Next Issue
Volume 13, May
Previous Issue
Volume 13, March
 
 

Diseases, Volume 13, Issue 4 (April 2025) – 37 articles

Cover Story (view full-size image): Diseases (ISSN: 2079-9721) provides an advanced forum for studies related to human diseases and conditions. It publishes original research, reviews, communications, and short notes as well as Special Issues on particular subjects. The aim of Diseases is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, the journal has no restriction on the maximum length of the papers. Full experimental details should be provided so that the results can be reproduced.
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
11 pages, 1096 KiB  
Article
Clinical Importance of B-Type Natriuretic Peptide Levels in Sinus Rhythm at 3 Months After Persistent Atrial Fibrillation Ablation
by Jumpei Saito, Toshihiko Matsuda, Yui Koyanagi, Katsuya Yoshihiro, Yuma Gibo, Soichiro Usumoto, Wataru Igawa, Toshitaka Okabe, Naoei Isomura and Masahiko Ochiai
Diseases 2025, 13(4), 126; https://doi.org/10.3390/diseases13040126 - 21 Apr 2025
Abstract
Background: B-type natriuretic peptide (BNP) levels after ablation have been associated with a risk of arrhythmia recurrence (AR) after atrial fibrillation (AF) ablation. In addition, baseline BNP levels were also predictors of AR after AF ablation. However, previous studies have not been clear [...] Read more.
Background: B-type natriuretic peptide (BNP) levels after ablation have been associated with a risk of arrhythmia recurrence (AR) after atrial fibrillation (AF) ablation. In addition, baseline BNP levels were also predictors of AR after AF ablation. However, previous studies have not been clear about whether sinus rhythm (SR) or AF was present at the time of BNP measurement. In this study, we investigated BNP levels in SR at 1,3 months after persistent AF ablation. Methods: We followed up 178 patients with persistent AF undergoing first-time arrhythmia ablation. BNP levels were measured before 1 and 3 months later after AF ablation in SR. The correlation between AR within 1 year after AF ablation and measured BNP levels was examined. Results: A total of 178 cases (81 males, mean age 69 (60, 74), mean CHA2DS2 Vasc score 2 (0, 4)) with persistent AF were included for ablation. BNP levels before AF ablation were not significantly different between AR and not AR patients. The BNP levels of AR patients were significantly elevated from 1 month to 3 months after the procedure compared with those without (−11.1 pg/mL (−53, 5.7) vs. 17.8 pg/mL (−58.3, 180.5), p < 0.0001). Elevated BNP levels in SR after AF ablation were a significant predictor of AR. Conclusions: Elevated BNP levels in SR 3 months after AF ablation compared with BNP levels 1 month after persistent AF ablation might be a significant prognostic factor in AR. Full article
Show Figures

Figure 1

9 pages, 1432 KiB  
Case Report
Patient with Secondary Amyloidosis Due to Crohn’s Disease on Hemodialysis Effectively Treated with Ferric Carboxymaltose Injections: A Case Report and Literature Review
by Masayo Ueno, Fumihito Hirai, Asami Fuji, Yuko Shimomura, Keiko Uemoto, Kosuke Masutani and Takao Saito
Diseases 2025, 13(4), 125; https://doi.org/10.3390/diseases13040125 - 21 Apr 2025
Abstract
Background: Almost all patients undergoing dialysis develop renal anemia and receive medicines such as erythropoietin and iron preparations. However, the conventional intravenous treatment with saccharated ferric oxide (SFO) is insufficient for these patients when they have incurable and persistent iron deficiency anemia due [...] Read more.
Background: Almost all patients undergoing dialysis develop renal anemia and receive medicines such as erythropoietin and iron preparations. However, the conventional intravenous treatment with saccharated ferric oxide (SFO) is insufficient for these patients when they have incurable and persistent iron deficiency anemia due to secondary amyloidosis. Therefore, we administered 500 mg of ferric carboxymaltose (FCM) to such a patient with Crohn’s disease. Case presentation: A 56-year-old man on maintenance hemodialysis had secondary amyloidosis due to Crohn’s disease. Additionally, he was anemic and received 40 mg of SFO weekly; however, his hemoglobin (Hb) level remained low at 7 g/dL. Therefore, 500 mg of FCM was administered bimonthly from the first to the fourth dose, and the Hb level temporarily increased compared to that after the previous SFO administration. Since bimonthly administration did not adequately maintain the Hb level, FCM was administered monthly from the 5th to 12th dose, which stabilized the Hb level at 10–12 g/dL. No side effects, such as hypophosphatemia, were observed. Conclusions: A single dose of 500 mg FCM administered once every 1–2 months stabilizes the Hb level and contributes to efficient iron utilization in patients with incurable anemia undergoing hemodialysis. Full article
Show Figures

Figure 1

30 pages, 1119 KiB  
Systematic Review
Rabies Vaccination and Public Health Insights in the Extended Arabian Gulf and Saudi Arabia: A Systematic Scoping Review
by Helal F. Hetta, Khalid S. Albalawi, Amal M. Almalki, Nasser D. Albalawi, Abdulmajeed S. Albalawi, Suleiman M. Al-Atwi, Saleh E. Alatawi, Mousa J. Alharbi, MeshaL F. Albalawi, Ahmad A. Alharbi, Hassabelrasoul Elfadil, Abdullah S. Albalawi and Reem Sayad
Diseases 2025, 13(4), 124; https://doi.org/10.3390/diseases13040124 - 21 Apr 2025
Abstract
Background and Aim: This systematic scoping review examines rabies-related incidents, interventions, and post-exposure immunoprophylaxis in the Arabian Gulf region and Saudi Arabian Peninsula. Methods: A comprehensive literature search was conducted in databases including PubMed, Scopus, WoS, MedLine, and Cochrane Library up to July [...] Read more.
Background and Aim: This systematic scoping review examines rabies-related incidents, interventions, and post-exposure immunoprophylaxis in the Arabian Gulf region and Saudi Arabian Peninsula. Methods: A comprehensive literature search was conducted in databases including PubMed, Scopus, WoS, MedLine, and Cochrane Library up to July 2024. Studies were included discussing the reported cases of rabies that received the PEP in all countries of the Arabian Gulf, their epidemiological data, the received schedules of vaccination, and their safety. The search was done by using the following terminologies: rabies vaccine, rabies human diploid cell vaccine, vaccine, Saudi Arabia, Bahrain, Iraq, Kuwait, Oman, Qatar, United Arab Emirates, Southwest Asia, Iran, West Asia, Western Asia, Persian Gulf, Arabian Gulf, Gulf of Ajam, Saudi Arabian Peninsula, and The Kingdom of Saudi Arabia. Results: The systematic scoping review included 36 studies, synthesizing findings from diverse research designs, including large-scale cross-sectional studies and case reports, spanning nearly three decades. Findings indicated that young males in urban areas are most at risk for animal bites, predominantly from domestic dogs and cats. While post-exposure prophylaxis (PEP) was generally administered within recommended timeframes, vaccination completion rates varied. Conclusions: The review highlighted gaps in public awareness about rabies risks and prevention. Vaccine safety profiles were generally favorable, with mostly mild-to-moderate side effects reported. The study underscores the need for enhanced public health education, standardized PEP protocols, and a One Health approach to rabies prevention. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology 2024)
Show Figures

Figure 1

11 pages, 1009 KiB  
Article
Correlation of Inflammatory Biomarkers and IgG4 Antibodies with Malaria in Cameroon’s Buea Municipality Children
by Jerome Nyhalah Dinga, Flora Ayah, Emmanuel Fondungallah Anu, Haowen Qin, Stanley Dobgima Gamua, Anthony Kukwah Tufon, Magloire Essissima Amougou and Rameshbabu Manyam
Diseases 2025, 13(4), 123; https://doi.org/10.3390/diseases13040123 - 21 Apr 2025
Abstract
Background: In recent decades, malaria has become a major worldwide public health problem in endemic countries, especially with children below five years. Malaria causes inflammation, and inflammatory biomarkers like α-1-glycoprotein (AGP) and C-reactive protein (CRP) are elevated in serum during malaria. This work [...] Read more.
Background: In recent decades, malaria has become a major worldwide public health problem in endemic countries, especially with children below five years. Malaria causes inflammation, and inflammatory biomarkers like α-1-glycoprotein (AGP) and C-reactive protein (CRP) are elevated in serum during malaria. This work aimed at assessing the serum levels of AGP (chronic inflammation) and CRP (acute inflammation) biomarkers and IgG4 and their correlation with malaria in children below five years in the Buea Health District of the South West Region of Cameroon. Methods: This cross-sectional study was carried out between February and April, 2024. AGP and CRP were measured using Q-7plex Human Micronutrient Measurement Kit while IgG4 levels were measured using Enzyme-Linked Immunosorbent Assay with 80 samples. Results: Serum AGP and CRP biomarker levels were significantly higher in malaria-positive children compared to malaria-negative children (p < 0.001 and p < 0.001, respectively). IgG4 levels were high in malaria-negative children (mean OD = 0.51) compared to children infected with the malaria parasite (mean OD = 0.29), in a manner that was statistically significant (p < 0.03). Hemoglobin (Hb) had a strong negative correlation with AGP (−0.62) and CRP (−0.46), meaning that as Hb levels increased, AGP and CRP levels decreased. CRP had a strong positive correlation with both age (0.3) and AGP (0.5), suggesting that as age increased or as AGP levels rose, CRP levels tended to increase as well. Conclusions: This study revealed that malaria causes alterations in the serum levels of AGP, CRP, and IgG4 in children below the age of 5 in the Buea municipality of Cameroon. It impacts immune responses by increasing the level of inflammation biomarkers like AGP and CRP and decreasing IgG4, a marker associated with immune regulation. Thus, this study helps the understanding of the inflammatory nature of malaria and could be expanded to aid in the broader public health efforts to control and prevent malaria, reduce its complications, and improve overall health outcomes in children in the Buea municipality. Full article
Show Figures

