Diseases

15 pages, 392 KiB

Open AccessSystematic Review

Functional Status in Elderly Kidney Transplant Recipients: A Systematic Review Evaluating Physical Function, Frailty, and Cognitive Impairment as Predictors of Post-Transplant Outcomes

by Hachem Araji, Yazan A. Al-Ajlouni, Jana Nusier, Walid Sange, Elie El-Charabaty and Suzanne El-Sayegh

Diseases 2025, 13(7), 229; https://doi.org/10.3390/diseases13070229 - 21 Jul 2025

Viewed by 273

Abstract

Background: The management of end-stage renal disease (ESRD) is undergoing a paradigm shift, with increasing emphasis on kidney transplantation as a preferred treatment modality for elderly patients (≥65 years), who constitute a substantial portion of new ESRD cases. Transplantation offers markedly superior survival [...] Read more.

Background: The management of end-stage renal disease (ESRD) is undergoing a paradigm shift, with increasing emphasis on kidney transplantation as a preferred treatment modality for elderly patients (≥65 years), who constitute a substantial portion of new ESRD cases. Transplantation offers markedly superior survival and quality of life (QoL) advantages compared to dialysis for this demographic. Nevertheless, key determinants such as frailty, physical functionality, and cognitive function have emerged as critical predictors of post-transplant success. Despite their relevance, standardized methodologies for evaluating these parameters in transplantation candidacy remain absent. This systematic review examines the influence of frailty, physical functionality, and cognitive function on outcomes in elderly kidney transplant recipients. Methods: Adhering to PRISMA guidelines, a rigorous literature search was conducted across PubMed, CINAHL, Embase, PsycINFO, and the Web of Science for studies published up to October 31, 2024. Relevant studies focused on elderly transplant candidates and examined correlations between frailty, physical functionality, or cognitive function and post-transplant outcomes. The Newcastle–Ottawa Scale was employed to evaluate studies quality. Results: Seven studies met the inclusion criteria. Five explored physical functionality, demonstrating that better pre-transplant physical performance predicts enhanced survival. Two studies addressed frailty, utilizing the Fried frailty phenotype, and linked frailty to elevated mortality and diminished QoL recovery. Notably, no studies explored cognitive function in elderly kidney transplant candidates or recipients and its association with post-transplant outcomes, exposing a salient gap in the literature. The included studies’ varied methodologies, reliance on single time-point assessments, and exclusive focus on kidney transplant recipients restrict both comparability among studies and the generalizability of findings to the broader end-stage renal disease (ESRD) population. Conclusions: These findings underscore the profound impact of physical functionality and frailty on transplant outcomes in the growing elderly kidney transplant population, illuminating the necessity for standardized assessment protocols and targeted pre-transplant interventions. The critical gap in cognitive function research underscores a vital direction for future investigation. This research received no external funding. This review is registered with PROSPERO under registration ID CRD42025645838. Full article

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8 pages, 530 KiB

Open AccessCase Report

An Unusual Case of Anuric Acute Kidney Injury Secondary to the Use of Low-Dose Acetazolamide as Preventive Management for Acute Mountain Sickness

by Marco Dominguez Davalos, Raúl Valenzuela Córdova, Celia Rodríguez Tudero, Elena Jiménez Mayor, Carlos Bedia Castillo, José C. De La Flor, Roger Leon Montesinos, Cristian León Rabanal, Michael Cieza Terrones and Javier A. Neyra

Diseases 2025, 13(7), 228; https://doi.org/10.3390/diseases13070228 - 21 Jul 2025

Viewed by 278

Abstract

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature [...] Read more.

Background/Objectives: Acetazolamide is widely used for acute mountain sickness (AMS) prophylaxis. Whilst generally safe, acute kidney injury (AKI) is a rare but serious adverse event. We present a case of anuric AKI following minimal exposure to acetazolamide, contributing to the limited literature on its nephrotoxicity at prophylactic doses. Methods: A 54-year-old previously healthy male ingested 250 mg/day of oral acetazolamide for two days. He developed acute anuria and lumbar pain. Diagnostic evaluation included laboratory tests, imaging, microbiological cultures, autoimmune panels, and diuretic response. No signs of infection, urinary tract obstruction, or systemic disease were found. Results: The patient met KDIGO 2012 criteria for stage 3 AKI, with peak serum creatinine of 10.6 mg/dL and metabolic acidosis. Imaging confirmed non-obstructive nephrolithiasis. Conservative treatment failed; intermittent hemodialysis was initiated. Renal function recovered rapidly, with the normalization of serum creatinine and urinary output by day 4. Conclusions: This case represents the lowest cumulative dose of acetazolamide reported to cause stage 3 AKI. The findings support a pathophysiological mechanism involving sulfonamide-induced crystalluria and intratubular obstruction. Physicians should consider acetazolamide in the differential diagnosis of AKI, even with short-term prophylactic use. Full article

