Diseases

13 pages, 1435 KB

Open AccessArticle

Long-Term Survival with Daratumumab, Lenalidomide and Dexamethasone in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients—A Survey from Two Italian Centers

by Vittorio Del Fabro, Lara Gullo, Giuliana Giunta, Giuseppina Uccello, Claudia Bellofiore, Cristina Lo Faro, Dario Leotta, Federica Elia, Veronica Vecchio, Chiara Sorbello, Ugo Consoli, Alessandra Romano, Francesco Di Raimondo, Manlio Fazio, Fabio Stagno and Concetta Conticello

Diseases 2026, 14(2), 81; https://doi.org/10.3390/diseases14020081 (registering DOI) - 21 Feb 2026

Abstract

Background: Multiple myeloma (MM) is a clonal plasma cell neoplasm representing the second most common hematological malignancy. The combination of daratumumab, lenalidomide and dexamethasone (D-Rd) was first approved by the EMA (European Medicines Agency) for the treatment of relapsed/refractory multiple myeloma (RRMM) patients, [...] Read more.

Background: Multiple myeloma (MM) is a clonal plasma cell neoplasm representing the second most common hematological malignancy. The combination of daratumumab, lenalidomide and dexamethasone (D-Rd) was first approved by the EMA (European Medicines Agency) for the treatment of relapsed/refractory multiple myeloma (RRMM) patients, and was subsequently approved for first-line therapy, based on the results of POLLUX and MAIA trials, respectively. Methods: In this survey, we retrospectively collected data from 96 consecutive transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients treated with the D-Rd combination. Results: The median age was 73 years; the median progression free survival (mPFS) and median overall survival (mOS) were not reached (NR); the overall response rate (ORR), defined as patients who obtained at least a partial response (PR), was 90%; 59% of patients achieved a very good partial response (VGPR) or better. A strong negative correlation was observed between treatment response and elevated beta-2-microglobulin levels. Conclusions: This study confirms the efficacy of the D-Rd combination as first-line therapy for TIE-NDMM patients, suggesting that achieving at least a PR—and particularly a VGPR—may represent a strong predictor of long-term remission and survival, even in the era of new combinations based on the use of quadruplets. Full article

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46 pages, 778 KB

Open AccessReview

Targeting Telomerase in Cancer: Vaccine-Based Strategies, Clinical Evidence, and Synergy with Immunotherapy

by Stella Baliou, Manolis N. Tzatzarakis, Andreas G. Tsantes, Elena Vakonaki, Petros Ioannou, Michalis Kyriakakis, Eleftheria Hatzidaki, Iordanis Pelagiadis, Eftichia Stiakaki and Aristides Tsatsakis

Diseases 2026, 14(2), 80; https://doi.org/10.3390/diseases14020080 - 20 Feb 2026

Abstract

With each replication cycle, telomeres shorten. Telomerase can slow or reverse the rate of telomere shortening. In the era of cancer immunotherapy, telomerase is a promising tumor-associated antigen due to its widespread and specific expression in cancer cells and its strong immunogenicity. Interestingly, [...] Read more.

With each replication cycle, telomeres shorten. Telomerase can slow or reverse the rate of telomere shortening. In the era of cancer immunotherapy, telomerase is a promising tumor-associated antigen due to its widespread and specific expression in cancer cells and its strong immunogenicity. Interestingly, telomerase-based vaccines eradicate telomerase-expressing cancer cells by increasing antigen-specific T-cell responses rather than by directly inhibiting telomerase enzymatic activity as telomerase inhibitors function. To support this, telomerase-based vaccines, including DNA, mRNA, peptide-, and cell-based vaccines, have been evaluated in clinical settings to elucidate their molecular mechanisms of action. The aim of this review is to present the clinical effectiveness of telomerase vaccines alone or in combination with immunotherapy. In particular, the therapeutic effectiveness of telomerase vaccines is influenced by the tumor microenvironment and can be substantially increased by combining them with immune checkpoint inhibitors. To further optimize telomerase-based vaccines, we discuss translational challenges and highlight the need for further optimization. Full article

17 pages, 1645 KB

Open AccessArticle

Identification of Novel Trypanosoma cruzi Cysteine Protease Inhibitors via Ligand-Based Virtual Screening of FDA-Approved Drugs with Trypanocidal Activity

by Lenci K. Vázquez-Jiménez, Alonzo González-González, Timoteo Delgado-Maldonado, Rogelio Gómez-Escobedo, Benjamín Nogueda-Torres, Ana Verónica Martínez-Vázquez, Eyrá Ortiz-Pérez, Charmina Aguirre-Alvarado, Verónica Alcántara-Farfán, Joaquín Cordero-Martínez, Lorena Rodríguez-Páez, Adriana Moreno-Rodriguez and Gildardo Rivera

Diseases 2026, 14(2), 79; https://doi.org/10.3390/diseases14020079 - 19 Feb 2026

Abstract

Background: Chagas disease is a major public health problem, especially in Latin American countries, and benznidazole and nifurtimox are currently the only drugs available for its treatment. However, they present several disadvantages, such as low availability, high toxicity, and limited efficacy, which often [...] Read more.

Background: Chagas disease is a major public health problem, especially in Latin American countries, and benznidazole and nifurtimox are currently the only drugs available for its treatment. However, they present several disadvantages, such as low availability, high toxicity, and limited efficacy, which often result in treatment discontinuation. In recent decades, bioinformatics studies have accelerated the field of drug repurposing, reducing time and costs. In this study, the aim was to identify novel cruzain inhibitors from the analogs of FDA-approved drugs with trypanocidal activity. Methods: A ligand-based virtual screen, along with molecular docking analysis, was carried out, and the selected compounds were evaluated for their trypanocidal activity against trypomastigotes of two endemic Mexican strains and their inhibitory activity on cysteine proteases. Results: A cefsulodin analog (LC₅₀ = 126.18 and 77.50 µM), two flucloxacillin analogs (LC₅₀ = 94.05 and 101.73 µM; 48.74 and 64.49 µM), and one piperacillin analog (LC₅₀ = 48.46 and 83.68 µM) had better trypanocidal activity and selectivity index against the NINOA and INC-5 strains than the reference drugs. Enzymatic evaluation showed that all four compounds inhibited cysteine proteases (IC₅₀ < 840.03 µM). Furthermore, molecular dynamics simulations predicted the stability of the compound–protein complex, while the docking test on human cathepsin L predicted their potential selectivity. Finally, our in silico analysis of ADMET properties showed that all compounds exhibited favorable profiles. Conclusions: These results encourage the development of new and more potent anti-Trypanosoma cruzi agents using FDA-approved drugs as scaffolds. Full article

