Differential Diagnosis of Suspected Chronic Obstructive Pulmonary Disease Exacerbations in the Acute Care Setting: Best Practice.

Patients with chronic obstructive pulmonary disease (COPD) may suffer from acute episodes of worsening dyspnea, often associated with increased cough, sputum, and/or sputum purulence. These exacerbations of COPD (ECOPDs) impact health status, accelerate lung function decline, and increase the risk of hospitalization. Importantly, close to 20% of patients are readmitted within 30 days after hospital discharge, with great cost to the person and society.

Deep learning for the detection of anatomical tissue structures and neoplasms of the skin on scanned histopathological tissue sections.

Basal cell carcinoma (BCC), squamous cell carcinoma (SqCC) and melanoma are among the most common cancer types. Correct diagnosis based on histological evaluation after biopsy or excision is paramount for adequate therapy stratification. Deep learning on histological slides has been suggested to complement and improve routine diagnostics, but publicly available curated and annotated data and usable models trained to distinguish common skin tumors are rare and often lack heterogeneous non-tumor categories.

Trajectories of cough without a cold in early childhood and associations with atopic diseases.

Background: Although children can frequently experience a cough that affects their quality of life, few epidemiological studies have explored cough without a cold during childhood.

Objectives: The objective of the study was to describe the latent class trajectories of cough from one to 10 years old and analyse their association with wheezing, atopy and allergic diseases.

Methods: Questions about cough, wheeze and allergic diseases were asked at 1, 1.

Is Zn the new Ca for TRPC6 channels in the myocardium?

Transient Receptor Potential (TRP) channels are nonselective cation channels, which are mainly permeable to Ca and Na but many of them are also permeable to Zn. In a new elegant study, a Zn-dependent pathway involving the TRP member TRPC6 and α1- as well as β-adrenoceptors (AR) was dissected in rodent myocytes. Norepinephrine-mediated activation of α1-AR induces Zn influx through TRPC6 channels, which reinforces β-AR-mediated positive inotropy and may help patients with heart failure.

Feasibility of flow-related enhancement brain perfusion MRI.

Purpose: Brain perfusion imaging is of enormous importance for various neurological diseases. Fast gradient-echo sequences offering flow-related enhancement (FREE) could present a basis to generate perfusion-weighted maps. In this study, we obtained perfusion-weighted maps without contrast media by a previously described postprocessing algorithm from the field of functional lung MRI.

Reduced humoral but stable cellular SARS-CoV-2-specific immunity in liver transplant recipients in the first year after COVID-19.

Mortality due to COVID-19 is not increased in immunosuppressed individuals after liver transplantation (OLT) compared to individuals without immunosuppression. Data on long-term protective immunity against SARS-CoV-2 in immunosuppressed convalescents, is limited. We prospectively measured immune responses against SARS-CoV-2 by quantifying antibodies against 4 different antigens (spike protein 1 and 2, receptor binding domain, nucleocapsid) and T cell responses by IFN-γ ELISPOT against 4 antigens (membrane, nucleocapsid, spike protein 1 and 2) in 24 OLT convalescents with immunosuppressive therapy longitudinally in the first year after COVID-19 including a booster vaccination in comparison to a matched cohort of non-immunosuppressed convalescents (non-IS-Con).

Costs of Pharmacological and Non-Pharmacological Interventions in Interstitial Lung Disease Management in Germany.

Introduction: Interstitial lung diseases (ILDs) are associated with a high economic burden, yet prospective data of the German healthcare system are sparse.

Objective: We assessed average ILD-related costs of pharmacological and non-pharmacological (hospitalizations, outpatient, rehabilitation, physiotherapy, and medical aids) interventions in ILD.

Methods: We used data from the multicenter, observational, prospective Exploring Clinical and Epidemiological Characteristics of Interstitial Lung Diseases registry to evaluate adjusted per capita costs and cost drivers for ILD-related healthcare costs over 4 years, using generalized estimating equation regression models.

Evaluation of image registration algorithms for 3D phase-resolved functional lung ventilation magnetic resonance imaging in healthy volunteers and chronic obstructive pulmonary disease patients.

The purpose of the current study was to assess the influence of the registration algorithms on the repeatability of three-dimensional (3D) phase-resolved functional lung (PREFUL) ventilation magnetic resonance imaging (MRI). Twenty-three healthy volunteers and 10 patients with chronic obstructive pulmonary disease (COPD) underwent 3D PREFUL MRI during tidal breathing. The registration of dynamically acquired data to a fixed image was executed using single-step, stepwise, and group-oriented registration (GOREG) approaches.

Comparing outcomes of ILD patients managed in specialised versus non-specialised centres.

Background: Early appropriate diagnosis and treatment of interstitial lung diseases (ILD) is crucial to slow disease progression and improve survival. Yet it is unknown whether initial management in an expert centre is associated with improved outcomes. Therefore, we assessed mortality, hospitalisations and health care costs of ILD patients initially diagnosed and managed in specialised ILD centres versus non-specialised centres and explored differences in pharmaceutical treatment patterns.

The pulmonary vasculature in lethal COVID-19 and idiopathic pulmonary fibrosis at single-cell resolution.

Aims: Severe acute respiratory syndrome coronavirus-2 infection causes COVID-19, which in severe cases evokes life-threatening acute respiratory distress syndrome (ARDS). Transcriptome signatures and the functional relevance of non-vascular cell types (e.g.

Maternal and perinatal obesity induce bronchial obstruction and pulmonary hypertension via IL-6-FoxO1-axis in later life.

