Combined medical-interventional approaches for the management of complex fungal balls: a case series as a viable alternative in non-surgical patients.

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections.

Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review.

Background: In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers to avoid the need for serial tissue biopsies.

Methods: A systematic review of scientific databases from 2012 until present was performed to identify studies fulfilling the inclusion criteria.

Intravital imaging of three different microvascular beds in SARS-CoV-2-infected mice.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the respiratory tract, where it infects the alveoli epithelial lining. However, patients have sequelae that extend well beyond the alveoli into the pulmonary vasculature and, perhaps, beyond to the brain and other organs. Because of the dynamic events within blood vessels, histology does not report platelet and neutrophil behavior.

Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy: A Prospective Multi-Centre Agreement Clinical Trial (CAN-ICE).

Transbronchial cryobiopsy (TBCB) for the diagnosis of interstitial lung disease (ILD) has shown promising results, but prospective studies with matched surgical lung biopsy (SLB) have yielded conflicting results. We aimed to assess within- and between-center diagnostic agreement between TBCB and SLB at both the histopathologic and multidisciplinary discussion (MDD) levels in patients with diffuse ILD. In a multicenter prospective study, we performed matched TBCB and SLB in patients referred for SLB.

Interleukin-4 Programmed Macrophages Suppress Colitis and Do Not Enhance Infectious-Colitis, Inflammation-Associated Colon Cancer or Airway Hypersensitivity.

The murine interleukin-4 treated macrophage (MIL4) exerts anti-inflammatory and pro-healing effects and has been shown to reduce the severity of chemical-induced colitis. Positing M(IL4) transfer as an anti-inflammatory therapy, the possibility of side-effects must be considered. Consequently, bone marrow-derived M(IL4)s were administered intraperitoneal injection to mice concomitant with infection (infections colitis), azoxymethane/dextran sodium sulphate (AOM/DSS) treatment [a model of colorectal cancer (CRC)], or ovalbumin sensitization (airway inflammation).

Canadian ROS proto-oncogene 1 study (CROS) for multi-institutional implementation of ROS1 testing in non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) harboring ROS proto-oncogene 1 (ROS1) gene rearrangements show dramatic response to the tyrosine kinase inhibitor (TKI) crizotinib. Current best practice guidelines recommend that all advanced stage non-squamous NSCLC patients be also tested for ROS1 gene rearrangements. Several studies have suggested that ROS1 immunohistochemistry (IHC) using the D4D6 antibody may be used to screen for ROS1 fusion positive lung cancers, with assays showing high sensitivity but moderate to high specificity.

PKCε stimulation of TRPV1 orchestrates carotid body responses to asthmakines.

Key Points: We have previously shown that carotid body stimulation by lysophosphatidic acid elicits a reflex stimulation of vagal efferent activity sufficient to cause bronchoconstriction in asthmatic rats. Here, we show that pathophysiological concentrations of asthma-associated prototypical Th2 cytokines also stimulate the carotid bodies. Stimulation of the carotid bodies by these asthmakines involves a PKCε-transient receptor potential vanilloid 1 (TRPV1) signalling mechanism likely dependent on TRPV1 S502 and T704 phosphorylation sites.

Patrolling Alveolar Macrophages Conceal Bacteria from the Immune System to Maintain Homeostasis.

During respiration, humans breathe in more than 10,000 liters of non-sterile air daily, allowing some pathogens access to alveoli. Interestingly, alveoli outnumber alveolar macrophages (AMs), which favors alveoli devoid of AMs. If AMs, like most tissue macrophages, are sessile, then this numerical advantage would be exploited by pathogens unless neutrophils from the blood stream intervened.

Intestinal fungi are causally implicated in microbiome assembly and immune development in mice.

The gut microbiome consists of a multi-kingdom microbial community. Whilst the role of bacteria as causal contributors governing host physiological development is well established, the role of fungi remains to be determined. Here, we use germ-free mice colonized with defined species of bacteria, fungi, or both to differentiate the causal role of fungi on microbiome assembly, immune development, susceptibility to colitis, and airway inflammation.

Canadian Multicenter Project on Standardization of Programmed Death-Ligand 1 Immunohistochemistry 22C3 Laboratory-Developed Tests for Pembrolizumab Therapy in NSCLC.

