Outcomes of Transcatheter Aortic Valve Replacement in the United Arab Emirates: Real-world, Single-centre Experience from an Emerging Programme.

Background: Data on outcomes of transcatheter aortic valve replacement (TAVR) in the Middle East, particularly in the United Arab Emirates (UAE), are limited. Whether centres with a low volume of patients requiring the procedure can achieve similar outcomes as those reported in pivotal clinical trials remains unclear. This study evaluates procedural outcomes of patients undergoing TAVR in a newly established programme in the UAE. Methods: Procedural outcomes of consecutive patients who underwent transfemoral TAVR at a single centre in the UAE between January 2016 and November 2021 were compared with those at centres in the lowest quartile (Q1) of procedural volume in the Transcatheter Valve Therapy Registry, which covers centres in the US. Results: Among the 183 patients included in the study, the median age was 76 years (interquartile range [IQR] 71-82), and 42.1% of patients were women, with a median Society of Thoracic Surgeons predicted risk of mortality score of 4.6 (IQR 2.9-7.5). Most of the patients (93.3%) received a balloon-expandable valve. All-cause death within 30 days, stroke and major vascular complications occurred in 0.6%, 0.6% and 2.2% of patients, respectively, compared with 3.1%, 2.2% and 4% in patients treated at Q1 hospitals. Conclusion: Patients undergoing transfemoral TAVR at an emerging centre in the Middle East had favourable outcomes compared with those performed at Q1 hospitals in the US. These findings suggest that careful patient selection for TAVR is critical and may help optimise patient outcomes, especially when procedural volumes are low.

Acupuncture treatment on the motor area of the scalp for motor dysfunction in children with cerebral palsy: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Scalp acupuncture has been widely used as treatment for motor dysfunction in children with cerebral palsy in China. Previous studies have failed to provide high-quality evidence to demonstrate the effectiveness of this treatment in children with cerebral palsy. No high-quality randomized controlled trials on scalp acupuncture have been published. The aim of this study is to evaluate the effectiveness of Jiao's scalp acupuncture when combined with routine rehabilitation treatment versus routine rehabilitation treatment alone for motor dysfunction in children with cerebral palsy. METHODS/DESIGN: This is a four-centre randomized controlled trial. One hundred cerebral palsy patients with motor dysfunction were enrolled. Patients will be allocated in a 1:1 ratio into either an acupuncture treatment group or a control group. Cerebral palsy patients in the control group will receive conventional rehabilitation treatment, whereas patients in the acupuncture group will receive a combination of scalp acupuncture and conventional rehabilitation treatment. Thirty-six treatment sessions will be performed over a 12-week period. The Gross Motor Function Measure and the Fine Motor Function Measure Scale will be assessed as the primary outcome measures. The Paediatric Evaluation of Disability Inventory and the Cerebral Palsy Quality of Life Questionnaire for Children will be selected as secondary outcome measures. All assessments will be conducted at baseline, week 4 (treatment 12), week 8 (treatment 24), week 12 (treatment 36) and week 24 (follow-up). DISCUSSION: This is the first trial evaluating the efficacy and safety of scalp acupuncture as a treatment for motor dysfunction in children with cerebral palsy. The results of this trial are expected to provide relevant evidence demonstrating that scalp acupuncture can be used as an effective rehabilitation treatment method for improving motor dysfunction in children with cerebral palsy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03921281. Registered on 19 April 2019.

δ-Opioid Receptor Activation Attenuates Hypoxia/MPP+-Induced Downregulation of PINK1: a Novel Mechanism of Neuroprotection Against Parkinsonian Injury.

There is emerging evidence suggesting that neurotoxic insults and hypoxic/ischemic injury are underlying causes of Parkinson's disease (PD). Since PTEN-induced kinase 1 (PINK1) dysfunction is involved in the molecular genesis of PD and since our recent studies have demonstrated that the δ-opioid receptor (DOR) induced neuroprotection against hypoxic and 1-methyl-4-phenyl-pyridimium (MPP+) insults, we sought to explore whether DOR protects neuronal cells from hypoxic and/or MPP+ injury via the regulation of PINK1-related pathways. Using highly differentiated rat PC12 cells exposed to either severe hypoxia (0.5-1% O2) for 24-48 h or varying concentrations of MPP+, we found that both hypoxic and MPP+ stress reduced the level of PINK1 expression, while incubation with the specific DOR agonist UFP-512 reversed this reduction and protected the cells from hypoxia and/or MPP+-induced injury. However, the DOR-mediated cytoprotection largely disappeared after knocking down PINK1 by PINK1 small interfering RNA. Moreover, we examined several important signaling molecules related to cell survival and apoptosis and found that DOR activation attenuated the hypoxic and/or MPP+-induced reduction in phosphorylated Akt and inhibited the activation of cleaved caspase-3, whereas PINK1 knockdown largely deprived the cell of the DOR-induced effects. Our novel data suggests a unique mechanism underlying DOR-mediated cytoprotection against hypoxic and MPP+ stress via a PINK1-mediated regulation of signaling.

