AIM:The effect of treatment response to anticoagulant therapy on prognosis of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear. METHODS:Forty-one patients with cirrhosis and first PVT treated with intravenous anticoagulant therapy between January 2015 and April 2018 at 10 Japanese hospitals were included. Treatment response was defined based on change in size of PVT after anticoagulant therapy as the following: complete response (CR, 0%), partial response (PR, ≤ 50%), stable disease (SD, 51%-100%), and progressive disease (PD, ≥ 101%). CR and PR were combined as the effective group and SD and PD formed as the ineffective group. RESULTS:The median age was 69 years, and 56% of the patients had Child-Pugh class B. Overall, 5 (12%) achieved CR, 22 (54%) achieved PR, 12 (29%) had SD and 2 (5%) had PD. During a median follow-up of 31.8 months from the date of assessment of treatment response, 17 patients died. The overall survival rates at 1- and 3-year were 82.5% and 65.1%, respectively. In the multivariate analysis, the model for end-stage liver disease-Na score was significantly associated with overall survival, whereas treatment response was not significant. Twenty-five patients experienced liver-related events with hospitalization, and the 3-year cumulative rate of liver-related events was 63.9%. In the multivariate analysis, treatment response was significantly associated with liver-related events. The 3-year cumulative rates of liver-related events were 56.7% and 75.5% in the effective and ineffective groups, respectively (p = 0.008). CONCLUSIONS:Among patients with cirrhosis, treatment response to anticoagulant therapy for PVT correlated with the incidence of liver-related hospitalization events.
Abstract Introduction: In RRMM, increasing rates of pt attrition and decreasing durability of responses with each line of therapy (LOT) necessitate early treatment (tx) with the most effective therapies. Immunotherapies that are widely accessible across different MM tx settings have the potential to change the trajectory of RRMM. Teclistamab (Tec), the first approved BCMA×CD3 bispecific antibody (BsAb) for heavily pretreated RRMM, provided deep, durable responses in MajesTEC-1, with improved efficacy and safety in earlier LOTs. Daratumumab (Dara), a standard-of-care (SoC) foundational CD38 targeted therapy with direct on-tumor activity, has been shown to deplete immunosuppressive T-cells and expand cytotoxic T-cells, creating an immune-permissive microenvironment for synergistic Tec-mediated killing of MM cells. MajesTEC-3 (NCT05083169) evaluates Tec-Dara vs SoC DPd/DVd in RRMM. We report initial results for this first phase 3 study of BsAb therapy in MM. Methods: Eligible pts had 1-3 prior LOTs including a PI and lenalidomide (Len; pts with 1 prior LOT must have been Len-refractory) with progressive disease (PD) on or after the last LOT. Pts with prior BCMA-directed therapy or refractory to anti-CD38 were excluded; prior anti-CD38 exposure was permitted. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. The Tec-Dara group received 28-day cycles (C) of Tec (1.5 mg/kg QW in C1-2 [C1 preceded by the approved step-up dose schedule]; 3 mg/kg Q2W in C3-6; and 3 mg/kg Q4W in C7+) with Dara; steroids were not required after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. Progression-free survival (PFS) by IRC was the primary endpoint; secondary endpoints included complete response or better (≥CR), overall response, minimal residual disease (MRD) negativity (10–5; next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety. Results: 587 pts were randomized (Tec-Dara, n=291; DPd/DVd, n=296). Median (range) age was 64 (25-88) yrs, median number of prior LOTs was 2 (1-3). With 34.5-mo median follow-up, Tec-Dara significantly improved PFS vs DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P<0.0001); mPFS was NR and 18.1 mo, and 36-mo PFS rate was 83.4% and 29.7%, respectively. PFS benefit was consistent across all prespecified and clinically relevant pt subgroups, including age ≥75 yrs, Len-refractory, high-risk cytogenetics, ≥60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposed. Significantly higher rates of ≥CR (81.8% vs 32.1%; OR, 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68-4.18), and MRD-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53-10.15) were observed with Tec-Dara (P<0.0001). There were 45 deaths with Tec-Dara and 96 with DPd/DVd, primarily due to PD (4.6%; 20.3%). OS significantly favored Tec-Dara (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001), including across all prespecified subgroups. The 36-mo OS rates were 83.3% and 65.0%, respectively and >90% of Tec-Dara pts alive at 6 mo were also alive at 30 mo. Median time to worsening of MM symptoms was NR with Tec-Dara vs 39.9 mo with DPd/DVd (HR, 0.50; 95% CI, 0.34-0.72; P=0.0002). At data cutoff, 49.4% of pts remained on study tx (Tec-Dara, 71.0%; DPd/DVd, 28.3%). Median tx duration was twice as long with Tec-Dara vs DPd/DVd (32.4 vs 16.1 mo). Frequency of grade 3/4 (Tec-Dara, 95.1%; DPd/DVd, 96.6%) and grade 5 (7.8%; 6.2%) treatment-emergent adverse events (TEAEs), were comparable (safety set: Tec-Dara, n=283; DPd/DVd, n=290). Serious TEAEs occurred in 70.7% Tec-Dara and 62.4% DPd/DVd pts; tx discontinuations due to TEAEs were low (4.6% vs 5.5%). Any grade infections occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd pts, respectively; grade 3/4 infections occurred in 54.1% and 43.4%. New onset grade ≥3 infections decreased over time, coinciding with transition to Q4W dosing and supported by antimicrobial and Ig prophylaxis guidance. CRS rate was 60.1% (grade 1/2: 44.2%/15.9%) and ICANS was 1.1% with Tec-Dara. Conclusion: We demonstrate the clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs. Infections with Tec-Dara were well managed with established protocols. This highly effective, off-the-shelf, immunotherapy combination represents a new SoC for RRMM as early as first relapse.
