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Introduction Transoral laser microsurgery represents the treatment of choice for early glottic cancer. Its use and effectiveness are mainly related to laryngeal exposure and deep extension of tumor. Histopathologic assessment of surgical margin presents a main issue about transoral laser microsurgery and complete oncological excision. Objective The aim was to analyze the impact of revision surgery on organ preservation and local disease control in patients with early glottic cancer treated by transoral laser microsurgery. Methods We carried out a retrospective study on a cohort of 153 patients with early glottic cancer (Tis, T1, T2) treated by transoral laser microsurgery. Resection margins were classified as follows: “free” if macroscopic margin-tumor distance was at least 2 mm, as “close” if it was less than 2 mm and “positive” if the margin was involved by carcinoma. Patients were divided into two groups: patients with free resection margins (Group A) and patients with positive, close or not-evaluable resection margins (Group B). Group A (36) underwent periodic followup. Group B (117) underwent a second look laser CO2 2 months after surgery. Fifteen patients of Group A with suspected persistence of carcinoma during followup underwent a second laser resection after a time interval of 4–8 months after first surgery. Overall survival, disease-free survival, disease-specific survival, ultimate local control with laser alone and organ preservation rates were estimated. Results Five-year overall survival rate and 5-year disease-specific survival were 100% in both groups. The five-year laryngeal preservation rate was 100% in Group A and 95.2% in Group B. Five-year disease-free survival was 92.15% and 5-year ultimate local control with laser alone in 92.15% of patients. Conclusion This study has demonstrated that revision Transoral Laser Microsurgery is able to confirm the oncological radicality in most cases, even in the case of positive, close or non-evaluable margins. Considering our results, according to our experience, the second look with CO2 laser is a therapeutic strategy to consider, even in the case of close or non-evaluable as well as positive margins.

Rationale and Objectives: To develop and validate a radiomic model, with radiomic features extracted from breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) from a 1.5T scanner, for predicting the malignancy of masses with enhancement. Images were acquired using an 8-channel breast coil in the axial plane. The rationale behind this study is to show the feasibility of a radio-mics-powered model that could be integrated into the clinical practice by exploiting only standard-of-care DCE-MRI with the goal of reducing the required image pre-processing (ie, normalization and quantitative imaging map generation).Materials and Methods: 107 radiomic features were extracted from a manually annotated dataset of 111 patients, which was split into discovery and test sets. A feature calibration and pre-processing step was performed to find only robust non-redundant features. An indepth discovery analysis was performed to define a predictive model: for this purpose, a Support Vector Machine (SVM) was trained in a nested 5-fold cross-validation scheme, by exploiting several unsupervised feature selection methods. The predictive model performance was evaluated in terms of Area Under the Receiver Operating Characteristic (AUROC), specificity, sensitivity, PPV and NPV. The test was performed on unseen held-out data.Results: The model combining Unsupervised Discriminative Feature Selection (UDFS) and SVMs on average achieved the best performance on the blinded test set: AUROC = 0.725 +/- 0.091, sensitivity = 0.709 +/- 0.176, specificity = 0.741 +/- 0.114, PPV = 0.72 +/- 0.093, and NPV = 0.75 +/- 0.114.Conclusion: In this study, we built a radiomic predictive model based on breast DCE-MRI, using only the strongest enhancement phase, with promising results in terms of accuracy and specificity in the differentiation of malignant from benign breast lesions.

Background Concerns regarding long-term durability of surgical repair for functional mitral regurgitation are based on short-term data, with few comparisons of ischemic (IMR) versus non-ischemic (NIFMR) etiology. Methods 788 consecutive patients receiving mitral repair for functional mitral regurgitation were evaluated from a prospectively maintained database. Patients with other surgical procedures were included. Propensity score matching was used to compare outcomes in IMR versus NIFMR. Results Unmatched IMR patients tended to be older men with greater comorbidities. 198 matched pairs of IMR versus NIFMR patients had similar demographics with relatively preserved ejection fraction 40±13% and end-systolic diameter 4.3±1.1cm. Concomitant coronary revascularization occurred in 70% of matched IMR patients. All patients received an annuloplasty ring, usually 24-26 mm. Heart failure class improved from 2.8 preop to 1.5 at 5 years (P =2+) mitral regurgitation (27±4% v 26±4%, P=0.4), severe regurgitation (10±3% v 8±2%, P=0.5), and mitral reoperation (3±1% v 3±1%, P=0.4) were not different between IMR v NIFMR. Recurrent moderate regurgitation was associated with heart failure readmission but not with mortality. Conclusions In propensity-matched patients, IMR versus NIFMR had worse survival but similar repair durability, with moderate regurgitation in 27% at 10 years and rare severe regurgitation or mitral reoperation. In selected patients with relatively preserved function, mitral repair for IMR or NIFMR can improve symptoms with durable mild regurgitation in most patients out to 10 years.

BACKGROUND: This study compared clinical and hemodynamic in-hospital outcomes of patients undergoing sutureless vs rapid deployment aortic valve replacement (SURD-AVR) in the large population of the Sutureless and Rapid Deployment International Registry (SURD-IR). METHODS: We examined 4695 patients who underwent isolated or combined SURD-AVR. The "sutureless" Perceval valve (LivaNova PLC, London, United Kingdom) was used in 3133 patients and the "rapid deployment" Intuity (Edwards Lifesciences, Irvine, CA) in 1562. Potential confounding factors were addressed by the use of propensity score matching. After matching, 2 well-balanced cohorts of 823 pairs (isolated SURD-AVR) and 467 pairs (combined SURD-AVR) were created. RESULTS: Patients who received Perceval and Intuity valves showed similar in-hospital mortality and rate of major postoperative complications. Perceval was associated shorter cross-clamp and cardiopulmonary bypass times. In the isolated SURD-AVR group, patients receiving Perceval were more likely to undergo anterior right thoracotomy incision. Postoperative transvalvular gradients were significantly lower for the Intuity valve compared with those of the Perceval valve, either in isolated and combined SURD-AVR. The Intuity valve was associated with a lower rate of postoperative mild aortic regurgitation. CONCLUSIONS: Our results confirm the safety and efficacy of SURD-AVR regardless of the valve type. The Perceval valve was associated with reduced operative times and increased anterior right thoracotomy incision. The Intuity valve showed superior hemodynamic outcomes and a lower incidence of postoperative mild aortic regurgitation. ispartof: ANNALS OF THORACIC SURGERY vol:114 issue:3 pages:758-+ ispartof: location:Netherlands status: published

Study design Systematic review and meta-analysis. Objective Historically, posterior approaches to the lumbar spine have allowed surgeons to manage degenerative conditions affecting the lumbar spine. However, spinal muscles injury, post-surgical vertebral instability, cerebrospinal fluid (CSF) leakage, and failed back surgery syndrome (FBSS) represent severe complications that may occur after these surgeries. Lumbar interbody fusion using anterior (ALIF), oblique (OLIF), or lateral (LLIF) approaches may represent valuable surgical alternatives, in case fusion is indicated on single or multiple levels. Methods The present study is a systematic review, conducted according to the PRISMA statement, of comparative studies on OLIF, and LLIF for degenerative spine disorders, and a meta-analysis of their clinical-radiological outcomes and complications. Results After screening 1472 papers on PubMed, Scopus, and Cochrane Library, only 3 papers were included in the present study. 318 patients were included for data meta-analysis, 128 in OLIF group, and 190 in LLIF group. There were no significative differences in terms of surgical (intraoperative blood loss and surgical duration) and clinical (VAS-back, VAS-leg, and ODI scores) outcomes, or fusion rates at last follow-up (> 2 years). Significantly higher rates of abdominal complications, system failure, and vascular injuries were recorded in the OLIF group. Conversely, postoperative neurological symptoms and psoas weakness were significatively more common in LLIF group. Conclusions The meta-analysis suggests that OLIF and LLIF are both effective for lumbar degenerative disorders, although each of them presents specific complications and this should represent a relevant element in the surgical planning.

