Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2.

Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model.

Survival following lung volume reduction procedures: results from the UK Lung Volume Reduction (UKLVR) registry.

Introduction: Lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement can produce substantial benefits in appropriately selected people with emphysema. The UK Lung Volume Reduction (UKLVR) registry is a national multicentre observational study set up to support quality standards and assess outcomes from LVR procedures at specialist centres across the UK.

Methods: Data were analysed for all patients undergoing an LVR procedure (LVRS/EBV) who were recruited into the study at participating centres between January 2017 and June 2022, including; disease severity and risk assessment, compliance with guidelines for selection, procedural complications and survival to February 2023.

An unexpected case of thoracic necrotising fasciitis.

Necrotising fasciitis (NF) is a life-threatening bacterial infection characterised by rapid tissue destruction, which can have severe consequences if not recognised early and treated promptly. It is most commonly caused by group A streptococcus entering the body through breaks in the skin. This case report describes a patient who presented with systemic signs of infection, including right axillary pain, following a recent intramuscular injection.

LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis.

The factors that determine fibrosis progression or normal tissue repair are largely unknown. We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signalling. Here, we report that liver kinase B1 (LKB1) inactivation in ATII cells inhibits autophagy and induces EMT as a consequence.

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease: Opportunities for therapy.

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid β (Aβ) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.

Clinical score for colorectal cancer patients with lung-limited metastases undergoing surgical resection: Meta-Lung Score.

Background: Radical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong's criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection.

Methods: We retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS).

Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer.

Fibroblasts are poorly characterised cells that variably impact tumour progression. Here, we use single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry (CIBERSORTx) to identify and characterise three major fibroblast subpopulations in human non-small cell lung cancer: adventitial, alveolar and myofibroblasts. Alveolar and adventitial fibroblasts (enriched in control tissue samples) localise to discrete spatial niches in histologically normal lung tissue and indicate improved overall survival rates when present in lung adenocarcinomas (LUAD).

Ambulatory chest drainage with advanced nurse practitioner-led follow-up facilitates early discharge after thoracic surgery.

Objectives: To demonstrate the safety and feasibility of advanced nurse practitioner-led (ANP-led) outpatient follow-up after discharge with ambulatory chest drains for prolonged air leak and excessive fluid drainage.

Methods: Patients discharged with ambulatory chest drains between January 2017 and December 2019 were retrospectively reviewed. Discharge criteria included air leak < 200 ml/min or fluid drainage > 100 ml/24 h on a digital drain.

Spatially resolved deconvolution of the fibrotic niche in lung fibrosis.

A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures.

Three Dimensional Modelling in the Optimisation of Chest Wall Resection and Reconstruction Following Metastatic Breast Cancer.

Two-dimensional computed tomography scans no longer offer the level of detail that many surgeons desire for more accurate and precise surgical intervention. Computed tomography image reconstruction into three dimensional (3D) virtual models with interactive capability is providing an enhanced understanding of the patient's anatomy and pathology allowing the surgeon to create tailored intraoperative plans, minimizing complications and maximizing the intended therapeutic outcome. In this case report we demonstrate the use of 3D image reconstruction software in the management of a 36-year-old female with metastatic breast cancer affecting the chest wall.

Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis.

Extracellular matrix (ECM) stiffening with downstream activation of mechanosensitive pathways is strongly implicated in fibrosis. We previously reported that altered collagen nanoarchitecture is a key determinant of pathogenetic ECM structure-function in human fibrosis (Jones et al., 2018).

Antibiotic-loaded Bone Cement in the Management of Neosternal Osteomyelitis.

Antibiotic-loaded bone cement is an alternative treatment option that can be used in the surgical management of osteomyelitis requiring bone resection and reconstruction. Current literature provides a focus on its use within the orthopedic patient group with scarce literature surrounding the cardiothoracic patient demographic. We hereby demonstrate the use of an antibiotic-loaded bone cement in the definitive management of neosternal osteomyelitis and nonunion, avoiding the need for further complex autografting and internal fixation.

Immunofluorescence-guided segmentation of three-dimensional features in micro-computed tomography datasets of human lung tissue.

Micro-computed tomography (µCT) provides non-destructive three-dimensional (3D) imaging of soft tissue microstructures. Specific features in µCT images can be identified using correlated two-dimensional (2D) histology images allowing manual segmentation. However, this is very time-consuming and requires specialist knowledge of the tissue and imaging modalities involved.

Chest Wall Silicone Granuloma Following Ruptured Silicone Breast Implant Causes Giant Chest Wall Abscess and Osteomyelitis: The First Report.

Silicone breast implant ruptures have been widely reported in the literature. Granuloma formation is a known complication of such ruptures with reported sites including the axillae, limbs, chest wall muscles, and internal organs, such as the lungs and the liver. To the best of our knowledge, there are no reported cases of a silicone granuloma causing osteomyelitis of the sternum and multiple ribs in the absence of infection.

Image-guided combined ablation and resection in thoracic surgery for the treatment of multiple pulmonary metastases: A preliminary case series.

Objectives: To demonstrate the feasibility and preliminary outcomes of a novel hybrid technique combining percutaneous microwave ablation and wire-assisted wedge resection for patients with multiple pulmonary metastases using intraoperative imaging.

