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Medscape
6 hours ago
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- Medscape
Adjuvant Triple Therapy Boosts Survival in Biliary Cancers
TOPLINE: Camrelizumab plus concurrent capecitabine and radiotherapy (combination treatment) improved overall survival (OS) and recurrence-free survival in patients with resectable extrahepatic cholangiocarcinoma (EHC) and gallbladder cancer. METHODOLOGY: Patients with EHC and gallbladder cancer have a high recurrence rate and poor survival after surgery. Existing adjuvant therapies provide limited benefit, underscoring the need for novel treatment combinations. This multicenter, randomized clinical trial investigated the safety and efficacy of chemoradiation with anti-PD-1 immunotherapy in these patients. A total of 93 patients with histologically confirmed EHC or gallbladder cancer (median age, 62 years; 52% women) who underwent curative resection with stage pT2-4 or N1M0 disease were randomly assigned to either the combination treatment group (n = 46) or the observation group (no anticancer treatment unless relapse was detected; n = 47). Those in the combination treatment group received 200 mg camrelizumab intravenously every 3 weeks, followed by concurrent 1330 mg/m 2 oral capecitabine twice daily with radiotherapy (45 Gy in 25 fractions for lymph nodes and 52.5-55.0 Gy for tumor beds). oral capecitabine twice daily with radiotherapy (45 Gy in 25 fractions for lymph nodes and 52.5-55.0 Gy for tumor beds). The primary endpoint was OS, and secondary endpoints were recurrence-free survival and adverse events (AEs). The median follow-up duration was 36 months. TAKEAWAY: The combination treatment significantly improved OS (hazard ratio [HR], 0.43; P = .004), with 3-year OS rate of 58.2% vs 30.5% in the observation group. The median recurrence-free survival was longer in the combination treatment group than in the observation group (26 months vs 13 months; HR, 0.46; P < .001), with the 3-year recurrence-free survival rate of 40.3% vs 17.2%. No treatment-related deaths were observed. The most common severe AEs of grade 3 or 4 were anemia (15%), radiation-associated dermatitis (11%), nausea (11%), and hand-foot syndrome (4%) in the combination group and anemia (4%), fatigue (4%), and neutropenia (4%) in the observation group. Subgroup analyses suggested patients with EHC vs gallbladder cancer and those with an Eastern Cooperative Oncology Group score of 0 and tumors ≤ 5 cm were more likely to benefit from the combination treatment. IN PRACTICE: 'We congratulate the authors for conducting and reporting an important clinical trial that moves the field forward. Considering the current level of evidence used to guide patient management after resection, we suspect this regimen may be adopted into practice even prior to the conduct of a phase 3 trial,' Edgar Ben-Josef, MD, University of Pennsylvania, Philadelphia, wrote, in an invited commentary on the new research published in JAMA Oncology. 'However, we would caution that this study should be viewed not as an ending but as a building block toward studies that demonstrate an even greater level of confidence [in] more effective adjuvant regimens for patients with biliary cancers. SOURCE: The study, led by Han Xiao, MD, The First Affiliated Hospital of Sun Yat-sen University in Guangzhou, China, was published online in JAMA Oncology. LIMITATIONS: This study was only conducted on Chinese patients, limiting generalizability to Western populations. Although the study met the predefined 2-year follow-up for all patients, both groups showed better-than-expected OS rates, resulting in fewer endpoint events than anticipated. Additionally, the open-label design and the combination of multiple treatments might have confounded efficacy assessment for each treatment component. DISCLOSURES: This study received project grants from the National Natural Science Foundation of China and the Science and Technology Program of Guangzhou. The authors reported having no relevant conflicts of interest. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
a day ago
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- Medscape
Urinalysis Patterns Help Spot Enterococcal UTIs in the ED
TOPLINE: A combination of a positive leukocyte esterase result and a negative nitrite result on urinalysis was associated with a sevenfold higher likelihood of Enterococcus-associated urinary tract infection (UTI) in emergency department (ED) patients. METHODOLOGY: Researchers conducted a secondary analysis of the multicenter UNTRIED study, which included 1836 patients (median age, 67 years) diagnosed with UTI in the ED. Patients were included if they had a monomicrobial positive urine culture and were excluded if their culture was negative, was polymicrobial, contained unidentified bacterial species, or was positive for Staphylococcus species. The primary outcome was a urinalysis showing a positive result for leukocyte esterase and a negative result for nitrite, along with predefined risk factors such as older age, male sex, recent antibiotic use, comorbidities, and urinary tract abnormalities. TAKEAWAY: Only 5% of the included patients had positive urine cultures for Enterococcus species, whereas the majority (70%) had