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Immune checkpoint blockade (ICB) expands the therapeutic options for metastatic lung cancer nowadays representing a standard frontline strategy as monotherapy or combination therapy, as well as an option in oncogene-addicted NSCLC after exhaustion of targeted therapies. Predictive markers are urgently needed, since only a minority of patients benefits from ICB, while serious adverse effects of immunotoxicity may occur. The study cohort included 43 ICB-treated metastatic lung adenocarcinoma showing long-term response (n = 16), rapid progression (n = 21) or intermediate patterns of response (n = 6). Lung biopsies acquired before initiation of ICB were analyzed by targeted mRNA expression profiling of 770 genes. Level and proportions of 14 immune cell types were estimated using characteristic gene expression signatures. Abundance of B cells (HR = 0.66, p = .00074), CD45+ cells (HR = 0.61, p = .01) and total TILs (HR = 0.62, p = .025) was associated with prolonged progression-free survival after ICB treatment. In a ROC analysis, B cells (AUC = 0.77, p = .0055) and CD45+ cells (AUC = 0.73, p = .019) predicted benefit of ICB, which was not the case for PD-L1 mRNA (AUC = 0.54, p = .72) and PD-L1 protein expression (AUC = 0.68, p = .082). Clustering of 79 candidate predictive markers identified among 770 investigated genes revealed two distinct predictive clusters which included cytotoxic cell or macrophage markers, respectively. In summary, targeted gene expression profiling was feasible using routine diagnostics biopsies. This study proposes B cells and total TILs as complementary predictors of ICB benefit in NSCLC. While further preferably prospective validation is required, gene expression profiling could be integrated in the routine diagnostic work-up complementing existing NGS protocols.This ongoing column is dedicated to providing information to our readers on managing legal risks associated with medical practice. We invite questions from our readers. The answers are provided by PRMS, Inc. (www.prms.com), a manager of medical professional liability insurance programs with services that include risk management consultation, education and on-site risk management audits, and other resources offered to health care providers to help improve patient outcomes and reduce professional liability risk. The answers published in this column represent those of only one risk management consulting company. Other risk management consulting companies or insurance carriers might provide different advice, and readers should take this into consideration. The information in this column does not constitute legal advice. For legal advice, contact your personal attorney. Note The information and recommendations in this article are applicable to physicians and other health care professionals so "clinician" is used to indicate all treatment team members.The much-anticipated 2014 European Union (EU) Clinical Trial Regulation requiring Layperson/ Plain Language Summaries (PLS) is slated for implementation in 2020. At the 10th Annual CNS Summit Conference (Fall 2019), a panel discussion was convened with the objective of evaluating the likelihood of the PLS legislation being implemented successfully in the EU and voluntarily (e.g., pro-actively) in the rest of the world. Points of the discussion embraced the notion that this is an excellent opportunity for the entire pharmaceutical industry. Moreover, in the United States, public opinion of the pharmaceutical industry hit an all-time low in 2019, surpassing the oil industry with regard to public distrust. For decades, clinical trial participants have stated that wanting to learn, in layperson terms, the results of the study was second only to wanting to learn the treatment group into which they were assigned under double-blind conditions. Our conclusion is that while confidentiality, commercial interests, total costs, regulatory concerns, as well as some operational aspects (i.e., patient access portals) are among the hurdles, our commentary strongly advocates systematic implementation not only within the EU, but that this should be implemented globally, without further delay.Objective The goal of the Depression Inventory Development (DID) project is to develop a comprehensive and psychometrically sound rating scale for major depressive disorder (MDD) that reflects current diagnostic criteria and conceptualizations of depression. We report here the evaluation of the current DID item bank using Classical Test Theory (CTT), Item Response Theory (IRT) and Rasch Measurement Theory (RMT). Methods The present study was part of a larger multisite, open-label study conducted by the Canadian Biomarker Integration Network in Depression (ClinicalTrials.gov NCT01655706). Trained raters administered the 32 DID items at each of two visits (MDD baseline, n=211 and Week 8, n=177; healthy participants baseline, n=112 and Week 8, n=104). The DID's "grid" structure operationalizes intensity and frequency of each item, with clear symptom definitions and a structured interview guide, with the current iteration assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anies. These items (along with previously evaluated items) will provide the basis for validation of a penultimate DID scale assessing anhedonia, cognitive slowing, concentration, executive function, recent memory, drive, emotional fatigue, guilt, self-esteem, hopelessness, tension, rumination, irritability, reduced appetite, insomnia, sadness, worry, suicidality, and depressed mood. The strategies adopted by the DID process provide a framework for rating scale development and