Obesity is a pre-disposing condition for chronic obstructive pulmonary disease, asthma, and pulmonary arterial hypertension. Accumulating evidence suggests that metabolic influences during development can determine chronic lung diseases (CLD). We demonstrate that maternal obesity causes early metabolic disorder in the offspring.

Therapeutic induction of Bcl2-associated athanogene 3-mediated autophagy in idiopathic pulmonary fibrosis.

Background: Exaggerated fibroblast proliferation is a well-known feature in idiopathic pulmonary fibrosis (IPF) which may be - in part - due to insufficient autophagy, a lysosome dependent cellular surveillance pathway. Bcl2-associated athanogene 3 (BAG3) is a pivotal co-chaperone of the autophagy pathway. Here, we studied whether therapeutic modulation of BAG3-mediated autophagy can rescue insufficient autophagy and impact IPF fibroblast proliferation.

Applying key learnings from the EMAX trial to clinical practice and future trial design in COPD.

Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a large, multicentre, multi-national, randomised, double-blind, 24-week trial. EMAX evaluated the efficacy and safety of dual bronchodilator therapy with umeclidinium bromide (UMEC)/vilanterol (VI) versus monotherapy with either UMEC or salmeterol (SAL) in symptomatic patients with chronic obstructive pulmonary disease (COPD) at low exacerbation risk who were not taking concomitant inhaled corticosteroid (ICS). EMAX generated evidence covering a wide range of patient-centred endpoints in COPD in addition to measures of lung function, clinical deterioration and safety.

Early Assessment of Chemotherapy Response in Advanced Non-Small Cell Lung Cancer with Circulating Tumor DNA.

Monitoring treatment efficacy early during therapy could enable a change in treatment to improve patient outcomes. We report an early assessment of response to treatment in advanced NSCLC using a plasma-only strategy to measure changes in ctDNA levels after one cycle of chemotherapy. Plasma samples were collected from 92 patients with Stage IIIB-IV NSCLC treated with first-line chemo- or chemoradiation therapies in an observational, prospective study.

Detection of SARS-CoV-2 by Mass Spectrometry.

Amplification of viral ribonucleic acid by real-time reverse transcriptase polymerase chain reaction is the gold standard to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, alternative reliable, fast, and cost-effective methods for the detection of SARS-CoV-2 are still needed. In this chapter, the mass spectrometry-based detection of amplified polymerase chain reaction products of SARS-CoV-2 genes from oral or nasopharyngeal swabs is described.

Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study.

Background: Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects.

Impact of switching from triple therapy to dual bronchodilation in COPD: the DACCORD 'real world' study.

Introduction: Chronic obstructive pulmonary disease (COPD) guidelines recommend reserving triple therapy of inhaled corticosteroid (ICS), long-acting β-agonist (LABA) and long-acting muscarinic antagonist (LAMA) for patients with exacerbations despite dual therapy. However, many patients receive triple therapy without a clear indication. For these patients, it would be useful to know whether ICS can be withdrawn.

Predicting the effectiveness of high-flow oxygen therapy in COVID-19 patients: a single-centre observational study.

Background: High-flow nasal cannula (HFNC) therapy is a helpful tool in the treatment of hypoxaemic respiratory failure. However, the clinical parameters predicting the effectiveness of HFNC in coronavirus-19 disease (COVID-19) patients remain unclear.

Methods: Sixteen COVID-19 patients undergoing HFNC in the Asklepios Lung Clinic Munich-Gauting, Germany between 16 March and 3 June 2020 were retrospectively included into the study.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) including Variant Analysis by Mass Spectrometry in Placental Tissue.

Among neonates, tested positive for SARS-CoV-2, the majority of infections occur through postpartum transmission. Only few reports describe intrauterine or intrapartum SARS-CoV-2 infections in newborns. To understand the route of transmission, detection of the virus or virus nucleic acid in the placenta and amniotic tissue are of special interest.

Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis.

Approximately 11.1% of all newborns worldwide are born preterm. Improved neonatal intensive care significantly increased survival rates over the last decades but failed to reduce the risk for the development of chronic lung disease (i.

PACS2-TRPV1 axis is required for ER-mitochondrial tethering during ER stress and lung fibrosis.

Endoplasmic reticulum (ER) and mitochondria (mito) play a vital role in alveolar type II cell (AEC2) homeostasis and are both stressed in patients with idiopathic pulmonary fibrosis (IPF). Up to now, no data are available with regard to ER-mito cross talk and tethering under conditions of IPF. We here demonstrate that ER-mitochondrial tethering is reduced upon experimental ER stress in vitro and in the IPF AECII ex vivo, and this is-at least in part-due to decreased phosphofurin acidic cluster sorting protein 2 (PACS-2, also called PACS2) protein levels.

Interclass Difference in Pneumonia Risk in COPD Patients Initiating Fixed Dose Inhaled Treatment Containing Extrafine Particle Beclometasone versus Fine Particle Fluticasone.

Background: Inhaled corticosteroids (ICS) afford therapeutic benefits in some COPD patients, but their widespread use is cautioned due to an increased risk of developing pneumonia. Subclass variations exist, and the risk profile differs for individual ICS. Formulation particle size has been identified as a potential effect modifier.

Clinical characterization of a novel alpha1-antitrypsin null variant: PiQ0.

The clinical characterization of a null variant of - PiQ0 - resulting in alpha1-antitrypsin (AAT) deficiency is described. This rare mutation (c.-5+5 G > A) has been previously identified but not clinically described.