Ultrasound-Guided Peripheral Nerve Blocks for Shoulder Dislocation in the Emergency Department: A Systemic Review.

BACKGROUND: Shoulder dislocations are among the most common orthopedic emergencies encountered in the emergency department (ED). Ultrasound-guided peripheral nerve blocks (USG-PNBs) are increasingly being used for acute pain management in the ED, but clinical evidence supporting their utility for shoulder dislocation is limited and often conflicting. OBJECTIVE: The aim of this review was to summarize and evaluate the utility of USG-PNB for analgesia during closed reduction of dislocated shoulders in the ED. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search of the PubMed, Scopus, and Cochrane databases was performed from database inception to September 2022. We included clinical studies examining USG-PNB for pain management of dislocated shoulders in the ED. Information collected from eligible studies included patient demographic characteristics, USG-PNB approach, alternate analgesia techniques, anesthetic regimens, clinical outcomes, and adverse events. RESULTS: Five studies met inclusion criteria, all of which were randomized controlled trials comparing USG-PNB with procedural sedation and analgesia. Pooled patient satisfaction scores were similar for both analgesia methods (3.5 ± 0.6 vs. 3.9 ± 0.6 out of 5; p = 0.76). Patients managed with procedural sedation and analgesia achieved higher rates of overall shoulder reduction (100% vs. 67%; p < 0.001) and successful reduction on the first attempt (86% vs. 48%; p < 0.001). The USG-PNB groups in all but one study had shorter lengths of ED stay. Overall, USG-PNB was associated with a lower risk of adverse events and complications (3.9% vs. 24.9%; p < 0.001), especially adverse respiratory events (0% vs. 14.7%; p < 0.001). CONCLUSIONS: USG-PNBs performed by adequately trained emergency physicians should be considered a safe and effective alternative for analgesia during closed reduction of dislocated shoulders in the ED, particularly in patients with cardiorespiratory comorbidities.

Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods.

Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.

The Role of PIEZO2 in Human Mechanosensation.

BACKGROUND: The senses of touch and proprioception evoke a range of perceptions and rely on the ability to detect and transduce mechanical force. The molecular and neural mechanisms underlying these sensory functions remain poorly defined. The stretch-gated ion channel PIEZO2 has been shown to be essential for aspects of mechanosensation in model organisms. METHODS: We performed whole-exome sequencing analysis in two patients who had unique neuromuscular and skeletal symptoms, including progressive scoliosis, that did not conform to standard diagnostic classification. In vitro and messenger RNA assays, functional brain imaging, and psychophysical and kinematic tests were used to establish the effect of the genetic variants on protein function and somatosensation. RESULTS: Each patient carried compound-inactivating variants in PIEZO2, and each had a selective loss of discriminative touch perception but nevertheless responded to specific types of gentle mechanical stimulation on hairy skin. The patients had profoundly decreased proprioception leading to ataxia and dysmetria that were markedly worse in the absence of visual cues. However, they had the ability to perform a range of tasks, such as walking, talking, and writing, that are considered to rely heavily on proprioception. CONCLUSIONS: Our results show that PIEZO2 is a determinant of mechanosensation in humans. (Funded by the National Institutes of Health Intramural Research Program.).

Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement.

Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of disorders characterized by lower extremity spasticity and weakness. Recently, the first de novo mutations in KIF1A were identified in patients with an early-onset severe form of complicated hereditary spastic paraplegia. We report two additional patients with novel de novo mutations in KIF1A, hereby expanding the genetic spectrum of KIF1A-related hereditary spastic paraplegia. Both children presented with spastic paraplegia and additional findings of optic nerve atrophy, structural brain abnormalities, peripheral neuropathy, cognitive/language impairment, and never achieved ambulation. In particular, we highlight the progressive nature of cerebellar involvement as captured on sequential magnetic resonance images (MRIs), thus linking the neurodegenerative and spastic paraplegia phenotypes. Exome sequencing in patient 1 and patient 2 identified novel heterozygous missense mutations in KIF1A at c.902G>A (p.R307Q) and c.595G>A (p.G199 R), respectively. Therefore, our report contributes to expanding the genotypic and phenotypic spectrum of hereditary spastic paraplegia caused by mutations in KIF1A.