Search Results (2,710)

Cryptosporidiosis is a significant zoonotic disease caused by Cryptosporidium species, primarily Cryptosporidium parvum, leading to serious economic losses in neonatal calves; the absence of an approved vaccine or fully effective treatment necessitates alternative therapeutic approaches. This study evaluated the therapeutic efficacy of albendazole (20 mg/kg, orally, 5 days) in naturally infected neonatal calves, comparing it to paromomycin (100 mg/kg, orally, 5 days) and an albendazole + paromomycin combination. Forty-eight Simmental calves (36 naturally infected, mean age of 14 days, and 12 healthy controls) were included. Infection was confirmed by rapid immunochromatographic tests, carbol fuchsin staining, nested PCR, and RFLP, identifying C. parvum as the causative agent. Fecal and blood samples were collected on days 0, 3, 7, 10, 20, and 30, alongside clinical evaluations and live weight measurements. Oocyst shedding declined significantly over the study period in all three treatment groups, with the paromomycin and albendazole + paromomycin groups showing a numerically earlier decline than the albendazole group; however, no statistically significant differences among the three treatment groups were detected at any individual sampling day. Fecal scores paralleled oocyst shedding patterns. No significant differences were detected among treatment groups in hematological, biochemical, or hepatorenal safety parameters. Albendazole demonstrated efficacy in reducing oocyst shedding in Cryptosporidium infection, suggesting it may serve as a viable alternative treatment option in field conditions. Full article

Background/Objectives: Inflammatory and hematologic indices derived from routine blood tests have been increasingly investigated as prognostic biomarkers in multiple myeloma (MM). However, their clinical utility remains inconsistent, and data on novel composite indices, such as the mean corpuscular volume-to-lymphocyte ratio (MCVL) and the cumulative inflammatory index (IIC), are lacking in MM. Methods: We conducted a retrospective study including 122 patients with newly diagnosed MM. Hematologic and inflammatory indices were evaluated at baseline and after four cycles of induction therapy. Associations with progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis, Cox regression models, and receiver operating characteristic (ROC) curve analysis. Results: Baseline inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune–inflammation index (SII), MCVL, and IIC, were not significantly associated with PFS or OS. ROC analysis demonstrated poor discriminative ability for all evaluated markers at both baseline and post-induction timepoints (AUC values close to or below 0.50). In contrast, post-induction inflammatory indices, particularly PLR, MLR, AISI, and SIRI, were significantly associated with PFS in both univariable and multivariable Cox regression analyses. Neither baseline nor post-induction MCVL and IIC showed independent prognostic value. Conclusions: Baseline inflammatory and erythrocyte-derived indices, including the novel composite markers MCVL and IIC, have limited prognostic utility in MM. In contrast, dynamic changes in inflammatory biomarkers during treatment may provide more clinically relevant information regarding disease progression. These findings support integrating longitudinal biomarker assessment into future risk stratification models for MM. Full article

Oxidative stress is increasingly recognized as a key contributor to the biology of hematological malignancies. Excessive production of reactive oxygen species disrupts redox homeostasis, promotes genomic instability, alters cellular signaling pathways, and influences disease progression, therapeutic response, and resistance mechanisms. Among the downstream consequences of oxidative stress, lipid peroxidation represents a major source of cellular injury, generating reactive aldehydes capable of amplifying molecular damage. Malondialdehyde, a stable end product of lipid peroxidation, has emerged as one of the most widely investigated biomarkers of oxidative damage in hematologic cancers. This review summarizes current evidence regarding the role of malondialdehyde across major hematological malignancies, including acute and chronic myeloid leukemias, Philadelphia-negative myeloproliferative neoplasms, lymphomas, and multiple myeloma. Available evidence consistently demonstrates significantly elevated MDA levels across major hematological malignancies, including acute and chronic myeloid leukemias, Philadelphia-negative myeloproliferative neoplasms, lymphomas, and multiple myeloma. Increased MDA concentrations are frequently associated with disease activity, relapse, impaired antioxidant defenses, thrombotic complications, treatment resistance, and therapy-related toxicity. Furthermore, experimental studies indicate that MDA accumulation closely parallels ferroptosis induction and may serve as a pharmacodynamic marker of lipid peroxide-mediated cell death. Overall, the reviewed literature identifies MDA as one of the most consistent biomarkers of oxidative stress and lipid peroxidation in hematological cancers. Although methodological standardization remains necessary, MDA appears to have potential diagnostic, prognostic, and therapeutic relevance and may contribute to identifying redox vulnerabilities that can be exploited by emerging ferroptosis-based treatment strategies. Full article

