Diseases

16 pages, 1323 KB

Open AccessSystematic Review

Impact of Resuscitative Endovascular Balloon Occlusion of the Aorta on In-Hospital and Short-Term Mortality: A Systematic Review and Meta-Analysis

by Hiroyuki Kamide, Shingo Kato, Naofumi Yasuda, Shungo Sawamura, Yoshinobu Ishiwata, Nobuyuki Horita, Ryusuke Sekii, Tomohiro Oshima, Zenjiro Sekikawa and Daisuke Utsunomiya

Diseases 2026, 14(4), 122; https://doi.org/10.3390/diseases14040122 - 27 Mar 2026

Abstract

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly employed in patients with hemorrhagic shock and cardiovascular collapse; however, its impact on mortality remains controversial. Differences in geographic regions and patient populations may influence clinical outcomes. Methods: We conducted a systematic [...] Read more.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly employed in patients with hemorrhagic shock and cardiovascular collapse; however, its impact on mortality remains controversial. Differences in geographic regions and patient populations may influence clinical outcomes. Methods: We conducted a systematic review and meta-analysis of observational studies comparing mortality between patients receiving REBOA and those managed without REBOA. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses were performed according to propensity score (PS) matching, trauma versus non-trauma populations, and geographic regions. Results: A total of 10 studies involving 18,611 patients were included. Overall, REBOA was not associated with a significant reduction in mortality compared with non-REBOA (pooled OR = 0.52, 95% CI: 0.19–1.39, p = 0.19). In PS-matched studies, the pooled OR was 0.82 (95% CI: 0.34–1.98, p = 0.66), whereas in non-PS-matched studies it was 0.40 (95% CI: 0.12–1.26, p = 0.12). Geographic analyses revealed no significant mortality benefit in either Western studies (OR = 0.47, 95% CI: 0.12–1.89; p = 0.29) or non-Western studies (OR = 0.60, 95% CI: 0.11–3.38; p = 0.56). No survival benefit was observed among trauma patients (OR = 0.57, 95% CI: 0.20–1.61; p = 0.29), whereas a significant reduction in mortality was observed in non-trauma patients (OR = 0.21, 95% CI: 0.05–0.88; p = 0.03). Conclusions: In this systematic review and meta-analysis, REBOA was not associated with a significant reduction in mortality in the overall population or in trauma patients. However, in a single small non-trauma study (n = 53), REBOA was associated with significantly reduced mortality; this finding is exploratory and requires confirmation in larger prospective studies. These findings suggest that the clinical benefit of REBOA may depend on patient population and underlying etiology of hemorrhage. Full article

► Show Figures

Figure 1

37 pages, 2507 KB

Open AccessSystematic Review

Efficacy and Safety of Endoscopic Strictureplasty and Stricturotomy for Crohn’s Disease-Associated Strictures: A Systematic Review and Current Perspective

by Elisa Abreu, Rolando Pinho, Fernando Magro and Maria Manuela Estevinho

Diseases 2026, 14(4), 121; https://doi.org/10.3390/diseases14040121 - 27 Mar 2026

Abstract

Objectives: Strictures are a major complication of Crohn’s disease (CD) affecting up to 20% of patients at diagnosis. Endoscopic balloon dilation (EBD) is the first-line endoscopic approach; however, it entails complications and a need for reintervention. Endoscopic stricturotomy (ESt) and stricturoplasty (ESTx) are [...] Read more.

Objectives: Strictures are a major complication of Crohn’s disease (CD) affecting up to 20% of patients at diagnosis. Endoscopic balloon dilation (EBD) is the first-line endoscopic approach; however, it entails complications and a need for reintervention. Endoscopic stricturotomy (ESt) and stricturoplasty (ESTx) are promising alternatives. This review aims to provide an up-to-date and comprehensive assessment of their efficacy and safety in CD-associated strictures. Methods: A literature search was performed until August 2025. Primary outcomes were clinical and technical success. Secondary outcomes included adverse events, additional endoscopic or surgical treatments, medication escalation, emergency department visits and hospitalization following intervention. A minimum of four studies were required for meta-analysis, and pooled estimates were calculated using random-effects meta-analysis. Study quality was assessed using CASP checklist. Results: Fifteen studies including 1050 IBD patients (470 CD) were included. Strictures were short (0.9–2.4 cm) and some had prior EBD (7.8–57.1%) or surgery (3.6–91%). Technical success of ESt ranged from 88% to 100% and clinical success from 50% to 96%. The bleeding rate was up to 11.8%, but perforation rate was mostly <2%. The need for additional intervention, endoscopic (18.2–66.6%) or surgical (0–18.2%), varied considerably. Additionally, ESTx’s technical success ranged from 91.7% to 100% whereas clinical success ranged from 71.4% to 91%, with bleeding ranging from 5.2% to 8.8% and perforation from 0% to 3.4%. Similarly, the need for additional endoscopic procedures (7.1–57.1%) and surgery (9.5–25%) varied considerably. Conclusions: ESt and ESTx are safe and effective for managing CD-related strictures, particularly when short, straight, accessible, fibrotic, anastomotic, or refractory to EBD. Full article

► Show Figures

Figure 1

15 pages, 708 KB

Open AccessArticle

Culture-Confirmed Bacterial Sepsis and Invasive Fungal Infection in Preterm Infants: NICU Resource Burden, Major Morbidity, and Caregiver Psychological Distress

by Sergiu Costescu, Adrian Ratiu, Bogdan Cerbu, Oana Cristina Costescu, Cosmin Citu, Aniko Maria Manea and Zoran Laurentiu Popa

Diseases 2026, 14(4), 120; https://doi.org/10.3390/diseases14040120 - 27 Mar 2026

Abstract

Background and Objectives: Very preterm infants are vulnerable to late-onset infection and prolonged NICU exposure, with potential downstream effects on caregiver health. We evaluated neonatal outcomes and caregiver psychosocial status across culture-confirmed infection phenotypes. Methods: We investigated a single-center prospective cohort (March 2023–December [...] Read more.

