Effect of diagnosis level of certainty on adherence to antibiotics' guidelines in ED patients with pneumonia: a post-hoc analysis of an interventional trial.

Background And Importance: Clinical diagnosis of community-acquired pneumonia (CAP) is difficult to establish with certainty. Adherence to antibiotic guidelines independently affects the prognosis of CAP patients.

Objective: We aimed to determine whether guidelines' adherence was related to CAP diagnosis level of certainty and could be reinforced accordingly to diagnosis improvement.

Abdominal Organ Transplantation: Noteworthy Literature in 2021.

This review highlights noteworthy literature pertinent to anesthesiologists and critical care physicians caring for patients undergoing abdominal organ transplantation. In 2021, we identified noteworthy papers from over 1,200 peer-reviewed publications on pancreatic transplantation, over 1,400 on intestinal transplantation, and over 9,000 on kidney transplantation. The liver transplantation section focuses on clinical trials and systematic reviews and meta-analyses published in 2021 and features 20 selected papers.

Management of moderate to severe traumatic brain injury: an update for the intensivist.

Traumatic brain injury (TBI) remains one of the most fatal and debilitating conditions in the world. Current clinical management in severe TBI patients is mainly concerned with reducing secondary insults and optimizing the balance between substrate delivery and consumption. Over the past decades, multimodality monitoring has become more widely available, and clinical management protocols have been published that recommend potential interventions to correct pathophysiological derangements.

Liver transplantation from active COVID-19 donors: Is it ethically justifiable?

The debate on the opportunity to use organs from donors testing positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in recipients with naïve resolved or active COVID-19 is ongoing. We aim to present the ethical analyses underlying the decision to perform liver transplantation (LT) in selected patients with resolved or active COVID-19 in Italy. We used Jonsen, Siegler, and Winslade's Four-Boxes casuistic method, addressing the four topics considered as constitutive of the essential structure of single clinical cases for their ethical analysis (medical indications, patient preferences, quality of life, and contextual features) to enable decision-making on a case-by-case basis.

Evaluation of a Gel Containing a Extract in an In Vivo Model of Wound Healing.

Inappropriate wound healing (WH) management can cause significant comorbidities, especially in patients affected by chronic and metabolic diseases, such as diabetes. WH involves several different, partially overlapping processes, including hemostasis, inflammation, cell proliferation, and remodeling. Oxidative stress in WH contributes to WH impairment because of the overexpression of radical oxygen species (ROS) and nitrogen species (RNS).

Paracrine signalling between intestinal epithelial and tumour cells induces a regenerative programme.

Tumours are complex ecosystems composed of different types of cells that communicate and influence each other. While the critical role of stromal cells in affecting tumour growth is well established, the impact of mutant cancer cells on healthy surrounding tissues remains poorly defined. Here, using mouse intestinal organoids, we uncover a paracrine mechanism by which intestinal cancer cells reactivate foetal and regenerative YAP-associated transcriptional programmes in neighbouring wildtype epithelial cells, rendering them adapted to thrive in the tumour context.

Anomalously high abundance of Crocosphaera in the South Pacific Gyre.

The unicellular diazotrophic cyanobacterium Crocosphaera contributes significantly to fixed nitrogen inputs in the oligotrophic ocean. In the western tropical South Pacific Ocean (WTSP), these diazotrophs abound thanks to the phosphorus-rich waters provided by the South Equatorial Current, and iron provided aeolian and subsurface volcanic activity. East of the WTSP, the South Pacific Gyre (SPG) harbors the most oligotrophic and transparent waters of the world's oceans, where only heterotrophic diazotrophs have been reported before.

Ultra-minimally invasive surgery in gynecological patients: a review of the literature.

In the last decade, Ultra-minimally invasive surgery (UMIS) including both minilaparoscopic (MH) and percutaneous (PH) endoscopic surgery achieved widespread use around the world. Despite UMIS has been reported as safe and feasible surgical procedure, most of the available data are drawn from retrospective studies, with a limited number of cases and heterogeneous surgical procedures included in the analysis. This literature review aimed to analyze the most methodologically valid studies concerning major gynecological surgeries performed in UMIS.

Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

Aims: To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19).

Methods: A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19.

Phase I Study of Safety, Tolerability, and Efficacy of Tebentafusp Using a Step-Up Dosing Regimen and Expansion in Patients With Metastatic Uveal Melanoma.

Purpose: This phase I study aimed to define the recommended phase II dose (RP2D) of tebentafusp, a first-in-class T-cell receptor/anti-CD3 bispecific protein, using a three-week step-up dosing regimen, and to assess its safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity in patients with metastatic uveal melanoma (mUM).

Methods: In this open-label, international, phase I/II study, HLA-A*02 or HLA-A*02:01+ patients with mUM received tebentafusp 20 μg once in week 1 and 30 μg once in week 2. Dose escalation (starting at 54 μg) began at week 3 in a standard 3 + 3 design to define RP2D.

