tbuckley/cabot-search huggingface dataset:
Prevalence of pathogenic non-<i>BRCA</i>1/2 gene variants in patients with suspected hereditary breast and ovarian cancer at a referral hospital in northeastern Brazil.
Authors: Rosane Oliveira Sant'Ana, Clarissa Gondim Picanço-Albuquerque, Isabelle Joyce de Lima Silva-Fernandes, Paulo Goberlanio de Barros Silva, Maria Júlia Barbosa Bezerra, Maria Claudia dos Santos Luciano, Marcos Venício Alves Lima
Journal: Journal of Clinical Oncology (2020)

e13602 Background: Breast cancer (BC) is associated with several hereditary syndromes (HS). Patients with clinical criteria for hereditary breast and ovarian cancer (HBOC) should be evaluated for the presence of pathogenic BRCA1/2 variants, although the absence of BRCA1/2 variants does not rule out HS. The purpose of this study was to evaluate the prevalence of pathogenic non- BRCA1/2 variants in patients with suspected HBOC. Methods: Suspected HBOC (NCCN criteria) patients (n = 267) from a Northeastern Brazilian referral cancer hospital were submitted to NGS 31-gene painel. Individuals testing negative for BRCA1/2 mutation (n = 210) remained in the present presentation. Data were analized by the chi-squared test and Fisher’s test ( p&lt; 0.05; SPSS 20.0). Results: Pathogenic/likely pathogenic (P/LP) non- BRCA1/2 variants were detected in 13.3% (n = 28/210) of the patients, all of whom had BC. The most prevalent variant was PALB2 (31%), followed by ATM and MUTYH (14.2%), and TP53 and PMS2 (10.7%). Among these patients 10.7% (n = 3/28) had triple negative tumors. Other gene variants ( BARD1, CHEK2, MLH1, MSH2, PMS1 and XRCC2) were observed at lower frequencies (3.5% each). DNA mismatch repair (MMR)/Lynch syndrome (LS) mutated genes were identified in 4/24 patients with BC. Rare microdeletions were identified in PALB2 (chr16:23652431-23652678 [exons 1-10] and TP53 (chr17:7.573.927-7.579.891 [exons 2-10]) , to our knowledge for the first time in the medical literature (ClinVar). In addition, one patient displayed a double pathogenic variant in ATM (c.67C &gt; T: p.[Arg23*]) and PALB2 (chr16:23652431-23652678 [exons 1-10]). Patients with and without P/LP did not differ with regard to clinical-pathological parameters or therapeutic profile. Conclusions: Patients with suspected HBOC should be evaluated for non- BRCA1/2 variants, including MMR. We also suggest considering BC among the malignancies associated with LS.
Institutional outcomes of whole brain radiotherapy for metastatic melanoma brain metastases.
Authors: Cecilia Jiang, Jeffrey M. Switchenko, David H. Lawson, Melinda Lynne Yushak, Mohammad Khurram Khan
Journal: Journal of Clinical Oncology (2020)

