Progression Of Chronic Disease Research Articles

Impact of the COVID-19 Pandemic on Blood Transfusion among Hospitalized Patients with Chronic Kidney Disease

Background and Objectives: Hematological disorders, especially chronic anemia and coagulation disorders, are common in patients with chronic kidney disease (CKD). Severe anemia is associated with increased cardiovascular morbidity and mortality in this special group of patients and is also responsible for decreased hope and quality of life. Despite the use of appropriate iron therapy and erythropoietin-stimulating agents, red blood cell transfusion is occasionally required, usually in the setting of acute bleeding or for correction of perioperative anemia. The COVID-19 pandemic has accelerated the progression of chronic diseases and worsened the outcomes for patients with nephrological conditions. As a precautionary measure against infections, patients’ access to hospitalization for their procedures has been reduced and their chronic complications, including hematological abnormalities, have gotten out of control. Materials and Methods: Our retrospective observational study was designed to evaluate the impact of the COVID-19 pandemic on blood transfusion for the patients with chronic kidney disease hospitalized in our emergency county medical unit, over a period of four years (2019–2022) who were admitted or at least referred for evaluation to the Nephrology department. We also followed the measures adopted to ensure the necessary blood products during this time. Results: Between 2190–2022, a total of 24,096 hospitalized patients were transfused at the Emergency County Clinical Hospital in Constanta, Romania. Meanwhile, in the nephrology and other medical or surgical wards of our medical unit, 1590 CKD patients were transfused with different blood derivatives. During the pandemic years, as expected, the number of transfused patients and transfused blood units decreased by 4% and 7%, respectively, in comparison with the pre-pandemic year, 2019. Unlike the general trend of transfusion activity, more patients with CKD transfused in 2022 (580) than before the pandemic (414 in 2019), and the number of blood units was higher in 2022 than in 2019 for red blood products and plasma. Between 2020–2022, from the total number of transfused patients in our study, 254 with CKD patients (16%) and 798 non-CKD (4%) died in-hospital. Conclusions: The adaptive strategies implemented to ensure the necessary blood products in the hospital during the COVID-19 pandemic mainly included restrictive transfusion and limitation of elective surgical procedures. The subject matter of the article is important as blood shortages are a problem that healthcare workers may encounter in future pandemics.

A comprehensive 26-color immunophenotyping panel to study the role of the gut-liver axis in chronic liver diseases.

The gut-liver axis includes the bidirectional communication between the gut and the liver, and thus covers signals from liver-to-gut and from gut-to-liver. Disruptions of the gut-liver axis have been associated with the progression of chronic liver diseases, including alcohol-related and metabolic dysfunction-associated steatotic liver disease and cholangiopathies. Immune cells and their expression of pattern recognition receptors, activation markers or immune checkpoints might play an active role in the communication between gut and liver. Here, we present a 26-color full spectrum flow cytometry panel for human cells to decipher the role of circulating immune cells in gut-liver communication during the progression of chronic liver diseases in a non-invasive manner, which has been optimized to be used on patient-derived whole blood samples, the most abundantly available clinical material. Our panel focuses on changes in pattern recognition receptors, including toll-like receptors (TLRs) or Dectin-1, and also includes other immunomodulatory molecules such as bile acid receptors and checkpoint molecules. Moreover, this panel can be utilized to follow the progression of chronic liver diseases and could be used as a tool to evaluate the efficiency of therapeutic targets directed against microbial mediators or modulating immune cell activation.

Core-fucose-specific Pholiota squarrosa lectin decreased hepatic inflammatory macrophage infiltration in steatohepatitis mice.

