No abstract

Pre-extinction administration of ∆9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 hours after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders.

IMPORTANCE Dermatofibrosarcoma protuberans (DFSP) has the potential for local destruction and recurrence, although it carries a low risk of metastasis. Complete surgical resection with negative margins is considered the gold standard for treatment; however, there are cases that are unresectable owing to tumor extension or size or owing to risk of cosmetic and/or functional impairment. Imatinib treatment has been used for locally advanced or metastatic DFSP.OBJECTIVE To evaluate the usefulness of imatinib for treating DFSP. EVIDENCE REVIEWWe conducted a systematic review on the PubMed and Embase databases for articles published from September 2002 through October 2017 using the key words "dermatofibrosarcoma" or "dermatofibrosarcoma protuberans" AND "therapy" AND "imatinib." References within retrieved articles were also reviewed to identify additional studies. Studies of adults with histologically proven DFSP treated with imatinib as monotherapy or as an adjuvant or neoadjuvant therapy to surgery were included. Extracted data were analyzed using descriptive statistics. PRISMA guidelines were followed. All analysis took place October through December 2017.FINDINGS Nine studies met inclusion criteria; 152 patients were included. The calculated mean patient age was 49.3 years (range, 20-73 years). Calculated mean tumor diameter was 9.9 cm (range, 1.2-49.0 cm). When COL1A1-PDGFβ protein translocation (collagen, type 1, alpha 1-platelet-derived growth factor β) was reported, it was present in 90.9% of patients (111 of 122). Complete response was seen in 5.2% of patients (8 of 152), partial response in 55.2% (84 of 152), stable disease in 27.6% (42 of 152), and progression in 9.2% (14 of 152). Four of the 152 patients (2.6%) were excluded from the analysis owing to unknown or unevaluable response. There were no differences in response rate using 400-mg or 800-mg daily doses (67.5% or 27 of 40 patients for 400-mg dose vs 67.1% or 49 of 73 patients for 800-mg dose complete or partial response; P > .99). Adverse events were present in at least 73.5% of cases (78 of 106); severe adverse events were present in 15.1% of cases (20 of 132). CONCLUSIONS AND RELEVANCEImatinib is a useful directed therapy in patients with DFSP who are not surgical candidates owing to disease extension or significant cosmetic or functional impairment. There seems to be no difference between 400-or 800-mg daily doses.

No abstract

Objectives It is unknown to what degree spontaneous improvement accounts for the large placebo response observed in antidepressant trials for Major Depressive Disorder (MDD). The purpose of this study was to estimate the spontaneous improvement observed in treatment-seeking individuals with acute MDD by determining the symptom change in depressed patients assigned to wait-list controls in psychotherapy studies. Method The databases PubMed and PsycINFO were searched to identify randomized, prospective studies randomizing outpatients to psychotherapy or a wait-list control condition for the treatment of acute MDD. Standardized effect sizes calculated from each identified study were aggregated in a meta-analysis to obtain a summary statistic for the change in depression scores during participation in a wait-list control. Results Ten trials enrolling 340 participants in wait-list control conditions were identified. The estimated effect size for the change in depression scores during wait-list control was 0.505 (95% CI 0.271 – 0.739, p < 0.001), representing an average improvement of 4 points on the Hamilton Rating Scale for Depression. Discussion Depressed patients acutely experience improvement even without treatment, but spontaneous improvement is unlikely to account for the magnitude of placebo response typically observed in antidepressant trials. These findings must be interpreted in light of the small number wait-list control participants available for analysis as well as certain methodological heterogeneity in the psychotherapy studies analyzed.

Background: Over 5 million basal and squamous cell skin cancers are diagnosed each year. Seventy to 80% of these cancers occur in the head and neck region, for which surgical excision is the standard treatment. As patient satisfaction and quality of life are among the most important outcomes in plastic and reconstructive surgery, understanding patient perception of aesthetic postoperative outcome is critical. The objective of this study was to assess aesthetic satisfaction following facial skin cancer surgery using the FACE-Q Skin Cancer Module in the context of sociodemographic and clinical factors. Methods: This is a single-center, cross-sectional study in a tertiary care cancer setting of patients who underwent facial skin cancer surgery from March 1, 2016, to March 31, 2018. Patients completed the FACE-Q Skin Cancer Satisfaction with Facial Appearance and Appraisal of Scar scales postoperatively, between May 21, 2018, and October 1, 2018. Results: Patients completed the Satisfaction with Facial Appearance (n = 405) and Appraisal of Scar scales (n = 408) postoperatively (response rate 39%). Lower postoperative facial appearance and scar satisfaction scores were associated with female gender, younger age (<65 years), surgery location on the lip or nose, repair by flap or graft, and greater defect size. Linear regression models established that younger age, female gender, nose location, and flap repair were independently predictive of lower aesthetic satisfaction. Conclusions: Sociodemographic factors, central facial location, and repair type strongly contribute to aesthetic satisfaction following facial skin cancer surgery. This patient-reported data may guide counseling regarding postoperative aesthetic outcome and inform patient expectations.

Group sample sizes were small and we did not include a trauma-exposed group without PTSD CONCLUSIONS: Both SAD and PTSD generalize expectations of an aversive outcome across CSs, even when a CS never signals an aversive outcome and PTSD may tend to over-expect threat. Fear learning and extinction abnormalities may be a core feature underlying shared symptoms across fear-based disorders.

No abstract