Escherichia coli infections. A urinalysis showing a positive result for leukocyte esterase and a negative result for nitrite was strongly associated with Enterococcus-positive cultures (adjusted odds ratio [aOR], 7.09; 95% CI, 3.73-13.47). Independent risk factors for Enterococcus infection included age 65 years or older (aOR, 1.92; 95% CI, 1.18-3.13), male sex (aOR, 1.77; 95% CI, 1.11-2.81), and antibiotic use in the past 90 days (aOR, 2.01; 95% CI, 1.28-3.15). IN PRACTICE: "This secondary analysis of the UNTRIED study indicates that adult patients who were ultimately diagnosed with Enterococcus-associated UTIs in the ED were seven times more likely to show a combination of positive leukocyte esterase and negative nitrite on urinalysis," the authors wrote. "This work should be used to inform future risk stratification to optimize empiric antibiotic selection in ED patients diagnosed with UTI," they added. SOURCE: The study was led by Anne E. Zepeski, Department of Emergency Medicine, University of Iowa Carver College of Medicine, Iowa City. It was published online on June 24, 2025, in the American Journal of Emergency Medicine. LIMITATIONS: The observational and retrospective nature of the study limited the ability to establish causal relationships. Variability in testing practices among participating hospitals affected the detection of Enterococcus infection. Laboratory practices varied across sites, potentially affecting nitrite and culture results. DISCLOSURES: The authors declared no funding or conflicts of interest. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
30-06-2025
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- Medscape
Golimumab Boosts Remission Rates in AxSpA
TOPLINE: Most patients with early, active axial spondyloarthritis (axSpA) achieved remission in a tight control treatment with golimumab, regardless of gut inflammation, in a small, single-arm study. METHODOLOGY: Researchers conducted a multicenter trial to evaluate the effectiveness of a tight control strategy with rapid escalation to TNF inhibition in early, active axSpA in relation to gut inflammation. They included 58 patients (mean age, 28.2 years; 41.4% women) who had an Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) ≥ 2.1 and less than 1 year of symptom duration. Patients took two different nonsteroidal anti-inflammatory drugs (NSAIDs) for 4 weeks and 50 mg golimumab every 4 weeks if needed to achieve inactive disease (ASDAS-CRP < 1.3) or improvement. The primary endpoint was the proportion of patients achieving sustained clinical remission (ASDAS-CRP < 1.3), determined at two consecutive visits with a 12-week interval. TAKEAWAY: Overall, 61.8% of patients achieved sustained clinical remission. Of the 72.7% who needed escalation to golimumab, 55% achieved sustained clinical remission. Microscopic gut inflammation was present in 28.6% of patients and was not predictive of achieving clinical remission (odds ratio, 1.50; 95% CI, 0.39-6.49). Relapse within 1 year occurred in 78.1% of patients who stopped treatment. Those who achieved sustained clinical remission with NSAIDs and golimumab had relapse rates of 91.7% and 70%, respectively. Male sex, no history of smoking, and lower disease activity were identified as predictors of sustained remission. IN PRACTICE: 'Our trial demonstrated that sustained inactive disease state is an achievable therapeutic goal in early axSpA,' the study authors wrote. SOURCE: This study was led by Zuzanna Łukasik, MD, and Ann-Sophie De Craemer, MD, PhD, Gent University Hospital, Gent, Belgium. It was published online on June 16, 2025, in Arthritis & Rheumatology. LIMITATIONS: A key challenge of the trial was recruiting patients with axSpA within the first year of symptom onset, resulting in a high screening failure rate. Additionally, repeated ileocolonoscopy at remission was performed in only a minority of patients, which limited analysis of the relationship between axial symptoms and gut inflammation. DISCLOSURES: This study received funding through a research grant from the Investigator Initiated Studies Program of Merck Sharp & Dohme Corp. Two authors reported receiving educational and research grants or personal fees from Merck Sharp & Dohme. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
12-06-2025
- Health
- Medscape
Dotinurad Lowers Urate More Effectively Than Febuxostat
Dotinurad 4 mg/d was superior to febuxostat 40 mg/d in achieving target serum urate levels (≤ 6.0 mg/dL) at week 24 in patients with gout, with both the drugs showing comparable safety profiles. METHODOLOGY: Researchers conducted a multicenter phase 3 trial to compare the efficacy and safety of dotinurad with febuxostat in Chinese patients with gout. They included 441 patients (mean age, 39.1 years; 1.8% women) with gout who were randomly assigned to receive either oral dotinurad (2 mg/d for 8 weeks, followed by 4 mg/d for 12 weeks) or febuxostat (40 mg/d for 20 weeks). The primary endpoint was the responder rate, defined as the proportion of patients achieving serum urate levels ≤ 6.0 mg/dL at week 24. Secondary outcomes included the responder rate at week 12, the mean percent reduction from baseline in serum urate levels, and the mean change from baseline in serum urate levels at week 4 through week 24. TAKEAWAY: At week 24, the responder rate was significantly higher for dotinurad 4 mg/d than for febuxostat 40 mg/d (73.6% vs 38.1%; adjusted difference, 35.9%; P < .0001). < .0001). At week 12, dotinurad 2 mg/d was noninferior to febuxostat 40 mg/d in terms of the responder rate (55.5% vs 50.5%; treatment difference, 5.2%; 95% CI, -3.7% to 14.2%). The mean percent reduction in serum urate levels from baseline at week 24 was higher in the dotinurad group than in the febuxostat group (45.9% vs 30.6%). The overall incidence of treatment-emergent adverse events (TEAEs) was comparable between the dotinurad and febuxostat groups, with low incidences of severe and serious TEAEs. IN PRACTICE: 'Dotinurad may offer a new urate-lowering treatment option to Chinese patients with gout as it demonstrated both efficacy and a good safety profile overall,' the authors wrote. SOURCE: This study was led by Jia Sun, MD, Zhujiang Hospital of Southern Medical University, Guangzhou, and Yu Wang, MD, PhD, Peking University First Hospital, Beijing, both in China. It was published online on May 26, 2025, in Arthritis & Rheumatology . LIMITATIONS: The relatively short study duration limited the assessment of long-term effects on gout flare recurrence. This study population was predominantly younger men, limiting generalizability across broader demographic groups. Lastly, this study was conducted only in Chinese patients with gout. DISCLOSURES: This research was funded by Eisai Co., Ltd. Four authors declared being employees of Eisai China or Eisai Co., Ltd, and others reported receiving honoraria from Eisai.
Medscape
06-06-2025
- Health
- Medscape
‘Enormous Burden' Cataloged in Relapsing Polychondritis
A large multicenter prospective cohort study has expanded 'the understanding of the range of manifestations of disease in patients with relapsing polychondritis [RP]' — particularly involving the ear, nose, throat, and musculoskeletal systems — as well as a high prevalence of organ damage, near-universal use of glucocorticoids, and frequent use of additional nonbiologic or biologic immunomodulatory therapies. METHODOLOGY: Researchers conducted a multicenter cohort study between 2017 and 2023 to evaluate clinical manifestations, treatment approaches, and the association between them in 195 patients with RP (median age, 48 years; 85.6% women). A diagnosis of RP was confirmed using comprehensive laboratory, radiographic, and other tests; all participants tested negative for proteinase 3 and myeloperoxidase. Data on clinical manifestations, organ damage, and medication history were collected at baseline study visits using standardized case report forms. Patients were grouped by treatment: Group 1 received glucocorticoids or no drugs, group 2 received nonbiologic immunosuppressive drugs (excluding JAK inhibitors) with or without glucocorticoids, and group 3 received JAK inhibitors or biologic drugs with or without nonbiologic immunosuppressives or glucocorticoids. TAKEAWAY: All patients presented with at least three clinical manifestations of RP, with a median of 11 manifestations per patient; all showed ear, nose, or airway involvement, and 83% had musculoskeletal manifestations. A substantial portion of patients (41%) developed organ damage, including sensorineural hearing loss (25%), auricular and saddle nose deformities (12% each), and subglottic stenosis (9%); among those who underwent dynamic CT of the chest, 31% had tracheomalacia, and 20% had bronchomalacia. Treatment groups 1, 2, and 3 comprised 19%, 28%, and 53% of patients, respectively; most patients (95%) received glucocorticoids, and a substantial proportion (81%) received additional immunomodulatory treatments. Patients in treatment group 3 had the highest rate of organ damage (62% vs 22% in group 2 and 15% in group 1) and were more likely to have arthritis and stenosis, whereas those in group 1 were less likely to experience nose pain. IN PRACTICE: 'Standardized assessment of disease activity is warranted for patients with RP for early detection and timely initiation of treatment. These findings also highlight the absence of a consensus approach to treatment for patients with RP and underscore the need for clinical trials and treatment guidelines in this disease to help reduce the enormous burden of disease for patients,' the authors wrote. SOURCE: This study was led by Roger Yang, MD, University of Pennsylvania, Philadelphia, and University of Montreal, Montreal, Quebec, Canada. It was published online on May 20, 2025, in ACR Open Rheumatology . LIMITATIONS: This study did not capture data on dose and duration of immunomodulatory medications or clinical features at treatment decisions. Treatment choices were made independently by clinicians and may have been influenced by factors such as drug availability or insurance, introducing variability. Moreover, the academic referral setting may have contributed to selection bias. DISCLOSURES: Two authors reported receiving support from the Vasculitis Clinical Research Consortium, Association des médecins rhumatologues du Québec, Institute for Translational Medicine and Therapeutics, and other sources. This research was also supported by the Relapsing Polychondritis Foundation and other generous donors to the Penn Relapsing Polychondritis Program.
