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11 pages, 1205 KB  
Article
Associations Between Anemia and Obstructive Sleep Apnea in Patients with Cystic and Non-Cystic Bronchiectasis: A Prospective Cross-Sectional Study
by Baran Balcan, Duygu Vezir, Ramazan Ocal, Caner Cinar, Erdal Aksoy, Yeliz Celik and Berrin Ceyhan
Biomedicines 2026, 14(4), 915; https://doi.org/10.3390/biomedicines14040915 - 17 Apr 2026
Abstract
Background: Anemia and obstructive sleep apnea (OSA) are prevalent comorbidities in bronchiectasis and may share overlapping pathophysiological mechanisms. However, their combined impact on clinical outcomes in bronchiectasis remains underexplored. We aimed to investigate the associations between anemia, OSA, and clinical characteristics in [...] Read more.
Background: Anemia and obstructive sleep apnea (OSA) are prevalent comorbidities in bronchiectasis and may share overlapping pathophysiological mechanisms. However, their combined impact on clinical outcomes in bronchiectasis remains underexplored. We aimed to investigate the associations between anemia, OSA, and clinical characteristics in patients with bronchiectasis, including cystic fibrosis (CF) and non-CF subtypes. Methods: 70 adults with bronchiectasis (35 CF-related, 35 non-CF) underwent polysomnography. Anemia was defined using standard hemoglobin < 13 g/dL for men and <12 g/dL for women. Clinical, nutritional, and sleep-related variables were assessed, and associations with anemia were evaluated. Results: Anemia was present in 24.3% of participants. Compared to non-anemic patients, those with anemia had significantly higher rates of female sex (38.5% vs. 6.5%, p = 0.002), nutritional problems (47.1% vs. 20.8%, p = 0.034), OSA prevalence (94.1% vs. 54.7%, p = 0.003), and annual hospitalizations (1.41 ± 0.41 vs. 0.43 ± 0.10, p = 0.002). In multivariate analysis, female sex (OR: 12.32; 95% CI: 3.12–45.96; p = 0.002) and OSA (OR: 4.70; 95% CI: 2.67–45.29; p = 0.007) remained independent predictors of anemia. Subgroup analysis showed a significant univariate association between OSA and anemia in CF patients (p = 0.045), while hospitalization frequency was an independent predictor of anemia in non-CF bronchiectasis (p = 0.040). Conclusions: Anemia in bronchiectasis is independently associated with female sex and OSA, with additional exploratory subgroup findings. These findings indicate an association between OSA and anemia within bronchiectasis populations; however, the cross-sectional design precludes conclusions regarding directionality or causality. Full article
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11 pages, 1156 KB  
Case Report
Diffuse Alveolar Hemorrhage Complicating Influenza A Infection in an Immunocompetent Infant: A Case Report with Focused Pediatric Review
by Hai Thien Do, Hung Trong Dinh, Vuong Minh Tran, Lam Van Nguyen, Tung Viet Cao and Ngoc Nu Hoang Tran
J. Clin. Med. 2026, 15(8), 3062; https://doi.org/10.3390/jcm15083062 - 17 Apr 2026
Abstract
Background: Influenza is a common cause of hospitalization in young children, particularly infants. While most infections are self-limited, severe and life-threatening complications may occur. Diffuse alveolar hemorrhage (DAH) is a rare pulmonary manifestation of influenza, predominantly reported in adults, and is exceedingly [...] Read more.
Background: Influenza is a common cause of hospitalization in young children, particularly infants. While most infections are self-limited, severe and life-threatening complications may occur. Diffuse alveolar hemorrhage (DAH) is a rare pulmonary manifestation of influenza, predominantly reported in adults, and is exceedingly uncommon in immunocompetent infants. Case Presentation: We report the case of an 8-month-old previously healthy female infant who presented with influenza A infection and rapidly progressed to acute respiratory failure and shock despite antiviral therapy. Bleeding was noted from the nasal cavity prior to clinical deterioration, and during emergent endotracheal intubation, blood was observed flooding the bronchial tree, consistent with massive pulmonary hemorrhage. Flexible bronchoscopy showed diffusely erythematous and friable airway mucosa without an identifiable focal bleeding source, and early bronchoalveolar lavage was nondiagnostic. Nasopharyngeal testing confirmed influenza A (H3). Laboratory findings revealed severe systemic inflammation, leukopenia with neutropenia, and anemia with normal coagulation parameters. Chest imaging demonstrated bilateral pulmonary infiltrates. After exclusion of autoimmune, coagulation, immunodeficiency, and alternative infectious causes, a diagnosis of diffuse alveolar hemorrhage secondary to influenza A infection was established. The patient was successfully managed with supportive care, antiviral therapy, tranexamic acid, and empiric antibiotics, without corticosteroid treatment, and made a full recovery. Conclusions: This case emphasizes that influenza-associated DAH in infants may occur without overt hemoptysis and may not demonstrate classical BAL findings early in the disease course. Clinicians should maintain a high index of suspicion in rapidly deteriorating infants with influenza and diffuse pulmonary infiltrates. The optimal role of corticosteroids remains uncertain and should be individualized. Full article
(This article belongs to the Section Infectious Diseases)
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19 pages, 1986 KB  
Article
Real-World Outcomes of Palbociclib with Endocrine Therapy in HR+/HER2− Metastatic Breast Cancer: A Retrospective Study from Saudi Arabia
by Abdalrhman H. Alanizi, Sarah N. Al-Shaiban, Reema Alotaibi, Reem Qubaiban, Esra’a Khader, Ahmed S. Alanazi, Hatoon Bakhribah, Nawal Alsubaie, Amani S. Alrossies, Sireen Abdul Rahim Shilbayeh and Ammena Y. Binsaleh
Cancers 2026, 18(8), 1270; https://doi.org/10.3390/cancers18081270 - 16 Apr 2026
Abstract
Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control [...] Read more.
Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice. Full article
(This article belongs to the Section Cancer Metastasis)
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14 pages, 903 KB  
Article
Clinical Outcomes of Peptide Receptor Radionuclide Therapy in Japanese Patients with Metastatic Rectal Neuroendocrine Tumors
by Takeshi Iizuka, Noritoshi Kobayashi, Damian Wild, Felix Kaul, Hiroaki Suzuki, Kengo Maehara, Naoki Okubo, Sho Tsuyuki, Shoko Takano, Yusuke Kurita, Masato Yoneda and Yasushi Ichikawa
Cancers 2026, 18(8), 1268; https://doi.org/10.3390/cancers18081268 - 16 Apr 2026
Abstract
Background/Purpose: Rectal neuroendocrine tumors (NETs) with distant metastases are uncommon, and evidence supporting the effectiveness of peptide receptor radionuclide therapy (PRRT) in this population remains limited, particularly in Asian cohorts. This study aimed to evaluate the clinical role and real-world outcomes of [...] Read more.
Background/Purpose: Rectal neuroendocrine tumors (NETs) with distant metastases are uncommon, and evidence supporting the effectiveness of peptide receptor radionuclide therapy (PRRT) in this population remains limited, particularly in Asian cohorts. This study aimed to evaluate the clinical role and real-world outcomes of PRRT in Japanese patients with somatostatin receptor-positive metastatic rectal NETs. Methods: We retrospectively analyzed 20 patients with metastatic rectal NETs who underwent PRRT at the University Hospital Basel (Switzerland) and Yokohama City University Hospital (Japan) between April 2015 and May 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included disease control rate (DCR), overall response rate (ORR), overall survival (OS), and adverse events (AEs). Exploratory subgroup analyses were performed according to clinical characteristics, including changes in serum neuron-specific enolase (NSE). Results: The median PFS was 18.9 months (95% CI, 13.5–24.3), and the median OS was 30.3 months (95% CI, 18.9–41.7). The DCR was 80.0%, and the ORR was 15.0%. Treatment responses included partial response in 3 patients, stable disease in 13, progressive disease in 3, and not evaluable in 1. The most common AEs were lymphopenia and anemia, and no secondary malignancies were observed. No clinical factors were significantly associated with PFS; however, higher baseline NSE levels showed a trend toward shorter PFS. Patients with post-treatment declines in NSE showed more favorable treatment responses. Conclusions: PRRT may provide durable disease control with a favorable safety profile in Japanese patients with metastatic rectal NETs. However, these findings should be interpreted with caution given the small sample size and heterogeneous patient population. Baseline NSE elevation and early post-treatment declines may serve as potential prognostic indicators. These results are hypothesis-generating and warrant validation in larger, multicenter studies. Full article
(This article belongs to the Section Cancer Metastasis)
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8 pages, 1457 KB  
Case Report
Pulmonary Aspergillosis in an Infant with Multiple Hepatic Hemangiomas
by Zuzanna Karp, Jakub Czarny, Katarzyna Adamczewska-Wawrzynowicz, Alicja Bartkowska-Śniatkowska, Katarzyna Jończyk-Potoczna and Katarzyna Derwich
Children 2026, 13(4), 556; https://doi.org/10.3390/children13040556 - 16 Apr 2026
Abstract
Background: Infantile hepatic hemangiomas (IHH) are common benign vascular tumors in infancy with diverse presentations. Methods: We report a 7-week-old infant presenting with hepatosplenomegaly, multiple skin and hepatic hemangiomas, anemia, and recurrent lung infections. Results: Treatment included propranolol, corticosteroids, and [...] Read more.
Background: Infantile hepatic hemangiomas (IHH) are common benign vascular tumors in infancy with diverse presentations. Methods: We report a 7-week-old infant presenting with hepatosplenomegaly, multiple skin and hepatic hemangiomas, anemia, and recurrent lung infections. Results: Treatment included propranolol, corticosteroids, and sirolimus, along with antifungal prophylaxis with fluconazole. The patient developed pneumothorax and pulmonary aspergillosis. Despite antifungal therapy with voriconazole and liposomal amphotericin B, along with surgical intervention, her condition deteriorated, resulting in multi-organ failure and death at 8.5 months of age. Conclusions: This case illustrates the complexity of IHH management and highlights the risk of severe infections during immunosuppressive therapy even when standard prophylaxis protocols are applied. Full article
(This article belongs to the Section Pediatric Hematology & Oncology)
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42 pages, 1514 KB  
Review
Perioperative Patient Blood Management: Evidence-Based Strategies for Surgeons and Anesthesiologists: A Narrative Review
by Taxiarchis Konstantinos Nikolouzakis, Epameinondas Evangelos Kantidakis, Richard Crawford, Riaan Pretorius, Orfeas Nikolaos Zaimakis and Emmanuel Chrysos
J. Clin. Med. 2026, 15(8), 3017; https://doi.org/10.3390/jcm15083017 - 15 Apr 2026
Abstract
Patient Blood Management (PBM) has evolved from a transfusion-centered practice to a structured, patient-focused perioperative strategy aimed at improving surgical outcomes while preserving blood resources. In the operating room, where bleeding risk is anticipated and modifiable, PBM requires proactive intervention rather than reactive [...] Read more.
Patient Blood Management (PBM) has evolved from a transfusion-centered practice to a structured, patient-focused perioperative strategy aimed at improving surgical outcomes while preserving blood resources. In the operating room, where bleeding risk is anticipated and modifiable, PBM requires proactive intervention rather than reactive transfusion. This review synthesizes current evidence on perioperative blood conservation strategies specifically relevant to surgeons and anesthesiologists. Preoperative optimization begins with systematic identification and correction of anemia, most commonly iron deficiency, using appropriately timed oral or intravenous iron therapy and, in selected cases, erythropoiesis-stimulating agents. Careful management of anticoagulant and antiplatelet therapies, early recognition of acquired or inherited coagulopathies, and protocol-driven reversal strategies further reduce perioperative hemorrhagic risk. Intraoperatively, blood conservation depends on meticulous surgical technique, respect for anatomical planes, minimally invasive approaches, and the judicious use of advanced energy devices and topical hemostatic agents. Pharmacologic interventions—particularly tranexamic acid administered with appropriate timing and dosing—have demonstrated consistent reductions in blood loss and transfusion requirements across multiple surgical disciplines. Goal-directed coagulation management guided by viscoelastic testing allows targeted correction of specific hemostatic deficits while minimizing unnecessary blood product exposure. Acute normovolemic hemodilution and intraoperative cell salvage provide additional benefit in selected high-blood-loss procedures. Collectively, these multimodal strategies shift perioperative care from product-driven transfusion toward physiology-based blood conservation. When embedded within institutional protocols and supported by multidisciplinary collaboration, perioperative PBM reduces transfusion exposure, decreases morbidity, shortens hospital stay, and promotes sustainable stewardship of blood resources without compromising patient safety. Full article
(This article belongs to the Section Hematology)
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15 pages, 714 KB  
Article
Micronutrient Deficiencies and Nutritional Status in Children with Celiac Disease: A Retrospective Study
by Demet Teker Düztaş, Mahmut Esat Tülüce and Gizem Özata Uyar
Children 2026, 13(4), 547; https://doi.org/10.3390/children13040547 - 15 Apr 2026
Abstract
Background and aim: Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten ingestion, and the only effective treatment is strict adherence to a gluten-free diet (GFD). Many factors, including limited dietary diversity and poor adherence, are associated with an increased risk [...] Read more.
Background and aim: Celiac disease (CD) is a systemic autoimmune disorder triggered by gluten ingestion, and the only effective treatment is strict adherence to a gluten-free diet (GFD). Many factors, including limited dietary diversity and poor adherence, are associated with an increased risk of specific micronutrient deficiencies and malnutrition. This study aims to evaluate the relationship between adherence to GFD, celiac antibody levels, micronutrient levels, and nutritional status in children with CD. Methods: This retrospective study was conducted on 402 children aged 2–18 years with a diagnosis of CD confirmed positive by anti-tTG IgA and duodenal biopsy, all of whom had been on GFD for at least six months. Demographic, anthropometric, clinical, serological, and biochemical data (including hemogram, serum iron, ferritin, vitamin D, folate, and B12 levels), and GFD adherence were collected from medical records. Results: Most individuals are girls (64.9%), with a mean age of 10.6 ± 4.20 years. Chronic malnutrition was observed in 29.4% of patients. Acute malnutrition was identified in 27.8% of children, and wasting was observed in 6.7%. Iron deficiency anemia was the most frequently encountered micronutrient deficiency among the patients (23.9%). The prevalence of stunting was significantly higher among individuals with positive tTG-IgA levels and poor adherence to the GFD. Conclusions: Poor adherence to the GFD and positive tTG-IgA levels were associated with higher rates of stunting, underlining the need for individualized dietary follow-up and regular monitoring of both nutritional status and serological response in children with CD. Full article
(This article belongs to the Section Pediatric Gastroenterology and Nutrition)
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14 pages, 318 KB  
Article
Smoking, Nutritional Status, and Their Associations with Hypertension and Hematological Disorders Among Hotel Workers: Implications for Indonesian Occupational Health Nursing
by Juli Dwi Prasetyono, Henny Permatasari, Agus Setiawan, Sigit Mulyono, Tantut Susanto and Muchtaruddin Mansyur
Int. J. Environ. Res. Public Health 2026, 23(4), 505; https://doi.org/10.3390/ijerph23040505 - 15 Apr 2026
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Abstract
Smoking remains one of the leading preventable causes of chronic disease and premature workplace mortality worldwide. This study examined the association between smoking and nutritional status and hypertension and hematological disorders among hotel workers and occupational health nurses’ role in Indonesia. This cross-sectional [...] Read more.
Smoking remains one of the leading preventable causes of chronic disease and premature workplace mortality worldwide. This study examined the association between smoking and nutritional status and hypertension and hematological disorders among hotel workers and occupational health nurses’ role in Indonesia. This cross-sectional study examined associations between smoking, nutritional status, and selected health outcomes among 366 hotel workers in Indonesia using routine medical check-up data. Logistic regression analyses were performed to assess the associations of smoking status and body mass index (BMI) categories with hypertension and hematological abnormalities (leukocytosis and anemia), after adjusting for age, gender, and job level. Older workers (40–69 years) and those categorized as overweight or obese had higher odds of hypertension than younger workers and those with normal BMI (ORs 2.63 and 1.37, respectively). Smoking was associated with a higher risk of leukocytosis (OR 0.395), reflecting increased risk among smokers due to variable coding. Older age and overweight status were strong predictors of hypertension, whereas smoking was associated with increased leukocytosis among hotel workers. These findings highlight the need for targeted OH interventions. Occupational health nurses should collaborate with management to strengthen WHP programs that encourage healthier lifestyles among employees. Full article
(This article belongs to the Special Issue Occupational Health Nursing in Diverse Settings)
15 pages, 1107 KB  
Article
Molecularly Adapted Antitumor Therapy for Newly Diagnosed Diffuse Large B-Cell Lymphoma: Two-Year Follow-Up Results
by Marat Mingalimov, Elena Baryakh, Andrey Misyurin, Laura Kesaeva, Hasmik Mkrtchyan, Elena Misyurina, Mariia Orlova, Tatiana Tolstykh, Ekaterina Zotina, Liliia Shimanovskaia, Tatiana Chudnova, Diana Ivanova, Olga Kochneva, Kseniya Tsurkina, Dmitry Lebedev, Georgii Tyshkevich, Natalia Bekreneva, Viktoriia Basova, Mikhail Donskoy, Sergej Rodnikov, Ivan Abramov, Natalia Bodunova, Saida Gadzhieva, Tatiana Semina, Sergey Andreev, Inna Samsonova and Mariana Lysenkoadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(8), 2983; https://doi.org/10.3390/jcm15082983 - 14 Apr 2026
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Abstract
Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogeneous, and approximately 30-50% of patients fail to achieve cure with standard R-CHOP. Genotype-directed first-line therapy may improve outcomes by targeting subtype-specific oncogenic pathways. This study evaluated the feasibility, efficacy, and safety of a molecularly [...] Read more.
Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogeneous, and approximately 30-50% of patients fail to achieve cure with standard R-CHOP. Genotype-directed first-line therapy may improve outcomes by targeting subtype-specific oncogenic pathways. This study evaluated the feasibility, efficacy, and safety of a molecularly adapted R-CHOP-X strategy with two-year follow-up. Methods: In this single-center, prospective, non-randomized study conducted between September 2023 and the data cut-off (16 September 2025), 43 adults with newly diagnosed DLBCL (excluding high-grade B-cell lymphoma, primary immune-privileged, and primary mediastinal large B-cell lymphomas) underwent tumor genotyping using the LymphGen classification after targeted sequencing: a 19-gene Sanger panel (Cohort 1, n = 35) or an expanded 60-gene panel (Cohort 2, n = 8; proof-of-concept). All patients received one initial cycle of R-CHOP as bridge therapy pending molecular profiling results, followed by five cycles of R-CHOP-X, with the additional agent (vorinostat, acalabrutinib, decitabine, or lenalidomide) selected according to molecular subtype. Response was assessed by PET/CT per Lugano criteria; adverse events were graded per NCI CTCAE v5.0. Results: The overall study population was predominantly high-risk: 72% had an IPI of 3–5, 58% had stage III–IV disease, and 67% exhibited a non-GCB immunophenotype. Expansion from the 19-gene to the 60-gene panel reduced unclassifiable (NOS) cases from 34% to 12%. The overall response rate was 100% (43/43); complete response among patients completing therapy was 100% (35/35). At two years, overall survival was 92% (95% CI 83–100%) and progression-free survival was 94% (95% CI 86–100%). Two early relapses occurred (NOS and N1 subtypes), both resulting in death. Grade 3–4 neutropenia, thrombocytopenia, and anemia occurred in 26%, 12%, and 7% of patients, respectively; no dose reductions or treatment discontinuations were recorded. Conclusions: Molecularly adapted R-CHOP-X is feasible and associated with high response rates and favorable two-year survival in newly diagnosed DLBCL, comparing favorably with historical R-CHOP outcomes in high-risk populations. Expanded genomic panels substantially improve molecular classifiability. These findings warrant validation in larger, multicenter, randomized clinical trials. Full article
(This article belongs to the Section Oncology)
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17 pages, 4426 KB  
Article
Plasma ACE and ACE2 Levels Are Altered in Patients with COVID-19
by Murat Oz, Wassim Chehadeh, Omamah Alfarisi and Farhan S. Cyprian
Viruses 2026, 18(4), 465; https://doi.org/10.3390/v18040465 - 14 Apr 2026
Viewed by 188
Abstract
Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin–angiotensin system (RAS) in COVID-19 [...] Read more.
Objective: The COVID-19 pandemic has strained healthcare systems and has been associated with substantial morbidity and mortality. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) enters host cells by binding to angiotensin-converting enzyme 2 (ACE2), implicating dysregulation of the renin–angiotensin system (RAS) in COVID-19 pathophysiology. Measurement of circulating RAS components, including ACE and ACE2, may therefore provide an insight into disease severity and underlying mechanisms. Subjects and Methods: In this retrospective cohort study, 224 adults with PCR-confirmed COVID-19 were stratified by World Health Organization disease-severity criteria into asymptomatic, mild, mild-pneumonia, severe, and critical groups. Plasma ACE and ACE2 concentrations were quantified by ELISA. Demographic, clinical, and laboratory data were extracted from electronic medical records. Results and Conclusions: Increasing disease severity was associated with higher mortality, elevated body mass index, and higher viral load estimates. Severe and critical illness was characterized by leukocytosis with neutrophilia, marked lymphopenia, anemia, elevated inflammatory and coagulation markers, renal dysfunction, and hypoalbuminemia. Plasma ACE2 levels declined progressively with increasing severity and were significantly lower in patients with mild-pneumonia, severe, or critical illness compared with asymptomatic or mild cases, showing a strong inverse correlation with severity. In contrast, plasma ACE levels increased significantly with disease severity. The resulting increase in the ACE/ACE2 ratio indicates a progressive shift toward the pro-inflammatory arm of the RAS, providing mechanistic insight into the COVID-19 pathophysiology. Full article
(This article belongs to the Section Coronaviruses)
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26 pages, 6269 KB  
Article
Iron Overload-Associated Oxidative Stress and Immune Cell Dysfunction in Thalassemia: Integrative Analysis of Hematological, Biochemical, and Flow Cytometric Biomarkers
by Sirichai Srichairatanakool, Narisara Paradee, Bishant Pokharel, Yanping Zhong, Onsaya Kerdto, Wuttipat Kiratipaisarl, Adisak Tantiworawit, Chatree Chai-Adisaksopha and Somdet Srichairatanakool
Antioxidants 2026, 15(4), 482; https://doi.org/10.3390/antiox15040482 - 14 Apr 2026
Viewed by 228
Abstract
Thalassemia is a hereditary hemoglobinopathy characterized by ineffective erythropoiesis, chronic hemolysis, and transfusion-related iron overload, which collectively contribute to oxidative stress and organ dysfunction. The present study aimed to investigate the relationships between iron metabolism, oxidative stress biomarkers, and immune cell function across [...] Read more.
Thalassemia is a hereditary hemoglobinopathy characterized by ineffective erythropoiesis, chronic hemolysis, and transfusion-related iron overload, which collectively contribute to oxidative stress and organ dysfunction. The present study aimed to investigate the relationships between iron metabolism, oxidative stress biomarkers, and immune cell function across different clinical conditions. Peripheral blood samples were obtained from healthy individuals and patients with iron deficiency anemia, obesity, thalassemia trait (TT), β-thalassemia HbE (BTE), and β-thalassemia major (BTM). Hematological parameters were measured using automated hematology analyzers, while biochemical indicators, including liver enzymes and bilirubin, were determined using clinical chemistry assays. Iron overload was evaluated using serum iron parameters and T2*-weighted magnetic resonance imaging. Oxidative stress biomarkers, including reduced glutathione, thiobarbituric acid-reactive substances, and total antioxidant capacity, were assessed spectrophotometrically. Flow cytometric analysis was used to measure reactive oxygen species, redox-active iron, and lipid peroxide levels in granulocytes and lymphocytes. Thalassemia patients exhibited severe anemia, elevated liver enzymes, increased bilirubin levels, and significant alterations in iron metabolism compared with healthy controls. Hepatic iron accumulation was more common than cardiac iron deposition, particularly in BTE patients. Granulocyte oxidative burst activity was significantly reduced in thalassemia patients, whereas lymphocyte responses remained relatively preserved. Increased variability in glutathione levels suggested activation of intracellular antioxidant defense mechanisms in response to chronic oxidative stress. These findings highlight the complex interplay between iron overload, oxidative stress, and the immune cell dysfunction associated with thalassemia, thereby providing insights into improved monitoring and therapeutic strategies. Full article
(This article belongs to the Special Issue Oxidative Stress in Hematologic Disease)
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12 pages, 565 KB  
Article
Associations Between Composite Host Vulnerability Score and Transfusion Outcomes After Trauma
by Yun-Chul Park, Young-Goun Jo, Hyun-Seok Jang, Eui-Sung Jeong and Ji-Hyoun Kang
Medicina 2026, 62(4), 732; https://doi.org/10.3390/medicina62040732 - 12 Apr 2026
Viewed by 209
Abstract
Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes [...] Read more.
Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes additional risk information beyond established factors remains incompletely understood. Materials and Methods: We conducted a retrospective cohort study of adult trauma patients using a single-center trauma registry. Host vulnerability was assessed using a composite score (CE; range 0–3) based on admission hypoalbuminemia (<3.5 g/dL), anemia (hemoglobin < 11 g/dL), and reduced renal function (estimated glomerular filtration rate < 60 mL/min/1.73 m2). Primary outcomes were any blood transfusion and massive transfusion, defined as transfusion of ≥10 units of packed red blood cells within 24 h of admission. Associations between CE score and transfusion outcomes were evaluated using univariable and multivariable logistic regression models adjusted for age, Injury Severity Score (ISS), admission lactate level, and systolic blood pressure (SBP). Results: Among 4105 trauma patients, transfusion requirements increased progressively with higher CE scores. Rates of any transfusion rose from 21.7% in patients with CE 0 to 78.6% in those with CE 3, while massive transfusion increased from 1.9% to 23.1% across the same categories. In multivariable analyses, each 1-point increase in CE score was independently associated with higher odds of any transfusion (adjusted odds ratio [aOR] 3.21, 95% confidence interval [CI] 2.80–3.68) and massive transfusion (aOR 1.73, 95% CI 1.45–2.07). Conclusions: A composite score reflecting host vulnerability at presentation was associated with bleeding severity and transfusion requirements after trauma, beyond injury severity and acute physiologic factors. These findings suggest that simple laboratory-based markers may provide additional information for early risk stratification of hemorrhagic outcomes after trauma. Full article
(This article belongs to the Special Issue Autoimmune Diseases: Advances and Challenges)
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15 pages, 840 KB  
Article
Evaluating Heat Shock Proteins as Biomarkers for Vaginal Fungal Infections
by Yazeed Albalawi and Mohammad Zubair
J. Clin. Med. 2026, 15(8), 2889; https://doi.org/10.3390/jcm15082889 - 10 Apr 2026
Viewed by 227
Abstract
Objective: The purpose of this study was to determine the biological association between host-derived HSP47 and fungal-derived HSP90 in the context of vulvovaginal candidiasis (VVC) and to examine their relationships with clinical, inflammatory, and metabolic phenotypes in infected and healthy women. Methods [...] Read more.
Objective: The purpose of this study was to determine the biological association between host-derived HSP47 and fungal-derived HSP90 in the context of vulvovaginal candidiasis (VVC) and to examine their relationships with clinical, inflammatory, and metabolic phenotypes in infected and healthy women. Methods: This study followed a six-month case–control design (February–July 2025) and was conducted at the University of Tabuk Hospital in Tabuk, Saudi Arabia. A total of 84 women aged 18–45 years were recruited, of which 42 were VVC-infected, and 42 were healthy controls. ELISA kits were used to test vaginal swabs for HSP47 and HSP90. Clinical, hematological, cytokine, and metabolic markers were also evaluated. Mann–Whitney U, Spearman correlation, and multiple linear regression tests were performed to analyze the data. Results: The levels of HSP47 and HSP90 were significantly higher among infected patients (2.29 ng/mL and 3341 ng/mL, respectively) when compared with controls (0.58 ng/mL and 1025.7 ng/mL; p < 0.001). Women who were infected were older (p = 0.02), but there were no significant differences in terms of BMI (p = 0.29). The levels of vitamin D and adiponectin were significantly decreased (p < 0.001), while pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, TGF-β, and IL-8) and WBC counts were higher compared to the control group. The hematology results were characterized by inflammation-related anemia and disturbed protein metabolism. The ROC analysis demonstrated good diagnostic performance, with an AUC of 1.0 in the case of HSP47 and 0.905 in the case of HSP90. In the case of the infected patients, the regression models were found to be weak (HSP90 R2 = 0.154; HSP47 R2 = 0.273), although HSP47 retained significant connections with IL-8 (p = 0.005) and IFN-γ (p = 0.028). Conclusions: High levels of HSP47 and HSP90 are observed in VVC, reflecting an epithelial stress response and fungal persistence. These HSPs have high diagnostic accuracy, which justifies their potential as biomarkers for the timely detection of VVC; they also have further implications as early biomarkers for prognostic and treatment monitoring support, despite the poor predictive models. This study has some limitations that must be addressed; in particular, the regression analyses failed to provide statistically significant predictive models, likely due to the limited sample size. In addition, the specificity of HSP90 and HSP47 for VVC in comparison with other vaginal infections was not evaluated. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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12 pages, 571 KB  
Article
Effect of Roxadustat and Erythropoietin on Glycated Hemoglobin of Non-Dialysis Type 2 Diabetic Nephropathy Anemia Patients
by Zhouxia Xiang, Wenqian Wei, Shunian Guo, Hanyu Meng and Shu Rong
Biomedicines 2026, 14(4), 845; https://doi.org/10.3390/biomedicines14040845 - 8 Apr 2026
Viewed by 319
Abstract
Objectives: To investigate the effects of Roxadustat and recombinant human erythropoietin (rHuEPO) on glycemic control and glycated hemoglobin (HbA1c) in non-dialysis type 2 diabetic kidney disease (DKD) patients with anemia. Methods: This retrospective study enrolled 449 patients, who were divided into [...] Read more.
Objectives: To investigate the effects of Roxadustat and recombinant human erythropoietin (rHuEPO) on glycemic control and glycated hemoglobin (HbA1c) in non-dialysis type 2 diabetic kidney disease (DKD) patients with anemia. Methods: This retrospective study enrolled 449 patients, who were divided into three groups—the rHuEPO group (n = 252), the Roxadustat group (n = 102), and the switch group (n = 95)—in which patients were converted from rHuEPO to Roxadustat. All treatments lasted for more than three months. Changes in HbA1c and other indicators within groups as well as differences among groups were evaluated. Results: In the rHuEPO group, HbA1c levels decreased from 7.08 ± 1.19 to 6.41 ± 0.60 (p < 0.001), and they returned to baseline levels by 6–12 months (p > 0.05). In the Roxadustat group, HbA1c fluctuated but none of the differences reached statistical significance (p > 0.05). In the switch group, HbA1c decreased during rHuEPO treatment (p < 0.05) and returned to baseline after switching to Roxadustat (p > 0.05). No significant changes in blood glucose levels were observed in any group after treatment (p > 0.05). Multivariate linear regression analysis showed that changes in iron metabolism parameters, erythrocyte parameters, inflammatory markers, and glucose-lowering or lipid-lowering regimens had no significant effect on the change in HbA1c in the Roxadustat group (F = 0.834, p = 0.620), while the multivariate model of rHuEPO group also lacked statistical significance (F = 1.142, p = 0.170). After treatment, all three groups showed improvements in anemia, iron metabolism, renal function, inflammatory markers, and lipid profiles compared with baseline (p < 0.05). Additionally, further improvements in these parameters were observed after the transition from rHuEPO to Roxadustat (p < 0.05). Compared with rHuEPO group, the Roxadustat group exhibited significantly greater increases in hemoglobin, red blood cell count, total iron-binding capacity, transferrin, and serum iron (p < 0.05). Conclusions: In non-dialysis DKD patients with anemia, rHuEPO can significantly decrease HbA1c values, while Roxadustat does not. Roxadustat offers advantages over rHuEPO in terms of efficacy and assessment of glycemic control. Full article
(This article belongs to the Special Issue Innovations in Kidney Disease: From Pathogenesis to Therapy)
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13 pages, 903 KB  
Case Report
Pregnancy and Peripartum Multidisciplinary Management in Wolfram Syndrome Type 1: A Case Report
by Gema Esteban-Bueno and María Luz Serrano Rodríguez
Diagnostics 2026, 16(8), 1117; https://doi.org/10.3390/diagnostics16081117 - 8 Apr 2026
Viewed by 635
Abstract
Background/Objectives: Wolfram syndrome type 1 (WS1) is a rare, progressive, multisystem neurodegenerative disorder characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. As survival has improved, an increasing number of affected women are reaching reproductive age. However, evidence on pregnancy [...] Read more.
Background/Objectives: Wolfram syndrome type 1 (WS1) is a rare, progressive, multisystem neurodegenerative disorder characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. As survival has improved, an increasing number of affected women are reaching reproductive age. However, evidence on pregnancy and peripartum management in WS1 remains scarce, and practical guidance is limited. This case report describes the multidisciplinary management of pregnancy and delivery in a woman with genetically confirmed WS1 and highlights key considerations for peripartum care. Case Presentation: A woman with genetically confirmed WS1 and long-standing multisystem involvement, including diabetes mellitus, diabetes insipidus, neurogenic bladder requiring frequent self-catheterization, progressive neurologic manifestations, and severe sensory impairment, achieved pregnancy through assisted reproduction with oocyte donation and was closely monitored by a multidisciplinary team. Due to persistent breech presentation, a planned external cephalic version was performed at 37 + 5 weeks’ gestation with immediate availability for cesarean delivery. After unsuccessful attempts, cesarean delivery was performed under combined spinal–epidural anesthesia. Peripartum management focused on strict glycemic control, careful monitoring of fluid balance and urine output, neuraxial anesthesia with proactive hemodynamic management, precautions related to the cochlear implant, and tailored communication strategies. Postpartum recovery was favorable, although anemia on postoperative day 1 required transfusion of one unit of packed red blood cells and intravenous iron therapy. Discussion and Conclusions: Pregnancy in WS1 represents a high-risk clinical scenario because of the coexistence of endocrine, urologic, and neurologic comorbidities, while published evidence on peripartum management remains limited. This case supports an individualized, multidisciplinary approach to obstetric and anesthetic planning and the use of a practical framework to optimize peripartum management and enhance maternal–fetal safety in this rare condition. Full article
(This article belongs to the Special Issue Recent Advances in Genomics for Prenatal Diagnosis)
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