Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor.

Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a ß-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and Car8wdl/wdl mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in Car8wdl/wdl mice to control levels. Open field and footprinting assays showed that propranolol did not correct ataxia in Car8wdl/wdl mice. In vivo recordings in awake mice revealed that propranolol modulates the spiking activity of control and Car8wdl/wdl Purkinje cells. Recordings in cerebellar nuclei neurons, the targets of Purkinje cells, also revealed altered activity in propranolol-treated control and Car8wdl/wdl mice. Next, we tested whether propranolol reduces tremor through ß1 and ß2 adrenergic receptors. Propranolol did not change tremor amplitude or cerebellar nuclei activity in ß1 and ß2 null mice or Car8wdl/wdl mice lacking ß1 and ß2 receptor function. These data show that propranolol can modulate cerebellar circuit activity through ß-adrenergic receptors and may contribute to tremor therapeutics.

Neuromodulation of the cerebellum rescues movement in a mouse model of ataxia.

Deep brain stimulation (DBS) relieves motor dysfunction in Parkinson's disease, and other movement disorders. Here, we demonstrate the potential benefits of DBS in a model of ataxia by targeting the cerebellum, a major motor center in the brain. We use the Car8 mouse model of hereditary ataxia to test the potential of using cerebellar nuclei DBS plus physical activity to restore movement. While low-frequency cerebellar DBS alone improves Car8 mobility and muscle function, adding skilled exercise to the treatment regimen additionally rescues limb coordination and stepping. Importantly, the gains persist in the absence of further stimulation. Because DBS promotes the most dramatic improvements in mice with early-stage ataxia, we postulated that cerebellar circuit function affects stimulation efficacy. Indeed, genetically eliminating Purkinje cell neurotransmission blocked the ability of DBS to reduce ataxia. These findings may be valuable in devising future DBS strategies.

Risk factors for 30-day readmission and indication for ERCP following laparoscopic cholecystectomy: a retrospective NSQIP cohort study.

BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the safest, most commonly performed surgical procedures, but postoperative complications including bile leak, retained stone, cholangitis, and gallstone pancreatitis following LC occur in up to 2.6% of cases and may require readmission with possible endoscopic retrograde cholangiopancreatography (ERCP) intervention. There is a paucity of literature on factors predictive of need for ERCP following LC. The goal of this study is to describe the prevalence and risk factors for readmission with indication for ERCP. METHODS: We queried the ACS/NSQIP 2012-2017 Participant User Files for patients who underwent LC. Patient demographics, comorbidities, operative characteristics, and postoperative outcomes were evaluated. Multivariate logistic regression was used to identify risk factors for readmission with indication for ERCP intervention. RESULTS: Of 275,570 patients, 11,010 (4.00%) were readmitted within the 30-day postoperative period. Among these, 930 (8.44%) were admitted with indication for ERCP intervention. On multivariate regression, readmissions were more likely in older patients, inpatients, and patients with baseline comorbidities, acute preoperative morbidity, and those discharged to care facilities. The use of intraoperative cholangiogram was associated with lower odds of readmission. Less than 10% of readmitted patients had an indication for ERCP. Those who were readmitted with an indication for ERCP were more likely to have undergone emergency surgery, experienced longer operative times, and had elevated preoperative LFTs or gallstone pancreatitis prior to surgery. The risk of 30-day mortality was significantly higher among patients who experienced any complications after their surgery (OR 13.03, 95% CI 10.57-16.07, p < 0.001). CONCLUSIONS: Older patients, patients with greater preoperative morbidity, and those discharged to care facilities were more likely to be readmitted for any reason following laparoscopic cholecystectomy, whereas patients with evidence of complicated gallstone disease were more likely to be readmitted with an indication for ERCP, even when controlling for the use of intraoperative cholangiogram. Initiatives aimed at reducing readmission with indication for ERCP should focus on these patient subgroups.

Social Media and the Dissemination of Research: Insights from the Most Widely Circulated Articles in Plastic Surgery.

