Oligomalt, a New Slowly Digestible Carbohydrate, Is Well Tolerated in Healthy Young Men and Women at Intakes Up to 180 Gram per Day: A Randomized, Double-Blind, Crossover Trial.

In this randomized, double-blind triple-crossover study (NCT05142137), the digestive tolerance and safety of a novel, slowly digestible carbohydrate (SDC), oligomalt, an α-1,3/α-1,6-glucan α-glucose-based polymer, was assessed in healthy adults over three separate 7-day periods, comparing a high dose of oligomalt (180 g/day) or a moderate dose of oligomalt (80 g/day in combination with 100 g maltodextrin/day) with maltodextrin (180 g/day), provided as four daily servings in 300 mL of water with a meal. Each period was followed by a one-week washout. A total of 24 subjects (15 females, age 34 years, BMI 22.2 kg/m2, fasting blood glucose 4.9 mmol/L) were recruited, of whom 22 completed the course. The effects on the primary endpoint (the Gastrointestinal Symptom Rating Score (GSRS)) showed a statistically significant dose dependency, albeit of limited clinical relevance, between a high dose of oligomalt and maltodextrin (mean (95% CI) 2.29 [2.04, 2.54] vs. 1.59 [1.34, 1.83], respectively; difference: [-1.01, -0.4], p < 0.0001), driven by the GSRS-subdomains "Indigestion" and "Abdominal pain". The GSRS difference ameliorated with product exposure, and the GSRS in those who received high-dose oligomalt as their third intervention period was similar to pre-intervention (mean ± standard deviation: 1.6 ± 0.4 and 1.4 ± 0.3, respectively). Oligomalt did not have a clinically meaningful impact on the Bristol Stool Scale, and it did not cause serious adverse events. These results support the use of oligomalt across various doses as an SDC in healthy, normal weight, young adults.

Safety and efficacy of an oral histone deacetylase inhibitor in systemic-onset juvenile idiopathic arthritis.

OBJECTIVE: The current treatment options for systemic-onset juvenile idiopathic arthritis (JIA) are methotrexate, steroids, and biologic agents. This study was undertaken to evaluate the safety of the orally active histone deacetylase inhibitor givinostat (ITF2357) and its ability to affect the disease. METHODS: Givinostat was administered orally, for up to 12 weeks at a dosage of 1.5 mg/kg/day, to 17 patients with systemic-onset JIA who had had active disease for ≥1 month. Disease activity was clinically assessed using the American College of Rheumatology Pediatric 30 (ACR Pedi 30), ACR Pedi 50, or ACR Pedi 70 criteria for improvement and a systemic feature score. The primary goal was safety and the primary efficacy end point was the number of patients completing 12 weeks of treatment who were responders. RESULTS: Givinostat was safe and well tolerated, with adverse events (AEs) being mild or moderate, of short duration, and self-limited. The 17 patients from the intent-to-treat population reported a total of 44 AEs, and the 9 patients in the per-protocol population reported a total of 25. Six AEs in 3 patients (nausea, vomiting, and fatigue) were related to the study drug, but each resolved spontaneously and no patient was withdrawn from the study due to drug-related AEs. In the per-protocol population at week 4, the improvement as measured by the ACR Pedi 30, ACR Pedi 50, and ACR Pedi 70, respectively, was 77.8%, 55.6%, and 22.2%, and this increased further to 77.8%, 77.8%, and 66.7% at week 12. The most consistent finding was the reduction in the number of joints with active disease or with limited range of motion. CONCLUSION: After 12 weeks, givinostat exhibited significant therapeutic benefit in patients with systemic-onset JIA, particularly with regard to the arthritic component of the disease, and showed an excellent safety profile.

A Decentralized Study Setup Enables to Quantify the Effect of Polymerization and Linkage of α-Glucans on Post-Prandial Glucose Response.

The complexity of the carbohydrate structure is associated with post-prandial glucose response and diverse health benefits. The aim of this study was to determine whether, thanks to the usage of minimally invasive glucose monitors, it was possible to evaluate, in a decentralized study setup, the post-prandial glycemic response (PPGR) of α-glucans differing systematically in their degree of polymerization (DP 3 vs. DP 60) and in their linkage structure (dextrin vs. dextran). Ten healthy subjects completed a double-blind, randomized, decentralized crossover trial, testing at home, in real life conditions, four self-prepared test beverages consisting of 25 g α-glucan dissolved in 300 mL water. The incremental area under the curve of the 120 min PPGR (2h-iAUC) was the highest for Dextrin DP 3 (163 ± 27 mmol/L*min), followed by Dextrin DP 60 (-25%, p = 0.208), Dextran DP 60 (-59%, p = 0.002), and non-fully caloric Resistant Dextrin (-68%, p = 0.002). These results show that a fully decentralized crossover study can be successfully used to assess the influence of both polymerization and structure of α-glucans on PPGR.

Acute dose-response effect of coffee-derived chlorogenic acids on the human vasculature in healthy volunteers: a randomized controlled trial.

