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Volume 13
Issue 11
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Diseases, Volume 13, Issue 11 (November 2025) – 31 articles

Cover Story (view full-size image): Heart failure with reduced ejection fraction (HFrEF) remains a condition with substantial mortality, even in stable outpatients receiving guideline-directed therapy. The blood urea/creatinine ratio (UCR) reflects both renal function and neurohormonal activation, yet its prognostic value in ambulatory settings has been unclear. In this study, we evaluated UCR at discharge from an outpatient heart failure service and found that UCR ≥95 was independently associated with increased all-cause mortality, even among patients with preserved renal function. These findings highlight UCR as a simple, accessible biomarker for identifying higher-risk patients in routine clinical practice. View this paper
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20 pages, 315 KB  
Review
Zinc Fortification and Supplementation to Reduce Diarrhea in Children: A Literature Review
by Sehar Iqbal, Zoha Imtiaz Malik, Maher Al Dabbas, Ishmal Akhtar and Aya Hussein
Diseases 2025, 13(11), 380; https://doi.org/10.3390/diseases13110380 - 20 Nov 2025
Viewed by 2870
Abstract
Background: Zinc deficiency is a major global health issue and appears to be responsible for risk of diarrhea and death, particularly in children under 5 years. This review therefore aimed to summarize the existing literature related to zinc supplementation and fortification for the [...] Read more.
Background: Zinc deficiency is a major global health issue and appears to be responsible for risk of diarrhea and death, particularly in children under 5 years. This review therefore aimed to summarize the existing literature related to zinc supplementation and fortification for the prevention of diarrhea. Methods: In this literature review, we discussed the zinc-related biochemistry and pathophysiology of diarrhea and role of zinc in reducing the risk of diarrhea in children. Moreover, this literature review particularly analyzed studies published between 2014 and 2025, including systematic reviews, meta-analyses, and randomized controlled trials focusing on zinc fortification and supplementation for the prevention of childhood diarrhea. The studies covered a range of zinc dosing regimens (5–20 mg daily), preventive and therapeutic approaches, and combined interventions in children. Main outcomes such as diarrhea duration, severity, recurrence, growth, and side effects were assessed across diverse low- and middle-income populations. Results: Routine zinc supplementation helps to reduce all-cause diarrhea and respiratory infections. Zinc supplementation consistently reduced both the duration and severity of diarrhea in children. Also, diarrhea episodes and frequency were reduced in children taking zinc supplementation. Lower doses (5–10 mg) were mostly recommended to reduce vomiting. Combined zinc and vitamin A supplementation further improved outcomes, while long-term low-dose zinc supplementation prevented diarrhea and infections. Conclusion: This review confirms that zinc supplementation and fortification are effective, affordable strategies for reducing childhood diarrhea. Supplementation during diarrheal episodes reliably shortens duration and severity, with long-term benefits lasting for months. Continued research and integrated approaches for dosing and delivery are needed for both low- and middle-income countries. Full article
7 pages, 190 KB  
Case Report
Undetectable Serum Level of Anti-Müllerian Hormone (AMH) in a Woman with an Unpredictable Hyper-Response During Controlled Ovarian Stimulation for an IVF-ICSI Program: Case Report
by Omar Sefrioui, Modou Mamoune Mbaye, Ismail Kaarouch, Smahane Aboulmaouahib, Latifa Ahbbas, Omar Touzani, Noureddine Louanjli and Bouchra Ghazi
Diseases 2025, 13(11), 379; https://doi.org/10.3390/diseases13110379 - 19 Nov 2025
Viewed by 857
Abstract
Background/Objectives: A decrease in serum AMH is generally associated with low ovarian response in assisted reproductive procedures, whether or not in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is performed. Methods: We report a case involving a 31-year-old woman who had never [...] Read more.
Background/Objectives: A decrease in serum AMH is generally associated with low ovarian response in assisted reproductive procedures, whether or not in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is performed. Methods: We report a case involving a 31-year-old woman who had never been pregnant and with irregular menstrual cycles. An ultrasound scan performed on the second day of the cycle showed several annular follicles, a high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio suggesting polycystic ovary syndrome (PCOS), and an undetectable serum level of AMH. Results: Despite these observations, she exhibited an unpredictable hyperresponse during controlled ovarian stimulation, followed by a failed pregnancy despite successful in vitro fertilization with ICSI and a good-quality thawed embryo transfer (4AA). Conclusions: This case highlights the challenges of relying solely on AMH as a predictive marker of ovarian response. Although AMH is widely used for assessing ovarian reserve and stimulation outcomes, its limitations become evident in atypical cases. The paradoxical hyperresponse observed here may result from alternative regulatory mechanisms influenced by elevated LH levels, enhanced gonadotropin receptor sensitivity, or local ovarian factors. This report underscores the need for a personalized, multidimensional approach combining hormonal profiles, ultrasound assessments, and clinical history to optimize stimulation protocols and mitigate risks such as ovarian hyperstimulation syndrome (OHSS). Such tailored protocols are essential for managing patients with complex profiles, particularly those with undetectable AMH levels. Further research is needed to explore the mechanisms behind these atypical ovarian responses, including the roles of genetic polymorphisms, inflammatory markers, and environmental factors. This case demonstrates the importance of cautious interpretation of AMH results and emphasizes the value of comprehensive evaluations in assisted reproductive technologies. Full article
15 pages, 1470 KB  
Article
Exploring Mitochondrial DNA Copy Number in Italian Children with ADHD: Implications for Neurobiological Mechanisms
by Luigi Citrigno, Annamaria Cerantonio, Ludovico Neri, Pierluigi Sebastiani, Alessia Colanardi, Gabriele Turacchio, Tiziana Del Beato, Beatrice Marziani and Anna Aureli
Diseases 2025, 13(11), 378; https://doi.org/10.3390/diseases13110378 - 19 Nov 2025
Viewed by 683
Abstract
Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently accompanied by behavioral dysregulation. While genetic factors involving monoaminergic systems have been implicated, emerging evidence suggests a role for mitochondrial dysfunction in ADHD pathophysiology. Mitochondrial DNA copy number (mtDNA-cn), a surrogate marker of mitochondrial [...] Read more.
Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition frequently accompanied by behavioral dysregulation. While genetic factors involving monoaminergic systems have been implicated, emerging evidence suggests a role for mitochondrial dysfunction in ADHD pathophysiology. Mitochondrial DNA copy number (mtDNA-cn), a surrogate marker of mitochondrial biogenesis and cellular energy demand, may reflect underlying neurobiological alterations and oxidative stress-related mechanisms relevant to ADHD. Methods: We assessed mtDNA-cn in the peripheral blood of 56 Italian children and adolescents with ADHD and 27 age- and sex-matched healthy controls. ADHD symptoms and aggressive behavior were evaluated using DSM-5 criteria and the Conners’ 3 Rating Scales. Genotyping was performed for MAOA (rs6323, rs1137070) and 5-HTT (rs4795541) polymorphisms. Results: ADHD patients showed significantly higher mtDNA-cn than controls (p = 0.002), supporting mitochondrial dysregulation. Comparing the ADHD patient subgroups with aggressive behavior and those without, a non-significant reduction in mtDNA-cn was observed in the first subgroup. Notably, individuals with the TT genotype (rs6323) or CC genotype (rs1137070) had significantly higher mtDNA-cn compared to controls with the same genotypes (p = 0.031). Similar increases were seen across all 5-HTT rs4795541 genotypes in ADHD patients. Conclusions: Our findings suggest that mitochondrial alterations may contribute to ADHD pathophysiology. The association between mtDNA-cn and monoaminergic gene variants highlights a potential link between neurotransmitter metabolism, oxidative stress, and mitochondrial function. Thus, mtDNA-cn may serve as a peripheral biomarker and therapeutic target in ADHD. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
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19 pages, 526 KB  
Review
Reframing Dental Anxiety: Cognitive Behavioral Therapy and Its Role in Phobia Treatment—A Narrative Review
by Dorina Stan, Dragoș Voicu, Pușica Zainea, Alexandra Toma and Anamaria Ciubară
Diseases 2025, 13(11), 377; https://doi.org/10.3390/diseases13110377 - 18 Nov 2025
Cited by 1 | Viewed by 1187
Abstract
Dental phobia is a disabling yet underdiagnosed condition that prevents many patients from seeking essential oral healthcare, leading to avoidable pain, disease progression, and reduced quality of life. Cognitive Behavioral Therapy (CBT) is the most widely supported psychological intervention for specific phobias and [...] Read more.
