Diseases

15 pages, 285 KiB

Open AccessReview

Posterior Urethral Valves and Fertility: Insight on Paternity Rates and Seminal Parameters

by Marcello Della Corte, Simona Gerocarni Nappo, Antonio Aversa, Sandro La Vignera, Francesco Porpiglia, Cristian Fiori and Nicola Mondaini

Diseases 2025, 13(1), 21; https://doi.org/10.3390/diseases13010021 - 17 Jan 2025

Abstract

Background: Posterior urethral valves (PUVs) represent the most common cause of male congenital lower urinary tract obstruction, often responsible for renal dysplasia and chronic renal failure. Despite recent improvements in patients’ outcomes thanks to prenatal ultrasound early diagnosis, PUVs can still impact sexual [...] Read more.

Background: Posterior urethral valves (PUVs) represent the most common cause of male congenital lower urinary tract obstruction, often responsible for renal dysplasia and chronic renal failure. Despite recent improvements in patients’ outcomes thanks to prenatal ultrasound early diagnosis, PUVs can still impact sexual function and fertility. This study aims to review the available evidence on fertility in PUV patients, examining paternity rates and semen parameters. Methods: A review was conducted of the PubMed, Cochrane, Scopus, and Embase databases. Studies focusing on fertility and paternity outcomes in PUV patients were selected, including case reports, case series, and retrospective and prospective studies. Results: A total of 15 studies met the inclusion criteria. The review revealed that PUV patients often exhibit compromised semen parameters, including low sperm count, reduced motility, and abnormal morphology, as well as alterations in seminal plasma. PUV diagnoses are common in adults exhibiting infertility and ejaculation disorders, suggesting PUVs cannot be considered only a pediatric disease. Paternity rates among PUV patients were rarely reported in extenso, hampering the correct assessment of the overall medium paternity rate and its comparison with that of healthy individuals. Lastly, seminal parameters were assessed in a minimal cohort of patients, therefore, they could not be considered representative. Conclusions: Fertility and seminal parameters in PUV patients represent an under-investigated area. PUVs can variably and non-univocally affect fatherhood, and they may be associated with compromised semen quality. Early intervention and long-term follow-up are essential to address potential fertility issues. Future research should focus on developing targeted strategies to preserve and enhance fertility in this patient population. Full article

(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)

14 pages, 1418 KiB

Open AccessCase Report

Hypercalcemia Following Adrenalectomy for Cushing Syndrome in a Patient with Post-Surgical Hypoparathyroidism

by Pietro Locantore, Alessandro Oliva, Gianluca Cera, Rosa Maria Paragliola, Roberto Novizio, Caterina Policola, Andrea Corsello and Alfredo Pontecorvi

Diseases 2025, 13(1), 20; https://doi.org/10.3390/diseases13010020 - 17 Jan 2025

Abstract

Background: Hypercalcemia is a frequently encountered laboratory finding in endocrinology, warranting accurate clinical and laboratory evaluation to identify its cause. While primary hyperparathyroidism and malignancies represent the most common causes, many other etiologies have been described, including some reports of hypercalcemia secondary to [...] Read more.

Background: Hypercalcemia is a frequently encountered laboratory finding in endocrinology, warranting accurate clinical and laboratory evaluation to identify its cause. While primary hyperparathyroidism and malignancies represent the most common causes, many other etiologies have been described, including some reports of hypercalcemia secondary to adrenal insufficiency. On the contrary, hypoparathyroidism is a relatively common cause of hypocalcemia, often arising as a complication of thyroid surgery. In real-world clinical practice, however, many challenges come into play, and a comprehensive approach may not be enough to establish a diagnosis. Case presentation: we describe a peculiar case of severe hypercalcemia occurring in a 47-year-old woman with a previous history of post-surgical permanent hypoparathyroidism treated with calcitriol (0.5 µg bid) and calcium carbonate (1 g qd), which persisted after withdrawal of these drugs. During her follow-up, an ACTH-independent Cushing syndrome was diagnosed, leading to a unilateral right adrenalectomy. In the two months following surgery, she was admitted to the emergency ward on three occasions because of severe, persistent, idiopathic hypercalcemia. On each occasion, parathyroid hormone levels were confirmed to be undetectable, with low vitamin D levels. Common and rare causes of hypercalcemia were excluded, and the persistence of severely elevated calcium levels led to the empirical use of intravenous clodronate, achieving remission of both hypercalcemia and, unexpectedly, hypoparathyroidism. After 8 months, due to borderline-reduced calcium, calcitriol at 0.5 µg qd was restarted. After 18 months of follow-up, the patient is well and normocalcemic, with low-dose calcitriol. Notably, the patient had no acute adrenal insufficiency, distinguishing this case from other post-adrenalectomy hypercalcemia reports. Conclusions: the history of hypoparathyroidism makes this case even more unusual, and it encourages careful follow-up of hypoparathyroid patients with Cushing syndrome. Ongoing observation, as well as new research on the physiopathology of cortisol and calcium metabolism, are needed to clarify the pathogenesis of this case. Full article

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20 pages, 1166 KiB

Open AccessReview

Elucidating the Role of the T Cell Receptor Repertoire in Myelodysplastic Neoplasms and Acute Myeloid Leukemia

by Georgios Petros Barakos, Vasileios Georgoulis, Epameinondas Koumpis and Eleftheria Hatzimichael

Diseases 2025, 13(1), 19; https://doi.org/10.3390/diseases13010019 - 17 Jan 2025

Abstract

T cells, as integral components of the adaptive immune system, recognize diverse antigens through unique T cell receptors (TCRs). To achieve this, during T cell maturation, the thymus generates a wide repertoire of TCRs. This is essential for understanding cancer evolution, progression, and [...] Read more.

