Diseases

20 pages, 1225 KB

Open AccessSystematic Review

Efficacy of Phytotherapy for Cancer-Related Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

by Silvio Matsas, Ursula Medeiros Araujo de Matos, Carolina Molina Llata and Auro del Giglio

Diseases 2026, 14(2), 39; https://doi.org/10.3390/diseases14020039 - 26 Jan 2026

Abstract

Background: Cancer-related fatigue (CRF) is one of the most common and burdensome symptoms faced by patients with cancer, yet effective drug-based treatments remain limited. In recent years, phytotherapeutic agents have drawn attention as complementary options, supported by plausible anti-inflammatory, antioxidant, and immunomodulatory mechanisms. [...] Read more.

Background: Cancer-related fatigue (CRF) is one of the most common and burdensome symptoms faced by patients with cancer, yet effective drug-based treatments remain limited. In recent years, phytotherapeutic agents have drawn attention as complementary options, supported by plausible anti-inflammatory, antioxidant, and immunomodulatory mechanisms. Methods: We performed a systematic review and meta-analysis to quantitatively synthesize randomized controlled trial evidence on the efficacy of phytotherapeutic interventions for cancer-related fatigue and to assess the certainty of evidence. Databases were searched from inception, with the final search update completed in October 2025. Eligible studies included adults with CRF and compared herbal interventions with placebo controls. Standardized mean differences (SMDs) were pooled using a DerSimonian–Laird random-effects model. We also evaluated risk of bias (RoB 2), publication bias, and certainty of evidence using GRADE. This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines. Results: Fourteen trials were included, studying agents such as Paullinia cupana, Panax ginseng, multi-herbal Traditional Chinese Medicine formulations, and other botanical extracts. Overall, phytotherapy provided a modest improvement in CRF (SMD = 0.31; 95% CI, 0.08–0.53; p = 0.022), though heterogeneity was substantial (I² = 56.7%). In subgroup analyses, only the group of “other formulations” demonstrated significant benefit; ginseng and guaraná did not demonstrate statistically significant effects. Most trials had high or unclear risk of bias, and the certainty of evidence was rated very low. Conclusions: Current evidence does not firmly support phytotherapeutic agents as effective treatments for CRF, hindered largely by methodological weaknesses, heterogeneous interventions, and imprecise effect estimates. Even so, the biological rationale and the variability in clinical responses point toward an opportunity for the emerging field of precision herbal oncology. Well-designed, multicenter trials are essential to determine whether phytotherapy can meaningfully contribute to CRF management. Full article

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27 pages, 2857 KB

Open AccessArticle

Comparative Analysis of Oral Microbiome in Indian Type 2 Diabetes Mellitus (T2DM) and Periodontitis Cohorts

by Meenakshi Murmu, Rajshri Singh, Rajesh Gaikwad, Akshaya Banodkar, Sagar Barage, Preethi Sudhakara and Aruni Wilson Santhosh Kumar

Diseases 2026, 14(2), 38; https://doi.org/10.3390/diseases14020038 - 23 Jan 2026

Abstract

Background: Type 2 diabetes mellitus (T2DM) and periodontitis are highly prevalent immune-inflammatory diseases that interact bidirectionally. However, how early-onset T2DM, periodontitis, and adverse lifestyle behaviors collectively remodel the gingival plaque microbiome at the ecological network level remains poorly understood in Indian populations. Methods: [...] Read more.

Background: Type 2 diabetes mellitus (T2DM) and periodontitis are highly prevalent immune-inflammatory diseases that interact bidirectionally. However, how early-onset T2DM, periodontitis, and adverse lifestyle behaviors collectively remodel the gingival plaque microbiome at the ecological network level remains poorly understood in Indian populations. Methods: A cross-sectional 16S rRNA gene (V3–V4) sequencing study was conducted on supragingival and subgingival plaque from 60 adults (30–40 years) recruited in Mumbai. Participants were categorized as healthy (H, n = 10), periodontitis (P, n = 10), T2DM (n = 20), and T2DM with periodontitis (T2DM_P, n = 20). Comprehensive demographic, anthropometric, metabolic, periodontal, dietary, lifestyle, and oral hygiene data were collected. Sequence data were processed using QIIME2–DADA2, followed by diversity, differential abundance, and genus-level co-occurrence network analyses (Spearman |r| ≥ 0.6, FDR < 0.05; core prevalence ≥ 70%). Results: α-diversity showed no marked depletion across groups, whereas Bray–Curtis β-diversity revealed significant global separation, with maximal dissimilarity between H and T2DM_P. Healthy individuals with favorable lifestyle behaviors harbored scaffold-forming taxa such as Corynebacterium matruchotii, Lautropia mirabilis, and Capnocytophaga spp. In contrast, P and T2DM_P groups showed enrichment of proteolytic, inflammation-adapted genera including Porphyromonas, Tannerella, Treponema, Fretibacterium, Peptostreptococcus, and Selenomonas. Network analysis revealed a shift from commensal-rich modular networks to densely connected, keystone-centered disease modules. Conclusion: Early-onset T2DM and periodontitis, particularly under adverse lifestyle behaviors, reorganize plaque microbial composition and interaction architecture rather than depleting diversity, highlighting plaque-based keystone taxa and networks as targets for microbiome-informed risk stratification and integrated medical–dental–lifestyle interventions. Full article

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17 pages, 1440 KB

Open AccessArticle

Safety and Effectiveness of Subcutaneous Immunotherapy with a Glutaraldehyde-Polymerized Mite Allergen Extract in Adults and Children with Allergic Rhinitis with or Without Asthma Due to Dermatophagoides

by Olalla Verdeguer Segarra, Zulay Almeida Sánchez, Silvia Quarta, Emilio Funes Vera, Oscar M. Gonzalez Jiménez, Guacimara Hernández Santana, Leticia Herrero Lifona, Paula López-González, Montserrat Martinez-Gomariz, Beatriz López-Cauce and Aída Gómez-Cardenosa

Diseases 2026, 14(2), 37; https://doi.org/10.3390/diseases14020037 - 23 Jan 2026

Abstract

Background/Objectives: The aim of this study was to evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) in allergic adults and children treated with a polymerized-glutaraldehyde undiluted mixture of house dust mites (HDMs) under routine clinical practice. Methods: This was an observational, ambispective, [...] Read more.