(This article belongs to the Section Respiratory Diseases)

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15 pages, 427 KiB

Open AccessReview

Therapeutic Implications of Menin Inhibitors in the Treatment of Acute Leukemia: A Critical Review

by Martina Canichella, Cristina Papayannidis, Carla Mazzone and Paolo de Fabritiis

Diseases 2025, 13(7), 227; https://doi.org/10.3390/diseases13070227 - 19 Jul 2025

Viewed by 395

Abstract

Menin inhibitors are a class of targeted agents that exemplify how a deeper understanding of leukemia pathogenesis can unify seemingly distinct genetic acute leukemia subgroups under a common therapeutic strategy. In particular, acute leukemia with NPM1 mutations (NPM1m) and KMT2A rearrangements ( [...] Read more.

Menin inhibitors are a class of targeted agents that exemplify how a deeper understanding of leukemia pathogenesis can unify seemingly distinct genetic acute leukemia subgroups under a common therapeutic strategy. In particular, acute leukemia with NPM1 mutations (NPM1m) and KMT2A rearrangements (KMT2Ar) represent the primary targets of this emerging drug class. Acute myeloid leukemia (AML) with NPM1m—which accounts for approximately 30% of AML cases and AML or acute lymphoblastic leukemia (ALL) with KMT2Ar—and is present in 5–10% of cases, shares a common pathogenetic mechanism: the aberrant activation of the MEIS1–HOXA axis. These leukemic subsets are associated with poor prognosis, particularly in the relapsed/refractory (R/R) setting. For KMT2Ar AML, the prognosis is especially dismal, with a median overall survival (OS) of 2.4 months and a complete remission (CR) rate of only 5%. In NPM1m AML, intensive chemotherapy achieves remission in approximately 80% of cases, but relapse remains a major challenge, occurring in nearly 50% of patients. Relapsed NPM1m AML is linked to a poor prognosis, with a median OS of 6.1 months (12-month OS: 30%) and a median relapse-free survival (RFS) of 5.5 months (12-month RFS: 34%). Menin inhibitors directly target the leukemogenic transcriptional program driven by HOX and MEIS1, disrupting oncogenic signaling and offering a promising therapeutic approach for these high-risk patients. This class of agents has rapidly progressed through clinical development, showing promising antileukemic activity in both treatment-naïve and R/R AML. Currently, six menin inhibitors are in clinical evaluation as monotherapy or in combination regimens: revumenib, ziftomenib, bleximenib (previously JNJ-75276617), enzomenib (previously DSP-5336), DS-1594, and BMF-219. In this review, we critically analyze the clinical development and therapeutic potential of the four most extensively studied menin inhibitors—revumenib, ziftomenib, bleximenib, and enzomenib. We discuss their efficacy, safety profiles, and potential roles within the current treatment algorithm. The continued clinical evaluation of menin inhibitors may redefine treatment paradigms for NPM1m and KMT2Ar AML and other acute leukemia with the aberrant MEIS1-HOXA axis, offering new hope for patients with limited therapeutic options. Full article

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

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8 pages, 482 KiB

Open AccessCase Report

Endovascular Treatment of a Symptomatic Vertebral Artery Aneurysm in a Puerperal Patient with Neurofibromatosis Type 1—A Case Report and Review of the Literature

by Nikola Mirkovic, Marko Prokic, Nikola Prodanovic, Tamara Nikolic Turnic, Nikola Andric, Tijana Prodanovic, Neda Arsenijevic, Ivan Simic, Dragan Knezevic and Aleksandar Matic

Diseases 2025, 13(7), 226; https://doi.org/10.3390/diseases13070226 - 18 Jul 2025

Viewed by 189

Abstract

Introduction: Primary extracranial vertebral artery aneurysms are sporadic in the general population. They are uncommon in individuals with neurofibromatosis type 1. During pregnancy or in the puerperium, the risk of aneurysm rupture in individuals with neurofibromatosis type 1 and extracranial aneurysms is elevated. [...] Read more.