Background/Objectives: Fluorescence in situ hybridization (FISH) is an established component of the diagnostic and prognostic workup of hematologic malignancies. However, most evidence supporting FISH interpretation originates from treatment-naïve diagnostic cohorts, providing limited insight into how cytogenetic findings evolve during longitudinal disease monitoring and therapeutic exposure. We retrospectively analyzed 1357 consecutive FISH assays performed in 1092 patients with hematologic malignancies between 2019 and 2023. Methods: Multivariable logistic regression identified predictors of aberration detection, while longitudinal analyses explored temporal changes in cytogenetic profiles among serially monitored patients. Observed abnormality rates were compared with published diagnostic benchmarks. Results: The cohort had a median age of 68 years and was predominantly composed of patients with myelodysplastic/myeloproliferative neoplasms (27.2%), multiple myeloma (26.9%), and chronic lymphocytic leukemia (21.6%). Overall, 29.2% of informative assays revealed cytogenetic abnormalities. Clinical indication was the strongest predictor of aberration detection. Compared with diagnostic samples, follow-up specimens showed significantly lower odds of abnormal findings (adjusted OR 0.48, 95% CI 0.36–0.64; p < 0.001), whereas relapse samples demonstrated higher odds (adjusted OR 1.82, 95% CI 1.28–2.59; p = 0.001). Increasing age was independently associated with abnormal FISH results (adjusted OR per decade 1.24, 95% CI 1.12–1.38; p < 0.001). Several canonical abnormalities occurred less frequently than expected from historical diagnostic series, including BCR::ABL1 within the chronic myeloid leukemia testing pathway and del(13q14) in both chronic lymphocytic leukemia and multiple myeloma. In contrast, del(17p), involving the TP53 locus, remained consistently represented across disease categories and was enriched in chronic lymphocytic leukemia relative to published diagnostic cohorts. Conclusions: Longitudinal assessment revealed increasing cytogenetic heterogeneity over time, with common lesions progressively declining and rare or complex abnormalities expanding from 16.3% to 36.7% of the observed cytogenetic landscape. The cytogenetic patterns detected by FISH in contemporary hematology practice are strongly associated with clinical context, disease stage, and treatment history; however, the cross-sectional and retrospective design precludes inference of causal influence. The divergence between real-world positivity rates and historical diagnostic benchmarks highlights the need for context-specific interpretation of cytogenetic findings. The persistence of TP53 loss across disease boundaries and the progressive diversification of aberrations over time underscore the dynamic nature of clonal evolution in hematologic malignancies. Full article

Hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndromes, lymphoma, and multiple myeloma, are characterized by profound biological heterogeneity and highly dynamic treatment trajectories that conventional, static prognostic systems incompletely capture. Cellular therapies, such as chimeric antigen receptor T-cell therapy and hematopoietic stem cell transplantation, offer potentially curative options for relapsed or refractory disease, yet outcomes remain highly variable, and management decisions regarding conditioning intensity, lymphodepletion, immunosuppression, and toxicity surveillance continue to be largely protocol-driven rather than individually adapted. Artificial intelligence (AI) and machine learning (ML) have demonstrated substantial promise in diagnostic support, prognostic stratification, and multimodal data integration across hematologic malignancies, but existing models remain predominantly static and related to pre-treatment in orientation, limiting their utility for real-time clinical guidance. This review summarizes current AI applications in hematologic oncology; critically compares the strengths, limitations, and clinical applicability of major AI model classes, including traditional machine learning, deep learning, multimodal integrative frameworks, reinforcement learning, digital twins, and emerging foundation models and large language models; and proposes an adaptive, multimodal paradigm. We examine key enabling technologies and address the clinical, regulatory, ethical, and implementation challenges that must be resolved before these systems can be deployed at the bedside. We argue that the central challenge facing the field is no longer whether AI can predict outcomes, but whether it can actively guide real-time therapeutic decisions, and that achieving this transition will require interdisciplinary collaboration, prospective validation, and governance frameworks capable of ensuring interpretability, equity, and clinical trustworthiness. Full article

Background/Objectives: Therapeutic leukapheresis is widely used to manage hyperleukocytosis in hematologic malignancies, yet the factors determining its efficacy remain incompletely defined. We aimed to identify clinical, biochemical, and procedural determinants of leukapheresis efficacy in a single-center cohort. Methods: We retrospectively analyzed 125 leukapheresis procedures performed in adult patients with hematologic malignancies between March 2012 and June 2026. At our institution, emergency leukapheresis is performed before the initiation of cytoreductive therapy, so all first procedures were treatment-naïve (repeat procedures could follow cytoreductive therapy). The primary endpoint was the white blood cell (WBC) reduction rate (%). Secondary endpoints were ≥30% and ≥50% reduction. Predictors of reduction were identified using univariate tests and multivariable regression, with within-patient correlation accounted for using cluster-robust standard errors, and pre- versus post-procedure biochemical changes were assessed for paired samples. Results: The median WBC reduction was 47.9%; ≥30% and ≥50% reduction were achieved in 75% and 42% of procedures, respectively. Reduction differed significantly by diagnosis (p < 0.001), being highest in ALL (57.4%) and lowest in CML (18.6%). In multivariable analysis, processed volume (β = 0.004, p < 0.001), inlet rate (β = −0.43, p < 0.001), acute leukemia (β = 10.4, p = 0.040), and baseline platelet count (β = −0.03, p = 0.036) were independent predictors. Leukapheresis significantly reduced LDH and uric acid levels (both p < 0.001). Conclusions: Leukapheresis efficacy is determined by disease subtype and modifiable procedural parameters. Higher processed volume and acute leukemia diagnosis were associated with greater WBC reduction, while CML blast crisis responds poorly. These findings support procedure optimization to maximize cytoreduction. Full article

Background/Objectives: Preeclampsia is a heterogeneous hypertensive disorder of pregnancy, and accessible hematologic indices may reflect maternal physiologic differences before the clinical syndrome becomes evident. This study evaluated whether the first-trimester hemoglobin-to-red cell distribution width (Hb/RDW) ratio was associated with later documented preeclampsia and assessed its discrimination, relation to disease severity, and association with maternal–neonatal outcomes in a tertiary-care cohort. Methods: This retrospective cohort study included 224 singleton pregnancies managed at a tertiary referral center between January 2024 and December 2025. Data extraction, anonymization, and analysis were performed after ethics approval (Approval No. 72; 2 March 2026). Participants were categorized as preeclampsia-negative (n = 131) or preeclampsia-positive (n = 93). Preeclampsia and severe features were defined according to American College of Obstetricians and Gynecologists criteria. The Hb/RDW ratio was calculated from routine first-trimester complete blood count parameters obtained before clinical diagnosis or final outcome classification. ROC analysis, multivariable logistic regression, multicollinearity assessment, events-per-variable evaluation, calibration testing, and exploratory incremental discrimination analyses were performed. Results: The first-trimester Hb/RDW ratio was higher in pregnancies later complicated by preeclampsia. Single-marker ROC analysis showed moderate discrimination (AUC = 0.687; bootstrap 95% CI: 0.618–0.755). At the 0.63 cut-off, sensitivity was 89.2%, specificity 47.3%, positive predictive value 54.6%, and negative predictive value 86.1%. In the primary multivariable model, Hb/RDW remained associated with later preeclampsia (adjusted OR per 0.1-unit increase = 1.45; 95% CI: 1.22–1.72; p < 0.001). However, Hb/RDW was not independently associated with severe preeclampsia among affected patients, fetal growth restriction, or composite maternal morbidity. VIF values ranged from 1.00 to 1.07. Secondary models for fetal growth restriction and composite maternal morbidity had borderline events-per-variable values and were interpreted as exploratory. Conclusions: First-trimester Hb/RDW was associated with later documented preeclampsia in this retrospective tertiary-care cohort, but its single-marker performance was modest and specificity was limited. The ratio should be interpreted as an inexpensive research marker of hematologic phenotype rather than a stand-alone screening, diagnostic, or management tool. Prospective multicenter validation with standardized first-trimester sampling and adjustment for hematinic and nutritional variables is required before clinical implementation. Full article

