tbuckley/cabot-search huggingface dataset:
Percutaneous transluminal septal myocardial ablation versus septal myectomy for treatment of patients with hypertrophic obstructive cardiomyopathy: a Meta-analysis
Authors: Xin Yi, Xue-jun Jiang, Xiao-yan Li, Yi Guo
Journal: BMJ (2013)

Objective
To evaluate the efficacy of percutaneous transluminal septal myocardial ablation (PTSMA) and septal myectomy (SM) for treatment of hypertrophic obstructive cardiomyopathy.


Methods
We searched all clinical controlled trials of PTSMA and SM in treatment of hypertrophic obstructive cardiomyopathy in Cochrane Library, PubMed, Web of Science, Wanfang Database and CNKI update to August, 2012. The selected studies in Chinese and English were used for Meta-analysis with software RevMan 5.0.


Results
Five studies including 286 cases (PTSMA:149, SM:137) were included in the study. Left ventricular outflow tract pressure was significantly reduced by SM treatment compared with PTSMA (OR=9.07, 95%CI: 0.96-17.18, P=0.030). There were no significant differences in interventricular septum thickness (OR=1.15, 95%CI: -0.79-3.10, P=0.240), left atrial diameter (OR=1.95, 95%CI: -0.16-4.07, P=0.070), left ventricular end-diastolic (OR=0.70, 95%CI: -0.79-2.19, P=0.360), end systolic diameter (OR=1.14, 95%CI: -1.65-3.93, P=0.420), degree of symptom improvement (chest pain: OR=1.07, 95%CI: 0.35-3.23, P=0.910; syncope: OR=0.32, 95%CI: 0.08-1.23, P=0.100), and postoperative mortality (OR=1.63, 95%CI: 0.46-5.76, P=0.450) between PTSMA and SM treatment; but the rates of pacemaker implantation (OR=5.91, 95%CI: 2.04-17.11, P=0.001) and reintervention treatment (OR=6.62, 95%CI: 1.20-36.62, P=0.030) in patients with PTMSA were significantly higher than those with SM.


Conclusions
There is no evidence to indicate that PTSMA can completely replace SM, as an alternative choice the therapy can be used according to left ventricular out flow tract pressure, symptoms, anatomy of target vessel and other conditions.


Key words: 
Cardiomyopathy, hypertrophic; Therapy; Meta-analysis
Impact of the molecular pathology of breast cancer on mortality rates and overall survival in a Haitian cancer clinic.
Authors: Joseph Bernard, Rebecca Henderson, Lynn Gabrielle Alexis, Doukens Patrick Gilbert, Lenz Sacha Christyl Pierre, Vincent A. DeGennaro
Journal: Journal of Clinical Oncology (2020)

e13588 Background: Breast cancer in the most common malignancy among women in Haiti and is mostly diagnosed at an advanced stage. While it is well known that molecular subtype is a prognostic factor, it needs to be investigated among Haitian patients with breast cancer. This study aimed to evaluate the impact of molecular classification of breast cancer on the survival of patients managed in Haiti’s largest cancer clinic. Methods: A retrospective study was conducted on the breast cancer patients of Innovating Health International (IHI) in Port-au-Prince, Haiti from January 2014 to December 2018. Chart review included all patients with breast cancer and tested for molecular classification. Data on variables such as date of admission, age, TNM staging, molecular classification, outcome and date of death were collected for the analysis. Mortality rate and median overall survival (OS) were estimated as of December 31 st , 2019 and stratified according to molecular subtypes. Results: Among the 948 breast cancer cases diagnosed for the study period, 234 (24.7%) of them had a complete molecular classification. The mean age was 51.5 years [range: 23-94]. 55.1% of the patients were ER-positive, among them 33.7% ER+/PR+/HER2-, 15.4% ER+/PR-/HER2-, 2.1% ER+/PR-/HER2+ and 3.8% ER+/PR+/HER+ (triple positive). There were overall 25.6% of luminal A and 29.5% of luminal B cases. 44.9% were ER-negative, among them 14.1% ER-/PR-/HER2+ (HER2-enriched) and 29.1% ER-/PR-/HER2- (triple-negative). 92.2% of the patients had advanced breast cancer (stages IIB to IV). 29.5% had metastatic breast cancer, 22.8% for luminal A cases, 27.0% for luminal B, 36.7% for HER2-enriched and 32.8% for TNBC. Overall mortality rate was 42.3%, respectively 33.3% for luminal A cases, 37.7% for luminal B, 42.4% for HER2-enriched cases and 55.9% for TNBC. Median OS was not yet reached for luminal A, luminal B and HER2-enriched breast cancer, with a respective mean survival of 52.4 months, 51.3 months and 51.6 months. However, OS was 30.6 months for triple-positive breast cancer and 23.7 months for TNBC. Conclusions: Patients with luminal A breast cancer were less likely to have metastatic disease and thus had lower mortality rate and better overall survival. This was likely due to its less aggressive biology and the availability of hormone therapy. Poor availability and inaccessibility of HER2-targeted drugs were the main cause of the higher mortality rate among HER2-enriched patients. TNBC remains the most aggressive subtype.
Disparities in clinical characteristics and treatment of multiple myeloma in African American patients.
Authors: Shivam Mathura, Daniel Lane, Eric Hansen, Andrew J. Belli, Priya Venkatesan, Ching-Kun Wang, Vicki Kay Fung, Xiaoqi Geng, Andrew D. Norden
Journal: Journal of Clinical Oncology (2020)