Recent findings in glycobiology revealed direct evidence of the involvement of oligosaccharide changes in human diseases, including liver diseases. Fucosylation describes the attachment of a fucose residue to a glycan or glycolipid. We demonstrated that fucosylated proteins are useful serum biomarkers for nonalcoholic fatty liver disease. Among fucosyltransferases, expression of alpha-1, 6-fucosyltransferase (Fut8), which produces core fucose, is frequently elevated during the progression of human chronic liver diseases. Previously, we discovered core-fucose-specific Pholiota squarrosa lectin (PhoSL) from Japanese mushroom Sugitake. Lectins are bioactive compounds that bind to glycan specifically, and various kinds of lectin have a variety of biological functions. Using high-fat and high-cholesterol (HFHC)-fed steatohepatitic mice, we found that core fucosylation increases in hepatic inflammatory macrophages. Antibody drugs bind to specific antigens and block protein function. We hypothesized that, like antibody drugs, PhoSL could have inhibitory effects on glycoproteins involved in steatohepatitis progression. PhoSL administration dramatically decreased hepatic macrophage infiltration and liver fibrosis-related gene expression. Using mouse macrophage-like cell RAW264.7, we found that PhoSL enhanced core-fucose-mediated activation of macrophage cell death by blocking interferon-γ/signal transducer and activator of transcription 1 (STAT1) signaling. Core-fucose-mediated cell death is a mechanism for the anti-inflammatory effects and anti-fibrotic effects of PhoSL on activated macrophages in steatohepatitic liver. In addition, PhoSL provides an anti-fibrotic effect by blocking transforming growth factor-β/SMAD family member 3 signaling in hepatic stellate cells. In conclusion, we found core-fucose-specific PhoSL administration could suppress steatohepatitis progression by decreasing inflammatory macrophage infiltration and fibrotic signaling in hepatic stellate cells.

Dysregulation of the Arachidonic Acid Pathway in Cystic Fibrosis: Implications for Chronic Inflammation and Disease Progression

Cystic fibrosis (CF) is the most common fatal genetic disease among Caucasian people, with over 2000 mutations in the CFTR gene. Although highly effective modulators have been developed to rescue the mutant CFTR protein, unresolved inflammation and persistent infections still threaten the lives of patients. While the central role of arachidonic acid (AA) and its metabolites in the inflammatory response is widely recognized, less is known about their impact on immunomodulation and metabolic implications in CF. To this end, here we provided a comprehensive analysis of the AA metabolism in CF. In this context, CFTR dysfunction appeared to complexly disrupt normal lipid processing, worsening the chronic airway inflammation, and compromising the immune responses to bacterial infections. As such, potential strategies targeting AA and its inflammatory mediators are being investigated as a promising approach to balance the inflammatory response while mitigating disease progression. Thus, a deeper understanding of the AA pathway dysfunction in CF may open innovative avenues for designing more effective therapeutic interventions.

The Role of Molecular and Cellular Aging Pathways on Age-Related Hearing Loss.

Aging, a complex process marked by molecular and cellular changes, inevitably influences tissue and organ homeostasis and leads to an increased onset or progression of many chronic diseases and conditions, one of which is age-related hearing loss (ARHL). ARHL, known as presbycusis, is characterized by the gradual and irreversible decline in auditory sensitivity, accompanied by the loss of auditory sensory cells and neurons, and the decline in auditory processing abilities associated with aging. The extended human lifespan achieved by modern medicine simultaneously exposes a rising prevalence of age-related conditions, with ARHL being one of the most significant. While our understanding of the molecular basis for aging has increased over the past three decades, a further understanding of the interrelationship between the key pathways controlling the aging process and the development of ARHL is needed to identify novel targets for the treatment of AHRL. The dysregulation of molecular pathways (AMPK, mTOR, insulin/IGF-1, and sirtuins) and cellular pathways (senescence, autophagy, and oxidative stress) have been shown to contribute to ARHL. However, the mechanistic basis for these pathways in the initiation and progression of ARHL needs to be clarified. Therefore, understanding how longevity pathways are associated with ARHL will directly influence the development of therapeutic strategies to treat or prevent ARHL. This review explores our current understanding of the molecular and cellular mechanisms of aging and hearing loss and their potential to provide new approaches for early diagnosis, prevention, and treatment of ARHL.

Immunobiology of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory progressive cholestatic liver disease. Genetic risk factors, presence of autoantibodies, the strong clinical link with inflammatory bowel disease (IBD), and associations with other autoimmune disorders all suggest a pivotal role for the immune system in PSC pathogenesis. In this review, we provide a comprehensive overview of recent immunobiology insights in PSC. A particular emphasis is given to immunological concepts such as tissue-residency and knowledge gained from novel technologies including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST). This review of the immunobiological landscape of PSC covers major immune cell types known to be enriched in PSC-diseased livers as well as recently described cell types whose biliary localization and contribution to PSC immunopathogenesis remain incompletely described. Finally, we emphasize the importance of time and space in relation to PSC heterogeneity as a key consideration for future studies interrogating the role of the immune system in PSC.

