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The incidence and biochemical consequences of rare tumor subtypes are often hard to study. Fibrolamellar liver cancer (FLC) is a rare malignancy affecting adolescents and young adults. To better characterize the incidence and biochemical consequences of this disease, we combined a comprehensive analysis of the electronic medical record and national payer data and found that FLC incidence is likely five to eight times higher than previous estimates. By employing unsupervised learning on clinical laboratory data from patients with hyperammonemia, we find that FLC-associated hyperammonemia mirrors metabolic dysregulation in urea cycle disorders. Our findings demonstrate that advanced computational analysis of rich clinical datasets can provide key clinical and biochemical insights into rare cancers.

BACKGROUND: Biliary cancers are rare, and few reported cases of brain metastases from primary biliary cancers exist, especially describing patients in the United States. This report assesses the proportion and incidence of brain metastases arising from primary biliary cancers [cholangiocarcinoma (CCA) and gallbladder cancer] at Stanford University and the University of California, San Francisco, describes clinical characteristics, and provides a case series. METHODS: We queried 3 clinical databases at Stanford and the University of California, San Francisco to retrospectively identify and review the charts of 15 patients with brain metastases from primary biliary cancers occurring between 1990 to 2020. RESULTS: Among patients with brain metastases analyzed at Stanford (3,585), 6 had a primary biliary cancer, representing 0.17% of all brain metastases. Among biliary cancer patients at the University of California, San Francisco (1,055), 9 had brain metastases, representing an incidence in biliary cancer of 0.85%. A total of 15 biliary cancer patients with brain metastases were identified at the two institutions. Thirteen out of 15 patients (86.7%, 95% CI: 59.5-98.3) were female. The median overall survival from primary biliary cancer diagnosis was 214 days (95% CI: 71.69-336.82 days) and subsequent OS from the time of brain metastasis diagnosis was 57 days (95% CI: 13.43-120.64 days). Death within 90 days of brain metastasis diagnosis occurred in 66.67% of patients (95% CI: 38.38-88.17). CONCLUSIONS: Brain metastases from primary biliary cancers are rare, with limited survival once diagnosed. This report can aid health care providers in caring for patients with brain metastases from primary biliary cancers.

Background: Cognitive therapy for social anxiety disorder (CT-SAD) is recommended by NICE (2013) as a first-line intervention. Take up in routine services is limited by the need for up to 14 ninety-min face-to-face sessions, some of which are out of the office. An internet-based version of the treatment (iCT-SAD) with remote therapist support may achieve similar outcomes with less therapist time. Methods: 102 patients with social anxiety disorder were randomised to iCT-SAD, CT-SAD, or waitlist (WAIT) control, each for 14 weeks. WAIT patients were randomised to the treatments after wait. Assessments were at pre-treatment/wait, midtreatment/wait, posttreatment/wait, and follow-ups 3 & 12 months after treatment. The pre-registered (ISRCTN 95 458 747) primary outcome was the social anxiety disorder composite, which combines 6 independent assessor and patient self-report scales of social anxiety. Secondary outcomes included disability, general anxiety, depression and a behaviour test. Results: CT-SAD and iCT-SAD were both superior to WAIT on all measures. iCT-SAD did not differ from CT-SAD on the primary outcome at post-treatment or follow-up. Total therapist time in iCT-SAD was 6.45 h. CT-SAD required 15.8 h for the same reduction in social anxiety. Mediation analysis indicated that change in process variables specified in cognitive models accounted for 60% of the improvements associated with either treatment. Unlike the primary outcome, there was a significant but small difference in favour of CT-SAD on the behaviour test. Conclusions: When compared to conventional face-to-face therapy, iCT-SAD can more than double the amount of symptom change associated with each therapist hour. [ABSTRACT FROM AUTHOR]

Objective: There is a growing body of evidence for the effectiveness of trauma-focused cognitive behavior therapy (TF-CBT) for posttraumatic stress disorder (PTSD), but few studies to date have investigated the mechanisms by which TF-CBT leads to therapeutic change. Models of PTSD suggest that a core treatment mechanism is the change in dysfunctional appraisals of the trauma and its aftermath. If this is the case, then changes in appraisals should predict a change in symptoms. The present study investigated whether cognitive change precedes symptom change in Cognitive Therapy for PTSD, a version of TF-CBT. Method: The study analyzed weekly cognitive and symptom measures from 268 PTSD patients who received a course of Cognitive Therapy for PTSD, using bivariate latent growth modeling. Results: Results showed that (a) dysfunctional trauma-related appraisals and PTSD symptoms both decreased significantly over the course of treatment, (b) changes in appraisals and symptoms were correlated, and (c) weekly change in appraisals significantly predicted subsequent reduction in symptom scores (both corrected for the general decrease over the course of therapy). Changes in PTSD symptom severity did not predict subsequent changes in appraisals. Conclusions: The study provided preliminary evidence for the temporal precedence of a reduction in negative trauma-related appraisals in symptom reduction during trauma-focused CBT for PTSD. This supports the role of change in appraisals as an active therapeutic mechanism. (Contains 3 tables, 1 figure, and 1 footnote.)

Negative self-images appear to play a role in the maintenance of social phobia and research suggests they are often linked to earlier memories of socially traumatic events. Imagery rescripting is a clinical intervention that aims to update such unpleasant or traumatic memories, and is increasingly being incorporated in cognitive behavioral therapy programs. In previous research, we have found that imagery rescripting was superior to a control condition in terms of its beneficial effects on negative beliefs, image and memory distress, fear of negative evaluation, and anxiety in social situations. In this article, we describe our imagery rescripting procedure. We consider the importance of updating negative imagery in social phobia, the theoretical basis for imagery rescripting, directions for future research, and how to conduct imagery rescripting, including potential problems and their solutions. (Contains 3 tables.)

Negative self-images are a maintaining factor in social phobia. A retrospective study (Hackmann, A., Clark, D.M., McManus, F. (2000). Recurrent images and early memories in social phobia. Behaviour Research and Therapy, 38, 601-610) suggested that the images may be linked to early memories of unpleasant social experiences. This preliminary study assessed the therapeutic impact of rescripting such memories. Patients with social phobia (N=11) attended 2 sessions, 1 week apart. The first was a control session in which their images and memories were discussed but not modified. The second was an experimental session in which cognitive restructuring followed by an imagery with rescripting procedure was used to contextualize and update the memories. No change was observed after the control session. The experimental session led to significant improvement in negative beliefs, image and memory distress and vividness, fear of negative evaluation, and anxiety in feared social situations. The results suggest that rescripting unpleasant memories linked to negative self-images may be a useful adjunct in the treatment of social phobia. (Contains 2 tables.)