tbuckley/cabot-search huggingface dataset:
Expanding the diagnostic yield of germline genetic testing in cancer patients using deep learning.
Authors: Saud H Aldubayan, Jake Conway, Leora Witkowski, Eric Kofman, Brendan Reardon, Sabrina Camp, Seunghun Han, Haitham Elmarakeby, Abdullah Al-Rubaish, Abdulsalam Al-Sulaiman, Amein Al-Ali, Amaro Taylor-Weiner, Eliezer Mendel Van Allen
Journal: Journal of Clinical Oncology (2020)

1518 Background: Germline genetic analysis is an essential tool for implementing precision cancer prevention and treatment. However, only a small fraction of cancer patients, even those with features suggestive of a cancer-predisposition syndrome, have detectable pathogenic germline events, which may in part reflect incomplete pathogenic variant detection by current gold-standard methods. Here, we leveraged deep learning approaches to expand the diagnostic utility of genetic analysis in cancer patients. Methods: Systematic analysis of the detection rate of pathogenic cancer-predisposition variants using the standard clinical variant detection method and a deep learning approach in germline whole-exome sequencing data of 2367 cancer patients (n = 1072 prostate cancer, 1295 melanoma). Results: Of 1072 prostate cancer patients, deep learning variant detection identified 16 additional prostate cancer patients with clinically actionable pathogenic cancer-predisposition variants that went undetected by the gold-standard method (198 vs. 182), yielding higher sensitivity (94.7% vs. 87.1%), specificity (64.0% vs. 36.0%), positive predictive value (95.7% vs. 91.9%), and negative predictive value (59.3% vs. 25.0%). Similarly, germline genetic analysis of 1295 melanoma patients showed that, compared with the standard method, deep learning detected 19 additional patients with validated pathogenic variants (93 vs. 74) with fewer false-positive calls (78 vs. 135) leading to a higher diagnostic yield. Collectively, deep learning identified one additional patient with a pathogenic cancer-risk variant, that went undetected by the standard method, for every 52 to 67 cancer patients undergoing germline analysis. Superior performance of deep learning, for detecting putative loss-of-function variants, was also seen across 5197 clinically relevant Mendelian genes in these cohorts. Conclusions: The gold-standard germline variant detection method, universally used in clinical and research settings, has significant limitations for identifying clinically relevant pathogenic disease-causing variants. We determined that deep learning approaches have a clinically significant increase in the diagnostic yield across commonly examined Mendelian gene sets.
Abstract 11350: Is Up-Regulation of Beta3-Adrenergic Receptor (AR) in the Diabetes Myocardium Detrimental or Beneficial?--Effects of Chronic Beta3-Adrenergic Receptors Blockade on Diabetic Cardiomyopathy in a Murine Model
Authors: Yixi Liu, Zhe Chen, Heng-Jie Cheng, Peng Zhou, Satoshi Masutani, Nobuyuki Ohte, Che Ping Cheng
Journal: Circulation (2018)

Background: The negative inotrope and up-regulation of β3-adrenergic receptors (AR) in diabetes mellitus (DM) human and animal hearts suggest a direct and contributing role of cardiac β3-AR activat...
Two-hole laparoscopic cholecystectomy: a report of 31 cases
Authors: Zhi-gang Ren
Journal: BMJ (2009)

The clinical data of 31 patients with calculus, cholecystitis or polyps of gall bladder who underwent two-hole laparoscopic cholecystectomy (LC) were analyzed. The procedures were accomplished successfully in 29 cases, and the surgical module was alternated to four-hole LC in 2 cases. There were no complications related to the surgical procedures. The results suggest that two-hole LC is a safe and effective method with minimal invasion.

Key words: 
Cholecystectomy biliary, laparoscopic;  Treatment outcome
Utilizing porcupine (PORCN) and DKK1 inhibition to improve anti-tumor immunity in a murine model of ovarian cancer.
Authors: Jaclyn Wall, Ashwini A. Katre, Selene Meza-Perez, Angelina Londono, Lyse Norian, Rebecca Christian Arend
Journal: Journal of Clinical Oncology (2020)

