Structural basis for the inhibition of βFXIIa by garadacimab.

Activated FXII (FXIIa) is the principal initiator of the plasma contact system and can activate both procoagulant and proinflammatory pathways. Its activity is important in the pathophysiology of hereditary angioedema (HAE). Here, we describe a high-resolution cryoelectron microscopy (cryo-EM) structure of the beta-chain from FXIIa (βFXIIa) complexed with the Fab fragment of garadacimab.

Management of post-Mohs surgical wounds with a hypothermically stored amniotic membrane: a case series.

Objective: The aim of this case series is to present an alternative approach to managing post-Mohs Micrographic Surgery (Mohs) wounds with hypothermically stored amniotic membrane (HSAM).

Method: A case series of patients with post-Mohs wounds is presented, with four patients referred for hard-to-heal wounds following a Mohs procedure that was performed 1-3 months previously. All wounds underwent weekly assessment, debridement, and application of HSAM and secondary dressings.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer-Accredited Facilities in the United States.

Purpose: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials.

Methods: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs.

Lysholm and KOOS QoL Demonstrate High Responsiveness in Patients Undergoing Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Background: There have been a large number of patient-reported outcome measures (PROMs) used to assess outcomes after anterior cruciate ligament (ACL) reconstruction (ACLR).

Purpose/hypothesis: The purpose was to determine which PROMs are being commonly used in randomized clinical trials (RCTs) to assess patients undergoing ACLR and to compare the responsiveness between them. It was hypothesized that the International Knee Documentation Committee (IKDC) score would be the most commonly used and responsive PROM among patients undergoing ACLR.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

Objective: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups.

Methods: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied.

Orthopaedic Sports Medicine Randomized Controlled Trials Infrequently Report on the Social Determinants of Health Factors of Their Patient Cohorts.

Purpose: To describe the prevalence of randomized controlled trials (RCTs) in orthopaedic sports medicine-related journals reporting on the social determinants of health (SDOH) of their patient cohorts, including factors receiving less attention, such as education level, employment status, insurance status, and socioeconomic status.

Methods: The PubMed/MEDLINE database was used to search for RCTs between 2020 and 2022 from 3 high-impact orthopaedic sports medicine-related journals: American Journal of Sports Medicine, Arthroscopy, and Journal of Shoulder and Elbow Surgery. The following information was extracted from each article: age, sex/gender, body mass index, year published, corresponding author country, and self-reported SDOH factors (race, ethnicity, education level, employment status, insurance status, and socioeconomic status).

C-terminal variants in CDC42 drive type I interferon-dependent autoinflammation in NOCARH syndrome reversible by ruxolitinib.

C-terminal variants in CDC42 encoding cell division control protein 42 homolog underlie neonatal-onset cytopenia, autoinflammation, rash, and hemophagocytic lymphohistiocytosis (NOCARH). Pyrin inflammasome hyperactivation has been shown to contribute to disease pathophysiology. However, mortality of NOCARH patients remains high despite inflammasome-focused treatments.

KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing.

KRAS is the most commonly mutated oncogene in advanced, non-squamous, non-small cell lung cancer (NSCLC) in Western countries. Of the various KRAS mutants, KRAS G12C is the most common variant (~40%), representing 10-13% of advanced non-squamous NSCLC. Recent regulatory approvals of the KRAS-selective inhibitors sotorasib and adagrasib for patients with advanced or metastatic NSCLC harboring KRASG12C have transformed KRAS into a druggable target.

Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

Background: It has been reported that people with COVID-19 and pre-existing autoantibodies against type I interferons are likely to develop an inflammatory cytokine storm responsible for severe respiratory symptoms. Since interleukin 6 (IL-6) is one of the cytokines released during this inflammatory process, IL-6 blocking agents have been used for treating people with severe COVID-19.

Objectives: To update the evidence on the effectiveness and safety of IL-6 blocking agents compared to standard care alone or to a placebo for people with COVID-19.

Comprehensive Analyses of Coagulation Parameters in Patients with Vascular Anomalies.

Background: Vascular anomalies comprise a diverse group of rare diseases with altered blood flow and are often associated with coagulation disorders. The most common example is a localized intravascular coagulopathy in venous malformations leading to elevated D-dimers. In severe cases, this may progress to a disseminated intravascular coagulopathy with subsequent consumption of fibrinogen and thrombocytes predisposing to serious bleeding.

