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23 pages, 2824 KB  
Article
Chronic IL-1 Exposure Attenuates IL-1 Response and Alters Gene Expression Regulation While Maintaining Therapeutic Sensitivity in BCa Cell Lines
by Rafah Falah, Roopal Dhar, Stephanie Yamauchi, Monica Bautista, Mohammed Kanchwala, Liu Yan, Dinesh Raju, Linyi Xu, Kylah Reliford, Afshan Nawas, Samrah Ali, Justin Fang, Ola Olaleye, Jyotsna Tera, Rana Abdelaziz, Reshmika Kanakala, Aniketh Sudunagunta, Subhash Eedarapali, Emmalee Burr, Basir S. Mansoor, Nicole Roos, Sydney Diep, Hiba Afaq, Niranjana Pillai Rajesh, Saanvi Manohar, Jennifer Odikpo, Abhinav K. Jain, Zhenyu Xuan, Chao Xing and Nikki A. Delkadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2026, 27(13), 6039; https://doi.org/10.3390/ijms27136039 (registering DOI) - 5 Jul 2026
Abstract
Chronic inflammation is a hallmark of the breast cancer tumor microenvironment and is also known to be associated with disease progression and therapeutic response. Interleukin-1 (IL-1) signaling has been widely studied in breast cancer biology; however, the long-term effect of sustained IL-1 exposure [...] Read more.
Chronic inflammation is a hallmark of the breast cancer tumor microenvironment and is also known to be associated with disease progression and therapeutic response. Interleukin-1 (IL-1) signaling has been widely studied in breast cancer biology; however, the long-term effect of sustained IL-1 exposure on hormone receptor-positive breast cancer cells remain poorly understood. In this study, we investigated how chronic IL-1 exposure influences inflammatory response, hormone dependency, and therapeutic sensitivity in ERα+/PR+ breast cancer models, MCF7 and T47D. Chronic IL-1 exposure attenuated response to subsequent acute IL-1 treatment, but the chronically exposed cells remained sensitive to serum deprivation, retained dependence on estrogen or progesterone receptor signaling, and responded robustly to endocrine and chemotherapeutic treatments. Extensive changes in basal gene expression and histone modification revealed that chronic IL-1 exposure alters transcriptional reprogramming and chromatin remodeling. Together, these findings demonstrate that chronic IL-1 signaling drives selective inflammatory response in hormone receptor-positive MCF7 and T47D breast cancer cells. This work underscores the continued therapeutic relevance of hormone receptor-targeted strategies in chronically inflamed tumors and provides insight into how sustained inflammatory stress shapes tumor behavior and gene regulation predicted to promote tumor progression. Full article
(This article belongs to the Special Issue Breast Cancer and Hormone Receptors: Molecular Insights)
12 pages, 2896 KB  
Article
Beating-Heart Coronary Artery Bypass Grafting in Patients with End-Stage Renal Failure: Short-Term Gains, Intermediate-Term Losses
by Louis Samuels, Suzanne Raws and Molly Casey
J. CardioRenal Med. 2026, 2(3), 9; https://doi.org/10.3390/jcrm2030009 (registering DOI) - 5 Jul 2026
Abstract
Introduction: Coronary artery bypass grafting (CABG) in patients with chronic kidney disease/chronic renal failure (CKD/CRF) poses additional surgical risk, both perioperatively and beyond, compared to their non-renal failure counterparts. Patients with end-stage renal disease (ESRD) are at particularly high risk for complications with [...] Read more.