Background and Objectives: Very preterm infants are vulnerable to late-onset infection and prolonged NICU exposure, with potential downstream effects on caregiver health. We evaluated neonatal outcomes and caregiver psychosocial status across culture-confirmed infection phenotypes. Methods: We investigated a single-center prospective cohort (March 2023–December 2025) of 87 preterm infants assigned to one of three groups: no proven infection (n = 44), bacterial sepsis (n = 31), or candidemia (n = 12). Neonatal outcomes included a composite adverse endpoint (death or major morbidity) and resource utilization. Caregivers completed the SF-36, WHOQOL-BREF, HADS, PHQ-9, GAD-7, and Body Image Scale near discharge. Results: Candidemia occurred later than bacterial sepsis (day of life 17.8 ± 4.8 vs. 10.1 ± 3.9; p < 0.001) and had a longer time to effective therapy (23.3 ± 9.5 vs. 13.3 ± 5.3 h; p = 0.004). The composite adverse outcome was 27.3% in the no-infection group versus 54.8% in the bacterial group and 58.3% in the candidemia group (p = 0.025); ROP requiring treatment increased from 4.5% to 29.0% and 25.0% (p = 0.012). Length of stay rose from 39.7 ± 10.2 to 50.1 ± 11.9 and 60.9 ± 13.1 days (p < 0.001), and ventilation days from 15.7 ± 7.6 to 23.3 ± 7.5 and 34.2 ± 10.4 (p < 0.001). Caregiver SF-36 mental health (MCS) scores decreased from 44.7 ± 7.5 to 38.5 ± 6.0 and 36.7 ± 6.4 (p < 0.001), while PHQ-9 scores increased from 9.4 ± 3.9 to 11.6 ± 3.3 and 15.5 ± 4.6 (p < 0.001); NICU burden correlated with PHQ-9 scores (r = 0.52, p < 0.001). Conclusions: Culture-confirmed infection, particularly candidemia, was associated with higher neonatal morbidity, markedly greater resource use, and substantial caregiver distress at discharge. Full article

► Show Figures

Figure 1

14 pages, 717 KB

Open AccessSystematic Review

Serum Procalcitonin in Culture-Confirmed Melioidosis: A Systematic Review and Meta-Analysis with Narrative Evaluation of Clinical and Prognostic Implications

by Jongkonnee Thanasai, Chaimongkhon Chanthot, Anchalee Chittamma, Supphachoke Khemla, Atthaphong Phongphithakchai, Moragot Chatatikun, Jitbanjong Tangpong, Sa-ngob Laklaeng and Wiyada Kwanhian Klangbud

Diseases 2026, 14(4), 119; https://doi.org/10.3390/diseases14040119 - 26 Mar 2026

Abstract

Background: Procalcitonin (PCT) is a biomarker of bacterial infection and sepsis severity, but its role in melioidosis remains unclear. This study aimed to synthesize available evidence on serum PCT levels in culture-confirmed melioidosis and explore associations with disease severity and mortality. Methods: We [...] Read more.

Background: Procalcitonin (PCT) is a biomarker of bacterial infection and sepsis severity, but its role in melioidosis remains unclear. This study aimed to synthesize available evidence on serum PCT levels in culture-confirmed melioidosis and explore associations with disease severity and mortality. Methods: We conducted a systematic review following PRISMA guidelines and registered the protocol with PROSPERO (CRD420251166979). PubMed, Embase, and Scopus were searched up to 30 October 2025. Observational studies reporting serum PCT levels in microbiologically confirmed melioidosis were included. Study quality was assessed using the Newcastle–Ottawa Scale (NOS) for observational studies. Random-effects models were used to calculate pooled mean PCT levels, with heterogeneity assessed by I². Sensitivity analyses were performed to explore the influence of historical and small-sample studies. Results: Seven studies comprising 284 patients with culture-confirmed melioidosis were included. The pooled mean PCT level was 14.46 ng/mL (95% CI: 4.59–24.33), with substantial heterogeneity (I² = 87.7%). Sensitivity analyses excluding the oldest study and the smallest sample size reduced heterogeneity but retained consistently elevated PCT levels across cohorts. Higher PCT concentrations were consistently observed among patients with septic shock, bacteremia, and fatal outcomes, although variability in definitions precluded quantitative synthesis of prognostic effect sizes. These findings were based on heterogeneous study-level comparisons and could not be synthesized quantitatively. Conclusions: PCT is markedly elevated in melioidosis and reflects the severity of systemic infection, supporting its potential role as an adjunctive biomarker for early risk stratification. However, substantial heterogeneity and limited sample sizes prevent the establishment of a melioidosis-specific prognostic threshold. Standardized, prospective, multicenter studies are required to clarify the independent prognostic value of PCT in melioidosis management. This study establishes a pooled estimate of serum PCT levels in melioidosis and demonstrates that these values are comparable to those observed in severe bacterial sepsis, supporting its interpretation as a marker of systemic inflammatory burden rather than a disease-specific biomarker. Full article

(This article belongs to the Section Infectious Disease)

► Show Figures

Figure 1

22 pages, 1832 KB

Open AccessReview

Interplay Among Endothelial Dysfunction, NLRP3 Pathway Activation, and microRNAs in the Pathogenesis of Preeclampsia

by Daniela Alves Pereira, Priscila Rezeck Nunes, Marcelo Rizzatti Luizon and Valéria Cristina Sandrim

Diseases 2026, 14(4), 118; https://doi.org/10.3390/diseases14040118 - 26 Mar 2026

Abstract

Preeclampsia (PE) is a leading cause of maternal and perinatal complications and is classified by early or late onset according to the gestational age. The complex pathogenesis of PE involves placental ischemia, oxidative stress, angiogenic imbalance, and inflammation, all of which contribute to [...] Read more.