BACKGROUND: The purpose of this study is to quantify the relationship between social media use and the dissemination of research across nontraditional channels. METHODS: Between June and August of 2016, the authors identified 10 plastic surgery journals with the highest impact factor and their 10 most widely circulated articles. Article age; journal impact factor; "distinguished" article designation; and social media metadata of the first authors, last authors, and journals were incorporated into a multivariate regression model to predict the Altmetric Attention Score, a quantitative measure of popularity across Web-based media platforms. RESULTS: A total of 100 articles, 181 authors, and 10 journals were identified. Older articles tended to be less popular. The article's popularity was associated with the journal's audience size, but not with the author's social media activity. For each 1000 additional Twitter followers of the journal of publication, the Altmetric score is greater by a factor of 1.72 (95 percent CI, 1.076 to 2.749), which is the equivalent of 72 percent more Tweets. There is also a small but statistically significant negative association between the author's social media audience size and the popularity of his or her articles: for every 1000 additional followers, the Altmetric score is lower by a factor of 0.822 (95 percent CI, 0.725 to 0.932), which is the equivalent of 17.8 percent fewer Tweets. CONCLUSION: The popularity of an article across social media platforms is associated with the journal's audience on social media, not with the magnitude of the author's social media activity.

Distraction Osteogenesis for Surgical Treatment of Craniosynostosis: A Systematic Review.

BACKGROUND: Distraction osteogenesis has been proposed as an alternative to cranial remodeling surgery for craniosynostosis, but technique descriptions and outcome analyses are limited to small case series. This review summarizes operative characteristics and outcomes of distraction osteogenesis and presents data comparing distraction osteogenesis to cranial remodeling surgery. METHODS: A systematic review of the literature was undertaken. Descriptive analysis, operative technical data, outcomes, or postoperative complications of distraction osteogenesis for craniosynostosis were included. RESULTS: A total of 1325 citations were reviewed, yielding 53 articles and 880 children who underwent distraction osteogenesis for craniosynostosis. Distraction plates were used in 754 patients (86 percent), whereas springs were used for the remaining 126 patients (14 percent). Standard and spring distraction osteogenesis was reported to successfully treat the primary condition 98 percent of the time. Suboptimal results were reported in 11 patients (1.3 percent), and minor complications were reported in 19.5 percent of cases (n = 172).Major complications were rare, occurring in 3.5 percent of cases (n = 31), and included two reported deaths. Absolute operative times and blood loss were marginally greater for cranial remodeling surgery cases, but the differences were not statistically significant. CONCLUSIONS: Distraction osteogenesis is an effective cranial vault remodeling technique for treating craniosynostosis. No statistical differences were found with respect to operative time, blood loss, need for transfusion, or intensive care unit resources compared with cranial remodeling surgery. Outcome studies with longer follow-up periods specifically investigating cost, relapse, and reoperation rates are necessary to effectively compare this treatment modality as an alternative to cranial remodeling surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The importance of timing in optimizing cranial vault remodeling in syndromic craniosynostosis.

BACKGROUND: The purpose of this study was to gain insight into the impact of age at repair on relapse rates in syndromic patients undergoing cranial vault remodeling. METHODS: Retrospective chart review was performed for patients surgically treated for syndromic craniosynostosis from 1990 to 2013. Surgical procedures were assigned a Whitaker category based on need for reoperation as follows: no additional surgery required (category I); minor contouring revisions required (II); major revisions required (III); or failure of original surgery (IV). Age at surgery was grouped as follows: younger than 6 months; aged 6 to 9 months; and older than 9 months. Multivariable logistic regression analysis was performed to determine the relationship between age at surgery and need for reoperation by Whitaker category. RESULTS: Fifty-two patients undergoing a total of 65 planned cranial vault remodeling procedures were included. Multivariate logistic regression analysis revealed that patients younger than 6 months at the time of primary surgery carried a 4.10 greater odds (95 percent CI, 1.31 to 12.87; p = 0.016) of requiring a subsequent major reoperation, and being older than 9 months of age carried a 13.2 greater odds (95 percent CI, 1.39 to 124.30; p = 0.024) of requiring a subsequent minor revision. CONCLUSIONS: Timing of surgery is an important factor to consider when planning vault remodeling in syndromic craniosynostosis. Based on our institution's experience, when there is no concern for elevated intracranial pressure the ideal operative window for these procedures in the syndromic population appears to be 6 to 9 months of age.