To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years.Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered.A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small ( 10 mL) (74%), medium (49%), or large ( 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment.Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN.• Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Objective To compare vascular complications in patients undergoing percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) using ultrasound guidance (USG) versus fluoroscopy guidance (FSG) for femoral access. Background In patients undergoing PCI, using the arterial femoral access increases the risk of vascular complications compared using the radial access. USG reduces time to access, number of attempts, and vascular complications compared with FSG, but the efficacy of USG has never been tested in the setting of CTO-PCI. Methods A total of 197 patients undergoing CTO-PCI using at least a femoral vascular access from November 2015 to September 2020 were screened. The primary outcome was a composite of local hematoma, pseudoaneurysm , retroperitoneal hemorrhage , arteriovenous fistula or hemoglobin drop ≥3 g/dL during hospitalization. The independent association between USG and the primary outcome of interest was explored. Results The primary outcome occurred in 17.3% of patients. Patients in the USG group had a significantly lower incidence of vascular complications compared with patients in the FSG group (8.5% vs. 21.0%, p = 0.039), driven by a reduction of localized hematomas (3.4% vs 13.0%, p = 0.042). After adjustment for type of CTO approach and heparin dose, USG was significantly associated with a reduced relative risk of the composite primary outcome (adjusted odds ratio 0.16, 95% confidence interval 0.05 to 0.51; p = 0.002). Conclusion USG in CTO-PCI is associated with a decreased risk of vascular complications, primarily driven by a reduction in local hematomas, especially in complex CTO-PCI where the larger use of heparin increases the risk of vascular complications.

Background: In advanced non-small-cell lung cancer, without activating mutations and with PD-L1≥50%, Pembrolizumab monotherapy is the therapeutic standard in Europe. Objective: To evaluate retrospectively the safety and efficacy of this drug and to investigate potential prognostic factors in daily clinical practice. Methods: From September 2017 to September 2019, 205 consecutive patients from 14 Italian Medical Oncology Units were enrolled in the study. Gender, Age (> or 90% or Results: At a median follow-up of 15.2 months, median progression-free and overall survival (mPFS and mOS) were 9.2 months (95% C.I., 4.8-13.5) and 15.9 months (95% C.I., not yet evaluable), respectively. Patients with Eastern Cooperative Oncology Group performance status (ECOG-PS) 2 had mPFS of 2.8 months (95% C.I., 2.1-3.4) and mOS of 3.9 months (95% C.I., 2.5-5.3). Patients with liver metastases at diagnosis had an mPFS of 3.2 months (95% C.I., 0.6-5.8) and an mOS of 6.0 months (95% C.I., 3.7-8.4). At multivariate analysis for OS gender, ECOG-PS 2, and presence of liver metastases were independent prognostic factors. Conclusion: Patients with ECOG-PS 2 derived little benefit from the use of first-line pembrolizumab. In patients with liver metastases, the association of pembrolizumab with platinum-based chemotherapy could be a better option than pembrolizumab alone.

Iatrogenic perforations are severe complications of gastrointestinal endoscopy; therefore, their management should be adequately planned. A 77-year-old man with a history of diverticulosis underwent a colonoscopy for anemia. During the procedure, an iatrogenic perforation occurred suddenly in the sigmoid colon, near a severe angle among the numerous diverticula. Through-the-scope clips were immediately applied to treat it and close mucosal edges. Laboratory tests showed increased levels of inflammation and infection, and although there were no complaints of abdominal pain, the patient had an extremely distended abdomen. A multidisciplinary board began management based on a conservative approach. Pneumoperitoneum was treated with computed tomography-assisted drainage. After 72 hours, his intestinal canalization and laboratory tests were normal. Though this adverse event is rare, a multidisciplinary board should be promptly gathered upon occurrence, even if the patient appears clinically stable, to consider a conservative approach and avoid surgical treatment.

Isolated posterior tibial tendon dislocation is a rare condition. Diagnosis can be challenging, especially in the acute clinical setting. Predisposing factors include shallow posterior tibial tendon groove and tear of the flexor retinaculum. We report the case of traumatic subluxation of the posterior tibial tendon, illustrating imaging findings and surgical technique. Posterior tibial tendon dislocation was detected using dynamic ultrasound, while magnetic resonance was essential for a comprehensive evaluation that included underlying predisposing anatomic abnormalities and associated pathologic conditions. Conservative treatment is often unsuccessful thus surgical approach was needed. Under ampliscopic guidance, a bone tunnel was created behind the retromalleolar groove. The posterior tibial tendon was located into the new groove and the retinaculum was re-attached and tightened by anchors and absorbable sutures at the anterior margin of the sulcus. At 12-month follow-up, the patient did not complain any residual pain and he was able to perform normal daily activities without any limitations and with no further tendon dislocations.

Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

This study aims to investigate the influence of interobserver manual segmentation variability on the reproducibility of 2D and 3D unenhanced computed tomography (CT)- and magnetic resonance imaging (MRI)-based texture analysis. Thirty patients with cartilaginous bone tumors (10 enchondromas, 10 atypical cartilaginous tumors, 10 chondrosarcomas) were retrospectively included. Three radiologists independently performed manual contour-focused segmentation on unenhanced CT and T1-weighted and T2-weighted MRI by drawing both a 2D region of interest (ROI) on the slice showing the largest tumor area and a 3D ROI including the whole tumor volume. Additionally, a marginal erosion was applied to both 2D and 3D segmentations to evaluate the influence of segmentation margins. A total of 783 and 1132 features were extracted from original and filtered 2D and 3D images, respectively. Intraclass correlation coefficient ≥ 0.75 defined feature stability. In 2D vs. 3D contour-focused segmentation, the rates of stable features were 74.71% vs. 86.57% (p p = 0.142), and 95.66% vs. 94.97% (p = 0.554) for CT and T1-weighted and T2-weighted images, respectively. Margin shrinkage did not improve 2D (p = 0.343) and performed worse than 3D (p p = 0.191), and those derived from T1-weighted and T2-weighted images were 76.0% vs. 78.2% (p = 0.285). 2D and 3D radiomic features of cartilaginous bone tumors extracted from unenhanced CT and MRI are reproducible, although some degree of interobserver segmentation variability highlights the need for reliability analysis in future studies.

Kabuki syndrome (KS) is a well-recognized disorder characterized by postnatal growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability. The syndrome is caused by KMT2D gene mutations or less frequently KDM6A gene mutations or deletions. We report a systematic evaluation of KS patients from Campania region of Italy; data were also compared with literature ones. We collected data of 15 subjects (8 males and 7 females with age range 10–26 years; mean age 16.9 years) with confirmed diagnosis of KS, representing the entire cohort of patients from Campania Region. Each patient performed biochemical testing and instrumental investigation. Neuro-intellectual development, cranio-facial dysmorphisms, and multisystem involvement data were collected retrospectively. For each category, type of defects and frequency of the anomalies were analyzed. Our observation shows that KS patients from Campania region have some particular and previously underscored, neurological and immunological findings. We found high prevalence of EEG’s abnormalities (43%) and MRI brain abnormalities (60%). Microcephaly resulted more common in our series (33%), if compared with major cohorts described in literature. Biochemical features of immunodeficiency and autoimmune diseases including thyroid autoimmunity, polyserositis, and vitiligo were observed with high prevalence (54.5%). Low immunoglobulins levels were a frequent finding. Lymphocyte class investigation showed significantly reduced CD8 levels in one patient.Conclusions: These data confirm great heterogeneity of clinical manifestations in KS and suggest to introduce further clinical diagnostic criteria in order to perform a correct and precocious diagnosis. What is Known• Kabuki syndrome is characterized by growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability• Immune dysfunction is a common finding but autoimmune diseases are rarely seen• Neurological features are common What is New• Some particular facial features could help gestalt diagnosis (hypertelorism, broad nasal bridge, micrognathia, tooth agenesis, cutaneous haemangiomas and strabismus)• Higher prevalence of autoimmune disorders than previously reported• Particular neurological features are present in this cohort (EEG and MRI brain abnormalities)