Association between FIASMA psychotropic medications and reduced risk of intubation or death in individuals with psychiatric disorders hospitalized for severe COVID-19: an observational multicenter study.

The acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications functionally inhibiting the acid sphingomyelinase/ceramide system (named FIASMA psychotropic medications) against COVID-19. We examined the potential usefulness of FIASMA psychotropic medications in patients with psychiatric disorders hospitalized for severe COVID-19, in an observational multicenter study conducted at Greater Paris University hospitals. Of 545 adult inpatients, 164 (30.

Multidimensional Fluorescence Imaging of Embryonic and Postnatal Mammary Gland Development.

Multidimensional fluorescence imaging represents a powerful approach for studying the dynamic cellular processes underpinning the development, function, and maintenance of the mammary gland. Here, we describe key multidimensional imaging strategies that enable visualization of mammary branching morphogenesis and epithelial cell fate dynamics during postnatal and embryonic mammary gland development. These include 4-dimensional intravital microscopy and ex vivo imaging of embryonic mammary cultures, in addition to methods that facilitate 3-dimensional imaging of the ductal epithelium at single-cell resolution within its native stroma.

Evolution of flowering time in a selfing annual plant: Roles of adaptation and genetic drift.

Resurrection studies are a useful tool to measure how phenotypic traits have changed in populations through time. If these trait modifications correlate with the environmental changes that occurred during the time period, it suggests that the phenotypic changes could be a response to selection. Selfing, through its reduction of effective size, could challenge the ability of a population to adapt to environmental changes.

Coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy.

Objective: To assess the relation between coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy.

Methods: Cross-sectional analysis of data collected in the SAVE study, which included patients with drug-resistant focal epilepsy during long-term EEG monitoring. Patients in whom both coffee consumption and data about seizure frequency, including focal to bilateral tonic-clonic seizures (FBTCS), were available were selected.

Relevance of biopsy-derived pancreatic organoids in the development of efficient transcriptomic signatures to predict adjuvant chemosensitivity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) patients are frequently treated by chemotherapy. Even if personalized therapy based on molecular analysis can be performed for some tumors, PDAC regimens selection is still mainly based on patients' performance status and expected efficacy. Therefore, the establishment of molecular predictors of chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments.

%TTD and %TUDD: New SAS macro programs to calculate the survival data of the time to deterioration for patient-reported outcomes data in oncology.

Background And Objective: Longitudinal analysis of patient-reported outcome (PRO) data remains challenging, as no standardization of statistical methods has been proposed, making comparison of PRO results between clinical trials difficult. In this context, the time to deterioration approach has recently been proposed and is regularly used as a modality of longitudinal PRO analysis in oncology.

Methods: Two new SAS macro programs were developed, %TTD and %TUDD, which implement longitudinal analysis of PRO data according to the time to deterioration approach.

Prognostic value of circulating tumour DNA in metastatic pancreatic cancer patients: post-hoc analyses of two clinical trials.

Objective: The prognostication of metastatic pancreatic adenocarcinoma (mPDAC) patients remains uncertain, mainly based on carbohydrate antigen 19-9 (CA19-9), with limited utility. Circulating tumour DNA (ctDNA) has been suggested as a prognostic factor, but its added value has been poorly explored. The objective was to determine whether ctDNA is an independent factor for the prognostication of mPDAC.

The Development and Implementation of an Autopsy/ Tissue Donation for Breast Cancer Research.

There is growing interest in tissue procurement for cancer research through autopsy. Establishing an autopsy/tissue donation programme for breast cancer research within an academic medical centre in the United States requires consideration, planning, multi-departmental collaboration and labour-intensive maintenance. It is the purpose of this paper to outline the necessary considerations in implementing and maintaining a tissue donation and autopsy programme within a breast cancer centre at a comprehensive cancer centre.

Evolution of Multicellularity.

The emergence of multicellular organisms was, perhaps, the most spectacular of the major transitions during the evolutionary history of life on this planet [...

Updates in Systemic Sclerosis Treatment and Applicability to Pediatric Scleroderma.

Juvenile-onset systemic sclerosis (jSSc) is a complex multisystem inflammatory-driven disease of fibrosis, requiring multifaceted treatment including pharmacologic therapy, supportive care, and lifestyle modification. Most regimens are adapted from adult SSc treatment given the rarity of the disease. Landmark trials over the past decade in adult SSc have led to 2 Food and Drug Administration-approved therapies for SSc-associated interstitial lung disease, and several ongoing trials of other biological agents are underway.

The use of normothermic machine perfusion to rescue liver allografts from expanded criteria donors.

The use of expanded criteria donors is one of the strategies used to overcome the gap between the demand for organs and the number of donors. Physicians debate the extent to which marginal grafts can be used. In recent years, normothermic machine perfusion (NMP) has been used to test liver viability before transplantation.