Tissue-specific and endogenous protein labeling with split fluorescent proteins.

The ability to label proteins by fusion with genetically encoded fluorescent proteins is a powerful tool for understanding dynamic biological processes. However, current approaches for expressing fluorescent protein fusions possess drawbacks, especially at the whole organism level. Expression by transgenesis risks potential overexpression artifacts while fluorescent protein insertion at endogenous loci is technically difficult and, more importantly, does not allow for tissue-specific study of broadly expressed proteins. To overcome these limitations, we have adopted the split fluorescent protein system mNeonGreen21-10/11 (split-mNG2) to achieve tissue-specific and endogenous protein labeling in zebrafish. In our approach, mNG21-10 is expressed under a tissue-specific promoter using standard transgenesis while mNG211 is inserted into protein-coding genes of interest using CRISPR/Cas-directed gene editing. Each mNG2 fragment on its own is not fluorescent, but when co-expressed the fragments self-assemble into a fluorescent complex. Here, we report successful use of split-mNG2 to achieve differential labeling of the cytoskeleton genes tubb4b and krt8 in various tissues. We also demonstrate that by anchoring the mNG21-10 component to specific cellular compartments, the split-mNG2 system can be used to manipulate protein localization. Our approach should be broadly useful for a wide range of applications.

Atypical RhoUV GTPases in development and disease.

RhoU and RhoV are members of the Rho family of small GTPases that comprise their own subfamily. RhoUV GTPases are classified as atypical due to the kinetics of their GTP/GDP binding cycles. They also possess unique N- and C-termini that regulate their subcellular localization and activity. RhoU and RhoV have been linked to cytoskeletal regulation, cell adhesion, and cell migration. They each exhibit distinct expression patterns during embryonic development and diseases such as cancer metastasis, suggesting they have specialized functions. In this review, we will discuss the known functions of RhoU and RhoV, with a focus on their roles in early development, organogenesis, and disease.

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.

Real-world incidence of venetoclax toxicities in British Columbia.

INTRODUCTION: Venetoclax is used to treat relapsed/refractory chronic lymphocytic leukemia (r/r CLL). Tumour lysis syndrome (TLS) is a serious toxicity associated with venetoclax, and real-world studies suggest that the incidence may be higher than in clinical trials. The purpose of this study is to describe the incidence of venetoclax toxicities in British Columbia (BC). METHODS: Retrospective review of electronic medical charts for patient characteristics and clinical outcomes of patients treated with venetoclax for r/r CLL in BC. Patients were classified according to their risk for developing TLS. The incidence of TLS was categorized based on laboratory metrics or clinical diagnosis. Other non-TLS toxicities were also collected. RESULTS: Of 33 patients identified, 40%, 33%, and 27% were at low, intermediate, and high risk for TLS, respectively. Laboratory TLS occurred in 1/33 patients (3%), and no clinical TLS was reported. Grade 3 or 4 toxicities occurred in 19/33 patients (58%). Of these, neutropenia was the most common, occurring in 16 patients (84%) followed by thrombocytopenia, which occurred in 8 patients (42%). CONCLUSIONS: The incidence of TLS in patients treated with venetoclax for r/r CLL in BC was lower than in other real-world studies. Findings may warrant further investigation to determine if the higher incidence of TLS in real-world reports may be mitigated through modifying TLS risk categorization and associated prophylactic measures. Neutropenia was the most common grade 3 or 4 venetoclax toxicity reported, and the incidence in BC is comparable to other centres.

Nodal signaling has dual roles in fate specification and directed migration during germ layer segregation in zebrafish.

During gastrulation, endodermal cells actively migrate to the interior of the embryo, but the signals that initiate and coordinate this migration are poorly understood. By transplanting ectopically induced endodermal cells far from the normal location of endoderm specification, we identified the inputs that drive internalization without the confounding influences of fate specification and global morphogenic movements. We find that Nodal signaling triggers an autocrine circuit for initiating endodermal internalization. Activation of the Nodal receptor directs endodermal specification through sox32 and also induces expression of more Nodal ligands. These ligands act in an autocrine fashion to initiate endodermal cell sorting. Our work defines an 'AND' gate consisting of sox32-dependent endodermal specification and Nodal ligand reception controlling endodermal cell sorting to the inner layer of the embryo at the onset of gastrulation.

Glypican 4 and Mmp14 interact in regulating the migration of anterior endodermal cells by limiting extracellular matrix deposition.