Introduction: The programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assay is used to select patients for first or second-line pembrolizumab monotherapy in NSCLC. The PD-L1 IHC 22C3 pharmDx assay requires an Autostainer Link 48 instrument. Laboratories without this stainer have the option to develop a highly accurate 22C3 IHC laboratory-developed test (LDT) on other instruments.

The Role of Airway Myofibroblasts in Asthma.

Airway remodeling is a characteristic feature of asthma and is thought to play an important role in the pathogenesis of airway hyperresponsiveness. Myofibroblasts are key structural cells involved in injury and repair, and there is evidence that dysregulation of their normal function contributes to airway remodeling. Despite the importance of myofibroblasts, a lack of specific cellular markers and inconsistent nomenclature have limited recognition of their key role in airway remodeling.

Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver.

A hallmark feature of inflammation is the orchestrated recruitment of neutrophils from the bloodstream into inflamed tissue. Although selectins and integrins mediate recruitment in many tissues, they have a minimal role in the lungs and liver. Exploiting an unbiased in vivo functional screen, we identified a lung and liver homing peptide that functionally abrogates neutrophil recruitment to these organs.

Expression of a constitutively active human mutant in hematopoietic cells produces an -dependent vasculopathy in mice.

STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disorder characterized by blood vessel occlusions, acral necrosis, myositis, rashes, and pulmonary inflammation that are the result of activating mutations in the STimulator of Interferon Genes (STING). We generated a transgenic line that recapitulates many of the phenotypic aspects of SAVI by targeting the expression of the human STING-N154S-mutant protein to the murine hematopoietic compartment. mice demonstrated failure to gain weight, lymphopenia, progressive paw swelling accompanied by inflammatory infiltrates, severe myositis, and ear and tail necrosis.

Preventing acute asthmatic symptoms by targeting a neuronal mechanism involving carotid body lysophosphatidic acid receptors.

Asthma accounts for 380,000 deaths a year. Carotid body denervation has been shown to have a profound effect on airway hyper-responsiveness in animal models but a mechanistic explanation is lacking. Here we demonstrate, using a rat model of asthma (OVA-sensitized), that carotid body activation during airborne allergic provocation is caused by systemic release of lysophosphatidic acid (LPA).

Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment.

Sepsis-associated encephalopathy manifesting as delirium is a common problem in critical care medicine. In this study, patients that had delirium due to sepsis had significant cognitive impairments at 12-18 months after hospital discharge when compared with controls and Cambridge Neuropsychological Automated Test Battery-standardized scores in spatial recognition memory, pattern recognition memory, and delayed-matching-to-sample tests but not other cognitive functions. A mouse model of S.

Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the absence of regulation by B cells.

Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11bL-selectinCXCR4 polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via β integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance.

Leukotriene B4-Mediated Neutrophil Recruitment Causes Pulmonary Capillaritis during Lethal Fungal Sepsis.

Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C.

Myofibroblasts are increased in the lung parenchyma in asthma.

Background: Increased airway smooth muscle is observed in large and small airways in asthma. Semi-quantitative estimates suggest that cells containing alpha smooth muscle actin (α-SMA) are also increased in the lung parenchyma. This study quantified and characterized α-SMA positive cells (α-SMA+) in the lung parenchyma of non-asthmatic and asthmatic individuals.

Varicella-Zoster Virus Gastritis: Case Report and Review of the Literature.

We report varicella-zoster virus (VZV) gastritis in a 70-year-old woman postchemotherapy for lymphoma, presenting with abdominal pain, vomiting, and delirium without rash. A gastric biopsy demonstrated viral inclusions but posed a diagnostic challenge as immunohistochemistry for cytomegalovirus and herpes simplex virus were negative, and VZV immunohistochemistry was not available. The patient developed a vesicular rash 7 days after her symptoms began.

An inhaled dose of budesonide induces genes involved in transcription and signaling in the human airways: enhancement of anti- and proinflammatory effector genes.

Although inhaled glucocorticoids, or corticosteroids (ICS), are generally effective in asthma, understanding their anti-inflammatory actions in vivo remains incomplete. To characterize glucocorticoid-induced modulation of gene expression in the human airways, we performed a randomized placebo-controlled crossover study in healthy male volunteers. Six hours after placebo or budesonide inhalation, whole blood, bronchial brushings, and endobronchial biopsies were collected.