Clinical outcomes: endoscopic resection of duodenal ampullary lesions.

Background: Ampullary adenomas are lesions at the duodenum's major papilla commonly associated with familial adenomatous polyposis (FAP) but may also occur sporadically. Historically, ampullary adenomas were removed surgically, however endoscopic resection has become the preferred method of resection. Most of the literature on management of ampullary adenomas are small single-center retrospective reviews. The objective of this study is to describe endoscopic papillectomy outcomes to further refine management guidelines. Methods: This is a retrospective study of patients who underwent endoscopic papillectomy. Demographic data were included. Details regarding lesions and procedures were also collected, including endoscopic impression, size, resection method and adjunctive therapies. Chi-square, Kruskal-Wallis rank-sum, and t-tests were performed. Results: A total of 90 patients were included. 60% patients (54 of 90) had pathology-proven adenomas. 14.4% of all lesions (13 of 90) and 18.5% of adenomas (10 of 54) were treated with APC. Among APC-treated lesions, 36.4% developed recurrence (4 of 11) vs. 7.1% developed residual lesion (1 of 14) (P=0.019). 15.6% of all lesions (14 of 90) and 18.5% of adenomas (10 of 54) reported complications, and the most common was pancreatitis (11.1% and 5.6%). Median follow-up time was 8 months for all lesions and 14 months (range, 1-177 months) for adenomas, with time to recurrence 30 and 31 months (range, 1-137 months), respectively. Recurrence was observed in 16.7% of all lesions (15 of 90) and 20.4% of adenomas (11 of 54). Endoscopic success was observed in 69.2% of all lesions (54 of 78) and 71.4% of adenomas (35 of 49) after removing patients lost to follow-up. Conclusions: Endoscopic papillectomy is an effective method for managing duodenal adenomas. Pathology-proven adenoma should undergo surveillance for at least 31 months. Lesions treated with APC may require closer follow-up and for a prolonged period.

COVID-19-Associated Liver Injury.

This review analyzes data regarding liver injury associated with COVID-19 infection. We discuss reported effects on the liver from both COVID-19 and COVID-19 treatment as well as pathophysiology, review the potential role of drug-induced liver injury as an etiology of COVID-19-associated liver injury, and touch on other reports of significant outcomes including COVID-19 cholangiopathy and autoimmune hepatitis. Finally, we review the implications of COVID-19 infection in liver transplant recipients.

Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC. Our literature search queried publications in Ovid MEDLINE, Ovid Embase, and Web of Science, and ultimately identified 24 original research publications to be included for analysis. We found that the role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, and ongoing randomized clinical trials PLENTY and Dulect 2020-1 will provide insight into the role of PD-1 and PD-L1 in liver transplant management in the future. This literature search and the resulting review represents the most thorough collection, analysis, and presentation of the literature on the subject to date.

Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients. METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded. RESULTS: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU. CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Highlights of the drug-induced liver injury literature for 2021.

INTRODUCTION: In 2021, over 3,000 articles on Drug-Induced Liver Injury (DILI) were published, nearly doubling the annual number compared to 2011. This review selected DILI articles from 2021 we felt held the greatest interest and clinical relevance. AREAS COVERED: A literature search was conducted using PubMed between 1 March 2021 and 28 February 2022. 86 articles were included. This review discusses new and established cases of hepatotoxins, including new FDA approvals and COVID-19 therapeutics. Developments in biomarkers and causality assessment methods are discussed. Updates from registries are also explored. EXPERT OPINION: DILI diagnosis and prognostication remain challenging. Roussel Uclaf Causality Assessment Method (RUCAM) is the best option for determining causality and has been increasingly accepted by clinicians. Revised Electronic Causality Assessment Method (RECAM) may be more user-friendly and accurate but requires further validation. Quantitative systems pharmacology methods, such as DILIsym, are increasingly used to predict hepatotoxicity. Oncotherapeutic agents represent many newly approved and described causes of DILI. Such hepatotoxicity is deemed acceptable relative to the benefit these drugs offer. Drugs developed for non-life-threatening disorders may not show a favorable benefit-to-risk ratio and will be more difficult to approve. As the COVID-19 landscape evolves, its effect on DILI deserves further investigation.