During embryogenesis, the germ layers, including the endoderm, undergo convergence and extension movements to narrow and elongate the body plan. In zebrafish, the dorsal migration of endodermal cells during gastrulation is controlled by chemokine signaling, but little is known about how they migrate during segmentation. Here, we show that glypican 4 (Gpc4), a member of the heparin sulfate proteoglycan family, is required for efficient migration of anterior endodermal cells during early segmentation, regulating Rac activation to maintain polarized actin-rich lamellipodia. An endoderm transplantation assay showed that Gpc4 regulates endoderm migration in a non-cell-autonomous fashion. Further analyses revealed that the impaired endoderm migration in gpc4 mutants results from increases in the expression and assembly of fibronectin and laminin, major components of the extracellular matrix (ECM). Notably, we found that matrix metalloproteinase 14 (Mmp14a/b) is required for the control of ECM expression during endoderm migration, with Gpc4 acting through Mmp14a/b to limit ECM expression. Our results suggest that Gpc4 is crucial for generating the environment required for efficient migration of endodermal cells, uncovering a novel function of Gpc4 during development.

TAEL: a zebrafish-optimized optogenetic gene expression system with fine spatial and temporal control.

Here, we describe an optogenetic gene expression system optimized for use in zebrafish. This system overcomes the limitations of current inducible expression systems by enabling robust spatial and temporal regulation of gene expression in living organisms. Because existing optogenetic systems show toxicity in zebrafish, we re-engineered the blue-light-activated EL222 system for minimal toxicity while exhibiting a large range of induction, fine spatial precision and rapid kinetics. We validate several strategies to spatially restrict illumination and thus gene induction with our new TAEL (TA4-EL222) system. As a functional example, we show that TAEL is able to induce ectopic endodermal cells in the presumptive ectoderm via targeted sox32 induction. We also demonstrate that TAEL can be used to resolve multiple roles of Nodal signaling at different stages of embryonic development. Finally, we show how inducible gene editing can be achieved by combining the TAEL and CRISPR/Cas9 systems. This toolkit should be a broadly useful resource for the fish community.

Preventable adverse drug events: Descriptive epidemiology.

AIM: Our objective was to identify preventable adverse drug events and factors contributing to their development. METHODS: We performed a retrospective chart review combining data from three prospective multicentre observational studies that assessed emergency department patients for adverse drug events. A clinical pharmacist and physician independently reviewed the charts, extracted data and rated the preventability of each adverse drug event. A third reviewer adjudicated all discordant or uncertain cases. We calculated the proportion of adverse drug events that were deemed preventable, performed multivariable logistic regression to explore the characteristics of patients with preventable events, and identified contributing factors. RESULTS: We reviewed the records of 1 356 adverse drug events in 1 234 patients. Raters considered 869 (64.1%) of adverse drug events probably or definitely preventable. Patients with mental health diagnoses (OR 1.8; 95% CI 1.3-2.5) and diabetes (OR 1.7; 95% CI 1.2-2.4) were more likely to present with preventable events. The medications most commonly implicated in preventable events were warfarin (9.4%), hydrochlorothiazide (4.5%), furosemide (4.0%), insulin (3.9%) and acetylsalicylic acid (2.7%). Common contributing factors included inadequate patient instructions, monitoring and follow-up, and reassessments after medication changes had been made. CONCLUSIONS: Our study suggests that patients with mental health conditions and diabetes require close monitoring. Efforts to address the identified contributing factors are needed.

Risk Factors for Misuse of Prescribed Opioids: A Systematic Review and Meta-Analysis.

STUDY OBJECTIVE: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective is to synthesize the available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing misuse among patients prescribed opioids for noncancer pain. METHODS: We performed a systematic search of the scientific and gray literature for studies reporting on risk factors for prescription opioid misuse. Two reviewers independently reviewed titles, abstracts, and full texts; extracted data; and assessed study quality. We excluded studies with greater than 50% cancer patients, palliative patients, and illicit opioid initiation. When possible, we synthesized the effect sizes of dichotomous risk factors and their associations with opioid misuse, using inverse-variance random-effects meta-analysis. We calculated the mean difference between opioid misusers and nonmisusers for continuous risk factors. When studies lacked homogeneity, we synthesized their results qualitatively. RESULTS: Of 9,629 studies, 65 met our inclusion criteria. Among patients with outpatient opioid prescriptions, the following factors were associated with the development of misuse: any current or previous substance use (odds ratio [OR] 3.55; 95% confidence interval [CI] 2.62 to 4.82), any mental health diagnosis (OR 2.45; 95% CI 1.91 to 3.15), younger age (OR 2.19; 95% CI 1.81 to 2.64), and male sex (OR 1.23; 95% CI 1.10 to 1.36). CONCLUSION: Although clinicians should endeavor to offer alternative pain management strategies to all patients, those who are younger, are male patients, and report a history of or current substance use or mental health diagnoses were associated with a greater risk of developing opioid misuse. Clinicians should consider prioritizing alternative pain management strategies for these higher-risk patients.

