Background Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and highly aggressive lymphoma with a dismal prognosis and no established standard therapy. Its frequent expression of BCL-2 provides a rationale for targeting this anti-apoptotic protein. Methods We report the case of a 34-year-old female with refractory MEITL who failed prior lines of therapy, including CHOPE and gemcitabine/oxaliplatin (GemOx) combined with golidocitinib. Based on positive BCL-2 expression by immunohistochemistry, a salvage regimen combining venetoclax with Gemox was administered. Results The treatment induced a rapid and significant clinical improvement. A follow-up PET/CT scan confirmed complete metabolic remission. The main adverse event was grade 4 neutropenia and thrombocytopenia with febrile neutropenia, attributable primarily to the Gemox backbone, which resolved with supportive care. The off-label use was approved by the institutional committee, and informed consent was obtained. Conclusion To our knowledge, this is the first report of successful treatment of refractory MEITL with a venetoclax-containing regimen. This case validates BCL-2 as a actionable therapeutic target in MEITL. Future efforts should focus on optimizing combination partners for venetoclax to improve efficacy and tolerability. The rationale for exploring venetoclax as post-transplant maintenance therapy in MEITL is also discussed.

Background: In high-risk non-muscle-invasive bladder cancer (NMIBC), adjuvant therapies, such as intravesical Bacillus Calmette–Guérin (BCG) instillation, are widely employed; however, BCG treatment poses challenges due to potential adverse effects and ongoing supply limitations. This study aimed to evaluate treatment patterns, therapeutic efficacy, incidence of adverse events, and clinical predictors of recurrence and progression in patients with high-grade pT1 urothelial carcinoma (HG-T1 UC) of the bladder. Methods: This retrospective cohort study included 204 patients diagnosed with HG-pT1 UC who underwent transurethral resection of bladder tumor (TURBT) at Toho University Sakura Medical Center between 2010 and 2021. Clinical data encompassing treatment modalities (BCG or intravesical chemotherapy), complications, and oncological outcomes were collected. Recurrence-Free Survival (RFS), Progression-Free Survival, and Cancer-Specific Survival were analyzed using Kaplan–Meier analyses and multivariate regression models. Results: Maintenance BCG therapy was significantly associated with prolonged RFS compared to other treatments, including among ‘very high-risk’ patients. However, 52.4% of patients receiving BCG maintenance experienced adverse events, with dose reductions required in 59% of cases. Notably, recurrence rates did not significantly differ based on dose reduction or the total number of BCG instillations. Tumor multiplicity emerged as an independent risk factor for recurrence. Conclusions: Although maintenance BCG therapy remains essential for managing HG-T1 UC, especially in high-risk patients, treatment should be individualized due to concerns about tolerability and availability. The study results support the importance of personalized strategies based on risk stratification as outlined in clinical guidelines for preventing recurrence in NMIBC.

Background Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC), also termed IgG4-related cholangitis (IRC), is a challenging immune-mediated biliary disease, frequently mimicking malignancies such as cholangiocarcinoma (CCA) or other sclerosing cholangitides like primary sclerosing cholangitis (PSC). Accurate diagnosis is critical to avoid unnecessary surgical interventions. Objective This mini-review aims to synthesize the most current evidence on the pathogenesis, diagnostic pitfalls, and management strategies for IgG4-SC, with a focused discussion on overcoming diagnostic dilemmas and addressing the significant challenge of disease relapse. Key findings The pathogenesis of IgG4-SC involves a complex interplay of genetic predisposition, environmental triggers (e.g., industrial vapors, dust, gases, fumes, and asbestos), and dysregulated adaptive immunity. A distinctive CD4+ T-cell response, dominated by T-helper 2 (Th2), follicular helper T (Tfh) cells, and regulatory T cells (Tregs), drives B-cell activation, oligoclonal expansion of IgG4+ plasmablasts, and progressive fibrosis. Notably, the discovery of IgG4/IgG1 autoantibodies against annexin A11 and laminin 511-E8 has provided insight into potential direct pathogenic mechanisms. Diagnosis relies on a multimodal approach integrating clinical presentation, characteristic imaging findings, elevated serum IgG4 levels (with levels >2× ULN being suggestive, and >4× ULN being highly specific), the IgG4/IgG1 ratio (>0.24), other organ involvement (notably type 1 autoimmune pancreatitis, AIP), supportive histopathology, and a rapid response to corticosteroid therapy. Despite high initial response rates to steroids, relapse occurs in 30%–50% of patients. Maintenance therapy with steroid-sparing immunomodulators (e.g., azathioprine, mycophenolate mofetil) or B-cell depleting agents such as rituximab is often required. The anti-CD19 monoclonal antibody inebilizumab has emerged as a potent new option for maintaining remission. Conclusion Maintaining a high index of clinical suspicion for IgG4-SC is essential in patients with obstructive jaundice and biliary strictures. Future efforts should focus on validating specific biomarkers (e.g., circulating plasmablasts, autoantibody profiles) and developing evidence-based protocols for long-term management to prevent fibrotic complications and reduce the relapse rate.