Dental phobia is a disabling yet underdiagnosed condition that prevents many patients from seeking essential oral healthcare, leading to avoidable pain, disease progression, and reduced quality of life. Cognitive Behavioral Therapy (CBT) is the most widely supported psychological intervention for specific phobias and has demonstrated significant efficacy in reducing dental anxiety and avoidance. This narrative review synthesizes recent evidence on CBT applications for phobia management, with particular emphasis on dental settings. In addition to reviewing established mechanisms of CBT, this paper highlights emerging adjunctive approaches such as virtual reality, eye movement desensitization and reprocessing (EMDR), and hypnosis. Special attention is given to pediatric populations, trauma-exposed individuals, and patients with neurodevelopmental disorders, who are often underrepresented in clinical research. The findings underscore the central role of CBT in addressing dental phobia while identifying gaps in standardized protocols, long-term outcomes, and accessibility across diverse healthcare contexts. Future research should prioritize controlled trials, cultural adaptations, and the integration of psychological training into dental curricula to enhance the translation of evidence into everyday practice. Full article
(This article belongs to the Special Issue Mental Health—Management and Care, Multidisciplinary Approaches and Perspectives)
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10 pages, 914 KB  
Case Report
Toxic Shock Syndrome in a 45-Year-Old Woman Possibly Associated with Tampon Use: A Case Report of Multiorgan Failure Due to Streptococcus agalactiae
by Tina Zavidić, Ema Dejhalla and David Zahirović
Diseases 2025, 13(11), 376; https://doi.org/10.3390/diseases13110376 - 16 Nov 2025
Viewed by 785
Abstract
Background: Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by Staphylococcus aureus or Streptococcus pyogenes. However, other streptococcal species, including Streptococcus agalactiae (group B Streptococcus (GBS)), can also cause TSS, sometimes leading to severe complications, [...] Read more.
Background: Toxic shock syndrome (TSS) is a rare but potentially fatal condition most often caused by Staphylococcus aureus or Streptococcus pyogenes. However, other streptococcal species, including Streptococcus agalactiae (group B Streptococcus (GBS)), can also cause TSS, sometimes leading to severe complications, such as multiorgan failure. Case Description: We report the case of a 45-year-old woman who developed TSS associated with tampon use. She presented with fever, chills, hypotension, and leg pain, progressing rapidly to septic shock and multiorgan failure. Blood and urine cultures revealed S. agalactiae group B, while a gynecological examination identified Ureaplasma urealyticum and S. agalactiae. Imaging demonstrated bilateral pneumonic infiltrates and pleural effusion. The patient required intensive care, vasopressor support, and broad-spectrum antibiotic therapy, leading to full clinical recovery. Discussion: Despite advances in tampon design, menstrual TSS remains a significant clinical concern. Early symptoms may be nonspecific, but rapid progression highlights the need for timely recognition and intervention. Although S. agalactiae is an uncommon cause of TSS, it should be considered in relevant clinical scenarios. Prompt empirical antibiotic therapy, followed by targeted treatment based on culture results, along with supportive intensive care, is essential to improve outcomes. Conclusions: Menstrual TSS continues to pose a serious health risk. Physicians should maintain a high index of suspicion in tampon users presenting with fever, rash, and shock. Early diagnosis and rapid initiation of appropriate therapy are crucial to reducing morbidity and mortality. Full article
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16 pages, 1304 KB  
Article
Causal Graphical Model of Bacterial Vaginosis in Pregnant Women
by Maricela García-Avalos, Juana Canul-Reich, Lil María Xibai Rodríguez-Henríquez and Erick Natividad De la Cruz-Hernández
Diseases 2025, 13(11), 375; https://doi.org/10.3390/diseases13110375 - 15 Nov 2025
Viewed by 425
Abstract
Background: This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated [...] Read more.
Background: This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated bacteria, these approaches lack visual tools to explore causal relationships and determine which are the most relevant. In contrast, the CGM generated in this study allows visualization of associated bacteria and their causal links, thereby identifying those most influential. Methods: Path Analysis (PA), a statistical structural equation modeling method, was used to construct the CGM, with emphasis on observable variables and to assess direct and indirect effects through correlations and covariances. PA was applied to an already-collected third-party dataset related to BV diagnosis, consisting of data from 132 pregnant women between 4 and 24 weeks of gestation. Results: The CGM, built using a theoretical model based on the Spearman correlation matrix, was validated through statistical metrics and by a clinical-biological expert. The resultant model highlights bacteria influencing BV diagnosis, specifically Mycoplasma hominis (Mh), Atopobium vaginae (Av), Gardnerella vaginalis (Gv), Megasphaera Type 1 (MT1), and Bacteria Associated with Bacterial Vaginosis Type 2 (BVAB2). Among them, MT1 and BVAB2 showed the strongest association with BV. Conclusions: The CGM effectively identifies causal associations among bacteria related to BV. Full article
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13 pages, 3681 KB  
Article
T Helper and Cytotoxic T Cells Play an Important Role in Acute Gastric Injury
by Irfan F. Corovic, Jelena M. Pantic, Isidora A. Stanisavljevic, Sladjana M. Pavlovic, Nemanja U. Jovicic, Ivan P. Jovanovic, Gordana D. Radosavljevic and Bojana J. Simovic Markovic
Diseases 2025, 13(11), 374; https://doi.org/10.3390/diseases13110374 - 15 Nov 2025
Viewed by 541
Abstract
Background: Inflammation plays a central role in the formation of peptic ulcers, yet the contribution of cellular immunity remains poorly defined. This study aimed to clarify the contribution of cellular immunity to acute gastric mucosal injury. Methods: BALB/c mice received 80% ethanol via [...] Read more.
Background: Inflammation plays a central role in the formation of peptic ulcers, yet the contribution of cellular immunity remains poorly defined. This study aimed to clarify the contribution of cellular immunity to acute gastric mucosal injury. Methods: BALB/c mice received 80% ethanol via oral gavage to induce acute gastric injury. Stomachs were examined macroscopically and histologically, and gastric tissues were analyzed by qPCR, ELISA, and flow cytometry for cytokine expression, immune cell infiltration, and apoptosis. Results: Administration of ethanol exacerbated acute gastric injury in mice, as evidenced by extensive macroscopic lesions and severe disruption of mucosal architecture. This damage was accompanied by marked infiltration of CD11c+ dendritic cells, together with an increased frequency of CD86-expressing and IL-12-producing dendritic cells. In addition, there was greater accumulation of both CD4+ and CD8+ T lymphocytes, including elevated numbers of CD4+ and CD8+ cells producing IFN-γ and IL-17, as well as CD8+CD107a+ cytotoxic cells. Alongside these cellular alterations, ethanol exposure was accompanied by elevated levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-17, and IFN-γ) in gastric tissue. In parallel, ethanol exposure also promoted epithelial cell apoptosis, further contributing to mucosal deterioration. Conclusions: Our findings reveal for the first time that both CD4+ and CD8+ T cells participate in sterile ethanol-induced acute gastric injury, emphasizing cellular immunity as an important yet insufficiently studied contributor to mucosal damage and highlighting the necessity for further mechanistic and translational research. Full article
(This article belongs to the Special Issue Diseases: From Molecular to the Clinical Perspectives)
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27 pages, 1422 KB  
Article
Stress, Anxiety, and Self-Efficacy in Hypertension: Evidence from a Romanian Case—Control Study
by Lucia Bubulac, Mirela Zivari, Irina Anca Eremia, Constantin Erena, Consuela-Mădălina Gheorghe, Iuliana-Raluca Gheorghe, Viorica Tudor, Claudia Florina Bogdan-Andreescu, Emin Cadar and Cristina-Crenguța Albu
Diseases 2025, 13(11), 373; https://doi.org/10.3390/diseases13110373 - 13 Nov 2025
Viewed by 1573
Abstract
Background: Hypertension and psychological distress often coexist, though evidence from Eastern Europe is still limited. Stress, anxiety, and self-efficacy influence blood pressure control and treatment adherence. Their effect on hypertension prevention and treatment has not been systematically evaluated in Romania. Aim: This study [...] Read more.