Figure 1

11 pages, 235 KiB  
Article
Clinical Trial: Effects of Autologous Dendritic Cell Administration on Renal Hemodynamics and Inflammatory Biomarkers in Diabetic Kidney Disease
by Endang Drajat, Aziza Ghanie Icksan, Jonny Jonny, Aditya Pratama Lokeswara, Bhimo Aji Hernowo, Elvita Rahmi Daulay and Terawan Agus Putranto
Diseases 2025, 13(4), 122; https://doi.org/10.3390/diseases13040122 - 21 Apr 2025
Abstract
Background: Diabetic kidney disease (DKD) is a significant risk factor for End-Stage Renal Disease, with a high global incidence and mortality rate. Hyperglycemia in DKD induces inflammation, contributing to glomerular hyperfiltration, fibrosis, and impaired renal function. Current therapies, including SGLT2 inhibitors, ACE inhibitors, [...] Read more.
Background: Diabetic kidney disease (DKD) is a significant risk factor for End-Stage Renal Disease, with a high global incidence and mortality rate. Hyperglycemia in DKD induces inflammation, contributing to glomerular hyperfiltration, fibrosis, and impaired renal function. Current therapies, including SGLT2 inhibitors, ACE inhibitors, and ARBs, show limited efficacy. Autologous dendritic cells (DCs) offer potential anti-inflammatory effects by reducing cytokine activity and fibrosis biomarkers. Methods: A quasi-experimental pretest–post-test design was conducted involving 29 DKD patients. Baseline blood and urine samples were collected for MMP-9, TGF-β, and Doppler ultrasound (PSV, EDV) measurements. The subjects received subcutaneous injections of autologous DCs, and follow-up measurements were conducted four weeks after treatment. The statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and linear regression. Results: After treatment, there were a significant decrease in PSV (from 47.1 ± 23.87 cm/s to 27.85 ± 20.53 cm/s, p = 0.044) and a significant increase in EDV (from 13 ± 5.32 cm/s to 15.7 ± 12.55 cm/s, p = 0.039). A strong correlation was observed between the TGF-β and MMP-9 levels (p = 0.001). Linear regression analysis showed reduced MMP-9 influence on the TGF-β after treatment, suggesting potential fibrosis reduction. Gender and UACR subgroup analyses revealed significant PSV and EDV improvements in females and the microalbuminuria group. Conclusion: Autologous dendritic cell therapy significantly improved renal hemodynamics and showed potential to reduce fibrosis by modulating TGF-β and MMP-9 levels in DKD patients, warranting further investigation. Full article
13 pages, 515 KiB  
Article
Exploring Self-Perceived Stress and Anxiety Throughout Pregnancy: A Longitudinal Study
by Mar Miguel Redondo, Cristina Liebana-Presa, Javier Pérez-Rivera, Cristian Martín-Vázquez, Natalia Calvo-Ayuso and Rubén García-Fernández
Diseases 2025, 13(4), 121; https://doi.org/10.3390/diseases13040121 - 19 Apr 2025
Viewed by 119
Abstract
Background: Anxiety and stress are common during pregnancy and can impact the health of the pregnant woman and the newborn. There is a lack of research focused on identifying weaknesses that promote equity in the care of pregnant women. The objective of this [...] Read more.
Background: Anxiety and stress are common during pregnancy and can impact the health of the pregnant woman and the newborn. There is a lack of research focused on identifying weaknesses that promote equity in the care of pregnant women. The objective of this study was to describe the levels of anxiety and stress during the three trimesters of pregnancy and to compare whether there are differences according to obstetric and gynecological variables. Methods: A descriptive prospective longitudinal and correlational observational study was carried out. Non-probability sampling was carried out with 176 women. The Pregnancy-Related Anxiety Questionnaire and the Perceived Stress Scale were used. Results: The prevalence of anxiety was 23.9%, 17%, and 17.6%, and mean stress scores reached 32.24, 33.02, and 49.74 in the first, second, and third trimesters, respectively. In comparison, without miscarriages, anxiety was higher during the first trimester. In multiparous women who had suffered a miscarriage, anxiety was higher in the first trimester. Conclusions: Anxiety is higher during the first trimester. Mean stress levels are higher during the third trimester compared to the other two trimesters. Care for these vulnerable pregnant women can impact society’s health system and align with the Sustainable Development Goals of Health and Well-being and Gender Equality in others. Full article
Show Figures

Figure 1

9 pages, 254 KiB  
Article
Factors Influencing Physical Performance and Quality of Life in Post-COVID-19 Patients
by Ajchamon Thammachai, Patchareeya Amput and Sirima Wongphon
Diseases 2025, 13(4), 120; https://doi.org/10.3390/diseases13040120 - 19 Apr 2025
Viewed by 95
Abstract
Background: This study aims to identify the factors related to demographic variables and physical performance associated with quality of life (QoL) in post-COVID-19 pa-tients who have recovered from mild infection and were not hospitalized. Methods: Seventy-four post-COVID-19 individuals who recovered from [...] Read more.
Background: This study aims to identify the factors related to demographic variables and physical performance associated with quality of life (QoL) in post-COVID-19 pa-tients who have recovered from mild infection and were not hospitalized. Methods: Seventy-four post-COVID-19 individuals who recovered from mild COVID-19 infec-tion were assessed for the baseline demographic variables (age, sex, height, weight, body mass index; BMI) and clinical information (comorbidities, duration of COVID-19 infection, and exercise habits). Vital signs (heart rate, blood pressure, and oxygen sat-uration; SpO2) were measured. Physical performance was evaluated for upper- and lower-limb muscle strength, ability of balance, and cardiorespiratory performance. All participants were assessed for QoL. Results: Hand grip strength was negatively asso-ciated with gender and age while positively associated with the duration of COVID-19. Quadricep strength also showed a negative association with gender and duration of COVID-19. Age was positively associated with multiple quality of life dimensions, while emotional role limitations were negatively associated with the duration of COVID-19 and waist circumference. Mental health was negatively linked to BMI. Conclusions: This study highlights the complex impact of COVID-19 on physical per-formance and QoL, revealing that older adults often report better QoL despite reduced muscle strength, particularly in women. The findings emphasize the need for targeted rehabilitation programs addressing both physical and emotional health for vulnerable groups. Full article
10 pages, 587 KiB  
Brief Report
Possible Significance of Neutrophil–Hemoglobin Ratio in Differentiating Progressive Supranuclear Palsy from Depression: A Pilot Study
by Michał Markiewicz, Natalia Madetko-Alster, Dagmara Otto-Ślusarczyk, Karolina Duszyńska-Wąs, Bartosz Migda, Patryk Chunowski, Marta Struga and Piotr Alster
Diseases 2025, 13(4), 119; https://doi.org/10.3390/diseases13040119 - 18 Apr 2025
Viewed by 166
Abstract
Background: Research has associated chronic inflammation with the evolution of neurological and psychiatric disorders. Neurodegenerative diseases, including Parkinson’s Disease (PD), Alzheimer’s Disease (AD), and less common ones such as Progressive Supranuclear Palsy (PSP), are commonly linked to depression. However, the pathomechanisms and the [...] Read more.
Background: Research has associated chronic inflammation with the evolution of neurological and psychiatric disorders. Neurodegenerative diseases, including Parkinson’s Disease (PD), Alzheimer’s Disease (AD), and less common ones such as Progressive Supranuclear Palsy (PSP), are commonly linked to depression. However, the pathomechanisms and the role of neuroinflammation in these disorders remain unclear; therefore, interest is increasing in easily accessible inflammatory morphological assessments of blood samples, such as the neutrophil-to-lymphocyte ratio (NLR), the neutrophil-to-monocyte ratio (NMR), and the neutrophil-to-hemoglobin ratio (N/HGBR). Methods: The authors analyzed 15 age-matched controls and 21 patients with PSP; the PSP group was additionally divided into 11 patients without depression (PSP) and 10 with depression (Beck Depression Inventory [BDI] ≥ 14) (PSP-D). Results: In the PSP-D group, the level of N/HGBR was significantly lower than in the controls (p = 0.01), but there were no significant differences in any other neutrophil-derived parameters or comparisons of morphological blood assessment. Patients with PSP-D exhibited a marginally significant decrease in neutrophil levels compared to the controls. Conclusions: This is the first study highlighting the possible significance of peripheral inflammatory factors in patients with PSP affected by depression. It highlights possible tendencies in the area of non-specific inflammatory markers and suggests their relation to affective disorders in PSP. Full article
(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)
Show Figures