Emerging Oral Pharmaceuticals for Dry Age-Related Macular Degeneration: Mechanism of Action, Current Clinical Status, and Future Directions.

Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there has been a flurry of research focused on discovering new targets to prevent worsening of dry AMD. In 2023, the US Food and Drug Administration approved the first two intravitreal complement inhibitors to slow the rate of geographic atrophy progression. However, serial intravitreal injections for a chronic progressive disease are burdensome for patients and have procedural risks. Therefore, there is significant research to discover novel oral medications to manage dry AMD. Several oral medications are currently in phase 2 and 3 clinical trials for dry AMD, whereas others have had recent readouts on their clinical trials and efficacy. The purpose of this review is to describe the therapeutic pathways currently being investigated and to provide an update on the clinical status of novel oral medications for the management of dry AMD. [Ophthalmic Surg Lasers Imaging Retina 2024;55:528-534.].

Enpp1 mutations promote upregulation of hedgehog signaling in heterotopic ossification with aging.

Heterotopic ossification of the tendon and ligament (HOTL) is a chronic progressive disease that is usually accompanied by thickening and ossification of ligaments and high osteogenic activity of the surrounding ligament tissue. However, the molecular mechanism of maintaining the cellular phenotype of HOTL remains unclear. We first constructed a model of HOTL, Enpp1flox/flox/EIIa-Cre mice, a novel genetic mouse system. Imaging, histological, and cell-level analyses were performed to investigate the progressive ossification of the posterior longitudinal ligament, Achilles tendons, and degeneration joints caused by Enpp1 deficiency. The results indicate that Enpp1 deficiency led to markedly progressive heterotopic ossification (HO), especially spine, and Achilles tendons, and was associated with progressive degeneration of the knees. The bone mass was decreased in the long bone. Furthermore, fibroblasts from Enpp1flox/flox/EIIa-Cre mice had greater osteogenic differentiation potential following induction by osteogenesis, accompanied by enhanced hedgehog (Hh) signaling. In addition, fibroblast cells show senescence, and aggravation of the senescence phenotype by further osteogenic induction. Our study indicated that with increasing age, mutations in Enpp1 promote ectopic ossification of spinal ligaments and endochondral ossification in tendons and further aggravate knee degeneration by upregulating hedgehog signaling.

Hunter’s syndrome: a rare case report

Hunter’s syndrome also known as mucopolysaccridosis-II (MPS-II) is a very rare X-linked recessive disease. It is a chronic progressive metabolic disease. The incidence of this condition is 1 in 1, 62,000 live births, mostly males. There is excessive accumulation of glycosaminoglycan (GAGs) in the lysosome in various parts of body due to the deficiency of enzyme iduronate sulphatase (IDS) and manifests with variety of clinical signs and symptoms. Four novel mutations in IDS gene are reported among families of Hunter syndrome tested by Sanger sequencing of IDS gene.

Optimalisasi Kesadaran Kesehatan Warga Desa Sarirogo dengan Sosialisasi Hidup Sehat dan Implementasi Medical Check-up

This study aims to thoroughly explore the role of medical check-ups in maintaining the basic physical health of the residents of Sarirogo Village, with a particular focus on the prevention of non-communicable diseases, which have been on the rise in the area. The background of this research is based on the fact that there is a high prevalence of non-communicable diseases, such as hypertension, diabetes, and cardiovascular diseases, that often go undetected in their early stages. This is primarily due to a lack of public awareness about the importance of regular health checkups, as well as limited access to adequate healthcare services. As a result, delayed diagnoses exacerbate the overall health conditions within the community. This study employs a qualitative approach using a literature review method to analyze sources from relevant scientific journals. These sources serve as the theoretical foundation to understand the relationship between the frequency of medical check-ups and the prevention of chronic disease progression. The findings of this study highlight the significant role that medical check-ups play in the early detection of various potentially life-threatening health conditions, thereby preventing the development of more serious illnesses. Based on these findings, this research emphasizes the urgent need to enhance the accessibility of regular medical check-up services for the residents of Sarirogo Village, alongside the necessity to raise collective awareness about the benefits of routine health screenings.