Background/Objectives: The aim of this study was to evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) in allergic adults and children treated with a polymerized-glutaraldehyde undiluted mixture of house dust mites (HDMs) under routine clinical practice. Methods: This was an observational, ambispective, controlled, real-world, multicenter study including patients ≥ 5 years with allergic rhinitis (AR), due to Dermatophagoides sensitization. Patients who started AIT with a D. pteronyssinus/D. farinae extract and those who continued symptomatic treatment were included in the treatment (DP&DF) and untreated (UT) groups, respectively. We evaluated adverse reactions (ARs) and changes in effectiveness variables through changes in symptoms, disease control, medication use, and patient- and investigator-reported outcomes. Results: We included 130 patients in the DP&DF group, and 90 (69.2%) adults, 23 adolescents (17.7%), 17 (13.1%) children, and 94 patients in the UT group. Patients received treatment for a mean (SD) of 9.01 (3.1) months at the time of evaluation. Seven (5.4%) patients, all adults, reported eight ARs, five local and three systemic (mean rate of 0.62 ARs per 100 injections); all recovered, and epinephrine was not required. The proportion of patients reporting no rhinitis symptoms at follow-up significantly increased (+13.6%; p < 0.001). Rhinitis frequency, intensity, and control significantly improved overall and in specific age groups. Similarly, the proportion of patients reporting no asthma symptoms at follow-up significantly increased (+29.0%; p < 0.001). The use of all symptomatic medications significantly decreased, while the UT group showed no significant changes, except for worsened asthma classification and control in specific age groups. Both investigators and patients perceived a marked improvement in symptoms and medication use, with high satisfaction scores reported on the visual analogue scale. Conclusions: A subcutaneous allergen extract with a mixture of HDMs is safe and effective for allergic rhinitis and asthma in adults and children in the real-world setting. Full article

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11 pages, 953 KB

Open AccessArticle

Early Post-Transplant Protein Biomarkers for Risk Stratification of Renal Allograft Dysfunction: Diagnostic Value and Clinical Chemistry Perspectives

by Andreea-Liana Bot (Rachisan), Paul Luchian Aldea, Bogdan Bulata, Dan Delean, Florin Elec and Mihaela Sparchez

Diseases 2026, 14(1), 36; https://doi.org/10.3390/diseases14010036 - 21 Jan 2026

Abstract

Background: Early recognition of renal allograft dysfunction requires biochemical markers capable of detecting molecular injury before functional decline becomes apparent. Serum creatinine, a late and nonspecific indicator of renal function, has limited value for early diagnosis. Protein biomarkers implicated in tubular injury, inflammation, [...] Read more.

Background: Early recognition of renal allograft dysfunction requires biochemical markers capable of detecting molecular injury before functional decline becomes apparent. Serum creatinine, a late and nonspecific indicator of renal function, has limited value for early diagnosis. Protein biomarkers implicated in tubular injury, inflammation, and immune activation—including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), β2-microglobulin, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—have emerged as promising alternatives. This study evaluated early post-transplant serum profiles of these biomarkers and their prognostic relevance for long-term graft outcomes. Methods: Nineteen adult recipients undergoing primary kidney transplantation were prospectively enrolled. Serum creatinine and protein biomarkers were measured 24 h post-transplant using validated immunochemical assays. Biomarker concentrations were compared with values from healthy controls, and correlations with renal function at 12 months were assessed. Receiver operating characteristic (ROC) analysis was used to evaluate predictive performance. Results: Significant biochemical alterations were observed at 24 h post-transplant. KIM-1 levels were markedly elevated compared with controls (74.50 ± 98.45 vs. 10.54 ± 17.19 ng/mL; p = 0.01), consistent with early tubular injury. IL-1β and NGAL showed upward trends without reaching statistical significance. β2-microglobulin and TNF-α levels did not differ substantially from control values. Serum KIM-1 correlated with serum creatinine both at 24 h (r = 0.35) and at 12 months (r = 0.40). ROC analysis identified a KIM-1 threshold of 24.5 ng/mL (AUC = 0.68) as a potential indicator of future graft dysfunction, outperforming serum creatinine (AUC = 0.64). Six patients experienced graft dysfunction at 12 months post-transplant, five of whom had serum creatinine values > 5 mg/dL at 24 h. Based on early creatinine levels, patients were stratified into low-risk (creatinine < 5 mg/dL; n = 10) and high-risk groups (creatinine > 5 mg/dL; n = 9). Mean KIM-1 concentrations were significantly higher in the high-risk group (110.68 ± 115.29 vs. 26.67 ± 18.05 ng/mL; p = 0.05), consistent with more severe early tubular injury. Conclusions: Among the evaluated biomarkers, KIM-1 demonstrated the strongest potential as an early biochemical indicator of renal allograft dysfunction. Its rapid post-transplant elevation underscores its sensitivity to early tubular injury. Further prospective validation in larger, multicenter cohorts is warranted. Full article

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15 pages, 621 KB

Open AccessArticle

Impact of Chronic Kidney Disease on Clinical, Laboratory, and Echocardiographic Features in Patients with Chronic Heart Failure

by Anastasija Ilić, Olivera Kovačević, Aleksandra Milovančev, Nikola Mladenović, Dragica Andrić, Dragana Dabović, Milana Jaraković, Srdjan Maletin, Teodora Pantić, Branislav Crnomarković, Mihaela Preveden, Ranko Zdravković, Anastazija Stojšić Milosavljević, Aleksandra Ilić, Lazar Velicki and Andrej Preveden

Diseases 2026, 14(1), 35; https://doi.org/10.3390/diseases14010035 - 20 Jan 2026

Abstract

Objective: The aim of this study was to evaluate the impact of chronic kidney disease (CKD) on clinical presentation, laboratory parameters, ECG, and echocardiographic features of patients with chronic heart failure (CHF). Methods: This retrospective cross-sectional study included 2227 patients hospitalized in a [...] Read more.

