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Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can generate severe pneumonia associated with high mortality. A bedside lung ultrasound (LUS) examination has been shown to have a potential role in this setting. The purpose of this study was to evaluate the potential prognostic value of a new LUS protocol (evaluation of 14 anatomic landmarks, with graded scores of 0-3) in patients with SARS-CoV-2 pneumonia and the association of LUS patterns with clinical or laboratory findings., Methods: A cohort of 52 consecutive patients with laboratory-confirmed SARS-CoV-2 underwent LUS examinations on admission in an internal medicine ward and before their discharge. A total LUS score as the sum of the scores at each explored area was computed. We investigated the association between the LUS score and clinical worsening, defined as a combination of high-flow oxygen support, intensive care unit admission, or 30-day mortality as the primary end point., Results: Twenty (39%) patients showed a worse outcome during the observation period; the mean LUS scores ± SDs were 20.4 ± 8.5 and 29.2 ± 7.3 in patients without and with worsening, respectively (P < .001). In a multivariable analysis, adjusted for comorbidities (>2), age (>65 years), sex (male), and body mass index (≥25 kg/m 2 ), the association between the LUS score and worsening (odds ratio, 1.17; 95% confidence interval, 1.05 to 1.29; P = .003) was confirmed, with good discrimination of the model (area under the receiver operating characteristic curve, 0.82). A median LUS score higher than 24 was associated with an almost 6-fold increase in the odds of worsening (odds ratio, 5.67; 95% confidence interval, 1.29 to 24.8; P = .021)., Conclusions: Lung ultrasound can represent an effective tool for monitoring and stratifying the prognosis of patients with SARS-CoV-2 pulmonary involvement., (© 2020 American Institute of Ultrasound in Medicine.)

Aims: Aim of the study was to verify the feasibility, safety and efficacy of pulmonary endarterectomy (PEA) in octogenarian patients with chronic thromboembolic pulmonary hypertension., Methods: We retrospectively analyzed 635 chronic thromboembolic pulmonary hypertension patients who underwent PEA at our center and were followed-up for at least 1 year. The end-points of the study were in-hospital mortality, hemodynamic results at 1 year and long-term survival., Results: In-hospital mortality was 4, 10 and 17%, respectively, for 259 patients under the age of 60 years, 352 aged between 60 and 79 years and 24 octogenarians (P = 0.006 octogenarians vs. <60 years). At multivariable analysis, age and pulmonary vascular resistances were independent risk factors for mortality (P = 0.021 and P < 0.001, respectively). At 1 year, the improvement in cardiac index was lower and the distance walked in 6 min was poorer for octogenarians than for the other two groups (both P = 0.001). Survival after hospital discharge was similar over a median follow-up period of 59 months (P = 0.113). Although in-hospital mortality and long-term survival are similar in octogenarians as compared with patients aged between 60 and 79, the improvement in cardiac index and in functional capacity at 1 year are lower in this very elderly population., Conclusion: Age over 80 years should not be a contraindication to PEA surgery in selected patients operated on in referral centers., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Aim: To compare the pharmacodynamic effect of an oral loading dose of 'noncoated' ASA 300 mg vs. an intravenous bolus injection of lysine acetylsalicylate 150 mg in patients with STEMI undergoing pPCI., Methods: This was a prospective single-center, open label, pharmacodynamic study, including nonconsecutive patients presenting at our catheterization laboratory with STEMI undergoing pPCI and not receiving ASA within the previous 7 days. Pharmacodynamic analyses were performed at five time points: baseline, and 1, 2, 4 and 12 h after the loading dose, and measured as ASA reaction units (ARU) by the Verify Now System. An ARU more than 550 was considered as nonresponsiveness to study drugs. The primary end point was the different rate of patients with ARU more than 550 at 2 h after the loading dose of oral vs. intravenous ASA. Secondary end points included the comparison of ARU more than 550 at the other time points and the comparison of continuous ARU at each time point., Results: The study was planned with a sample size of 68 patients, but it was prematurely stopped due to slow enrollment after the inclusion of 23 patients, 12 randomized to oral ASA and 11 to intravenous lysine acetylsalicylate. At 2 h the rate of patients with ARU more than 550 was numerically but not significantly higher in patients receiving oral ASA as compared with intravenous lysine acetylsalicylate (33 vs. 14.2%; Δ -0.19, 95% confidence interval -0.59-0.21, P = 0.58). The difference over time was NS (P = 0.98), though the prevalence of ARU more than 550 was higher at the other time points. Both routes of administration reduced ARU values over time, though with no overall significant difference between profiles (P overall = 0.48)., Conclusion: In patients with STEMI undergoing pPCI the rate of nonresponsiveness to ASA was not different comparing an oral 'noncoated' loading dose of ASA with an intravenous bolus injection of lysine acetylsalicylate. However, as patient enrollment was prematurely terminated, this study is underpowered to draw a definite conclusion., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Few studies addressed the issue of risk stratification in patients with residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). This study tested the potential added value of parameters that have not been included in existing risk models., Methods: We evaluated 546 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent PEA and were followed-up for a median period of 58 months., Results: Among the 242 with residual PH, 27 died and had 127 a clinical worsening event. At univariable analysis, the parameters associated with poor survival were pulmonary vascular resistance (PVR) ≥425 dyn·s·cm -5 (p ≤ 0.001), mean pulmonary artery pressure (mPAP) ≥38 mmHg (p = 0.003) and pulmonary artery compliance (CPA) ≤1.8 ml/mmHg (p = 0.014). In the bivariable models including either PVR or mPAP as first parameter, the addition of CPA was not statistically significant. The parameters associated with poor clinical worsening were CPA ≤1.8 ml/mmHg (p < 0.001), PVR ≥425 dyn·s·cm -5 (p = 0.002), arterial oxygen tension (PaO2) ≤ 75 mmHg (p = 0.003), mPAP ≥38 mmHg (p = 0.008). In a multivariable analysis which included PVR ≥425 as the first parameter, the addition of both CPA ≤1.8 ml/mmHg and of PaO2 ≤ 75 mmHg significantly improved prognostic stratification (Harrel's C of the model = 0.64, p < 0.001). Noticeably, the lower tertile of the model's predictor index identified a subgroup of 91 patients who had an event rate numerically similar to that of patients without residual PH., Conclusions: Risk stratification in residual PH can be refined if CPA and PaO2 are considered in association with standard hemodynamic parameters., Competing Interests: Declaration of competing interest Stefano Ghio and Andrea Maria D'Armini performed consulting work for Actelion Pharmaceuticals, Ltd. and Merck Sharp Dohme. The other authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Chronic renal antibody-mediated rejection (ABMR) is a common cause of allograft failure, but an effective therapy is not available. Extracorporeal photopheresis (ECP) has been proven successful in chronic lung and heart rejection, and graft versus host disease. The aim of this study was to evaluate the effectiveness of ECP in chronic ABMR patients., Patients and Methods: We investigated ECP treatment in 14 patients with biopsy-proven chronic ABMR and stage 2-3 chronic renal failure. The primary aim was to e valuate the eGFR lowering after 1 year of ECP therapy. The ECP responders (R) showed eGFR reduction greater than 20% vs the basal levels. We also evaluated the effectiveness of ECP on proteinuria, anti-HLA antibodies (HLAab), interleukin 6 (IL-6) serum levels, and CD3, CD4, CD8, CD19, NK, Treg and T helper 17 (Th17) circulating cells., Results: Three patients dropped out of the study. The R patients were eight (72.7%) out of the 11 remaining patients. Because ECP was not associated with any adverse reaction, the R patients continued such treatment for up to 3 years, showing a persisting eGFR stabilization. Twenty four hour proteinuria did not increase in the R patients over the follow-up when compared to the non-responder patients (NR). In the R patients, the HLAab levels were reduced and completely cleared in six out of eight patients when compared with the NR patients. The NR HLAab levels also increased after the discontinuation of the ECP. The ECP in the R patients showed a decrease in CD3, CD4, CD8, CD19, and NK circulating cells. The ECP treatment in the R patients also induced Tregs and Th17 cell increases, and a decrease of the IL-6 serum levels., Conclusions: ECP abates the HLAab titer and renal failure progression in patients with chronic renal ABMR, modulating the immune cellular and humoral responses.

