Can extending time between vital sign checks improve sleep in hematopoietic stem cell transplant patients? Testing feasibility, acceptability, and preliminary efficacy.

BACKGROUND: Patients undergoing hematopoietic stem cell transplant (HSCT) experience barriers to quality sleep. Frequent vital sign checks are necessary early posttransplant given risk of complications but can disrupt sleep. This study tested feasibility and acceptability of extending time between checking vitals (EVs) from every 4 to every 6 h to improve sleep. PROCEDURE: HSCT patients ages 8-21 years (N = 50, mean age = 14.06, SD = 3.58) and their caregivers were enrolled 1-2 days prior to transplant, and 40 patients completed the 15-day study (NCT04106089). Patients wore an actigraph to estimate sleep and provided self- and caregiver-report of sleep. Sleep was observed for nights 0 to +4 posttransplant, and patients were then randomized to EVs either Days +5 to +9 or +10 to +14. Patients were assessed daily for medical eligibility to receive EVs; on days patients were eligible, nightshift nurses (N = 79) reported EV acceptability. RESULTS: Of 200 potential nights for EVs (5 nights x 40 patients), patients were eligible for EVs on 126 nights (63% of eligible nights), and patients received EVs on 116 (92%) of eligible nights. Most patients received EVs ≥3 nights (n = 26, 65%, median = 3 nights). Most patients (85%), caregivers (80%), and nurses (84%) reported that patients used the additional 2 h during EVs for sleep, with reporters indicating moderate to high acceptability. There was preliminary evidence of efficacy indicated by caregiver-reported sleep disturbance and actigraphy-estimated improvements in sleep efficiency during EVs. CONCLUSION: Extending time between vitals checks is highly acceptable to patients, caregivers, and nurses, and may offer a feasible approach to improve sleep in pediatric HSCT.

Phase I/II trial of plinabulin in combination with nivolumab and ipilimumab in patients with recurrent small cell lung cancer (SCLC): Big ten cancer research consortium (BTCRC-LUN17-127) study.

BACKGROUND: Plinabulin is a GEF-H1 releasing agent with an immune-enhancing function. We report results from a multicenter Phase I/II study (NCT03575793) assessing plinabulin in combination with nivolumab and ipilimumab for the treatment of recurrent SCLC. METHODS: In Phase I, patients were enrolled using a 3 + 3 design to determine dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D). Patients received nivolumab (1 mg/kg), ipilimumab (3 mg/kg), and plinabulin (in escalating doses) on day 1 of each 21-day cycle for 4 cycles followed by maintenance with plinabulin and nivolumab. In phase II, patients with recurrent PD(L)1 inhibitor resistant SCLC were enrolled. The primary objective was median progression-free survival (PFS). RESULTS: Between 9/2018 and 2/2023, 39 patients were enrolled, and 36 patients received study treatment and were evaluable for safety (16 in Phase I; 20 in Phase II). In the phase I dose-escalation, there were 2 DLTs; grade 3 altered mental status lasting <24 h and grade 3 infusion reaction. The Plinabulin RP2D was determined to be 30 mg/m2. Common TRAEs were vomiting (44 %), nausea (42 %), and infusion reaction (36 %); 6 % of patients had a ≥grade 3 TRAE. Five patients (14 %) had ≥grade 3 irAEs; there were no cases of immune-related pneumonitis. In the efficacy analysis in 27 patients, the median PFS was 1.6 months (95 % CI 1.2 to 2.7) and the trial did not meet the pre-specified target median PFS of 3.5 months. Four patients treated at 30 mg/m2 had PR (confirmed 1, unconfirmed 3); 5 patients had SD with a CBR of 33 %. Two of 8 patients treated in phase I at the lower 20 mg/m2 dose had confirmed PR, with 1 patient on the drug regimen for >90 cycles. The median OS and follow-up time were 5.5 months and 2.5 months respectively. CONCLUSIONS: Plinabulin in combination with nivolumab and ipilimumab was tolerable at the dose of 30 mg/m2. While the clinical responses in PD-1 resistant SCLC were limited, some patients had a long duration of response. The number of ≥grade 3 irAE with the combination were lower than expected.

Racial disparities in rates of invasiveness of resected intraductal papillary mucinous neoplasms in the United States.

BACKGROUND: Racial and ethnic disparities have been observed in the multidisciplinary management of pancreatic ductal adenocarcinoma. Intraductal papillary mucinous neoplasm is the most common identifiable precursor to pancreatic ductal adenocarcinoma, where early surgical intervention before the development of an invasive intraductal papillary mucinous neoplasm improves survival. The association of race/ethnicity with the risk of identifying invasive intraductal papillary mucinous neoplasms during resection has not been previously defined. METHODS: The American College of Surgeons National Quality Improvement Program targeted pancreatectomy database (2014-2021) was queried for patients with race/ethnicity data who underwent resection of an intraductal papillary mucinous neoplasm. Backward Wald logistic regression modeling (P ≤ 0.05 for entry; P > .10 for removal) was used to identify independent predictors of invasion. RESULTS: A total of 4,505 cases of resected intraductal papillary mucinous neoplasms were identified, with 923 (20.5%) demonstrating invasive intraductal papillary mucinous neoplasms. The cohort of individuals other than non-Hispanic Whites were significantly more likely to have invasive intraductal papillary mucinous neoplasms (White, 19.9%; Black, 24.2%; Asian, 23.7%; Hispanic, 22.6%; P = .026). Such disparity could not be explained by greater comorbidity, as non-White patients were significantly younger (age <65 years: 41.7% vs 33.2%, P < .001) and had better physical status (American Society of Anesthesiologists score ≤2: 28.8% vs 25.2%, P = .053). After controlling for clinicodemographic variables, being an individual of race/ethnicity other than White was independently associated with higher odds of invasive intraductal papillary mucinous neoplasms (odds ratio, 1.280; 95% confidence interval, 1.046-1.566; P = .017). No differences in postoperative morbidity were observed. CONCLUSION: In a national cohort of patients with resected intraductal papillary mucinous neoplasms, individuals who identified as being of race/ethnicity other than White were significantly more likely to have invasive intraductal papillary mucinous neoplasms during surgical resection.