Objective: The aim of this study was to evaluate the impact of chronic kidney disease (CKD) on clinical presentation, laboratory parameters, ECG, and echocardiographic features of patients with chronic heart failure (CHF). Methods: This retrospective cross-sectional study included 2227 patients hospitalized in a tertiary care center due to CHF. Patients were divided into two groups based on the presence of CKD, defined as eGFR < 60 mL/min/1.73 m². Demographic, clinical, laboratory, and echocardiographic data were collected for all patients. Comparative analyses were performed to assess differences in cardiovascular risk factors, comorbidities, laboratory parameters, and echocardiographic findings between the two groups. Results: The proportion of men was significantly higher in the non-CKD group, whereas women predominated in the CKD group (p < 0.001). Dyspnea, orthopnea, leg swelling, claudication, and expectoration were significantly more frequent in patients with CKD, while chest pain and palpitations were more common in the non-CKD group (all p < 0.05). A significant difference in the distribution of NYHA functional classes was observed between the groups (p < 0.001), with NYHA class IV being more prevalent in the CKD group and classes II and III more frequent in the non-CKD group. Levels of CRP and NT-proBNP were significantly higher in the CKD group (p < 0.001). In-hospital mortality was 2.5-fold higher in patients with CKD (28.6% vs. 11.1%; p < 0.001). Conclusions: Coexistence of CKD was associated with a more severe clinical presentation, advanced functional limitation, and a distinct laboratory and echocardiographic profile in CHF patients. Full article

(This article belongs to the Special Issue Insights into the Management of Cardiovascular Disease Risk Factors)

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15 pages, 1147 KB

Open AccessSystematic Review

A Systematic Review and Meta-Analysis on the Effectiveness and Safety of Tranexamic Acid for Postpartum Haemorrhage in Patients with Haemorrhagic Disorders

by Victor Abiola Adepoju, Abdulrakib Abdulrahim, Bukola Olanrewaju Olaniyi, Qorinah Estiningtyas Sakilah Adnani and Shankar Biswas

Diseases 2026, 14(1), 34; https://doi.org/10.3390/diseases14010034 - 19 Jan 2026

Abstract

Background: Postpartum haemorrhage (PPH) remains the leading cause of maternal mortality globally. Women with inherited or unexplained bleeding disorders such as von Willebrand disease (VWD), factor XI deficiency (FXI), platelet function disorders, or bleeding disorder of unknown cause (BDUC) face a higher risk. [...] Read more.

Background: Postpartum haemorrhage (PPH) remains the leading cause of maternal mortality globally. Women with inherited or unexplained bleeding disorders such as von Willebrand disease (VWD), factor XI deficiency (FXI), platelet function disorders, or bleeding disorder of unknown cause (BDUC) face a higher risk. While tranexamic acid (TXA) is routinely used in obstetric care, its specific efficacy and safety in these populations remain unclear. Methods: A systematic review and meta-analysis followed PRISMA 2020 guidelines (PROSPERO: CRD420251082349). Databases searched included PubMed, Scopus, Web of Science, and Dimensions. Studies evaluating TXA for PPH prevention or treatment in women with bleeding disorders were included. Six cohort studies (2016–2024) involving 213 deliveries met the criteria. Three contributed to a meta-analysis on primary PPH; the other three were synthesised narratively. Results: TXA use was associated with a 56% reduction in primary PPH risk (risk ratio 0.44; 95% CI: 0.27–0.70; p = 0.0007), with no observed heterogeneity (I² = 0%). Because contributing cohorts were phenotypically heterogeneous (BDUC, FXI, mixed), the pooled effect reflects an average across disorders rather than disorder-specific efficacy. TXA also appeared to reduce secondary and severe PPH in some cohorts. However, bleeding occurred in 26–36% of high-risk deliveries despite prophylaxis. No maternal deaths or thromboembolic events were reported in 136 TXA-exposed cases. Attribution was complicated by concurrent use of desmopressin and platelet transfusions. Most studies had moderate to severe bias. Conclusions: TXA significantly lowers the risk of primary PPH in women with bleeding disorders and appears safe. Despite this, residual bleeding underscores the need for trials to optimise TXA use alongside disease-specific strategies. However, this conclusion is derived from only six observational studies with heterogeneous patient populations and co-interventions. The evidence remains preliminary and should be interpreted cautiously. TXA should be considered as part of a multimodal postpartum haemorrhage management algorithm rather than a stand-alone therapy. Full article

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15 pages, 1887 KB

Open AccessArticle

Annurca Apple Extract and Colorectal Cancer Prevention: Preliminary In Silico Evaluation of Chlorogenic Acid

by Ludovico Abenavoli, Giuseppe Guido Maria Scarlata, Maria Luisa Gambardella, Domenico Morano, Nataša Milošević, Maja Milanović and Nataša Milić

Diseases 2026, 14(1), 33; https://doi.org/10.3390/diseases14010033 - 14 Jan 2026

Abstract

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. Despite therapeutic advances, prevention through dietary bioactives remains a promising strategy. The Annurca apple (Malus pumila Miller cv. Annurca), a Mediterranean food rich in chlorogenic acid, exhibits antioxidant [...] Read more.

