Diseases

12 pages, 250 KB

Open AccessArticle

Efficacy of Polyvinylpyrrolidone–Zinc Gluconate and Taurine Gel in the Prophylaxis of Oral Mucositis in Adults Undergoing High-Dose Chemotherapy and Allogeneic Stem Cell Transplantation

by Gaetana Porto, Annalisa Pitino, Mercedes Gori, Martina Pitea, Maria Eugenia Alvaro, Giovanni Luigi Tripepi, Giorgia Policastro, Fortunata Martino, Rosalba Daniela Minniti, Jessyca Germano’, Barbara Loteta, Giovanna Utano, Erica Bilardi, Francesca Cogliandro, Caterina Alati, Violetta Marafioti, Graziella D’Arrigo and Massimo Martino

Diseases 2025, 13(12), 408; https://doi.org/10.3390/diseases13120408 - 18 Dec 2025

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Abstract

Background: Oral mucositis (OM) is a significant complication after allogeneic stem cell transplantation. Objectives: This prospective, observational cohort study assessed the effectiveness of a polyvinylpyrrolidone-zinc gluconate and taurine (PVP-ZG-TAU) oral gel in managing OM. The primary objective was to determine whether the gel [...] Read more.

Background: Oral mucositis (OM) is a significant complication after allogeneic stem cell transplantation. Objectives: This prospective, observational cohort study assessed the effectiveness of a polyvinylpyrrolidone-zinc gluconate and taurine (PVP-ZG-TAU) oral gel in managing OM. The primary objective was to determine whether the gel reduced the incidence and grade of OM and accelerated its resolution. Methods: The study enrolled 82 patients; 39 received the PVP-ZG-TAU gel, and 43 represented a historical control group. To prevent oral mucositis, both groups maintained good oral hygiene. In the experimental group, patients received three sprays of PVP-ZG-TAU gel, three times a day, from the start of conditioning chemotherapy until day +15 after allo-SCT. Results: In the PVP-ZG-TAU group, 79.1% patients experienced grade 1–2 OM and 20.9% experienced grade 3–4 OM. In the control group, 74.4% had grade 1–2 OM, and 25.6% had grade 3–4 OM (p = ns). Resolution occurred significantly faster in the PVP-ZG-TAU group, with an 84% resolution rate per 100 person-weeks, compared with 62% in the control group. Cox regression analysis revealed that treatment was associated with a 68% greater likelihood of earlier resolution (adjusted hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.03–2.74; p = 0.036). Conclusions: These findings suggest that PVP-ZG-TAU can reduce OM duration and serve as a supportive intervention for allo-SCT patients. Full article

16 pages, 1960 KB

Open AccessArticle

Gaps in Community-Based Screening for Non-Communicable Diseases in Saudi Arabia

by Ghadeer Al Ghareeb, Zaenab M. Alkhair, Zainab Alradwan, Hussain Alqaissoom, Horiah Ali Soumel, Khadijah R. Alsaffar, Fatema Muhaimeed, Burair Alsaihati, Mohammad N. Alkhrayef and Ibrahim Alradwan

Diseases 2025, 13(12), 407; https://doi.org/10.3390/diseases13120407 - 18 Dec 2025

Viewed by 1174

Abstract

Background: Non-communicable diseases (NCDs) such as cardiovascular diseases, diabetes, obesity, and cancer are the leading cause of mortality globally and in Saudi Arabia, accounting for more than 70% of all deaths. Despite national initiatives offering free preventive services, screening uptake remains low. This [...] Read more.

Background: Non-communicable diseases (NCDs) such as cardiovascular diseases, diabetes, obesity, and cancer are the leading cause of mortality globally and in Saudi Arabia, accounting for more than 70% of all deaths. Despite national initiatives offering free preventive services, screening uptake remains low. This study aimed to describe the demographic and clinical characteristics of individuals participating in community-based NCD screening campaigns in the Eastern Province of Saudi Arabia and to evaluate screening uptake, compliance, and diagnostic outcomes. Methods: A retrospective cross-sectional analysis was conducted among 3106 adults screened at volunteer-driven community campaigns held between January 2023 and December 2024. Screening included anthropometric measurements, blood pressure assessment, and glucose testing, followed by eligibility evaluation for osteoporosis and cancer screening. Uptake and compliance were verified using electronic health records. Descriptive and inferential statistical analyses were applied. Results: Participants were 64% male and 36% female, with a mean age of 41.4 ± SD years. Obesity, hypertension, and diabetes were identified in 32%, 31%, and 12% of participants overall. Gender-stratified prevalence showed higher obesity among females at 36% (95% CI 32.3 to 38.1) and higher hypertension and diabetes among males at 36% (95% CI 34.0 to 38.2) and 14% (95% CI 12.1 to 15.2), respectively. Uptake among eligible individuals was 51% for dual-energy X-ray absorptiometry (DEXA), 47% for fecal immunochemical testing (FIT), 43% for Pap smear, and 39% for mammography. Diagnostic findings demonstrated substantial undetected disease burden, including osteoporosis in 41% (95% CI 26.0 to 56.8) of DEXA scans, a FIT positivity rate of 5% (95% CI 1.5 to 10.3), abnormal Pap cytology in 3% (95% CI 1.1 to 7.5), and BI-RADS 0 mammograms in 19% (95% CI 11.9 to 29.5), reflecting incomplete assessments requiring further evaluation. Conclusions: Community-based campaigns can effectively resolve limited engagement in health promotional activities and detect substantial burdens of undiagnosed NCDs. However, improvements in referral tracking, follow-up systems, and culturally tailored health education are essential to enhance screening compliance and early detection outcomes. These results can be utilized to inform public policies by extending screening services to additional areas, increasing investment in preventive health campaigns, and enhancing the capacity of the health system. Full article

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16 pages, 3190 KB

Open AccessArticle

Establishment of a Flow Cytometry Protocol for Binarily Detecting Circulating Tumor Cells with EGFR Mutation

by Cheng-Yu Chang, Chia-Chun Tu, Shian-Ren Lin, Chih-Hao Fang, Po-Wei Tseng, Wan-En Liao, Li-Yun Huang, Shiu-Lan Wang, Wan-Yu Lai, Yee Chao, Yen-Ling Chiu and Jan-Mou Lee

Diseases 2025, 13(12), 406; https://doi.org/10.3390/diseases13120406 - 17 Dec 2025

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Abstract

Background: Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond well to EGFR tyrosine kinase inhibitors (TKIs), but current EGFR mutation profiling relies on invasive tumor biopsies. Developing less invasive approaches, particularly proteomic evaluation of circulating tumor cells (CTCs) for EGFR mutation profiling, [...] Read more.

Background: Patients with EGFR-mutated non-small cell lung cancer (NSCLC) respond well to EGFR tyrosine kinase inhibitors (TKIs), but current EGFR mutation profiling relies on invasive tumor biopsies. Developing less invasive approaches, particularly proteomic evaluation of circulating tumor cells (CTCs) for EGFR mutation profiling, remains crucial. Methods: A flow cytometry method for detecting EGFR^L858R-bearing CTCs was established by spiking NCI-H1975 cells into blood from cancer-naive donors. The method was then applied to blood samples from 21 NSCLC patients and 10 cancer-naive donors. Results: The gating strategy was defined by CD45⁻CK-7/8⁺CK-14/15/16/19⁻EpCAM⁺vimentin⁺EGFR^L858R, with a cut-off value of 5 cells/mL. The method yielded positive results in all seven patients with the EGFR^L858R mutation and negative results in all ten cancer-naive donors. Compared to the PCR-based reference method, the approach showed 100% positive and 71% negative agreement. Crucially, our in-house method detected EGFR^L858R-bearing CTCs in three patients initially identified as EGFR wild-type and one patient with a different EGFR mutation. The remaining samples were concordant with PCR. Notably, two patients with these discordant results received EGFR-TKIs and experienced partial responses. Conclusions: This study introduces a feasible, less invasive proteomic approach for binarily detecting EGFR mutations in CTCs, offering a novel means for patient identification. Full article

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12 pages, 338 KB

Open AccessArticle

Association of Vitamin D Deficiency with Diabetic Nephropathy in Type 2 Diabetes: A Hospital-Based Cross-Sectional Study

by Shafia Bashir, Geer Mohammad Ishaq, Insha Mushtaq, Mohammad Ashraf Ganie, Imtiyaz Wani, Muteb Alanazi, Ibrahim Asiri, Arshad Hussain, Kashif Ullah Khan and Sirajudheen Anwar

Diseases 2025, 13(12), 405; https://doi.org/10.3390/diseases13120405 - 17 Dec 2025

Viewed by 1048

Abstract

Background/Objective: Diabetic nephropathy (DN), a key microvascular complication of type 2 diabetes (T2DM), drives significant morbidity, mortality, and healthcare costs. Vitamin D deficiency has been linked to renal dysfunction, but its role in DN remains unclear. This study assessed the association between vitamin [...] Read more.

