tbuckley/cabot-search huggingface dataset:
Abstract 449: The H2 Domain in the Connexin43 Carboxyl Terminus Regulates Cardioprotection From Ischemia Reperfusion Injury
Authors: JIngbo Jiang, Joseph A Palatinus, Huamei He, Jegan Lyyathurai, L Jane Jourdan, Daniel Hoagland, Geert Bultynck, Zhen Wang, Kevin Schey, Steven Poelzing, Francis X McGowan, Robert G Gourdie
Journal: Circulation Research (2017)

Cardiac ischemia-reperfusion (IR) injury occurs in patients with acute coronary syndromes undergoing percutaneous intervention to re-establish blood flow in blocked or narrowed arteries. Presently, there are no therapies approved to prevent the loss of heart muscle, scar tissue formation and contractile dysfunction that result from IR injury. We have previously reported that α CT1, a Connexin 43 (Cx43) mimetic peptide currently in Phase III testing in humans (GAIT1; NCT02667327) as a therapy for chronic skin wounds (PMID:27856288; 25072595), improves contractile function of mouse hearts following injury in association with increases in PKCε-mediated phosphorylation of Cx43 at serine 368 (S368) (PMID: 21273554). Here, we report that induction of S368 phosphorylation and cardioprotection from IR injury by α CT1 involves direct protein-protein interaction of α CT1 with a short alpha-helical sequence within the Cx43 carboxyl terminus (CT) termed the H2 domain. The interacting protein domains involved in Cx43 S368 phosphorylation were identified and validated by a combination of techniques including tandem mass spectroscopy, surface plasmon resonance, immunoprecipitation and thermal shift assays. These studies indicated that α CT1 induced S368 phosphorylation (pS368) via a novel mechanism involving interaction between a pair of positively charged lysines (K344, K345) in the Cx43 CT H2 domain and a cluster of negatively charged amino acids i α CT1. It is further shown that the known ability of α CT1 to interact with Zonula Occludens-1 (ZO-1), has no direct role in either the induction of S368 phosphorylation or protection from IR injury. Finally, we identify a small, novel variant of α CT1 ( α CT11 - RPRPDDLEI, Mr 1110) that penetrates myocyte membranes, induces S368 phosphorylation and robustly preserves ventricular contractile function and cardiac muscle when administered after ischemic injury. Data on Cx43 hemichannel dependence of α CT11 uptake by cells will be presented. Our results indicate that selective targeting of the secondary structure and phospho-status of the Cx43 CT by small peptidergic drugs may provide a novel and potent pharmacological approach to preservation of cardiac muscle following IR injury.
REFLECT real-world evidence (RWE) prospective study update: Efficacy and safety results of Sandoz biosimilar rituximab (SDZ-RTX) for the treatment of diffuse large B-cell lymphoma (DLBCL).
Authors: Manfred Welslau, Norbert Walter Marschner, Burkhard Joerg Otremba, Julian Topaly, Larissa Bittencourt da Silva
Journal: Journal of Clinical Oncology (2020)

8060 Background: SDZ-RTX (Rixathon) is approved in more than 20 countries and regions, including highly regulated markets e.g. Europe, Japan and Switzerland for all labeled indications of reference rituximab. REFLECT is the first prospective post-approval study to evaluate a rituximab biosimilar as a curative therapy in untreated pts with CD20 + DLBCL. This interim analysis adds up efficacy and additional safety results on the previously presented data (Welslau et al, ASCO and EHA 2019). Methods: Adult patients (pts) were treated with SDZ-RTX and cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) according to the product label. The primary endpoint is to evaluate the effectiveness of Rixathon measured by complete response (CR) rate at the end of treatment. Secondary endpoints are overall response rate (ORR), progression-free survival at 24 months and adverse events (AEs). Data were collected at baseline and all scheduled treatment and follow-up visits, which is still ongoing. No imputation was made for missing values, and endpoints are summarized descriptively. Results: As of Sep 30, 2019, 170 pts were enrolled, and R-CHOP treatment was close to completion. The median age of pts was 70 years, and 52% were women. Overall, 38% of pts completed the first 12-month observation period, 41% were ongoing, while 21% of pts discontinued. Most of the pts (~80%) had an ECOG score of 0 (35%) or 1 (46%). Early staging (I–II2), low to intermediate disease risk (IPI 0-2), and known B symptoms were reported for 55%, 50%, and 30% of pts, respectively. CR rate at the end of treatment was 57% (defined as the revised response criteria for malignant lymphoma by Cheson et al, 2007 that excludes complete remission/unconfirmed [CRu]). Summary of efficacy is reported in the Table. Overall, 83% of pts experienced AEs, the most common being anemia (23%), fatigue (21%), and polyneuropathy (15%). Treatment-related AEs were reported for 28% of pts. Rates of any serious AEs (SAEs) and treatment-related SAEs were 37% and 6.5%, respectively. On-treatment deaths and all deaths were reported in 2.4% and 4.7% of pts, respectively. Conclusions: REFLECT is the first prospective post-approval study to evaluate a rituximab biosimilar as a curative therapy in untreated pts with DLBCL. This interim analysis results re-confirms the expected safety and efficacy profile for DLBCL patients treated with R-CHOP. [Table: see text]
Lipid-lowering therapy in the post-statin era
Authors: Lijun Ma, Qing He
Journal: BMJ (2019)

