Neuromuscular disease - Gene transfer for children

Successful gene transfer therapy (GTT) provides a functional copy of a gene to appropriate tissues for affected patients. While technically difficult, GTT holds great promise for treating and even curing previously fatal diseases. GTT for Spinal Muscular Atrophy is available commercially and ongoing studies continue to show it is safe and effective. Subclinical liver dysfunction is more common in older, heavier children receiving higher vial loads. Human trials support preclinical studies showing early timing of therapy is important. GTT for Duchene Muscular Dystrophy has required strategic approaches to create mini- and micro-dystrophin genes that will fit into available viral vectors. There are multiple ongoing studies that overall demonstrate good safety and efficacy. GTT for X-Linked Myotubular Myopathy is being studied in an ongoing trial that has shown improvement in respiratory function (including ventilator independence), neuromuscular function, and histopathological evaluation. Three patients with severe cholestatic liver dysfunction have died. Evaluation is ongoing to better understand these events. While GTT for neuromuscular disorders holds significant promise, it is not without risks and requires in-depth knowledge of the disease, abundant pre-clinical work, careful patient education, and ongoing patient care. There are a number of key questions that must be considered regarding the feasibility of expanding GTT to new disorders These examples illustrate how advances in GTT benefit children on a population level and may themselves benefit from early detection by NBS. By becoming involved in advocacy at state and federal levels, families and physicians can impact newborn screening policy and implementation regarding these disorders.

Timing of early laparoscopic cholecystectomy for acute calculous cholecystitis: a meta-analysis of randomized clinical trials

Background Early cholecystectomy for acute cholecystitis has proved to reduce hospital length of stay but with no benefit in morbidity when compared to delayed surgery. However, in the literature, early timing refers to cholecystectomy performed up to 96 h of admission or up to 1 week of the onset of symptoms. Considering the natural history of acute cholecystitis, the analysis based on such a range of early timings may have missed a potential advantage that could be hypothesized with an early timing of cholecystectomy limited to the initial phase of the disease. The review aimed to explore the hypothesis that adopting immediate cholecystectomy performed within 24 h of admission as early timing could reduce post-operative complications when compared to delayed cholecystectomy. Methods The literature search was conducted based on the Patient Intervention Comparison Outcome Study (PICOS) strategy. Randomized trials comparing post-operative complication rate after early and delayed cholecystectomy for acute cholecystitis were included. Studies were grouped based on the timing of cholecystectomy. The hypothesis that immediate cholecystectomy performed within 24 h of admission could reduce post-operative complications was explored by comparing early timing of cholecystectomy performed within and 24 h of admission and early timing of cholecystectomy performed over 24 h of admission both to delayed timing of cholecystectomy within a sub-group analysis. The literature finding allowed the performance of a second analysis in which early timing of cholecystectomy did not refer to admission but to the onset of symptoms. Results Immediate cholecystectomy performed within 24 h of admission did not prove to reduce post-operative complications with relative risk (RR) of 1.89 and its 95% confidence interval (CI) [0.76; 4.71]. When the timing was based on the onset of symptoms, cholecystectomy performed within 72 h of symptoms was found to significantly reduce post-operative complications compared to delayed cholecystectomy with RR = 0.60 [95% CI 0.39;0.92]. Conclusion The present study failed to confirm the hypothesis that immediate cholecystectomy performed within 24 h of admission may reduce post- operative complications unless surgery could be performed within 72 h of the onset of symptoms.

Uretero-Pelvic Junction Stenosis: Considerations on the Appropriate Timing of Correction Based on an Infant Population Treated with a Minimally-Invasive Technique

There is no univocal consensus about timing of intervention and best surgical approach for infants with asymptomatic uretero-pelvic junction obstruction (UPJO). We conducted a retrospective analysis of patients undergoing one-trocar-assisted pyeloplasty (OTAP) in a 13 year range period by creating two homogenous groups (indications for surgery were the same for all patients): patients operated on in the first 90 days of life (34 patients; Group 1) and patients operated on between 3 and 12 months of life (34 patients; Group 2). We observed no statistically significant differences between groups in regard to mean operative time, conversion rate to open surgery, mean hospital stay, early complications (urinary leakage) rate and mean antero-posterior diameter (APD) reduction rate. Moreover, no statistical improvement was seen between groups in regard to separate renal function (SRF) at 1-year-follow-up renogram. Thanks to the HSS calculated before and 1 year after surgery, we registered an important improvement in Group I patients (p = 0.023). In our study, there was no significant evidence, in terms of intraoperative data and early postoperative outcomes, between patients who underwent an early pyeloplasty and those who underwent a delayed correction. Nevertheless, we registered a significant improvement in those patients with an impaired SRF that underwent an early surgical correction, especially in terms of urinary flow. Even though this study cannot definitely establish the superiority of early timing of correction, it is evident that further research is needed to clarify this aspect.

