tbuckley/cabot-search huggingface dataset:
Access to breast/ovarian genetic testing: 20 years of a multidisciplinary program.
Authors: Fatima H Vaz, Teresa Duarte, Pedro Teixeira, Rosario Sepulveda, Pedro Louro, Paula Rodrigues, Irina Coelho, Joana Parreira, Fátima Rodrigues, Ana Clara, Ana Luis, Isalia Miguel, Sandra Bento, Juliette Dupont, Patricia Machado, Sidonia Santos, Sofia Fragoso
Journal: Journal of Clinical Oncology (2020)

e14015 Background: After institutional and ethical review, a multidisciplinary Breast/Ovarian Cancer Family Risk program started in January 2000. Core team included medical oncologists, molecular biologists, medical geneticists and specialized nurses. Besides access to genetic testing (GT), predictive risk analysis and tailored surveillance plans were provided for women without criteria for GT, and carriers of germline pathogenic/likely pathogenic variants (PV/LPV) were included in prospective follow up. Methods: Descriptive statistics concerning patients (pts), medical visits and genetic tests performed under the program from January 2000-December 2019. Results:A total of 28400 medical appointments (including multidisciplinary meetings with radiology, breast and plastic surgery and gynecology) were performed for 10100 pts: 9281 women (92%) and 819 men (8%), with an average of 46,0 years (45,6 and 51,1 respectively). Most pts were referred from our cancer center or were invited for cascade testing (8044, 79,6%), although we accepted referrals from external health services (2056 pts). GT: 5665 tests performed (4454 for index pts (IP) and 1211 for family relatives); 3170 (71%) IP consented only in BRCA1/2 and 1284 IP (29%) in sequential/panel testing. Detection rate for IP testing was 12,5% [440 BRCA1/2; 118 Other Hereditary Syndromes (OSH)]. OHS IP: CHEK2(32), ATM(14), TP53(11), MUTYH(12), PALB2(10), RAD51D(10), RAD51C(9), BLM(5), BRIP1(4), RAD50 (4), PTEN(2), MSH2(2), MLH1(1) FAM175A(1), BARD1(1). Six- hundred and twenty-six IP with previous inconclusive results consented on panel testing and 62(9,9%) were diagnosed with a non- BRCA1/2 PV/LPV. Until June 2019, 915 BRCA1/2 pts were included in a registry for prospective follow up. Conclusions: our program has allowed for access to Breast/Ovarian GT and risk management in the National Health Service, for the past 20 years. Twenty per cent of all pts are referrals from external health services. The ever increasing challenges to the resources of the program include: new indications for GT, the increase in priority pts for GT due to more therapy options, risk dynamics in previous registered families, evolving molecular methodologies and the management of families with complex genetic variants. The growing number of pts, including men, led to a recent change in the label of the program (Breast/Ovarian/Prostate Cancer Family Risk) and new approaches to promote access of specific populations to GT (like telegenetics) are being tested.
RE-MIND study: A propensity score-based 1:1 matched comparison of tafasitamab + lenalidomide (L-MIND) versus lenalidomide monotherapy (real-world data) in transplant-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Grzegorz S. Nowakowski, Thomas David Rodgers, Dario Marino, Maurizio Frezzato, Anna Maria Barbui, Claudia Castellino, Erika Meli, Nathan Hale Fowler, Bruce A. Feinberg, Sascha Tillmanns, Stephan Parche, Guenter Fingerle-Rowson, Mark Winderlich, Sumeet Vijay Ambarkhane, Gilles A. Salles, Pier Luigi Zinzani
Journal: Journal of Clinical Oncology (2020)