Introduction: Coronary artery bypass grafting (CABG) in patients with chronic kidney disease/chronic renal failure (CKD/CRF) poses additional surgical risk, both perioperatively and beyond, compared to their non-renal failure counterparts. Patients with end-stage renal disease (ESRD) are at particularly high risk for complications with prognoses limited by cardiovascular (e.g., myocardial infarction, heart failure, stroke) and non-cardiovascular (e.g., infection) conditions associated with the disease itself and the treatment of it (i.e., dialysis). For decades, cardiac surgeons have continued to offer CABG to patients with ESRD on dialysis with variable success. The purpose of this report is to describe a relatively contemporary analysis of CABG surgery in ESRD patients utilizing a pump-assisted beating-heart technique with the analysis of and comparison to outcomes reported by other investigators as well as predictions generated by the Society of Thoracic Surgery outcome tool. We report both short- and intermediate-term outcomes. Methods: From 1 January 2019 through 31 May 2025, the data from all consecutive patients undergoing BH-CABG at a single institution by a single surgeon were collected. Demographic information as well as a preoperative risk assessment was performed using the Society of Thoracic Surgeon (STS) Risk Assessment tool. The BH-CABG was performed via median sternotomy with maintenance of normothermia and ventilation throughout the case. Postoperative outcomes were recorded including mortality, major morbidity, and length of stay (LOS). Hospital/operative results were compared to the STS risk calculations. On-going intermediate-term follow-up beyond the index hospitalization was completed using direct or indirect methods (i.e., clinic, telephone, email). Results: There were 439 BH-CABG patients during the study period. Fifty-nine patients (13.4%) had ESRD on HD. There were 39 men and 20 women with a mean age of 61 years (41–76 years). Fifty-one (86%) underwent pump-assisted BH-CABG (PADCAB) and eight patients underwent complete off-pump BH-CABG (OPCAB). The mean ejection fraction (EF) was 48% (15–70%). The mean number of grafts was 2.3 (1 to 4) and the mean cardiopulmonary bypass (CPB) time for the PADCAB cases was 80 min (34 to 118 min). Patient presentation consisted of the following: one with cardiogenic shock, one with cardiac arrest, two with STEMI, 18 with NSTEMIs, 10 with CHF, five with NSTEMI/CHF, six with unstable angina (USA), and 16 with a positive stress test in preparation for renal transplant consideration. There was one operative mortality (1.7%), one stroke (1.7%), no reoperation for bleeding, no deep sternal wound infection, one prolonged ventilation (1.7%), and one prolonged length of stay (1.7%); overall mortality/morbidity was 5.1%. Comparatively, the STS-predicted mortality was 5.7%, stroke 2.2%, reoperation for bleeding 3.5%, deep sternal wound infection 0.6%, prolonged ventilation 17.8%, prolonged LOS 14.8%, and combined mortality/morbidity 26.8%. Thirty-six of the 59 patients remained alive (61%) in the follow-up period. Twenty-three patients expired (39%) in the follow-up: 11 of cardiac issues, eight of sepsis, two of stroke, one of gastrointestinal issues, and one of cancer. The average duration of survival for expired patients was 2.28 years (13 days to 5 years and 4 months). Nine patients (15%) underwent renal transplantation and six of them remained alive (67%). Conclusions: CABG surgery in patients with ESRD is complicated with historically high mortality and morbidity. The results of this study demonstrate significant improvement in the reduction in hospital mortality and morbidity. However, intermediate-term outcomes remain poor with a preponderance of cardiovascular and infectious deaths. A trend toward improved intermediate-term outcomes appears in patients in whom CABG surgery was performed for purposes of renal transplantation. Full article
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30 pages, 2309 KB  
Review
Cutaneous Staphylococcus aureus Infections in Renal Edema Across Kidney Disease and the Intensive Care Unit: Pathophysiological Mechanisms, Clinical Implications, and Therapeutic Challenges
by Mariana-Emilia Caragea, Daniel Cosmin Caragea, Marius Bogdan Novac, Lidia Boldeanu, Mohamed-Zakaria Assani, Dragoș Forțofoiu, Vlad Pădureanu, Mihail Virgil Boldeanu, Dragoș-Marian Popescu and Cristin Constantin Vere
Int. J. Mol. Sci. 2026, 27(13), 6038; https://doi.org/10.3390/ijms27136038 (registering DOI) - 5 Jul 2026
Abstract
Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), remains a leading cause of skin and soft tissue infections (SSTIs) worldwide. Patients with renal edema, including those with nephrotic syndrome and chronic kidney disease (CKD), and critical illness, are particularly susceptible because of barrier [...] Read more.
Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), remains a leading cause of skin and soft tissue infections (SSTIs) worldwide. Patients with renal edema, including those with nephrotic syndrome and chronic kidney disease (CKD), and critical illness, are particularly susceptible because of barrier dysfunction, immune impairment, and altered antimicrobial pharmacokinetics. This narrative review examines the mechanisms linking renal edema to increased susceptibility to cutaneous S. aureus infection and discusses their diagnostic and therapeutic implications. Three interconnected pathophysiological pathways appear central to this susceptibility: disruption of the cutaneous barrier, nephrotic and uremic immune dysfunction, and impaired lymphatic immune surveillance. These abnormalities facilitate bacterial colonization, and invasion, while S. aureus further exploits the renal host through adhesins, toxins, biofilm formation, and immune-evasion mechanisms. The review also highlights the challenges of managing severe staphylococcal infections in patients with kidney disease and critical illness, where augmented renal clearance, expanded volume of distribution, extracorporeal renal support, and fluctuating renal function may substantially influence antimicrobial exposure. Current management requires early recognition, source control, individualized antimicrobial selection, renal-adapted dosing, therapeutic drug monitoring, and antimicrobial stewardship. Although emerging anti-virulence and immunomodulatory strategies show promise, most remain at the preclinical or early translational stage. Overall, renal edema should be regarded as a biologically active modifier of host–pathogen interactions that contributes to increased susceptibility to cutaneous S. aureus infection across the spectrum of kidney disease. Full article
(This article belongs to the Section Molecular Microbiology)
35 pages, 895 KB  
Review
What Do We Know About Immune System Aging from Human and Animal Studies?
by Marta Cąkała-Jakimowicz, Anna Domaszewska-Szostek and Monika Puzianowska-Kuźnicka
Int. J. Mol. Sci. 2026, 27(13), 6037; https://doi.org/10.3390/ijms27136037 (registering DOI) - 5 Jul 2026
Abstract
Aging is accompanied by complex structural and functional immune system changes driven by genomic instability, epigenetic alterations, mitochondrial dysfunction, telomere attrition, loss of proteostasis, deregulated nutrient sensing, and the accumulation of senescent cells exhibiting a senescence-associated secretory phenotype, which altogether lead to severe [...] Read more.