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. Despite therapeutic advances, prevention through dietary bioactives remains a promising strategy. The Annurca apple (Malus pumila Miller cv. Annurca), a Mediterranean food rich in chlorogenic acid, exhibits antioxidant and anti-inflammatory effects. This study evaluated, via molecular docking, the multi-target interaction profile of chlorogenic acid against key CRC-related proteins. Methods: The optimized 3D structure of chlorogenic acid was docked to ten protein targets implicated in CRC pathogenesis, using the GOLD v.2022.3.0 software. Validation of the docking protocol was achieved by re-docking native ligands (RMSD ≤ 2.0 Å). Binding affinities were assessed by ChemPLP scoring, and interaction networks were visualized in Maestro Schrödinger. Results: Chlorogenic acid displayed consistent binding across all evaluated targets (ChemPLP 57.12–69.66), showing the highest affinity for nAChR (69.66), CXCR2 (65.13), ERβ (63.18) and TGFBR2 (62.94). The ligand formed multiple hydrogen bonds and π-π stacking interactions involving Asp1040 (VEGFR-1), Cys919 (VEGFR-2), Lys320 (CXCR2), and Tyr195 residues (nAChR), contributing to strong complex stabilization. Interaction patterns in CYP19A1, ERβ, and ERRγ suggested potential modulation of hormonal and metabolic signaling. The compound also demonstrated stable binding to mTOR (60.01), indicating a possible inhibitory role in proliferative pathways. Collectively, these findings reveal a broad, polypharmacological binding profile involving angiogenic, inflammatory, and hormonal regulators. Conclusions: Chlorogenic acid acts as a promising multi-target ligand in CRC prevention, with our in silico evidence supporting its ability to modulate diverse oncogenic pathways. Further experimental studies are warranted to confirm its efficacy and translational potential. Full article

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21 pages, 5439 KB

Open AccessArticle

Multi-Task Deep Learning Model for Automated Detection and Severity Grading of Lumbar Spinal Stenosis on MRI: Multi-Center External Validation

by Phatcharapon Udomluck, Watcharaporn Cholamjiak, Jakkaphong Inpun and Waragunt Waratamrongpatai

Diseases 2026, 14(1), 32; https://doi.org/10.3390/diseases14010032 - 14 Jan 2026

Abstract

Background/Objectives: Accurate and reproducible grading of lumbar spinal stenosis (LSS) is clinically critical for guiding treatment decisions and patient management, yet manual assessment remains challenging due to imaging variability and inter-observer subjectivity. To address these limitations, this study aimed to evaluate the [...] Read more.

Background/Objectives: Accurate and reproducible grading of lumbar spinal stenosis (LSS) is clinically critical for guiding treatment decisions and patient management, yet manual assessment remains challenging due to imaging variability and inter-observer subjectivity. To address these limitations, this study aimed to evaluate the generalizability of deep learning–based feature extraction methods—VGG19, ConvNeXt-Tiny, and DINOv2—combined with classical machine learning classifiers for automated multi-grade LSS assessment. Automated grading enables objective, reproducible, and scalable assessment of lumbar spinal stenosis severity, addressing key limitations of manual interpretation. Methods: Axial MRI images were processed using pretrained VGG19, ConvNeXt-Tiny, and DINOv2 models to extract deep features. Logistic Regression, Support Vector Machine (SVM), and LightGBM were trained on internal datasets and externally validated using MRI data from the University of Phayao Hospital. Performance was assessed using accuracy, precision, recall, F1-score, confusion matrices, and multi-class ROC curves. Results: VGG19-based features yielded the strongest external performance, with Logistic Regression achieving the highest accuracy (0.9556) and F1-score (0.9558). External validation further demonstrated excellent discrimination, with AUC values ranging from 0.994 to 1.000 across all severity grades. SVM (0.9333 accuracy) and LightGBM (0.9222 accuracy) also performed well. ConvNeXt-Tiny showed stable cross-model performance, while DINOv2 features exhibited reduced generalizability, especially with LightGBM (accuracy 0.6222). Most classification errors occurred between adjacent grades. Conclusions: Deep convolutional features—particularly VGG19—combined with classical machine learning classifiers provide robust and generalizable LSS grading across external MRI data. Despite advances in modern architectures, CNN-based feature extraction remains highly effective for spinal imaging and represents a practical pathway for clinical decision support. Full article

(This article belongs to the Special Issue Frailty and Frequent Hospitalizations in Older Adults: Risk, Management, and Interventions)

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28 pages, 833 KB

Open AccessReview

An Integrative Review of the Cardiovascular Disease Spectrum: Integrating Multi-Omics and Artificial Intelligence for Precision Cardiology

by Gabriela-Florentina Țapoș, Ioan-Alexandru Cîmpeanu, Iasmina-Alexandra Predescu, Sergio Liga, Andra Tiberia Păcurar, Daliborca Vlad, Casiana Boru, Silvia Luca, Simina Crișan, Cristina Văcărescu and Constantin Tudor Luca

Diseases 2026, 14(1), 31; https://doi.org/10.3390/diseases14010031 - 13 Jan 2026

Abstract

Background/Objectives: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide and increasingly are recognized as a continuum of interconnected conditions rather than isolated entities. Methods: A structured narrative literature search was performed in PubMed, Scopus, and Google Scholar for publications [...] Read more.

Background/Objectives: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide and increasingly are recognized as a continuum of interconnected conditions rather than isolated entities. Methods: A structured narrative literature search was performed in PubMed, Scopus, and Google Scholar for publications from 2015 to 2025 using combinations of different keywords: “cardiovascular disease spectrum”, “multi-omics”, “precision cardiology”, “machine learning”, and “artificial intelligence in cardiology”. Results: Evidence was synthesized across seven major clusters of cardiovascular conditions, and across these domains, common biological pathways were mapped onto heterogeneous clinical phenotypes, and we summarize how multi-omics integration, AI-enabled imaging and digital tools contribute to improved risk prediction and more informed clinical decision-making within this spectrum. Conclusions: Interpreting cardiovascular conditions as components of a shared disease spectrum clarifies cross-disease interactions and supports a shift from organ- and syndrome-based classifications toward mechanism- and data-driven precision cardiology. The convergence of multi-omics, and AI offers substantial opportunities for earlier detection, individualized prevention, and tailored therapy, but requires careful attention to data quality, equity, interpretability, and practical implementation in routine care. Full article

(This article belongs to the Section Cardiology)

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15 pages, 609 KB

Open AccessReview

Inclisiran in Dyslipidemia with High Residual Platelet Reactivity

by Dina Kapsultanova, Sholpan Zhangelova, Friba Nurmukhammad, Zulfiya Makasheva, Orazbek Sakhov, Tamara Galkina, Farida Rustamova, Dana Akhmentayeva and Botakoz Aubakirova

Diseases 2026, 14(1), 30; https://doi.org/10.3390/diseases14010030 - 12 Jan 2026

Abstract

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets [...] Read more.