e18041 Background: Epithelial ovarian cancers (EOC) are immunologically “cold” tumors and consequently have seen limited success with immunotherapy. Wnt-beta/catenin signaling is dysregulated in multiple cancers, including EOC, and is characterized by immune exclusion. Porcupine (PORCN) is the enzyme necessary for secretion of Wnt ligands, which is required for activation of Wnt/beta-catenin signaling. Up-regulation of the Wnt/beta-catenin pathway leads to increased levels of the target gene DKK1, which plays a role in immune exclusion. Our goal is to improve the tumor immune response via targeting Wnt-signaling in EOC. Methods: We utilized a syngeneic murine model (ID8 cell line) deficient in p53 (ID8p53 −/− ) with and without the addition of a Luciferase tag (Luc+/-) to assess the effect of treatment with a PORCN inhibitor, CGX-1321, with and without DKN-01, a monoclonal antibody targeting DKK1. Mice were treated with vehicle/control, CGX-1321, DKN-01, or CGX-1321/DKN-01. Treatment was given for either 14 or 31 days. In Luc+ mice, bioluminescence imaging was performed weekly. Following mouse sacrifice, omental weights and ascites volume were measured. Omental tumor was used for flow cytometry and representative samples were sent for NanoString analysis. Results: Treatment with CGX-1321 for 14 days reduced omental weight and ascites volume in Luc- mice only (p = 0.02); however, earlier and extended treatment with CGX-1321 and CGX-1321/DKN-01 in Luc+ mice decreased omental weight (p = 0.008 and 0.0025); mice treated with CGX did not develop any ascites with the same treatment schedule. While treatment with DKN-01 alone did not decrease omental weight, treatment with DKN-01 and combination CGX-1321/DKN-01 increased total percentage of NK cells (p = 0.0192 and 0.0070). CGX-1321 and DKN-01 alone and in combination increased the total percentage of CD8+ T cells in omental tumors (p = 0.0238, 0.037, and 0.0127). Conclusions: CGX-1321 decreased omental weight and ascites volume, while DKN-01 increased the cellular percentage of NK cells. Both DKN-01 and CGX-1321 increased CD8+ T cells. Wnt-inhibition is therapeutically promising in EOC, and the combination of a PORCN inhibitor with DKN-01 could improve the response to immune checkpoint blockage and further investigation is warranted.
Inpatient outcomes and predictors of mortality in patients with gastrointestinal malignancies presenting with sepsis: A nationwide analysis.
Authors: Parth Desai, Ishaan Vohra, Bashar Attar, Vatsala Katiyar, Prasanth Lingamaneni, Krishna Rekha Moturi, Sindhu Janarthanam Malapati, Sunny R K Singh, Maryam Zia, Kunnal Batra, Shweta Gupta
Journal: Journal of Clinical Oncology (2020)

4045 Background: Sepsis is a frequent cause of morbidity and mortality in patients with malignancy. However, there is paucity of literature on mortality, hospital charges and overall healthcare utilization among patients with GI malignancy, which we hope to characterize in this study. Methods: We queried retrospective data from the Nationwide Inpatient Sample (NIS) database for the year 2016. Sepsis (Dx1) was identified using ICD-10 code as primary diagnosis in patients with known GI malignancies (Dx2). Univariate and multivariate Poisson regression analysis was done to study outcomes. Propensity score matching was done to minimize confounding factors. Primary outcome was inpatient mortality. Secondary outcomes were Length of Stay (LOS), Total Charge (TOTCHG) and ICU admission. Results: A total of 43,240 patients with GI malignancy were admitted in 2016 with sepsis. Two most common GI malignancies admitted with sepsis were colorectal (35%) and hepato-cellular cancer (HCC) (28.2%). Overall mortality in GI cancer was 19.8% vs 10.2% in all cancers (p&lt;0.01). There was male (59%) and Caucasian (63%) preponderance. Out of all hospital admissions for GI malignancy, 41.4% were secondary to sepsis. E. coli (31%) infection and gram-negative bacteremia (15%) were the most common causes of sepsis. Sepsis with GI malignancy was associated with length of stay of 7.4 days vs 5.4 days (coef 2.44, 95% CI 2.3-6.7 p=0.04) and a mean hospital charge of $88,728 vs $ 54, 668 (coef 34,140, 95% CI 44,264-90,646, p&lt;0.01) as compared to without sepsis. After adjusting for demographic and patient related variables, independent predictors of mortality were old age, uninsured, African Americans, septic shock requiring pressor support, AKI, inpatient hemodialysis, metabolic encephalopathy and acute respiratory failure. Conclusions: Sepsis poses a substantial healthcare burden in patients with GI malignancy and is a major cause of mortality. Early antibiotic treatment is necessary for sepsis control in patients with GI malignancy. [Table: see text]
Predictors of post-mastectomy radiation (PMRT) in node-negative breast cancer patients.
Authors: Laura Sheriff, Erin Cordeiro, Jacob Hardy, Amanda Roberts
Journal: Journal of Clinical Oncology (2020)