Introduction: Primary extracranial vertebral artery aneurysms are sporadic in the general population. They are uncommon in individuals with neurofibromatosis type 1. During pregnancy or in the puerperium, the risk of aneurysm rupture in individuals with neurofibromatosis type 1 and extracranial aneurysms is elevated. Rupture of a vertebral artery aneurysm is an emergency condition and can be fatal. Case presentation: We present the case of a 33-year-old woman in the puerperium with neurofibromatosis type 1 who had a vertebral symptomatic artery aneurysm. During a previous hospitalization, two months before the treatment of the vertebral aneurysm, a same-sided aneurysm of the thyrocervical trunk was successfully treated with endovascular coiling because of aneurysm rupture. In this case report, the vertebral artery aneurysm was successfully managed using a flow diverter stent graft. Conclusions: This is the first reported case of a successfully treated symptomatic vertebral artery aneurysm with a flow diverter stent graft in a patient with neurofibromatosis type 1 during the early puerperium. Endovascular treatment with a stent graft is a minimally invasive, safe, and effective treatment for patients with vertebral artery aneurysms. Early diagnosis of non-ruptured vertebral artery aneurysms is a crucial as well as appropriate treatment, which should be undertaken in a timely manner to prevent serious complications or a fatal outcome. Full article

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13 pages, 3385 KiB

Open AccessReview

Efficacy of Dupilumab in a Young Woman with Refractory Cutaneous Lichen Planus: A Case-Based Review

by Cristina Guerriero, Luisa Boeti, Francesco Mastellone, Giulia Coscarella, Gennaro Marco Falco, Gerardo Palmisano, Helena Pelanda, Ketty Peris and Donato Rigante

Diseases 2025, 13(7), 225; https://doi.org/10.3390/diseases13070225 - 18 Jul 2025

Viewed by 375

Abstract

Background: Cutaneous lichen planus (CLP) is a chronic inflammatory T cell-mediated disease driven by a mixed Th1 and Th2 lymphocyte population, for which many of the currently available treatments have poor efficacy. Aim: The aim of this study was to indicate the clinical [...] Read more.

Background: Cutaneous lichen planus (CLP) is a chronic inflammatory T cell-mediated disease driven by a mixed Th1 and Th2 lymphocyte population, for which many of the currently available treatments have poor efficacy. Aim: The aim of this study was to indicate the clinical success of dupilumab administration after two years of treatment in a case of longstanding CLP and to perform a review of the medical literature related to the use of dupilumab in different dermatologic settings and in CLP. Case presentation: One 26-year-old woman with a previous history of atopic dermatitis had a long-lasting skin condition, referred to as a suspected lichen, which started when she was 7 years old. Her disease exhibited a relapsing–remitting course with severe bouts of pruritus over a very long period. The final histological diagnosis of CLP was confirmed at the age of 26. Starting dupilumab (injected subcutaneously at a dose of 600 mg followed by a maintenance dose of 300 mg every two weeks) resolved the skin scenery of this patient, who is currently in full remission. Conclusions: The remarkable recovery from CLP obtained via treatment with dupilumab in this single-patient case study emphasizes the potential therapeutic implications of targeting the Th2 pathway in this skin disorder. Full article

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9 pages, 215 KiB

Open AccessArticle

Psychotic Symptoms in Cataract Patients Without Overt Psychosis Are Ameliorated Following Successful Cataract Surgery

by Georgios D. Floros, Ioanna Mylona and Stylianos Kandarakis

Diseases 2025, 13(7), 224; https://doi.org/10.3390/diseases13070224 - 18 Jul 2025

Viewed by 219

Abstract

Background: Cataract is the leading cause of severe, non-traumatic vision loss worldwide, leading to multiple adverse outcomes in mental health, including depression, anxiety, and cognitive decline; however, the relationship to psychotic symptoms remains unclear. While congenital vision loss appears protective against psychosis, acquired [...] Read more.

Background: Cataract is the leading cause of severe, non-traumatic vision loss worldwide, leading to multiple adverse outcomes in mental health, including depression, anxiety, and cognitive decline; however, the relationship to psychotic symptoms remains unclear. While congenital vision loss appears protective against psychosis, acquired vision loss or acute deprivation are inducing psychotic symptoms. Methods: This study of 200 consecutive cataract patients, with severe vision loss, compares Paranoid Ideation and Psychoticism symptoms pre surgery, measured with the SCL-90-R scale, to those symptoms that persisted two months post-surgery. Results: The results confirm the hypothesis that cataract surgery is associated with a reduction in those symptoms (Wilcoxon Z = 5.425, p < 0.001 for Paranoid Ideation and Wilcoxon Z = 6.478, p < 0.001 for Psychoticism). Higher improvement in those variables was associated with higher improvement in visual acuity while controlling for age, gender and stressful life events during the past six months. Conclusions: Those results point to the importance of addressing loss of visual function especially in patients with pre-existing psychotic symptoms or signs of cognitive decline. Full article