Aging is accompanied by complex structural and functional immune system changes driven by genomic instability, epigenetic alterations, mitochondrial dysfunction, telomere attrition, loss of proteostasis, deregulated nutrient sensing, and the accumulation of senescent cells exhibiting a senescence-associated secretory phenotype, which altogether lead to severe consequences including altered antimicrobial defense, the overproduction of autoantibodies, and chronic, low-grade inflammation (inflammaging). In this article, we summarize age-related alterations in the function of primary and secondary lymphoid organs, including the bone marrow, thymus, spleen, and lymph nodes. The involution of these organs leads to impaired hematopoiesis, reduced production of naïve lymphocytes, and immune microenvironment disruption. We also describe aging-related impairment of the activity of neutrophils, macrophages, dendritic cells and natural killer cells, as well as dysregulation of T and B lymphocyte responses. Specifically, these alterations include a decline in naïve cell populations, an accumulation of memory and exhausted cells, and a reduction in the diversity of antigen receptors. Consequently, older individuals exhibit increased susceptibility to infections, cancer, and autoimmune diseases, along with diminished vaccine efficacy. Understanding the mechanisms underlying immune aging could lay the foundation for developing therapeutic strategies and lifestyle interventions to mitigate the adverse effects of this unfavorable process. Full article
(This article belongs to the Special Issue Understanding Aging in Health and Disease)
29 pages, 2234 KB  
Review
Epigenetic Regulation of Modulatory Neurotransmitter System Integrity in the Aging Brain: A Scoping Review Across the Lifespan
by Khalid W. Freij, Arshiya Akbar, Philemon Domoyeri, Nunaya Polycarp, Dylan R. Higginbotham, Itika Arora and Edwin N. Aroke
Life 2026, 16(7), 1122; https://doi.org/10.3390/life16071122 (registering DOI) - 5 Jul 2026
Abstract
Age-related changes in neurotransmitter systems contribute to declines in cognitive, emotional, and motor function, yet the biological mechanisms linking these changes to aging are not completely understood. Epigenetic regulation offers a promising framework to bridge this gap. DNA methylation-based biomarkers of biological aging [...] Read more.
Age-related changes in neurotransmitter systems contribute to declines in cognitive, emotional, and motor function, yet the biological mechanisms linking these changes to aging are not completely understood. Epigenetic regulation offers a promising framework to bridge this gap. DNA methylation-based biomarkers of biological aging (i.e., epigenetic clocks) capture cumulative and dynamic aspects of biological aging that may reflect vulnerability in neural systems beyond chronological age. However, whether these indices track with the integrity of neurotransmitter systems has not been systematically examined. This scoping review synthesizes evidence across human studies to evaluate how epigenetic aging processes influence neurotransmitter gene regulation and system function across the lifespan. We included 109 studies spanning 2005–2026. GABAergic genes (GAD1, GABRA2) showed the most consistent and reproducible age-related promoter hypermethylation across the cortex, inversely correlated with mRNA expression and corroborated by MRS evidence of cortical GABA decline. Dopaminergic and serotonergic evidence during normative aging was sparse; most epigenetic data in these systems came from disease cohorts. Histone modifications converged on neurotransmission and synaptic-plasticity loci, predominantly in Alzheimer’s disease tissue. Subcortical and brainstem nuclei central to monoaminergic and cholinergic systems remain under-investigated for normative aging epigenetic processes. Environmental and social determinants, socioeconomic status, childhood adversity, and chronic stress, were consistently associated with accelerated peripheral epigenetic aging, but brain-specific data are scarce. Full article
(This article belongs to the Special Issue Cortical Development and Neurotransmission)
17 pages, 1197 KB  
Article
Comorbidity Profiles at Diagnosis in Rheumatoid Arthritis Versus Psoriatic Arthritis: A Nationwide Polish Claims-Based Study
by Wojciech Zaręba, Mateusz Szeląg, Krzysztof Batko, Piotr Krawiec, Marcin Stajszczyk, Krzysztof Podwójcic, Zbigniew Żuber, Magdalena Krajewska-Włodarczyk and Bogdan Batko
J. Clin. Med. 2026, 15(13), 5249; https://doi.org/10.3390/jcm15135249 (registering DOI) - 5 Jul 2026
Abstract
Background: Nationwide epidemiologic data on comorbidity burden in early rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are limited. We compared coded diagnoses for concurrent disorders in incident RA and PsA based on administrative healthcare data (AHC). Methods: This retrospective cohort study [...] Read more.
