Search Results (609)

Background/Objectives: Chronic recurrent multifocal osteomyelitis/chronic nonbacterial osteomyelitis (CRMO/CNO) is an auto-inflammatory bone disease for which optimal treatment and imaging-based monitoring remain incompletely defined. Methods: We conducted a single-center retrospective review of nine pediatric patients with CRMO/CNO treated with tumor necrosis factor inhibitors (TNFis). Clinical improvement was assessed using Visual Analog Scale (VAS) pain scores, erythrocyte sedimentation rate (ESR), and physical examination findings. Radiographic assessment used longitudinal, site-specific magnetic resonance imaging (MRI) scored with a simplified approach adapted from the Chronic Nonbacterial Osteomyelitis Magnetic Resonance Imaging Scoring (CROMRIS) system. Results: Our cohort was composed of six females and three males with a median age of seven years. TNFi monotherapy was initiated as a first-line therapy (n = 4) or step-up (n = 5). During a median follow-up time of 26 months, treatment was tolerated well, except for the emergence of psoriasis in three patients (n = 3), among whom one necessitated treatment change. Eight patients on TNFis achieved clinical remission, including five with complete resolution of MRI lesions. Conclusions: In this small, single-center case series, TNFi monotherapy was associated with sustained disease control, as reflected by clinical improvement and MRI-documented lesion resolution. These findings emphasize the need for validation of our observations in larger multi-center cohorts. Full article

Background/Objectives: The prognostic and predictive values of biomarkers in fertility-sparing management of atypical hyperplasia (AH) and endometrial cancer (EC) remain ill-defined. We aimed to identify the impact of tumour profiles on oncologic and reproductive outcomes to inform clinical decision-making. Methods: We conducted a systematic review and meta-analysis by searching MEDLINE, PubMed, Embase, Cochrane Library, Scopus, Google Scholar, and ClinicalTrials.gov, up to July 2026. We intended to include comparative studies or clinical trials, in English or French, assessing outcomes according to molecular or hormonal profiles in reproductive-aged women diagnosed with AH or EC. The primary outcome was the best overall complete remission (CR). Pooled odds ratios (ORs) were calculated using a random-effects model with logit transformation and restricted maximum likelihood estimation. Risk of bias was assessed using the Newcastle–Ottawa scale (NOS). The study protocol was registered in PROSPERO (CRD42025632885). Results: Eighteen retrospective studies comprising 965 patients were included. No specific molecular profile (NSMP) tumours demonstrated significantly higher odds of CR (OR 2.04, 95% CI 1.33–3.11). p53-abnormal (p53abn) and deficient mismatch repair (dMMR) tumours were significantly less likely to achieve CR compared to NSMP (OR 3.87, 95% CI 1.80–8.29 and OR 2.48, 95% CI 1.44–4.29, respectively). POLE-mutated (POLEmut) tumours showed CR comparable to NSMP (OR 1.39, 95% CI 0.60–3.24). Progesterone receptor (PR) positivity was strongly associated with CR (OR 7.73, 95% CI 2.77–21.63). Conclusions: NSMP and PR-positivity represented a favourable prognosis and potential prediction of CR. POLEmut tumours demonstrated CR rates comparable to NSMP, whereas p53abn and dMMR demonstrated unfavourable outcomes. These findings support a biologically tailored approach to patient selection for fertility-sparing management. Full article

A 14-year-old neutered male domestic shorthair cat was evaluated for long-standing, non-pruritic, crusty skin lesions on the pinnae, neck, and ventral abdomen that had persisted for at least 4 years. The histopathological examination of biopsies from the neck and abdomen revealed multicentric squamous cell carcinoma in situ confined to the epidermis. Papillomavirus diagnostics on ear crusts using PCR, rolling circle amplification (RCA), and next-generation sequencing (NGS) identified coinfection with Felis catus papillomavirus type 7 (FcPV7) and a putative novel feline papillomavirus type. This is the first reported case of multicentric carcinoma in situ with coinfection by these two papillomaviruses. The condition was successfully managed medically with topical imiquimod cream applied twice weekly for 3 months, resulting in complete clinical remission. Over 1.5 years of follow-up, they remained well. Two mild recurrences on the dorsal neck were effectively controlled with a short repeat course of imiquimod. This case report documents coinfection with different feline papillomavirus types in a cat and highlights an efficacious, practical, non-surgical treatment with the topical immunomodulatory imiquimod cream. Full article