In vitro evidence of antioxidant and anti-inflammatory effects of a new nutraceutical formulation explains benefits in a clinical setting of COPD patients.

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.

Renal arterial resistance index before and after vericiguat administration: Should it be considered the fantastic five?

BackgroundHeart failure (HF) is a chronic-progressive disease. Once established, it is almost impossible to obtain a restitutio ad integrum of the cardiac function, but current strategies aim at slowing down the progression towards the terminal stages of the disease, which inevitably lead to the exitus. On the basis of these considerations, it appears clear that pharmacological interventions applied in this clinical condition should prevent first the development of the disease, by controlling the risk factors for HF thus reducing the onset of the disease, second slowing the disease evolution towards the terminal phases thus containing clinical symptoms and reducing the number of hospitalizations. In this scenario, the add-on therapy with vericiguat seems promising as reported in the VICTORIA study without affecting renal function. Several evidence indicates that renal arterial resistance index (RRI) seems to better reflect cardiovascular damage also in HF patients, thus affecting patients prognosis MethodsIn the present study we have analyzed the effect of vericiguat administration in 27 HF patients specifically evaluating RRI. ResultsVericiguat signicantly reduces RRI. ConclusionsThe findings of the present study seems to indicate that vericiguat, beyond its primary mechanism of action, might offer an additional advantage in HF patients.

Metabolic Reprogramming of Astrocytes in Pathological Conditions: Implications for Neurodegenerative Diseases.

Astrocytes play a pivotal role in maintaining brain energy homeostasis, supporting neuronal function through glycolysis and lipid metabolism. This review explores the metabolic intricacies of astrocytes in both physiological and pathological conditions, highlighting their adaptive plasticity and diverse functions. Under normal conditions, astrocytes modulate synaptic activity, recycle neurotransmitters, and maintain the blood-brain barrier, ensuring a balanced energy supply and protection against oxidative stress. However, in response to central nervous system pathologies such as neurotrauma, stroke, infections, and neurodegenerative diseases like Alzheimer's and Huntington's disease, astrocytes undergo significant morphological, molecular, and metabolic changes. Reactive astrocytes upregulate glycolysis and fatty acid oxidation to meet increased energy demands, which can be protective in acute settings but may exacerbate chronic inflammation and disease progression. This review emphasizes the need for advanced molecular, genetic, and physiological tools to further understand astrocyte heterogeneity and their metabolic reprogramming in disease states.

MicroRNA levels in patients with chronic hepatitis B virus and HIV coinfection in a high-prevalence setting; KwaZulu-Natal, South Africa

BackgroundHepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load.MethodsPlasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels.ResultsSignificantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients.ConclusionThis study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.

Analysis of risk factors affecting postoperative neurological recovery in patients with cervical spine fracture in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease that mainly affects the spine and involves the sacroiliac and peripheral joints. Low-energy trauma can often lead to spinal fractures and spinal cord injuries (SCIs), the treatment of AS is challenging. The prognosis of neurological function in patients with AS cervical fracture and SCI is a major problem that must sought clinician attention on urgent basis. A total of 106 patients with AS cervical fractures who underwent surgical treatment at Shanghai Changzheng Hospital between August 2009 and 2021 were included in this study. All the patients were divided into 2 groups (improved group and the control group) based on their neurological function improvement at 1 year mark after the surgery. The baseline characteristics, perioperative factors, and procedural outcomes of all the patients including injury type, AS drug treatment, the injured segment, ossified anterior longitudinal ligament injury, spinal hypersignal, decompression time window, operation duration, blood loss, preoperative and postoperative American Spinal Injury Association (ASIA) score were recorded and analyzed. Among the 106 patients, 79 demonstrated improved neurological function at 1 year mark after the surgery. Binary univariate logistic regression analysis revealed significant differences in injury type (P = .018), ossified anterior longitudinal ligament injury (P = .01), operation duration (P = .002), spinal hypersignal (P = .001), preoperative ASIA score (P < .001), and prior AS drug treatment (P = .012). No significant differences were observed in the other variables (P > .05). Binary multivariate logistic regression analysis identified spinal hypersignal (OR = 37.185, P = .028), preoperative ASIA score (OR = 0.16, P = .012) and previous AS drug treatment (OR = 0.296, P = .049) as factors associated with postoperative neurological function improvement. The preoperative ASIA score and previous drug treatment of AS were identified as protective factors affecting the improvement of neurological functions in patients with AS cervical fracture after surgery. Preoperative T2-weighted spinal hypersignal was identified as an independent risk factor affecting the improvement of neurological function recovery in patients with AS cervical fracture after the surgery.