T cells, as integral components of the adaptive immune system, recognize diverse antigens through unique T cell receptors (TCRs). To achieve this, during T cell maturation, the thymus generates a wide repertoire of TCRs. This is essential for understanding cancer evolution, progression, and the efficacy of immunotherapies. Myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) are hematological neoplasms that are characterized by immune evasion mechanisms, with immunotherapy giving only modest results thus far. Our review of TCR repertoire dynamics in these diseases reveals distinct patterns: MDS patients show increased TCR clonality with disease progression, while AML exhibits varied TCR signatures depending on disease stage and treatment response. Understanding these patterns has important clinical implications, as TCR repertoire metrics may serve as potential biomarkers for disease progression and treatment response, particularly in the context of immunotherapy and stem cell transplantation. These insights could guide patient stratification and treatment selection, ultimately improving therapeutic outcomes in MDS and AML. Full article

(This article belongs to the Section Oncology)

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24 pages, 1140 KiB

Open AccessArticle

The Relationship Between Cervicovaginal Infection, Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia in Romanian Women

by Anca Daniela Brăila, Cristian-Viorel Poalelungi, Cristina-Crenguţa Albu, Constantin Marian Damian, Laurențiu Mihai Dȋră, Andreea-Mariana Bănățeanu and Claudia Florina Bogdan-Andreescu

Diseases 2025, 13(1), 18; https://doi.org/10.3390/diseases13010018 - 16 Jan 2025

Abstract

Cervical intraepithelial neoplasia (CIN) is a premalignant cervical condition closely linked to persistent high-risk HPV infection, a major risk factor for cervical cancer. This study aims to investigate the relationship between cervicovaginal infections, HPV infection, and CIN development in 94 Romanian women with [...] Read more.

Cervical intraepithelial neoplasia (CIN) is a premalignant cervical condition closely linked to persistent high-risk HPV infection, a major risk factor for cervical cancer. This study aims to investigate the relationship between cervicovaginal infections, HPV infection, and CIN development in 94 Romanian women with cervical lesions. Comprehensive assessments included HPV genotyping, cytology, colposcopy, and histopathology. In 53.20% of cases, vaginal infections were identified, with Candida albicans most frequently associated with HPV. Histopathology revealed 48.94% low-grade CIN, 42.55% high-grade CIN, and 8.51% invasive carcinoma. There was a strong correlation between high-risk HPV types (especially HPV 16 and 18), colposcopic findings, histopathology, and age. This study emphasizes the mutual effect of cervicovaginal infections and HPV infection in increasing the risk of developing CIN and cervical cancer among Romanian women. Persistent infection with high-risk HPV types, particularly HPV 16 and 18, has been confirmed as a primary driver of CIN and cervical cancer progression. Full article

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9 pages, 629 KiB

Open AccessArticle

Targeting Soluble Amyloid Oligomers in Alzheimer’s Disease: A Hypothetical Model Study Comparing Intrathecal Pseudodelivery of mAbs Against Intravenous Administration

by Manuel Menendez-Gonzalez

Diseases 2025, 13(1), 17; https://doi.org/10.3390/diseases13010017 - 16 Jan 2025

Abstract

Background/Objective: Neurotoxic soluble amyloid-β (Aβ) oligomers are key drivers of Alzheimer’s pathology, with evidence suggesting that early targeting of these soluble forms may slow disease progression. Traditional intravenous (IV) monoclonal antibodies (mAbs) face challenges, including limited brain penetration and risks such as amyloid-related [...] Read more.

Background/Objective: Neurotoxic soluble amyloid-β (Aβ) oligomers are key drivers of Alzheimer’s pathology, with evidence suggesting that early targeting of these soluble forms may slow disease progression. Traditional intravenous (IV) monoclonal antibodies (mAbs) face challenges, including limited brain penetration and risks such as amyloid-related imaging abnormalities (ARIA). This hypothetical study aimed to model amyloid dynamics in early-to-moderate Alzheimer’s disease (AD) and compare the efficacy of IV mAn with intrathecal pseudodelivery, a novel method that confines mAbs in a subcutaneous reservoir for selective amyloid clearance in cerebrospinal fluid (CSF) without systemic exposure. Methods: A mathematical framework was employed to simulate Aβ dynamics in patients with early-to-moderate AD. Two therapeutic approaches were compared: IV mAb and intrathecal pseudodelivery of mAb. The model incorporated amyloid kinetics, mAb affinity, protofibril size, and therapy-induced clearance rates to evaluate the impact of both methods on amyloid reduction, PET negativity timelines, and the risk of ARIA. Results: Intrathecal pseudodelivery significantly accelerated Aβ clearance compared to IV administration, achieving amyloid PET scan negativity by month 132, as opposed to month 150 with IV mAb. This method demonstrated no ARIA risk and reduced amyloid reaccumulation. By targeting soluble Aβ species more effectively, intrathecal pseudodelivery emerged as a safer and more efficient strategy for early AD intervention. Conclusions: Intrathecal pseudodelivery offers a promising alternative to IV mAbs, overcoming challenges associated with blood–brain barrier penetration and systemic side effects. Further research should focus on optimizing this approach and exploring combination therapies to enhance clinical outcomes in AD. Full article