Background/Objective: Diabetic nephropathy (DN), a key microvascular complication of type 2 diabetes (T2DM), drives significant morbidity, mortality, and healthcare costs. Vitamin D deficiency has been linked to renal dysfunction, but its role in DN remains unclear. This study assessed the association between vitamin D status and DN versus T2DM without nephropathy. Methods: This cross-sectional hospital-based study included 399 participants (299 DN, 100 T2DM without nephropathy) at a tertiary endocrine clinic. Demographic, clinical, and biochemical data, including serum 25(OH)D, were collected. Chi-square and Mann–Whitney compared categorical and continuous variables, respectively, and multinomial logistic regression assessed the association between vitamin D status and DN (p < 0.05). Results: Patients with DN were older (58.2 ± 7.95 vs. 51.4 ± 9.94 years, p < 0.001), had more advanced CKD (stages 2–3b: 84.6% vs. 20.0%, p < 0.001), and higher albuminuria (moderate: 80.3% vs. 19.0%; severe: 18.4% vs. 0%, p < 0.001). They also showed poorer glycemic control, elevated urea and creatinine, lower serum albumin, dyslipidemia, elevated liver enzymes, and higher uric acid (all p < 0.05). Vitamin D deficiency was more prevalent in DN (37.7% vs. 8.0%, p < 0.001). Unadjusted multinomial regression indicated that T2DM patients without nephropathy had a 91% lower risk of vitamin D deficiency (RRR 0.09; 95% CI 0.04–0.19, p < 0.001) and an 87% lower risk of insufficiency (RRR 0.13; 95% CI 0.05–0.26, p < 0.001) compared with DN patients. After adjusting for age, HbA1c, creatinine, duration of diabetes and eGFR, the reduced risk of deficiency remained significant (RRR 0.04; 95% CI 0.01–0.16, p < 0.001), while the association with insufficiency was no longer significant (p = 0.310). Conclusions: This study shows a significant association between vitamin D deficiency and diabetic nephropathy, though its cross-sectional design precludes causal inference. Reverse causality and residual confounding cannot be excluded. Patients with DN had poorer glycemic control, dyslipidemia, and renal function, along with more frequent vitamin D deficiency. Routine vitamin D monitoring may support early detection and risk stratification in T2DM. 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, 2240 KB

Open AccessCase Report

Unusual Neuropsychiatric Presentation of Cryptococcus neoformans Meningoencephalitis in an Immunosuppressed Patient with Rheumatoid Arthritis: A Case Report

by Sinthia Vidal-Cañas, Manuel David Mayoral-Valencia, Esteban Artunduaga-Cañas, Esteban Pineda-Arias, Danna Alejandra Betancourt Cañas and Daniela Arturo-Terranova

Diseases 2025, 13(12), 404; https://doi.org/10.3390/diseases13120404 - 17 Dec 2025

Cited by 2 | Viewed by 888

Abstract

Central nervous system (CNS) cryptococcosis caused by Cryptococcus neoformans is a severe opportunistic infection that primarily affects individuals with impaired cellular immunity. Although the classic presentation includes headache, fever, and meningeal signs, chronically immunosuppressed patients may develop atypical neuropsychiatric manifestations, leading to diagnostic [...] Read more.

Central nervous system (CNS) cryptococcosis caused by Cryptococcus neoformans is a severe opportunistic infection that primarily affects individuals with impaired cellular immunity. Although the classic presentation includes headache, fever, and meningeal signs, chronically immunosuppressed patients may develop atypical neuropsychiatric manifestations, leading to diagnostic delays. We report the case of a 53-year-old man with rheumatoid arthritis (RA) receiving long-term prednisolone and etanercept therapy, who presented with a 7-day history of depressive mood, anhedonia, social withdrawal, irritability, and progressive confusion. Neurological examination revealed disorientation without focal deficits. Brain imaging showed only mild cortical atrophy, and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, low glucose, and elevated protein levels. Multiplex PCR (FilmArray^®) of CSF identified Cryptococcus neoformans, CSF positive to C. neoformans. The patient was treated with liposomal amphotericin B followed by fluconazole, resulting in gradual improvement of both neurological and psychiatric symptoms. This case highlights an unusual presentation of CNS cryptococcosis in a non-HIV immunosuppressed patient with RA, emphasizing that acute psychiatric or cognitive changes can be the predominant manifestation. Clinicians should consider fungal infections in the differential diagnosis of acute neuropsychiatric symptoms in patients receiving chronic corticosteroid and biologic therapy. Early recognition and molecular diagnosis can facilitate timely antifungal treatment, potentially improving prognosis and reducing morbidity associated with delayed therapy. This report underscores the importance of awareness of atypical presentations of opportunistic infections in immunosuppressed populations. Full article

(This article belongs to the Section Infectious Disease)

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18 pages, 8516 KB

Open AccessArticle

CT-Based Attenuation Correction Algorithm for Quantitative L-Shell X-Ray Fluorescence Imaging of Gold Nanoparticles in Murine Tumor Tissues

by Marin Lohff, Gerret Haroske, Theresa Staufer, Jan Scheunemann, Florian Ziegler, Jannis Haak, Kazuya Kabayama, Xuhao Huang, Koichi Fukase and Florian Grüner

Diseases 2025, 13(12), 403; https://doi.org/10.3390/diseases13120403 - 16 Dec 2025

Viewed by 725

Abstract

Background: Gold nanoparticles (GNPs) are widely used in nanomedicine as drug carriers, including in targeted radionuclide therapy where therapeutic radionuclides are bound to GNPs. Quantitative assessment of their biodistribution is essential. X-ray fluorescence imaging (XFI) is well suited for detecting high-Z elements, but [...] Read more.

Background: Gold nanoparticles (GNPs) are widely used in nanomedicine as drug carriers, including in targeted radionuclide therapy where therapeutic radionuclides are bound to GNPs. Quantitative assessment of their biodistribution is essential. X-ray fluorescence imaging (XFI) is well suited for detecting high-Z elements, but its quantitative accuracy is compromised by strong attenuation effects, particularly in L-shell XFI where low-energy fluorescence (~10 to 12 keV) is heavily absorbed in tissue. Methods: We developed a computed tomography (CT)-guided attenuation correction algorithm for L-shell XFI. The method generates energy-dependent attenuation maps from co-registered CT data and performs voxel-wise corrections along both excitation and emission paths. The approach was tested on an ex vivo murine tumor sample resected three hours after intratumoral injection of 34.7 μg PEG-modified GNPs. Results: Application of the CT-guided correction substantially improved the relative accuracy of L-shell XFI reconstructions compared to uncorrected data. The corrected distribution maps showed consistent mass recovery across different measurement geometries, demonstrating that the algorithm compensates for the theoretically expected attenuation due to heterogeneous biological tissue. Conclusions: This study provides a proof-of-principle that CT-based attenuation correction enables more reliable and quantitative L-shell XFI of GNPs in biological samples. The approach represents a promising step toward accurate nanoparticle biodistribution assessment in biomedical research, including preclinical studies in targeted radionuclide therapy. Full article

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18 pages, 2702 KB

Open AccessArticle

Fluid Shear Stress Modulates Inflammation in Breast Cancer Microenvironment

by Abir Abdullah Alamro, Ohood Amin AlSuwaidi, Amani Ahmed Alghamdi, Saba Abdi, Atekah Hazzaa Alshammari and Reem Nasser Alotaibi

Diseases 2025, 13(12), 402; https://doi.org/10.3390/diseases13120402 - 15 Dec 2025

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Abstract

Background: Fluid shear stress (FSS) is a biomechanical force that can produce phenotypic changes in the cells that are directly in contact with the flow of fluid. Accumulating evidence indicates high FSS to possess the potential ability to prevent tumor development and suppress [...] Read more.

Background: Fluid shear stress (FSS) is a biomechanical force that can produce phenotypic changes in the cells that are directly in contact with the flow of fluid. Accumulating evidence indicates high FSS to possess the potential ability to prevent tumor development and suppress cancer growth. However, the exact mechanism of its antitumorigenic effects is still not clear. Objective: In this study, we aimed to investigate the effect of FSS on breast cancer microenvironment via macrophage modulation. Methods: We exposed THP-1 like-macrophages to different levels of FSS. The supernatant from THP1-like-macrophages after exposure to FSS was used as conditioned medium (FSS-CM). Subsequently, we analyzed human breast cancer cells, MCF-7, and endothelial cells, as well as HUVECs cultured with FSS-CM. Results: Study outcomes have demonstrated that low FSS-CM inhibited apoptosis as well as induced tumor migration in MCF-7 cells. Conversely, high FSS-CM promoted apoptosis, inhibited tumor migration, and induced G1-phase arrest in MCF-7 cells. Furthermore, low FSS-CM was found to promote proliferation of HUVECs. Conclusions: In conclusion, this study highlights the complex interplay between FSS and cancer cell behavior. Our findings provide in vitro evidence that high FSS exerts an anti-cancer effect by promoting THP-1-like macrophage polarization toward an anti-tumor phenotype, leading to increased apoptosis and reduced migration in MCF-7 cells. These results suggest that the modulation of macrophage polarization may underlie the therapeutic potential of high FSS in suppressing breast cancer progression. Full article

(This article belongs to the Section Oncology)

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13 pages, 747 KB

Open AccessArticle

Association Between Obesity and Serum Leptin Levels in Brazilian Female Shift Workers

by Raquel Toresan Andretta, Janaína Cristina da Silva, Anderson Garcez, Ingrid Stähler Kohl, Karina Giane Mendes, Thais Basso, Maria Teresa Anselmo Olinto and Heloísa Theodoro

Diseases 2025, 13(12), 401; https://doi.org/10.3390/diseases13120401 - 15 Dec 2025

Cited by 1 | Viewed by 780

Abstract

Background: Leptin is a hormone that plays a crucial role in regulating energy homeostasis and it is associated with adiposity. Women engaged in work shifts are often exposed to circadian disruption and metabolic changes that may contribute to increased adiposity and hormonal imbalance. [...] Read more.