BACKGROUND: Epidemiological studies have reported lower risk of cardiovascular disease with moderate coffee consumption. In addition, emerging evidence indicates that consumption of coffee beverages enriched in chlorogenic acids (CGAs) may influence blood pressure and endothelial function, suggesting that the beneficial cardiovascular effect of coffee may relate to its CGA content. OBJECTIVES: We conducted a double-blind randomized crossover trial to test the effect of acute consumption of a decaffeinated green coffee extract (DGCE), rich in CGAs, on endothelial function in healthy subjects. METHODS: We compared 3 different doses of DGCE (302, 604, and 906 mg, respectively) with a placebo. Endothelial function was defined as the percentage change in the internal diameter of the brachial artery in response to flow-mediated dilation (%FMD). In addition, we followed the plasma concentration-time profiles of 25 systemic CGA metabolites over 24 h after DGCE consumption and we explored the relation between systemic concentrations of CGAs and the effect on %FMD. RESULTS: The DGCE formulations containing different amounts of CGAs resulted in dose-proportional increases in overall total polyphenol concentrations. The systemic appearance of total CGAs was biphasic, in agreement with previous results suggesting 2 sites of absorption in the gastrointestinal tract. Compared with the placebo group, a significant FMD increase (>1%) was observed 8.5, 10, and 24 h after consumption of 302 mg DGCE (∼156.4 mg CGAs). The differences with placebo observed in the other 2 groups were not statistically significant. Evaluation of the relation between phenolic exposure and %FMD showed a positive tendency toward a larger effect at higher concentrations and different behavior of CGA metabolites depending on the conjugated chemical position. CONCLUSIONS: We demonstrated an acute improvement in %FMD over time after ingestion of a DGCE, explained at least partly by the presence in the blood circulation of CGAs and their metabolites. This trial was registered at clinicaltrials.gov as NCT03520452.

A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms.

A phase II A study was conducted to evaluate the safety and efficacy of Givinostat, a novel Histone-Deacetylases inhibitor, in patients with Polycythaemia Vera (PV, n = 12), Essential Thrombocythaemia (ET, n = 1) and Myelofibrosis (n = 16), bearing the JAK2V617F mutation. The study was approved by the local ethics committees and all human participants gave written informed consent. Givinostat was given orally for 24 weeks at a starting dose of 50 mg twice daily. The median treatment duration was 20 weeks. Reasons for treatment discontinuation were disease progression (n = 6), grade 2 thrombocytopenia (n = 1), psychiatric symptoms (n = 1) and withdrawn consent (n = 2). A dose reduction was applied in 10 patients while a temporary interruption occurred in 15. Among 13 PV/ET patients, 1 complete, 6 partial and 4 no responses were documented at study end while 2 patients went off-study, prematurely. Three major responses were registered among 16 MF patients. Pruritus disappeared in most patients and reduction of splenomegaly was observed in 75% of PV/ET and 38% of MF patients. Reverse transcription polymerase chain reaction identified a trend to reduction of the JAK2V617F allele burden. Givinostat was well tolerated and could induce haematological response in most PV and some MF patients.

Laparoscopic approach to müllerian derivatives in a male with mixed gonadal dysgenesis.

Müllerian derivatives are a frequent finding in patients with external genital ambiguity. In cases in which their removal is indicated, traditional surgical approaches are both invasive and associated with risks. We report a case of mixed gonadal dysgenesis in which a large prostatic utricle was successfully removed via laparoscopy.

Mortality and long term morbidity in esophageal atresia: the reduced impact of low birth weight and maturity on surgical outcome.

Progress in perinatal and postoperative techniques has reduced the prognostic role of traditional risk factors in esophageal atresia (EA). This paper reports on 75 cases of esophageal anomalies observed between 1992 and 2002 and followed after surgery from a minimum of six months to a maximum of ten years (mean five years). The impact on survival of birth weight, week of delivery, associated anomalies and need of ventilatory support at birth are discussed. Twenty-four patients were born before 37 weeks of gestation, 18 weighed less than 2000 g.; major anomalies affected 11 neonates, 23 cases required mechanical ventilation at birth. Seventy-four patients were operated on with a 90.6% survival rate; no deaths were related to surgical treatment. Three cases required reoperation for postoperative complications. Birth weight and week of delivery did not seem to influence outcome; this is affected by severe associated cardiovascular anomalies and the need of ventilation at birth. Follow up at 24 months on 51 patients, revealed respiratory problems in 12 cases and severe gastro-esophageal reflux in 16. This affected quality of life of EA patients and required long term medical attention; improvement with growth was observed. No correlation between perinatal conditions and late sequelae could be demonstrated in our series.

Sacrococcygeal teratoma. Outcome and management. An analysis of 17 cases.

AIMS: The authors compare their experience of 17 cases of sacrococcygeal teratoma (SCT) with the literature in an attempt to clarify the natural history of this tumor and to identify factors related to its prognosis and management. METHODS: The obstetrical, neonatal and surgical data were analyzed for 17 cases of SCT observed between July 1985 and December 1998. RESULTS: Three fetuses died in utero or shortly after birth. In the remaining 14, the tumors were removed. Twelve of the infants are currently tumor-free, with good sphincter control and lower-limb function. The remaining two died: one had a malignant tumor, and the other had a recurrence of an embryonal carcinoma. Recurrent tumors (mature histotypes) were also removed from two of the 12 patients who survived. CONCLUSIONS: Benign SCTs generally have favorable prognosis. Negative prognostic factors for SCT include solid tumors, those detected early in pregnancy, malignant histotypes, polyhydramnios, placentomegaly, and fetal hydrops.