Figure 1

11 pages, 1326 KiB  
Article
False-Positive Galactomannan Test Results in Multiple Myeloma
by Shingen Nakamura, Yusaku Maeda, Ryohei Sumitani, Masahiro Oura, Kimiko Sogabe, Hikaru Yagi, Shiro Fujii, Takeshi Harada, Ken-ichi Matsuoka and Hirokazu Miki
Diseases 2025, 13(4), 118; https://doi.org/10.3390/diseases13040118 - 17 Apr 2025
Viewed by 122
Abstract
Background/Objectives: Invasive pulmonary aspergillosis (IA) is a common infectious disease in patients with hematological diseases. The prevention, early detection, and establishment of treatment strategies for IA are important. The serum galactomannan antigen (GM) mycological test for IA diagnosis, included in the mycology criteria [...] Read more.
Background/Objectives: Invasive pulmonary aspergillosis (IA) is a common infectious disease in patients with hematological diseases. The prevention, early detection, and establishment of treatment strategies for IA are important. The serum galactomannan antigen (GM) mycological test for IA diagnosis, included in the mycology criteria of the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG), is widely used because of its high sensitivity and specificity. However, false-positive results are a concern. Methods: We retrospectively analyzed all GM tests performed at our department in the clinical practice setting between April 2003 and January 2012. Results: Of the 330 cases and 2155 samples analyzed, 540 (25%) were positive (≥0.5). Among the underlying diseases, positivity rates were the highest for multiple myeloma (MM), with 61.3%. By type, positivity rates for IgG, IgA, Bence-Jones protein, and IgD were 71.7%, 33.3%, 57.1%, and 34.6%, respectively. Seventeen out of eighteen cases that were GM-positive at MM diagnosis were false positives, according to the 2008 EORTC/MSG criteria. The IgG and GM values were not directly correlated. Of the seventeen false-positive cases identified, two developed IA during anti-myeloma treatments, and GM values did not become negative during the treatment in most cases. Conclusions: Although subclinical IA may be included in a higher GM index, the results may be prone to false positives; particularly in IgG-type MM, the results should thus be interpreted cautiously. Full article
Show Figures

Figure 1

15 pages, 479 KiB  
Review
Neurogenic Bladder in Children with Myelomeningocele
by Aleksandar Sič, Borko Stojanović and Miroslav Đorđević
Diseases 2025, 13(4), 117; https://doi.org/10.3390/diseases13040117 - 17 Apr 2025
Viewed by 187
Abstract
Myelomeningocele (MMC), a severe congenital anomaly resulting from neural tube closure defects, poses significant urological challenges necessitating specialized care. This review explores the intricate landscape of MMC within urological practice, advocating for a multidisciplinary approach to optimize patient outcomes. By surveying diverse treatment [...] Read more.
Myelomeningocele (MMC), a severe congenital anomaly resulting from neural tube closure defects, poses significant urological challenges necessitating specialized care. This review explores the intricate landscape of MMC within urological practice, advocating for a multidisciplinary approach to optimize patient outcomes. By surveying diverse treatment modalities, this review aims to offer insights into enhancing urological management strategies for MMC and guiding future research directions. At the heart of the conversation lies the pathophysiology of neurogenic bladder dysfunction in children with MMC, with a particular focus on the complexities of diagnosis and the various paradigms guiding urological management. Common complications such as recurrent urinary tract infections are examined alongside non-surgical interventions like intermittent catheterization (CIC) and pharmacotherapy, notably oxybutynin. Additionally, surgical options including botulinum toxin injection and reconstructive procedures are explored to enhance urological outcomes for affected children. By unpacking the complexities of neurogenic bladder dysfunction in MMC, this review emphasizes the imperative of a collaborative, multidisciplinary approach in urological care, ultimately aiming to enhance patient well-being and functional outcomes. Full article
Show Figures

Figure 1

11 pages, 1703 KiB  
Article
The Effect of Autologous Dendritic Cell Therapy on Renal Perfusion in Diabetic Kidney Disease: Analysis of Doppler Ultrasound and Angiogenesis Biomarkers
by Ardianto Pramono, Jonny, Djuwita Adi Wahyono, Aditya Pratama Lokeswara, Enda Cindylosa Sitepu, Ermi Girsang and Terawan Agus Putranto
Diseases 2025, 13(4), 116; https://doi.org/10.3390/diseases13040116 - 16 Apr 2025
Viewed by 141
Abstract
Background: Diabetes mellitus (DM) is a global health challenge with a severe health burden. Approximately 40% of diabetic patients develop diabetic kidney disease (DKD), leading to kidney failure. Autologous dendritic cell therapy may enhance renal function by modulating vascular markers. Methods: Involving 35 [...] Read more.
Background: Diabetes mellitus (DM) is a global health challenge with a severe health burden. Approximately 40% of diabetic patients develop diabetic kidney disease (DKD), leading to kidney failure. Autologous dendritic cell therapy may enhance renal function by modulating vascular markers. Methods: Involving 35 patients, this quasi-experimental study assessed the pulsatility index (PI), resistive index (RI), vascular endothelial growth factor (VEGF), and endothelin levels before and four weeks following autologous dendritic cell administration. Results: A significant reduction in median PI was found from 1.61 ± 0.63 to 1.21 ± 0.26 (p < 0.001). The increase in mean RI was insignificant from 0.74 ± 0.07 to 0.75 ± 0.06 (p = 0.17). The median VEGF showed a slight reduction from 522.10 ± 608.6 to 473.70 ± 550 (p = 0.589) and endothelin from 1.74 ± 0.71 to 1.63 ± 0.76 (p = 0.554). Conclusions: This study shows that autologous dendritic cell therapy may improve kidney perfusion in DKD patients, indicated by a significant reduction in the PI. These findings suggest potential therapeutic benefits for renal perfusion in DKD. Full article
Show Figures

Figure 1

20 pages, 3056 KiB  
Review
Artificial Sweeteners: A Double-Edged Sword for Gut Microbiome
by Helal F. Hetta, Nizar Sirag, Hassabelrasoul Elfadil, Ayman Salama, Sara F. Aljadrawi, Amani J. Alfaifi, Asma N. Alwabisi, Bothinah M. AbuAlhasan, Layan S. Alanazi, Yara A. Aljohani, Yasmin N. Ramadan, Noura H. Abd Ellah and Abdelazeem M. Algammal
Diseases 2025, 13(4), 115; https://doi.org/10.3390/diseases13040115 - 15 Apr 2025
Viewed by 643
Abstract
Background and Aim: The human gut microbiome plays a crucial role in maintaining health. Artificial sweeteners, also known as non-nutritive sweeteners (NNS), have garnered attention for their potential to disrupt the balance of the gut microbiome. This review explores the complex relationship [...] Read more.
Background and Aim: The human gut microbiome plays a crucial role in maintaining health. Artificial sweeteners, also known as non-nutritive sweeteners (NNS), have garnered attention for their potential to disrupt the balance of the gut microbiome. This review explores the complex relationship between NNS and the gut microbiome, highlighting their potential benefits and risks. By synthesizing current evidence, we aim to provide a balanced perspective on the role of AS in dietary practices and health outcomes, emphasizing the need for targeted research to guide their safe and effective use. Methods: A comprehensive literature review was conducted through searches in PubMed and Google Scholar, focusing on the effects of artificial sweeteners on gut microbiota. The search utilized key terms including “Gut Microbiome”, “gut microbiota”, “Eubiosis”, “Dysbiosis”, “Artificial Sweeteners”, and “Nonnutritive Sweeteners”. Results: NNS may alter the gut microbiome, but findings remain inconsistent. Animal studies often report a decrease in beneficial bacteria like Bifidobacterium and Lactobacillus, and an increase in harmful strains such as Clostridium difficile and E. coli, potentially leading to inflammation and gut imbalance. Disruptions in short-chain fatty acid (SCFA) production and gut hormone signaling have also been observed. However, human studies generally show milder or no significant changes, highlighting the limitations in translating animal model findings directly to humans. Differences in study design, dosage, exposure time, and sweetener type likely contribute to these varied outcomes. Conclusions: While NNS offer certain benefits, including reduced caloric intake and improved blood sugar regulation, their impact on gut microbiome health raises important concerns. The observed reduction in beneficial bacteria and the rise in pathogenic strains underscore the need for caution in NNS consumption. Furthermore, the disruption of SCFA production and metabolic pathways illustrates the intricate relationship between diet and gut health. Full article
(This article belongs to the Special Issue Microbiota in Human Disease)
Show Figures