8 pages, 1541 KiB

Open AccessCase Report

Atypical Rapid Onset of Olmesartan-Induced Enteropathy with Recurrence After Rechallenging

by Lila Bekkai, Aymen Ibn Majah, Laurine Verset, Lucas Jacobs, Charline Danneel, Okyay Elkilic, Frédéric Collart, Joëlle Nortier and Maxime Taghavi

Diseases 2025, 13(7), 223; https://doi.org/10.3390/diseases13070223 - 18 Jul 2025

Viewed by 255

Abstract

Background: Olmesartan-induced enteropathy is a rare complication of a widely used angiotensin II receptor blocker. Patients usually present with chronic diarrhea and weight loss. Histologically, villous atrophy and intraepithelial lymphocyte infiltrates within the duodenum confirm the diagnosis. The prognosis is usually good after [...] Read more.

Background: Olmesartan-induced enteropathy is a rare complication of a widely used angiotensin II receptor blocker. Patients usually present with chronic diarrhea and weight loss. Histologically, villous atrophy and intraepithelial lymphocyte infiltrates within the duodenum confirm the diagnosis. The prognosis is usually good after withdrawal of the offending drug. Case presentation: Here, we report the case of a 76-year-old woman who developed a severe form of Olmesartan-induced enteropathy complicated by acute kidney injury and acute recurrence after drug rechallenge. After definite cessation of the drug, the patient did not experience any gastrointestinal (GI) symptom recurrence after 6 months of follow-up. However, she experienced chronic kidney disease stage G3b. Histological analysis did not show any villous atrophy or intraepithelial lymphocyte infiltrates within the duodenum or the colon biopsy. Discussion and conclusion: This case highlights the broad spectrum of clinical manifestations and histological findings in Olmesartan-induced enteropathy. It also highlights the importance of rapid diagnosis in order to limit organ damage such as chronic kidney disease. Full article

(This article belongs to the Special Issue ‘Rare Syndromes: Diagnosis and Treatment’ in 2024–2026)

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14 pages, 1342 KiB

Open AccessArticle

Establishing the First Genetic Variant Registry for Breast and Ovarian Cancer in Colombia: Insights and Implications

by Robert de Deugd, Julián Camilo Riano, Esther de Vries, Andrés F. Cardona, July Rodriguez, Ana Fidalgo-Zapata, Yesid Sanchez, Santiago Sanchez, Justo Olaya, Daniel de Leon, Carlos Andrés Ossa, Humberto Reynales, Paula Quintero, Elizabeth Vargas, Ute Hamann and Diana Torres

Diseases 2025, 13(7), 222; https://doi.org/10.3390/diseases13070222 - 18 Jul 2025

Viewed by 279

Abstract

Background: Genetic insights from diverse populations are key to advancing cancer detection, treatment, and prevention. Unlike other Latin American countries, Colombia lacks a centralized registry for germline and somatic mutations in breast and ovarian cancer. This study describes the country’s first national variant [...] Read more.

Background: Genetic insights from diverse populations are key to advancing cancer detection, treatment, and prevention. Unlike other Latin American countries, Colombia lacks a centralized registry for germline and somatic mutations in breast and ovarian cancer. This study describes the country’s first national variant registry, and the occurrence of recurrent mutations and potential founder effects in Colombia. Methods: To address this gap, we implemented the first capturing protocol using the REDCap system. In a group of 213 breast and/or ovarian cancer patients harboring genetic mutations, we collected genetic, clinical, and demographic data from 13 regional centers across Colombia. Statistical analyses assessed variant distribution and patient demographics. Results: Among 229 identified variants (105 germline, 124 somatic), most were classified as pathogenic or likely pathogenic (72.4% germline, 87% somatic). BRCA1 and BRCA2 accounted for the majority of recurrent mutations. Germline recurrent variants (seen >3 times) were recorded for BRCA1 (77.7%; 21/27) and BRCA2 (22.3%; 6/27). Similarly, recurrent somatic variants were identified for BRCA1 (82.6%; 38/46) and BRCA2 (17.4%; 8/46). Notably, four recurrent variants were previously reported as founder mutations: BRCA1 c.1674del (14.3% germline and 23.7% somatic), BRCA1 c.3331_3334del (33.3% germline and 52.6% somatic), BRCA1 c.5123C>A (52.4% germline and 23.7% somatic), and BRCA2 c.2808_2811del (50% germline and 50% somatic). Most cases originated from the Andean region, highlighting regional disparities. Conclusions: This registry offers the first overview of genetic variants in Colombian breast and ovarian cancer patients. Recurrent and region-specific mutations highlight the need for population-focused data to guide targeted screening and personalized care strategies. Full article