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12 pages, 239 KiB

Open AccessArticle

Impact of Preoperative and Intraoperative Factors on Postoperative Outcomes in Patients with Colorectal Cancer: A 10-Year Retrospective Study

by Lucian Flavius Herlo, Ioana Golu, Alexandra Herlo, Claudia Raluca Balasa Virzob, Ionescu Alin, Stela Iurciuc, Ionut Eduard Iordache, Luana Alexandrescu, Doina Ecaterina Tofolean and Raluca Dumache

Diseases 2025, 13(1), 16; https://doi.org/10.3390/diseases13010016 - 15 Jan 2025

Abstract

Background and Objectives: Colorectal cancer is a major contributor to global cancer morbidity and mortality. Surgical resection remains the cornerstone of treatment, but postoperative complications can significantly affect patient outcomes. Identifying factors that influence postoperative morbidity and mortality is crucial for optimizing patient [...] Read more.

Background and Objectives: Colorectal cancer is a major contributor to global cancer morbidity and mortality. Surgical resection remains the cornerstone of treatment, but postoperative complications can significantly affect patient outcomes. Identifying factors that influence postoperative morbidity and mortality is crucial for optimizing patient care. This study aims to evaluate the impact of preoperative, intraoperative, and postoperative factors on surgical outcomes in patients with colorectal cancer. Methods: A retrospective cohort study was conducted on 688 patients who underwent colorectal cancer surgery within a 10-year period. Data collected included demographic information, comorbidities, laboratory values, surgical details, and postoperative outcomes. Statistical analyses were performed using chi-square tests for categorical variables and t-tests for continuous variables. Multivariate logistic regression was used to identify independent predictors of postoperative complications and mortality. Results: Postoperative complications occurred in 28.5% of patients, and the 30-day mortality rate was 5.2%. Preoperative factors such as elevated C-reactive protein (CRP) levels (p < 0.001), low albumin levels (p = 0.003), a high American Society of Anesthesiologists (ASA) score (p < 0.001), and presence of comorbidities like diabetes and hypertension (p = 0.005) were significantly associated with increased postoperative complications. Intraoperative factors such as blood loss greater than 500 mL (p < 0.001) and longer operative time (p = 0.021) were also significant predictors of adverse outcomes. Multivariate analysis identified elevated CRP (OR 2.1, 95% CI 1.5–2.9), low albumin (OR 1.8, 95% CI 1.3–2.5), and blood loss > 500 mL (OR 2.4, 95% CI 1.7–3.4) as independent predictors of postoperative complications. Conclusions: Preoperative inflammatory markers, nutritional status, ASA score, comorbidities, and intraoperative factors like blood loss significantly influence postoperative outcomes in colorectal cancer surgery. Recognizing these risk factors allows for better preoperative optimization and surgical planning, potentially reducing postoperative morbidity and mortality. Full article

20 pages, 270 KiB

Open AccessArticle

The Development and Initial Validation of the REST Questionnaire: A Multidimensional Tool for Assessing Fatigue in Individuals with and Without a History of Cancer

by Giuseppe Di Lorenzo, Carlo Buonerba, Raffaele Baio, Eleonora Monteleone, Francesco Passaro, Antonio Tufano, Vittorino Montanaro, Vittorio Riccio, Ilaria Gallo, Francesca Cappuccio, Federica Fortino, Anna Buonocore, Federica Monaco, Antonio Verde, Anna Rita Amato, Oriana Strianese, Ferdinando Costabile and Luca Scafuri

Diseases 2025, 13(1), 15; https://doi.org/10.3390/diseases13010015 - 15 Jan 2025

Abstract

Background: Fatigue is a prevalent and complex condition with significant impacts on well-being. Existing fatigue assessments often lack comprehensiveness or practicality for general population studies. Methods: This study validated the REST Questionnaire, a novel fatigue assessment tool, in a sample of 268 adults. [...] Read more.

Background: Fatigue is a prevalent and complex condition with significant impacts on well-being. Existing fatigue assessments often lack comprehensiveness or practicality for general population studies. Methods: This study validated the REST Questionnaire, a novel fatigue assessment tool, in a sample of 268 adults. Psychometric properties, including internal consistency and construct validity, were evaluated. REST scores were correlated with WHO-5 well-being, BMI, self-rated health, and chronic conditions. Exploratory factor analysis identified underlying dimensions of fatigue. Results: The REST Questionnaire demonstrated excellent internal consistency (Cronbach’s alpha = 0.918) and construct validity. Higher fatigue scores were associated with lower well-being, female gender, and the presence of certain chronic conditions (cancer, kidney stones, gastric ulcers). Two distinct fatigue dimensions, “physical fatigue and functional impacts” and “emotional and social consequences”, were identified. Conclusions: The REST Questionnaire is a reliable and valid tool for assessing fatigue in the general population. Its multidimensional framework and sensitivity to comorbidities offer valuable insights for research and public health applications, with the potential to inform targeted interventions aimed at improving well-being. Full article

11 pages, 491 KiB

Open AccessSystematic Review

Yaws in Africa: Past, Present and Future

by Ezekiel K. Vicar, Shirley V. Simpson, Gloria I. Mensah, Kennedy K. Addo and Eric S. Donkor

Diseases 2025, 13(1), 14; https://doi.org/10.3390/diseases13010014 - 14 Jan 2025

Abstract

Background: Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands. Yaws is currently endemic in at least [...] Read more.

