Diseases

15 pages, 3148 KiB

Open AccessArticle

Uric Acid Causes Pancreatic β Cell Death and Dysfunction via Modulating CHOP-Mediated Endoplasmic Reticulum Stress Pathways

by Xueyan Li, Yunan Chen, Lei Su and Jialin He

Diseases 2025, 13(7), 213; https://doi.org/10.3390/diseases13070213 - 7 Jul 2025

Abstract

Background: Uric acid has been proposed as a diabetogenic factor while its effect on pancreatic β cell function remains elusive. This study aimed to explore the impact of uric acid levels on β cell function and delineate its underlying molecular mechanisms. Methods: Both [...] Read more.

Background: Uric acid has been proposed as a diabetogenic factor while its effect on pancreatic β cell function remains elusive. This study aimed to explore the impact of uric acid levels on β cell function and delineate its underlying molecular mechanisms. Methods: Both in vivo hyperuricemia diet-induced mouse models and in vitro pancreatic β cell models were utilized. Results: A progressive decrease in glucose-stimulated insulin secretion and increase in β cell apoptosis were observed in the hyperuricemia diet-induced mouse model, and these could be effectively restored by urate-lowering therapy. The dose- and time-dependent direct effects of uric acid on β cell apoptosis and insulin secretion were further confirmed in both INS-1E cells and primary isolated islets. Mechanistically, the primary role of expression of the endoplasmic reticulum stress marker C/EBP homologous protein (CHOP) was detected by RNA sequencing, and the inflammatory factor NLRP3 and pro-apoptotic genes were significantly upregulated by uric acid treatment. Conclusions: Together, our findings indicate a direct crosstalk between uric acid and β cells via CHOP/NLRP3 pathway, providing a new understanding of the diabetogenic effect of uric acid. Full article

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14 pages, 607 KiB

Open AccessSystematic Review

Analgesic and Neuroprotective Roles of Dexmedetomidine in Spine Surgery: A Systematic Review

by Spyridoula Roberta Afrati, Ioanna Lianou, Angelos Kaspiris, Vasileios Marougklianis, Anastasia Kotanidou and Spiros G. Pneumaticos

Diseases 2025, 13(7), 212; https://doi.org/10.3390/diseases13070212 - 6 Jul 2025

Abstract

Objectives: The incidence of postoperative pain in patients that undergo spinal interventions is significantly increased, affecting their functional outcomes and quality of life. Dexmedetomidine (DEX) belongs to the category of centrally acting nonopioid agents with highly selective α2 adrenoreceptor agonist activity that are [...] Read more.

Objectives: The incidence of postoperative pain in patients that undergo spinal interventions is significantly increased, affecting their functional outcomes and quality of life. Dexmedetomidine (DEX) belongs to the category of centrally acting nonopioid agents with highly selective α2 adrenoreceptor agonist activity that are frequently applied in spinal surgery based on its antinociceptive and anxiolytic properties. Although many studies displayed the effectiveness of DEX in postoperative pain management, the impact of DEX on functional improvement after spinal surgeries is still debatable. Purpose: This systematic review focuses on the intraoperative and postoperative role of dexmedetomidine (DEX) as an analgesic agent in elective and emergency adult spine surgery. Methods: An electronic literature review search was conducted via Web of Science and PubMed to assess the impact of DEX on postoperative pain management, postoperative delirium (POD), and postoperative cognitive dysfunction (POCD). Discussion: Twenty-one studies were retrieved, three of which were review articles. The effects of DEX were studied for up to 48 h postoperatively. In most cases, its administration was associated with reduced intraoperative and postoperative opioid consumption. However, findings on pain control were less conclusive due to heterogeneity in dosing protocols, concomitant medications, the timing of administration, and pain scoring systems. DEX appears to reduce the incidence of POD and POCD, particularly when used in combination with other drugs. Conclusions: Although the present study supports that the intraoperative administration of dexmedetomidine decreases the pain intensity and/or opioid consumption as well as the development of POD and POCD in patients undergoing spinal surgeries during the first 24 h postoperatively, the current literature should be expanded to allow for the safe generalisation of findings over longer follow-up periods. Further research into the neuroprotective, analgesic, and anti-inflammatory roles of DEX is warranted. Full article

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11 pages, 561 KiB

Open AccessArticle

Impact of Race on Admission, Clinical Outcomes, and Disposition in Cholangiocarcinoma: Insights from the National Inpatient Database

by Tijin A. Mathew, Teresa M. Varghese, Nithya Krishnakumaran, George M. Varghese, Khwaja S. Haq, Akshita Khosla, Rojymon Jacob and Gina Vaccaro

Diseases 2025, 13(7), 211; https://doi.org/10.3390/diseases13070211 - 4 Jul 2025

Abstract

Background: Cholangiocarcinoma, malignancies arising from the intrahepatic and extrahepatic bile ducts, has increased in incidence in the United States over the past few decades. The reported incidence of cholangiocarcinomas is high, particularly in specific racial groups such as Asian and Pacific Islander patients. [...] Read more.