Atherosclerotic cardiovascular disease is one of the leading causes of death and disability worldwide. Dyslipidemia mainly with elevated LDL-C is closely related to atherosclerotic cardiovascular disease. Statins are the most effective drugs for lowering LDL-C and play an important role in the prevention and treatment of atherosclerotic cardiovascular disease. However, a considerable number of patients receiving statin therapy can not tolerate its adverse reactions or their low-density lipoprotein can not meet the standard, and the cardiovascular risk remains high. The clinical application of new lipid-lowering drugs such as ezetimibe, PCSK9 inhibitors and cholesterol ester transfer protein(CETP) inhibitors has marked the post-statin era of lipid-lowering therapy.


Key words: 
Dyslipidemia; Lipid-lowering therapy; Statin; Ezetimibe; PCSK9 inhibitor
Brucellosis presenting as fever of unknown origin admitted in a general hospital of non-endemic area: a clinical analysis of 11 cases
Authors: Zhen Hu
Journal: BMJ (2017)

Objective
To analyze the clinical characteristics of brucellosis presenting as fever of unknown origin in non-endemic area.


Methods
Clinical data of 11 patients with fever of unknown origin, who were admitted in a general hospital of non-endemic area from Jan 2013 to Jan 2017 and diagnosed as brucellosis by blood culture, were retrospectively analyzed.


Results
There were 8 males and 3 females aged 40-70 years.The patients were admitted with or without accompanied symptoms.The patients were initially presented in rheumatology (1 case), neurology (1 case), emergency (4 cases), hematology (1 case), orthopedics (2 cases) and pneumology (2 cases) departments, respectively.The time from onset to presentation was 0.5-7.0 months.The clinical manifestations were nonspecific, and blood cultures of Brucella were positive between 2 to 5 weeks with a mean of 3 weeks. Time to diagnosis was 1 to 9 months with a mean of 4 months.All patients were transferred to infectious hospital when the diagnosis was confirmed.The telephone follow-up showed that none of the patients had fever after discharged.


Conclusion
Brucellosis should not be neglected in the differential diagnosis of FUO in non-endemic area, and blood culture is important for a definitive diagnosis.


Key words: 
Fever of unknown origin; Brucellosis; Blood culture
Pragmatic health education for stroke prevention from the perspective of patients and the public in China
Authors: Jing Lin, Mei Yang, Ming Liu
Journal: BMJ (2019)

脑卒中是由多种病因或危险因素综合作用所致的复杂疾病，目前缺乏单一的特异性治疗方法，一旦发生常常后果严重危害巨大，因此预防更加重要。从患者和公众角度出发采取实效性科普教育方式有利于取得更好效果。
Risk factors of recurrent ischemic stroke in elderly patients
Authors: Jie Xu, Yi Wu, Jie Chen, Jie Liu
Journal: BMJ (2012)

Five hundred elderly patients with ischemic stroke admitted from January 2008 to December 2010 were enrolled in the study,including 352 recurrent cases and 148 primary cases.There was a positive correlation of stroke recurrence with age,blood pressure,blood glucose and lipid levels,smoking and alcohol consumption of patients(P ＜0.05 ); while the stroke recurrence was negatively correlated with physical exercise(P ＜ 0.05).Stepwise multiple regression analysis indicated that the blood pressure,blood glucose and lipid levels were risk factors for the recurrence of ischemic stroke in elderly patients.