e12608 Background: Post-mastectomy radiation (PMRT) reduces the risk of locoregional failure for women with an elevated risk of recurrence from breast cancer. Therefore, PMRT is often indicated for women with node positive breast cancer including those with only 1-3 nodes involved. The need for PMRT in node negative breast cancer patients is less established. The objective of our study was to review the predictors of PMRT in women with node-negative breast cancer and evaluate the overall recurrence rates. Methods: A retrospective chart review was completed. Women with node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy at a regional breast cancer center between January 1st,2011 and December 31st, 2017 were included. Patient and tumor characteristics, treatment details and recurrence data were recorded. The primary outcome was recommendation of PMRT. Univariate analysis was completed and then a multivariable logistic regression was completed to determine independent predictors for PMRT. Results: Overall, 235 women with node-negative breast cancer underwent mastectomy and sentinel lymph node biopsy during the study period. Forty-three (18.3%) patients were recommended to undergo PMRT, with 39 of the 43 patients completing the recommended treatment. PMRT was offered more often to younger women (p&lt;0.001), women with multifocal/centric disease (p=0.002), large tumors (p&lt;0.001), high grade tumors (p &lt; 0.001), lymphovascular positive tumors (p=0.04) and estrogen-negative disease (p =0.017). On multivariable analysis, the odds of radiation recommendation were highest for patients with high grade disease (OR 5.81, 95%CI: 2.08 – 16.20) followed by multifocal/centric disease (OR 3.12, 95%CI: 1.26 – 7.70). There were no differences in overall recurrence between patients who underwent PMRT versus those who did not have PMRT (p = 0.31). Conclusions: A moderate percentage of node negative patients are offered PMRT. Independent predictors for recommendation of PMRT in node negative patients are: decreasing age, increasing tumor size, multifocal/centric disease and higher grade disease. Surgeons can use this information to counsel patients regarding the possible need for PMRT, especially in the setting of planned immediate reconstruction.
Case-based learning: individualized treatment and comprehensive management for early diabetic kidney disease
Authors: Yuxia Kong, Jiatang Zheng, Aimei Dong
Journal: BMJ (2018)

Diabetic kidney disease (DKD) is a common microvasscular complication in diabetic patients. It is necessary for general practitioner to recognize the early DKD, and give individualized treatment and comprehensive management. This article presents a patient with diabetic kidney disease, to whom individualized treatment and comprehensive management were given. Hopefully the case-based learning would help general practitioners to early recognize DKD and to give timely treatment and effective control of diabetic nephropathy.


Key words: 
Diabetes, type 2; Diabetic nephropathy; General practitioner; Individualized medicine
Stereotatic radiosurgery for residual lesions of pineal nongerminomatous germ cell tumors after conventional radiotherapy: A retrospective study.
Authors: Mingyao Lai, Juan Li, Qingjun Hu, Jiangfen Zhou, Lei Wen, Cheng Zhou, Zhaoming Zhou, Shaoqun Li, Changguo Shan, Linbo Cai
Journal: Journal of Clinical Oncology (2020)