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2

13 p.-3 fig.-1 tab., Background: Disrupted endothelial BMP9/10 signaling may contribute to the pathophysiology of both hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH), yet loss of circulating BMP9 has not been confirmed in individuals with ultra-rare homozygous GDF2 (BMP9 gene) nonsense mutations. We studied two pediatric patients homozygous for GDF2 (BMP9 gene) nonsense mutations: one with PAH (c.[76C>T];[76C>T] or p.[Gln26Ter];[Gln26Ter] and a new individual with pulmonary arteriovenous malformations (PAVMs; c.[835G>T];[835G>T] or p.[Glu279Ter];[Glu279Ter]); both with facial telangiectases., Methods: Plasma samples were assayed for BMP9 and BMP10 by ELISA. In parallel, serum BMP activity was assayed using an endothelial BRE-luciferase reporter cell line (HMEC1-BRE). Proteins were expressed for assessment of secretion and processing., Results: Plasma levels of both BMP9 and BMP10 were undetectable in the two homozygous index cases and this corresponded to low serum-derived endothelial BMP activity in the patients. Measured BMP9 and BMP10 levels were reduced in the asymptomatic heterozygous p.[Glu279Ter] parents, but serum activity was normal. Although expression studies suggested alternate translation can be initiated at Met57 in the p.[Gln26Ter] mutant, this does not result in secretion of functional BMP9., Conclusion: Collectively, these data show that homozygous GDF2 mutations, leading to a loss of circulating BMP9 and BMP10, can cause either pediatric PAH and/or "HHT-like" telangiectases and PAVMs. Although patients reported to date have manifestations that overlap with those of HHT, none meet the Curaçao criteria for HHT and seem distinct from HHT in terms of the location and appearance of telangiectases, and a tendency for tiny, diffuse PAVMs., This study was supported by British Heart Foundation Grant/Award Numbers: FS/15/62/323032, RG/13/4/30107, and RG/19/3/34265; Consejo Superior de Investigaciones Científicas (CSIC) Grant/Award Number: 201920E022; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Grant/ Award Numbers: ISCIII-CB06/07/0038 and CNV-234-PRF-360.

Aim of this retrospective, multicenter study was to evaluate early and mid-term clinical and hemodynamic results of patients who underwent surgical aortic valve replacement (SAVR) with Intuity rapid-deployment bioprostheses (RDB) (Edwards Lifesciences, Irvine, CA). We analyzed data from the Italian Registry of Intuity Valve (INTU-ITA registry) that is a national, real-world and independent from the industry registry. Preoperative variables were defined according to EuroSCORE and postoperative outcomes according to Valve Academic Research Consortium (VARC). Survival distribution was evaluated using the Kaplan-Meier approach. A Cox-Proportional Hazard Model was employed to assess the effect of the covariates on patients’ survival. The registry included 1687 patients from 23 centers (June 2012-September 2019). Aortic cross clamp time for isolated SAVR was 55 minutes (IQR: 45–70 minute). Postoperative pace-maker rate was 6.3%. At discharge transaortic peak and mean gradients were: 18 mm Hg (IQR: 14–23 mm Hg) and 10 mmHg (IQR: 8–13 mm Hg), respectively. Indexed effective orifice area was 1.10 cm2/m2 (IQR: 0.91–1.31 cm2/m2) and the incidence of severe patient-prosthesis mismatch was 0.6%. Hemodynamic data for all valve sizes remained stable during follow-up. Thirty-day overall mortality was 1.8% (30 patients), and at follow-up it was 5.3% (89 patients). Kaplan-Meier overall survival was 95.5% (94.3–96.7%); 90.7% (88.3–93.1%); 86.4% (82.6–90.4%) at 1, 3, and 5 years, respectively. Serum creatinine (HR: 1.36; 95%CI: 1.04–1.81; p = 0.0397) and cross-clamp time (HR: 1.01; 95%CI: 1.002–1.017; p = 0.0077) were identified as independent predictors of mortality. According to our data from the INTU-ITA registry, SAVR with RDB provides good early clinical and hemodynamic results that are confirmed at follow-up.

Chronic hepatitis B virus (HBV) infection is the major aetiology of hepatocellular carcinoma (HCC). The optimal goal of therapy, hepatitis B surface antigen (HBsAg) loss and anti-HBs production, is achieved rarely and HBsAg-associated HCC risk is well recognized. Here we review the role of HBsAg in HCC, the link between HBsAg and HCC recurrence post-liver transplantation or resection, and the implications for therapy. HBV-associated carcinogenesis is a multifactorial process. The observation that HBV-related HCC can occur in the absence of cirrhosis is compatible with a direct oncogenic effect of the virus, which may occur via multiple mechanisms, including those mediated by both mutated and unmutated HBsAg. HCC recurrence in HBsAg-positive patients post-liver transplantation has been reported in 10%-15% of patients and is likely to be because of expansion of residual HCC tumour cell populations containing integrated HBV DNA, which expand and independently replicate HBV, leading to the recurrence of both HCC and HBV. The direct role of HBsAg in HCC recurrence post-liver resection is less clear. Cirrhosis is the most important risk factor for HCC development, and precancerous cirrhotic liver remains after resection, with the potential to undergo malignant transformation regardless of the existence of HBV-derived oncogenic drivers. The role of HBsAg in the development of HCC and its recurrence post-surgical intervention has multiple implications for therapy and suggests a potential role for immunotherapy in the future management of HCC, in particular post-liver transplantation. Use of hepatitis B immunoglobulins that target HBsAg directly, alongside immune-oncology therapies, may be relevant in this setting.

OBJECTIVES Worldwide, lung ultrasound (LUS) was utilized to assess coronavirus disease 2019 (COVID-19) patients. Often, imaging protocols were however defined arbitrarily and not following an evidence-based approach. Moreover, extensive studies on LUS in post-COVID-19 patients are currently lacking. This study analyses the impact of different LUS imaging protocols on the evaluation of COVID-19 and post-COVID-19 LUS data. METHODS LUS data from 220 patients were collected, 100 COVID-19 positive and 120 post-COVID-19. A validated and standardized imaging protocol based on 14 scanning areas and a 4-level scoring system was implemented. We utilized this dataset to compare the capability of 5 imaging protocols, respectively based on 4, 8, 10, 12, and 14 scanning areas, to intercept the most important LUS findings. This to evaluate the optimal trade-off between a time-efficient imaging protocol and an accurate LUS examination. We also performed a longitudinal study, aimed at investigating how to eventually simplify the protocol during follow-up. Additionally, we present results on the agreement between AI models and LUS experts with respect to LUS data evaluation. RESULTS A 12-areas protocol emerges as the optimal trade-off, for both COVID-19 and post-COVID-19 patients. For what concerns follow-up studies, it appears not to be possible to reduce the number of scanning areas. Finally, COVID-19 and post-COVID-19 LUS data seem to show differences capable to confuse AI models that were not trained on post-COVID-19 data, supporting the hypothesis of the existence of LUS patterns specific to post-COVID-19 patients. CONCLUSIONS A 12-areas acquisition protocol is recommended for both COVID-19 and post-COVID-19 patients, also during follow-up.

Objectives Treatment approach of myasthenia gravis (MG) is still debated; corticosteroids alone or in combination with immunosuppressive agents are the most used drugs. Azathioprine (AZA) has been shown to be effective for MG with a significant steroid-sparing activity, although burdened by side effects. Few studies on methotrexate (MTX) administration showed controversial results. In this cohort, we evaluated the role of MTX as a effective steroid-sparing agent. Methods Fifteen MG patients treated with MTX, previously treated with AZA for at least 12 months, with poor benefits and uncomfortable side effects AZA related, have been selected. Each patient was evaluated through MG-Activity of Daily Living and Quantitative MG scores 5 times/yr. Results Patients treated with MTX had a significant improvement of MG-Activity of Daily Living and Quantitative MG scores. Furthermore, all patients reduced prednisone dosage, and none complained of side effects. Conclusions We suggest MTX is effective and well tolerated and could be considered as a steroid-sparing agent in MG treatment.