Background: Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands. Yaws is currently endemic in at least 15 countries, but adequate surveillance data are lacking. In line with the WHO’s effort to improve early detection, diagnosis, and proper management leading to the eventual eradication of yaws, this article reviews the existing literature on yaws in Africa to highlight the epidemiological pattern, genetic variability, diagnosis modalities, treatment, and control strategies, the challenges and prospects for yaws eradication. Methods: We searched PubMed and Scopus databases to identify published data in line with the review objectives. Results: One hundred and eighty-eight peer-reviewed articles were identified by PubMed and Scopus, out of which thirty were eligible. The studies covered 11 African countries, with the reported prevalence ranging from 0.50% to 43.0%. Conclusions: There is a great prospect for eradication if countries capitalize on the availability of simple, inexpensive, and well-tolerated oral treatment that has proven effective, validated point-of-care diagnostic tests and new molecular tests. Countries should embark on integrated disease control efforts to increase sustainability and improve the quality of life for people living with this NTD in poor communities. Full article

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14 pages, 974 KiB

Open AccessReview

A Scoping Review of Eosinophilic Pneumonia and Antidepressants: An Association Not to Be Overlooked

by Jaron Steiner, Leonie Steuernagel, Fotios Drakopanagiotakis, Konstantinos Bonelis and Paschalis Steiropoulos

Diseases 2025, 13(1), 13; https://doi.org/10.3390/diseases13010013 - 13 Jan 2025

Abstract

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. [...] Read more.

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms “eosinophilic pneumonia AND antidepressants”. Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis. Full article

(This article belongs to the Section Respiratory Diseases)

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13 pages, 1535 KiB

Open AccessArticle

Prevalence of Vitamin K2 Deficiency and Its Association with Coronary Artery Disease: A Case–Control Study

by Sameh A. Ahmed, Abdulaziz A. Yar, Anas M. Ghaith, Rayan N. Alahmadi, Faisal A. Almaleki, Hassan S. Alahmadi, Waleed H. Almaramhy, Ahmed M. Alsaedi, Man K. Alraddadi and Hussein M. Ismail

Diseases 2025, 13(1), 12; https://doi.org/10.3390/diseases13010012 - 11 Jan 2025

Abstract

Background/Objectives: Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding [...] Read more.

Background/Objectives: Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding the association between serum levels of vitamin K2 analogs in different CAD types and examines their correlations with clinical risk parameters in CAD patients. Methods: This case–control study enrolled CAD patients and healthy controls to assess and compare serum concentrations of two vitamin K2 analogs including menaquinone-4 (MK-4) and menaquinone-7 (MK-7) via ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). CAD risk factors were evaluated and related to serum levels of vitamin K2 analogs. The CAD group was further subdivided into stable angina, STEMI, NSTEMI, and unstable angina groups to investigate potential differences in vitamin K2 analog levels. Results: Patients experiencing acute coronary syndrome exhibited notably reduced serum levels of MK-4 and MK-7 (1.61 ± 0.66, and 1.64 ± 0.59 ng/mL, respectively) in comparison to the control group (2.29 ± 0.54, and 2.16 ± 0.46 ng/mL, respectively), with MK-4 and MK-7 displaying stronger associations with CAD risk indicators. Notable variations in vitamin K2 analog levels were found between CAD patients and control groups (p < 0.001). Unstable angina patients showed the lowest serum levels of MK-4 and MK-7. Conclusions: The present study demonstrated a higher prevalence rate of vitamin K2 deficiency among patients with CAD. The most pronounced decrease in MK-4 and MK-7 was observed in unstable angina patients. Moreover, these outcomes indicate the imperative requirement for an integrative approach that incorporates metabolic, lipid, and vitamin K2-related pathways in the risk stratification and management of CAD. Full article

(This article belongs to the Section Cardiology)

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12 pages, 587 KiB

Open AccessArticle

A Survey of the Knowledge, Attitudes and Practices of a Sample of Albanian Medical Students in Relation to Occupational Exposure to Biological Agents

by Lorenzo Ippoliti, Luca Coppeta, Ersilia Buonomo, Giuseppina Somma, Giuseppe Bizzarro, Cristiana Ferrari, Andrea Mazza, Agostino Paolino, Claudia Salvi, Vittorio Caputi, Antonio Pietroiusti and Andrea Magrini

Diseases 2025, 13(1), 11; https://doi.org/10.3390/diseases13010011 - 10 Jan 2025

Abstract

(1) Background: Exposure to blood carries the risk of transmission of many infectious diseases. Healthcare workers (HCWs), including hospital-based medical students, face high and often under-reported rates of exposure to needlestick and sharps injuries. Previous studies have shown that students’ knowledge of infection [...] Read more.