8020 Background: Patients with R/R DLBCL ineligible for autologous stem cell transplant (ASCT) have a poor prognosis. In these patients, tafasitamab (anti-CD19 antibody) plus lenalidomide (LEN) has shown encouraging results in the open-label, single-arm, phase II L-MIND study (n = 81; NCT02399085). To evaluate the contribution of tafasitamab to the activity of this doublet, we conducted a global, real-world study of patients treated with LEN monotherapy (RE-MIND; NCT04150328). Here we present the primary analysis of a 1:1 patient-level matched comparison between the L-MIND and RE-MIND cohorts. Methods: Patients treated with LEN monotherapy for R/R DLBCL were enrolled in the observational, retrospective RE-MIND cohort. As in L-MIND, patients had 1–3 prior systemic therapies, including ≥1 CD20-targeting regimen; were aged ≥18 years; and were not eligible for ASCT. A 1:1 estimated propensity score (ePS) matching methodology ensured balancing of nine pre-specified baseline covariates. The primary analysis set, Matched Analysis Set 25 (MAS25), included patients who received a LEN starting dose of 25 mg/day. The primary endpoint was investigator-assessed best objective response rate (ORR). Key secondary endpoints included overall survival (OS) and complete response (CR) rate. Results: 490 patients were enrolled in RE-MIND across 58 centers in the US and Europe, of which 140 fulfilled the ePS matching criteria. The MAS25 included 76 patients each from the two cohorts. Baseline characteristics between cohorts were comparable. The primary endpoint was met with a significantly better ORR of 67.1% (95% CI: 55.4–77.5) for the L-MIND cohort versus 34.2% (95% CI: 23.7–46.0) for the RE-MIND cohort (odds ratio 3.89; 95% CI: 1.90–8.14; p &lt; 0.0001). The CR rate was 39.5% (95% CI: 28.4–51.4) in the L-MIND cohort and 13.2% (95% CI: 6.5–22.9) in the RE-MIND cohort. A significant difference in OS favored the L-MIND cohort (HR = 0.499; 95% CI: 0.317–0.785). ORR and CR outcomes in the RE-MIND cohort were similar to the published literature for LEN monotherapy in R/R DLBCL. Conclusions: Significantly better ORR, CR and OS indicate potential synergistic effects of the tafasitamab + LEN combination in ASCT-ineligible R/R DLBCL. ePS-based 1:1 matching allows robust estimation of the treatment effect of tafasitamab when added to LEN. RE-MIND demonstrates the utility of real-world data in interpreting non-randomized trials. Clinical trial information: NCT04150328 .
A phase II double-blind, randomized clinical trial assessing the tolerability of two different ratios of cannabis in patients with glioblastoma multiforme (GBM).
Authors: Judith Lacey, Janet Margaret Schloss, Justin Sinclair, Amie Steel, Mike Sughrue, Charles Teo, David Sibbritt
Journal: Journal of Clinical Oncology (2020)

2530 Background: Cannabis has been used for cancer-related symptoms but few trials have assessed quality of life or tolerability, and trials assessing tumour response or survival remain scarce. Treatment for recurrent glioblastoma (rGBM) remains palliative with poor prognosis. The tolerability of THC-containing cannabis products, and their effect on symptoms and quality of life in people with rGBM patients is poorly defined but is essential before efficacy trials can be conducted. Methods: We conducted a randomised double-blinded trial assessing the tolerability of two preparations of cannabis in 88 people with rGBM. The two preparations used different cannabidiol (CBD) to tetrahydrocannibidiol (THC) ratios; 1:1 (5.8mg/ml:5.6mg/ml) and 1:4 (3.8mg/ml:15mg/ml). Daily evening doses were individually monitored and titrated. Outcomes included disease response by FACT-Br, MRI imaging 12 weekly, blood pathology, NCI-CTC and clinical monitoring. Symptom assessments were performed 4 weekly for 12 weeks. Results: 921 people volunteered for screening across Australia, with 642 excluded, 92 recruited with 88 enrolled. 61 participants completed 12-week follow-up (attrition 30%). Both cannabis oils were well tolerated. Total FACT-Br was similar for both preparations, however, statistical significance was found for the physical section (p = 0.025) and functional (p = 0.014) identifying the 1:1 ratio as the more appropriate combination. Comparing groups to baseline, participants reported improvement of sleep (p = 0.009), improved energy (p = 0.015), and contentment with QoL (p = 0.006). Total cohort compared to baseline, participants reported improvement of sleep (p = 0.0001), pain (p = 0.046), nausea (p = 0.017), anxiety (p = 0.005) and seizure activity (p = 0.022). There were no major adverse events attributable to the cannabis with main side effects noted as dizziness, drowsiness, tiredness, and dry mouth. No abnormal blood pathology nor variance in NCI-CTCAE scores were observed. Conclusions: A single nightly dose of THC-containing cannabis was well tolerated in patients in both groups with rGBM and significantly improved sleep and functional wellbeing and QOL in a sample of patients compared to baseline. From this trial, the 1:1 ratio has been identified as the better tolerated product with suprerior symptom and QoL outcomes compared to the 1:4 product. Clinical trial information: ACTRN12617001287325 .
Partha Kar: Covid-19—time for parity in commissioning diabetes services
Authors: Partha Kar
Journal: BMJ (2020)

