Waldenström macroglobulinemia: a challenging case treated with anti-CD19 CAR-T cell therapy. / 华氏巨球蛋白血症：抗CD19嵌合抗原受体Tç»†èƒžç–—æ³•æ²»ç–—çš„æŒ‘æˆ˜æ€§ç— ä¾‹.

Waldenström macroglobulinemia (WM) is characterized by lymphoplasmacytic lymphoma associated with large amounts of monoclonal immunoglobulin M (IgM) protein (Owen et al., 2003). Common signs and symptoms include fatigue due to anemia, lymph node enlargement, hepatosplenomegaly, thrombocytopenia, symptoms related to high viscosity, and peripheral neuropathy, among others. Despite significant advances in WM treatment, this type of indolent lymphoma remains incurable, with a wide array of patient outcomes (Ruan et al., 2020). In recent years, chimeric antigen receptor T (CAR-T) cell therapy targeting cluster of differentiation 19 (CD19) has shown unprecedented response rates and durability in the treatment of B-cell malignancies. In this report, we describe a challenging case of WM that involved multiple extramedullary sites, relapsed, and was refractory to chemotherapy, immunotherapy, and targeted therapy. After anti-CD19 CAR-T cell therapy, the tumor burden significantly decreased and the patient's condition remained stable at the writing of this report.

Stress granules in cancer: Adaptive dynamics and therapeutic implications.

Stress granules (SGs), membrane-less cellular organelles formed via liquid-liquid phase separation, are central to how cells adapt to various stress conditions, including endoplasmic reticulum stress, nutrient scarcity, and hypoxia. Recent studies have underscored a significant link between SGs and the process of tumorigenesis, highlighting that proteins, associated components, and signaling pathways that facilitate SG formation are often upregulated in cancer. SGs play a key role in enhancing tumor cell proliferation, invasion, and migration, while also inhibiting apoptosis, facilitating immune evasion, and driving metabolic reprogramming through multiple mechanisms. Furthermore, SGs have been identified as crucial elements in the development of resistance against chemotherapy, immunotherapy, and radiotherapy across a variety of cancer types. This review delves into the complex role of SGs in cancer development and resistance, bringing together the latest progress in the field and exploring new avenues for therapeutic intervention.

A Mystery in a Case: Unraveling the Complexity of Bing-Neel Syndrome.

Waldenström's macroglobulinemia (WM) is a B-cell non-Hodgkin's lymphoma characterized by clonal IgM-secreting lymphoplasmacytic cell proliferation. Bing-Neel syndrome (BNS) is a rare complication of WM that results in the infiltration of the central nervous system (CNS) with IgM-secreting lymphoplasmacytic cells. This case study presents a 75-year-old Caucasian male with a history of WM and Agent Orange exposure who ultimately was diagnosed with BNS. This patient posed unique diagnostic challenges as the patient experienced clinical symptoms despite the absence of MRI abnormalities and therapeutic challenges.

Prognostic factors in Chinese patients with immunoglobulin light chain amyloidosis: a scoping review and meta-analysis.

OBJECTIVE: This scoping review and meta-analysis aimed to map the evidence regarding prognostic factors in Chinese patients with immunoglobulin light chain (AL) amyloidosis and to identify current research gaps. METHODS: We searched EMBASE, PubMed, and CNKI databases from their inception to 15 September 2021. All studies investigated the association between any prognostic factor and target outcomes, including overall survival (OS), progression-free survival (PFS), and end-stage renal disease (ESRD) in Chinese patients with AL amyloidosis. RESULTS: This scoping review included 52 studies, of which 44 with 6,432 patients contributed to the multivariate prognostic analysis. Multivariate analysis identified a total of 106 factors that correlated with OS, 16 factors with PFS, and 18 factors with ESRD. Five prognostic factors were significantly associated with PFS, and 11 prognostic factors were significantly associated with ESRD. Meta-analysis was only available for prognostic factors without heterogeneous cutoff values, for which hazard ratios (HRs) and their 95% confidence intervals (CIs) were reported. Meta-analysis showed that bone marrow plasma cells (BMCs) (HR: 1.96, 95% CI: 1.21-3.19, p < 0.05) and interventricular septal thickness (IVST) (HR: 1.23, 95% CI: 1.10-1.38, p < 0.05) were independently associated with OS. CONCLUSION: The significant prognostic factors associated with OS, PFS, and ESRD in Chinese patients with AL amyloidosis were related to plasma cell tumor load, biological characteristics, cardiac involvement, renal involvement, population characteristics, and treatment. Further studies should explore additional prognostic factors in patients with AL amyloidosis to develop prognostic models.