(1) Background: Exposure to blood carries the risk of transmission of many infectious diseases. Healthcare workers (HCWs), including hospital-based medical students, face high and often under-reported rates of exposure to needlestick and sharps injuries. Previous studies have shown that students’ knowledge of infection control varies, highlighting the importance of pre-placement training. This study aims to assess knowledge, attitudes and practices regarding these risks in a population of medical students from Albania. (2) Methods: A validated questionnaire was administered to 134 medical students in an Italian hospital in May 2023. It assessed HBV vaccination status, adherence to infection control practices, knowledge of pathogen transmission, exposure incidents and attitudes towards infected patients. Three additional questions addressed air-borne transmission of tuberculosis and vaccination recommendations for healthcare workers. (3) Results: Most students (64%) reported being aware of occupational exposure risks. While 93% and 87%, respectively, recognised HIV and HBV as blood-borne pathogens, fewer recognised Treponema pallidum (44%). Awareness of post-exposure prophylaxis for HIV was high (85%), but although 75% reported having received training, only 45% felt it was adequate. Statistical analysis revealed an association between knowledge of infection control, awareness of pathogen transmission and understanding of the importance of vaccination. (4) Conclusions: Our study highlights gaps in medical students’ knowledge of occupational infections and highlights the need for improved pre-clerkship education. Improved education could reduce anxiety, ethical issues and misconceptions and promote safer healthcare practices. Full article

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13 pages, 3163 KiB

Open AccessArticle

Valproic Acid Enhances Venetoclax Efficacy in Targeting Acute Myeloid Leukemia

by Renshi Kawakatsu, Kenjiro Tadagaki, Kenta Yamasaki, Yasumichi Kuwahara and Tatsushi Yoshida

Diseases 2025, 13(1), 10; https://doi.org/10.3390/diseases13010010 - 8 Jan 2025

Abstract

Background: Acute myeloid leukemia (AML) is a common and aggressive form of leukemia, yet current treatment strategies remain insufficient. Venetoclax, a BH3-mimetic approved for AML treatment, induces Bcl-2-dependent apoptosis, though its therapeutic efficacy is still limited. Therefore, new strategies to enhance the effect [...] Read more.

Background: Acute myeloid leukemia (AML) is a common and aggressive form of leukemia, yet current treatment strategies remain insufficient. Venetoclax, a BH3-mimetic approved for AML treatment, induces Bcl-2-dependent apoptosis, though its therapeutic efficacy is still limited. Therefore, new strategies to enhance the effect of venetoclax are highly sought. Valproic acid (VPA), commonly used for epilepsy, has also been studied for potential applications in AML treatment. Methods: AML cells were treated with venetoclax, with or without VPA. Cell viability was assessed using the trypan blue dye exclusion assay, while cell cycle progression was analyzed by flow cytometry. The expression of pro-apoptotic proteins Bax and Bak was measured by RT-qPCR. Results: Venetoclax and VPA individually had only mild effects on AML cell proliferation. However, their combination significantly inhibited cell growth and triggered pronounced cell death. This combination also led to the cleavage of poly (ADP-ribose) polymerase (PARP), a substrate of caspases, indicating activation of apoptosis. VPA treatment upregulated the expression of Bax and Bak, further supporting apoptosis induction. The cell death induced by the venetoclax–VPA combination was predominantly apoptotic, as confirmed by the near-complete blockade of cell death by a pan-caspase inhibitor. Conclusions: Our study demonstrates that VPA enhances venetoclax-induced apoptosis in AML cell lines, providing a novel role for VPA and suggesting a promising combinatory strategy for AML treatment. These findings offer valuable insights into potential clinical applications of venetoclax and VPA in AML management. Full article

(This article belongs to the Special Issue Targeted Therapies for Acute Leukemias)

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13 pages, 242 KiB

Open AccessArticle

Robotic Surgery from a Gynaecological Oncology Perspective: A Global Gynaecological Oncology Surgical Outcomes Collaborative Led Study (GO SOAR3)

by Faiza Gaba, Karen Ash, Oleg Blyuss, Dhivya Chandrasekaran, Marielle Nobbenhuis, Thomas Ind, Elly Brockbank and on behalf of the GO SOAR Collaborators

Diseases 2025, 13(1), 9; https://doi.org/10.3390/diseases13010009 - 6 Jan 2025

Abstract

Background/Objectives: For healthcare institutions developing a robotic programme, delivering value for patients, clinicians, and payers is key. However, the impact on the surgeon, training pathways, and logistics are often overlooked. We conducted a study on the impact of robotic surgery on surgeons, access [...] Read more.

