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Hatice Kilic,1 Nurdan Kokturk,2 Gulcin Sari,3 Mustafa Cakir41Department of Pulmonary Medicine, Ankara Atatürk Training and Research Hospital, 2Department of Pulmonary Medicine, School of Medicine, Gazi University School of Medicine, 3Department of Pulmonary Medicine, Dr. Nafiz Körez Sincan Devlet Hastanesi, 4Department of Public Health, School of Medicine, Gazi University, Ankara, TurkeyIntroduction: Little is known about whether there is any sex effect on chronic obstructive lung disease (COPD) exacerbations. This study is intended to describe the possible sex-associated differences in exacerbation profile in COPD patients.Methods: A total of 384 COPD patients who were hospitalized due to exacerbation were evaluated retrospectively for their demographics and previous and current exacerbation characteristics.Results: The study was conducted on 109 (28%) female patients and 275 (72%) male patients. The mean age was 68.30±10.46 years. Although females had better forced expiratory volume in 1 second and near-normal forced vital capacity, they had much impaired arterial blood gas levels (partial oxygen pressure [PO2] was 36.28 mmHg vs 57.93 mmHg; partial carbon dioxide pressure [PCO2] was 45.97 mmHg vs 42.49 mmHg; P=0.001), indicating severe exacerbation with respiratory failure. More females had two exacerbations and two hospitalizations, while more men had one exacerbation and one hospitalization. Low adherence to treatment and pulmonary embolism were more frequent in females. Females had longer time from the onset of symptoms till the admission and longer hospitalization duration than males. Comorbidities were less in number and different in women (P

HLA‐A*26:01:36 differs from the closest allele HLA‐A*26:01:01 by a nucleotide change at the position 114. [ABSTRACT FROM AUTHOR]

Occupational exposure to manganese (Mn) primarily occurs through the inhalation of manganese-containing fumes and dust, with welding environments being significant sources of such exposure. Elevated levels of Mn in welding fumes can lead to a neurological syndrome known as manganism. A 28-yr-old male welder with 14 yr of experience, is presenting with complaints of forgetfulness, reasoning disorder, and decreased mental functions persisting for 10 yr. Three months ago, when he started working at the new workplace, he underwent employment screening conducted by the workplace physician. During this screening process, the physician identified a high whole blood Mn level of 25.9 µg/l. The diagnosis of manganism in this patient was established based on exposure to Mn and its compounds, high levels of Mn detected in the whole blood, hyperactive patellar reflexes observed during the physical examination, cranial Magnetic Resonance Imaging (MRI) findings consistent with manganism and complaints reported by the patient that are characteristic of manganism. In this report, the aim is to emphasize the significance of taking a comprehensive occupational history and to draw attention the potential health hazards associated with Mn and its compounds.

Background: In order for cancers to progress, they must evade elimination by CD8 T cells or other immune mechanisms. CD8 T cells recognize and kill tumor cells that display immunogenic tumor peptides bound to MHC I molecules. One of the ways that cancers can escape such killing is by reducing expression of MHC I molecules, and loss of MHC I is frequently observed in tumors. There are multiple different mechanisms that can underly the loss of MHC I complexes on tumor and it is currently unclear whether there are particular mechanisms that occur frequently and, if so, in what types of cancers. Also of importance to know is whether the loss of MHC I is reversible and how such loss and/or its restoration would impact responses to immunotherapy. Here, we investigate these issues for loss of IRF1 and IRF2, which are transcription factors that drive expression of MHC I pathway genes and some killing mechanisms., Methods: Bioinformatics analyses of IRF2 and IRF2-dependent gene transcripts were performed for all human cancers in the TCGA RNAseq database. IRF2 protein-DNA-binding was analyzed in ChIPseq databases. CRISRPcas9 was used to knock out IRF1 and IRF2 genes in human and mouse melanoma cells and the resulting phenotypes were analyzed in vitro and in vivo., Results: Transcriptomic analysis revealed that IRF2 expression was reduced in a substantial subset of cases in almost all types of human cancers. When this occurred there was a corresponding reduction in the expression of IRF2-regulated genes that were needed for CD8 T cell recognition. To test cause and effect for these IRF2 correlations and the consequences of IRF2 loss, we gene-edited IRF2 in a patient-derived melanoma and a mouse melanoma. The IRF2 gene-edited melanomas had reduced expression of transcripts for genes in the MHC I pathway and decreased levels of MHC I complexes on the cell surface. Levels of Caspase 7, an IRF2 target gene involved in CD8 T cell killing of tumors, were also reduced. This loss of IRF2 caused both human and mouse melanomas to become resistant to immunotherapy with a checkpoint inhibitor. Importantly, these effects were reversible. Stimulation of the IRF2-deficient melanomas with interferon induced the expression of a functionally homologous transcription factor, IRF1, which then restored the MHC I pathway and responsiveness to CPI., Conclusions: Our study shows that a subset of cases within most types of cancers downregulates IRF2 and that this can allow cancers to escape immune control. This can cause resistance to checkpoint blockade immunotherapy and is reversible with currently available biologics., Competing Interests: Consent for publication: All authors agreed on the final version of the article and submission to Journal of Experimental & Clinical Cancer Research.