PURPOSE: Clinical models to identify patients at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are limited, and the underlying pathophysiology of this common post-transplant complication remains poorly understood. We sought to identify whether pre-transplant levels of circulating proteins reporting on immune activation and inflammation are associated with incident PGD. METHODS: The study population consisted of 219 adult heart transplant recipients identified between 2016 and 2020 at Duke University Medical Center, randomly divided into derivation (n = 131) and validation (n = 88) sets. PGD was defined using modified ISHLT criteria. Proteomic profiling was performed using Olink panels (n = 354 proteins) with serum samples collected immediately prior to transplantation. Association between normalized relative protein expression and PGD was tested using univariate and multivariable (recipient age, creatinine, mechanical circulatory support, and sex; donor age; ischemic time) models. Significant proteins identified in the derivation set (p < 0.05 in univariate models), were then tested in the validation set. Pathway enrichment analysis was used to test candidate biological processes. The predictive performance of proteins was compared to that of the RADIAL score. RESULTS: Nine proteins were associated with PGD in univariate models in the derivation set. Of these, only CLEC4C remained associated with PGD in the validation set after Bonferroni correction (OR [95% CI] = 3.04 [1.74,5.82], p = 2.8×10(−4)). Patterns of association were consistent for CLEC4C in analyses stratified by biventricular/left ventricular and isolated right ventricular PGD. Pathway analysis identified interferon-alpha response and C-type lectin signaling as significantly enriched biologic processes. The RADIAL score was a poor predictor of PGD (AUC = 0.55). CLEC4C alone (AUC = 0.66, p = 0.048) and in combination with the clinical covariates from the multivariable model (AUC = 0.69, p = 0.018) improved discrimination for the primary outcome. CONCLUSIONS: Pre-transplantation circulating levels of CLEC4C, a protein marker of plasmacytoid dendritic cells (pDCs), may identify HT recipients at risk for PGD. Further studies are needed to better understand the potential role pDCs and the innate immune response in PGD.

Introduction: Immune checkpoint blockade of programmed death-1 (PD-1) receptor and its ligand (PD-L1) has contributed to efficacy in many tumor types, with clinical responses observed in a proportion of patients (pts) with Hodgkin lymphoma and rare non-Hodgkin lymphoma subtypes. A recent study demonstrated that combination treatment with anti-PD-L1 and anti-CD38 agents contributed to a stronger anti-tumor immune response compared with anti-PD-L1 monotherapy. Isatuximab, an anti-CD38 monoclonal antibody, is approved for use in multiple myeloma. Cemiplimab, an anti-PD-1 monoclonal antibody, is approved for use in cutaneous squamous cell carcinoma, basal cell carcinoma, and non-small cell lung cancer. Methods: This Phase 1/2 open-label study (NCT03769181) was designed to assess the safety, tolerability, and efficacy of isatuximab in combination with cemiplimab (Isa+Cemi) in pts with relapsed and refractory classic Hodgkin's lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), and peripheral T-cell lymphoma (PTCL). The primary objectives of Phase 1 were to characterize the safety and tolerability of Isa+Cemi and to confirm the recommended Phase 2 dose. Phase 2 used a Simon's 2-stage design to assess the complete response rate in Cohort A1 (anti-PD-1/PD-L1 naïve cHL; n=18; median age, 36 years; 55.6% male; ≥2 prior regimens, 100%) and to assess the objective response rate in Cohorts A2 (cHL progressing after PD-1/PD-L1 therapy; n=12; median age, 33 years; 58.3% male; ≥2 prior regimens, 100%), B (DLBCL; n=17; median age, 64 years; 70.6% male; ≥2 prior regimens, 100%), and C (PTCL; n=11; median age, 69 years; 63.6% male; ≥2 prior regimens, 9.1%). Pts received Isa+Cemi for up to 96 weeks. In Phase 1, the isatuximab dose was 10 mg/kg every week (Cycle 1), every 2 weeks (Cycle 2-6), or every 3 weeks (Cycle 7+). The cemiplimab dose was 250 mg every 2 weeks (Cycle 1-6) or 350 mg every 3 weeks (Cycle 7+). An interim analysis was performed when the last pt in Phase 2 was followed up for 24 weeks. The efficacy evaluation was based on Simon's 2-stage design with 85% power at a 5% 1-sided alpha level for each cohort. At least 8 (44.4%) and 3 (30.0%) responses were required in Cohorts B and C, respectively, in Phase 2 Stage 1 to advance to Phase 2 Stage 2. Results: Isa+Cemi demonstrated a manageable safety profile with no new safety signals. No dose-limiting toxicities were observed, confirming the recommended Phase 2 dose. Treatment-emergent adverse events (TEAEs) were reported in 83.3% (Cohort A1) and 100% (Cohorts A2, B, C) of pts. Grade ≥3 TEAEs occurred in 5.6%, 8.3%, 70.6%, and 81.8% of pts in Cohorts A1, A2, B, and C, respectively. There were no pts in Cohorts A1 or A2 who reported TEAEs leading to definitive discontinuation; 5.9% and 27.3% of pts in Cohorts B and C experienced TEAEs leading to definitive discontinuation. No Grade 5 TEAEs with fatal outcome were reported in Cohorts A1 or A2. There were 4 deaths reported during the on-treatment period in Cohort B (progressive disease, n=2; intestinal perforation, n=1; urinary tract infection, n=1) and 2 in Cohort C (unknown, n=1; progressive disease, n=1). Infusion reactions were reported in 38.9%, 75.0%, 52.9%, and 72.7% of pts in Cohorts A1, A2, B, and C, respectively; there was 1 (9.1%) Grade ≥3 infusion reaction reported in Cohort C. Pharmacokinetics (PK) analyses suggested no effect of cemiplimab on isatuximab PK, and vice versa. Based on Lugano 2014 criteria, 55.6% (Cohort A1), 33.3% (Cohort A2), 5.9% (Cohort B), and 9.1% (Cohort C) of pts in the all-treated population achieved a complete or partial response. Median progression-free survival was 8.38 months (95% CI: 2.72-not calculable [NC]), 8.28 months (95% CI: 2.6-NC), 2.37 months (95% CI: 0.46-2.69), and 2.66 months (95% CI: 0.43-2.99) in Cohorts A1, A2, B, and C, respectively. Conclusion: In this study, Isa+Cemi had a manageable safety profile. Clinical efficacy was observed in pts with cHL, with increased responses observed in pts who had not previously received anti-PD-1/PD-L1 therapy compared with those who progressed on anti-PD-1/PD-L1 therapy. For Cohorts B (DLBCL) and C (PTCL), results of the interim efficacy analysis did not meet prespecified criteria to continue enrollment in Phase 2 Stage 2. Most pts with DLBCL were primary refractory/bulky and discontinued rapidly, which may have contributed to the lack of activity with this combination. Disclosures Carlo-Stella: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Oncology: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Research Funding. Zinzani: TG Therapeutics Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ImmuneDesign: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck Sharp & Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sureda: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Casasnovas: TAKEDA: Consultancy, Research Funding; Gilead/Kite: Consultancy, Research Funding; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy; ROCHE: Consultancy, Research Funding. Carpio: Regeneron, TAKEDA, Celgene, Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travels and accommodation. Bouabdallah: Abbvie: Honoraria; Sandoz: Consultancy, Honoraria; Kite/Gilead: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Roche: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses; Takeda: Consultancy, Honoraria, Other: Travel/Accommodations/Expenses. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria. Kim: Celltrion: Research Funding; Dong-A Pharmaceutical: Research Funding; Kyowa Kirin: Research Funding; Sanofi: Research Funding; IGM Biosciences: Research Funding; Eisai: Research Funding; Johnson & Johnson: Research Funding; Roche: Research Funding. Cordoba: Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADCTherapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Koh: Pfizer: Consultancy; Jassen: Honoraria; AstraZeneca: Honoraria; Novartis: Honoraria; GSK: Honoraria; Roche: Honoraria; Takeda: Honoraria. Alves: Janssen, Cilag, Gilead, Takeda, Astrazeneca, Roche, Abbvie: Consultancy, Honoraria. Chamuleau: Gilead: Research Funding; Genmab: Research Funding; Celgene: Research Funding. Lopez-Guillermo: Roche, Gilead/Kite, Celgene, Novartis, Janssen, AbbVie, Spectrum: Consultancy, Honoraria, Research Funding. Van Der Poel: Roche, Janssen, Abbvie: Honoraria. Abbadessa: Sanofi: Current Employment. Meng: Sanofi: Current Employment. Ji: Sanofi: Current Employment. Lepine: Sanofi: Other: Contractual relationship. Saleem: Sanofi: Current Employment. Ribrag: PharmaMar: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Epizyme: Honoraria, Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; MSD Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Argen-X: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Astex Pharmaceuticals: Research Funding; Infinity Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Based on the Phase III ICARIA-MM study, isatuximab (Sarclisa) is approved in a number of countries in combination with pomalidomide and dexamethasone for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. Based on the Phase III IKEMA study, isatuximab in combination with carfilzomib and dexamethasone is approved in the United States for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy, and in the European Union for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Cemiplimab (Libtayo) is an anti-PD-1 antibody approved for the treatment of the following: 1) patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation; 2) patients with locally advanced or metastatic basal cell carcinoma previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate; and 3) patients with NSCLC and high tumor PD-L1 expression as determined by an FDA-approved test, with no EGFR, ALK, or ROS1 aberrations, and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation or metastatic.

