Lung Ultrasound for the Exclusion of Pneumothorax after Interventional Bronchoscopies—A Retrospective Study

A chest X-ray (CXR) is recommended after bronchoscopies with an increased risk of pneumothorax (PTX). However, concerns regarding radiation exposure, expenses and staff requirements exist. A lung ultrasound (LUS) is a promising alternative for the detection of PTX, though data are scarce. This study aims to investigate the diagnostic yield of LUS compared to CXR, to exclude PTX after bronchoscopies with increased risk. This retrospective single-centre study included transbronchial forceps biopsies, transbronchial lung cryobiopsies and endobronchial valve treatments. Post-interventional PTX screening consisted of immediate LUS and CXR within two hours. In total, 271 patients were included. Early PTX incidence was 3.3%. Sensitivity, specificity, and the positive and negative predictive values of LUS were 67.7% (95% CI 29.93–92.51%), 99.2% (95% CI 97.27–99.91%), 75.0% (95% CI 41.16–92.79%) and 98.9% (95% CI 97.18–99.54%), respectively. PTX detection by LUS enabled the immediate placement of two pleural drains along with the bronchoscopy. With CXR, three false-positives and one false-negative were observed; the latter evolved into a tension-PTX. LUS correctly diagnosed these cases. Despite low sensitivity, LUS enables early diagnosis of PTX, thus preventing treatment delays. We recommend immediate LUS, in addition to LUS or CXR after two to four hours and monitoring for signs and symptoms. Prospective studies with higher sample sizes are needed

Transbronchial Cryobiopsy Compared to Forceps Biopsy for Diagnosis of Acute Cellular Rejection in Lung Transplants: Analysis of 63 Consecutive Procedures

BACKGROUND Acute cellular rejection (ACR) is a complication after lung transplantation (LTx). The diagnosis of ACR is based on histologic findings using transbronchial forceps biopsy (FB). However, its diagnostic accuracy is limited because of the small biopsy size and crush artifacts. Transbronchial cryobiopsy (CB) provides a larger tissue size compared with FB. METHODS FB and CB were obtained consecutively during the same bronchoscopy (February 2020-April 2021). All biopsies were scored according to the ISHLT criteria by three pathologists. Interobserver agreement was scored by the kappa index. We assessed the severity of bleeding and the presence of pneumothorax. RESULTS In total, 35 lung transplant recipients were included, and 126 CBs and 315 FBs were performed in 63 consecutive bronchoscopies. ACR (A1-A3, minimal-moderate) was detected in 18 cases (28.6%) by CB, whereas ACR was detected in 3 cases (4.8%) by FB. Moderate and severe bleeding complicated FB and CB procedures in 23 cases (36.5%) and 1 case (1.6%), respectively. Pneumothorax occurred in 6.3% of patients. The interobserver agreement was comparable for both CB and FB. CONCLUSIONS CB provided an improved diagnostic yield for ACR diagnosis, leading to reclassification and changes in treatment strategies in 28.6% of cases. Prospective studies should better define the role of CB after LTx

Implementation of the Combined--Nonlinear Condensation Transformation

We discuss several applications of the recently proposed combined nonlinear-condensation transformation (CNCT) for the evaluation of slowly convergent, nonalternating series. These include certain statistical distributions which are of importance in linguistics, statistical-mechanics theory, and biophysics (statistical analysis of DNA sequences). We also discuss applications of the transformation in experimental mathematics, and we briefly expand on further applications in theoretical physics. Finally, we discuss a related Mathematica program for the computation of Lerch's transcendent.Comment: 23 pages, 1 table, 1 figure (Comput. Phys. Commun., in press

Stochastic population models hindcast population trajectory and breeding history of an endangered parrot