The significant prognostic factors associated with OS, PFS, and ESRD in Chinese patients with AL amyloidosis were related to plasma cell tumor load, biological characteristics, cardiac involvement, renal involvement, population characteristics, and treatment.Meta-analysis showed there was a significant association between BMCs or interventricular septal thickness and OS.

Impact of monocytic differentiation on acute myeloid leukemia patients treated with venetoclax and hypomethylating agents.

INTRODUCTION: Although the combination of venetoclax (VEN) and hypomethylating agents (HMAs) results in impressive efficacy in acute myeloid leukemia (AML), there is still a subset of patients who are refractory. We investigated the outcomes of AML patients with monocytic differentiation who were treated with frontline VEN/HMA. METHODS: A total of 155 patients with newly diagnosed AML treated with frontline VEN/HMA were enrolled in the study. Monocyte-like AML was identified by flow cytometry with typical expression of monocytic markers, and M5 was identified according to French, American, and British category. We compared the outcomes of patients with different characteristics. RESULTS: The rate of complete remission (CR) and CR with incomplete recovery of blood counts (CRi), progression-free survival (PFS), and overall survival (OS) in monocyte-like AML were inferior to those in nonmonocyte-like AML (CR/CRi rates, 26.7% vs. 80.0%, p < 0.001; median PFS, 2.1 vs. 8.8 months, p < 0.001; median OS, 9.2 vs. 19 months, p = 0.013). CR/CRi rate in M5 was lower than that in non-M5 (60.7% vs. 75.5%, p = 0.049). Multivariate analyses showed that monocyte-like AML was associated with lower odds of CR/CRi and higher risk of progression. CONCLUSION: Our study suggested that newly diagnosed AML with a monocytic immunophenotype had a poor prognosis with VEN/HMA treatment.

TP53 and KMT2D mutations associated with worse prognosis in peripheral T-cell lymphomas.

There are limited studies on mutation profiling for Peripheral T-cell lymphomas (PTCL) in the Chinese population. We retrospectively analyzed the clinical and genetic landscape of 66 newly diagnosed Chinese patients. Targeted next-generation sequencing (NGS) was performed for tissues from these patients. At least one mutation was detected in 60 (90.9%) patients, with a median number of 3 (0-7) mutations, and 32 (48.5%) cases detected with more than 4 mutations. The genes with higher mutation frequencies were TET2, RHOA, DNMT3A, IDH2, TP53, STAT3, and KMT2D respectively. When mutant genes are classified by functional group, the most prevalent mutations are related to epigenetics and signal transduction. IPI ≥2, PIT ≥2, and failure to achieve partial remission (PR) were factors for inferior progression-free survival (PFS) and overall survival (OS). Multivariate analysis showed TP53 was an adverse factor for PFS (HR, 3.523; 95% CI, 1.262-9.835; p = 0.016), and KMT2D was an adverse factor for OS (HR, 10.097; 95% CI, 1.000-101.953; p = 0.048). Mutation profiling could help differentiate distinct types of PTCL and serve as a useful tool for determining treatment options and prognoses.

Effectiveness of postoperative superficial radiotherapy following the keloid-cross-flap surgery for auricular keloid: A prospective cohort study.