Background/Objectives: To determine treatment-free probability after persistent low-level human chorionic gonadotropin (hCG) elevation following complete remission from gestational trophoblastic neoplasia (GTN) and examine its association with the early hCG course. Methods: This single-center retrospective study included patients treated in 2015–2022 for gestational choriocarcinoma or invasive mole who developed ≥3 post-remission hCG results >5 and ≤1000 U/L over ≥14 days. The primary endpoint was retreatment for GTN recurrence. Kaplan–Meier analysis estimated treatment-free probability from the first low-level hCG elevation. Exploratory landmark analyses at 60, 90, and 180 days stratified patients still under observation by pre-landmark peak hCG (≤20 versus >20 U/L). Results: Forty-six patients contributed 595 hCG measurements. Thirty-five developed recurrence requiring retreatment; 11 remained recurrence-free. All patients whose first low-level hCG exceeded 20 U/L (n = 11) developed recurrence. Treatment-free probability was 30.4% at 1 year and 24.2% at 2 years. At the 60-, 90-, and 180-day landmarks, 365-day treatment-free probability was higher with pre-landmark peak hCG ≤ 20 U/L than >20 U/L: 68.4% versus 9.1%, 70.6% versus 22.2%, and 92.3% versus 14.3%, respectively. All 35 retreated patients achieved hCG ≤ 5 U/L after treatment. Conclusions: Most patients with persistent low-level hCG after remission from GTN developed recurrence. For patients still under observation at 60, 90, or 180 days, a peak hCG of 20 U/L or lower before the landmark was associated with higher treatment-free probability over the following year. Continued surveillance after clinical and imaging assessment is reasonable in this subgroup. Full article

Background: Liver transplantation is the standard treatment for children with advanced hepato-blastoma when complete resection is not feasible. However, transplantation may be contraindicated because of persistent metastatic disease, severe comorbidities, poor clinical condition, or donor-related limitations. Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) has emerged as a potential rescue strategy in highly selected patients. This study evaluated the feasibility, safety, and oncological outcomes of ALPPS in pediatric hepatoblastoma. Methods: A retrospective analysis was performed of four consecutive children with advanced hepatoblastoma who underwent classical ALPPS between 2013 and 2025 in two specialized centers. Patient characteristics, indications, future liver remnant (FLR) volumetry, perioperative outcomes, complications, and oncological follow-up were reviewed. Results: The median age at surgery was 22 months. In all patients, the FLR was considered insufficient for one-stage hepatectomy, leading to ALPPS. Rapid hypertrophy of the FLR was achieved in every case, allowing completion of the second stage after a median of 8.5 days (range, 7–11 days). FLR volume increased by 50–89% following the first stage. Despite successful liver hypertrophy, outcomes remained poor in three patients. One patient died intraoperatively from venous air embolism during the second stage, two died from disease recurrence despite aggressive multimodal treatment, and one remains in complete clinical and radiological remission following ALPPS and adjuvant chemotherapy. Conclusions: ALPPS reliably induces rapid FLR hypertrophy and may provide a potentially curative option for carefully selected children when liver transplantation is not feasible. However, its substantial perioperative risk and generally unfavorable oncological outcomes support its role only as a rescue procedure in experienced pediatric hepatobiliary centers. Further multicenter studies are needed to better define indications and patient selection. Full article