Key words: 
Cerebrovascular accident;  Risk factors
Home-based management of cancer patients (CPs) experiencing toxicities while on anticancer treatment: The impact of a nurse-led telephone triage (NTT).
Authors: Lorenzo Calvetti, Marta Tealdo, Roberta Cimenton, Angela Gentile, Rachele Pretto, Monica Pavan, Barbara Gasparin, Gaetana Pagiusco, Rocco De Vivo, Laura Merlini, Giuseppe Aprile
Journal: Journal of Clinical Oncology (2020)

2002 Background: Novel organization models are needed to ensure early management of new treatment-related toxicity of anticancer treatments. Aim of this prospective observational study was to evaluate the impact of the introduction of NTT in reducing hospitalization of CPs. Methods: CPs on active medical treatment at the Department of Oncology of San Bortolo Hospital (Vicenza, Italy) were given instructions to refer to NTT in case of treatment-related adverse events (TRAEs). The service was opened Mon to Fri from 8am to 8pm. Assessment of TRAEs was performed by trained oncology nurses according to the CTCAE scale and subsequent actions were taken according to the severity of the events. The assessment was made under supervision of a medical oncologist in charge of the service while on duty. Primary endpoint of the study was to compare the rate of hospitalization of CPs on anticancer treatment after the introduction of NTT compared to 2017-2018 period. Results: From September 2018 to September 2019 1,075 patients received systemic anticancer treatment (versus 936 patients in the equivalent 2017 – 2018 period). Total consultations at NTT were 429; 581 TRAEs were reported. 117 patients reported more than one TRAE. CTCAE were graded as G1 237 (40.8%), G2 231 (39.8%) or G3-G4 113 (19.4%). The most common grade ≥ 3 TRAE was fever (38 events (33.6%) that resulted a febrile neutropenia in 7 cases) followed by cancer pain (15 (13.3%)) and fatigue (9 (8%)). In the observation period, 109 CPs on treatment were hospitalized versus 138 in the 2017-2018 period with a normalized hospitalization rate of 10.1% versus 14.7 % (p = 0.002, chi-square) with a reduction of normalized number of hospitalizations of 44 (estimated cost savings of 380.160 euros). Conclusions: Our results provided evidence of successful implementation of the NTT system in reducing rates of hospitalization through emergency room in cancer patients receiving modern medical treatments.
The effectiveness of comprehensive psychological Intervention for preoperative stress response for sterility women
Authors: Xiao-hu An, Tao Xu, Da-song Yu
Journal: BMJ (2009)

To evaluate the effectiveness of comprehensive psychological intervention for reducing the preoperative stress response in sterility women. Forty sterility women were equally divided into intervention group and control group. Heart rate(HR), blood pressure(BP), Zung anxiety grade and depression grade scores(SAS, SDS) were recorded; serum concentrations of glucose (GLU), cortieosteroid (Cor), adrenocorticotropic hormone(ACTH) and angiotensin (A Ⅱ) were measure in both groups at admission and before operation. These parameters before surgery were significant higher than those at admission for control group(P 0.05). The results indicate that comprehensive psychological intervention can reduce the preoperative stress response of sterility patients.

Key words: 
Psychotherapy;  Infertility, female
Application of START method in general practice teaching clinic of Shanghai Huangdu Community Health Service Center
Authors: Liang Chen, Jing Zhou, Tao Wang, Lina Gong, Qiang Li, Xiuping Xia, Weiwei Zhang
Journal: BMJ (2020)

From April 2017 to September 2019, the START (standardized reception, teaching, analysis, research, training) method was adopted to train 50 general practitioners at the community general practice teaching clinic of Shanghai Huangdu Community Health Service Center. After 3 months of training, the progress of clinical competence and teaching ability were assessed. After training, the scores of clinical skills and communication skills were significantly higher than those before training (P 0.05). The scores of the ability for building physician-patient relationship, collecting information and providing feedback, understanding complaints from patients′ perspective, sharing information and obtaining informed consents were higher than that before training (all P<0.01). The teaching ability of plan design and teaching method were significantly improved compared with that before training (all P<0.01). The satisfaction rate of START method was 96.0%(48/50). The START method applied in community teaching clinic can significantly improve the clinical competency and teaching ability of general practitioners.