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets or exhibit inadequate platelet inhibition. Inclisiran, a PCSK9-targeting small interfering RNA, represents an emerging approach for long-term LDL-C reduction. Methods: A narrative review of the literature published between 2009 and 2025 was performed using PubMed, Scopus, Web of Science, and MEDLINE. Studies evaluating the addition of inclisiran to standard lipid-lowering therapy in patients with dyslipidemia and HRPR, assessed using the VerifyNow assay, were included. Illustrative clinical cases from Kazakhstan were analyzed to demonstrate real-world changes in LDL-C levels and platelet reactivity following insufficient response to conventional treatment. The review had a descriptive design. Results: Available evidence indicates that a significant proportion of high- and very-high-risk patients do not achieve LDL-C targets or are unable to tolerate high-intensity statin therapy. Inclisiran consistently induces sustained reductions in LDL-C and circulating PCSK9 levels. Emerging data suggest a potential indirect modulation of platelet reactivity associated with intensive lipid lowering. In patients at extreme cardiovascular risk—including those after coronary artery bypass grafting (CABG) and with long-standing multivessel coronary artery disease—inclisiran therapy was associated with marked LDL-C reduction and a trend toward normalization of platelet reactivity. Conclusions: Assessment of platelet function using the VerifyNow assay may improve identification of residual thrombotic risk in patients with advanced atherosclerotic disease. Inclisiran appears to be a promising adjunctive therapy for dyslipidemic patients with persistently elevated cardiovascular risk and HRPR despite standard treatment. Further prospective studies are warranted to clarify the relationship between intensive LDL-C lowering, platelet reactivity, and clinical outcomes, and to optimize integrated lipid-lowering and antiplatelet strategies. Full article

(This article belongs to the Special Issue Feature Papers in Section 'Cardiology' in 2024–2025)

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17 pages, 696 KB

Open AccessArticle

Real-World Evidence Evaluation of Respiratory Syncytial Virus (RSV) Vaccines: Deep Dive into Vaccine Adverse Events Reporting System

by Thamir M. Alshammari, Mohammed K. Alshammari and Hind M. Alosaimi

Diseases 2026, 14(1), 29; https://doi.org/10.3390/diseases14010029 - 9 Jan 2026

Abstract

Background: Respiratory Syncytial Virus is a predominant source of morbidity and mortality, particularly among babies, the elderly, and immunocompromised patients. Recent developments in RSV vaccines, approved by the FDA for high-risk groups, have highlighted the necessity for post-marketing surveillance to evaluate their [...] Read more.

Background: Respiratory Syncytial Virus is a predominant source of morbidity and mortality, particularly among babies, the elderly, and immunocompromised patients. Recent developments in RSV vaccines, approved by the FDA for high-risk groups, have highlighted the necessity for post-marketing surveillance to evaluate their real-world safety and efficacy. Method: This study utilized data from the Vaccine Adverse Event Reporting System (VAERS) covering RSV vaccine administration between 2023 and May 2025. The VAERS database reported data on vaccine types, including Arexvy^®, Abrysvo^®, and mRESVIA^® was analyzed for adverse events and vaccination errors. The demographic information, vaccination trends, and hospitalizations post-vaccination among the vaccinated individuals were accessed. Results: The analysis revealed that the most common adverse events were mild, such as injection site pain, erythema, fatigue, and extremity pain. The data also showed a gradual increase in hospitalization rates from 4.8% in 2023 to 7.5% in 2025. Vaccination errors, including inappropriate administration during pregnancy and excess doses, were also observed. A notable trend was the growing proportion of patients who experienced no adverse events, with the highest rate of symptom-free reports seen in 2025 (25.9%). Conclusions: RSV vaccines demonstrate a generally acceptable safety profile based on post-marketing surveillance data. However, the observed increase in hospitalization rates, vaccination errors, and pregnancy-related outcomes warrants continued active surveillance and cautious interpretation. Full article

(This article belongs to the Section Respiratory Diseases)

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12 pages, 816 KB

Open AccessSystematic Review

Can DPP-4 Inhibitors Improve Glycemic Control and Preserve Beta-Cell Function in Type 1 Diabetes Mellitus? A Systematic Review

by Henrique Villa Chagas, Lucas Fornari Laurindo, Victória Dogani Rodrigues, Jesselina Francisco dos Santos Haber, Eduardo Federighi Baisi Chagas and Sandra Maria Barbalho

Diseases 2026, 14(1), 28; https://doi.org/10.3390/diseases14010028 - 9 Jan 2026

Abstract

Background/Objectives: The objective was to analyze the effects of Dipeptidyl Peptidase-4 (DPP-4) inhibitors on glycemic control, insulin dose, and preservation of β-pancreatic function (C-peptide) in patients with type 1 diabetes mellitus (T1DM). Methods: A systematic review was performed following the Preferred [...] Read more.