The patient was a woman in her 60s. Contrast-enhanced CT revealed a large, heterogeneously enhancing mass centered beneath the left diaphragm. A biopsy confirmed the diagnosis as gastric gastrointestinal stromal tumor (GIST), classified as cT4, N0, M1, clinical Stage Ⅳ. Treatment with imatinib at 400 mg/day was initiated. After 8 months the tumor appeared to shrink, and a PET scan was performed. The PET scan revealed localized FDG uptake in the ileocecal region only. Further investigation led to a diagnosis of colon cancer. With the possibility of resistance to treatment, surgical resection was planned together with ileo-cecal resection for colon cancer. Laparoscopy-assisted local gastrectomy, tumor resection combined splenectomy, and peritoneal nodules resection with omentectomy were performed. After surgery, patient continued imatinib again, and is alive without progression.
Sodium–glucose co-transporter 2 inhibitors (SGLT2i) have become essential in the management of heart failure. Their prognostic benefits are consistent across older adults, frail, and underweight patients, but there may be potential adverse effects on the skeletal muscle. In this prospective single-centre observational study, 117 patients with stable congestive heart failure received 10 mg of empagliflozin daily between February 2023 and October 2024. At baseline and again after 6 months, we measured the following nutritional, frailty, and quality-of-life indices (GNRI, CONUT, mini nutritional assessment (MNA), KCCQ-12, Barthel index, clinical frailty scale) and urinary titin N-fragment (U-titin), a biomarker of skeletal muscle degradation. After exclusion, 93 patients (median age 79 years; 40
The Sequential Organ Failure Assessment (SOFA)-2 score was developed to better reflect contemporary critical care practice by incorporating modern organ support modalities and updated thresholds based on recent data. However, the generalizability of this framework to intensive care unit (ICU) populations beyond the development cohort, particularly across organ support subgroups and major disease categories, remains uncertain. We aimed to evaluate the external validity of SOFA-2 using the OneICU database, a large Japanese critical care database with comprehensive domain-level data. Adult ICU stays between February 2013 and August 2025 were included and classified into two cohorts: those with complete SOFA-1 and SOFA-2 component data on the day of ICU admission, and those with complete SOFA-2 data on that day. Discriminatory performance for ICU mortality was evaluated using the area under the receiver operating characteristic curve (AUROC) and compared between SOFA-1 and SOFA-2 using the DeLong test. Subgroup analyses were performed by major organ support device use and across disease categories. Among 152,883 eligible ICU stays, 67,116 had complete SOFA-1 and SOFA-2 data, and 121,443 had complete SOFA-2 data. SOFA-2 showed a slightly higher AUROC for ICU mortality than SOFA-1 (0.859 vs. 0.853; p < 0.001), although the absolute difference was small. Across subgroups defined by mechanical circulatory support use, SOFA-2 showed higher discrimination than SOFA-1. Discrimination was similar in other device-defined subgroups and in patients readmitted to the ICU. SOFA-2 also demonstrated good discrimination across major diagnostic groups. SOFA-2 showed similar discrimination for ICU mortality compared with SOFA-1 and maintained broadly comparable performance across clinically relevant subgroups, supporting its applicability for early severity assessment in heterogeneous ICU populations.