Figure 1

12 pages, 1548 KiB  
Systematic Review
Seroprevalence and Serotypes of Dengue Virus Infection in Ghana: A Systematic Review and Meta-Analysis
by Isaac Boamah, Alex Odoom, Kwamena W. C. Sagoe and Eric S. Donkor
Diseases 2025, 13(4), 114; https://doi.org/10.3390/diseases13040114 - 14 Apr 2025
Viewed by 254
Abstract
Background: Dengue virus (DENV) infection poses a serious and growing public health threat in many tropical and subtropical regions worldwide, including Ghana. Despite the heightened risks due to suitable climatic conditions and the presence of competent vectors, the epidemiology of DENV in Ghana [...] Read more.
Background: Dengue virus (DENV) infection poses a serious and growing public health threat in many tropical and subtropical regions worldwide, including Ghana. Despite the heightened risks due to suitable climatic conditions and the presence of competent vectors, the epidemiology of DENV in Ghana remains poorly understood, underscoring the critical need for a comprehensive assessment of the burden and circulation of the virus in the country. Methods: The review was conducted in accordance with the PRISMA guidelines. A literature search was conducted using the PubMed, Web of Science, and Scopus databases from inception to 24 September 2024. Studies presenting primary DENV seroprevalence data among Ghanaian populations were included. Quality was assessed using JBI tools. Meta-analyses estimated pooled prevalence with 95% CIs using random-effects models. Heterogeneity was evaluated using I2 statistic. Results: A total of nine studies met the selection criteria, with eight studies involving febrile patients and one involving blood donors. The pooled seroprevalence rates were 33.3% (95% CI: 16.2–50.4%) for IgG, 5.9% (95% CI: 0–12.5%) for IgM, 1.5% (95% CI: 0.4–2.6%) for DENV RNA, and 32.3% (95% CI: 0–68.5%) for IgG/IgM combined. Notably, the IgG seroprevalence exhibited substantial heterogeneity (I2 = 99%). DENV-2 and DENV-3 were the predominant serotypes identified. There was potential bias in seroprevalence estimates from hospital-based febrile samples. Conclusions: This review has established the prevalence and circulation of DENV serogroups in Ghana. The higher seropositivity and heterogeneity underscore the need for standardized large-scale surveillance to optimize disease characterization and guide control. Integrating dengue prevention into existing vector control programs could help reduce risks in Ghana. Full article
Show Figures

Figure 1

16 pages, 2016 KiB  
Systematic Review
Prevalence and Antimicrobial Resistance of Typhoid Fever in Ghana: A Systematic Review and Meta-Analysis
by Frederick Kungu, Aaron Awere-Duodu and Eric S. Donkor
Diseases 2025, 13(4), 113; https://doi.org/10.3390/diseases13040113 - 14 Apr 2025
Viewed by 284
Abstract
Background/Objectives: Typhoid fever caused by Salmonella enterica serovar Typhi remains an important public health problem in Ghana. Understanding the epidemiology and antimicrobial resistance patterns of S. Typhi is crucial to guide the treatment and control of typhoid fever. This systematic review and meta-analysis [...] Read more.
Background/Objectives: Typhoid fever caused by Salmonella enterica serovar Typhi remains an important public health problem in Ghana. Understanding the epidemiology and antimicrobial resistance patterns of S. Typhi is crucial to guide the treatment and control of typhoid fever. This systematic review and meta-analysis aimed to estimate the prevalence of typhoid fever in Ghana and describe the antibiotic susceptibility profiles. Methods: Literature searches were conducted using the PubMed repository and three databases: Scopus, Web of Science, and ScienceDirect. Observational studies reporting typhoid fever prevalence among Ghanaian participants diagnosed by culture or Widal test and published between 1 January 2004 and 16 August 2024 were eligible. Quality was assessed using standardized JBI critical appraisal checklists. Random-effects meta-analysis with a 95% confidence interval was performed to estimate pooled prevalence and conduct subgroup analyses. Results: A total of 22 studies involving 228,107 participants were included in the systematic review. The pooled prevalence of typhoid fever was 4.14% (95% CI: 2.78–5.75). Blood culture detected more cases (3.68%) than stool culture (1.16%). Multidrug resistance was documented in 20–66% of isolates, and ciprofloxacin had the lowest prevalence of resistance (0–17%). Conclusions: This review highlights the substantial typhoid fever burden and evolving antimicrobial resistance in Ghana. Continuous surveillance of the disease is warranted to optimize empiric treatment and control strategies, given the resistance to first-line drugs. Enhanced prevention through water, sanitation, and vaccination programs is imperative. Full article
Show Figures

Figure 1

8 pages, 394 KiB  
Article
Benchmark for Setting ACTH Cell Dosage in Clinical Regenerative Medicine for Post-Operative Hypopituitarism
by Tatsuma Kondo, Hidetaka Suga, Kazuhito Takeuchi, Yutaro Fuse, Yoshiki Sato, Toshiaki Hirose, Harada Hideyuki, Yuichi Nagata and Ryuta Saito
Diseases 2025, 13(4), 112; https://doi.org/10.3390/diseases13040112 - 10 Apr 2025
Viewed by 202
Abstract
Background/Objectives: Our objective is to develop hormone-producing pituitary cells that can function in the same manner as the human body and provide more effective treatments than current hormone replacement therapy. We have already established a technique for generating hypothalamic–pituitary organoids using feeder-free human [...] Read more.
Background/Objectives: Our objective is to develop hormone-producing pituitary cells that can function in the same manner as the human body and provide more effective treatments than current hormone replacement therapy. We have already established a technique for generating hypothalamic–pituitary organoids using feeder-free human pluripotent stem cells (hPSCs) and demonstrated their effectiveness in vivo through transplantation into hypopituitary mouse models. To prospectively determine the upper limit of transplanting adenohypophyseal cells into humans, we investigated the human maximum secretion capacity of adrenocorticotropic hormone (ACTH) and growth hormone (GH). Methods: We analyzed data from 28 patients with pituitary adenomas, among whom 16 evinced no abnormality of ACTH secretion and 12 showed no GH secretion on corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone-2 (GHRP-2) stimulation testing. Results: The average ACTH peak value after CRH stimulation tests was 97.2 pg/mL, and the average GH peak value after GHRP-2 stimulation tests was 25.1 ng/mL. Conclusions: These data will likely serve as benchmarks of ACTH and GH secretion when transplanting cultured cells into humans. Full article
Show Figures

Figure 1

16 pages, 1289 KiB  
Review
Beneficial Probiotics with New Cancer Therapies for Improved Treatment of Hepatocellular Carcinoma
by Moeka Nakashima, Akari Fukumoto and Satoru Matsuda
Diseases 2025, 13(4), 111; https://doi.org/10.3390/diseases13040111 - 7 Apr 2025
Viewed by 221
Abstract
Hepatocellular carcinoma (HCC) is a malignant form of primary liver cancer. Intricate networks linked to the host immune system may be associated with the pathogenesis of HCC. A huge amount of interdisciplinary medical information for the treatment of HCC has been accumulated over [...] Read more.
Hepatocellular carcinoma (HCC) is a malignant form of primary liver cancer. Intricate networks linked to the host immune system may be associated with the pathogenesis of HCC. A huge amount of interdisciplinary medical information for the treatment of HCC has been accumulated over recent years. For example, advances in new immunotherapy have improved the results of treatment for HCC. This approach can be advantageously combined with standard conventional treatments such as surgical resection to improve the therapeutic effect. However, several toxic effects of treatments may pose a significant threat to human health. Now, a shift in mindset is important for achieving superior cancer therapy, where probiotic therapy may be considered, at least within the bounds of safety. The interplay between the gut microbiota and immune system could affect the efficacy of several anticancer treatments, including of immune checkpoint therapy via the alteration of Th17 cell function against various malignant tumors. Here, some recent anticancer techniques are discussed, whereby the growth of HCC may be effectively and safely repressed by probiotic therapy. Full article
Show Figures