Recent data on the impact of covid-19 on people with diabetes has produced a range of responses.1 The data suggest that diabetes is an independent risk factor for mortality related to covid-19, with type 1 diabetes carrying a higher risk than type 2. The scientific community has tried to decipher the signals, and reactions in the diabetes community have ranged from relief to anxiety.

Overall, the data don’t present huge surprises, but some nuggets require further investigation. The fact that diabetes is a risk factor for a poor outcome with any infection is not a surprise per se. Splitting risks on the basis of type, although eyebrow raising to some, is again not fundamentally new. As any physiology or medical textbook will tell you, the basic tenets of types 1 and 2 diabetes …
DNA damage repair (DDR) gene mutations (mut) are predictors of response to platinum-based chemotherapy in advanced pancreatic cancer (PC) patients (pts).
Authors: Helena Verdaguer, Magda Guardiola-Fernandez, Francesco M Mancuso, Daniel Acosta, Elvira Buxó, Jorge Hernando, Marc Diez, Berta Laquente, Iosune Baraibar, Javier Ros, Alejandro Garcia, Judit Matito, Agatha Martin, Alexandre Sierra, Guillermo Villacampa, Cristina Molero, Josep M Miquel, Ana Vivancos, Rodrigo Dienstmann, Teresa Macarulla
Journal: Journal of Clinical Oncology (2020)

e16805 Background: Somatic DDR mut have been reported in close to 10% of PC samples. In this study we investigate their predictive value for response to platinum-based chemotherapy. Methods: Case-control study with pts deriving response to oxaliplatin-based treatment (partial or complete response at any line) [n = 30] versus no response (progression in first restaging at 1 st line) [n = 18]. An in-house NGS panel test of 420 genes was performed on tumor samples. DDR mut were classified in 2 subgroups: (a) functional BRCA1, BRCA2 or PALB2; and (b) any functional DDR gene mut, including those in (a). Results: 48 pts were included, median ages was 54.5 years (30-74), 29 male, 26 were diagnosed with stage IV, 36 pts (75%) received FOLFIRINOX and 37 received platinum-based chemotherapy as 1 st . line treatment. Prevalence of DDR mut are described in the table. Among responders, 3 tumors had BRCA2 mt, 3 BRCA1, 2 ATM, and 1 each with BRCA2 + MSH2, PALB2, PMS2, MUYTH, RECQL4 + MDC1. Among non-responders 1 tumor each had ATM, FANCD2 and BLM. Median progression-free survival (PFS) with oxaliplatin-based chemotherapy in pts with BRCA1, BRCA2 or PALB2 mut tumors was 21.7 months (95% CI 12.3-NA); among those with any DDR mt was 12.3 months (95% CI 9.13-NA); while in pts whose tumors had no DDR mut was 6.4 months (95% CI 3.07-13)(Log-rank P-value = 0.02 comparison subgroup [a] vs. others; P-value = 0.1 subgroup [b] vs. others). Conclusions: The subgroup of pts with PC whit tumors harboring DDR gene mut, particularly functional BRCA1, BRCA2 or PALB2, have higher response rate and longer PFS with oxaplatin-based chemotherapy. [Table: see text]
Landscape of immune-checkpoint inhibitors in hepatocellular carcinoma: A systematic review with meta-analysis.
Authors: Dmitrii Shek, Scott A. Read, Adnan Nagrial, Bo Gao, Golo Ahlenstiel
Journal: Journal of Clinical Oncology (2020)