Background/Objectives: The objective was to analyze the effects of Dipeptidyl Peptidase-4 (DPP-4) inhibitors on glycemic control, insulin dose, and preservation of β-pancreatic function (C-peptide) in patients with type 1 diabetes mellitus (T1DM). Methods: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with a search in the PubMed database. Five randomized clinical trials evaluating the use of different DPP-4 inhibitors in patients with T1DM were selected, measuring parameters including glycated hemoglobin (HbA1c), C-peptide, time in glycemic target/range (TIR), and daily insulin dose. Results: HbA1c showed significant reduction in some studies and no significant alterations in others. TIR increased in one study (~77.87% → ~84.40%). C-peptide showed variable effects across studies. The insulin dose did not show a substantial reduction. Conclusions: DPP-4 inhibitors demonstrated modest benefits for glycemic control and preservation of β-cell function in T1DM, but these effects were inconsistent due to methodological heterogeneity. Standardized studies are needed to define beneficial subgroups and long-term efficacy. 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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11 pages, 1729 KB

Open AccessCase Report

Intradermal Application of Allogenic Wharton’s Jelly Mesenchymal Stem Cells for Chronic Post-Thoracotomy Wound in an Elderly Patient After Coronary Artery Bypass Grafting: Clinical Case with Brief Literature Review

by Anastassiya Ganina, Abay Baigenzhin, Elmira Chuvakova, Naizabek Yerzhigit, Anuar Zhunussov, Aizhan Akhayeva, Larissa Kozina, Oleg Lookin and Manarbek Askarov

Diseases 2026, 14(1), 27; https://doi.org/10.3390/diseases14010027 - 8 Jan 2026

Abstract

Background: Chronically non-healing thoracic wounds after cardiac and non-cardiac thoracotomy, including cases when coronary artery bypass grafting (CABG) is performed, represent a great clinical challenge. It is often that a conservative treatment of the wounds does not provide effective regeneration of the damaged [...] Read more.

Background: Chronically non-healing thoracic wounds after cardiac and non-cardiac thoracotomy, including cases when coronary artery bypass grafting (CABG) is performed, represent a great clinical challenge. It is often that a conservative treatment of the wounds does not provide effective regeneration of the damaged tissues. It is especially critical in patients with infected wounds, in patients owning a systemic infection, and in elderly people. Methods: The article presents a case report of successful treatment of a 63-year-old man with refractory chronic osteomyelitis of the sternum and mediastinitis four years after CABG, complicated by COVID-19 at the time of reconstructive surgery. Due to the low effectiveness of conservative treatment methods, a two-stage approach was applied: radical surgical wound debridement followed by infiltration of the wound with allogenic mesenchymal stromal cells (MSCs) of Wharton’s jelly (WJ-MSCs). Results: This double-stage therapy successfully modulated the inflammatory environment and stimulated granulation, facilitating final thoracoplasty and osteosynthesis. The patient achieved complete healing of the sternum, demonstrating benefits of WJ-MSCs in treating conservative treatment-resistant infections in the surgical wound. Conclusions: The advantages of using perinatal mesenchymal stem cells, with WJ-MSCs as a type of this class of MSCs, were demonstrated in treating chronically infected sternal surgical wounds. We also compared their regenerative properties to other stem cell types like bone marrow MSCs. Full article

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21 pages, 1561 KB

Open AccessArticle

Predictors of Severe Herpes Zoster: Contributions of Immunosenescence, Metabolic Risk, and Lifestyle Behaviors

by Mariana Lupoae, Fănică Bălănescu, Caterina Nela Dumitru, Aurel Nechita, Mădălina Nicoleta Matei, Simona Claudia Ștefan, Alin Laurențiu Tatu, Elena Niculet, Alina Oana Dumitru, Andreea Lupoae and Dana Tutunaru

Diseases 2026, 14(1), 26; https://doi.org/10.3390/diseases14010026 - 8 Jan 2026

Abstract

Background: Herpes zoster (HZ) represents a substantial public health concern among aging populations, yet regional variability in clinical patterns and risk determinants remains insufficiently documented. In southeastern Romania, epidemiological data are limited, and the combined influence of demographic, behavioral, and metabolic factors on [...] Read more.

Background: Herpes zoster (HZ) represents a substantial public health concern among aging populations, yet regional variability in clinical patterns and risk determinants remains insufficiently documented. In southeastern Romania, epidemiological data are limited, and the combined influence of demographic, behavioral, and metabolic factors on disease severity has not been systematically evaluated. Methods: We performed a retrospective observational study including 100 consecutive patients diagnosed with HZ between 2019 and 2023 in a dermatology department in southeastern Romania. Demographic characteristics, lifestyle behaviors, anthropometric status, clinical manifestations, and outcomes were extracted from medical records. Associations between categorical variables were assessed using Chi-square tests and Cramer’s V, while interaction patterns were explored through log-linear modeling. Heatmaps were generated in Python (version 3.10) using the Matplotlib library (version 3.7.1) to visualize distribution patterns and subgroup relationships. Results: The cohort showed a marked age dependence, with 77% of cases occurring in individuals ≥ 60 years, consistent with immunosenescence-driven reactivation. Women represented 59% of cases, and 84.7% of female patients were postmenopausal. Urban residents predominated (91%). Vesicular eruption (84%) and acute pain (79%) were the most frequent symptoms. Localized HZ was observed in 81% of cases, while ophthalmic involvement (11%) and disseminated forms (8%) were less common. Lifestyle factors significantly influenced clinical severity: smokers, alcohol consumers, and sedentary individuals exhibited higher proportions of postherpetic neuralgia (PHN) and ocular complications (p < 0.001). Overweight and obese patients demonstrated a higher burden of PHN, suggesting a role for metabolic inflammation, although BMI was not associated with incidence. No significant association between age category and complication type was detected, likely due to small subgroup sizes despite a clear descriptive trend toward increased severity with advanced age. Conclusions: These findings support a multifactorial model of HZ severity in southeastern Romania, shaped by age, lifestyle behaviors, hormonal status, and metabolic risk. While incidence patterns align with international data, the strong impact of modifiable factors on complication rates highlights the need for targeted prevention and individualized risk assessment. Results offer a regional perspective that may inform future multicenter investigations. Full article

(This article belongs to the Section Infectious Disease)

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14 pages, 1733 KB

Open AccessArticle

Increasing Numbers of Persons with Sleeping Problems in Sweden

by Mona Nilsson and Lennart Hardell

Diseases 2026, 14(1), 25; https://doi.org/10.3390/diseases14010025 - 8 Jan 2026

Abstract

Objectives: This study investigated sleeping problems in the Swedish population based on the Swedish National Board of Health and Welfare’s national patient register on numbers of patients in specialized outpatient care diagnosed with codes for sleeping problems. Methods: Numbers of patients per year [...] Read more.