Background: Nationwide epidemiologic data on comorbidity burden in early rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are limited. We compared coded diagnoses for concurrent disorders in incident RA and PsA based on administrative healthcare data (AHC). Methods: This retrospective cohort study used AHCs from the National Health Fund between 2009 and 2021. Using composite proxy definitions for RA and PsA diagnosis (combination of ICD-10 codes and prescription data), we identified all new cases of RA and PsA between 2019 and 2021. We utilized a ten-year lookback window for the accrual of concurrent disorder claims. Age-, sex-, serostatus- and calendar year-adjusted models were considered. Crude, relative and adjusted prevalence estimates were calculated using generalized linear models. Results: Using NHF data, we identified 36,285 and 1603 patients with incident RA/PsA, respectively. We estimated the burden of 31 multisystem comorbidities. Most disorders (N = 23, 74.2%) were more frequently coded among RA patients, while only liver diseases were significantly more prevalent in PsA. Chronic back pain (+21.2 pp) and osteoarthritis (+18.3 pp) were tied to the greatest absolute differences, likely mirroring medical contact patterns throughout the differential diagnostic process. Hospitalization due to heart failure and stroke, but not myocardial infarction, was more common in RA vs. PsA. Conclusions: Newly diagnosed patients with RA and PsA show distinct patterns of healthcare utilization for multiple organ disorders. Early RA may be tied to higher comorbidity rates not fully explained by age and sex, as compared to PsA; further studies are necessary to clarify these observations. Full article
(This article belongs to the Special Issue Clinical Updates on Rheumatoid Arthritis: 2nd Edition)
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15 pages, 815 KB  
Article
Management of Infected, Non-Responsive Atopic Dermatitis in a Romanian Center
by Raluca-Gabriela Miulescu, Ioana Roșca, Alexandru-Neculai Pavel, Ruxandra-Cristina Marin, Andreea Teodora Constantin, Monica Costescu, Elena Poenaru, Daniela Eugenia Popescu and Oana Andreia Coman
J. Clin. Med. 2026, 15(13), 5248; https://doi.org/10.3390/jcm15135248 (registering DOI) - 5 Jul 2026
Abstract
Background: Atopic dermatitis is a chronic inflammatory skin disease in children, frequently associated with skin barrier dysfunction, immune dysregulation, and dysbiosis. Infected, treatment-resistant lesions may increase disease severity and complicate management, particularly in the presence of Staphylococcus aureus colonization. Objectives: To [...] Read more.
Background: Atopic dermatitis is a chronic inflammatory skin disease in children, frequently associated with skin barrier dysfunction, immune dysregulation, and dysbiosis. Infected, treatment-resistant lesions may increase disease severity and complicate management, particularly in the presence of Staphylococcus aureus colonization. Objectives: To characterize the microbiological profile of infected, non-responsive pediatric atopic dermatitis, evaluate short-term clinical outcomes following individualized treatment, and identify predictors of disease severity. Methods: This observational analytical study included 41 children with atopic dermatitis recruited at Saint Constantin Hospital, Brașov, Romania, between September 2025 and February 2026. Eligible patients fulfilled the Hanifin and Rajka criteria and presented with infected, treatment-resistant lesions. Skin cultures were subjected to an antibiogram and antifungigram. Disease severity was assessed using the Patient-Oriented Eczema Measure (POEM) and SCORAD at baseline, 7 days, and 30 days. Repeated-measures ANOVA, mixed ANOVA, and hierarchical linear regression were used for statistical analysis. Results: Staphylococcus aureus was the predominant pathogen, followed by other bacterial species. Both POEM and SCORAD scores improved significantly over the 30-day follow-up, with marked improvement after 7 days and further reduction by day 30. Although patients with S. aureus colonization and those receiving systemic therapy tended to have higher disease severity, neither factor significantly influenced the trajectory of clinical improvement. Baseline disease severity was the strongest predictor of 30-day POEM and SCORAD outcomes, whereas demographic and perinatal characteristics did not independently predict short-term clinical outcomes. Conclusions: Individualized management was associated with significant improvements in clinician-assessed disease severity and patient-reported symptoms during the 30-day follow-up. Staphylococcus aureus, particularly methicillin-sensitive S. aureus (MSSA), was the most frequently isolated pathogen. Baseline disease severity was the strongest predictor of short-term clinical outcomes, whereas the evaluated demographic and perinatal characteristics did not provide additional predictive value in this cohort. Larger prospective controlled studies are needed to confirm these findings. Full article
(This article belongs to the Section Dermatology)
21 pages, 1867 KB  
Article
Long-Term Trends and Prognosis in Cardiovascular Mortality in the Kazakhstani Population Living Around the Semipalatinsk Nuclear Test Site
by Dariya Shabdarbayeva, Lyudmila Pivina, Nailya Chaizhunussova, Andrey Orekhov, Galiya Alibayeva, Meruyert Massabayeva, Assel Baibussinova, Gulnara Batenova, Zhanargul Smailova, Saulesh Apbassova, Saule Kozhanova, Madina Abenova, Alexandra Lipikhina, Asset Izdenov, Diana Ygiyeva, Raushan Dosmagambetova and Altay Dyussupov
Int. J. Environ. Res. Public Health 2026, 23(7), 874; https://doi.org/10.3390/ijerph23070874 (registering DOI) - 5 Jul 2026
Abstract
Background: The purpose of the study is the assessment of mortality from cardiovascular diseases (CVDs) and their dose–response relationships and the calculation of the number of years of life lost (YLL) in Kazakhstani residents living in territories around the Semipalatinsk nuclear test site. [...] Read more.