e14504 Background: The management of melanoma with multiple brain metastases (MBM) is complex given improvements in targeted agents, immunotherapy, and radiotherapy. Whole brain radiation therapy (WBRT) is a radiotherapy technique with limited outcomes data. We report our institutional outcomes for MBM patients receiving WBRT and assess whether certain clinical factors impact prognosis. Methods: A retrospective review of a single institution database was performed. Patients diagnosed with MBM from 2000-2018 treated with WBRT, with or without systemic treatments, were included. Post-WBRT brain MRI scans were assessed at timed intervals for radiographic response. Clinical and treatment variables associated with overall survival (OS), progression free survival (PFS), intracranial failure-free survival (IFFS), and local failure-free survival (LFFS) were assessed. Data was collected on radiation-induced side effects, including radionecrosis, hemorrhage, and memory deficits. Results: Of 1347 patients treated with WBRT from 2000-2018, 63 patients had melanoma. 69% of patients had ≥5 brain metastases at the time of WBRT, 68% had extracranial disease, and 71% received steroids during their overall treatment course. Most had received previous therapies and had WBRT as a last resort. Median WBRT dose was 30 Gray over 10 fractions. Median follow-up was 4.0 months. Six-month OS, PFS, IFFS, and LFFS were 52.7%, 20.4%, 52.3%, and 43%. Median OS, PFS, IFFS, and LFFS were 7.0 months, 2.2 months, 6.1 months, and 4.9 months. Performance status correlated with OS on univariate and multivariate analysis. BRAFi was the only systemic therapy to significantly impact OS on univariate analysis (HR 0.24, 95% CI 0.07-0.79, p = 0.019), although this was not seen on multivariate analysis. There was a 19% rate of memory deficits. Among the 46 patients with post-WBRT brain scans, 17% had radionecrosis and 28% had intralesional hemorrhage. Not all radiographically noted radiotoxicities were clinically significant, although hemorrhage decreased IFFS on both univariate and multivariate analysis. Conclusions: Outcomes for MBM patients receiving WBRT indicate that WBRT remains a worthy option to control intracranial disease. Treatment-related effects such as hemorrhage, necrosis, or cognitive changes are considerations. Median PFS and IFFS suggest that systemic disease control continues to be the greater issue. The role of WBRT should be re-evaluated in the modern era, which features advanced imaging detection ability, newer systemic agents, and improved steroid avoidance strategies.
Attach importance to anxiety and depressive symptoms in medical disorders
Authors: Zhu Suoyu
Journal: BMJ (2016)

在综合医院，躯体疾病与焦虑、抑郁常常共现。一方面，焦虑、抑郁可能是躯体疾病的早期症状；另一方面，躯体症状可成为主诉而掩盖焦虑、抑郁，而躯体疾病伴发的焦虑、抑郁常常对躯体疾病本身产生诸多影响。临床医师对躯体疾病伴发的焦虑、抑郁需采取综合干预措施。
Safety and preliminary efficacy of rogaratinib in combination with atezolizumab in a phase Ib/II study (FORT-2) of first-line treatment in cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (UC) and <i>FGFR</i> mRNA overexpression.
Authors: Jonathan E. Rosenberg, Pablo Gajate, Rafael Morales-Barrera, Jae-Lyun Lee, Andrea Necchi, Nicolas Penel, Vittorina Zagonel, Mitchell Robert Sierecki, Ana-Maria Piciu, Peter Ellinghaus, Randy F. Sweis
Journal: Journal of Clinical Oncology (2020)

5014 Background: Programmed cell-death ligand 1 (PD-L1) overexpression is a mechanism for immune escape in UC. Rogaratinib, an oral pan-FGFR1-4 inhibitor, showed promising efficacy in a Phase I study in pts with solid tumors, including UC, with FGFR1-3 mRNA overexpression (Schuler et al. Lancet Oncol 2019). This Phase Ib/II study is evaluating rogaratinib in combination with atezolizumab, a PD-L1 inhibitor, in pts with FGFR-positive, locally advanced or metastatic UC (NCT03473756). We report results from the Phase Ib study. Methods: Cisplatin-ineligible pts with untreated metastatic UC were eligible if high FGFR1 or 3 mRNA was detected by RNA in situ hybridization of archival tissue (RNAscope). Pts were treated at a starting dose of rogaratinib 800 mg p.o. BID and atezolizumab 1200 mg i.v. on day 1 (21-day cycle). Primary objectives were safety, tolerability, and determination of the recommended Phase II dose. Results: 27 pts were treated (rogaratinib 800 mg + atezolizumab, n = 11; rogaratinib 600 mg + atezolizumab, n = 16); 85% were male, median age was 72 years (range 47-83), 37% had an ECOG PS of 1, and 96% had negative/low PD-L1 expression. Most common treatment-emergent adverse events (TEAEs) were diarrhea (63%), hyperphosphatemia (44%), and urinary tract infection (37%). Dose interruption/reduction due to AEs occurred in 67%/37% of pts; TEAEs lead to discontinuation in 45.5% (800 mg) and 12.5% (600 mg). Most common grade 3/4 TEAEs were increased lipase without pancreatitis (11%), rash, and increased alanine aminotransferase (7% each). Rogaratinib-related unique TEAEs were hyperphosphatemia (44%) and retinal pigment epithelium detachment (4%). The maximum tolerated dose (MTD) was rogaratinib 600 mg BID based on lower overall frequency of AEs. Of 23 evaluable pts (600 mg, n = 13; 800 mg, n = 10), overall 9 (39%) pts had an objective response (RECIST v1.1); 3 (13%) pts had a complete response (600 mg: 2/13 pts), 6 (26%) pts had a partial response (600 mg: 5/13 pts), and 6 (26%) pts had stable disease (600 mg: 4/13 pts). Conclusions: Rogaratinib with atezolizumab showed promising efficacy and safety in cisplatin-ineligible pts with tumor FGFR1 or 3 mRNA-positive UC, with nearly all pts demonstrating low or negative PD-L1 expression. Pts are being enrolled at the MTD of rogaratinib 600 mg BID plus atezolizumab. Clinical trial information: NCT03473756 .
Prostate specific antigen testing as disease surveillance and monitoring five years after definitive therapy for localized prostate cancer.
Authors: Ibrahim M. Asiri, Ewan Kemar Cobran
Journal: Journal of Clinical Oncology (2020)