Acute myeloid leukemia (AML) harboring KMT2A rearrangements (KMT2A-r) accounts for approximately 5–10% of newly diagnosed cases and represents a high-risk AML subtype associated with poor clinical outcomes despite intensive treatment strategies, including allogeneic hematopoietic stem cell transplantation (HSCT). KMT2A-r AML is also characterized by a higher incidence of extramedullary disease compared with other AML subtypes. Therapeutic options for patients with relapsed/refractory (R/R) disease, particularly after post-HSCT relapse, remain extremely limited. In recent years, menin inhibitors have emerged as a promising targeted therapeutic class for KMT2A-r and NPM1-mutated AML by disrupting the aberrant HOX/MEIS1 transcriptional program. Revumenib, a first-in-class menin inhibitor, has shown encouraging efficacy in early-phase clinical trials. Other menin inhibitors, including ziftomenib, bleximenib, and enzomenib, have also demonstrated clinical activity, with distinct pharmacokinetic, pharmacodynamic, and safety profiles. We report the case of a 36-year-old patient with KMT2A-r AML who relapsed after HSCT with both bone marrow and hepatic involvement. Compassionate-use treatment with revumenib (160 mg twice daily on days 1–28 of each 28-day cycle) induced, after two treatment cycles, complete hematologic remission with no detectable abnormal myeloid blast population by multiparameter flow cytometry (MFC) and complete radiological resolution of hepatic lesions. However, despite prior intrathecal CNS-directed therapy and sustained systemic disease control, the patient subsequently developed an isolated central nervous system (CNS) relapse. This case highlights a potential discordance between systemic and CNS disease control during menin inhibitor therapy and emphasizes the need for further investigation into CNS surveillance and disease management in patients achieving deep systemic responses. Full article

Background: Balkan nephropathy (BEN), caused by chronic dietary exposure to aristolochic acid (AA), is a tubulointerstitial kidney disease strongly associated with upper-tract urothelial carcinoma (UTUC). Patient and graft survival, the cumulative incidence and timing of post-transplant UTUC, and the burden of non-urothelial malignancy after kidney transplantation remain poorly defined. Methods: We retrospectively analyzed all patients with BEN as the primary cause of end-stage kidney disease transplanted at University Hospital Center Zagreb between October 1973 and December 2023. Outcomes included patient and graft survival, the incidence and timing of post-transplant UTUC, and burden of non-urothelial malignancies. Results: Of 2282 kidney transplants performed in the study period, 44 (2%) were in patients with BEN. The median age at transplantation was 56 years, and the median dialysis vintage was 3.7 years. After 10 years (median) of follow up, among 34 patients with adequate follow-up, 16 (47%) developed a de novo malignancy: eight (24%) UTUC, one renal cell carcinoma, four other solid tumors, and three hematological. UTUC was diagnosed between 6 months and 15 years post-transplant (median 7 years); five of eight patients died within one year of diagnosis. Five- and ten-year patient survival rates were 82% and 54.5%. Conclusions: Kidney transplantation in patients with BEN carries a lifelong cancer risk dominated by UTUC. Prophylactic bilateral nephroureterectomy should be the default management strategy when feasible, with lifelong surveillance extending beyond the urothelium. Full article

Chemotherapy-induced immune dysregulation remains a major challenge in patients with advanced solid tumors. β-Glucan has been reported to possess immunomodulatory properties; however, its longitudinal effects on immune homeostasis during chemotherapy remain unclear. In this prospective, randomized phase II study, patients receiving chemotherapy were assigned to receive β-glucan powder (with L-glutamine and bioactive protein from bovine colostrum), β-glucan capsules (with L-glutamine), or standard care. Clinical outcomes, serial hematologic parameters, longitudinal immune profiling, and an in vitro Jurkat T-cell viability assay were evaluated. Compared with controls, β-glucan supplementation improved the disease control rate, accelerated neutrophil recovery, and maintained a more stable neutrophil-to-lymphocyte ratio during chemotherapy. Longitudinal immune profiling demonstrated greater stability of T-cell, NK-cell, NKT-cell, and KIR (CD158)-expressing immune-cell populations in β-glucan supplementation groups, suggesting attenuation of chemotherapy-induced immune remodeling. Both β-glucan formulations showed comparable immunomodulatory effects, although the expression of CD158b(+) and CD158i(+) NK-cell subsets remained more stable in the powder group during later treatment. In vitro, β-glucan significantly reduced Jurkat T-cell viability, indicating direct biological activity in addition to its clinical immunomodulatory effects. These findings suggest that β-glucan supplementation helps preserve immune homeostasis during chemotherapy and may serve as a promising adjunctive immunonutritional strategy for patients with advanced solid tumors. Full article

