Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.

Previous studies have suggested that the gut microbiome influences the response to checkpoint inhibitors (CPIs) in patients with cancer. CBM588 is a bifidogenic live bacterial product that we postulated could augment CPI response through modulation of the gut microbiome. In this open-label, single-center study (NCT03829111), 30 treatment-naive patients with metastatic renal cell carcinoma with clear cell and/or sarcomatoid histology and intermediate- or poor-risk disease were randomized 2:1 to receive nivolumab and ipilimumab with or without daily oral CBM588, respectively. Stool metagenomic sequencing was performed at multiple timepoints. The primary endpoint to compare the relative abundance of Bifidobacterium spp. at baseline and at 12 weeks was not met, and no significant differences in Bifidobacterium spp. or Shannon index associated with the addition of CBM588 to nivolumab-ipilimumab were detected. Secondary endpoints included response rate, progression-free survival (PFS) and toxicity. PFS was significantly longer in patients receiving nivolumab-ipilimumab with CBM588 than without (12.7 months versus 2.5 months, hazard ratio 0.15, 95% confidence interval 0.05-0.47, P = 0.001). Although not statistically significant, the response rate was also higher in patients receiving CBM588 (58% versus 20%, P = 0.06). No significant difference in toxicity was observed between the study arms. The data suggest that CBM588 appears to enhance the clinical outcome in patients with metastatic renal cell carcinoma treated with nivolumab-ipilimumab. Larger studies are warranted to confirm this clinical observation and elucidate the mechanism of action and the effects on microbiome and immune compartments.

Implementing texting programs in the P.O.W.E.R. (preventing obesity with eating right) medical group visit for weight loss.

BACKGROUND: The effect of incorporating mobile technology to support participants' lifestyle change and weight loss in medical group visits has not been well studied in a safety-net setting. RATIONALE AND DESIGN: Thus, the rationale of the current study was to examine the effect of text messaging in a medical group visit, and test the effect of two texting programs (12 weeks and 20 weeks), compared to those who did not receive text-messaging in the Preventing Obesity With Eating Right (POWER) group visit program. The primary outcome was weight loss. RESULTS: We found that those enrolled in the 20-week and 12-week texting programs attended more group visit sessions than those enrolled in the POWER group only (p < 0.001). Both POWER and POWER + 20-week texting groups had a significant reduction in weight at their final group visit compared to their baseline (POWER, 114 ± 27 kg vs. 112 ± 26 kg, p < 0.001; POWER + 20-week texting, 111 ± 28 kg vs. 109 ± 28 kg, p < 0.01), but not the 12-week texting group (114 ± 29 kg vs. 113 ± 29 kg, p = 0.22), with no differences between the groups. The number of group visits was correlated with a decrease in weight (rs  = 0.12, p < 0.05). CONCLUSION: In conclusion, text messaging programs led to more attendance in the medical group visits, but not greater weight loss or reduction in HbA1c than the POWER group obesity program alone. Further studies are needed to maximize the beneficial effects of texting programs in medical group visits in underserved minority populations.

Nebulized hypertonic saline for bronchiolitis: a randomized clinical trial.

IMPORTANCE: Bronchiolitis is one of the most common and costly respiratory diseases in infants and young children. Previous studies have shown a potential benefit of nebulized hypertonic saline; however, its effect in the emergency department (ED) setting is unclear. OBJECTIVE: To compare the effect of nebulized 3% hypertonic saline vs 0.9% normal saline on admission rate and length of stay in infants with bronchiolitis. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, randomized clinical trial during 3 consecutive bronchiolitis seasons from March 1, 2008, through April 30, 2011. We recruited a convenience sample of patients younger than 24 months with a primary diagnosis of viral bronchiolitis presenting to the ED of 2 urban free-standing tertiary children's hospitals. We excluded patients who were premature (gestational age, <34 weeks) or who had chronic pulmonary disease, immune deficiency, cardiac disease, or previous episodes of wheezing or inhaled bronchodilator use. Of eligible patients who were approached, 161 (26.6%) declined to participate. INTERVENTIONS: Patients received 4 mL of 3% sodium chloride (hypertonic saline [HS group]) or 0.9% sodium chloride (normal saline [NS group]) inhaled as many as 3 times in the ED. Those admitted received the assigned medication every 8 hours until discharge. All treatment solutions were premedicated with albuterol sulfate. MAIN OUTCOMES AND MEASURES: Hospital admission rate, length of stay for admitted patients, and Respiratory Distress Assessment Instrument score. RESULTS: A total of 197 patients were enrolled in the NS group and 211 in the HS group. Admission rate in the 3% HS group was 28.9% compared with 42.6% in the NS group (adjusted odds ratio from logistic regression, 0.49 [95% CI, 0.28-0.86]). Mean (SD) length of stay for hospitalized patients was 3.92 (5.24) days for the NS group and 3.16 (2.11) days for the HS group (P = .24). The Respiratory Distress Assessment Instrument score decreased after treatment in both groups; however, we found no significant difference between groups (P = .35). CONCLUSIONS AND RELEVANCE: Hypertonic saline given to children with bronchiolitis in the ED decreases hospital admissions. We can detect no significant difference in Respiratory Distress Assessment Instrument score or length of stay between the HS and NS groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00619918.

Liver failure with coagulopathy, hyperammonemia and cyclic vomiting in a toddler revealed to have combined heterozygosity for genes involved with ornithine transcarbamylase deficiency and Wilson disease.

A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2-3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 µmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four others cases have been reported, three of which presented with cyclic vomiting. Further evaluation in our case revealed elevated urine (198.8 µg/g creatinine) and liver (103 µg/g dry weight) copper content, and a heterozygous mutation in the Wilson disease gene, ATP7B. Our patient, now aged 5 years, has remained in excellent health with normal growth and development on fasting avoidance, a modified vegan diet, and sodium phenylbutyrate.These five cases demonstrate that generalized liver dysfunction/failure is a potential serious complication of OTC deficiency, although not a common one, and suggests that an ALT and PT should be obtained in OTC patients during episodes of hyperammonemia. Cyclic vomiting is a known presentation of OTC deficiency; it is not known if comorbid liver failure predisposes toward this phenotype. We propose that the heterozygote state in ATP7B increases the liver copper content, thus predisposing our patient with OTC deficiency to develop liver failure during a hyperammonemic episode. Our present case is an example of the opportunity of molecular diagnostics to identify putative modifier genes in patients with atypical presentations of genetic disorders.