Background: Hypertension and psychological distress often coexist, though evidence from Eastern Europe is still limited. Stress, anxiety, and self-efficacy influence blood pressure control and treatment adherence. Their effect on hypertension prevention and treatment has not been systematically evaluated in Romania. Aim: This study evaluated the associations between stress, anxiety, and self-efficacy in Romanian adults with and without hypertension to identify modifiable psychological factors relevant for integrated cardiovascular management. Methods: A retrospective case–control study was conducted among 215 adults, including individuals with hypertension and normotensive controls. Participants completed validated questionnaires assessing stress vulnerability, perceived stress, state and trait anxiety, self-efficacy, and Type A behavior, together with demographic and occupational data. Results: Hypertensive participants reported higher stress vulnerability, perceived stress, and anxiety, as well as lower self-efficacy, compared with controls. Type A behavior showed no association with hypertension. These differences remained consistent after accounting for demographic characteristics. Conclusions: Hypertension in Romanian adults is associated with a distinct psycho-emotional profile characterized by elevated stress and anxiety and reduced self-efficacy. Type A personality showed no association. The results emphasize the importance of recognizing and addressing modifiable psychological determinants in hypertension care. Integrating psychosocial assessment with personalized interventions, including mindfulness-based approaches, digital health support, and nurse-led telemonitoring, could improve treatment adherence, reduce emotional burden, and contribute to overall cardiovascular health. This region-specific evidence supports expanding hypertension management to include psychological care alongside standard medical approaches. Full article
(This article belongs to the Special Issue Insights into the Management of Cardiovascular Disease Risk Factors)
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14 pages, 1132 KB  
Article
Silicosis and Pulmonary Functions Among Residents Exposed to Dust in Saraburi Thailand
by Narongkorn Saiphoklang, Pitchayapa Ruchiwit, Apichart Kanitsap, Pichaya Tantiyavarong, Pasitpon Vatcharavongvan, Srimuang Palungrit, Kanyada Leelasittikul, Apiwat Pugongchai and Orapan Poachanukoon
Diseases 2025, 13(11), 372; https://doi.org/10.3390/diseases13110372 - 13 Nov 2025
Viewed by 902
Abstract
Background: Silicosis is a lung disease caused by inhalation of crystalline silica dust, leading to lung fibrosis, respiratory symptoms, and impaired lung function. This study aimed to determine the prevalence of silicosis, asthma, and chronic obstructive pulmonary disease (COPD), and to identify [...] Read more.
Background: Silicosis is a lung disease caused by inhalation of crystalline silica dust, leading to lung fibrosis, respiratory symptoms, and impaired lung function. This study aimed to determine the prevalence of silicosis, asthma, and chronic obstructive pulmonary disease (COPD), and to identify factors associated with abnormal pulmonary function among residents living in dust-exposed areas in Thailand. Methods: A cross-sectional study was conducted from March 2024 to July 2024 among adults aged 18 years or older in Saraburi, Thailand. Data collected included demographics, comorbidities, respiratory symptoms, risk of silicosis, chest radiographs, and spirometry (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and bronchodilator responsiveness (BDR)). Silicosis was confirmed based on a history of significant silica exposure and characteristic chest radiographic findings. Results: Among 290 participants (55.9% female, mean age 47.6 ± 16.4 years), the prevalence of silicosis, asthma, and COPD was 0.3%, 4.5%, and 10.3%, respectively. Abnormal chest radiographs were observed in 8.3%, and abnormal lung function in 34.1%, including restrictive lung patterns (16.6%), airway obstruction (9.0%), mixed defects (2.8%), and small-airway disease (5.9%). BDR was observed in 4.8%. Logistic regression identified increasing age as a significant predictor of abnormal lung function. Conclusions: Silicosis prevalence was lower than that of asthma and COPD, but abnormal pulmonary function—especially restrictive defects—was common. Notably, the prevalence of asthma and COPD was higher than previously reported community-based diagnosis rates, suggesting potential underdiagnosis. Older age was associated with a higher likelihood abnormal lung function. These findings highlight the need for targeted surveillance, preventive measures, and public health interventions to mitigate the respiratory impacts of dust exposure in community settings Full article
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51 pages, 7121 KB  
Case Report
Total Reversal of ALS Confirmed by EMG Normalization, Structural Reconstitution, and Neuromuscular–Molecular Restoration Achieved Through Computerized Brain-Guided Reengineering of the 1927 Nobel Prize Fever Therapy: A Case Report
by M. Marc Abreu, Mohammad Hosseine-Farid and David G. Silverman
Diseases 2025, 13(11), 371; https://doi.org/10.3390/diseases13110371 - 12 Nov 2025
Viewed by 11187
Abstract
Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application [...] Read more.
Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application of therapeutic fever to ALS using Computerized Brain-Guided Intelligent Thermofebrile Therapy (CBIT2). This fully noninvasive treatment, delivered through an FDA-approved computerized platform, digitally reengineers the 1927 Nobel Prize-recognized malarial fever therapy into a modern treatment guided by the Brain–Eyelid Thermoregulatory Tunnel. CBIT2 induces therapeutic fever through synchronized hypothalamic feedback, activating heat shock proteins, which are known to restore proteostasis and neuronal function. Case presentation: A 56-year-old woman was diagnosed with progressive ALS at the Mayo Clinic, with electromyography (EMG) demonstrating fibrillation and fasciculation indicative of denervation corroborated by neurological and MRI findings; the patient was informed that she had an expected survival of three to five years. A neurologist from Northwestern University confirmed the diagnosis and thus maintained the patient on FDA-approved ALS drugs (riluzole and edaravone). Her condition rapidly worsened despite pharmacological treatment, and she underwent CBIT2, resulting in (i) electrophysiological reversal with complete disappearance of denervation; (ii) biomarker correction, including reductions in neurofilament and homocysteine, IL-10 normalization (previously linked to mortality), and robust HSP70 induction; (iii) restoration of gait, swallowing, respiration, speech, and cognition; (iv) reconstitution of tongue structure; and (v) return to complex motor tasks, including golf, pickleball, and swimming. Discussion: This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT2 may extend to Alzheimer’s, Parkinson’s, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT2 establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT2 now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation. Amid a global brain health crisis, fever-based therapies may offer a path to preserve thought, memory, movement, and independence for the more than one-third of humanity currently affected by neurological disorders. Full article
(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)
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9 pages, 344 KB  
Article
The Diagnostic Utility of the Triptorelin Stimulation Test Compared to the Standard Gonadotropin-Releasing Hormone Stimulation Test in Children with Idiopathic Central Precocious Puberty
by Giorgio Sodero
Diseases 2025, 13(11), 370; https://doi.org/10.3390/diseases13110370 - 12 Nov 2025
Viewed by 785
Abstract
Background: Central precocious puberty (CPP) is diagnosed through a combination of clinical, auxological, and biochemical parameters, with pharmacological stimulation tests considered the diagnostic gold standard. In recent years, triptorelin, a long-acting Gonadotropin-Releasing Hormone (GnRH) analog, has been increasingly adopted in clinical practice due [...] Read more.
Background: Central precocious puberty (CPP) is diagnosed through a combination of clinical, auxological, and biochemical parameters, with pharmacological stimulation tests considered the diagnostic gold standard. In recent years, triptorelin, a long-acting Gonadotropin-Releasing Hormone (GnRH) analog, has been increasingly adopted in clinical practice due to limited availability of native GnRH. Objective: To compare the clinical, auxological, and hormonal profiles of girls diagnosed with idiopathic CPP using either the classical GnRH stimulation test or the triptorelin test. Methods: This retrospective study included 136 female patients diagnosed with CPP and followed for at least two years at a single pediatric endocrinology unit. Of these, 101 underwent a GnRH stimulation test, and 35 were assessed using the triptorelin test. Baseline and stimulated hormonal parameters, growth data, and IGF-1 levels were collected. A multivariate linear regression model was used to explore the influence of age, test type, and other covariates on the LH peak response. Results: Anthropometric and baseline hormonal parameters were comparable between the two groups. The LH peak was significantly higher in the GnRH group (9.8 ± 3.1 IU/L at 60 min) than in the triptorelin group (6.8 ± 2.4 IU/L at 4 h). FSH levels were also significantly lower following triptorelin stimulation (p = 0.004), while the LH/FSH ratio did not differ significantly. Multivariate analysis confirmed that triptorelin was associated with a lower LH peak (β = −2.2, p = 0.008), particularly in younger patients, with a significant interaction between age and test type (β = 0.6, p = 0.022). Conclusions: Both GnRH and triptorelin stimulation tests are valid tools for CPP diagnosis. However, the GnRH test appears to elicit a more robust LH response, especially in younger patients, whereas the triptorelin test is associated with delayed and lower LH peaks. Full article
(This article belongs to the Special Issue Recent Therapeutic Advances in Gynecological Diseases and Clinical Management)
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12 pages, 6117 KB  
Case Report
Treatment of Neglected Elbow Dislocation with Secondary Heterotopic Ossification
by Mihai Tudor Gavrilă, Vlad Cristea and Cristea Stefan
Diseases 2025, 13(11), 369; https://doi.org/10.3390/diseases13110369 - 11 Nov 2025
Viewed by 648
Abstract
A traumatic elbow dislocation that remains unreduced for more than three weeks is considered a neglected elbow dislocation. We report a case of a patient with a neglected elbow dislocation combined with a terrible triad injury (elbow dislocation with fractures of the coronoid [...] Read more.