A Low Expression of NRF2 Enhances Oxidative Stress and Autophagy in Myofibroblasts, Promoting Progression of Chronic Obstructive Pulmonary Disease.

The inflammation phenotypes are often closely related to oxidative stress and autophagy pathway activation, which could be developed as a treatment target. The aim of this study was to explore the underlying mechanism of inflammation in chronic obstructive pulmonary disease (COPD). The lung tissue single-cell RNA-seq (scRNA-seq) dataset of GSE171541 was downloaded from the Gene Expression Omnibus (GEO) database. The marker genes were obtained from the CellMarker database. "Seurat" and "harmony" R packages were used for single-cell profiling analysis. Then, the "AUCell" R package was employed to calculate the reactive oxygen species (ROS) and autophagy pathway scores. Gene regulation network analysis was performed by applying the "SCENIC" package, followed by conducting correlation analysis with Spearman's rank correlation method. The cigarettes were used to develop a traumatic model in mice, and the expression of relevant genes was measured by qRT-PCR. The scRNA-seq analysis classified 12 cell subgroups in which the contractility of myofibroblasts was closely associated with the progression of COPD. Further analysis showed that ROS and autophagy pathways were significantly activated in myofibroblasts and that the nuclear factor erythroid 2-related factor 2 (NRF2) and its mediated oxidative stress pathway were inhibited in myofibroblasts. In addition, the downregulated NRF2 gene was negatively correlated with the expression of autophagy and ROS activation. In the traumatic mice model, NRF2 was downregulated in COPD mice but further elevated in the COPD+NRF2 mice group. Interestingly, the mRNA levels of Kelchlike ECH-associated protein 1 (Keap1), NADPH oxidase (NOX), and Cathepsin B (CTSB) were upregulated in COPD group in comparison to the control group but they were downregulated by NRF2. These results suggested that low-expressed NFR2 promoted autophagy and ROS pathway activation in myofibroblasts for COPD progression. We identified a cell myofibroblast cluster closely associated with COPD progression using the scRNA-seq analysis. The downregulated NFR2, as a key risk factor, mediated myofibroblast death by activating the oxidative stress and autophagy pathway for COPD progression.

Do we neglect nutrition in childhood interstitial lung disease?

Growth failure and inadequate weight gain are common problems in childhood interstitial lung diseases (chILD) and these children usually need high calories. It is important to manage both pulmonary functions and nutrition as part of their overall treatment plan and early interventions will help children to improve their quality of life and slow the progression of chronic lung disease. Nutritional evaluation on routine clinical follow-up is important, although there are not any specific guidelines for chILD. Nutritional education, high balanced energy, protein, and fat diet will assist to improve weight gain and maintenance of adequate nutrition status in children with ILD.

Enhancing Outcomes in Chronic Fibrotic Interstitial Lung Disease Through Aggressive Management of Nintedanib-Induced Adverse Drug Reactions: A Retrospective Analysis.

Nintedanib, a tyrosine kinase inhibitor, is integral in slowing pulmonary fibrosis progression in chronic fibrotic interstitial lung disease (ILD). However, the occurrence of adverse drug reactions (ADRs) often limits its use, leading to treatment discontinuation, typically within 3-12 months. Discontinuation adversely affects patient outcomes. The study investigated whether aggressive ADR management can prolong nintedanib therapy and improve patient outcomes. This retrospective, single-center study enrolled Taiwanese patients with chronic fibrotic ILD who were treated with nintedanib from January 2016 to December 2022 in Kaohsiung Chang Gung Memorial Hospital. Patients were categorized into those who discontinued treatment within 180 days and those continuing beyond. Management of ADRs was identified through concurrent prescriptions for symptoms such as nausea, vomiting, diarrhea, or hepatic dysfunction. Baseline demographics, comorbidities, pulmonary function tests, and instances of acute exacerbation were analyzed. The study enrolled 94 patients, with 71 (75.5%) experiencing ADRs. Among these, 41 (43.6%) discontinued nintedanib within 180 days. The administration of medications for managing nausea/vomiting [17 (41.5%) versus 36 (67.9%), p = 0.0103] and diarrhea [12 (29.3%) versus 33 (62.3%), p = 0.0015] was less frequent in the discontinued group compared with the continued group. Additionally, a higher incidence of acute exacerbation was observed in the discontinued group (34.1% versus 20.8%, p = 0.016). Aggressive management of ADRs may enhance patient tolerance to nintedanib, potentially prolonging treatment duration and improving outcomes in chronic fibrotic ILD.