Introduction This study aimed to describe the use of awake prone positioning (APP) and conventional oxygen therapy (COT) in patients with suspected coronavirus disease (COVID-19) and respiratory failure in a limited-resource setting. Methods This was a retrospective cohort study of hospitalized patients aged ≥18 years old who were placed in an awake prone position due to hypoxemic respiratory failure and suspected COVID-19. The patients were selected from a tertiary center in Cartagena, Colombia, between March 1, 2020, and August 31, 2020. Demographic, clinical, and laboratory variables were collated, and all the variables were compared between the groups. Results The median age of the participants was 63 (IQR, 48.8-73) years (survivors: 59 [IQR, 43.568] years vs. non-survivors: 70 [IQR, 63-78] years, P ≤ .001). Of the 1470 patients admitted for respiratory symptoms, 732 (49.8%) were hospitalized for more than 24 h, and 212 patients developed respiratory failure and required COT and APP (overall hospital mortality, 34% [73/212]). The mean rank difference in PaO2/FiO2 before and after APP was higher in the survivors than in the non-survivors (201.1-252.6, mean rank difference = 51.5, P = .001 vs. 134.1-172.4, mean rank difference = 38.28, P = .24, respectively). Conclusion While using COT in conjunction with APP can improve respiratory failure in patients with suspected COVID-19 in low-resource settings, persistent hypoxemia after APP can identify patients with higher mortality risk. More evidence is needed to establish the role of this strategy.

Aims: The emerging biliary colonization of microorganisms in patients with biliary diseases may be devastating. Recent evidence suggests that age and gender may influence changes in the microbial composition of gut microbiota. To study the relationship between these parameters on bile microbiota, we retrospectively reviewed positive bile cultures following an endoscopic retrograde cholangiopancreatography (ERCP) in a QA-certified academic surgical unit of a single institution. Methods: 449 positive bile cultures from 172 Italian patients with diseases of the biliopancreatic system hospitalized from 2006 through 2017 were investigated for aerobic, anaerobic, and fungal organisms. The patients were stratified into four age intervals (22−66, 67−74, 75−81, and 82−93 years) and followed up for five years. Results: Gram-positive bacteria (GPB) was negatively associated with age only in multivariate analysis (Rpartial = −0.114, p = 0.017), with younger patients prone to harbor GPB and older patients likely to have Gram-negative bacteria (GNB). There was a definite link with the male gender using both univariate and multivariate analysis (p < 0.001). Enterococcus spp. was the most common strain identified in patients with GPB except for patients aged 67−74 years for male (95.2%) and female (80.9%) patients. Escherichia coli and Klebsiella spp. were most frequent than others in every group analyzed. Analogous results were found for bacteria Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas spp. and Stenotrophomonas spp. apart of the 2nd quartile. Conclusions: Our study strengthens the bond of age and gender with bile microbiota composition and suggests that further investigations may be required in targeting the aging microbiome. Other studies should also focus on Mediterranean epidemiological characteristics and antibiotic resistance surveillance system strategies

Background: The association between the quantity and composition of skeletal muscle and the decline in physical function in elderly is poorly understood. Therefore, the primary aim of this cross-over study was to investigate the association between thigh intermuscular adipose tissue (IMAT) infiltration, appendicular muscle mass, and risk of fall in postmenopausal osteoporotic elder women. Second, we examined the differences in muscle mass, IMAT, and risk of fall in the same sample of older subjects after being classified as sarcopenic or nonsarcopenic on the basis of the dual-energy X-ray absorptiometry (DXA)-based Appendicular Skeletal Muscle Mass Index (ASMMI). Methods: Twenty-nine subjects (age: 72.4 ± 6.8; BMI: 23.0 ± 3.3; and T-score: −2.7 ± 0.2) completed the following clinical evaluations: (1) whole-body DXA to assess the ASMMI; (2) magnetic resonance to determine the cross-sectional muscle area (CSA) and IMAT of thigh muscles, expressed both in absolute (IMATabs) and relative (IMATrel) values; and (3) risk of fall assessment through the OAK system (Khymeia, Noventa Padovana, Italy). The existence of a correlation between the risk of fall (OAK scores, an automated version of the Brief-BESTest) and the clinical parameters (ASMMI, CSA, IMATrel, and IMATabs) was tested by the Pearson’s correlation index while data homogeneity between sarcopenic and nonsarcopenic subjects was tested through unpaired Student t tests or with the Mann-Whitney rank test. Effect sizes (ES) were used to determine the magnitude of the effect for all significant outcomes. Results: Eleven subjects were classified as sarcopenic and 18 as nonsarcopenic based on their ASMMI (cutoff value: 5.5 kg/m2). A positive correlation between OAK and CSA was observed (r2 = 0.19; p = 0.033), whereas a negative correlation between OAK and IMATrel was detected (r2 = 0.27; p = 0.009). No correlations were observed between OAK and ASMMI and between ASMMI and IMATrel. Sarcopenic subjects showed significantly lower weight (p = 0.002; ES = 1.30, large), BMI (p = 0.0003; ES = 1.82, large), CSA (p = 0.010; ES = 1.17, moderate), and IMATabs (p = 0.022; ES = 1.63, large) than nonsarcopenic individuals, whereas OAK scores and IMATrel were similar between groups. Discussion/Conclusion: Increased IMAT and lower CSA in the thigh muscles are associated with higher risk of fall while ASMMI, a value of appendicular muscle mass, was not associated with physical performance in older adults.

Aims The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry aims to study the care and outcomes of patients diagnosed with infective endocarditis (IE) and compare findings with recommendations from the 2015 ESC Clinical Practice Guidelines for the management of IE and data from the 2001 Euro Heart Survey. Methods and results Patients (n = 3116) aged over 18 years with a diagnosis of IE based on the ESC 2015 IE diagnostic criteria were prospectively identified between 1 January 2016 and 31 March 2018. Individual patient data were collected across 156 centres and 40 countries. The primary endpoint is all-cause mortality in hospital and at 1 year. Secondary endpoints are 1-year morbidity (all-cause hospitalization, any cardiac surgery, and IE relapse), the clinical, epidemiological, microbiological, and therapeutic characteristics of patients, the number and timing of non-invasive imaging techniques, and adherence to recommendations as stated in the 2015 ESC Clinical Practice Guidelines for the management of IE. Conclusion EURO-ENDO is an international registry of care and outcomes of patients hospitalized with IE which will provide insights into the contemporary profile and management of patients with this challenging disease.

