Hsuolsson8866

We read with great interest the Special Article by Jhaveri et al. entitled "Responsible Inclusion of Pregnant Individuals in Eradicating Hepatitis C virus."1 This article is timely and draws attention to pregnant women, a subpopulation that has been ignored in the study of hepatitis C (HCV) treatment. Pregnancy is an ideal window of opportunity due to the high engagement in healthcare of reproductive-aged women. The AASLD/ IDSA, USPSTF and CDC now all recommended universal HCV screening during pregnancy which will lead to increased diagnosis of HCV during pregnancy. However, the American College of Obstetrics and Gynecology (ACOG) has been hesitant to recommend universal screening due to the lack of treatment available during pregnancy.2 Jhaveri et al. identified only one pharmacokinetic study of sofosbuvir/ledipasvir, which demonstrated safety, tolerability, and effectiveness of direct-acting antiviral (DAA) therapy in nine pregnant women. Guidance from the AASLD/ IDSA suggests that "women who become pregnant while on DAA therapy should discuss the risks versus benefits of continuing treatment with their physicians."3 This "guidance" puts providers in the difficult position of providing advice with minimal published data on DAA safety in pregnancy.

Telemedicine may be particularly well-suited for myasthenia gravis (MG) due to the disorder's need for specialized care, its hallmark fluctuating muscle weakness, and the potential for increased risk of virus exposure among patients with MG during the coronavirus disease 2019 (COVID-19) pandemic during in-person clinical visits. A disease-specific telemedicine physical examination to reflect myasthenic weakness does not currently exist.

This paper outlines step-by-step guidance on the fundamentals of a telemedicine assessment for MG. The Myasthenia Gravis Core Exam (MG-CE) is introduced as a MG-specific, telemedicine, physical examination, which contains eight components (ptosis, diplopia, facial strength, bulbar strength, dysarthria, single breath count, arm strength, and sit to stand) and takes approximately 10 minutes to complete.

Pre-visit preparation, remote ascertainment of patient-reported outcome scales and visit documentation are also addressed.

Additional knowledge gaps in telemedicine specific to MG care are identified for future investigation.

Additional knowledge gaps in telemedicine specific to MG care are identified for future investigation.

Cholangiocarcinoma (CCA) is characterized by high resistance to chemotherapy and poor prognosis. Several oncogenic pathways converge on activation of extracellular signal-regulated kinase 5 (ERK5), whose role in CCA has not been explored. The aim of this study was to investigate the role of ERK5 in the biology of CCA.

ERK5 expression was detected in two established (HuCCT-1 and CCLP-1) and two primary human intrahepatic CCA cell lines (iCCA58 and iCCA60). ERK5 phosphorylation was increased in CCA cells exposed to soluble mediators. In both HuCCT-1 and CCLP-1 cells, ERK5 was localized in the nucleus, and exposure to fetal bovine serum (FBS) further increased the amount of nuclear ERK5. In human CCA specimens, ERK5 mRNA expression was increased in tumor cells and positively correlated with portal invasion. ERK5 protein levels were significantly associated with tumor grade. Growth, migration, and invasion of CCA cells were decreased when ERK5 was silenced using specific short hairpin RNA (shRNA). Proteasome inhibitor The inhibitory effects on CCA cell proliferation, migration and invasion were recapitulated by treatment with small molecule inhibitors targeting ERK5. In addition, expression of the angiogenic factors VEGF and angiopoietin 1 was reduced after ERK5 silencing. Conditioned medium from ERK5-silenced cells had a lower ability to induce tube formation by human umbilical vein endothelial cells and to induce migration of myofibroblasts and monocytes/macrophages. In mice, subcutaneous injection of CCLP-1 cells silenced for ERK5 resulted in less frequent tumor development and smaller size of xenografts compared with cells transfected with nontargeting shRNA.

ERK5 is a key mediator of growth and migration of CCA cells and supports a protumorigenic crosstalk between the tumor and the microenvironment.

ERK5 is a key mediator of growth and migration of CCA cells and supports a protumorigenic crosstalk between the tumor and the microenvironment.

The schizophrenia guidelines in Japan and many other countries describe clozapine as the first-choice drug for patients with treatment-resistant schizophrenia. However, there have been no reports to date on the effects of the introduction of clozapine on the prescription of other antipsychotics and concomitant drugs.

In this study, we retrospectively investigated the prescription of antipsychotics and concomitant drugs before vs 6months after and 12months after switching to clozapine.

Clozapine was introduced to 62 patients with treatment-resistant schizophrenia, and 51 patients continued on clozapine therapy. Six months after switching to clozapine, there was a significant decrease in the mean number of antipsychotic drugs (2.04±0.75 vs 1.10±0.30 p<0.001) and in the mean chlorpromazine equivalent value (1024±73mg/day vs 781±391mg/day p<0.001) compared to before switching. Moreover, antipsychotic monotherapy increased from 24% to 90% after switching to clozapine. In addition, the number of concomitant benzodiazepines, anti-parkinson drugs and antidepressants also significantly decreased 6 and 12months after switching to clozapine (p<0.001 for benzodiazepines and anti-parkinson drugs, and p<0.05 for antidepressants).

Our study suggests that switching to clozapine may reduce the use of antipsychotic combination therapy, and may also reduce the number of concomitant drugs.

Our study suggests that switching to clozapine may reduce the use of antipsychotic combination therapy, and may also reduce the number of concomitant drugs.

Non-white patients are underrepresented in left atrial appendage occlusion (LAAO) trials, and racial disparities in LAAO periprocedural management are unknown.

We assessed sociodemographics and comorbidities of consecutive patients at our institution undergoing LAAO between 2015 and 2020, then in adjusted analyses, compared procedural wait time, procedural complications, and post-procedure oral anticoagulation (OAC) use in whites versus non-whites.

Among 109 patients undergoing LAAO (45% white), whites had lower CHA

DS

VASc scores, on average, than non-whites (4.0vs. 4.8, p=.006). There was no difference in median time from index event (IE) or initial outpatient cardiology encounter to LAAO procedure (whites 10.5vs. non-whites 13.7 months, p=.9; 1.9vs. 1.8 months, p=.6, respectively), and there was no difference in procedural complications (whites 4%vs. non-whites 5%, p=.33). After adjusting for CHA

DS

VASc score, OAC use at discharge tended to be higher in whites (OR 2.4, 95% CI [0.9-6.0], p=.07).