Key words: 
Community health center; In-service training; Clinical competence; Teaching
Retrospective analysis of Peptide Receptor Radionuclide Therapy (PRRT) in Japanese patients with unresectable neuroendocrine tumor.
Authors: Noritoshi Kobayashi, Damian Wild, Felix Kaul, Yasushi Ichikawa
Journal: Journal of Clinical Oncology (2020)

e16700 Background: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is an innovative treatment for inoperable or metastasized, well/moderately differentiated, neuroendocrine tumors (NETs). Currently PRRT cannot be performed in Japan, because there is no approval and insurance cover until now. Methods: We rely on University Hospital Basel to perform PRRT for Japanese patients with NET since 2011. In this retrospective analysis we evaluated the efficacy and safety of PRRT for Japanese patients with NET (IRB B180100019). Inclusion criteria were pathologically confirmed NET, inoperable or metastasized disease, and visible tumor uptake in the pre-therapeutic somatostatin receptor scintigraphy. We excluded patients with concurrent antitumor treatment, concomitant severe illness, and pre-existing severe hematologic, renal, and liver damage. 5.55GBq(150mCi) of 177 Lu-DOTATOC was used as standard treatment and patients received three infusions every 8 weeks. Until end of 2017, combination treatment with 90 Y-DOTATOC and 177 Lu-DOTATOC was performed using the same protocol. We checked blood count and renal function parameter every two weeks after PRRT. CT or MRI examination were performed 10-12 weeks after the last PRRT cycle. We evaluated the morphological changes according to RECIST 1.1 criteria. With the execption of Somatostatin analogues further treatments were refrained until tumor progression. Results: Thirty-three patients (male: 16, female: 17) were recruited with a median age of 56 years. (range: 26-71). Primary lesions were pancreas (n = 18), rectum (n = 6), small intestine (n = 3), stomach (n = 1), and other locations (n = 5). The period between diagnosis and PRRT was about 3years. Median Ki67 index was 6.3% (range: 0.7%-30%). Partial response rate was 39.3% and disease control rate is 63.6%. Progression free survival (PFS) was 421 days (95%CI:269-572 days) and overall survival was 580 days (95%CI:259-900days). We compared PFS with the treatment line (front line: first or second-line vs late line: third or fourth-line), there was no significant difference between the two groups (front line: 329.0 days vs late line: 497.0 days Log Rank test P = 0.189). Conclusions: PRRT in Japanese patients with NET was effective and a reliable treatment option.
Results from TreeTopp: A randomized phase II study of the efficacy and safety of varlitinib plus capecitabine versus placebo in second-line (2L) advanced or metastatic biliary tract cancer (BTC).
Authors: Milind M. Javle, Do-Youn Oh, Masafumi Ikeda, Wei-Peng Yong, Nicola McIntyre, Bertil Lindmark, Mark McHale
Journal: Journal of Clinical Oncology (2020)

4597 Background: Patients with advanced or metastatic BTC who progress on first-line (1L) gemcitabine-based doublet chemotherapy have few 2L treatment options. Varlitinib is a reversible small molecule pan human epidermal growth factor receptor (HER) inhibitor with low nanomolar potency against HER1 (EGFR), HER2 and HER4 with promising early results in advanced BTC. Methods: TreeTopp (NCT03093870) was a global, multicenter, double blind phase 2 study in which patients with advanced BTC who progressed after 1L therapy that included ≥6 doses of gemcitabine, with radiographically measurable disease based on RECIST v1.1, ECOG PS 0 or 1 and albumin ≥3 g/dL were randomized (1:1) to varlitinib (300 mg BID) plus capecitabine (1000 mg/m 2 BID 14 days on/ 7 off)(V+C) or placebo plus capecitabine (P+C). The dual primary endpoints were Objective Response Rate (ORR) and Progression Free Survival (PFS) defined as the time from randomization to radiological progression assessed by Independent Central Review. Secondary end points included Overall Survival (OS). Results: Overall, 127 patients were randomized (V+C, n = 64; P+C, n = 63) from May−Dec 2018 and demographics/baseline characteristics were generally well balanced, although the V+C arm had a lower proportion of females vs. P+C (31% vs. 48%). The odds ratio for ORR was numerically higher with V+C vs. P+C was 2.278 (9.4% vs. 4.8%, p = 0.42), the HR for PFS for V+C vs. P+C was 0.90 (median PFS, 2.8 vs. 2.8 months; p = 0.63), and the HR for OS for P+C vs. V+C was 1.11 (median OS, 7.8 vs. 7.5 months; p = 0.66). Although not powered to evaluate sub-group interactions, in sub-group analysis, V+C showed PFS benefit versus P+C in two sub-groups; gallbladder cancer (GBC, HR = 0.55, 95% CI: 0.25, 1.22; median PFS, 2.9 vs. 1.6 months) and females (HR = 0.59, 95% CI: 0.28, 1.23; median PFS, 4.1 vs. 2.8 months). There was no PFS benefit for V+C vs. P+C among males and non-GBC. Toxicities were generally balanced between arms apart from a slightly higher incidence of hyperbilirubinemia, diarrhea and fatigue in the V+C vs. P+C arm. Grade 3/4 toxicities were reported in 66% and 59% of patients in the V+C and P+C arms, respectively. Conclusions: V+C is well tolerated but did not improve ORR, PFS or OS vs. P+C in 2L advanced BTC. Exploratory analyses suggested that patients with GBC and female patients achieved comparatively higher median PFS with V+C vs. P+C. Clinical trial information: NCT03093870 .
Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: A randomized, placebo-controlled, double-blind, phase III study.
Authors: Qiu Li, Shukui Qin, Shanzhi Gu, Xiaoming Chen, Lizhu Lin, Zishu Wang, Aibing Xu, Xi Chen, Cuncai Zhou, Zhenggang Ren, Lin Yang, Li Xu, Yuxian Bai, Lei Chen, Jun Li, Hongming Pan, Bangwei Cao, Weijia Fang, Ping Yan, Chunlei Jin
Journal: Journal of Clinical Oncology (2020)

