Durability of symptomatic responses obtained with adjunctive vagus nerve stimulation in treatment-resistant depression

Objective: To compare the durations of response achieved with adjunctive vagus nerve stimulation (VNS + TAU) vs treatment as usual (TAU) alone in treatment-resistant depression (TRD) over a 5-year period in the TRD registry. Materials and methods: Data from 271 participants on TAU and 328 participants on VNS + TAU were analyzed. Response was defined as \u3e /=50% decrease in baseline Montgomery-Asberg Depression Rating Scale (MADRS) score at postbaseline visit and was considered retained until the decrease was \u3c 40%. MADRS was obtained quarterly in year 1 and biannually thereafter. Time-to-events were estimated using Kaplan-Meier method and compared using log-rank test. HR was estimated using Cox proportion hazard model. Results: In the VNS + TAU arm, 62.5% (205/328) of participants had a first response over 5 years compared with 39.9% (108/271) in TAU. The time to first response was significantly shorter for VNS + TAU than for TAU (P \u3c 0.01). For responders in the first year, median time to relapse from first response was 10.1 months (Q1=4.2, Q3=31.5) for VNS + TAU vs 7.3 months (Q1=3.1, Q3=17.6) for TAU (P \u3c 0.01). HR=0.6 (95% CI: 0.4, 0.9) revealed a significantly lower chance for relapse in VNS + TAU. Probability of retaining first response for a year was 0.39 (0.27, 0.51) for TAU and 0.47 (0.38, 0.56) for VNS + TAU. Timing of the onset of the response did not impact the durability of the response. Conclusion: VNS therapy added to TAU in severe TRD leads to rapid onset and higher likelihood of response, and a greater durability of the response as compared to TAU alone

A role for ΔfosB in calorie restriction-induced metabolic changes

Background: Calorie restriction (CR) induces long-term changes in motivation to eat highly palatable food and, in body weight regulation, through an unknown mechanism. Methods: After a period of CR and refeeding, mice were assessed by behavioral and metabolic studies and for levels of the transcription factor ΔFosB. The ΔFosB levels were then increased specifically in nucleus accumbens (NAc) with viral-mediated gene transfer, and behavioral and metabolic studies were conducted. Results: We show that accumulation of ΔFosB in the NAc shell after CR in mice corresponds to a period of increased motivation for high fat reward and reduced energy expenditure. Furthermore, ΔFosB overexpression in this region increases instrumental responding for a high fat reward via an orexin-dependent mechanism while also decreasing energy expenditure and promoting adiposity. Conclusions: These results suggest that ΔFosB signaling in NAc mediates adaptive responses to CR.Instituto Multidisciplinario de Biología Celula

A role for ΔfosB in calorie restriction-induced metabolic changes

Background: Calorie restriction (CR) induces long-term changes in motivation to eat highly palatable food and, in body weight regulation, through an unknown mechanism. Methods: After a period of CR and refeeding, mice were assessed by behavioral and metabolic studies and for levels of the transcription factor ΔFosB. The ΔFosB levels were then increased specifically in nucleus accumbens (NAc) with viral-mediated gene transfer, and behavioral and metabolic studies were conducted. Results: We show that accumulation of ΔFosB in the NAc shell after CR in mice corresponds to a period of increased motivation for high fat reward and reduced energy expenditure. Furthermore, ΔFosB overexpression in this region increases instrumental responding for a high fat reward via an orexin-dependent mechanism while also decreasing energy expenditure and promoting adiposity. Conclusions: These results suggest that ΔFosB signaling in NAc mediates adaptive responses to CR.Instituto Multidisciplinario de Biología Celula

Reconceptualising treatment-resistant depression as difficult-to-treat depression