A traumatic elbow dislocation that remains unreduced for more than three weeks is considered a neglected elbow dislocation. We report a case of a patient with a neglected elbow dislocation combined with a terrible triad injury (elbow dislocation with fractures of the coronoid process and radial head). Initially, the patient was managed with three weeks of cast immobilization followed by physiotherapy. However, six months after the trauma, he presented to our clinic with severe heterotopic ossification, significant pain, and nearly complete elbow stiffness. An open surgical intervention was performed, involving excision of the heterotopic bone, reduction in the dislocation, and suturing of the anterior capsule to the coronoid process. Given the irreparable fracture of the radial head, radial head arthroplasty was also performed. At 18-month follow-up, the elbow was stable and pain-free, with flexion–extension of 80°, pronation of 85°, and supination of 80°. This case underscores the critical importance of early diagnosis and intervention to prevent long-term complications in neglected elbow dislocations. Full article
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16 pages, 720 KB  
Article
Risk Factors and Predictive Parameters of Necrotizing Enterocolitis in Preterm Infants—A Single-Center Retrospective Study
by Tamas Toth, Angela Borda, Reka Borka-Balas, Manuela Cucerea, Emoke Andrea Szasz, Horea Gozar and Radu-Alexandru Prisca
Diseases 2025, 13(11), 368; https://doi.org/10.3390/diseases13110368 - 10 Nov 2025
Viewed by 807
Abstract
Background and Objectives: Necrotizing enterocolitis (NEC) represents a severe gastrointestinal emergency in preterm infants. The aim of this study was to identify risk factors and predictive parameters for NEC requiring surgery and to evaluate associated short-term outcomes. Materials and Methods: We [...] Read more.
Background and Objectives: Necrotizing enterocolitis (NEC) represents a severe gastrointestinal emergency in preterm infants. The aim of this study was to identify risk factors and predictive parameters for NEC requiring surgery and to evaluate associated short-term outcomes. Materials and Methods: We conducted a retrospective study in preterm neonates diagnosed with NEC admitted to a tertiary neonatal intensive care unit (NICU) between January 2015 and May 2025. Demographic data, perinatal events, risk factors, clinical signs, imaging findings, and outcomes were analyzed, with a particular focus on surgically managed cases. Descriptive and inferential statistical methods were applied. Results: Forty-four infants met the inclusion criterion. The mean gestational age (GA) was 29.34 ± 4.3 weeks, and the mean birth weight was 1100 ± 563 g. According to Bell’s severity index, 45.5% had Bell Stage I, 36.4% Stage II, and 18.2% Stage III. Eleven patients (25%) required surgery. All surgical patients had abdominal distension, and 63.6% had bilious gastric residue. Abdominal X-ray showed pneumoperitoneum in 72.7% and pneumatosis intestinalis in 27.3% of cases. Laboratory abnormalities, including thrombocytopenia, elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and hyponatremia (45.5%; 133 ± 6.95 mmol/L), were frequently associated with surgical NEC. A lower GA and birth weight correlated with a higher Bell stage (p = 0.0085 and p = 0.0291). Overall mortality was 29.5% (13/44); surgical mortality was 9.1% (1/11). Conclusions: In this single-center lot, low gestational age and birth weight, abdominal distension with bilious residuals, systemic inflammation, and hyponatremia were frequent among infants who required surgery. Selected infants may benefit from early surgery even without perforation, but inferences are limited by this study’s sample size and retrospective design. Prospective multi-center studies are needed to validate predictors and refine surgical timing. Full article
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17 pages, 259 KB  
Article
Psychological and Psychosocial Effects of Cancer on Young Patients and Survivors in Italy: A Mixed-Methods Study on the Challenges and Meaning-Making Factors
by Martina Gentile, Lucia Ronconi, Marco Romeo, Ciro De Vincenzo, Elena Burattini, Chiara Rutigliano, Nicola Santoro, Giulia Zucchetti, Franca Fagioli and Ines Testoni
Diseases 2025, 13(11), 367; https://doi.org/10.3390/diseases13110367 - 10 Nov 2025
Viewed by 1199
Abstract
Background: Pediatric oncological diagnoses and treatments pose complex biopsychosocial challenges for both patients and their families. These experiences can significantly disrupt daily life, evoke intense emotional responses, and raise concerns about the future, often leading to long-term psychological implications. Objective: This study aimed [...] Read more.
Background: Pediatric oncological diagnoses and treatments pose complex biopsychosocial challenges for both patients and their families. These experiences can significantly disrupt daily life, evoke intense emotional responses, and raise concerns about the future, often leading to long-term psychological implications. Objective: This study aimed to assess the emotional functioning of children undergoing cancer treatment and to explore the lasting psychological effects reported by young adult survivors of pediatric cancer. Methods: A mixed-methods approach was employed. In total, 52 minors and their caregivers were recruited from two pediatric oncology units in Italy (Turin and Bari), while 18 young adults diagnosed during childhood were recruited from clinical and community settings in Ancona and Bari. Standardized instruments were used to evaluate emotional symptoms and broader psychological functioning in the pediatric sample, while self-report measures assessed psychological well-being and quality of life in the young adult group. To complement these data, semi-structured interviews were conducted with the young adult survivors to investigate the long-term psychosocial and psychological impacts of pediatric cancer. Results: The quantitative results indicate generally low levels of psychological distress in both groups. However, the qualitative findings reveal the complexity of post-cancer identity, highlighting experiences of resilience, emotional ambivalence, and redefinition of self. Conclusions: These results underscore the importance of addressing the psychological well-being of pediatric oncology patients and young adult survivors beyond the medical treatment phase, with a focus on long-term psychosocial support and individualized care. Full article
(This article belongs to the Special Issue Mental Health—Management and Care, Multidisciplinary Approaches and Perspectives)
10 pages, 1332 KB  
Article
In Vitro Activity of Silver-Bound Titanium Dioxide (TiAB) Against Multidrug-Resistant Vaginal Pathogens
by Lorenzo Drago, Luigi Regenburgh De La Motte, Erika Stefàno, Vincenzo Minasi, Loredana Deflorio, Sofia Benedetti and Fabiana Giarritiello
Diseases 2025, 13(11), 366; https://doi.org/10.3390/diseases13110366 - 10 Nov 2025
Viewed by 654
Abstract
Background: Gynecological infections, including bacterial vaginosis, vulvovaginal candidiasis, and recurrent urinary tract infections, represent a major clinical burden and are often complicated by biofilm formation and antimicrobial resistance. Novel non-antibiotic strategies are urgently needed. We previously demonstrated the antimicrobial activity of silver-bound titanium [...] Read more.