e14516 Background: To evaluate the safety and efficacy of stereotatic radiosurgery (SRS) in treating residual lesions of pineal non-germinomatous germ cell tumors (NGGCTs) after conventional radiotherapy. Methods: The patients admitted to Guangdong Sanjiu Brain Hospital from 1 January 2008 to 31 December 2018 who diagnosed with pineal NGGCTs pathologically or clinically were retrospectively analyzed. Among those, the patients received conventional radiotherapy with or without SRS were included. The residual lesions after radiotherapy were defined with a maximum diameter &gt; 10mm. Prognosis related parameters such as local control rate, progress-free survival, overall survival and treatment-related toxicity were determined. Results: The median follow-up time was 34 months (range 8-142 months). The objective response rate and disease control rate were 71.4% and 95.2%, respectively. Three-year progression-free survival rate was 85.2% and 3-year total survival rate was 88.0%. The univariate analysis revealed that both age and concurrent chemotherapy were not correlated with the prognosis (P = 0.286, 0.824). Partial tumor resection before radiotherapy and chemotherapy, AFP&gt;500ng/ml, and no more than 4 cycles of adjuvant chemotherapy were poor prognostic factors (P = 0.037, 0.010, 0.006). Moreover, no acute radiation response was observed after treatment with SRS. Only 1 out of 27 patients (3.7%) had brain neurotoxicity related to a prolonged course of radiochemotherapy. Conclusions: SRS for residual lesions of NGGCTs following conventional radiotherapy appears to be well tolerant and improved local control. However, the combination of conventional radiotherapy and SRS warrants further investigations in a large-scale randomized controlled clinical trials.
Presentation and Outcomes of Patients with ESKD and COVID-19
Authors: Anthony M. Valeri, Shelief Y. Robbins-Juarez, Jacob S. Stevens, Wooin Ahn, Maya K. Rao, Jai Radhakrishnan, Ali G. Gharavi, Sumit Mohan, S. Ali Husain
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Immunosuppression and a high prevalence of comorbidities among patients with ESKD on dialysis raise concerns that such patients may have an elevated risk of severe coronavirus disease 2019 (COVID-19). However, the outcomes for COVID-19 in this patient population are not clear. In their study of 59 patients with ESKD and COVID-19 receiving dialysis at a New York City medical center, the authors found that although the presentation of patients on dialysis with COVID-19 was similar to that of the general population, these patients have poor outcomes, including 31% overall mortality and 75% mortality among those requiring mechanical ventilation. In addition, higher levels of inflammatory markers associated with severe disease. This information will help inform care of patients on dialysis who develop COVID-19 and reinforces the importance of infection control measures when treating this vulnerable population. Background The relative immunosuppression and high prevalence of comorbidities in patients with ESKD on dialysis raise concerns that they may have an elevated risk of severe coronavirus disease 2019 (COVID-19), but outcomes for COVID-19 in such patients are unclear. Methods To examine presentation and outcomes of COVID-19 in patients with ESKD on dialysis, we retrospectively collected clinical data on 59 patients on dialysis who were hospitalized with COVID-19. We used Wilcoxon rank sum and Fischer exact tests to compare patients who died versus those still living. Results Two of the study’s 59 patients were on peritoneal dialysis, and 57 were on hemodialysis. Median age was 63 years, with high prevalence of hypertension (98%) and diabetes (69%). Patients who died were significantly older than those still living (median age, 75 versus 62 years) and had a higher median Charlson comorbidity index (8 versus 7). The most common presenting symptoms were fever (49%) and cough (39%); initial radiographs most commonly showed multifocal or bilateral opacities (59%). By end of follow-up, 18 patients (31%) died a median 6 days after hospitalization, including 75% of patients who required mechanical ventilation. Eleven of those who died had advanced directives against intubation. The remaining 41 patients (69%) were discharged home a median 8 days after admission. The median initial white blood cell count was significantly higher in patients who died compared with those still living (7.5 versus 5.7×10 3 / μ l), as was C-reactive protein (163 versus 80 mg/L). Conclusions The association of COVID-19 with high mortality in patients with ESKD on dialysis reinforces the need to take appropriate infection control measures to prevent COVID-19 spread in this vulnerable population.
Evaluation of clinical competence training model for general practitioners in Shanghai
Authors: Xia Huiling, Liu Yao, Gu Jie, Shou Juan, Zhu Shanzhu
Journal: BMJ (2016)

Objective
To evaluate the clinical competence training model for community general practitioners (GPs).


Methods
Total 759 Gps participated in clinical ability training course (training group) between July 2011 and October 2012. The course included lectures, group discussion, role play, simulation for theoretical teaching; and video demonstration, scene teaching and medical simulator for physical examination and surgical skill training. Other 703 Gps without participating in training course were selected as control group. The examination consisting of theoretical and clinical skill tests were carried out and the results were compared between two groups.


Results
The participants included 260 males (34.2%) and 499 females (65.8%) were with an average service year of 13.9±7.0 and 72.8% of them hold bachelor degree. There were no significant differences in gender composition, work seniority and educational level between the two groups (P>0.05). Before and after training the total scores of the training group were (67.39±8.57) and (73.62±7.19) respectively, ( 68.67±8.31) and (65.73±9.02) respectively for the control group. Before training, the total score and theoretical results of control group were significantly higher than those of training group (all P<0.01), and there was no significant difference between the two groups in physical examination and operation skill. After training, the total scores and the individual scores (written examination, physical examination and operation skill) of training group were significantly increased, compared with those before training (all P<0.01), and those of control group (all P<0.01).