BACKGROUND AND PURPOSE: Retaining partial keloid skin to make cross flaps (keloid-cross-flap surgery) is a modification of the core excision. This study aimed to compare the effectiveness of superficial radiotherapy versus compression therapy after keloid-cross-flap surgery. MATERIALS AND METHODS: In this prospective cohort study, auricular keloid patients were consecutively screened from January 2019 to December 2021. They underwent keloid-cross-flap surgery and then enter either the superficial radiotherapy or the compression treatment group. The primary outcome was the one-year keloid recurrence rate. Secondary outcomes included: non-completion rate of adjuvant treatment; Patient and Observer Scar Assessment Scale (POSAS) scores and auricular aesthetics scores, evaluated by a four-point Likert scale (1 = poor to 4 = excellent) of non-recurring patients. Propensity score matching (PSM) was used to eliminate potential confounding factors. RESULTS: 123 patients were included in the superficial radiotherapy group and 128 in the compression treatment group. Non-completion rate was significantly higher in the compression treatment group (17.97 %), while the loss rate was comparable between the two groups. Overall, 13 patients (13.54 %) relapsed in superficial radiotherapy group, while 22 patients (25.58 %) in compression group (p < 0.05). After PSM, 59 patients in each group were analyzed, and the recurrence rate was lower in the superficial radiotherapy group (13.56 %). Of relapse-free patients, no significant difference was found in PSAS scores, OSAS scores or aesthetic scores between the two groups. CONCLUSION: Keloid-cross-flap surgery could provide favorable morphologic repair of the auricular keloid, and postoperative superficial radiotherapy shows higher compliance and lower recurrence rate comparing to compression treatment.

Translation, Cultural Adaptation and Validation of the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) in Chinese.

BACKGROUND: Rhinoplasty requires balanced consideration of function and aesthetics, necessitating a precise evaluation tool. A reliable and validated patient-reported measure, the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) evaluates both aspects but was previously unavailable in Chinese. This study fills that gap by providing a Chinese version. OBJECTIVES: This study aims to translate, culturally adapt, and validate a Chinese iteration of the SCHNOS (C-SCHNOS) for appraising the functional and aesthetic outcomes among Chinese patients post-rhinoplasty, furnishing a reliable and efficacious assessment tool for Chinese users. METHODS: Following international guidelines, the SCHNOS questionnaire was translated and culturally adapted for Chinese use. Its psychometric properties, including internal consistency, correlations, and reproducibility, were evaluated among Chinese natives in Sichuan Province from March 2022 to January 2023. RESULTS: The C-SCHNOS was administered to 110 Chinese natives, showing high internal consistency, Cronbach's α of 0.81 for SCHNOS-O (Obstructive domain), 0.92 for SCHNOS-C (Cosmetic domain). Spearman correlations for SCHNOS-O (0.36-0.65) and SCHNOS-C (0.51-0.74) were positive and significant. Test-retest reliability analyses revealed strong Spearman correlations for SCHNOS-O (r=0.87) and SCHNOS-C (r=0.90). Responsiveness was statistically significant for SCHNOS-O (P < 0.001) but not for SCHNOS-C (P=0.222). Exploratory factor analysis and parallel tests indicated that C-SCHNOS maintained a single-factor structure, with eigenvalues exceeding the critical values (2.55 for SCHNOS-O and 4.35 for SCHNOS-C), reflecting excellent unidimensionality. CONCLUSIONS: The SCHNOS questionnaire was successfully translated into Chinese and culturally adapted. The C-SCHNOS is a dependable and valid instrument for use in Chinese population undergoing functional or cosmetic rhinoplasty.

Impact of additional cytogenetic aberrations at diagnosis on prognosis of adults patients with Philadelphia chromosome positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation: a retrospective analysis.

