Natural history of acid sphingomyelinase deficiency among European patients during childhood and adolescence: A retrospective observational study.

Acid sphingomyelinase deficiency (ASMD) is a rare, lysosomal storage disease with limited evidence on its natural history. This retrospective, medical record abstraction study aimed to characterize the natural history of ASMD (types B and A/B) during childhood and adolescence. Recruiting sites were European centers (i.e., France, Germany, Italy, and the United Kingdom) from the ASCEND-Peds trial (NCT02292654); these sites were targeted because of the rarity of ASMD and specialized care provided at these centers. The study population comprised ASMD trial patients (before exposure to treatment) and ASMD non-trial participants who were managed at the same trial sites. Overall, 18 patients were included (11 trials; 7 non-trials; median [Q1; Q3] age at ASMD diagnosis: 2.5 [1.0; 4.0] years). Median follow-up duration was 10.0 years. Frequently reported medical conditions were hepatobiliary (17 [94.4%]) and blood and lymphatic system disorders (16 [88.9%]). Adenoidectomy (3 [16.7%]) was the most commonly reported surgical procedure; gastroenteritis (5 [27.8%]) was the most frequently reported infection, and epistaxis (6 [33.3%]) was the most commonly reported bleeding event. Abnormal spleen (16 [88.9%]) and liver (15 [83.3%]) size and respiratory function (8 [44.4%]) were commonly reported during physical examination. Overall, 11 (61.1%) patients were hospitalized; 6 (33.3%) patients had emergency room visits. Findings were consistent with published literature and support the current understanding of natural history of ASMD.

No evidence for changes in skeletal muscle mass or weight during first-line chemotherapy for metastatic colorectal cancer.

BACKGROUND: Studies over the past 10 years strongly support an association between skeletal muscle mass (SMM) depletion and outcome in metastatic colorectal cancer (mCRC). Factors influencing SMM changes over time are, however, poorly studied. We analyzed the impact of SMM on overall survival and chemotherapy toxicities in mCRC patients treated with first-line chemotherapy. Changes in weight and body composition were evaluated during follow-up. METHODS: Patients enrolled in the randomized phase II ACCORD trial comparing two chemotherapy regimens were screened. Body composition parameters (SMM, adipose tissue) were assessed prospectively with computed tomography (CT) imaging, and toxicities were recorded. Mixed models were used to assess weight and BC changes during 4 months of treatment follow-up. RESULTS: Among 145 patients included in ACCORD, 76 had available baseline CT scans and were included in the current study. Mean age was 60.6 ± 10.0 years, 50% were women, 82% had colon cancer, and 62% had two or more metastatic sites. At baseline, 49% had lost at least 5% of their initial weight, including 26% who had lost more than 10%; 53% had SMM depletion. In this homogenous cohort, there were no statistically significant associations between SMM depletion and overall survival, progression-free survival or chemotherapy toxicity. There were no decreases in weight or SMM during follow-up. Weight and SMM changes were not influenced by diarrhea either grade 3-4 or any grade (reported in 74% of patients). For patients with weight loss ≥10% at baseline, SMM increased significantly after 4 months of follow-up and after disease stabilization following chemotherapy (P = 0.008). CONCLUSIONS: In a homogenous mCRC cohort, SMM depletion was not associated with survival or chemotherapy toxicity. Despite most patient experiencing diarrhea, no changes in weight or SMM were found during 4 months of follow-up. However, hypotheses deriving from our exploratory study have to be tested in further larger sample size studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT00423696 (2011).

Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease.

OBJECTIVE: Patients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome. METHODS: In a prospective study of the REISAMIC registry of grade ≥2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other. RESULTS: We identified 45 patients with 53 AIDs in REISAMIC. The cancer diagnoses included melanoma (n = 36), non-small-cell lung cancer (n = 6) and others (n = 3). The most frequent pre-existing AIDs were vitiligo (n = 17), psoriasis (n = 12), thyroiditis (n = 7), Sjögren syndrome (n = 4) and rheumatoid arthritis (n = 2). Twenty patients (44.4%) presented with at least one irAE: eleven of these were associated with a pre-existing AID ('AID flare'). Treatment with anti-PD-1 antibodies was maintained in 15 of the 20 patients with an irAE. The IrAE-free survival time was significantly shorter in AID patients (median: 5.4 months) than in AID-free patients (median: 13 months, p = 2.1 × 10-4). The AID and AID-free groups did not differ significantly with regard to the overall survival time and objective response rate (p = 0.38 and 0.098, respectively). CONCLUSION: In patients treated with anti-PD-1 antibody, pre-existing AID was associated with a significantly increased risk of irAEs. Our results indicate that cancer treatments with anti-PD-1 antibodies are just as effective in AID patients as they are in AID-free patients.

Dietary antioxidant capacity and all-cause and cause-specific mortality in the E3N/EPIC cohort study.

PURPOSE: The cellular oxidative stress (balance between pro-oxidant and antioxidant) may be a major risk factor for chronic diseases. Antioxidant capacity of human diet can be globally assessed through the dietary non-enzymatic antioxidant capacity (NEAC). Our aim was to investigate the relationship between the NEAC and all-cause and cause-specific mortality, and to test potential interactions with smoking status, a well-known pro-oxidant factor. METHODS: Among the French women of the E3N prospective cohort study initiated in 1990, including 4619 deaths among 1,199,011 persons-years of follow-up. A validated dietary history questionnaire assessed usual food intake; NEAC intake was estimated using a food composition table from two different methods: ferric ion reducing antioxidant power (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hazard ratio (HR) estimates and 95 % confidence intervals (CI) were derived from Cox proportional hazards regression models. RESULTS: In multivariate analyses, FRAP dietary equivalent intake was inversely associated with mortality from all-causes (HR for the fourth vs. the first quartile: HR4 = 0.75, 95 % CI 0.67, 0.83, p trend < 0.0001), cancer, and cardiovascular diseases. Similar results were obtained with TRAP. There was an interaction between NEAC dietary equivalent intake and smoking status for all-cause and cardiovascular disease mortality, but not cancer mortality (respectively, for FRAP, p inter = 0.002; 0.013; 0.113, results were similar with TRAP), and the association was the strongest among current smokers. CONCLUSION: This prospective cohort study highlights the importance of antioxidant consumption for mortality prevention, especially among current smokers.

Role of Epidural Analgesia within an ERAS Program after Laparoscopic Colorectal Surgery: A Review and Meta-Analysis of Randomised Controlled Studies.

Introduction. Epidural analgesia has been a cornerstone of any ERAS program for open colorectal surgery. With the improvements in anesthetic and analgesic techniques as well as the introduction of the laparoscopy for colorectal resection, the role of epidural analgesia has been questioned. The aim of the review was to assess through a meta-analysis the impact of epidural analgesia compared to other analgesic techniques for colorectal laparoscopic surgery within an ERAS program. Methods. Literature research was performed on PubMed, Embase, and the Cochrane Library. All randomised clinical trials that reported data on hospital stay, postoperative complications, and readmissions rates within an ERAS program with and without an epidural analgesia after a colorectal laparoscopic resection were included. Results. Five randomised clinical trials were selected and a total of 168 patients submitted to epidural analgesia were compared to 163 patients treated by an alternative analgesic technique. Pooled data show a longer hospital stay in the epidural group with a mean difference of 1.07 (95% CI 0.06-2.08) without any significant differences in postoperative complications and readmissions rates. Conclusion. Epidural analgesia does not seem to offer any additional clinical benefits to patients undergoing laparoscopic colorectal surgery within an ERAS program.