Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan.

INTRODUCTION: Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS: The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS: A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION: Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.

The effectiveness of oral anti-SARS-CoV-2 agents in non-hospitalized COVID-19 patients with nonalcoholic fatty liver disease: a retrospective study.

Background: The effectiveness of the novel oral antiviral agents, nirmatrelvir plus ritonavir and molnupiravir, in treating COVID-19 in patients with nonalcoholic fatty liver disease is unclear. Objective: To assess the effectiveness of novel oral antiviral agents against COVID-19 among patients with nonalcoholic fatty liver diseases. Methods: This retrospective cohort study used the TriNetX Research Network to identify non-hospitalized patients with COVID-19 and nonalcoholic fatty liver disease between 1 January 2022, and 30 June 2023. Propensity score matching was used to form two matched cohorts treated with or without nirmatrelvir-ritonavir or molnupiravir. Results: In the two matched cohorts of 6,358 patients each, the use of novel oral antiviral agents was associated with a significantly lower risk of all-cause emergency department visits, hospitalization, or mortality (6.59% versus 8.24%; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.70-0.91). The novel antiviral group had a significantly lower risk of all-cause emergency department visits (HR, 0.85; 95% CI, 0.74-0.99). Additionally, the incidence of hospitalization was significantly lower in the oral antiviral group than in the control group (HR, 0.71; 95% CI, 0.55-0.90). There were no deaths in the oral antiviral group but 12 deaths in the control group. Conclusion: Novel oral antiviral agents are beneficial for treating COVID-19 in patients with nonalcoholic fatty liver disease.

The Efficacy of On-Site Integration Screening and Microelimination Programs for Chronic Hepatitis C in a Detection Center: A Comparison of the Treatment Outcomes and Characteristics of Incarcerated Patients and Outpatients.

We aimed to analyze the different patient characteristics and treatment outcomes (such as sustained viral response, SVR) between incarcerated patients with chronic hepatitis C (CHC) and those with CHC from the outpatient department through an on-site integrated screening and microelimination program in a detection center. In this retrospective study, which ran from May 2021 to April 2022, we included 32 consenting male prisoners aged at least 20 years who were willing to participate in the study. Members of the control group (who received DAAs in an outpatient setting) were selected from the treated CHC patient databank of individuals who received DAA regimens at Chi Mei Hospital between January 2021 and December 2022. The patients in the two groups did not differ significantly in terms of age, FIB-4 score, HCV RNA, HBV coinfection, hemogram findings, coagulation profiles, and renal function tests. However, the patients in the incarcerated group had a significantly different genotype distribution compared to the control group, significantly lower liver enzyme levels, and higher albumin and bilirubin levels compared to those in the control group. The rate of SVR to DAA treatment obtained among incarcerated patients did not differ significantly from that obtained among patients in the control group. Loss to follow-up (for several reasons) is a major reason for treatment discontinuation among these patients.

Cholestatic Hepatitis with Concomitant Nephrotic Syndrome due to Secondary Syphilis in a Young Man.

Introduction: Syphilis, an ancient sexually transmitted disease, is recognized as a systemic infection disease manifesting with diverse symptoms and variations. Secondary syphilis characterized by systemic symptoms resulted from hematogenous and lymphatic dissemination of the infection, may include manifestations such as hepatitis and nephrotic syndrome. However, the simultaneous occurrence of hepatitis and nephrotic syndrome in secondary syphilis is rare. Case Presentation: A young man presented with fatigue, abnormal liver function tests, and hyperbilirubinemia and had history of men who have sex with men (MSM). Serological tests confirmed the diagnosis of secondary syphilis, and kidney biopsy indicated membranous nephritis. After antibiotic treatment, the patient experienced resolution of proteinuria, and liver enzyme levels returned to normal. Conclusion: Syphilis should be considered in the differential diagnosis of simultaneous liver and kidney dysfunction, particularly in patients engaging in high-risk sexual behavior. This case highlights the importance of considering syphilis in young patients with MSM and presenting with unexplained nephrotic syndrome and liver abnormalities.

Acute kidney injury in patients with COVID-19 compared to those with influenza: a systematic review and meta-analysis.