Objectives: This study investigated sleeping problems in the Swedish population based on the Swedish National Board of Health and Welfare’s national patient register on numbers of patients in specialized outpatient care diagnosed with codes for sleeping problems. Methods: Numbers of patients per year and per 100,000 inhabitants in various age groups: 0–4, 5–19, 20–39, 40–59, and 60+ years diagnosed each year between 2001 and 2024 with the ICD codes G47 (sleep disorders) or F51 (non-organic sleep disorders) as main diagnosis were assessed. Results: The highest increase for sleep disorders was seen among children, adolescents, and young adults. All results are given per 100,000 persons. In the age group 0–4 years, the numbers of sleep disorders (G47) increased from 41.5 in 2001 to 215.8 in 2024. The corresponding results in the age group 5–19 years were 13.8 and 235.6, respectively. In the age group 20–39 years, 40.4 were diagnosed in 2001 and 220.9 in 2024. For subjects aged 40–59 years, 169.5 were diagnosed in 2001 and 362.8 in 2024, and for persons aged 60+ years, 116.4 were diagnosed in 2001 and 322.9 in 2024. No major changes in the numbers of persons with F51, non-organic sleep disorders, were observed. Conclusions: Sleeping problems can be caused by several factors; however, the rapid increase in recent years has temporally coincided with an increase in the public’s exposure to microwave radiofrequency (RF) radiation and increasing use of screens. RF radiation and use of screens may negatively impact sleep. Full article

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18 pages, 1786 KB

Open AccessSystematic Review

Comparative Evaluation of the Prognostic Accuracy of IL-6 and Angiopoietin-2 for Early Severity Assessment in Acute Pancreatitis: A Systematic Review

by Kairat Shakeev, Dmitriy Klyuyev, Alina Ogizbayeva, Aigul Baltabayeva, Olga Avdienko and Xenia Derevyashkina

Diseases 2026, 14(1), 24; https://doi.org/10.3390/diseases14010024 - 7 Jan 2026

Abstract

Background: Early identification of patients at risk for severe acute pancreatitis (SAP) remains a major clinical challenge. Circulating biomarkers reflecting systemic inflammation (IL-6) and endothelial dysfunction (Ang-2) have emerged as promising tools for improving early prediction of persistent organ failure and other adverse [...] Read more.

Background: Early identification of patients at risk for severe acute pancreatitis (SAP) remains a major clinical challenge. Circulating biomarkers reflecting systemic inflammation (IL-6) and endothelial dysfunction (Ang-2) have emerged as promising tools for improving early prediction of persistent organ failure and other adverse outcomes. Objective: To systematically synthesize and compare the diagnostic and prognostic performance of IL-6 and Ang-2 as early biomarkers of severity in adult patients with acute pancreatitis. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251177279). PubMed, Scopus, and Web of Science were searched for studies published between 2000 and August 2025. Studies included adult patients (≥18 years) in whom IL-6 and/or Ang-2 levels were measured within 72 h of symptom onset or hospital admission, and where indices of diagnostic accuracy (AUC, sensitivity, specificity, or threshold values) were reported. Results: Fifteen cohort studies met the inclusion criteria. IL-6 demonstrated a consistent association with SAP and persistent organ failure, with AUC values ranging from 0.69 to 0.99; the highest accuracy was observed within the first 24 h. Specificity varied substantially across studies. Ang-2 showed uniformly high prognostic accuracy (AUC 0.79–0.98), reliably predicting persistent organ failure, multiorgan dysfunction, infected necrosis, and mortality. Conclusions: IL-6 exhibits high but heterogeneous diagnostic performance (AUC 0.69–0.99), whereas Ang-2 demonstrates consistently high accuracy (AUC 0.79–0.98) across study designs. Combined evaluation of inflammatory and endothelial pathways appears to offer the most robust strategy for early prediction of persistent organ failure in acute pancreatitis. Full article

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15 pages, 2675 KB

Open AccessReview

Incidental Cardiac Uptake on ^99mTc-HMDP Bone Scintigraphy in Oncology Patients: Two Cases of Transthyretin Amyloid Cardiomyopathy with Literature Review

by Naoya Matsuki, Toru Awaya, Jin Endo, Taeko Kunimasa, Tatsuya Gomi, Yasushi Okamoto and Hidehiko Hara

Diseases 2026, 14(1), 23; https://doi.org/10.3390/diseases14010023 - 7 Jan 2026

Abstract

Background: Bone scintigraphy using technetium-99m hydroxymethylene diphosphonate (^99mTc-HMDP) is extensively employed to detect bone metastases. However, incidental myocardial uptake may indicate wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), a frequently overlooked diagnosis with important clinical implications. Case Presentation: Two elderly female patients with [...] Read more.