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25 pages, 821 KiB

Open AccessReview

Cellular and Molecular Bases for the Application of Polyphenols in the Prevention and Treatment of Cardiovascular Disease

by Carlo Caiati and Emilio Jirillo

Diseases 2025, 13(7), 221; https://doi.org/10.3390/diseases13070221 - 15 Jul 2025

Viewed by 531

Abstract

Background: Cardiovascular disease (CVD) is very widespread in countries with a Western-style diet, representing one of the major causes of morbidity. Genetic factors, obesity, diabetes, dyslipidemia, smoking, and ageing are risk factors for CVD outcomes. From a pathogenic point of view, the condition [...] Read more.

Background: Cardiovascular disease (CVD) is very widespread in countries with a Western-style diet, representing one of the major causes of morbidity. Genetic factors, obesity, diabetes, dyslipidemia, smoking, and ageing are risk factors for CVD outcomes. From a pathogenic point of view, the condition of low-grade inflammation of the arteries leads to endothelial damage and atherosclerosis development. Nowadays, a broad range of drugs is available to treat CVD, but many of them are associated with side effects. Therefore, alternative therapeutic remedies need to be discovered in combination with conventional drugs. A balanced diet rich in fruits and vegetables, e.g., the Mediterranean diet, has been shown to lower the incidence of CVD. Plant-derived polyphenols are ingested in food, and these compounds can exert beneficial effects on human health, such as antioxidant and anti-inflammatory activities. Objective: In the present review, the cellular and molecular bases of the beneficial effects of polyphenols in the prevention and treatment of CVD will be pointed out. Methods: This review has been conducted on the basis of a literature review spanning mainly the last two decades. Results: We found that an increased dietary intake of polyphenols is associated with a parallel decrease in chronic disease incidence, including CVD. Conclusion: Despite a plethora of preclinical studies, more clinical trials are needed for a more appropriate treatment of CVD with polyphenols. Full article

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11 pages, 1319 KiB

Open AccessBrief Report

Myxoid Liposarcoma of the Thigh in Early Puerperium—Rare Case Report and Narrative Review

by Tomasz Machałowski, Piotr Gutowski, Edyta Zagrodnik, Aleksandra Godlewska, Katarzyna Śmieja, Oliwia Kawałek, Anna Grzymała-Figura, Sylwester Michał Ciećwież, Katarzyna Gross-Kępińska, Małgorzata Szczuko and Maciej Ziętek

Diseases 2025, 13(7), 220; https://doi.org/10.3390/diseases13070220 - 14 Jul 2025

Viewed by 221

Abstract

Background: Liposarcoma (LPS) is a rare malignant tumor, but it is also one of the most common adult soft-tissue sarcomas. Myxoid liposarcoma (MLPS) accounts for 30% of all LPS cases. Diagnosis during pregnancy and the puerperium is very rarely reported, and only a [...] Read more.

Background: Liposarcoma (LPS) is a rare malignant tumor, but it is also one of the most common adult soft-tissue sarcomas. Myxoid liposarcoma (MLPS) accounts for 30% of all LPS cases. Diagnosis during pregnancy and the puerperium is very rarely reported, and only a few cases have been reported in the thigh. Case presentation: We report the case of a 36-year-old female patient on the 11th day of the puerperium after a cesarean section. The patient presented to the gynecology ward owing to the sudden appearance of a tumor in the medial part of her right thigh. The lesion was non-painful, mobile, soft, approximately 20 cm in diameter, and protruded above the level of the rest of the thigh surface. A suspicion of hematoma was raised. The final diagnosis was high-grade MLPS. Conclusions: An MLPS diagnosis is uncommon in female patients and even rarer during pregnancy. This case represents a novel occurrence, as the first instance in which symptoms manifested during the puerperium. Proper treatment and early detection could improve disease outcomes. Full article

(This article belongs to the Special Issue ‘Rare Syndromes: Diagnosis and Treatment’ in 2024–2026)

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20 pages, 2523 KiB

Open AccessArticle

The Association of VDR, CYP2R1, and GC Gene Polymorphisms, Dietary Intake, and BMI in Regulating Vitamin D Status

by Carmina Mariana Stroia, Annamaria Pallag, Maria Vrânceanu, David de Lorenzo, Keith Anthony Grimaldi, Csaba Robert Pallag, Kinga Vindis, Diana Bei, Cristina Burlou-Nagy (Fati) and Timea Claudia Ghitea

Diseases 2025, 13(7), 219; https://doi.org/10.3390/diseases13070219 - 14 Jul 2025

Viewed by 732

Abstract

Vitamin D plays a crucial role in bone health and immune function, with serum 25(OH)D levels influenced by genetic, dietary, and metabolic factors. Background/Objectives: This study investigated the impact of VDR rs731236, CYP2R1 rs10741657, and GC rs2282679 polymorphisms, body mass index (BMI), and [...] Read more.