Methods for evaluating adverse drug event preventability in emergency department patients.

BACKGROUND: There is a high degree of variability in assessing the preventability of adverse drug events, limiting the ability to compare rates of preventable adverse drug events across different studies. We compared three methods for determining preventability of adverse drug events in emergency department patients and explored their strengths and weaknesses. METHODS: This mixed-methods study enrolled emergency department patients diagnosed with at least one adverse drug event from three prior prospective studies. A clinical pharmacist and physician reviewed the medical and research records of all patients, and independently rated each event's preventability using a "best practice-based" approach, an "error-based" approach, and an "algorithm-based" approach. Raters discussed discordant ratings until reaching consensus. We assessed the inter-rater agreement between clinicians using the same assessment method, and between different assessment methods using Cohen's kappa with 95% confidence intervals (95% CI). Qualitative researchers observed discussions, took field notes, and reviewed free text comments made by clinicians in a "comment" box in the data collection form. We developed a coding structure and iteratively analyzed qualitative data for emerging themes regarding the application of each preventability assessment method using NVivo. RESULTS: Among 1356 adverse drug events, a best practice-based approach rated 64.1% (95% CI: 61.5-66.6%) of events as preventable, an error-based approach rated 64.3% (95% CI: 61.8-66.9%) of events as preventable, and an algorithm-based approach rated 68.8% (95% CI: 66.1-71.1%) of events as preventable. When applying the same method, the inter-rater agreement between clinicians was 0.53 (95% CI: 0.48-0.59), 0.55 (95%CI: 0.50-0.60) and 0.55 (95% CI: 0.49-0.55) for the best practice-, error-, and algorithm-based approaches, respectively. The inter-rater agreement between different assessment methods using consensus ratings for each ranged between 0.88 (95% CI 0.85-0.91) and 0.99 (95% CI 0.98-1.00). Compared to a best practice-based assessment, clinicians believed the algorithm-based assessment was too rigid. It did not account for the complexities of and variations in clinical practice, and frequently was too definitive when assigning preventability ratings. CONCLUSION: There was good agreement between all three methods of determining the preventability of adverse drug events. However, clinicians found the algorithmic approach constraining, and preferred a best practice-based assessment method.

Clinical Evaluation of Large Diameter Rigid-Gas Permeable Versus Soft Toric Contact Lenses for the Correction of Refractive Astigmatism. A MultiCenter Study.

PURPOSE: This study aims to address the clinical performance of a large diameter rigid gas permeable lens (LRGP) in a group of subjects with low-to-moderate (0.75-2.75 D) refractive astigmatism. An additional goal was to determine whether soft toric or LRGP contact lenses performed better objectively in the correction of astigmatism and to determine which modality is preferred by subjects. METHODS: This was a multisite prospective cross-over clinical study. Ten asymptomatic contact lens wearers per site (four university clinics) were recruited and randomly assigned to group A or group B. Group A was assigned to start wearing Comfilcon A soft toric lens first, for two weeks, and then crossed over to LRGP lenses (Boston XO, 14.3 mm diameter miniscleral lens). Group B initially wore LRGP lenses and then crossed over to soft toric lenses. For each type of lens worn, low-contrast and high-contrast visual acuity (VA) were evaluated at distance. At the conclusion of the study, after two months, all subjects completed a questionnaire in which they were asked to indicate their preference for one type of lens (soft toric or LRGP) and to rate the quality of vision in day-to-day activities. RESULTS: Thirty-six of 38 (94.7%) subjects completed the study with 75% preferring the vision of the LRGP lens as compared to the soft toric lenses worn in the study. 52.7% expressed a preference to continue with this modality despite only 38.8% reporting that these LRGP lenses are easy or very easy to handle. Wear time, subjective comfort, and subjective vision ratings exhibited no significant difference between the two groups. CONCLUSIONS: In a population of asymptomatic contact lens wearers, LRGP lenses can be considered as a good alternative to soft toric lenses for the correction of refractive astigmatism.

Cross-cultural verification of the EORTC QLQ-C15-PAL questionnaire in mainland China.

