1.Transplacental digoxin treatment for fetal supraventricular arrhythmias: Insights from Chinese fetuses.
Chuan WANG ; Li ZHAO ; Shuran SHAO ; Haiyan YU ; Shu ZHOU ; Yifei LI ; Qi ZHU ; Xiaoliang LIU ; Hongyu DUAN ; Hanmin LIU ; Yimin HUA ; Kaiyu ZHOU
Chinese Medical Journal 2025;138(12):1499-1501
2.Impact of the LAmbre device on left atrial appendage adjacent structures and left atrium
Zhengdan GE ; Dehong KONG ; Zhenyi GE ; Chunqiang HU ; Xiaochun ZHANG ; Haiyan CHEN ; Daxin ZHOU ; Xianhong SHU ; Cuizhen PAN
Chinese Journal of Ultrasonography 2024;33(2):142-150
Objective:To explore the effects of the LAmbre device and mitral annulus(MA), as well as left atrium(LA) in patients with non-valvular atrial fibrillation(NVAF) after left atrial appendage closure (LAAC) using real-time-three-dimensional transesophageal echocardiography (3D TEE).Methods:Fity-six consecutive patients who underwent LAAC with the LAmbre device in Zhongshan Hospital of Fudan University from June 2019 to March 2023 were retrospectively enrolled, with no or less than moderate mitral regurgitation (MR). All patients underwent pre-operative and follow-up two-and three-dimensional transesophageal echocardiography (2D TEE, 3D TEE) at 60 days after the operation. The quantitative parameters of MA and LA were obtained by offline analysis using QLab 13.0 (Philips Healthcare, Andover, MA). Importantly, mitral annular measurements were made at seven time points throughout the cardiac cycle: early diastole, mid-diastole, late diastole, mitral valve closure, early systole, mid-systole, and late systole, which facilitates constructing the dynamic model of MA to assess the annular morphology and dynamics.Results:The values of AP diameter (APD), AL-PM diameter (ALPMD), 3D annulus circumference (3DAC), 3D annulus area (3DAA) decreased significantly compared with pre-operative values at all time points of the cardiac cycle (all P<0.05), while non-planar angle (NPA) and AH/CD were not apparently changed (all P>0.05 ). Throughout the cardiac cycle, MA showed regular changes, gradually increased in systole with the saddle shape deepened, and gradually decreased in diastole with the saddle shape shallowed.During systole, there was an increase in the rate of change of AP in MA [pre-operative (3.01±2.64)%, post-operative (3.81±3.51)%, P=0.037] after LAAC, with no significant difference in the rate of change of ALPM, 3DAC, and 3DAA.Meanwhile, we observed an evident reduction in LA minimal volume (LAVmin) [pre-operative (78.36±25.16)ml, post-operative (70.73±22.78)ml, P=0.004] and an obvious increase in LA ejection function [pre-operative (22.88±10.09)%, post-operative (31.41±12.28)%, P<0.05] during follow-up. Conclusions:3D TEE can accurately assess the impact of LAAC on the MA and LA. The LAmbre device can affect the morphology of MA, as well as the structure and function of LA, while the change of the dynamics of MA is not so prominent.
