Plasmablastic lymphoma (PBL) is a rare and highly aggressive subtype of B-cell lymphoma that lacks standardized treatment. We report a 52-year-old woman who presented with back pain and lower limb weakness. Imaging and biopsy confirmed PBL involving the thoracic vertebra. The patient received daratumumab combined with CHOP chemotherapy followed by autologous stem cell transplantation and daratumumab maintenance, achieving durable complete remission for over 22 months without significant toxicity. This case highlights the potential efficacy of CD38-targeted therapy in newly diagnosed PBL and supports daratumumab plus CHOP as a feasible frontline regimen.

Importance:Epigenetic dysregulation is associated with the pathogenesis and progression of diffuse large B-cell lymphoma (DLBCL). MYC/BCL2 double-expressor lymphoma (DEL), a distinct population of DLBCL defined by MYC and BCL2 coexpression, refers to poor prognosis after standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy. Tucidinostat (or chidamide), an oral, selective histone deacetylase inhibitor, has shown promising activity in DEL. Objective:To evaluate efficacy and safety of tucidinostat plus R-CHOP vs R-CHOP alone as first-line treatment for patients with DEL. Design, Setting, and Participants:This randomized, double-blind, placebo-controlled phase 3 trial enrolled patients from May 21, 2020, through July 25, 2022, with follow-up to June 26, 2025. The trial was conducted at 40 study centers in China; a total of 423 eligible patients were enrolled. Interventions:Patients were randomly assigned in a 1:1 ratio to receive oral tucidinostat (20 mg on days 1, 4, 8, and 11 of each 21-day cycle) or matching placebo, plus 6 cycles of R-CHOP. Patients with a complete response after combination therapy received either tucidinostat or placebo maintenance up to 24 weeks. Main Outcomes and Measures:The primary end point was event-free survival. Secondary end points included complete response rate, progression-free survival, disease-free survival, overall survival, and tolerability. Results:Among 423 patients randomized (median age, 63 years; 47.5% male), the median follow-up duration from randomization was 41.3 months. The tucidinostat group demonstrated a 28% lower risk of disease progression, relapse after complete response, death, or initiation of new therapy for residual disease compared with the placebo group (stratified hazard ratio, 0.72 [95% CI, 0.54-0.96]; P = .02), with a 2-year event-free survival rate of 60.3% vs 50.5%, respectively. The complete response rate was 73.0% vs 61.8% (difference, 11.1% [95% CI, 2.3%-20.0%]), respectively. Increased toxicity associated with treatment was observed in the tucidinostat group but generally manageable with supportive care. Conclusions and Relevance:Tucidinostat plus R-CHOP significantly improved event-free survival, with manageable toxicity in patients newly diagnosed with DEL. This trial is the first to demonstrate the benefit of an epigenetic modulator in DLBCL, offering a new first-line therapeutic approach dually targeting MYC and BCL2 oncoprotein for this high-risk population. Trial Registration:ClinicalTrials.gov Identifier: NCT04231448.

Quercetin is a bioflavonoid that is abundant and easy to extract, and has beneficial effects such as anti-cancer, anti-inflammatory, and antioxidant properties. We have demonstrated that oral administration of quercetin in an animal model inhibits bladder cancer (BCa), with inhibition rates of 48.5% (100 mg/kg) and 51.41% (200 mg/kg), respectively. Additionally, quercetin treatment reverses gut microbiota dysbiosis in the model mice. Metabolomics results showed that L-serine had the highest correlation coefficient with tumor weight in model mice (r = 0.935), and oral quercetin reduced L-serine levels by modulating the abundance of Escherichia-Shigella in the gut microbiota. Transcriptomic sequencing results revealed that quercetin treatment downregulates the expression of phosphoserine phosphatase (PSPH), inhibiting the serine synthesis pathway (SSP) and reducing L-serine levels in the body, thus exerting anti-tumor effects. Fecal microbiota transplantation (FMT) experiments reproduced the pharmacological results of oral quercetin treatment for BCa and identified Escherichia coli Nissle 1917 as capable of inhibiting BCa growth by metabolizing L-serine. In conclusion, quercetin effectively inhibits the progression of BCa by comprehensively regulating L-serine levels in the body at both endogenous and exogenous levels.

