tbuckley/cabot-search huggingface dataset:
Effects of ectopic pregnancy treatment on ovarian response
Authors: Qing-hong Zhao, Jing Yang, Nan Yu, Tai-lang Yin, Jian-ye Fang
Journal: BMJ (2012)

A total of 183 patients of ectopic pregnancy due to tubal factors were divided into the methotrexate (MTX),conservative surgery and salpingectomy groups.The dose of gonadotropin,counts of harvested oocytes and high-quality embryos and pregnancy rate were compared among three groups to analyze the differences of in vitro fertilization and embryo transfer (IVF-ET).And the above parameters showed no significant differences (P ＞0.05 ).The clinical pregnancy rate of the conservative group was higher than the other two groups.And the difference was statistically significant compared with salpingectomy ( P ＜ 0.05 ).It suggested that the treatments of ectopic pregnancy had some effects on the outcome of IVF-ET.The pregnancy rate was slightly higher in the conservative surgery group.

Key words: 
Pregnancy ectopic; Fertilization in vitro
Prognostic value of tumor: Infiltrating lymphocytes and androgen receptors correlation in triple negative breast cancer.
Authors: Ana Tecic Vuger, Robert Separovic, Ljubica Vazdar, Mirjana Pavlovic, Sanda Sitic, Ana Tecic Vuger, Bozena Sarcevic, Damir Vrbanec
Journal: Journal of Clinical Oncology (2020)

e12571 Background: Little is known about correlation of tumor infiltrating lymphocytes (TIL) and androgen receptors (AR) and their joint effect on early triple-negative breast cancer (TNBC) prognosis. Analyzes to date evaluated mostly stromal TIL (sTIL) and intratumoral (iTIL), but not separately in central tumor (CT) and invasive margin (IM). Methods: We retrospectively analyzed consecutive sample of 152 early TNBC patients treated at our institution 2009-2012. TIL and AR were assessed using standard FFPE samples, TIL according to International Working Group for Evaluation of TIL recommendation, sTIL and iTIL in CT and IM, and AR by immunohistochemistry. Results: Median age was 58, 84% NOS, median T 2.2cm, 41% N+, 22%, 59% and 19% in stage I, II and III, respectively. Radical mastectomy was performed in 39%, adjuvant chemotherapy in 88% and radiotherapy in 74% of patients. Positive AR defined as ≥1% nuclear-stained cells, were expressed in 31%, and AR≥10% in 26% of patients. Median TIL content was: sTIL 19%, iTIL 5%, TIL in CT 5%, at IM 18%, sTIL in CT (CTs) 5%, iTIL in CT (CTi) 1%, sTIL at IM (IMs) 30%, and iTIL at IM (IMi) 5%. Prevalence of intermediate or high TIL content, defined as ≥10% was: CTs in 48%, CTi in 23%, IMs in 86%, and IMi in 47% of cases. In bivariable analysis all TIL indicators were significantly associated with longer OS, while AR was not. After adjustment for potential confounders using Cox proportional hazard regression, significant predictors of OS were sTIL (p0.007), IM TIL (p0.002), IMs (p0.001), and IMi (p0.030). In all cases higher TIL content was associated with longer OS. Although AR was not significant predictor of OS, it's interactions with TIL IMs and IMi was. There was no significant difference in OS between patients with high IMs and low IMs and AR0, but those with high IMs and AR≥1 had HR0.22 (p0.045) for death compared to patients with low IMs and AR0. Also, no difference for high IMi and low IMi and AR0, but patients with high IMi and AR≥1 had HR0.10 (p0.028) for death compared to patients with low IMi and AR0. Conclusions: Section analysis reveals frequent intermediate to high density and statistically significant prognostic impact of TIL on IM. That directs question towards role of different tumor compartments. Furthermore, combination of high expression of IMs and IMi with AR≥1 appears to be associated with longer OS than in patients with high IMs and IMi but with AR0. The correlations between AR and all TIL studied are extremely small, indicating their independence, but if so, their interaction in impact on OS is particularly interesting.
Myelodysplastic syndrome and acute myeloid leukemia as side effect of PARP inhibitors.
Authors: Samip R. Master, Richard P. Mansour
Journal: Journal of Clinical Oncology (2020)