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and is characterized by pronounced molecular heterogeneity that is not always fully captured by standard histopathological assessment. Circulating tumor DNA (ctDNA) is increasingly regarded as a promising liquid-biopsy biomarker that enables non-invasive molecular tumor profiling, assessment of tumor burden, dynamic monitoring of treatment response, and detection of measurable/minimal residual disease (MRD). Modern analytical platforms, ranging from PCR-based assays to next-generation sequencing approaches, including CAPP-Seq and PhasED-Seq, have substantially expanded the possibilities of molecular monitoring in DLBCL. This review summarizes current data on the biological characteristics of ctDNA, contemporary methods for its analysis, concordance between ctDNA and tumor-tissue mutational profiles, and the clinical significance of baseline ctDNA levels, early molecular response, post-treatment MRD status, and molecular surveillance during remission. Special attention is given to ctDNA monitoring in patients receiving novel immunotherapies, including CAR-T cell therapy, bispecific antibodies, and antibody–drug conjugates. Emerging multi-omic approaches integrating genomic, epigenomic, and fragmentomic data are discussed as promising future directions. Key limitations of clinical implementation include insufficient standardization of preanalytical and analytical workflows, the confounding effect of clonal hematopoiesis of indeterminate potential, variability across technological platforms, and the lack of completed prospective randomized interventional studies demonstrating improved outcomes when therapy is modified according to ctDNA status. Overall, ctDNA is currently a highly informative prognostic biomarker in DLBCL; however, its full implementation as a predictive tool for treatment selection requires further harmonization, prospective validation, and confirmation in interventional clinical trials. Full article

Background: The global prevalence of anxiety and internalizing disorders in adolescence has increased epidemiologically over the past decade, compounded by the impact of the COVID-19 pandemic and the expansion of digital social networks. Despite the availability of empirically based interventions, their systematic implementation in Spanish educational settings—especially in socioeconomically vulnerable environments—remains insufficient. This study aimed to assess the emotional symptomatology profile in a sample of adolescents enrolled in the 2nd year of Compulsory Secondary Education (CSE) and to describe the changes in symptomatology observed after implementation of a multicomponent intervention program in an ordinary school setting. Methods: a quasi-experimental single-group repeated-measures design was used, with pretest–posttest measurements (T1–T2). The sample included 79 participants (age in completed years: M = 13.28 years, SD = 0.64; range: 12–15; 49.4% female, 44.3% male, 6.3% undisclosed), selected by convenience at IES Estuaria (Huelva). The assessment instrument was the Revised Child Anxiety and Depression Scale (RCADS-47), which measures total anxiety, total internalization, and six clinical subdimensions aligned with DSM-5: generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD), separation anxiety (SA), social phobia (SP), and obsessive–compulsive disorder (OCD). The intervention consisted of five multicomponent group workshops (45 min/session; three class groups) integrating emotional psychoeducation, receptive music therapy, cognitive–behavioral emotional regulation, assertive communication, and body expression/mindfulness. Results: At pretest, Social Phobia (SP) showed the highest clinical impairment, significantly affecting more females (66.67%) than males (20.00%). Generalized Anxiety Disorder (GAD) also presented high impairment in females. Significant correlations between pairs of subdimensions revealed a high comorbidity pattern. Following the intervention, reductions in clinically significant levels were observed across all dimensions. Matched-pairs Wilcoxon signed-rank tests confirmed statistically significant score reductions from T1 to T2 in Total Anxiety, Total Internalization, Social Phobia, and Generalized Anxiety Disorder (all p < 0.05), with the largest effect for Social Phobia (r = 0.46); no significant change was detected for Panic Disorder, Separation Anxiety, Major Depressive Disorder, or Obsessive–Compulsive Disorder, although the direction of change favored improvement in all cases. Conclusions: The multicomponent intervention program produced improvements in emotional symptomatology over the short-term follow-up period, although without achieving complete clinical remission in any subdimension. The persistent sex differences—with greater residual impairment in the female group after intervention—underscore the need to incorporate a gender perspective in the design of school emotional health programs. High comorbidity rates between subdimensions support the utility of transdiagnostic approaches. Implications for school nursing practice and future research are discussed. Full article