Background: Gynecological infections, including bacterial vaginosis, vulvovaginal candidiasis, and recurrent urinary tract infections, represent a major clinical burden and are often complicated by biofilm formation and antimicrobial resistance. Novel non-antibiotic strategies are urgently needed. We previously demonstrated the antimicrobial activity of silver-bound titanium dioxide (TiAB) against multidrug-resistant bacteria isolated from dermatological infections. Objectives: We evaluated whether TiAB, at concentrations used in marketed medical devices, exerts antibacterial and antifungal effects against clinically relevant vaginal isolates by determining Minimum Inhibitory Concentration/ Minimum Bactericidal and Fungicidal Concentration (MIC, MBC/MFC), and time–kill kinetics. Methods: A total of 73 clinical isolates were collected from vaginal swabs, including Staphylococcus aureus (MSSA, MRSA), Escherichia coli (ESBL+ and non-ESBL), Klebsiella pneumoniae, Enterococcus spp., Streptococcus agalactiae, and Candida albicans. Minimum inhibitory concentrations (MICs) and minimum bactericidal/fungicidal concentrations (MBCs/MFCs) were determined by broth microdilution, and bactericidal activity was confirmed by time-kill assays. Results: TiAB exhibited potent activity against Gram-negative bacteria, with median MIC values of 1–2% (w/v) for E. coli and K. pneumoniae. Gram-positive isolates, including S. agalactiae and Enterococcus spp., showed higher MIC values (2–4%). Candida albicans displayed fungistatic inhibition at 4%. Time-kill assays confirmed rapid bactericidal effects for Gram-negative isolates within 8 h at 2× MIC, while Gram-positive bacteria required prolonged exposure. Conclusions: These findings extend previous evidence of TiAB’s antimicrobial properties to gynecological pathogens, supporting its potential as a topical, non-antibiotic option for managing vaginal infections in an era of rising antimicrobial resistance. Further in vivo validation is warranted. Full article
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17 pages, 647 KB  
Article
Residual Platelet Reactivity and Dyslipidemia in Post-CABG Patients Undergoing Repeat Revascularization: Insights from Kazakhstan
by Aisulu Mussagaliyeva, Sholpan Zhangelova, Laura Danyarova, Friba Nurmukhammad, Dina Kapsultanova, Orazbek Sakhov, Farida Rustamova, Akhmetzhan Sugraliyev and Dana Akhmentayeva
Diseases 2025, 13(11), 365; https://doi.org/10.3390/diseases13110365 - 9 Nov 2025
Cited by 1 | Viewed by 480
Abstract
Background: Coronary artery bypass grafting (CABG) remains a standard revascularization strategy for patients with advanced coronary artery disease (CAD). However, a considerable proportion of patients experience recurrent ischemia requiring repeat revascularization. Residual platelet reactivity (RPR) and dyslipidemia are recognized as key factors contributing [...] Read more.
Background: Coronary artery bypass grafting (CABG) remains a standard revascularization strategy for patients with advanced coronary artery disease (CAD). However, a considerable proportion of patients experience recurrent ischemia requiring repeat revascularization. Residual platelet reactivity (RPR) and dyslipidemia are recognized as key factors contributing to graft failure and disease progression. Methods: This observational study was conducted at a tertiary cardiology center in Kazakhstan. A total of 195 post-CABG patients who underwent repeat coronary angiography between 2023 and 2024 recruitment period for recurrent ischemic symptoms within 6–36 months after surgery were included. Clinical characteristics, comorbidities, lipid profiles, and antiplatelet response were analyzed. RPR was measured using the VerifyNow P2Y12 assay when available. Dyslipidemia was defined according to the 2019 and 2021 European guidelines. Results: Elevated RPR was identified in 45% of patients (n = 90) despite dual antiplatelet therapy (p < 0.01). Poor lipid control was frequent among those who underwent repeat percutaneous coronary intervention (PCI), particularly elevated levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (p < 0.05). Both elevated RPR and dyslipidemia were independently associated with native coronary disease progression and graft failure (RPR: OR = 2.8; 95% CI 1.4–5.6; p = 0.003; dyslipidemia: OR = 2.2; 95% CI 1.1–4.3; p = 0.02). The use of ezetimibe was independently associated with a significantly lower risk of repeat stenting (OR = 0.12; 95% CI 0.02–0.75; p = 0.023). Smokers were younger, had lower blood pressure, and less frequently presented with diabetes or chronic kidney disease, demonstrating a pattern consistent with the “smoker’s paradox.” Conclusions: Residual platelet reactivity and dyslipidemia are common and clinically relevant predictors of repeat revascularization after CABG. Optimization of antiplatelet and lipid-lowering therapy should be prioritized in secondary prevention for this high-risk population. These findings are particularly important in Kazakhstan, where post-CABG management strategies warrant further improvement. Full article
(This article belongs to the Section Cardiology)
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21 pages, 734 KB  
Article
Clinical Profiles, Management, and Outcomes of Complicated Pneumonia in Children: A Retrospective Study from Tertiary Centers in Jordan
by Lina Alshadfan, Muna Kilani, Saleh Abualhaj, Osama Abu-Salah, Mohammad Ghassab Deameh, Ahmad Nidal Al-Faouri, Mustafa Elayyan, Randa Othman and Reem Abuzraiq
Diseases 2025, 13(11), 364; https://doi.org/10.3390/diseases13110364 - 8 Nov 2025
Viewed by 1177
Abstract
Background: Complicated pneumonia (CP) in children presents in various forms—including empyema, necrotizing pneumonia (NP), necrotizing pneumonia with pleural effusion (NP + PE), and parapneumonic pleural effusion (PPE)—and is associated with significant morbidity despite advances in antimicrobial therapy. This study aimed to describe and [...] Read more.
Background: Complicated pneumonia (CP) in children presents in various forms—including empyema, necrotizing pneumonia (NP), necrotizing pneumonia with pleural effusion (NP + PE), and parapneumonic pleural effusion (PPE)—and is associated with significant morbidity despite advances in antimicrobial therapy. This study aimed to describe and compare the clinical characteristics, laboratory findings, antibiotic use, and outcomes across different CP subtypes in hospitalized children and to assess the impact of prior antibiotic use on presentation and treatment outcomes. Methods: This retrospective observational study included 58 children admitted with CP to tertiary hospitals in Jordan. Patients were categorized into four subtypes: empyema (n = 4), NP (n = 4), NP + PE (n = 17), and PPE (n = 33). Demographic data, clinical features, laboratory results, antibiotic regimens, and clinical outcomes were analyzed. Multivariable regression was used to identify predictors of prior antibiotic use. Results: Fever and cough were the most common symptoms (96.6%). Over 40% of patients had received antibiotics prior to admission. Those pre-treated had significantly longer symptom duration (8.2 vs. 4.5 days, p < 0.001), longer hospitalization (18.2 vs. 14.6 days, p = 0.023), and more frequent chest tube insertion (66.7% vs. 35.3%, p = 0.019). Streptococcus pneumoniae was the most common organism isolated in culture-positive cases. Vancomycin-based regimens were the most frequently used treatments. Univariate regression analysis showed that patients with prior antibiotic use had significantly higher odds of longer hospitalization duration (OR = 1.11, p = 0.028) and chest tube insertion (OR = 3.67, p = 0.021). Conclusions: Complicated pneumonia in children remains a diverse and clinically significant condition. The findings demonstrate that prolonged symptom duration prior to hospitalization and certain clinical interventions were associated with prior antibiotic exposure. These results provide insight into local disease patterns and prescribing behaviors, which may help inform strategies to optimize antimicrobial stewardship and improve care pathways for affected children. Full article
(This article belongs to the Section Respiratory Diseases)
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38 pages, 2695 KB  
Review
Research Progress on the Efficacy and Mechanism of Acupuncture in Treating Chronic Gastritis
by Jing He, Hongye Wang, Cong Che, Anjie Wang, Ru Nie, Jinghong Tan, Jialin Jia, Zijian Liu, Tie Li and Guojuan Dong
Diseases 2025, 13(11), 363; https://doi.org/10.3390/diseases13110363 - 7 Nov 2025
Viewed by 2403
Abstract
Chronic gastritis (CG) is a prevalent digestive disorder. It progresses through multiple stages, has an insidious onset, and can lead to severe complications if untreated. Modern treatments primarily aim to eradicate Helicobacter pylori and relieve symptoms. However, drug resistance and adverse effects often [...] Read more.
Chronic gastritis (CG) is a prevalent digestive disorder. It progresses through multiple stages, has an insidious onset, and can lead to severe complications if untreated. Modern treatments primarily aim to eradicate Helicobacter pylori and relieve symptoms. However, drug resistance and adverse effects often limit their effectiveness. As a primary traditional Chinese medicine (TCM) therapy, acupuncture treats CG through multi-target mechanisms. This review systematically outlines the classification and pathology of CG. It also comprehensively analyzes animal and clinical studies on acupuncture for CG from the past decade. The study summarizes the mechanisms of acupuncture and related therapies for CG, covering gastric mucosal function, metabolism, intestinal flora, gastrointestinal hormones, apoptosis, inflammation, and oxidative stress. It further explores the relationships among diseases, interventions, acupoints, and molecular pathways. Additionally, it compares the therapeutic profiles of different external therapies. The review also examines the current state of clinical research, including the selection of acupoints, treatment duration, and outcome assessment. The results demonstrate that external therapies effectively alleviate common CG symptoms such as abdominal distension, acid reflux, and stomach pain. These treatments also improve gastric mucosal health and modulate serum levels of inflammatory factors, oxidative stress markers, and gastrointestinal hormones. In vivo experiments using chronic non-atrophic gastritis (CNAG) and chronic atrophic gastritis (CAG) models confirm these benefits, showing changes in key biomarkers and elucidating potential mechanisms. Nevertheless, future high-quality, large-sample clinical trials are still needed to firmly establish efficacy. Further mechanistic studies are also needed to validate the interconnections among relevant signaling pathways. Full article
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13 pages, 696 KB  
Article
Blood Urea/Creatinine Ratio and Mortality in Ambulatory Patients with Heart Failure with Reduced Ejection Fraction
by Andrew S. Oswald, Muhammad S. Hussain, Mohsin H. K. Roshan, Filippo Pigazzani, Anna-Maria Choy, Faisel Khan, Ify R. Mordi and Chim C. Lang
Diseases 2025, 13(11), 362; https://doi.org/10.3390/diseases13110362 - 7 Nov 2025
Cited by 1 | Viewed by 810
Abstract
Background: Chronic heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, and renal dysfunction is common in these patients. Blood urea/creatinine ratio (UCR) has been identified as a potential prognostic marker, reflecting both renal function and neurohormonal activity. We assessed [...] Read more.
