tbuckley/cabot-search huggingface dataset:
Clinicopathologic features of invasive breast cancer (BC) diagnosed in carriers of germline <i>PALB2</i>, <i>CHEK2</i> and <i>ATM</i> pathogenic variants.
Authors: Danika Scott, Kerry Kingham, Rachel Hodan, Cindy Ma, Meredith Mills, James M. Ford, Allison W. Kurian, Melinda L. Telli
Journal: Journal of Clinical Oncology (2020)

1549 Background: While germline pathogenic variants (PVs) in BRCA1/2 account for a large proportion of hereditary breast cancer (BC), PVs in PALB2, CHEK2 and ATM are increasingly detected. However, the phenotype and clinical features of invasive BC with these PVs have not been fully described. Methods: We identified patients with a PV or likely PV in PALB2, CHEK2 or ATM tested clinically at Stanford between 2014 - 2019 who provided informed consent to be included in a prospective cancer genetics registry. Data on baseline demographics, genetic testing history, and clinicopathologic features of diagnosed BC were collected. For patients with a subsequent diagnosis of metastatic BC, we calculated disease-free interval (DFI). Results: 130 patients met inclusion criteria for analysis: ATM (N=39), CHEK2 (N=58), PALB2 (N=33). Nearly all (98.5%) were women, with 2 male BC in ATM carriers. Non-Hispanic White ethnicity was most common in ATM (64.1%, 95% CI 48.4%-77.3%) and CHEK2 carriers (69.0%, 95% CI 56.1%-79.4%), but comprised only 39.4% (95% CI 24.7%-56.4%) in PALB2 carriers. Asian/Pacific Islander (24.2%, 95% CI 12.6%-41.3%) and Hispanic (30.3%, 95% CI 17.3%-47.5%) ethnicities were enriched among PALB2 mutation carriers. In total, 97.7% learned of their PV status only after a preceding diagnosis of BC and 43.1% were diagnosed with BC at age ≤ 45. Data regarding invasive BC subtypes, incidence of subsequent primary BC, and metastatic recurrence are listed below in the table. Additional data on stage, grade and sites of metastatic spread will be presented. Conclusions: We observed clinically important differences in the spectrum of BC subtypes among carriers of ATM, CHEK2 and PALB2 PVs, in addition to racial/ethnic differences with Asian/Pacific Islander and Hispanic ethnicity enriched among carriers of PALB2 PVs. [Table: see text]
Effects of Fosinopril vs Amlodipine on brachial ankle pulse wave velocity and pulse pressure in patients of primary hypertension
Authors: Xia-ping Xiang, Han-yin Yuan, Xin-hui Ning, Yu Liu, Wen-jun Wang
Journal: BMJ (2008)

A total of 560 patients with primary hypertension were divided into two groups.Of them,260 were treated with Fosinopril(10～20 mg once daily),and the other 300 were treated with Amlodipine (5～10 mg once daily).The treatment lasted for 12 months in both groups.The levels of blood pressure (BP)、braehial ankle pulse wave velocity(baPWV)and pulse pressure(PP)were examined at baseline,6 month and 12 month with automatic analysis system of arteriosclerosis.BP in Amlodipine group(132/76 mm Hg)decreased more significantly than Fosinopril group(136/85 mm Hg),but Fosinopril group showed more remarkable changes in baPWV(1310 cm/s)and PP(52 mm Hg)than Amlodipine group(1400 cm/s and 56 mm Hg).

Key words: 
Antihypertensive agents; Pulse wave velocity
Tobacco still haunting Kentuckians: Adolescent and young adult (AYA) cancer trend from the Kentucky SEER database.
Authors: Aasems Jacob, Saurabh Parasramka, Zhonglin Hao, Eric B. Durbin
Journal: Journal of Clinical Oncology (2020)