Background and Clinical Significance: Intravascular large B-cell lymphoma (IVLBCL) is an exceedingly rare and aggressive malignancy characterized by the selective growth of lymphoma cells within blood vessel lumina. This malignancy often presents with non-specific systemic manifestations, making diagnosis challenging. Neurological symptoms and cutaneous findings are typical, whereas thrombotic events are uncommon at the initial presentation. We report a unique case of IVLBCL with MYC and BCL2 rearrangements (“double-hit” genetics), diagnosed following mechanical thrombectomy; Case Presentation: A 79-year-old woman presented with acute right-lower-limb swelling due to extensive iliofemoral deep vein thrombosis. Mechanical thrombectomy was performed, and the histopathological and genetic examination of the retrieved material revealed IVLBCL. Subsequent staging with positron emission tomography-computed tomography (PET-CT) demonstrated an FDG-avid tumor thrombus confined to the right internal iliac vein, without any lymphadenopathy or solid tumor mass. The patient was successfully treated with a combination of systemic chemoimmunotherapy and targeted radiotherapy and remained in complete remission for more than four years after diagnosis; Conclusions: We report a potentially unique case of double-hit IVLBCL diagnosed using endovascular thrombectomy. This underscores the therapeutic and diagnostic potential of mechanical thrombectomy systems in the detection of intravascular malignancies and the critical importance of the routine histopathological examination of all thrombectomy specimens. Despite negative thrombolysis data from the ATTRACT and CAVA trials, mechanical thrombectomy may improve venous hemodynamics and may reduce post-thrombotic syndrome (PTS) in pelvic thrombosis. Here, mechanical thrombectomy followed by right iliac vein stenting achieved excellent technical and clinical outcomes. Full article

Background: Anxiety disorders are prevalent and debilitating. Given challenges in maintaining mindfulness at one-month remission, integrative approaches targeting anxiety and psychological resources (especially mindfulness) have gained interest. This study aimed to assess the effectiveness of adding biofeedback to the treatment of anxiety disorders. Methods: Inpatients with anxiety disorder (ICD10 F40/F41) were randomized to three groups: (1) biofeedback for enhancing mindfulness (BFB, n = 76); (2) medication therapy (MT, escitalopram 10 mg/day, n = 46); and (3) combined therapy (BFB + MT, CT, n = 66). Per-protocol analysis: 180 completers; ITT: all 188 randomized patients. The primary outcomes were changes in the Hamilton Anxiety Rating Scale (HAM-A) total score and the Five Facet Mindfulness Questionnaire total score, assessed at baseline, after 10 days of treatment, and at one-month follow-up. The HAM-A assessor was blinded to group allocation. Results: In the per-protocol analysis, the BFB and CT groups showed a significantly greater reduction in the HAM-A score than the MT group did. For example, post-treatment, the mean difference between BFB and MT groups was –6.30 points (95% CI: –9.12 to –3.48, p = 0.00046). The BFB and CT groups did not differ significantly. For mindfulness, the BFB and CT groups showed an increase, whereas the MT group showed a decrease (BFB vs. MT: mean difference 30.28 points, 95% CI: 23.54–37.02, p < 0.000001). Intention-to-treat (ITT) analysis (n = 188) confirmed the robustness of these findings. Conclusions: BFB appears to be a promising approach for reducing anxiety and fostering mindfulness skills; these findings suggest it may be worth exploring further as a potential component of comprehensive therapy for anxiety disorders. Clinical Trial Registration: ClinicalTrials.gov NCT07628153 (retrospectively registered). The trial was retrospectively registered, and the primary analysis was conducted on a per-protocol population. Full article