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13 pages, 1114 KB

Open AccessArticle

Predictors of Long-Term Prognosis Focused on Kidney Function in Patients with Chronic Coronary Syndrome

by Katarzyna Charkiewicz-Szeremeta, Emilia Sawicka-Śmiarowska, Marlena Dubatówka, Małgorzata Knapp, Klaudia Mickiewicz, Jacek Jamiołkowski, Andrzej Raczkowski, Marcin Kondraciuk, Anna Szpakowicz, Katarzyna Ptaszyńska and Karol A. Kamiński

Diseases 2026, 14(2), 78; https://doi.org/10.3390/diseases14020078 - 19 Feb 2026

Abstract

Background: The number of patients with chronic coronary syndromes (CCS) is growing, influenced by factors such as increasing life expectancy and prevalence of risk factors. Thus, cardiovascular (CV) disease remains the leading cause of mortality and morbidity worldwide. The main objective of the [...] Read more.

Background: The number of patients with chronic coronary syndromes (CCS) is growing, influenced by factors such as increasing life expectancy and prevalence of risk factors. Thus, cardiovascular (CV) disease remains the leading cause of mortality and morbidity worldwide. The main objective of the study was to identify factors associated with long-term survival in patients with chronic coronary syndrome, with a focus on kidney function described by eGFR and albuminuria (assessed by uACR). Methods: The study comprised a total of 257 patients from Bialystok (Poland), aged ≤ 80 years, who 6–18 months earlier were hospitalized for acute coronary syndrome or elective myocardial revascularization. During the 80-month follow-up, 40 (15.6%) patients died, while there was no information about three (1.2%) patients. Patients with preserved eGFR and without albuminuria were characterized by the longest survival, with deterioration of prognosis in groups of progressive kidney dysfunction as defined by KDIGO based on eGFR and uACR. The primary endpoint was death from any cause. Results: Those who survived the 80-month follow-up period were younger (p < 0.001), had a lower waist circumference (p = 0.028), higher diastolic blood pressure (p = 0.026), lower NTproBNP (p < 0.001) and hsCRP (p = 0.001) concentrations, reduced eGFR (p = 0.004) and increased ACR (p = 0.023) were strongly associated with mortality. In logistic regression analysis with stepwise elimination of variables, the strongest factors affecting survival were hemoglobin concentration, left ventricle ejection fraction (LVEF) and hsCRP. Conclusions: Measurement of albuminuria, in addition to eGFR, allows patients to be correctly classified into CV risk categories and facilitates appropriate treatment of patients with CCS. Higher diastolic blood pressure (but still within normal range) was found in patients who later survived 6 years. Measurements of hsCRP, hemoglobin concentration and LVEF help to identify CCS patients at the highest risk of mortality in long-term follow-up. Full article

(This article belongs to the Section Cardiology)

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30 pages, 1830 KB

Open AccessArticle

Gut Microbiome Recovery in Clostridioides difficile Infection Patients Receiving Multi-Strain Probiotics During Convalescence: A Prospective Pilot Series of Longitudinal Dynamics

by Dorin Novacescu, Talida Georgiana Cut, Adelina Baloi, Alexandra Herlo, Ioana-Melinda Luput-Andrica, Andra Elena Saizu, Amelia Uzum, Maria Daniela Mot, Flavia Zara, Dorel Sandesc, Voichita Elena Lazureanu and Adelina Marinescu

Diseases 2026, 14(2), 77; https://doi.org/10.3390/diseases14020077 - 18 Feb 2026

Abstract

Background/Objectives: Clostridioides difficile infection (CDI) is a major healthcare-associated infection associated with profound antibiotic-induced gut microbiome disruption that frequently persists after clinical resolution. This pilot study aimed to characterize early post-infectious gut microbiome recovery following an inaugural CDI episode and to descriptively [...] Read more.

Background/Objectives: Clostridioides difficile infection (CDI) is a major healthcare-associated infection associated with profound antibiotic-induced gut microbiome disruption that frequently persists after clinical resolution. This pilot study aimed to characterize early post-infectious gut microbiome recovery following an inaugural CDI episode and to descriptively assess microbiome remodeling during adjunctive multi-strain probiotic supplementation. Methods: Adult patients with mild-to-moderate CDI were prospectively enrolled after completing standard antimicrobial therapy and received a 30-day course of a high-potency, 10-strain probiotic formulation. Stool samples were collected before and after supplementation and analyzed using 16S rRNA gene sequencing with microbiome-inferred functional profiling, alongside targeted screening for enteric protozoa and yeasts. Results: Five patients completed paired analyses. At baseline, all patients exhibited severe dysbiosis characterized by markedly reduced microbial diversity, depletion of Actinobacteria and short-chain fatty acid-producing taxa, expansion of Proteobacteria, and unfavorable inferred metabolic signatures. After supplementation, four of five patients were observed to exhibit increased microbial diversity and partial improvement in global dysbiosis indices. Microbiome recovery was heterogeneous and non-linear, involving variable reductions in Proteobacteria, recovery of Actinobacteria, or both, with incomplete normalization of taxonomic balances and inferred functions. Enterotype shifts were observed in three patients, consistent with ecological reorganization rather than full restoration. Baseline protozoal colonization resolved in affected patients, while fungal dynamics showed clearance or species-level replacement. No early CDI recurrences were observed during follow-up. Conclusions: Interpretation is limited by the single-arm design without a control group, which precludes distinguishing supplementation-associated changes from natural post-antibiotic recovery. Even so, our findings highlight the complexity and inter-individual variability of early post-CDI microbiome recovery and support further investigation of integrative microbiome profiling to describe post-infectious dysbiosis dynamics. Full article

