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Bowen Chen,1,2,* Linzhi Zhang,2,3,* Jiamin Cheng,2,* Tong Wu,2 Jin Lei,2,4 Xu Yang,5 Rongling Zhang,6 Rifaat Safadi,7 Yinyin Li,2 Tongguo Si,3 Yinying Lu1,2,8,9 1Peking University 302 Clinical Medical School, Beijing, People’s Republic of China; 2Senior Department of Hepatology, the 5th Medical Center of the PLA General Hospital, Beijing, People’s Republic of China; 3Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China; 4Guizhou Medical University, Guiyang, People’s Republic of China; 5Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 7Liver Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel; 8Center for Synthetic & System Biology, Tsinghua University, Beijing, People’s Republic of China; 9Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yinying Lu, Peking University 302 Clinical Medical School, No. 100, Middle Road of the West 4th Ring, Beijing, 100039, People’s Republic of China, Email luyinying1973@163.com Tongguo Si, Tianjin Medical University Cancer Institute and Hospital, Tiyuan North Huanhu West Road, Hexi District, Tianjin, 300060, People’s Republic of China, Email sitg77@163.comPurpose: This study aimed to investigate the incidence rate and risk factors for hepatic encephalopathy (HE) among unresectable hepatocellular carcinoma (uHCC) patients with liver cirrhosis who received sorafenib or lenvatinib treatment.Patients and Methods: uHCC patients with cirrhosis who received first-line sorafenib or lenvatinib treatment between September 2014 and February 2021 were continually reviewed in our single-center retrospective study. The Hepatic Encephalopathy Scoring Algorithm was used to evaluate the occurrence and grade of HE during treatment, and logistic regression models were used to further explore the risk factors for HE.Results: A total of 454 eligible patients were enrolled in our study, with 214 and 240 patients in the sorafenib and lenvatinib groups, respectively. At time of data cut-off (2021– 12), the incidence of HE in sorafenib group (4.2%, 95% CI:2– 7%) was significantly lower than that in lenvatinib group (11.3%,95% CI:7– 15%) (p = 0.006), with alcoholic cirrhosis [OR: 5.857 (95% CI: 1.519– 22.591)], Child-Pugh > 7 [OR: 3.023 (95% CI: 1.135– 8.053)], blood ammonia ≥ 38.65 μmol/L [OR: 4.693 (95% CI: 1.782– 12.358)], total bile acid ≥ 29.5 μmol/L [OR: 11.047 (95% CI: 4.414– 27.650)] and duration of treatment ≥ 5.6 months [OR: 4.350 (95% CI: 1.701– 11.126)] to be risk factors for the occurrence of HE during first-line systemic therapy.Conclusion: In our study, for off-label uHCC patients (Child-Pugh > 7) with alcoholic cirrhosis, hyperammonemia, hypercholesterolemia, and estimated longer duration of treatment, the application of lenvatinib has to be cautious, which needs to be confirmed in future clinical trials.Keywords: hepatic encephalopathy, hepatocellular carcinoma, liver cirrhosis, sorafenib, lenvatinib

Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by [greater than or equal to]1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was -29.1 IU l.sup.-1 (95% CI = -41.6 to -16.5). Early termination due to adverse events (AEs) was In a phase 2b study, inhibition of hepatic stearoyl-CoA desaturase in patients with nonalcoholic steatohepatitis was safe and tolerated; although reductions in liver fat were not significant, changes in liver enzymes and histology were observed., Author(s): V. Ratziu [sup.1] , L. de Guevara [sup.2] , R. Safadi [sup.3] , F. Poordad [sup.4] , F. Fuster [sup.5] , J. Flores-Figueroa [sup.6] , M. Arrese [sup.7] , [...]

Dua’ Al-Maharma,1 Reema Safadi,1 Muayyad Ahmad,2 Suhaila Halasa,1 Manar Nabolsi,2 Jennifer Dohrn3 1Maternal and Child Health Department, School of Nursing, The University of Jordan, Amman, Jordan; 2Clinical Nursing Department, School of Nursing, The University of Jordan, Amman, Jordan; 3School of Nursing, Columbia University, New York, NY, USACorrespondence: Dua’ Al-MaharmaDepartment of Maternal and Child Health Nursing, School of Nursing, The University of Jordan, Amman 11942, JordanTel +962 6 5355000 Ext 23179Fax +9626−5300244Email d.maharma@ju.edu.joPurpose: Refugee women are vulnerable to sexually transmitted infections (STIs) due to risk factors associated with displacement. This study aimed to assess the knowledge, attitudes, and practices related to STIs among Syrian refugee mothers in Jordan.Methods: A cross-sectional correlational study was conducted with a convenience sample of 523 Syrian refugee mothers in host communities in Jordan.Results: A moderately positive relationship between the mothers’ knowledge of and attitudes towards STIs (p