Background: Leptin is a hormone that plays a crucial role in regulating energy homeostasis and it is associated with adiposity. Women engaged in work shifts are often exposed to circadian disruption and metabolic changes that may contribute to increased adiposity and hormonal imbalance. Thus, this study aimed to investigate the association between general and abdominal obesity and serum leptin levels among female shift workers. Methods: This cross-sectional study included a sample of 302 female employees from a group of plastic manufacturing industries in southern Brazil. Serum leptin levels were measured, with values > 15.2 ng/mL classified as elevated. General obesity (body mass index ≥ 30 kg/m²) and abdominal obesity (waist circumference ≥ 88 cm) were assessed. Associations were examined using Poisson regression with robust variance. Results: The mean age of participants was 35.4 ± 10.1 years. The mean serum leptin concentration in the sample was 33.6 ng/mL (95% Confidence Interval [CI]: 30.6–36.6), and the prevalence of altered serum leptin levels was 78.1% (95% CI: 73.5–82.8). After adjustment for potential confounders, women with obesity showed a 63% higher probability of having elevated leptin levels (Prevalence Ratio [PR] = 1.63; 95% CI: 1.32–2.02; p < 0.001) compared with those without obesity. Additionally, significant associations were observed with work shift and physical activity. However, abdominal obesity was not statistically significant after adjustment. Conclusions: Obesity was independently associated with elevated serum leptin levels among female shift workers, suggesting that excess adiposity remains a key determinant of leptin dysregulation in this population. Full article

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11 pages, 563 KB

Open AccessArticle

The Application of Stepwise Pelvic Devascularisation in the Management of Severe Placenta Accreta Spectrum as Part of the Soleymani and Collins Technique for Caesarean Hysterectomy: Surgical Description and Evaluation of Short- and Long-Term Outcomes

by Hooman Soleymani majd, Lamiese Ismail, Prasanna Supramaniam, Aakriti Aggarwal, Annie E. Collins, Lee Lim, Susan Addley, Alicia Hunter, Lexie Pert, Theophilus Adu-Bredu, Pedro Pinto, Ammar Al Naimi, Jacopo Conforti, Karin Fox and Sally L. Collins

Diseases 2025, 13(12), 400; https://doi.org/10.3390/diseases13120400 - 15 Dec 2025

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Abstract

Background: Severe (FIGO grade 3b & c) placenta accreta spectrum (PAS) is potentially a life-threatening condition due to catastrophic haemorrhage at delivery. Consequently, interventional radiology (IR) techniques are often employed to prevent massive blood loss, but this is not always readily available, is [...] Read more.

Background: Severe (FIGO grade 3b & c) placenta accreta spectrum (PAS) is potentially a life-threatening condition due to catastrophic haemorrhage at delivery. Consequently, interventional radiology (IR) techniques are often employed to prevent massive blood loss, but this is not always readily available, is costly, and can cause significant morbidity, including distal limb ischaemia due to thrombus formation. We believe that internal iliac ligation under direct vision is a safe option to control bleeding. We sought to evaluate the short- and long-term outcomes relating to this technique compared to IR. Methods: This is a mixed-methods cohort study of women with severe PAS who underwent hysterectomy with either surgical devascularisation, as part of the Soleymani and Collins (SAC) technique, or IR insertion of internal iliac balloon catheters, in a UK tertiary referral centre for PAS between 2011 and 2022. Only women with intraoperative diagnosis of very severe PAS (FIGO stage 3b & c) were included in this study. Results: Of the 22 women invited to participate in the long-term component of the study, 59% agreed. Women in the surgical devascularisation group experienced no adverse short or late sequelae related to internal iliac arterial ligation. Pelvic devascularisation (11 patients, 41%) demonstrated a reduction in median estimated blood loss, 1600 millilitres vs. 2500 millilitres in the IR balloon catheter group (p = 0.04). Conclusions: We have demonstrated that the SAC technique for surgical devascularisation is a safe method for achieving haemorrhage control during caesarean hysterectomy for severe PAS. It also appears to be at least as effective at haemorrhage control as IR balloon occlusion of the internal iliac vessels. Full article

(This article belongs to the Special Issue Recent Therapeutic Advances in Gynecological Diseases and Clinical Management)

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14 pages, 624 KB

Open AccessArticle

by Pier Luigi Zinzani, Nicola Battaglia, Mario Lapecorella, Guido Gini, Maria Cristina Cox, Stefan Hohaus and Antonio Pinto

Diseases 2025, 13(12), 399; https://doi.org/10.3390/diseases13120399 - 15 Dec 2025

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Abstract

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) exhibits substantial clinical heterogeneity and poor prognosis in relapsed/refractory (R/R) settings. PRO-MIND is a prospective, multicenter real-world study evaluating tafasitamab–lenalidomide followed by tafasitamab monotherapy in patients with transplant-ineligible R/R DLBCL in Italy. This ad hoc, cross-sectional, [...] Read more.

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) exhibits substantial clinical heterogeneity and poor prognosis in relapsed/refractory (R/R) settings. PRO-MIND is a prospective, multicenter real-world study evaluating tafasitamab–lenalidomide followed by tafasitamab monotherapy in patients with transplant-ineligible R/R DLBCL in Italy. This ad hoc, cross-sectional, baseline analysis aimed to characterize health-related quality of life (HRQoL) and symptom burden before tafasitamab–lenalidomide initiation in the PRO-MIND cohort. Methods: Thirty-eight patients across 30 centers completed the EORTC QLQ-C30 and QLQ-NHL-HG29 questionnaires at pretreatment baseline, prior to starting tafasitamab–lenalidomide. EORTC QLQ-C30 scores (0–100) were compared with age-specific normative values for the Italian general population using Welch’s t-test. Differences of ≥5 points were considered clinically meaningful and ≥10 points clearly clinically important. Effect sizes (Cohen’s d) were calculated to complement p-values for between-group comparisons. Results: Compared with normative data, the PRO-MIND cohort had significantly lower EORTC QLQ-C30 functioning scores for physical (Δ 12.7, p = 0.0135), role (Δ 16.1, p = 0.0168), social (Δ 15.2, p = 0.0019), and cognitive (Δ 8.5, p = 0.0460) functioning. Symptom scales revealed worse fatigue (Δ 14.8, p = 0.0097), insomnia (Δ 13.9, p = 0.0291), appetite loss (Δ 9.4, p = 0.0435), and pain (Δ 8.7, p = 0.0430) in the PRO-MIND cohort versus normative data, with effect sizes in the small-to-moderate range. EORTC QLQ-NHL-HG29 scores indicated a high prevalence of concerns about future health (84.2%), disease recurrence (81.6%), and dependency (78.9%), as well as physical symptoms, including lack of energy (71.1%), sleep difficulties (63.2%), and pain or discomfort (60.5%). Conclusions: This cross-sectional, baseline-only analysis of the PRO-MIND real-world cohort showed that patients with transplant-ineligible R/R DLBCL scheduled to receive tafasitamab–lenalidomide already had pronounced impairments in physical, role, social, and cognitive functioning, along with substantial fatigue, insomnia, pain, appetite loss, and psychological concerns. These baseline benchmarks underscore the importance of systematic HRQoL assessment and targeted supportive interventions focusing on these domains before and during treatment. Future longitudinal PRO-MIND analyses will complement these findings by describing how HRQoL evolves after tafasitamab–lenalidomide initiation. Full article

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10 pages, 574 KB

Open AccessArticle

Prevalence and Impact on Quality of Life of Small Intestinal Bacterial Overgrowth (SIBO)-Related Symptoms in Patients with Upper Gastrointestinal Cancer

by Rosa Rosania, Achim J. Kaasch, Katrin Bose, Friedrich Sinner, Christian Müller, Jochen Weigt, Verena Keitel and Marino Venerito

Diseases 2025, 13(12), 398; https://doi.org/10.3390/diseases13120398 - 13 Dec 2025

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Abstract

Introduction: Although patients with upper gastrointestinal (GI) cancer have an increased risk of developing small intestinal bacterial overgrowth (SIBO) due to disease- and treatment-related factors, SIBO remains underdiagnosed in oncology. Aim and Methods: This prospective study evaluated the prevalence of SIBO and its [...] Read more.