Background: The purpose of the study is the assessment of mortality from cardiovascular diseases (CVDs) and their dose–response relationships and the calculation of the number of years of life lost (YLL) in Kazakhstani residents living in territories around the Semipalatinsk nuclear test site. Materials and Methods: The study is based on the State Scientific Automated Medical Registry (SSAMR) database. The study included 3482 residents of the Abay and Beskaragai districts exposed to radiation and 1886 residents of the Kokpekty district (control group). The median equivalent radiation dose for the exposed group was 864.0 mSv, compared to 64.4 mSv in the control group. The study period was from 1949 to 2024. Results: Mortality rates in the exposed group exceeded those of the comparison group throughout the study. The relative risk (RR) of mortality was 1.41 for all CVDs, 2.0 for stroke, 7.88 for chronic cerebrovascular disease (CCVD), and 2.39 for congenital heart disease (CHD). Age-standardized mortality rates were higher in the radiation-exposed population, with the highest excess risk recorded in 1960–1964 (RR = 5.31; 95% CI 4.32–6.53). The number of YLL from acute myocardial infarction (AMI) was 6097.0 in the exposed group versus 5893.0 in the comparison group, 3857.5 from hemorrhagic stroke versus 1996.9, and 2696.6 from CHD versus 957.7. An increase in radiation dose by 1 cSv was associated with an 8.5% increase in the odds of death from CVDs (OR = 1.085; 95% CI 1.075–1.094; p < 0.001). Radiation dose demonstrated good predictive ability for mortality from cardiovascular diseases (AUC = 0.700). Conclusions: The results indicate an increased risk of CVD mortality among residents of radiation-contaminated areas of Kazakhstan throughout the study period. Full article
(This article belongs to the Section Environmental Health)
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13 pages, 716 KB  
Article
Fragility Score in Radiographic Axial Spondyloarthritis Assessed with Radiofrequency Echographic Multi-Spectrometry (REMS)
by Elena Bischoff, Stoyanka Vladeva, Nikola Kirilov and Fabian Bischoff
Life 2026, 16(7), 1121; https://doi.org/10.3390/life16071121 (registering DOI) - 5 Jul 2026
Abstract
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the sacroiliac joints and spine and is associated with an increased risk of fractures due to persistent inflammation, reduced mobility and treatment-related factors. In radiographic axSpA (r-axSpA), assessment of bone mineral density (BMD) using [...] Read more.
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the sacroiliac joints and spine and is associated with an increased risk of fractures due to persistent inflammation, reduced mobility and treatment-related factors. In radiographic axSpA (r-axSpA), assessment of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) may be limited by structural spinal changes. This cross-sectional study, conducted between March 2024 and June 2025, evaluated skeletal fragility in patients with r-axSpA using Radiofrequency Echographic Multi-Spectrometry (REMS)-derived Fragility Score (FS). Ninety patients with r-axSpA and sex-matched healthy controls underwent clinical assessment and REMS evaluation of lumbar spine and hip BMD, T-scores and spinal FS. Patients with r-axSpA had lower body mass index and higher rates of smoking, prior fractures and inflammatory markers compared with controls, while disease activity reflected a moderate burden. No significant differences in BMD or T-scores were observed between groups. However, FS was significantly higher in patients with r-axSpA (46.6 ± 15.4 vs. 31.2 ± 13.3, p = 0.004), corresponding to a higher fracture risk category, whereas correlations between FS and clinical parameters were not statistically significant. These findings suggest that REMS-derived FS may identify increased skeletal fragility in r-axSpA beyond conventional BMD measurements. Full article
(This article belongs to the Section Radiobiology and Nuclear Medicine)
14 pages, 1045 KB  
Article
Eustachian Tube Obstruction Grade as an Independent Determinant of Audiological and Quality-of-Life Outcomes in Pediatric Chronic Adenoiditis: A Retrospective Cohort Study
by Diana Szekely, Flavia Zara, Raul Patrascu, Cristina Stefania Dumitru, Alina Cristina Barb, Dorin Novacescu, Antonia Armega Anghelescu, Alexia Manole, Dan Iovanescu and Gheorghe Iovanescu
Medicina 2026, 62(7), 1297; https://doi.org/10.3390/medicina62071297 (registering DOI) - 5 Jul 2026
Abstract
Background and Objectives: Eustachian tube (ET) dysfunction links adenoidal disease to persistent middle ear dysfunction in children, yet the independent contribution of ET orifice obstruction grade to audiological outcomes and health-related quality of life remains unquantified after adjustment for anatomical and inflammatory [...] Read more.
