated with several neurodevelopmental disorders, including KS. In this work, we applied a KS-specific DNAm signature in a cohort of 13 individuals with KMT2D VUS and clinical features suggestive or overlapping with KS. We succeeded in correctly classifying all the tested individuals, confirming diagnosis for three subjects and rejecting the pathogenic role of 10 VUS in the context of KS. In the latter group, exome sequencing allowed to identify the genetic cause underlying the disorder in three subjects. By testing five individuals with postzygotic pathogenic KMT2D variants, we also provide evidence that DNAm profiling has power to recognize pathogenic variants at different levels of mosaicism, identifying 15% as the minimum threshold for which DNAm profiling can be applied as an informative diagnostic tool in KS mosaics., (© 2024. The Author(s), under exclusive licence to European Society of Human Genetics.)

Background: The superiority of anatomical resection (AR) vs. non-anatomical resection (NAR) in the surgical management of hepatocellular carcinoma (HCC) is debated. ARs are well-defined procedures, whereas the lack of NAR standardization results in heterogeneous outcomes. This study aimed to introduce the SegSubTe classification for NAR detailing the appropriateness of the level of surgical section of the Glissonean pedicles feeding the tumor., Methods: A single-center retrospective analysis of pre- and postoperative imaging of consecutive patients treated with NAR for single HCC between 2012 and 2020 was conducted. The quality of surgery was assessed classifying the type of vascular supply and the level of surgical section (segmental, subsegmental or terminal next to the tumor) of vascular pedicles feeding the HCCs; then, the population was divided in "SegSubTe-IN" or "SegSubTe-OUT" groups, and the tumor recurrence and survival were analyzed., Results: Ninety-seven patients who underwent NAR were included; 76% were SegSubTe-IN and 24% were SegSubTe-OUT. Total disease recurrence, local recurrence and cut-edge recurrence in the SegSubTe-IN vs. SegSubTe-OUT groups were 50% vs. 83% (P = 0.006), 20% vs. 52% (P = 0.003) and 16% vs. 39% (P = 0.020), respectively. SegSubTe-OUT odds ratio for local recurrence was 4.1 at univariate regression analysis. One-, three-, and five-year disease-free survival rates in the SegSubTe-IN vs. SegSubTe-OUT groups were 81%, 58% and 35% vs. 46%, 21% and 11%, respectively (P < 0.001)., Conclusions: The SegSubTe classification is a useful tool to stratify and standardize NAR for HCC, aiming at improving long-term oncological outcomes and reducing the heterogeneity of quality of NAR for HCC., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Introduction : The increase in the use of mobile apps since the COVID-19 pandemic, even among people with multiple sclerosis (PwMS) and health care providers (HCPs), has enabled access to reliable information, symptoms monitoring and management, and social connections. The pandemic has undoubtedly contributed to the acceleration of the "digital revolution." But how far has it progressed for the MS communities? Methods : Italian Google Play and App Store were queried, selecting MS-specific apps in English or Italian language and usable by a wide public. Results: Fifty-four (n = 54) MS-specific apps were identified; most were PwMS-oriented (83%), free of charge (94%), and in English language (76%). The 45 PwMS-oriented apps focused on increasing MS knowledge (71%), tracking symptoms (33%), and promoting networking with peers or HCPs (38%). The 13 HCPs-oriented tools addressed education and updates on MS (62%), disease assessment and management (54%), and research (15%). Google Search tool was also queried to find non-MS-specific apps to fulfill some unmet domains (as sleep, pain, sexual or mental health). Twenty-four additional apps were listed to provide a valuable contribution. Conclusion : The "digital revolution" led to increasingly customized tools for PwMS, especially as m-health or social-networking apps. However, apps to support other specific MS-relevant domains, appealing HCPs-oriented apps, and specific mobile tools for MS caregivers are still lacking. The absence of data assessing the usability and quality of MS apps in ecologically contexts leads to not reliable conclusions about potential benefits. A strong dialogue between MS communities and the digital industry is encouraged to fill this gap.