Introduction: Although patients with upper gastrointestinal (GI) cancer have an increased risk of developing small intestinal bacterial overgrowth (SIBO) due to disease- and treatment-related factors, SIBO remains underdiagnosed in oncology. Aim and Methods: This prospective study evaluated the prevalence of SIBO and its impact on symptom-related quality of life (QoL) in patients with current or prior upper GI cancer. Between April 2021 and May 2022, patients reporting SIBO-related symptoms like bloating and/or diarrhea completed a standardized symptom questionnaire. QoL impact was scored from 0 (none) to 3 (severe). Patients with scores > 1 and no recent antibiotic use underwent upper endoscopy with duodenal aspirate. SIBO was defined as >10³ CFU/mL. Results: Ninety patients were enrolled (51% female; median age of 65 years): 35% had pancreatic, 34% gastric, 17% biliary, and 14% esophageal cancer. Sixty reported SIBO-related symptoms: 35% reported bloating, 11% diarrhea, and 54% both. Of these, 36 underwent endoscopy; 53% were diagnosed with SIBO. Among SIBO-positive patients, 95% reported bloating and 58% reported diarrhea. Prior abdominal surgery was recorded in 63% of SIBO cases. Conclusions: SIBO was identified in more than half of symptomatic upper GI cancer patients, with a strong association with bloating and previous abdominal surgery. These findings emphasize the importance of clinical awareness and appropriate diagnostic evaluation for SIBO in this high-risk group to improve symptom control and quality of life. Full article

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9 pages, 1447 KB

Open AccessCase Report

A Rare Case of Cervicofacial Nocardiosis and Associated Mandibular Osteomyelitis: Therapeutic Challenges in a Transplant Patient

by Parth M. Dhamelia, Bhargav P. Patel, Gabriel Godart, Shifa Karatela, Rohit Chitale, Ravi Durvasula and Justin Oring

Diseases 2025, 13(12), 397; https://doi.org/10.3390/diseases13120397 - 12 Dec 2025

Viewed by 777

Abstract

Cervicofacial actinomycosis is a well-recognized infectious disease caused by Actinomyces, a Gram-positive filamentous bacterium. In contrast, Nocardia, a morphologically similar, hyphae-forming organism, is an exceedingly rare cause of cervicofacial abscesses, and even more uncommon associated osteomyelitis of mandible. We present such [...] Read more.

Cervicofacial actinomycosis is a well-recognized infectious disease caused by Actinomyces, a Gram-positive filamentous bacterium. In contrast, Nocardia, a morphologically similar, hyphae-forming organism, is an exceedingly rare cause of cervicofacial abscesses, and even more uncommon associated osteomyelitis of mandible. We present such a case involving a kidney transplant recipient who presented with opioid-induced constipation, along with left jaw pain and swelling. CT scan of the soft tissue in the neck revealed a complex cervicofacial abscess with enhancement of underlying mandible. Culture growth and RNA sequencing of USG-guided aspirate identified a Nocardia species closely related to N. beijingensis/exalbida. The patient initially received broad-spectrum antibiotics, including ceftriaxone, imipenem, and trimethoprim-sulfamethoxazole (TMP-SMX). Imipenem was later discontinued in view of new-onset unexplained encephalopathy and replaced with linezolid, which was subsequently switched to minocycline following thrombocytopenia development. Minocycline therapy was intended for a total of 12 months. TMP-SMX was avoided long-term due to avoid nephrotoxicity risk in kidney transplant patients. On six-month follow-up, the patient showed clinical and radiological improvement; minocycline was discontinued after additional six months. This case highlights the importance of considering Nocardia as a differential diagnosis in immunosuppressed patients presenting with cervicofacial symptoms, especially following orofacial surgery or trauma. Early recognition, prompt diagnosis, and appropriate antibiotic therapy with adequate bone penetration seem crucial for optimal management and may help avoid the need for surgical intervention. Full article

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28 pages, 502 KB

Open AccessSystematic Review

Zinc and Type 2 Diabetes: A Systematic Review with a Narrative Synthesis of Their Bidirectional Relationship and Clinical Perspectives for Personalized Nutritional Support

by Evgeniya Klein, Daria Velina, Sherzodkhon Mutallibzoda, Svetlana Tefikova, Olga Orlovtseva, Alexander N. Kosenkov, Dmitry Kulikov and Igor Nikitin

Diseases 2025, 13(12), 396; https://doi.org/10.3390/diseases13120396 - 11 Dec 2025

Cited by 1 | Viewed by 3110

Abstract

Background: Type 2 diabetes mellitus (T2DM) remains one of the most significant public health problems, and its incidence rate is steadily increasing worldwide despite scientific and technological progress in the field of medicine. The focus of research in this area is gradually shifting [...] Read more.

Background: Type 2 diabetes mellitus (T2DM) remains one of the most significant public health problems, and its incidence rate is steadily increasing worldwide despite scientific and technological progress in the field of medicine. The focus of research in this area is gradually shifting from classic risk factors—such as obesity, sedentary lifestyle and genetic predisposition—toward additional, potentially modifiable contributors such as micronutrient imbalances; among them are disturbances in zinc homeostasis that may influence glucose metabolism and oxidative stress. Objective: This systematic review with narrative synthesis aims to examine the bidirectional relationship between zinc status and T2DM and to evaluate whether zinc screening and personalized nutritional support could contribute to comprehensive metabolic management. Methods: A literature search was conducted in the PubMed database and the Cochrane library for studies published between 2010 and 2024. Studies assessing zinc status or supplementation in relation to the risk, progression, or management of T2DM were included. Data were synthesized narratively, focusing on clinical and mechanistic evidence. Results: Thirty studies met the inclusion criteria. Evidence indicates that zinc imbalance (both deficiency and excess) is associated with T2DM risk and outcomes. Zinc deficiency may impair insulin synthesis and signaling, promote oxidative stress and inflammation, while excessive zinc intake may induce metabolic disturbances. T2DM itself may lead to reduced zinc status via altered absorption and increased excretion. While some studies suggest modest improvements in glycemic or lipid parameters following zinc supplementation, findings remain inconsistent and context-dependent. The prevalence of suboptimal zinc status in certain populations supports the rationale for targeted screening rather than routine supplementation. Conclusions: Zinc is mechanistically involved in insulin synthesis, antioxidant defense, and inflammation control, but current clinical evidence does not justify its use as a therapeutic agent in T2DM. Instead, assessment of zinc status and individualized correction of deficiency may represent a component of personalized nutritional support, particularly for patients with long disease duration, poor dietary quality, or genetic predispositions affecting zinc metabolism. 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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13 pages, 1519 KB

Open AccessArticle

Clinical Implications of Upregulated RSAD2 Gene Expression in Hepatocellular Carcinoma

by Leung Li, Nelson L. S. Tang, Stephen L. Chan, David Ryan Johnson, Frankie Mo, Jane Koh, Tsz-Ki Kwan, Edwin P. Hui, Landon Long Chan, Kit F. Lee, Simon Chun Ho Yu and Winnie Yeo

Diseases 2025, 13(12), 395; https://doi.org/10.3390/diseases13120395 - 8 Dec 2025

Viewed by 867

Abstract

Background: JAK/STAT interferon signaling interacts with the PI3K/AKT/mTOR pathway to drive hepatocellular carcinoma (HCC) progression and metastasis. RSAD2, an interferon-inducible gene, is upregulated by the PI3K/AKT/mTOR pathway and serves as a key factor for metabolic reprogramming to promote stem-like properties of [...] Read more.

Background: JAK/STAT interferon signaling interacts with the PI3K/AKT/mTOR pathway to drive hepatocellular carcinoma (HCC) progression and metastasis. RSAD2, an interferon-inducible gene, is upregulated by the PI3K/AKT/mTOR pathway and serves as a key factor for metabolic reprogramming to promote stem-like properties of cancer stem cells and tumor proliferation. In patients with resected HCC, RSAD2 upregulation showed an association with microvascular invasion, which is a proven risk factor for developing HCC metastasis. This clinical observation was compatible with preclinical findings. On the other hand, RSAD2 upregulation has been reported to confer poor prognosis in breast and gastric cancers. However, further clinical study of RSAD2 in HCC is lacking. As a result, we investigated the clinical implications of RSAD2 gene expression in HCC patients, in terms of its associations with survival, the presence of extra-hepatic metastasis, and other clinical manifestations. Methods: We studied 309 treatment-naïve HCC patients, as well as data from the TCGA and GTEx databases. Results:RSAD2 gene expression was differentially upregulated in HCC tumors when compared to normal liver tissues (p < 0.01). Elevated RSAD2 mRNA levels in the blood and the presence of extra-hepatic metastasis were independent prognostic factors for poor overall survival (OS) (p < 0.01). The median OS of patients with high RSAD2 expression vs. low expression were 5.4 vs. 14.2 months, respectively (p < 0.01). A high RSAD2 mRNA level was significantly correlated with the presence of extra-hepatic metastasis, nutritional disturbance, and functional impairment after controlling for confounding clinical factors (p < 0.05). Conclusions: High RSAD2 gene expression is associated with poorer OS, the presence of extra-hepatic metastasis, and quality-of-life disturbances in HCC patients. Full article

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11 pages, 263 KB

Open AccessArticle

Relationship Between Apolipoprotein E Genotypes, Unhealthy Weight Status, and Cognitive Impairment in Older Adults of Predominantly African Descent

by Jean-Pierre Clotilde, Livy Nicolas, Laurent Larifla, Fritz-Line Velayoudom, Stanie Gaete, Yann Ancedy, Ingrid Cirederf, Rosan Fanhan and Lydia Foucan

Diseases 2025, 13(12), 394; https://doi.org/10.3390/diseases13120394 - 6 Dec 2025

Viewed by 649

Abstract

Background: Apolipoprotein E4 (APOE4) represents a major genetic risk factor for Alzheimer’s disease. Objectives: We aimed to analyze the relationship between cognitive impairment (CI), unhealthy weight status, and APOE genotypes in individuals of predominantly African descent aged 55 years and more. [...] Read more.