Vitamin D plays a crucial role in bone health and immune function, with serum 25(OH)D levels influenced by genetic, dietary, and metabolic factors. Background/Objectives: This study investigated the impact of VDR rs731236, CYP2R1 rs10741657, and GC rs2282679 polymorphisms, body mass index (BMI), and dietary vitamin D intake on vitamin D status. Methods: A total of 230 adults were classified into four BMI categories: normal weight (NW), overweight (OW), obesity class I (OB), and obesity class II/III (OP). Participants completed a Food Frequency Questionnaire (FFQ) and a 7-day Food Frequency Diary (FFD). Genotyping was performed using TaqMan assays, and serum 25(OH)D was quantified via spectrophotometry. Statistical analyses included ANOVA and multiple linear regression. Results: The VDR rs731236 CC genotype, CYP2R1 rs10741657 AG/GG, and GC rs2282679 AC/CC were associated with lower serum vitamin D levels. A higher BMI was significantly correlated with reduced serum 25(OH)D (p < 0.001), with BMI emerging as the strongest predictor of vitamin D status. FFQ-based dietary intake showed a modest positive correlation with 25(OH)D (r = 0.47, p < 0.001). Conclusions: BMI and genetic variants in VDR, CYP2R1, and GC significantly influence vitamin D metabolism. Personalized interventions addressing genetic predispositions and weight management may improve vitamin D status. Full article

(This article belongs to the Special Issue Metabolic Disorders: Insights into Pathogenesis and Novel Therapeutic Strategies)

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14 pages, 273 KiB

Open AccessArticle

From Blood to Outcome: Inflammatory Biomarkers in Rectal Cancer Surgery at a Romanian Tertiary Hospital

by Georgiana Viorica Moise, Catalin Vladut Ionut Feier, Vasile Gaborean, Alaviana Monique Faur, Vladut Iosif Rus and Calin Muntean

Diseases 2025, 13(7), 218; https://doi.org/10.3390/diseases13070218 - 13 Jul 2025

Viewed by 291

Abstract

Background: Systemic inflammatory markers have emerged as accessible and reproducible tools for oncologic risk stratification, yet their prognostic value in rectal cancer remains incompletely defined, particularly in acute surgical settings. This study aimed to assess six inflammation-based indices—NLR, PLR, MLR, SII, SIRI, and [...] Read more.

Background: Systemic inflammatory markers have emerged as accessible and reproducible tools for oncologic risk stratification, yet their prognostic value in rectal cancer remains incompletely defined, particularly in acute surgical settings. This study aimed to assess six inflammation-based indices—NLR, PLR, MLR, SII, SIRI, and AISI—in relation to tumor stage, recurrence, and outcomes among patients undergoing emergency versus elective resection for rectal cancer. Methods: We retrospectively evaluated 174 patients treated between 2018 and 2024. Pre-treatment blood counts were used to calculate inflammatory indices. Clinical and pathological parameters were correlated with biomarker levels using univariate and multivariate analyses. Results: Pre-treatment inflammation markers were significantly elevated in patients requiring emergency surgery (e.g., NLR: 3.34 vs. 2.4, p = 0.001; PLR: 204.1 vs. 137.8, p < 0.001; SII: 1008 vs. 693, p = 0.007), reflecting advanced tumor biology and immune activation. Notably, these patients also had higher rates of stage IV disease (p = 0.029) and permanent stoma (p = 0.002). Post-treatment, recurrence was paradoxically associated with significantly lower levels of SII (p = 0.021), AISI (p = 0.036), and PLR (p = 0.003), suggesting a potential role for immune exhaustion rather than hyperinflammation in early relapse. Conclusions: Inflammatory indices provide valuable insights into both tumor local invasion and host immune status in rectal cancer. Their integration into perioperative assessment could improve prognostication, particularly in emergency presentations. Post-treatment suppression of these markers may identify patients at high risk for recurrence despite initial curative intent. Full article

(This article belongs to the Section Oncology)

16 pages, 982 KiB

Open AccessArticle

Prognostic Role of TSH Within Euthyroid T2DM Patients with Retinopathy: A 3-Year Cohort Study

by Nilgun Tan Tabakoglu and Mehmet Celik

Diseases 2025, 13(7), 217; https://doi.org/10.3390/diseases13070217 - 12 Jul 2025

Viewed by 189

Abstract

Background/Objectives: We aimed to determine how baseline TSH levels relate to clinical outcomes over a three-year follow-up in euthyroid patients with T2DR. Methods: This single-center retrospective cohort study included 363 euthyroid T2DR patients who were followed for three years after baseline TSH measurement. [...] Read more.