(This article belongs to the Special Issue Recent Advances in Gastroenterology and Nutrition (2nd Edition))

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15 pages, 5108 KB

Open AccessArticle

Diagnosis and Management of Patients with Cardiac Sarcoidosis by a Regional Specialist Service

by Rebecca Godfrey, Otto Fenske, Raj Selvaraju, Ana Frappell, Emine Cicek, Imad Mohamed Imran, Achuth Hosur, Eleonora Manca, Nitasha Singh, Susan Ellery, Victoria Parish, David Hildick-Smith, Jack McCready, Sabina Dizdarevic, Rachel Buxton-Thomas, John Silberbauer and Alexander Liu

Diseases 2026, 14(2), 76; https://doi.org/10.3390/diseases14020076 - 17 Feb 2026

Abstract

Background: Cardiac sarcoidosis (CS) is associated with potentially serious complications, including heart failure and life-threatening arrhythmias. The diagnosis and management of CS is multifaceted, requiring a multi-disciplinary team (MDT)-based approach. A new regional CS clinical service was established in Sussex County (UK) in [...] Read more.

Background: Cardiac sarcoidosis (CS) is associated with potentially serious complications, including heart failure and life-threatening arrhythmias. The diagnosis and management of CS is multifaceted, requiring a multi-disciplinary team (MDT)-based approach. A new regional CS clinical service was established in Sussex County (UK) in January 2025. This service is based on a core of cardiologists working with a wider MDT, including specialists in pulmonary sarcoidosis, nuclear medicine and cardiac electrophysiology. This study assessed the clinical performance of this new service. Methods: Patients with suspected CS referred to the Sussex CS Service between January and December 2025 were included, as compared to a control cohort of patients referred for CS assessment before the service was conceived. Results: Of the 51 CS service referrals, 13 patients fulfilled the Heart Rhythm Society (HRS) criteria, all of whom were correctly diagnosed with CS, whilst only two out of seven HRS-positive control patients were correctly diagnosed. In the 38 HRS-negative CS service referrals, 8 patients (21%) were still given a clinical CS diagnosis compared to none in the HRS-negative controls. Of the 21 patients diagnosed with CS, 7 (33%) had active myocardial inflammation and 8 (38%) had LV systolic dysfunction. Where indicated, immunosuppressive and heart failure therapies were initiated in all patients. Eight CS patients (38%) underwent implantable cardioverter defibrillator implantation. No deaths or heart failure hospitalisations occurred within the first 11 months. Conclusions: An MDT-based CS service model can provide multi-faceted care to patients, without major short-term adverse outcomes. The service model replicability and long-term outcomes require further assessment. Full article

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13 pages, 409 KB

Open AccessArticle

Factors Associated with GLP-1 Receptor Agonist Use in Patients with Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Retrospective Propensity-Score Matched Analysis

by Georgios Vournas, Leonidas Mourgos, Michael Doumas, Evangelos N. Liberopoulos, Kalliopi Kotsa and Theocharis Koufakis

Diseases 2026, 14(2), 75; https://doi.org/10.3390/diseases14020075 - 17 Feb 2026

Abstract

Background: Atherosclerotic cardiovascular disease (ASCVD) frequently coexists with type 2 diabetes (T2D), amplifying morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RA) confer significant cardiovascular benefits and are recommended for patients with T2D and established ASCVD. However, real-world use may not reflect a complication-driven [...] Read more.

Background: Atherosclerotic cardiovascular disease (ASCVD) frequently coexists with type 2 diabetes (T2D), amplifying morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RA) confer significant cardiovascular benefits and are recommended for patients with T2D and established ASCVD. However, real-world use may not reflect a complication-driven therapeutic approach. Methods: This retrospective study included adults with T2D and established ASCVD (prior myocardial infarction, ischemic stroke, transient ischemic attack, or symptomatic peripheral arterial disease) consecutively admitted to the internal medicine and cardiology departments of a tertiary hospital over a 60-day period. Pre-admission medication use, comorbidities, and laboratory parameters were recorded. Factors associated with GLP-1 RA use were assessed using logistic regression before and after 1:1 propensity score (PS) matching. Results: Among 202 eligible patients, 49 (24.3%) were treated with a GLP-1RA. GLP-1RA users were younger (71.9 vs. 77.8 years, p < 0.001), had lower hypertension prevalence (61.2% vs. 78.4%, p = 0.02), and were more frequently on insulin (69.4% vs. 25.5%, p < 0.001) and sodium-glucose cotransporter 2 inhibitors (55.1% vs. 28.1%, p = 0.001). After PS matching (48 pairs), demographic and comorbidity differences were attenuated, although insulin remained strongly associated with GLP-1RA therapy (Odds Ratio 11.85, p < 0.001). Neither cardiovascular disease burden—captured through the presence of multiple cardiovascular comorbidities—nor renal function were independently associated with GLP-1RA use after adjustment. Conclusions: In patients with T2D and established ASCVD, GLP-1RA use was more strongly associated with the intensity of glucose-lowering therapy—particularly insulin use—than with cardiovascular or renal risk profiles. These findings should be interpreted with caution given the retrospective observational design and the limited availability of glycated hemoglobin, anthropometry and diabetes duration data. However, they suggest that, in real-world clinical practice, GLP-1RA prescribing may remain predominantly glucose-centric rather than complication-driven, underscoring the need for improved implementation of contemporary diabetes guidelines. Full article

(This article belongs to the Section Cardiology)

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16 pages, 1789 KB

Open AccessArticle

Awareness and Perceived Risk Factors of Chronic Kidney Disease Among Patients with Diabetes in the Northern Borders of Saudi Arabia: Implications for a Strategic Monitoring and Management Plan

by Safya E. Esmaeel, Altaf Saleh Mahdi Alanazi Alnzi, Nouf Mofareh Mulahed Alanazi, Rose Dahi Khamis Alanazi, Amal Mohammed Shahi Alruwaili, Areeb Rawaf Mohammed Alanzi, Ahad Wadi Alnagzi Alanazi, Yousef Wasmi Alenezi, Ahmed Saleh Alanazi, Rimas Khalid A. Alanazi, Baraah Abu Alsel, Eslam K. Fahmy and Manal S. Fawzy

Diseases 2026, 14(2), 74; https://doi.org/10.3390/diseases14020074 - 16 Feb 2026

Abstract

Background/Objectives: Chronic kidney disease (CKD) poses a significant health burden for individuals with diabetes mellitus, increasing morbidity and mortality. Understanding CKD and its risk factors is essential for early detection, effective management, and prevention of complications. This study aimed to assess CKD [...] Read more.