3601 Background: Acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS) have been rarely noted in patients on PARP inhibitors. The actual incidence is unknown and it has been put has warning/precaution of FDA label for olaparib, niraparib and rucaparib. Methods: The FDA has made the data on the adverse effects of various treatments available to the general public through the FDA Adverse Events Reports System (FAERS) public dashboard. We investigated the adverse events reported for PARP inhibitors like olaparib, niraparib and rucaparib for the years 2017-2019 to find out the number of patients who had acute leukemia or myelodysplastic syndrome reported while on those medications. Results: A total of 8151 adverse events were reported between 2017 and 2019 for olaparib, niraparib and rucaparib. Out of which, 6077 were serious and 1121 deaths were reported. There were 237 reports of AML and MDS, which compromise 2.9 % of total events reported. We also looked that cyclophosphamide data for comparison purposes during the same period. There were 29,162 adverse events reported for cyclophosphamide, out of which 963 i.e. 3.3% were AML and MDS. For olaparib, 2523 adverse events were reported and 173 (6.8%) were MDS/AML. For niraparib, 5496 adverse events were reported and 41(0.7%) were MDS/AML. For rucaparib, 153 adverse events were reported and 4 (2.6%) were MDS/AML. Conclusions: Based on this retrospective data, AML/MDS is an adverse event in pts of PARP inhibitors and needs to be monitored. Pts on olaparib seem to have high risk of AML/MDS compared to other two to PARP inhibitors.
Effects of metformin onplasma lactic acid level in patients with type 2 diabetes
Authors: 焦玲, 吕莺, 张璎珞
Journal: BMJ (2009)

：One hundred andthirty-six adult patients with type 2 diabetes ( ≥40 years, body mass index > 24) were assigned to thelow-dose Mefformin, high-dose Mefformin, and control groups. Plasma lactic acid level wasdetected with ultraviolet enzyme kinetics assay. Our data showed that plasma lactic acidof the low-dose or high-dose mefformin group was significantly higher than the controlgroup (2.314 vs. 2.511, P  2. 2 mmol/L) was found in some patients ( Mefformin group vs. Control group: X2 =7.43, P   5.0 mmol/L was found. Insulin resistanceindex and hemoglobin Alc were similar between the 3 groups. Thus, mefformin may notincrease the risk of lactic acidosis in diabetic patients with normal cardiorespiratoryand renal function.

Key words: 
Diabetes mellitus,type 2; Metformin
Violence and chronic pain in cancer patients in northeastern Mexico.
Authors: Adelina Alcorta-Garza, Fernando Alcorta-Nuñez, Antonia Gloria Alcorta-Garza, Juan Francisco Gonzalez Guerrero, Celia Beatriz Gonzalez-Alcorta, Jan Alejandro Montiel-Labastida, Maria Lourdes Garza-Rodriguez, Oscar Vidal-Gutiérrez
Journal: Journal of Clinical Oncology (2020)

