Early reduction in postoperative pain is associated with improved long-term function after shoulder arthroplasty: a retrospective case series.

PURPOSE: Mixed modalities are frequently utilized in total shoulder arthroplasty (TSA) to control pain, improve patient satisfaction, reduce narcotics use and facilitate earlier discharge. We investigate the relationship between early postoperative pain control and long-term functional outcomes after shoulder arthroplasty. METHODS: A retrospective review identified 294 patients (314 shoulders) who underwent anatomic or reverse TSA and received a continuous cervical paravertebral nerve block perioperatively. Opioid and non-opioid analgesics were also available to the patients in an "as needed" capacity to augment perioperative pain control. In addition to demographic and surgical characteristics, the impact on functional outcomes of relative pain (i.e., a patient's subjective pain relative to the entire cohort), pain gradient (i.e., the slope of a patient's subjective pain), and opioid consumption during the first 24 h postoperatively were assessed. Shoulder function was assessed using validated outcome measures collected at 2 year follow-up. Outcomes were measured using American Shoulder and Elbow Surgeons questionnaire (ASES), Shoulder Pain and Disability Index (SPADI), SPADI-130, Raw and Normalized Constant Score, SST-12 and UCLA score. RESULTS: Patients younger than 65, females, reverse TSA, revisions, and preoperative opioid users had worse functional outcomes. On univariate analysis, increased pain perioperatively (> 50% percentile relative pain) was associated with decreased function at 2 years when analyzed with all seven outcome scores (P < .001 for all), reaching minimal clinically important difference (MCID) using the Constant Score. On multivariate analysis, increased pain in the first 24 h postoperatively (assessed on a continuous scale) was independently associated with worse ASES, SPADI, and SPADI-130 scores. Intraoperative ketamine administration and opioid consumption in the 24 h postoperative period did not influence long-term shoulder function. CONCLUSION: Patients reporting reduced pain after TSA demonstrated improved shoulder function with the Constant score at 2 years postoperatively in both univariate and multivariate analysis. Larger-scale investigation may be warranted to see if this is true for other functional outcome measures. LEVEL OF EVIDENCE: III, treatment study.

Site-specific modifications to AAV8 capsid yields enhanced brain transduction in the neonatal MPS IIIB mouse.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal disease caused by defective production of the enzyme α-N-acetylglucosaminidase. It is characterized by severe and complex central nervous system degeneration. Effective therapies will likely target early onset disease and overcome the blood-brain barrier. Modifications of adeno-associated viral (AAV) vector capsids that enhance transduction efficiency have been described in the retina. Herein, we describe for the first time, a transduction assessment of two intracranially administered adeno-associated virus serotype 8 variants, in which specific surface-exposed tyrosine (Y) and threonine (T) residues were substituted with phenylalanine (F) and valine (V) residues, respectively. A double-mutant (Y444 + 733F) and a triple-mutant (Y444 + 733F + T494V) AAV8 were evaluated for their efficacy for the potential treatment of MPS IIIB in a neonatal setting. We evaluated biodistribution and transduction profiles of both variants compared to the unmodified parental AAV8, and assessed whether the method of vector administration would modulate their utility. Vectors were administered through four intracranial routes: six sites (IC6), thalamic (T), intracerebroventricular, and ventral tegmental area into neonatal mice. Overall, we conclude that the IC6 method resulted in the widest biodistribution within the brain. Noteworthy, we demonstrate that GFP intensity was significantly more robust with AAV8 (double Y-F + T-V) compared to AAV8 (double Y-F). This provides proof of concept for the enhanced utility of IC6 administration of the capsid modified AAV8 (double Y-F + T-V) as a valid therapeutic approach for the treatment of MPS IIIB, with further implications for other monogenic diseases.

A case of West Nile virus encephalitis accompanied by diabetic ketoacidosis and rhabdomyolysis.

INTRODUCTION: We present here a case of West Nile Virus (WNV) encephalitis that initially presented with diabetic ketoacidosis and rhabdomyolysis. CASE PRESENTATION: A 35-year-old male with no past medical history presented to the emergency department complaining of polydipsia, generalized weakness, lightheadedness, and visual disturbances of one week duration. He was found to be in diabetic ketoacidosis. His hemoglobin A1c was 11%. The patient was appropriately treated for diabetic ketoacidosis and it resolved on hospital day 1. On hospital day 2, the patient developed a fever of 101.6 °F and his mental status became severely altered. He developed auditory and visual hallucinations. IgM and IgG antibodies to West Nile Virus were positive in the cerebral spinal fluid (CSF). The patient's creatine kinase level rose to 118,400 U/L during his hospitalization and eventually returned to baseline. The patient made a full recovery with no residual neurologic deficits after an 11 day hospital course. DISCUSSION: In this patient, neuroinvasive WNV was confirmed with positive CSF IgM. The patient's newly diagnosed diabetes likely contributed to his susceptibility to neuroinvasive disease. Furthermore, WNV encephalitis in a background of DKA has not been previously described in the literature and this case demonstrates WNV neuroinvasive disease should be in the differential diagnosis for patients presenting with unexplained neurological symptoms. CONCLUSION: Diagnosis of neuroinvasive WNV is imperative to stop unnecessary therapies, limit further diagnostic evaluation, help predict patient outcomes, direct public health prevention measures, and further provide investigations into the clinical conditions that define the spectrum of WNV disease.