Relative effectiveness of the second booster COVID-19 vaccines against laboratory confirmed SARS-CoV-2 infection in healthcare workers: VEBIS HCW VE cohort study (1 October 2022-2 May 2023).

Introduction: Repeated COVID-19 booster vaccination was recommended in healthcare workers (HCWs) to maintain protection. We measured the relative vaccine effectiveness (rVE) of the second booster dose of COVID-19 vaccine compared to the first booster, against laboratory-confirmed SARS-CoV-2 infection in HCWs.

Methods: In a prospective cohort study among HCWs from 12 European hospitals, we collected nasopharyngeal or saliva samples at enrolment and during weekly/fortnightly follow-up between October 2022 and May 2023.

Methods of diagnosis and rehabilitation of dysphagia in patients with spinal cord injury: a systematic review.

Introduction: Latest epidemiological metrics put a global prevalence of 20.6 million people suffering from spinal cord injury (SCI), leading to a burden of functional disability, deterioration in quality of life and reduced life expectancy. A thorough statement of diagnostic methods and treatment protocols for swallowing disorders after SCI stands as a major priority to streamline patient care and cost-sharing.

3D variability analysis reveals a hidden conformational change controlling ammonia transport in human asparagine synthetase.

Advances in X-ray crystallography and cryogenic electron microscopy (cryo-EM) offer the promise of elucidating functionally relevant conformational changes that are not easily studied by other biophysical methods. Here we show that 3D variability analysis (3DVA) of the cryo-EM map for wild-type (WT) human asparagine synthetase (ASNS) identifies a functional role for the Arg-142 side chain and test this hypothesis experimentally by characterizing the R142I variant in which Arg-142 is replaced by isoleucine. Support for Arg-142 playing a role in the intramolecular translocation of ammonia between the active site of the enzyme is provided by the glutamine-dependent synthetase activity of the R142 variant relative to WT ASNS, and MD simulations provide a possible molecular mechanism for these findings.

Incidence of SARS-CoV-2 Infection Among European Healthcare Workers and Effectiveness of the First Booster COVID-19 Vaccine, VEBIS HCW Observational Cohort Study, May 2021-May 2023.

European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up.

Prediction of breast cancer Invasive Disease Events using transfer learning on clinical data as image-form.

Background And Objective: Detecting patients at high risk of occurrence of an Invasive Disease Event after a first diagnosis of breast cancer, such as recurrence, distant metastasis, contralateral tumor and second tumor, could support clinical decision-making processes in the treatment of this malignancy. Though several machine learning models analyzing both clinical and histopathological information have been developed in literature to address this task, these approaches turned out to be unsuitable for describing this problem.

Methods: In this study, we designed a novel artificial intelligence-based approach which converts clinical information into an image-form to be analyzed through Convolutional Neural Networks.

Monovalent XBB.1.5 COVID-19 vaccine effectiveness against hospitalisations and deaths during the Omicron BA.2.86/JN.1 period among older adults in seven European countries: A VEBIS-EHR network study.

Background: We aimed to estimate XBB.1.5 vaccine effectiveness (VE) against COVID-19-related hospitalizations and deaths during BA.

An Interesting Case of X-linked Hypohidrotic Ectodermal Dysplasia.

We report a case of a patient with genetic sequencing-confirmed X-linked hypohidrotic ectodermal dysplasia without the typical characteristic hair growth abnormalities with the disorder. While this patient had already received guidance from a genetic counselor about his condition, many cases of ectodermal dysplasia go underdiagnosed or misdiagnosed due to mild or atypical presentations. With gene therapies emerging, the authors hope to highlight the importance of recognizing the disorder in patients who have not yet received a diagnosis to better manage their clinical course and guide future life decisions.

Tricuspid regurgitation and heart failure: the fate of treated vs. untreated cohort in the percutaneous era.

Aims: Tricuspid regurgitation (TR) is associated with heart failure (HF) and reduced survival. Within a short-time period, transcatheter tricuspid valve repair or replacement (TTVR/TTVr) for TR has evolved from innovation to clinical reality. The present study's aim is to provide 1-year results between TR patients treated with TTVR and TTVr compared with untreated patients, in terms of cardiac survival, rehospitalization, right-side HF symptom development, and New York Heart Association (NYHA) improvement.

Gender differences in outcomes after left atrial appendage closure with Watchman FLX device: insights from the Italian-FLX registry.

Introduction: Recent studies have shown gender differences in cardiovascular outcomes after left atrial appendage closure (LAAC), highlighting different complication rates and adverse events, particularly in short-term assessments. As a result, there remains a significant knowledge gap on how these differences directly impact the efficacy and safety of LAAC procedures. The aim of this retrospective study was to investigate the clinical outcomes of LAAC in women and men using the Watchman FLX device.

Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer.

The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment.

The Effect of Upright Stance and Vision on a Cognitive Task in Elderly Subjects and Patients with Parkinson's Disease.

Standing compared to sitting enhances cognitive performance in healthy subjects. The effect of stance on cognitive performance has been addressed here in patients with Parkinson's disease (PwPD). We hypothesized that a simple cognitive task would be less enhanced in PwPD by standing with respect to sitting, because of a larger cognitive effort for maintenance of standing posture than in healthy subjects.

Effectiveness of XBB.1.5 Monovalent COVID-19 Vaccines During a Period of XBB.1.5 Dominance in EU/EEA Countries, October to November 2023: A VEBIS-EHR Network Study.

Using a common protocol across seven countries in the European Union/European Economic Area, we estimated XBB.1.5 monovalent vaccine effectiveness (VE) against COVID-19 hospitalisation and death in booster-eligible ≥ 65-year-olds, during October-November 2023.