Background: Bone scintigraphy using technetium-99m hydroxymethylene diphosphonate (^99mTc-HMDP) is extensively employed to detect bone metastases. However, incidental myocardial uptake may indicate wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), a frequently overlooked diagnosis with important clinical implications. Case Presentation: Two elderly female patients with a history of breast cancer were subjected to ^99mTc-HMDP bone scintigraphy as part of a routine evaluation for possible bone metastases. Both cases demonstrated incidental myocardial uptake (Perugini Grade 2 and Grade 3, respectively), raising suspicion for ATTRwt-CM, which was subsequently confirmed by endomyocardial biopsy. Review of the Literature: We reviewed published studies reporting cardiac uptake on bone scintigraphy, summarizing the frequency, patient demographics, and tracer types, and emphasizing the clinical relevance of this finding in cancer patients. Conclusions: In oncology patients, bone scintigraphy performed during routine metastatic screening may facilitate early detection of ATTRwt-CM, enabling timely diagnosis and treatment initiation, potentially improving clinical outcomes. Full article

(This article belongs to the Special Issue Feature Papers in Section 'Cardiology' in 2024–2025)

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12 pages, 787 KB

Open AccessCase Report

Clinical Patterns of Rocuronium and Cisatracurium Use in Acute Respiratory Distress Syndrome: A Retrospective Cohort Study

by Imran Khan, Ariel Hendin, Bernadett Kovacs, Dominic Seguin, Caitlin Richler, Christine Landry and Pierre Thabet

Diseases 2026, 14(1), 22; https://doi.org/10.3390/diseases14010022 - 6 Jan 2026

Abstract

Background: Neuromuscular blockade (NMB) is frequently used in moderate-to-severe acute respiratory distress syndrome (ARDS) to optimize ventilatory synchrony and minimize ventilator-induced lung injury. However, comparative real-world data on different NMB strategies remain limited. Objective: To describe patterns of neuromuscular blockade use in ARDS [...] Read more.

Background: Neuromuscular blockade (NMB) is frequently used in moderate-to-severe acute respiratory distress syndrome (ARDS) to optimize ventilatory synchrony and minimize ventilator-induced lung injury. However, comparative real-world data on different NMB strategies remain limited. Objective: To describe patterns of neuromuscular blockade use in ARDS and describe clinical outcomes across four NMB strategies: intermittent rocuronium, continuous cisatracurium, escalation from rocuronium to cisatracurium, and de-escalation from cisatracurium to rocuronium. Methods: A retrospective chart review was conducted in an 18-bed tertiary ICU at Hôpital Montfort (Ottawa, Canada) between November 2021 and March 2025. Adult ARDS patients who received NMB for >24 h were included. Continuous variables (age, ventilation time, ICU stay) were summarized as means ± SD and median [IQR]; categorical variables (sex, ARDS etiology, mortality) as counts and percentages. Inferential testing was limited to baseline characteristics; clinical outcomes were summarized descriptively. Results: Fifty-one patients met inclusion criteria: rocuronium (n = 20), cisatracurium (n = 14), rocuronium→cisatracurium (n = 8), and cisatracurium→rocuronium (n = 9). Mean ventilation durations were 280, 195, 272, and 262 h, respectively; corresponding ICU stays were 245, 237, 380, and 299 h. Mortality ranged from 25% to 56%. Escalation from rocuronium to cisatracurium typically reflected persistent dyssynchrony or worsening oxygenation, whereas de-escalation occurred in improving patients with residual ventilatory drive. Variability in corticosteroid use, adjunctive proning, and epoprostenol were potential confounders. Conclusions: Distinct NMB use patterns in ARDS reflect bedside clinical judgment rather than predefined thresholds. Patient trajectory and dyssynchrony severity appear to drive NMBA escalation decisions more than oxygenation indices alone. These findings highlight the need for prospective studies defining standardized criteria for NMB initiation, escalation, and weaning in ARDS. Full article

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28 pages, 4255 KB

Open AccessArticle

Segmentation-Guided Hybrid Deep Learning for Pulmonary Nodule Detection and Risk Prediction from Multi-Cohort CT Images

by Gomavarapu Krishna Subramanyam, Kundojjala Srinivas, Veera Venkata Raghunath Indugu, Dedeepya Sai Gondi and Sai Krishna Gaduputi Subbammagari

Diseases 2026, 14(1), 21; https://doi.org/10.3390/diseases14010021 - 6 Jan 2026

Abstract

Background: Lung cancer screening using low-dose computed tomography (LDCT) demands not only early pulmonary nodule detection but also accurate estimation of malignancy risk. This remains challenging due to subtle nodule appearances, the large number of CT slices per scan, and variability in radiological [...] Read more.

Background: Lung cancer screening using low-dose computed tomography (LDCT) demands not only early pulmonary nodule detection but also accurate estimation of malignancy risk. This remains challenging due to subtle nodule appearances, the large number of CT slices per scan, and variability in radiological interpretation. The objective of this study is to develop a unified computer-aided detection and diagnosis framework that improves both nodule localization and malignancy assessment while maintaining clinical reliability. Methods: We propose Seg-CADe-CADx, a dual-stage deep learning framework that integrates segmentation-guided detection and malignancy classification. In the first stage, a segmentation-guided detector with a lightweight 2.5D refinement head is employed to enhance nodule localization accuracy, particularly for small nodules with diameters of 6 mm or less. In the second stage, a hybrid 3D DenseNet–Swin Transformer classifier is used for malignancy prediction, incorporating probability calibration to improve the reliability of risk estimates. Results: The proposed framework was evaluated on established public benchmarks. On the LUNA16 dataset, the system achieved a competitive performance metric (CPM) of 0.944 for nodule detection. On the LIDC-IDRI dataset, the malignancy classification module achieved a ROC-AUC of 0.988, a PR-AUC of 0.947, and a specificity of 97.8% at 95% sensitivity. Calibration analysis further demonstrated strong agreement between predicted probabilities and true malignancy likelihoods, with an expected calibration error of 0.209 and a Brier score of 0.083. Conclusions: The results demonstrate that hybrid segmentation-guided CNN–Transformer architectures can effectively improve both diagnostic accuracy and clinical reliability in lung cancer screening. By combining precise nodule localization with calibrated malignancy risk estimation, the proposed framework offers a promising tool for supporting radiologists in LDCT-based lung cancer assessment. Full article

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