Preeclampsia (PE) is a leading cause of maternal and perinatal complications and is classified by early or late onset according to the gestational age. The complex pathogenesis of PE involves placental ischemia, oxidative stress, angiogenic imbalance, and inflammation, all of which contribute to impaired placentation and widespread maternal endothelial dysfunction. These mechanisms drive hypertension, multi-organ involvement, and increased long-term cardiovascular risk. Parallel research highlighted the role of the NLRP3 inflammasome, a multiprotein complex that, upon activation, increases the gene expression, processing, and release of the pro-inflammatory cytokines IL-1β and IL-18. The NLRP3 pathway is markedly upregulated in placentas from pregnant women with PE, where endogenous danger signals stimulate inflammasome activation and amplify inflammation. Increasing evidence indicates that microRNAs (miRNAs) help regulate inflammatory processes, including the NLRP3 inflammasome, thereby affecting placental function and maternal adaptation. Although several immunoregulatory miRNAs may influence NLRP3 activity, their specific contribution to inflammasome regulation in PE remains insufficiently understood. Understanding these interactions could reveal new therapeutic targets for PE. In this narrative review, we explore the interconnected roles of endothelial dysfunction, inflammasome activation, and miRNA-mediated regulation in the pathogenesis of PE. Full article

► Show Figures

Figure 1

11 pages, 238 KB

Open AccessReview

Critical Care Sedation: Emerging Clinical Considerations and Risks of Volatile Anesthetics for Sedation: A Narrative Review

by Austin M. Breaux, Garret R. Miller, Harrison D. Cooper, Kristin Nicole Bembenick, Aishwarya Reddy, Shahab Ahmadzadeh, Sahar Shekoohi and Alan D. Kaye

Diseases 2026, 14(4), 117; https://doi.org/10.3390/diseases14040117 (registering DOI) - 25 Mar 2026

Abstract

Volatile anesthetics have steadily become more popular in intensive care units for sedation for reasons related to their beneficial pharmacokinetic and pharmacodynamic properties. Common anesthetics such as isoflurane and sevoflurane rapidly reach sedative levels in the body, but they are also rapidly eliminated, [...] Read more.

Volatile anesthetics have steadily become more popular in intensive care units for sedation for reasons related to their beneficial pharmacokinetic and pharmacodynamic properties. Common anesthetics such as isoflurane and sevoflurane rapidly reach sedative levels in the body, but they are also rapidly eliminated, allowing for quick recovery. These agents have minimal impact on the liver and kidneys, which makes them attractive options when compared to other agents including opioids, benzodiazepines, ketamine, and propofol. Use of delivery systems like AnaConDa^® (Anaesthetic Conserving Device; Sedana Medical AB, Danderyd, Sweden) has enabled providers to easily use these agents in the Intensive Care Unit (ICU). In this regard, they have recently provided additional beneficial consideration during intravenous drug shortages seen during the COVID-19 pandemic and at other times. These agents have shown organ-protective effects in the kidneys and lungs, which may even reduce the total time spent in the ICU. Pharmacodynamically, these anesthetics mediate their effects through central nervous system ion channels to exert analgesic and anxiolytic actions, thereby minimizing effects in the kidneys and lungs. These agents are primarily eliminated via exhalation, which makes them potential options for those with liver or kidney failure. This narrative review examines current efficacy and risks of using volatile anesthetics for sedation in the ICU setting and clinical roles for the future. Full article

18 pages, 610 KB

Open AccessReview

Applications of Extended Platelet Profiles in Clinical Practice

by Yi Yuan Zhou and Robert W. Maitta

Diseases 2026, 14(4), 116; https://doi.org/10.3390/diseases14040116 - 25 Mar 2026

Abstract

Thrombocytopenia is a frequent complication of patients presenting emergently across the world for a wide array of etiologies. From patients who develop thrombocytopenia due to invasive neoplastic disease affecting the bone marrow to patients who develop immune complications secondary to the formation of [...] Read more.

Thrombocytopenia is a frequent complication of patients presenting emergently across the world for a wide array of etiologies. From patients who develop thrombocytopenia due to invasive neoplastic disease affecting the bone marrow to patients who develop immune complications secondary to the formation of auto-antibody responses that drive patients’ platelet counts lower or even cause infection, these patients stress the clearest need for prompt tests to discern the more likely thrombocytopenic-inducing cause. It is in this setting that looking at other platelet variables easily obtainable from modern hematology analyzers has gained traction. One of the elements found in extended platelet profiles are immature platelets (youngest and newly released platelets), also known as reticulated platelets, which are readily measurable from a complete blood count. One of the advantages of obtaining these counts is that they represent the immediate response of the bone marrow to the thrombocytopenia and, depending on etiology inducing the thrombocytopenia, they also provide information on the marrow’s response to therapeutic approaches. It is in this context that this review will present information of how these relatively novel platelet parameters can be used in clinical practice and how they can be a rapid gauge of the body’s response to disease processes leading to platelet losses. Thrombocytopenias resulting from infection (sepsis, viremia), autoantibody formation (immune thrombocytopenia and immune-mediated thrombotic thrombocytopenic purpura), immune dysregulation (systemic lupus erythematosus), and iatrogenic (drug-induced) will be discussed and used to explain how these young platelet measurements can provide valuable clinical information. Full article

(This article belongs to the Special Issue Research Topics in Thrombosis-Inducing Diseases)

► Show Figures

Figure 1

12 pages, 2960 KB

Open AccessSystematic Review

Spondylodiscitis Following Oxygen–Ozone Therapy: A Case Report of Lactobacillus iners Infection and a Systematic Literature Review

by Calogero Velluto, Giovan Giuseppe Mazzella, Michele Inverso, Maria Ilaria Borruto, Andrea Perna, Riccardo Totti, Laura Scaramuzzo and Luca Proietti

Diseases 2026, 14(3), 115; https://doi.org/10.3390/diseases14030115 - 23 Mar 2026

Abstract

Background: Oxygen–ozone (O₂–O₃) therapy is a minimally invasive treatment for discogenic lumbar pain. Although rare, spinal infections—specifically spondylodiscitis—have been reported following intradiscal injections. To date, Lactobacillus iners has not been described as a causative agent in this context. Case [...] Read more.