The gut microbiota plays a crucial role in the study of drug efficacy and metabolism. YZG-331 exhibits significant sedative and hypnotic effects. However, the oral bioavailability of YZG-331 in female mice remains low at 27.7%, and it exhibits instability in the gut microbiota, undergoing rapid metabolism, with the intestinal hydrolytic metabolite M2 identified as the characteristic metabolite. Both the underlying mechanisms of YZG-331 therapeutic effects on insomnia and its enzyme-mediated metabolic pathways involving the gut microbiota remain incompletely elucidated. In this study, we found that YZG-331 regulated the tryptophan metabolism and 5-HT production pathways by the gut microbiota. Specifically, YZG-331 increased the abundance of Lactobacillus and Muribaculaceae in the gut, with Lactobacillus reuteri playing a critical role in both the metabolic processes of YZG-331 and the biosynthesis of tryptophan-derived metabolites. YZG-331 enhanced the activation of the tetrahydrobiopterin (BH4) cofactor system, which subsequently promoted tryptophan hydroxylase (TPH) activity, thereby enhancing 5-HT production. Furthermore, YZG-331 and M2 increased intestinal butyric acid levels, thereby promoting sleep regulation and supporting the restoration of the intestinal barrier. Overall, our study provided the first evidence highlighting the crucial role of the gut microbiota in the therapeutic mechanism and metabolic processing of YZG-331 in the treatment of insomnia.

Background Mucosa-associated lymphoid tissue (MALT) lymphoma is classically linked to NF-κB activation, but its broader regulatory hierarchy remains unclear. We analyzed public multi-omics datasets to prioritize regulatory candidates and to assess whether IL6ST/IL6-related signals recur across secondary and exploratory molecular layers. Methods We integrated bulk transcriptomic, DNA methylation, and single-cell RNA-sequencing datasets and applied master regulator analysis, signature scoring, random-effects and Bayesian evidence synthesis, Bayesian latent-axis modeling, and shared-specific multi-cohort network analysis. Results STAT6 was the top network-inferred regulator (adjusted P = 3.8 × 10⁻⁹⁴) and remained top-ranked in GSE25550 (adjusted P = 3.4 × 10⁻¹³). Regulon-size diagnostics and top-target truncation supported robustness. In GSE25638, the STAT6 target-expression score and IL6ST/JAK-STAT pathway score were both higher in MALT than in the strict normal B-cell reference, but their within-MALT coupling weakened after marker-score adjustment and did not replicate cleanly in GSE25550. IL6 showed the most reproducible gene-level upregulation across expression contexts (pooled effect = + 0.406, 95% CI 0.253–0.559; P = 1.9 × 10⁻⁷), whereas IL6ST was upregulated in the integrated analysis (log₂FC = + 0.588, adjusted P = 1.7 × 10⁻⁵). Bayesian and shared-specific network models constrained interpretation to partial cross-layer coherence. Single-cell analysis showed restricted IL6 detection in a STREAK cluster subset, while ligand-receptor screening, methylation, and chromatin layers remained exploratory. Conclusion Public-data integration prioritizes STAT6 as the primary regulatory candidate in MALT lymphoma. IL6ST/IL6-related signals should be interpreted as secondary, cohort-dependent findings that require functional validation.