δ-Opioid Receptor-Nrf-2-Mediated Inhibition of Inflammatory Cytokines in Neonatal Hypoxic-Ischemic Encephalopathy.

Neonatal hypoxic-ischemic encephalopathy (HIE) causes serious neurological disability; there are, however, currently few promising therapies for it. We have recently shown that δ-opioid receptor (DOR) is neuroprotective by downregulating TNF-α. Since hypoxia-ischemia (HI) triggers a robust inflammatory response, which exacerbates HI brain damage, we investigated, in this study, whether DOR activation could regulate inflammatory cytokine expression, thereby playing a protective effect on the neonatal brain under HI. Twenty-five neonatal rats were randomly divided into five groups: (1) control (control); (2) HI; (3) HI with saline (HI + NS); (4) DOR activation with UFP-512 (a potent and specific DOR agonist) under HI conditions (HI + U); and (5) DOR inhibition using NT treatment under HI conditions (HI + NT). The rats were sacrificed by decapitation at 24 h after HI, and their brains were rapidly removed for measurements. The protein expression of TNF-α, IL-6, ICAM-1, IL-10, IL-18, NQO-1, Nrf-2, and HO-1 was measured using Western blot. In the hemispheres exposed to HI, DOR activation significantly decreased the expressions of TNF-α, IL-6, and ICAM-1 in the cortex, while it significantly increased IL-10 and had no effect on IL-18 in the same region. In contrast, DOR had no appreciable effect on inflammatory cytokine expression in non-cortical tissues including hippocampal, subcortical, and cerebellar tissues. Moreover, HI stress triggered an upregulation of Nrf-2 nuclear protein as well as some of its downstream anti-inflammatory genes such as HO-1 and NQO-1 in the cortex, while DOR activation further augmented such a protective reaction against HI injury. DOR plays an important role in protecting against HI by regulating the expression of inflammatory and anti-inflammatory cytokines in the cortex, which is likely mediated by the Nrf-2/HO-1/NQO-1 signaling.

Acupuncture treatment on the motor area of the scalp for motor dysfunction in patients with ischemic stroke: study protocol for a randomized controlled trial.

BACKGROUND: Scalp acupuncture has shown a remarkable treatment efficacy on motor dysfunction in patients with stroke in China, especially the motor area of Jiao's scalp acupuncture, which is the most widely used treatment. However, previous studies have summarized that the clinical curative effect of acupuncture treatment for stroke remains uncertain. Meanwhile, no randomized controlled trials on Jiao's scalp acupuncture have been performed. The aim of this study is to evaluate the efficacy and safety of Jiao's scalp acupuncture for motor dysfunction in ischemic stroke. METHODS/DESIGN: This is an assessor- and analyst-blinded, randomized controlled trial. One hundred and eight stroke patients with motor dysfunction meeting the inclusion criteria will be allocated by a 1:1 ratio into either an acupuncture treatment group or a control group. Stroke patients in the control group will receive conventional rehabilitation treatment, whereas a combination of Jiao's scalp acupuncture and conventional rehabilitation treatment will be applied to the acupuncture group. Forty treatment sessions will be performed over an 8-week period. The Fugl-Meyer Assessment scale will be assessed as the primary outcome measure. The Modified Barthel Index, the Stroke-Specific Quality of Life, and the Stroke Syndrome of Traditional Chinese Medicine scales will be selected as secondary outcome measurements. All assessments will be conducted at baseline, week 4 (treatment 20), week 8 (treatment 40), week 12 (follow-up), and week 16 (follow-up). DISCUSSION: This is the first trial evaluating the efficacy and safety of Jiao's scalp acupuncture for motor dysfunction in ischemic stroke. The results of this trial are expected to provide relevant evidence demonstrating that Jiao's scalp acupuncture can be used as an effective rehabilitation treatment method for improving motor dysfunction in ischemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02871453 . Registered on 17 July 2016.