Background: Mesenteric panniculitis (MP) is a chronic fibroinflammatory disorder of the mesenteric adipose tissue and is frequently considered an idiopathic condition. Its association with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), remains poorly characterized, with only limited evidence available in the literature. In addition to presenting a clinical case, we performed a narrative review of the literature regarding the relationship between MP and IBD, including epidemiology, pathophysiological mechanisms, diagnostic challenges, and therapeutic approaches. Case Presentation: We report the case of a 32-year-old woman with UC in deep clinical, endoscopic, and histological remission while receiving vedolizumab therapy, who developed symptomatic MP diagnosed by contrast-enhanced computed tomography. Infectious, neoplastic, and selected fibroinflammatory causes were excluded during the diagnostic work-up. Histological confirmation was not obtained. The patient was treated with prednisone and tamoxifen, resulting in complete clinical and radiological remission while vedolizumab therapy was continued. Conclusions: This case describes the rare co-occurrence of MP and UC in deep remission during ongoing vedolizumab treatment. Given the absence of histological confirmation and the frequently idiopathic nature of MP, a causal relationship with either UC activity or vedolizumab therapy cannot be established. The observation should therefore be regarded as hypothesis-generating. Further studies are required to clarify the potential relationship between MP, IBD, and biologic therapies. Full article

Natural killer cell large granular lymphocytic leukemia (NK-LGLL) is a rare and heterogenous lymphoproliferative disorder. This study retrospectively evaluated 35 consecutive Chinese patients (median age 58 years) to evaluate their unique clinical–biological profiles and treatment responses. Our Chinese population exhibited a distinct comorbidity spectrum, characterized by a lower prevalence of concurrent arthritis (2.9%) and secondary malignancies, compared with Western cohorts. At diagnosis, 31.4% of the cohort had neutropenia, 42.9% had anemia, and 31.4% had thrombocytopenia. The median large granular lymphocyte count was 3.9 × 10⁹/L (range 0.11–114.8 × 10⁹/L; IQR 1.9 × 10⁹/L, 5.9 × 10⁹/L). Immunophenotyping consistently identified as a CD3- CD56+ clone. Notably, genomic profiling via NGS revealed a STAT3 mutation rate of 14.3%. Regarding therapeutic efficacy, frontline immunosuppressive therapy with cyclophosphamide or cyclosporine was associated with favorable clinical responses (best overall response, complete remission rate 66.7% for both). Additionally, sirolimus emerged as a potentially highly effective salvage option, yielding an overall response rate of 85.7% (95%CI 42.1–99.6%) and complete remission rate of 57.1%. With an estimated 3-year overall survival rate of 85.6% (95%CI 73.3%, 99.8%), our findings suggest a generally indolent clinical course of NK-LGLL in this Chinese cohort and highlight the potential of mTOR inhibition in refractory cases, warranting further prospective investigation. Full article

Background: Chronic inflammatory bowel diseases (IBDs), specifically Crohn’s disease and ulcerative colitis, present substantial clinical challenges characterized by a relapsing-remitting course. These conditions often lead to serious complications and significantly impair nutritional status, physical development, and overall quality of life. Methods: This unicentric, prospective, open-label, alternation-based comparative study investigated the efficacy of vitamin D₃ supplementation in adolescents with IBD. Patients aged 15–25 years were randomly assigned to receive either 1000 IU/day or 2000 IU/day of cholecalciferol for 6 months as an adjuvant to standard care. Eighty patients completed the study. Results: By month 6, remission was achieved in 52.5% of patients receiving 1000 IU/day (Group A) and 87.5% of those receiving 2000 IU/day (Group B). Significant differences were observed between groups regarding disease activity (p = 0.007), C-reactive protein levels (30.17 ± 15.74 mg/L vs. 62.82 ± 37.14 mg/L; p < 0.001), and fecal calprotectin levels. Conclusions: The machine learning models demonstrated consistent performance in assessing inflammatory indicators, with a weighted average recall exceeding 72% (Random Forest: 82.50%). No adverse effects were reported. Supplementation with 2000 IU/day of vitamin D₃ for 6 months was associated with more favorable clinical and biochemical outcomes than 1000 IU/day in this single-center open-label study as an adjunct to standard treatment in adolescents and young adults with IBD. The results suggest that higher doses of vitamin D may be beneficial in achieving remission and reducing systemic inflammation. Full article