4507 Background: Chinese patients (pts) account for more than 50% of hepatocellular carcinoma (HCC) cases in the world and have special features in etiology, biological behavior, treatment strategy and prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib, an inhibitor targeting vascular endothelial growth factor receptor-2, in Chinese pts with pretreated advanced HCC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 trial done in 31 sites in China, pts with HCC who had received at least one line of systemic therapy (including sorafenib and oxaliplatin-based chemotherapy, which is another first-line standard-of-care in China) and had Child-Pugh liver function class A or B ≤7 points were enrolled. The pts were randomly assigned (2:1) to receive 750 mg apatinib orally once daily or placebo and stratified by ECOG performance status (0 or 1), previous sorafenib treatment (yes or no), and extrahepatic spread and/or macrovascular invasion (yes or no) in 28-day treatment cycles. The primary endpoint was overall survival (OS). Results: Between Apr 01, 2014 and May 03, 2017, 393 pts were randomized and received at least one dose of study treatment (261 in apatinib arm and 132 in placebo arm). The median OS was significantly longer with apatinib than that with placebo (8.7 months [95% CI 7.5-9.8] vs 6.8 months [95% CI 5.7-9.1]; hazard ratio 0.785 [95% CI 0.617-0.998]; p=0.0476). Pts in the apatinib arm also had prolonged median progression free survival (PFS) compared with those in the placebo arm (4.5 months [95% CI 3.9-4.7] vs 1.9 months [95% CI 1.9-2.0]; hazard ratio 0.471 [95% CI 0.369-0.601]; p˂0.0001). The objective response rate was 10.7% (95% CI 7.2-15.1) with apatinib versus 1.5% (95% CI 0.2-5.4) with placebo. Treatment-related adverse events (TRAEs) were reported in 250 (97.3%) pts in the apatinib arm and 92 (70.8%) pts in the placebo arm. The most common TRAEs of grade 3 and 4 were hypertension (71 [27.6%] pts in the apatinib arm vs 3 [2.3%] pts in the placebo arm), hand-foot syndrome (46 [17.9%] vs 0), decreased platelet count (34 [13.2%] vs 1 [0.8%]), and decreased neutrophil count (27 [10.5%] vs 0). 24 (9.3%) pts with apatinib and 13 (10.0%) pts with placebo died due to adverse events, and none were deemed treatment-related by investigators. Conclusions: Apatinib significantly prolonged OS and PFS in Chinese pts with pretreated advanced HCC, and was well tolerated with a manageable safety profile. Clinical trial information: NCT02329860 .
Decision making in treatment of valvular diseases
Authors: Ning Zhu, Lei Li
Journal: BMJ (2012)

心脏瓣膜病仍是我国常见病之一，瓣膜病的根本治疗是手术修复或瓣膜置换，对于临床医生来说选择患者的手术时机及手术方式不是一个简单的、按照指南即可确定的问题。本文对左心瓣膜病变的处理原则做简明介绍。