The Role of Hyaluronic Acid for Soft Tissue Indications: A Systematic Review and Meta-Analysis.

CONTEXT: Soft tissue injuries are often treated with injectables such as corticosteroids and platelet-rich plasma (PRP) to reduce inflammation and promote healing. There is increasing evidence examining the use of hyaluronic acid (HA) for the management of soft tissue injuries. OBJECTIVE: To evaluate the treatment effect and role of HA for available soft tissue indications. DATA SOURCES: A search of PubMed, MEDLINE, EMBASE, and CENTRAL from the inception date of each database through February 24, 2021, was conducted for all randomized controlled trials (RCTs) involving the use of HA for soft tissue indications. Two reviewers independently screened articles for eligibility and extracted data from included studies for analysis. We assessed risk of bias for all included studies and pooled outcomes using a fixed-effects model. Outcomes (ie, function and pain relief) were categorized to short-term (<6 weeks, 6-12 weeks) and mid-term (>12 weeks) data. We present effect estimates as mean differences (MDs) and standardized mean differences (SMDs) and present the estimate of effect of HA for available indications in relation to available comparators. STUDY DESIGN: Meta-analysis of RCTs. LEVEL OF EVIDENCE: Level 1. RESULTS: Of the 6930 articles screened, 19 RCTs (n = 1629 patients) were eligible and included in this review. HA was evaluated across a variety of soft tissue indications including rotator cuff disease, elbow pain, ankle sprains, Achilles tendinopathy, patellar tendinopathy, and trigger finger. Of the 19 RCTs, 11 were placebo-controlled and 9 used active comparators (PRP, cortisone, prolotherapy, or extracorporeal shockwave therapy). The pooled treatment effect of HA across most soft indications against placebo and active comparators demonstrated benefit in short-term pain <6 weeks (MD visual analogue scale [VAS] 2.48, 95% CI 2.31-2.65) and 6 to 12 weeks (MD VAS 2.03, 95% CI 1.86-2.20). Mid-term pain relief also favored HA over comparators across indications >12 weeks from administration (MD VAS 3.57, 95% CI 3.35-3.78). High heterogeneity was present with rotator cuff (10 trials, I2 = 94%), and elbow tendinopathy (2 trials, I2 = 99%). We identified uncertain benefit for trigger finger (2 trials, I2 = 67%). Heterogeneity for ankle sprains, patellar tendinopathy and Achilles tendinopathy could not be assessed as they only had 1 trial each. CONCLUSION: This systematic review and meta-analysis support HA's efficacy in the treatment of a variety of soft tissue indications. Understanding the relative effects of HA to other injectable modalities requires additional, large trials.

Pharmacological Treatment in the Management of Glenohumeral Osteoarthritis.

Glenohumeral osteoarthritis (GH-OA) is a common cause of shoulder pain and is characterized by articular cartilage thinning, glenoid bone loss and deformity, osteophytosis, and other associated changes. The prevalence is estimated to be between 85 and 94% in men and women over the age of 80 years. A diagnosis of GH-OA is established based on clinical history, physical examination, and radiographic assessments. Non-pharmacological treatment options may serve as adjuvants to other therapies and should be incorporated for a more holistic approach to management. Pharmacological treatments include oral agents such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, corticosteroids and antidepressants. The National Institute for Health and Care Excellence (NICE) UK guidelines recommend NSAIDS as the first-line drugs for OA; topical forms of some of these agents can also be used. However, clinical evidence is largely lacking for its use in GH-OA, although patients with other types of OA, especially the knee and hip, are using these products in efforts to relieve joint pain. Intra-articular injections such as platelet-rich plasma, cortisone, and hyaluronic acid are usually used to control symptoms in moderate to advanced arthritis or in non-surgical candidates. Other non-surgical treatment options include suprascapular nerve block and radiofrequency ablation, and these options have been studied on different levels of evidence. Furthermore, all these treatments have their own indications, contraindications, and adverse effects profiles. Surgical treatment of GH-OA is reserved for patients who do not respond to conservative management or who suffer from debilitating symptoms that severely impair their quality of life.Level of Evidence IV, review article.

Neurological and cardiac responses after treatment with miglustat and a ketogenic diet in a patient with Sandhoff disease.

Sandhoff disease is a progressive neurodegenerative disorder characterized by accumulation of GM2 gangliosides. We describe a 6-year-old male with coarse facial features, developmental delay, refractory seizures, hypertrophic cardiomyopathy, who was later found to have Sandhoff disease. Previous studies have revealed that caloric restriction in combination with miglustat increased survival and motor behavior in mouse model of Sandhoff disease. These findings suggest that combination therapy may result in improved outcomes for patients with Sandhoff. Initiation of treatment with miglustat and a ketogenic diet was followed by improvement of the patient's seizure control and cardiac function. Further clinical investigation is required to better determine the benefit of management in late-onset forms of Sandhoff disease.

Malonyl coenzyme A decarboxylase deficiency: early dietary restriction and time course of cardiomyopathy.

Malonyl coenzyme A (CoA) decarboxylase (MCD) deficiency is a rare autosomal recessive organic acidemia characterized by varying degrees of organ involvement and severity. MCD regulates fatty acid biosynthesis and converts malonyl-CoA to acetyl-CoA. Cardiomyopathy is 1 of the leading causes of morbidity and mortality in this disorder. It is unknown if diet alone prevents cardiomyopathy development based in published literature. We report a 10-month-old infant girl identified by newborn screening and confirmed MCD deficiency with a novel homozygous MLYCD mutation. She had normal echocardiogram measurements before transition to high medium-chain triglycerides and low long-chain triglycerides diet. Left ventricular noncompaction development was not prevented by dietary interventions. Further restriction of long-chain triglycerides and medium-chain triglycerides supplementation in combination with angiotensin-converting enzyme inhibitors helped to improve echocardiogram findings. Patient remained asymptomatic, with normal development and growth. Our case emphasizes the need for ongoing cardiac disease screening in patients with MCD deficiency and the benefits and limitations of current dietary interventions.