Construction of metal interpretable scoring system and identification of tungsten as a novel risk factor in COPD

Numerous studies have highlighted the correlation between metal intake and deteriorated pulmonary function, emphasizing its pivotal role in the progression of Chronic Obstructive Pulmonary Disease (COPD). However, the efficacy of traditional models is often compromised due to overfitting and high bias in datasets with low-level exposure, rendering them ineffective in delineating the contemporary risk trends associated with pulmonary diseases. To address these limitations, we embarked on developing advanced, interpretable models, crucial for elucidating the intricate mechanisms of metal toxicity and enriching the domain knowledge embedded in toxicity models. In this endeavor, we scrutinized extensive, long-term metal exposure datasets from NHANES to explore the interplay between metal and pulmonary functionality. Employing a variety of machine-learning approaches, we opted for the “Mixer of Experts” model for its proficiency in identifying a myriad of toxicological trends and sensitivities. We conceptualized and illustrated the TSAP (Toxicity Score at Population-level), a metal interpretable scoring system offering performance nearly equivalent to the amalgamation of standard interpretable methods addressing the “black box” conundrum. This streamlined, bifurcated procedural analysis proved instrumental in discerning established risk factors, thereby uncovering Tungsten as a novel contributor to COPD risk. SynopsisTSAP achieved satisfied performance with transparent interpretability, suggesting tungsten intake need further action for COPD prevention.

Evaluation of treatment response with serial CT in patients with non-tuberculous mycobacterial pulmonary disease.

In patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD), the response to treatment is evaluated based on microbiological, clinical, and radiological data. However, little is known about the dynamics of CT findings. The aim of this study was to evaluate CT changes in NTM-PD in order to define radiological criteria for treatment success. Retrospective multicenter study (Hannover, Heidelberg, Gauting). Sixty patients with NTM-PD and at least two consecutive CT scans were included. Scoring for NTM-PD was performed by evaluating variables of bronchiectasis, mucus plugging, bronchiolitis, cavities, nodules, and consolidations on an ordinal scale from 0 to 3. Differences between baseline and follow-up were calculated, and patients with/without cultural conversion were compared using the Mann-Whitney U-test. For paired comparison of the two consecutive CT scans the Wilcoxon test was used. Comparing patients with and without culture conversion, there were significant differences in temporal changes of bronchiectasis (p < 0.001), cavities (p = 0.006), bronchiolitis (p < 0.001), consolidations (p = 0.004), and total score (p < 0.001). Nodules showed no significant differences between groups (p = 0.060). The Wilcoxon test showed significant differences between both CTs in patients with a microbiological cure for the total score (p < 0.001), cavities (p = 0.005), bronchiolitis (p < 0.001), and consolidations (p = 0.021) with a decrease after microbiological cure, whereas bronchiectasis (p = 0.102) and nodules (p = 0.18) stayed stable. In the case of persistently positive cultures, there was an increase in the total score (p = 0.010) which was attributable to progressivebronchiectasis (p < 0.001). Cavities, consolidations, and bronchiolitis are useful to assess treatment response, whereas bronchiectasis and nodules may remain stable despite successful treatment. Cavities, consolidations, and bronchiolitis can assess treatment response whereas bronchiectasis and nodules may remain stable despite successful treatment. In persistently positive cultures, bronchiectasis showed an increase over time indicating that NTM-PD is a progressive chronic disease. Little is known about CT changes in nontuberculous mycobacteriapulmonary disease (NTM-PD) and criteria to evaluate treatment response. In the case of culture conversion, cavities and bronchiolitis decreased whereas bronchiectasis and nodules remained stable. Cavities and bronchiolitis can evaluate treatment response in NTM, but bronchiectasis and nodules may persist despite successful treatment.