Background: Apolipoprotein E4 (APOE4) represents a major genetic risk factor for Alzheimer’s disease. Objectives: We aimed to analyze the relationship between cognitive impairment (CI), unhealthy weight status, and APOE genotypes in individuals of predominantly African descent aged 55 years and more. Genotyping of two single-nucleotide polymorphisms, rs7412 and rs429358, of the APOE gene was performed. Results: Among 310 individuals, the mean age was 75.64 years, the mean BMI was 25.94 kg/m², and the prevalence of CI was 18.1%. Most subjects were ε3/ε3 carriers (49%), while ε2-carriers and ε4-carriers represented 14.5% and 36.5%, respectively. Older age, the presence of undernutrition, and APOE4 carriers were more frequently found in underweight vs. non-underweight individuals and in those with CI vs. those without CI. The adjusted odds ratios for prevalent CI were nearly four times higher for underweight individuals compared to obese individuals. Those carrying two ε4 alleles exhibited three times the odds of CI (OR = 3.31 (95% CI: 1.15–9.91), p = 0.026) compared to those with no ε4 alleles. Conclusions: In this cross-sectional study, being underweight and carrying the ApoE ε4 allele were independently associated with cognitive impairment. These findings suggest that monitoring weight changes and APOE genotypes in older adults may have clinical significance. Full article

22 pages, 1489 KB

Open AccessReview

Chronic Hepatitis C in the Direct-Acting Antivirals Era: Carcinogenesis and Clinical Implications

by Yucel Aydin, Ramazan Kurt, Veysel Tahan and Ebubekir Daglilar

Diseases 2025, 13(12), 393; https://doi.org/10.3390/diseases13120393 - 5 Dec 2025

Viewed by 992

Abstract

Chronic hepatitis C virus (HCV) infection remains a major global health burden, responsible for substantial morbidity and mortality despite the advent of curative antiviral therapy. HCV induces hepatic injury and carcinogenesis through direct viral effects, persistent inflammation, oxidative stress, and metabolic disturbance. The [...] Read more.

Chronic hepatitis C virus (HCV) infection remains a major global health burden, responsible for substantial morbidity and mortality despite the advent of curative antiviral therapy. HCV induces hepatic injury and carcinogenesis through direct viral effects, persistent inflammation, oxidative stress, and metabolic disturbance. The introduction of direct-acting antivirals (DAAs) has revolutionized therapy, achieving sustained virologic response rates exceeding 95% and transforming HCV from a chronic, progressive disease into a curable infection. Nevertheless, viral eradication does not fully normalize hepatic or systemic risk. Patients with advanced fibrosis or cirrhosis continue to face an elevated incidence of hepatocellular carcinoma (HCC) and other complications, reinforcing the need for long-term monitoring. This review summarizes current knowledge of the molecular mechanisms underlying HCV-mediated carcinogenesis, the partial restoration of hepatic homeostasis following DAA-induced cure, and the clinical implications for surveillance and management in the post-HCV era. By integrating insights from molecular virology, immunopathogenesis, and clinical hepatology, the review highlights how persistent epigenetic and inflammatory footprints may sustain oncogenic potential even after viral clearance. A comprehensive understanding of these processes is essential for optimizing HCC prevention strategies, guiding surveillance policies, and advancing future therapeutic innovations aimed at complete hepatic recovery. Full article

(This article belongs to the Special Issue Viral Hepatitis: Diagnosis, Treatment and Management—2nd Edition)

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15 pages, 1287 KB

Open AccessArticle

Colorectal Cancer in the U.S., 1999–2021: Declining Rates, Rising Concerns, and Persistent Disparities

by Qais Bin Abdul Ghaffar, Sayed Maisum Mehdi Naqvi, Garrett Shields, Ebubekir Daglilar and Harleen Chela

Diseases 2025, 13(12), 392; https://doi.org/10.3390/diseases13120392 - 4 Dec 2025

Viewed by 1291

Abstract

Background: Colorectal cancer (CRC) incidence and mortality have declined in the United States over the past two decades, yet disparities persist by age, sex, race/ethnicity, and geography. To characterize population-level survival signals, we examined trends in age-adjusted incidence rates (AAIR), mortality rates (AAMR), [...] Read more.

Background: Colorectal cancer (CRC) incidence and mortality have declined in the United States over the past two decades, yet disparities persist by age, sex, race/ethnicity, and geography. To characterize population-level survival signals, we examined trends in age-adjusted incidence rates (AAIR), mortality rates (AAMR), and the mortality-to-incidence ratio (AAMIR) from 1999 to 2021, stratified by key subgroups. Methods: This retrospective analysis utilized de-identified data from the CDC WONDER United States Cancer Statistics database, encompassing incident CRC cases (SEER codes 21041–21052) and deaths (ICD-10 codes C18–C20) in adults aged 20 years and older. Age-adjusted rates (per 100,000, 2000 U.S. standard population) and AAMIR were calculated using Stata 17.0. Joinpoint regression identified trends (annual or average annual percent change [APC/AAPC], p < 0.05). Results: Among 3,489,881 cases and 1,225,986 deaths, AAIR decreased from 78.24 (1999) to 50.79 (2021; AAPC: −2.20%, 95% CI: −2.52 to −1.89), AAMR decreased from 29.34 to 17.92 (AAPC: −2.33%, −2.46 to −2.20), and AAMIR from 0.375 to 0.353 (AAPC: −0.08%, −0.47 to 0.30; p = 0.669). Women showed a significant AAMIR decline (AAPC: −0.29%), unlike men (AAPC: 0.07%). Young adults (20–39 years) had rising AAIR (AAPC: 2.42%) and AAMR (0.87%) but improving AAMIR (AAPC: −1.71%). Non-Hispanic Black individuals had the highest AAMIR (0.400 in 2021; AAPC: −0.54%). The Northeast had the most favorable AAMIR trend (AAPC: −0.40%), while the Midwest, South, and West were stable. States like New Jersey and Massachusetts achieved low AAMIR (0.292 and 0.304 in 2021), contrasting with Nebraska and Arizona (0.402 in both). Conclusions: Although colorectal cancer incidence and mortality have declined substantially in the United States from 1999 to 2021, the mortality-to-incidence ratio improved only marginally and remained markedly uneven across subgroups. Targeted interventions—enhancing screening and treatment access for men, racial/ethnic minorities, younger adults, and high-burden regions and states—can promote equitable outcomes. Full article

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

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25 pages, 820 KB

Open AccessSystematic Review

Musculoskeletal Sequelae of Post-COVID-19 Syndrome: A Systematic Review

by Claudia Tatiana Zuñiga-Jimenez, Diego Fernando Rojas-Esguerra, Aida Paola Muñoz-Martinez, Diana Carolina Mendoza-Guzman and Jorge Enrique Daza-Arana

Diseases 2025, 13(12), 391; https://doi.org/10.3390/diseases13120391 - 3 Dec 2025

Viewed by 2768

Abstract

Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute [...] Read more.