ABSTRACT Background and Aims Achieving endoscopic response (ER), defined as a > 50% reduction from baseline in Simple Endoscopic Score for Crohn's disease (SES‐CD) score, following induction therapy for Crohn's disease (CD) has been linked to improved 1‐year outcomes. We evaluated the impact of ER at the end of maintenance (EOM) on long‐term clinical outcomes. Methods Data from a Phase 3 randomized trial (IM‐UNITI, ustekinumab) and a Phase 2 trial (GALAXI 1, guselkumab and ustekinumab) were analyzed using multivariable statistical methods. The relationship between ER at the EOM (Week 48) and outcomes at Week 96, including clinical remission, hospitalization, and surgery, was assessed. Results Endoscopic and clinical remission data at the EOM were available for 461 patients. ER at EOM was significantly associated with higher odds of clinical remission (odds ratio [OR] = 1.91; p < 0.05) at Week 96. ER was also linked to reduced inflammatory burden, with higher odds of C‐reactive protein normalization (OR = 2.19; p < 0.005). Forty‐one patients were hospitalized or required surgery during the long‐term extension, with higher event rates among those without ER at the EOM ( p = 0.1237). Conclusions ER after 48 weeks of maintenance therapy was associated with a greater likelihood of clinical remission and improved quality of life at 1 year. Data also suggest lower hospitalization and surgery rates for those who achieve ER. Larger studies are needed to substantiate long‐term reductions in hospitalizations and surgeries.

Dual costimulation blockade with the CD154-specific fusion protein dazodalibep and belatacept for prophylaxis of kidney allograft rejection.

Background Non-small cell lung cancer (NSCLC) with brain metastasis (BM) is associated with poor prognosis. For those patients with MET exon 14 skipping mutation (METex14), although MET tyrosine kinase inhibitors (MET TKIs) have emerged, but their efficacy remains limited, with the median progression-free survival (PFS) no more than 14 months. Herein, we present a case of a NSCLC patient with BM and METex14, who achieved prolonged PFS of 41 months following brain radiotherapy initiation and camrelizumab (a PD-1 inhibitor). Case presentation A 75-year-old man was diagnosed with lung adenocarcinoma with BM and METex14. He received 7 months of crizotinib as first-line therapy, after that, the lung and brain lesions enlarged. Then, programmed cell death-ligand 1 (PD-L1) showed the tumor proportion score (TPS) approximately 80%, he underwent brain radiotherapy combined with camrelizumab immunotherapy. After treatment, the lesions in the patient’s lung and brain were significantly reduced. Camrelizumab maintenance therapy was continued for 20 months until the appearance of pulmonary aspergillosis, with the patient achieving a PFS of 41 months. Conclusion The combination of brain radiotherapy and camrelizumab demonstrated efficacy in a lung adenocarcinoma patient with BM and METex14. These findings suggest that immunotherapy may represent a potential treatment approach for high PD-L1 expression of METex14 NSCLC patients, warranting further investigation in larger cohorts.

