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Background and Objectives: The prognostic impact of ventricular fibrillation (VF) recurrences after a successful shock in out-of-hospital cardiac arrest (OOHCA) is still poorly understood, and some evidence suggests a potential pro-arrhythmic effect of chest compressions in this setting. In the present analysis, we looked at the short-term and long-term prognosis of VF recurrences in OOHCA. And their potential association with chest compressions. Materials and Methods: The Progetto Vita, prospectively collecting data on all resuscitation efforts in the Piacenza province (Italy), was used for the present analysis. From the 461 OOHCAs found in a shockable rhythm, only those with optimal ECG tracings and good audio recordings (160) were assessed. Rhythms other than VF post-shock were analyzed five seconds after shock delivery and survival to hospital admission, hospital discharge, and long-term survival data over a 14-year follow-up were collected. Results: Population mean age was 64.4 ± 16.9 years, and 31.9% of all patients were female. Mean time to EMS arrival was 5.9 ± 4.5 min. Short- and long-term survival without neurological impairment were higher in patients without VF recurrence when compared to patients with VF recurrence, independently from the pre-induction rhythm (p < 0.001). After shock delivery, VF recurrence was higher when chest compressions were resumed early after discharge and more vigorously. Conclusions: VF recurrences after a shock could worsen short and long-term survival. The potential pro-arrhythmic effect of chest compressions should be factored in when considering the real risks and benefits of this procedure.

The most relevant manifestation of coronavirus disease 2019 (COVID-19) is interstitial pneumonia. Several lung ultrasound (US) protocols for pneumonia diagnosis are used in clinical practice, but none has been proposed for COVID-19 patients’ screening in the emergency department. We adopted a simplified 6-scan lung US protocol for COVID-19 pneumonia diagnosis (LUSCOP) and compared its sensitivity with high resolution computed tomography (HRCT) in patients suspected for COVID-19, presenting to one Emergency Department from February 21st to March 15th, 2020, during the outbreak burst in northern Italy. Patients were retrospectively enrolled if both LUSCOP protocol and HRCT were performed in the Emergency Department. The sensitivity of LUSCOP protocol and HRCT were compared. COVID-19 pneumonia's final diagnosis was based on real-time reverse-transcription polymerase chain reaction from nasal-pharyngeal swab and on clinical data. Out of 150 suspected COVID-19 patients, 131 were included in the study, and 130 had a final diagnosis of COVID-19 pneumonia. The most frequent lung ultrasonographic features were: bilateral B-pattern in 101 patients (77%), B-pattern with subpleural consolidations in 26 (19.8%) and lung consolidations in 2 (1.5%). LUSCOP Protocol was consistent with HRCT in correctly screening 130 out of the 131 COVID-19 pneumonia cases (99.2%). In one case COVID-19 pneumonia was excluded by both HRCT and lung US. LUSCOP protocol showed optimal sensitivity and can be proposed as a simple screening tool for COVID-19 pneumonia diagnosis in the context of outbreak burst areas where prompt isolation of suspected patients is crucial for patients’ and operators’ safety.

Central nervous system lymphomas (CNSL) are a heterogeneous group of generally aggressive tumors whose prognosis varies significantly, being more favorable in patients with primary disease and poorer in those with secondary lymphoma. Current treatments typically involve intensive chemotherapy followed by consolidation with autologous stem cell transplantation or whole-brain radiotherapy. However, if the disease relapses, there is no established standard of care. The recent approval of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for systemic B-cell lymphomas has shifted the treatment landscape for previously incurable patients. Even though this therapy was initially underexplored in the setting of CNSL due to safety and efficacy concerns, it could offer a new therapeutic avenue for these patients. In this review, we will provide a concise overview of the current treatment strategies for CNSL, highlighting their key limitations, including relapse rates and long-term toxicity. Following this, we will explore the most important studies and clinical trials on CNSL, focusing on recent advancements in anti-CD19 CAR T-cell therapy. This comprehensive analysis will offer insights into the successes and challenges of treating CNSL effectively.

ObjectiveSudden cardiac arrest (SCA) is a rare but tragic event during amateur sports activities. Our aim is to analyse whether availability of automated external defibrillators (AEDs) in amateur sports centres could impact on SCA survival.MethodsThis is an observational study. During an 18-year period, data regarding exercise-related SCA in sports centres were prospectively collected. Survival rates and time to response were compared between centres with an AED already available and centres where an AED was not already present.ResultsOut of 252 sports facilities, 207 (82%) acquired an AED during follow-up while 45 (18%) did not. From 1999 to 2014, there were 26 SCAs (24 (92%) men, 54±17 years old) with 15 (58%) of them in centres with on-site AED. Neurologically intact survival rates were 93% in centres with on-site AED and 9% in centres without (P<0.001). Presence of on-site AED, presence of shockable rhythm, first assistance by a lay bystander and time to defibrillation were all related to neurological intact survival, but the presence of on-site AED was the only independent predictor in the multivariate analysis. The use of on-site AED resulted in a lower time to first shock when compared with emergency medical system-delivered AED (3.3±1.4min vs 7.3±3.2 min; P=0.001).ConclusionsThe presence of on-site AEDs is associated with neurologically intact survival after an exercise-related SCA. Continuous efforts are recommended in order to introduce AEDs in sports and fitness centres, implement educational programmes and increase common awareness about SCA.