Background: Oxygen–ozone (O₂–O₃) therapy is a minimally invasive treatment for discogenic lumbar pain. Although rare, spinal infections—specifically spondylodiscitis—have been reported following intradiscal injections. To date, Lactobacillus iners has not been described as a causative agent in this context. Case Presentation: A 55-year-old immunocompetent woman presented with progressive lumbosciatica and elevated inflammatory markers three months after intradiscal O₂–O₃ therapy. MRI revealed L4–L5 spondylodiscitis with paravertebral involvement. Surgical biopsy confirmed L. iners as the pathogen. She underwent decompression and received targeted intravenous antibiotics, achieving full clinical and radiological recovery. Methods: A systematic literature review was performed using PubMed, MEDLINE, and Scopus to identify reports of spondylodiscitis following oxygen–ozone therapy. Six cases were included based on predefined inclusion criteria. Results: The 8 identified cases involved a range of pathogens, including Staphylococcus aureus, Streptococcus beta-haemolyticus, Escherichia coli, Achromobacter xylosoxidans, Mycobacterium abscessus, and Streptococcus intermedius, and one culture-negative infection. Clinical presentations varied from radiculopathy to sepsis. Management strategies encompassed both conservative (antibiotics alone) and surgical approaches, depending on neurological status and abscess formation. Outcomes were favorable in all cases except one fatality. Conclusions: This report is the first to describe L. iners spondylodiscitis in an immunocompetent patient following O₂–O₃ therapy. Clinicians should vigilantly evaluate post-infiltration spinal infections, maintain a low threshold for imaging and biopsy, and implement pathogen-targeted antibiotic regimens, with surgical intervention as needed. Full article

► Show Figures

Figure 1

11 pages, 2029 KB

Open AccessCase Report

Giant Malignant Phyllodes Tumor with Secondary Thyroid Involvement

by Daciana Grujic, Teodora Hoinoiu, Catalin-Alexandru Pirvu, Mihai Iliescu-Glaja, Simona Cerbu, Silviu Cristian Suciu, Daniel Pit, Cristina Marinela Oprean and Horia Cristian

Diseases 2026, 14(3), 114; https://doi.org/10.3390/diseases14030114 - 22 Mar 2026

Abstract

Background/Objectives: Phyllodes tumors are rare fibroepithelial neoplasms of the breast, accounting for less than 1% of all breast tumors and approximately 2–3% of breast fibroepithelial tumors. They can be benign, borderline, or malignant, depending on cellular atypia and stromal invasion. Although most [...] Read more.

Background/Objectives: Phyllodes tumors are rare fibroepithelial neoplasms of the breast, accounting for less than 1% of all breast tumors and approximately 2–3% of breast fibroepithelial tumors. They can be benign, borderline, or malignant, depending on cellular atypia and stromal invasion. Although most display local behavior, malignant forms can metastasize hematogenously, most frequently to the lungs, bones, and liver, with lymph node metastases being exceptional. Case Presentation: We analyzed the case of a 47-year-old woman with a phyllodes breast tumor weighing approximately 5 kg. The tumor evolved slowly over five years, followed by accelerated growth, cutaneous necrosis, superinfection, and severe anemia. Total mastectomy was performed, and histopathological examination confirmed the diagnosis of a malignant phyllodes tumor. Five months after surgery and adjuvant radiotherapy, the patient developed laterocervical metastases with thyroid invasion and life-threatening tracheal compression, an extremely rare presentation for this type of tumor in adults. Discussion/Conclusions: This case illustrates the aggressive and unpredictable behavior of malignant phyllodes tumors and underscores the necessity of careful oncological monitoring and a multidisciplinary approach, given their potential for dissemination to unusual locations. Full article

► Show Figures

Figure 1

15 pages, 272 KB

Open AccessArticle

Association Between HLA Polymorphisms and Non-Alcoholic Fatty Liver Disease in Patients with Rheumatoid Arthritis: An Observational Study

by Tatjana Zekić, Nataša Katalinić, Filip Blažić, Nada Starčević Čizmarević and Aleksandar Čubranić

Diseases 2026, 14(3), 113; https://doi.org/10.3390/diseases14030113 - 22 Mar 2026

Abstract

Background/Objectives: This observational study investigated associations between human leukocyte antigen (HLA) polymorphisms and imaging-defined hepatic steatosis (non-alcoholic fatty liver disease—NAFLD) and liver fibrosis in patients with rheumatoid arthritis (RA). Methods: Steatosis was assessed by transient elastography (FibroScan) and defined as controlled attenuation parameter [...] Read more.

Background/Objectives: This observational study investigated associations between human leukocyte antigen (HLA) polymorphisms and imaging-defined hepatic steatosis (non-alcoholic fatty liver disease—NAFLD) and liver fibrosis in patients with rheumatoid arthritis (RA). Methods: Steatosis was assessed by transient elastography (FibroScan) and defined as controlled attenuation parameter (CAP) ≥ 275 dB/m; fibrosis was defined as liver stiffness measurement ≥ 8 kPa. We tested 11 frequent HLA alleles (HLA-A*02, HLA-B*07, HLA-B*08, HLA-B*27, HLA-B*35, HLA-B*44, HLA-B*51, HLA-DRB1*11, HLA-DRB1*14, HLA-DRB1*15, and HLA-DRB1*16). Associations were evaluated using multivariable logistic regression (individual and omnibus models) adjusted for age, body mass index (BMI), triglycerides, and glucose. Results: A total of 176 patients with rheumatoid arthritis were enrolled. NAFLD/steatosis was present in 35.2% of patients (n = 62), and fibrosis in 10.8% (n = 19). No HLA allele was significantly associated with steatosis or fibrosis after correction for multiple testing. BMI and triglycerides were independently associated with steatosis (BMI OR 1.22, 95% CI 1.12–1.34; triglycerides OR 1.48, 95% CI 1.04–2.18). For fibrosis, HLA-DRB1*15 showed the strongest trend-level association (OR ~2.6–2.9) but did not remain significant after correcting for multiple testing. Conclusions: In this RA cohort, metabolic factors (particularly BMI and triglycerides) were the dominant predictors of CAP-defined steatosis. No robust association between the tested HLA markers and steatosis or fibrosis was identified. Trend-level signals—most notably HLA-DRB1*15 for fibrosis—should be considered hypothesis-generating and warrant replication in larger, adequately powered cohorts. Full article

