Efficacy and Safety of Valproic Acid for Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis.

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disorder classified into four types based on the age of onset of the disease. Early onset is correlated with a higher mortality rate, mainly due to respiratory complications. Valproic acid (VPA) is a histone deacetylase (HDAC) inhibitor that has shown positive results on SMA both in experimental and cohort studies. OBJECTIVES: This systematic review and meta-analysis aimed to investigate the efficacy and safety of VPA in patients with SMA. METHODS: Eleven databases were systematically searched on 30 May 2017 for clinical trials that reported the efficacy and safety of VPA in SMA patients. The primary outcome was the efficacy of VPA in terms of gross motor function and expression of both full-length spinal motor neuron (SMN) gene (FL-SMN) and exon 7-lacking SMN. The secondary outcome was the safety of VPA in terms of reported adverse effects. The protocol was registered at PROSPERO (CRD42017067203). RESULTS: Five of the ten included studies were used in the meta-analysis (n = 126). The overall effect estimate, comparing pre- and post-VPA treatment, regardless of carnitine co-administration and design of the studies, showed significant improvement in gross motor function (standard mean difference [SMD] = 0.302, 95% confidence interval [CI] 0.048-0.556, P = 0.02) using the Hammersmith Functional Motor Scale (HFMS), Modified Hammersmith Functional Motor Scale (MHFMS), and MHFMS-Extend, with no significant heterogeneity. Similarly, in non-randomized controlled studies, the results indicated that there was a significant improvement detected (SMD = 0.335, 95% CI 0.041-0.628, P = 0.025), with no significant heterogeneity. Meanwhile, our results suggest that there was no significant improvement in treatment with co-administered carnitine (SMD = 0.28, 95% CI - 0.02 to 0.581, P = 0.067). No significant differences were found between pre- and post-VPA treatment co-administered with carnitine, in terms of the change in FL-SMN and exon 7-lacking SMN. Qualitative synthesis showed that other motor functions were not improved, while respiratory function test results were contradictory. Regarding the safety of the treatment, a double-blind, randomized, placebo-controlled trial reported no statistically significant differences for adverse events (AEs) between groups. Moreover, most of the included studies reported no serious AEs related to VPA use, although weight gain, gastrointestinal symptoms and respiratory symptoms were notable problems. CONCLUSIONS: Our study suggests that VPA treatment results in an improvement in gross motor functions for SMA patients, but not in other assessments of motor function or, possibly, in respiratory function. Furthermore, VPA appears to be a relatively safe drug, although treatment may be associated with a wide range of AEs (including body weight increase, fatigue, fever, flu-like symptoms, irritability, and pain). Double-blind, randomized, controlled trials are required to confirm these findings.

The Impact of Bariatric Surgery on Type 2 Diabetes Mellitus and the Management of Hypoglycemic Events.

Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations. An extensive literature search was conducted on PubMed and Google Scholar using keywords such as gastric bypass, T2DM, bariatric surgery, GLP-1, GIP, and post bariatric hypoglycemia. Restrictive-malabsorptive procedures are most effective in treating T2DM patients based on changes induced in appetite through regulation of gastrointestinal hormones, with decreased hunger and increased satiation. We provide a review of bariatric surgery influence on T2DM and management of post-intervention hypoglycemic events. Post-bariatric surgery hypoglycemia is a serious complication especially when patients develop life-threatening neuroglycopenia with loss of consciousness and seizure. The avoidance of this adverse event may be achieved by strict dietary modification including a restriction on carbohydrates as well as foods with high glycemic index. Further research will provide more information on post-bariatric surgery hyperinsulinemic hypoglycemia pathophysiology and management.

A Brief Review of Non-invasive Monitoring of Respiratory Condition for Extubated Patients with or at Risk for Obstructive Sleep Apnea after Surgery.

Obstructive sleep apnea (OSA) is one of the important risk factors contributing to postoperative airway complications. OSA alters the respiratory physiology and increases the sensitivity of muscle tone of the upper airway after surgery to residual anesthetic medication. In addition, the prevalence of OSA was reported to be much higher among surgical patients than the general population. Therefore, appropriate monitoring to detect early respiratory impairment in postoperative extubated patients with possible OSA is challenging. Based on the comprehensive clinical observation, several equipment have been used for monitoring the respiratory conditions of OSA patients after surgery, including the continuous pulse oximetry, capnography, photoplethysmography (PPG), and respiratory volume monitor (RVM). To date, there has been no consensus on the most suitable device as a recommended standard of care. In this review, we describe the advantages and disadvantages of some possible monitoring strategies under certain clinical conditions. According to the literature, the continuous pulse oximetry, with its high sensitivity, is still the most widely used device. It is also cost-effective and convenient to use but has low specificity and does not reflect ventilation. Capnography is the most widely used device for detection of hypoventilation, but it may not provide reliable data for extubated patients. Even normal capnography cannot exclude the existence of hypoxia. PPG shows the state of both ventilation and oxygenation, but its sensitivity needs further improvement. RVM provides real-time detection of hypoventilation, quantitative precise demonstration of respiratory rate, tidal volume, and MV for extubated patients, but no reflection of oxygenation. Altogether, the sole use of any of these devices is not ideal for monitoring of extubated patients with or at risk for OSA after surgery. However, we expect that the combined use of continuous pulse oximetry and RVM may be promising for these patients due to their complementary function, which need further study.