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With the recent urbanization and globalization, the adult obesity rate has been increasing, which was paralleled with a dramatic surge in the incidence and prevalence of nonalcoholic fatty liver disease (NAFLD). NAFLD poses a growing threat to human health as it represents the most common cause of chronic liver disease in developed countries. It encompasses a wide spectrum of conditions starting from a build-up of fat in hepatocytes (steatosis), to developing inflammation (steatohepatitis), and reaching up to cirrhosis. It is also associated with higher rates of cardiovascular mortalities. Therefore, proper timely treatment is essential and weight loss remains the cornerstone in the treatment of obesity-related liver diseases. When diet, exercise, and lifestyle changes are not successful, the current recommendation for weight loss includes antiobesity medications and bariatric endoscopic and surgical interventions. These interventions have shown to result in significant weight loss and improve liver steatosis and fibrosis. In the current literature review, we highlight the expected outcomes and side effects of the currently existing options to have a weight-centric NAFLD approach.

To assess long-term outcomes of cooled radiofrequency ablation (CRFA) of genicular nerves for chronic knee pain due to osteoarthritis (OA).A prospective, observational extension of a randomized, controlled trial was conducted on adults randomized to CRFA. Subjects were part of a 12-month clinical trial comparing CRFA of genicular nerves to a single hyaluronic injection for treatment of chronic OA knee pain, who then agreed to visits at 18- and 24-months post CRFA and had not undergone another knee procedure since. The subjects were evaluated for pain using the Numeric Rating Scale (NRS) function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), subjective benefit using the Global Perceived Effect (GPE) scale, quality of life using the EuroQol-5-Dimensions-5 Level (EQ-5D-5L) questionnaire, and safety.Of 57 subjects eligible, 36 enrolled; 32 completed the 18-month visit with a mean NRS score of 2.4 and 22 (69%) reporting ≥50% reduction in pain from baseline (primary endpoint); 27 completed the 24-month visit, with a mean NRS of 3.4 and 17 (63%) reporting ≥50% pain relief. Functional and quality of life improvements persisted similarly, with mean changes from baseline of 53.5% and 34.9% in WOMAC total scores, and 24.8% and 10.7% in EQ-5D-5L Index scores, at 18- and 24-months, respectively. There were no identified safety concerns in this patient cohort.In this subset of subjects, CRFA of genicular nerves provided durable pain relief, improved function, and improved quality of life extending to 24 months post procedure, with no significant safety concerns.