Goals The present survey from the Italian Society of Digestive Endoscopy (SIED-Societa Italiana di Endoscopia Digestiva) was aimed at reporting infection control practice and outcomes at Digestive Endoscopy Units in a high-incidence area. Background Lombardy was the Italian region with the highest coronavirus disease-2019 (COVID-19) prevalence, at the end of March 2020 accounting for 20% of all worldwide deaths. Joint Gastro-Intestinal societies released recommendations for Endoscopy Units to reduce the risk of the contagion. However, there are few data from high-prevalence areas on adherence to these recommendations and on their efficacy. Methods A survey was designed by the Lombardy section of SIED to analyze (a) changes in activity and organization, (b) adherence to recommendations, (c) rate of health care professionals' (HCP) infection during the COVID-19 outbreak. Results In total, 35/61 invited centers (57.4%) participated; most modified activities were according to recommendations and had filtering face piece 2/filtering face piece 3 and water-repellent gowns available, but few had negative-pressure rooms or provided telephonic follow-up; 15% of HCPs called in sick and 6% had confirmed COVID-19. There was a trend (P=0.07) toward different confirmed COVID-19 rates among endoscopists (7.9%), nurses (6.6%), intermediate-care technicians (3.4%), and administrative personnel (2.2%). There was no correlation between the rate of sick HCPs and COVID-19 incidence in the provinces and personal protective equipment availability and use, whereas an inverse correlation with hospital volume was found. Conclusions Adherence to recommendations was rather good, though a minority were able to follow all recommendations. Confirmed COVID-19 seemed higher among endoscopists and nurses, suggesting that activities in the endoscopy rooms are at considerable viral spread risk.

Purpose The aim of this paper is to present and validate a framework for assessing healthcare facilities in low-resource settings to collect evidence and inform policies on the harmonisation, regulation and contextualised design of medical devices. Methods A literature review and focus groups with several experts of medical device design, clinical engineering, health technology assessment and management, allowed the creation of a protocol, comprising two parts: a semi-structured interview and electrical safety measures. Results Three hospitals were assessed in Benin and three in Uganda. All the health centres resulted to be facing typical challenges for low-resource settings, including the lack of funding, expertise, a well-established maintenance program, spare parts and consumables, and unreliable power supplies. Conclusion As there is a paucity of information regarding low-resource settings, the proposed framework can be used by clinical or biomedical engineers to assess and thereby propose actions for improving the conditions of healthcare settings.

OBJECTIVES This study aims to investigate the incidence and determinants of major early adverse events in low-risk patients undergoing isolated coronary artery bypass grafting (CABG). METHODS The multicentre E-CABG registry included 7352 consecutive patients who underwent isolated CABG from January 2015 to December 2016. Patients with an European System for Cardiac Operative Risk Evaluation (EuroSCORE) II of RESULTS Out of 2397 low-risk patients, 11 (0.46%) died during the index hospitalization or within 30 days from surgery. Five deaths were cardiac related, 4 of which were secondary to technical failures. We estimated that 8 out of 11 deaths were potentially preventable. Logistic regression model identified porcelain aorta [odds ratio (OR) 34.3, 95% confidence interval (CI) 1.3–346.3] and E-CABG bleeding grades 2–3 (OR 30.2, 95% CI 8.3–112.9) as independent predictors of hospital death. CONCLUSIONS Mortality and major complications, although infrequently, do occur even in low-risk patients undergoing CABG. Identification of modifiable causes of postoperative adverse events may be useful to develop preventative strategies to improve the quality of care of patients undergoing cardiac surgery. Clinical Trial Registration NCT02319083 (https://clinicaltrials.gov/ct2/show/NCT02319083).

Acute promyelocytic leukemia (APL) accounts for up to 10% of all childhood acute myeloid leukemia cases with a median age at presentation of 9–12 years and a higher incidence in Italy, China, and L...

Elderly individuals with chronic disorders tend to develop inflammaging, a condition associated with elevated levels of blood inflammatory markers, and increased susceptibility to chronic disease progression. Native and adaptive immunity are both involved in immune system senescence, kidney fibrosis and aging. The innate immune system is characterized by a limited number of receptors, constantly challenged by self and non-self stimuli. Circulating and kidney resident myeloid and lymphoid cells are all equipped with pattern recognition receptors (PRRs). Recent reports on PRRs show kidney overexpression of toll-like receptors (TLRs) in inflammaging autoimmune renal diseases, vasculitis, acute kidney injury and kidney transplant rejection. TLR upregulation leads to proinflammatory cytokine induction, fibrosis, and chronic kidney disease progression. TLR2 blockade in a murine model of renal ischemia reperfusion injury prevented the escape of natural killer cells and neutrophils by inflammaging kidney injury. Tumor necrosis factor-α blockade in endothelial cells with senescence-associated secretory phenotype significantly reduced interleukin-6 release. These findings should encourage experimental and translational clinical trials aimed at modulating renal inflammaging by native immunity blockade.

The diagnosis of coeliac disease (CD) in adult patients requires the simultaneous assessment of clinical presentation, serology, and typical histological picture of villous atrophy. However, several years ago, the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines approved new criteria for the diagnosis in children: Biopsy could be avoided when anti-transglutaminase antibody (TGA) values exceed the cut-off of × 10 upper limit of normal (ULN) and anti-endomysium antibodies are positive, independently from value. This "no biopsy" approach is a decisive need for pediatric population, allowing to avoid stressful endoscopic procedures in children, if unnecessary. This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh's classification. Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels. Therefore, we aim to perform a narrative review on the topic in adults. Despite that some studies confirmed that the × 10 ULN threshold value has a very good diagnostic performance, several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture. In conclusion, the heterogeneity of study reports as well as some conditions, which may hamper the serological diagnosis of CD (such as seronegative CD and non-celiac villous atrophy) and are much more common in adults than in children, could represent a limitation for the "no biopsy" approach to CD diagnosis in patients outside the pediatric age.

Whiteflies are sap-sucking insects responsible for high economic losses. They colonize hundreds of plant species and cause direct feeding damage and indirect damage through transmission of devastating viruses. Modern agriculture has seen a history of invasive whitefly species and populations that expand to novel regions, bringing along fierce viruses. Control efforts are hindered by fast virus transmission, insecticide-resistant populations, and a wide host range which permits large natural reservoirs for whiteflies. Augmentative biocontrol by parasitoids while effective in suppressing high population densities in greenhouses falls short when it comes to preventing virus transmission and is ineffective in the open field. A potential source of much needed novel control strategies lays within a diverse community of whitefly endosymbionts. The idea to exploit endosymbionts for whitefly control is as old as identification of these bacteria, yet it still has not come to fruition. We review where our knowledge stands on the aspects of whitefly endosymbiont evolution, biology, metabolism, multitrophic interactions, and population dynamics. We show how these insights are bringing us closer to the goal of better integrated pest management strategies. Combining most up to date understanding of whitefly–endosymbiont interactions and recent technological advances, we discuss possibilities of disrupting and manipulating whitefly endosymbionts, as well as using them for pest control.

Purpose The use of allografts in primary anterior cruciate ligament reconstruction (ACLR) is increasing although they are still supposed to be associated to greater risk of re-rupture due to a slower and less efficient graft maturation. The aim of this prospective randomized controlled study was to compare the graft maturation after ACLR with allograft and autograft by MRI at 6- and 12-month follow-up and integrate these data with the functional and clinical results observed at 6-, 12- and 60-month follow-up. Methods Fifty patients with indication to primary ACLR were randomly and equally divided into hamstring autograft or allograft tendon groups. The graft maturation was measured at 6- and 12-month follow-up by the SNQ score and other radiological parameters on MRI scans. Clinical and functional recovery was evaluated by Lysholm score, Visual Analogues Scale, Tegner activity scale and modified Cincinnati knee rating system at 6, 12 and 60 months after surgery to estimate the predictive value of the radiological parameters for clinical outcomes. Return-to-sport (ACL-RSI) was measured 60 months after surgery. Results Three patients had retear of the neo-ligament (two from Auto group and one from Allo group). All the clinical/functional parameters significantly improved over time, with no statistically significant difference between the groups. At 6 months, the SNQ value was significantly higher in the Auto than in the Allo group (12.9 vs 7.9, p = 0.038), but at 12 months they were comparable (9.8 vs 10.4). The 6-month SNQ values did not correlate with the clinical scores, whereas the 12-month SNQ values significantly correlated with the Cincinnati score, Lysholm score and Tegner activity scale collected at 60-month follow-up. Conclusion No clinical or functional differences have been found between the two treatment groups, supporting the suitability of using allograft in primary ACLR, when available. The results at MRI scans showed a different graft maturation trend in the two groups, with allografts being more reactive in the first 6 months. MRI together with the subjective evaluation allows to evaluate objectively the status of the neo-ligamentization process and therefore helps the surgeon to dictate the individual time for return-to-sport. Level of evidence Level I. Supplementary Information The online version contains supplementary material available at 10.1007/s00167-021-06785-4.