Herbal and dietary supplement induced liver injury: Highlights from the recent literature.

Herbal-induced liver injury (HILI) is an important and increasingly concerning cause of liver toxicity, and this study presents recent updates to the literature. An extensive literature review was conducted encompassing September 2019 through March 2021. Studies with clinically significant findings were analyzed and included in this review. We emphasized those studies that provided a causality assessment methodology, such as Roussel Uclaf Causality Assessment Method scores. Our review includes reports of individual herbals, including Garcinia cambogia, green tea extract, kratom as well as classes such as performance enhancing supplements, Traditional Chinese medicine, Ayurvedic medicine and herbal contamination. Newly described herbals include ashwagandha, boldo, skyfruit, and 'Thermo gun'. Several studies discussing data from national registries, including the United States Drug-Induced Liver Injury (DILI) Network, Spanish DILI Registry, and Latin American DILI Network were incorporated. There has also been a continued interest in hepatoprotection, with promising use of herbals to counter hepatotoxicity from anti-tubercular medications. We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration. The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.

Long-term outcomes of stereotactic body radiation therapy (SBRT) with fiducial tracking for inoperable stage I non-small cell lung cancer (NSCLC).

BACKGROUND: Stereotactic 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. METHODS: In 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. RESULTS: Sixty-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. CONCLUSIONS: Despite 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.

Training Substance Use Disorder Counselors in Cognitive Behavioral Therapy for Depression: Development and Initial Exploration of an Online Training Program.

INTRODUCTION: Evidence based psychotherapies (EBPs) remain underutilized. Models for EBP training and implementation that are cost-effective, minimally disruptive, and sufficiently flexible are needed. Internet-based technology is a promising platform, but questions remain about how this technology can address the barriers to implementation. We developed and examined the implementation of an online training for the Building Recovery by Improving Goals, Habits, and Thoughts (BRIGHT) intervention-a manualized, sixteen-session group depression treatment for individuals with substance use disorders (SUDs). We explored the feasibility of replacing in-person BRIGHT training with a self-paced, online training. METHODS: A highly partnered and iterative process was followed to translate the written BRIGHT manual and associated didactic training materials into a media rich, interactive, and detailed (12-16 h) online training. Subsequently, 8 volunteer counselors across 7 Veterans' Affairs SUD programs completed the training. Semi-structured interviews focused on the counselors' experiences and their plans for implementing BRIGHT groups. A template approach, using a mixture of deductive and inductive coding, was used for data analyses. FINDINGS: The most important barrier to completing training was a lack of protected time. Most counselors were not afforded protected time and reported a sometimes frustrating and fragmented training experience. Many used personal time at work and at home to complete the work. Facilitators to completing the training included positive reactions/attitudes towards the training modules, supervisor support, counselor dedication, and strong beliefs supporting providing services for depression. Many counselors were also concerned about the feasibility of fitting 16 group sessions (2h each) into their program's clinical schedule, but many had devised potential solutions or "work-arounds" to accommodate or approximate the recommended treatment course (e.g., using lunch times, reducing some content/exercises). CONCLUSION: This work contributes to the literature on implementation of complex EBPs and addresses the strengths and limitations of web-based technologies in supporting the implementation of EBPs.

Training Addiction Counselors to Implement an Evidence-Based Intervention: Strategies for Increasing Organizational and Provider Acceptance.

One barrier to widespread public access to empirically supported treatments (ESTs) is the limited availability and high cost of professionals trained to deliver them. Our earlier work from two clinical trials demonstrated that front-line addiction counselors could be trained to deliver a manualized, group-based cognitive behavioral therapy (GCBT) for depression, a prototypic example of an EST, with a high level of adherence and competence. This follow-up article provides specific recommendations for the selection and initial training of counselors, and for the structure and process of their ongoing clinical supervision. Unique challenges in working with counselors unaccustomed to traditional clinical supervision are highlighted. The recommendations are based on comprehensive feedback derived from clinician notes taken throughout the clinical trials, a focus group with counselors conducted one year following implementation, and interviews with key organization executives and administrators.