e19008 Background: Based upon interesting recent published findings, we characterize disparities in clinical characteristics, treatment patterns, and outcomes for African American (AA) patients with multiple myeloma (MM) using real-world (RW) data. Methods: A random sample of patients diagnosed with MM were selected from the COTA RW database for the retrospective analysis to be stratified by race, AA (n=395) and other (n=396). To adjust for differences in age and gender, case-control matching was performed. Patient characteristics and treatment patterns were summarized. A Cox proportional hazards model was used to evaluate the relationship between patient characteristics and time to stem cell transplant (SCT). Overall Survival (OS) was calculated using the Kaplan-Meier method. Results: Median time from diagnosis of active MM to start of first-line (1L) treatment was longer among AA as compared to the other cohort (23 vs. 17 days respectively, p=0.01); VRD was the most common 1L therapy (17.39% vs. 18.58% respectively). The percent of patients receiving SCT was similar across racial cohorts (64.56% vs. 66.16%), but AA patients had a longer time to first SCT (234 vs. 204.50 days, p=0.01). Among all patients, Charlson Comorbidity index (CCI) score of 0 (HR: 2.85, CI: 1.77-4.58) and CCI score of 1-2 (HR: 2.79, CI: 1.73-4.49) were significantly associated with an increased likelihood of receiving a SCT. MM diagnosis at an older age was associated with a lower likelihood of receiving a SCT (HR: 0.97, CI: 0.96-0.98). AA cohort exhibited a higher incidence of prior history of MGUS (10.63% vs 8.08%). Cytogenetic profile of the AA and other cohorts are shown in the Table below. Median OS was similar between the AA and other cohorts (145.61 vs. 146.50 months, respectively, p=0.88). Conclusions: AA patients had a longer duration of time to 1L therapy and 1st SCT in our RW study. Despite these differences in time to treatment, OS was similar across racial groups. Future studies are needed to explore the significance of our RW findings and other potentially important clinical characteristics. [Table: see text]
Therapeutic vulnerabilities among KRAS G12C mutant (mut) advanced cancers based on co-alteration (co-alt) patterns.
Authors: Maliha Nusrat, Jason Roszik, Vijaykumar Holla, Tiantian Cai, Meiyue Hong, Oluwadara Coker, Benny Johnson, Jordi Rodon Ahnert, Filip Janku, Scott Kopetz, Kenna Rael Shaw, Funda Meric-Bernstam, David S. Hong
Journal: Journal of Clinical Oncology (2020)