Figure 1

13 pages, 726 KiB  
Systematic Review
Onychomycosis Endonyx: A Systematic Review
by Ernesto De-La-Rosa-Garibay, Roberto Arenas, Martha Y. Herrera-Castro, Alicia Valdez-Gaona, Gabriela Moreno-Coutiño, Paola Berenice Zarate-Segura, Fernando Bastida-González, Erick Martínez-Herrera and Rodolfo Pinto-Almazán
Diseases 2025, 13(4), 110; https://doi.org/10.3390/diseases13040110 - 7 Apr 2025
Viewed by 254
Abstract
Background/Objectives: Endonyx onychomycosis is a chronic infection of the nail plate that presents as milky white discoloration, without hyperkeratosis or onycholysis, and was originally described as being caused by T. soudanense and T. violaceum. Methods: In the present review, the definitions used [...] Read more.
Background/Objectives: Endonyx onychomycosis is a chronic infection of the nail plate that presents as milky white discoloration, without hyperkeratosis or onycholysis, and was originally described as being caused by T. soudanense and T. violaceum. Methods: In the present review, the definitions used in the different articles and the clinical characteristics of patients diagnosed with this onychomycosis variant were analyzed through a systematic review of the reported cases in the literature using the terms “endonyx” AND “onychomycosis” in PUBMED, SciELO, SCOPUS, Web of Science, and Google Academics databases. Results: We found 28 articles with a total of 175 patients diagnosed with endonyx onychomycosis, mainly reported in Asia and Africa. Nine papers presented detailed descriptions. From these, a total of 15 immunocompetent patients were registered, and the etiological agents reported were Trichophyton soudanense, T. rubrum, T. violaceum, T. tonsurans, and Fusarium spp. After analyzing the definitions employed in the remaining articles, only 47.3% cited or described a concept consistent with the original description. The other 47.3% of the studies lacked a traceable criterion for the diagnosis of these cases. Moreover, most studies analyzed their data at a global level, describing little information to provide specific insights into the endonyx variant. Conclusions: Emphasis on clinical description and histopathological analysis is essential to confirm the role of less commonly reported fungi, and more accurate diagnostic and treatment protocols for this condition are mandatory. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology 2024)
Show Figures

Figure 1

17 pages, 636 KiB  
Article
Is Oral Function Associated with the Development of Sarcopenic Obesity and Sarcopenia in Older Adults? A Prospective Cohort Study
by Sho Shirotori, Yoko Hasegawa, Koutatsu Nagai, Hiroshi Kusunoki, Shogo Yoshimura, Kana Tokumoto, Hirokazu Hattori, Kayoko Tamaki, Kazuhiro Hori, Hiromitsu Kishimoto and Ken Shinmura
Diseases 2025, 13(4), 109; https://doi.org/10.3390/diseases13040109 - 5 Apr 2025
Viewed by 234
Abstract
Background: Sarcopenic obesity, defined as the concurrent loss of muscle mass and adipose tissue accumulation, is associated with reduced physical function and poor health status in older adults. Although oral function can impact the overall health of older adults, its role in the [...] Read more.
Background: Sarcopenic obesity, defined as the concurrent loss of muscle mass and adipose tissue accumulation, is associated with reduced physical function and poor health status in older adults. Although oral function can impact the overall health of older adults, its role in the development of sarcopenic obesity remains unclear. Herein, we aimed to examine the association between oral function and the incidence of sarcopenic obesity. Methods: This longitudinal cohort study included 597 independent older adults (aged ≥65 years) from Tamba-Sasayama, a rural region of Japan, who participated in academic studies between June 2016 and December 2023. Participants underwent surveys at least twice, with a minimum two-year interval. The participants were divided into four groups (robust, obese, sarcopenic, and sarcopenic obese) according to their health condition. Sarcopenic obesity was diagnosed based on the guidelines of the Japanese Working Group on Sarcopenic Obesity. The oral function was evaluated by assessing the number of remaining teeth, tongue pressure, occlusal force, masticatory performance, and oral diadochokinesis. Cox proportional hazards regression analysis evaluated the association between oral function and the incidence of sarcopenic obesity after adjusting for relevant confounders. Results: The sarcopenic obesity group was older, had lower skeletal muscle mass, and inferior physical function. This cohort also had the highest prevalence of hypertension and significantly fewer remaining teeth. The proportion of individuals with sarcopenic obesity was 1.7% of the total population, with 2.8% in the obesity group at baseline, and 8.0% of those were diagnosed with sarcopenia progressing to sarcopenic obesity. The Cox regression model revealed that reduced tongue pressure was significantly associated with an increased risk of sarcopenic obesity, with a hazard ratio of 0.906 (95% confidence interval: 0.829–0.990; p = 0.028), independent of other variables related to sarcopenia and obesity. Conclusions: Our findings suggest that oral function is associated with the incidence of sarcopenic obesity but not with that of sarcopenia or obesity alone. Full article
Show Figures

Figure 1

2 pages, 147 KiB  
Correction
Correction: Theodorakis, N.; Nikolaou, M. The Human Energy Balance: Uncovering the Hidden Variables of Obesity. Diseases 2025, 13, 55
by Nikolaos Theodorakis and Maria Nikolaou
Diseases 2025, 13(4), 108; https://doi.org/10.3390/diseases13040108 - 3 Apr 2025
Viewed by 121
Abstract
There was an error in the original publication [...] Full article
12 pages, 1185 KiB  
Article
Relationships of Isolated Nocturnal Hypertension with Glomerular Filtration Rate and Albuminuria
by Caterina Carollo, Giulio Geraci, Alessandra Sorce, Raffaella Morreale Bubella, Emanuele Cirafici, Maria Elena Ciuppa, Salvatore Evola and Giuseppe Mulè
Diseases 2025, 13(4), 107; https://doi.org/10.3390/diseases13040107 - 2 Apr 2025
Viewed by 180
Abstract
Background/Objectives: Isolated nocturnal hypertension (INH) represents a unique phenotype that can only be identified through ambulatory blood pressure monitoring (ABPM). An increasing body of evidence suggests a significant association between INH and heightened cardiovascular morbidity, mortality, and, more recently, kidney disease progression. Considering [...] Read more.
Background/Objectives: Isolated nocturnal hypertension (INH) represents a unique phenotype that can only be identified through ambulatory blood pressure monitoring (ABPM). An increasing body of evidence suggests a significant association between INH and heightened cardiovascular morbidity, mortality, and, more recently, kidney disease progression. Considering these findings, this study aims to retrospectively assess the prevalence of INH and its relationship with glomerular filtration rate (GFR) and albumin excretion rate (AER) in a large cohort of hypertensive patients. Methods: A total of 1340 subjects selected from the patients of our European Hypertension Excellence Centre of the University of Palermo were enrolled. Biochemical tests, urinalysis, 24 h ambulatory blood pressure monitoring, and collection of anamnestic and anthropometric data were performed on each patient. Results: In our cohort, the prevalence of INH was 11%. Logistic regression analyses revealed that male sex, AER, and eGFR were significantly associated with the INH phenotype. AER ≥ 5.8 µg/min predicted the presence of INH with 73.7% sensitivity and 58.4% specificity. An eGFR < 60 mL/min/1.73 m2 was also correlated with INH, although its predictive value was less prominent. Multivariable regression models confirmed that AER and eGFR, along with male sex, were independent predictors of INH. In patients with normal blood pressure, AER and metabolic syndrome were also associated with INH. CKD (AER < 30 mg/day and eGFR < 60 mL/min/1.73 m2) was significantly linked to INH. Conclusions: Our research confirms the direct relationship between AER and INH and the inverse relationship between GFR and INH, thus underlining the leading role of renal function in the onset of INH, as widely observed in the literature. The confirmed association between renal markers and INH in the subgroup of subjects with a clinically normal blood pressure could help us to identify the subjects who should undergo ABPM. Full article
(This article belongs to the Special Issue Cardiovascular Risk Stratification in Hypertension)
Show Figures