Background: COVID-19 and influenza can both lead to acute kidney injury (AKI) as a common complication. However, no meta-analysis has been conducted to directly compare the incidence of AKI between hospitalized patients with COVID-19 and influenza. The objective of our study aims to investigate the incidence and outcomes of AKI among hospitalized patients between these two groups. Materials and methods: A systematic search of PubMed, Embase, and Cochrane databases was conducted from December 2019 to August 2023 to identify studies examining AKI and clinical outcomes among hospitalized patients with COVID-19 and influenza. The primary outcome of interest was the incidence of AKI, while secondary outcomes included in-hospital mortality, recovery from AKI, hospital and ICU stay duration. The quality of evidence was evaluated using Cochrane and GRADE methods. Results: Twelve retrospective cohort studies, involving 17,618 hospitalized patients with COVID-19 and influenza, were analyzed. COVID-19 patients showed higher AKI incidence (29.37% vs. 20.98%, OR: 1.67, 95% CI 1.56-1.80, p < 0.01, I2 = 92.42%), and in-hospital mortality (30.95% vs. 5.51%, OR: 8.16, 95% CI 6.17-10.80, p < 0.01, I2 = 84.92%) compared to influenza patients with AKI. Recovery from AKI was lower in COVID-19 patients (57.02% vs., 80.23%, OR: 0.33, 95% CI 0.27-0.40, p < 0.01, I2 = 85.17%). COVID-19 patients also had a longer hospital stay (SMD: 0.69, 95% CI 0.65-0.72, p < 0.01, I2 = 98.94%) and longer ICU stay (SMD: 0.61, 95% CI 0.50-0.73, p < 0.01, I2 = 94.80%) than influenza patients. In our study, evidence quality was high (NOS score 7-9), with low certainty for AKI incidence and moderate certainty for recovery form AKI by GRADE assessment. Conclusion: COVID-19 patients had higher risk of developing AKI, experiencing in-hospital mortality, and enduring prolonged hospital/ICU stays in comparison to influenza patients. Additionally, the likelihood of AKI recovery was lower among COVID-19 patients.

Emotion regulation difficulties and sleep quality in adolescence during the early stages of the COVID-19 lockdown.

INTRODUCTION: Adolescence is a period of vulnerability for emotion regulation and sleep difficulties, risks that might be compounded by intense COVID-19 lockdowns and challenges. The aim of this study was to investigate how sleep quality related to emotion regulation difficulties in adolescents during lockdown in Perú. METHODS: Participants were 2563 adolescents enrolled in Innova school in Perú (11 - -17 years) in May 2020. Hypotheses were derived from exploring one half of the sample, preregistered at https://osf.io/fuetz/, and then confirmed in the second half of the sample. Participants completed subjective surveys of sleep quality (short PSQI) and the Difficulties in Emotion Regulation Scale Short Form (DERS-SF). RESULTS: Worse sleep quality was robustly associated with more difficulties in emotion regulation across both samples. The association was found particularly for emotion regulation subscales related to the ability to engage in goal directed behavior in the face of distress, emotional clarity and strategies to deal with feeling distressed. In contrast, there was no robust association between sleep and the ability to regulate impulses in the context of negative emotions, and no association with the ability to accept emotions. Girls and older adolescents robustly endorsed worse sleep quality and more difficulties in emotion regulation. LIMITATIONS: The cross-sectional nature of this study prevents us from determining the direction of the association. Data were collected using adolescent self-report which, while informative of adolescent perceptions, might diverge from objective measures of sleep or emotion regulation difficulties. CONCLUSIONS: Our findings with adolescents in Perú contribute to our understanding of the association between sleep and emotion regulation at a broader global scale.

Associations Between Dimensional Persistence of ADHD and Adult Sleep Quality in a Prospective Study of Girls.

OBJECTIVES: We investigated the prospective association between (a) ADHD symptom dimensions, including their persistence and (b) adult sleep quality in a female sample, covarying adult depressive symptoms. METHODS: Participants comprised four persistence groups (persisters, partials, desisters, and comparison) based on overall ADHD diagnosis and separate dimensions of inattention and hyperactivity/impulsivity (HI) in childhood, late adolescence, and early adulthood, featuring girls with (n = 140) and without (n = 88) carefully diagnosed ADHD. RESULTS: Only persistence of inattention predicted lower adult sleep quality when covarying young-adult depression, which was also a significant predictor. When additionally covarying stimulant medication use in adulthood, inattention persistence lost significance, although depression maintained significance, with medication use predicting worse sleep quality. CONCLUSIONS: Persistence of inattentive (but not HI) symptoms was significantly related to adult sleep quality in the context of concurrent depression. Sleep quality is an important outcome for research on and treatment for ADHD.

Iatrogenic Kaposi sarcoma of the small bowel in Crohn's disease following short-term use of immunomodulators: a case report and review of the literature.