BACKGROUND: Simplified by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30), EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) is specifically applied to evaluating palliative care patients' quality of life. AIM: This study examined cross-cultural adaptability and validity of QLQ-C15-PAL for evaluating quality of life of palliative care patients with advanced cancer in mainland China. PARTICIPANTS AND DESIGN: From May to October 2013, 243 palliative care patients in Tianjin Cancer Hospital completed the EORTC QLQ-C30. We extracted QLQ-C15-PAL data for analysis. Physicians completed the Eastern Cooperative Oncology Group Performance Status score and mental state assessment for each patient. RESULTS: A total of 243 patients completed the study. The compliance rate was high, with missing rate for each item ranging from 0% to 2.1%. In addition to emotional function, the remaining dimensions demonstrated a high reliability (Cronbach's alpha > 0.7). Whether we divided patients into two groups according to their Eastern Cooperative Oncology Group Performance Status or divided patients into three groups according to mental status, both sets of results showed significant differences in QLQ-C15-PAL subscale scores (p < 0.05), indicating that the QLQ-C15-PAL scale could be used to distinguish between the aforementioned subgroups. Overall quality of life was moderately correlated with fatigue (r = -0.406) but weakly correlated with other subscales. The proportion of variance (R(2)) ranged from 0.848 to 0.903, which showed that QLQ-C15-PAL subscale scores explained between 84.8% and 90.3% of the original QLQ-C30 score distribution. CONCLUSION: The Chinese version of the EORTC QLQ-C15-PAL questionnaire has high reliability and validity and is therefore suitable for clinical use in China to determine health-related quality of life in Chinese patients with advanced cancer.

Validation of EORTC IN-PATSAT32 for Chinese cancer patients.

PURPOSE: The aim of this study is to test the psychometric properties and acceptability of the European Organization for Research and Treatment of Cancer (EORTC) inpatient satisfaction with care questionnaire 32 (IN-PATSAT32) for evaluating Chinese cancer patients and to analyze the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction. METHODS: Three hundred two cancer inpatients in Tianjin Cancer Institution and Hospital from June 2013 to December 2013 were recruited for this study. All participants self-administered the EORTC IN-PATSAT32 and EORTC quality of life questionnaire-core 30 (QLQ-C30). Psychometric evaluation of the validity, reliability, acceptability, as well as the influence of age, educational level, diagnostic time, and tumor stage on patient satisfaction, was conducted. RESULTS: A favorable internal consistency reliability was confirmed, as the Cronbach's α coefficients were >0.80 for all scales in the EORTC IN-PATSAT32, ranging from 0.849 to 0.944. Multi-trait scaling analysis showed that all item-scale correlation coefficients met the standard of convergent validity, and 79.3 % met the standard of discriminant validity. Weak correlations were found between the scales and single items of the EORTC IN-PATSAT32 and EORTC QLQ-C30, proving the validity of EORTC IN-PATSAT32. None of the EORTC IN-PATSAT32 scales were able to discriminate between patients across age categories, while significant influences of educational level on doctors' and nurses' conduct, as well as influences of diagnostic time and tumor stage on nurses' conduct, and information provision scales were discovered. The questionnaire was easily understood with a satisfactory acceptability. CONCLUSIONS: The EORTC IN-PATSAT32 appears to be a reliable, valid, and acceptable instrument to use on cancer patients and is appropriate for measuring the patient satisfaction of Chinese patients.

A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish.

Members of the Slit family of secreted ligands interact with Roundabout (Robo) receptors to provide guidance cues for many cell types. For example, Slit/Robo signaling elicits repulsion of axons during neural development, whereas in endothelial cells this pathway inhibits or promotes angiogenesis depending on the cellular context. Here, we show that miR-218 is intronically encoded in slit2 and slit3 and that it suppresses Robo1 and Robo2 expression. Our data indicate that miR-218 and multiple Slit/Robo signaling components are required for heart tube formation in zebrafish and that this network modulates the previously unappreciated function of Vegf signaling in this process. These findings suggest a new paradigm for microRNA-based control of ligand-receptor interactions and provide evidence for a novel signaling pathway regulating vertebrate heart tube assembly.

Viral esophagitis in non-human immunodeficiency virus patients: a case-control study.

