COPD basal cells are primed towards secretory to multiciliated cell imbalance driving increased resilience to environmental stressors.

Introduction: Environmental pollutants injure the mucociliary elevator, thereby provoking disease progression in chronic obstructive pulmonary disease (COPD). Epithelial resilience mechanisms to environmental nanoparticles in health and disease are poorly characterised.

Methods: We delineated the impact of prevalent pollutants such as carbon and zinc oxide nanoparticles, on cellular function and progeny in primary human bronchial epithelial cells (pHBECs) from end-stage COPD (COPD-IV, n=4), early disease (COPD-II, n=3) and pulmonary healthy individuals (n=4).

Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage circuit of fibrogenic cell states in hPCLS.

Mass spectrometry-based autoimmune profiling reveals predictive autoantigens in idiopathic pulmonary fibrosis.

Autoimmunity plays a role in certain types of lung fibrosis, notably connective tissue disease-associated interstitial lung disease (CTD-ILD). In idiopathic pulmonary fibrosis (IPF), an incurable and fatal lung disease, diagnosis typically requires clinical exclusion of autoimmunity. However, autoantibodies of unknown significance have been detected in IPF patients.

Physical Function of RA patients Tapering Treatment-A Post Hoc Analysis of the Randomized Controlled RETRO Trial.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here, we analyzed the impact of tapering or stopping DMARD treatment on the physical function of RA patients.

Non-Oncogene Addiction of -Mutant Cancers to IL-1β via Versican and Mononuclear IKKβ.

-mutant cancers are frequent, metastatic, lethal, and largely undruggable. While interleukin (IL)-1β and nuclear factor (NF)-κB inhibition hold promise against cancer, untargeted treatments are not effective. Here, we show that human -mutant cancers are addicted to IL-1β via inflammatory versican signaling to macrophage inhibitor of NF-κB kinase (IKK) β.

The provisional OMERACT ultrasonography score for giant cell arteritis.

Objectives: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.

Methods: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds.

Transcroporal Artificial Urinary Sphincter Placement With Closure of Corporal Bodies-A Long-Term Analysis of Functional Outcomes.

Objectives: An artificial urinary sphincter (AUS) is the gold standard for postoperative stress urinary incontinence (SUI). The transcorporal AUS (TC) placement constitutes the main salvage option in high-risk patients suffering from SUI with fragile urethras. The literature analyzing long-term outcomes with respect to explantation rates, continence, and erectile function is scarce.

An In Vivo Inflammatory Loop Potentiates KRAS Blockade.

KRAS (KRAS proto-oncogene, GTPase) inhibitors perform less well than other targeted drugs in vitro and fail clinical trials. To investigate a possible reason for this, we treated human and murine tumor cells with KRAS inhibitors deltarasin (targeting phosphodiesterase-δ), cysmethynil (targeting isoprenylcysteine carboxylmethyltransferase), and AA12 (targeting KRAS), and silenced/overexpressed mutant KRAS using custom-designed vectors. We showed that -mutant tumor cells exclusively respond to KRAS blockade in vivo, because the oncogene co-opts host myeloid cells via a C-C-motif chemokine ligand 2 (CCL2)/interleukin-1 beta (IL-1β)-mediated signaling loop for sustained tumorigenicity.

KRAS signaling in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) arises from mesothelial cells lining the pleural cavity of asbestos-exposed individuals and rapidly leads to death. MPM harbors loss-of-function mutations in BAP1, NF2, CDKN2A, and TP53, but isolated deletion of these genes alone in mice does not cause MPM and mouse models of the disease are sparse. Here, we show that a proportion of human MPM harbor point mutations, copy number alterations, and overexpression of KRAS with or without TP53 changes.

Prognostic phenotypes of early-stage lung adenocarcinoma.

Background: Survival after curative resection of early-stage lung adenocarcinoma (LUAD) varies and prognostic biomarkers are urgently needed.

Methods: Large-format tissue samples from a prospective cohort of 200 patients with resected LUAD were immunophenotyped for cancer hallmarks TP53, NF1, CD45, PD-1, PCNA, TUNEL and FVIII, and were followed for a median of 2.34 (95% CI 1.