Purpose: The aim of this registry was to assess technical success, procedural safety and mid- to long-term follow-up results of the Silk Vista "Mama" (SVM) flow diverter (BALT, Montmorency, France) for the treatment of proximal intracranial aneurysms., Methods: Between August 2020 and March 2022, data from nine Italian neurovascular centres were collected. Data included patients' clinical presentation, aneurysms' size, location and status, technical details, overall complications and mid- to long-term angiographic follow-up., Results: Forty-eight aneurysms in 48 patients were treated using the SVM. Most aneurysms were small (≤ 10 mm: no. 29, 60%) and unruptured (no. 31, 65%); 13 aneurysms were recurrent after coiling or clipping. 37/48 aneurysms involved the internal carotid artery (77%). Optimal opening and complete wall apposition of the device were achieved in 46 out of 48 cases (96%). Four intra- or periprocedural complications occurred (two thrombotic complications successfully resolved, one cerebellar ischemia, one perirenal hematoma), without new neurological deficit. No significant intra-stent stenosis or stent displacement was observed during follow-up. No FD-related morbidity nor mortality was reported. At midterm (6-12 months) to long-term (> 12 months) follow-up, complete aneurysm occlusion (OKM D) was achieved in 76% of cases. Eighty-eight percent of patients had complete aneurysm occlusion or entry remnant (OKM D + C)., Conclusions: Our experience suggests that the new generation of low-profile SVM flow diverter for the treatment of proximal intracranial aneurysms is safe and effective, with low rates of intraprocedural complications and acceptable mid- to long-term occlusion rate., (© 2024. The Author(s).)

Background: Femorally inserted central catheters are increasingly used, especially after the COVID-19 pandemic, also thanks to widespread of tunneling techniques that allow the exit site to be moved away from the groin., Methods: In this retrospective observational study, femorally inserted catheters, with exit site at mid-thigh and the tip in Inferior vena cava or in Inferior vena cava at the junction with right atrium, have been observed and complications have been analyzed. All catheters were inserted by trained Nurses of a tertiary hospital Vascular Access Team., Results: In 142 catheters (126 inserted via common femoral vein and 16 inserted via superficial femoral vein) and 3060 catheter days, we observed an infection rate of 1.3 events/1000 catheter days (all of them in oncologic patients and up to 30 days of catheterization), 2 cases of thrombotic events (1.41%) and 17 cases of accidental removal (11.97%). Other rare complications, as primary malposition, tip migration, arterial pseudoaneurysm, have been recorded. The average length of catheters inserted, from the exit site to the tip, was 47.6 ± 2.4 cm., Conclusion: The attention to the correct position of the tip, the exit site at mid-thigh and the new techniques during insertion make these femoral catheters as safe as other central vascular access devices. For this kind of central access device, a catheter at least 50 cm long is needed., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA., Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up., Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections., Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception., (© 2024. The Author(s).)

Introduction: Single-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce., Methods: In this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m 2 in cycle 1, increasing to 80 mg/m 2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more)., Results: One-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0-73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8-82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events., Conclusions: In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule., Clinical Trial Registration Number: EudraCT 2014-003860-19., Competing Interests: Declarations of competing interest GF: scientific coordinator and principal investigator of the study; participated in advisory boards, acted as a speaker, and conducted training sessions on behalf of Pierre Fabre. NM-J: received consultancy fees from AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Pierre Fabre, Roche, and GSK; and travel support from Roche, AstraZeneca, Pfizer, and Novartis. MM: received personal fees from Roche, Novartis, and Eisai; and other financial support from Roche and Lilly. LC: received honoraria from AstraZeneca, MSD, and Pfizer; Novartis, and Gilead. MP: received consultancy fees from AstraZeneca, Novartis, Pfizer, Eli Lilly, and Amgen. EP: received consultancy fees from AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Pierre Fabre, Roche, and GSK; research funding from Daiichi Sankyo, Pfizer, Lilly, Novartis, Seattle Genetics, AstraZeneca, and Roche; and travel support from AstraZeneca, GSK, Pfizer, Lilly, and GSK. JE: received consultancy fees from AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Pierre Fabre, Roche, and Tesaro; research funding from Daiichi Sankyo, Pfizer, Lilly, Novartis, Seattle Genetics, AstraZeneca, Roche, and Odonate; and travel support from AstraZeneca, Daiichi Sankyo, Celgene, Pfizer, Novartis, Lilly, and Tesaro. AR: received honoraria for participating in advisory boards for Boehringer Ingelheim, Bristol Myers Squibb, and MSD; and in internal training events at Pfizer and AstraZeneca. MEC: participated in an