Despite strong guideline support, single maintenance and reliever therapy (SMART) for asthma is underused in the US. Limited insurance coverage of SMART-compatible inhalers remains a major barrier to its adoption. To compare the annual asthma management costs of SMART vs traditional therapy from a US health care payer perspective. This economic evaluation used a probabilistic decision-tree model with Monte Carlo simulations to compare the total asthma management costs for patients prescribed SMART vs traditional therapy, conducting analyses from September 1, 2024, to March 13, 2025. Input data were extracted through a systematic review of 6 randomized clinical trials as well as current asthma guidelines. SMART vs traditional therapy. The main outcome was annual asthma-related costs to health care payers. Model inputs, including exacerbation rates and expected inhaler utilization, were extracted from prior randomized clinical trials. Morbidity data and medication costs were obtained from national databases and inflated to 2024 US dollars. Analyses used a 1-year time horizon and were repeated with and without quality-adjusted life-years (QALYs) considered. The model includes 11 988 individuals with moderate to severe asthma who participated in the randomized clinical trials. For patients prescribed SMART, the estimated total annual cost of asthma management was $2181 (95% CI, $1606-$2939) per patient compared with $2235 (95% CI, $1595-$3267) for traditional therapy. SMART was associated with an incremental gain of 0.0006 QALYs (95% CI, 0.0003-0.0011 QALYs) per patient. SMART was less costly in 57% of simulations when QALYs were excluded, was more cost-effective in 67% of simulations when QALYs were included, and produced a mean incremental net monetary benefit of $118 (95% CI, -$344 to $663) per patient per year. The findings of this economic analysis suggest that SMART was associated with modest cost savings and improved health outcomes compared with traditional asthma therapy. Given its cost-effectiveness, demonstrated effectiveness, and strong guideline endorsement, expanding insurance coverage of SMART may reduce asthma-related morbidity while lowering costs to US health care payers.

ABSTRACTWith the improvement of survival in multiple myeloma (MM), therapy‐related acute myeloid leukemia (t‐AML) has emerged as a clinically relevant second primary malignancy (SPM). We report a case of MM evolving into t‐AML after multi‐agent chemotherapy and review the literature on therapy‐related leukemias in MM. We report a case of a patient diagnosed with primary plasma cell leukemia (IgG‐λ type, R‐ISS stage III) who achieved complete remission following maintenance therapy with daratumumab, lenalidomide, and dexamethasone after receiving a treatment regimen based on proteasome inhibitors. The patient progressed to therapy‐related acute myeloid leukemia 18 months later, and we present the clinical features. Additionally, we conducted a literature review. Given the patient's age and debilitated physical condition, treatment with azacitidine combined with venetoclax was administered. Following the treatment, the patient developed grade IV post‐chemotherapy myelosuppression complicated by infection and extensive ischemic stroke. Despite aggressive supportive care, the patient's condition continued to deteriorate and he succumbed in August 2025. This case illustrates the leukemogenic risk of cytotoxic exposure in MM, highlights the adverse genetic profile of therapy‐related AML, and emphasizes the need for vigilant monitoring and preventive strategies in long‐term MM survivors.

Resminostat for maintenance treatment in patients with advanced-stage mycosis fungoides or Sézary syndrome: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Neuropsychologic impact of MOGAD: A patient reported outcomes study.

A novel BRCA mutation classification system reveals differential responses to PARP inhibition and prognostic outcomes in epithelial ovarian cancer: a multicenter study.