Institutions, Policy, and Non-Communicable Diseases (NCDs) in Latin America

Research has underscored the agenda-setting and policy implementation advantages associated with the concentration of political and policy-making authority. But to what extent does this concentration of authority within health policy-making institutions determine the early timing and depth of non-communicable disease (NCD) policies? Are other factors within and outside of government more important? Comparing one Latin American country exhibiting a strong concentration of political and policy-making authority, Mexico, to one that does not, Brazil, we find that weaker, fragmented political and policy-making powers in Brazil expedited the creation and implementation of NCD programs. As seen in Brazil, our findings suggest that the factors that account for the earlier adoption of NCD policies and successful implementation are the early institutionalisation of societal interests and pressures within the bureaucracy, the “bottom-up” diffusion of early policy ideas, and international policy recommendations. This institutional, participatory, and ideational approach may provide more important predictors for explaining variation in NCD policies.

Hyperinflammation in COVID-19 Obese Patients Treated With Tocilizumab: A Successful Case Series

The cytokine storm syndrome has been suggested as a mechanism in the pathophysiology of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; COVID-19 [coronavirus disease 2019]) infection. Drugs such as tocilizumab, an interleukin-6 antagonist, have shown good results in other scenarios of hyperinflammatory state and might also be effective in COVID-19 disease. However, the best dosing regimen and the timing of infusion is currently unknown, specifically in obese patients. We report the first cases of tocilizumab administration in obese patients during the first days of COVID-19 worsening hypoxemia. This infusion was not adjusted by weight, following the manufacturer maximal dose limit. We kept a strict monitoring for possible infections, prior and during the treatment. All patients showed good improvements on chest-computed tomography images and oxygenation and were discharged from hospital shortly after, without complications or intubation. This case series highlights that tocilizumab seems to be effective to treat hyperinflammation of critical COVID-19 obese patients, even when the infusion of the ideal dose is not feasible to be administered. It also shows the importance of early timing in the decision to treat and the relevance of infections exclusion prior to the induction of immunosuppression by tocilizumab.

Endoscopic Sphenopalatine Artery Ligation in Posterior Epistaxis

Introduction: Posterior epistaxis brings us with a more challenging condition that can even threaten the life of a patient. Approaching the posterior nasal cavity is not an easy task because of its anatomical complexity and impending vision by turbinate. Increase endoscopic anatomic details of lateral nasal wall and endoscopic expertise with high definition camera leads to a higher success rate of endoscopic sphenopalatine artery ligation.Methods: This prospective study was conducted in patients with refractory posterior epistaxis between January 2017 to December 2019. All patient who had undergone Endoscopic Sphenopalatine artery ligation were included in this study. The site of bleeding was confirmed with the help of a rigid endoscope. Bipolar cauterization or clipping was performed to stop bleeding. Data analysis was done by using SPSS 26.0 version.Results: Twenty nine patients who had undergone Endoscopic sphenopalatine artery for posterior epistaxis were included during this study period. The mean age of the patient was 53.31 ± 18.65years. The site of bleeding was mostly from the left in 20 (75.9%) cases and 10 (34.4%) cases had severe bleeding that needed a blood transfusion. No recurrence of bleeding was found during follow up period. The severity of bleeding was significantly correlated with the age of patients (p<0.003). Out of 29 patient, 27 patients had undergone bipolar diathermy and 2 patients clipping was done.Conclusion: Sphenopalatine artery ligation is an effective management strategy for surgical control of refractory epistaxis. The early timing of sphenopalatine artery ligation may lead to reductions in length of stay.

The State of Litter of Pigs in the Conditions of the Complex

The state of litter of large white pigs in industrial conditions was studied. Embryonic mortality is higher during the first 30 days of littering (21.6%) – in the period of histotrophic feeding of fetuses – before the beginning of placental connection formation. whereas during the whole period of pregnancy it is 38.4%. In a number of sows at different periods of littering. the number of corpus luteum and the number of fetuses from the side of the corresponding fertile horn do not coincide. that which indicates the migration of embryos into contralateral horn in the early timing of pregnancy. Fetuses growth rate is higher by the 45-days pregnancy. In the litter of pigs there are normotrophic (full-fledged. large-fetused). hypotrophic (small-weight) and stillborn pigs. There is close inverse relationship (r = -0.98 between fertility and full-fledgeness of piglets в гнездеin the nest. wherein the number of hypotrophic and stillborn ones as the number of newborns in the litter increases has direct positive correlation (r = + 0.98). The more piglets in the litter. the fewer full-fledged ones. and on the contrary. the number of hypotrophic and stillborns is increasing.