BACKGROUND Knee osteoarthritis is a painful and sometimes debilitating disease that often affects patients for years. Current treatments include short-lasting and often repetitive nonsurgical options, followed by surgical intervention for appropriate candidates. Cooled radiofrequency ablation (CRFA) is a minimally invasive procedure for the treatment of pain related to knee osteoarthritis. This trial compared the efficacy and safety of CRFA with those of a single hyaluronic acid (HA) injection. METHODS Two hundred and sixty subjects with knee osteoarthritis pain that was inadequately responsive to prior nonoperative modalities were screened for enrollment in this multicenter, randomized trial. One hundred and eighty-two subjects who met the inclusion criteria underwent diagnostic block injections and those with a minimum of 50% pain relief were randomized to receive either CRFA on 4 genicular nerves or a single HA injection. One hundred and seventy-five subjects were treated (88 with CRFA and 87 with HA). Evaluations for pain (Numeric Rating Scale [NRS]), function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), quality of life (Global Perceived Effect [GPE] score and EuroQol-5 Dimensions-5 Level [EQ-5D-5L] questionnaire), and safety were performed at 1, 3, and 6 months after treatment. RESULTS Demographic characteristics did not differ significantly between the 2 study groups. A total of 158 subjects (76 in the CRFA group and 82 in the HA group) completed the 6-month post-treatment follow-up. In the CRFA group, 71% of the subjects had ≥50% reduction in the NRS pain score (primary end point) compared with 38% in the HA group (p < 0.0001). At 6 months, the mean NRS score reduction was 4.1 ± 2.2 for the CRFA group compared with 2.5 ± 2.5 for the HA group (p < 0.0001). The mean WOMAC score improvement at 6 months from baseline was 48.2% in the CRFA group and 22.6% in the HA group (p < 0.0001). At 6 months, 72% of the subjects in the CRFA group reported improvement in the GPE score compared with 40% in the HA group (p < 0.0001). CONCLUSIONS CRFA-treated subjects demonstrated a significant improvement in pain relief and overall function compared with subjects treated with a single injection of HA. No serious adverse events related to either procedure were noted, and the overall adverse-event profiles were similar. LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background Safe and effective non-surgical treatments are an important part of the knee osteoarthritis (OA) treatment algorithm. Cooled radiofrequency ablation (CRFA) and hyaluronic acid (HA) injections are two commonly used modalities to manage symptoms associated with knee OA. Methods A prospective 1:1 randomized study was conducted in 177 patients comparing CRFA to HA injection with follow-ups at 1, 3, 6 and 12 months. HA subjects with unsatisfactory outcomes at 6-months were allowed to crossover and receive CRFA. Knee pain (numeric rating scale = NRS), WOMAC Index (pain, stiffness and physical function), overall quality of life (global perceived effect = GPE, EQ-5D-5 L), and adverse events were measured. Results At 12-months, 65.2% of subjects in the CRFA cohort reported ≥50% pain relief from baseline. Mean NRS pain score was 2.8 ± 2.4 at 12 months (baseline 6.9 ± 0.8). Subjects in the CRFA cohort saw a 46.2% improvement in total WOMAC score at the 12-month timepoint. 64.5% of subjects in the crossover cohort reported ≥50% pain relief from baseline, with a mean NRS pain score of 3.0 ± 2.4 at 12 months (baseline 7.0 ± 1.0). After receiving CRFA, subjects in the crossover cohort had a 27.5% improvement in total WOMAC score. All subjects receiving CRFA reported significant improvement in quality of life. There were no serious adverse events related to either procedure and overall adverse event profiles were similar. Conclusion A majority of subjects treated with CRFA demonstrated sustained knee pain relief for at least 12-months. Additionally, CRFA provided significant pain relief for HA subjects who crossed over 6 months after treatment. Trial registration This trial was registered on ClinicalTrials.gov, NCT03381248. Registered 27 December 2017

It well known that long-lasting hyperglycaemia disrupts neuronal function and leads to neuropathy and other neurodegenerative diseases. The α-ketoglutarate analogue (DMOG) and the caspase-inhibitor “Ac-LETD-CHO are potential neuroprotective molecules. Whether their protections may also extend glucotoxicity-induced neuropathy is not known. Herein, we evaluated the possible cell-protective effects of DMOG and Ac-LETD-CHO against hyperglycaemia-induced reactive oxygen species and apoptosis in ND7/23 neuronal cells. The impact of glucotoxicity on the expression of HIF-1α and a panel of micro-RNAs of significance in hyperglycaemia and apoptosis was also investigated.ND7/23 cells cultured under hyperglycaemic conditions showed decreased cell viability and elevated levels of ROS production in a dose- and time-dependent manner. However, presence DMOG (500 µM) and/or Ac-LETD-CHO (50 µM) counteracted this effect and increase cell viability concomitant with reduction in ROS production, DNA damage and apoptosis. AcLETD-CHO suppressed hyperglycaemia-induced caspase 3 activation in ND7/23 cells. Both DMOG and Ac-LETD-CHO increased HIF-1α expression paralleled with the suppression of miR-126–5p, miR-128–3p and miR-181 expression and upregulation of miR-26b, 106a-5p, 106b-5p, 135a-5p, 135b-5p, 138–5p, 199a-5p, 200a-3p and 200c-3p expression.We demonstrate a mechanistic link for the DMOG and Ac-LETD-CHO protection against hyperglycaemia-induced neuronal dysfunction, DNA damage and apoptosis and thereby propose that pharmacological agents mimicking these effects may represent a promising novel therapy for the hyperglycaemia-induced neuropathy.