Figure 1

12 pages, 925 KiB  
Article
Surgery Versus Chemoradiation Therapy for Oropharyngeal Squamous Cell Carcinoma: A Multidimensional Cross-Sectional Study
by Giuseppe Riva, Dario Gamba, Simone Moglio, Giuseppe Carlo Iorio, Chiara Cavallin, Umberto Ricardi, Mario Airoldi, Andrea Canale, Andrea Albera and Giancarlo Pecorari
Diseases 2025, 13(4), 106; https://doi.org/10.3390/diseases13040106 - 2 Apr 2025
Viewed by 187
Abstract
Background/Objectives: The management of oropharyngeal squamous cell carcinoma (OPSCC) often involves multidisciplinary decision-making to optimize patient outcomes. Surgery and chemoradiation therapy (CRT) represent the two main treatment modalities. The aim of this cross-sectional study was to provide a comprehensive analysis of quality of [...] Read more.
Background/Objectives: The management of oropharyngeal squamous cell carcinoma (OPSCC) often involves multidisciplinary decision-making to optimize patient outcomes. Surgery and chemoradiation therapy (CRT) represent the two main treatment modalities. The aim of this cross-sectional study was to provide a comprehensive analysis of quality of life, speech, swallowing, sleep, psychological distress, and nutritional status in OPSCC patients treated with either surgery or CRT. Methods: Thirty subjects were divided into two groups based on treatment modality (>12-month follow-up): (A) surgery ± adjuvant treatment (15 patients); (B) exclusive CRT (15 patients). A multidimensional evaluation was performed by means of validated questionnaires. The following parameters were analyzed: quality of life, speech, swallowing, sleep quality, risk of sleep apnea, sleepiness, psychological distress, pain, and nutritional status. Results: No statistically significant difference was found between the two study groups for every parameter. The EORTC QLQ-C30 globally showed a good quality of life in both groups. Poor sleep quality was observed in 9 (60%) subjects in group A and in 6 (40%) patients in group B, respectively. Low, intermediate and high risk of malnutrition was observed in 73.3%, 20.0% and 6.7% of cases in group A, and in 93.3%, 6.7% and 0.0% in group B, respectively. Conclusions: Surgery and exclusive chemoradiotherapy appear to yield similar long-term outcomes across all evaluated dimensions, including quality of life, speech, swallowing, sleep, psychological distress, and nutritional status. Full article
Show Figures

Figure 1

12 pages, 2224 KiB  
Article
Prevalence of Depressive Disorders in Operatively Treated Pelvic Trauma Patients
by Piotr Walus, Jakub Ohla, Rafał Wójcicki, Tomasz Pielak, Jakub Bulski, Michał Wesołowski, Gazi Huri and Jan Zabrzyński
Diseases 2025, 13(4), 105; https://doi.org/10.3390/diseases13040105 - 31 Mar 2025
Viewed by 164
Abstract
Aim: The aim of this study is to assess the prevalence of depressive disorders in patients with pelvic fractures treated surgically at our center in the years 2017–2022. Materials and Methods: The study included 75 patients, 57 men and 18 women, operated on [...] Read more.
Aim: The aim of this study is to assess the prevalence of depressive disorders in patients with pelvic fractures treated surgically at our center in the years 2017–2022. Materials and Methods: The study included 75 patients, 57 men and 18 women, operated on in our center in the years 2017–2022 due to acetabular fracture and pelvic ring injury. Factors such as age, gender, chronic pain measured with the VAS scale, and the incidence of suicidal thoughts were also analyzed. The participants completed the Beck Depression Inventory (BDI). Results: Thirty-five out of the seventy-five patients showed symptoms of depression (BDI score > 11), which is 47%, with an average score of 29 (p < 0.0001). Women obtained an average BDI score of 23, which corresponds to moderate depression on Beck’s scale (p < 0.008). The correlation between BDI score and chronic pain in pelvic trauma patients has been found to be positive (p < 0.0003; r = 0.4094). Furthermore, women in our studied population reported suicidal thoughts more often than men (44% vs. 14%; p < 0.01). No statistically significant correlation was found between the occurrence of depression and the length of hospital stay and the patient’s age (p < 0.5 and p < 0.06, respectively). Conclusions: The prevalence of depression in the pelvic trauma patients of the studied population has been determined to be 47%. Full article
Show Figures

Figure 1

12 pages, 1359 KiB  
Article
Quality Management Outweighs Pandemic: Retrospective Analysis Shows Improved Quality of Care for Staphylococcus aureus Bacteremia Despite SARS-CoV-2
by Lena Jakoby, Ernst Molitor, Nico T. Mutters, Ruth Weppler, Dominic Rauschning and Manuel Döhla
Diseases 2025, 13(4), 104; https://doi.org/10.3390/diseases13040104 - 30 Mar 2025
Viewed by 215
Abstract
Background: Staphylococcus aureus bacteremia (SAB) is of great clinical relevance, as it is the most common type of bacteremia. Several studies show that the quality of care and thus the outcome can be positively influenced by the involvement of infectious disease specialists and [...] Read more.
Background: Staphylococcus aureus bacteremia (SAB) is of great clinical relevance, as it is the most common type of bacteremia. Several studies show that the quality of care and thus the outcome can be positively influenced by the involvement of infectious disease specialists and structured programs like Antimicrobial Stewardship (AMS). In 2020, the SARS-CoV-2 pandemic occurred, which dominated the healthcare system and global events during this time. At the same time, a standard operational procedure (SOP) for SAB quality management (SABQM) was introduced in a German maximum-care hospital with 500 beds. Additionally, voluntary AMS team consultations were introduced in June 2021. This work addresses whether the introduction of SABQM has led to an improvement in the quality of care for SAB, despite the possible negative influences of the pandemic. Methods: Retrospective statistical analyses were conducted on all 145 cases coded as SAB at this hospital during the “pre-pandemic” period (2017 to 2019, 75 cases) and the pandemic period (2020 to 2022, 70 cases). Population parameters and quality management parameters were extracted from the clinical patient documentation. In a first analysis, the SARS-CoV-2 status served as a discriminatory parameter to determine its influence on the quality of care within the “pandemic period”. In a second analysis, the period served as a discriminatory parameter to determine its influence on the quality of care. In a third analysis, the use of AMS team consultation served as a discriminatory parameter to determine its influence on the quality of care in a subgroup of 42 cases from June 2021 to 2022. Results: The SARS-CoV-2 status had no influence on the population parameters or the quality management parameters. Between both analyzed periods, there was an improvement in the quality management parameters, with statistically significant higher rates of follow-up blood cultures, transthoracic echocardiography and adequate antibiotic therapy. AMS team consultation led to a relevant, but not statistically significant improvement in the quality management indicators. Conclusions: An SOP for SABQM leads to an improvement in the quality of care, even under the possible negative influences of a pandemic. AMS team consultations further strengthen this positive influence, even if this is not statistically significant due to the small number of cases in the subgroup analyzed. Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology 2024)
Show Figures

Figure 1

31 pages, 4421 KiB  
Review
Phytochemicals as Chemo-Preventive and Therapeutic Agents Against Bladder Cancer: A Comprehensive Review
by Orestis Porfyris, Paraskevi Detopoulou, Theodora Adamantidi, Alexandros Tsoupras, Dimitris Papageorgiou, Anastasios Ioannidis and Andrea Paola Rojas Gil
Diseases 2025, 13(4), 103; https://doi.org/10.3390/diseases13040103 - 30 Mar 2025
Viewed by 214
Abstract
Bladder cancer has a high incidence worldwide and is characterized by a high recurrence rate, metastatic potential, and a significant socioeconomic burden. Conventional treatment modalities usually exhibit serious adverse complications, which also negatively affect patients’ quality of life. In the context of exploring [...] Read more.
Bladder cancer has a high incidence worldwide and is characterized by a high recurrence rate, metastatic potential, and a significant socioeconomic burden. Conventional treatment modalities usually exhibit serious adverse complications, which also negatively affect patients’ quality of life. In the context of exploring new treatment approaches with fewer side effects, the utilization of natural compounds as alternative and/or complementary therapeutic options seems appealing. In the present study, the potential use and effects of various bioactive phytochemicals, including curcumin, resveratrol, epigallocatechin, genistein, and several others, in bladder cancer treatment are thoroughly reviewed. A special focus is given to their potential to beneficially modulate important molecular signaling pathways and mechanisms affecting cell survival, proliferation, migration, and apoptosis, which play a crucial role in the pathogenesis of bladder cancer, such as the PI3K/AKT/mTOR, Ras/Raf/MEK/MAPK, Wnt/β-Catenin, Notch, Hedgehog, Hippo, JAK2/STAT3, and PAF/PAF-receptor pathways. Nevertheless, most studies have been conducted in cell cultures and animal models. Due to differences in genetics and metabolism, more clinical trials are needed to ensure the bio-efficacy of these phytochemicals in humans. Full article
Show Figures