(This article belongs to the Special Issue Treatment Strategies and Immune Responses in Rheumatic Diseases)

► Show Figures

Graphical abstract

11 pages, 245 KB

Open AccessArticle

Clinical and Demographic Features of Primary Biliary Cholangitis in Kazakhstan

by Aisulu Gainutdin, Alexander Nersesov, Komori Atsumasa, Aigul Raissova, Saltanat Madenova, Laura Yerdaliyeva, Dinara Suleimenova and Balday Issenova

Diseases 2026, 14(3), 112; https://doi.org/10.3390/diseases14030112 - 20 Mar 2026

Abstract

Background/Objectives: Primary biliary cholangitis (PBC) is a chronic immune-mediated cholestatic liver disease with increasing global prevalence. However, data on this disease from Central Asia are lacking. We aimed to describe the clinical, serological, and treatment characteristics of PBC patients in Kazakhstan. Methods: This [...] Read more.

Background/Objectives: Primary biliary cholangitis (PBC) is a chronic immune-mediated cholestatic liver disease with increasing global prevalence. However, data on this disease from Central Asia are lacking. We aimed to describe the clinical, serological, and treatment characteristics of PBC patients in Kazakhstan. Methods: This study was a multicenter, retrospective, observational study including adults diagnosed with PBC between 2014 and 2022 across seven hepatology centers in Kazakhstan. Clinical presentation, laboratory parameters, autoimmune comorbidities, liver disease severity, and ursodeoxycholic acid (UDCA) treatment response were assessed. Biochemical response at 1 year was evaluated using Paris-1 and Barcelona criteria. Results: A total of 230 patients were included; 93.9% were female and 91.3% were of Asian ethnicity, with a median age at diagnosis of 53 years. Cirrhosis was present at diagnosis in 50.2% of the patients. PBC with autoimmune hepatitis (AIH) features was identified in 56.1% of the patients and was associated with higher rates of cirrhosis, portal hypertension complications, antinuclear antibody (ANA) positivity, and higher elastography indices compared with isolated PBC. Overall, approximately 55% of the patients achieved a biochemical response to UDCA at 1 year, with similar response rates between patients with PBC and those with PBC with AIH features. Conclusions: This first comprehensive study of PBC in Kazakhstan demonstrates late disease presentation with a high burden of cirrhosis and frequent AIH features. Despite advanced disease, about half of the patients achieved biochemical remission on UDCA. These findings underscore the need for earlier diagnosis and optimized management strategies for PBC in Kazakhstan and similar settings in Central Asia. Full article

(This article belongs to the Section Gastroenterology)

► Show Figures

Graphical abstract

17 pages, 491 KB

Open AccessReview

Pediatric Dialysis: From Acute Kidney Injury to Chronic Renal Replacement Therapies: Challenges and Perspectives in Resource-Limited Countries

by Djilali Batouche, Djamila Djahida Batouche, Zoheir Zakaria Addou, Souhila Fatima Bouchama, Rabia Okbani, Siham Simerabet, Nadia Faiza Benatta, Soulef Saadi-Ouslim and Miloud Lahmer

Diseases 2026, 14(3), 111; https://doi.org/10.3390/diseases14030111 - 19 Mar 2026

Abstract

Background: Pediatric kidney failure, whether acute or chronic, constitutes a major public health issue because of its impact on survival, linear growth, neurocognitive development, and long-term quality of life. While high-income countries have markedly improved outcomes through early diagnosis, advanced dialysis technologies, [...] Read more.

Background: Pediatric kidney failure, whether acute or chronic, constitutes a major public health issue because of its impact on survival, linear growth, neurocognitive development, and long-term quality of life. While high-income countries have markedly improved outcomes through early diagnosis, advanced dialysis technologies, and kidney transplantation, management remains limited in low- and middle-income countries, particularly in the Maghreb region. Objective: This review aims to provide an updated synthesis of pediatric kidney failure, with emphasis on renal replacement therapy modalities and the specific challenges encountered in resource-limited contexts, particularly in Algeria. Methods and Content: We successively address the pathophysiological and clinical bases of pediatric acute kidney injury and chronic kidney disease, followed by a discussion of available therapeutic strategies: peritoneal dialysis, intermittent hemodialysis, continuous renal replacement therapy, and pediatric kidney transplantation. Particular attention is given to organizational constraints, actual availability of modalities, limited access to consumables and immunosuppressive therapies, and the specificities of pediatric kidney care in the Maghreb region in comparison with international recommendations. Perspectives: Improving outcomes for children with kidney failure in Maghreb countries requires a multidimensional approach integrating early screening, strengthening peritoneal dialysis programs, structured development of pediatric kidney transplantation, and enhanced regional and international collaboration. Reinforcing local research capacity and participation in international registries are essential steps toward reducing disparities in care and adapting global guidelines to local realities. Full article

► Show Figures

Figure 1

17 pages, 730 KB

Open AccessArticle

Healthcare Resource Consumption and Related Costs of People Living with HIV and Antiviral Treatment: A Retrospective Observational Study in Italy

by Luca Degli Esposti, Stefania Mazzoni, Maria Cappuccilli, Franco Maggiolo, Sergio Lo Caputo, Silvia Nozza, Lucia Taramasso, Anna Marra and Mario Pittorru

Diseases 2026, 14(3), 110; https://doi.org/10.3390/diseases14030110 - 18 Mar 2026

Abstract

Background/Objectives: Among the antiretroviral therapies (ARTs) recently introduced for people living with HIV (PLWH), the fixed-dose combination of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) became reimbursable in Italy in June 2019. Methods: This study evaluated drug utilization, healthcare resource consumption and direct costs [...] Read more.