Resumen Antecedentes y objetivo La paquimeningitis hipertrofica es un proceso inflamatorio fibrosante infrecuente de la duramadre intracraneal. En la mayor parte de los casos la causa es desconocida y se denomina paquimeningitis hipertrofica idiopatica (PHI). La sintomatologia audiovestibular asociada es poco frecuente y su patogenia no esta aclarada. Materiales y metodos Se realizo una revision sistematica de literatura medica de los casos publicados de PHI asociados a sintomatologia audiovestibular desde el ano 2000 hasta febrero de 2020. Se siguieron los criterios PRISMA para revisiones sistematicas evaluando las bases de datos electronicas PubMED, Web of Science y Cochrane. Se complementa con el caso clinico de una adolescente que empezo con neuritis vestibular en el contexto de PHI atendida en nuestro servicio. Resultados Se han revisado 5 articulos con casos publicados de PHI que asociaban sintomatologia audiovestibular. Se encontraron un total de 7 casos (5 mujeres y 2 varones), con edades comprendidas entre los 27 y 68 anos, con diagnostico de PHI. El 100% presentaron sintomatologia audiovestibular. A diferencia de nuestra paciente, todos presentaron hipoacusia neurosensorial uni- o bilateral. No se ha encontrado ningun otro caso descrito de asociacion entre PHI y neuritis vestibular. El tratamiento empleado fueron los corticoides, con los que se consiguio mejoria en el 87,5% de los pacientes. Conclusiones Las manifestaciones vestibulares en el contexto de una PHI son muy poco frecuentes. La patogenesis no esta clara. La principal causa de la hipoacusia y la sintomatologia vestibular podria ser el atrapamiento de los nervios en el conducto auditivo interno con dano neuronal secundario.

The McCluskey index has been used as a tool to predict massive bleeding (6 red blood cells units) during orthotropic liver transplantation. The objective of this study is to verify its efficacy at our institution.Between May 1998 and December 2017, we performed 1216 orthotropic liver transplantations, of which 1016 had sufficient data registered with respect to hemoderivative transfusion. We divided these patients into groups based on the original study of McCluskey. This study was approved by the ethical committee of our Institution and was performed in accordance with the Declaration of Helsinki.The mean Model for End-Stage Liver Disease score in the 4 groups was 7.5 (range, 7-8) for low risk; 13 (range, 3-32) for medium risk, 17 (range, 8-41) for high risk, and 25 (range, 11-36) for very high risk (P.001). No significant differences were observed regarding body mass index or hospital stay. No differences have been found in the number of suboptimal donors among the groups. With respect to hemoderivative transfusions, we observed the following for red blood cells: 7 (range, 6-8) units for low risk; 5.5 (range, 0-74) for medium risk; 7 (range, 0-73) for high risk, and 12 (range, 5-30) for very high risk (P.001) and transfusion of plasma: 12 (range, 10-15) units for low risk; 11 (range, 0-89) for medium risk; 14 (range, 0-76) for high risk, and 13 (range, 3-30) for very high risk (P = .001).The McCluskey index is a good indicator of the risk of hemorrhage and hence the necessity of transfusion.

La linfoadenectomia cervicale e una procedura comune per il carcinoma della tiroide. Alcune delle complicanze sono congruenti con quelle della chirurgia tiroidea, in particolare lesione del nervo laringeo ricorrente e ipoparatiroidismo, nonche sanguinamento e infezione della ferita chirurgica. Complicanze specifiche della dissezione linfonodale laterocervicale sono le lesioni dei nervi accessori, frenico e ipoglosso, del tronco del plesso cervicale e ancora lesioni delle ghiandole salivari e del sistema linfatico, in particolare lesioni a carico del dotto toracico. La maggior parte di queste complicanze e molto rara, con un’incidenza inferiore all’1%. Una profonda conoscenza anatomica e un’attenta tecnica di dissezione danno un contributo decisivo alla riduzione al minimo delle complicanze.

The durability of surgical repair for degenerative versus ischemic mitral regurgitation (MR) is thought to be markedly different. We, therefore, examined late outcomes and durability for mitral repair in a large cohort of patients receiving a single annuloplasty device.A total of 749 consecutive patients receiving mitral repair for degenerative mitral regurgitation (DMR) or ischemic mitral regurgitation (IMR) were evaluated from a prospective database. Patients with tricuspid or maze surgery were included. Papillary muscle rupture and mixed valve etiologies were excluded. Outcomes were compared for IMR versus DMR.Patients with DMR were younger and less urgent. Patients with IMR had mean end-systolic diameter 4.5 ± 1.1 cm. All patients received the same complete semirigid annuloplasty device with median ring size 32 mm for DMR and 24 mm for IMR. New York Heart Association failure class improved from 2.8 to 1.5 (p .001). Patients with DMR had lower operative mortality (1/384 [0.3%] vs. 26/365 [7%], p .0001) and shorter length of stay. A 15-year survival was better with DMR (63% ± 3% vs. 13% ± 2%, p .001). At 10 years, the incidence of recurrent ≥2+ MR (10% ± 2% vs. 16% ± 2%, p = .16) was not significantly different. Predictors of recurrent ≥2+ MR were female gender (odds ratio [OR]: 3.0 (1.9-4.8, p .0001), and prior operation (OR: 2.4 [1.3-4.5], p = .02) but not IMR (OR: 1.4 [0.9-2.3], p = .15).In this series, where patients with IMR had relatively preserved ventricular dimensions, the primary determinants of late recurrent MR were female gender and prior operation but not IMR versus DMR. Selected patients with IMR can obtain relatively durable mitral repair despite higher operative risk and lower survival compared to DMR.

Sarcopenia is a progressive, generalized skeletal muscle disorder characterized by reduction of muscle mass and strength. It is associated with increased adverse outcomes including falls, fractures, physical disability, and mortality, particularly, in elderly patients. Nowadays, sarcopenia has become a specific imaging biomarker able to predict clinical outcomes of patients. Muscle fibre reduction has shown to be an unfavourable pre-operative predictive factor in patients with cancer, and is associated with worse clinical outcomes in terms of postoperative complications, morbidity, mortality, and lower tolerance of chemoradiation therapy. Several imaging modalities, including dual-energy X-ray absorptiometry, CT, MRI, and US can be used to estimate muscle mass and quality to reach the diagnosis of sarcopenia. This article reviews the clinical implications of sarcopenia, how this condition can be assessed through different imaging modalities, and future perspectives of imaging of sarcopenia.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted liver transplant (LT) activity across the world, with notable decreases in the number of donations and procedures in most Western countries, in particular throughout the first wave. The cumulative incidence of COVID-19 in LT recipients (with estimates ranging from 0.34% to 1.56%) appears to be at least comparable to that observed for the general population. Clinical and radiological features at presentation are also similar to non-transplant patients. The risk of death among LT recipients requiring hospital admission is high (from 12% to 19%), although some authors have suggested that overall mortality may be actually lower compared to the general non-transplant population. It is likely that these poor outcomes may be mainly influenced by the older age and higher comorbidity burden of LT recipients, rather than by the transplant status itself. In fact, it has been hypothesized that post-transplant immunosuppression would exert a protective role, with special focus on tacrolimus-containing regimens. There is scarce evidence to guide the optimal management of post-transplant COVID-19 and the use of antiviral or immunomodulatory therapies, although both clinical practice and guidelines support the dose reduction or withdrawal of anti-proliferative agents such as mofetil mycophenolate. Preliminary reports suggest that the antibody response to messenger RNA vaccines is significantly impaired as compared to non-immunocompromised individuals, in line with other transplant populations. Finally, it is foreseeable that the future will be conditioned by the emerging variants of severe acute respiratory syndrome coronavirus 2 with increased transmissibility among LT recipients.