Background/Objectives: For healthcare institutions developing a robotic programme, delivering value for patients, clinicians, and payers is key. However, the impact on the surgeon, training pathways, and logistics are often overlooked. We conducted a study on the impact of robotic surgery on surgeons, access to robotic surgical training, and factors associated with developing a successful robotic programme. Method: In our international mixed-methods study, a customised web-based survey was circulated to gynaecological oncologists. The Wilcoxon rank-sum test and Fisher’s exact test, tested the hypothesis of the differences in continuous and categorical variables. Multiple linear regression was used to model the effect of variables on outcomes adjusting for gender, age, and postgraduate experience. Outcomes included situational awareness, surgeon fatigue/stress, and the surgical learning curve. Qualitative data were collected via in-depth semi-structured interviews using an inductive theoretical framework to explore access to surgical training and logistical considerations in the development of a successful robotic programme. Results: In total, 94%, 45%, and 48% of survey respondents (n = 152) stated that robotic surgery was less physically tiring/mentally tiring/stressful in comparison to laparoscopic surgery. Our data suggest gender differences in the robotics learning curve with men six times more likely to state robotic surgery had negatively impacted their situational awareness in the operating theatre (OR = 6.35, p ≤ 0.001) and 2.5 times more likely to state it had negatively impacted their surgical ability due to lack of haptic feedback in comparison to women (OR = 2.62, p = 0.046). Women were more risk-averse in case selection, but there were no self-reported differences in the intra-operative complication rates between male and female surgeons (OR = 1, p = 0.1). In total, 22/25 robotically trained surgeons interviewed did not follow a structured curriculum of learning. Low and middle income country centres had less access to robotic surgery. The success of robotic programmes was measured by the number of cases performed per annum, with 74% of survey respondents stating that introducing robotics increased the proportion of surgeries performed by minimal access surgery. There was a distinct lack of knowledge on the environmental impact of robotic surgery. Conclusions: Whilst robotic surgery is considered a landmark innovation in surgery, it must be responsibly implemented through effective training and waste minimisation, which must be a key metric in measuring the success of robotic programmes. Full article

14 pages, 15003 KiB

Open AccessArticle

Is Lung Disease a Risk Factor for Sudden Cardiac Death? A Comparative Case–Control Histopathological Study

by Ioana Radu, Anca Otilia Farcas, Septimiu Voidazan, Carmen Corina Radu and Klara Brinzaniuc

Diseases 2025, 13(1), 8; https://doi.org/10.3390/diseases13010008 - 6 Jan 2025

Abstract

Background/Objectives: Sudden cardiac death (SCD) constitutes approximately 50% of cardiovascular mortality. Numerous studies have established an interrelation and a strong association between SCD and pulmonary diseases, such as chronic obstructive pulmonary disease (COPD). The aim of this study is to examine the presence [...] Read more.

Background/Objectives: Sudden cardiac death (SCD) constitutes approximately 50% of cardiovascular mortality. Numerous studies have established an interrelation and a strong association between SCD and pulmonary diseases, such as chronic obstructive pulmonary disease (COPD). The aim of this study is to examine the presence of more pronounced cardiopulmonary histopathological changes in individuals who died from SCD compared to the histopathological changes in those who died from violent deaths, in two groups with comparable demographic characteristics, age and sex. Methods: This retrospective case–control study investigated the histopathological changes in cardiac and pulmonary tissues in two cohorts, each comprising 40 cases of SCD and 40 cases of violent death (self-inflicted hanging). Forensic autopsies were conducted at the Maramureș County Forensic Medicine Service, Romania, between 2019 and 2020. Results: The mean ages recorded were 43.88 years (SD 5.49) for the SCD cohort and 41.98 years (SD 8.55) for the control cohort. In the SCD cases, pulmonary parenchyma exhibited inflammatory infiltrate in 57.5% (23), fibrosis in 62.5% (25), blood extravasation in 45% (18), and vascular media thickening in 37.5% (15), compared to the control cohort, where these parameters were extremely low. In myocardial tissue, fibrosis was identified in 47.5% (19) and subendocardial adipose tissue in 22.5% (9) of the control cohort. Conclusions: A close association exists between SCD and the histopathological alterations observed in the pulmonary parenchyma, including inflammation, fibrosis, emphysema, blood extravasation, stasis, intimal lesions, and vascular media thickening in intraparenchymal vessels. Both the histopathological modifications in the pulmonary parenchyma and vessels, as well as those in myocardial tissue, were associated with an increased risk of SCD, ranging from 2.17 times (presence of intimal lesions) to 58.50 times (presence of interstitial and perivascular inflammatory infiltrate in myocardial tissue). Full article

(This article belongs to the Section Cardiology)

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19 pages, 4176 KiB

Open AccessHypothesis

Advanced Glycation End-Product-Modified Heat Shock Protein 90 May Be Associated with Urinary Stones

by Takanobu Takata, Shinya Inoue, Kenshiro Kunii, Togen Masauji, Junji Moriya, Yoshiharu Motoo and Katsuhito Miyazawa

Diseases 2025, 13(1), 7; https://doi.org/10.3390/diseases13010007 - 2 Jan 2025

Abstract

Background: Urinary stones (urolithiasis) have been categorized as kidney stones (renal calculus), ureteric stones (ureteral calculus and ureterolith), bladder stones (bladder calculus), and urethral stones (urethral calculus); however, the mechanisms underlying their promotion and related injuries in glomerular and tubular cells remain unclear. [...] Read more.

