Abstract We analyzed the impact of the diagnosis-to-treatment interval (DTI) on survival in patients with CD5-positive diffuse large B-cell lymphoma (CD5 + DLBCL), using a data set of newly diagnosed patients. Among the 336 eligible patients, 247 (74%) received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), and 89 (26%) were treated with dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The median DTI was 18 days (range 0–118). The short DTI (≤ 14 days) group included 135 patients (40%), and the long DTI (> 14 days) group included 201 patients (60%). Compared with the long DTI group, the short DTI group had more aggressive disease characteristics. Both the progression-free survival (PFS) (P = 0.01) and the overall survival (OS) (P < 0.01) were significantly inferior in the short DTI group compared with those in the long DTI group. Among 89 patients who received DA-EPOCH-R, no significant differences in PFS (P = 0.92) or OS (P = 0.86) were observed between the two groups. Multivariate analysis revealed that no DA-EPOCH-R was a risk factor for PFS in the short DTI group (P = 0.06). A short DTI was a negative prognostic factor in our CD5 + DLBCL cohort. DA-EPOCH-R could be considered a potential treatment option for patients with a short DTI.
We thank Dr. Shah for his insightful commentary on our report identifying reduced perfusion pressure (PP) as a predictor of protein-losing enteropathy (PLE) after the Fontan procedure. We agree that PP is an indirect marker and that Fontan-associated PLE is multifactorial, with gut dysbiosis among its contributors. We propose, however, that these downstream changes share a common upstream origin-the chronic hemodynamic burden of the Fontan circulation-and outline an integrated, multidisciplinary approach to clarifying the mechanisms of PLE.
OBJECTIVE:Evaluate long-term efficacy, safety, and tolerability of once-weekly somapacitan, a long-acting growth hormone (GH) derivative, in children born small for gestational age (SGA) with short stature, including after switching from daily GH. DESIGN:REAL5 (NCT03878446) is a global, randomized, open-label, controlled phase 2 study comprising a 26-week main phase, 26-week extension I, and an ongoing 4-year extension II. METHODS:Sixty-two children born SGA with short stature were recruited at 38 clinics across 12 countries and randomized (1:1:1:1:1) to somapacitan (0.16, 0.20, or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day) until week 52 (inclusive main phase and extension I). Sixty participants entered extension II. Forty-eight participants switched to somapacitan 0.24 mg/kg/week from cohorts randomized to daily GH or lower somapacitan doses. Fifty-five children completed 208 weeks of treatment. Novel safety and efficacy results from week 52 to 208 are presented here. RESULTS:Across all treatment arms, continuous increases in height standard deviation scores were observed from week 52 to week 208, including after switch to somapacitan 0.24 mg/kg/week. The safety and tolerability profile for somapacitan 0.24 mg/kg/week was similar to the well-established safety and tolerability profile for daily GH in SGA. Patient preference questionnaire results indicate that most respondents (87%) prefer somapacitan over daily GH. Most respondents (80%) answered that they expect to be more adherent to treatment with somapacitan. CONCLUSIONS:These results support long-term continuous efficacy, safety, and tolerability of GH therapy with somapacitan 0.24 mg/kg/week for up to 4 years in children born SGA, including after switching from daily GH. CLINICALTRIALS.GOV:NCT03878446.
ABSTRACT Background Although prophylactic broad‐spectrum antibiotics can reduce postoperative complications after pancreaticoduodenectomy (PD), the optimal regimen remains uncertain. This study evaluated the impact of prophylactic cefepime (CFPM) on surgical site infection (SSI) and severe morbidity after PD with preoperative biliary drainage. Methods Among 352 patients who underwent PD from 2010 to 2023, 163 patients met the inclusion criteria. Cefmetazole (CMZ) or cefazolin (CEZ) were administered as prophylactic antibiotics before May 2016, and CFPM thereafter. Short‐term outcomes were compared between patients receiving CMZ/CEZ and those receiving CFPM. Risk factors for SSI and severe morbidity were assessed by multivariate logistic regression. Results The CFPM group (n = 100) had more neoadjuvant chemotherapy, a higher rate of metallic stent placement, and a longer interval between initial biliary drainage and surgery, but less portal vein resection, lower blood loss, and fewer transfusions than the CMZ/CEZ group. Rates of superficial/deep incisional SSI and organ/space SSI were markedly lower with CFPM (3.0% vs. 44.4%, p < 0.001; and 10.0% vs. 36.5%, p < 0.001, respectively), which were associated with a reduction in Enterobacter cloacae infection. Severe morbidity was also reduced in the CFPM group (18.0% vs. 39.7%, p = 0.002). Use of CMZ/CEZ was independently associated with increased SSI and severe morbidity (OR = 10.6, p < 0.001; and OR = 3.53, p = 0.001). Emergence of resistant organisms did not differ between groups. Conclusions Prophylactic CFPM may reduce SSIs and severe morbidity after PD with preoperative biliary drainage.
PURPOSELatin America (LATAM), home to over 650 million people, remains under-represented in global oncology trials despite a growing cancer burden. This study aimed to evaluate the evolution of LATAM participation in phase III oncology trials over the past decade, with a focus on site distribution, cancer types studied, therapeutic classes investigated, and demographic reporting.METHODSWe conducted a cross-sectional analysis of global phase III oncology trials registered on ClinicalTrials.gov between January 1, 2013, and December 31, 2022. Trials were included if they studied anticancer therapies and listed at least one LATAM site. We extracted data on trial geography, cancer type, treatment modality, control group, and Hispanic ethnicity reporting. Trends in proportional regional site representation and therapy class were assessed using the Mann-Kendall trend test.RESULTSA total of 172 phase III trials with LATAM sites were identified, representing 2,609 of 29,718 global sites (8.8%). Brazil (45.8%), Argentina (18.6%), and Mexico (13.0%) accounted for over 75% of LATAM trial sites. LATAM's proportional site representation increased modestly from 7.1% in 2013 to 9.3% in 2021 (Bonferroni-adjusted P = .040), but no individual country showed a statistically significant increase. The most frequently studied cancers were lung (26.7%), breast (22.1%), and genitourinary (16.3%). Targeted therapies (42.4%) and immunotherapies (33.1%) dominated, whereas hormone therapy declined over time. Hispanic ethnicity was reported in only 61.6% of trials, with no improvement over time.CONCLUSIONAlthough LATAM's participation in global oncology trials has increased, it remains geographically concentrated and demographically under-reported. Structural and policy efforts are needed to improve trial equity and align research with regional cancer burdens.