e13626 Background: Kentucky has the highest incidence and mortality for AYA cancers in the US. When the incidence of AYA cancers increased 4% between 2012-16 nationally, it was 12.3% in the state of Kentucky. Understanding the burden and factors associated with it may help develop effective risk reduction strategies. Methods: SEER database was used for analyzing population estimates (2012-2016) while records from the NCI-designated cancer center in the state was used to assess current trends and clinicopathologic features. Pearson test was used to estimate correlation and Kaplan-Meier and Cox regression models were used to compare survival outcomes. Results: A total of 5825 AYA patients were identified in the state’s SEER database between 2012-16. A majority (62.4%) were female, from non-Appalachian region (71%) and rural counties (64%). Thyroid, breast, melanoma, cervical and CNS malignancies were the most common. While sarcoma, leukemia and gastric cancer decreased in incidence, breast, melanoma, cervical and colorectal cancer have increased from 2012-2016, similar to a general trend nation-wide. County-wise estimation of cancer incidence showed a significant correlation with prevalence of smoking (Pearson r = 0.34, p &lt; 0.001) independent of educational, employment or economic status. A total of 1129 AYA cancer patients treated between 2016-19 at the Markey Cancer Center were analyzed. Baseline characteristics were similar to statewide trend. About 10% of the cancers were metastatic at diagnosis and 14% died from the disease. Nearly half (44%) of the patients were smokers. Smoking was independently associated with higher risk of death (HR 0.46 95%CI 0.33, 0.64, p &lt; 0.0001) and early cancer recurrence (HR 0.56, 95%CI 0.3, 0.9, p = 0.026). Metastatic disease at diagnosis was also more common among smokers compared to non-smokers. (58% vs 41%, p = 0.002). There was no significant difference in OS or risk of recurrence between rural/urban or Appalachian/Non-Appalachian counties. Conclusions: The high prevalence of smoking (24.3%), especially among youth (14.3%) could be the root of the higher incidence of AYA cancers in the state of KY although multiple socio-economic and geographic factors might be influencing. Second-hand smoke exposure at home is also the highest in the country at 32% with rates as high as 80% in some counties. Awareness about these disturbing statistics is required to set in motion more community and legislative interventions to reduce cancer incidence among the youth.
Patient-reported physical and mental health of socioeconomically disadvantaged cancer patients.
Authors: Aaron Gehr, Yan Lu, Bhavna Tanna, Kalyani Narra, Bassam Ghabach, Rohit P. Ojha
Journal: Journal of Clinical Oncology (2020)

e19041 Background: Patient-reported outcomes (PROs) are extensively described for cancer patients with access to care, but little information is available about PROs for socioeconomically disadvantaged cancer patients with barriers to care. Therefore, we aimed to compare patient-reported mental and physical health between newly diagnosed cancer patients at an urban safety-net cancer center and the general population. Methods: We used data collected during implementation of a quality improvement pilot initiative to integrate PROs into clinical care at the JPS Oncology and Infusion Center (Fort Worth, TX), which is a Comprehensive Community Cancer Program. The Patient-Reported Outcomes Measurement Information System (PROMIS) 10-item Global Health Survey was used to ascertain mental, physical, and social health for newly diagnosed cancer patients between August and December 2019. Our outcomes of interest were the mental and physical health subdomains. We computed T-scores, where a score of 50 represents the mean for the U.S. general population with a standard deviation (SD) of 10. We defined severely impaired health as subdomain scores ≥2 SDs below the mean. In addition, we estimated standardized morbidity ratios (SMR) and corresponding 95% confidence limits (CL) to compare the observed number of patients with severe impairment of mental or physical health with the expected number of patients with severe impairment. For example, an SMR = 1.0 implies that the observed number of severely impaired individuals in the study population is equal to the expected number in the general population. Results: Our study population comprised 59 patients, of whom 73% were aged &lt; 65 years, 51% were female, and 54% were racial/ethnic minorities. Breast (21%) and lung (21%) cancers were the most common diagnoses. The frequency of severely impaired physical health for our population was 4.4 times higher than the general population (SMR = 4.4, 95% CL: 1.6, 9.6), whereas no patients in our study population reported severely impaired mental health (SMR = 0, 95% CL: 0, 2.2). Conclusions: Our results suggest that socioeconomically disadvantaged cancer patients have substantially impaired physical health but not mental health at diagnosis. These findings may be useful for raising awareness about the importance of systematically ascertaining PROs and using the results to allocate resources for delivering care to safety-net cancer patients.
A preliminary investigation on patients with undifferentiated spondyloarthropathy in a Chinese population
Authors: 廖泽涛, 古洁若, 邓星河, 魏秋静
Journal: BMJ (2007)