Background: Urinary stones (urolithiasis) have been categorized as kidney stones (renal calculus), ureteric stones (ureteral calculus and ureterolith), bladder stones (bladder calculus), and urethral stones (urethral calculus); however, the mechanisms underlying their promotion and related injuries in glomerular and tubular cells remain unclear. Although lifestyle-related diseases (LSRDs) such as hyperglycemia, type 2 diabetic mellitus, non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, and cardiovascular disease are risk factors for urolithiasis, the underlying mechanisms remain unclear. Recently, heat shock protein 90 (HSP90) on the membrane of HK-2 human proximal tubular epithelium cells has been associated with the adhesion of urinary stones and cytotoxicity. Further, HSP90 in human pancreatic and breast cells can be modified by various advanced glycation end-products (AGEs), thus affecting their function. Hypothesis 1: We hypothesized that HSP90s on/in human proximal tubular epithelium cells can be modified by various types of AGEs, and that they may affect their functions and it may be a key to reveal that LSRDs are associated with urolithiasis. Hypothesis 2: We considered the possibility that Japanese traditional medicines for urolithiasis may inhibit AGE generation. Of Choreito and Urocalun (the extract of Quercus salicina Blume/Quercus stenophylla Makino) used in the clinic, Choreito is a Kampo medicine, while Urocalun is a characteristic Japanese traditional medicine. As Urocalun contains quercetin, hesperidin, and p-hydroxy cinnamic acid, which can inhibit AGE generation, we hypothesized that Urocalun may inhibit the generation of AGE-modified HSP90s in human proximal tubular epithelium cells. Full article

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19 pages, 1010 KiB

Open AccessReview

Exploring microRNA-Mediated Immune Responses to Soil-Transmitted Helminth and Herpes Simplex Virus Type 2 Co-Infections

by Roxanne Pillay, Pragalathan Naidoo and Zilungile L. Mkhize-Kwitshana

Diseases 2025, 13(1), 6; https://doi.org/10.3390/diseases13010006 - 1 Jan 2025

Abstract

Over the last two decades, the field of microRNA (miRNA) research has grown significantly. MiRNAs are a class of short, single-stranded, non-coding RNAs that regulate gene expression post-transcriptionally. Thereby, miRNAs regulate various essential biological processes including immunity. Dysregulated miRNAs are associated with various [...] Read more.

Over the last two decades, the field of microRNA (miRNA) research has grown significantly. MiRNAs are a class of short, single-stranded, non-coding RNAs that regulate gene expression post-transcriptionally. Thereby, miRNAs regulate various essential biological processes including immunity. Dysregulated miRNAs are associated with various infectious and non-infectious diseases. Recently co-infection with soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2) has become a focus of study. Both pathogens can profoundly influence host immunity, particularly in under-resourced and co-endemic regions. It is well known that STHs induce immunomodulatory responses that have bystander effects on unrelated conditions. Typically, STHs induce T-helper 2 (Th2) and immunomodulatory responses, which may dampen the proinflammatory T-helper 1 (Th1) immune responses triggered by HSV-2. However, the extent to which STH co-infection influences the host immune response to HSV-2 is not well understood. Moreover, little is known about how miRNAs shape the immune response to STH/HSV-2 co-infection. In this article, we explore the potential influence that STH co-infection may have on host immunity to HSV-2. Because STH and HSV-2 infections are widespread and disproportionately affect vulnerable and impoverished countries, it is important to consider how STHs may impact HSV-2 immunity. Specifically, we explore how miRNAs contribute to both helminth and HSV-2 infections and discuss how miRNAs may mediate STH/HSV-2 co-infections. Insight into miRNA-mediated immune responses may further improve our understanding of the potential impact of STH/HSV-2 co-infections. Full article

(This article belongs to the Topic miRNAs in Pathophysiology of Disease)

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12 pages, 1176 KiB

Open AccessArticle

A Systematic Review and Meta-Analysis of Prophylactic Vasopressors for the Prevention of Peri-Intubation Hypotension

by Hollie Saunders, Subekshya Khadka, Rabi Shrestha, Hassan Z. Baig and Scott A. Helgeson

Diseases 2025, 13(1), 5; https://doi.org/10.3390/diseases13010005 - 31 Dec 2024

Abstract

Background/Objectives: Peri-intubation hypotension is a known complication of endotracheal intubation. In the hospital setting, peri-intubation hypotension has been shown to increase hospital mortality and length of stay. The use of prophylactic vasopressors at the time of sedation induction to prevent peri-intubation hypotension has [...] Read more.

Background/Objectives: Peri-intubation hypotension is a known complication of endotracheal intubation. In the hospital setting, peri-intubation hypotension has been shown to increase hospital mortality and length of stay. The use of prophylactic vasopressors at the time of sedation induction to prevent peri-intubation hypotension has been raised. This systematic review and meta-analysis aims to review the safety and efficacy of this practice. Methods: The study was fully registered with PROSPERO on 13 October 2022, and screening for eligibility was initiated on 20 September 2024. Randomized controlled trials, along with retrospective or prospective cohort studies, were included in the search. The terms “peri-intubation hypotension”, “vasopressors”, “intubation”, and “anesthesia induced hypotension” were used to search the title/summary in PubMed, Cochrane Library, and Google Scholar databases. An assessment of bias for each study was conducted using the Newcastle-Ottawa Quality Assessment Scale. The primary outcome was the rate of hypotension peri-intubation. Any complications secondary to hypotension or vasopressors were the secondary outcome. Results: We identified 13 studies, which were all randomized controlled studies, to include in the final analysis. The risk ratio for preventing peri-intubation hypotension was 1.6 (95% CI, 1.2–2.14) with the use of prophylactic phenylephrine while giving propofol versus no prophylactic vasopressors and 1.28 (95% CI 1.03–1.60) with the use of ephedrine. Conclusions: These findings suggest that in patients undergoing intubation in the operating room with propofol, prophylactic vasopressors given with induction for intubation decrease the odds of hypotension. Full article