Figure 1

12 pages, 379 KiB  
Article
Study of Adult and Pediatric Spanish Patients with Cryptogenic Splenomegaly and Splenectomy
by Marta Morado Arias, Jesús Villarrubia Espinosa, Isidro Vitoria Miñana, Enrique Calderón Sandubete, Víctor Quintero and Miguel Ángel Torralba-Cabeza
Diseases 2025, 13(4), 102; https://doi.org/10.3390/diseases13040102 - 30 Mar 2025
Viewed by 191
Abstract
Introduction: The differential diagnosis of splenomegaly is a complex process that encompasses a wide variety of diseases. Moreover, it is not always standardized and lacks a definitive consensus on which tests should be performed and in what order. Gaucher disease (GD) and acid [...] Read more.
Introduction: The differential diagnosis of splenomegaly is a complex process that encompasses a wide variety of diseases. Moreover, it is not always standardized and lacks a definitive consensus on which tests should be performed and in what order. Gaucher disease (GD) and acid sphingomyelinase deficiency (ASMD) are lysosomal diseases (LD) that present with splenomegaly, the diagnosis of which requires a high index of suspicion and specific biochemical and genetic techniques. The aim of the project for the education and diagnosis of Gaucher disease and acid sphingomyelinase deficiency (PREDIGA) was to conduct educational training alongside an observational, multicenter, ambispective, cross-sectional, single-cohort study among patients having an enlarged spleen or undergone splenectomy to further assess these subjects to exclude two lysosomal diseases, namely GD and ASMD. Methods: Using dried blood spot (DBS) testing, we identified patients with abnormally low values of the enzymes glucocerebrosidase and acid sphingomyelinase, who then underwent sequencing of the GBA1 and SPMD1 genes, respectively. The study involved 34 hospitals and 52 medical specialists. Results: We identified 220 patients (208 adults and 12 children under 18 years) with cryptogenic splenomegaly or who had undergone splenectomy (12 patients) without having reached a diagnosis. The median age was 11 years (interquartile range [IQR] 3–16) in the pediatric population and 51 years (IQR 38–65) in the adult population. Lower-than-normal enzyme values were detected in 19 DBSs, confirming eight positive cases, which corresponded to six patients with GD and two with ASMD. The rest of the DBSs with low enzyme activity were not genetically confirmed (58%). We determined that lysosomal diseases accounted for 3.6% of cryptogenic splenomegaly/splenectomy cases in our setting: 2.7% were GD and 0.9% ASMD, in a ratio of 1 ASMD patient to every 3 GD patients. Lyso-GL1 values in patients with GD were elevated in all but one individual, corresponding to a child diagnosed at 4 months old. The variants detected in the GBA1 gene were consistent with the most frequent variants found in Spain. Discussion/Conclusion: The development and implementation of this protocol for the education and diagnosis of cryptogenic splenomegaly/splenectomy, even in asymptomatic patients, constitutes a comprehensive, simple, rapid, and effective screening method for the diagnosis of GD and ASMD. Full article
(This article belongs to the Section Rare Syndrome)
Show Figures

Figure 1

13 pages, 674 KiB  
Article
A Pilot Study on the Analysis of Circulating miRNA Upregulation in Laryngeal Cancer
by Crina Oana Pintea, Marius Pricop, Edward Seclaman, Nicolae Constantin Balica, Kristine Guran, Delia Ioana Horhat and Cristian Ion Mot
Diseases 2025, 13(4), 101; https://doi.org/10.3390/diseases13040101 - 30 Mar 2025
Viewed by 168
Abstract
Background and Objectives: Laryngeal cancer poses a significant clinical challenge, with late-stage diagnosis contributing to high morbidity and mortality. Circulating microRNAs (miRNAs) represent promising, minimally invasive biomarkers for earlier detection and improved therapeutic monitoring. This pilot study focused exclusively on miRNAs found to [...] Read more.
Background and Objectives: Laryngeal cancer poses a significant clinical challenge, with late-stage diagnosis contributing to high morbidity and mortality. Circulating microRNAs (miRNAs) represent promising, minimally invasive biomarkers for earlier detection and improved therapeutic monitoring. This pilot study focused exclusively on miRNAs found to be upregulated in laryngeal carcinoma patients, aiming to elucidate their diagnostic and prognostic relevance. Methods: A total of 50 participants meeting standardized inclusion criteria were recruited from the ENT Clinic in Timișoara. Of these, 30 patients provided paired blood samples before and after treatment (surgical or non-surgical). Samples were pooled into three preoperative groups (P1, P2, P3) and three corresponding postoperative groups (C1, C2, C3). miRNAs were extracted from plasma and exosomes, and relative expression was measured by qPCR (Qiagen platform). Statistical analyses included Mann–Whitney U tests, receiver operating characteristic (ROC) curves, and logistic regression. Results: Seven miRNAs consistently exhibited significant upregulation preoperatively. Notably, hsa-miR-424-5p displayed a mean fold change of 4.59 (p = 0.0091) relative to postoperative samples, while hsa-miR-186-5p increased by 2.19-fold (p = 0.0030). hsa-miR-15b-5p also showed a substantial preoperative upregulation of 1.77-fold (p = 0.0057). In ROC analyses, hsa-miR-424-5p yielded an area under the curve (AUC) of 0.82 (95% CI 0.70–0.94), with 78% sensitivity and 80% specificity in distinguishing preoperative from postoperative status. Logistic regression indicated that elevated levels of hsa-miR-424-5p (OR = 1.56, 95% CI 1.10–2.20) and hsa-miR-186-5p (OR = 1.32, 95% CI 1.02–1.68) significantly predicted the preoperative disease state. Conclusions: These data underscore the potential of upregulated circulating miRNAs to serve as biomarkers for active laryngeal cancer and to monitor treatment response. Although preliminary, the findings encourage further research with larger cohorts and additional endpoints. With thorough validation, upregulated miRNAs could be integrated into clinical workflows, enhancing diagnostic precision, risk stratification, and postoperative surveillance in laryngeal cancer. Full article
Show Figures

Figure 1

10 pages, 1270 KiB  
Article
Yield of Multimodal Imaging in Iris Amelanotic Lesions: A Masked Case-Control Study
by Rachel Shemesh, Iris Moroz, Meira Neudorfer and Vicktoria Vishnevskia-Dai
Diseases 2025, 13(4), 99; https://doi.org/10.3390/diseases13040099 - 28 Mar 2025
Viewed by 234
Abstract
Objectives: To examine the yield of multimodal imaging of iris amelanotic lesions and evaluate the clinical relevance of these imaging techniques. Methods: In this masked case-control study, imaging, including slit lamp photos, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT) scans [...] Read more.
Objectives: To examine the yield of multimodal imaging of iris amelanotic lesions and evaluate the clinical relevance of these imaging techniques. Methods: In this masked case-control study, imaging, including slit lamp photos, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT) scans of patients diagnosed with iris amelanotic lesions were examined. Seven patients diagnosed with an iris amelanotic lesion were matched by gender and age to seven melanotic iris nevi of similar size and location. Two ocular imaging experts assessed the images in a masked manner and identified which lesion was melanotic and which was amelanotic based on their characteristics. Results: From 2010 to 2021, seven patients were diagnosed with amelanotic iris lesions. All were female; the mean (±SD) age at presentation was 46.3 years (±18). These patients were matched with seven female patients with pigmented iris lesions, with a mean (±SD) age of 49.8 years (±20). Hypopigmented lesions were hyporreflective and had minimal shadowing of the iris behind them, and the basement membrane of the iris could be seen on AS-OCT. Hypopigmented lesions could be delineated from the iris stroma on AS-OCT. In contrast, hyperpigmented lesions were hyperreflective, with significant shadowing blocking the basement membrane and iris stroma. Conclusions: AS-OCT is non-touch and provides substantial information about diagnosing amelanotic nevi. It is more widely available and, in many countries, it is performed by technicians, thus freeing the physician’s time and increasing productivity. Full article
Show Figures