validation.Objective The objective was to study latency to first event among patients with psychogenic nonepileptic seizures compared (PNES) to epileptic seizures (ES) in an epilepsy monitoring unit (EMU). Introduction PNES are common imitators of ES. This study investigates latency to first event in patients with PNES compared to patients with ES. Methods We performed a retrospective chart review of patients admitted to our EMU from March 2016 to October 2017. We identified patients with PNES and ES. Patients with other nonepileptic events and mixed PNES (epilepsy plus PNES) were excluded. Patient demographics, baseline seizure frequency, length of EMU stay and time from admission to first event were recorded. Results In total, 111 patients with PNES and 121 patients with ES were included. The mean age (in years) was 42 and 38, respectively. The average baseline seizure frequency was four times higher in the PNES group than the ES group. Greater than half (52%) of the patients with PNES and about one third (38%) of the patients with ES had an event within the first 24 hours. The average time to first event was 20.88 hours for the PNES group and 30.99 hours for the ES group (p less then 0.01). The median latency to first event was 14 hours for the PNES group and 23 hours for the ES group. The average length of EMU stay was significantly longer in the ES group (70.82 hours) than the PNES group (53.95 hours). Conclusion The average time to first event is shorter for PNES than in ES. In patients with high pre-EMU clinical suspicion for PNES, relatively shorter EMU monitoring (24 to 48 hours) can confirm diagnosis. buy XL413 This phenomenon might improve cost-effectiveness of EMU monitoring in patients with PNES.Objective The contribution of components in cognitive behavior therapy (CBT) to the total reduction of depression symptoms has not been well elucidated, and previous studies couldn't exclude the human factors in the therapy. Design This is a secondary analysis of a randomized, controlled trial comparing automated smartphone CBT without human factors plus antidepressant switch against antidepressant switch alone among patients with antidepressant-resistant depression. The present CBT consisted of self-monitoring, behavioral activation, and cognitive restructuring. We used linear regression to predict the overall pre- to post-symptom improvement based on improvement achieved by sessions teaching each cognitive or behavioral skill. The overall improvement was measured with the Beck Depression Inventory-II and the session-to-session improvement with K6. Results Of the 164 participants originally enrolled in the study, 94 participants who completed all K6 evaluation were included in the primary analyses. The results indicated that K6 score reduction in the first half of behavioral activation significantly predicted BDI-II score reduction. The sensitivity analysis including 162 participants did not change the result. link2 K6 score reductions after other CBT sessions did not significantly predict BDI-II score reduction. Conclusion The behavioral activation seems to contribute to the total reduction of depressive symptoms even if human factors are excluded by using automated smartphone CBT.DEPARTMENT EDITORS Julie P. Gentile, MD Professor and Chair, Department of Psychiatry, Wright State University, Boonshoft School of Medicine, Dayton, Ohio Allison E. Cowan, MD Associate Professor, Department of Psychiatry, Wright State University, Boonshoft School of Medicine, Dayton, Ohio EDITORS' NOTE The patient cases presented in Psychotherapy Rounds are composite cases written to illustrate certain diagnostic characteristics and to instruct on treatment techniques. The composite cases are not real patients in treatment. Any resemblance to a real patient is purely coincidental. ABSTRACT Eye movement desensitization and reprocessing (EMDR) is a specific treatment modality that utilizes bilateral stimulation to help individuals who have experienced trauma. This stimulation can occur in a variety of forms, including left-right eye movements, tapping on the knees, headphones, or handheld buzzers, known as tappers. This type of psychotherapy allows the individuals to redefine their self-assessment and responses to a given traumatic event in eight defined steps. link3 While EMDR is relatively new type of psychotherapy, existing literature has demonstrated positive results using this form of therapy when treating patients with post-traumatic stress disorder (PTSD) by utilizing eye movements to detract from negative conceptualizations as a response to a specific trigger, while reaffirming positive self-assessments. Research indicates that EMDR could be a promising treatment for mental health issues other than PTSD, including bipolar disorder, substance use disorders, and depressive disorders. In this article, the eight fundamental processes of EMDR are illustrated through a composite case vignette and examined alongside relevant research regarding its efficacy in treating PTSD.Meralgia paresthetica (MP) is an uncommon entrapment mononeuropathy that is characterized by a sudden onset of paresthesia and numbness in the anterolateral surface of the thigh. Palmithoylethanolamide (PEA) is commonly used in the treatment of chronic pelvic pain and compressive neuropathies. Herein, we describe an otherwise healthy 28-year-old patient affected by posttraumatic MP for three months who was successfully treated with PEA (1200mg/day). Further studies are needed to better investigate the potential use of PEA as therapeutic drug in peripheral neuropathies, including MP, to avoid or delay more invasive surgical treatments.