Objectives: It was aimed to determine the factors affecting the development of chronic obstructive pulmonary disease (COPD) in pneumoconiosis cases., Methods: Pneumoconiosis cases were divided into two groups as those with only pneumoconiosis and those with coexistence of pneumoconiosis and COPD. Demographic data, smoking habits, pulmonary function test, radiological findings, and occupational risk factors of the cases were compared., Results: Chronic obstructive pulmonary disease was detected in 134 of 465 pneumoconiosis cases (28.8%) included in the study. It was determined that patients who developed COPD were statistically significantly older, had longer exposure duration, had lower forced expiratory volume in 1 second, forced vital capacity, and forced expiratory volume in 1 second/forced vital capacity values, and had more pulmonary symptoms. Chronic obstructive pulmonary disease development was more common in sandblasting workers, dental technicians, and miners than in other occupations., Conclusion: It has been shown that the risk of developing COPD is high in cases of pneumoconiosis, independent of smoking, especially in certain occupational groups., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

CD8 T cells recognize cancers when they detect antigenic peptides presented on a tumor's surface MHC-I molecules. Since MHC-I antigen presentation is not essential for cell growth or survival, many cancers inactivate this pathway, and thereby escape control by CD8 T cells. Such immune evasion allows cancers to progress and also become resistant to CD8 T- cell-based immunotherapies, such as checkpoint blockade. Here, we review recent findings about the various different mechanisms that cancers use to impair antigen presentation, the consequence of such changes, and, in some cases, the potential to reverse these defects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Pulmonary artery pseudoaneurysms are uncommon. They may occur secondary to trauma, infectious diseases, vasculitis syndromes, neoplasms, congenital diseases, and pulmonary hypertension. Due to increasing number of cardiac interventions, iatrogenic complications are among the major causes of pulmonary artery pseudoaneurysms.In this report, we present a 6-month-old patient with pulmonary pseudoaneurysm that occurred following pulmonary balloon angioplasty for the relief of a pulmonary band.

Congenital rupture of tricuspid chordae tendinea leading to severe tricuspid insufficiency is an extremely rare pathology associated with signs and symptoms of congestive heart failure presenting at birth. If the diagnosis and treatment of this pathology are not made early in life fetal demise may become inevitable.We herein present a neonate with central cyanosis and congestive heart failure due to rupture of an anterior leaflet chordae resulting in severe insufficiency of the tricuspid valve who was treated with appropriate surgery.

Purpose: Supplementing investigator-specified variables with large numbers of empirically identified features that collectively serve as 'proxies' for unspecified or unmeasured factors can often improve confounding control in studies utilizing administrative healthcare databases. Consequently, there has been a recent focus on the development of data-driven methods for high-dimensional proxy confounder adjustment in pharmacoepidemiologic research. In this paper, we survey current approaches and recent advancements for high-dimensional proxy confounder adjustment in healthcare database studies., Methods: We discuss considerations underpinning three areas for high-dimensional proxy confounder adjustment: (1) feature generation-transforming raw data into covariates (or features) to be used for proxy adjustment; (2) covariate prioritization, selection, and adjustment; and (3) diagnostic assessment. We discuss challenges and avenues of future development within each area., Results: There is a large literature on methods for high-dimensional confounder prioritization/selection, but relatively little has been written on best practices for feature generation and diagnostic assessment. Consequently, these areas have particular limitations and challenges., Conclusions: There is a growing body of evidence showing that machine-learning algorithms for high-dimensional proxy-confounder adjustment can supplement investigator-specified variables to improve confounding control compared to adjustment based on investigator-specified variables alone. However, more research is needed on best practices for feature generation and diagnostic assessment when applying methods for high-dimensional proxy confounder adjustment in pharmacoepidemiologic studies., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objective: This study aimed to determine the occupational and clinical characteristics of patients with progressive massive fibrosis (PMF) and factors related to the development and severity of PMF., Methods: Personal, occupational, radiological, and functional findings of 129 patients diagnosed with PMF were evaluated., Results: Sandblasting workers were found to be diagnosed with pneumoconiosis at an earlier age than those in other professions. The dust exposure durations of sandblasting and ceramic workers were significantly less than those of workers in other occupations. Statistically, a significant negative correlation was found between lung functions and small opacity size, small opacity profusion score, and large opacity size. No relationship was found between large opacity size and smoking status, concomitant tuberculosis, and duration of dust exposure., Conclusions: An effective surveillance system that considers factors that accelerate pneumoconiosis progression should be established., Competing Interests: Conflict of interest: No conflict of interest was declared by the authors., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Background: Hepatitis E viruses (HEV) are an underestimated global cause of enterically transmitted viral hepatitis, which may persist in immunocompromised hosts, posing a risk for progressive liver fibrosis with limited treatment options. We previously established liver-humanized mice as a model for chronic HEV infections, which can be cleared by a 2-week pegylated (peg)-Interferon(IFN)α treatment course. However, severe side effects may hamper the use of IFNα in immunocompromised transplant recipient patients. IFNλ may be a valuable alternative, as its receptor is less ubiquitously expressed., Aims: In this study, we assess the in vitro and in vivo potency of pegIFNλ to induce innate immune signalling in liver cells and to clear a persistent HEV infection in liver-humanized mice., Methods & Results: We found that human liver cells expressed the IFNλ receptor (IFNLR1) and are responsive to pegIFNλ. Treatment with pegIFNλ of liver-humanized mice persistently infected with HEV genotype 3 showed that pegIFNλ was well tolerated. Dose escalation studies showed that although HEV was not cleared at pegIFNλ doses up to 0.12 mg/kg for a maximum of 8 weeks, a dose of 0.3 mg/kg pegIFNλ treatment resulted in complete clearance of HEV antigen and HEV RNA from the liver in 8 out of 9 liver-humanized mice., Conclusions: PegIFNλ is well tolerated in mice and leads to clearance of a persistent HEV infection in liver-humanized mice., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)