QuestionDoes adding the histone deacetylase inhibitor tucidinostat to R-CHOP improve clinical outcomes in patients with newly diagnosed MYC/BCL2 double-expressor lymphoma?FindingsIn this randomized phase 3 clinical trial that included 423 patients, event-free survival was significantly improved with tucidinostat plus R-CHOP compared with placebo plus R-CHOP (hazard ratio, 0.72), with a generally manageable safety profile.MeaningThese findings support the use of an epigenetic modulator (tucidinostat) combined with R-CHOP as a first-line treatment for MYC/BCL2 double-expressor lymphoma, a biologically distinct entity of diffuse large B-cell lymphoma associated with poor prognosis after standard R-CHOP immunochemotherapy. ImportanceEpigenetic dysregulation is associated with the pathogenesis and progression of diffuse large B-cell lymphoma (DLBCL). MYC/BCL2 double-expressor lymphoma (DEL), a distinct population of DLBCL defined by MYC and BCL2 coexpression, refers to poor prognosis after standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy. Tucidinostat (or chidamide), an oral, selective histone deacetylase inhibitor, has shown promising activity in DEL.ObjectiveTo evaluate efficacy and safety of tucidinostat plus R-CHOP vs R-CHOP alone as first-line treatment for patients with DEL.Design, Setting, and ParticipantsThis randomized, double-blind, placebo-controlled phase 3 trial enrolled patients from May 21, 2020, through July 25, 2022, with follow-up to June 26, 2025. The trial was conducted at 40 study centers in China; a total of 423 eligible patients were enrolled.InterventionsPatients were randomly assigned in a 1:1 ratio to receive oral tucidinostat (20 mg on days 1, 4, 8, and 11 of each 21-day cycle) or matching placebo, plus 6 cycles of R-CHOP. Patients with a complete response after combination therapy received either tucidinostat or placebo maintenance up to 24 weeks.Main Outcomes and MeasuresThe primary end point was event-free survival. Secondary end points included complete response rate, progression-free survival, disease-free survival, overall survival, and tolerability.ResultsAmong 423 patients randomized (median age, 63 years; 47.5% male), the median follow-up duration from randomization was 41.3 months. The tucidinostat group demonstrated a 28% lower risk of disease progression, relapse after complete response, death, or initiation of new therapy for residual disease compared with the placebo group (stratified hazard ratio, 0.72 [95% CI, 0.54-0.96]; P = .02), with a 2-year event-free survival rate of 60.3% vs 50.5%, respectively. The complete response rate was 73.0% vs 61.8% (difference, 11.1% [95% CI, 2.3%-20.0%]), respectively. Increased toxicity associated with treatment was observed in the tucidinostat group but generally manageable with supportive care.Conclusions and RelevanceTucidinostat plus R-CHOP significantly improved event-free survival, with manageable toxicity in patients newly diagnosed with DEL. This trial is the first to demonstrate the benefit of an epigenetic modulator in DLBCL, offering a new first-line therapeutic approach dually targeting MYC and BCL2 oncoprotein for this high-risk population.Trial RegistrationClinicalTrials.gov Identifier: NCT04231448 This randomized clinical trial conducted in China evaluates the efficacy and safety of the histone deacetylase inhibitor tucidinostat plus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) vs R-CHOP alone as first-line treatment for patients with MYC/BCL2 double-expressor lymphoma.

Purpose: Platinum-based chemotherapy is considered as salvage therapy to relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients. However, treatment failure due to drug resistance occurs in some patients, particularly those with Exportin 1 (XPO1) overexpression. This study investigates whether XPO1 inhibition enhances platinum sensitivity in DLBCL subtypes.Methods: XPO1 expression in DLBCL was predicted using online datasets. Cell lines representing DLBCL subtypes were treated with varying concentrations of the XPO1 inhibitor selinexor (XPO1i), cisplatin (CDDP), and oxaliplatin (OXA), alone or in combination. Cellular viability was assessed via CCK-8 assay, while apoptosis rates and reactive oxygen species (ROS) levels were measured by flow cytometry. Protein levels of XPO1 and pro-apoptotic cytokines were evaluated using Western blotting.Results: Bioinformatic analysis revealed elevated XPO1 expression in DLBCL. Both XPO1i and platinum-based therapy inhibited cellular viability and promoted apoptosis across DLBCL subtypes in a dose-dependent fashion. The combination of XPO1i at its IC50 and CDDP synergistically suppressed cell viability across both activated B-cell-like- and germinal-center B-cell-like (GCB)-DLBCL subtypes compared to CDDP monotherapy. The combination of XPO1i at its IC30 and OXA synergistically led to a greater reduction in cell viability, along with enhanced induction of apoptosis and ROS accumulation in GCB-DLBCL cells. In OCI-Ly8 and OCI-Ly1 cells, OXA alone inhibited phosphorylation of AKT and mTOR while increasing phosphorylation of JNK, ATM, and p53, and expression of γH2AX; these effects were potentiated by the combination of XPO1i and OXA.Conclusion: XPO1 inhibition enhances platinum-induced cytotoxicity in GCB-DLBCL, supporting clinical evaluation of XPO1i-platinum combinations as salvage therapy.