Background/Objectives: Among the antiretroviral therapies (ARTs) recently introduced for people living with HIV (PLWH), the fixed-dose combination of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) became reimbursable in Italy in June 2019. Methods: This study evaluated drug utilization, healthcare resource consumption and direct costs among ART-naïve adults initiating B/F/TAF or other non-bictegravir-based regimens, identified from June 2019 to September 2022 within administrative databases of healthcare entities covering approximately nine million citizens. Baseline clinical characteristics at first ART prescription were compared across B/F/TAF-treated patients, those receiving other ART regimens, and non-HIV controls, while treatment outcomes during follow-up were evaluated among PLWH receiving B/F/TAF or other ARTs; healthcare consumption and costs were assessed after propensity score matching within the PLWH cohorts only. Results: Overall, 374 individuals initiated B/F/TAF and 5576 other ARTs. Patients treated with B/F/TAF showed greater adherence and persistence, with multivariate analyses confirming a lower risk of discontinuation or switching (HR = 0.66, 95% CI 0.57–0.76, p < 0.001) and a higher likelihood of adherence (HR = 2.40, 95% CI 1.58–3.64, p < 0.001). After matching, the B/F/TAF group exhibited lower 12-month consumption of non-HIV medications, fewer non-HIV hospitalizations, and reduced total healthcare costs, particularly for non-HIV drug prescriptions compared to other ART users. Conclusions: Overall, B/F/TAF was associated with better treatment continuity and meaningful cost savings. Full article

► Show Figures

Figure 1

16 pages, 319 KB

Open AccessReview

Intravascular Lymphoma Associated with the Female Genital Tract—Diagnostic Considerations, Therapeutic Approaches, and Outcomes

by Aleksandar Ristic, Marija Rovcanin, Ana Tomic, Aleksandar Rakic, Nebojsa Zecevic and Svetlana Jankovic

Diseases 2026, 14(3), 109; https://doi.org/10.3390/diseases14030109 - 17 Mar 2026

Abstract

Intravascular lymphoma (IVL) is an uncommon subtype of non-Hodgkin’s extranodal lymphoma, distinguished by the proliferation of neoplastic cells within the lumen of small- to medium-sized arteries, with various organs recorded as impacted. The objective of this study was to evaluate the current literature [...] Read more.

Intravascular lymphoma (IVL) is an uncommon subtype of non-Hodgkin’s extranodal lymphoma, distinguished by the proliferation of neoplastic cells within the lumen of small- to medium-sized arteries, with various organs recorded as impacted. The objective of this study was to evaluate the current literature about IVL and its involvement in the female genital tract, including an overview of diagnostic methods, imaging, and pathological features, selected therapy modalities, and outcomes in patients afflicted by this malignancy. We performed a narrative review with a systematic identification and presentation of published cases of IVL affecting the female genital tract. A literature search was carried out across PubMed, Scopus, and Web of Science for relevant studies presenting data on IVL affecting the female genital tract. Case reports and series that met predefined inclusion and exclusion criteria specified by the modified PECOS (“Population,” “Exposure,” “Comparison,” “Outcomes,” and “Study design”) framework were included. Patients most commonly presented with abnormal vaginal bleeding, pelvic pain, and B symptoms. Fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT), often performed alongside abnormal laboratory findings such as elevated lactate dehydrogenase (LDH), played a key role in raising suspicion for hematologic involvement of the female genital tract and guiding biopsy. Most cases represented B-cell intravascular lymphoma and were treated with Rituximab plus (CHOPR-CHOP) based chemotherapy, frequently combined with hysterectomy. Full article

19 pages, 2133 KB

Open AccessArticle

Integrated Functional and Histopathological Modulation of Chronic Thioacetamide-Induced Liver Fibrosis by Mesenchymal Stem Cell Therapy in a Preclinical Model

by Anthony Brayan Rivera Prado, Luis Lloja Lozano, Daysi Zulema Diaz Obregón, Víctor Hugo Carbajal Zegarra, Joel De León Delgado, Jhon Wilfredo Pando Mayta, Alexis German Murillo Carrasco, Kelly Geraldine Yparraguirre Salcedo and Claudio Willbert Ramirez Atencio

Diseases 2026, 14(3), 108; https://doi.org/10.3390/diseases14030108 - 15 Mar 2026

Abstract

Background: Chronic liver fibrosis is a progressive pathological condition characterized by excessive extracellular matrix deposition and architectural remodeling, which may ultimately lead to cirrhosis and liver failure. Although mesenchymal stem cells (MSCs) exhibit antifibrotic and immunomodulatory properties, their therapeutic effects in established chronic [...] Read more.