Background: There is much interest in drug development to prevent rebleeding after symptomatic hemorrhage (SH) in cerebral cavernous malformations (CCM) and its neurologic sequelae. A recent randomized prospective controlled trial (AT CASH EPOC clinicaltrials.gov NCT02603328) demonstrated that atorvastatin for up to 2 years was safe but did not significantly alter CCM iron deposition or SH rates. However, the consequences of discontinuing atorvastatin in CCM patients remain unknown. Given reports of rebound effects with discontinuation of statins, we here hypothesize that SH recurs more frequently in hemorrhagic CCMs after discontinuation of atorvastatin than placebo. Methods: We conducted 12-month (±1 month) post-treatment follow-up of all 80 patients randomized in the AT CASH EPOC trial (41 atorvastatin, 39 placebo) to identify potential recurrent SH from the date of trial drug discontinuation. Every SH was adjudicated by review of imaging and corresponding symptoms. Patients were excluded for < 90% compliance with study drug or its discontinuation <3 months during the trial, and for lack of follow-up. Cases were censored during follow-up upon CCM resection/radiation or atorvastatin initiation/re-initiation. Results: Follow-up included 33 patients who had been randomized to placebo and 32 who had taken atorvastatin.During follow-up, 4 SH events occurred at 3, 49, 84, and 225 days after atorvastatin discontinuation, and only 1 SH 395 days after discontinuing placebo. Kaplan–Meier curves demonstrated significantly lower symptomatic hemorrhage-free survival in the atorvastatin-discontinuation group (log-rank chi=4.136, p=0.042). The Gehan–Breslow–Wilcoxon test (chi=4.080, p=0.043) highlighted early divergence in recurrent SH risk. The hazard ratio was 0.162 (95% CI 0.027–0.977) for placebo vs. atorvastatin discontinuation. Conclusion: While there was no difference in SH rates during 2 years of treatment with atorvastatin versus placebo in randomized clinical trial, discontinuation of atorvastatin was associated with a significantly higher and earlier risk of recurrent SH compared with placebo discontinuation. This raises concern for a rebound effect during the year after statin withdrawal in hemorrhagic CCM patients, potentially mediated by reactivation of Rho-associated kinase. Additional studies are warranted to confirm these observations and to assess whether statin tapering or maintenance therapy can mitigate the risk of discontinuation in hemorrhagic CCM.

The purpose of this review is to highlight recent findings in the diagnosis, biology, risk-stratification, and treatment of soft tissue sarcomas (STS) in children. In rhabdomyosarcoma (RMS), FOXO1 fusion status has been confirmed as an important prognostic factor. Among fusion-negative RMS, TP53 and MYOD1 mutations and detectable circulating tumor DNA at diagnosis are associated with inferior event-free survival in intermediate-risk disease. Delayed primary excision is associated with a reduced risk of local failure whereas radiotherapy dose escalation in large tumors has not improved local control. Maintenance therapy with vinorelbine and oral cyclophosphamide following induction chemotherapy in the RMS2005 trial led to improved survival. In non-rhabdomyosarcoma soft tissue sarcomas, the addition of pazopanib, a multitargeted receptor tyrosine kinase inhibitor, to upfront therapy did not improve survival. Atezolizumab is approved for alveolar soft part sarcoma, larotrectinib for NTRK fusion-positive STS, and afamitresgene autoleucel remains under evaluation in children with synovial sarcoma. Encouraging early results have been reported with tazemetostat and immune checkpoint inhibitors in epithelioid sarcoma and trastuzumab in desmoplastic small round cell tumor, respectively. Pediatric STS are rare and biologically heterogeneous. Genomic advances have refined risk stratification and uncovered therapeutic targets; further progress relies on international collaboration and trials.

Efficacy and safety of ketamine maintenance therapy in treatment-resistant depression: A systematic review of treatment protocols and clinical outcomes.

Patient-derived 3D bioprinted glioblastoma models with defined physicochemical ECM properties for long-term maintenance and CAR-T therapy evaluation

Temporal immune effects of Oral ketamine on PTSD: Transcriptomic evidence of short-term inflammation suppression and sustained immune Remodelling.

IntroductionNiraparib and bevacizumab are two principal maintenance therapies for newly diagnosed advanced ovarian cancer (AOC) patients with BRCA wild-type (BRCAwt) status, regardless of homologous recombination deficiency (HRD). In China, however, a considerable proportion of BRCAwt patients have unknown or untested HRD status, complicating treatment selection.MethodsTo evaluate and compare the efficacy of niraparib and bevacizumab as maintenance therapy for BRCAwt AOC, we conducted a retrospective cohort study using real-world clinical data. Descriptive statistics were used to summarize clinical and demographic characteristics. Progression-free survival (PFS) was estimated using Kaplan-Meier analysis and compared using a stratified Cox proportional hazards model. A multivariable Cox regression was performed to adjust for potential confounding variables. Exploratory subgroup analyses were conducted, and propensity score matching (PSM) was applied as a sensitivity analysis.ResultsA total of 94 patients were included, with 51 receiving niraparib and 43 receiving bevacizumab. The median PFS was not reached in the niraparib group versus 13.77 months (95% CI, 4.12-23.41) in the bevacizumab group (HR = 0.240, 95% CI, 0.128-0.451; P < .001). After covariate adjustment, the median PFS was 19.55 months (95% CI, 9.40-NA) with niraparib and 8.64 months (95% CI, 4.53-NA) with bevacizumab, with an adjusted HR of 0.282 (95% CI, 0.136-0.587; P = .001). In the PSM sensitivity analysis, the median PFS was not reached (95% CI, 19.55-NR) in the niraparib group and was 18.33 months (95% CI, 8.90-25.26) in the bevacizumab group (HR = 0.360, 95% CI, 0.176-0.736; P = .005).ConclusionThis analysis suggests that niraparib may provide a progression-free survival advantage compared with bevacizumab in BRCAwt AOC patients, with both regimens appearing to be generally well tolerated in the real-world setting. These findings offer preliminary reference value for maintenance treatment selection in patients with newly diagnosed BRCAwt AOC.