BACKGROUND:Eltrombopag is an effective second-line therapy for immune thrombocytopenia (ITP), but its long-term efficacy is limited. All-trans retinoic acid (ATRA) has immunomodulatory effects targeting ITP pathophysiology. We investigated whether combining ATRA with eltrombopag improves long-term outcomes for glucocorticoid-resistant or relapsed ITP. METHODS:We conducted a multicenter, randomized, open-label trial in adults with glucocorticoid-resistant or relapsed ITP (platelets <30×109/l). Patients were randomly assigned 1:1 to ATRA (12 weeks) plus eltrombopag or eltrombopag monotherapy. The primary outcome was an 18-month sustained response (platelet count ≥30×109/l without clinically significant bleeding or rescue therapy). RESULTS:Ninety-six patients were randomly assigned, 48 per group. At 18 months, 60% (29/48) in the ATRA-plus-eltrombopag group achieved a sustained response, versus 35% (17/48) in the monotherapy group (odds ratio: 2.78; 95% confidence interval [CI]: 1.22-6.37; P=0.014). The combination was associated with a higher complete response rate (79% vs. 58%; 95% CI for difference, 2 to 39 percentage points) and longer median response duration (75 vs. 37 weeks; hazard ratio for relapse, 0.45; 95% CI, 0.23-0.86). Adverse events were comparable between groups, with no grade 3-4 events or treatment-related deaths. However, clinically significant bleeding of World Health Organization grades 2 or 3 was 21% in the combination group at baseline compared with 10% in the monotherapy group. CONCLUSIONS:In patients with glucocorticoid-resistant or relapsed ITP, a 12-week ATRA course with eltrombopag significantly enhanced the 18-month sustained response rate compared to eltrombopag alone. (Funded by Capital Health Research and Development of Special Fund and others; ClinicalTrials.gov number, NCT05438875.).

Background: Adding daratumumab to initial therapy in randomized controlled trials (RCTs) for newly diagnosed multiple myeloma (MM) enhances deep remission and prolongs progression-free survival (PFS). Given the differences between trial-eligible and real-world patients, and healthcare access variability in developing countries, real-world data are essential to complement RCT evidence. Methods: We analyzed 761 newly diagnosed MM patients treated with (n = 177) or without (n = 584) daratumumab as first-line therapy from 2017 to 2023 across southern China. Propensity score matching (PSM) generated cohorts of 158 and 278 patients, respectively, matched for stage, cytogenetic abnormalities, and regimen type. Responses were evaluated per International Myeloma Working Group criteria, and measurable residual disease (MRD) was assessed via next-generation multiparameter flow cytometry. Results: The daratumumab group demonstrated significantly higher rates of ≥ very good partial response (85.0

BRUIN CLL-321 is the first prospective, randomized study conducted in covalent BTK inhibitor (cBTKi) pretreated chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients. In this heavily pretreated population, pirtobrutinib significantly improved progression-free survival (PFS) compared to investigator's choice (IC) of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BendaR). This report presents results from Chinese patients enrolled in BRUIN CLL-321, who were randomized 1:1 to pirtobrutinib (200 mg once daily) or IC of BendaR (idelalisib is not approved in China). End-points included independent review committee (IRC)-assessed PFS, investigator (INV)-assessed PFS, overall survival (OS), event-free survival (EFS), time to next treatment (TTNT) and safety. Among 40 Chinese patients (pirtobrutinib n = 19; BendaR n = 21), IRC-assessed PFS favoured pirtobrutinib (stratified hazard ratio [HR] = 0.281; 95% confidence interval [CI], 0.070-1.125, nominal p = 0.0554), with median PFS not reached versus 10.6 months with BendaR; INV-assessed PFS supported these findings. TTNT (HR = 0.150; 95% CI, 0.031-0.728) and EFS (HR = 0.322; 95% CI, 0.094-1.101) were also improved. A trend towards OS benefit was observed (HR = 0.343; 95% CI, 0.031-3.787). Pirtobrutinib showed a favourable safety profile, with fewer grade ≥3 treatment-emergent adverse events (36.8% vs. 93.3%) and serious adverse events (15.8% vs. 46.7%). These findings support pirtobrutinib as a clinically active and tolerable option for cBTKi-pretreated Chinese CLL/SLL population.

Observational studies have reported associations between multiple sclerosis (MS) and hematologic malignancies (HM), but findings remain inconsistent. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association summary statistics for MS (n = 115,803) and HM (n = 218,792). Primary causal estimates were obtained with the inverse-variance-weighted (IVW) estimator, complemented by prespecified sensitivity analyses for heterogeneity and pleiotropy. Genetically proxied liability to MS was associated with higher odds of leukemia (unspecified subtype) (odds ratio [OR] 1.311, 95% confidence interval [CI] 1.002-1.716, P = 0.048) and Hodgkin lymphoma (HL) (OR 1.224, 95% CI 1.052-1.425, P = 0.009), with no evidence for other leukemia, lymphoma, or plasma-cell neoplasm subtypes (all P > 0.05). Tests indicated no substantial heterogeneity or directional pleiotropy for the leukemia (unspecified subtype) or HL analyses. These results provide genetic evidence consistent with an elevated risk of select HM subtypes among individuals with higher genetic liability to MS; however, the signals should be interpreted cautiously and validated in larger, multi-ancestry datasets and with additional causal frameworks.