e17602 Background: The National Comprehensive Cancer Network, in 2007, recommends prostate specific antigen (PSA) testing every 6-12 months for the first 5 years following definitive treatment for localized prostate cancer. We compared guideline-concordant PSA testing, as disease surveillance and monitoring, in African-American (AA) and Caucasian (CA) men 5-years after definitive therapy. Methods: A total of 19,377 CA and 1,995 AA men from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database diagnosed with prostate cancer and received definitive treatments from 2007 through 2016 were included. Multivariate log-binomial regression model were used to examine the effect of demographic and clinical characteristics on the likelihood of not receiving at least one PSA surveillance test annually for the first 5 years following definitive treatment. Results: Overall, receipt of surveillance testing and monitoring was high, with 97% of CA men and 94% of AA men receiving at least one test the first year after treatment and approximately 81% of CA men and 77% of AA men receiving at least one test in the fifth year after treatment. Risk of not receiving a test in AA men declined with time compared to CA men, in the first year (Relative Risk [RR], 1.68, 95% CI, 1.37-2.07) and the fifth year (RR, 1.07, 95% CI, 0.98-1.18) since treatment. Further, non-married men and men with intermediate risk had a higher risk of not receiving a surveillance test. Conclusions: Most men received guideline-concordant PSA testing 5-years after definitive therapy. The decline in PSA surveillance overtime reflects the need for continued long-term survivorship care planning and coordination. [Table: see text]
Effect of 5As model based on integrated hospital and community team management on self-management behavior in stroke high-risk population
Authors: Qian Wang, Xiaoci He, Xiao Zhi, Peng Wu, Yanfeng Wang, Kepin Sun, Ting Zhang, Rongying Wang
Journal: BMJ (2018)

Objective
To evaluate the effect of5As(ask, advice, assess, assist, arrange) model based on thetwo-in-one teammanagement (integrated hospital and community health service center management team) on the self-management behavior in stroke high-risk population.


Method
A stroke risk screening was conducted among 1 196 residents aged ≥40 years selected by cluster sampling in a community of Shijiazhuang city from March 2016 to March 2017, and 218 high-risk individuals were identified. The high risk individuals were randomly divided into intervention group and control group. The control group received routine health instruction, the intervention group was managed bytwo-in-one teamwith 5As model. Stroke prevention knowledge questionnaire and self-evaluation scale were applied for evaluation before and after intervention.


Results
Before intervention, scores of the stroke prevention knowledge and self-management behavior in the intervention group and the control group were (21.6±4.7) and (130.8±6.4) points, (20.4±5.0) and (131.4±6.3) points, respectively (t=1.79, P=0.08; t=0.67, P=0.50). After intervention, the scores of prevention knowledge and self-management behavior in the intervention group were higher than those in the control group [(30.5±5.1) vs. (21.7±6.0) points, t=16.83, P=0.00; (158.3±19.0) vs. (135.6±20.0)points, t=7.85, P=0.00].