Background/Objectives: Chronic kidney disease (CKD) poses a significant health burden for individuals with diabetes mellitus, increasing morbidity and mortality. Understanding CKD and its risk factors is essential for early detection, effective management, and prevention of complications. This study aimed to assess CKD awareness as the primary outcome and to explore self-reported CKD prevalence and associated factors as secondary outcomes among patients with diabetes in the Northern Border Region, Saudi Arabia. Methods: A cross-sectional survey was conducted among 389 adults with a self-reported physician diagnosis of diabetes in the specified region, using a validated, self-administered online questionnaire. Data were analyzed to evaluate CKD awareness and identify perceived risk factors and factors associated with self-reported CKD. Results: Of the participants, 182 (46.8%) demonstrated good awareness of CKD, while the self-reported prevalence of CKD was 83 (21.3%). Males and unmarried participants were more likely to have good CKD awareness (p = 0.008 and 0.009, respectively). Significant associations were observed between self-reported CKD prevalence and age, sex, type of diabetes, family history of kidney disease, and comorbidities (all p < 0.05). Multivariate logistic regression showed that hypertension was strongly associated with self-reported CKD [aOR = 5.77; 95% CI: 3.12–10.67; p < 0.001], as was heart disease [aOR = 4.21; 95% CI: 1.35–13.13; p = 0.013]. Conclusions: Patients with diabetes in this region exhibited moderate awareness of CKD, with higher awareness among males and unmarried individuals. Hypertension and cardiac disease were significantly associated with self-reported CKD. These findings underscore the importance of targeted education, routine evidence-based screening, and structured management strategies for CKD within diabetes care and provide a basis for a regional strategic plan to strengthen CKD monitoring among patients with diabetes. Full article

(This article belongs to the Special Issue From Monitoring to Management: Addressing Challenges in Type 1 and Type 2 Diabetes Care)

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12 pages, 478 KB

Open AccessArticle

Predictors of Secondary Pulmonary Hypertension-Related Hospitalizations and Subsequent Mortality in Adults with Obstructive Sleep Apnea

by Hassaan Imtiaz, Adil Sarvar Mohammed, Avilash Mondal, Lakshmi Sai Meghana Kodali, Sai Gautham Kanagala, Rupak Desai, Umera Yasmeen, Haritha Darapaneni, Muhammad Usman Ghani, Shweta Kambali, Shrinivas Kambali and Mohd S. Kanjwal

Diseases 2026, 14(2), 73; https://doi.org/10.3390/diseases14020073 - 16 Feb 2026

Abstract

Background: Secondary pulmonary hypertension (SPH) predicts poor outcomes in obstructive sleep apnea (OSA) patients. This study examines sex/racial disparities, predictors, and inpatient mortality in SPH-related OSA hospitalizations. Methods: We used the National Inpatient Sample (2019) and ICD-10 codes to identify OSA-related hospitalizations with [...] Read more.

Background: Secondary pulmonary hypertension (SPH) predicts poor outcomes in obstructive sleep apnea (OSA) patients. This study examines sex/racial disparities, predictors, and inpatient mortality in SPH-related OSA hospitalizations. Methods: We used the National Inpatient Sample (2019) and ICD-10 codes to identify OSA-related hospitalizations with SPH. The burden of SPH and disparities by sex/race were assessed. We also compared the odds and predictors of in-hospital mortality in OSA patients with vs. without SPH. Results: Of total adult OSA hospitalizations (n = 2,317,136, median age of 66 [56–74] years, and males: 57.2%), 9.4% (218,795/2,317,136) had SPH. Females vs. males (11.3% vs. 8.1%) and Blacks vs. other race groups (13.5%) with OSA had a higher prevalence of SPH. The SPH cohort often consisted of females (51 vs. 41.9%), Blacks (20.9 vs. 14.0%), Medicare-insured (73.4 vs. 60.6%), and non-elective admissions (89.2 vs. 74.4%) vs. the non-SPH cohort. The SPH cohort also had a higher burden of complicated HTN (52.9 vs. 36.3%), DM with complications (42.7 vs. 32.4%), COPD (52.5 vs. 36.9%), history of prior MI (11.4 vs. 9.6%), and venous thromboembolism (10.4 vs. 8.4%). However, in-hospital mortality was more likely to be in males (OR 1.12; 95%CI 1.00–1.25, p = 0.048) vs. females, and OSA patients with metastatic cancer (OR 2.73; 95%CI 2.04–3.65) and solid non-metastatic tumors (OR 1.65; 95%CI 1.26–2.15) (p < 0.001). Conclusions: The prevalence of SPH with OSA was greater in females and Blacks, whereas males and Whites had higher subsequent inpatient mortality. More prospective studies are needed to understand the role of comorbidities on survival outcomes. Full article

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10 pages, 751 KB

Open AccessArticle

Association of Sarcopenia with Lower Adiponectin Levels and Reduced Estimated Appendicular Lean Mass in Patients with Metabolic Syndrome: A Cross-Sectional Study

by Juan Antonio Suárez-Cuenca, Pablo Zermeño-Ugalde, Diana Elisa Díaz-Jiménez, Juan Antonio Pineda-Juárez, Deyanhira Palacios-Colunga, Alejandro Hernández-Patricio, Eduardo Vera-Gómez, Areli Romero-López, María Fernanda Kuri-Pineda, Andrea Ramírez-Coyotecatl, Dulce Cecilia Vázquez-Ramos, José Gutiérrez-Salinas, Silvia García, Christian Alejandro Delaflor-Wagner, Christian Gabriel Toledo-Lozano, Luis Montiel-López, María Angélica Díaz-Aranda and Alberto Melchor-López

Diseases 2026, 14(2), 72; https://doi.org/10.3390/diseases14020072 - 14 Feb 2026

Abstract

Background: Sarcopenia is a progressive muscle disorder associated with metabolic syndrome (MS), in which early impairments in muscle strength and quality precede muscle mass loss. Simple, non-invasive measures such as handgrip strength, estimated appendicular skeletal muscle mass (eASM), and phase angle (PA) may [...] Read more.