Understanding the population dynamics of endangered species is crucial to their conservation. Stochastic population models can be used to explore factors involved in population change, contributing to the understanding of a species’ population dynamics. Norfolk Island Green Parrots Cyanoramphus cookii have undergone significant population fluctuations in the last 50 years. Since 2013, most nestlings hatched in managed, predator-proofed nest sites have been individually marked. These nests have been considered the primary source of population growth. Yet, in 2021, most adult birds were unmarked, raising the question of whether unmarked parrots have been entering the population through undetected breeding in natural nests, and to what extent. We modelled Green Parrot population growth between 2013 and 2021 using stochastic population models in VORTEX to explore the potential dynamics involved in the observed population growth. Basic models involving breeding only in managed nests produced population estimates between 158 and 266, whereas more complex models that included breeding in unmanaged nests, and accounted for the large proportion of unmarked birds, produced population estimates between 360 and 1,041. We conclude that natural nests may have played a significant role in the population growth since 2013. If this is the case, broad-scale predator control may be largely responsible. Furthermore, our study shows how population models may be used to infer underlying demographic processes and inform conservation strategies, even in instances of data scarcity. Our method can be applied to other threatened species, and may prove particularly useful for small populations whose population dynamics remain unclear

Genetic diversity and inbreeding in an endangered island-dwelling parrot population following repeated population bottlenecks

Genetic diversity and population structure can have important implications for the management of threatened species. This is particularly true for small, isolated populations that have experienced significant declines or population bottlenecks. The Norfolk Island green parrot Cyanoramphus cookii is an endangered species at risk of inbreeding and loss of genetic diversity due to its restricted range and the population bottlenecks experienced in recent decades. To assess the severity of inbreeding and loss of genetic diversity in the population we analyzed single nucleotide polymorphisms (SNPs) for 157 unique genetic samples collected from nestlings and randomly captured adult birds between 2015 and 2022. We also assessed the population for genetic structure, calculated sex ratios, and looked for evidence of past population bottlenecks. Our analysis revealed that 17.83% of individuals sampled were highly inbred (F > 0.125), although expected heterozygosity (HE) did not significantly differ from observed heterozygosity (HO) and the average inbreeding coefficient was low. The estimated effective population size (Ne) was 43.8 and we found no evidence of genetic structure. Demographic simulations provided support for scenarios including multiple population bottlenecks, when compared to those with a single population bottleneck or no past bottlenecks. We discuss the implications of our findings for the future management of the species including any potential attempt to establish an insurance population via translocation. Our study highlights the importance of considering population genetics when determining appropriate management actions for threatened species and the need to assess non-model species on an individual basis

Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors

CME: Konservative und invasive Behandlungsmethoden in der Therapie des Lungenemphysems

Die COPD (chronic obstructive pulmonary disease) kennzeichnet sich durch eine persistierende und progrediente Einschränkung des Atemflusses aus, die durch eine chronische Entzündung der Atemwege bedingt ist. Das Lungenemphysem wird weitgehend als eine Spätfolge verstanden, wobei es dabei zur irreversiblen Zerstörung der Alveolen mit konsekutiver Überblähung kommt. Als Hauptursache in den Industrienationen gilt der Zigarettenkonsum, weshalb das primäre Therapieziel der Rauchstopp darstellt. Die Behandlung ist abhängig vom Schweregrad der Erkrankung, sowie den vorhandenen Komorbiditäten. Nach Ausschöpfung aller konservativer Massnahmen stellen bei sistiertem Zigarettenkonsum die chirurgische oder endoskopische Lungenvolumenreduktion oder in Abhängigkeit von Alter und Komorbiditäten eine Lungentransplantation eine mögliche Therapieoptionen dar. COPD (chronic obstructive pulmonary disease) describes a progressive lung disease characterized by airflow limitation due to chronic bronchitis. Lung emphysema as a consequence of chronic bronchitis results from an irreversible destruction of alveolar walls with consecutive hyperinflation. In industrial nations most cases are caused by inhaling pollutants, mainly cigarettes which makes smoking cessation the first and ultimate goal. Therapy depends on the severity of the disease and its comorbidities. If conservative therapy does not lead to a sufficient treatment control, surgical or endoscopic lung volume reduction or even lung transplantation have to be considered in selected cases

Olefinic peptide nucleic acid (OPA)

The olefinic peptide nucleic acid analogues (OPA) monomers containing the bases thymine and adenine were synthesised in 11 steps. Fully modified oligomers containing these units were prepared and their pairing properties assessed by means of UV-melting experiment

Fluorinated peptide nucleic acid

The fluorinated olefinic peptide nucleic acid analogue (F-OPA) monomer containing the base thymine was synthesised in 13 steps. PNAs containing this unit were prepared and their pairing properties assessed by means of UV-melting experiment