The addition of CD38-targeted monoclonal antibodies, such as daratumumab and isatuximab, to standard treatment regimens has been shown to improve progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM). However, the benefits in specific subgroups, particularly high-risk multiple myeloma (HRMM) defined by cytogenetic abnormalities, remain controversial.We conducted a systematic search of the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing induction regimens with and without anti-CD38 monoclonal antibodies in NDMM. A meta-analysis was performed to evaluate the minimal residual disease (MRD)-negative status rate and PFS.Eleven RCTs comprising 5,588 patients (915 HRMM) were included. Among them, 2,874 received anti-CD38 antibody–containing regimens, while 2,714 received the same backbone without antibody. Addition of anti-CD38 antibodies significantly increased MRD negativity in both transplant-eligible (TE) (pooled odd ratio [OR], 2.32; 95% CI, 1.74–3.11) and transplant-ineligible (TIE) (pooled OR, 3.26; 95% CI, 2.20–4.84) NDMM. Stratified analysis in TE NDMM showed improved MRD negativity in HRMM (pooled OR, 2.01; 95% CI, 1.41–2.88) and standard-risk MM (SRMM) (pooled OR, 2.74; 95% CI, 1.99–3.84). Anti-CD38 therapy also significantly prolonged PFS in TE NDMM (pooled HR, 0.52; 95% CI, 0.38–0.69) and TIE NDMM (pooled HR, 0.55; 95% CI, 0.49–0.61), with overall survival (OS) benefit observed in TIE patients. Subgroup analyses indicated consistent PFS improvement across cytogenetic risk, age, performance status, International Staging System (ISS) stage, and renal function. Safety analysis demonstrated increased grade 3–4 infections (pooled OR, TE: 1.30; TIE: 1.58), neutropenia (pooled OR, 1.85), and thrombocytopenia (pooled OR, 1.34) with anti-CD38 therapy.Our findings suggest that the addition of anti-CD38 monoclonal antibody to induction regimens in NDMM significantly improve MRD negativity and PFS across risk groups and patient populations but are associated with increased hematologic and infectious toxicities. These findings support the use of anti-CD38 therapy in both TE and TIE NDMM, while careful monitoring for adverse events is warranted.