Service-continuity in distributed computing can be enhanced by designing self-organized systems, with a non-fixed structure, able to modify their structure and organization, as well as adaptively react to internal and external environment changes. In this paper, an architecture exploiting a bio-inspired management approach, i.e., the functioning of cell metabolism, for specialized computing environments in Service-Oriented Networks (SONs) is proposed. Similar to the processes acting in metabolic networks, the nodes communicate to each other by means of stimulation or suppression chains giving rise to emergent behaviors to defend against foreign invaders, attacks, and malfunctioning. The main contribution of this work is a novel bio-inspired methodology for SON analysis to improve the network reliability and robustness for maintaining service-continuity. To show the effectiveness of the proposed computational framework, an embedded Field-Programmable Gate Array (FPGA) prototyped SON for a relevant healthcare imaging application is also outlined. In particular, our case study extracts and analyzes the Cerebral Vascular Tree from Magnetic Resonance Angiography series via a Maximum Intensity Projection algorithm; the proposed solution addresses and implements some basic issues of an interesting diagnosis tool for cerebral aneurysm detection. The prototyped system was tested and evaluated in terms of execution time and used resource analysis, by achieving a 4× speed-up factor compared to the software counterpart.

Background Autosomal recessive congenital ichthyoses (ARCI) are a genetically heterogeneous group of rare and chronic disorders characterized by generalized skin scaling and hyperkeratosis, erythroderma, and palmoplantar keratoderma. Additional features include ectropion, eclabium, ear deformities, foul-smell, joints contractures and walking problems, recurrent infections, as well as pruritus and pain. No curative therapy is available and disease care mainly relies on daily application of topical emollients and keratolytics to the whole-body surface. Altogether, disease signs and symptoms and treatment modalities have a major impact on quality of life of patients and their caregivers. However, very few studies have evaluated the family disease burden in ARCI. Methods We have performed an Italian multicenter cross-sectional study to assess the secondary disease impact on family members of pediatric and adult patients with ARCI, using a validated dermatology-specific questionnaire, the family dermatology life quality index (FDLQI). Disease severity was assessed by the dermatologist in each center. Results Seventy-eight out of 82 patients who were accompanied by at least one family member filled the FDLQI. Forty-eight (61.5%) patients were aged less than 18 years. The mean FDLQI score was 10.3 (median 10), and the most affected dimensions were (1) time needed for care, (2) extra-housework, and (3) household expenditure. Higher total FDLQI score significantly correlated with more severe disease score (P = 0.003). Features associated with greater family burden included recurrent infections (P = 0.004), foul-smell (P = 0.009), palmoplantar keratoderma (P = 0.041), but also presence of scales on the face (P = 0.039) and ear deformities (P = 0.016). Conclusions Our findings highlight the major socio-economic and psychological burden imposed by ARCI on the QoL of family caregivers. In addition, they show that global evaluation of disease impact also on family members is an essential part of patient-reported outcomes. Finally, our data underline the need to develop specific measures for family support.

BACKGROUND Vascular complications still represent an important issue after transcatheter aortic valve implantation (TAVI). AIMS The aim of this study was to evaluate the effectiveness of upfront use of an adjunctive Angio-Seal (AS) plug-based system on top of suture-based devices (SBDs) for endovascular haemostasis after transfemoral (TF) TAVI. METHODS From January 2019 to April 2020, 332 consecutive patients with preprocedural computed tomography angiography (CTA) assessment underwent fully percutaneous TF-TAVI. The primary outcomes were 30-day major vascular complications and major or life-threatening (LT) bleeding due to endovascular closure system failure. A total of 246 TF-TAVI patients (123 pairs), undergoing either isolated SBD or SBD+AS, were matched using the propensity-score method. RESULTS At 30 days, patients receiving SBD+AS had lower rates of major/LT bleeding (1.6% vs 8.9%, odds ratio [OR] 0.17, 95% confidence interval [CI]: 0.04-0.78; p

COVID-19 pandemic led to a worldwide increase of hospitalizations for interstitial pneumonia with thrombosis complications, endothelial injury and multiorgan disease. Common CT findings include lung bilateral infiltrates, bilateral ground-glass opacities and/or consolidation whilst no current laboratory parameter consents rapidly evaluation of COVID-19 risk and disease severity. In the present work we investigated the association of sFLT-1 and CA 15.3 with endothelial damage and pulmonary fibrosis. Serum sFlt-1 has been associated with endothelial injury and sepsis severity, CA 15.3 seems an alternative marker for KL-6 for fibrotic lung diseases and pulmonary interstitial damage. We analysed 262 SARS-CoV-2 patients with differing levels of clinical severity; we found an association of serum sFlt-1 (ROC AUC 0.902, decision threshold > 90.3 pg/mL, p p 24.8 U/mL, p

Background We applied an artificial intelligence-based model to predict fragility fractures in postmenopausal women, using different dual-energy x-ray absorptiometry (DXA) parameters. Methods One hundred seventy-four postmenopausal women without vertebral fractures (VFs) at baseline (mean age 66.3 ± 9.8) were retrospectively evaluated. Data has been collected from September 2010 to August 2018. All subjects performed a spine x-ray to assess VFs, together with lumbar and femoral DXA for bone mineral density (BMD) and the bone strain index (BSI) evaluation. Follow-up exams were performed after 3.34 ± 1.91 years. Considering the occurrence of new VFs at follow-up, two groups were created: fractured versus not-fractured. We applied an artificial neural network (ANN) analysis with a predictive tool (TWIST system) to select relevant input data from a list of 13 variables including BMD and BSI. A semantic connectivity map was built to analyse the connections among variables within the groups. For group comparisons, an independent-samples t-test was used; variables were expressed as mean ± standard deviation. Results For each patient, we evaluated a total of n = 6 exams. At follow-up, n = 69 (39.6%) women developed a VF. ANNs reached a predictive accuracy of 79.56% within the training testing procedure, with a sensitivity of 80.93% and a specificity of 78.18%. The semantic connectivity map showed that a low BSI at the total femur is connected to the absence of VFs. Conclusion We found a high performance of ANN analysis in predicting the occurrence of VFs. Femoral BSI appears as a useful DXA index to identify patients at lower risk for lumbar VFs.

Supplemental Digital Content is available in the text., Background. Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves. Methods. In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020. Results. Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53–71] versus 59 y [IQR: 49–68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157). Conclusions. We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.

Type 2 diabetes (T2DM) is known to be associated with increased cardiovascular (CV) morbidity and mortality. Over time, the CV Risk of patients with T2DM has been assessed according to various methods, often borrowed from different populations. Nevertheless, never have been evaluated changes in insulin absorption due to improper injection technique and responsible for further, well recognized CV-R factors as high glycemic variability, frequent hypoglycemia, and unsatisfactory glycemic control. Aim of the study was to intensify diabetes and its own comorbidities treatment, and in addition reduce the impact of injection technique of insulin to evaluate possible improvement in the CV-R score and NHYA score in 4499 insulin-treated T2DM subjects with (LH+) and without lipohypertrophy (LH-) due to improper injection habit. The educational training and the treatment intensification significantly reduced glycemic control, hypoglycemia rate and the mean amplitude of glycemic variability, expecially in LH+ subjects, adding new knowledge to a global intervention addressed to reduce the devastating impact to the increased cardiovascular risk of diabetic people, inclusive of the risk due to LHs

Supplemental Digital Content is available in the text., The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0–3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1–24 months postimplant and were categorized as: low TTR (10–39%), moderate TTR (40–69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.