Background: Chronic liver fibrosis is a progressive pathological condition characterized by excessive extracellular matrix deposition and architectural remodeling, which may ultimately lead to cirrhosis and liver failure. Although mesenchymal stem cells (MSCs) exhibit antifibrotic and immunomodulatory properties, their therapeutic effects in established chronic liver fibrosis remain incompletely defined. This study aimed to evaluate the biochemical, hematological, and histopathological effects of MSC therapy in a chronic thioacetamide-induced liver fibrosis model. Methods: A controlled preclinical experimental study was conducted using rats with liver fibrosis induced by intraperitoneal thioacetamide administration for 24 weeks. Animals were allocated into three groups: control, untreated fibrosis, and fibrosis treated with MSCs derived from human umbilical cord tissue after fibrosis establishment. Serum biochemical markers, hematological parameters, and liver histopathology were assessed. Fibrosis severity was evaluated using hematoxylin–eosin and Masson’s trichrome staining and graded according to the METAVIR scoring system. Results: Thioacetamide exposure induced chronic liver injury characterized by marked elevations in serum transaminases, reduced albumin and total protein levels, hematological alterations, and early-to-intermediate fibrosis stages (METAVIR F1–F2). MSC-treated animals exhibited approximately 40–45% reductions in transaminase levels, partial recovery of hepatic synthetic function, and attenuation of hematological alterations. Histopathological analysis demonstrated a reduction in fibrotic burden and limitation of fibrogenic progression within METAVIR F1–F2 stages. Conclusions: MSC therapy partially mitigates biochemical, hematological, and histopathological alterations associated with chronic thioacetamide-induced liver fibrosis, supporting its potential as a modulatory strategy to attenuate fibrogenic progression and stabilize liver function rather than as a curative intervention. Full article

► Show Figures

Figure 1

9 pages, 433 KB

Open AccessArticle

Maternal Outcomes Associated with Delayed Cord Clamping in Hypertensive Disorders of Pregnancy: A Cross-Sectional Study

by Aigerim Turekulova, Nurzhamal Dzhardemaliyeva, Heike Rabe and Mukhtar Kulimbet

Diseases 2026, 14(3), 107; https://doi.org/10.3390/diseases14030107 - 13 Mar 2026

Abstract

Background/Objectives: Delayed umbilical cord clamping (DCC) is widely recommended for neonatal benefit; however, concerns persist among professionals that DCC may increase the risk of postpartum hemorrhage. There is a higher risk of postpartum hemorrhage in women with hypertensive disorders of pregnancy (HDP). We [...] Read more.

Background/Objectives: Delayed umbilical cord clamping (DCC) is widely recommended for neonatal benefit; however, concerns persist among professionals that DCC may increase the risk of postpartum hemorrhage. There is a higher risk of postpartum hemorrhage in women with hypertensive disorders of pregnancy (HDP). We aimed to evaluate the association between umbilical cord clamping timing and maternal blood loss in term pregnancies, including those complicated by HDP. Methods: We conducted a cross-sectional study of women delivering at three major hospitals in Almaty, Kazakhstan (August 2020–March 2021). The primary outcome was maternal blood loss. Secondary outcomes included hemoglobin (Hb) and red blood cell (RBC) change from pre-delivery to discharge. Multivariable models were adjusted for maternal age, parity and hypertension category. Results: Two hundred and seven women were analyzed (early cord clamping ≤ 60 (ECC) n = 21; delayed cord clamping 60–119 s (DCC60s) n = 161; delayed cord clamping ≥ 120 s (DCC120s) n = 25). Baseline characteristics were similar across groups except for hypertension distribution. Median blood loss did not differ significantly (255–260 mL; p = 0.9128). Adjusted models confirmed no association between clamping category and blood loss (RoM: ECC vs. DCC60s 0.97; 95% CI 0.93–1.01; DCC120s vs. DCC60s 1.01; 95% CI 0.96–1.07). Conclusions: Among term births in Almaty, including HDP-affected pregnancies, delayed umbilical cord clamping was not associated with increased maternal blood loss or hematologic decline. These findings indicate that DCC does not appear to increase maternal bleeding risk in high-risk obstetric populations and are broadly in line with current international recommendations. Further prospective research is warranted to evaluate specific subgroups, including severe preeclampsia. Full article

► Show Figures

Graphical abstract

13 pages, 778 KB

Open AccessArticle

Trends and Demographics of Hepatorenal Syndrome-Related Mortality in the U.S., 1999–2024: A CDC WONDER Analysis

by Syed Faisal Ali, Julia Natche, Mahendrakumar Achlaram Chaudhari, Hassan Abbasi, Sammy Dawoud, Hany Dawoud, Amna Shoaib, Hersh Tilokani, Harleen Kaur Chela and Arsal Zafar

Diseases 2026, 14(3), 106; https://doi.org/10.3390/diseases14030106 - 12 Mar 2026

Abstract

Background: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis, marked by rapid renal function decline and poor prognosis. Although clinical predictors of HRS outcomes have been extensively studied, less is known about how demographic factors influence mortality patterns. Methods: This analysis [...] Read more.

Background: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis, marked by rapid renal function decline and poor prognosis. Although clinical predictors of HRS outcomes have been extensively studied, less is known about how demographic factors influence mortality patterns. Methods: This analysis utilized CDC WONDER data to assess U.S. mortality trends for hepatorenal syndrome (HRS) in adults aged ≥25 years from 1999 to 2024. We calculated crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 100,000 and analyzed temporal trends using Joinpoint regression to determine the annual percentage change (APC) and average annual percentage change (AAPC). Results: From 1999 to 2024, 118,894 HRS-associated deaths were recorded. The overall AAMR decreased significantly from 2.43 in 1999 to 2.12 in 2024, with an AAPC of (AAPC −0.69% [95% CI: −0.90% to −0.51%]). Males consistently exhibited higher AAMRs than females (Males: 2.62 vs. Females: 1.63 in 2024). When stratified by race, the highest AAMR in 2024 was observed among non-Hispanic (NH) American Indian or Alaska Native populations (11.02), followed by Hispanic or Latino (2.58), NH White (2.23), NH Black or African American (1.30), and NH Asian or Pacific Islander populations (0.72). Regionally, the highest mortality was observed in the West, followed by the Midwest, South, and Northeast (2.88, 2.00, 1.92, and 1.53, respectively, in 2024). Rural areas (2.44) consistently exhibited higher AAMRs than urban areas (1.91) throughout the study period. Conclusions: HRS-related mortality has decreased modestly in the U.S over the last 26 years, yet significant inequities remain across population subgroups and regions. Mortality is disproportionately higher among males, NH American Indian or Alaska Native individuals, and residents of rural and western areas, highlighting the continued necessity for focused public health strategies. Full article