Background: Sarcopenia is a progressive muscle disorder associated with metabolic syndrome (MS), in which early impairments in muscle strength and quality precede muscle mass loss. Simple, non-invasive measures such as handgrip strength, estimated appendicular skeletal muscle mass (eASM), and phase angle (PA) may aid early detection, while adipokines link muscle dysfunction to metabolic regulation. Objective: In the present study, we aimed to evaluate the association between sarcopenia markers and PA in patients with MS. Methods: A cross-sectional study was conducted in patients with MS, at a third-level hospital in Mexico City. Sarcopenia was assessed by handgrip strength and eASM; body composition and PA were measured using bioelectrical impedance; and plasma adipokines were quantified by ELISA. Results: Seventy-four (mean age, 57.7 years; 75% female; BMI, 32.5 kg/m²) participants with MS were included. Handgrip strength correlated with eASM (r = 0.64; p < 0.01) and PA (rho = 0.43; p < 0.01), and eASM also correlated with PA (rho = 0.40; p < 0.01) and predicted higher PA values (OR = 2.74; p = 0.042). The sarcopenic subgroup had lower brachial circumference and plasma adiponectin. Conclusions: Sarcopenia is frequent in MS and associated with lower adiponectin, suggesting a vulnerable condition. Functional/structural markers of sarcopenia showed significant correlation with PA, whereas combined methods may enhance the early detection and management of muscle deterioration in metabolic disease. Full article

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14 pages, 525 KB

Open AccessArticle

Factors Associated with Maternal Mortality from COVID-19 in Pernambuco, Brazil (2020–2021): A Case–Control Study

by Tacilene Luzia da Silva, Cristine Vieira do Bonfim, Ulisses Ramos Montarroyos and Carlos Alexandre Antunes de Brito

Diseases 2026, 14(2), 71; https://doi.org/10.3390/diseases14020071 - 14 Feb 2026

Abstract

Background: The COVID-19 pandemic has contributed to the increase in maternal mortality due to the direct effects of the viral infection and the indirect effects caused by the overload of health services, and the resulting economic and social crises. This study aims to [...] Read more.

Background: The COVID-19 pandemic has contributed to the increase in maternal mortality due to the direct effects of the viral infection and the indirect effects caused by the overload of health services, and the resulting economic and social crises. This study aims to analyze sociodemographic, gestational, and clinical factors associated with maternal deaths from COVID-19 in Pernambuco between 2020 and 2021. Method: The study included 37 cases (deaths) and 112 controls (survivors). Crude and adjusted odds ratios were estimated using conditional and Firth’s penalized logistic regression models, respectively, to evaluate sociodemographic, gestational, and clinical factors. Results: In the bivariate analysis, the main factors associated with maternal death from COVID-19 were ≤8 years of schooling, the postpartum period, multiparity, oxygen saturation below 95%, obesity, and diabetes mellitus. The presence of fever and cough was associated with a lower probability of death. The independent factors that remained associated with maternal death were the postpartum period (aOR: 80.78; 95% CI: 16.54–394.37), parity ≥ 1 (aOR: 5.74; 95% CI: 1.16–28.22), and oxygen saturation below 95% (aOR: 7.16; 95% CI: 1.37–37.44), with fever acting as a possible protective factor (aOR: 0.08; 95% CI: 0.01–0.42). Factors such as obesity and diabetes were not independent predictors in the final multivariable model. Conclusions: The findings reinforce that maternal death is a multifactorial phenomenon. The relevance of this investigation lies in identifying clinical and obstetric vulnerability profiles in a region heavily impacted by the health crisis. Knowledge gained from past crises contributes to the improvement of public health strategies and clinical management protocols, aiming to mitigate preventable maternal deaths in future public health emergencies. Full article

(This article belongs to the Section Infectious Disease)

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16 pages, 2038 KB

Open AccessArticle

Host Serum Biomarker Signatures in Mycobacteriologically Cured Pulmonary Tuberculosis Patients with Persistent Lung Inflammation on 18F-FDG PET/CT

by Bongani Motaung, Solima Sabeel, Mumin Ozturk, Trevor S. Mafu, Muki Shey, Sandra L. Mukasa, Karen Wolmarans, Fareda Jakoet-Bassier, Ashleigh Taylor, Antoneta Mashinyira, Tessa Kotze, Friedrich Thienemann and Reto Guler

Diseases 2026, 14(2), 70; https://doi.org/10.3390/diseases14020070 - 12 Feb 2026

Abstract

Background: Pulmonary inflammation is a widely recognized characteristic of active tuberculosis (TB). Although standard TB treatment is effective, a substantial proportion of mycobacteriologically cured TB patients experience persistent pulmonary inflammation, which can lead to long-term lung impairment, post-tuberculosis lung disease (PTLD) and potentially [...] Read more.

Background: Pulmonary inflammation is a widely recognized characteristic of active tuberculosis (TB). Although standard TB treatment is effective, a substantial proportion of mycobacteriologically cured TB patients experience persistent pulmonary inflammation, which can lead to long-term lung impairment, post-tuberculosis lung disease (PTLD) and potentially TB recurrence. Methods: We conducted a case–control study to compare host serum biomarker profiles in individuals with minimal (TLG < 50 SUVbw*mL, n = 37) versus extensive (TLG ≥ 50 SUVbw*mL, n = 34) persistent lung inflammation following completion of standard drug-sensitive TB treatment. Lung inflammation was measured by 18F-FDG PET/CT scan using total lung glycolysis (TLG) as a surrogate marker. All participants had negative sputum cultures at four months of TB treatment, and blood samples were collected at treatment completion (month six). A Luminex^® multiplex assay performed on the Bio-Plex^® 200 platform was used to analyze 48 host serum biomarkers involved in cytokine/chemokine signaling. Results: Following multiple t-test analysis, fifteen biomarkers were significantly elevated (p < 0.05) in participants with extensive persistent lung inflammation compared to those with minimal inflammation. Among these, 14 demonstrated potential as discriminatory markers, with area under the curve (AUC) values ranging from 0.707 to 0.806, sensitivities ranging from 47.06% to 73.53%, and specificities ranging from 70.27% to 83.78%. Notably, 13 of these 16 candidate biomarkers significantly correlated with TLG values, further supporting their potential clinical utility. Conclusion: We report associations between serum inflammatory mediators and persistent pulmonary inflammation following mycobacterial clearance in TB patients, highlighting their potential as diagnostic biomarkers that could potentially meet the target product profile (TPP) criteria. Full article