Background: Cholangiocarcinoma, malignancies arising from the intrahepatic and extrahepatic bile ducts, has increased in incidence in the United States over the past few decades. The reported incidence of cholangiocarcinomas is high, particularly in specific racial groups such as Asian and Pacific Islander patients. Race also significantly impacts disparities in healthcare utilization and clinical outcomes. Our study focused on the impact of race on admission, clinical outcomes, and disposition of cholangiocarcinoma. Methods: We performed a retrospective analysis of cholangiocarcinoma-related hospital admissions, using the National Inpatient Sample for the year 2022. Patients were stratified according to race into the following groups: White, African American, Hispanic, Asian or Pacific Islander, Native American, and Other. The data analysis was performed using STATA/BE version 18.5. Univariable and multivariable logistic regression models were applied to evaluate the relationship between race and clinical and healthcare utilization outcomes. Results: In 2022, 7479 hospitalizations were recorded for cholangiocarcinoma in the United States. Among these, 65.99% were White, 13.27% Hispanic, and 10.13% African American. There was a statistically significant difference in gender distribution across racial groups (p < 0.001), with males comprising the majority in all groups. Males outnumbered females in all racial groups except among the Hispanic group. Significant racial disparities in mortality were observed, with White patients showing a mortality rate of 6.69%, compared to higher rates among African American (9.76%), Native American (8.51%), and Asian or Pacific Islander (8.09%) patients, while Hispanic (5.04%) and Other (5.88%) groups had lower rates (p < 0.001). Conclusions: The study underscores the racial disparities among cholangiocarcinoma hospitalizations, with African American, Native American, and Asian patients facing disproportionately higher mortality and poorer in-hospital outcomes compared to White patients. This analysis highlights the healthcare strategies and policy reforms to promote equitable treatment by mitigating these disparities and to improve cholangiocarcinoma outcomes. Full article

(This article belongs to the Section Oncology)

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12 pages, 535 KiB

Open AccessArticle

Fibrin Monomer and Systemic Lupus Erythematosus Reactivation During Pregnancy: A Retrospective Study

by Tran Thi Kieu My, Hoang Thi Ha, Nguyen Huu Truong, Dao Thi Thiet, Nguyen Khanh Ha, Tran Dang Xoay, Linus Olson and Bach Quoc Khanh

Diseases 2025, 13(7), 210; https://doi.org/10.3390/diseases13070210 - 3 Jul 2025

Abstract

Background: Pregnancies in patients with systemic lupus erythematosus (SLE) have always been considered high-risk. D-dimer is known for its role in excluding the diagnosis of thrombosis and has been associated with lupus reactivation; however, its physiological elevation during pregnancy limits its utility in [...] Read more.

Background: Pregnancies in patients with systemic lupus erythematosus (SLE) have always been considered high-risk. D-dimer is known for its role in excluding the diagnosis of thrombosis and has been associated with lupus reactivation; however, its physiological elevation during pregnancy limits its utility in this population. Fibrin monomer (FM) has been shown in multiple studies to remain stable in pregnant women. The objectives of this study were to evaluate D-dimer and FM levels, as well as to assess the role of FM in SLE activity during pregnancy. Methods: The subjects included 76 pregnant women with SLE diagnosed according to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. The assessment of disease activity was in accordance with the Systemic Lupus Erythematosus Pregnancy Disease Activity Index (SLEPDAI). Results: The log₁₀-transformed D-dimer (LtDD) and FM (LtFM) concentrations in the pregnant women with lupus were 1.229 (0.722–1.953) and 4.17 (3.01–5.34) µg/mL, respectively. A multivariate regression indicated that 59.1% of the variation in LtDD was influenced by the gestational age and SLEPDAI, while only 18.3% of the fluctuation in LtFM was affected by these factors. The concentration of LtFM was an independent factor in predicting SLE flare and disease activity level according to the SLEPDAI in pregnant women. Conclusions: In conclusion, this study’s findings suggest that elevated levels of both D-dimer and FM were observed in pregnant patients with SLE. However, only FM levels can be used as a prognostic factor in assessing the risk of SLE reactivation during pregnancy. Full article

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15 pages, 1463 KiB

Open AccessArticle

Persistent Changes in Hormones and Growth Factors Involved in Ageing in Patients That Recovered from Severe COVID-19

by Alice Cuchi-Cabral, André C. Palma, Guilherme A. Nogueira, Henrique Ceretta Oliveira, Suzimar F. Benato Fusco, Maria L. Moretti, Licio A. Velloso and Eliana P. Araujo

Diseases 2025, 13(7), 209; https://doi.org/10.3390/diseases13070209 - 3 Jul 2025

Abstract

Background: The coronavirus disease-19 pandemic affected millions of people and its long-term impact on the health of survivors is under evaluation. Objectives: In this study, we hypothesized that severe coronavirus disease-19 could promote long-term changes in the blood levels of hormones and growth [...] Read more.