Background/Objectives: COVID-19 infection is a respiratory illness that affects multiple body systems, including the musculoskeletal system. In August 2024, Colombia reported 6 million infections and a 2.2% mortality rate related to COVID-19. Post-COVID-19 syndrome (PCS) is a chronic condition occurring after the acute infection, typically characterized by fatigue, weakness, pain, and sarcopenia, impacting the patient’s quality of life (QoL). This systematic review aimed to identify musculoskeletal sequelae, including peripheral muscle strength, fatigue, and QoL, in patients with PCS. Methods: We searched the PubMed, Scopus, and Web of Science databases for cross-sectional, case–control, and cohort studies focusing on musculoskeletal sequelae in patients with COVID-19 infection published between 2020 and 2025. Study quality and risk of bias were assessed using the MINORS and the ROBINS-E scales, respectively. Results: Thirteen studies (n = 5657 patients) met the eligibility criteria. Seventy-six percent of studies indicated muscle weakness as the most common sequela, primarily in older adults and individuals with comorbidities (obesity, diabetes, and chronic obstructive pulmonary disease). General fatigue (reported in 76% of the studies) significantly influenced patients’ daily lives, whereas 90% of patients reported some level of deterioration in their QoL, primarily regarding mental health, bodily pain, and physical performance. Conclusions: Patients with PCS who required mechanical ventilation showed reduced muscle strength and poor physical performance, especially older adults. Inactive individuals had worse musculoskeletal sequelae, while physical activity was associated with better strength levels. Although QoL improved after 12 months, the combination of aerobic exercise with adequate nutrition is essential to promote muscle recovery, reduce fatigue, and improve overall functional capacity in post-COVID-19 patients. Full article

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17 pages, 619 KB

Open AccessArticle

Effects of Short-Term (20-Day) Alternate-Day Modified Fasting and Time-Restricted Feeding on Fasting Glucose and IGF-1 in Obese Young Women

by Dian Aristia Rachmayanti, Purwo Sri Rejeki, Raden Argarini, Hermina Novida, Sri Soenarti, Shariff Halim, Chy’as Diuranil Astrid Permataputri and Sheeny Priska Purnomo

Diseases 2025, 13(12), 390; https://doi.org/10.3390/diseases13120390 - 1 Dec 2025

Viewed by 3850

Abstract

Background: Obesity is a metabolic condition that may impair insulin sensitivity and disrupt glucose homeostasis. Since insulin and glucose affect insulin-like growth factor-1 (IGF-1), disruptions in this axis may elevate the risk of chronic diseases. Intermittent fasting (IF) modulates metabolic parameters, but the [...] Read more.

Background: Obesity is a metabolic condition that may impair insulin sensitivity and disrupt glucose homeostasis. Since insulin and glucose affect insulin-like growth factor-1 (IGF-1), disruptions in this axis may elevate the risk of chronic diseases. Intermittent fasting (IF) modulates metabolic parameters, but the impacts on glucose regulation and IGF-1 remain underexplored. This study aimed to assess the short-term effects of two IF types, time-restricted feeding (TRF) and alternate-day modified fasting (ADMF), on fasting blood glucose (FBG) and IGF-1 in obese young women. Methods: A quasi-experimental pretest–posttest control group design was conducted over 20 days. The 31 subjects were allocated into ADMF (n = 10), TRF (n = 11), and Control (n = 10). After excluding dropouts and outliers, the final sample consisted of 22 subjects (ADMF = 7, TRF = 8, Control = 7). FBG and IGF-1 serum were measured pre- and post-intervention. Results: The FBG post-intervention significantly increased in TRF (p = 0.001) and ADMF (p = 0.036) groups, but not in Controls. Only the TRF group showed a significant reduction in IGF-1 levels (p < 0.001). Nevertheless, the ADMF group exhibited substantial decreases in body weight (p = 0.047) and visceral fat (p = 0.017). Conclusions: A 20-day IF in obese young women induced distinct metabolic effects: TRF lowered IGF-1, ADMF reduced adiposity, and both regimens increased FBG. These findings suggest that early changes in glucose regulation are highly dependent on the specific dietary regimen used. Specifically, TRF predominantly influences endocrine regulation (IGF-1 axis), while ADMF favours adiposity reduction. The concurrent rise in FBG may reflect a transient shift in glucose homeostasis during the early stages of fasting. Full article

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19 pages, 577 KB

Open AccessSystematic Review

Palliative Care in Chronic Heart Failure: A Systematic Review of Its Impact on Symptoms, Quality of Life, and Decision-Making Process

by Tatiana Dramba, Andrei-Emilian Popa, Mihaela Poroch, Gema Bacoanu, Irina Mihaela Esanu, Elena Popa and Vladimir Poroch

Diseases 2025, 13(12), 389; https://doi.org/10.3390/diseases13120389 - 1 Dec 2025

Cited by 2 | Viewed by 2421

Abstract

Background: Palliative care has emerged as a key component in the management of chronic heart failure, addressing persistent physical and psychosocial symptoms that often remain insufficiently controlled by conventional cardiology. This systematic review aimed to evaluate the impact of palliative care interventions on [...] Read more.

Background: Palliative care has emerged as a key component in the management of chronic heart failure, addressing persistent physical and psychosocial symptoms that often remain insufficiently controlled by conventional cardiology. This systematic review aimed to evaluate the impact of palliative care interventions on symptom burden, quality of life (QoL) and decision-making processes in adults with chronic heart failure. Methods: A systematic search of PubMed, Scopus and Web of Science identified studies published between January 2005 and February 2025. Eligible designs included randomized controlled trials, observational cohorts and qualitative studies. The review followed PRISMA 2020 guidelines. Methodological quality was assessed using the Cochrane Risk of Bias 2.0 (RoB 2.0), Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) and Joanna Briggs Institute (JBI) appraisal tools. Due to heterogeneity in study designs and outcomes, a narrative synthesis was conducted. Results: Nineteen studies met the inclusion criteria. Palliative care interventions consistently reduced dyspnea, fatigue, anxiety and depression and were associated with improved functional status and QoL. Integrated palliative–cardiology programs were linked to fewer hospital readmissions, shorter hospital stays and increased documentation of advance care planning. However, methodological variability, small sample sizes and non-standardized outcome measures limited comparability across studies. Conclusions: The evidence supports the early incorporation of palliative care into routine management of chronic heart failure. Early, multidisciplinary and patient-centered approaches enhance clinical and psychosocial outcomes while improving healthcare efficiency and ensuring that care aligns with patients’ goals, values and quality-of-life priorities. Full article

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14 pages, 509 KB

Open AccessReview

Sepsis and the Liver

by Eleni V. Geladari, Anastasia-Amalia C. Kalergi, Apostolos A. Evangelopoulos and Vasileios A. Sevastianos

Diseases 2025, 13(12), 388; https://doi.org/10.3390/diseases13120388 - 28 Nov 2025

Viewed by 3619

Abstract

Background/Objectives: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes. Methods: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently. [...] Read more.

Background/Objectives: Sepsis-associated liver injury (SALI) is a critical and often early complication of sepsis, defined by distinct hyper-inflammatory and immunosuppressive phases that shape patient phenotypes. Methods: Characterizing these phases establishes a foundation for immunomodulation strategies tailored to individual immune responses, as discussed subsequently. Results: The initial inflammatory response activates pathways such as NF-κB and the NLRP3 inflammasome, leading to a cytokine storm that damages hepatocytes and is frequently associated with higher SOFA scores and a higher risk of 28-day mortality. Kupffer cells and infiltrating neutrophils exacerbate hepatic injury by releasing proinflammatory cytokines and reactive oxygen species, thereby causing cellular damage and prolonging ICU stays. During the subsequent immunosuppressive phase, impaired infection control and tissue repair can result in recurrent hospital-acquired infections and a poorer prognosis. Concurrently, hepatocytes undergo significant metabolic disturbances, notably impaired fatty acid oxidation due to downregulation of transcription factors such as PPARα and HNF4α. This metabolic alteration corresponds with worsening liver function tests, which may reflect the severity of liver failure in clinical practice. Mitochondrial dysfunction, driven by oxidative stress and defective autophagic quality control, impairs cellular energy production and induces hepatocyte death, which is closely linked to declining liver function and increased mortality. The gut-liver axis plays a central role in SALI pathogenesis, as sepsis-induced gut dysbiosis and increased intestinal permeability allow bacterial products, including lipopolysaccharides, to enter the portal circulation and further inflame the liver. This process is associated with sepsis-related liver failure and greater reliance on vasopressor support. Protective microbial metabolites, such as indole-3-propionic acid (IPA), decrease significantly during sepsis, removing key anti-inflammatory signals and potentially prolonging recovery. Clinically, SALI most commonly presents as septic cholestasis with elevated bilirubin and mild transaminase changes, although conventional liver function tests are insufficiently sensitive for early detection. Novel biomarkers, including protein panels and non-coding RNAs, as well as dynamic liver function tests such as LiMAx (currently in phase II diagnostics) and ICG-PDR, offer promise for improved diagnosis and prognostication. Specifying the developmental stage of these biomarkers, such as identifying LiMAx as phase II, informs investment priorities and translational readiness. Current management is primarily supportive, emphasizing infection control and organ support. Investigational therapies include immunomodulation tailored to immune phenotypes, metabolic and mitochondrial-targeted agents such as pemafibrate and dichloroacetate, and interventions to restore gut microbiota balance, including probiotics and fecal microbiota transplantation. However, translational challenges remain due to limitations of animal models and patient heterogeneity. Conclusion: Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI. Full article

(This article belongs to the Section Gastroenterology)

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21 pages, 1911 KB

Open AccessArticle

Immunological Monitoring During Anti-CD20 Therapies to Predict Infection Risk and Treatment Response in Multiple Sclerosis Patients

by Gabriel Torres Iglesias, Ana Martínez-Feito, Laura Otero-Ortega, MariPaz López-Molina, Inmaculada Puertas, Andrea Gonzalez-Torbay, Claudia Geraldine Rita, Mireya Fernández-Fournier, Sara Sánchez Velasco, Beatriz Chamorro, Exuperio Díez-Tejedor and Eduardo López-Granados

Diseases 2025, 13(12), 387; https://doi.org/10.3390/diseases13120387 - 28 Nov 2025

Viewed by 1730

Abstract

Background: Immunological monitoring in multiple sclerosis (MS) patients treated with disease-modifying drugs may help predict infectious complications and guide treatment. The main objective of this study was to evaluate whether anti-CD20 treatments in MS patients induce immunodeficiency and whether certain immunological parameters can [...] Read more.