(This article belongs to the Section Respiratory Diseases)

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14 pages, 529 KB

Open AccessArticle

Burden and Clinical Impact of Hepatitis D Virus Co-Infection Among HBsAg-Positive Patients in Mauritania

by Mohamed Abdawa, Mohamed Hemeyine, Isabelle Chemin, Françoise Lunel-Fabiani and Mohamed Vall Mohamed Abdellahi

Diseases 2026, 14(2), 69; https://doi.org/10.3390/diseases14020069 - 12 Feb 2026

Abstract

Background: Hepatitis B virus (HBV) infection remains highly endemic in sub-Saharan Africa, where hepatitis delta virus (HDV) co-infection substantially worsens liver disease outcomes. Mauritania has long been suspected to be a high-burden setting for HBV-HDV co-infection, yet contemporary data describing its clinical and [...] Read more.

Background: Hepatitis B virus (HBV) infection remains highly endemic in sub-Saharan Africa, where hepatitis delta virus (HDV) co-infection substantially worsens liver disease outcomes. Mauritania has long been suspected to be a high-burden setting for HBV-HDV co-infection, yet contemporary data describing its clinical and virological impact remain limited. Methods: We conducted a hospital-based cross-sectional study at the National Institute of Hepato-Virology (INHV) in Nouakchott, including 401 HBsAg-positive patients. Demographic, clinical, biological, and virological data were collected. HDV serology and RNA testing were performed when available. Liver disease severity, including cirrhosis and hepatocellular carcinoma (HCC), was assessed using clinical, biological, and imaging criteria. Results: HDV antibodies were detected in 31.9% of HBsAg-positive patients, confirming Mauritania as a hyper-endemic area for HDV. HDV co-infection was strongly associated with advanced liver disease, with HDV antibodies present in 86.4% of cirrhotic patients and 82.4% of those with HCC. Patients with HDV infection frequently exhibited suppressed HBV DNA levels, reflecting viral interference. A substantial proportion of patients presented with decompensated cirrhosis or HCC at diagnosis, and nearly 70% were treatment-naïve. Overall, HDV co-infection emerged as the principal driver of severe liver disease in this cohort. Conclusions: HBV/HDV co-infection is highly prevalent in Mauritania and is associated with a wide clinical spectrum ranging from asymptomatic infection to decompensated cirrhosis and hepatocellular carcinoma. HDV co-infection is the principal driver of severe liver disease, often occurring despite low or undetectable HBV DNA levels. Systematic HDV screening among all HBsAg-positive individuals is urgently needed to improve risk stratification, guide therapeutic decisions, and reduce liver-related morbidity and mortality. Full article

(This article belongs to the Section Infectious Disease)

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13 pages, 370 KB

Open AccessArticle

Pharmacological Management of Delirium in Older Adults in the Emergency Department: Clinical Outcomes

by Angela Soler-Sanchis, Francisco Miguel Martínez-Arnau and Pilar Pérez-Ros

Diseases 2026, 14(2), 68; https://doi.org/10.3390/diseases14020068 - 12 Feb 2026

Abstract

Background/Objectives: Delirium is frequent and serious in older adults attending the emergency department (ED), but evidence on its pharmacological management in this setting is limited. This study aimed to quantify the pharmacological treatment of delirium in older adults in the ED and examine [...] Read more.

Background/Objectives: Delirium is frequent and serious in older adults attending the emergency department (ED), but evidence on its pharmacological management in this setting is limited. This study aimed to quantify the pharmacological treatment of delirium in older adults in the ED and examine its association with subsequent hospital admission. Methods: A cross-sectional study was conducted between November 2021 and June 2022 in a Spanish ED. The sample included 153 adults aged 65 years or older with clinician-diagnosed delirium. Clinical, triage, and medication data were obtained from electronic medical records, and associations with hospital admission were analysed using multivariable logistic regression. Results: Ninety-one participants (59.5%) were hospitalised. Antipsychotic, analgesic, and benzodiazepine use was associated with hospitalisation. Absence of an underlying cause was a protective factor. The logistic regression model was significant. Conclusions: By identifying the most frequently administered pharmacological treatments for delirium in older adults in the ED and describing their association with hospitalisation, this study provides key insights into real-world clinical practice patterns in this setting. Full article

(This article belongs to the Special Issue Diseases: From Molecular to the Clinical Perspectives)

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14 pages, 265 KB

Open AccessArticle

Factors Associated with Perinatal Depression and Anxiety Among Pregnant and Postpartum Women: A Cross-Sectional Study Based on Questionnaire Data

by Byung Soo Kang, Jisoo Um, Subeen Hong, Hae-Jung Park, Joo Hyun Park, Jihyun Hwang, Tae-Suk Kim and Hyun Sun Ko

Diseases 2026, 14(2), 67; https://doi.org/10.3390/diseases14020067 - 11 Feb 2026

Abstract

Background/Objectives: Perinatal depression and anxiety are significant mental health concerns, and pharmacological treatments often pose considerable challenges. Therefore, this study aimed to evaluate the mental health status of pregnant and postpartum women and identify the factors affecting perinatal depression and anxiety. Methods [...] Read more.