Background/Objectives: We aimed to determine how baseline TSH levels relate to clinical outcomes over a three-year follow-up in euthyroid patients with T2DR. Methods: This single-center retrospective cohort study included 363 euthyroid T2DR patients who were followed for three years after baseline TSH measurement. Patients were stratified into tertiles based on TSH values belonging to the standard clinical limits (0.35–4.50 mIU/L). Binary and multivariate logistic regression analyses, along with non-linear modeling, were used to evaluate the prognostic impact of TSH and its interaction with age on mortality. The study adhered to the STROBE guidelines. Results: In the first year of follow-up, Group 1 (TSH 0.35–1.24 mIU/L) had significantly higher rates of mortality and combined outcomes compared to Group 2 (TSH 1.24–1.94 mIU/L; p = 0.025 and p = 0.041, respectively). Group 2 had a lower risk (OR for mortality = 0.349, p = 0.004; OR for combined outcome = 0.358, p = 0.007). Between TSH and TSH tertiles, a non-linear, inverted U-shaped relationship was observed, with the lowest mortality risk near 2.0 mIU/L. A significant interaction between TSH and age was found for third-year mortality (p = 0.016). Conclusions: TSH values showed a non-linear association with outcomes in euthyroid T2DR patients. Group 2 was linked to the lowest risk. Given the significantly higher mortality and combined complications identified within Group 1, closer monitoring and individualized follow-up strategies may be warranted for these patients. Additionally, TSH’s impact on long-term mortality increased with age, supporting its use alongside age for risk stratification in T2DR. Full article

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16 pages, 3132 KiB

Open AccessArticle

Role of Renin–Angiotensin System and Macrophages in Breast Cancer Microenvironment

by Abir Abdullah Alamro, Moudhi Abdullah Almutlaq, Amani Ahmed Alghamdi, Atekah Hazzaa Alshammari, Eman Alshehri and Saba Abdi

Diseases 2025, 13(7), 216; https://doi.org/10.3390/diseases13070216 - 10 Jul 2025

Viewed by 279

Abstract

Background/Objectives: The renin–angiotensin system (RAS) is well-established as a moderator of cardiovascular equilibrium and blood pressure. Nevertheless, growing evidence indicates that angiotensin II (Ang II), the principal RAS effector peptide, together with additional constituents, is involved in various malignancies. Since the immune system [...] Read more.

Background/Objectives: The renin–angiotensin system (RAS) is well-established as a moderator of cardiovascular equilibrium and blood pressure. Nevertheless, growing evidence indicates that angiotensin II (Ang II), the principal RAS effector peptide, together with additional constituents, is involved in various malignancies. Since the immune system is an important aspect in tumor development, this study sought to investigate the role of Ang II in the crosstalk between tumor-associated macrophages (TAMs) and breast cancer cells in the tumor microenvironment (TME). Methods: We treated THP-1-like macrophages with 100 nM Ang II for 24 h. The culture media thus obtained was used as conditioned media and applied at 50% on MCF-7 and MDA-MB-231 breast cancer cell lines. The effects of the conditioned media on cancer cell lines were then investigated by various methods such as a cell proliferation assay, migration assay, polarization assay, and by the detection of apoptosis and reactive oxygen species (ROS) generation. Results: We demonstrated that in vitro Ang II promotes macrophage polarization toward proinflammatory M1-like macrophages and anti-inflammatory M2-like macrophages. Interestingly, Ang II, through macrophages, showed varied effects on different breast cancer cell lines, promoting tumor growth and progression in MCF-7 while inhibiting tumor growth and progression in MDA-MB-23. Conclusions: This study has provided clear evidence that Ang II in the TME modulates TAM polarization and secretions, leading to different effects based on the type of breast cancer. Full article

(This article belongs to the Section Oncology)

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19 pages, 2151 KiB

Open AccessSystematic Review

Optimizing Stereotactic Intracranial Neoplasm Treatment: A Systematic Review of PET Integration with Gamma Knife Radiosurgery

by Robert C. Subtirelu, Eric M. Teichner, Milo Writer, Kevin Bryan, Shiv Patil, Talha Khan, Lancelot Herpin, Raj N. Patel, Emily Christner, Chitra Parikh, Thomas Werner, Abass Alavi and Mona-Elisabeth Revheim