Figure 1

25 pages, 14510 KiB  
Article
Impacts of Forest Bathing (Shinrin-Yoku) in Female Participants with Depression/Depressive Tendencies
by Qing Li, Norimasa Takayama, Masao Katsumata, Hiroshi Takayama, Yukako Kimura, Shigeyoshi Kumeda, Takashi Miura, Tetsuya Ichimiya, Ruei Tan, Haruka Shimomura, Amane Tateno, Tsunemi Kitagawa, Yoichiro Aoyagi and Michiko Imai
Diseases 2025, 13(4), 100; https://doi.org/10.3390/diseases13040100 - 28 Mar 2025
Viewed by 610
Abstract
Background: It has been reported that forest bathing significantly reduced negative emotions and increased the positive feelings in both healthy males and females, as well as increasing blood serotonin in healthy males, indicating the potential for a beneficial effect on depressive status. However, [...] Read more.
Background: It has been reported that forest bathing significantly reduced negative emotions and increased the positive feelings in both healthy males and females, as well as increasing blood serotonin in healthy males, indicating the potential for a beneficial effect on depressive status. However, an improvement effect of forest bathing on participants with depression has not been reported so far. Therefore, in order to fill this gap, this study examined the effect of forest bathing on depression in female participants with depression/depressive tendencies. Methods: Thirty-one females aged 40.1 ± 2.4 years with depression/depressive tendencies were recruited after obtaining informed consent. The study employed a randomized crossover design to compare forest bathing with city walking. They participated in day trips to a Japanese cypress forest park and to a city area of Nagano Prefecture as a control in June 2023. On both trips, they walked 2.5 km (for 90 min) in the morning and afternoon, respectively, for a total of 5.0 km per day. Blood samples were taken at 4 pm for the measurements before forest bathing on the first day and after the walking in forest and unban sites on the second and third days, at the same hospital. Concentrations of oxytocin, IGF-1, serotonin and lactic acid in blood were measured. SDS scores were calculated and the POMS test and questionnaires for subjective fatigue symptoms and sleep quality were administered before and after each trip. Temperature, humidity and illuminance were also measured in the forest and urban environments. The Nippon Medical School Central Ethics Committee approved this study. Results: Forest bathing significantly decreased SDS scores compared to city walk and the baseline, and the effect lasted for one week after forest bathing. Forest bathing also significantly increased the concentrations of blood serotonin in participants who were not taking antidepressants, significantly increased the levels of oxytocin and IGF-1 in blood, significantly increased the scores for positive feelings, and reduced the scores for negative emotions compared with city walking in the POMS test. In addition, forest bathing reduced subjective fatigue symptoms and improved sleep quality. Conclusions: These findings provided scientific evidence to contribute to understanding forest bathing as a potential intervention for preventing depression, and future research on males should further explore these effects. Full article
Show Figures

Figure 1

30 pages, 1024 KiB  
Review
An Analysis of Primary Hyperparathyroidism in Individuals Diagnosed with Multiple Endocrine Neoplasia Type 2
by Ana-Maria Gheorghe, Claudiu Nistor, Alexandru-Florin Florescu and Mara Carsote
Diseases 2025, 13(4), 98; https://doi.org/10.3390/diseases13040098 - 27 Mar 2025
Viewed by 237
Abstract
Background: Primary hyperparathyroidism (PHPT) represents a multi-faced disease with a wide spectrum of manifestations. Familial forms of PHPT (affecting up to 10% of the cases) involve a particular category that encompasses a large range of hereditary syndromes, including parathyroid hyper-function, frequently in the [...] Read more.
Background: Primary hyperparathyroidism (PHPT) represents a multi-faced disease with a wide spectrum of manifestations. Familial forms of PHPT (affecting up to 10% of the cases) involve a particular category that encompasses a large range of hereditary syndromes, including parathyroid hyper-function, frequently in the setting of a multi-glandular disease. Objective: The aim was to analyze the most recent findings regarding PHPT in multiple endocrine neoplasia type 2 (MEN2) to a better understanding of the timing with respect to the associated ailments, MEN2-related PHPT (MEN2-PHPT) clinical and genetic particularities, optimum diagnostic, and overall management, particularly, surgical outcomes. Methods: This was a PubMed-based compressive review with regard to the latest data published in English from January 2020 until January 2025, using the following keywords: “primary hyperparathyroidism” and “multiple endocrine neoplasia”, “multiple endocrine neoplasia type 2”, “MEN2”, or “MEN2A”. We included original full-length studies of any study design that provided clinically relevant data in MEN2-PHPT and excluded reviews, meta-analysis, and case reports/series. Results: A total of 3783 individuals confirmed with MEN2 or RET pathogenic variants carriers were analyzed across 14 studies that provided data on PHPT. The prevalence of MEN2-PHPT subjects varied between 7.84% and 31.3%, with particularly low rates in non-index patients (3.8%). PHPT was the first syndrome manifestation in 0.9% of MEN2 patients. In terms of gender distribution, females represented 42.85% or 54.9% (similar rates between women and men, and only a single cohort showed a female rate up to 80%). Most subjects were diagnosed with PHPT and underwent surgery in the third or fourth decade of life. The highest median age at MEN2 diagnosis was 42 years. The youngest patients were RET pathogenic variants carriers who underwent (genetic) screening with median ages of 12 or 14 years. RET pathogenic variants analysis (n = 10/14 studies) showed that 16.67% of patients with p.Cys634Arg and 37.5% of those with p.Cys611Tyr had symptomatic PHPT, while those with p.Cys618Phe and p.Leu790Phe were asymptomatic. Timing analysis with respect to the medullary thyroid carcinoma diagnosis showed synchronous PHPT diagnosis in 80% and metachronous in 10% of MEN2 patients; with respect to MEN2-pheochromocytoma, synchronous diagnosis of PHPT was found in 56%, while pheochromocytoma was identified before PHPT in 22% of the cases and after PHPT in 22%. Studies (n = 10/14, N = 156 subjects with MEN2-PHPT) on parathyroidectomy identified that 72.7% to 100% of the individuals underwent surgery, typically performed in adulthood, at ages spanning from a mean of 34.7 to 48.5 years. The post-surgery outcomes varied (e.g., the rate for persistent PHPT was of 0%, 8% to 16.7%; recurrent PHPT of 12.5% to 23%; permanent hypoparathyroidism of 33% to 46%; permanent unilateral vocal cord palsy of 0% up to16.7%). Data regarding the number of involved glands (n = 7, N = 77): the prevalence of multi-glandular disease was pinpointed between 12.5% and 50%. Conclusions: MEN2-PHPT involved unexpected high rates of single-gland involvement (from 33.3% to 87.5%), probably due to an early detection across genetic screening. Traditional female higher prevalence in PHPT was not confirmed in most MEN2 cohorts. As expected, a younger age at PHPT diagnosis and surgery than seen in non-MEN2 patients was identified, being tidily connected with the syndromic constellation of tumors/malignancies. Overall, approximately, one out of ten patients were further confirmed with MEN2 starting with PHPT as the first clinically manifested element. Full article
Show Figures

Figure 1

12 pages, 739 KiB  
Article
Impact of Cardiovascular–Kidney–Metabolic Syndrome Staging on Myocardial Infarction Outcomes: A Retrospective Analysis of 2.7 Million Patients
by Ronny Shabtai, Marlon Villaga Gatuz, Adam Folman, Maguli S. Barel, Rami Abu-Fanne, Dmitry Abramov, Mamas A. Mamas, Ariel Roguin and Ofer Kobo
Diseases 2025, 13(4), 97; https://doi.org/10.3390/diseases13040097 - 27 Mar 2025
Viewed by 951
Abstract
Background: Cardiovascular–kidney–metabolic (CKM) syndrome, recently defined by the American Heart Association, encompasses the interplay between obesity, diabetes, chronic kidney disease, and cardiovascular disease. This study aimed to investigate the impact of CKM syndrome severity on outcomes in patients with acute myocardial infarction [...] Read more.
Background: Cardiovascular–kidney–metabolic (CKM) syndrome, recently defined by the American Heart Association, encompasses the interplay between obesity, diabetes, chronic kidney disease, and cardiovascular disease. This study aimed to investigate the impact of CKM syndrome severity on outcomes in patients with acute myocardial infarction (AMI). Methods: A retrospective analysis was conducted using the National Inpatient Sample database from 2016 to 2019. Adult patients hospitalized with AMI were stratified into CKM Stages 0–4 based on ICD-10 codes. Multivariable logistic regression models were used to examine associations between CKM stages and in-hospital procedures and outcomes. Results: The study analyzed 2,768,154 AMI cases. Advanced CKM stages were associated with older age and a higher proportion of males. Patients with severe CKM were more likely to undergo invasive procedures. Coronary angiography showed the strongest association in CKM Stage 4A (aOR: 6.86, 95% CI: 6.73–6.99, p-value < 0.001) and Stage 4B (aOR: 3.87, 95% CI: 3.80–3.95, p-value < 0.001). Similarly, the likelihood of PCI was highest in Stage 4A (aOR: 5.93, 95% CI: 5.79–6.08, p-value < 0.001) and Stage 4B (aOR: 4.14, 95% CI: 4.04–4.24, p-value < 0.001). Notably, patients with CKM Stage 0 demonstrated higher odds of adverse outcomes compared to other stages. Conclusions: This study reveals a complex relationship between CKM syndrome severity and AMI outcomes. Patients with advanced CKM stages were more likely to undergo invasive procedures, and those without CKM risk factors unexpectedly showed worse outcomes. Among Stages 1–4B, no consistently graded association emerged between the CKM stage and adverse outcomes. These findings warrant further investigation into underlying mechanisms and long-term prognosis. Full article
Show Figures

Figure 1

Previous Issue
Next Issue
Back to TopTop