Additional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myeloid leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph + ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred thirty-six adult patients with Ph + ALL were included in the study and retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. ACAs are observed in 60 cases (44%). ACAs detected in more than 5% of cases were defined as major-route and encompass: +der(22), +der(9), + 8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in + 8[66.7% vs.23.7%, P = 0.024; 77.8% vs. 23.7%, P = 0.0087], -7[53.8% vs. 23.7%, P = 0.035%; 61.5% vs. 32.9%, P = 0.033], and complex karyotypes[42.9% vs. 23.7%, P = 0.027; 47.6% vs. 23.7%] compared with t(9;22) sole. Additionally, the 3-year CIR for Ph + ALL with + der(22) is 44% vs. 23.7% for t(9;22) sole(P = 0.045). The 3-year overall survival (OS) in the - 7 group is 46.5%, which is statistically significant compared with the other groups(P = 0.001). In multivariate analyses, three years CIR and PFS are statistically significant in + der(22), + 8, -7 and complex karyotype compared with t(9;22) sole(P < 0.05). More importantly, Ph + ALL with - 7 was negatively associated with the rate of 3-year OS(P = 0.012). Thus, ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL.

Disruption of DNA-PKcs-mediated cGAS retention on damaged chromatin potentiates DNA damage-inducing agent-induced anti-multiple myeloma activity.

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.

Guillain-Barr Syndrome Caused by Cytomegalovirus after Multiple Myeloma Treatment.

BACKGROUND: Both humoral and cell-mediated immunity of the patient affected by multiple myeloma (MM) are impaired; thus, infection is the main cause of the onset of symptoms and death caused by MM. Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barre syndrome (GBS) is thought to be related to immune damage, and most patients have cytomegalovirus (CMV), Epstein-Barr virus (EBV), or mycoplasma infection before onset. Cases of GBS secondary to MM are rare. METHODS: We provide a case of GBS caused by cytomegalovirus infection after MM treatment, and briefly review the existing literature. RESULTS: Secondary GBS after MM. This patient received active treatment. The clinical symptoms are gradually improving. CONCLUSIONS: The use of bortezomib has the risk of reactivating the virus. It is more about the reactivation of hep-atitis B virus. Nonetheless, cytomegalovirus and Epstein-Barr virus shall have our attention. Patients with MM need to monitor CMV, regularly, especially during the treatment of bortezomib. At the same time, they also need to closely monitor the symptoms and signs of the nervous system to guard against the occurrence of GBS.

Impact of p-cresol on hydrogen sulfide and ammonia treatment by biotrickling filter and the production of nitrous oxide.

Biotrickling filter (BTF) is often used for purification of waste gas from swine houses, with vital information still needed regarding interaction effects among multiple gas pollutants removal and also the formation of byproducts especially nitrous oxide (N2O, a strong greenhouse gas) due to the relative high NH3 concentration level compared to other gases. In this study, gas removal and N2O production were compared between two BTFs, where the inlet gas of BTF-1 contained NH3 and H2S while p-cresol was additionally supplied to BTF-2. At inlet load (IL) between 3.67 and 18.91 g m-3 h-1, removal efficiencies of NH3 exceeded 95% for both BTFs. As alternative strategy, adding thiosulfate improved H2S removal. Interestingly, presence of p-cresol to some extent promoted H2S removal at IL of 0.56 g m-3 h-1possibly due to effect on pH value of circulating solution. Similar to NH3, removal efficiencies of p-cresol were higher than 95% at an average IL of 2.98 g m-3 h-1. Gas residence time, pH of circulating solution and inlet loading were identified as key factors affecting BTF performance, but the response of individual gas compound to these factors was not consistent. Overall, p-cresol enhanced N2O generation although the effects were not always significant. High-throughput sequencing results showed that Proteobacteria accounted for the largest proportion of relative abundance and BTF-2 had much richer microbial diversity compared to BTF-1. Thermomonas, Comamonas, Rhodanobacter and other bacterial genus capable of denitrification were detected in both BTFs, and their corresponding abundances in BTF-2 (10.9%, 8.7% and 5.2%) were all greater than those in BTF-1 (0.4%, 0.3% and 2.0%), indicating that more denitrification may occur within BTF-2 and higher N2O could have been generated. This study provided evidence that organic gas components, served as carbon source, may increase the N2O production from BTF when treating waste gases containing NH3.

Simultaneous removal of ammonia and sulfur odorants in biotrickling filters and N2O production.