Background: FCR (fludarabine, cyclophosphamide, and rituximab) has been demonstrated to improve outcomes in previously untreated Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) CLL patients, but only for suitable patients, which limits it clinical application.Lower toxicity strategies, such as Bendamustine-Obinutuzumab or Bendamustine-Rituximab, demonstrated better tolerability but did not achieve comparable efficacy.BTK inhibitors (BTKi) are recommended for long-term therapy in CLL/SLL and time-limited treatment regimen has been hot topics. In fit patients, exploration of time-limited therapy models such as fixed-duration or MRD-guided therapies has shown promising results. However, such exploration were needed in unfit patients.Orelabrutinib is a novel, potent, and highly selective BTK inhibitor that offers better deep remission compared to other BTK inhibitors.Therefore, this study aims to explore a more effective treatment regimen for unfit patients with newly diagnosed CLL/SLL by using Orelabrutinib plus Bendamustine and Obinutuzumab (OBG) regimen as first-line therapy. The first stage analysis was published at 66th ASH meeting and this time we report the update of interim analysis. Methods: This is a multiple-center, phase II, single-arm study aimed at evaluating the efficacy and safety of OBG regimen as first-line treatment for CLL/SLL unfit patients without 17p-/TP53 mutations. Unfit defined as patients age > 65 years old or CIRS scores≥6.The primary endpoints include the rate of complete response (CR) combined with undetectable minimal residual disease (uMRD) at the end of 7 cycles (CR/CRi & uMRD, with patients achieving incomplete CR categorized as CRi). The secondary endpoints include CRR, ORR, and safety. Dosage regimen:Orelabrutinib 150 mg, po, qd, D1-D28;Bendamustine: 70 mg/m², intravenous injection, administered on Day 2 and Day 3 of Cycle 1, and on Day 1 and Day 2 of Cycles 2-6. Obinutuzumab: Cycle 1: 100 mg on day 1, 900 mg on day 2 (or 1000 mg on day 1), and 1000 mg on days 8 & 15. Cycle 2-6, 1000 mg/m² on Day 1. Each treatment cycle lasts 28 days. The first cycle us BG regiment to reduce tumor burden, followed by 5 cycles of OBG, and then one cycle of orelabrutinib monotherapy. Result: From December 2023 to March 2025, a total of 13 patients were enrolled, all of whom completed at least 4 cycles of treatment, with 11 patients completing 7 cycles. The median age was 66 years (range: 53–70). 76.9% patients were males and 23.1% were females. ECOG PS scores were distributed as follows: score of 0 in 69.2% and score of 1 in 30.8%. Rai staging showed that 38.5% patients were stage I/II, while 61.5% were III/IV. IGHV mutation was present in 76.9% of the patients. Efficacy results: 72.7% (7/11) had achieved CR&uMRD at the end of all 7 cycles, with an ORR of 100% and 100% achieved PB uMRD4. Among all patients who completed at least four cycles (n=13), ORR was 92.3%, and 46.2% achieved CR. Safety results: Among all treated patients, ≥Grade-3 AEs occurred in four patients (include 3 neutropenia, 2 thrombocytopenia, 2 infections, 1 involving herpes zoster). All patients fully recovered from the adverse event without any impact on their subsequent treatment. No cases were reported for hypertension (any grade), atrial fibrillation (any grade), or bleeding events (≥Grade-3) across all participants treated during this study period. Conclusions: The Time-Limited Treatment of OBG regimen shows efficacy in unfit CLL/SLL patients, which achieved high rates of complete response combined with undetectable minimal residual disease. Safety analysis indicates that the OBG regimen is well-tolerated and adverse events are manageable. These findings support further investigation of the OBG regimen to optimize treatment outcomes in this patient population.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

The incorporation of CD38-targeted monoclonal antibodies into induction therapy has improved outcome in patients with newly diagnosed multiple myeloma (NDMM), yet the benefit across risk subgroups remains controversial. We conducted a systematic search of the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing induction regimens with and without anti-CD38 monoclonal antibodies (daratumumab or isatuximab) and assessed the efficacy and safety of anti-CD38-based induction regimens in NDMM. Primary outcomes were minimal residual disease (MRD)-negativity and progression-free survival (PFS). Eleven trials encompassing 5588 patients, including 915 with high-risk multiple myeloma (HRMM), were included. Anti-CD38-containing regimens significantly increased MRD-negativity in both transplant-eligible (TE; pooled odds ratio [OR], 2.32; 95% confidence interval [CI], 1.74-3.11) and transplant-ineligible (TIE; pooled OR, 3.26; 95% CI, 2.20-4.84) patients. Among TE patients, MRD-negativity improved in both HRMM (pooled OR, 2.01; 95% CI, 1.41-2.88) and standard-risk MM (pooled OR, 2.74; 95% CI, 1.99-3.84). Anti-CD38 therapy also significantly prolonged PFS in TE (pooled hazard ratio [HR], 0.52; 95% CI, 0.38-0.69) and TIE NDMM (pooled HR, 0.55; 95% CI, 0.49-0.61), with an overall survival benefit observed in TIE patients. PFS improvement was consistent across cytogenetic risk and clinical subgroups. Grade 3 or 4 infections and hematologic toxicities occurred more frequently with anti-CD38 regimens. In summary, anti-CD38-based induction improves depth of response and PFS across NDMM populations, including high-risk disease, with increased but manageable toxicity.