Treatment tapering and stopping in patients with rheumatoid arthritis in stable remission (RETRO): a multicentre, randomised, controlled, open-label, phase 3 trial.

Background: Owing to increasing remission rates, the management of patients with rheumatoid arthritis in sustained remission is of growing interest. The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis in stable remission to test whether remission could be retained without the need to take DMARD therapy despite an absence of symptoms.

Methods: RETRO was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, parallel-group phase 3 trial in patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation who were in sustained Disease Activity Score using 28 joints with erythrocyte sedimentation rate (ESR) remission (score <2·6 units).

Anastomoses (Superficial Cervical Ansa) Between the Cervical Plexus and Peripheral Facial Nerve Branches: Implications for Regional Anesthesia in Carotid Endarterectomies - Anatomical Study.

Purpose: Sensory innervation in the carotid triangle involves the cervical plexus, cranial nerves, and the sympathetic trunk. This innervation also applies to skin incision, including various anatomical structures with potentially different innervation, such as the skin (dermatomes), the platysma (myotomes), and the superficial layer of the cervical fascia (fasciotomes), as well as retromandibular retractor insertion (co-innervation: V, VII). The aim of this anatomical study was to develop an injection technique for carotid endarterectomies to additionally block anastomoses between the transverse cervical nerve (TCN), the cervical branch VII (CB VII), and the marginal mandibular branch VII (MMB VII).

Complete division of the pedicle of the forehead flap is possible after 1 week of engraftment in selected patients.

Background: Recent studies have demonstrated that early division of the forehead flap (FHF) is possible if angiography is performed or a remnant of the pedicle is left behind. Whether or not careful selection of patients allows for complete division of the pedicle has not been studied.

Objective: To assess if careful selection of patients allows for early complete division of the FHF.

Serious Complications After Epidural Catheter Placement: Two Case Reports.

Thoracic epidural analgesia (TEA) is a standard procedure in multimodal analgesia applied in major thoracic and abdominal surgeries. Two cases are presented with serious complications related to TEA. In both cases, earlier reaction of the treating physicians to patient-reported sensory symptoms could have prevented the complicated course.

OMERACT definition and reliability assessment of chronic ultrasound lesions of the axillary artery in giant cell arteritis.

Objectives: To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise.

Methods: A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals.

Erosive Pustular Dermatosis of the Scalp: Clinicopathological Correlation Leading to a Definition of Diagnostic Criteria.

Introduction: Erosive pustular dermatosis of the scalp (EPDS) is frequently misdiagnosed as epithelial tumor or trauma. To the authors’ knowledge, no international guidelines or consistent recommendations for treatment of EPDS exist, and histological findings often are labeled as nonspecific.

Objective: This study aimed to identify clinical and histological characteristics unique to EPDS to aid diagnosis.

Surgical treatment of proximal femoral fractures in high-risk geriatric patients under peripheral regional anesthesia : A prospective feasibility study.

Background And Objective: Due to changing demographics geriatric patients with multiple comorbidities and proximal femoral fractures are an increasing patient population. In these patient groups, peripheral regional anesthesia could become increasingly more important besides established procedures, such as neuraxial or general anesthesia. The aim of this single center feasibility study was to evaluate a combined blockade technique of the lumbosacral plexus for three predefined subgroups depending on the type of hip fracture.

Prevalence of Elbow Joint Arthritis and Enthesitis in Rheumatoid Arthritis.

Objectives: The prevalence of elbow joint arthritis in rheumatoid arthritis (RA) assessed by ultrasound has not yet been investigated.

Methods: We investigated 102 patients with RA and 50 patients without rheumatological disease. Both elbow joints were examined by ultrasound for effusion, hypervascularization, and enthesitis.

Restoration of leg length and offset correlates with trochanteric pain syndrome in total hip arthroplasty.

Persistent pain around the greater trochanter is a common complication after total hip arthroplasty. Restoration of biomechanics such as leg length, femoral und acetabular offset is crucial in THA. The purpose of this study was to evaluate postoperative differences of these parameters after THA and to analyze their association to greater trochanteric pain syndrome.