Background: Immunological monitoring in multiple sclerosis (MS) patients treated with disease-modifying drugs may help predict infectious complications and guide treatment. The main objective of this study was to evaluate whether anti-CD20 treatments in MS patients induce immunodeficiency and whether certain immunological parameters can predict the risk of infection and response to treatment. Methods: This retrospective, observational, single-centre study included MS patients who started treatment with ocrelizumab or rituximab and received follow-up in the Neuroimmunology Unit of our centre between January 2017 and January 2023. The study was conducted in collaboration with the Immunology Department of this hospital. Results: Fifty-five patients were included, with a mean age of 47 years and a follow-up period of 24 months. Analyses of lymphocyte subpopulations (T, B, NK) and immunoglobulin levels (IgG, IgA, IgM) were performed before treatment and at 6-, 12- and 24-month follow-ups. In addition, we carried out an exhaustive study of B cells in the baseline analysis. Sixty-four percent of patients presented infections, mostly due to COVID-19. Three patients developed cryptogenic organising pneumonia. IgG hypogammaglobulinemia was the main risk factor for developing infections. Patients with infections had fewer mature memory B cells and a lower percentage of NK cells. Furthermore, a lower proportion of naïve and mature memory B cells was associated with inflammatory activity and disease progression, respectively. The absence of CD20 depletion during follow-up was associated with clinical worsening. Conclusions: Baseline immunophenotype and immunological monitoring can help predict the risk of infections and the efficacy of anti-CD20 therapy in MS patients. Full article

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14 pages, 845 KB

Open AccessFeature PaperArticle

Impact of an Evidence-Based Bundle on Catheter-Associated Sepsis Incidence in Neonatal Intensive Care: A Quality Improvement Project

by Anna Sala, Valentina Pivetti, Francesca Castoldi, Francesca Viaroli, Marco Chiera, Gianluca Lista and Francesco Cavigioli

Diseases 2025, 13(12), 386; https://doi.org/10.3390/diseases13120386 - 28 Nov 2025

Viewed by 1112

Abstract

Background: Central line-associated bloodstream infections (CLABSIs) in neonatal intensive care units (NICUs) pose a significant risk, especially for very low birth weight infants due to their immature immune systems and the need for invasive procedures. The implementation of evidence-based bundles, as recommended by [...] Read more.

Background: Central line-associated bloodstream infections (CLABSIs) in neonatal intensive care units (NICUs) pose a significant risk, especially for very low birth weight infants due to their immature immune systems and the need for invasive procedures. The implementation of evidence-based bundles, as recommended by international guidelines, has proven effective in significantly reducing CLABSI rates, improving clinical outcomes, and lowering hospital costs. However, evidence from long-term, real-world quality-improvement programs in European NICUs—especially those using repeated PDSA cycles and detailed monitoring across multiple periods—remains limited. Methods: This quality improvement prospective study, conducted in the NICU of “V. Buzzi” Children’s Hospital, aimed to reduce high CLABSI rates using a plan-do-study-act (PDSA) framework. A multidisciplinary team developed and implemented a new evidence-based central line bundle in 2021, focusing on standardized practices, enhanced training, and monitoring. The study analyzed 594 CVCs placed in 348 neonates across a total 4-years period (P1–P12). Results: Implementation of a central line bundle significantly reduced CLABSI rates from 29.1 to 2.2 per 1000 CVC days (p-value 0.002), with notable variations during intermediate periods. Birth weight and study period progression were the only variables significantly associated with CLABSI reduction. Conclusions: Infection rates dropped significantly post-intervention, achieving zero in one of the latest periods: continuous monitoring, staff training, and targeted interventions were pivotal. Future efforts will focus on refining practices, increasing tunneled centrally inserted central catheter (CICC) use, and sustaining prevention measures. Full article

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20 pages, 918 KB

Open AccessSystematic Review

Circulating Interleukin-6 as a Prognostic Biomarker for Mortality in Melioidosis: A Systematic Review and Meta-Analysis

by Supphachoke Khemla, Chaimongkhon Chanthot, Anchalee Chittamma, Jongkonnee Thanasai, Atthaphong Phongphithakchai, Moragot Chatatikun, Jitbanjong Tangpong, Sa-ngob Laklaeng and Wiyada Kwanhian Klangbud

Diseases 2025, 13(12), 385; https://doi.org/10.3390/diseases13120385 - 27 Nov 2025

Cited by 2 | Viewed by 966

Abstract

Background: Melioidosis, caused by Burkholderia pseudomallei, remains a major cause of sepsis-related mortality in tropical regions. Despite effective antimicrobial therapy, deaths frequently result from dysregulated host inflammation rather than uncontrolled bacterial replication. Interleukin-6 (IL-6), a key mediator of systemic inflammation, has been [...] Read more.

Background: Melioidosis, caused by Burkholderia pseudomallei, remains a major cause of sepsis-related mortality in tropical regions. Despite effective antimicrobial therapy, deaths frequently result from dysregulated host inflammation rather than uncontrolled bacterial replication. Interleukin-6 (IL-6), a key mediator of systemic inflammation, has been proposed as a prognostic biomarker in sepsis, but its predictive value in melioidosis has not been systematically evaluated. Methods: A systematic review and meta-analysis were performed following PRISMA 2020 guidelines (PROSPERO CRD420251152797). MEDLINE, Embase, and Scopus were searched from inception to 15 March 2025. Eligible studies included patients with culture-confirmed melioidosis reporting circulating IL-6 concentrations stratified by survival outcome. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random effects models. Heterogeneity and robustness were examined through leave-one-out and sensitivity analyses. Publication bias assessment was not performed due to insufficient study numbers (n = 4). Results: Eight studies were included qualitative systematic review, and four studies comprising 411 patients were eligible for quantitative meta-analysis. Pooled analysis demonstrated significantly higher IL-6 levels among non-survivors compared with survivors (SMD = 0.80, 95% CI 0.02–1.57; I² = 86.3%). Leave-one-out diagnostics indicated no single study unduly influenced the pooled effect. Sensitivity analysis excluding the largest dataset reduced heterogeneity to 34.5% and yielded an SMD of 0.51 (95% CI −0.28–1.30), maintaining the same direction of association. Conclusions: Circulating IL-6 levels are elevated in fatal melioidosis and may serve as a promising prognostic biomarker for mortality. Although interstudy heterogeneity was substantial, the association remained consistent in direction across populations and analytical methods despite the limited number of eligible studies. These findings support further prospective validation of IL-6 in clinical risk stratification and host response-guided management of severe melioidosis, though larger multicenter studies are needed to confirm these preliminary findings. Full article

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13 pages, 666 KB

Open AccessArticle

Hospital-Acquired Infections Caused by Acinetobacter baumannii: A Comparative Analysis of Risk Factors with Other ESKAPE-E Pathogens in a Third-Level IMSS Hospital in Yucatan Mexico

by Jael del Rosario Eb-Rejón, José Ramón Paniagua-Sierra, Carlos Gracida-Osorno and Gloria María Molina-Salinas

Diseases 2025, 13(12), 384; https://doi.org/10.3390/diseases13120384 - 26 Nov 2025

Cited by 2 | Viewed by 1243

Abstract

Background: Acinetobacter baumannii is classified within the ESKAPE-E group of pathogens, recognized for its role in causing severe infections, and is often associated with various healthcare-related infection (HAIs) types, particularly in intensive care units. This opportunistic pathogen is distinguished by its considerable antibiotic [...] Read more.