BACKGROUND:Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin's lymphoma with distinct clinical and molecular heterogeneity. DLBCL that arises in extranodal organs is particularly linked to poor prognosis. This study aimed to determine the clinical and molecular characteristics of extranodal involvement (ENI) in DLBCL and assess the actual survival status of the patients. METHODS:In this population-based cohort study, we investigated the clinical features of 5,023 patients newly diagnosed with DLBCL. Their clinical conditions, eligibility criteria, and sociodemographic details were recorded and analyzed. Gene panel sequencing was performed on 1,050 patients to discern molecular patterns according to ENI. RESULTS:The 2-year overall survival (OS) rate was 76.2% [95% confidence interval (CI), 74.0%-78.2%], and the 5-year OS rate was 67.9% (95% CI, 65.2%-70.4%). The primary treatment was immunochemotherapy with rituximab. Specific lymphoma involvement sites, especially the bones, bone marrow, and central nervous system, were identified as independent adverse prognostic factors. A high prevalence of non-germinal center B-cell (non-GCB) phenotype and myeloid differentiation primary response 88 (MYD88)/CD79B mutations were noted in lymphomas affecting the breasts, skin, uterus, and immune-privileged sites. Conversely, the thyroid and gastrointestinal tract showed a low occurrence of non-GCB phenotype. Remarkably, patients with multiple ENIs exhibited a high frequency of MYD88, tet methylcytosine dioxygenase 2 (TET2), CREB binding protein (CREBBP) mutations, increased MYD88L265P and CD79B mutation (MCD)-like subtypes, and poor prognosis. Genetic subtype-guided immunochemotherapy showed good efficacy in subgroup analyses after propensity score matching with 5-year OS and progression-free survival rates of 85.0% (95% CI, 80.6%-89.5%) and 72.1% (95% CI, 67.3%-76.7%). CONCLUSIONS:In the rituximab era, this large-scale retrospective analysis from Asia confirmed the poor prognosis of DLBCL with multiple ENIs and underscored the efficacy of genetic subtype-guided immunochemotherapy in treating extranodal DLBCL.

In this multicenter study, we aimed to identify the prognostic factors for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients who received autologous stem cell transplantation (ASCT) in the era of novel agents and chimeric antigen receptor (CAR) T-cell therapy. A total of 82 relapsed/refractory DLBCL patients receiving ASCT across four transplant centers were enrolled. The 3-year probabilities of disease progression, non-relapse mortality (NRM), progression-free survival (PFS), and overall survival (OS) were 23.5%, 2.8%, 73.7%, and 91.4%, respectively. Patients who received Pola-R-CHP before ASCT had a higher disease progression rate (85.7% vs. 18.4%, P = 0.034) and a poorer PFS (0% vs. 79.9%, P < 0.001) after ASCT compared with those who did not receive Pola-R-CHP. Patients who received BTKi before ASCT had a higher disease progression rate (60.0% vs. 18.2%, P = 0.025) and a poorer PFS rate (23.8% vs. 81.8%, P < 0.001) after ASCT compared with those who did not receive BTKi. In multivariate analysis, receiving novel agents before ASCT was independently associated with a higher risk of disease progression and worse PFS. In summary, we observed the heterogeneity of relapsed/refractory DLBCL patients who achieved therapies response and received ASCT, and some of them might not benefit from ASCT.

Background: Klebsiella pneumoniae bloodstream infection (KP-BSI) is a severe and potentially fatal complication in patients with acute leukemia. The increasing prevalence of carbapenem-resistant (CR) and multidrug-resistant (MDR) strains presents significant therapeutic challenges and may worsen clinical outcomes. Methods: We retrospectively analyzed 161 adult patients with acute leukemia who developed KP-BSI. Clinical features, antimicrobial susceptibility, treatment regimens, and outcomes were recorded. Multivariate logistic regression was performed to identify risk factors associated with CRKP and MDR-KP BSI, as well as predictors of 30-day mortality. Results: Among the 161 cases of KP-BSI, 14 (8.7%) were due to CRKP, and 81 (50.3%) were MDR-KP. Prior use of carbapenems was an independent risk factor for CRKP (OR 10.34; 95% CI, 2.90–55.01; P < .001), while prior aminoglycoside use was associated with decreased risk of CRKP (OR 0.042; P < .001) and MDR-KP (OR 0.371; P < .001). Hematopoietic stem cell transplantation (HSCT) was independently associated with MDR-KP infection (OR 6.04; P < .001). The overall 30-day mortality rate was 9.9%, but significantly higher in CRKP cases compared to non-CRKP cases (28.6% vs. 8.2%; P < .001). On multivariate analysis, pulmonary infection (OR 5.88; P = .017) and leukemia disease status (OR 0.246; P = .043) were independent predictors of 30-day mortality. Conclusion: CRKP and MDR-KP pose serious threats to patients with acute leukemia and KP-BSI. Prior antibiotic exposure and HSCT are significant risk factors. Timely initiation of appropriate empirical therapy is critical for improving survival in this high-risk population.