Background & Aims: Reduced muscle mass represents one of the top ranked phenotypic criteria for malnutrition proposed by the Global Leadership Initiative on Malnutrition. Although height-indexed fat-free mass (FFMI) thresholds have been proposed as useful surrogate measures of reduced muscle mass, the independent prognostic value of BIA-derived FFMI by bioelectric impedance analysis (BIA) in patients with cancer still needs to be fully explored., Methods: Data on body mass index (BMI), 6-month percentage of weight loss (%WL), FFMI by BIA and quality of life (QoL by EORTC Quality of Life Questionnaire [EORTC QLQ-C30]) of Italian and German patients observed prospectively until death or censoring were used (N = 1217). Patients were stratified in 5 risk categories according to a robustly validated scoring system based on BMI and %WL. Low FFMI was defined as follows: men, <17 kg/m 2 ; women, <15 kg/m 2 ., Results: Reduced FFMI was found in 234 patients (19.2%). After a median follow-up of 57 months [25th-75th, 31-60], 620 patients (50.9%) had died. The study detected differences in survival between patients presenting with and without reduced FFMI (14.0 months vs. 45.1 months; P < 0.001). The fully-adjusted hazard ratio of mortality for low FFMI was 1.46 [95%CI, 1.18-1.81] (P < 0.001). Low FFMI was also independently associated with reduced QoL: fully-adjusted odds ratio, 1.50 [95%CI, 1.00-2.25] (P = 0.050)., Conclusions: Reduced FFMI by BIA independently predicted survival and was associated with impaired QoL. Altered body composition should always be considered in all patients with cancer as additional phenotypic criterion of poor prognosis and BIA offers the possibility of multiple, noninvasive bedside assessments., Competing Interests: Conflict of interest All Authors certify that there are no affiliations with or involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The persistence or recurrence of symptoms in patients with coeliac disease (CD), despite a gluten-free diet (GFD), must prompt further work-up for excluding refractory CD (RCD). The aim of this study was to assess the accuracy of serum markers in predicting refractoriness in CD patients. This study included 72 patients affected by CD followed-up at our center, namely 49 uncomplicated CD before and after GFD and 23 RCD. Serum levels of chromogranin A (CgA) and β2-microglobuline were measured at baseline and at follow-up (median time of 13 months) in each group of patients. Cut-off points for each marker were estimated to differentiate RCD from uncomplicated CD patients. Serum levels of CgA and β2-microglobuline were significantly higher in patients with RCD compared to uncomplicated CD ( p < 0.001), both at baseline and at follow-up, with no significant difference between RCD type 1 and type 2. The estimated cut-off point for CgA was 90.2 ng/mL (sensitivity 83%, specificity 100%), while for β2-microglobuline it was 696 mcg/L (sensitivity 100%, specificity of 100%). To conclude, CgA and β2-microglobuline could be useful serological markers of refractoriness in CD, with the ability to discriminate those patients who should undergo upper gastrointestinal endoscopy for making a definite diagnosis.

Background: Colorectal cancer (CRC) diagnosed before the age of 50, known as early-onset CRC (eoCRC), is considered uncommon. We aimed at analysing the incidence of preneoplastic and neoplastic lesions of the colon and rectum in patients under 50 years old and to identify possible predictors Methods: We retrospectively collected data from 1778 patients under 50 years old (mean age 39.9±7.8) referred for colonoscopy between 2015-2018. Cumulative incidence of adenomas and eoCRC was assessed. Multivariable regression models were fitted Results: The cumulative incidence for adenomas was 11.0% (95% CI 9-12), while it was 1.5% (95% CI 1-2) for eoCRC (metastatic disease in 13/27 patients). Age as a continuous variable was associated with the presence of adenomas (incidence rate ratio 1.06; 95% CI 1.03-1.09; p<0.001). EoCRC arose in most cases in the rectum (13/27, 48.1%). Age ≥40 was the main risk factor (OR 2.25; 95% CI 1.35-3.73; p=0.002) for both adenomas (160/196 patients, 81.6%) and eoCRC (20/27 patients, 74.1%), while smoking seemed to have no role (p=0.772). The presence of alarm symptoms was statistically significant at bivariable analysis for eoCRC only (OR 3.70; 95% CI 1.49-9.22; p=0.005), as well as having multiple gastrointestinal symptoms (OR 19.85; 95% CI 2.64-149.42; p=0.004). Only 3/27 (11.1%) patients with eoCRC had a family history for CRC Conclusions: A high cumulative incidence rate of both adenomas and eoCRC was found, this latter occurring more common in patients aged 40-49, without apparent risk factors. The presence of alarm symptoms or multiple gastrointestinal symptoms led to a late diagnosis., (Copyright © 2021. Published by Elsevier B.V.)

Background & Aims: Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients are not conclusive. The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity., Methods: In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 h since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (<30 - ≥20 ng/mL), moderately deficient (<20 - ≥10 ng/mL), severely deficient (<10 ng/mL)., Results: The prevalence of 25(OH)vitamin D insufficiency, moderate deficiency and severe deficiency was 13.2%, 22.5% and 54.3%, respectively. 25(OH)Vitamin D deficiency (<20 ng/mL) was not associated with COVID-19 clinical features and outcomes. Unexpectedly, after adjusting for major confounders, a significant positive association between increasing 25(OH)vitamin D levels and in-hospital mortality (on a continuous logarithmic scale, odds ratio = 1.73 [95% CI, 1.11 to 2.69]; P = .016) was observed., Conclusions: Very low 25(OH)vitamin D levels were highly prevalent and suggestive of deficiency among our hospitalized severe COVID-19 patients, but low 25(OH)vitamin D levels were not associated with outcome variables. Whether 25(OH)vitamin D adequacy may influence clinical outcomes in COVID-19 and the unexpected correlation between higher 25(OH)vitamin D levels and mortality require further investigations by large intervention trials., Competing Interests: Conflict of interest None of the authors have conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

While de novo donor-specific HLA antibodies (dnDSAs) have a detrimental impact on kidney graft outcome, the clinical significance of de novo non donor-specific antibodies (dnNDSAs) is more controversial. We retrospectively evaluated for Ab development and characteristics of dnNDSAs serially collected post-transplant sera and, when available, graft biopsy eluates, from 144 non-sensitized, primary pediatric kidney recipients, consecutively transplanted at a single center between 2003 and 2017, using HLA class I and class II single-antigen flow-bead assays (SAB). The results were compared with clinical-pathologic data from HLA antibody negative and HLA dnDSA-positive patients. Forty-five out of 144 patients developed dnNDSAs (31%). Among the dnNDSA-positive patients, 86% displayed one or more class I/II antibodies recognizing antigens included in the CREG/shared epitope groups that also comprise the mismatched donor HLA antigens. Despite potential pathogenicity, as suggested by their occasional presence within the graft, dnNDSAs displayed significantly lower MFI, and limited complement binding and graft homing properties, when compared with dnDSAs. In parallel, the graft survival probability was significantly lower in patients with dnDSA than in those with dnNDSA or without HLA antibodies (p < 0.005). Indeed, the dnNDSA-positive patients remaining dnDSA-negative throughout the posttransplant period did not develop clinical antibody mediated rejection and graft loss, and maintained good graft function at a median follow-up of 9 years. The biological characteristics of dnNDSAs may account for the low graft damaging capability when compared to dnDSAs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: Many countries reported an increase of out-of-hospital cardiac arrests (OHCAs) and mortality during the COVID-19 pandemic. However, all these data refer to regional settings and national data are still missing. We aimed to assess the OHCA incidence and population mortality during COVID-19 pandemic in whole Switzerland and in the different regions (Cantons) according to the infection rate., Methods: We considered OHCAs and deaths which occurred in Switzerland after the first diagnosed case of COVID-19 (February 25th) and for the subsequent 65 days and in the same period in 2019. We also compared Cantons with high versus low COVID-19 incidence., Results: A 2.4% reduction in OHCA cases was observed in Switzerland. The reduction was particularly high (-21.4%) in high-incidence COVID-19 cantons, whilst OHCAs increased by 7.7% in low-incidence COVID-19 cantons. Mortality increased by 8.6% in the entire nation: a 27.8% increase in high-incidence cantons and a slight decrease (-0.7%) in low-incidence cantons was observed. The OHCA occurred more frequently at home, CPR and AED use by bystander were less frequent during the pandemic. Conversely, the OHCAs percentage in which a first responder was present, initiated the CPR and used an AED, increased. The outcome of patients in COVID-19 high-incidence cantons was worse compared to low-incidence cantons., Conclusions: During the COVID-19 pandemic in Switzerland mortality increased in Cantons with high-incidence of infection, whilst not in the low-incidence ones. OHCA occurrence followed an opposite trend showing how variables related to the health-system and EMS organization deeply influence OHCA occurrence during a pandemic., (© 2021 The Author(s).)

The relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients with severe COVID-19, some of whom succumbed. A control population of healthy subjects was included. Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes, with an increased proportion of mature natural killer (NK) cells and low T-cell numbers. NK cells and CD8 + T cells overexpressed T-cell immunoglobulin and mucin domain-3 (TIM-3) and CD69. NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1 (PD-1) positive cells and reduced frequencies of natural killer group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- and sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing NK cells, associated with a reduced ability to secrete interferon (IFN)γ. Patients with poor outcome showed a contraction of immature CD56 bright and an expansion of mature CD57 + FcεRIγ neg adaptive NK cells compared to survivors. Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors. Of note, monocytes secreted abundant quantities of IL-6, IL-8, and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69, PD-1 and TIM-3 expression and restoration of CD8 + T cell numbers. A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection, probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes. These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.

Purpose: This cross-sectional study aimed at comparing the quality of life (Qol), the prevalence of psychiatric diagnosis and pharmacological treatment in 104 candidates to bariatric surgery according to the degree of obesity (class 2 vs. class ≥ 3 obesity)., Methods: All surgical candidates underwent a detailed psychiatric interview based on DSM-5 criteria, including sociodemographic, clinical, psychological and psychiatric data. Participants completed the Binge Eating Scale (BES) and the 12-Item Short Form Health Survey (SF-12)., Results: Overall, bariatric candidates reported a significant impairment in the physical (PCS 38.8 [95% CI 36.2-41.5]) and mental (MCS 42.2 [95% CI 40.4-43.9]) components of Qol compared to population norms (p < 0.001 for both). Subjects with class 2 obesity scored significantly lower in the MCS compared to those with class 3 (38.7 (8.1) vs. 43.6 (8.4), p = 0.008). No other statistically significant differences were found between the two groups in terms of sociodemographic and clinical variables., Conclusion: These data support the usefulness of Qol assessment in bariatric candidates as a sensible screening parameter, especially in patients with lower BMI, in whom MCS could identify the need for early psychosocial intervention., Level of Evidence: Level III, case-control analytic study.

Background: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer., Patients and Methods: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability., Results: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status., Conclusions: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.

Background & Aims: Estimation errors associated with bioelectric impedance evaluation may affect the accuracy of body composition and its prognostic value. We evaluated the prognostic value of a new body composition parameter (Nutrigram®) obtained from bioimpedance vectorial analysis-derived body cell mass and its association with nutritional and functional status., Design: Data of Italian and German cancer patients observed prospectively until death were used. Multivariable models (adjusted for age, gender, hydration status, performance status, and disease's stage) were built in both cohorts to assess the association between body composition outcome parameters (low fat-free mass [FFM], <15 [females] and <17 [males] kg/m 2 ; low standardized phase angle [SPA], <-1.65; low Nutrigram®, <510 [females] and <660 [males] mg/24 h/m) and 1-year all-cause mortality, low body mass index (BMI; <20 [<70 years] and <22 [≥70 years] kg/m 2 ), clinically significant weight loss (WL; ≥10% in 6 months) and low handgrip strength (HG; <20 [females] and <30 [males] kg)., Results: Low Nutrigram® was independently associated with mortality in both Italian (HR = 1.84 [95%CI, 1.18-2.86]; P = 0.007) and German cohorts (HR = 1.52 [95%CI, 1.17-2.07]; P = 0.008). Low FFMI and low SPA did not predict survival in the German cohort. In patients with low Nutrigram®, worse nutritional and functional status were observed in both study populations. Performance of models addressing the study endpoints showed substantial consistency with both cohorts, particularly of those including low Nutrigram®., Conclusions: We validated a new prognostic body composition parameter, which is easier to interpret than standard nutritional parameters and may be useful for identifying cancer patients at nutritional risk, requiring early nutritional support., Competing Interests: Conflict of interest All Authors certify that there are no affiliations with or involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the manuscript., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: A multidisciplinary consensus document (MCD) provided a follow-up strategy after percutaneous coronary intervention (PCI) based on individual risk profiles: A, high; B, intermediate; and C, low., Aim: To assess patterns of follow-up after PCI and to evaluate the potential reduction of cardiologic examinations with the application of the MCD., Methods: The post-PCI registry was carried out at 31 Italian Hospitals and included consecutive patients undergoing PCI. We collected cardiologic consults (CC), noninvasive stress tests (ST), and echocardiograms (EC) actually performed at 12 months and we compared them with the expected by the MCD., Results: We included 1,113 patients (58% with acute coronary syndrome) that underwent 1,567 CC, 398 ST, and 612 EC. The performed CC and ST were significantly lower compared to the expected, respectively [1.6 (95% CI, 1.5-1.7) vs. 1.9 (95% CI, 1.8-2.0), and 0.40 (95% CI, 0.4-0.5) vs. 0.61 (95% CI, 0.6-0.7), p < .001]; the performed EC were significantly higher [0.6 (95% CI, 0.6-0.7) vs. 0.3 (95% CI, 0.3-0.37), p < .001]. Patients at moderate low risk had an excess of noninvasive tests whereas patients at higher risk received less examinations than the expected. The individual risk profile was an independent predictor of increased number of cardiac examination in patients at intermediate and low risk [profile B, OR 2.56 (95%CI 1.38-4.75); profile C, OR 27.00 (95%CI 8.13-89.62), p < .001]., Conclusion: In real world patients undergoing PCI, the intensity of follow-up at 12 months appeared not based on individual risk profile, with a higher numbers of examinations, particularly EC, performed in low risk subjects., (© 2020 Wiley Periodicals, Inc.)

Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood., Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative)., Results: A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]., Conclusion: Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background Short ECG P-wave duration has recently been demonstrated to be associated with higher risk of atrial fibrillation (AF). The aim of this study was to assess the rate of AF recurrence after pulmonary vein isolation in patients with a short P wave, and to mechanistically elucidate the observation by computer modeling. Methods and Results A total of 282 consecutive patients undergoing a first single-pulmonary vein isolation procedure for paroxysmal or persistent AF were included. Computational models studied the effect of adenosine and sodium conductance on action potential duration and P-wave duration (PWD). About 16% of the patients had a PWD of 110 ms or shorter (median PWD 126 ms, interquartile range, 115 ms-138 ms; range, 71 ms-180 ms). At Cox regression, PWD was significantly associated with AF recurrence ( P =0.012). Patients with a PWD <110 ms (hazard ratio [HR], 2.20; 95% CI, 1.24-3.88; P =0.007) and patients with a PWD ≥140 (HR, 1.87, 95% CI, 1.06-3.30; P =0.031) had a nearly 2-fold increase in risk with respect to the other group. In the computational model, adenosine yielded a significant reduction of action potential duration 90 (52%) and PWD (7%). An increased sodium conductance (up to 200%) was robustly accompanied by an increase in conduction velocity (26%), a reduction in action potential duration 90 (28%), and PWD (22%). Conclusions One out of 5 patients referred for pulmonary vein isolation has a short PWD which was associated with a higher rate of AF after the index procedure. Computer simulations suggest that shortening of atrial action potential duration leading to a faster atrial conduction may be the cause of this clinical observation.