Background: The coronavirus disease-19 pandemic affected millions of people and its long-term impact on the health of survivors is under evaluation. Objectives: In this study, we hypothesized that severe coronavirus disease-19 could promote long-term changes in the blood levels of hormones and growth factors known to be involved in the regulation of ageing. Methods: We evaluated 49 patients that recovered from severe COVID-19 and compared them with matched controls that were never infected by the virus. The blood levels of growth hormone, insulin-like growth factor-1, insulin, brain-derived neurotrophic factor, nerve growth factor, oxytocin, ghrelin, platelet-derived growth factor, fibroblast growth factor-1, and transforming growth factor-beta were determined using enzyme-linked immunosorbent assays. Results: After six months of recovery, patients presented reduced blood levels of growth hormone, insulin-like growth factor-1, brain-derived neurotrophic factor, and platelet-derived growth factor. Fifteen months after, the reductions in the blood levels of all four hormones/growth factors persisted. Conclusions: Our study advances the field by identifying hormones and growth factors involved in ageing that undergo persistent changes in patients that recover from severe COVID-19. Further studies could explore the potential of the identified hormones/growth factors as therapeutic targets for the late complications and accelerated ageing that may affect patients recovering from severe COVID-19. Full article

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12 pages, 203 KiB

Open AccessReview

Descriptive Analysis of Reported Adverse Events Associated with Vitiligo Medications Using FDA Adverse Event Reporting System (FAERS) Databases 2013–2023

by Saleh F. Alqifari, Musaab Habibulla Gari, Jeff J. Guo, Shoroq Alamin, Aya K. Esmail, Abdullah K. Esmail, Heba R. Hamad, Ahmed Aljabri, Amirah M. Alatawi, Laila A. Albishi, Mohammed Olaythah Alraddadi and Helal F. Hetta

Diseases 2025, 13(7), 208; https://doi.org/10.3390/diseases13070208 - 2 Jul 2025

Abstract

Vitiligo, an autoimmune disorder causing depigmented skin patches, includes two types, segmental (SV) and non-segmental (NSV). Previously, NSV was off-label treated using Calcineurine inhibitors (Tacrolimus and Pimecrolimus). In 2022, the FDA approved Ruxolitinib cream, targeting the JAK/STAT pathway for NSV treatment based on [...] Read more.

Vitiligo, an autoimmune disorder causing depigmented skin patches, includes two types, segmental (SV) and non-segmental (NSV). Previously, NSV was off-label treated using Calcineurine inhibitors (Tacrolimus and Pimecrolimus). In 2022, the FDA approved Ruxolitinib cream, targeting the JAK/STAT pathway for NSV treatment based on promising results. This research conducts a retrospective descriptive safety assessment of Tacrolimus, Pimecrolimus, and Ruxolitinib safety in vitiligo treatment, utilizing the FDA Adverse Event Reporting System (FAERS) database spanning the period from 2013 to 2023 and including patients aged 2 years and above, encompassing both brand and generic names. A total of 844 adverse event reports involving 388 patients were extracted and categorized into dermatological and systemic groups for analysis. Tacrolimus resulted in 12 hospitalizations, two life-threatening events, and four disabilities. Pimecrolimus exhibited urticaria and pigmentation disorders, with tooth fracture as the primary systemic event. Pericarditis was the predominant systemic side effect of Ruxolitinib, followed by anemia, headache, and urosepsis. Local dermatological side effects reported were generally mild, not warranting treatment cessation. In conclusion, vitiligo significantly impacts patients’ psychological well-being, necessitating continuous post-marketing safety monitoring for topical medications. Full article

18 pages, 3589 KiB

Open AccessReview

Hepatocellular Carcinoma: A Comprehensive Review

by Nisar Amin, Javaria Anwar, Abdullahi Sulaiman, Nadia Nikolaeva Naumova and Nadeem Anwar

Diseases 2025, 13(7), 207; https://doi.org/10.3390/diseases13070207 - 2 Jul 2025

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and remains one of the leading causes of cancer-related mortality. Its incidence continues to rise worldwide, and it is currently the fastest-growing cancer by incidence in the United States. HCC most often arises [...] Read more.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and remains one of the leading causes of cancer-related mortality. Its incidence continues to rise worldwide, and it is currently the fastest-growing cancer by incidence in the United States. HCC most often arises in the context of chronic liver disease, particularly cirrhosis. While chronic viral hepatitis (hepatitis B and C) has traditionally been the primary etiologic factor, recent advances in antiviral therapies and prevention strategies have shifted the epidemiological landscape. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease are increasingly prominent risk factors, especially in Western populations. This shift underscores the need for targeted risk factor modification, improved early detection, and enhanced surveillance protocols. The management of HCC necessitates a multidisciplinary approach, incorporating locoregional therapies, surgical resection, liver transplantation, and systemic therapies for advanced-stage disease. Recent advances in systemic treatments, including immune checkpoint inhibitors and combination therapies, have transformed the therapeutic landscape. Despite these developments, significant challenges persist in optimizing treatment, identifying predictive biomarkers, and personalizing therapy. Ongoing research is focused on refining molecular classifications and advancing precision medicine strategies to improve outcomes. This review provides a comprehensive overview of the etiology, surveillance strategies, diagnostic approaches, molecular features, and current treatment modalities for HCC. Full article

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

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15 pages, 609 KiB

Open AccessArticle

CD79A and IL7R mRNA Levels in the Cerebrospinal Fluid of Adults with Acute B-Cell Lymphoblastic Leukemia: A Pilot Study

by Andrea Iracema Milán Salvatierra, Juan Carlos Bravata Alcántara, Víctor Manuel Alvarado Castro, Estibeyesbo Said Plascencia Nieto, Faustino Cruz Leyto, Mónica Tejeda Romero, Jorge Cruz Rico, Bogar Pineda Terreros, Sandra López Palafox, Adriana Jiménez, Juan Ramón Padilla Mendoza, José Bonilla Delgado, Catalina Flores-Maldonado and Enoc Mariano Cortés Malagón

Diseases 2025, 13(7), 206; https://doi.org/10.3390/diseases13070206 - 1 Jul 2025

Abstract

Background/Objectives: In adults with B-cell acute lymphoblastic leukemia (B-ALL), central nervous system (CNS) involvement represents a significant clinical challenge due to its association with adverse outcomes. Infiltration of blast cells into the CNS is primarily detected via cerebrospinal fluid (CSF) microscopy, the current [...] Read more.