advisory board for Eli Lilly and Pierre Fabre. CdA, GV, RR and CTTM: employees of Pierre Fabre. BK-B, MU, HB, SM, JBC, TP, and NC: no conflicts to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: Catheter ablation (CA) of ventricular tachycardia (VT) has become an important tool to improve clinical outcomes in patients with appropriate transvenous implantable cardioverter defibrillator (ICD) shocks. The aim of our analysis was to test whether VT ablation (VTA) impacts long-term clinical outcomes even in subcutaneous ICD (S-ICD) carriers., Methods and Results: International Subcutaneous Implantable Cardioverter Defibrillator (iSUSI) registry patients who experienced either an ICD shock or a hospitalization for monomorphic VT were included in this analysis. Based on an eventual VTA after the index event, patients were divided into VTA+ vs. VTA- cohorts. Primary outcome of the study was the occurrence of a combination of device-related appropriate shocks, monomorphic VTs, and cardiovascular mortality. Secondary outcomes were addressed individually. Among n = 1661 iSUSI patients, n = 211 were included: n = 177 experiencing ICD shocks and n = 34 hospitalized for VT. No significant differences in baseline characteristics were observed. Both the crude and the yearly event rate of the primary outcome (5/59 and 3.8% yearly event rate VTA+ vs. 41/152 and 16.4% yearly event rate in the VTA-; log-rank: P value = 0.0013) and the cardiovascular mortality (1/59 and 0.7% yearly event rate VTA+ vs. 13/152 and 4.7% yearly event rate VTA-; log-rank P = 0.043) were significantly lower in the VTA + cohort. At multivariate analysis, VTA was the only variable remaining associated with a lower incidence of the primary outcome [adjusted hazard ratio 0.262 (0.100-0.681), P = 0.006]., Conclusion: In a real-world registry of S-ICD carriers, the combined study endpoint of arrhythmic events and cardiovascular mortality was lower in the patient cohort undergoing VTA at long-term follow-up., Clinicaltrials.gov Identifier: NCT0473876., Competing Interests: Conflict of interest: A.D.R. is a consultant for Abbott. M.C. has received speaker honoraria from Abbott and Biosense Webster. L.K. worked as a proctor for Boston Scientific. R.T. is a consultant for Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and he received speaker’s honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and LifeTech and research grants from Abbott, Biosense Webster, and LifeTech. A.B. has received consultant and/or speaker fees from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, Bristol Myers Squibb, Cook Medical, Daiichi Sankyo, Medtronic, Pfizer, and Spectranetics/Philips., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Schizophrenia is thought to reflect aberrant connectivity within cortico-cortical and reentrant thalamo-cortical loops, which physiologically integrate and coordinate the function of multiple cortical and subcortical structures. Despite extensive research, reliable biomarkers of such "dys-connectivity" remain to be identified at the onset of psychosis, and before exposure to antipsychotic drugs. Because slow waves travel across the brain during sleep, they represent an ideal paradigm to study pathological conditions affecting brain connectivity. Here, we provide proof-of-concept evidence for a novel approach to investigate slow wave traveling properties in First-Episode Psychosis (FEP) with high-density electroencephalography (EEG). Whole-night sleep recordings of 5 drug-naïve FEP and 5 age- and gender-matched healthy control subjects were obtained with a 256-channel EEG system. One patient was re-recorded after 6 months and 3 years of continuous clozapine treatment. Slow wave detection and traveling properties were obtained with an open-source toolbox. Slow wave density and slow wave traveled distance (measured as the line of longest displacement) were significantly lower in patients (p < 0.05). In the patient who was tested longitudinally during effective clozapine treatment, slow wave density normalized, while traveling distance only partially recovered. These preliminary findings suggest that slow wave traveling could be employed in larger samples to detect cortical "dys-connectivity" at psychosis onset., (© 2024. The Author(s).)

Spondylodiscitis following sacral colpopexy for Pelvic Organ Prolapse (POP) represents a rare complication with severe consequences. Authors performed a literature search, from 2000 to 2022, to set a narrative review of literature. Spondylodiscitis is an uncommon but dangerous side effect of a routine surgical treatment that needs to be identified and treated right away to prevent worsening clinical consequences. Suboptimal dissection of the sacral promontory and/or site infection are associated with spondylodiscitis. When spondylodiscitis is suspected, advanced imaging methods should be used, and surgical excision shouldn't be put off after a failed course of treatment. Authors presented a case-video of a 68-year-old woman who reported severe lower back pain 7 weeks after surgery, in which sacral spondylodiscitis was diagnosed and laparoscopically treated. In this case, a laparoscopic tack and mesh removal from promontory was carried out following the patient's continued lower back pain and the antibiotic therapy's incomplete radiological remission of spondylodiscitis. The patient's radiological findings and symptoms completely resolved two weeks following the procedure., Competing Interests: None., (IJCEP Copyright © 2024.)

Purpose: To describe the ocular clinical and imaging findings of a patient with isolated vitreous metastasis, confirmed by vitreous biopsy, from an anaplastic lymphoma kinase (ALK)-positive metastatic lung cancer., Methods: Case report., Results: A 47-year-old woman with a history of metastatic ALK-positive lung cancer was referred by her oncologist because of unilateral blurred vision over 4 weeks. The fundus examination showed vitreous opacities with clumps of nonpigmented cells, without vasculitis or retinitis, whereas optical coherence tomography showed hyperreflective deposits on the inner retinal surface with no retinal involvement. Diagnostic vitrectomy revealed neoplastic cells with ALK mutation., Conclusion: This is the first report that documents a case of isolated vitreous metastasis from ALK-positive lung cancer in a patient under targeted therapy to treat metastatic lung cancer. We emphasize the importance of multimodal imaging, diagnostic vitrectomy, and a pathologist's cooperation to provide essential information about diagnosis and effective treatment.

Femorally inserted Central Catheters are increasingly used also for medium and long-term catheterization as an alternative to Centrally and Peripherally inserted Central Catheters. If certified as "power injectable," they may be used for contrast media injection during radiological examinations. It is important to consider the risk that, as with other types of catheters, the injection of contrast media could cause migration or damage to the device. The case of a Femoral catheter migration in hepatic vein, during CT scan, is described., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Vascular complications are a major issue in V-A ECMO and can affect long term outcome. Among these, Artero-Venous (AV) fistulas may lead to right heart failure. Case History: A 73-years patient supported with V-A ECMO for post-cardiotomy biventricular failure developed right heart failure after V-A ECMO decannulation, requiring V-A ECMO recannulation. The presence of an AV femoral fistula was incidentally revealed during femoral vein cannulation, from which oxygenated blood was unexpectedly drawn. The angiographic assessment confirmed the presence of a fistula between superficial femoral artery and vein, at the site of the first venous ECMO cannulation. This was caused by the venous cannula that inadvertently passed across the artery and created an AV fistula that was opened by the venous cannula removal. The exclusion of the endovascular fistula allowed the right heart failure resolution. Conclusions: In the presence of right heart failure after recent vascular manipulation, AV fistula should be ruled out., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of the present study, conducted by a working group of the Italian Association of Medical Physics (AIFM), was to define typical z-resolution values for different digital breast tomosynthesis (DBT) models to be used as a reference for quality control (QC). Currently, there are no typical values published in internationally agreed QC protocols., Methods: To characterize the z-resolution of the DBT models, the full width at half maximum (FWHM) of the artifact spread function (ASF), a technical parameter that quantifies the signal intensity of a detail along reconstructed planes, was analyzed. Five different commercial phantoms, CIRS Model 011, CIRS Model 015, Modular DBT phantom, Pixmam 3-D, and Tomophan, were evaluated on reconstructed DBT images and 82 DBT systems (6 vendors, 9 models) in use at 39 centers in Italy were involved., Results: The ASF was found to be dependent on the detail size, the DBT angular acquisition range, the reconstruction algorithm and applied image processing. In particular, a progressively greater signal spread was observed as the detail size increased and the acquisition angle decreased. However, a clear correlation between signal spread and angular range width was not observed due to the different signal reconstruction and image processing strategies implemented in the algorithms developed by the vendors studied., Conclusions: The analysis led to the identification of typical z-resolution values for different DBT model-phantom configurations that could be used as a reference during a QC program., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design., Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement., Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event., Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD., Competing Interests: Conflict of interest: K. Waeijen-Smit, M. Crutsen, S. Keene, T.J. Ringbæk, F. Fabbian, C-t. Lun, B. Ergan, C. Estebam, J.M. Quintana Lopez, C.L. Chang, R.J. Hancox, E. Shafuddin, H. Ellis, C. Janson, G. Gudmundsson, D. Epstein, A. Lacoma, C. Osadnik, I. Alia, F. Spannella, Z. Karakurt, H. Mehravaran, C. Utens, M.D. de Kruif, F.W.S. Ko, S.P. Trethewey, K. Vermeersch, S. Zilberman-Itskovich, C. Echevarria, R.T.M. Sprooten, P. Faverio, H.J. Prins and S. Houben-Wilke have no grants or personal fees to report. Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi and Grifols and research grants from Grifols. Conflict of interest: E. Crisafulli has received honoraria for lecturing, scientific advisory boards and participation in clinical studies for AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis, Qbgroup and Sanofi. Conflict of interest: A. Torres reports speaker/consulting honoraria from Pfizer, MSD, Janssen and Biomerieux. Conflict of interest: C. Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the University of Basel, the University Hospital Basel, the KTI, Abbott, Beckman Coulter, BRAHMS, Idorsia, LSI-Medience, Ortho Diagnostics, Novartis, Roche, Siemens, SpinChip and Singulex, as well as speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Idorsia, Novartis, Osler, Roche, SpinChip and Sanofi, all outside the submitted work. Conflict of interest: P. Schuetz has received grants from Nestle, Abbot, bioMerieux and Thermofisher outside the submitted work. Conflict of interest: E. Mekov has received grants and personal fees from Chiesi, and speaker or consulting fees from AstraZeneca and Chiesi. Conflict of interest: T.H. Harries is supported by a National Institute for Health and Care Research Academic Clinical Lectureship. Conflict of interest: J.L. López-Campos has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies or writing for publications for (alphabetical order): AstraZeneca, Bial, Boehringer, Chiesi, CSL Behring, Faes, Ferrer, Gebro, Grifols, GSK, Megalabs, Menarini and Novartis. Conflict of interest: C.S. Ulrik has received personal fees and grants from AstraZeneca, Chiesi, Boehringer Ingelheim, GSK, Novartis, Sanofi, Menarini, TEVA, ALK-Abello, Takeda, Orion Pharma, TFF Pharmaceuticals and Covis Pharma outside the submitted work. Conflict of interest: J. Dominguez has received honoraria for lectures from Oxford Immunotec (UK) and received payments for license transference from GenID (Germany), and grants from La Fundació La Marató TV3, Instituto de Salud Carlos III (CP03/00112), Catalan Pulmonology Society (SOCAP), Catalan Pulmonology Foundation (FUCAP) and Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Conflict of interest: A.M. Turner reports research grants outside the submitted work from AstraZeneca, Resmed, Phillips, Chiesi, Grifols, CSL Behring and NIHR, and honoraria from GSK and Boehringer Ingelheim. Conflict of interest: D. Bumbacea has received grants and personal fees in the last 3 years from AstraZeneca, Eli Lilly, Novartis, Sanofi and Synairgen outside of the submitted work. Conflict of interest: PBM has received grants and personal fees from Philips, ResMed, Breas, Chiesi, Fischer & Paykel and, Sanofi outside the submitted work. Conflict of interest: J. Steer has received grants and honoraria, outside the submitted work, from Chiesi, Menarini Group, AstraZeneca and Pfizer. Conflict of interest: S.C. Bourke has received research grants from GSK (BEC COPD IRAS 285200), and additional support from Radiometer for an NIHR-funded study (NIVOW IRAS 313485), Philips, ResMed, and Pfizer Open Air, took part in clinical advisory boards with Philips and AstraZeneca, and has received honoraria from Boehringer Ingelheim, Chiesi, GSK, and AstraZeneca. Conflict of interest: N. Lane reports research grants from Bright Northumbria and The ResMed Foundation; and nonfinancial support from Chiesi and BREAS outside the submitted work. Conflict of interest: J. de Batlle acknowledges receiving financial support from Instituto de Salud Carlos III (Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund, “Investing in your future”. Conflict of interest: R. Russell has received personal fees, outside of the submitted work, from AstraZeneca, Chiesi, Covis, GlaxoSmithKline and Boehringer Ingelheim. Conflict of interest: J.L. Cross has received grants from National Institute of Health Research. Conflict of interest: M.A. Spruit has received grants from the Netherlands Lung Foundation, Stichting Asthma Bestrijding, AstraZeneca, Boehringer Ingeheim, TEVA and CHIESI outside the submitted work. Conflict of interest: S.O. Simons has received grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Chiesi outside the submitted work. Conflict of interest: F.M.E. Franssen has received grants and personal fees from AstraZeneca, Chiesi, Boehringer Ingelheim, Glaxosmithkline, Novartis and MSD outside the submitted work. Conflict of interest: All authors declare no conflicts of interest in relation to the present study., (Copyright ©The authors 2024.)

Objectives: In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient's respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes., Design: Retrospective observational cohort study., Setting: Twenty-four Italian ICUs from February 2020 to May 2020., Patients: Mechanically ventilated ICU patients with COVID-19-induced respiratory failure., Intervention: The transition period from CMV to PSV was evaluated. We defined it as "failure of assisted breathing" if the patient returned to CMV within the first 72 hours., Measurements and Main Results: Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao 2 /Fio 2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99-1.00; p = 0.003). Patients in the success group displayed a better trend in Pao 2 /Fio 2 , Paco 2 , plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42-3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04)., Conclusions: Our study emphasizes that the Pao 2 /Fio 2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Evidence-based indications for intracranial pressure (ICP) monitoring in patients with traumatic brain injury (TBI) are lacking. The aim of this study was to analyze the main factors that guided the decision-making of invasive ICP monitoring in a large cohort of TBI patients from our institution., Methods: This is a retrospective, single centre, observational study including adult TBI patients consecutively admitted to our Neurointensive Care Unit over 20 years. Logistic regression analyses were performed to identify potential factors associated with the decision for ICP monitor insertion. A decision tree was developed to identify the combination of factors with the highest statistical power to predict the decision for ICP monitor insertion., Results: A total of 857 adult patients were included in the analysis. The decision to monitor ICP was strongly related to different factors, including Glasgow Coma Scale (GCS), computed tomography (CT) scan classification, pupils' reactivity, and patients' prognosis at the admission calculated by the International Mission on Prognosis in Traumatic Brain Injury (IMPACT) score (P<0.01). Results from the decision tree showed an overall ability of the 72% in the prediction of ICP monitoring and that, among the factors analyzed, CT findings had the primarily and strongest discrimination power., Conclusions: The decision to insert an invasive ICP monitoring in patients with TBI is multifactorial. Among the different factors analysed in our cohort of TBI patients, prognostication factors as for IMPACT score and in particular CT findings could potentially explain the decision making for ICP monitoring.

Background: Female sexual function in pregnancy is an under-investigated topic by care providers. This study aimed to investigate the sexual function and the impact of traditional risk factors for pelvic floor disorders (PFDs) during the third trimester of pregnancy., Methods: This is a secondary analysis of a multicenter cross-sectional study conducted in eight hospitals in Italy and Italian-speaking Switzerland. Women at the third trimester of pregnancy aged 18 years and over completed the Italian-PFQPP questionnaire anonymously., Results: Overall, 927 patients in the third trimester of pregnancy answered the questionnaire. About 29.5% of women reported reduced or absent sexual activity. The less reported symptom was coital incontinence (1.3%), while painful intercourses was the most frequent one (50.3%). Nicotine abuse was associated with traumatic sexual intercourses, impaired vaginal sensibility, and negative impact on sexual life and well-being. Familiarity for pelvic floor disorder resulted as a risk factor for coital incontinence (OR=3.61)., Conclusions: Sexual symptoms, with pain during intercourses being the most widely reported, are extremely common in the third trimester of pregnancy and can greatly affect quality of life. Familiarity for pelvic floor disorders and nicotine abuse resulted as significant risk factors for at least one sexual symptom.

Background: Laparoscopic sacral colpopexy (LSC) is the gold standard treatment for women with apical/anterior pelvic organ prolapse (POP). For isolated posterior vaginal prolapse, instead, the literature suggests fascial native tissue repair. This is a retrospective 2-year quality-of-life follow-up study after laparoscopic posterior plication (LPP) combined with LSC in patients with anterior/apical prolapse combined with severe posterior colpocele. The primary endpoint was to evaluate the subjective outcomes quality of life (QoL), sexual function, and patient satisfaction rate. The secondary endpoint was to evaluate perioperative and anatomical outcomes at the 2-year follow-up., Methods: A total of 139 consecutive patients with anterior and/or apical prolapse (POP-Q stage ≥ II) and severe posterior vaginal prolapse (posterior POP-Q stage ≥ III) were retrospectively selected from our database among women who underwent, from November 2018 to February 2021, a "two-meshes" LSC. The patients were classified into Group A (81 patients; LSC plus LPP) and Group B (67 patients; LSC alone). The primary endpoint was evaluated using the Patient Global Impression of Improvement (PGI-I), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), the Pelvic Floor Impact Questionnaire-7 (PFIQ-7), the Female Sexual Distress Scale (FSDS), the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), and the EuroQol (EQ-5D). The secondary endpoint was studied using the POP-Q study and an intra-, peri-, and post-operative complications assessment. Two-year follow-up data were analyzed for the study., Results: At 2 years, all women showed a statistically significant amelioration of their symptoms on the QoL questionnaires. We found a statistical difference in favor of posterior plication in terms of the PGI-I successful outcome rate (Group A versus B: 85.3% versus 67.1%), FSDS (median 11 versus 21), and PISQ-12 (median 89 versus 62) ( p < 0.05 for all comparisons). A significant improvement of all EQ-5D values was observed from baseline to 2-year follow-up, and only for the "pain/discomfort" domains did we observe a significant improvement in LSC plus LPP patients versus LSC alone ( p < 0.05). LSC plus LPP women showed, at 2 years, a significant amelioration of their Ap and GH POP-Q points. We observed no statistical differences in terms of intra-post-operative complications or anatomic failure rate between groups., Conclusions: Our LPP approach to LSC appears to be a safe, feasible, and effective treatment for advanced pelvic organ prolapse with a significant impact on the patient's general health and sexual quality of life. Adding laparoscopic posterior vaginal plication to "two-meshes" sacral colpopexy is recommended in patients with apical/anterior prolapse and concomitant severe posterior colpocele. This surgical approach, in addition to improving the anatomical results of these patients, is associated with a significant improvement in sexual and quality of life indexes.

Background: Optimal consolidation for young patilents with relapsed/refractory (R/R) follicular lymphoma (FL) remains uncertain in the rituximab era, with an unclear benefit of autologous stem cell transplantation (ASCT). The multicenter, randomized, phase III FLAZ12 (NCT01827605) trial compared anti-CD20 radioimmunotherapy (RIT) with ASCT as consolidation after chemoimmunotherapy, both followed by rituximab maintenance., Patients and Methods: Patients (age 18-65 years) with R/R FL and without significant comorbidities were enrolled and treated with three courses of conventional, investigator-chosen chemoimmunotherapies. Those experiencing at least a partial response were randomized 1 : 1 to ASCT or RIT before CD34+ collection, and all received postconsolidation rituximab maintenance. Progression-free survival (PFS) was the primary endpoint. The target sample size was 210 (105/group)., Results: Between August 2012 and September 2019, of 164 screened patients, 159 were enrolled [median age 57 (interquartile range 49-62) years, 55% male, 57% stage IV, 20% bulky disease]. The study was closed prematurely because of low accrual. Data were analyzed on 8 June 2023, on an intention-to-treat basis, with a 77-month median follow-up from enrollment. Of the 141 patients (89%), 70 were randomized to ASCT and 71 to RIT. The estimated 3-year PFS in both groups was 62% (hazard ratio 1.11, 95% confidence interval 0.69-1.80, P = 0.6662). The 3-year overall survival also was similar between the two groups. Rates of grade ≥3 hematological toxicity were 94% with ASCT versus 46% with RIT (P < 0.001), and grade ≥3 neutropenia occurred in 94% versus 41%, respectively (P < 0.001). Second cancers occurred in nine patients after ASCT and three after radioimmunotherapy (P = 0.189)., Conclusions: Even if prematurely discontinued, our study did not demonstrate the superiority of ASCT versus RIT. ASCT was more toxic and demanding for patients and health services. Both strategies yielded similar, favorable long-term outcomes, suggesting that consolidation programs milder than ASCT require further investigation in R/R FL., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: COVID-19 is associated with increased nursing workload, therefore a high nurse-to-patient ratio would be required., Aim: To analyse difference in nursing workload, as expressed with the Nursing Activities Score (NAS), between COVID-19 patients versus control patients without COVID-19 disease (NCOVID-19 group) in an Italian Extracorporeal Membrane Oxygenation (ECMO) centre., Study Design: Retrospective analysis of prospectively collected data, enrolling consecutive patients admitted to a general Intensive Care Unit, between 1st May 2019 and 28th February 2021. A multivariate analysis was then performed to assess if COVID-19 disease was an independent predictor of higher NAS and to assess which other factors and procedures are independently associated with increased workload., Results: We enrolled 574 patients, of which 135 (24%) were in the COVID-19 group and 439 (76%) in the NCOVID-19 group. The average NAS was higher in the COVID-19 group (79 ± 11 vs. 65 ± 15, T = -10.026; p < 0.001). Prone positioning, continuous renal replacement therapy (CRRT) and ECMO were used more frequently in the COVID-19 group. A higher fraction of patients in the COVID group showed colonization from multidrug resistant bacteria. COVID-19 group had a higher duration of mechanical ventilation and longer ICU stay. The COVID-19 diagnosis was independently associated with a higher NAS. Other independent predictors of higher NAS were the use of prone positioning and continuous renal replacement therapy (CRRT). Colonization from multidrug resistant bacteria and ECMO support were not independently associated with higher NAS., Conclusions: The higher nursing workload in COVID-19 patients is mainly due to specific procedures required to treat the most hypoxemic patients, such as prone positioning. Colonization with multidrug resistant bacteria and ECMO support were not independently associated with a higher NAS., Relevance to Clinical Practice: Higher workload in COVID-19 patients was due to specific interventions, such as prone positioning and CRRT, with the related nursing activities, as continuous presence at patient's bed, mobilization, positioning and complex hygienic procedures., (© 2023 British Association of Critical Care Nurses.)

Competing Interests: Conflicts of interest: All authors – none to declare.

Breast cancer is a major cause of death among females. Great advances have been made in treating this disease, and aromatase inhibitors (AIs) have been recognized as the cornerstone. They are characterized by high efficacy and low toxicity. The authors reviewed the available literature and defined state-of-the-art AI management. This study was designed to assist clinicians in addressing the need to equally weigh patients' needs and disease control rates in their everyday clinical practice. Today, AIs play a central role in the treatment of hormone receptor-positive breast cancer. In this study, an expert panel reviewed the literature on the use of AIs, discussing the evolution of their use in various aspects of breast cancer, from pre- and postmenopausal early breast cancer to metastatic breast cancer, along with their management regarding efficacy and toxicity. Given the brilliant results that have been achieved in improving survival in everyday clinical practice, clinicians need to address their concerns about therapy duration and the adverse effects they exert on bone health, the cardiovascular system, and metabolism. Currently, in addition to cancer treatment, patient engagement is crucial for improving adherence to therapy and supporting patients' quality of life, especially in a selected subset of patients, such as those receiving an extended adjuvant or combination with targeted therapies. A description of modern technologies that contribute to this important goal is provided., Competing Interests: DG declares grants and/or presentations at congresses and/or participation in scientific boards organized by Novartis, Pfizer, Lilly, Istituto Gentili, Accord, Roche. RB declares grants and/or presentations at congresses and/or participation in scientific boards organized by AZ, BI, Novartis, MSD, Otsuka, Lilly, Roche, Amgen, GSK, Eisai. OG declares advisory role for Eisai, MSD, Seagen, Gilead and honoraria from Pierre Fabre, Novartis, Eli-Lilly IP has received grants for presentations at congresses and participation in scientific boards from: Novartis, Lilly, Pfizer, Gentili, Seagen, Eisai, Astra Zeneca, Gilead, Pierre Fabre. SP has received personal fees presentations at congresses and/or participation in scientific boards/speaker/meetings from Novartis, Roche, Bristol Myers Squibb, AstraZeneca, Pfizer, Lilly, Eisai, Seagen, Daiichi Sankyo, MSD, Exact Sciences, Gilead. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Generali, Berardi, Caruso, Cazzaniga, Garrone, Minchella, Paris, Pinto and De Placido.)

Background: Hypertrophic cardiomyopathy (HCM) and Fabry disease cardiomyopathy (FD) are phenocopies, as they show left ventricular hypertrophy (LVH). The left atrium (LA) is emerging as a potential marker of disease severity in both cardiomyopathies. The present study compares HCM and FD cardiomyopathy with similar degree of LVH, exploring LA morpho-functional parameters and the correlates of clinical outcome., Methods: We performed a comprehensive CMR-based comparison between 30 HCM and 30 FD patients matched on age, sex, BSA, LV mass and major cardiovascular risk factors affecting LA remodeling (arterial hypertension and diabetes). 30 healthy controls were also included. CMR feature tracking (CMR-FT) analysis, T1 mapping and conventional parameters were evaluated. Patients also underwent transthoracic echocardiography for LV diastolic function assessment. Clinical events at follow-up were collected (atrial and ventricular events, bradyarrhythmia, heart failure (HF) hospitalization and death)., Results: HCM patients showed greater LA remodeling compared to FD patients, namely higher LA end-systolic volume index (LAVi max), lower LA-ejection fraction (LA-EF) and worse reservoir (εs) and booster function (εa) (all p < 0.05). Accordingly, these parameters have demonstrated good potential for distinguishing between FD and HCM (AUC 0.68-0.73, all p < 0.05), with LAVi max being an independent predictor for HCM diagnosis (OR 1.07, 95%CI 1.011-1.132, p 0.02). Moreover, in HCM patients a significant association between εs and HF occurrence was observed at 2-year follow-up (OR 0.85, 95%CI 0.72-0.99, p 0.04)., Conclusions: In HCM, LA remodeling is greater than in FD cardiomyopathy with similar LVH, and reservoir strain is associated with HF at follow-up., Competing Interests: Declaration of Competing Interest A. Camporeale: Honoraria for presentations and board meetings from Amicus Therapeutics, Sanofi-Genzyme and Shire. Research grant from Amicus Therapeutics. M. Pieroni: speaker and advisory board honoraria, and travel support from Sanofi-Genzyme, Amicus Therapeutics and Shire. F. Pieruzzi: Honoraria from Sanofi-Genzyme, Shire and Amicus Therapeutics., (Copyright © 2023 Elsevier B.V. All rights reserved.)