D3/Penta 21 clinical trial design: A randomised non-inferiority trial with nested drug licensing substudy to assess dolutegravir and lamivudine fixed dose formulations for the maintenance of virological suppression in children with HIV-1 infection, aged 2 to 15 years.

Background: There is increasing interest in utilising two-drug regimens for HIV treatment with the goal of reducing toxicity and improve acceptability. The D3 trial evaluates the efficacy and safety of DTG/3TC in children and adolescents and includes a nested pharmacokinetics(PK) substudy for paediatric drug licensing.

Methods: D3 is an ongoing open-label, phase III, 96-week non-inferiority randomised controlled trial(RCT) conducted in South Africa, Spain, Thailand, Uganda and the United Kingdom.

Treatment of Thoracic SMARCA4-Deficient Undifferentiated Tumors: Where We Are and Where We Will Go.

Recently, the fifth edition of the WHO classification recognized the thoracic -deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with deficiency because of the different clinicopathological characteristics of these two diseases. SMARCA4-UT mainly occurs in young to middle-aged adults and involves a large mass compressing the tissues surrounding the mediastinum and lung parenchyma. Unfortunately, SMARCA4-UT shows a high probability of recurrence after upfront surgery as well as radiotherapy resistance; moreover, chemotherapy has low efficacy.

Explainable 3D CNN based on baseline breast DCE-MRI to give an early prediction of pathological complete response to neoadjuvant chemotherapy.

Background: So far, baseline Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) has played a key role for the application of sophisticated artificial intelligence-based models using Convolutional Neural Networks (CNNs) to extract quantitative imaging information as earlier indicators of pathological Complete Response (pCR) achievement in breast cancer patients treated with neoadjuvant chemotherapy (NAC). However, these models did not exploit the DCE-MRI exams in their full geometry as 3D volume but analysed only few individual slices independently, thus neglecting the depth information.

Method: This study aimed to develop an explainable 3D CNN, which fulfilled the task of pCR prediction before the beginning of NAC, by leveraging the 3D information of post-contrast baseline breast DCE-MRI exams.

Neck muscle spasticity in patients with disorder of consciousness: a pilot study.

Background: Disorder of consciousness (DOC) is a state of prolonged altered consciousness due to severe acquired brain injury (ABI). DOC can be differentiated into coma, unresponsive wakefulness syndrome (UWS), or minimally conscious state (MCS) depending on the behavioral features observed and their relationship to the level of consciousness. Spasticity is one of the most frequently reported medical comorbidities in DOC patients.

Mutational Analysis of Circulating Tumor DNA in Patients With Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving Palbociclib: Results From the TREnd Trial.

Purpose: To identify prognostic circulating biomarkers to cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), we performed a mutational analysis on circulating tumor DNA (ctDNA) samples from patients included in the TREnd trial, which randomly assigned patients to receive the CDK4/6i palbociclib alone or with the endocrine treatment (ET) to which they had progressed.

Methods: Forty-six patients were enrolled in this substudy. Plasma was collected before treatment (T0), after the first cycle of therapy (T1), and at the time of progression (T2).

Selective CDK7 Inhibition Suppresses Cell Cycle Progression and MYC Signaling While Enhancing Apoptosis in Therapy-resistant Estrogen Receptor-positive Breast Cancer.

Purpose: Resistance to endocrine therapy (ET) and CDK4/6 inhibitors (CDK4/6i) is a clinical challenge in estrogen receptor (ER)-positive (ER+) breast cancer. Cyclin-dependent kinase 7 (CDK7) is a candidate target in endocrine-resistant ER+ breast cancer models and selective CDK7 inhibitors (CDK7i) are in clinical development for the treatment of ER+ breast cancer. Nonetheless, the precise mechanisms responsible for the activity of CDK7i in ER+ breast cancer remain elusive.

Consolidative thoracic radiation therapy for extensive-stage small cell lung cancer in the era of first-line chemoimmunotherapy: preclinical data and a retrospective study in Southern Italy.

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses.

Relative vaccine effectiveness against COVID-19 hospitalisation in persons aged ≥ 65 years: results from a VEBIS network, Europe, October 2021 to July 2023.

To monitor relative vaccine effectiveness (rVE) against COVID-19-related hospitalisation of the first, second and third COVID-19 booster (vs complete primary vaccination), we performed monthly Cox regression models using retrospective cohorts constructed from electronic health registries in eight European countries, October 2021-July 2023. Within 12 weeks of administration, each booster showed high rVE (≥ 70% for second and third boosters). However, as of July 2023, most of the relative benefit has waned, particularly in persons ≥ 80-years-old, while some protection remained in 65-79-year-olds.

Hypothermia: Beyond the Narrative Review-The Point of View of Emergency Physicians and Medico-Legal Considerations.

Hypothermia is a widespread condition all over the world, with a high risk of mortality in pre-hospital and in-hospital settings when it is not promptly and adequately treated. In this review, we aim to describe the main specificities of the diagnosis and treatment of hypothermia through consideration of the physiological changes that occur in hypothermic patients. Hypothermia can occur due to unfavorable environmental conditions as well as internal causes, such as pathological states that result in reduced heat production, increased heat loss or ineffectiveness of the thermal regulation system.

Clinical and functional characterization of p.Gly444Ser variant: From a fetal phenotype to a previously undisclosed postnatal phenotype.

gene encodes the alpha-1 chain of type-II procollagen. Heterozygous pathogenic variants are associated with the broad clinical spectrum of genetic diseases known as type-II collagenopathies. We aimed to characterize the NM_001844.