Conclusion
The 5As intervention model based on the two-in-one team management can improve stroke prevention knowledge and self-management behavior among stroke high-risk individuals in the community.


Key words: 
Patient Care management; Community health services; Stroke; Primary prevention
重症急性胰腺炎并发胃内霉菌感染一例
Authors: 张建芳, 杜荣莲
Journal: BMJ (2009)

患者女,39岁.因中上腹痛伴呕吐3 h于2006年6月11日入院.入院前1 h进食高脂食物后出现中上腹部疼痛,向腰背部放射,伴恶心、呕吐数次,为胃内容物,腹痛呈持续性胀痛,阵发性加重,无发热、腹泻。
Clinical features of 11 cases of renal cortical abscess
Authors: 蔡涛, 潘曙光
Journal: BMJ (2007)

目的 探讨肾皮质脓肿的诊断与治疗方法,减少误诊率.方法 对1991年3月至2003年6月诊治的11例肾皮质脓肿患者的临床资料进行回顾性分析.结果 11例患者中,治疗前确诊9例(82%),7例行脓肿切开引流术治疗后痊愈,1例经皮肾脓肿穿刺因引流不畅后改脓肿切开引流术治疗后痊愈,静脉应用抗生素治愈1例;2例(18%)误诊为肾癌,行根治性肾切除术.结论 肾皮质脓肿的确诊需结合临床表现、实验室检查、影像学检查进行综合分析.脓肿切开引流术是主要的治疗方法。
Application of nail-bed lengthening for fingertip injuries: a report of 36 cases
Authors: Gong-lin Zhang
Journal: BMJ (2008)

Objective To summarize clinical experience in application of nail-bed lengthening operation for fingertip injuries.Methods From September 2003 to May 2007,36 patients (25 men and 11 women) aged 16 -45 years (26 in average) with nail defect by fingertip injuries underwent reconstruction operation using nail-bed lengthening at Orthopaedics and Traumatology Hospital of Taizhou,with the thumb involved in 15 cases,the index finger in 10 cases,the middle finger in eight eases and the ring finger in three case.A skin rectangle with thickness of 2 - 3 mm and width as that of the nail was resected at the skin edge 5 -6 mm distant from the epenychium,without damage to underlying subcutaneous vascular network, and U-shape skin flap was delicately slid proximally with its ends sutured.Results All surgical operations for nail lengthening were uneventful and clinically satisfactory,and the appearance of the thumb or other fingers was good during follow-up for six months to three years (19 months in average).Conclusions Nail lengthening for fingertip injuries with nail defect is a simple and effective surgical operation which could improve the appearance of the thumb and other fingers.

Key words: 
Nail diseases; Reconstructive surgical procedures; Skin transplantation
Good's syndrome with pulmonary lesions: 3 case reports with literature review
Authors: Ran Li, Yanliang Ma, Jing'an Wei, Fang Han, Zhaolong Cao
Journal: BMJ (2014)

Three cases of Good's syndrome with pulmonary lesions in our hospital from June 1, 2010 to June 1, 2013 were retrospective analyzed and relevant literatures were reviewed. Clinical manifestation, characteristics of pulmonary lesions, diagnosis and treatment were summarized. Abnormality of lymphocyte subpopulation to varying degrees in peripheral blood was detected in all 3 cases. However none showed hypogammaglobulinemia. If thymoma patients developed recurrent respiratory infections, Good's syndrome should be considered. Pulmonary manifestations of Good's syndrome have lesions similar to those of diffuse panbronchiolitis or interstitial lung disease. Early screening of immune competency and treatment for immunodeficiency may improve prognosis.