Conclusions
The clinical competences training model can improve the theoretical knowledge and clinical ability of community general practitioners.


Key words: 
Clinical competence; General practitioner; Training
Treatment of hypertensive basal ganglia cerebral hemorrhage with different surgical approaches
Authors: Yonghua Cui, Yongben Xia, Zhengquan Yu, Zhangming Wang, Xiaowen Zhu, Cheng Zhang
Journal: BMJ (2018)

According to the locations of main hematomas, 60 patients with hypertensive basal ganglia hemorrhage were surgically treated through different approaches from June 2014 to September 2017. Thirty six cases with anterior hematoma near the Sylvian point were treated through transsylvian-transinsular approach, 24 cases with the posterior hematoma far from the Sylvian point were treated through translower-rolandic-point (transLRP) transinsular approach (n=11) or transsuperior-temporal-sulcus (transSTS) transinsular approach (n=13), respectively. All patients were followed up for at least 6 months and evaluated by Glasgow Outcome Scale. Fourteen patients showed good recovery, 25 patients showed moderate disability, 18 patients showed severe disability, one patients showed vegetative survival and two patients died.


Key words: 
Intracerebral hemorrhage, hypertensive; Basal ganglia; Surgical approach
Clinical analysis of two cases of epidermal nevus syndrome and a review of literature
Authors: Zhi-hong Zhuo, Huai-li Wang, Tie-zheng Gao
Journal: BMJ (2010)

Clinical, radiological and pathological presentations in two children with epidermal nevus syndrome were analyzed and relevant literature was reviewed.Two patients both had typical epidermal nevus and abnormal cerebral radiography, which was associated with mental retardation, epilepsy, language and movement retardation.One case was complicated with an ocular tumor.Pathological investigations of the epidermal nevus revealed papilliform proliferation in squamous epidermis.The disorder may have a systemic involvement besides cutaneous lesions, with a predilection for the central nervous system.Early diagnosis and therapy may help to improve patients life quality.

Key words: 
Epidermal nevus syndrome
Tumor lymphocytic infiltration impacts recurrence in endometrioid-type endometrial carcinoma.
Authors: Monica Avila, Bryan M. Fellman, Russell Broaddus
Journal: Journal of Clinical Oncology (2020)

e15239 Background: Endometrial cancers that have mismatch repair deficiency are associated with higher numbers of tumor-associated lymphocytes, but the clinical significance of this observation is unknown. Our objective was to quantify CD3+ and CD8+ tumor lymphocytes of MMR intact (MMRi) and MMRd endometrioid-type endometrial carcinomas and determine if there was an association with survival. Methods: MMRd was defined as endometrial carcinomas with loss of MLH1 expression due to MLH1 gene methylation and determined by immunohistochemistry. MMRi was defined as positive expression of MLH1, MSH2, MSH6, and PMS2. This was followed by Aperio image-based quantification was used to assess CD3+ and CD8+ lymphocyte populations in different regions of the primary endometrial carcinomas, including tumor periphery (tumor-myometrial interface), tumor center (bounded on all sides by tumor), and tumor hotspot (area with highest number of lymphocytes). Recurrence-free survival was estimated using Kaplan Meier and Cox regression. Median follow up time was 44 months. Results: 180 patients with endometrial carcinoma were analyzed of which 132 were MMRi and 48MMRd. The MMRd group had significantly higher levels of CD3+ and CD8+ lymphocytes regardless of which tumor region was assessed (Figure 1a, P &lt; 0.001). Lymphocyte counts in both MMRd and MMRi groups had wide standard deviations such that there was some overlap in counts between the groups (Figure 1). Both MMRd and higher CD3+ counts were associated with worse recurrence-free survival. CD3+ quantification in the tumor periphery captured 21/23 recurrences (Figure 1b, HR = 8.04; 95% CI: 1.88 -34.31; p = 0.005); this included all of the MMRd cases that recurred and 7 MMRi cases with higher numbers of CD3+ lymphocytes that also recurred. Conclusions: MMRd endometrial cancers have increased numbers of CD3+ lymphocytic infiltrates within the primary tumor. Higher CD3+ infiltration is associated with greater risk of recurrence regardless of tumor location. In predicting tumor recurrence, lymphocytic counts performed better than assessment of MMR. Thus, quantification of CD3+ lymphocytes should be explored as a predictive biomarker.