Background/Objectives: In adults with B-cell acute lymphoblastic leukemia (B-ALL), central nervous system (CNS) involvement represents a significant clinical challenge due to its association with adverse outcomes. Infiltration of blast cells into the CNS is primarily detected via cerebrospinal fluid (CSF) microscopy, the current gold standard diagnostic method, although it has limitations in terms of sensitivity. Quantitative polymerase chain reaction (qPCR) offers higher sensitivity and can support the diagnosis of CNS infiltration. This study assessed the mRNA expression levels of CD79A and IL7R in CSF to evaluate their potential for detecting CNS involvement in adults with B-ALL. Methods: CSF samples were collected from adults with B-ALL. The classification criteria for CNS Leukemia (CNS status) were used to evaluate CNS involvement. RNA was extracted from the CSF, and quantitative reverse transcription PCR (RT-qPCR) was used to measure the CD79A and IL7R mRNA expression levels. Results: A total of 19 treatment-naïve adult patients with B-ALL were enrolled over a 19-month period. Four (21%) patients had CNS3 status. Four (21%) patients had CNS3 status. The results also showed that the expression levels of CD79A and IL7R mRNA were significantly higher (median fold change = 0.62 and 2.12, p < 0.05, respectively) in the group with CNS3. Furthermore, using the Haldane-Anscombe correction and Fisher’s exact test, we demonstrated an association between IL7R and CNS3 expression (odds ratio = ∞, due to zero CNS+ in the IL7R group, p < 0.05). Conclusions: CD79A and IL7R mRNA levels in CSF could be potential biomarkers for detecting CNS involvement in adult patients with B-ALL. Full article

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13 pages, 2203 KiB

Open AccessArticle

Salmonella Typhi-Exposed Placentae: Chorionic Villi Histomorphology and Neonatal Birthweight

by Patience B. Tetteh-Quarcoo, Joana Twasam, Kevin Kofi Adutwum-Ofosu, John Ahenkorah, Bismarck Afedo Hottor, Nicholas T. K. D. Dayie, Peter Ofori Appiah, Emmanuel Afutu, Fleischer C. N. Kotey, Emilia Asuquo Udofia, Nii Koney-Kwaku Koney, Benjamin Arko-Boham and Eric S. Donkor

Diseases 2025, 13(7), 205; https://doi.org/10.3390/diseases13070205 - 30 Jun 2025

Abstract

Background: Salmonella infections impose a substantial global health burden, with an estimated 95.1 million cases occurring annually. Pregnant women exhibit a heightened vulnerability due to pregnancy-specific immune adaptations and dietary habits that increase their risk of Salmonella exposure, facilitating possible damage to the [...] Read more.

Background: Salmonella infections impose a substantial global health burden, with an estimated 95.1 million cases occurring annually. Pregnant women exhibit a heightened vulnerability due to pregnancy-specific immune adaptations and dietary habits that increase their risk of Salmonella exposure, facilitating possible damage to the placental barrier. Despite this significant burden, Salmonella-associated placental pathology remains poorly understood, particularly its impact on foetal development through microstructural alterations. Aim: This study utilised stereology to assess histomorphological and functional alterations in term placentae of Salmonella Typhi-exposed placentae, compared to unexposed controls. Methods: A hospital-based case-control study was conducted in Ghana. Of 237 screened women, 62 placentae were selected for analysis, comprising 31 Salmonella-exposed cases (IgG/IgM-positive in placental and cord blood) and 31 gestational age-matched controls (IgG/IgM-negative). Placental tissues were processed for histology and stereology. Neonatal birthweights were also compared. Results: Stereological assessment revealed significantly higher mean volume densities of syncytial knots in the study group (0.4755 ± 0.04) compared to the controls (0.3342 ± 0.04, p = 0.0219). Syncytial denudation was increased in the study group (0.8113 ± 0.09) relative to the controls (0.1975 ± 0.08, p < 0.0001). Foetal capillary volume density was also significantly elevated in the study group (5.1010 ± 0.32) compared to the controls (3.562 ± 0.47, p < 0.0001). In contrast, intervillous space volume was significantly reduced in the study group (9.5810 ± 0.05) compared to the controls (11.593 ± 0.26, p = 0.0053). Neonates of exposed mothers showed a non-significant reduction in birthweight. Conclusion: Salmonella Typhi exposure in pregnancy induces subtle, yet significant alterations in placental architecture, compromising villous integrity and vascular organisation. Although birthweight may appear unaffected, the observed changes point to reduced placental efficiency and merit further research into their developmental consequences and long-term effects on babies. Full article

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23 pages, 3242 KiB

Open AccessHypothesis

Vaxtherapy, a Multiphase Therapeutic Protocol Approach for Longvax, the COVID-19 Vaccine-Induced Disease: Spike Persistence as the Core Culprit and Its Downstream Effects

by Jose Crespo-Barrios

Diseases 2025, 13(7), 204; https://doi.org/10.3390/diseases13070204 - 30 Jun 2025

Abstract

Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these [...] Read more.

Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these mechanisms. Methods: A narrative synthesis of peer reviewed literature from 2021 to 2025 on spike related injury and vaccine adverse events was conducted, supplemented by clinical case series and mechanistic observations from long COVID. The findings were arranged into a four stage therapeutic sequence ordered by pathophysiological precedence. Results: Stage one aims to reopen hypoperfused tissue through oral fibrinolytics that degrade fibrin amyloid resistant microclots; stage two intends to neutralise circulating or tissue bound spike via a receptor binding domain monoclonal antibody cocktail; stage three seeks to eliminate reactivated viral or microbial reservoirs with targeted antivirals or antimicrobials once perfusion is improved; and stage four aspires to support tissue repair with mitochondrial supplements and, when indicated, cell based therapies. Omitting or reordering stages may reduce efficacy or foster resistance. Conclusions: This hypothesis driven framework outlines a biologically plausible roadmap for longvax research. By matching interventions to specific mechanisms (fibrinolysis, spike neutralisation, pathogen clearance and regeneration), it aims to guide controlled trials and compassionate pilot programs directed at durable recovery rather than chronic symptom management. Full article

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18 pages, 2465 KiB

Open AccessCase Report

Pancreatic Endometriosis Coexisting with a Splenic Mesothelial Cyst: A Rare Case Report and Review of the Literature

by Daniel Paramythiotis, Antonia Syrnioti, Dimitrios Tsavdaris, Aikaterini Smprini, Alexandros Mekras, Athanasios Apostolidis and Angeliki Cheva

Diseases 2025, 13(7), 203; https://doi.org/10.3390/diseases13070203 - 30 Jun 2025

Abstract

Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity [...] Read more.

Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity to other pancreatic diseases. At the same time, splenic mesothelial cysts are also rare and typically benign. This report presents a unique case of pancreatic endometriosis coexisting with a splenic mesothelial cyst in a 31-year-old woman. The patient presented to the emergency department with complaints of persistent epigastric and low back pain. She noted having similar symptoms approximately a year prior. Her past medical history was otherwise unremarkable, and there was no known family history of pancreatic disease or neoplasms. Initial imaging revealed a 3.8 cm cystic lesion in the pancreatic tail, with features suggestive of mucinous cystadenoma. Following clinical evaluation and confirmation of the cyst’s nature through endoscopic ultrasound-guided biopsy, the patient subsequently underwent laparoscopic distal pancreatectomy and splenectomy due to worsening symptoms. Gross examination revealed a multilocular pancreatic cyst with a smooth, hemorrhagic wall. Microscopic analysis showed the cyst to be lined by cuboidal to columnar epithelium, consistent with pancreatic endometriosis, confirmed by immunohistochemical staining. The spleen showed cystic formations, diagnosed as a multifaceted mesothelial cyst. In conclusion, this report is the first to document the coexistence of pancreatic endometriosis and splenic mesothelial cysts, highlighting the importance of accurate imaging and pathologic evaluation in the diagnosis of these rare conditions. Early diagnosis and surgical intervention lead to favorable outcomes, reinforcing the importance of comprehensive diagnostic strategies. Full article

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12 pages, 1682 KiB

Open AccessArticle

Microsatellite Instability and BAT-26 Marker Expression in a Mexican Prostate Cancer Population with Different Gleason Scores

by Ana K. Flores-Islas, Manuel A. Rico-Méndez, Marisol Godínez-Rubí, Martha Arisbeth Villanueva-Pérez, Erick Sierra-Díaz, Ana Laura Pereira-Suárez, Saul A. Beltrán-Ontiveros, Perla Y. Gutiérrez-Arzapalo, José M. Moreno-Ortiz and Adrián Ramírez-de-Arellano

Diseases 2025, 13(7), 202; https://doi.org/10.3390/diseases13070202 - 30 Jun 2025

Abstract

Background/Objectives: Prostate cancer (PCa) is one of the most common cancers in men worldwide. While standard treatments often provide good initial results, many patients eventually develop resistance and experience a more aggressive relapse. Microsatellite instability (MSI) involves variations in the lengths of microsatellite [...] Read more.