3.Value of non-invasive left ventricular myocardial work in the diagnosis of myocardial ischemia in coronary heart disease
Yingjie ZHAO ; Furong HE ; Wei HE ; Weifeng GUO ; Shihai ZHAO ; Zhenyi GE ; Zhifeng YAO ; Haiyan CHEN ; Cuizhen PAN ; Xianhong SHU
Chinese Journal of Clinical Medicine 2024;31(3):411-419
Objective To evaluate the diagnostic value of myocardial work related parameters in coronary ischemia patients with coronary artery disease(CAD)coronary ischemia using non-invasive left ventricular pressure strain loop(PSL),taking fraction flow reservation(FFR)as the gold standard.Methods From December 2020 to December 2021,53 clinically suspected CAD patients were prospectively enrolled.All patients underwent echocardiography,invasive coronary angiography and FFR measurement.According to the results of coronary angiography,patients were divided into myocardial ischemia group(n=24,FFR≤0.80)and non-myocardial ischemia group(n=29,FFR>0.80).PSL was used for off-line analysis to obtain the global work index(GWI),global constructive work(GCW),global wasted work(GWW),global work efficiency(GWE),global positive work(GPW),and global systolic constructive work(GSCW)and other myocardial work parameters.The differences of parameter values between the two groups were compared.The diagnostic efficacy of work parameters in myocardial ischemia was analyzed by ROC curve.Results Compared with the non-myocardial ischemia group,GWI,GCW,GPW and GSCW were significantly decreased in the myocardial ischemia group at the 18-,16-,and 12-segment levels(P<0.001).The ROC curve showed that the AUC results of GWI,GCW,GPW,GSCW at the 18-segment level were 0.803(95%CI 0.679-0.927),0.807(95%CI 0.687-0.928),0.822(95%CI 0.708-0.936),0.819(95%CI 0.703-0.935).The optimal cut-off value of GWI was 1 676.3 mmHg%,and the sensitivity,specificity and accuracy of predicting myocardial ischemia were 70.8%,86.2%and 79.2%,respectively.The optimal cut-off value of GCW was 1 999.4 mmHg%,and the sensitivity,specificity and accuracy of predicting myocardial ischemia were 75.0%,82.8%and 79.2%,respectively.Conclusions Analyzing myocardial work using PSL has good significance for screening suspected myocardial ischemia in CAD patients.
4.Echocardiography evaluation of myocardial strain and ventricular dyssynchrony after implantation of leadless pacemaker Micra AV
Zibire FULATI ; Ziqing YU ; Wen LIU ; Haiyan CHEN ; Xianhong SHU
Chinese Journal of Clinical Medicine 2024;31(5):705-711
Objective To explore the left and right ventricular myocardial strain and dyssynchrony in patients with Micra AV leadless pacing implantation,and to further analyze the impact of implantation site on myocardial strain and dyssynchrony.Methods A retrospective study was conducted on 43 patients with Micra AV implantation and 20 patients with high-degree atrioventricular block(Ⅱdegree typeⅡandⅢdegree atrioventricular block)at the Department of Cardiology,Zhongshan Hospital from April 2023 to December 2023.The demographic information and clinical characteristics of the patients were collected.Echocardiography and speckle tracking imaging techniques were used to obtain conventional echocardiographic parameters,myocardial strain,and dyssynchrony indices of patients in the two groups,including global longitudinal strain(GLS),free wall longitudinal strain(FWLS),peak strain dispersion(PSD)of 18 left ventricular segments,PSD of 6 right ventricular segments,and other indices.According to the implantation location of Micra AV,the patients were further divided into middle group(right ventricular septum),high group(right ventricular inflow tract),and low group(apical region),and the differences in myocardial strain and dyssynchrony indices among the three subgroups were compared.Results The left ventricular GLS(LVGLS),right ventricular GLS(RVGLS),and right ventricular FWLS(RVFWLS)of the Micra AV group were significantly lower than those of the conduction block group(P<0.001),and the right ventricular dyssynchrony of the Micra AV group was significantly higher than that of the conduction block group(P<0.05).Comparison of myocardial strain and dyssynchrony at different implantation sites showed that the LVGLS of the high implantation group was significantly higher than that of the middle and low implantation groups,and the left ventricular dyssynchrony index Yu was significantly lower than that of the middle group(P<0.05);the right ventricular ejection fraction(RVEF)of the low implantation group was significantly lower than that of the high group,and the right ventricular 6-segment PSD was significantly higher than that of the middle and high implantation groups(P<0.05).Conclusions Compared with patients with high-degree atrioventricular block,patients with Micra AV leadless pacing have reduced left and right ventricular strain,and the implantation of low position had greater effect.