BACKGROUND: Kaposi sarcoma is a vascular tumor highly related to human herpesvirus-8 and Kaposi sarcoma-associated herpesvirus. Kaposi sarcoma usually manifests as skin or mucosal lesions; involvement in visceral organs such as the gastrointestinal tract is rare. Kaposi sarcoma can occur in immunocompromised patients receiving immunosuppressive therapy, in which case it is known as iatrogenic Kaposi sarcoma or drug-induced Kaposi sarcoma. Intestinal Kaposi sarcoma in patients with inflammatory bowel disease is extremely rare. CASE PRESENTATION: A 46-year-old East Asian male with recently diagnosed Crohn's disease was administered azathioprine and prednisolone; however, the patient complained of persistent abdominal pain and diarrhea following treatment. Endoscopy revealed small bowel Kaposi sarcoma. The patient was treated with systemic chemotherapy successfully without relapse. CONCLUSIONS: This is the fifth case of Kaposi sarcoma developed over the small intestine in a patient with Crohn's disease following administration of immunomodulators. Additionally, this case indicated that even short-term immunomodulator use can induce Kaposi sarcoma in patients with inflammatory bowel disease. Thus, in patients with inflammatory bowel disease, if symptoms are aggravated or do not abate after immunomodulators prescription, and before intending to upgrade immunomodulators, endoscopy should be considered. Finally, chemotherapy can also be considered if both medication withdrawal and surgical intervention are not feasible.

Stem Cell-Based Delivery of Gold/Chlorin e6 Nanocomplexes for Combined Photothermal and Photodynamic Therapy.

Combining photothermal and photodynamic modalities has shown encouraging therapeutic efficacy against various malignant cancers. Developing a delivery method for targeting and penetrating tumors is still a major focus for advancing this therapeutic approach. Herein, we report a novel strategy involving the utilization of stem cells as a live carrier to codeliver photothermal and photodynamic agents for cancer therapy. To this end, a novel gold nanorod (AuNR)-PEG-PEI (APP)/chlorin e6 (Ce6)-loaded adipose-derived stem cell (ADSC) system is proposed in which AuNRs and Ce6 act as the photothermal and photodynamic agents, respectively. To integrate with stem cells, the APP/Ce6 nanocomplexes exhibit advantages of low drug leakage, low cytotoxicity, efficient cellular uptake, and redox-responsive release. After loading of APP/Ce6 nanocomplexes, the ADSCs still maintained good tumor tropism and were capable of penetrating into the tumor spheroids. The photothermal effect induced by exposure to near-infrared light irradiation at 808 nm promoted the release of Ce6 from the stem cells into the surroundings and hence increased its availability to treat cancer cells. APP/Ce6-loaded ADSCs exerted effective dose-dependent in vitro anticancer activities via anticipated photothermal and photodynamic effects. In a murine CT26 colon cancer model, APP/Ce6 delivered by ADSCs resulted in superior tumor suppression compared to other delivery strategies. It was also noted that in vivo applications of APP/Ce6-loaded ADSCs did not induce noticeable detrimental effects on normal tissues/organs.

When supervisors perceive non-work support: test of a trickle-down model.

Using the trickle-down model as the theoretical foundation, we explored whether subordinates' perceived supervisory non-work support (subordinates' PSNS) mediates the relationship between supervisors' perception of higher-level managers' non-work support (supervisors' PSNS) and subordinates' organizational citizenship behaviors. Using dyadic data collected from 132 employees and their immediate supervisors, we found support for the aforementioned mediation process. Furthermore, supervisors' perceived in-group/out-group membership of subordinates moderated the aforementioned supervisors' PSNS-subordinates' PSNS relationship, such that this relationship is stronger for out-group subordinates. Theoretical and practical implications and future research directions are discussed.

Abusive supervision and workload demands from supervisors: exploring two types of supervisor-related stressors and their association with strain.

Our study aimed to identify two types of stressors from supervisors: abusive supervision (AS) and workload demands from supervisors (WDS). AS reflects the relationship dimension of supervisor-related stressors, and WDS reflects the task dimension of supervisor-related stressors. In Study 1, we attempted to distinguish between AS and WDS. The results of confirmatory factor analysis showed that AS and WDS are two distinct dimensions of supervisor-related stressors. In Study 2, we utilized job demands-resources model and investigated whether AS and WDS can uniquely predict subordinates' emotional exhaustion (EE). We also explored whether perceived job characteristics (PJCs) have differential moderating effects on the relationships between the two dimensions of supervisor-related stressors (AS and WDS) and EE. Consistent with our predictions, the results showed that both AS and WDS have incremental predictive effects on EE after controlling for the effect of the other. The results also revealed that PJCs weaken the WDS-EE relationship, not the AS-EE relationship. We discussed the theoretical and practical implications at the end.

The moderating role of personality traits on emotional intelligence and conflict management styles.

In a sample of 442 part-time MBA and undergraduate students, the relationships between emotional intelligence and the integrating style and between emotional intelligence and the dominating style of conflict management were moderated by extraversion. In addition, agreeableness moderated the relationships between emotional intelligence and compromising style and between emotional intelligence and dominating style.