Is unawareness of psychotic disorder a neurocognitive or psychological defensiveness problem?

We examined whether deficits in attention and perceptual encoding as well as psychological defensiveness were associated with impaired awareness of disorder in schizophrenia. The Scale for Unawareness of Mental Disorder (SUMD) was administered to 52 outpatients with a recent onset of schizophrenia approximately 1-2 months following hospital discharge. Two versions of the Continuous Performance Test (CPT) were used to measure attentional impairment--the Degraded Stimulus CPT (DS-CPT) and a memory-load version (3-7 CPT). Three scales from the Minnesota Multiphasic Personality Inventory were used as indicators of psychological defensiveness: Scales L (Lie), K (Correction), and R (Repression). The Classification and Regression Tree (CART) program, a nonparametric statistical method, was used to identify relationships among multiple predictor variables and to provide optimal splitting scores for each predictor variable. Different combinations of poor target discrimination (d') on the 3-7 CPT and a cautious response style on the DS-CPT were associated with the three levels of overall unawareness of having a mental disorder. For nonpsychotic patients, better target discrimination (d') on the 3-7 CPT tended to be associated with better awareness of having a mental disorder. In contrast, unawareness among the patients who were psychotic at the time of the SUMD administration was not discriminated by attentional measures, but was associated with a combination of two measures of psychological defensiveness from the MMPI reflecting guardedness, psychological suppression, attempting to present oneself in a socially desirable light, and social acquiescence. Generally similar associations were found for two other dimensions of poor insight: unawareness of the beneficial effects of antipsychotic medication, and inability to attribute unusual thoughts and hallucinatory experiences to a mental disorder.

Relatives' affective style and the expression of subclinical psychopathology in patients with schizophrenia.

High expressed emotion (EE) is a measure of hostile, critical, and emotionally overinvolved attitudes expressed by a family member about a psychiatrically ill relative during an interview conducted in the patient's absence. EE is a robust predictor of relapse in schizophrenia, yet attempts to identify clinical characteristics that differentiate patients from high versus low EE families have mostly yielded negative findings. However, in a previous study, we found that patients with schizophrenia from high EE families exhibited greater levels of subclinical psychopathology when interacting with family members than did patients from low EE families. Patients from high EE families (N=32) also demonstrated considerable heterogeneity in their expression of subclinical psychopathology. The present study extends our previous work by demonstrating that this heterogeneity in patient subclinical psychopathology was associated with the extent to which family members expressed high EE congruent behaviors--as measured by the affective style (AS) coding system--when directly interacting with their patient-relative. Elevations in anxious/agitated behaviors and hostile/unusual behaviors were observed among patients whose high EE relatives behaved in a manner consistent with their EE status. These findings support a complex, bidirectional model of the role of high EE attitudes in influencing the course of schizophrenia.

Are communication deviance and expressed emotion related to family history of psychiatric disorders in schizophrenia?

Studies have reported that certain measures of intrafamilial transactions are associated with an increased risk both for the initial onset of schizophrenia and for its recurrence following the initial episode of disorder. Two of the most studied of these are communication deviance (CD), a measure of subclinical thought disorder expressed in speech, and expressed emotion (EE), defined as notable attitudes of criticism and/or emotional overinvolvement manifested in a semistructured interview. A previous study (Goldstein et al. 1992) examined whether these two measures were associated with the presence of a diagnosable psychiatric disorder in the biological parents of recent-onset schizophrenia patients. In general, they were not. The present study went one step further. It examined whether these same measures were correlated with family history of schizophrenia or affective disorder in the biological parents and siblings of these same parents. High EE was not associated with a greater family history of schizophrenia spectrum disorders among the parent's parents and siblings but was unexpectedly found to be inversely associated with familial affective disorders. In contrast, CD was associated with a family history of schizophrenia spectrum disorders among the parent's parents and siblings. The findings are consistent with the possibility that CD may be an indicator of a genetic vulnerability factor for schizophrenia.