Key words: 
Good's syndrome; Lung diseases
Superior therapy response predictions for patients with pancreatic cancer (PDAC) using Cellworks Singula: MyCare-009-05.
Authors: Gordon Taylor Moffat, Drew Watson, Shweta Kapoor, Kunal Ghosh Ghosh Roy, Rajan Parashar, Aftab Alam, Aktar Alam, Anuj Tyagi, Divya Singh, Pallavi Kumari, Nikita Ray Choudhary, Neha Gupta, Preethi Elangovan, Rema Mandal, Vijayashree P S, Prashant Nair, Zakir Husain, Diwyanshu Sahu, Nirjhar Mundkur, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2020)

e16766 Background: Current therapy for PDAC is modestly effective. Therapy selection guidelines are typically limited to single aberrations and ignore relevant patient-specific omics. These alterations create patient-specific resistance pathways that cancer cells use to resist one-mutation one-drug Physician Choice therapies. Singula™ utilizes the novel Cellworks Omics Biology Model (CBM), which predicts patient-specific biomarker and phenotype response of a personalized diseased cell to drug agents, radiation and cell signaling. We test the hypothesis that Singula is a more accurate predictor of patient-specific therapy response to targeted agents compared to Physician Choice. Methods: The performance of the Singula Classifier of patient therapy response was evaluated in an independent retrospective cohort of N = 52 Stage I - IV PDAC patients aged 35-85, whose omics data were included in TCGA and ICGC. The accuracy of Singula was compared to the accuracy of prescribed therapies and clinical outcomes. Comparisons in the accuracy were enabled using McNemar’s test to account for the correlation between Singula and physician recommendations. Logistic regression was used to model complete response (CR) as a function of age, prescribed therapies, and Singula against non-response (NR). Likelihood ratio tests were performed to assess if Singula provides predictive information beyond prescribed therapy and age alone. Similar analyses were performed for progression-free survival (PFS) and overall survival (OS) using proportional hazards regression. Results: Singula is a superior predictor of CR compared to Physician Choice (McNemar’s χ 2 = 26.0, p-value &lt; 0.0001), with an overall accuracy of 94.2% (84.1%, 98.8%) compared to 40.4% (27.0%, 54.9%) for Physician Choice. In regressions, Singula (p = 0.0023) remained a significant predictor of CR, but prescribed therapy (p = 0.3885) and age (p = 0.1148) were nonsignificant. Singula was also the only significant predictor of PFS (p = 0.0002) and OS (p = 0.0096). For all 28 true negatives, alternative therapy selections with predicted response were generated. Conclusions: Singula is a superior predictor of PDAC response to therapy compared to Physician Choice. The Singula report can validate therapy selection decision, potentially increasing median PFS and OS and provides alternative therapy selections for non-responders. Prospective validation is needed. [Table: see text]
Effect of first-line spartalizumab + dabrafenib + trametinib on immunosuppressive features detected in peripheral blood and clinical outcome in patients (pts) with advanced BRAF V600–mutant melanoma.
Authors: Reinhard Dummer, Kelly Biette, Daniel Gusenleitner, Radha Ramesh, Celeste Lebbe, Victoria Atkinson, Mario Mandalà, Paul D. Nathan, Ana Arance, Erika Richtig, Naoya Yamazaki, Caroline Robert, Dirk Schadendorf, Hussein Abdul-Hassan Tawbi, Paolo Antonio Ascierto, Antoni Ribas, Keith Flaherty, Eduard Gasal, Jan C. Brase, Georgina V. Long
Journal: Journal of Clinical Oncology (2020)