We are heartened that our consensus statement1 on difficult-to-treat depression has provoked robust debate. As pointed out by Lisa Cosgrove and colleagues,2 our proposed definition and model of care for difficult-to-treat depression is not derived from a systematic review or a Delphi technique. The term difficult-to-treat depression had previously been proposed to address semantic and conceptual issues with the so-called treatment-resistant depression model, for patients where achieving sustained remission proves elusive.3 We aimed to extend the discussion regarding this proposal, focusing on practical clinical advice. As the concept of difficult-to-treat depression is new, there is no literature to systematically review. The literature around the management of so-called treatment-resistant depression has been reviewed on many occasions, but this literature was only of partial relevance to our aims. Not only is there no universally accepted definition of treatment-resistant depression, but those that are used rarely if ever take into account psychotherapeutic or neurostimulatory treatments, or how to account for differential efficacy among treatments.4, 5 At the core of the proposed difficult-to-treat depression model is the importance of taking a holistic approach and considering all treatment options available. A systematic review of all treatments for depression was not practical. As a result, our consensus was based on the culmination of extensive discussion and deliberation among 15 international experts in the management of depression from across three continents, and the national guidelines for the treatment of depression from the countries represented. Rather than through a Delphi technique, we arrived at a consensus through many iterative reviews of the manuscript until all 15 contributors were comfortable with all the statements being discussed. However, we wish to clarify two key points that we feel Cosgrove and colleagues might have misunderstood

The Concise Health Risk Tracking-self Report: Psychometrics Within A Placebo-controlled Antidepressant Trial Among Depressed Outpatients

Background/aims: While substantial prior research has evaluated the psychometric properties of the 12-item Concise Health Risk Tracking-Self Report (CHRT-SR12), a measure of suicide propensity and suicidal thoughts, no prior research has investigated its factor structure, sensitivity to change over time, and other psychometric properties in a placebo-controlled trial of antidepressant medication, nor determined whether symptoms change throughout treatment. Methods: Participants in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study (n=278) provided data to evaluate the factor structure and sensitivity to change over time of the CHRT-SR12 through eight weeks of a clinical trial in which participants received either placebo or antidepressant medication (sertraline). Results/Outcomes: Factor analysis confirmed two factors: propensity (comprised of first-order factors including pessimism, helplessness, social support, and despair) and suicidal thoughts. Internal consistency (α’s ranged from 0.69–0.92) and external validity were both acceptable, with the total score and propensity factor scores significantly correlated with total scores and single-item suicidal-thoughts scores on the self-report Quick Inventory of Depressive Symptoms and the clinician-rated 17-item Hamilton Rating Scale for Depression. Through analyzing CHRT-SR12 changes over eight treatment weeks, the total score and both the factors decreased regardless of baseline suicidal thoughts. Change in clinician-rated suicidal thoughts was reflected by change in both the total score and propensity factor score. Conclusions/interpretation: These results confirm the reliability, validity, and applicability of the CHRT-SR12 to a placebo-controlled clinical trial of depressed outpatients receiving antidepressant medication

A Mini-Open, Dorsal Approach for Scaphoid Fracture Fixation With a Ligament Sparing Arthrotomy

There are several surgical approaches that are currently used to address nondisplaced scaphoid waist fractures, including percutaneous fixation, limited exposure fixation, and traditional open techniques through a volar or dorsal approach. Although percutaneous fixation has some theoretical advantages, it is much more difficult to achieve an accurate starting point for a headless compression screw. The purpose of this paper is to describe a simple, dorsal, mini-open approach to the scaphoid that minimizes incision size, extensor tendon dissection, capsular trauma, and vascular disruption, while still allowing for direct visualization of the proximal pole and optimal exposure for accurate screw placement. As a case report, we retrospectively evaluated 80 consecutive patients with closed scaphoid fractures. There were 2 groups, with 44 patients (age: 24±10 y) receiving a percutaneous dorsal approach and 36 patients (age: 30±16 y) treated with a mini-open approach. All scaphoid fractures were acute or fibrous nonunions (<6 mo from injury, except for one) treated with cannulated headless compression screws. Intraoperative and postoperative complications were measured and evaluated for each group to assess for differences between the percutaneous approach and the mini-open technique. We found no significant difference in complication rate with the mini-open dorsal technique compared with the dorsal percutaneous approach (8.3% vs. 4.5%, respectively). Therefore, we suggest consideration of this mini-open dorsal approach for scaphoid fracture fixation as a useful and safe technique

A Retrospective Review of Differences in Complication Rates between Dorsal Percutaneous and Mini-Open Surgical Fixation of Scaphoid Fractures