Background: Cytomegalovirus (CMV) reactivation and graft-versus-host disease (GVHD) are major causes of morbidity and non-relapse mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although their association has been extensively investigated, the temporal relationship between these complications and their impact on survival remain incompletely understood, particularly in centers where routine letermovir prophylaxis is unavailable and CMV is managed using a pre-emptive treatment strategy. This study evaluated the bidirectional temporal association between CMV reactivation and GVHD using time-dependent analyses and assessed their impact on survival in a real-world allo-HSCT cohort. Methods: We retrospectively analyzed 100 consecutive adult patients who underwent allo-HSCT for hematologic malignancies between January 2016 and February 2025. CMV surveillance was performed by weekly quantitative CMV-DNA PCR, and reactivation was managed using a standardized pre-emptive treatment strategy. Patients who relapsed or died within the first 100 days after transplantation were excluded. The incidence, temporal sequence, risk factors, and prognostic impact of CMV reactivation and GVHD were evaluated. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan–Meier method, while temporal associations were assessed using time-dependent Cox regression analyses. Results: CMV reactivation occurred in 72 patients (72%), whereas GVHD developed in 51 patients (51%). Among patients who experienced both complications, CMV reactivation preceded GVHD in 32 patients, while GVHD preceded CMV reactivation in 14 patients. Older recipient age (42.3 ± 13.5 vs. 35.4 ± 11.2 years, p = 0.018) and older donor age (37.2 ± 10.9 vs. 32.5 ± 9.7 years, p = 0.048) were associated with CMV reactivation. Older donor age was also associated with GVHD development (38.1 ± 10.7 vs. 33.6 ± 10.5 years, p = 0.037). The median time to CMV reactivation was 37 days, and CMV end-organ disease occurred in 13.9% of affected patients. No significant differences in OS or RFS were observed according to CMV reactivation or GVHD status in the day-100 landmark cohort. In the AML subgroup, both CMV reactivation and GVHD showed a trend toward inferior OS and RFS without reaching statistical significance. Time-dependent Cox regression demonstrated that CMV reactivation independently increased the subsequent risk of GVHD (HR 2.93, 95% CI 1.51–5.69; p = 0.001), whereas GVHD also independently increased the subsequent risk of CMV reactivation (HR 1.98, 95% CI 1.06–3.71; p = 0.032). Conclusions: CMV reactivation was highly prevalent after allo-HSCT and frequently preceded GVHD, supporting a bidirectional temporal relationship between these complications. Older donor age was associated with both CMV reactivation and GVHD. Although survival did not significantly differ according to CMV or GVHD status in this day-100 landmark cohort, clinically important CMV-related complications, including end-organ disease and platelet engraftment failure requiring eltrombopag, remained common. These findings indicate that a standardized pre-emptive strategy did not completely prevent CMV-associated morbidity. Because letermovir was not evaluated in this cohort, any potential benefit of prophylaxis should be interpreted as an inference from external evidence rather than as a direct finding of this study. Prospective multicenter studies incorporating immune reconstitution analyses are warranted. Full article

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-associated premalignant state defined by somatic mutations in hematopoietic cells at a variant allele frequency (VAF) ≥2% in the absence of overt hematologic malignancy. Among CHIP-associated mutations, JAK2 V617F is of particular interest because it occupies a dual biological and clinical role: it is both the principal driver of BCR::ABL1-negative myeloproliferative neoplasms (MPNs) and a clonal hematopoiesis variant conferring approximately 12-fold cardiovascular risk in selected cohorts, exceeding that reported for common DTA CHIP variants. Quantitative assessment of JAK2 V617F allele burden is therefore clinically relevant across the full disease continuum—from subclinical clonal expansion to MPN diagnosis, prognostic stratification, and therapeutic monitoring—as VAF thresholds correlate with disease phenotype, thrombotic risk, molecular response, and fibrotic progression. Digital PCR platforms, including droplet digital PCR (ddPCR) and chip-based digital PCR, have emerged as highly sensitive and reproducible methods for absolute JAK2 V617F quantification without the need for standard curves, with reported limits of detection as low as 0.01%. In this review, we synthesize current evidence on the molecular biology of JAK2-driven clonal hematopoiesis, the clinical significance of allele burden quantification, and the analytical performance of digital PCR compared with quantitative PCR and next-generation sequencing. We interpret these findings through a systems biology lens that draws together JAK-STAT signaling networks and thrombo-inflammatory pathways including inflammasome-dependent IL-1 signaling, clonal architecture, and bone marrow microenvironmental remodeling. We also discuss published quantitative models in which JAK2 V617F allele burden is treated as a dynamic state variable, while emphasizing that the present review offers a conceptual synthesis rather than a new computational model. We provide a structured comparative synthesis of published digital PCR analytical performance data, a stage-adapted proposal for clinical monitoring, and schematic models to guide future implementation. Overall, the evidence supports digital PCR as a precision tool for monitoring JAK2 V617F clonal dynamics across the CHIP–MPN spectrum, and points to several priorities: assay standardization, harmonized reporting, external quality assessment, and prospective clinical validation. Full article