10034 Background: Spartalizumab + dabrafenib + trametinib has previously shown a high response rate of 78% (28 of 36 pts), with a complete response (CR) rate of 42%. A correlative analysis of gene expression signatures (GES)/pathways using whole-transcriptome RNA-seq data from tissue showed that pts with a CR had significantly lower expression levels of immunosuppressive factors in the tumor microenvironment (TME) at baseline (BL). Here we analyze BL peripheral blood markers in the same cohort of pts to assess whether liquid markers can also predict response and clinical outcome to spartalizumab + dabrafenib + trametinib. Methods: The Phase III COMBI-i study (NCT02967692) is evaluating spartalizumab + dabrafenib + trametinib in pts with previously untreated BRAF V600–mutant unresectable or metastatic melanoma. In parts 1 (safety run-in; n = 9) and 2 (biomarker cohort; n = 27), blood and tissue samples were collected at BL, on treatment after 2-3 wk and 8-12 wk, and at disease progression. Lactate dehydrogenase (LDH) and other blood-based markers (including cytokine profiling [n = 45] and blood RNA-seq [114 signatures]) were assessed in all 36 pts. Pts were divided into 2 groups of 24 and 12 pts based on progression-free survival (PFS) of &gt; 1 or &lt; 1 y. Results: In addition to LDH, previously described blood markers such as neutrophil to lymphocyte ratio (NLR) and plasma IL-8 were identified among other neutrophil and immunosuppressive features as top candidates associated with PFS &gt; 1 y. Low plasma IL-8 levels were also associated with CR, and multivariate models suggested that IL-8 may add independent predictive value to LDH and NLR for PFS &gt; 1 y and CR. Pts with high IL-8 levels in the circulation were characterized by high neutrophil chemokine signaling (ρ = 0.553) and high neutrophil markers (ρ = 0.466) in the tumor as measured by RNA-seq GES levels. We observed a decrease in plasma IL-8 levels from BL upon treatment with spartalizumab + dabrafenib + trametinib. Conclusions: Our peripheral blood marker analysis confirmed recent findings from tissue samples that intratumoral immunosuppressive features may preclude a CR and are associated with poor outcomes. High BL plasma IL-8 levels may be associated with an immunosuppressive TME. Further validation is warranted; the randomized placebo-controlled part 3 of COMBI-i is ongoing. Clinical trial information: NCT02967692.
Clinical features of patients with bronchiectasis of different types
Authors: Weili Sheng, Yongxiang Zhang, Fengxian Yin, Ying Zhao, Yanan Liu, Tao Yang, Jianyong Liao
Journal: BMJ (2018)

Objective
To investigate the clinical features of patients with bronchiectasis of different types.


Methods
One hundred and twenty two patients with bronchiectasis at stable stage were recruited from January 2014 to July 2015. The patients were typed as cystic bronchiectasis (n=45) or non-cystic bronchiectasis (n=77) by high resolution CT (HRCT), expectoration bronchiectasis (n=80) or dry brochiectasis (n=42) by clinical symptoms, bacterial colonization (n=42) or non-bacterial colonization (n=80) by sputum culture. The modified British Medical Research Council (mMRC) dyspnea scale, Leicester Cough Questionnaire (LCQ), St George′s Respiratory Questionnaire (SGRQ) and pulmonary function test were used to assess the clinical features, and the episodes of exacerbations and hospitalization, and mortality during 1-year follow-up were documented.


Results
mMRC dyspnea scale(1.90±0.94 vs. 2.90±1.09, t=-5.040), LCQ (16.20±4.60 vs. 11.20±2.20, t=8.114), SGRQ (36.80±13.10 vs. 52.06±22.10, t=-4.780), FEV1% pred (68.45±26.50 vs. 52.22±20.60, t=3.458), FVC% pred (72.20±26.32 vs. 63.10±21.42, t=2.058), FEV1/FVC (75.14±20.52 vs. 58.12±19.82, t=4.546 ), diffusing capacity of the lung for carbon monoxide (DLCO) (76.24±28.40 vs. 54.32±21.20, t=4.400), episodes of exacerbations (Z=-8.272 ) and hospitalization during 1-year follow-up [6(14.29%) vs. 29(36.25%), χ2=6.495] in patients with dry bronchiectasis were significantly better than those in patients with expectoration bronchiectasis (all P 0.05) among patients with different types of bronchiectasis.


Conclusion
Patients with cystic, bacterial colonization and expectoration types of bronchiectasis seem to have more severe symptoms, more episodes of exacerbations and hospitalizations than those of non-cystic, non-bacteria colonization and dry types of bronchiectasis.


Key words: 
Bronchiectasis; Phenotype; Respiratory function tests; Bacteriology
脊髓裂并糖尿病双足Charcot关节病一例
Authors: 洪焕玉, 王海, 周智勇, 王振海, 杜伟
Journal: BMJ (2008)

患者男,54岁,因双踝轻微扭伤肿胀、活动受限3个月于2006年9月21日入院.既往有糖尿病史12年,最高血糖20.7 mmol/L,平时血糖控制在9.0～10.0 mmol/L.查体:双踝关节肿胀,自内踝上1 cm以下皮肤颜色变暗,未触及明显压痛区。