Background: Chronic heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, and renal dysfunction is common in these patients. Blood urea/creatinine ratio (UCR) has been identified as a potential prognostic marker, reflecting both renal function and neurohormonal activity. We assessed whether a UCR ≥ 95 at discharge from an outpatient service was associated with increased mortality. Methods: This retrospective study reviewed 337 patients (age 72.7 ± 14.3 years; 64.7% Male; Mean LVEF 33.2 ± 8.9%) with HFrEF referred to the Heart Failure Nurse Service at NHS Tayside for optimisation of heart failure medication. Cox proportional hazards models were used to assess the association between UCR and all-cause mortality. Results: Receiver operating characteristic (ROC) analysis identified a UCR threshold of 95 (area under the curve [AUC] 0.701) as predictive of mortality. Results demonstrated that a UCR ≥ 95 was independently associated with increased mortality (HR 1.85, 95% CI 1.09–3.14, p = 0.022). A high UCR was associated with increased mortality even in patients with preserved eGFR, a group typically considered at lower risk (HR 4.03, 95% CI 1.50–10.9, p = 0.006). Conclusions: These findings suggest that UCR could be a useful addition for identifying high-risk patients who may benefit from closer monitoring and more aggressive intervention following optimisation of heart failure medication. Full article
(This article belongs to the Special Issue Insights into the Management of Cardiovascular Disease Risk Factors)
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9 pages, 414 KB  
Article
Psychiatric Comorbidities in Parkinson’s Disease: A Moroccan Perspective on Anxiety and Depression
by Khaoula Elcadi, Oussama Cherkaoui Rhazouani, Nissrine Louhab, Najib Kissani and Mohamed Chraa
Diseases 2025, 13(11), 361; https://doi.org/10.3390/diseases13110361 - 6 Nov 2025
Viewed by 691
Abstract
Background/Objectives: An individual’s quality of life is greatly impacted by the motor and non-motor symptoms of Parkinson’s disease (PD), which include anxiety and depression. Using the Hospital Anxiety and Depression Scale (HADS), this study sought to determine the prevalence of anxiety and depression [...] Read more.
Background/Objectives: An individual’s quality of life is greatly impacted by the motor and non-motor symptoms of Parkinson’s disease (PD), which include anxiety and depression. Using the Hospital Anxiety and Depression Scale (HADS), this study sought to determine the prevalence of anxiety and depression in Moroccan patients with Parkinson’s disease (PD) and investigate any possible associations with clinical characteristics and pharmacological treatment. Methods: The HADS was used to assess 100 PD patients in total. Clinical and demographic information, including prescription drug use, was gathered. The relationships between HADS scores and clinical factors were evaluated using Pearson’s correlation. Results: According to the HADS assessment, 20% of respondents had no anxiety symptoms, 17% had borderline symptoms, and 63% of patients reported definite anxiety symptoms. Of those with depression, 24% showed no symptoms, 14% were borderline, and 62% were certain. The average HADS-A and HADS-D scores were 2.34 and 2.43, respectively. L-DOPA alone was used to treat half of the patients, while combinations of Trivastal, Sifrol, anticholinergics, or antidepressants were given to the other half. There were no discernible correlations between HADS scores and clinical or demographic traits. Conclusions: The HADS is a useful instrument for assessing anxiety and depression in PD patients. Regardless of the method of treatment or stage of the disease, psychiatric symptoms are prevalent. For PD patients to benefit from early interventions and achieve an improved quality of life, routine screening is crucial. Full article
(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)
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20 pages, 3826 KB  
Article
MicroRNA Signatures in Serous Ovarian Cancer: A Comparison of Prognostic Marker Targets in African Americans and Caucasians
by Jane M. Muinde, Celina Romi Yamauchi, Joseph Cruz, Alena A. McQuarter, Kyah Miller, Umang Sharma, Skyler Schiff, Isaac Kremsky, Saied Mirshahidi, Cody S. Carter and Salma Khan
Diseases 2025, 13(11), 360; https://doi.org/10.3390/diseases13110360 - 6 Nov 2025
Viewed by 832
Abstract
Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those [...] Read more.
Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article
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27 pages, 1312 KB  
Review
Type 3 Diabetes: Linking Insulin Resistance to Cognitive Decline
by Brooke Chapple, Emily Bayliss, Seth Woodfin, Merritt Smith, Jeremiah Winter and William Moore
Diseases 2025, 13(11), 359; https://doi.org/10.3390/diseases13110359 - 5 Nov 2025
Viewed by 3973
Abstract
Type 3 diabetes (T3D) is characterized by chronic insulin resistance and insulin deficiency in the brain, leading to neuronal death, inflammation, oxidative stress, apoptosis, and synaptic dysfunction. These pathological processes contribute to cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. However, despite [...] Read more.
Type 3 diabetes (T3D) is characterized by chronic insulin resistance and insulin deficiency in the brain, leading to neuronal death, inflammation, oxidative stress, apoptosis, and synaptic dysfunction. These pathological processes contribute to cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. However, despite increasing evidence that links insulin resistance to cognitive impairment, the precise mechanisms that underly T3D remain largely unknown. This highlights a critical gap in research and potential therapeutic strategies. Given the significant impact of diet on metabolic health, investigating the correlation between the gut–brain axis may offer novel insights into the prevention and management of T3D. This review aims to elucidate the potential connections between insulin resistance and cognitive decline while also proposing interventions to slow aging and reduce the risk of early cognitive decline. At the same time, we acknowledge that the classification of type 3 diabetes is debatable and there is uncertainty as to whether insulin resistance is a primary driver or secondary manifestation of neurodegeneration. Full article
(This article belongs to the Special Issue Research Progress in Neurodegenerative Diseases)
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14 pages, 1146 KB  
Case Report
Intraoral Epidermoid Cyst: Case Report and Literature Review
by Ana Andabak Rogulj, Danica Vidović Juras, Božana Lončar Brzak, Ivana Škrinjar, Bruno Špiljak and Sven Seiwerth
Diseases 2025, 13(11), 358; https://doi.org/10.3390/diseases13110358 - 5 Nov 2025
Viewed by 1210
Abstract
Background/Objectives: Epidermoid cysts are benign lesions originating from germinative epithelium, characterized by a keratin-filled cavity. They are histopathologically classified as epidermoid, dermoid, or teratoid. Intraoral cases are exceedingly rare, comprising less than 0.01% of all oral cystic lesions, most frequently affecting the floor [...] Read more.