Methods: We describe our technique and present a retrospective case series of 4 patients undergoing iCART at our institution between August 2018 and January 2020. Procedures were performed in a hybrid operating suite using the ARTIS Pheno cone beam computerized tomography scanner (Siemens Healthineers, Erlangen, German).

Endobronchial Valves in the Management of Persistent Air Leak in Coronavirus Disease 2019.

Pneumothorax and persistent air leak are documented complications of severe acute respiratory syndrome coronavirus 2 infection. Patients who fall into this category are often poor candidates for invasive thoracic surgical intervention. Endobronchial valves offer an effective and less invasive treatment option and can successfully treat persistent air leak and support the weaning of patients with severe acute respiratory syndrome coronavirus 2 pneumonia off ventilation.

Bidirectional epithelial-mesenchymal crosstalk provides self-sustaining profibrotic signals in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the prototypic progressive fibrotic lung disease with a median survival of 2 to 4 years. Injury to and/or dysfunction of the alveolar epithelium is strongly implicated in IPF disease initiation, but the factors that determine whether fibrosis progresses rather than normal tissue repair occurs remain poorly understood. We previously demonstrated that zinc finger E-box-binding homeobox 1-mediated epithelial-mesenchymal transition in human alveolar epithelial type II (ATII) cells augments transforming growth factor-β-induced profibrogenic responses in underlying lung fibroblasts via paracrine signaling.

Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy.

Immune-checkpoint blockade (ICB) has shown remarkable clinical success in boosting antitumor immunity. However, the breadth of its cellular targets and specific mode of action remain elusive. We find that tumor-infiltrating follicular regulatory T (T) cells are prevalent in tumor tissues of several cancer types.

Effectiveness, cost-effectiveness and safety of gabapentin versus placebo as an adjunct to multimodal pain regimens in surgical patients: protocol of a placebo controlled randomised controlled trial with blinding (GAP study).

Introduction: Gabapentin is an antiepileptic drug currently licensed to treat epilepsy and neuropathic pain but has been used off-label to treat acute postoperative pain. The GAP study will compare the effectiveness, cost-effectiveness and safety of gabapentin as an adjunct to standard multimodal analgesia versus placebo for the management of pain after major surgery.

Methods And Analysis: The GAP study is a multicentre, double-blind, randomised controlled trial in patients aged 18 years and over, undergoing different types of major surgery (cardiac, thoracic or abdominal).

Tracheal leiomyoma mimicking asthma for over 20 years.

Benign tracheal tumours have an incidence of 1 in 1,000,000, of which leiomyomas represent only 1%. We report a case of tracheal leiomyoma masquerading as asthma for over 20 years. A 48-year-old man presented aged 26 years with asthma symptoms unresponsive to treatments and an obstructive spirometry pattern.

M1 tumor-associated macrophages boost tissue-resident memory T cells infiltration and survival in human lung cancer.

Background: The role of tumor-associated macrophages (TAMs) in determining the outcome between the antitumor effects of the adaptive immune system and the tumor's anti-immunity stratagems, is controversial. Macrophages modulate their activities and phenotypes by integration of signals in the tumor microenvironment. Depending on how macrophages are activated, they may adopt so-called M1-like, antitumor or M2-like, protumor profiles.

Paracrine SPARC signaling dysregulates alveolar epithelial barrier integrity and function in lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic scarring disease in which aging, environmental exposure(s) and genetic susceptibility have been implicated in disease pathogenesis, however, the causes and mechanisms of the progressive fibrotic cascade are still poorly understood. As epithelial-mesenchymal interactions are essential for normal wound healing, through human 2D and 3D in vitro studies, we tested the hypothesis that IPF fibroblasts (IPFFs) dysregulate alveolar epithelial homeostasis. Conditioned media from IPFFs exaggerated the wound-healing response of primary human Type II alveolar epithelial cells (AECs).

Delayed post-traumatic presentation of severe sternal osteomyelitis: A strong multidisciplinary effort and a novel reconstruction technique for a challenging case.

Sternal osteomyelitis is a morbid and challenging condition, which can rarely occur after trauma, with no established consensus over best therapeutic options. In this case, a 47-year-old man with history of intravenous drug use presented 11 weeks after a minor blunt chest trauma with a severe necrotizing osteomyelitis involving sternum, muscles, fascia and subcutaneous tissue and positive blood cultures for Methicillin Sensitive . Alongside tailored antibiotic therapy, extensive surgical debridement was performed, leaving a full thickness 3 × 4 cm sternal defect and a large skin defect.

Vasomotion Drives Periarterial Drainage of Aβ from the Brain.

In this issue of Neuron, van Veluw et al. (2020) show that elimination of solutes from the brain along arterial walls is driven by low-frequency arteriolar oscillations and suggest that age-related reduction of this vasomotion may contribute to impaired clearance of Aβ.

Autophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries to an ageing, susceptible alveolar epithelium. Ageing is a risk factor for IPF and incidence has been demonstrated to increase with age. Decreased (macro)autophagy with age has been reported extensively in a variety of systems and diseases, including IPF.