Khadeejeh Al dasoqi,1 Reema Safadi,1 Eman Badran,2 Asma Sa’d Basha,3 Sue Jordan,4 Muayyad Ahmad5 1Department of Maternal and Child Health Nursing, School of Nursing, University of Jordan, Amman, Jordan; 2Department of pediatrics, School of Medicine, University of Jordan, Amman, Jordan; 3Department of Obstetrics and Gynecology, School of Medicine, University of Jordan, Amman, Jordan; 4Department of Nursing, Swansea University, Swansea, UK; 5Clinical Nursing Department, School of Nursing, University of Jordan, Amman, Jordan Objective: This study aimed to examine the rates of initiation and continuation of breastfeeding (BF) and their relationship with mothers’ sociodemographic, obstetric, neonatal, and medical interventions.Methods: Data were collected from 199 first-time Jordanian mothers using medical records, face-to-face interviews within 24 hours of birth, and two telephone interviews at 6 weeks and 6 months after birth.Results: The rate of BF initiation within the first 4 hours after birth was only 13%. The rate of exclusive BF at 6 weeks was 25.5%, and this rate dropped to 2.1% at 6 months. Mothers who initiated BF before discharge were older, were employed, had normal vaginal birth, and had undergone antenatal or after-birth BF education. Infants’ birth weight or gender was not interrelated with BF initiation. There was no relationship between initiation and continuation of BF and use of medications for labor pain or for induction/augmentation. The only significant relationship was found between the dose of ergometrine and BF failure and painful BF at 6 weeks.Conclusion: There is a need for increasing health care providers and public awareness about the role of intrapartum medications and procedures on the initiation and continuation of BF at 6 weeks and 6 months after birth. Keywords: exclusive breastfeeding, ergometrine, obstetric procedures, intrapartum medication, Jordan

Mahmud Mahamid1,3, Reuven Mader4, Rifaat Safadi1,2 1Liver Unit, Holy Family Hospital, Nazareth, Israel; 2Hadassah Medical Center, Jerusalem, Israel; 3Shaare Zedek Medical Center, Jerusalem, Israel; 4Rheumatology Unit, Ha’emek Medical Center, Afula, Israel Background: Elevation of liver enzymes in rheumatoid arthritis patients treated with tocilizumab (Actemra®) or anakinra (Kineret®) is a well-documented phenomenon. However, characterization of liver histology has not been defined in most cases. Similarly, the factors involved in decisions regarding discontinuation of treatment and outcome have not been discussed in the literature to any significant extent. Cases: Two women with rheumatoid arthritis refractory to standard therapies are reported here. One was treated with tocilizumab and the other with anakinra, and both developed toxic liver effects. Liver biopsy in both cases showed focal necrosis of hepatocytes – a hallmark of drug toxicity – with steatosis and early fibrosis. Inflammatory infiltrates were prominent in the patient treated with anakinra but not in the tocilizumab-treated patient. However, FibroTest (Assistance publique – Hôpitaux de Paris, Paris, France) in the latter patient showed an inflammatory activity of A2 and was staged as F2, and the histology also showed hemorrhagic areas. Although both patients were overweight and both had been exposed to steroids, the steatosis and steatohepatitis were considered to be related to drug hepatotoxicity. Other possible etiologies for liver injury were excluded. Discontinuation of anakinra led to rapid normalization of liver enzymes. The patient receiving tocilizumab developed hepatosplenomegaly but had normal liver enzymes. In spite of the hepatosplenomegaly, the tocilizumab treatment was continued since the patient had not responded to other drugs. There was a good response to the tocilizumab treatment and the liver biopsy showed only insignificant, reversible liver injury. At follow-up at 6-months the patient remains stable. Conclusion: As cases showing tocilizumab or anakinra liver toxicity are appearing more frequently to the authors, a full assessment for liver injury is recommended in patients given those drugs, with careful consideration of the decision to continue or discontinue treatment. Further studies with long-term follow-up analysis are mandatory to guide appropriate management strategies. Keywords: anakinra, interleukin receptors, liver injury, rheumatoid arthritis, tocilizumab

Mahmud Mahamid1,3, Kalman Paz3, Rifaat Safadi1,21Liver Unit, Holy Family Hospital, Nazareth, Israel; 2Hadassah Medical Center, 3Shaare Zedek Medical Center, Jerusalem, IsraelAbstract: Elevation of liver enzymes in patients with rheumatoid arthritis treated with the biological agents, tocilizumab and anakinra, is now well documented. However, histological characterization of these effects and outcomes has not been defined. Here we report toxic liver effects in two women with rheumatoid arthritis, refractory to all nonbiological therapies, following treatment with anakinra and tocilizumab. Liver biopsy in both cases showed focal necrosis of hepatocytes as a hallmark of drug toxicity, along with steatosis and early fibrosis. In addition, the patient treated with anakinra demonstrated inflammatory changes. Tocilizumab was continued with no further deterioration in liver function. Withdrawal of anakinra led to rapid normalization of liver function. The biological agents, tocilizumab and anakinra, may result in significant histological hepatic changes, including necrosis, but despite this, the outcome appears to be good.Keywords: tocilizumab, anakinra, interleukin receptors, lymphocytes, liver injury, rheumatoid arthritis

Presents a study that used thermal electromotive force (EMF) to follow phase transitions in a specimen. Discussion on the differential thermal analysis of individual specimens by thermal EMF measurement; Observation on temperature difference between specimens; Result of the study.