Introduction: Delayed initiation of mepolizumab may influence long-term disease control and the achievement of clinical and functional outcomes in patients with uncontrolled severe asthma (SUA), but no definitive conclusions have yet been established regarding the optimal timing for biologic initiation. The aim of this study was to evaluate, in a real-world clinical setting, the effect of delayed mepolizumab initiation—from the moment patients first met EMA eligibility criteria—on the treatment response (using the EXACTO scale), clinical remission (according to SEPAR-REMAS criteria) and lung function at 12 months and 3 years after treatment initiation. Material and Methods: We conducted a retrospective observational cohort study including 148 patients with SUA treated with mepolizumab from January 2017 to November 2024 in our hospital. Patients were stratified into tertiles according to delay: ≤5 months, 6–19 months, and >19 months. Baseline demographic, clinical, and lung function characteristics were analyzed. Results: Patients with shorter delay exhibited distinct significance baseline profiles, including higher eosinophil counts, lower BMI and current smoker, and better pre-treatment lung function (p < 0.05). Shorter delay was significantly associated with higher rates of good/complete response according to the EXACTO scale at both 12 months and 3 years (p < 0.05). Clinical remission rates were numerically higher in the early-treatment group, although differences did not reach statistical significance. No significant differences in lung function outcomes were observed between delay groups at either 12 months or 3 years. Conclusions: In conclusion, earlier initiation of mepolizumab after meeting EMA criteria is associated with improved clinical response, although it does not significantly influence remission rates or lung function recovery. These findings underscore the importance of timely treatment initiation and reinforce the relevance of accurate phenotypic and endotypic characterization to optimize biologic selection in SUA. Full article

The treatment of chronic lymphocytic leukemia (CLL) has shifted from chemoimmunotherapy to targeted therapy, resulting in improved outcomes and patient survival. The aim of this study was to evaluate the efficacy and safety of venetoclax-based regimens in patients with relapsed/refractory CLL, as well as their effectiveness in patients previously treated with ibrutinib. We retrospectively analyzed 98 patients with CLL who received venetoclax in the second or later lines of therapy in Slovakia between 2018 and 2024. The median age was 68 years, and treatment was administered either as monotherapy or in combination with rituximab. Response to treatment was assessed according to the iwCLL 2018 criteria and clinical practice. Patients who achieved complete hematologic and clinical remission but did not undergo confirmatory bone marrow examination were classified as having unconfirmed complete remission (uCR). An overall response was achieved in the majority of patients (in 99%), with 2% achieving complete remission, 65% incomplete complete remission and 32% partial remission. At a median follow-up of 34 months, median overall survival was not reached (mean 52.5 months), and median progression-free survival was 45 months. Survival outcomes were evaluated using Kaplan–Meier analysis. Patients previously treated with ibrutinib had significantly worse outcomes (p = 0.022). Adverse events were predominantly hematological (64%), with 19% being grade 3–4. In line with the conclusions of clinical trials and retrospective analysis from real-life practice, we can say that venetoclax-based treatment regimens are highly effective in patients with CLL in higher lines of treatment, with acceptable and well-manageable toxicity. Full article

Anorexia nervosa (AN) in adolescence is associated with substantial morbidity and complex family processes. Family-based approaches are the best-established psychosocial treatments, but remission rates remain modest and broader family and emotional processes are often only partly addressed. This case series describes the development and preliminary evaluation of a behavior-analytic family intervention combining parent-led refeeding with structured work on parental socioemotional and educational skills. Eight families were screened, five entered treatment, and four completed a 20-session outpatient protocol delivered weekly over approximately six months, with assessments at baseline, post-treatment, and three-month follow-up. Outcomes included anthropometric indicators, menstrual status, eating-disorder psychopathology, adolescent and caregiver functioning, parenting style, perceived family support, and parent satisfaction. Among completer families, attendance was 100%. Mean BMI increased from 16.72 at baseline to 18.91 post-treatment and 19.03 at follow-up; mean EDE-Q total score decreased from 4.25 to 1.40 and 0.73, respectively. All four adolescents achieved physiological remission and reliable EDE-Q improvement by follow-up; three also met multidimensional remission criteria. The intervention was feasible, acceptable, and clinically promising, but larger studies with independent assessment and comparison conditions are needed. Full article