Background/Objectives: Perinatal depression and anxiety are significant mental health concerns, and pharmacological treatments often pose considerable challenges. Therefore, this study aimed to evaluate the mental health status of pregnant and postpartum women and identify the factors affecting perinatal depression and anxiety. Methods: This cross-sectional study included 286 pregnant and postpartum women who completed questionnaires, including the Patient Health Questionnaire-9 (PHQ-9), Korean Version of the Edinburgh Postnatal Depression Scale (K-EPDS), and Generalized Anxiety Disorder-7 (GAD-7). Results: Symptoms of depression and anxiety were prevalent among participants. PHQ-9-positive cases were significantly less frequent in women from nuclear families, and their Pregnancy Stress Scale scores were significantly higher. K-EPDS-positive women had significantly lower rates of wanted pregnancies and marital satisfaction. GAD-7-positive cases showed significantly lower rates of wanted pregnancies, lower levels of social support, and higher Pregnancy Stress Scale scores. Conclusions: These findings highlight key psychosocial factors associated with perinatal depression and anxiety among pregnant and postpartum women, underscoring the importance of comprehensive mental health assessment during the perinatal period. Full article

37 pages, 952 KB

Open AccessReview

Detection for New Biomarkers of Tuberculosis Infection Activity Using Machine Learning Methods

by Anna An. Starshinova, Adilya Sabirova, Olesya Koroteeva, Igor Kudryavtsev, Artem Rubinstein, Arthur Aquino, Andrey S. Trulioff, Ekaterina Belyaeva, Anastasia Kulpina, Raul A. Sharipov, Ravil K. Tukfatullin, Nikolay Y. Nikolenko, Anton Mikhalev, Andrey A. Savchenko, Alexandr Borisov and Dmitry Kudlay

Diseases 2026, 14(2), 66; https://doi.org/10.3390/diseases14020066 - 11 Feb 2026

Abstract

Background/Objectives: Latent tuberculosis infection (LTBI) represents a critical reservoir for subsequent development of active tuberculosis (ATB) and poses significant challenges for early diagnosis and disease prevention. Traditional immunological assays, such as interferon-gamma release assays (IGRAs), are limited in their ability to reliably distinguish [...] Read more.

Background/Objectives: Latent tuberculosis infection (LTBI) represents a critical reservoir for subsequent development of active tuberculosis (ATB) and poses significant challenges for early diagnosis and disease prevention. Traditional immunological assays, such as interferon-gamma release assays (IGRAs), are limited in their ability to reliably distinguish LTBI from ATB. Recent advances in high-throughput omics technologies and machine learning (ML) approaches offer new opportunities for precise, biomarker-based differential diagnostics. Methods: Transcriptomic and proteomic profiling of host immune responses has revealed reproducible gene and protein signatures associated with LTBI and ATB. The integration of ML techniques—including feature selection, dimensionality reduction, multimodal learning, and explainable AI—facilitates the construction of robust diagnostic models. Single-modality signatures, derived from RNA-seq, microarrays, or proteomic assays, are complemented by multimodal approaches that incorporate soluble mediators, immunological readouts, and imaging-derived features. Deep learning frameworks, such as convolutional neural networks and transformer-based architectures, enhance the extraction of complex molecular and structural patterns from high-dimensional datasets. Results: ML-driven analyses of transcriptomic and proteomic data consistently outperform conventional immunological tests in terms of sensitivity, specificity, and clinical applicability. Multimodal integration further improves diagnostic accuracy and robustness. These advances support the translational development of concise, quantitative reverse transcription PCR (qRT-PCR)-based biomarker panels suitable for routine clinical application, enabling early and reliable differentiation between LTBI and ATB. Overall, the combination of high-throughput omics and AI-based analytical frameworks provides a promising pathway for enhancing global tuberculosis diagnostics. Conclusions: This review provides a structured and critical synthesis of transcriptomic and proteomic biomarker research for LTBI and ATB discrimination, with a particular emphasis on machine learning–based analytical frameworks. Unlike previous narrative reviews, we systematically compare data-generating platforms, modelling strategies, validation approaches, and sources of heterogeneity across studies. We further identify key translational barriers, including cohort homogeneity, platform dependency, and limited external validation, and propose directions for future research aimed at improving clinical applicability. Full article

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11 pages, 3709 KB

Open AccessCase Report

Report on Successful Treatment of Refractory MAC 2 Lung Disease in Two Elderly Patients with Inhaled Liposomal Amikacin (ALIS) at Half the Standard Dose

by Kenjiro Nagai and Syo Nagai

Diseases 2026, 14(2), 65; https://doi.org/10.3390/diseases14020065 - 11 Feb 2026

Abstract

“Nontuberculous mycobacteria” (NTM) is a general term for mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. In Japan, 90% of pulmonary NTM disease cases are caused by two species, Mycobacterium avium and M. intracellulare, which are collectively referred to as Mycobacterium [...] Read more.

“Nontuberculous mycobacteria” (NTM) is a general term for mycobacteria other than the Mycobacterium tuberculosis complex and Mycobacterium leprae. In Japan, 90% of pulmonary NTM disease cases are caused by two species, Mycobacterium avium and M. intracellulare, which are collectively referred to as Mycobacterium avium complex (MAC) due to their biochemical similarity. Pulmonary MAC disease is broadly classified into fibrocavitary and nodular/bronchiectatic types, each of which exhibits distinctive pathological features. The pulmonary NTM disease incidence has been found to be 14.7 cases per 100,000 population per year, suggesting that Japan has the highest incidence of this disease in the world, and its incidence has also been shown to have already exceeded that of pulmonary tuberculosis. In addition, many elderly people have weakened immune systems, which often causes a decline in comprehension, and many medications for this have side effects, making it difficult to continue taking them and leading to treatment difficulties. The two cases reported here were both elderly women with refractory MAC lung disease, but they had different phenotypes: a fibrocavitary type and a long-standing, progressive nodular and bronchiectatic type. Treatment was performed with a regimen using Riposomal amikacin (ALIS), which is an aminoglycoside antibiotic that works by binding to bacterial Riposomes and inhibiting protein synthesis. Using amikacin Riposomal technology and a specialized inhaler, ALIS efficiently reaches alveolar macrophages, directly killing the MAC bacteria within. However, the unique administration method requires inhaler cleaning, making continued use difficult given the characteristics of patients with refractory MAC pulmonary disease. Even when treatment is possible, frequent side effects, such as hoarseness and dysphonia, while not severe, further contribute to the difficulty of initiating treatment. In both cases reported here, continued administration of rifampicin was difficult due to side effects such as liver damage and loss of appetite, and the patients’ conditions were also resistant to treatment, so ALIS was chosen, as it is thought to be more effective than other drugs and to have fewer systemic side effects. The patient had a limited understanding of how to clean the inhaler and how to inhale, making continued treatment difficult; therefore, we explained the efficacy and safety of ALIS to the patient’s family. Inhalation therapy is an effective method for delivering medication directly to the lungs, where the disease is located, while reducing systemic side effects. Until now, no inhalation therapy has existed for pulmonary MAC disease, and inhalation therapy itself is still a groundbreaking treatment administration method. This is the first case in the world where therapeutic efficacy has been confirmed with fewer than half the number of treatments required for standard treatment. Furthermore, as a new drug delivery method, inhalation offers a novel treatment option when existing medications are unavailable or ineffective for some reason, and it may be safe for use in elderly patients. Full article

