Exocrine Pancreatic Insufficiency Induced by Immune Checkpoint Inhibitors.

BACKGROUND: Scant data describe exocrine pancreatic insufficiency (EPI) secondary to immune checkpoint inhibitor (ICI) use. The goal of this study is to describe the incidence, risk factors, and clinical characteristics of patients with ICI-related EPI. PATIENTS AND METHODS: A single center, retrospective case-control study was performed of all ICI-treated patients at Memorial Sloan Kettering Cancer Center between January 2011 and July 2020. ICI-related EPI patients had steatorrhea with or without abdominal discomfort or weight loss, started pancrelipase after initiation of ICI, and demonstrated symptomatic improvement with pancrelipase. Controls were matched 2:1 by age, race, sex, cancer type, and year of ICI start. RESULTS: Of 12 905 ICI-treated patients, 23 patients developed ICI-related EPI and were matched to 46 controls. The incidence rate of EPI was 1.18 cases per 1000 person-years and the median onset of EPI was 390 days after the first dose of ICI. All 23 (100%) EPI cases had steatorrhea that improved with pancrelipase, 12 (52.2%) had weight loss, and 9 (39.1%) had abdominal discomfort; none had changes of chronic pancreatitis on imaging. Nine (39%) EPI patients had episodes of clinical acute pancreatitis preceding the onset of EPI, compared to 1 (2%) control (OR 18.0 (2.5-789.0), P < .001). Finally, the EPI group exhibited higher proportions of new or worsening hyperglycemia after ICI exposure compared with the control group (9 (39.1%) vs. 3 (6.5%), P < .01). CONCLUSION: ICI-related EPI is a rare but clinically significant event that should be considered in patients with late onset diarrhea after ICI treatment and often is associated with development of hyperglycemia and diabetes.

High-dose squalene ingestion increases type I procollagen and decreases ultraviolet-induced DNA damage in human skin in vivo but is associated with transient adverse effects.

BACKGROUND: Evidence for beneficial effects of squalene on ultraviolet (UV)-induced photoageing of the skin is lacking. AIM: To investigate whether squalene supplementation improves signs and molecular markers of photoageing in human skin in vivo. METHODS: In total, 40 female volunteers aged > 50 years received two different doses [13.5 g/day (low-dose group) and 27 g/day (high-dose group)] of squalene for 90 days. At baseline and at the completion of the study, facial wrinkles were measured using skin replicas. Skin samples were taken to compare type I procollagen and matrix metalloproteinase 1 mRNA levels by real-time reverse-transcriptase PCR, and for type I procollagen immunostaining. Skin samples were also taken 24 h after 2 x minimal erythema dose (MED) of UV irradiation before and after squalene intake to assess UV-induced thymine dimer formation and keratinocytic apoptosis. RESULTS: In total, 37 subjects completed the trial. Transient loose stool was experienced by 35% of volunteers in the low-dose group and 55% in the high-dose group. Facial wrinkles decreased significantly (P < 0.05) in the high-dose group, while procollagen type I mRNA levels and MED increased significantly in the low-dose group. Procollagen immunostaining tended to increase in both groups. Facial erythema decreased and pigmentation increased significantly in both groups. UV-induced keratinocytic apoptosis and thymine dimer staining were substantially reduced in both groups. CONCLUSIONS: Daily ingestion of 13.5 or 27 g of squalene per day resulted in antiageing effects in photoaged skin. However, in view of the frequent incidence of loose stool experienced by the subjects, the risk-benefit ratio of high-dose squalene supplementation is too high to recommend it for treating skin ageing.

[Intestinal mucosa absorption and esterification of 14C oleic acid during treatment with neomycin]. / Assorbimento ed esterificazione di acido oleico C14 nella mucosa intestinale del ratto durante trattamento con neomicina.

Neomycin administered to rats subjected to lymphatic fistula and treated with 14C-labelled oleic acid did not decrease either the absorption or the esterification of this organic acid. The results appear to indicate that neomycin has no effect on the intestinal mucosa.

[14C-labelled triolein absorption and esterification in rats treated with neomycin]. / Assorbimento ed esterificazione di trioleina C14 in ratti trattati con neomicina mediante fistola linfatica.

Intragastrically administered 14C-triolein was observed in fistula-derived lymph from rats treated with neomycin and controls. Absorption was much reduced in the treated animals, indicating (contrary to the literature data) that neomycin malabsorption also occurs in this species. The slight amount absorbed followed normal routes. It is suggested that the antibiotic acts on the intestinal content and not on the mucosa.