Diseases 2025, 13(7), 215; https://doi.org/10.3390/diseases13070215 - 10 Jul 2025

Viewed by 369

Abstract

Objective: Traditional imaging modalities for the planning of Gamma Knife radiosurgery (GKRS) are non-specific and do not accurately delineate intracranial neoplasms. This study aimed to evaluate the utility of positron emission tomography (PET) for the planning of GKRS for intracranial neoplasms (ICNs) and [...] Read more.

Objective: Traditional imaging modalities for the planning of Gamma Knife radiosurgery (GKRS) are non-specific and do not accurately delineate intracranial neoplasms. This study aimed to evaluate the utility of positron emission tomography (PET) for the planning of GKRS for intracranial neoplasms (ICNs) and the post-GKRS applications of PET for patient care. Methods: PubMed, Scopus, and ScienceDirect were searched in order to assemble relevant studies regarding the uses of PET in conjunction with GKRS for ICN treatment. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to identify relevant studies on the use of PET in conjunction with GKRS. Particular emphasis was placed on review articles and medical research investigating tumor delineation and post-operative care. Relevant studies were selected and assessed based on quality measures, including study design, sample size, and significance. Inclusion and exclusion criteria were used to examine the yield of the initial search (n = 105). After a secondary review, the included results were identified (n = 50). Results: This study revealed that PET imaging is highly accurate for the planning of GKRS. In fact, many cases indicate that it is more specific than traditional imaging modalities. PET is also capable of complementing traditional imaging techniques through combination imaging. This showed significant efficacy for the planning of GKRS for ICNs. Conclusions: While PET shows a multitude of applications for the treatment of ICNs with GKRS, further research is necessary to assemble a complete set of clinical guidelines for treatment specifications. Importantly, future studies need a greater standardization of methods and expanded trials with a multitude of radiotracers. Full article

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15 pages, 286 KiB

Open AccessReview

Neoadjuvant Stereotactic Ablative Radiotherapy in Pancreatic Ductal Adenocarcinoma: A Review of Perioperative and Long-Term Outcomes

by Robert Michael O’Connell and Emir Hoti

Diseases 2025, 13(7), 214; https://doi.org/10.3390/diseases13070214 - 8 Jul 2025

Viewed by 353

Abstract

The incidence of pancreatic ductal adenocarcinoma (PDAC) is continuing to rise globally, while overall survival continues to be poor. Margin-negative (R0) surgical resection is essential to improve patient outcomes. With increasing understanding of the importance of anatomy and biology to establishing the resectability [...] Read more.

The incidence of pancreatic ductal adenocarcinoma (PDAC) is continuing to rise globally, while overall survival continues to be poor. Margin-negative (R0) surgical resection is essential to improve patient outcomes. With increasing understanding of the importance of anatomy and biology to establishing the resectability of PDAC, neoadjuvant therapy (NAT) has emerged as an important strategy to achieve an R0 resection, particularly for those with borderline resectable (BR-PDAC) and locally advanced disease (LA-PDAC). However, despite the multiple randomised controlled trials (RCTs) published in recent years, the optimum regime has yet to be fully established. The role of neoadjuvant chemoradiation therapy (CRT) remains controversial, possibly allowing for improved local disease control at a potential cost of interrupting systemic treatment. The emergence of stereotactic ablative radiotherapy (SABR), in place of conventional radiation therapy, improves patient tolerance of NAT and may improve local tumour control for patients with PDAC during limited fractions, minimising systemic therapy interruption. A particular niche for SABR may be as part of NAT for LA-PDAC, potentially converting a minority of patients with favourable biology to allow for resection. While pancreaticoduodenectomy can be technically challenging following NAT, there is no difference in the rate of major morbidity or mortality post operatively. Indeed, post-operative pancreatic fistula (POPF) rates may be lower following NAT. Overall, however, evidence for SABR in a neoadjuvant setting for BR- and LA-PDAC remains sparse. Full article

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

Viewed by 352

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

Viewed by 329

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

Viewed by 288

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

Viewed by 269

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

Viewed by 923

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

Viewed by 439

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

Viewed by 854

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

Viewed by 389

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

Viewed by 649

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

Viewed by 1714

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

Viewed by 296

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

Viewed by 332

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

Viewed by 390

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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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

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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

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Diseases, Volume 13, Issue 7 (July 2025) – 41 articles

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