Pediatric cardiac arrest (PCA), although rare, is associated with high mortality. Deviations from international management guidelines are frequent and associated with poorer outcomes. Different strategies/devices have been developed to improve the management of cardiac arrest, including cognitive aids. However, there is very limited experience on the usefulness of interactive cognitive aids in the format of an app in PCA. No app has so far been tested for its usability and effectiveness in guiding the management of PCA. To develop a new audiovisual interactive app for tablets, named PediAppRREST, to support the management of PCA and to test its usability in a high-fidelity simulation-based setting. A research team at the University of Padova (Italy) and human-machine interface designers, as well as app developers, from an Italian company (RE:Lab S.r.l.) developed the app between March and October 2019, by applying an iterative design approach (ie, design-prototyping-evaluation iterative loops). In October-November 2019, a single-center nonrandomized controlled simulation-based pilot study was conducted including 48 pediatric residents divided into teams of 3. The same nonshockable PCA scenario was managed by 11 teams with and 5 without the app. The app user's experience and interaction patterns were documented through video recording of scenarios, debriefing sessions, and questionnaires. App usability was evaluated with the User Experience Questionnaire (UEQ) (scores range from -3 to +3 for each scale) and open-ended questions, whereas participants' workload was measured using the NASA Raw-Task Load Index (NASA RTLX). Users' difficulties in interacting with the app during the simulations were identified using a structured framework. The app usability, in terms of mean UEQ scores, was as follows: attractiveness 1.71 (SD 1.43), perspicuity 1.75 (SD 0.88), efficiency 1.93 (SD 0.93), dependability 1.57 (SD 1.10), stimulation 1.60 (SD 1.33), and novelty 2.21 (SD 0.74). Team leaders' perceived workload was comparable (P=.57) between the 2 groups; median NASA RTLX score was 67.5 (interquartile range [IQR] 65.0-81.7) for the control group and 66.7 (IQR 54.2-76.7) for the intervention group. A preliminary evaluation of the effectiveness of the app in reducing deviations from guidelines showed that median time to epinephrine administration was significantly longer in the group that used the app compared with the control group (254 seconds versus 165 seconds; P=.015). The PediAppRREST app received a good usability evaluation and did not appear to increase team leaders' workload. Based on the feedback collected from the participants and the preliminary results of the evaluation of its effects on the management of the simulated scenario, the app has been further refined. The effectiveness of the new version of the app in reducing deviations from guidelines recommendations in the management of PCA and its impact on time to critical actions will be evaluated in an upcoming multicenter simulation-based randomized controlled trial.

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen−) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen−. Sixteen Gen+/Phen− (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH−) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (−19.8 ± 0.4 vs. −22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen− subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment.

High-risk Human Papillomavirus (HPV) infection is the main etiological factor for cervical carcinogenesis, although genetic cofactors also play a role. Single-nucleotide variants (SNVs) in the CTLA4 gene can alter the gene expression and immune response against HPV, influencing cervical malignancy progression. This study analyzed the association of the alleles, genotypes, and haplotypes of the CTLA4 SNVs rs5742909 (−318 C>T), rs231775 (+49 A>G), and rs3087243 (+6230 G>A) with HPV infection, the development of low-grade squamous intraepithelial lesions (LSILs), high-grade squamous intraepithelial lesions (HSILs), and cervical cancer in 445 women treated by the public health service of Paraná, Brazil. Peripheral blood and cervical secretion samples were collected for genomic DNA extraction, CTLA4 SNV genotyping, and HPV detection via PCR. Statistical analyses used p < 0.05. The HPV-negative control group included 181 women, while the HPV-positive group included 264 women. The HPV-positive group was divided into no lesion (n = 84), LSILs (n = 19), HSILs (n = 56), and cervical cancer (n = 105). The T allele of −318 C>T and the TAG haplotype were associated with increased susceptibility to HPV infection, HSILs, and cervical cancer. These findings suggest that the T allele of −318 C>T and the TAG haplotype may serve as potential molecular biomarkers for HPV susceptibility and worse prognosis.

Total bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa has been challenging. Previously proposed markers were shown to be co-expressed by different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cultured holoclones, identifying Paired Like Homeodomain 2 (PITX2) as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up corneal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors that were differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of transplanted corneas.

A pump as turbine (PAT) can be a cost-effective and versatile solution to recover energy in several fields of application. However, its optimal exploitation requires a reliable and general methodology for selecting the optimal turbomachine. To this purpose, this paper presents and validates a comprehensive methodology that identifies the best turbomachine (i.e., the one that maximizes the recovered energy) by considering two hydraulic sites and forty-five PATs. In both sites, the methodology correctly identifies the best PAT, which allows for the recovery of up to 45% of the available hydraulic energy. To further investigate PAT potential, an additional layout of installation, which comprises two PATs installed in parallel, is also considered. The operation of both PATs is optimally scheduled to maximize energy recovery. As a result, the energy recovered by the best pair of PATs is almost 50% of the available hydraulic energy. An in-depth analysis about PAT operation (i.e., operating range, causes of wasted energy, timeframe of operation and PAT efficiency) reveals that the installation of two PATs is actually recommended in just one of the two considered sites.