目的 探讨我国未分化脊柱关节病(USpA)患者的临床特征以及欧洲脊柱关节病研究组(ESSG)和Amor标准在USpA患者诊断中的价值.方法 纳入研究的USpA患者112例,收集并分析临床资料,包括记录ESSG和Amor标准各参数资料.结果 本组112例USpA患者中,男女比例为1.67:1,平均年龄31岁;脊柱是最常见的起病部位,占44.2%,其余依次为臀部(37.2%)、其他肌腱端炎(如跟腱压痛9.3%)、外周关节炎(3.5%)、腹股沟(1.2%).疾病在病程中累及中轴关节的患者占83.9%,仅有极少数USpA患者有虹膜炎或葡萄膜炎(2例)和心脏传导系统受累(1例).45例骶髂关节X线平片未发现2级或更严重的骶髂关节炎改变的USpA患者行骶髂关节MRI检查,其中86.7%有异常MRI改变,2/3呈现有急性炎症特征;USpA患者的药物治疗主要是非甾类抗炎药(NSAIDs),达98.2%,约32.1%的USpA患者曾不规则用过柳氮磺胺吡啶(SASP),约16.1%患者曾经用过甲氨喋呤.采用ESSG和Amor标准诊断的敏感性分别是73.2%和54.5%.结论 我国USpA的主要临床特征是炎性下腰背痛,尤其结合HLA-B27和骶髂关节MRI检查在USpA早期诊断中有重要价值;ESSG和Amor标准在我国USpA患者的诊断中有较好的应用价值。
Phase I/II study of vorolanib plus nivolumab in patients with thoracic malignancies: immunotherapy (IO) correlatives to differentiate responders from nonresponders.
Authors: Katy Beckermann, Christine M. Bestvina, Jennifer G. Whisenant, Hossein Borghaei, Taofeek Kunle Owonikoko, Lynne D Berry, Yu Shyr, Chris Liang, Giovanni Selvaggi, Heather A. Wakelee, Leora Horn
Journal: Journal of Clinical Oncology (2020)

e21019 Background: VEGF inhibition is suggested to enhance innate T cell function, activate dendritic cells, block recruitment of regulatory T cells, and decrease myeloid-derived suppressor cells. Vorolanib is a tyrosine kinase inhibitor that is structurally similar to sunitinib but designed to improve safety without compromising efficacy. Response to checkpoint inhibitors in patients with thoracic tumors is limited, thus we designed this multi-institutional, phase I/II study (NCT03583086) to explore safety and efficacy of combining vorolanib and nivolumab. Here we present updated results in the NSCLC, thymic, and SCLC cohorts, including patients previously treated with single agent IO. Methods: The Phase I maximum tolerated dose was 200 mg vorolanib and 240 mg nivolumab q2w. Phase II is ongoing and uses a two-stage MinMax design to assess the objective response rate (RR) in SCLC, thymic carcinoma, and three NSCLC cohorts: 1) IO naïve; 2) primary refractory, defined as radiographic progression &lt; 12 weeks of starting IO; and 3) acquired resistance, defined as achieving at least stable disease ≥12 weeks to IO followed by progression. Results: As of December 2019, 37 patients had enrolled, 38% female, 11% never smokers, median age 66. The disease control rate (DCR) across all cohorts is 65% (20/31 evaluable patients) and the RR is 13% (4/31). In the NSCLC cohort, the overall RR is 14% (3/21); the RR is 33% (2/6) in IO naïve patients, including 2 on therapy &gt; 17 months. RR in the NSCLC patients with acquired resistance is 14% (1/7) with an 86% (6/7) DCR. No responses in the primary refractory cohort but the DCR is 50% (4/8). DCR in the SCLC and thymic cohorts is 40% (2/5) and 50% (2/4), respectively; 1 thymic patient had a partial response with a complete response in target lesions. Exploratory correlatives, including mass cytometry analysis and single cell gene expression, are being performed in order to understand changes in macrophages and T cell activation markers to differentiate the underlying biology of the tumor and the microenvironment between responders and nonresponders. Conclusions: The addition of vorolanib nearly doubled the RR in the IO naïve NSCLC patients compared to historical data with single agent nivolumab. Additionally, 67% of NSCLC patients with prior IO achieved at least stable disease, 1 patient with acquired resistance had a response. Correlatives that may help define biomarkers of response to therapy will be presented among different cohorts of patients. Clinical trial information: NCT03583086 .
Contrasting genomic profiles in post-systemic treatment metastatic sites (MET), pretreatment primary tumors (PT), and liquid biopsies (LB) of clinically advanced prostate cancer (PC).
Authors: Andrea Necchi, Petros Grivas, Gennady Bratslavsky, Oleg Shapiro, Joseph M Jacob, Ethan Sokol, Jonathan Keith Killian, Douglas I. Lin, Shakti H. Ramkissoon, Eric Allan Severson, Richard Huang, Brian Michael Alexander, Jeffrey Venstrom, Venkataprasanth P. Reddy, Kimberly McGregor, Julia Andrea Elvin, Alexa Betzig Schrock, Dean Pavlick, Natalie Danziger, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2020)