5.Speckle tracking imaging technique evaluates the impact of combined immune checkpoint inhibitors,trastuzumab,and chemotherapy on cardiac function in patients with advanced HER2-positive gastric adenocarcinoma
Fulati ZIBIRE ; Wen LIU ; Haiyan CHEN ; Yan WANG ; Xianhong SHU ; Leilei CHENG
Chinese Journal of Clinical Medicine 2024;31(4):537-543
Objective To evaluate the effects of combining immune checkpoint inhibitors,trastuzumab,and chemotherapy on the left and right ventricular function in patients with advanced gastric adenocarcinoma expressing human epidermal growth factor receptor 2(HER2).Methods 25 patients with advanced HER2-positive gastric adenocarcinoma who received HER2-ASTRUM therapy(sruili monoclonal antibody combined with trastuzumab and DOS regimen)underwent echocardiographic examinations at baseline(T1),after completion of 4 cycles(T2),and 6 cycles(T3)of chemotherapy.Left ventricular strain,left ventricular myocardial work,right ventricular strain,and ejection fraction were further analyzed.Results Compared with T1,both T2 and T3 showed a decrease in left ventricular ejection fraction(LVEF),(T1,T2,and T3 were[67.3±2.7]%,[63.0±2.9]%and[61.3±3.2]%,P<0.05).T3 showed a decrease in right ventricular ejection fraction(RVEF),([59.3±7.8]%vs[43.7±6.6]%,P<0.05),while T2 showed no significant change in RVEF.Both right ventricular global longitudinal strain(RVGLS),(T1,T2,and T3 were[-25.7±5.7]%,[-22.4±5.3]%and[-19.1±3.6]%,respectively;P<0.05)and right ventricular free-wall longitudinal strain(RVFWLS),(T1,T2,and T3 were[-20.9±4.7]%,[-18.9±4.1]%and[-16.1±3.9]%,P<0.05)decreased in all three time points.The global work index(GWI)was lower in T2 and T3 than in T1(P<0.05),while the global constructive work(GCW),global wasted work(GWW),and global work efficiency(GWE)did not show significant changes.Conclusions Combination of trastuzumab,immune checkpoint inhibitors,and chemotherapy has an impact on left ventricular strain,LVEF,and right ventricular strain,as well as GWI,in HER2-positive patients with gastric adenocarcinoma.Left ventricular global longitudinal strain(LVGLS),RVFWLS,and RVGLS can more sensitively monitor cardiac function and detect cardiac dysfunction related to cancer treatment in a timely manner.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Value of evaluating segmental myocardial work heterogeneity in the prediction of cardiac resynchronization therapy response
Mengruo ZHU ; Yanan WANG ; Yufei CHENG ; Haiyan CHEN ; Xianhong SHU
Chinese Journal of Ultrasonography 2024;33(6):468-474
Objective:To explore the value of myocardial work difference between left ventricular lateral wall and septum at baseline in the prediction of cardiac resynchronization therapy (CRT) response and compare their predictive performance with conventional echocardiographic parameters.Methods:One hundred and six heart failure patients who were retrospectively recruited from January 2021 to January 2023, underwent speckle tracking echocardiography before CRT and at 6-month follow-up.Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), as well as segmental myocardial work index (MWI), constructive work (CW), wasted work (WW) and myocardial work efficiency (MWE), were acquired from non-invasive left ventricular pressure-strain loops before CRT. The differences of all myocardial work indices between left ventricular lateral wall and septum (L-S) at the mid-ventricular level, namely, L-S MWI, L-S CW, L-S WW and L-S MWE were calculated. Response to CRT was defined as left ventricular end-systolic volume reduction ≥15% at 6-month follow-up.Results:CRT response was present in seventy-eight (74%, 78/105) patients. ①At baseline, responders exhibited significantly higher GWI and GCW than non-responders (both P<0.05). ②Besides, L-S MWI, L-S CW, L-S WW and L-S MWE were significant higher in CRT responders than in non-responders at baseline (all P<0.01). ③In multivariate regression analysis, baseline LV end-diastolic volume (LVEDV) ( OR=0.993, 95% CI=0.987-0.999, P=0.020), interventricular mechanical delay (IVMD) ( OR=1.025, 95% CI=1.001-1.050, P=0.040) and L-S MWI ( OR=1.002, 95% CI=1.001-1.003, P=0.001) were identified as independent predictors of CRT response. ④ROC analysis demonstrated that L-S MWI (AUC=0.830, P<0.001) was the most powerful predictor of CRT response and was superior to LVEDV (AUC=0.718, P<0.01) and IVMD (AUC=0.704, P=0.001). ⑤L-S MWI >884 mmHg% was recommended to predict CRT response with the optimal sensitivity of 76% and specificity of 86%. Conclusions:The noninvasive evaluation of myocardial work heterogeneity between left ventricular lateral wall and septum is more valuable than conventional parameters in predicting CRT response and guiding patient selection before CRT, which helps to further improve CRT response rate.