3625 Background: Oncogenic KRAS mut drive cancers and confer therapeutic resistance by activating MAPK signaling. Inhibiting KRAS has been elusive until the recent promising phase I trials with KRAS G12C inhibitors (i). We characterized frequencies of KRAS G12C mut and gene co-alt among advanced cancer patients (pts) to identify therapeutic vulnerabilities for combination development. Methods: We analyzed next generation sequencing datasets from MD Anderson Cancer Center (MDACC, n = 42,316) and AACR GENIE (n = 56,970). Genes and individual alterations were annotated for potential actionability with approved or investigational drugs and grouped into 12 oncogenic pathways. Frequencies of potential drug combinations with KRAS G12Ci were estimated per tumor type based on co-occurrence of potentially actionable alterations. Results: KRAS G12C was present in 850/34,801 (2.4%) advanced solid tumor and 22/7698 (0.3%) hematologic malignancy pts in MDACC dataset; and 1422 (2.5%) pts in AACR GENIE. Among solid tumor pts, 798 had histology data and 640 had ≥46 gene profiling. Most common cancers were non-small cell lung (NSCLC, 67%), colorectal (CRC, 24%), other gastrointestinal (oGI, 4%) and gynecologic (gyn, 2%). KRAS G12C prevalence was 19.5% (441/2265) in NSCLC and 4.2% (146/3469) in CRC. Genes most commonly co-altered were TP53 (42%), STK11 (17%) and MET (11%) in NSCLC; TP53 (58%), APC (54%) and PIK3CA (24%) in CRC; TP53 (42%), APC (21%) and ATM (21%) in oGI; TP53 (56%), PIK3CA (25%), and PTEN (19%) in gyn cancers. These co-alt did not impact overall survival. In both datasets, as compared to KRAS wild, KRAS G12C was significantly co-altered with STK11 in NSCLC; PIK3CA and SMAD4 in CRC (P &lt; 0.05 for all). EGFR mut in NSCLC and BRAF mut in CRC rarely co-occurred with KRAS G12C (P &lt; 0.01). Most frequently co-altered oncogenic pathways in NSCLC, CRC, oGI and gyn cancers respectively included PI3K (27, 32, 33, 44 %), receptor tyrosine kinases (13, 16, 42, 13 %) and DNA damage repair (12, 10, 38, 19 %). Potentially actionable co-alt frequencies suggest that combining KRAS G12Ci with mTORi or PI3Ki would be indicated most frequently, in 24% and 13% of all pts respectively. Conclusions: KRAS G12Ci development is most relevant for NSCLC, gastrointestinal and gyn cancers. The co-alt patterns highlight relevant oncogenic pathways and candidate drugs for future combination therapies. Co-inhibition of PI3K-mTOR and MAPK pathways has shown synergism in prior pre-clinical studies but had poor tolerance in pts. There is opportunity to revisit this approach with the new KRAS G12Ci.
Clinical efficacy of ONC201 in thalamic H3 K27M-mutant glioma.
Authors: Abed Rahman Kawakibi, Rohinton Tarapore, Sharon L. Gardner, Sylvia Christine Kurz, Patrick Y. Wen, Isabel Arrillaga-Romany, Tracy Batchelor, Nicholas A. Butowski, Ashley Love Sumrall, Nicole A. Shonka, Rebecca A. Harrison, John Frederick De Groot, Minesh P. Mehta, Yazmin Odia, Matthew David Hall, Timothy Francis Cloughesy, Benjamin M. Ellingson, Yoshie Umemura, Joshua E. Allen, Carl Johannes Koschmann
Journal: Journal of Clinical Oncology (2020)