(This article belongs to the Section Gastroenterology)

► Show Figures

Figure 1

13 pages, 807 KB

Open AccessArticle

Tear Film Interferometry, Meibography, and Optical Coherence Tomography Angiography for Rosacea

by Matteo Capobianco, Marco Zeppieri, Federico Visalli, Francesco Pellegrini, Leandro Inferrera, Rosa Giglio, Irene Gattazzo, Francesco Cappellani, Fabiana D’Esposito and Caterina Gagliano

Diseases 2026, 14(3), 105; https://doi.org/10.3390/diseases14030105 - 12 Mar 2026

Abstract

Background/Objectives: Rosacea is a chronic inflammatory dermatosis that may involve the eye, causing surface and adnexal damage that can precede cutaneous signs. Detecting subclinical ocular changes is clinically important because early ocular surface dysfunction may be missed on routine examination yet progress to [...] Read more.

Background/Objectives: Rosacea is a chronic inflammatory dermatosis that may involve the eye, causing surface and adnexal damage that can precede cutaneous signs. Detecting subclinical ocular changes is clinically important because early ocular surface dysfunction may be missed on routine examination yet progress to corneal complications, allowing earlier preventive management when identified. We prospectively evaluated subclinical ocular alterations in cutaneous rosacea using a combined, fully non-invasive high-tech imaging workflow—tear film interferometry, infrared meibography, and exploratory retinal optical coherence tomography angiography (OCT-A)—including patients without clinically evident ocular involvement. Methods: Sixteen patients with cutaneous rosacea (mean age 44.3 ± 11.2 years; 4 males, 12 females) were enrolled and divided into: Group 1—rosacea with clinically evident ocular involvement (n = 11); Group 2—rosacea without clinical ocular involvement (n = 5). Six age-matched healthy subjects served as controls (Group 3). All underwent LipiView II^® interferometry and meibography to quantify lipid-layer thickness (LLT, nm) and meibomian gland (MG) loss score (1 = normal–4 = severe), plus retinal OCT-A (Optovue Inc., Fremont, CA, USA). ANOVA with post hoc Tukey test assessed inter-group differences. Results: OCT-A showed no significant alterations in superficial or deep retinal plexuses across groups (p > 0.05). Conversely, LLT was significantly reduced in both rosacea groups vs. controls (OD: 45.5 ± 21.4 nm and 67.4 ± 10.1 nm vs. 92.7 ± 8.2 nm; OS: 40.4 ± 15.3 nm and 66.4 ± 10.1 nm vs. 96.0 ± 6.7 nm; p < 0.001). MG score was markedly higher (worse) in rosacea (OD: 3.63 ± 0.50 and 3.20 ± 0.83 vs. 1.83 ± 0.75; OS: 3.45 ± 0.68 and 3.40 ± 0.54 vs. 1.66 ± 0.81; p < 0.001). Ocular symptoms were reported by 85% of patients yet slit-lamp examination revealed surface alterations in 58% of asymptomatic cases. Conclusions: Tear film interferometry and meibography detect early ocular surface impairment in rosacea—even in the absence of clinical signs—while retinal microvasculature appears unaffected. Routine ophthalmologic screening of all rosacea patients could enable prompt treatment of subclinical dysfunction, potentially preventing corneal complications. Retinal OCTA metrics were not significantly different in this small pilot cohort, and these negative findings should be interpreted cautiously pending larger studies. Full article

► Show Figures

Figure 1

10 pages, 424 KB

Open AccessArticle

Bevacizumab and Tocotrienol in Recurrent Platinum-Resistant Ovarian Cancer, and the Role of HOXA9 as a Prognostic Biomarker

by Elisabeth Emanuel Graae, Louise Faaborg, Rikke Fredslund Andersen, Lars Ulrik Fokdal and Caroline Brenner Thomsen

Diseases 2026, 14(3), 104; https://doi.org/10.3390/diseases14030104 - 12 Mar 2026

Abstract

Background/Objectives: Platinum resistant ovarian cancer represents a treatment challenge due to lack of efficient treatments and the absence of prognostic biomarkers. The circulating tumor DNA (ctDNA), methylated homebox A9 (meth-HOXA9), has been suggested as a biomarker for ovarian cancer, and might have a [...] Read more.

Background/Objectives: Platinum resistant ovarian cancer represents a treatment challenge due to lack of efficient treatments and the absence of prognostic biomarkers. The circulating tumor DNA (ctDNA), methylated homebox A9 (meth-HOXA9), has been suggested as a biomarker for ovarian cancer, and might have a clinical impact in terms of predicting progression and supporting clinical decision making. Hence, this study investigated the prognostic value of meth-HOXA9 in platinum resistant recurrent ovarian cancer (PR-ROC) treated with bevacizumab and tocotrienol. Methods: Twenty patients with platin-resistant recurrent ovarian cancer were prospectively enrolled in this non-randomized phase II study. The treatment consisted of bevacizumab (Avastin) 10 mg/kg intravenously every three weeks and tocotrienol (Traptol) capsules 300 mg orally three times daily as a continuous treatment. The Level of meth-HOXA9 was measured at baseline and every three weeks. Results: The overall survival (OS) in the cohort was 7.5 months (95% CI 3.0–10.0), and the progression free survival was 4 months (95% CI 1.4–6.6). Comparing meth-HOXA9 ctDNA levels at baseline, there was no statistic significant difference in OS (p = 0.23). Conclusions: Treatment was well tolerated in this heavily pretreated cohort of PR-ROC patients with expected poor prognostic outcomes, with a few individuals showing extraordinary response in terms of progression free survival. The study was not powered to reproduce evidence of potential of meth-HOXA9 as a prognostic biomarker in PR-ROC. Full article

► Show Figures

Figure 1

Journal Description

Diseases

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI