Cardiovascular Pharmacology

Arrhythmia mechanisms in human induced pluripotent stem cell-derived cardiomyocytes Despite major efforts by clinicians and researchers, cardiac arrhythmia remains a leading cause of morbidity and mortality in the world. Experimental work has relied on combining high-throughput strategies with standard molecular and electrophysiological studies, which are, to a great extent, based on the use of animal models. As this poses major challenges for translation, the progress in the development of novel antiarrhythmic agents and clinical care has been mostly disappointing. Recently, the advent of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has opened new avenues for both basic cardiac research and drug discovery: now there is an unlimited source of CMs of human origin, both from healthy individuals and patients with cardiac diseases. Understanding arrhythmic mechanisms is one the main use-cases of hiPSC-CMs, in addition to pharmacological cardiotoxicity and efficacy testing, in vitro disease modeling, developing patient-specific models and personalized drugs, and regenerative medicine. Here, we review the advances that the hiPSC-based modeling systems have brought so far regarding the understanding of both arrhythmogenic triggers and substrates, while also briefly speculating about the possibilities in the future. Corresponding author: Jussi T. Koivumäki, Arvo Ylpön katu 34, FI-33520 Tampere, Finland, +358 40 5813 290, jussi.koivumaki@iki.fi This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

A Perspective on Personalized Therapies in Hypertrophic Cardiomyopathy A dominant mechanism of sudden cardiac death in the young is the progression of maladaptive responses to genes encoding proteins linked to hypertrophic cardiomyopathy (HCM). Most are mutant sarcomere proteins that trigger the progression by imposing a biophysical defect on the dynamics and levels of myofilament tension generation. We discuss approaches for personalized treatments that are indicated by recent advanced understanding of the progression Corresponding Author: R. John Solaro, PhD, Department of Physiology and Biophysics (M/C 901), University of Illinois at Chicago, College of Medicine, 835 South Wolcott Avenue, Chicago, IL 60612, eMail: solarorj@uic.edu Online date: 00 00, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Heat shock protein 70 is associated with cardioversion outcome and recurrence of symptomatic recent onset atrial fibrillation in hypertensive patients Accumulating evidence indicates that heat shock proteins (HSPs) may represent a suitable biomarker to predict atrial fibrillation (AF). We investigated the relation of circulating heat shock protein 70 (sHSP70) with inflammatory cytokines and recurrence of symptomatic recent onset AF (ROAF). We enrolled 90 patients with ROAF (duration from onset of symptoms ≤24 hours) and 30 controls. Patients received amiodarone for cardioversion and rhythm control. The association of serum HSP70, interleukin-2 (sIL-2) and interleukin-4 (sIL-4) with the presence, cardioversion and AF recurrence within a year was investigated. TLR4 signaling dependence for IL-2 and IL-4 induction in response to stimulation with HSP70 was tested in rat aortic vascular smooth muscle cell (SMC) cultures. Patients had higher sHSP70 and sIL-2 and lower sIL-4 compared to controls. sHSP70 was independently associated with ROAF (P=0.005) and correlated with sIL-2 (r =0.494, P<0.001) and sIL-4 (r=-0.550, P<0.001). By 48 hours 71/90 patients were cardioverted, with non-cardioverted patients having higher sHSP70 and sIL-2 and lower sIL-4, which were the only independent factors associated with cardioversion. AF recurred in 38/71 cardioverted patients in one year. A cut-off value of sHSP70 ≥0.65 ng/ml and sIL-2 ≥0.21 pg/ml were the only independent factors associated with AF recurrence (HR: 3.311, 95% CI: 1.503-7.293, P=0.003 and HR: 3.144, 95% CI: 1.341-7.374, P=0.008, respectively). Exposure of SMC to HSP70 in vitro increased the expression of IL-2 (5x) and IL-4 (1.5x) through TLR4-dependent and receptor-independent mechanisms. In conclusion, sHSP70 and sIL-2 might constitute a prognostic tool for determining the cardioversion and recurrence likelihood in ROAF. Corresponding author: Dr. Angelos G. Rigopoulos, MD, FESC, Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120 Halle (Saale), Germany, Tel.: +49 176 79844001, Fax: +49 345 5572072 E-Mail: angelos.rigopoulos@gmail.com Online date: 00 00, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Circular RNA circ-BANP regulates ox-LDL-induced endothelial cell injury through targeting the miR-370/TXNIP axis Dysfunction of endothelial cells is now recognized as an important contributor to the pathogenesis of atherosclerosis (AS). Circular RNAs (circRNAs) have been demonstrated to be involved in AS pathogenesis. The purpose of this study was to explore the biological action of circRNA BTG3 associated nuclear protein (circ-BANP, hsa_circ_0040824) on the dysfunction of human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL). The levels of circ-BANP, miR-370 and thioredoxin-interacting protein (TXNIP) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Subcellular fractionation assay was used to determine the localization of circ-BANP, and ribonuclease R (RNase R) assay was performed to evaluate the stability of circ-BANP. Cell viability, apoptosis, migration, invasion and tube formation abilities were assessed by the Cell Counting Kit-8 (CCK-8), flow cytometry, transwell, and tube formation assays. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). Targeted relationships among circ-BANP, miR-370 and TXNIP were confirmed by a dual-luciferase reporter assay. Our data showed that circ-BANP expression was up-regulated in AS blood and ox-LDL-induced HUVECs. The inhibition of circ-BANP promoted cell viability, migration, invasion, tube formation, and repressed cell inflammation and apoptosis in ox-LDL-induced HUVECs, demonstrating that circ-BANP silencing alleviated ox-LDL-induced HUVEC injury. Mechanistically, circ-BANP directly targeted miR-370. Moreover, miR-370 mediated the regulation of circ-BANP in ox-LDL-induced cell injury in HUVECs. TXNIP was a target of miR-370, and miR-370 overexpression relieved ox-LDL-induced HUVEC injury by down-regulating TXNIP. Furthermore, circ-BANP modulated TXNIP expression by targeting miR-370. Our findings demonstrated that circ-BANP regulated ox-LDL-induced cell injury in HUVECs at least in part through targeting the miR-370/TXNIP axis, illuminating circ-BANP as a potential target for AS detection and treatment. Corresponding author: Lijun Gao, Department of General Internal Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Zhongjing Building, No. 16369, Jingshi Road, Lixia District, Jinan, Shandong, 250014, China, Tel: +86-0531-68617110; E-mail: gljsdzhyy0812@163.com Online date: 00 00, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Evaluation of sacubitril/valsartan initiation in outpatient heart failure patients Despite sacubitril/valsartan being on the market since 2015, clinicians are still determining the best way to initiate therapy in order to optimize outcomes and minimize potential for side effects. The purpose of this study is to investigate real-world outpatient experience of prescribing sacubitril/valsartan therapy based on appropriate patient selection, dosing conversion, and tolerability. This retrospective cohort study evaluated patients prescribed sacubitril/valsartan therapy in cardiology clinics associated with an academic institution between February 1, 2016 and August 30, 2018. Patients were excluded if they were less than 18 years of age, enrolled in a clinical trial involving sacubitril/valsartan, or had insufficient data. The primary outcome was to determine how many heart failure patients initiated on sacubitril/valsartan were done so appropriately based on guideline and package insert recommendations. Select secondary outcomes included rates of adverse events and need for adjustment of concomitant heart failure medications. A total of 250 patients were included in this study. For the primary outcome, 125 patients (50%) were appropriately initiated on sacubitril/valsartan. Those who were inappropriately initiated on the medication experienced more symptoms of hypotension (16% in appropriate start group vs. 28% in inappropriate start group; p=0.022) and required more dose decreases of sacubitril/valsartan (6% in appropriate start group vs. 13% in inappropriate start group; p=0.049). In outpatient clinical practice, almost half of patients initiated on sacubitril/valsartan were done so outside of guideline recommendations, which was associated with an increased risk of hypotension and dose reductions. Corresponding Author: Lindsey Rerick, PharmD, Allegheny Health Network, West Mifflin, PA UNITED STATES Online date: 00 00, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Lipoprotein(a) reduction with proprotein convertase subtilisin/kexin type 9 inhibitors: a systematic review and meta-analysis. Lipoprotein(a) (Lp(a)) is a cardiovascular factor, for which there is no approved specific lowering treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to have lowering effects on Lp(a). Aim of this systematic review is to synthesize the current literature and quantify the effects of PCSK9 inhibitors on the serum Lp(a) levels in human subjects. Double-blind, phase 2 or 3, randomized controlled trials comparing PCSK9 inhibitors (alirocumab or evolocumab) to placebo and/or ezetimibe and/or other lipid lowering therapy were deemed eligible for inclusion. We searched MEDLINE (via PubMed), CENTRAL, Scopus and Web of Science as of 17 June 2020. Quality assessment was performed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2). Forty-three studies were identified (64107 patients randomized) and 41 studies were included in the quantitative analysis. PCSK9 inhibitors reduced Lp(a) levels by -26.7% (95% CI -29.5% to -23.9%) with a significant heterogeneity within studies. There was significant difference in Lp(a) change from baseline according to comparator (placebo: mean -27.9%, 95% CI -31.1% to -24.6% vs. ezetimibe: mean -22.2%, 95% CI -27.2% to -17.2%, p=0.04) and duration of treatment (≤12 weeks: mean -30.9%, 95% CI -34.7% to -27.1% vs. >12 weeks: mean -21.9%, 95% CI -25.2% to -18.6%, p<0.01). Meta-regression analysis showed that only the mean percentage change from baseline LDL-C due to the intervention is significantly associated with the effect size difference (p<0.0001). PCSK9 inhibitors reduced LDL-C by -54% (95% CI -57.6% to -50.6%). There is substantial efficacy of the currently approved PCSK9 inhibitors in the lowering of Lp(a) levels. Dedicated RCTs are needed to establish the benefit of this intervention. Corresponding author: George Giannakoulas, MD, PhD, Associate Professor of Cardiology, Aristotle University of Thessaloniki, AHEPA Hospital, Cardiology Department, Stilp. Kiriakidi 1, 54637, Thessaloniki, Greece, Tel: +302313303589, Email: ggiannakoulas@auth.gr Online date: 00 00, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Is spironolactone the preferred renin-angiotensin-aldosterone inhibitor for protection against COVID-19? The high mortality of specific groups from COVID-19 highlights the importance of host-viral interactions and the potential benefits from enhancing host defenses. SARS-CoV-2 requires angiotensin converting enzyme (ACE)2 as a receptor for cell entry and infection. While both ACE inhibitors and spironolactone can upregulate tissue ACE2, there are important points of discrimination between these approaches. The virus requires proteolytic processing of its spike protein by transmembrane protease receptor serine type 2 (TMPRSS2) to enable binding to cellular ACE2. Since TMPRSS2 contains an androgen promoter, it may be downregulated by the antiandrogenic actions of spironolactone. Furin and plasmin also process the spike protein. They are inhibited by protease nexin 1 or serine E2 (PN1) that is upregulated by angiotensin II but downregulated by aldosterone. Therefore, spironolactone should selectively downregulate furin and plasmin. Furin also promotes pulmonary edema while plasmin promotes hemovascular dysfunction. Thus, a downregulation of furin and plasmin by PN1 could be a further benefit of MRAs beyond their well established organ protection. We review the evidence that spironolactone may be the preferred RASSi to increase PN1 and decrease TMPRSS2, furin and plasmin activities and thereby to reduce viral cell binding, entry, infectivity and bad outcomes. This hypothesis requires direct investigation. Address for correspondence: Christopher Wilcox, MD, PhD, 3800 Reservoir Road, NW, PHC F6003, Washington, DC 20007, Fax: 877-625-1483, Email: wilcoxch@georgetown.edu Sources of Funding: Work in CSW's laboratory is supported by the Smith-Kogod Family Trust, the Gildenhorn-Speisman Family Trust, the Georgetown University Hypertension Research Center and the Walters Family Chair of Cardiovascular Research, all located in Washington DC. Disclosures: CSW, none. BP, none. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Intermittent optogenetic tachypacing of atrial engineered heart tissue induces only limited electrical remodelling Atrial tachypacing is an accepted model for atrial fibrillation (AF) in large animals and in cellular models. Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CM) provide a novel, human source to model cardiovascular diseases. Here we investigated whether optogenetic tachypacing of atrial-like hiPSC-CMs grown into engineered heart tissue (aEHT) can induce AF-remodeling. After differentiation of atrial-like cardiomyocytes from hiPSCs using retinoic acid, aEHTs were generated from ∼1 million atrial-like hiPSC-CMs per aEHT. AEHTs were transduced with lentivirus expressing channelrhodopsin-2 to enable optogenetic stimulation by blue light pulses. AEHTs underwent optical tachypacing at 5 Hz for 15 s twice a minute over three weeks and compared to transduced spontaneously beating isogenic aEHTs (1.95±0.07 Hz). Force and action potential duration did not differ between spontaneously beating and tachypaced aEHTs. Action potentials in tachypaced aEHTs showed higher upstroke velocity (138±15 V/s vs. 87±11 V/s, n=15-13/3; p=0.018), possibly corresponding to a tendency for more negative diastolic potentials (73.0±1.8 mV vs. 68.0±1.9 mV; p=0.07). Tachypaced aEHTs exhibited a more irregular spontaneous beating pattern (beat-to-beat scatter: 0.07±0.01 vs. 0.03±0.004 s, n=15-13/3; p=0.008). Targeted expression analysis showed higher RNA levels of KCNJ12 (Kir2.2, inward rectifier (IK1); 69±7 vs. 44±4, p=0.014) and NPPB (NT-proBNP; 39690±4834 vs. 23671±3691; p=0.024). Intermittent tachypacing in aEHTs induces some electrical alterations found in AF and induces an arrhythmic spontaneous beating pattern, but does not affect resting force. Further studies using longer, continuous, or more aggressive stimulation might clarify the contribution of different rate patterns on the changes in aEHT mimicking the remodeling process from paroxysmal to persistent atrial fibrillation. Address for Correspondence: PD. Dr. med. Torsten Christ, Institut für Experimentelle Pharmakologie und Toxikologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany, Tel +49 40 7410 52180, Fax+49 40 7410 54876, E-mail address: t.christ@uke.de * These authors contributed equally # Current Address: Nanion Technologies GmbH, Ganghoferstraße 70a, 80339 München, Germany. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Knockdown of long non-coding RNA SNHG14 protects H9c2 cells against hypoxia-induced injury by modulating miR-25-3p/KLF4 axis in vitro Cyanotic congenital heart disease (CCHD) is the main cause of death in infants worldwide. Long non-coding RNAs (lncRNAs) have been pointed to exert crucial roles in development of CHD. The current research is designed to illuminate the impact and potential mechanism of lncRNA SNHG14 in CCHD in vitro. The embryonic rat ventricular myocardial cells (H9c2 cells) were exposed to hypoxia to establish the model of CCHD in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine relative expressions of SNHG14, miR-25-3p and KLF4. Cell viability was determined by MTT assay. Lactate dehydrogenase (LDH) was measured by an LDH assay kit. Apoptosis-related proteins (Bax and Bcl-2) and KLF4 were detected by Western Blot. The targets of SNHG14 and miR-25-3p were verified by dual-luciferase reporter (DLR) assay. SNHG14 and KLF4 were up-regulated, while miR-25-3p was down-regulated in hypoxia-induced H9c2 cells and cardiac tissues of patients with CCHD compared with their controls. Knockdown of SNHG14 or overexpression of miR-25-3p facilitated cell viability, while depressing cell apoptosis and release of LDH in hypoxia-induced H9c2 cells. MiR-25-3p was a target of SNHG14 and inversely modulated by SNHG14. MiR-25-3p could directly target KLF4 and negatively regulate expression of KLF4. Repression of miR-25-3p or overexpression of KLF4 reversed the suppression impacts of sh-SNHG14 on cell apoptosis and release of LDH as well as the promotion impact of sh-SNHG14 on cell viability in hypoxia-induced H9c2 cells. Sh-SNHG14 protected H9c2 cells against hypoxia-induced injury by modulating miR-25-3p/KLF4 axis in vitro. Corresponding author: Zhaoyun Cheng, Address: Department of Cardiovascular Surgery, Fuwai Central China Cardiovascular Hospital, Heart Center of Henan Provincial People's Hospital, No.1, Fuwai Road, Zhengdong New District, Zhengzhou City, Henan Province, 451464, China. Phone number: 86-13903712068, Email: chengzhaoyun287@163.com Conflict of Interest: The authors have no conflict of interest to disclose. Received July 20, 2020 Accepted November 05, 2020 Online date: 00 00, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Leonurine Attenuates Myocardial Fibrosis through Upregulation of miR-29a-3p in Mice Post-myocardial Infarction Abstract: Myocardial fibrosis (MF) is a pathological process that accelerates cardiac remodeling in myocardial infarction (MI), and miR-29 has become one of the foci of research into MF. As an alkaloid extracted from Herba leonuri, leonurine (LE) has been found to be an effective natural active ingredient for inhibiting fibrosis in many preclinical experiments. However, whether LE protects against MF after MI through modifying miR-29 remains unclear. The present study aimed to investigate the therapeutic effects of LE on MF, and to elucidate the underlying mechanisms involved. A mouse model of MI was established, followed by administration of LE for 4 weeks. We found that LE effectively improved cardiac function, and attenuated fibrosis and cardiac remodeling in mice post-MI. In vitro, LE simultaneously inhibited proliferation and migration of neonatal mouse cardiac fibroblasts (CFs) exposed to angiotensin II (Ang II), and the activation of collagen synthesis and myofibroblast generation was markedly suppressed by LE. Notably, we found that all mature miR-29 family members were downregulated in the myocardial tissues of mice post-MI, while, LE significantly upregulated miR-29a-3p expression, and such upregulation was also detected in LE-treated CFs under Ang II stimulation. Knockdown of miR-29a-3p by a specific miRNA inhibitor upregulated the protein levels of TGF-β, Collagen III, and Collagen I in CFs, and completely reversed the antifibrotic effects of LE on CFs. Our study suggests that LE exerts cardioprotective effects against MF, possibly through the upregulation of miR-29a-3p. Corresponding author: Dr. Jiadan Yang. Department of Pharmacy, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing 400016, P.R. China. E-mail address: yangjiadan11@126.com The authors report no conflicts of interest. † These two authors contributed equally to this work. Online date: 00 00, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Medical Sciences

The Journey of MAMCJMS - Looking back with satisfaction! Pawanindra Lal MAMC Journal of Medical Sciences 2020 6(3):149-150

Responding to the COVID-19 Pandemic: the Experience and the Road Ahead for the Largest Medical College in India's Capital City Nandini Sharma MAMC Journal of Medical Sciences 2020 6(3):151-152

COVID 19 Pandemic: Managing One: Preventing Another Mohit D Gupta MAMC Journal of Medical Sciences 2020 6(3):153-155

Response to COVID-19: Best Practices From the Department of Community Medicine of a Medical College in Delhi Nandini Sharma, Bratati Banerjee, Shivani Rao, Amod Laxmikant Borle, Nidhi Bhatnagar, Pragya Sharma, Rajesh Kumar, Mongjam Meghachandra Singh, Panna Lal, Gajendra Singh Meena, Suneela Garg MAMC Journal of Medical Sciences 2020 6(3):156-162 Public health response and measures are vital to contain an infectious disease outbreak/epidemic. The discipline of Community Medicine, which provides comprehensive primary health care to the entire population at all times, plays a crucial role in times of disease outbreak/epidemic also, being equipped with skills in providing managerial, clinical, and community care, through policy making, surveillance activities, preventive strategies, primary care, capacity building, and awareness generation in addition to generation of evidence-based strategies. The Departments of Community Medicine in Medical Colleges can play a crucial role in this direction and should be involved to share the expertise as well as the best practices adopted, which will go a long way in containing an epidemic at the earliest. The Department of Community Medicine of a leading Medical College in Delhi, along with the clinical departments, is playing a stellar role in response to the pandemic of Corona Virus Disease of 2019 (COVID-19). This article highlights the response to the situation, the challenges faced, and the success stories. Activities have been categorized as Fair, Good, and Best. Activities that are routinely performed are taken to be “Fair” and activities that are beyond routine activities have been labelled “Good”. “Best” practices have been identified to be those that involve representation at the national/State/District level, activities for capacity building, contribution toward evidence generation, and work with risk of exposure. The best practices adopted by the Department of Community Medicine of this institution can be collated for future use in teaching hospitals where Community Medicine departments are equipped with manpower skilled to face such a challenge. It will serve as a blueprint for action, if the need be, for handling similar situations in the future.

Surgery in Covid 19 Times: A Comprehensive Review Lovenish Bains, Anurag Mishra, Lalit Gupta, Rajdeep Singh, Pawanindra Lal MAMC Journal of Medical Sciences 2020 6(3):163-175 The problems faced by surgeons are unique during the Covid pandemic. In the absence of concrete information, we have to resort to extreme degrees of precautions during surgery. Precautions have to start from the point patient enters the hospital, to the point he is discharged. Changes in the patient flow and having sanitization protocols can help in this regard. Since the epidemiology of SARS-Cov 2 is still evolving, the consent process has to necessarily include the risks involved. Preoperative testing is not full proof and the increased risk for the COVID positive patient undergoing surgery has to be communicated. The operating room has to be modified with regard to the number of air changes, an aspect which the surgeons were unaware of prior to this pandemic. Changes in the follow-up protocol, such as use of telemedicine, will help minimize patient contact.

Imaging Appearances of Pediatric Hepatic Masses − A Review Shruti Mittal, Sapna Singh, Radhika Batra MAMC Journal of Medical Sciences 2020 6(3):176-185 In the pediatric population, a wide spectrum of focal liver lesions is seen, which can be categorised into congenital, inflammatory or neoplastic origin. Majority of the patients with focal liver masses present with abdominal pain, abdominal distention or palpable abdominal lump. However, some lesions can be detected incidentally. After physical examination and clinical history, imaging plays a vital role in evaluating pediatric patients with suspected focal liver lesions. Abdominal radiography may provide some imaging findings suggesting the presence of focal hepatic mass such as hepatomegaly, presence of calcification and displacement of bowel loops. Ultrasound is the first line imaging modality as it does not involve ionising radiation. It can detect, characterise and provide the extent of lesion. However, computerised tomography and magnetic resonance imaging are performed subsequently for further characterisation of liver lesions on the basis of morphology, vascularity, enhancement pattern and for detection of associated metastases in malignant neoplasms. In this review article, we aim to describe the imaging appearances of various benign and malignant hepatic mass lesions in the paediatric age group and to provide differential diagnosis for liver lesions in a child on the basis of available imaging and clinical data. Imaging is therefore essential for making prompt and accurate diagnosis which further helps in appropriate treatment and optimal patient management.

Acute Hepatitis B or Chronic Hepatitis B with Acute Exacerbation: Differentiating Clinical, Biochemical, Immunonological, and Virological Parameters Ravi Kant Thakur, Sunit Kumar Shukla, Vinod Kumar Dixit, Dawesh Yadav, Piyush Thakur, Tuhin Mitra MAMC Journal of Medical Sciences 2020 6(3):186-193 Background and Aims: Acute hepatitis B virus (HBV) infection and chronic HBV infection presenting as acute illness have differing prognosis. Differentiation between acute viral hepatitis B (AVH-B) and chronic hepatitis B with an acute exacerbation (CHB-AE) is difficult if prior hepatitis B surface antigen (HBsAg) status is unknown. This prospective study was undertaken to screen various factors that could help with this differentiation. Methods: All consecutive patients presenting with AVH-B like illness were enrolled in this study and were evaluated as per predefined study protocol. Patients were divided into AVH-B and CHB-AE groups based on HBsAg status at the end of 6 months. Results: Significant differences in clinical and laboratory parameters were found between AVH-B and CHB-AE. No statistically significant difference in prodromal symptoms and jaundice was seen. Ascites (40%) and hepatic encephalopathy (10%) were seen only in patients with CHB-AE (P = 0.002 and 0.244, respectively). Anti-hepatitis B virus core antigen immunoglobulin M (IgM anti-HBc) levels ≥10.15 signal-cutoff-ratio (S/CO) had positive predictive value (PPV) and negative predictive value (NPV) of 90% for diagnosis of AVH-B. Hepatitis B virus deoxyriboNucleic acid (HBV DNA) levels ≥25032 IU/mLhas 62.5% PPV and 69% NPV for diagnosis of CHB-AE. Alpha-feto protein (AFP) at >22.5 ng/mLmL for diagnosing CHB-AE has PPV and NPV of 83% and 62%, respectively. All six mortalities were seen in CHB-AE group with median survival of 2 months. Conclusions: Differentiation of AVH-B and CHB-AE is important as management and prognosis differ. Low IgM anti-HBc levels (<10.15 S/CO), high HBV DNA levels (≥25032 IU/mLmL), and high AFP (>22.5 ng/mL) favor CHB-AE over AVH-B.

Methods to Handle Incomplete Data Vinny Johny, Mariamma Philip, Swathi Augustine MAMC Journal of Medical Sciences 2020 6(3):194-198 Context: The major question for data analysis is determining the appropriate analytic approach in the presence of incomplete observations. The most common solution to handle missing data in a data set is imputation, where missing values are estimated and filled in. An important problem of imputation is to maintain the statistical significance of the data set. Aim: To compare different imputation techniques − complete case analysis, last observation carried forward (LOCF), mean imputation, hot deck Imputation, regression imputation, and multiple imputation (MI). Settings and Design: The data for the study were collected from a prospective study to find out the predictors of early response to treatment in drug naïve schizophrenia patients from a tertiary care centre, India. Methods and Material: The present study tries to compare four imputation methods: complete case analysis, LOCF, mean imputation, hot deck Imputation, regression imputation and MI, in filling up the missing values of the outcome variable. Statistical analysis used: Paired t test was used to compare the imputation methods. Results: At the fourth week, the positive and negative syndrome scale scores were missing for about a minority of the subjects (41%). Mean imputation differed significantly from LOCF (P = 0.001), regression imputation (P = 0.010) and MI (P = 0.002). LOCF differed significantly from all these methods − regression imputation (P = 0.001), hot deck imputation (P = 0.011) and MI (P = 0.001). Conclusions: LOCF and mean imputation methods are different from other imputation methods, and there is no difference between hot deck imputation, MI, and regression imputation.

Evaluation of Safety and Efficacy of Postpartum Intrauterine Contraceptive Devices (PPIUCD) in Vaginal and Caesarean Section Deliveries: A Hospital Based Study Radha Agarwal, Shubhra Singh MAMC Journal of Medical Sciences 2020 6(3):199-203 Background: Immediate postpartum intrauterine contraceptive device (PPIUCD) is a lucrative postpartum family planning method which provide an effective reversible contraception for women in delivery settings. PPIUCD can be inserted post-placental, intra-caesarean and within 48 hours postpartum. We conducted this study to determine the outcome, satisfaction rate and continuation rate of PPIUCD. Materials and Method: This was a prospective observational study conducted in a tertiary care teaching institute. CuT 380A was inserted within 10 minutes of placental delivery in accepters who fulfilled the Medical Eligibility Criteria and had no contraindications for PPIUCD. They were then followed up for 3 months. A Cohort of 260 vaginal and caesarean deliveries with PPIUCD in situ were studied over seven months period and follow-up results were compared between Vaginal and Caesarean groups. Result: Overall expulsion rate was 8.47%, removal rate was 14.83% and continuation rate was 76.7%. There was no significant difference in removal rate of two groups. Spontaneous expulsion occurred in 8.47% cases and were significantly higher in vaginal insertion group (p value 0.0017). Overall complication rate was low. No case of perforation or accidental pregnancy was reported. Conclusion: PPIUCD is a safe, highly effective, long acting, cost effective method of postpartum contraception, which can be used during institutional delivery visit and eliminates the need for a return visit to start contraception. PPIUCD is a strong weapon in the family planning armory and should be encouraged in both vaginal and caesarean deliveries.

Patients Knowledge of Prescribed Medications and Factors Affecting it in a Tertiary Care, Public, Teaching Hospital in New Delhi, India Vandana Roy, Vandana Tayal, Anirudh Kansal MAMC Journal of Medical Sciences 2020 6(3):204-210 Objectives: To study patients’ knowledge about their prescribed medication and factors affecting it. Patients and Methods: An observational, cross-sectional study was conducted in 500 outpatients in the Medicine department of a tertiary care teaching hospital. The patients were interviewed about prescribed medicines using a structured questionnaire. The average consultation time and average dispensing time was also recorded for 100 interactions each. Results: Among 500 patients interviewed, 55% were females. Hindi was the primary language in 99.6% of the patients and majority of the patients 75.2% could not read English. The mean total score for patients’ medication knowledge was 38.87 ± 10.42 (maximum 60). 95% of participants had ‘Adequate to Good Knowledge’, and 5% had ‘Poor Knowledge’. Only 1.8% of the patients surveyed had complete knowledge of their prescribed medications. Various factors like age > 60 years, female gender, illiteracy, inability to read English, the doctor informing the patient only in writing and the pharmacist not explaining the medication information were associated with lower scores. The average consultation time was 284.6 ± 172.87 seconds and the average dispensing time was 60.45 ± 22.3 seconds. Conclusion: Overall the patients appear to have an adequate basic knowledge of their prescribed medications despite inability to understand the language and less time given for doctor patient pharmacist interaction. Interventions are required to improve health care providers understanding of what is required to educate the patients about the same. This is especially so for patients with risk factors contributing to their low knowledge about prescribed treatment.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Blood Pressure Monitoring

Validation of the single-cuff oscillometric blood pressure monitor InBody BPBIO750 for public spaces according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization Universal Standard Objective The aim of this study was to evaluate the accuracy of the single upper-arm cuff oscillometric blood pressure (BP) monitor InBody BPBIO750 developed for self-measurement by adults in public spaces (kiosk) according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018). Methods Subjects were recruited to fulfil the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. Results A total of 102 subjects were recruited and 85 were analyzed [mean age 56.7 ± 15.4 (SD) years, 40 men, arm circumference 32.3 ± 5.3 cm, range 22–42 cm]. For validation criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 2.2 ± 6.1/−2.2 ± 5.2 mmHg (systolic/diastolic). For criterion 2, the SD of the averaged BP differences between the test device and reference BP per subject was 5.00/4.63 mmHg (systolic/diastolic). Conclusion The InBody BPBIO750 device fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in general population and can be recommended for clinical use in adults. Received 14 September 2020 Accepted 16 November 2020 Correspondence to George S. Stergiou, MD, FRCP, Hypertension Center STRIDE-7, National and Kapodistrian University of Athens, School of Medicine, Third Department of Medicine, Sotiria Hospital, 152 Mesogion Avenue, Athens 11527, Greece, Tel: +30 2107763117; fax: +30 2107719981; e-mail: gstergi@med.uoa.gr Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Association between inter-arm difference in SBP and central blood pressure in a Beijing community cohort Objective The inter-arm SBP difference (IASBPD) can serve as a predictor of cardiovascular disease (CVD). In this study, we aimed to determine the relationship between IASBPD and central blood pressure (CBP). Methods The study cohort comprised of 7842 eligible individuals. Their BPs were assessed simultaneously in both arms using an Omron BP-203RPEIII vascular profiler, and the IASBPD was measured as the absolute difference in these values (absolute value of left minus right). The CBP was noninvasively measured using an Omron HEM-9000AI device. Multivariate regression analysis was used to assess the association between the central SBP (cSBP) and the IASBPD. Results An IASBPD of ≥10 mmHg was positively associated with the cSBP (β = 2.26; 95% confidence interval, 1.04–3.48; P < 0.001). The interaction test showed no significant interactions between the IASBPD and any of the assessed covariates (age group; sex; BMI; smoking status; heart rate group; the presence of hypertension, diabetes, or CVD; and antihypertensive drug use) when the cSBP was used as the outcome in the subgroup analysis. Conclusion The mechanism underlying the ability of the IASBPD to predict CVD may partly involve an increase in the CBP. Received 8 February 2020 Accepted 9 November 2020 Correspondence to Yan Zhang, Division of Cardiology, Peking University First Hospital Dahongluochang Street, Xicheng District, Beijing, 100034, China, Tel: +86 136 2106 2738; fax: +86 10 6613 7748; e-mail: drzhy1108@163.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Relation between nocturnal decline in blood pressure and choroidal thickness: a comparative analysis in dipper vs. non-dipper hypertensive patients Purpose To compare choroidal thickness (ChT) and echocardiographical changes in patients with dipper and non-dipper systemic arterial hypertension (HT). Methods Patients with HT were evaluated in two groups according to the 24-hour ambulatory BP monitoring. Compared to day-time values, those whose night-time SBP decreased ≥10% were defined as dippers, and those whose SBP decreased <10% were defined as non-dippers. Transthoracic echocardiography was conducted in all patients. ChT and central macular thickness were measured with spectral-domain optical coherence tomography. ChT was obtained at the subfoveal, 1500 µm nasal and temporal to the fovea. Results Thirty non-dipper (18 females and 12 males) and 23 dipper (16 females and seven males) hypertensive patients were recruited. Sex distribution and the mean age were similar between the groups (P = 0.472; P = 0.12). Disease duration was longer in the non-dipper group (8 ± 3.39 vs. 4.96 ± 1.19 years, P = 0.001). The non-dipper group had lower ChT in subfoveal and temporal locations (P = 0.02 and 0.03, respectively) and higher left atrial volume index (LAVI) and pulmonary valve maximum flow (PV-max; P < 0.001). The night-time SBP was negatively correlated with ChT (P = 0.048) and positive correlated with LAVI and PV-max (P < 0.05). However those correlations were not significant when were controlled by the possible confounding factors as disease duration, age and gender. Conclusion Non-dipper HT patients may have thinner choroid than dippers due to longer duration of HT and higher ambulatory BP levels. Received 27 May 2020 Accepted 28 October 2020 Correspondence to Sedat Tas, MD, Department of Cardiology Manisa City Hospital, 45040 Manisa, Turkey, Tel: +905052919458; e-mail: sedattas2000@yahoo.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Could aortic arch calcification help in detection of hypertensive retinopathy? Objective Hypertension-induced end-organ damage is one of the important determinants of morbidity and mortality in patients with hypertension. All types of hypertension-induced end-organ damages start with vascular damage. Vascular calcification is a marker of vascular damage and aortic arch calcification (AAC) is one of the easily identifiable types of vascular calcification. We hypothesized that AAC predicts retinopathy in hypertensive patients. Methods Consecutive hypertensive patients without diabetes mellitus were included. Chest radiography in the posterior-anterior was used to assess the presence of AAC. All patients underwent ophthalmologic examination for retinopathy. Results We included 495 hypertensive patients in this study. Of these, 306 (62%) had hypertensive retinopathy. Patients with hypertensive retinopathy had significantly higher prevalence of AAC as compared to the patients without hypertensive retinopathy (88% vs. 22%, P < 0.001). We found a strong and positive correlation between hypertensive retinopathy and AAC grades (r = 639, P < 0.001). Receiver operator characteristics curve analysis yielded a strong predictive ability of AAC for the presence of hypertensive retinopathy [area under curve = 0.814, 95% confidence interval (CI): 0.775–0.853, P < 0.0001]. In multivariate logistic regression analysis, presence of AAC [odds ratio (OR) 13.128; CI: 7.894–21.832] and serum glucose levels (OR 1.020; CI: 1.003–1.037) were strongly and independently associated with hypertensive retinopathy. Conclusion Presence of AAC on chest radiograph is strongly and independently associated with retinopathy in nondiabetic hypertensive patients. This simple, inexpensive and widely available tool may help in early detection of retinopathy in patients with hypertension. Received 22 October 2019 Accepted 8 October 2020 Correspondence to Adem Adar, MD, Department of Cardiology, Karabuk University Faculty of Medicine, Karabuk, Turkey, Tel: +90 507 231 68 78; e-mail: aadar@karabuk.edu.tr Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Abnormal diurnal blood pressure profile and hypertension-mediated organ damage in nondiabetic chronic kidney disease G1-G3b patients Objective Chronic kidney disease (CKD) is associated with high cardiovascular risk. Prevalence of hypertension and hypertension-mediated organ damage (HMOD) increases with CKD progression. Nocturnal blood pressure (BP) is a strong predictor of cardiovascular complications. This cross-sectional study investigated the link between the diurnal BP profile and HMOD in nondiabetic CKD G1-G3b patients. Methods We investigated 109 CKD patients and 41 apparently healthy persons as controls. All subjects underwent 24-ambulatory blood pressure monitoring (ABPM), echocardiography with left ventricular mass index (LVMI) calculation and pulse wave velocity (PWV) measurement. Results Hypertension was present in 84% of CKD patients. SBP-24 and DBP-24, SBP-day and DBP-day did not differ between CKD and controls. Significant differences were found in SBP-night and DBP-night. The nondipping BP profile (SBP-night/SBP-day ratio ≥0.9) was found in 62% of CKD patients and 32% of controls (P < 0.005). Nocturnal hypertension was found in 56% of CKD patients. LVMI was higher in CKD compared to controls, higher in nondipping than dipping CKD patients, and higher in patients with nocturnal hypertension than without nocturnal hypertension. Abnormal left ventricular geometry was found in 72% nondipping and 43% dipping CKD patients. PWV was higher in CKD than in controls, in patients with nocturnal hypertension than without nocturnal hypertension but did not differ between CKD nondippers and dippers. Conclusion The nondipping BP profile and nocturnal hypertension are associated with HMOD in G1-G3b CKD patients. Hence, there is a need for more extensive use of ABPM for individual risk assessment and personalization of antihypertensive treatment in CKD patients. Received 5 May 2020 Accepted 22 September 2020 Correspondence to Paweł Stróżecki, MD, PhD, Department of Transplantology and Surgery, University Hospital No 1, Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland, Tel: +48 525854386; fax: +48 525854450; e-mail: st_pawel@cm.umk.pl Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Association of vitamin D deficiency with arterial stiffness in newly diagnosed hypertension Objective Vitamin D has beneficial effects on vascular endothelial function, blood pressure (BP) and arterial stiffness. Arterial stiffness increases in early-stage hypertensive patients and it is a strong predictor of cardiovascular morbidity and mortality. The purpose of this study was to assess the association between serum 25-hydroxyvitamin D (25-OH D) levels and arterial stiffness in patients with newly diagnosed hypertension. Method Our study included 100 newly diagnosed hypertensive patients (63 male, 37 female and mean age: 51.7 ± 10.3 years) without cardiovascular disease, malignancy, chronic kidney disease and diabetes mellitus. Patients were divided into two groups: vitamin D deficiency group (<20 ng/ml) and normal vitamin D group (≥20 ng/ml). Twenty-four-hour, daytime and nighttime ambulatory BP readings were recorded. Mobil-O-Graph ARC solver algorithm was used to evaluate arterial stiffness parameters of pulse wave velocity (PWV) (m/s), augmentation index normalized with 75/min heart rate (Alx@75). Results Patients with vitamin D deficency had higher values of Alx@75 and PWV values (20.9 ± 9 vs. 16.8 ± 6.9, P = 0.018 and 8.37 ± 1.16 vs. 6.9 ± 0.9, P = 0.001, respectively) despite similar 24-hour ambulatory BP monitoring in both groups. Level of serum calcium was significantly higher in vitamin D deficiency group (9.5 ± 0.23 vs. 9.3 ± 0.12, P = 0.007). Nighttime SBP was higher in vitamin D deficiency group (133.2 ± 14.3 mmHg vs. 126.3 ± 17.2 mmHg; P = 0.03) and also, vitamin D deficiency group had non-dipping SBP pattern compared to normal Vitamin D group (P = 0.013). Conclusion Vitamin D deficiency is associated with increased arterial stiffness in newly diagnosed hypertensive patients in terms of increased PWV and Alx@75 values. Received 20 May 2020 Accepted 28 September 2020 Correspondence to Sinem Cakal, MD, Department of Cardiology, Haseki Training and Research Hospital, Uğur Mumcu, Belediye Sokak No:7, 34265 Sultangazi/İstanbul, Turkey, Tel: +(90) 505 755 17 70; fax: +(90) 212 453 20 00; e-mail: sinemdnz@gmail.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Evaluation of cuff deflation and inflation rates on a deep learning-based automatic blood pressure measurement method: a pilot evaluation study Objective The aim of this study was to evaluate the performance of using a deep learning-based method for measuring SBPs and DBPs and the effects of cuff inflation and deflation rates on the deep learning-based blood pressure (BP) measurement (in comparison with the manual auscultatory method). Methods Forty healthy subjects were recruited. SBP and DBP were measured under four conditions (i.e. standard deflation, fast deflation, slow inflation and fast inflation) using both our newly developed deep learning-based method and the reference manual auscultatory method. The BPs measured under each condition were compared between the two methods. The performance of using the deep learning-based method to measure BP changes was also evaluated. Results There were no significant BP differences between the two methods (P > 0.05), except for the DBPs measured during the slow and fast inflation conditions. By applying the deep learning-based method, SBPs measured from fast deflation, slow inflation and fast inflation decreased significantly by 3.0, 3.5 and 4.7 mmHg (all P < 0.05), respectively, in comparison with the standard deflation condition. Whereas, corresponding DBPs measured from the slow and fast inflation conditions increased significantly by 5.0 and 6.8 mmHg, respectively (both P < 0.05). There were no significant differences in BP changes measured by the two methods in most cases (all P > 0.05, except for DBP change in the slow and fast inflation conditions). Conclusion This study demonstrated that the deep learning-based method can achieve accurate BP measurement under the deflation and inflation conditions with different rates. Received 18 June 2020 Accepted 28 October 2020 Correspondence to Peiyu He, PhD, College of Electronics and Information Engineering, Sichuan University, Chengdu 610064, China, Tel: +8602885463873; e-mail: hpysbsy@163.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Hemodynamic response to heated water immersion in older individuals with hypertension The aim of this study was to evaluate blood pressure (BP), heart rate, arterial stiffness and endothelial reactivity responses to heated water immersion in older individuals with hypertension. Thirty-five sedentary individuals (67 ± 5 years) under treatment for hypertension were randomly assigned to water-based [n = 20; 30 min of seated resting in a heated swimming pool (30–32 ºC)] or land-based group [n = 15; 30 min of seated resting in a quiet room with controlled temperature (21–23 ºC)]. BP, heart rate, arterial stiffness and endothelial reactivity were measured before, immediately after (post) and 45 min after (recovery) each session. Heart rate reduced (P < 0.05) during the land-based session, and the reduction was maintained at post (~7 bpm) and recovery (~9 bpm), but no heart rate changes occurred during and after the water-based session. Systolic/diastolic BP increased (P = <0.001) at post (~29/10 mmHg) and recovery (~10/7 mmHg) in the water-based group, but not in the land-based group. No significant changes in pulse wave velocity and endothelial reactivity occurred in both groups. These results suggest that the hemodynamic response to heated water immersion should be taken into account when assessing the effect of heated water-based exercise on postexercise hypotension in older individuals with hypertension. Received 24 June 2020 Accepted 13 October 2020 Correspondence to Emmanuel Gomes Ciolac, PhD, Faculdade de Ciências, Departamento de Educação Física, Laboratório de Pesquisas em Exercício Físico e Doenças Crônicas, Universidade Estadual Paulista – UNESP, Avenue Engenheiro Luiz Edmundo Carrijo Coube 14-06, Bauru, Brazil,17033-360, Tel: +55 14 3103 9437; fax: +55 14 3103 6082; e-mail: emmanuel.ciolac@unesp.br/Twitter: @ProfessorCiolac Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Validation of the blood pressure measurement technology used in the Novacor Diasys 3 (DIS-0001-00) upper arm device for ambulatory blood pressure measurement, according to the requirements of the AAMI/ANSI/ISO 81060-2: 2013 standard (for both a general study and a cardiac-stress study in adults) and of the European Society of Hypertension International Protocol revision 2010 Objective The objective of this study was to determine the accuracy of the oscillometric blood pressure measurement technology of the Novacor Diasys 3 (model number DIS-0001-00) blood pressure monitor, intended for ambulatory blood pressure measurement, when used with the recommended Standard (ACC-0213-00), Large (ACC-0214-00) and Paediatric (ACC-0215-00) cuffs. Methods The Novacor Diasys 3 (model number DIS-0001-00) was evaluated according to the requirements of the AAMI/ANSI/ISO 81060-2:2013 standard, including an additional cardiac-stress study, a requirement for ambulatory blood pressure measurement devices. It was also validated according to the requirements of the European Society of Hypertension International Protocol revision 2010. The protocol requirements for all thee studies were followed precisely. Results The Novacor Diasys 3 (model number DIS-0001-00) fulfilled all of the requirements for a pass in each of the three studies. In the primary AAMI/ANSI/ISO 81060-2:2013 study, the Criterion 1 errors were +3.9 mmHg ± 2.9 mmHg for SBP and +3.4 ± 2.5 mmHg for DBP. Conclusion The Novacor Diasys 3 (model number DIS-0001-00), when used with the recommended cuffs, can be recommended for ambulatory blood pressure measurement in the adult population. Received 22 June 20209September2020 Accepted 17 September 2020 Correspondence to Neil Atkins, Medaval Ltd., Unit 107, SBC, Serpentine Ave., Ballsbridge, Dublin D04 H522, Ireland, Tel: +353 1 664 3768; e-mail: neil.atkins@medaval.ie Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Prevalence of aberrant blood pressure readings across two automated intraoperative blood pressure monitoring systems among patients undergoing caesarean delivery Objectives Aberrant automated blood pressure (BP) readings during caesarean delivery may lead to disruptions in monitoring. The present study compared the frequency of aberrant BP readings across two types of commercially available BP monitoring systems in use during caesarean delivery. Methods This was a retrospective observational study using two comparable patient cohorts that resulted from simultaneous introduction of two types of monitors into a single obstetric surgical center in which similar patients were treated for the same surgical procedure by the same set of clinicians during the same year. Our primary hypothesis was that aberrant readings were significantly associated with the type of monitor being used for BP measurement, controlling for a variety of relevant covariates as specified in the analytic plan Results A total of 1418 cesarean delivery patients met inclusion criteria. Gaps of at least 6 min in machine-captured BP readings occurred in 159 (21.1%) of cases done in the operating room using a Datex-Ohmeda monitor vs. 183 (27.5%) of cases in the operating rooms using Phillips monitors (P = 0.005). In multivariable logistic regression analysis, the relative odds of the occurrence of monitoring gaps was 35% higher in rooms with the Phillips BP monitors as compared to the Datex-Ohmeda monitor while controlling for pre-specified covariates (odds ratio = 1.35, 95% confidence interval = 1.04–1.74, P = 0.02). Conclusion The present analysis suggests that aberrant BP readings for parturients undergoing caesarean delivery are significantly different between the two types of automated BP monitoring systems used in the operating rooms at our institution. Received 15 July 2020 Accepted 22 September 2020 Correspondence to Robert B. Schonberger, MD MHS, Department of Anesthesiology, Yale School of Medicine, TMP-3, 333 Cedar Street, P.O. Box 208051, New Haven, CT 06520-8051, USA, Tel: +203 785 2802; fax: +203 785 6664; e-mail: robert.schonberger@yale.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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Traditional Chinese Medicine

The effect of hormones of the hypothalamic-pituitary-target gland axes in a kidney-yang deficiency syndrome model Agra Darmawati Ayu, Wen Pan, Zou-Qin Huang, Ling Zhao World Journal of Traditional Chinese Medicine 2020 6(4):363-369 Kidney-yang deficiency syndrome (KYDS) is a diagnostic pattern in the traditional Chinese medicine. Studies have shown that KYDS is related to the functional disorder of hormones of the hypothalamic-pituitary-target gland axes. The standard procedure used to mimic KYDS is the injection of a high dose of exogenous glucocorticoid (hydrocortisone and corticosterone). Such a model showed symptoms such as exhaustion, body twists, cold limbs, lying crowded together, decreased rectal temperature, sexual dysfunction, decreased reaction speed, reduced spontaneous activity, hair loss, loss of appetite, and weight loss. Moreover, the model manifested an imbalance in mutual control among the hormones of the pituitary-target gland axes, including adrenocorticotrophic hormone, CORT, CRH, thyroid-stimulating hormone, triiodothyronine, thyroxine, T, E2, follicle-stimulating hormone, luteinizing hormone, and 17-OHCS.

Chinese herbal medicine for the treatment of human immunodeficiency virus/acquired immune deficiency syndrome-associated diarrhea: A protocol for the systematic review and meta-analysis of randomized clinical trials Bai-Lin Chen, Ming-Zhu Zhang, Zi-Wei Huang, Hong-Rui Zhang, Chang Xu, Jing Li, Zhen-Wei Liu, Feng Jiang, Xun Li, Nicola Robinson, Jian-Ping Liu World Journal of Traditional Chinese Medicine 2020 6(4):370-376 Diarrhea can occur at an early or advanced stage of acquired immunodeficiency syndrome (AIDS) as a usual symptom in people with human immunodeficiency virus (HIV) infection. While it is usually not fatal, it can influence patients' quality of life seriously. It has shown to be efficacious and improves people's immune status to a certain extent to treat HIV/AIDS-related diarrhea on the basis of syndrome differentiation and treatment or Chinese herbs plus conventional treatment. Therefore, it may have a good application potential. Here, we outline a protocol for the systematic review of this health-care intervention, with the aim to evaluate the beneficial effects and safety of Traditional Chinese Medicine (TCM) for patients who suffer from HIV/AIDS-associated diarrhea. Randomized controlled trials that compare Chinese herbs with placebo or other effective treatments will be searched and included, in spite of publication status or language. The primary outcomes include diarrhea frequency and fecal character. The databases we will search as follows: China Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (SinoMed), Wanfang Data, China National Knowledge Infrastructure, PubMed and the CENTRAL in Cochrane Library. Two authors will respectively conduct the screening of trials, data extraction, and use the Cochrane risk of bias tool to assess the methodological quality. We will analyze the data and perform a meta-analysis if possible. We intend to identify potential therapeutic modalities that may be of benefit to inform clinical practice by supplying existing evidence of the helpful effects and safety of TCM to treat patients suffering from HIV/AIDS-associated diarrhea.

Exosome is an important novel way of acupuncture information transmission Ning-Cen Li, Ming-Yue Li, Zhong-Xi Lu, Mu-Yang Li, Xue-Mao Zhuo, Yong Chen, Ting-Ting Wang, Li-Ying Xing, Mei-Juan Wang, Kai Shan, Ze-Lin Chen, Calista Hui-Min Lim, Bo Chen, Yi Guo World Journal of Traditional Chinese Medicine 2020 6(4):377-383 As a physical stimulation of the body surface, the process of transmitting acupuncture information from acupoints to target organs through meridians and collaterals is complex, and network regulation is the most basic mode of acupuncture. Exosomes are membrane vesicles formed by various types of cells and secreted to the extracellular matrix through a series of regulation. We speculate that exosomes and their carriers, as important carriers of communication among neurons, endocrine cells, and immune cells, may play an important role in the process of acupuncture information transmission. Exosome in the acupoint area is an important interactive form of transformation from physical information to chemical information. Circulating exosome is an important means of delivery for acupuncture to play an important role in the network regulation. The structure and information molecules of exosomes are the important material bases for acupuncture effect. Through experimental research, it was found that acupuncture can regulate the release of exosome and may have a certain relationship with acupuncture effect. Therefore, exosome may play an important role in the process of acupuncture information transmission, which is an important new way of acupuncture information transmission.

Neuroendocrine-immune regulating mechanisms for the anti-inflammatory and analgesic actions of acupuncture Zhi-Fang Xu, Shou-Hai Hong, Shen-Jun Wang, Xue Zhao, Yang-Yang Liu, Sha-Sha Ding, Yuan Xu, Kuo Zhang, Nan-Nan Yu, Zhong-Xi Lu, Fu-Ming Yang, Yi-Nan Gong, Qin-Qin He, Kun Yu, Yi-Ping Zhang, Bao-Min Dou, Lin Yao, Ya-Wen Yan, Tao Yang, Yan-Fang Zhang, Bao-Hu Liu, Yong-Ming Guo, Hsuah-Nee-Connie Wong, Yi Guo World Journal of Traditional Chinese Medicine 2020 6(4):384-392 Pain and inflammatory diseases are important clinical indications of acupuncture, which have been widely accepted in the international community. Previous studies have been focusing on rapid analgesia of acupuncture through the regulation of nervous system, but few studies on the inflammation regulatory mechanisms in which acupuncture inhibits the peripheral sensitization-induced pain. Based on studies concerning acupoint mechanisms of acupuncture actions and related researches on acupuncture regulating neuroendocrine and immune systems, we put forward the scientific hypothesis that acupuncture regulates neuroendocrine-immune (NEI) network and key response media therein, so as to achieve anti-inflammatory and analgesic effects in target organs. We have established a platform for acupuncture at ST36 to alleviate inflammatory pain in adjuvant induced arthritic rats. Based on the complex network analysis of multi-dimensional data from multi-time point and multi-site detection of NEI common signaling molecules, we have clarified the regulatory effects of acupuncture on NEI network and corresponding downstream immune network. Results indicated that monocytes/macrophages are the key targeting cells of acupuncture regulation, and acupuncture may display the anti-inflammatory and analgesic effects by regulating polarization of T cells in lymph nodes and polarization of M1/M2 macrophages in inflamed joints/paws. In addition, we have spotted a key molecule for acupuncture analgesia, CXCL1, as well as clarified the novel central analgesic mechanism of acupuncture mediated by CXCL1/CXCR2 desensitization. Thereby, we have provided novel evidence of the anti-inflammatory and analgesic actions of acupuncture through regulating NEI network and several key substances, highlighting a systemic research paradigm for investigating mechanisms of acupuncture actions.

Medicinal plant of Bletilla striata: A review of its chemical constituents, pharmacological activities, and quality control Sai Jiang, Meng-Yun Wang, Han-Wen Yuan, Qian Xie, Yang Liu, Bo-Shu Li, Yu-Qing Jian, Chang-Xiao Liu, Hua-Yong Lou, Atta-Ur-Rahman , Wei-Dong Pan, Wei Wang World Journal of Traditional Chinese Medicine 2020 6(4):393-407 Bletilla striata belongs to the family Orchidaceae, and it is mainly distributed in East Asia. The tubers of B. striata have been utilized in Traditional Chinese Medicine for various ailments, such as hematemesis, tuberculosis, malignant ulcers, hemorrhoids, traumatic bleeding, and chapped skin. Phytochemical investigation on B. striata has resulted in the identification of 192 monomeric compounds, including bibenzyls, phenanthrene derivatives, triterpenoids and its saponins, steroids and its saponins, malic acid derivatives, and anthocyanins. Moreover, B. striata polysaccharide is another typical chemical constituent of this plant. Pharmacology studies have shown that the plant possesses wound healing, antimicrobial, anticancer, antioxidative, and antiviral activities. This review aims to provide the latest and comprehensive information on chemical constituents, pharmacological activities, and quality control of B. striata and to identify future research needs.

The fruits of Xanthium sibiricum Patr: A review on phytochemistry, pharmacological activities, and toxicity Hai Jiang, Xue-jiao Wang, Liu Yang, Jia-Xu Zhang, A-Jiao Hou, Wen-Jing Man, Song Wang, Bing-You Yang, Kelvin Chan, Qiu-Hong Wang, Hai-Xue Kuang World Journal of Traditional Chinese Medicine 2020 6(4):408-422 In recent years, drug development and research have gradually shifted from chemical synthesis to biopharmaceutical and natural drugs. Natural medicines, such as traditional Chinese medicine, have been among the first studied because of their long medicinal history, simplicity, and the relatively low cost of research. Among them, Xanthii Fructus (XF) is famous for the treatment of sinusitis. In this article, the achievements of research on XF from 1953 to 2020 are systematically reviewed, focusing on the aspects of chemical constituents, pharmacological effects, clinical applications, toxicity and side effects, and processing methods. To date, there have been significant advances in both the phytochemistry and pharmacology of XF. Some traditional uses have been validated and clarified in modern pharmacological studies. However, its mechanism of action in the treatment of allergic diseases has not been satisfactorily explained. Further in vitro and in vivo studies are required to rationally develop new drugs and to elucidate the therapeutic potential of XF. A comprehensive evaluation of XF and an understanding of network pharmacology are also needed.

Research progress on processing and processing methods in Salvia miltiorrhiza production areas Qin-Rong Liu, Li-Na Zhao, Yi-Shuo Wang, Yong-Guang Han, Zhen-Ling Zhang, Yu-Quan Wu World Journal of Traditional Chinese Medicine 2020 6(4):423-431 Salvia miltiorrhiza is one of the 40 most commonly used traditional Chinese medicinal materials in clinics. It is effective in activating blood circulation, removing blood stasis, relieving pain through the meridian, clearing the heart and removing irritations, and cooling blood and eliminating blemishes. Each main production area has developed a unique production method and processing technology, in accordance with local conditions. The processed products included in Chinese Pharmacopoeia are purified and wine-fried S. miltiorrhiza. In addition, the Chinese province's standards include the vinegar-fried and wine-fried types. S. miltiorrhiza is produced in more areas and is more extensively processed, with large variations in specifications. The challenge in establishing a uniform quality standard affects the clinical application of decoction pieces. This review has explored the books of the past dynasties, summarized the relevant literature published in the past three decades, discussed the processing methods of S. miltiorrhiza, and provided a basis for further research on the processing method of the original sample. In particular, we integrate fresh cut processing as the starting point for in-depth research, discuss the processing technology specifications, and formulate quality product standards.

Ginsenoside 3β-O-Glc-DM (C3DM) enhances the antitumor activity of Taxol on Lewis lung cancer by targeting the interleukin-6/Jak2/STAT3 and interleukin-6/AKT signaling pathways Mei Tang, Lu-Lu Huang, Qian-Qian Du, Chen Yan, An-Di Gu, Jin-Ling Yang, Yan Li World Journal of Traditional Chinese Medicine 2020 6(4):432-440 Objective: Nonsmall-cell lung cancer (NSCLC) is an aggressive, highly chemoresistant disease. Taxol is an effective chemotherapeutic drug widely used for the treatment of NSCLC. However, the clinical use of Taxol is limited due to the occurrence of adverse side effects under high therapeutic doses. Therefore, it is desirable to explore combination therapy to reduce the dose of chemotherapeutic drugs and achieve excellent outcomes. A biosynthetic ginsenoside, 3-O-β-D-glucopyranosyl-dammar-24-ene-3β, 20S-diol (3β-O-Glc-DM, C3DM) is obtained from microbial fermentation by metabolic engineering. Based on previous study findings, we aimed to explore the mechanism of combination therapy with C3DM and Taxol and its increasing antitumor effect on Lewis lung cancer (LLC) in this study. Materials and Methods: A thiazolyl blue tetrazolium bromide (MTT) assay was performed to evaluate cell viability; the apoptotic effect was studied using cell apoptosis assay. The Lewis tumor xenograft experiment was performed to determine the effects of C3DM combined with Taxol on tumor growth in vivo, and western blotting was performed to analyze protein expressions. Results: C3DM effectively inhibited the proliferation of NSCLC cells. Moreover, C3DM increased the antiproliferative activity of Taxol and significantly enhanced cell apoptosis induced by Taxol in Lewis lung cancer cells. C3DM alone also suppressed Lewis tumor growth and enhanced the antitumor activity of Taxol in vivo. Western blot analysis revealed that the effects of the antiproliferation and apoptosis induction of C3DM treatment alone or in combination with Taxol on Lewis lung cancer were mediated by inhibiting the interleukin-6 (IL-6)/Jak2/STAT3 and IL-6/AKT signaling pathways. Conclusions: The results showed that C3DM has the potential to be used in combination therapy with Taxol against NSCLC.

Risk factors associated with recurrence within 90 days of ischemic stroke onset in chinese medicine hospital: A national cross-sectional study in China Yang Gao, Yan-Ming Xie, Ye-Feng Cai, Xiao-Ming Shen, De-Xi Zhao, Ying-Zhen Xie, Yin Zhang, Gui-Qian Wang, Xu Wei, Rui-Li Wei World Journal of Traditional Chinese Medicine 2020 6(4):441-447 Objective: The short- and long-term risk factors for stroke recurrence may be different. This study is aimed to determine the risk factors for recurrence within 90 days in patients with ischemic stroke in China. Method: This was cross-sectional registry-based study in Chinese medicine hospitals from eight provinces and ten cities in China between November 3, 2016 and May 28, 2018. Two thousand one hundred and twenty patients with ischemic stroke aged between 35 and 80 years. Stroke recurrence was defined as an outcome indicator. Computed tomography/magnetic resonance imaging was used as a diagnostic tool for stroke recurrence. Patients' age, sex, height, weight, body mass index (BMI), education level, medical history, family history, smoking, and drinking were recorded. Routine laboratory examinations were performed. Associated factors were investigated by calculating the odds ratio (OR) using logistic regression modeling. Results: In all, 2120 patients were included in the study, 712 (33.6%) of whom were women and 1408 (66.4%) were men, with a mean age of 62.84 ± 9.35 years. Eighty-two patients experienced stroke recurrence within 90 days, and the accumulative recurrence rates of stroke were 3.9% (95% confidence interval [CI], 3.0%–4.7%). The binary logistic analysis showed that previous history of one (OR = 8.113; 95% CI, 4.497–14.637), two (OR = 8.848; 95% CI, 4.025–9.449), or ≥3 ischemic strokes (OR = 24.599; 95% CI, 9.307–65.018), and BMI <18.5 kg/m2 (OR = 2.842; 95% CI, 1.000–8.075) were independently associated with stroke recurrence within 90 days. Conclusions: The accumulative recurrence rate of ischemic stroke was 3.9% within 90 days. Number of previous history of ischemic stroke and BMI <18.5 kg/m2 were independent risk factors for stroke recurrence. Medical history and solar terms of ischemic stroke were not found to be associated with stroke recurrence within 90 days. Effective secondary prevention for patients with a previous history of ischemic stroke is urgently needed to address this stroke recurrence burden.

Electroacupuncture alleviates neuropathic pain by modulating Th2 infiltration and inhibiting microglial activation in the spinal cord of rats with spared nerve injury Bin Liu, Wei Long, Ru-Rong Wang World Journal of Traditional Chinese Medicine 2020 6(4):448-455 Objective: The objective is to explore the potential mechanisms mediating the analgesic effect of electroacupuncture (EA) for neuropathic pain. Materials and Methods: Sprague-Dawley (SD) rats were used to establish a spared nerve injury (SNI) model of neuropathic pain. The intensity of neuropathic pain was measured by assessing the mechanical withdrawal threshold and thermal withdrawal latency. Immunofluorescent analysis and western blotting were performed to evaluate the activation of microglia and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling in the L4-6 spinal cord of SD rats. The infiltration of Th2 and expression of interleukin-10 (IL-10) in the L4-6 spine were analyzed by flow cytometry and enzyme-linked immunosorbent assay. Results: Behavioral test results demonstrated that SNI-induced hyperalgesia was significantly ameliorated by EA stimulation at “Zusanli” (ST36) and “Yanglingquan” (GB34) points. In addition, EA therapy significantly suppressed microglia activation and phosphorylation of JAK2/STAT3 in the L4-6 spine of rats with SNI. Moreover, EA promoted the infiltration of Th2 and secretion of IL-10 in the L4-6 spine of rats with SNI. Conclusions: The study findings indicate that EA stimulation mediated the infiltration of Th2 in the spinal cord of rats with SNI. In addition, EA inhibited microglial activation in the L4-6 spine of rats with SNI.

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December 16, 2020 Listen to the latest Radiology: AI podcast. Paul Yi interviews Eliot Siegel on the past, present, and future of radiology AI. Latest Articles Original Research   Radiomics Repeatability Pitfalls in a Scan-Rescan MRI Study of Glioblastoma   Radiomic feature extraction from MRI can be highly variable, and although preprocessing can improve the repeatability of these features, there is a lack of consistency in performance improvement across feature types and sequences; identification of repeatable and informative features should be a prerequisite in radiomics studies.   Katharina V. Hoebel, Jay B. Patel…Jayashree Kalpathy-Cramer Commentary: The Pursuit of Generalizability to Enable Clinical Translation of Radiomics Pallavi Tiwari, Ruchika Verma Just Accepted An early version of our most recently accepted research Original Research   Combining Initial Radiographs and Clinical Variables Improves Deep Learning Prognostication of Patients with COVID-19 from the Emergency Department Young Joon (Fred) Kwon, Danielle Toussie…Anthony B. Costa Publish Your Work in an RSNA Journal RSNA.org | RSNA News™ | RSNA Journals | Contact Us   © 2020 Radiological Society of North America | 820 Jorie Blvd., Suite 200 | Oak Brook, IL 60523-2251 TEL U.S. & Canada: 1-888-600-0064 | TEL Outside U.S. & Canada: 1-630-590-7770 Privacy Policy | View Web Version To update your e-mail preferences, click here.

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