e16632 Background: The WHO estimates that liver cancer will cause 1 million deaths by 2030. Hepatocellular carcinoma (HCC) is a primary liver malignancy causing 4.3% of all cancer deaths in 2019 in Australia. Kinase inhibitors are standard of care (SoC) for metastatic HCC with median overall survival (mOS) of &lt; 13 months. This meta-analysis primarily aimed to determine objective response rate (ORR) of immune-checkpoint inhibitors (ICIs) in advanced HCC. Methods: Potentially relevant clinical studies were identified through PUBMED, Scopus, ASCO and ESMO databases. Studies evaluating ICIs in patients with HCC and reporting efficacy outcomes were considered as eligible. Publication bias was assessed with Funnel plots. Data analysis was performed employing fixed and random effects model depending on study heterogeneity evaluating by I 2 statistic. STATA v16 software was used for all statistical considerations. Results: 12 single arm phase II/III studies and 2 randomized clinical trials on ICIs in HCC were included into this analysis. First-line ICI: Primary forest plot established the median ORR was 26.2% (95% CI 24.7 to 27.9) in patients treated with first line ICIs monotherapy; in comparison, ORR of current SoC sorafenib is 2-3% and lenvatinib 18.8%. Moreover, nivolumab resulted in 9.8 months of OS in Child-Pugh class B (CPB) patients, previously eligible only for supportive care due to a low efficacy of sorafenib (mOS &lt; 4.5 months). Second-line ICI: Secondary forest plot established that nivolumab at 1 mg/kg with ipilimumab 3 mg/kg Q3W resulted in mOS of 23 months with ORR of 32% in sorafenib-progressors. In comparison, current second line SoC regorafenib has mOS of 10.6 months and ORR of 17%. Conclusions: This meta-analysis suggests that ICIs may be superior (ORR) to SoC sorafenib in advanced HCC, particularly nivolumab. Secondly, nivolumab with ipilimumab were confirmed to provide higher OS in sorafenib progressors as compared to regorafenib. Of note, many of the studies included were only available in abstract form and final reporting is pending. Nevertheless, our results support higher efficacy of ICIs in HCC patients.
Detection of monosodium urate crystals with dual-energy CT in gout patients
Authors: Dong Tang, Xiaoman Wang, Le Qi, Dongmei Wang
Journal: BMJ (2019)

Objective
To evaluate the application of the dual-energy CT (DECT) in detection of monosodium urate (MSU) crystals in gout patients.


Methods
The imaging and clinical data of 101 patients with suspected gout were retrospectively analyzed, including 64 cases of clinically diagnosed gout (gout group) and 37 non-gout cases (non-gout group). The DECT examination was performed for 85 joints in gout group and 42 joints in non-joint group. The value of DECT in detection of MSU crystals was evaluated with receiver operating characteristic (ROC) curve.


Results
There were significant differences in gender (χ2=5.32, P=0.03) and blood uric acid levels (t=1.95, P=0.04) between gout and non-gout groups. The detection rate of MSU in gout group was significantly higher than that of non-gout group (χ2=30.52, P<0.001). The area under the ROC curve (AUC) of DECT in detection of was 0.74±0.05 (Mean±SE), 95%CI: 0.64-0.85. The sensitivity, specificity, positive predictive value and negative predictive value of the DECT in detection of gouty stone was 0.844, 0.703, 83.1% and 72.2%, respectively.


Conclusion
The dual-energy CT has high sensitivity, specificity and reliability for the detection and diagnosis of monosodium urate crystals in joints of gout patients.


Key words: 
Radiography, dual-energy scanned projection; Gout; Arthritis, gouty; Crystallization, uric acid
Clinicopathologic features and survival outcomes of signet cell carcinoma of the appendix: Analysis of the SEER database.
Authors: Kamelah Abushalha, Wa'el Tuqan, Sara Albagoush, Sawsan Abulaimoun, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2020)

e16147 Background: Signet ring cell carcinoma of the appendix (SRCCA) is an exceedingly rare tumor, and limited data are available on the characteristics and survival probabilities of this tumor. Methods: Surveillance, Epidemiology, and End Results (SEER) database was used to identify 527 patients diagnosed with SRCCA between 2000 and 2015. The database was used to examine demographic information. Survival analysis was made by Kaplan-Meier and compared by log-rank test. Cox proportional hazards model was adopted for prognostic variable evaluation. Results: The majority of SRCCA patients were female (63.9%) and white (83.8%), with a mean age at diagnosis of 56 years. Histologically; 60% of the tumors were of high grade (poorly-differentiated and undifferentiated). The majority of patients were diagnosed with metastatic disease (61.3%) and received surgical treatment (86.5%), with sub-total colectomy was the most common surgery performed (45.6%). Median overall survival was 26 months, with a cancer-specific survival at three-year and five-years of 39% and 18.4%, respectively. There was a 10-year difference in median survival time based on sex (females vs males; 23 vs 33 months respectively). On bivariate analysis; factors associated with significantly increased mortality (p &lt; 0.05), include increased age (HR 1.02), female gender (HR 1.33), AJCC T category (T4 compared to T0; HR 1.96), AJCC N category (N1 compared to N0; HR 1.9) and AJCC M category (M1 compared to M0: HR 2.62). Factors associated with improved survival (p &lt; 0.05) included treatment by surgical resection; total colectomy (HR 0.47) and sub-total colectomy (HR 0.45) . Conclusions: This is the largest study to date on SRCCA. Older white females are most commonly affected and often diagnosed at advanced stage and grade.
山东枣庄地区消化门诊肠易激综合征流行病学调查
Authors: 刘春安, 柴同海, 刘红军, 时均文, 王慎菊
Journal: BMJ (2004)

肠易激综合征(irritable bowel syndrome,IBS)是一种常见的功能性肠病,表现为腹痛、腹泻和便秘,或腹泻与便秘交替而不能用其他原因来解释.近年来其发病率似有逐渐增加趋势.2001年12月至2002年11月,我们对3 400例IBS患者进行了临床流行病学调查。
Diagnostic value of 3.0T dynamic contrast-enhanced MRI and diffusion weighted imaging for common parotid tumors
Authors: Dongyang Yu, Ben Shan, Yong Liu, Lei Han, Min Xu
Journal: BMJ (2018)

Thirty nine patients with pathologically confirmed parotid tumors, including 18 cases of pleomorphic adenomas, 12 cases of papillary cystadenoma lymphomatosum and 9 cases of malignant tumors, were enrolled in the study. Characteristics on routine MR image, diffusion weighted imaging (DWI), time-signal intensity curve (TIC) and apparent diffusion coefficient (ADC) value in different types of tumors were evaluated. There were significant differences in imaging features between benign and malignant tumors (P<0.01). The TIC types were A, B and C for pleomorphic adenomas, papillary cystadenoma lymphomatosum and malignant tumors, respectively. The mean ADC value of pleomorphic adenomas was significantly higher than that of papillary cystadenoma lymphomatosum and malignant tumors (P<0.01). No significant difference in ADC values between papillary cystadenoma lymphomatosum and malignant tumors was detected (P=0.73). The study indicates that MR plain scan combined with dynamic contrast enhanced MRI and DWI may be helpful in pre-operative differentiation of common parotid tumors.


Key words: 
Parotid neoplasms; Magnetic resonance imaging; Image enhancement, dynamic; Diffusion magnetic resonance imaging
A single institution experience of brain metastases and pancreatic adenocarcinoma: Patients' treatments and outcomes.
Authors: Etienne Gouton, Brice Chanez, Simon Launay, Elika Loir, Laurence Moureau-Zabotto, Olivier Turrini, Marine Gilabert
Journal: Journal of Clinical Oncology (2020)