Background/Objectives: Epidermoid cysts are benign lesions originating from germinative epithelium, characterized by a keratin-filled cavity. They are histopathologically classified as epidermoid, dermoid, or teratoid. Intraoral cases are exceedingly rare, comprising less than 0.01% of all oral cystic lesions, most frequently affecting the floor of the mouth. While usually asymptomatic, they may become painful due to infection or growth. Because of their rarity in sites such as the upper lip, they may be clinically misdiagnosed, making awareness crucial for accurate management. Methods: Diagnosis is primarily clinical and histopathological, with imaging reserved for complex or deep-seated lesions. Complete surgical excision is the standard treatment to prevent recurrence. In this case, diagnostic evaluation included careful clinical inspection, assessment of consistency and mobility, and excisional biopsy with subsequent histopathological confirmation. Results: We report a rare case of a 68-year-old female presenting with a painless, slow-growing swelling of the upper lip. Clinical examination revealed a solitary, whitish, mobile lesion. Histopathological analysis confirmed an epidermoid cyst. The lesion was surgically excised under local anesthesia, with no recurrence observed at six-month follow-up. The outcome highlights the success of surgical management and the importance of monitoring even when the lesion appears benign. Conclusions: Although uncommon in the upper lip, epidermoid cysts should be considered in the differential diagnosis of submucosal swellings. Complete surgical excision offers a favorable outcome and prevents recurrence. Reporting such rare presentations expands clinical awareness and assists in differentiating these lesions from other pathologies of the oral cavity. Full article
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9 pages, 679 KB  
Case Report
Radiation Recall Pneumonitis with Pneumocystis jirovecii Superinfection and Treatment Induced Hyponatremia in a Patient with Non-Small-Cell Lung Cancer
by Aleksandra Piórek, Adam Płużański, Dariusz M. Kowalski and Maciej Krzakowski
Diseases 2025, 13(11), 357; https://doi.org/10.3390/diseases13110357 - 4 Nov 2025
Cited by 1 | Viewed by 734
Abstract
Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are standard treatments for advanced non-small-cell lung cancer (NSCLC), especially in patients with high PD-L1 expression or symptoms such as superior vena cava syndrome (SVCS). Both therapies carry a risk of pulmonary toxicity, which may be [...] Read more.
Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are standard treatments for advanced non-small-cell lung cancer (NSCLC), especially in patients with high PD-L1 expression or symptoms such as superior vena cava syndrome (SVCS). Both therapies carry a risk of pulmonary toxicity, which may be exacerbated by opportunistic infections due to corticosteroid use. We report a unique case of a 65-year-old man with squamous-cell NSCLC and high PD-L1 expression (80%), who developed a rare complication: radiation recall pneumonitis (RRP), with superimposed Pneumocystis jirovecii pneumonia and severe symptomatic hyponatremia induced by trimethoprim/sulfamethoxazole (TMP-SMX). The coexistence of these three complications—radiotherapy- and immunotherapy-associated lung injury, opportunistic infection, and electrolyte imbalance—represents an exceptional clinical scenario not previously described in the literature. This report highlights the importance of differential diagnosis, early recognition of complications, and close monitoring of electrolytes in NSCLC patients undergoing complex treatment regimens. Full article
(This article belongs to the Section Oncology)
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15 pages, 2835 KB  
Article
Global Epidemiology of Smoking and Liver Cancer from 1990 to 2021
by Jinguo Wang, Yang Ma, Aixu Duan and Xiaoming Fan
Diseases 2025, 13(11), 356; https://doi.org/10.3390/diseases13110356 - 3 Nov 2025
Viewed by 738
Abstract
Liver cancer is a prevalent and highly malignant tumor worldwide, and smoking has been suggested as a potentially significant risk factor, but this association remains understudied and not widely recognized. This study utilized global epidemiological data (1990–2021) from open access databases, analyzing smoking-related [...] Read more.
Liver cancer is a prevalent and highly malignant tumor worldwide, and smoking has been suggested as a potentially significant risk factor, but this association remains understudied and not widely recognized. This study utilized global epidemiological data (1990–2021) from open access databases, analyzing smoking-related liver cancer burden and trends by age, sex, region, and country using mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs), with projections for disease burden in 2040. The results show that from 1990 to 2021, the global number of smoking-attributable liver cancer deaths increased (cumulative growth: 67.10%; annual growth rate: 1.63%), while the age-standardized mortality rate (ASMR) declined. Similarly, global DALYs rose (cumulative growth: 49.5%; annual growth rate: 1.32%), yet age-standardized DALY rates (ASDRs) decreased. Significant disparities were observed across gender, age groups, regions, and countries, with higher burdens in males and in regions such as East Asia. Projections indicate that by 2040, both the ASMR and ASDR for smoking-associated liver cancer will decline significantly, particularly among the male population. In conclusion, although the burden of liver cancer related to smoking is on a downward trend, there are still significant demographic and regional differences. Future efforts should prioritize strengthened public health policies, targeted interventions, and further research into the smoking–liver cancer relationship to enhance prevention and control strategies. Full article
(This article belongs to the Topic Dietary Habits in Liver Health and Disease: Preclinical and Clinical Studies)
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18 pages, 373 KB  
Review
Navigating the Latest Hepatitis B Virus Reactivation Guidelines
by Zeyad Elharabi, Jowana Saba and Hakan Akin
Diseases 2025, 13(11), 355; https://doi.org/10.3390/diseases13110355 - 1 Nov 2025
Viewed by 4293
Abstract
Hepatitis B virus (HBV) infection is a global health concern with an estimated 254 million people with chronic HBV infection. The utilization of immunosuppressive therapies (ISTs) is increasing and expanding continuously with new agents being implemented across multiple medical disciplines. The occurrence of [...] Read more.
Hepatitis B virus (HBV) infection is a global health concern with an estimated 254 million people with chronic HBV infection. The utilization of immunosuppressive therapies (ISTs) is increasing and expanding continuously with new agents being implemented across multiple medical disciplines. The occurrence of HBV reactivation (HBVr) during or after IST varies from 15% to 50% in HBsAg-positive individuals and can be higher than 75% after stem cell transplantation. HBVr is gaining increasing significance in contemporary clinical practice. The American Gastroenterological Association (AGA) in 2025, the European Association for the Study of the Liver (EASL) in 2025, and the Asian Pacific Association for the Study of the Liver (APASL) in 2021, published their most recent clinical guidelines as major societies in the area, which enables us to better predict and manage HBVr. This narrative review focuses on comparing these three current guidelines, highlighting key similarities and differences to provide valuable guidance for practitioners navigating the complex, sometimes conflicting recommendations, thereby aiding clinicians in their decision-making. The risk of HBVr during IST has been stratified into three categories in all three guidelines: high (>10%), moderate (1–10%), and low (<1%). The effectiveness of prophylaxis scales with baseline risk for HBV reactivation. Prophylaxis is clearly cost-effective for high-risk patients, potentially beneficial for those at moderate risk, and generally may not be justified for low-risk individuals. Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are all highly effective in preventing HBV reactivation during immunosuppression and all are considered to be economically viable options for HBVr high risk patients. When selecting among these agents, safety considerations—particularly renal and bone toxicity—and insurance coverage remain the primary factors directing clinical decision-making. Full article
(This article belongs to the Special Issue Viral Hepatitis: Diagnosis, Treatment and Management)
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20 pages, 1161 KB  
Review
The Systemic Link Between Oral Health and Cardiovascular Disease: Contemporary Evidence, Mechanisms, and Risk Factor Implications
by Florinel Cosmin Bida, Florin Razvan Curca, Raoul-Vasile Lupusoru, Dragos Ioan Virvescu, Mihaela Scurtu, Gabriel Rotundu, Oana Maria Butnaru, Teona Tudorici, Ionut Luchian and Dana Gabriela Budala
Diseases 2025, 13(11), 354; https://doi.org/10.3390/diseases13110354 - 31 Oct 2025
Cited by 1 | Viewed by 3557
Abstract
Background: Oral health plays a critical role in systemic wellbeing, with growing evidence supporting strong associations between oral conditions and cardiovascular disease (CVD). These connections extend beyond periodontal disease and involve oral microbiota imbalance, systemic inflammation, and oral side effects of cardiovascular pharmacotherapy. [...] Read more.
Background: Oral health plays a critical role in systemic wellbeing, with growing evidence supporting strong associations between oral conditions and cardiovascular disease (CVD). These connections extend beyond periodontal disease and involve oral microbiota imbalance, systemic inflammation, and oral side effects of cardiovascular pharmacotherapy. Objective: To explore these links, a narrative literature review was performed using PubMed, Scopus, and ScienceDirect, covering studies published between 2000 and 2025. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and ScienceDirect for studies published between January 2000 and May 2025. Both MeSH and free-text terms related to oral health, periodontal disease, systemic inflammation, endothelial dysfunction, and atherosclerosis were used. Eligible studies included observational and interventional research, systematic reviews, and meta-analyses. Key findings: The evidence consistently supports an association between chronic periodontal inflammation and cardiovascular risk, mediated by systemic dissemination of proinflammatory cytokines (IL-6, TNF-α, CRP) and microbial products that promote endothelial activation and atherogenesis. Interventional data indicate that periodontal therapy may reduce systemic inflammatory burden and improve vascular parameters, though heterogeneity across studies limits causal inference. Conclusions: Current findings highlight a significant oral–systemic connection through inflammatory and endothelial mechanisms. Strengthening interdisciplinary collaboration between dental and cardiovascular care providers is essential to translate this evidence into preventive and therapeutic practice. Further longitudinal and mechanistic studies are required to confirm causality and guide clinical integration. Full article
(This article belongs to the Special Issue Insights into the Management of Cardiovascular Disease Risk Factors)
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15 pages, 2449 KB  
Article
Impact of Becoming a Certified Oncologic Center of Pancreatic Surgery: Evaluation of Single-Center Perioperative Results and Quality of Life Before and After Implementation of a Certified Center
by Jan-Paul Gundlach, Thorben Fedders, Steffen Markus Heckl, Thomas Becker and Julius Pochhammer
Diseases 2025, 13(11), 353; https://doi.org/10.3390/diseases13110353 - 31 Oct 2025
Viewed by 388
Abstract
Background: Centralization and certification mark constant processes in everyday clinical routine. Despite the continuously rising number of certified pancreatic cancer (PAC) centers in recent years, fewer than 40% of PAC resections are still performed in certified institutions nationwide. The main objective of the [...] Read more.