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18 pages, 1460 KiB

Open AccessArticle

Persistent Post-COVID-19 Olfactory Dysfunction and Its Association with Autonomic Nervous System Function: A Case–Control Study

by Lojine Ayoub, Abeer F. Almarzouki, Rajaa Al-Raddadi and Mohamed A. Bendary

Diseases 2025, 13(1), 4; https://doi.org/10.3390/diseases13010004 - 28 Dec 2024

Abstract

Background: Following the Coronavirus Disease 2019 (COVID-19) pandemic, many patients have reported ongoing smell and taste issues. This study aims to investigate the prevalence of olfactory and gustatory dysfunction among patients with a history of COVID-19 and its association with autonomic dysfunction and [...] Read more.

Background: Following the Coronavirus Disease 2019 (COVID-19) pandemic, many patients have reported ongoing smell and taste issues. This study aims to investigate the prevalence of olfactory and gustatory dysfunction among patients with a history of COVID-19 and its association with autonomic dysfunction and disability. Patient and Methods: This case–control study included a COVID-19 group (n = 82) and a control group (n = 82). Olfactory dysfunction, including parosmia and taste problems, was explored using self-reports and the Quick Smell Identification Test (QSIT). The association between post-COVID-19 disability severity and taste and smell alterations was also analyzed. Moreover, autonomic function was evaluated using the Composite Autonomic Symptom Scale-31 (COMPASS-31) to assess the association between autonomic and olfactory dysfunction. Results: Significantly higher rates of ongoing smell (26.8%) and taste (14.6%) dysfunction were reported for the post-COVID-19 group compared to the control group. Post-COVID-19 patients reported 36.6 times more smell issues and 8.22 times more taste issues than controls. Parosmia scores were significantly worse in the post-COVID-19 group, while QSIT scores showed no significant difference between the groups. However, those with worse QSIT scores exhibited significantly more ongoing smell issues. No significant association was observed between disability and altered smell or taste. Higher secretomotor dysfunction scores were significantly associated with abnormal QSIT scores and worse parosmia scores; the other domains of the COMPASS-31 scale showed no significant associations. Conclusions: The findings indicated a potential link between autonomic and olfactory dysfunction. Further studies are needed to elucidate the mechanisms underlying persistent olfactory and autonomic dysfunction in post-COVID-19 patients. Full article

(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2024: The Post-pandemic Era)

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16 pages, 1169 KiB

Open AccessArticle

Appendicular Skeletal Muscle Index Is Positively Related to Mediterranean Diet Adherence in University Students

by Paraskevi Detopoulou, Olga Magni, Ioanna Pylarinou, Despoina Levidi, Vassilios Dedes, Milia Tzoutzou, Konstantina Argyri, Evangelia Fappa, Aristea Gioxari and George Panoutsopoulos

Diseases 2025, 13(1), 3; https://doi.org/10.3390/diseases13010003 - 28 Dec 2024

Abstract

Skeletal muscle is associated with cardiometabolic health. The appendicular skeletal muscle index (aSMI) represents the skeletal muscle mass “corrected” for height and constitutes a clinically applicable feature of sarcopenia. The relation of the aSMI with dietary habits is not clear, especially in young [...] Read more.

Skeletal muscle is associated with cardiometabolic health. The appendicular skeletal muscle index (aSMI) represents the skeletal muscle mass “corrected” for height and constitutes a clinically applicable feature of sarcopenia. The relation of the aSMI with dietary habits is not clear, especially in young adults. The present pilot study aimed to investigate the relationship between the aSMI and Mediterranean diet adherence in young adults. A cross-sectional study of 151 university students was conducted. Anthropometry and bioimpedance analysis (TANITA-MC780) were performed. The aSMI was calculated as the sum of the upper and lower extremity muscle masses divided by height squared. The HPAQ questionnaire was used for physical activity evaluation. A validated food frequency questionnaire was used for dietary assessment, and the Mediterranean Diet Score (MedDietScore) was calculated. Multivariate linear regression models with log-aSMI as a dependent variable were applied. The MedDietScore was positively related to log-aSMI in the total sample (B = 0.009, SE = 0.004, p = 0.05, R² for total model = 71%) irrespective of gender, age, ΒΜΙ, smoking, physical activity, and academic year and in males (B = 0.027, SE = 0.011, p = 0.023 R² for total model = 37%) irrespective οf age and ΒΜΙ. The positive association of the MedDietScore with aSMI supports the importance of the adoption of a Mediterranean dietary pattern—rich in plant proteins and antioxidant/anti-inflammatory compounds—in maintaining/attaining muscle mass in young subjects. Full article

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