Background/Objectives: Prostate cancer (PCa) is one of the most common cancers in men worldwide. While standard treatments often provide good initial results, many patients eventually develop resistance and experience a more aggressive relapse. Microsatellite instability (MSI) involves variations in the lengths of microsatellite base repeats in cells. Assessing the frequency of MSI is essential, as it may identify candidates for immune checkpoint inhibitors, which have shown promising outcomes. This study focuses on evaluating the MSI frequency in Mexican PCa patients and exploring its potential relationship with tumor aggressiveness. Methods: In this study, 116 formalin-fixed paraffin-embedded tumoral tissue biopsies from Mexican patients with PCa were collected from Hospital Civil de Culiacán and Pathology and Nephropathology, Diagnosis and Research Center, in the period from 2021 to 2024. The Gleason score was assessed, and the MSI was performed by multiplex PCR with a panel of five markers (NR-27, NR-21, NR-24, BAT-25, and BAT-26). High microsatellite instability (MSI-H) was defined as two or more unstable markers, low microsatellite instability (MSI-L) as an unstable marker, and microsatellite stability (MSS) as no unstable marker. Results: We found 19.83% (23/116) MSI PCa patients, of which 21.74% (5/23) were MSI-H, and 78.26% (18/23) were MSI-L. We found a major distribution of MSI-positive cases (50% (11/22)) in Gleason score 9 patients, corresponding to prognostic group 5. In addition, we found most of the instability in the BAT-26 marker in MSI PCa patients (60.87% (14/23)). Conclusions: This study is the first to evaluate the frequency of MSI in PCa within the Mexican population. Among the Mexican patients with MSI-positive PCa, there was a predominant Gleason score 9 and a majority instability of the BAT-26 marker. Full article

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17 pages, 4289 KiB

Open AccessCase Report

Subcutaneous Panniculitis-like T-Cell Lymphoma: Diagnostic Challenge and Successful Multimodal Management with Integra^® Dermal Matrix—Case Report and Review of the Literature

by Daniel Pit, Teodora Hoinoiu, Bogdan Hoinoiu, Simona Cerbu, Maria Iordache, Adrian Vaduva, Diana Szilagyi, Claudia Ramona Bardan, Panche Taskov, Zorin Petrisor Crainiceanu, Miruna Samfireag and Razvan Bardan

Diseases 2025, 13(7), 201; https://doi.org/10.3390/diseases13070201 - 30 Jun 2025

Abstract

Background/Objectives: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and aggressive cutaneous lymphoma, often misdiagnosed due to nonspecific clinical features. Early diagnosis and treatment remain challenging. Methods: We report the case of a 31-year-old female with a chronic non-healing gluteal wound initially treated [...] Read more.

Background/Objectives: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare and aggressive cutaneous lymphoma, often misdiagnosed due to nonspecific clinical features. Early diagnosis and treatment remain challenging. Methods: We report the case of a 31-year-old female with a chronic non-healing gluteal wound initially treated as an abscess. The lack of improvement prompted repeated investigations, culminating in the diagnosis of SPTCL with an alpha–beta T-cell phenotype. Results: Management involved combined chemotherapy and surgical wound reconstruction. Six cycles of CHOEP-21 chemotherapy led to complete clinical remission. A soft tissue defect superinfected with multidrug-resistant organisms was successfully reconstructed using Integra Dermal Regeneration Template followed by split-thickness skin grafting. Conclusions: This case highlights the diagnostic complexity of SPTCL and the therapeutic potential of dermal matrix application in complex wound management, especially in immuno-compromised patients. Full article

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18 pages, 3288 KiB

Open AccessArticle

Hypovitaminosis D Does Not Aggravate the Progression of Gentamicin-Induced Kidney Injury in Rats

by Ana Lívia D. Maciel, Amanda L. Deluque, Beatriz M. Oliveira, Cláudia S. Souza, Heloísa D. C. Francescato, Cleonice Giovanini, Francisco J. A. de Paula, Terezila M. Coimbra and Rildo A. Volpini

Diseases 2025, 13(7), 200; https://doi.org/10.3390/diseases13070200 - 28 Jun 2025

Abstract

Background/Objectives: Gentamicin is one of the most effective and widely used antibiotics to treat serious infections. In addition to its bactericidal properties, gentamicin has a nephrotoxic effect that results in acute kidney injury (AKI). AKI may be intensified by hypovitaminosis D. This [...] Read more.

Background/Objectives: Gentamicin is one of the most effective and widely used antibiotics to treat serious infections. In addition to its bactericidal properties, gentamicin has a nephrotoxic effect that results in acute kidney injury (AKI). AKI may be intensified by hypovitaminosis D. This study evaluated the effect of hypovitaminosis D in the progression of gentamicin-induced renal injury. Methods: Male Wistar Hannover rats received a standard (SD) or a vitamin D-free diet (VitD^—) before gentamicin treatment. After that, we divided the animals into four groups: Ctrl VitD, SD diet, and saline injection; Ctrl VitD^—, VitD^— diet, and saline injection; Genta VitD, SD diet, and gentamicin injection (40 mg/kg; IM); Genta VitD^—, VitD^— diet, and gentamicin injection (40 mg/kg; IM). After the end of gentamicin treatment, we followed the animals for 5 days (protocol 1) and 30 days (protocol 2). Results: The Genta VitD group (protocol 1) presented impaired renal function. Regarding morphological analyses, the Genta VitD group presented necrotic tubules (protocol 1) and atrophied tubules (protocol 2). In the inflammatory scenario, the Genta VitD group presented an increase in the number of CD68+ cells, as well as in the levels of interleukin 1β (protocols 1 and 2). In addition, gentamicin-treated animals (protocols 1 and 2) presented an increased renal expression of vimentin and fibronectin. Despite the notable changes in functional, inflammatory, and structural parameters induced by gentamicin, hypovitaminosis D did not aggravate the renal injury in this experimental model. Conclusion: Hypovitaminosis D did not aggravate the progression of gentamicin-induced renal injury in rats. Full article

14 pages, 247 KiB

Open AccessArticle

Self-Efficacy in Breast Cancer Patients: A Pre–Post Study of a Brief Digital Psychosocial Intervention

by Dimitrios Charos, Maria Andriopoulou, Giannoula Kyrkou, Anna Deltsidou, Glykeria Vaina and Victoria Vivilaki

Diseases 2025, 13(7), 199; https://doi.org/10.3390/diseases13070199 - 28 Jun 2025

Abstract

Background: Breast cancer significantly impacts the social relationships and self-efficacy of affected patients. Purpose: To investigate the role of self-efficacy and the ability to maintain social relationships in breast cancer patients during the postoperative period. Method: This study is a brief intervention study [...] Read more.