Background: Centralization and certification mark constant processes in everyday clinical routine. Despite the continuously rising number of certified pancreatic cancer (PAC) centers in recent years, fewer than 40% of PAC resections are still performed in certified institutions nationwide. The main objective of the certification is the enhancement of patient survival. Furthermore, certification is intended to improve structural quality, multidisciplinary cooperation, and the transparency of treatment pathways. In addition, it should have a positive effect on patient satisfaction. However, it requires the substantial effort of all partners involved. We aim to illustrate both advantages and limitations of the certification process. Methods: We analyzed perioperative outcomes of patients undergoing pancreatic resection for PAC (ICD C25) before and after our center’s first certification, and benchmarked these results against national data from the German Cancer Society. In addition, we analyzed quality of life (QoL) longitudinally using the validated QLQ-C30 questionnaire administered preoperatively and at 1, 4, and 18 months postoperatively. Results: The study cohort included 47 patients treated in the three years prior to certification and 130 patients during the subsequent seven years as a certified center. The mean annual number of PAC resections increased from 15 (ranged 14–18) to 19 (ranged 10–26). In-hospital mortality, length of stay, and rate of exploration-only procedures remained unchanged. Indicators of procedural quality, such as the number of harvested lymph nodes (p = 0.1485) and the precision of histopathological assessment, improved slightly but not significantly. QoL scores generally improved after discharge in both groups; however, functional scales and symptom measures demonstrated unexpectedly inferior values following certification, possibly reflecting higher case complexity. Conclusion: Achieving and maintaining certification requires substantial and continuous effort from all disciplines involved. While major improvements in morbidity, mortality, and long-term QoL were not observed, certification ensured clearer delegation of responsibilities, standardized documentation, and structured quality control. We therefore consider the certification process valuable for promoting multidisciplinary collaboration, maintaining high treatment volumes, and ensuring transparent oncological care pathways. Full article
(This article belongs to the Section Oncology)
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14 pages, 253 KB  
Article
Quantitative Analysis of Selected Circulating Hematological Biomarkers, Essential Minerals, Vitamins, and Thyroid Hormones in Females Affected by Hair Loss
by Saad Al-Fawaeir and Ibrahim Al-Odat
Diseases 2025, 13(11), 352; https://doi.org/10.3390/diseases13110352 - 29 Oct 2025
Viewed by 6374
Abstract
Purpose: To assess the association between hair loss in females and various biomarkers including hemoglobin, iron, ferritin, zinc, selenium, calcium, vitamin D, vitamin B12, folic acid, and thyroid hormones. Patients and methods: This study enrolled 100 women presenting with hair loss and 100 [...] Read more.
Purpose: To assess the association between hair loss in females and various biomarkers including hemoglobin, iron, ferritin, zinc, selenium, calcium, vitamin D, vitamin B12, folic acid, and thyroid hormones. Patients and methods: This study enrolled 100 women presenting with hair loss and 100 age-matched healthy controls. Venous blood samples were collected for analysis of hematological, hormonal and biochemical parameters. Results: The mean age of participants was comparable between groups (43.06 ± 10.76 vs. 41.39 ± 7.94 years; p = 0.88). Hair loss in females had significantly lower mean levels of Hb (11.45 ± 0.39 vs. 13.09 ± 0.46 g/dL; p < 0.001), iron (70.14 ± 7.85 vs. 94.42 ± 5.61 µg/dL; p < 0.001) and ferritin (39.34 ± 3.71 vs. 48.09 ± 5.31 ng/mL), all with p < 0.001. Serum levels of selenium (67.11 ± 5.53 vs. 71.45 ± 4.05 µg/L), zinc (86.07 ± 3.98 vs. 88.87 ± 2.03 µg/L), copper (90.71 ± 3.48 vs. 104.84 ± 5.38 µg/L), and calcium (8.61 ± 0.28 vs. 9.11 ± 0.27 mg/dL) were significantly reduced in women with hair loss (p < 0.001). Thyroid hormones were also significantly lower in the hair loss group, including TSH (1.74 ± 0.25 vs. 2.35 ± 0.39 µIU/mL) and FREE T4 (1.11 ± 0.11 vs. 1.32 ± 0.12 ng/dL), despite remaining within the normal reference ranges. Patients also showed lower serum folate (6.17 ± 0.63 vs. 6.96 ± 0.41 ng/mL), vitamin B12 (185.52 ± 35.27 vs. 258.30 ± 52.84 pg/mL), and vitamin D (26.32 ± 2.98 vs. 32.20 ± 3.76 ng/dL) levels (p < 0.001). Conclusions: Hair loss in females is significantly associated with reduced levels of circulating hemoglobin, iron, copper, selenium, vitamin D, vitamin B12, folate, thyroid-stimulating hormone and FREE T4 hormone. Full article
14 pages, 832 KB  
Article
Risk Factors for Recurrent Hip Fractures Following Surgical Treatment of Primary Osteoporotic Hip Fractures in Chinese Older Adults
by Yuzhu Wang, Wenhui Shen, Jiayi Jiang, Lin Wang, Qing Xia, Yunchao Shao and Lu Cao
Diseases 2025, 13(11), 351; https://doi.org/10.3390/diseases13110351 - 27 Oct 2025
Viewed by 778
Abstract
Objectives: Hip fractures associated with osteoporosis are indicative of high rates of both disability and mortality. The objective of this study was to analyze the risk factors for recurrent hip fractures following primary osteoporotic hip fracture surgery in older adult patients. Methods: A [...] Read more.
Objectives: Hip fractures associated with osteoporosis are indicative of high rates of both disability and mortality. The objective of this study was to analyze the risk factors for recurrent hip fractures following primary osteoporotic hip fracture surgery in older adult patients. Methods: A single-center, retrospective cohort study was conducted on 376 patients suffering from primary osteoporotic hip fractures from 1 January 2020 to 31 December 2021. Multivariate logistic regression was used to identify risk factors for recurrent hip fractures. Results: The study observed 376 patients over a period of three years. The incidence of recurrent hip fractures was 20.5% (77/376). Multiple logistic regression analysis revealed that age ≥ 85 years (odd ratios [OR] = 3.127, 95% confidence interval [CI] = 1.672–5.849, p < 0.001), chronic obstructive pulmonary disease (COPD) (OR = 3.794, 95%CI = 1.747–8.236, p < 0.001), and Parkinson’s disease (PD) (OR = 2.744, 95%CI = 1.249–6.028, p = 0.012) were independent risk factors for recurrent hip fractures; antiosteoporosis drugs (OR = 0.243, 95%CI = 0.131–0.451, p < 0.001), duration of antiosteoporosis drug therapy (OR = 0.564, 95%CI = 0.283–0.830, p = 0.003) and serum albumin ≥ 35 g·L−1 (OR = 0.413, 95%CI = 0.194–0.881, p = 0.022) were independent protective factors for recurrent hip fractures. The receiver operating characteristic (ROC) curve demonstrated that the AUC was 0.802, the sensitivity was 77.8%, and the specificity was 75.5%. A significantly higher three-year mortality rate was observed among patients with recurrent hip fractures (26.0% vs. 15.4%, p = 0.029). Conclusions: Older patients with advanced age, COPD and PD were at greater risk of recurrent hip fractures. Early nutrition intervention and antiosteoporosis drug therapy may decrease the incidence of recurrent hip fractures in older patients, thereby reducing mortality. Full article
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