Research on the stability evaluation of biotrickling filters (BTFs) under harsh conditions and the bacterial adaptation process still needs to be improved. Herein, BTFs with polypropylene plastic (PP) and ceramic raschig rings (CRR) were investigated for a better understanding of the biodegradation of ammonia (NH3), hydrogen sulfide (H2S), and dimethyl sulfide (DMS). The results showed an excellent performance in removal efficiency (RE) for NH3 (91.6 %-99.9 %), H2S (RE: 55.3 %-99.5 %), and DMS (RE: 10.6 %-99.9 %). It was found that a more apparent positive correlation between N2O emission and pressure drop in CRR BTF (R2 = 0.92) than in PP BTF (R2 = 0.79) (P < 0.01). Low temperature promotes an increase in the abundance ofComamonasandBacillus. The polysaccharides in PP and CRR reactors decreased by 78.6 % and 68.1 % when temperature reduced from 25℃ to 8℃. This work provides a novel insight into understanding bacterial survival under harsh BTF environments.

Clinical outcomes of pomalidomide-based and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma: A real-world cohort study in China.

BACKGROUND: Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. METHODS: This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. RESULTS: The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009). CONCLUSIONS: In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.

Surgical treatment outcomes of acetabular posterior wall and posterior column fractures using 3D printing technology and individualized custom-made metal plates: a retrospective study.

BACKGROUND: Fractures involving the posterior acetabulum with its rich vascular and neural supply present challenges in trauma orthopedics. This study evaluates the effectiveness of 3D printing technology with the use of custom-made metal plates in the treatment of posterior wall and column acetabular fractures. METHODS: A retrospective analysis included 31 patients undergoing surgical fixation for posterior wall and column fractures of the acetabulum (16 in the 3D printing group, utilizing 3D printing for a 1:1 pelvic model and custom-made plates based on preoperative simulation; 15 in the traditional group, using conventional methods). Surgical and instrument operation times, intraoperative fluoroscopy frequency, intraoperative blood loss, fracture reduction quality, fracture healing time, preoperative and 12-month postoperative pain scores (Numeric Rating Scale, NRS), hip joint function at 6 and 12 months (Harris scores), and complications were compared. RESULTS: The surgical and instrument operation times were significantly shorter in the 3D printing group (p < 0.001). The 3D printing group exhibited significantly lower intraoperative fluoroscopy frequency and blood loss (p = 0.001 and p < 0.001, respectively). No significant differences were observed between the two groups in terms of fracture reduction quality, fracture healing time, preoperative pain scores (NRS scores), and 6-month hip joint function (Harris scores) (p > 0.05). However, at 12 months, hip joint function and pain scores were significantly better in the 3D printing group (p < 0.05). Although the incidence of complications was lower in the 3D printing group (18.8% vs. 33.3%), the difference did not reach statistical significance (p = 0.433). CONCLUSION: Combining 3D printing with individualized custom-made metal plates for acetabular posterior wall and column fractures reduces surgery and instrument time, minimizes intraoperative procedures and blood loss, enhancing long-term hip joint function recovery. CLINICAL TRIAL REGISTRATION: 12/04/2023;Trial Registration No. ChiCTR2300070438; http://www.chictr.org.cn .

Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma.

PURPOSE: To explore the prognostic and therapeutic role of Epstein-Barr Virus (EBV) on peripheral T-cell lymphoma (PTCL). METHODS: Totally 262 newly diagnosed PTCL patients who were hospitalized from January 2014 to December 2022 were retrospectively enrolled. Molecular analysis included 31 eligible patients. EBV-encoded RNA (EBER) presence in tumor tissue and EBV DNA levels in patients at baseline (DNA1) and after 4 cycles of chemotherapy (DNA4) were assessed. RESULTS: Our findings revealed that the EBER-positive cohort exhibited significant differences compared to counterparts in overall survival (OS, P = 0.047) and progression-free survival (PFS, P = 0.009). Both DNA1 and DNA4 were significantly associated with inferior OS. Multivariate analysis demonstrated that DNA4 independently affected PTCL prognosis for OS (hazard ratio = 5.1617; 95% confidence interval 1.1017-24.1831; P = 0.037). Treatment with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus azacytidine regimen showed a better OS compared to CHOP or CHOP plus etoposide for patients with partially positive EBER and EBER positive statuses (P = 0.192), although the improvement was not statistically significant. This study delineated the genetic paradigm of PTCL, comparing genetic differences by EBV status and found that EBER partially positive plus positive patients were more likely to have DNMT3A (P = 0.002), RHOAG17V (P = 0.023), and TET2 mutations (P = 0.032). CONCLUSION: EBER, DNA1, and DNA4 emerged as sensitive markers for prognosis. CHOP plus azacytidine might present a preferable option for PTCL patients with DNA methylation due to EBV infection.