Abstract Objective  We retrospectively reviewed the complications of 80 cases of scaphoid screw fixation in acute fractures and early nonunions comparing dorsal percutaneous and mini-open approaches. Methods  We performed a chart review of all patients who underwent surgical fixation of a scaphoid fracture or a nascent nonunion using a dorsal percutaneous or dorsal mini-open technique by a single surgeon. We collected data on patient demographics, including age and smoking status, time to surgery, fracture type, union, and the major and minor complications that occurred in each group. Fisher's exact tests were used to compare the complication rates between the groups. Results  We identified 80 patients who underwent surgical fixation. Of these, 44 underwent percutaneous fixation and 36 underwent mini-open fixation. All fractures went on to heal. There was a total of five complications identified. There were no major complications in the percutaneous group, but one major complication in the mini-open group (a delayed union that eventually healed at 6 months). There were two minor complications in each group. There was no statistically significant difference in total, major, or minor complication rates between the groups. Conclusions  This study suggests that a dorsal percutaneous surgical technique for scaphoid fracture repair does not affect the complication rate despite prior literature to the contrary. Both techniques analyzed produce excellent rates of union with very low complication rates. Surgeon-specific technique rather than operative approach or exposure may be responsible for previously reported complication rates in the fixation of scaphoid fractures. Level of Evidence  This is a level III, therapeutic study

Endoscopic Lumbar Surgery: The State of the Art in 2019

This study was aimed to provide a brief historical perspective to facilitate appreciation of current techniques, describe outcomes of endoscopic lumbar surgery relative to those of existing techniques, and identify topics in need of study and future directions for the field of endoscopic lumbar surgery. Using the PubMed database, a comprehensive search was conducted to identify peer-reviewed English language articles pertaining to endoscopic lumbar surgery. Lack of focus on pertinent techniques or lack of outcome measures constituted exclusion criteria. A majority of included articles were published from 2015–2019. A context with which to appreciate the application of endoscopic lumbar techniques is established. An abundance of case series and several recent comparison studies have documented the benefits and potential pitfalls of these methods in the past two decades. The advantages of endoscopic lumbar spine surgery are widely touted to include reduced perioperative morbidity, including blood loss, operative time and immediate postoperative recovery, minimal structural trauma resulting from surgery, generally positive patient report outcome scores and the potential to contain costs. Additional high-quality research assessing outcomes of endoscopic lumbar surgery are certainly needed and currently expected given the rapid expansion of the field in recent years

The most influential publications in cervical myelopathy

Management of cervical myelopathy (CM) has continued to evolve through a better understanding of the long-term outcomes of this diagnosis as well as improved diagnostic guidelines. More recent literature continues to expand the field, but certain publications can be distinguished from others due to their lasting impact. Using the Clarivate Analytics Web of Science, search phrases were used to identify publications pertaining to CM. The fifty most cited articles were isolated. The frequency of citations, year of publication, country of origin, journal of publication, level of evidence (LOE), article type, as well as contributing authors and institutions were recorded. We also highlighted the five most cited articles (per year) from the past 10 years. Publications included ranged from 1952–2011, with the plurality of articles published during 2000–2009 (n=21; 42%). The most cited paper was Hillibrand’s 1999 reporting of adjacent segment disease rates following cervical fusions, followed by Hirabayashi’s 1983 review of his cervical laminoplasty outcomes. The third most cited was Brain’s 1952 review of the manifestations of cervical spondylosis. Spine contributed the most publications (n=26; 52%). A LOE of III was the most common (n=30; 60%). Clinical outcome articles were the most frequent type (n=28; 56%). Osaka University (Japan) and Kazou Yonenobu had the most contributions. Ames or Fehlings were the first or last author in each of the five most influential articles from the past 10 years. This bibliometric citation analysis identifies the most influential articles regarding CM. There are few publications with a high LOE, and more high powered studies are needed. Knowledge of these “classic” publications allows for a better overall understanding of the diagnosis, treatment, and future direction of research of CM

Amyloidoma: a review and case report

Amyloidoma is a solitary mass of amyloid protein that arises in patients with or without evidence of systemic amyloidosis, and can be found in a variety of different organ systems. Herein, we describe three cases of localized biopsy-positive amyloidomas with no evidence of systemic involvement-primary amyloidoma. Our cases include a patient with a paraspinal soft tissue amyloidoma, a patient with multiple primary amyloidomas involving the thoracic cavity and flank, and a patient with insulin-injection induced amyloidoma of the left shoulder. We present these cases to provide further insights into the clinical presentation of this uncommon clinical entity. We review the pathophysiology of amyloidosis and discuss our cases in the context of previous reports of amyloidoma