3617 Background: Diffuse midline gliomas, H3 K27M-mutant are associated with a poor prognosis compared to H3 wild-type gliomas and have no effective therapy following first-line radiation. ONC201 is a bitopic DRD2 antagonist and allosteric ClpP agonist that has shown encouraging single agent efficacy in recurrent H3 K27M-mutant gliomas located in various midline structures of the brain. In addition to tumor and immune cells, the pharmacodynamics of ONC201 extend to stromal cells that can mediate a bystander antitumor response in preclinical models. Given this observation and that the thalamus has the highest extrastriatal expression of DRD2, we report the clinical experience of ONC201 in a subgroup of H3 K27M-mutant glioma patients with primary tumors located in the thalamus. Methods: We analyzed 29 thalamic H3 K27M-mutant glioma patients treated with ONC201 in clinical trials enrolled as of 5/22/19. Nineteen enrolled with recurrent disease whereas 10 enrolled following radiation prior to recurrence. Twelve patients enrolled on NCT03295396, 10 NCT03416530, 4 NCT02525692, and 3 expanded access. Median age was 22 years old (range: 5-70) and baseline KPS was 80 (range: 60-90). Median time from radiation to start of ONC201 was 1.8 months (range: 0.2-8.7) for non-recurrent patients and 7.2 months (range: 1.4-102.0) for recurrent patients. Results: As of 12/18/2019, PFS6 and OS12 measured relative to initiation of ONC201 are 26.3% and 36.8%, respectively, in the recurrent group. For patients initiating ONC201 post-radiation prior to recurrence, median PFS or OS have not been reached with a median follow up of 21.9 months (8.6-26.6) from diagnosis, which surpass historical OS of 13.5 months. Best response for evaluable recurrent patients by RANO: 1 CR, 3 PR, 4 SD, 8 PD, 3 not reported; for non-recurrent patients: 2 PR, 4 SD, 1 PD, 3 not reported. Median duration of response for recurrent patients is 14.0 months (2.0-33.1). ONC201 was well tolerated and no dose-limiting toxicities or treatment discontinuations due to toxicity occurred. Furthermore, H3 K27M cell-free tumor DNA in plasma and CSF correlated with MRI response. Conclusions: In summary, single agent ONC201 administered at recurrence or following radiation, demonstrates promising clinical efficacy in thalamic H3 K27M-mutant glioma patients. Investigations are ongoing to assess whether micro-environmental DRD2 expression correlates with responses of thalamic H3 K27M-mutant glioma to ONC201. Clinical trial information: NCT03295396, NCT03416530, NCT02525692 .
布-加综合征延误诊断一例
Authors: 徐涛, 刘福旭, 张颖, 孙远杰
Journal: BMJ (2005)

患者男,39岁.因间断腹胀乏力6年于1999年5月入院.10年前患结核性胸膜炎行抗痨治疗,治疗方案及治疗后肝功能情况不详,无长期大量饮酒史.曾于1993年6月因腹胀乏力入院.查体:肝于肋下3.0 cm、剑突下 5.0 cm,可触及,表面光滑,边缘钝,质硬,移动性浊音阳性。
A randomized controlled trial of a self-administered, online decision-aid (“Navya Patient Preference Tool”) to reduce decisional conflict in women with early breast cancer.
Authors: Shalaka P Joshi, Lakshmi Ramarajan, Ojas Deshpande, Elizabeth Fernandes, Vaibhav Vanmali, Rohini W Hawaldar, Sadhana Kannan, Vani Parmar, Nita S. Nair, Sudeep Gupta, Rajendra A. Badwe
Journal: Journal of Clinical Oncology (2020)

7033 Background: Shared decision making to confront choices with clinical equipoise, has been the privilege of those patients with access to time intensive consults with oncologists. We conducted a randomized controlled trial for breast cancer patients to use an online, self-administered, out-of-the-medical-encounter decision aid (DA) to choose between breast conserving surgery (BCS) and mastectomy. Methods: Navya Patient Preference Tool (Navya PPT) is a multilingual DA based on adaptive conjoint analysis of tradeoffs between cost, adverse effects of radiation, and breast conservation. Prior analysis established high internal reliability and external validity of the Navya PPT. Eligible cT1/2, cN0 breast cancer patients planned for surgery were block randomized, in 1:1:1 ratio, to receive the research questionnaire (RQ) to measure decisional conflict on choice of surgery (control, arm 1), Navya PPT followed by RQ (experimental, arm 2) or Navya PPT followed by RQ administered with key male family member (experimental, arm 3). Groups were stratified with respect to age, socio-economic status (SES) and educational level. The study was powered to detect a decrease in Decisional Conflict Index (DCI) by 0.25 (β-0.8, two sided α- 0.01). Results: Between June 2017 and December 2019, 247/255 patients were randomized to arm 1 (83), arm 2 (84), and arm 3 (80). Median age was 48 years (IQR 23-76), and median pT size was .5 cm (0.5-6 cm). 59% of patients were middle or lower SES and 46.2% had ≤ 12th grade education. DCI was significantly reduced in arm 2 as compared with arm 1 (1.34 vs. 1.65, Cohen’s d 0.49 (± 0.31) p&lt;0.05) as well as in arm 3 as compared with arm 1 (1.30 vs. 1.65, Cohen’s d 0.54 (± 0.31) p&lt;0.05). 80% (± 6%) of patients underwent surgery of choice as determined by Navya PPT. BCS rate was similar in all three arms (85.2, 88.9 and 86.5% respectively (p=0.779). Conclusions: Online, self-administered, adaptive DAs used out of the medical encounter can reduce decisional conflict and increase access to shared decision making for every patient; especially in practices with low doctor to patient ratios. Clinical trial information: IEC/0116/1619/001 .
甲硝唑致严重龟头溃烂二例
Authors: 姜文忠, 李淑华, 张凤林, 赵舒畅
Journal: BMJ (2006)