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13 pages, 1145 KB

Open AccessFeature PaperArticle

Left Atrial Strain as a Marker of Supraventricular Arrhythmia Risk in Type 2 Diabetes Mellitus

by Laura-Cătălina Benchea, Larisa Anghel, Vasile Maciuc, Nicoleta Dubei, Răzvan-Liviu Zanfirescu, Gavril-Silviu Bîrgoan, Mircea Ovanez Balasanian, Radu Andy Sascău and Cristian Stătescu

Diseases 2026, 14(2), 64; https://doi.org/10.3390/diseases14020064 - 11 Feb 2026

Abstract

Background/Objectives: To determine whether left atrial (LA) strain by speckle-tracking echocardiography can identify supraventricular arrhythmia risk in patients with type 2 diabetes mellitus (T2DM) without overt structural heart disease. Methods: Prospective, single-center observational cohort study including 107 adults: 57 with T2DM and 50 [...] Read more.

Background/Objectives: To determine whether left atrial (LA) strain by speckle-tracking echocardiography can identify supraventricular arrhythmia risk in patients with type 2 diabetes mellitus (T2DM) without overt structural heart disease. Methods: Prospective, single-center observational cohort study including 107 adults: 57 with T2DM and 50 age-matched controls. Participants underwent clinical assessment and echocardiography at baseline and 12 months. LA reservoir, conduit, and contractile strain (LASr, LAScd, LASct) were measured; left atrial volume indexed (LAVI) and LA stiffness index (LASI) were calculated. The primary endpoint was clinically significant supraventricular arrhythmia at 12 months on 24 h Holter (atrial fibrillation (AF)/atrial flutter (AFL) ≥ 30 s and/or excessive supraventricular ectopy). Predictors were assessed using penalized logistic regression and discrimination by ROC analysis. Results: At baseline and 12 months, T2DM showed impaired LA mechanics versus controls (baseline: LASr 20.1 ± 5.7 vs. 25.8 ± 6.3%, LAScd −11.6 ± 4.2 vs. −15.6 ± 4.9%, LASct −9.9 ± 3.2 vs. −13.1 ± 3.7%; all p < 0.001) and higher LASI (0.4 ± 0.2 vs. 0.3 ± 0.1, p < 0.001). LAVI was higher in T2DM at 12 months (34.0 ± 7.0 vs. 29.9 ± 6.5 mL/m², p = 0.003). Supraventricular arrhythmias occurred in 20/57 patients (35.1%) of the T2DM vs. 1/50 patients (2.0%) of the control group (p < 0.001). Arrhythmias were assessed by 24 h Holter monitoring at the 12-month follow-up. In T2DM, LAScd provided the best single-parameter discrimination (AUC 0.692), with an optimal cut-off around −8% (sensitivity 55.6%, specificity 81.8%); a LAScd+left ventricular ejection fraction (LVEF) model improved AUC to 0.772. Conclusions: In this prospective observational cohort, T2DM was associated with subclinical LA dysfunction and a higher burden of supraventricular arrhythmias. LAScd emerged as the most clinically informative LA deformation marker for arrhythmic risk stratification and may support targeted rhythm surveillance in diabetic patients. These findings require external validation in larger, independent multicenter cohorts. Full article

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14 pages, 895 KB

Open AccessArticle

Occupational Stress and Altered Serum Leptin Among Female Workers in Southern Brazil

by Cláudia Lorenzi Caberlon, Janaína Cristina da Silva, Anderson Garcez, Harrison Canabarro de Arruda, Ingrid Stähler Kohl, Heloísa Marquardt Leite, Maria Teresa Anselmo Olinto and Heloísa Theodoro

Diseases 2026, 14(2), 63; https://doi.org/10.3390/diseases14020063 - 9 Feb 2026

Abstract

Background: Leptin is a peptide hormone produced by white adipose tissue and is essential for the regulation of appetite and energy homeostasis. Evidence suggests that leptin concentrations may vary according to emotional and psychosocial conditions, such as occupational stress, particularly in vulnerable populations, [...] Read more.

Background: Leptin is a peptide hormone produced by white adipose tissue and is essential for the regulation of appetite and energy homeostasis. Evidence suggests that leptin concentrations may vary according to emotional and psychosocial conditions, such as occupational stress, particularly in vulnerable populations, including female workers. Accordingly, this study aimed to examine the association between occupational stress and altered serum leptin levels among female workers. Methods: A cross-sectional design was applied to a sample of 302 female workers employed in plastic manufacturing plants in southern Brazil. Serum leptin concentrations were quantified, and values exceeding 15.2 ng/mL were considered elevated. Occupational stress was measured using the short version of the Job Stress Scale. Associations between occupational stress and elevated leptin levels were estimated using Poisson regression models with robust variance adjustment. Results: The mean age of the participants was 35.4 years (SD [standard deviation] = 10.1). Elevated serum leptin levels were observed in 78.1% of the sample (95% CI: 73.5–82.8), whereas 21.9% (95% CI: 17.2–26.5) were classified as experiencing occupational stress. After controlling for relevant confounding variables, including obesity, women experiencing occupational stress showed a 15% higher probability of elevated leptin levels compared with those without occupational stress (prevalence ratio [PR] = 1.15; 95% CI: 1.02–1.30; p = 0.022). Conclusions: Occupational stress was independently linked to increased serum leptin concentrations among female workers, suggesting that psychosocial stressors in the workplace may play a role in the disruption of leptin regulation in this population. Full article

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