e16737 Background: Brain metastases (BM) occur extremely rare in pancreatic adenocarcinoma (PDAC) and few data are available regarding those patients‘ care and outcomes. Methods: We performed a retrospective monocentric analysis of our database to identify patients (pts) diagnosed with PDAC and BM from July 1997 to December 2019. Results: 16 pts were eligible among 4900 pts diagnosed with PDAC in our institution (0.3%). Median age was 64 years (38.2-74.6) with 50% female. At diagnosis, 68.8% were metastatic including 27.3% with synchronous BM. About 1/3 pts had ≥ 2 lines of chemotherapy before BM. BM were discovered from neurological symptoms in 62% of cases and either with systematic brain CT/MRI or unknown in 19% for both. BM treatment was: surgery (25%), whole brain radiation therapy (RT) (43.8%), stereotactic RT (6.3%), radiosurgery (6.3%), best supportive care (BSC) or unknown (6.3%). At follow-up cutoff date (01/01/2020), most of pts were dead (75%), 2 were alive and 2 lost of follow-up. Mean interval between initial diagnosis and BM was 9.9 months (mths) (0-73). Median time to develop BM was different between pts with non-metastatic or metastatic disease at diagnosis: 16.3 mths (6.5-44) and 4.2 mths (0-36.1), respectively (HR = 0.43 (CI95: 0.14-1.09; p = 0.09)). Median overall survival (mOS) was 14.5 mths (1.6-80.2). Definitely, the non-metastatic group at diagnosis had better survival with mOS of 40.2 mths (24.7-80.2) compared to 6.5 mths (1.7-49.8) for the metastatic group (HR = 0.24 (CI95: 0,06-0,63; p = 0.012)). The median survival period after diagnosis of BM was only 3.4 mths (0.5-13.7). Pts who underwent BM surgery had better survival with a median survival from surgery of 5.5 months (4-13.7) compared to RT (0.8 mths (0.4-2)) or BSC (0.6 mths (0.5-5.9)). HR for surgery versus RT was 0.12 (CI95: 0.02-0.31; p = 0.003). After BM diagnosis, 43.8% of patients had a systemic chemotherapy, without objective response on BM. One interesting metastatic pt with BRCA1 mutation achieved a complete response (CR) after FOLFIRINOX. One BM occurred 2 years after diagnosis, was treated with surgery + RT but relapsed 4.5 mths later with new BM. Extra-cranial CR was persistent. This pt, still alive, had the longest survival period after diagnosis of BM (13.7 mths) and OS (49.8 months). Conclusions: To our knowledge, this is one of the largest cohort reported of BM in PDAC. Very few cases exist to guide therapy. Surgery appears to be the best treatment for BM, when feasible. Further investigations are still needed to understand the pathogenicity of BM in pancreatic cancer.
预防后尿道断裂手术治疗后勃起功能障碍的探讨
Authors: 夏永强, 侯绍瑜, 范先明, 王鹏飞, 张敏
Journal: BMJ (2007)

后尿道断裂引起的勃起功能障碍(ED)发生率为2.6%～75.0%[1-2].本组自1993年8月至2005年7月,对54例后尿道断裂患者分别行3种改良尿道会师术,降低了ED发生率.报告如下。
从TRIP项目探索优化社区慢病防控效果的可行性途径
Authors: 朱慧楠, 王桂云, 宋娜娜, 蒋捷, 霍勇
Journal: BMJ (2012)

随着人们生活方式的改变和社会人口老龄化进程的加速,疾病的流行模式从传染性疾病转向慢性非传染性疾病.在医务工作者的不断实践和探索中,各种科研成果、循证医学证据、指南和共识相继问世,期望能在最大程度上延缓疾病的进展,预防合并症的发生,尽可能使最广大范围患者获益.而目前临床工作中,存在着医务人员对循证医学证据、指南缺乏认识和重视,慢性病管理不够规范,患者教育缺乏应有的力度等问题,科研成果转化为使广大人群获益的愿望远未能得以实现,如何将医学成果落实到病人,是我们面临的一个重要课题.卫生部医政司和中国医师协会牵头的“医疗质量万里行——降压在行动”(TRIP)项目是一项有益的尝试。
Clinical research progress on type 2 myocardial infarction
Authors: Guangqiang Wang
Journal: BMJ (2018)

Type 2 myocardial infarction is an important part in all types of myocardial infarction, with the characteristics of high incidence, varied clinical manifestations and high mortality. For type 2 myocardial infarction, the pathophysiological mechanism is not fully clear yet and the curative efficacy is not definite. This article reviews the recent clinical research progress on type 2 myocardial infarction.


Key words: 
Myocardial infarction