例1 男,45岁.于3 d前经我院消化科诊断为十二指肠溃疡和幽门螺杆菌(HP)阳性.治疗采用中华医学会消化病学会推荐的HP根除治疗质子泵抑制剂(PPI)三联疗法一线方案2(奥美拉唑标准剂量+甲硝唑0.4 g+克拉霉素0.5 g),每日3次,7 d为1个疗程[1].服用3 d后,全身不适,龟头、包皮奇痒,伴烧灼感,局部红肿,4 h后包皮内黏膜、龟头出现溃烂,并有脓血性分泌物渗出,疼痛难忍。
MRI changes in patients with newly diagnosed glioblastoma treated as part of a phase II trial with bavituximab, radiation, and temozolomide.
Authors: Ina Ly, Jonathan Cardona, Kevin Lou, Andrew Beers, Ken Chang, James Brown, David A. Reardon, Isabel Arrillaga-Romany, Deborah Anne Forst, Justin T Jordan, Eudocia Quant Lee, Jorg Dietrich, Lakshmi Nayak, Patrick Y. Wen, Ugonma Nnenna Chukwueke, Tracy Batchelor, William T. Curry, Jayashree Kalpathy-Cramer, Elizabeth Robins Gerstner
Journal: Journal of Clinical Oncology (2020)

2546 Background: Glioblastoma and tumor endothelial cells express phosphatidylserine (PS), a highly immunosuppressive membrane phospholipid. Bavituximab – a chimeric monoclonal antibody – binds to β2-glycoprotein 1 (β2-GP1) to form a complex of β2-GP1 with PS, resulting in immune activation against tumor cells and anti-angiogenic effects. Phase I/II trials in other solid cancers demonstrated response rates up to 75% when bavituximab was given with cytotoxic chemotherapy. Pre-clinical data in glioblastoma models suggested synergistic effects of PS blockade, radiation, and temozolomide. Methods: 33 adult patients with IDH-wild-type, MGMT-methylated or -unmethylated newly diagnosed glioblastoma were enrolled in this phase II trial (NCT03139916) and received 6 weeks of chemoradiation, followed by 6 cycles of adjuvant temozolomide (C1-C6 aTMZ). Bavituximab (3 mg/kg) was given weekly, starting week 1 of chemoradiation, for 18 weeks with the option to continue if tolerated. Physiologic MRIs were performed pre-treatment, pre-C1, pre-C3, and pre-C5 aTMZ. Within the enhancing tumor region, median tumor K trans (reflecting vascular permeability) and relative cerebral blood flow (rCBF) were measured. Median percent changes during treatment were compared to pre-treatment values. Results: Median progression-free survival (mPFS) was 8 months. Based on a median overall survival (mOS) of 17.1 months, patients were categorized into above-median survivors (AMS) and below-median survivors (BMS). All patients had pre-treatment scans. 31 had evaluable pre-C1, 25 had pre-C3, and 7 had pre-C5 scans. Compared to BMS, AMS had a greater reuction in enhancing tumor volume and rCBF, and a greater increase in K trans during treatment (table). One patient remains on study; 23 patients have died. Bavituximab was well tolerated. Conclusions: mPFS and mOS in patients treated with bavituximab, radiation and temozolomide were comparable to standard chemoradiation and aTMZ. Lower rCBF in AMS may reflect decreased tumor perfusion while higher K trans could imply enhanced drug delivery to the tumor. Bavituximab induces changes in tumor vasculature that may improve survival in a subset of patients. Clinical trial information: NCT03139916 . [Table: see text]
Correlation of existence and number of mutations in DDR signaling pathway genes with poor survival after resection of colorectal liver metastases.
Authors: Kun Wang, Hongwei Wang, Kemin Jin, Xiaoyu Zhang, Chunhe Yang, Baocai Xing
Journal: Journal of Clinical Oncology (2020)