e24113 Background: Chronic cancer pain generates fear and anguish in cancer patients. It is suffered by 64% of patients with metastatic or terminal disease, 59% of patients in early and intermediate stages, and 33% of patients cured from cancer. They require a psychosocial support network. This network has been proposed as an essential tool to reduce the negative impact of the symptoms and psychosocial implications of cancer on the quality of life of patients. Patients with dysfunctional family networks can add to the pain of suffering cancer when they suffered or suffer violence. Cancer and pain test all personal resources and the patient's support network where family functioning is capital for quality of life. Methods: Descriptive, comparative and correlational study. A sample was taken for convenience with the prior consent of the patients who attend the outpatient clinic of the Pain Clinic of the Oncology Service, of the University Center Against Cancer of the University Hospital “Dr. José Eleuterio González” in Nuevo León. The questionnaires were applied during a session of 25 to 30 minutes. It was requested to answer the scales to assess the level of intra-family functioning, intra-family violence, quality of life, measuring psychosocial and health variables; as well as for the detection of the type and quality of psychosocial support perceived by the subjects. Results: A total of 207 research subjects were included in the study, the average age was 49 years of age (minimum 12, maximum 81 years of age), 23% men and 77% women. Marital status: married 52%, home-based 63%; monthly income less than $120 USD (n = 75, 37%). The quality of life index and chronic cancer pain had a high linear correlation with the variables of family violence, psychosocial support, family functioning, somatic symptoms, among other variables studied. Fatigue was the symptom most frequently associated with the decrease in the quality of life index. Conclusions: The satisfaction of perceived social support is a factor associated with the quality of life in patients with chronic cancer pain, however, the number of caregivers is not. There was no relationship between the size of the network and satisfaction with it. Also, the symptoms associated with chronic cancer pain affect the quality of life, identity, social functionality and roles, which in turn impact the quality of life perceived by the patient. This study supports our comprehensive intervention programs and new protocols to promote the quality of life of cancer patients.
Validation of 4-marker protein panel for the early detection of lung cancer using PLCO samples.
Authors: Johannes Fahrmann, Ehsan Irajizad, Jody Vykoukal, Nikul Patel, Jennifer B Dennison, Eunice Murage, Edwin Justin Ostrin, Samir Hanash
Journal: Journal of Clinical Oncology (2020)

9024 Background: We have previously demonstrated that a protein panel consisting of ProSFTPB, CEA, CA125 and CYFRA21.1 may improve lung cancer risk assessment and has potential to define eligibility for computed tomography screening. Herein, we aimed to validate the classifier performance of the 4-marker protein panel using pre-diagnostic serum samples from the PLCO cohort. We additionally explored the additive value of diacetylspermine (DAS) with the 4-marker protein panel for identifying lung cancer cases. Methods: ProSFTPB, CEA, CA125 and CYFRA21.1 levels were measured in baseline sera of 537 lung cancer cases (76 SCLC/461 NSCLC) diagnosed within 6 years of baseline blood draw and 3772 cancer-free controls using bead-based immunoassays. DAS was measured using ultrahigh performance liquid chromatography mass spectrometry. Samples were analyzed in a double-blinded randomized fashion. Results: Overall classification performance (receiver operating characteristic area under the curve (ROAUC)) of the 4-marker panel for delineating lung cases diagnosed within 1 year and 1 to 2 years of baseline blood draw from cancer-free controls was 0.78 (95% CI: 0.74-0.82) and 0.73 (95% CI: 0.68-0.78), respectively. Classification performances of the 4-marker panel amongst lung cancer cases diagnosed within 1 year of baseline blood draw stratified into adenocarcinoma, squamous cell carcinoma and small cell lung cancer subtypes yielded ROAUCS of 0.78 (95% CI: 0.72-0.85), 0.76 (95% CI: 0.69-0.83) and 0.79 (95% CI: 0.68-0.90), respectively. Sub-analyses adjusting for smoking status yielded comparable ROAUC point estimates. Comparison of the 4-marker performance amongst non-NLST and NLST eligible lung cancer patients diagnosed within 1 year of baseline blood draw in comparison to matched cancer-free controls resulted in ROAUCs of 0.71 (95% CI: 0.63-0.79) and 0.74 (95% CI: 0.69-0.80), respectively. Analyses evaluating the additive classifier performance of serum DAS with that of the 4-marker protein panel revealed statistically significant improvement (McNemar Exact Test 2-sided p &lt; 0.05) in sensitivity at high specificity derived from youden index for SCLC and squamous cell carcinoma cases diagnosed within 2 years from baseline blood draw, respectively, in comparison to the 4-marker protein panel alone. Conclusions: We have validated the performance of the 4-marker panel for early detection of lung cancer in the PLCO pre-diagnostic cohort. We further demonstrate that DAS can complement the 4-marker protein panel and identify more SCLC and squamous cell carcinoma cases.
Response to: ‘Increasing incidence of autoantibody-negative RA is replicated and is partly explained by an aging population’ by Matthijssen<i>et al</i>
Authors: Elena Myasoedova, John Davis, Eric L Matteson, Cynthia S Crowson
Journal: Annals of the Rheumatic Diseases (2020)