Babesia aktasi is a recently discovered species that is highly prevalent in native goats in Türkiye’s Mediterranean region. Although it does not induce clinical disease in local breeds, it causes severe illness in Saanen goats, manifesting with high fever, anemia, hemoglobinuria, and jaundice. Imidocarb dipropionate (IMDP) has been reported to be therapeutically effective against Babesia species. This study aimed to evaluate the therapeutic efficacy of IMDP and its ability to eliminate the parasite in experimentally infected Saanen goats. Twelve goats were assigned to treatment and control groups (n = 5 per group) and infected using fresh blood from two splenectomized donors. All goats developed clinical babesiosis, with parasitemia ranging from 3.8% to 22. Semi-nested PCR specific to B. aktasi was performed for 30 days post-treatment. Following treatment with IMDP (1.2 mg/kg), clinical signs resolved by the third and fourth days, and parasitemia became microscopically undetectable. However, one goat in the treatment group and four goats in the control group died shortly after infection. Hematological parameters (HCT, RBC, HB) decreased during infection but normalized in surviving animals. Notably, B. aktasi DNA remained detectable by PCR up to 30 days after treatment. These findings indicated that IMDP resolved clinical signs and eliminated microscopically detectable parasitemia; however, it may not completely eliminate the parasite at the molecular level in B. aktasi infections. The results of this study provide valuable information for optimizing therapeutic approaches and improving our understanding of treatment responses in new species B. aktasi. Full article

Background and Clinical Significance: Skin-limited Langerhans cell histiocytosis (LCH) is a clinically heterogeneous disease, ranging from self-healing forms to fulminant multi-organ failure, the latter being more often described in infants, especially preterm neonates. The optimal therapy for cutaneous LCH remains controversial; the possibilities vary from a watchful waiting approach to systemic chemotherapy. Case Presentation: This case report describes an exceptionally rare and clinically challenging course of skin-limited LCH in a prematurely born infant treated at the Department of Oncology and Hematology, Children’s Hospital Zagreb, Croatia. At presentation, the patient exhibited several features suggestive of aggressive disease biology. However, therapeutic decision-making was complicated by extreme prematurity and young age, both of which significantly increased vulnerability to treatment-related toxicity. Following failure of topical therapy, systemic treatment was initiated according to the LCH-IV trial, primarily due to concerns regarding potential evolution into multisystem LCH. During treatment, the patient developed multiple life-threatening complications, namely severe infections (Staphylococcus aureus endocarditis, Pneumocystis jirovecii pneumonia, and Enterobacter cloacae sepsis), aggravated by secondary hypogammaglobulinemia, neutropenia, and iatrogenic adrenal insufficiency. Conclusions: The varied nature of cutaneous LCH underscores the necessity for a tailored treatment approach. When deciding on the treatment modality, clinicians should weigh the benefits of aggressive therapies, ensuring better disease control, against the potential for severe adverse effects, particularly in young, fragile infants with immature immunity. Full article

Our study examined the impact of IL6 −174 G/C (rs1800795) and IL18 −607 C/A (rs1946518) promoter polymorphisms on susceptibility to rheumatoid arthritis (RA) and protein/mRNA levels. RA patients had significantly higher serum IL-6 and IL-18 levels than controls; healthy men had higher IL-18 than women (p < 0.001). Conversely, IL6 mRNA expression was lower in RA patients than controls (p = 0.037). No link was found between rs1800795 and RA susceptibility; however, the CC genotype was less frequent among RA patients than controls, suggesting potential protection (OR = 0.55). Also, the −174 G allele was probably associated with RF positivity (OR = 1.4). In RA patients, no significant association was detected between the −174 G/C polymorphism and either IL6 mRNA expression or circulating IL-6 levels. Among healthy individuals, carriers of the GG genotype showed higher IL6 mRNA expression (p = 0.024). No association was observed between rs1946518 and RA risk or clinical features, or between systemic IL18 mRNA, IL-18 levels, and rs1946518 genotypes in RA patients. In summary, rs1800795 showed borderline association with disease risk and autoantibody presence, whereas rs1946518 was not associated with RA susceptibility, cytokine levels, or key clinical characteristics in our cohort. Full article