Importance: Electrocardiography (ECG) is an important tool to triage patients with out-of-hospital cardiac arrest (OHCA) after return of spontaneous circulation (ROSC). An immediate coronary angiography after ROSC is recommended only in patients with an ECG that is diagnostic of ST-segment elevation myocardial infarction (STEMI). To date, the benefit of this approach has not been demonstrated in patients with a post-ROSC ECG that is not diagnostic of STEMI., Objective: To assess whether the time from ROSC to ECG acquisition is associated with the diagnostic accuracy of ECG for STEMI., Design, Setting, and Participants: This retrospective, multicenter cohort study (the Post-ROSC Electrocardiogram After Cardiac Arrest study) analyzed consecutive patients older than 18 years who were resuscitated from OHCA between January 1, 2015, and December 31, 2018, and were admitted to 1 of the 3 participating centers in Europe (Pavia, Italy; Lugano, Switzerland; and Vienna, Austria)., Exposure: Only patients who underwent coronary angiography during hospitalization and who acquired a post-ROSC ECG before the angiography were enrolled. Patients with a nonmedical cause of OHCAs were excluded., Main Outcomes and Measures: The primary end point was false-positive ECG findings, defined as the percentage of patients with post-ROSC ECG findings that met STEMI criteria but who did not show obstructive coronary artery disease on angiography that was worthy of percutaneous coronary angioplasty., Results: Of 586 consecutive patients who were admitted to the 3 participating centers, 370 were included in the analysis (287 men [77.6%]; median age, 62 years [interquartile range, 53-70 years]); 121 (32.7%) were enrolled in the participating center in Pavia, Italy; 38 (10.3%) in Lugano, Switzerland; and 211 (57.0%) in Vienna, Austria. The percentage of false-positive ECG findings in the first tertile of ROSC to ECG time (≤7 minutes) was significantly higher than that in the second (8-33 minutes) and third (>33 minutes) tertiles: 18.5% in the first tertile vs 7.2% in the second (odds ratio [OR], 0.34; 95% CI, 0.13-0.87; P = .02) and 5.8% in the third (OR, 0.27; 95% CI, 0.15-0.47; P < .001). These differences remained significant when adjusting for sex (≤7 minutes: reference; 8-33 minutes: OR, 0.32; 95% CI, 0.12-0.85; P = .02; >33 minutes: OR, 0.26; 95% CI, 0.14-0.47; P < .001), age (≤7 minutes: reference; 8-33 minutes: OR, 0.34; 95% CI, 0.13-0.89; P = .03; >33 minutes: OR, 0.27; 95% CI, 0.15-0.46; P < .001), number of segments with ST-elevation (≤7 minutes: reference; 8-33 minutes: OR, 0.35; 95% CI, 0.15-0.81; P = .01; >33 minutes: OR, 0.28; 95% CI, 0.15-0.52; P < .001), QRS duration (≤7 minutes: reference; 8-33 minutes: OR, 0.35; 95% CI, 0.14-0.87; P = .02; >33 minutes: OR, 0.27; 95% CI, 0.15-0.48; P < .001), heart rate (≤7 minutes: reference; 8-33 minutes: OR, 0.35; 95% CI, 0.13-0.93; P = .04; >33 minutes: OR, 0.29; 95% CI, 0.15-0.55; P < .001), epinephrine administered (≤7 minutes: reference; 8-33 minutes: OR, 0.35; 95% CI, 0.13-0.98; P = .045; >33 minutes: OR, 0.27; 95% CI, 0.16-0.48; P < .001), shockable initial rhythm (≤7 minutes: reference; 8-33 minutes: OR, 0.35; 95% CI, 0.13-0.96; P = .04; >33 minutes: OR, 0.26; 95% CI, 0.15-0.46; P < .001), and 3 or more shocks administered (≤7 minutes: reference; 8-33 minutes: OR, 0.36; 95% CI, 0.13-1.00; P = .05; >33 minutes: OR, 0.27; 95% CI, 0.16-0.48; P < .001) in bivariable analyses., Conclusions and Relevance: This study suggests that early ECG acquisition after ROSC in patients with OHCA is associated with a higher percentage of false-positive ECG findings for STEMI. It may be reasonable to delay post-ROSC ECG by at least 8 minutes after ROSC or repeat the acquisition if the first ECG is diagnostic of STEMI and is acquired early after ROSC.

Background: Prevalence and outcomes of coronavirus disease (COVID)-19 in relation to immunomodulatory medications are still unknown. The aim of the study is to investigate the impact of glucocorticoids and immunosuppressive agents on COVID-19 in a large cohort of patients with chronic immune-mediated inflammatory arthritis., Methods: The study was conducted in the arthritis outpatient clinic at two large academic hospitals in the COVID-19 most endemic area of Northern Italy (Lombardy). We circulated a cross-sectional survey exploring the prevalence of severe acute respiratory syndrome-coronavirus-2 nasopharyngeal swab positivity and the occurrence of acute respiratory illness (fever and/or cough and/or dyspnea), administered face-to-face or by phone to consecutive patients from 25 February to 20 April 2020. COVID-19 cases were defined as confirmed or highly suspicious according to the World Health Organization criteria. The impact of medications on COVID-19 development was evaluated., Results: The study population included 2050 adults with chronic inflammatory arthritis receiving glucocorticoids, conventional-synthetic (cs), or targeted-synthetic/biological (ts/b) disease-modifying drugs (DMARDs). Laboratory-confirmed COVID-19 and highly suspicious infection were recorded in 1.1% and 1.4% of the population, respectively. Treatment with glucocorticoids was independently associated with increased risk of COVID-19 (adjusted OR [95% CI] ranging from 1.23 [1.04-1.44] to 3.20 [1.97-5.18] depending on the definition used). Conversely, patients treated with ts/bDMARDs were at reduced risk (adjusted OR ranging from 0.46 [0.18-1.21] to 0.47 [0.46-0.48]). No independent effects of csDMARDs, age, sex, and comorbidities were observed., Conclusions: During the COVID-19 outbreak, treatment with immunomodulatory medications appears safe. Conversely, glucocorticoids, even at low-dose, may confer increased risk of infection., Trial Registration: Retrospectively registered. Not applicable.

We analyzed 160 young Waldenström Macroglobulinemia (WM) patients with a median age of 49 years (range 23-55 years), diagnosed between January 2000 and January 2019 in 14 Italian centers. At diagnosis, 70% of patients were asymptomatic. With a median follow-up of 5.6 years, 57% have been treated. As initial therapy 79% of patients received chemo-immunotherapy, 13% a chemo-free induction and 8% chemotherapy only. At relapse or progression, 6% underwent an autologous stem cell transplantation. Overall, 19% of patients received ibrutinib during the course of the disease. According to IPSSWM, 63% were classified as low risk, 27% as intermediate risk and 10% as high risk. Five-year OS was shorter in high-risk as compared with low or intermediate risk patients (92.9% vs 100% P = .002). According to revised IPSSWM, 92% were classified as very low or low risk and 8% as intermediate risk, with a shorter 5-year OS in the latter group (87.5% vs 100%, P = .028). The OS of young WM patients was not significantly reduced as compared with age-matched, sex-matched and calendar year-matched general population. Early diagnosis, absence of high-risk features in symptomatic patients and high efficacy of modern treatments are the main determinants of the excellent outcome of young WM patients., (© 2020 Wiley Periodicals LLC.)

Background: Peripheral facial palsy is a pathological condition caused by a wide range of etiologies. A damage of VII cranial nerve produces facial disfigurement and limitations in daily life activities, such as drinking, eating and speaking. As a consequence, patients may experience psychological distress and social isolation. To counsel and design a patient-tailored rehabilitation for patients affected by peripheral facial palsy, physical and social limitations should be considered. Moreover, the knowledge of factors associated with disability plays a key role in the early identification and adequate care of patients with higher risk to develop psychological distress and participation restrictions., Aim: To evaluate activity limitations, psychological distress and participation restrictions of patients affected by peripheral facial palsy seeking for rehabilitation and to identify individual and disease-specific factors associated to disability., Design: Cross-sectional study., Setting: Consultation hour dedicated to facial palsy patients in the outpatient clinic of a Rehabilitation Unit., Population: One hundred eighty-six outpatients with recent or chronic peripheral facial palsy at the first assessment at our Rehabilitation Unit., Methods: Using multiple linear regression models, we evaluated the association between the two subscales of Facial Disability Index (FDI) and the composite score of Sunnybrook Facial Grading System, as well as the association between the two FDI subscales and other clinical and demographic variables., Results: Activity limitations correlate with the severity of palsy, while psychological distress and participation restrictions do not correlate with the neurological impairment. The correlation between the severity of palsy and both activity limitations and participation restrictions is influenced by palsy etiology. Activity limitations decrease with time from palsy onset, while psychological distress and participation restrictions are more severe in women., Conclusions: Beyond severity, also etiology, time from onset and gender influence disability after facial palsy. These factors should be considered in counselling and planning a patient-tailored multidisciplinary rehabilitative treatment., Clinical Rehabilitation Impact: Our study highlights the individual and pathology-associated factors related to activity limitations and participation restrictions in patients with peripheral facial palsy. These elements should be considered in the definition of a patient-tailored rehabilitative plan and in the organization of a multidisciplinary care.

Background: Sarcopenia is a disease associated with aging and a negative prognosis. Consensus-based treatment consists in targeting muscle mass and function through physical exercise, optimization of protein intake, and vitamin D supplementation, but evidence is lacking. We evaluated the safety and efficacy of a muscle-targeted nutritional support on the outcome of a physical exercise rehabilitation programme., Methods: In a single-site, double-blind, randomized, controlled trial (NCT03120026; May 2017 to December 2018), old (≥65 years) adults [N = 140 (63% female patients; age, 81 ± 6 years)] without severe cognitive impairment, who were found to have sarcopenia by European Working Group on Sarcopenia in Older People 2010 criteria and hospitalized for physical rehabilitation, were randomized to receive until discharge (for at least 4 weeks and up to 8 weeks) a whey protein-based nutritional formula enriched with leucine and vitamin D or an iso-caloric control formula twice daily in addition to a standard hospital diet. The primary endpoint was the change in 4 m gait speed per month. Key secondary endpoints addressed the change in physical performance: chair-stand test, timed up and go test, and short physical performance battery. Other secondary outcomes were the change in functional status, muscle strength and mass, cognitive status, and quality of life. The proportion of patients who improved their rehabilitation intensity profile and overall economic benefits (using length of stay and duration of rehabilitation as surrogate measures) were also evaluated., Results: A total of 161 patients were screened and 140 were randomized to study interventions. Thirteen patients (experimental, n = 6; placebo, n = 7) discontinued the intervention because they disliked the product and intention-to-treat analyses were based on patients reassessed at discharge [n = 127 (66% female patients; age, 81 ± 6 years)]. Supplementation with the experimental formula (n = 64) resulted in greater increase in mean gait speed {0.061 m/s/month [95% confidence interval (CI), 0.043 to 0.080]} than placebo [n = 63; -0.001 m/s/month (95%CI, -0.008 to 0.006)]: mean difference, 0.063 m/s/month (95%CI, 0.043 to 0.082) (P < 0.001). A significant effect was also found for muscle mass (P < 0.03) and all key secondary outcomes, functional and cognitive endpoints (P < 0.001 for all). Supplementation resulted also in higher proportion of patients improving their rehabilitation intensity profile (P = 0.003) and being discharged home (P = 0.002); shorter rehabilitation (P < 0.001); and hospital stay (P < 0.001)., Conclusions: In old adults with sarcopenia admitted to hospital for rehabilitation the consumption of a whey protein-based nutritional formula enriched with leucine and vitamin D improved physical performance and function, as well as muscle mass, and reduced the intensity and costs of care., (© 2020 The Authors. Published by John Wiley & Sons Ltd. on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Hyperimmune plasma from Covid-19 convalescent is a potential treatment for severe Covid-19. We conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease with moderate-to-severe Acute Respiratory Distress Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma (neutralizing antibodies titer ≥1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety. The study observed 46 patients from March, 25 to April, 21 2020. Patients were aged 63, 61% male, of them, 30 were on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Bilateral infiltrates on chest X-ray was present in 36 patients (84%). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days as compared to an expected 15% from the National Statistics and 30% from a small concurrent cohort of 23 patients. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related). In conclusion, Hyperimmune plasma in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma banking, development of standardized pharmaceutical products and monoclonal antibodies.

Introduction: The sudden increase in the number of critically ill patients following a disaster can be overwhelming., Study Objective: The main objective of this study was to assess the real number of available and readily freeable beds ("bed surge capacity") and the availability of emergency operating rooms (OR) in a maximum emergency using a theoretical simulation., Patients and Methods: The proportion of dismissible patients in four areas (Medical Area, Surgical Area, Sub-intensive Care Units, Intensive Care Units) and three emergency OR was assessed at 2 and 24 hours after a simulated maximum emergency. Four scenarios were modeled. Hospitalization and surgical capacities were assessed on weekdays and holidays. The creation of new beds was presumed by the possibility of moving patients to a lower level of care than that provided at the time of detection, of dislocation of patients to a discharge room, with care transferred to lower-intensity hospitals, rehabilitation, or discharge facilities. The Phase 1 table-top simulations were conducted during the weekday morning hours. In particular, the 24-hour table-top simulations of a hypothetical event lasted about 150 minutes compared to those conducted at 2 hours, which were found to be longer (about 195 minutes). Phase 2 was conducted on two public holidays and a quick response time was observed within the first 40 minutes of the start of the test (about 45% of departments)., Results: The availability of simulated beds was greater than that indicated in the maximum emergency plans (which was based solely on the census of beds). Patients admitted to Intensive Care and The Sub-Intensive Area may be more difficult to move than those in low-intensity care. The availability of emergency OR was not problematic. Age influenced the possibility of remitting/transferring patients., Conclusion: Simulation in advance of a maximum emergency is helpful in designing an efficient response plan., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Ceresa et al.)

Aim: Several studies reported a lower proportion of laypeople cardio-pulmonary resuscitation (CPR) in female victims of out-of-hospital cardiac arrest (OHCA). We aimed to verify how sixteen-years of state-wide initiatives impacted on gender-differences in OHCA treatment and survival., Methods: All the 2481 consecutive OHCAs of presumed cardiac origin occurred between 2002 and 2018 in the Swiss Ticino Canton and in which a resuscitation was attempted, were included. Emergency medical system (EMS)-witnessed OHCAs were excluded., Results: Time from call to CPR decreased from 9-min in 2002-2006 to 5-min in 2015-2018 (p < 0.01) and until 2014, it was longer in women. Survival to discharge increased overall from 11% in 2002-2006 to 23% in 2015-2018 (p < 0.001) related to telephone-assisted CPR development (period 2011-2014) and first responder and layperson recruitment via a mobile application (period 2015-2018). In males, survival increased from 12% to 25% (p = 0.001) with a statistically significant increase in odds of survival in 2007-2010 (OR 1.6 95%CI 1.1-2.3; p = 0.001), in 2011-2014 (OR 2 95%CI 1.4-2.8; p = 0.001), and in 2015-2018 (2.4 95%CI 1.7-3.3; p = 0.001) compared to 2002-2006. On the other hand, in females, survival increased from 7% to 18% (p < 0.001), with a corresponding increase in the odds of survival of almost 3 times from 2002-2006 to 2015-2018 time period (OR 2.9 95%CI 1.5-5.8, p = 0.001). No difference in survival probability was observed according to gender when adjusted for age, presenting rhythm, year-groups, OHCA location, EMS arrival time, witnessed status and laypeople-CPR., Conclusions: State-wide initiatives can significantly increase the chances of survival in both male and female victims of OHCAs, by increasing the probability to receive CPR in a shorter time span., (© 2020 The Authors.)

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there has been an open debate on the impact of biological drugs used in the treatment of psoriasis. To define whether patients under treatment with biologics suffer from increased morbidity and mortality from COVID-19, compared to psoriatic patients treated only with topical drugs, we designed an observational monocentric prevalence study recording the personal and clinical data of psoriatic patients, with focus on the presentation of signs and symptoms related to COVID-19 in the period of time ranging from 1 January 2020 to 31 May 2020. A total of 180 patients were enrolled into two groups: 100 patients in the topical therapy group and 80 patients in the biological therapy group. No statistically significant difference was found between the groups regarding the prevalence of COVID-19 infection and symptoms at a bivariable analysis with adjustment for confounders. In conclusion, psoriatic patients under treatment with biologics do not seem to be more susceptible to COVID-19 compared to other psoriatic patients and we suggest not interrupting treatment with biological drugs, even in areas suffering from active outbreaks of the disease., (© 2020 Wiley Periodicals LLC.)

Global pandemics call for large and diverse healthcare data to study various risk factors, treatment options, and disease progression patterns. Despite the enormous efforts of many large data consortium initiatives, scientific community still lacks a secure and privacy-preserving infrastructure to support auditable data sharing and facilitate automated and legally compliant federated analysis on an international scale. Existing health informatics systems do not incorporate the latest progress in modern security and federated machine learning algorithms, which are poised to offer solutions. An international group of passionate researchers came together with a joint mission to solve the problem with our finest models and tools. The SCOR Consortium has developed a ready-to-deploy secure infrastructure using world-class privacy and security technologies to reconcile the privacy/utility conflicts. We hope our effort will make a change and accelerate research in future pandemics with broad and diverse samples on an international scale., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Little is known regarding coronavirus disease 2019 (COVID-19) clinical spectrum in non-Asian populations. We herein describe the impact of COVID-19 on liver function in 100 COVID-19 consecutive patients (median age 70 years, range 25-97; 79 males) who were admitted to our internal medicine unit in March 2020. We retrospectively assessed liver function tests, taking into account demographic characteristics and clinical outcome. A patient was considered as having liver injury when alanine aminotransferase (ALT) was > 50 mU/ml, gamma-glutamyl transpeptidase (GGT) > 50 mU/ml, or total bilirubin > 1.1 mg/dl. Spearman correlation coefficient for laboratory data and bivariable analysis for mortality and/or need for intensive care were assessed. A minority of patients (18.6%) were obese, and most patients were non- or moderate-drinkers (88.5%). Liver function tests were altered in 62.4% of patients, and improved during follow-up. None of the seven patients with known chronic liver disease had liver decompensation. Only one patient developed acute liver failure. In patients with altered liver function tests, PaO 2 /FiO 2  < 200 was associated with greater mortality and need for intensive care (HR 2.34, 95% CI 1.07-5.11, p = 0.033). To conclude, a high prevalence of altered liver function tests was noticed in Italian patients with COVID-19, and this was associated with worse outcomes when developing severe acute respiratory distress syndrome.

Background and Aims: It is unknown whether the prognostic role of diabetes (T2DM) in outpatients with chronic heart failure (CHF) is independent of the most important echocardiographic markers of poor prognosis. The aims of this analysis were to evaluate whether T2DM modifies the risk of mortality in CHF patients stratified by etiology of disease or by right-ventricular to pulmonary arterial coupling at echocardiography and to evaluate how T2DM interacts with the prognostic role of cardiac plasma biomarkers., Methods and Results: This is a retrospective analysis of 1627 CHF outpatients who underwent a complete echocardiographic examination. During a median follow-up period of 63 months 255 patients died. Poor right-ventricular to pulmonary arterial coupling and reduced left ventricular ejection fraction were independent predictors of outcome, whereas ischemic etiology and T2DM were not. T2DM interacted with etiology increasing the risk of mortality by 32% among patients with ischemic disease (p = 0.003). Elevated hsTNI plasma levels were associated with poor survival in T2DM but not in non-diabetic patients., Conclusion: T2DM signals a worse outcome in ischemic CHF patients regardless of the echocardiographic phenotype. High plasma levels of hsTNI are stronger predictors of mortality in CHF patients with T2DM than in patients without diabetes., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020. Published by Elsevier B.V.)

Galectin-3 is a circulating biomarker of fibrosis whose prognostic role in pulmonary arterial hypertension (PAH) has not been fully explored. We undertook a pilot study to evaluate the relationship between galectin-3 plasma levels and validated risk scores in PAH. The study included 70 PAH patients admitted to a single referral center from June 2016 to June 2018. Patients were stratified according to the REVEAL 2.0 risk score, according to the parameters suggested by the European Society of Cardiology and European Respiratory Society (ESC/ERS) Guidelines, and according to a focused echocardiographic assessment of right heart performance. The association between galectin-3 levels and risk profiles was evaluated by generalized linear regression model with adjustment for etiology. Galectin-3 plasma levels increased linearly in the three risk strata based on the REVEAL 2.0 score (from 16.0 ± 5.7 in low-risk to 22.4 ± 6.3 in intermediate-risk and in 26.9 ± 7.7 ng/mL in high-risk patients ( p for trend < 0.001). Galectin-3 levels were significantly lower in low-risk patients defined according to the prognostic parameters of ESC/ERS Guidelines (delta between low-risk and intermediate/high-risk = -9.3, 95% CI -12.8 to -5.8, p < 0.001, p < 0.001). Additionally, galectin-3 levels were lower in the low-risk profile defined on the basis of the echocardiographic evaluation of right heart performance (delta between low-risk and intermediate-/high-risk = -6.3, 95% CI -9.9 to -2.7, p = 0.001). Galectin-3 plasma levels are directly associated with several risk profiles in PAH patients. The prognostic role of this biomarker in PAH is worthwhile to be explored in larger prospective studies.

Background and Purpose: Interventional Neuroradiology (INR) procedures are often complex, requiring prolonged high-dose exposures. This leads to increased radiation exposure to both patient and operating staff. The purpose of this study is to identify parameters related to the complexity of acute ischemic stroke (AIS) procedures that increase patient exposure and derive DRLs according to ICRP 135., Methods: Data from 145 patients treated for AIS between 2017 and 2019 in a Hub Stroke center were retrospectively analyzed. Dosimetric parameters, demographic and clinical data were collected for each patient. The INR operator and the fluoroscopy system used were included., Results: A multivariable analysis was performed to identify which parameters significantly influence the dosimetric data. Thrombus location and the use of stent retriever were noted as the most likely parameters of complex INR procedures. Male sex is an indicator of complex procedure only with regards to the Kerma area product and the air kerma. Patient age significantly affects the exposure time alone. Senior or more experienced operator's data demonstrated reduced patient's exposure time and therefore the KAP and Kar values. The type of X-ray equipment influenced the outcome of the procedure in terms of number of images acquired. Typical values obtained are 168 Gycm 2 , 0.68 Gy, 19 min and 181 images., Conclusion: Typical values derived in this study promote patient dose optimization, when considering the complexity of INR procedures. The clinical variables related to the complexity of procedure that mainly affect the dosimetric data in our experience are thrombus location and use of stent retrievers., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: Oral melphalan and dexamethasone (MDex) were considered a standard of care in light-chain (AL) amyloidosis. In the past decade, bortezomib has been increasingly used in combination with alkylating agents and dexamethasone. We prospectively compared the efficacy and safety of MDex and MDex with the addition of bortezomib (BMDex)., Methods: This was a phase III, multicenter, randomized, open-label trial. Patients were stratified according to cardiac stage. Patients with advanced cardiac stage (stage IIIb) amyloidosis were not eligible. The primary end point was hematologic response rate at 3 months. This trial is registered with ClinicalTrials.gov identifier NCT01277016., Results: A total of 109 patients, 53 in the BMDex and 56 in the MDex group, received ≥ 1 dose of therapy (from January 2011 to February 2016). Hematologic response rate at 3 months was higher in the BMDex arm (79% v 52%; P = .002). Higher rates of very good partial or complete response rates (64% v 39%; hazard ratio [HR], 2.47; 95% CI, 1.30 to 4.71) and improved overall survival, with a 2-fold decrease in mortality rate (HR, 0.50; 95% CI, 0.27 to 0.90), were observed in the BMDex arm. Grade 3 and 4 adverse events (the most common being cytopenia, peripheral neuropathy, and heart failure) were more common in the BMDex arm, occurring in 20% versus 10% of cycles performed., Conclusion: BMDex improved hematologic response rate and overall survival. To our knowledge, this is the first time a controlled study has demonstrated a survival advantage in AL amyloidosis. BMDex should be considered a new standard of care for AL amyloidosis.

Competing Interests: None declared.

Background: The aim of the present prospective study (ClinicalTrials.gov Identifier: NCT02111538) was to assess the prognostic value of phase angle (PhA), derived from bioimpedance vectorial analysis (BIVA), in patients affected by systemic amyloid light-chain (AL) amyloidosis. Methods: One hundred-twenty seven consecutive newly diagnosed, treatment-naïve patients with histologically confirmed AL amyloidosis were enrolled. Nutritional assessment including BIVA-derived PhA was performed before treatment initiation. Results: PhA was associated with unintentional weight loss, caloric intake and the physical component of quality of life (QoL). After a median follow-up of 16.3 months (25th-75th percentile: 8.4-28.9 months), 49 (38.6%) subjects had died. At multivariable Cox proportional hazard analysis, PhA ≤4.3 independently predicted survival (HR = 2.26 [95%CI, 1.04-4.89]; p  = .038]) after controlling for hydration status, haematologic response to treatment and modified Mayo Clinic cardiac stage. There was no effect modification of PhA on mortality by cardiac stage (P for interaction = 0.61). Conclusions: In AL amyloidosis, BIVA-derived PhA is associated with the common parameters implied in malnutrition assessment and QoL, and adjusted for hydration independently predicts survival. Due to its feasibility, BIVA should be systematically considered for the nutritional and clinical assessment of AL patients, in whom nutritional intervention trials are warranted.

Objectives: To develop a quantitative score based on colour duplex sonography (CDS) to predict the diagnosis and outcome of GCA., Methods: We selected patients with positive CDS and confirmed diagnosis of GCA recruited into the TA Biopsy (TAB) vs Ultrasound in Diagnosis of GCA (TABUL) study and in a validation, independent cohort. We fitted four CDS models including combinations of the following: number and distribution of halos at the TA branches, average and maximum intima-media thickness of TA and axillary arteries. We fitted four clinical/laboratory models. The combined CDS and clinical models were used to develop a score to predict risk of positive TAB and clinical outcome at 6 months., Results: We included 135 GCA patients from TABUL (female: 68%, age 73 (8) years) and 72 patients from the independent cohort (female: 46%, age 75 (7) years). The best-fitting CDS model for TAB used maximum intima-media thickness size and bilaterality of TA and axillary arteries' halos. The best-fitting clinical model included raised inflammatory markers, PMR, headache and ischaemic symptoms. By combining CDS and clinical models we derived a score to compute the probability of a positive TAB. Model discrimination was fair (area under the receiver operating characteristic curve 0.77, 95% CI: 0.68, 0.84). No significant association was found for prediction of clinical outcome at 6 months., Conclusion: A quantitative analysis of CDS and clinical characteristics is useful to identify patients with a positive biopsy, supporting the use of CDS as a surrogate tool to replace TAB. No predictive role was found for worse prognosis., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: To determine the out-of-hospital cardiac arrest (OHCA) rates and occurrences at municipality level through a novel statistical model accounting for temporal and spatial heterogeneity, space-time interactions and demographic features. We also aimed to predict OHCAs rates and number at municipality level for the upcoming years estimating the related resources requirement., Methods: All the consecutive OHCAs of presumed cardiac origin occurred from 2005 until 2018 in Canton Ticino region were included. We implemented an Integrated Nested Laplace Approximation statistical method for estimation and prediction of municipality OHCA rates, number of events and related uncertainties, using age and sex municipality compositions. Comparisons between predicted and real OHCA maps validated our model, whilst comparisons between estimated OHCA rates in different yeas and municipalities identified significantly different OHCA rates over space and time. Longer-time predicted OHCA maps provided Bayesian predictions of OHCA coverages in varying stressful conditions., Results: 2344 OHCAs were analyzed. OHCA incidence either progressively reduced or continuously increased over time in 6.8% of municipalities despite an overall stable spatio-temporal distribution of OHCAs. The predicted number of OHCAs accounts for 89% (2017) and 90% (2018) of the yearly variability of observed OHCAs with prediction error ≤1OHCA for each year in most municipalities. An increase in OHCAs number with a decline in the Automatic External Defibrillator availability per OHCA at region was estimated., Conclusions: Our method enables prediction of OHCA risk at municipality level with high accuracy, providing a novel approach to estimate resource allocation and anticipate gaps in demand in upcoming years., Competing Interests: AA is a consultant to Boston Scientific, Backbeat, Biosense Webster, Cairdac, Corvia, Microport CRM, Philips, Radcliffe Publisher. He received speaker fee from Boston Scientific, Medtronic, and Microport. He participates in clinical trials sponsored by Boston Scientific, Medtronic, Philips. He has intellectual properties with Boston Scientific, Biosense Webster, and Microport CRM. All other authors have no conflict of interest to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The aim of the Mont Blanc Study was to investigate the relationship between intraocular pressure (IOP), central corneal thickness (CCT), and altitude in healthy subjects. Thirty-three eyes of 33 healthy volunteers (mean age: 24.8 years, 17 females) had their IOP measured with Perkins and I-Care tonometers and their CCT using ultrasound pachymetry at three locations in Italy with different altitudes: Pavia, (PV), 77 meters above sea level (a.s.l); Courmayeur (CM), 1300 meters a.s.l; Pointe Helbronner (PH), 3466 meters a.s.l.). The measurements were performed at 9 am, 11 am, 1 pm and 3 pm (±30') in indoor settings (mean temperature of 19°C) in PV and PH. At 9 am, CCT and IOP were measured outdoor (mean temperature of -1.4°C) at PH. The mean values of the IOP curve decreased from PV to PH with the Perkins (p = 0.02) and I-Care tonometers (p = 0.001). Instead, CCT increased upon ascension from PV to PH (p = 0.01), and from CM to PH (p = 0.002). When exposed to sub-zero temperature, the IOP increased (p<0.001), while the CCT did not change (p = 0.30). The results suggest that IOP significantly decreased and CCT significantly increased upon ascension from the sea level to higher altitudes., Competing Interests: The authors have declared that no competing interests exist.

Since the end of 2019, a new coronavirus strain has been reported in the Chinese province of Wuhan, indicated as 2019-nCoV or SARS-CoV-2. In February 2020, the first case of transmission on Italian soil was reported. On March 09, 2020, at the time of protocol design, the Italian Ministry of Health reported 10,149 people who had contracted the virus; of these, 8514 were positive, of which 5038 were hospitalized with symptoms (59.2%) and 877 in intensive care (10.3%), while the remaining 2599 were in home isolation; 631 were deceased (6.2%) and 1004 healed (9.9%). To date there are no studies in the literature that demonstrate its feasibility and efficacy in the context of the worldwide SARS-CoV-2 epidemic. Based upon the little existing evidence, we planned to assess the efficacy of the infusion of hyperimmune plasma in COVID-19 patients in a one-arm proof-of-concept clinical trial. The primary objective of our study is to evaluate the efficacy of the administration of plasma taken from convalescent donors of COVID-19 to critically ill patients with COVID-19 in terms of their survival. Death from any cause will be considered. The main limit of this study is its one-arm proof-of-concept design with only 43 patients enrolled. However, in the absence of previous evidence, larger and/or randomized trials did not appear to be ethically acceptable. Moreover, the results from this study, if encouraging, will allow us to plan further informed large clinical trials. Trial registration: NCT04321421 March 23, 2020.

Background: Transbronchial lung cryobiopsy (TBLC) has been introduced recently in the diagnosis of interstitial lung diseases. We aimed to evaluate the prognostic significance of the distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases with the use of TBLC data in multidisciplinary team (MDT) diagnosis., Methods: In this single-centre, retrospective, investigator-initiated comparative study, we evaluated consecutive patients without a definite usual interstitial pneumonia pattern on high-resolution CT, who presented to the GB Morgagni Hospital (Forlì, Italy), and who underwent TBLC (Jan 1, 2011, to Dec 31, 2014) or surgical lung biopsy (SLB; Jan 1, 2002, to Dec 31, 2016). Three pathologists reviewed the specimens, masked to clinical information. MDT evaluation was done before and after biopsy. The primary endpoint was the prognostic significance of the MDT diagnostic separation between idiopathic pulmonary fibrosis and other interstitial lung diseases in patients undergoing TBLC. Mortality was evaluated by means of Cox regression analysis., Findings: We evaluated 500 consecutive cases, 426 of which were included: 266 had TBLC and 160 had SLB. 189 patients had idiopathic pulmonary fibrosis, 143 had other fibrotic interstitial lung diseases, and 94 had non-fibrotic interstitial lung diseases. Patients undergoing TBLC had more comorbidities and better preserved lung function compared with those undergoing SLB; among patients with a final MDT diagnosis of idiopathic pulmonary fibrosis, patients undergoing TBLC were older, had more comorbidities, and had a different post-biopsy treatment profile than those who received SLB. The distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases made by MDT diagnosis on the basis of TBLC biopsy had clear prognostic significance, with a 5-year transplant-free survival of 68% (95% CI 57-76) in patients with an MDT idiopathic pulmonary fibrosis diagnosis based on TBLC compared with 93% (87-96) in patients without an idiopathic pulmonary fibrosis diagnosis based on TBLC (hazard ratio 5·28, 95% CI 2·72-10·04; p<0·0001). This distinction remained statistically significant in a multivariate analysis controlling for age, sex, smoking status, comorbidities, pulmonary function, and high-resolution CT patterns (p=0·02)., Interpretation: TBLC makes an important diagnostic contribution in interstitial lung disease, on the basis of the prognostic distinction between idiopathic pulmonary fibrosis and other interstitial lung diseases when TBLC findings are included in multidisciplinary diagnosis., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Over the last 30 years, the incidence of pediatric urolithiasis (PU) has been increasing and the surgical management has evolved toward a minimally invasive approach (MIA). We reported the experience of two Centers of Pediatric Surgery in the management of PU, focusing on MIA as first choice in treatment. Methods: Data were retrospectively analyzed from October 2009 to October 2019 in children with urolithiasis who were admitted to two referral Italian Centers of Pediatric Surgery. Demographic and clinical data of the patients, features of the urolithiasis, type of surgery were considered. Results: Seventy patients (7.3 ± 5.0 years) with normal renal function were treated for calculi in the pyelocaliceal system (45.7%), ureter (34.3%), bladder (4.3%), urethra (1.4%), and multiple locations (14.3%). Size of calculi was >10 mm in 55.7% of cases (kidney>bladder/urethra>multiple>ureter, p = 0.01). Symptoms were present in 75.7% of patients. Family history was positive in 16.9% of cases. MIA was performed in 59 patients (84.3%): 11.8% shockwave lithotripsy (kidney>ureter>multiple); 32.2% ureteral retrograde surgery (ureteral>other localizations); 30.5% retrograde intrarenal surgery (kidney>other localizations); and 25.4% other procedures including percutaneous nephrolithotomy, cystoscopic bladder stone removal or laser cystolithotripsy (kidney>bladder>multiple). Preoperative stenting was necessary in 52.8% of cases. Four MIA procedures (6.9%, kidney>ureter/multiple) were converted to open surgery. Open surgery was required as first approach in 15.7% of patients (kidney>ureter>multiple) who needed urgent surgery or had associated congenital renal anomalies. In 18/70 of children (25.7%), with prevalence of stones in kidney and multiple location ( p < 0.01), a second procedure completed the treatment (88.8% MIA). Intraoperative difficulties were recorded in 8.5% of cases, without difference between location and size of calculi. Late complications (5.7%) were related to displacement and infection of the ureteral stent. Conclusions: MIA resulted to be feasible in more than 75% of primary surgery and in more than 85% of cases requiring a second procedure. Preoperative stent was mandatory in more than 50% of children. The technological evolution allowed to overcome many of the technical difficulties related to the approach to the papilla and lower calyxes. Open surgery is reserved for selected cases and endoscopic surgery represents the best choice of treatment for PU., (Copyright © 2020 Destro, Selvaggio, Lima, Riccipetitoni, Klersy, Di Salvo, Marinoni, Calcaterra and Pelizzo.)

Background The coexistence of celiac disease (CD) and obesity/overweight is not unusual. Objective We investigate the prevalence and clinical presentation of CD, detected by screening, among children with excessive weight gain. Methods We enrolled 200 children referred for overweight/obesity to our outpatient clinic. Medical history during pregnancy and childhood and lifestyle variables were recorded. Patients were screened for CD with total immunoglobulin A (IgA), IgA anti-transglutaminase (tTG-IgA) and IgA anti-endomysial antibodies (EMA-IgA). In subjects with positive autoantibodies, esophagogastroduodenoscopy (EGDS) was performed and genetic testing for HLA DQ2 and/or DQ8 haplotypes was tested. Results CD positive antibodies (tTg-IgA and EMA-IgA) were detected in eight patients (4%); in all subjects CD diagnosis was confirmed by HLA-DQ2 and/or DQ8 compatibility and EGDS. No association between CD and medical history during pregnancy and childhood or lifestyle variables was noted; however, a dietary difference was identified with those testing positive for CD also reporting a lower weekly consumption of fruits and vegetables (p=0.04). Headache was reported more frequently in patients with than without CD (p=0.04). Familiar positivity for autoimmune diseases was revealed in CD patients (p=0.01). Conclusion CD should be considered in children with excessive weight gain. Familial predisposition to other autoimmune diseases may represent a risk factor for development of CD. Even though the relationship between headache and CD is not well defined, the patients with headache of unknown origin should be screened for CD.

Surgical mortality is the most significant measure of outcome in surgical healthcare. The objective was to assess surgical 30 days mortality and improve the identification of predictors for personalized risk stratification of patients undergoing elective and emergency surgery. The study was conducted as a single-center cohort retrospective observational study, based on the analysis of data collected from patients surgically treated from 2002 to 2014 in a multi-disciplinary research and care referral hospital with global case mix of 1.27. The overall in-hospital mortality rate was 1.89% (95% CI 1.82-1.95). In the univariable analysis, numerous predictors were significantly associated with in-hospital death following surgery. In the multivariable model, age, BMI (Body Mass Index), ASA score, department, planned surgical complexity, surgical priority, previous surgeries in the same hospitalization, cardiovascular, pulmonary, hepato-renal comorbidities, drug intolerance, cancer and AIDS were independently associated with mortality after surgery. At logistic regression, the computed SMATT score (graded 0-100), generated on the basis of multivariate analysis, demonstrated a good discrimination (10-fold cross-validated AUC-ROC 0.945, 95%CI 0.941-0.948) and correctly classified 98.5% of those admissions with a probability of death >50%. The novel SMATT score, based on individual preoperative and surgical factors, accurately predicts mortality and provides dynamic information of the risk in redo/reoperative surgery.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1 + immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1 + cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1 + microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Aims: The Swiss national registry on percutaneous mitral valve interventions (MitraSwiss) was established in 2011 to monitor safety/efficacy of percutaneous mitral valve repair (PMVR) with the MitraClip device. The aim of this analysis was to report the outcome after PMVR in a real-world, all-comers population and its predictors after inclusion of more than 1,200 patients, stratifying the results according to mitral regurgitation (MR) aetiology. Here we report the in-hospital, short and midterm outcomes of all patients prospectively enrolled., Methods and Results: Since 2011, MitraSwiss has enrolled 1,212 patients with moderate and severe MR of functional (FMR) or degenerative (DMR) aetiology treated with PMVR in 10 centres. Pre-specified endpoints included clinical, echocardiographic and functional parameters with follow-up planned up to five years. Outcomes are compared according to MR aetiology. Acute procedural success was achieved in 91.5% of cases, with no differences between FMR and DMR and sustained good midterm results. NYHA class and pulmonary pressure improved significantly in both cohorts. Cumulative probability of death at five years was 54% (95% CI: 45-63) in FMR and 45% (95% CI: 37-54) in DMR (HR 1.15, p=0.009). Age, anaemia, impaired renal function and reduced left ventricular ejection fraction resulted in being independent predictors of death at five years., Conclusions: In a large contemporary cohort of non-surgical patients with severe MR, the safety and effectiveness of PMVR have been confirmed. At midterm follow-up, mortality and MACE were lower in DMR patients, though MR aetiology was not directly and independently associated with outcome.

Background: Christmas and New Year's holidays are risk factors for hospitalization, but the causes of this "holiday effect" are uncertain. In particular, clinical complexity (CC) has never been assessed in this setting. We therefore sought to determine whether patients admitted to the hospital during the December holiday period had greater CC compared to those admitted during a contiguous non-holiday period., Methods: This is a prospective, longitudinal study conducted in an academic ward of internal medicine in 2017-2019. Overall, 227 consecutive adult patients were enrolled, including 106 cases (mean age 79.4±12.8 years, 55 females; 15 December-15 January) and 121 controls (mean age 74.3±16.6 years, 56 females; 16 January-16 February). Demographic characteristics, CC, length of stay, and early mortality rate were assessed. Logistic regression analyses for the evaluation of independent correlates of being a holiday case were computed., Results: Cases displayed greater CC (17.7±5.5 vs 15.2±5.9; p = 0.001), with greater impact of socioeconomic (3.51±1.7 vs 2.9±1.7; p = 0.012) and behavioral (2.36±1.6 vs 1.9±1.8; p = 0.01) CC components. Cases were also significantly frailer according to the Edmonton Frail Scale (8.0±2.8 vs 6.4±3.1; p<0.001), whilst having similar disease burden, as measured by the CIRS comorbidity index. Age (OR 1.02; p = 0.039), low income (OR 1.97, 95% CI 1.10-3.55; p = 0.023), and total CC (OR 1.06; p = 0.014) independently correlated with the cases. Also, cases showed a longer length of stay (median 15.5 vs 11 days; p = 0.0016) and higher in-hospital (12 vs 4 events; p = 0.021) and 30-day (14 vs 6 events; p = 0.035) mortality., Conclusions: Patients hospitalized during the December holiday period had worse health outcomes, and this could be attributable to the grater CC, especially related to socioeconomic (social deprivation, low income) and behavioral factors (inappropriate diet). The evaluation of all CC components could potentially represent a useful tool for a more rational resource allocation over this time of the year., Competing Interests: The authors have declared that no competing interests exist.

Aims: An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far. We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve., Methods and Results: We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019. The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019). A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001)., Conclusion: The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome. Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)