Response to: 'Increasing incidence of autoantibody-negative RA is replicated and is partly explained by an aging population' by Matthijssen et alWe thank Matthijssen and colleagues for their interest in our study on the epidemiology of rheumatoid arthritis (RA), where we have reported a significant increase in incidence of rheumatoid factor (RF)-negative RA and a decrease in RF-positive RA in 2005-2014 compared with previous decades. 1Matthijssen et al have independently assessed the incidence of anticitrullinated peptide antibody (ACPA)-negative and ACPA-positive RA in the Leiden Early Arthritis Cohort.In concordance with our findings, they found increasing incidence of ACPA-negative RA but not ACPA-positive RA. 2 Further, Matthijssen et al proposed that ageing of the population can be an important contributor to these trends and estimated that the rate of increase of new ACPA-negative RA cases in the next 20 years will outpace that of ACPA-positive RA (11% vs 2% increase, respectively), thus substantially increasing the prevalence of ACPA-negative RA.Taken together with our findings, these results strengthen the argument that the serological profile of RA is changing in recent years, and autoantibody-negative RA is becoming more common in the new millennium.These findings have broad implications for both clinical practice and research.First, autoantibody-negative RA is a more clinically challenging disease subset due to diagnostic uncertainty in early disease with multiple potential mimickers, and frequent difficulty with timely choice of effective treatment. 3his highlights the need for increased awareness of autoantibodynegative RA among physicians, in order to facilitate timely rheumatology referral and initiation of treatment.Second, classification of RA based on RF and ACPA is conditional to the available and validated immunological assays, while the search for additional immunological and clinical subsets within autoantibody-negative RA continues. 4Refining the understanding of pathophysiology and classification of RA disease beyond the current immunological disease markers may lead to improvement in RA diagnosis and management, opening new avenues for individualised treatment selection for different RA subtypes.
Khorana score as a predictive tool of venous thromboembolism in cancer patients in rural practice.
Authors: Ahmed Khalil, Daniel Ortolano, Thomas Simunich, Mohamed Saad Eldin, Munawwar Hussain, Sheetal L. Higbee
Journal: Journal of Clinical Oncology (2020)

e24049 Background: The Centers for Disease Control and Prevention (CDC) estimates that 60,000 to 100,000 Americans die from venous thromboembolism (VTE) annually, costing the U.S. healthcare system $7–10 billion each year. VTE is a leading cause of mortality in cancer patients, and risk is particularly elevated in rural areas, where cancer death rates are higher than in metropolitan areas. The Khorana score has been shown to predict VTE incidence before starting treatment and as such identify those patients that would benefit most from VTE prophylaxis. We aimed to replicate the utility of the Khorana score on a rural population of cancer patients to help address VTE in advance. Methods: From our electronic health records system, we extracted data from cancer patients (age ≥ 18 years) who had begun chemotherapy from 2017-January through 2019-August. Patients who were pregnant, had undergone hormonal therapy or major surgeries within three months prior to VTE diagnosis, or had a history of coagulation disorders or VTE prior to starting chemotherapy were excluded. A Khorana score (0—6, interval = 1) was calculated for each prior to their starting chemotherapy and was used for VTE risk stratification, 0 – low; 1,2 – intermediate; ≥3 – high. We hypothesized that VTE occurrence during the first 6 months following the start of treatment would be positively associated with risk category. Results: The 144, mostly female (64%), cancer patients meeting inclusion had a mean age of 75 years (range 48—95) and VTE risk stratification: 10% (15) high, 67% (96) intermediate, and 23% (33) low. In the first 6 months of starting treatment, 6% (9/144) developed VTE, with a prevalence of 20% (3/15) amongst patients stratified as high risk, 5% (5/96) of intermediate, and 3% (1/33) of the low risk group. A linear-by-linear association of the observed Khorana scores with VTE occurrence implies a meaningful positive association between VTE risk stratification by Khorana score and VTE, chi-square (1,144) = 4.018, p = .045. Conclusions: The trend of higher VTE prevalence in intermediate and high risk patients supports the observed positive association between Khorana score VTE risk category and a greater percentage of patients experiencing VTEs with increasing risk. This trend may likely be amplified with application to a larger number of patients. The study limitations include the lack of diversity of organ affection and sample size, specifically upon risk stratification. However, initiating a discussion about the risks and benefits of VTE prophylaxis prior to starting treatment is of outmost importance.
Association of tumor mutations with arterial thromboembolism risk in patients with solid cancer.
Authors: Ka-wai Ho, Dipti Gupta, Kelly L Bolton, Andrew Jeffrey Dunbar, Peter Willeit, Gerald A. Soff, Justin Jee, Ahmet Zehir, Yolanda Bryce, Robert Sidlow, Sean M. Devlin, Omar Nahhas, Babak B. Navi, Simon Mantha
Journal: Journal of Clinical Oncology (2020)