Background and Objectives: Eustachian tube (ET) dysfunction links adenoidal disease to persistent middle ear dysfunction in children, yet the independent contribution of ET orifice obstruction grade to audiological outcomes and health-related quality of life remains unquantified after adjustment for anatomical and inflammatory confounders. Because conventional anatomical grading (e.g., the Cassano classification) does not directly characterize the degree of ET orifice compromise, it may underestimate the functional threat to middle ear ventilation; this study is the first to quantify the independent predictive value of endoscopic ET obstruction grade. This study aimed to evaluate ET obstruction grade as an independent determinant of hearing thresholds, middle ear pressure, and quality-of-life impairment in children with chronic adenoiditis and otitis media with effusion. Materials and Methods: A retrospective cohort of 236 children (aged 3–12 years) was analyzed. ET orifice obstruction was graded endoscopically as none, partial, or complete. Primary outcomes included pure tone average (PTA), middle ear pressure (MEP), and OSA-18 total score. Multivariate linear and logistic regression models were fitted, adjusting for age, sex, Cassano grade, neutrophil-to-lymphocyte ratio (NLR), allergic status, and acute otitis media frequency. The modifying role of mucosal appearance (edematous versus fibrotic/remodeling) on quality-of-life outcomes was also assessed. Results: ET obstruction was absent in 42 (17.8%), partial in 114 (48.3%), and complete in 80 (33.9%) children. PTA increased progressively across groups (22.2 ± 5.5 to 36.2 ± 6.7 dB; p < 0.001), as did OSA-18 scores (44.9 ± 7.9 to 80.4 ± 10.3; p < 0.001). In adjusted analysis, each obstruction increment independently predicted a 5.57 dB PTA increase (95% CI 4.37–6.77; p < 0.001), a 14.89-point OSA-18 increase (95% CI 12.87–16.92; p < 0.001), and 5.12-fold higher odds of PTA > 30 dB (95% CI 2.84–9.24; p < 0.001). Persistent middle ear dysfunction at six months occurred in 7.1%, 26.3%, and 61.3% across obstruction grades. Among children with complete obstruction, fibrotic mucosa was associated with higher OSA-18 scores than edematous mucosa (82.3 vs. 76.8; p = 0.02). Conclusions: ET obstruction grade independently determines audiological and quality-of-life outcomes in pediatric chronic adenoiditis. Mucosal remodeling further amplifies quality-of-life burden in complete obstruction. These findings support routine ET endoscopic grading in pediatric otorhinolaryngology risk stratification. Full article
(This article belongs to the Special Issue Advances in Otorhinolaryngologic Diseases)
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16 pages, 259 KB  
Review
Tear Film Changes Following Anterior Segment Surgery: A Comprehensive Review of Pathophysiology, Clinical Features, and Recovery Time Course
by Rafaella Datseri, Nikolaos Ktistakis and Alena Furdová
Life 2026, 16(7), 1117; https://doi.org/10.3390/life16071117 (registering DOI) - 5 Jul 2026
Abstract
Tear film instability and dry eye disease (DED) are among the most common postoperative complaints after anterior segment surgery. Cataract surgery, corneal refractive procedures, keratoplasty, glaucoma filtration surgery, and pterygium excision can all disrupt ocular surface homeostasis through mechanisms that include corneal denervation, [...] Read more.