Transparency and reporting characteristics of COVID-19 randomized controlled trials.

Background: In the context of the COVID-19 pandemic, randomized controlled trials (RCTs) are essential to support clinical decision-making. We aimed (1) to assess and compare the reporting characteristics of RCTs between preprints and peer-reviewed publications and (2) to assess whether reporting improves after the peer review process for all preprints subsequently published in peer-reviewed journals.

Methods: We searched the Cochrane COVID-19 Study Register and L·OVE COVID-19 platform to identify all reports of RCTs assessing pharmacological treatments of COVID-19, up to May 2021.

Visual performance, safety and patient satisfaction after bilateral implantation of a trifocal intraocular lens in presbyopic patients without cataract.

Background: The aim was to evaluate the safety and efficacy of a trifocal intraocular lens (IOL) for the correction of presbyopia and to assess patient satisfaction.

Methods: Records from three centres were reviewed to select presbyopic patients having undergone bilateral refractive lens exchange and implantation of the AT LISA tri 839MP multifocal IOL. Postoperatively, monocular and binocular distance, intermediate and near visual acuities, corrected and uncorrected, and subjective refraction were measured.

Contact sensitization to iron: A potentially underestimated metal allergen and elicitor of complications in patients with metal implants.

Background: Little is known about sensitization to iron (Fe) in private, occupational, and medical settings, particulary implantology.

Objectives: To investigate sensitization to metals, particularly to Fe, both in pre-implant individuals with presumed metal allergy and in patients with suspected metal implant allergy. To further characterize Fe-sensitized individuals.

Interleukin-1 blocking agents for treating COVID-19.

Background: Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be beneficial in people with COVID-19.

Objectives: To assess the effects of IL-1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID-19. We will update this assessment regularly.

Lethal and sublethal effects of insecticides on the survival and reproduction of Brevipalpus yothersi (Acari: Tenuipalpidae).

The overuse of insecticides to control vector insects such as Diaphorina citri Kuwayama in citrus groves has altered the population dynamics of pest mites. Among phytophagous mites, population outbreaks of citrus leprosis mite, Brevipalpus yothersi Baker, have been increasingly intense and frequent in Brazilian citrus groves. Despite the great importance of the B.

A structural model of a Ras-Raf signalosome.

The protein K-Ras functions as a molecular switch in signaling pathways regulating cell growth. In the human mitogen-activated protein kinase (MAPK) pathway, which is implicated in many cancers, multiple K-Ras proteins are thought to assemble at the cell membrane with Ras effector proteins from the Raf family. Here we propose an atomistic structural model for such an assembly.

[Impact of the Covid-19 pandemic on psychological disorders in adolescents and young adults].

The current pandemic and its economic and social consequences increase the stress of young people and their families. For the most vulnerable young people, this situation of increased or cumulative stress may be a risk factor for the emergence or relapse of psychological disorders. In this article, we propose a brief literature review of the research published on this issue since the emergence of the crisis put in perspective of local observations and possible interventions for practitioners.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020.

Kidney Transplantation From Hepatitis C Viremic Deceased Donors to Aviremic Recipients in a Real-world Setting.

Unlabelled: Transplantation of hepatitis C viremic (HCV+) deceased donor kidney transplants (DDKT) into aviremic (HCV-) recipients is a strategy to increase organ utilization. However, there are concerns around inferior recipient outcomes due to delayed initiation of direct-acting antiviral (DAA) therapy and sustained HCV replication when implemented outside of a research setting.

Methods: This was a retrospective single-center matched cohort study of DDKT recipients of HCV+ donors (cases) who were matched 1:1 to recipients of HCV- donors (comparators) by age, gender, race, presence of diabetes, kidney donor profile index, and calculated panel-reactive antibody.

Ancient and modern genomes unravel the evolutionary history of the rhinoceros family.

Only five species of the once-diverse Rhinocerotidae remain, making the reconstruction of their evolutionary history a challenge to biologists since Darwin. We sequenced genomes from five rhinoceros species (three extinct and two living), which we compared to existing data from the remaining three living species and a range of outgroups. We identify an early divergence between extant African and Eurasian lineages, resolving a key debate regarding the phylogeny of extant rhinoceroses.