Background: Breast cancer significantly impacts the social relationships and self-efficacy of affected patients. Purpose: To investigate the role of self-efficacy and the ability to maintain social relationships in breast cancer patients during the postoperative period. Method: This study is a brief intervention study in the same population group (within-subjects intervention study), in two measurements (pre-test and post-test), conducted in 58 breast cancer patients hospitalized in oncology hospitals in Athens (February 2021–November 2021). The following validated scales were used: the Social Relationship Coping Efficacy Scale (SRCE), the Family Support Scale (FS-12), and the Family Problem Solving Communication Scale (FPSC). Results: The mean age of the participants was 52 years. No statistically significant differences were observed in the scales after the intervention. The degree of change in the scales had minimal differences across all types of treatment. However, there was a statistically significant correlation between the change in the SRCE and the FPSC (p = 0.043), which suggests that the improvement in the ability to maintain social relationships is related to the strengthening of family communication. Conclusions: The intervention had a positive effect on maintaining social relationships and improving communication for problemsolving ability, although the overall changes in the scales were not statistically significant. Full article

18 pages, 1357 KiB

Open AccessArticle

Dramatic Deterioration of Subclinical Hyperparathyroidism in Children and Adolescents During the Post-COVID-19 Period

by Maria Loutsou, Eleni Dermitzaki, Rodis D. Paparodis, Aspasia N. Michoula, Nicholas Angelopoulos, Panagiotis Christopoulos, Stavros Diamantopoulos, George Mastorakos, Ioanna N. Grivea and Dimitrios T. Papadimitriou

Diseases 2025, 13(7), 198; https://doi.org/10.3390/diseases13070198 - 27 Jun 2025

Abstract

Background: Vitamin D is a steroid hormone, essential for the immune system and bone health. Since the sun is meant to provide at least 80% of daily vitamin D requirements, the COVID-19 pandemic is likely to have induced a considerable influence on calcium [...] Read more.

Background: Vitamin D is a steroid hormone, essential for the immune system and bone health. Since the sun is meant to provide at least 80% of daily vitamin D requirements, the COVID-19 pandemic is likely to have induced a considerable influence on calcium metabolism. Methods: We analyzed data from 1138 children, seen in an outpatient pediatric endocrinology clinic from 2022–2023. Vitamin D status was classified as deficiency if 25(OH)D ≤ 20 ng/mL, insufficiency < 30 ng/mL, and sufficiency ≥ 30 ng/mL. Results: Overall, 60.8% of children had vitamin D deficiency or insufficiency worsened with age (p < 0.005), and with adolescent males having higher 25(OH)D concentrations than females (p < 0.05). A negative correlation was found between 25(OH)D and BMI SDS (R² = 0.02, p < 0.001), and 25(OH)D concentrations varied seasonally, decreasing in winter. Subclinical hyperparathyroidism [parathyroid hormone (PTH) > 45 pg/mL) and normal calcium] was found in 21.5% of children, with 73.5% of them being vitamin D deficient or insufficient. A negative correlation between PTH and 25(OH)D was observed, with PTH plateauing at 25(OH)D above 40 ng/mL (p < 0.001). Conclusions: Compared to the pre-pandemic data (2016–2018), with only 5.1% of children having subclinical hyperparathyroidism (p < 0.001), these findings suggest a marked deterioration in vitamin D status and calcium metabolism in children, with possible unforeseen consequences for bone, immune, and general health. Full article

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23 pages, 8395 KiB

Open AccessReview

Revisiting Fat Content in Bone Lesions: Paradigms in Bone Lesion Detection

by Ali Shah, Neel R. Raja, Hasaam Uldin, Sonal Saran and Rajesh Botchu

Diseases 2025, 13(7), 197; https://doi.org/10.3390/diseases13070197 - 27 Jun 2025

Abstract

Bone lesions encountered as part of radiology practice can bring diagnostic challenges, both when encountered incidentally or suspected as a primary bone lesion, and in patients at risk of metastases or marrow-based malignancies. Differentiating benign from malignant bone marrow lesions is critical, yet [...] Read more.