e13537 Background: Patients with cancer have an increased risk of arterial thromboembolic events (ATE). Clinical characteristics such as medical comorbidities, cancer type, cancer stage and a history of smoking are established risk factors for ATE, but scant data exist about the effect of cancer-specific genomic alterations. We aimed to determine whether individual tumor mutations influence ATE risk. Methods: We performed a retrospective cohort study using tumor mutational data from adults with solid cancers who had MSK-IMPACT testing at Memorial Sloan Kettering Cancer Center between 2014 and 2016. MSK-IMPACT is an FDA-authorized DNA sequencing panel targeting 341+ oncogenes and tumor suppressor genes identifying mutations, copy number alterations, and gene fusions in solid malignancies. The primary ATE outcome was defined as ischemic stroke, myocardial infarction or coronary revascularization and detected by systematic electronic health record assessments. Patients were followed up to one year from the date of tissue-matched blood control sampling to the first ATE or death. We used Cox proportional hazards regression adjusting for age, cancer type, cytotoxic chemotherapy treatment (time-dependent) and tobacco use to determine hazard ratios (HR) of individual genes for ATE risk. We adjusted for multiple comparisons using the Benjamini-Hochberg method. Results: Among 11,317 patients, mean age was 59 years (SD = 14 years) and 55% were women. The most frequent cancers were lung (16%), breast (15%), and colorectal (10%), and 73% were metastatic. During a median follow-up of 253 days, 151 patients had an ATE (1.3%). In multivariable analysis, genomic alterations in KRAS (HR, 2.11; CI, 1.41-3.16), STK11 (HR, 2.62; 95% CI, 1.49-4.59), and ROS1 (HR, 5.3; 95% CI, 1.93-14.58) were independently associated with an increased risk of ATE. Presence of clonal hematopoiesis was not found to be associated with an increased risk of ATE in this cohort (HR, 0.96; 95% CI, 0.63-1.47). Conclusions: In a large genomic tumor-profiling registry of patients with solid cancers, alterations in KRAS, STK11, and ROS1 were associated with an increased risk of ATE independent of cancer type. [Table: see text]
Application of Leichester assessment package in consultation skill training for general practitioners at outpatient clinic
Authors: Liang Chen, Weiwei Zhang, Xiuping Xia, Jing Zhou
Journal: BMJ (2018)

Thirty-five general practitioners (GPs) from Huangdu Subdistrict Community Health Center of Anting Township were trained for clinical skills and communication skills in consultation at outpatient department by using Leichester assessment package (LAP) from January 2016 to December 2016. The clinical skills and communication skills were assessed before and after 1 year of training. The results showed that compared to those before training the clinical skill and communication skill were significantly increased after the training. The scores of medical history taking, clinical reasoning and health education, as well as the scores of building doctor-patient relationship, collecting information and providing feedback, understanding complaints from patient perspective, sharing information and obtaining informed consents after the training were all higher than those before training (all P<0.05). However, there were no significant differences in scores of history writing and interview time before and after training. The study showed that Leichester assessment package can effectively improve the training of clinical skills and communication skills for GPs, and it can be applied for future training.


Key words: 
Clinical competence; General practitioners; Leichester assessment package