8.Dose-adjusted concentrations of Posaconazole oral suspension in hematopoietic stem cell transplantation patients and analysis of the influential factors
Lin DONG ; Yishuo SHU ; Zhonghua DONG ; Qiaoyan YI ; Hongjuan LI ; Yan GU ; Yan HAN ; Guoyu DING ; Yuqi ZHAO ; Xiaoyue ZHANG ; Xue LI ; Ziyun LIN ; Kai MU ; Yilei YANG ; Haiyan SHI ; Hongmei WANG
China Pharmacy 2023;34(24):3025-3029
OBJECTIVE To analyze the dose-adjusted concentrations of Posaconazole oral suspension in patients undergoing hematopoietic stem cell transplantation (HSCT) and their influential factors. METHODS Data were collected from hospitalized HSCT patients admitted to the First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital) from January 2021 to April whtwhm@yeah.net 2023 who took Posaconazole oral suspension for the prevention of invasive fungal disease (IFD) and received blood concentration of posaconazole. The rate of concentration attainment and clinical failure rate of posaconazole for the prevention of IFD were evaluated, and one-way and multiple linear regression analyses were performed for the influential factors of dose-adjusted concentrations (C0/D) of posaconazole. RESULTS A total of 44 patients were enrolled; the mean C0 of posaconazole in patients was (0.99±0.94) µg/mL, and 20 patients had a C0≥0.7 μg/mL, with a concentration attainment rate of 45.45% for the prevention of IFD; 13 cases were clinical failures, with a clinical failure rate of 29.55%. Of 24 patients who did not achieve C0/D of posaconazole for IFD prophylaxis, one patient was a clinical failure despite timely dose adjustment of posaconazole in seven patients; seven of the thirteen patients who did not undergo dose adjustment were clinical failures; and the remaining four patients were switched to other antifungal agents. The results of univariate analysis showed that gender, body mass index (BMI), renal function, combined use of sodium phenytoin, omeprazole and metoclopramide had a significant effect on the C0/D of posaconazole (P<0.05); the results of multivariate linear regression analysis showed that gender, BMI and combined use of sodium phenytoin were the independent factors affecting the C0/D of posaconazole (P<0.05). CONCLUSIONS Significant individual differences are reflected in the blood concentration of Posaconazole oral suspension; gender, BMI and combined use of sodium phenytoin are independent factors affecting the C0/D of posaconazole.
9.Standard for monitoring and evaluation of two-dimensional- and three-dimensional-transesophageal echocardiography during transcatheter tricuspid valve replacement
Cuizhen PAN ; Wei LI ; Daxin ZHOU ; Yuan ZHANG ; Wenzhi PAN ; Shasha CHEN ; Jing SHI ; Haiyan CHEN ; Dehong KONG ; Yu LIU ; Zhenyi GE ; Chunqiang HU ; Kefang GUO ; Xianhong SHU ; Junbo GE
Chinese Journal of Ultrasonography 2023;32(5):449-454
Transcatheter tricuspid valve intervention is the new frontier of interventional cardiology. The LuX-Valve is a radial force-independent orthotopic tricuspid valve replacement device developed in China. The LuX-Valve Plus transcatheter tricuspid valve replacement (TTVR) system is changed from the trans-atrial to the transjugular approach, which further reduces trauma and pulmonary complications compared with the first generation LuX-Valve. The first-in-human study has been completed at Zhongshan Hospital, Fudan University and an exploratory multicentre clinical study is underway. Echocardiography plays an important role in pre-TTVR screening, intraoperative guidance and postoperative evaluation and follow-up, especially two-dimensional transoesophageal echocardiography (2D-TEE) and three-dimensional transoesophageal echocardiography (3D-TEE). However, there is a lack of appropriate intraoperative guidance and assessment protocols. In this study, we briefly described the protocols and imaging considerations for intraoperative 2D-TEE and 3D-TEE to ensure the successful implantation of TTVR.
10.Effects of Black Raspberry Supplementation on Methylation Pathways in Vav-cre Asxl1 fl/fl Tet2 fl/fl Double Knockout Mice with Early-stage Myelodysplastic Syndrome
Athena DONG ; Yi-Wen HUANG ; Ben NIU ; Ruiling LIU ; Weijie WU ; Haiyan GAO ; Jianhua YU ; Li-Shu WANG
Journal of Cancer Prevention 2023;28(4):212-218
Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl ), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

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