e16004 Background: Patients of colorectal cancer with liver metastatic (CRLM) show various in recurrence and prognosis. Previous researches have revealed that the disfunction of DNA damage repair (DDR) signaling pathways was correlative with oncogenesis and poor prognosis. Here we aimed to determine the impact of DDR gene mutations on survival in patients undergoing CRLM resection. Methods: Tumor tissues from 164 patients with CRLM were collected for next generation sequencing (NGS). Single nucleotide variants, indels, and copy number variations were obtained from a 620-gene panel, including 68 genes in 7 DDR signaling pathways. Correlations of mutations in DDR genes with overall survival (OS) and recurrence-free survival (RFS) were determined by using Kaplan-Meier analysis. Results: 152/164 of patients carried at least one of DDR gene alternations. The most frequently mutated gene was TP53 (132/164), followed by CHEK2 (21/164), BRCA2 (10/164), ATM (9/164), PRKDC (8/164), FANCM (8/164), ATR (7/164), POLE (5/164), BRCA1 (4/164), POLD (3/164). Survival analysis indicated that TP53 mutations were not correlated with OS and RFS (P = 0.38 and 0.21). Further analysis in the TP53 mut subgroup showed that the patients with other DDR gene mutations (64/132, 48.48%) exhibited a significantly worse OS than the wild type ones (P = 0.04). Especially, gene alternations involving in the Fanconi anemia (FA) pathway were significantly associated with worse OS and RFS (P = 0.0014 and 0.006). Interestingly, besides the TP53 mutation, patients carrying more than 2 other DDR gene mutations (10/64, 15.63%) also showed worse OS and RFS than patients with single mutation and wild type in DDR genes. (OS: 19 vs 35 months, P = 0.053; RFS: 3 vs 11 months, P = 0.084). Conclusions: Mutations in DDR signaling pathways predicted worse survival in TP53-mutated CRLM patients after surgery. These findings may be useful for clinical decision making in patients with tumor characteristics associated with poor prognosis and for risk stratification of patients in future clinical studies.
Listeria monocytogenes bacteremia in third trimester of pregnancy: case report with literature review
Authors: Guqin Zhang, Huaqin Pan, Fang Yu, Jiong Yang
Journal: BMJ (2018)

One case of Listeria monocytogenes bacteremia in third trimester of pregnancy admitted in Zhongnan Hospital was reported. And 25 cases of maternal listeriosis were retrieved from domestic literature search up to March 2017. The clinical features of 26 cases were analyzed. The newly reported case was a 27-year-old primigravida at 37 weeks 5 days of gestation presenting with fever for 23 days. Listeria monocytogenes was identified in blood culture. She was treated with intravenous piperacillin sodium and tazobactam sodium for 3 weeks and recovered. At 39 weeks 4 days of gestation, she gave birth of a male baby by vaginal delivery. The newborn baby was healthy with negative Listeria monocytogene in blood culture. The age of onset of all 26 cases was (30.2 ± 4.7)years. There were 1, 13 and 12 patients with listeriosis diagnosed in the first, second and third trimester of pregnancy, respectively. The median time from onset to symptom presentation was 2 days. Clinical manifestations included fever (92%, 24/26), leukocytosis (75%, 18/24), abdominal pain (27%, 7/26), fetal movement decrease or lose (23%, 6/26) and vaginal bleeding (15%, 4/26). Listeria monocytogenes were isolated from blood (11 cases), uterus swab (7 cases), amniotic fluid (2 cases) and so on. High proportion of adverse pregnancy outcomes occurred (88%, 22/25). All gravidae recovered well after the termination of pregnancy. The empirical antibiotics did not cover those sensitive to listeria in all patients. Patients with maternal listeriosis often presented with acute fever and a high incidence of adverse pregnancy outcomes, however, empirical antibiotics can hardly cover Listeria monocytogene. Thus, clinicians should improve awareness of listeriosis to avoid missed diagnosis and misdiagnosis.


Key words: 
Pregnancy complications, infectious; Listeria monocytogenes; Listeriosis