Tear film instability and dry eye disease (DED) are among the most common postoperative complaints after anterior segment surgery. Cataract surgery, corneal refractive procedures, keratoplasty, glaucoma filtration surgery, and pterygium excision can all disrupt ocular surface homeostasis through mechanisms that include corneal denervation, inflammation, goblet cell loss, and meibomian gland dysfunction. The severity and duration of postoperative dry eye vary substantially according to the surgical procedure performed. This review summarises current evidence on the pathophysiology, clinical manifestations, objective tear film changes, and recovery patterns following major anterior segment interventions. Particular emphasis is placed on standardised, non-invasive assessment methods, including tear breakup time, tear meniscus height, meibography, and validated symptom questionnaires. Procedure-specific recovery trajectories are compared to distinguish transient postoperative tear film instability from persistent chronic dry eye disease. Evidence-based management strategies, including preoperative risk stratification, intraoperative optimisation, and multimodal postoperative therapy, are also reviewed. Understanding these distinct recovery patterns may improve surgical planning, patient counselling, early intervention, visual outcomes, and patient satisfaction. Full article
(This article belongs to the Section Medical Research)
11 pages, 867 KB  
Article
Evaluating Outcomes in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease and Vitamin D Deficiency
by Tiana Dodd, Arpit Sharma, Nisar Amin, Veysel Tahan, Ebubekir Daglilar and Nikki Duong
Diseases 2026, 14(7), 243; https://doi.org/10.3390/diseases14070243 (registering DOI) - 4 Jul 2026
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease (CLD) globally and is closely linked to metabolic risk factors and systemic inflammation. Emerging evidence suggests that vitamin D deficiency may influence MASLD severity and outcomes, though limited [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease (CLD) globally and is closely linked to metabolic risk factors and systemic inflammation. Emerging evidence suggests that vitamin D deficiency may influence MASLD severity and outcomes, though limited real-world data often assess long-term clinical outcomes in MASLD patients stratified by vitamin D status. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2006–2025). Adult patients with MASLD were stratified into two cohorts based on serum 25-hydroxyvitamin D levels: normal (≥30 ng/mL) and deficient (<20 ng/mL). Patients with other CLD, malignancy, decompensated cirrhosis, and relevant confounding conditions were excluded. Primary outcomes included all-cause mortality, hospital readmissions, and ICU admissions at 1-year and 5-year follow-up. Results: After propensity score matching, 6959 patients were included in each cohort. Compared with patients with normal vitamin D levels, those with vitamin D deficiency had significantly higher rates of hospital readmissions, ICU admissions, and all-cause mortality at both 1-year and 5-year follow-up. A 1 year, readmissions occurred in 10% vs. 6%, ICU admissions 2.6% vs. 1.2%, and mortality 1.5% vs. 0.5% of patients (p = 0.01). Similar findings were observed at 5 years, with higher rates of readmissions 15% vs. 10%, ICU admissions 4.4% vs. 2.4% and mortality 3.2% vs. 1.3% in the vitamin D-deficient cohort (p = 0.01). Conclusions: Vitamin D deficiency was associated with significantly increased mortality, hospital readmissions, and ICU admissions among patients with MASLD. Our findings suggest that vitamin D status may represent a valuable prognostic indicator in this population. Although the observational nature of this study precluded establishing causality, our results support the consideration of routine assessment of vitamin D levels in patients with MASLD. Further prospective and mechanistic studies are needed to determine whether vitamin D supplementation can improve outcomes in this population. Full article
(This article belongs to the Section Gastroenterology)
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17 pages, 2151 KB  
Article
Investigating the Kidney–Gut–Brain Axis in CKD: Uremic Toxins and Brain Microhemorrhages
by Yitong Zhao, Su Mi Lee, Whitney Li, David Floriolli, Peter Chang, Yoko Narasaki, Amy S. You, Kamyar Kalantar-Zadeh, Connie M. Rhee, Han Liu, Tiffany Tran, Annlia Paganini-Hill, Mark Fisher and Wei Ling Lau
Int. J. Mol. Sci. 2026, 27(13), 6020; https://doi.org/10.3390/ijms27136020 (registering DOI) - 4 Jul 2026
Abstract
Alterations of gut microbiota are common in chronic kidney disease (CKD) and contribute to increased uremic toxins including indoxyl sulfate (IS), p-cresyl sulfate (pCS) and trimethylamine N-oxide (TMAO), which are linked to cerebrovascular disease risk. This study examined the kidney–gut–brain axis in CKD [...] Read more.
Alterations of gut microbiota are common in chronic kidney disease (CKD) and contribute to increased uremic toxins including indoxyl sulfate (IS), p-cresyl sulfate (pCS) and trimethylamine N-oxide (TMAO), which are linked to cerebrovascular disease risk. This study examined the kidney–gut–brain axis in CKD mice and in dialysis patients. Male and female mice with adenine-induced CKD were fed a high-amino-acid (HAA) diet to increase precursors of gut-derived uremic toxins. A subgroup of mice received antibiotics in drinking water to suppress gut microbiota and evaluate its role in toxin generation. Behavior tests, gut microbiome composition and brain histology for cerebral microhemorrhages were analyzed. CKD mice had higher serum levels of creatinine, cystatin C and gut-derived toxins, a 2.5-fold increase in brain microhemorrhages, and decreased locomotor activity. The HAA diet significantly increased serum TMAO but not IS and pCS, and all three toxins were reduced by antibiotic therapy. Sex differences were observed; in male animals, higher TMAO was associated with increased brain microhemorrhages, whereas in female mice, pCS was associated with brain microhemorrhage burden. The suppression of toxins with antibiotics improved working memory in male animals. Gut microbiota analysis revealed the expansion of Lactobacillus and Ileibacterium in CKD mice. The HAA diet and antibiotics altered gut microbiota composition without changing alpha diversity. The human study utilized biobanked serum samples and a retrospective review of brain imaging scans in a hemodialysis patient cohort; TMAO levels were associated with increased lobar microbleeds. Our study supports a role for bacterial-derived uremic toxins in the kidney–gut–brain axis and cerebral microhemorrhage formation in CKD. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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11 pages, 223 KB  
Review
Medical and Surgical Management of Hidradenitis Suppurativa
by John W. Frew and Falk G. Bechara
J. Clin. Med. 2026, 15(13), 5238; https://doi.org/10.3390/jcm15135238 (registering DOI) - 4 Jul 2026
Abstract
Background: HS is a chronic inflammatory skin disease in which inflammatory nodules and abscesses coexist with tunnels, fibrosis, and scarring. This dual biology explains why medical therapy often improves inflammatory dissease activity without fully addressing fixed tissue damage, whereas surgery can achieve durable [...] Read more.