Bone lesions encountered as part of radiology practice can bring diagnostic challenges, both when encountered incidentally or suspected as a primary bone lesion, and in patients at risk of metastases or marrow-based malignancies. Differentiating benign from malignant bone marrow lesions is critical, yet can be challenging due to overlapping imaging characteristics. One key imaging feature that can assist with diagnosis is the presence of fat within the lesion. Fat can be present either macroscopically (i.e., visible on radiographs, computed tomography (CT), and conventional magnetic resonance imaging (MRI)), or microscopically, detected through specialised MRI techniques such as chemical shift imaging (CSI). This comprehensive review explores the diagnostic significance of both macroscopic and microscopic fat in bone lesions and discusses how its presence can point towards benignity. We illustrate the spectrum of fat-containing bone lesions, encompassing both typical and atypical presentations, and provide practical imaging strategies to increase diagnostic accuracy by utilising radiographs, CT, and MRI in characterising these lesions. Specifically, CSI is highlighted as a non-invasive method for evaluating intralesional fat content, to distinguish benign marrow entities from malignant marrow-replacing conditions based on quantifiable signal drop-off. Furthermore, we detail imaging pitfalls with a focus on conditions that can mimic malignancy (such as aggressive haemangiomas) and collision lesions. Through a detailed discussion and illustrative examples, we aim to guide radiologists and clinicians in recognising reassuring imaging features while also identifying scenarios where further investigation may be warranted. Full article

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10 pages, 395 KiB

Open AccessArticle

Lipoprotein(a) and Blood Monocytes as Factors for Progression of Carotid Atherosclerosis in Patients with Premature Coronary Heart Disease

by Alexandra V. Tyurina, Olga I. Afanasieva, Marat V. Ezhov, Elena A. Klesareva, Tatiana V. Balakhonova and Sergei N. Pokrovsky

Diseases 2025, 13(7), 196; https://doi.org/10.3390/diseases13070196 - 26 Jun 2025

Abstract

Background. Elevated lipoprotein(a) [Lp(a)] levels are a key factor in the early formation and progression of atherosclerosis. Monocytes in individuals with an elevated Lp(a) level are represented by an activated inflammatory phenotype and have an increased ability for transendothelial migration. This work studies [...] Read more.

Background. Elevated lipoprotein(a) [Lp(a)] levels are a key factor in the early formation and progression of atherosclerosis. Monocytes in individuals with an elevated Lp(a) level are represented by an activated inflammatory phenotype and have an increased ability for transendothelial migration. This work studies the association between Lp(a), monocytes, and the progression of carotid atherosclerosis in patients with premature coronary heart disease (CHD). Methods. This study included 102 patients with CHD manifested before 55 in men and 60 in women who underwent two carotid duplex scans with an interval of 5 [3; 8] years. The criteria for the progression of carotid atherosclerosis were the appearance of new plaque and an increase in stenosis by >10% in any of the six segments. The lipid profile, Lp(a), and hematology with the calculation of the lymphocyte–monocyte ratio (LMR) were determined in all the patients. Results. The median blood monocyte count was 0.54 × 10⁹/L, and the median LMR was 4.18. In 70 patients, we revealed the criteria for carotid atherosclerosis progression. The groups did not differ by demographics, risk factors, or the blood lipid and lipoprotein levels, except for Lp(a); this concentration was higher in the patients with carotid atherosclerosis progression. The odds of atherosclerosis progression were highest in the patients with an elevated Lp(a) level and a blood monocyte count above the median (16.8, 3.4–83.0, p < 0.001). Carotid atherosclerosis progression was associated with LMR < 4.18 and an elevated Lp(a) level (OR = 4.3, 1.1–17.2, p = 0.04) and not associated with the patients with Lp(a) levels < 30 mg/dL and an LMR above the median. Conclusions. An elevated Lp(a) level and monocyte count provide the highest probability of the progression of carotid atherosclerosis in patients with premature CHD. Full article

(This article belongs to the Section Cardiology)

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15 pages, 868 KiB

Open AccessReview

Hematopoietic Stem Cell Transplant in Adult Patients with Fanconi Anemia: A Review

by Bradley Rockwell, Prakriti Ramamurthy, Jhannine Alyssa Verceles, Amanda Lombardo, Amit Verma and Dennis L. Cooper

Diseases 2025, 13(7), 195; https://doi.org/10.3390/diseases13070195 - 25 Jun 2025

Abstract

Fanconi anemia (FA) is characterized by faulty DNA repair and is associated with bone marrow failure, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). Because of the more widespread use of next-generation sequencing (NGS) and increased testing for germline mutations in young patients [...] Read more.

Fanconi anemia (FA) is characterized by faulty DNA repair and is associated with bone marrow failure, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). Because of the more widespread use of next-generation sequencing (NGS) and increased testing for germline mutations in young patients with MDS and AML, FA is increasingly being first diagnosed in adults, many of whom lack classical physical stigmata. Hematopoietic stem cell transplant is the only cure for the hematologic manifestations of FA but there are several unique considerations in FA patients, including first maintaining a high index of suspicion for the diagnosis in patients with minimal phenotypic abnormalities, second an exaggerated sensitivity to alkylating agents and radiation, precluding the use of standard myeloablative conditioning regimens despite the young age of most of the patients, and lastly a marked propensity for squamous cell cancers of the upper aerodigestive tract and anogenital region, likely further increased by the drugs used in conditioning and by chronic inflammation in patients who develop graft-versus-host disease. Despite a growing number of FA patients surviving into adulthood or first being diagnosed with FA as an adult, there is minimal literature describing transplant methodology and outcomes. In the following case-based review of a patient, we incorporate recent findings from the literature on the care of this challenging patient population. Full article

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