Evaluation of the association between glutathione S-transferase polymorphisms and susceptibility to cutaneous melanoma: a systematic review and meta-analysis.

Introduction: Glutathione S-transferase (GST) enzymes play a crucial role in detoxification by catalysing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Polymorphisms in GST genes may influence the susceptibility to various cancers, including melanoma. Aim: We reported a systematic review and meta-analysis to evaluate the association between GST polymorphisms and susceptibility to cutaneous melanoma. Material and methods: A comprehensive search of four databases, namely PubMed, Scopus, Cochrane Library, and Web of Science, was conducted to gather pertinent studies up until 24 August 2023. No restrictions were imposed during the search. The analysis included 32 studies and was broken down into subgroups based on ethnicity, control source, control matching, quality score, and sample size. Results: The forest plot analyses on GSTM1, GSTT1, combined GSTM1/GSTT1, and GSTP1 polymorphisms in relation to melanoma risk showed no statistically significant differences between the case and control groups, except for the recessive model of GSTP1 polymorphism. The analysis revealed significant associations between GSTM1 polymorphisms and melanoma risk in Asians and in studies with a sample size of less than 200. For the combined GSTM1/GSTT1 polymorphisms, a significant association was found in hospital-based controls. Conclusions: While this study enhances our understanding of the genetic factors influencing melanoma risk, it also highlights the need for further research. The current evidence is not sufficient to confirm or reject the intervention effect. Future research should consider gene-gene and gene-environment interactions, which could offer a more comprehensive understanding of the complex biology of melanoma.

The ratio of serum urea nitrogen to albumin is a better predictor of OS in MM patients than urea nitrogen alone.

Introduction Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analysed MM patients' clinical data to explore the role of sUN and serum urea nitrogen/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients. Methods We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate adjusted Cox regression analysis, Kaplan‒Meier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study. Results There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with ß2-microglobulin (ß2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with OS, although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. ß2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost ß2-MG and LDH's predictive value and sUAR had a higher predictive value. Conclusion This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with ß2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.

Personalized Federated Graph Learning on Non-IID Electronic Health Records.

Understanding the latent disease patterns embedded in electronic health records (EHRs) is crucial for making precise and proactive healthcare decisions. Federated graph learning-based methods are commonly employed to extract complex disease patterns from the distributed EHRs without sharing the client-side raw data. However, the intrinsic characteristics of the distributed EHRs are typically non-independent and identically distributed (Non-IID), significantly bringing challenges related to data imbalance and leading to a notable decrease in the effectiveness of making healthcare decisions derived from the global model. To address these challenges, we introduce a novel personalized federated learning framework named PEARL, which is designed for disease prediction on Non-IID EHRs. Specifically, PEARL incorporates disease diagnostic code attention and admission record attention to extract patient embeddings from all EHRs. Then, PEARL integrates self-supervised learning into a federated learning framework to train a global model for hierarchical disease prediction. To improve the performance of the client model, we further introduce a fine-tuning scheme to personalize the global model using local EHRs. During the global model updating process, a differential privacy (DP) scheme is implemented, providing a high-level privacy guarantee. Extensive experiments conducted on the real-world MIMIC-III dataset validate the effectiveness of PEARL, demonstrating competitive results when compared with baselines.