Safety and Dosing Study of Glucagon‐Like Peptide 2 in Children With Intestinal Failure

Background and Aims: A glucagon‐like peptide 2 (GLP‐2) analogue is approved for adults with intestinal failure, but no studies of GLP‐2 have included children. This study examined the pharmacokinetics, safety, and nutritional effects of GLP‐2 in children with intestinal failure. Methods: Native human GLP‐2(1‐33) was synthesized following good manufacturing practices. In an open‐label trial, with parental consent, 7 parenteral nutrition–dependent pediatric patients were treated with subcutaneous GLP‐2 (20 µg/kg/d) for 3 days (phase 1) and, if tolerated, continued for 42 days (phase 2). Nutritional treatment was directed by the primary caregivers. Patients were followed to 1 year. Results: Seven patients were enrolled (age: 4.0 ± 0.8 years; bowel length, mean ± SEM: 24% ± 4% of predicted). All were parenteral nutrition dependent since birth, receiving 44% ± 5% of calories by parenteral nutrition. GLP‐2 treatment had no effect on vital signs (blood pressure, heart rate, and temperature) and caused no significant adverse events. Peak GLP‐2 levels were 380 pM (day 3) and 295 pM (day 42), with no change in half‐life or endogenous GLP‐2 levels. Nutritional indices showed a numeric improvement in z scores and citrulline levels; the z score was maintained while citrulline levels returned to baseline once GLP‐2 was discontinued. Conclusions: GLP‐2 was well tolerated in children, with a pharmacokinetic profile similar to that of adults. There were no changes in endogenous GLP‐2 release or metabolism. These results suggest that GLP‐2 ligands may be safely used in pediatric patients; larger trials are suggested to investigate nutritional effects.     

Outcome of distal end clavicle fractures treated with locking plates

Purpose: Fractures of the lateral end of the clavicle are relatively uncommon. These fractures are unstable due to the various deforming forces which act on the fragments as well as the small distal fracture fragment. At most times the deforming forces are not taken into consideration, and the fracture is not fixed securely. In this study, we assessed a fixation technique using the precontoured locking plates to find out whether it provided a stable fixation with good functional outcome. Methods: Totally, 32 patients with lateral end clavicle fracture (Neer''s Type II) were included in the study. After the informed consent and preoperative investigations were obtained, open reduction and internal fixation was done using a 3.5 mm precontoured superior locking plate with lateral extension under general anesthesia. Postoperative X-rays were done on day 1 and every 6 weeks after operation, until radiological union was achieved. The postoperative pain was assessed using Visual Analogue Scale (VAS) on postoperative days 1, 2 and 10. Postoperatively arm pouch sling was given for 2 weeks followed by active mobilization. Patients were asked to do their daily routine work and avoid lifting heavy weights. The functional outcome was assessed at the end of 2nd and 6th months with the help of Disabilities of the Arm, Shoulder and Hand (DASH) scoring. Results: There were no intraoperative complications in the procedure. The mean VAS score on postoperative day 1 was found to be 5 which decreased to 3 on day 2 and 0 on day 10. The mean DASH score was calculated as 11.63 at the end of postoperative month 2 and then 4.6 at the end of month 6. There was one case of malunion in whom the overhead abduction was restricted but was not painful and was managed conservatively. Conclusion: The precontoured locking plates with lateral extension may be a good method to fix the fractures of the lateral end clavicle, which provide a stable fixation with good functional outcome with very few instances of stiffness and decreased range of motion of the shoulder with the hook plates and failure of fixation in screw and K-wire fixations. It may well be the answer to the fixation questions of the lateral clavicle fractures, although larger comparative studies between the surgical treatment methods are required to confirm the same.     

Potential Risks and Benefits of Multiple Sclerosis Immune Therapies in the COVID-19 Era: Clinical and Immunological Perspectives

Coronavirus SARS-CoV2 has emerged as one of the greatest infectious disease health challenges in a century. Patients with multiple sclerosis (MS) have a particular vulnerability to infections through their use of immunosuppressive disease-modifying therapies (DMTs). Specific DMTs pose particular risk based on their mechanisms of action (MOA). As a result, patients require individualized approaches to starting new treatments and continuation of therapy. Additionally, vaccinations must be considered carefully, and individuals on long-term B cell–depleting therapies may have diminished immune responses to vaccination, based on preserved T cells and diminished but present antibody titers to influenza vaccines. We review the immunology behind these treatments and their impact on COVID-19, as well as the current recommendations for best practices for use of DMTs in patients with MS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01008-7.Key Words: Multiple sclerosis, SARS-CoV2, disease-modifying therapy, vaccination, COVID-19, immunology     

Endovascular treatment of vein of Galen dural arteriovenous fistula presenting as dementia

Dural arteriovenous fistula (DAVF) is an important cause of neurological dysfunction that is often misdiagnosed, especially in elderly population. Galenic DAVFs are a subtype of the rare falcotentorial DAVFs with a high risk of hemorrhage and aggressive clinical course. In most cases, DAVFs present with pulsatile tinnitus, headache, or orbital symptoms such as chemosis and proptosis. We report a patient with DAVF of Vein of Galen presented with progressive dementia, treated by Onyx embolisation and had good clinical outcome.     

Potential contribution of gut microbiota and systemic inflammation on HIV vaccine effectiveness and vaccine design

The quest for an effective HIV-1 vaccine began as soon as the virus causing AIDS was identified. After several disappointing attempts, results of the Phase-III RV144 trial in Thailand were a beacon of hope for the field demonstrating correlation between protection and immunological markers. In order to optimize vaccine response, we underline results from yellow fever and hepatitis B vaccines, where protective responses were predicted by the pre-vaccination level of immune activation in healthy individuals. Such findings support the assessment and reduction of pre-vaccine immune activation in order to optimize vaccine response. Immune activation in healthy individuals can be influenced by age, presence of CMV infection, gut dysbiosis and microbial translocation. We speculate that the level of immune activation should therefore be assessed to better select participants in vaccine trials, and interventions to reduce inflammation should be used to increase protective HIV vaccine response.