Background: HS is a chronic inflammatory skin disease in which inflammatory nodules and abscesses coexist with tunnels, fibrosis, and scarring. This dual biology explains why medical therapy often improves inflammatory dissease activity without fully addressing fixed tissue damage, whereas surgery can achieve durable local control but does not treat diffuse inflammatory burden. Contemporary international guidelines increasingly endorse multimodal and medicosurgical care. Objective: To critically compare the evidence supporting medical and surgical management of HS, with emphasis on outcomes, indications, limitations, and clinical decision-making relevant to contemporary practice. Methods: A structured review was undertaken using PubMed/MEDLINE, the Cochrane Library, and major dermatology guideline sources, with searches updated to 7 May 2026. Priority was given to clinical guidelines, systematic reviews and meta-analyses, randomized controlled trials, and higher-quality observational studies. Evidence was synthesized narratively because endpoints, populations, and follow-up intervals differed markedly across medical and surgical studies. Results: Medical evidence is strongest for biologic therapy in moderate-to-severe inflammatory HS. Weekly adalimumab improved week-12 HiSCR in the phase 3 PIONEER trials; secukinumab improved week-16 and week-52 outcomes in SUNSHINE/SUNRISE; and bimekizumab improved week-16 HiSCR50 in BE HEARD I/II. Surgical evidence is strongest for wide excision in structurally advanced disease, particularly when compared with local excision or incision and drainage. Meta-analytic data consistently show lower recurrence after wide excision than after local excision, and lower recurrence after flap or graft reconstruction than after primary closure. Combined therapy is increasingly supported: peri-operative adalimumab improved outcomes in SHARPS, and surgery plus adalimumab outperformed adalimumab alone in a pragmatic 12-month RCT. Conclusions: HS is best managed by matching treatment to disease phenotype. Medical therapy is essential for inflammatory control; surgery is essential for persistent tunnels, fibrosis, and scarred regional disease. The strongest overall clinical position is an integrated, multidisciplinary model in which systemic therapy reduces inflammatory load and surgery definitively treats irreversible tissue damage. Full article
14 pages, 333 KB  
Article
Association Between Dietary Regimen and Renal Function Parameters in African Pygmy Hedgehogs (Atelerix albiventris)
by Kristina Spariosu, Ana Pešić, Ksenija Nešić, Diana Brozić, Jelena Francuski Andrić, Branislav Vejnović and Miloš Vučićević
Animals 2026, 16(13), 2066; https://doi.org/10.3390/ani16132066 (registering DOI) - 4 Jul 2026
Abstract
African pygmy hedgehogs (APHs) are increasingly kept as companion animals, yet evidence-based nutritional recommendations for this species remain limited. Commercial cat or kitten diets are still commonly used by owners and veterinarians in practice, despite being formulated exclusively for domestic cats rather than [...] Read more.
African pygmy hedgehogs (APHs) are increasingly kept as companion animals, yet evidence-based nutritional recommendations for this species remain limited. Commercial cat or kitten diets are still commonly used by owners and veterinarians in practice, despite being formulated exclusively for domestic cats rather than for hedgehogs with omnivorous–insectivorous feeding habits. This cross-sectional study evaluated the association between dietary regimen and serum biochemical parameters associated with renal function in APHs. Blood samples were collected from 19 client-owned APHs aged 12–68 months: 10 hedgehogs fed a commercial kitten diet and 9 fed a commercial APH-specific diet. Serum concentrations of blood urea nitrogen, creatinine, phosphorus, and calcium were measured, and the nutritional composition of the two diets was compared using manufacturer declarations and targeted laboratory analyses. Hedgehogs fed the commercial kitten diet had significantly higher serum blood urea nitrogen (p = 0.0133), creatinine (p = 0.0279), and phosphorus (p = 0.0279) concentrations than those fed the APH-specific diet, whereas serum calcium concentrations did not differ significantly (p = 0.3846). These differences occurred despite similar dietary phosphorus content, while the commercial kitten diet had higher declared fat and lower fiber content. The findings suggest that dietary regimen may be associated with alterations in renal biochemical profiles in APHs and support the use of species-appropriate diets in clinical practice. Full article
(This article belongs to the Special Issue Nutrition, Physiology and Metabolism of Companion Animals)
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