Meta-analysis of recurrence rate and influencing factors of bipolar disorder.

Neuroblastoma is the most common extracranial solid tumor of childhood and remains a leading cause of cancer-related mortality in pediatric patients. Characterized by marked clinical and biological heterogeneity, the disease ranges from spontaneously regressing tumors in infants to highly aggressive, treatment-resistant malignancies in older children. Advances in molecular biology and genomics have significantly improved understanding of neuroblastoma pathogenesis, revealing the critical role of genetic and epigenetic alterations—such as MYCN amplification, ALK mutations, and chromosomal aberrations—in disease behavior and prognosis. Contemporary risk stratification systems now integrate clinical, biological, and molecular features to guide therapy more precisely. Management strategies have evolved toward risk-adapted, multimodal approaches. Low- and intermediate-risk patients often achieve excellent outcomes with surgery alone or limited chemotherapy, whereas high-risk neuroblastoma requires intensive multimodal treatment including induction chemotherapy, surgical resection, high-dose chemotherapy with autologous stem cell rescue, radiotherapy, and maintenance therapy. The incorporation of immunotherapeutic approaches, particularly anti-GD2 monoclonal antibodies, has significantly improved survival in high-risk disease. Emerging therapies such as targeted agents, radiopharmaceuticals, and cellular immunotherapies are further expanding the therapeutic landscape. Despite these advances, high-risk and relapsed neuroblastoma remain associated with substantial morbidity and mortality. Ongoing challenges include treatment resistance, long-term toxicity, and disparities in access to advanced therapies. Continued progress will depend on integrating molecular profiling into clinical decision-making, refining risk-adapted treatment strategies, and expanding international collaborative research efforts. This narrative review summarizes current knowledge on neuroblastoma epidemiology, biology, staging, and treatment, highlighting recent advances and future directions aimed at improving outcomes for affected children.

This study aimed to evaluate the efficacy and safety of poly(ADP-ribose) polymerase inhibitor (PARPi) rechallenge combined with bevacizumab as maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer previously treated with a PARPi. KGOG 3056/NIRVANA-R is a multicenter, single-arm, phase II trial that enrolled 44 patients with platinum-sensitive recurrent ovarian cancer who had received ≥2 prior lines of platinum-based chemotherapy and prior PARPi maintenance. Eligible patients achieving a response to the most recent platinum therapy received daily niraparib and triweekly bevacizumab until disease progression or unacceptable toxicity. The primary endpoint was the 6-month progression-free survival (PFS) rate, analyzed using Simon's two-stage design with adaptive statistical inference. The primary endpoint was met, with 26 of 44 patients (59.1%) remaining progression-free at 6 months. The estimated 6-month PFS rate was 68% [95% confidence interval (CI), 55%-85%], and the median PFS was 11.5 months [95% CI, 7.9-not reached]. Subgroup analyses suggested greater benefit in patients with a longer treatment-free interval after the penultimate chemotherapy and in those who achieved a complete response to the most recent chemotherapy. Grade ≥3 treatment-related adverse events occurred in 27.3% of patients, with no treatment-related deaths or new safety signals observed. This is the first report of PARPi rechallenge with bevacizumab as maintenance therapy in this setting. The combination demonstrated promising efficacy, particularly in patients with favorable platinum responsiveness, and warrants further investigation in biomarker-driven studies.