Nanotherapeutic approach to treat diabetic foot ulcers using tissue-engineered nanofiber skin substitutes: A review

Background and aimsDiabetes mellitus (DM) is a chronic metabolic disease associated with long-term multisystem complications, among which nonhealing diabetic foot ulcers (DFUs) are recognized as major cause of morbidity and mortality. Treating DFUs with surgical procedures such as synthetic or biological skin grafts or skin substitutes has several limitations, where none of the currently available skin substitutes is ideal.MethodsOVID/Medline and PubMed databases were searched using the Medical Subject Heading (MeSH) or Title/Abstract words (“diabetic foot ulcers”, “skin substitutes”, and “nanofibers”), to identify published research studies on DFUs and nanofibers.ResultsElectrospinning nanotechnology is being used in the biomedical field to produce polymeric nanofibers impregnated with drugs for wound healing, burns and diabetic ulcers. Those nanofibers also enable seeding of cells into them and culturing them in vitro to synthesize tissue-like structures. Knowing the advantages of generating patient-specific induced pluripotent stem cells (iPSCs) and organoids in three-dimension (3D), including skin organoids, it is worth mingling these technologies to develop tissue-engineered biological skin substitutes.ConclusionNanofiber-skin substitutes hold promise for treatment of patients suffering from DFUs and inspire novel strategies that could be applied to other organ systems as well, introducing a new era of “regenerative and personalized medicine”.     

The development of biological therapies for neurological diseases: moving on from previous failures

Introduction: Although years of research have expanded the use of biologics for several clinical conditions, such development has not yet occurred in the treatment of neurological diseases. With the advancement of biologic technologies, there is promise for these therapeutics as novel therapeutic approaches for neurological diseases.

Areas covered: In this article, the authors review the therapeutic potential of different types of biologics for the treatment of neurological diseases. Preclinical and clinical studies that investigate the efficacy and safety of biologics in the treatment of neurological diseases, namely Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson disease, multiple sclerosis, and stroke, were reviewed. Moreover, the authors describe the key challenges in the development of therapeutically safe and effective biologics for the treatment of neurological diseases.

Expert opinion: Several biologics have shown promise in the treatment of neurological diseases. However, the complexity of the CNS, as well as a limited understanding of disease progression, and restricted access of biologics to the CNS has limited successful development. Therefore, more research needs to be conducted to overcome these hurdles before developing effective and safe biologics for neurological diseases. The emergence of new technologies for the design, production and delivery of biologics will accelerate translating biologics to the clinic.     

Laparoscopic Sleeve Gastrectomy Versus Banded Roux-en-Y Gastric Bypass for Diabetes and Obesity: a Prospective Randomised Double-Blind Trial

Background

There are very few randomised, blinded trials comparing laparoscopic sleeve gastrectomy (LSG) versus laparoscopic Roux-en-Y gastric bypass (LRYGB) in achieving remission of type 2 diabetes (T2D), particularly silastic ring (SR)-LRYGB. We compared the effectiveness of (LSG) versus SR-LRYGB among patients with T2D and morbid obesity.

Methods

Prospective, randomised, parallel, 2-arm, blinded clinical trial conducted in a single Auckland (New Zealand) centre. Eligible patients aged 20–55 years, T2D of at least 6 months duration and BMI 35–65 kg/m² were randomised 1:1 to LSG (n = 58) or SR-LRYGB (n = 56) using random number codes disclosed after anaesthesia induction. Primary outcome was T2D remission defined by different HbA1c thresholds at 1 year. Secondary outcomes included weight loss, quality of life, anxiety and depressive symptoms, post-operative complications and mortality.

Results

Mean ± standard deviation (SD) pre-operative BMI was 42.5 ± 6.2 kg/m², HbA1c 63 ± 16 mmol/mol (30% insulin-treated, 28% had diabetes duration over 10 years). Proportions achieving HbA1c ≤ 38 mmol/mol, < 42 mmol/mol, < 48 mmol/mol and < 53 mmol/mol without diabetes medication at 1 year in SR-LRYGB vs LSG were 38 vs 43% (p = 0.56), 52 vs 49% (p = 0.85), 75 vs 72% (p = 0.83) and 80 vs 77% (p = 0.82), respectively. Mean ± SD % total weight loss at 1 year was greater after SR-LRYGB than LSG: 32.2 ± 7.7 vs 27.1 ± 7.5%, respectively (p < 0.001). Gastrointestinal complications were more frequent after SR-LRYGB (including 3 ulcers, 1 anastomotic leak, 1 abdominal bleeding). Quality of life and depression symptoms improved significantly in both groups.

Conclusion

Despite significantly greater weight loss after SR-LRYGB, there was similar T2D remission and psychosocial improvement after LSG and SR-LRYGB at 1 year.

Trial Registration

Prospectively registered at Australia and New Zealand Clinical Trials Register (ACTRN 12611000751976) and retrospectively registered at Clinical Trials (NCT1486680).

     

The many faces of peroxisomal disorders: Lessons from a large Arab cohort

Defects in the peroxisomes biogenesis and/or function result in peroxisomal disorders. In this study, we describe the largest Arab cohort to date (72 families) of clinically, biochemically and molecularly characterized patients with peroxisomal disorders. At the molecular level, we identified 43 disease-causing variants, half of which are novel. The founder nature of many of the variants allowed us to calculate the minimum disease burden for these disorders in our population ~1:30 000, which is much higher than previous estimates in other populations. Clinically, we found an interesting trend toward genotype/phenotype correlation in terms of long-term survival. Nearly half (40/75) of our peroxisomal disorders patients had documented survival beyond 1 year of age. Most unusual among the long-term survivors was a multiplex family in which the affected members presented as adults with non-specific intellectual disability and epilepsy. Other unusual presentations included the very recently described peroxisomal fatty acyl-CoA reductase 1 disorder as well as CRD, spastic paraparesis, white matter (CRSPW) syndrome. We conclude that peroxisomal disorders are highly heterogeneous in their clinical presentation. Our data also confirm the demonstration that milder forms of Zellweger spectrum disorders cannot be ruled out by the “gold standard” very long chain fatty acids assay, which highlights the value of a genomics-first approach in these cases.