Background: Acinetobacter baumannii is classified within the ESKAPE-E group of pathogens, recognized for its role in causing severe infections, and is often associated with various healthcare-related infection (HAIs) types, particularly in intensive care units. This opportunistic pathogen is distinguished by its considerable antibiotic resistance and is associated with prolonged hospital stays, high medical costs, and increased mortality rates. Objective: This study investigated factors associated with HAIs caused by A. baumannii, versus other ESKAPE-E pathogens, to identify distinguishing intrinsic and extrinsic factors that guide the control and prevention of HAIs within our hospital. Methods: This study included patients from a Third-Level IMSS Hospital in Mérida, Mexico, between 2018 and 2022, with 54 cases (HAIs caused by A. baumannii) and 108 matched controls (HAIs caused by other ESKAPE-E pathogens). Results: Ventilator-associated pneumonia was the most frequent HAI in both groups, followed by catheter-related bloodstream infections. Comorbidities were more common in patients with HAIs caused by A. baumannii than in those with other ESKAPE-E pathogens. Most patients received antimicrobial treatment before HAIs development. Bivariate analysis showed that comorbidities and prior meropenem and linezolid treatment were significant risk factors, whereas multivariate analysis identified comorbidities and prior meropenem use as risk factors for A. baumannii HAIs versus other ESKAPE-E pathogens. Most A. baumannii isolates were extensively drug-resistant (90.7%), with 84% showing carbapenem resistance. Conclusions: This study highlights the importance of optimizing antimicrobial use and measures to mitigate A. baumannii HAIs. These findings have significant implications for infection control and antimicrobial stewardship in healthcare settings. Full article

(This article belongs to the Section Infectious Disease)

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23 pages, 2391 KB

Open AccessSystematic Review

Regional Cerebral Oxygen Saturation and Risk of Delirium: A Systematic Review and Meta-Analysis

by Begoña Rochina-Rodríguez, Francisco Miguel Martínez-Arnau and Pilar Pérez-Ros

Diseases 2025, 13(12), 383; https://doi.org/10.3390/diseases13120383 - 25 Nov 2025

Cited by 1 | Viewed by 1607

Abstract

Background: Delirium onset is associated with increased comorbidity and mortality. Identifying reliable delirium biomarkers remains challenging. Regional cerebral oxygen saturation (rSO₂) offers an objective, easily obtainable measure suitable for hospital monitoring. Objective: We aimed to analyse the relationship between regional cerebral [...] Read more.

Background: Delirium onset is associated with increased comorbidity and mortality. Identifying reliable delirium biomarkers remains challenging. Regional cerebral oxygen saturation (rSO₂) offers an objective, easily obtainable measure suitable for hospital monitoring. Objective: We aimed to analyse the relationship between regional cerebral oxygen saturation (rSO₂) values obtained by near-infrared spectroscopy (NIRS) and the subsequent development of delirium. Methods: Studies eligible for inclusion in our systematic review evaluated rSO₂ values obtained by NIRS or a used a similar method to study hospitalised patients aged 18 years or older, some of whom subsequently developed delirium. We searched MEDLINE, Scopus and Web of Science without restrictions to 24 March 2024. Two review authors independently assessed the methodological quality of the included studies using Joanna Briggs Institute Critical Appraisal tools. Using a random-effects model in RevMan v 5.4.0 (Cochrane Collaboration, Oxford, UK), we analysed baseline and minimum rSO₂ values. Results were presented as means and mean differences (MDs) with their 95% confidence intervals (CIs). We followed PRISMA guidelines and registered our review protocol in PROSPERO (CRD42024523573). Results (or Findings): We included 22 studies (20 in the meta-analysis) published between 2009 and 2024 and involving 5757 participants. The delirium group had a lower mean baseline rSO₂ value (62.47%, 95% CI 58.40 to 66.55) compared with the non-delirium group (64.24%, 95% CI 61.33 to 67.15). Meta-analysis of effect estimates confirmed this result (MD −2.92%, 95% CI −4.38 to −1.47). The MD between the delirium and non-delirium group was larger among patients assessed with the INVOS device and patients who underwent cardiac surgery. Studies that analysed baseline values according to sensor location showed a larger MD in rSO₂ values obtained via a right-sided sensor. Conclusions: Our results show lower baseline and minimum rSO₂ in hospitalised patients who subsequently developed delirium. The difference varies according to the type of surgery and type of NIRS monitor. Full article

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

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13 pages, 1262 KB

Open AccessCase Report

Early CytoSorb Hemoadsorption in a Neutropenic Acute Myeloid Leukemia Patient with Carbapenem-Resistant Pseudomonas Septic Shock and ARDS

by Wei-Hung Chang, Ting-Yu Hu and Li-Kuo Kuo

Diseases 2025, 13(12), 382; https://doi.org/10.3390/diseases13120382 - 24 Nov 2025

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Abstract

Neutropenic patients with acute myeloid leukemia (AML) are at high risk for severe, multidrug-resistant infections. Sepsis due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) in this population often leads to septic shock and acute respiratory distress syndrome (ARDS), with historically poor outcomes. CytoSorb™ hemoadsorption has [...] Read more.

Neutropenic patients with acute myeloid leukemia (AML) are at high risk for severe, multidrug-resistant infections. Sepsis due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) in this population often leads to septic shock and acute respiratory distress syndrome (ARDS), with historically poor outcomes. CytoSorb™ hemoadsorption has been proposed as an adjunctive therapy for refractory septic shock, but evidence in hematologic malignancies remains limited. This report describes a 29-year-old male with newly diagnosed AML complicated by neutropenic fever, bacteremia due to CRPA, and subsequent hospital-acquired pneumonia progressing to ARDS. Despite multiple antibiotic regimens and aggressive intensive care management, including mechanical ventilation, prone positioning, and continuous renal replacement therapy (CRRT), the patient developed refractory septic shock with persistent lactic acidosis and elevated inflammatory markers. Early adjunctive CytoSorb hemoadsorption was initiated, guided by maximal CytoScore criteria, as part of a comprehensive supportive strategy. Following CytoSorb therapy, the patient demonstrated transient hemodynamic and biochemical improvement; however, profound neutropenia and multi-organ failure persisted. Microbiological clearance of CRPA was not achieved; given confirmed colistin susceptibility and unknown carbapenemase mechanism, a salvage combination of colistin plus ceftazidime–avibactam was employed. Transient hemodynamic improvement was observed after CytoSorb initiation; however, cytokine assays were not performed, and microbiological clearance was not achieved, precluding any mechanistic attribution to CytoSorb. This case highlights the complexity of managing CRPA sepsis and ARDS in neutropenic AML patients, and the challenges in attributing observed clinical improvement to CytoSorb therapy in the context of multiple simultaneous interventions. The absence of cytokine assays (e.g., IL-6, TNF-α) precludes any mechanistic attribution of observed changes to cytokine adsorption, and interpretation should remain descriptive rather than causal. Observed transient changes occurred amid simultaneous interventions (broad-spectrum antibiotics, CRRT, prone ventilation, corticosteroids, and filgrastim), precluding attribution to any single therapy, including CytoSorb. Given the fatal outcome and persistent CRPA positivity, the clinical impact of this observation is limited, and the generalizability of a single-case report is restricted. Cautious interpretation is warranted, and CytoSorb may be considered as part of a comprehensive care bundle rather than as a standalone solution. Alternative tetracycline-based combinations were reviewed but not adopted under our center’s salvage protocol for this XDR presentation. Future studies are warranted to clarify its clinical benefit and optimal timing in this population. Full article

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14 pages, 249 KB

Open AccessReview

Biological and Therapeutic Roles of Stem Cells in Head and Neck Carcinoma: Implications for Maxillofacial Surgery

by Luca Michelutti, Alessandro Tel, Marco Zeppieri, Chiara Martinazzo, Massimo Robiony, Caterina Gagliano, Fabiana D’Esposito, Matteo Capobianco and Marieme Khouyyi

Diseases 2025, 13(12), 381; https://doi.org/10.3390/diseases13120381 - 22 Nov 2025

Viewed by 811

Abstract

Background: Head and neck carcinomas represent a heterogeneous group of aggressive malignancies with often poor prognosis and high recurrence rates. In recent years, the identification and characterization of cancer stem cells (CSCs) within these tumors have profoundly reshaped our understanding of tumorigenesis, [...] Read more.

Background: Head and neck carcinomas represent a heterogeneous group of aggressive malignancies with often poor prognosis and high recurrence rates. In recent years, the identification and characterization of cancer stem cells (CSCs) within these tumors have profoundly reshaped our understanding of tumorigenesis, resistance mechanisms, and metastatic potential in this anatomical district. Cancer stem cells (CSCs) play a central role in therapeutic resistance, recurrence, and metastatic progression in head and neck squamous cell carcinoma (HNSCC), particularly within the anatomically complex maxillofacial region. This review has synthesized recent advances in CSC biology, including marker heterogeneity, stemness-associated pathways, and interactions with the tumor microenvironment. Methods: A narrative review of the available literature was conducted, focusing on studies dealing with cancer stem cells in head and neck carcinoma and their implications for maxillofacial surgery. Results: We have critically examined emerging systemic and locoregional CSC-targeted therapies, highlighting inhibitors of Notch, Wnt/β-catenin, Hedgehog, and Hippo/YAP pathways, ALDH and ABC transporter inhibitors, autophagy modulators, nanoparticle-based delivery systems, and CSC-directed immunotherapies. The implications of these approaches for surgical planning, resection margins, and postoperative disease control in maxillofacial oncology have been discussed. To enhance clarity and analytical value, we have incorporated two comprehensive tables summarizing CSC markers and therapeutic strategies. Collectively, the evidence indicates that integrating CSC-oriented diagnostics and therapeutics into multimodal management may improve long-term outcomes for patients with maxillofacial HNSCC. Conclusions: This review highlights the critical need for integrating CSC-focused research into clinical practice to develop more effective, personalized, and durable treatment strategies. Such an approach could enhance oncologic control, reduce recurrence, and improve functional outcomes for patients undergoing complex oncologic procedures in the maxillofacial region. Full article

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Diseases, Volume 13, Issue 12 (December 2025) – 28 articles

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