Background: Esophagitis, inflammation of the esophagus, can result from various causes, including reflux, infections, food allergies, medications, and trauma. Infectious esophagitis is the third most common cause after gastroesophageal reflux disease (GERD) and eosinophilic esophagitis worldwide. The primary causes of infectious esophagitis are candida esophagitis and viral esophagitis (VE) caused by herpes simplex virus (HSV) or cytomegalovirus (CMV). VE is typically associated with immunosuppression, with risk factors such as malignancy, chemotherapy, organ transplant, and human immunodeficiency virus (HIV). Infectious esophagitis is prevalent in about one-third of untreated acquired immunodeficiency syndrome (AIDS) patients, but recent reports indicate an increase in VE cases among immunocompetent individuals. This study aims to explore risk factors and patient demographics in non-HIV individuals. Methods: A case-control study that included patients 18 years and older diagnosed with HSV or CMV esophagitis who were identified through histopathologic examination or immunohistochemical staining. Cases were obtained by searching pathology reports between 2009-2022 from five MedStar Health Hospitals in the District of Columbia and Maryland. Controls were selected based on International Classification of Diseases (ICD) codes for esophagogastroduodenoscopy (EGD) with negative VE results within the same period. Patient demographics, comorbidities, laboratory parameters, endoscopic findings, and potential risk factors were collected through chart review. Results: Out of 40,224 cases between 2009-2022, 50 cases of VE were identified, with 30 cases attributed to HSV, 19 cases to CMV, and one case of HSV/CMV coinfection. Hematemesis was the predominant symptom in patients with HSV (33%), while dysphagia was more prevalent in CMV patients (42%). The most common finding during EGD was ulceration in HSV patients (67%) and esophagitis in CMV patients (37%). Patients with VE had a higher likelihood of a history of immunosuppressive therapy, organ transplant, active malignancy, and systemic steroid use. However, a significant portion (34%) had no identifiable risk factors. Conclusions: The study's findings contribute to a better understanding of the clinical characteristics and risk factors associated with VE in non-HIV patients. The identification of immunosuppression and specific risk factors can aid in early detection, appropriate management, and targeted interventions for VE. Further research is warranted to explore the rising incidence of VE in immunocompetent individuals and to optimize preventive strategies and treatment approaches for this condition.

Tissue-specific and endogenous protein labeling with split fluorescent proteins.

The ability to label proteins by fusion with genetically encoded fluorescent proteins is a powerful tool for understanding dynamic biological processes. However, current approaches for expressing fluorescent protein fusions possess drawbacks, especially at the whole organism level. Expression by transgenesis risks potential overexpression artifacts while fluorescent protein insertion at endogenous loci is technically difficult and, more importantly, does not allow for tissue-specific study of broadly expressed proteins. To overcome these limitations, we have adopted the split fluorescent protein system mNeonGreen21-10/11 (split-mNG2) to achieve tissue-specific and endogenous protein labeling in zebrafish. In our approach, mNG21-10 is expressed under a tissue-specific promoter using standard transgenesis while mNG211 is inserted into protein-coding genes of interest using CRISPR/Cas-directed gene editing. Each mNG2 fragment on its own is not fluorescent, but when co-expressed the fragments self-assemble into a fluorescent complex. Here, we report successful use of split-mNG2 to achieve differential labeling of the cytoskeleton genes tubb4b and krt8 in various tissues. We also demonstrate that by anchoring the mNG21-10 component to specific cellular compartments, the split-mNG2 system can be used to manipulate protein function. Our approach should be broadly useful for a wide range of applications.

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.

Endodermal cells use contact inhibition of locomotion to achieve uniform cell dispersal during zebrafish gastrulation.

The endoderm is one of the three primary germ layers that ultimately gives rise to the gastrointestinal and respiratory epithelia and other tissues. In zebrafish and other vertebrates, endodermal cells are initially highly migratory with only transient interactions among one other, but later converge together to form an epithelial sheet. Here, we show that during their early, migratory phase, endodermal cells actively avoid each other through contact inhibition of locomotion (CIL), a characteristic response consisting of 1) actin depolymerization and membrane retraction at the site of contact, 2) preferential actin polymerization along a cell-free edge, and 3) reorientation of migration away from the other cell. We found that this response is dependent on the Rho GTPase RhoA and EphA/ephrin-A signaling - expression of dominant-negative (DN) RhoA or treatment with the EphA inhibitor dasatinib resulted in behaviors consistent with loss of CIL, including increased contact duration times and decreased likelihood of migration reorientation after contact. Computational modeling predicted that CIL is required to achieve the efficient and uniform dispersal characteristic of endodermal cells. Consistent with our model, we found that loss of CIL via DN RhoA expression resulted in irregular clustering of cells within the endoderm. Together, our results suggest that endodermal cells use EphA2- and RhoA-dependent CIL as a cell dispersal and spacing mechanism, demonstrating how local interactions can give rise to tissue-scale patterns.

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.

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.