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Drug-induced liver injury (DILI) remains an important, yet challenging diagnosis for physicians. Each year, additional drugs are implicated in DILI and this year was no different, with more than 1400 articles published on the subject. This review examines some of the most significant highlights and controversies in DILI-related research over the past year and their implications for clinical practice. Several new drugs were approved by the US Food and Drug Administration including a number of drugs implicated in causing DILI, particularly among the chemotherapeutic classes. The COVID-19 pandemic was also a major focus of attention in 2020 and we discuss some of the notable aspects of COVID-19-related liver injury and its implications for diagnosing DILI. Updates in diagnostic and causality assessments related to DILI such as the Roussel Uclaf Causality Assessment Method are included, mindful that there is still no single biomarker or diagnostic tool to unequivocally diagnose DILI. Glutamate dehydrogenase received renewed attention as being more specific than alanine aminotransferase. There were a few new reports of previously unrecognized hepatotoxins, including immune modulators and novel gene therapy drugs that we highlight. Updates and new developments of previously described hepatotoxins, such as immune checkpoint inhibitors and anti-tuberculosis drugs are reviewed. Finally, novel technologies such as organoid culture systems to better predict DILI preclinically may be coming of age and determinants of hepatocyte loss, such as calculating P ALT are poised to improve our current means of estimating DILI severity and the risk of acute liver failure.

Disproportionately greater deficits in semantic relative to phonemic verbal fluency are seen in Alzheimer's disease (AD) and have been attributed to neurodegenerative changes in the temporal lobe. Amnestic (AMN) mild cognitive impairment (MCI), which often represents incipient AD, is also characterized by early temporal lobe neuropathology, but previous comparisons of verbal fluency between AD and AMN MCI have yielded mixed results. We examined semantic and phonemic verbal fluency performance in 399 individuals (78 AD, 138 AMN MCI, 72 non-amnestic MCI, and 111 cognitively normal controls). Similar verbal fluency patterns were seen in AMN MCI and AD; both groups exhibited disproportionately poorer performance on semantic verbal fluency relative to normal controls. However, relative verbal fluency indices performed more poorly than individual semantic or phonemic verbal fluency indices for discriminating AMN MCI or AD participants from normal controls, suggesting that they are unlikely to provide additional utility for predicting progression from MCI to AD.

BackgroundStereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) is considered standard of care in the medically inoperable patient population. Multiple methods of SBRT delivery exist including fiducial-based tumor tracking, which allows for smaller treatment margins and avoidance of patient immobilization devices. We explore the long-term clinical outcomes of this novel fiducial-based SBRT method.MethodsIn this single institutional retrospective review, we detail the outcomes of medically inoperable pathologically confirmed stage I NSCLC. Patients were treated with the Cyberknife SBRT system using a planning target volume (PTV) defined as a 5-mm expansion from gross tumor volume (GTV) without creation of an internal target volume (ITV). Dose was delivered in three or five equal fractions of 10 to 20 Gy. Pretreatment and posttreatment pulmonary function test (PFT) changes and evidence of late radiological rib fractures were analyzed for the majority of patients. Actuarial local control, locoregional control, distant control, and overall survival were calculated using the Kaplan-Meier method.ResultsSixty-one patients with a median age of 75 years were available for analysis. The majority (80 %) of patients were deemed to be medically inoperable due to underlying pulmonary dysfunction. Eleven patients (18 %) developed symptomatic pneumothoraces secondary to fiducial placement under CT guidance, which precipitously dropped to 0 % following transition to bronchoscopic fiducial placement. The 2-year rib fracture risk was 21.4 % with a median time to rib fracture of 2.9 years. PFTs averaged over all patients and parameters demonstrated small absolute declines, 5.7 % averaged PFT decline, at approximately 1 year of follow-up, but only the diffusing capacity of lung for carbon monoxide (DLCO) demonstrated a statistically significant decline (10.29 vs. 9.01 mL/min/mmHg, p = 0.01). Five-year local control, locoregional control, and overall survival were 87.6, 71.8, and 39.3 %, respectively.ConclusionsDespite reduced treatment margins and lack of patient immobilization, SBRT with fiducial-based tumor tracking achieves clinically comparable long-term outcomes to other linac-based SBRT approaches.

Five Minute Speech Sample Expressed Emotion (FMSS-EE) was examined in families of youth with depressive disorders, nondepressed youth with attention deficit/hyperactivity disorder (ADHD), and community controls screened for the absence of depression and ADHD. Consistent with the hypothesis that FMSS-EE shows some specificity as a risk factor for depression, rates of critical EE were significantly higher among mothers of youth with depression as compared to mothers of nondepressed youth with ADHD, or mothers of controls. When both mothers' and fathers' scores were used to generate family EE ratings, rates of overall EE and critical EE were significantly higher for the depressed group than the control group, but the nondepressed ADHD group did not differ significantly from the other groups. Results support the hypothesis that critical EE in mothers shows some specificity as a risk factor or correlate of depression in youth.

Providing a unified treatment approach to meet the substance abuse and mental health needs of clients is the preferred model for addressing co-occurring disorders. Using a Cognitive Behavioral Therapy (CBT) approach, we developed a group-based integrated treatment for depression and substance use disorders (SUD) that could be delivered by counselors in SUD treatment settings, and evaluated its feasibility and acceptability. We conducted an in-depth case study examining one implementation of the treatment using 15 focus groups with clients (N=7) and semi-structured interviews with counselors (N=2) and administrators (N=3). Using CBT as a treatment approach was widely accepted by clients, counselors and administrators. Clients stated the treatment was applicable to multiple aspects of their lives and allowed them to recognize their clinical improvements over time. Counselors and administrators discussed challenges for long-term feasibility. Key decisions used to develop the treatment and recommendations for implementing integrated care in SUD settings are discussed.

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These data suggest that a complex transactional model is necessary to understand how family attitudes evolve during the course of a relatives' schizophrenic disorder.