5534 Background: Comprehensive genomic profiling (CGP) was done on pre-systemic treatment (pre) PT, post-treatment (post) MET sites and LB in PC to uncover differences in genomic alterations (GA) and potential impact on therapy selection. Methods: 1,294 PC tissues and 782 LB underwent hybrid-capture based CGP. PT biopsies and resections were compared with post-treatment MET biopsies from bone (BO), liver (LIV), lung (LU), brain (BN), lymph node (LN) and soft tissue (ST) sites and LB. TMB was determined on up to 1.1 Mbp of sequenced DNA for tumor samples. Tumor cell PD-L1 IHC was measured (Dako 22C3). Results: Differences in alteration frequencies between PT, MET and LB for selected genes are shown in the Table. TMPRSS2:ERG fusion frequencies were similar between PT and MET (35% vs 33%) but varied between MET sites (27% in BO and ST to 40% in LN). GA in AR were lowest in pre PT (2%) and highest in MET (24% in LU to 50% in LIV). BN had the highest GA/tumor (8) and the most PTEN GA. BRCA2 GA frequency varied from 0% in BN to 15% in LI. Potential predictors of IO response included CDK12 GA (16% in LU) and MSI high status (29% in BN). High PD-L1 expression was found in only two cases (LN) and low PD-L1 expression was relatively uncommon. ERBB2 amplifications were increased in MET compared with PT. RB1 GA were increased in LIV cases. LB GA had a similar increase in AR and TP53 GA to MET and appeared to be a blend of MET site biopsies across alteration frequencies. Conclusions: CGP of PT, MET and LB in PC demonstrates differences most likely associated with exposure to systemic therapies. Differences identified in the MET GA landscape suggest that liquid biopsies may capture a broader range of therapeutic opportunities for PC patients. [Table: see text]
Final overall survival (OS) from PROSPER: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC).
Authors: Cora N. Sternberg, Karim Fizazi, Fred Saad, Neal D. Shore, Ugo De Giorgi, David F. Penson, Ubirajara Ferreira, Petro Ivashchenko, Eleni Efstathiou, Katarzyna Madziarska, Michael Paul Kolinsky, Daniel Iracema Cubero, Bettina Noerby, Fabian Zohren, Xun Lin, Katharina Modelska, Jennifer Sugg, Joyce Leta Steinberg, Maha H. A. Hussain
Journal: Journal of Clinical Oncology (2020)

5515 Background: PROSPER previously demonstrated a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) (hazard ratio [HR] 0.29; 95% CI 0.24-0.35; P &lt; .001) in men with nmCRPC and rapidly rising prostate-specific antigen (PSA) who received ENZA. When first reported, OS was immature with only 165 of 596 (28%) prespecified deaths. Here we report results from the final OS analysis. Methods: Men with nmCRPC, PSA doubling time ≤ 10 mo, and PSA ≥ 2 ng/mL at screening continued androgen deprivation therapy (ADT) and were randomized 2:1 to ENZA 160 mg or PBO. OS treatment effect was assessed using a group sequential testing procedure with O’Brien-Fleming-type alpha spending function ( P ≤ .021 required for statistical significance). Medians were estimated using the Kaplan-Meier method; 95% CIs using a stratified Cox regression model. Results: As of Oct 15, 2019 (median follow-up ≈ 48 mo), there were 466 deaths (288 [30.9%] and 178 [38.0%] in the ENZA and PBO arms, respectively). ENZA significantly prolonged OS compared with PBO (HR 0.73; 95% CI 0.61-0.89; P = .0011). Median OS was 67.0 mo (95% CI 64.0-not reached) in the ENZA arm and 56.3 mo (95% CI 54.4-63.0) in the PBO arm. Subsequent antineoplastic therapies were initiated after treatment discontinuation by 310 (33%) men in the ENZA arm vs 303 (65%) in the PBO arm. Median duration of treatment was 33.9 mo vs 14.2 mo with ENZA vs PBO, respectively. Grade ≥ 3 adverse events (AEs) were reported by 48% of men in the ENZA arm vs 27% in the PBO arm (16% vs 6% were drug related, respectively). AEs with event rates per 100 patient-yr that were ≥ 2 points higher with ENZA vs PBO were falls (9 vs 4), fatigue (14 vs 12), and hypertension (7 vs 5). Conclusions: ENZA treatment resulted in a statistically significant 27% reduced risk of death compared with PBO, demonstrating that initiation of ENZA + ADT before the onset of detectable metastasis improves OS in men with CRPC and rapidly rising PSA. This OS benefit ensues despite crossover from the PBO arm to ENZA and higher rates of subsequent antineoplastic therapies in men from the PBO arm. Safety was consistent with previous clinical trials. This final OS analysis from PROSPER provides prospective validation of MFS as a potential surrogate endpoint for OS in nmCRPC and supports the continued use of ENZA + ADT as a standard of care in men with nmCRPC and rapidly rising PSA. Clinical trial information: NCT02003924 .
Primary mediastinal large B-cell lymphoma: clinical analysis of 19 cases
Authors: Jie Sun, Hua Ren, Ze-jian Li
Journal: BMJ (2010)

Objective To study clinical manifestations, diagnosis, treatment, as well as effect of surgical operation, of primary mediastinal large B-cell lymphoma (PMBCL).Methods Data of 19 patients of PMBCL with complete clinical and pathological records hospitalized at Peking Union Medical College Hospital during 1998 to 2008 were retrospectively reviewed and analyzed.Kaplan-Meier method was used to estimate their survival time and survival rate in comparison of efficacy in those with surgical operation to those without it.Results Overall three-year survival rate was 54% for all the 19 patients, 55% for those with surgical operation and 54% without it, respectively, with an average survival time of 44 months, 44 months for those with surgical operation and 42 months without it, respectively, but not reaching at statistical significance.Symptoms of superior vena cava syndrome in five cases at admission relieved immediately after surgical operation, but symptoms of superior vena cava syndrome in three of nine cases in non-surgical group relieved gradually one to three weeks after chemotherapy.Conclusions Surgical operation has no significant effect on survival in patients with PMBCL, but it can relieve syndrome of superior vena cava syndrome and provide accurate pathological diagnosis.

Key words: 
Mediastinal neolasms;  Lymphoma,large-cell;  Diagnosis;  Kaplan-Meiers estimate
C-Peptide Levels in Subjects Followed Longitudinally Before and After Type 1 Diabetes Diagnosis in TrialNet
Authors: Magdalena M. Bogun, Brian N. Bundy, Robin S. Goland, Carla J. Greenbaum
Journal: Diabetes Care (2020)

OBJECTIVE Insulin secretion declines rapidly after diagnosis of type 1 diabetes, followed by a slower rate of change. Previous studies have demonstrated that the C-peptide decline begins before the clinical diagnosis. Changes in insulin secretion in the same individuals studied from preclinical stages through and after clinical diagnosis have not been previously reported. RESEARCH DESIGN AND METHODS Antibody-positive relatives undergo sequential oral glucose tolerance testing (OGTT) as part of TrialNet’s Pathway to Prevention study and continue both OGTT and mixed-meal tolerance testing (MMTT) as part of the Long-term Investigational Follow-up in TrialNet study if they develop type 1 diabetes. We analyzed glucose and C-peptide data obtained from 80 TrialNet subjects who had OGTT before and after clinical diagnosis. Separately, we compared C-peptide response to OGTT and MMTT in 127 participants after diagnosis. RESULTS C-peptide did not change significantly until 6 months before the clinical diagnosis of type 1 diabetes and continued to decline postdiagnosis, and the rates of decline for the first 6 months postdiagnosis were similar to the 6 months prediagnosis. There were no significant differences in MMTT and OGTT C-peptide responses in paired tests postdiagnosis. CONCLUSIONS This is the first analysis of C-peptide levels in longitudinally monitored patients with type 1 diabetes studied from before diagnosis and continuing to the postdiagnosis period. These data highlight the discordant timing between accelerated β-cell dysfunction and the current glucose thresholds for clinical diagnosis. To preserve β-cell function, disease-modifying therapy should start at or before the acute decline in C-peptide.
David Oliver: Covid-19 has highlighted the NHS’s strengths and weaknesses
Authors: David Oliver
Journal: BMJ (2020)

Those of us involved daily in NHS machinations and policy have long been aware of the service’s strengths and weaknesses, well before they were stress tested to new levels by the covid-19 pandemic. But issues that were hiding in plain sight are now in the spotlight, front and centre.

Covid-19 has held up a mirror to our culture, structure, and system resilience. The selflessness and commitment on show among NHS staff have been astonishing. We don’t work in war zones, and although our physical and mental wellbeing are often at long term risk from the job under normal circumstances, this is the first …
Ulcerative colitis with cerebral venous sinus thrombosis: a case report and literature review
Authors: Qiu Han, Bin Ye, Ying Zhao
Journal: BMJ (2016)

颅内静脉窦血栓是一种缺血性脑血管病，发生率低，缺乏特异临床表现，容易误诊、漏诊。颅内静脉窦血栓常见病因为脱水、妊娠、产褥期、口服避孕药、颅面部及全身感染等。溃疡性结肠炎导致颅内静脉窦血栓少见。报道我院1例溃疡性结肠炎并颅内静脉窦血栓患者的临床资料。
Endoscopic treatment of intramural fistula and mucosal tear after peroral endoscopic myotomy
Authors: Pietro Familiari, Rosario Landi, Francesca Mangiola, Camilla Vita, Ivo Boskoski, Andrea Tringali, Guido Costamagna
Journal: Endoscopy (2020)

Peroral endoscopic myotomy (POEM) is a safe procedure, with few reported adverse events [1] [2] [3]. The integrity of the mucosal flap at the end of the procedure is crucial to prevent leakages and infections. We report on a rare complication after POEM.
Precise early detection of gastric cancer and blood cell circuit.
Authors: Oleg Kshivets
Journal: Journal of Clinical Oncology (2020)

e16512 Background: Significance of blood cell circuit in terms of early detection of gastric cancer (GC) was investigated. Methods: In trial (1975-2020) consecutive cases after surgery, monitored 136 GC patients (GCP) (m = 90, f = 46; distal gastrectomies = 95, proximal gastrectomies = 34, total gastrectomies = 7) with pathologic stage IA (tumor size = 1.81±0.70 cm; adenocarcinoma = 136; T1N0M0 = 136; G1 = 67, G2 = 26, G3 = 43, 5-year survival = 100%) and 120 healthy donors (HD) (m = 69, f = 51) were reviewed. Variables selected for study were input levels of blood cell circuit, sex, age, TNMG. Differences between groups were evaluated using discriminant analysis, clustering, nonlinear estimation, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing. Results: It was revealed that early detection of GC from HD (n = 256) significantly depended on: leucocytes (abs, total), segmented neutrophils (%, abs, total), lymphocytes (%), monocytes (%, abs, total), stick neutrophils (%, abs, total), eosinophils (%, abs, total) (P = 0.007-0.000). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships of early detection of GC and lymphocytes (rank = 1), segmented neutrophils (rank = 2), monocytes (3), stick neutrophils (4), leucocytes (5), eosinophils (6). Correct detection of early GCP was 100% by neural networks computing (error = 0.000; area under ROC curve = 1.0). Conclusions: Early detection of GC from HD significantly depended on blood cell circuit.