tbuckley/cabot-search huggingface dataset:
Initial results from a phase II study (TACTI-002) in metastatic non-small cell lung or head and neck carcinoma patients receiving eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab.
Authors: Enriqueta Felip, Bernard Doger, Margarita Majem, Enric Carcereny, Matthew Krebs, Julio Antonio Peguero, Patricia Roxburgh, Martin Forster, Pawan Bajaj, Timothy Dudley Clay, Frederic Triebel
Journal: Journal of Clinical Oncology (2020)

3100 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and then CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses than observed with pembrolizumab alone. We hereby report initial results of a phase II trial (NCT03625323). Methods: A predefined number of patients (pts) are recruited into this 3-cohort trial irrespective of PD-L1 expression; part A: 1 st line, PD-X naïve NSCLC; part B: 2 nd line, PD-X refractory NSCLC and part C: 2 nd line PD-X naive HNSCC. The study has a Simon's 2-stage design, with objective response rate (ORR) as primary endpoint. Secondary endpoints include disease control rate, progression free and overall survival, PK, PD and immunogenicity. Additional pts (N2) will be recruited for each part if pre-specified thresholds for ORR are met. Up to 109 pts will be enrolled. Efti is administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). The study was approved by ethic committees and institutional review boards. Results: Between 04 Mar 19 and 31 Jan 2020, 48 pts were enrolled and evaluated for safety and exposure. The median age was 66 yrs (range 48-84) and 73 % were male. The ECOG was 0 in 50 % and 1 in 50 % of pts, respectively. Pts received a median of 5 (7) and in total 311 (413) pembrolizumab (efti) administrations, respectively. Three pts (6.3 %) discontinued study treatment due to AEs. The most common ( &gt; 10%) adverse events (AEs) being cough (31 %), asthenia (23 %), decreased appetite (19 %), fatigue (19 %), dyspnea (17 %), diarrhea (15 %) and constipation 13 %). From part A all pts (n = 17) were evaluated. Eight pts (47 %) had a partial response (iPR) and six (35 %) had stable disease according to iRECIST representing an ORR (DCR) of 47 % (82 %). irPRs were observed in all different PD-L1 groups ( &lt; 1%; ≥ 1 % ≤49 %; ≥ 50 %). Ten (10; 59 %) pts are still on therapy (8+ months). In part C stage 1 15/18 pts are evaluable and six (40 %) had an iPR to date. Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in all comer PD-L1 1 st line NSCLC and 2 nd line HNSCC. Stage 2 has opened for both parts. Clinical trial information: NCT03625323 .
Interview skills for first visit patient in general practice clinic
Authors: Juanjuan Liu
Journal: BMJ (2017)

The patients encountered in general practice clinic often are the first visit patients with complex symptoms and uncertain etiology. The interview skill is crucial for effectively obtaining the medical history and thoughts of patient, based of which the correct diagnosis and proper treatment can be made. This article briefly discusses the interview mode and skills in general practice.


Key words: 
General practitioners; Interview
Glycemic Monitoring and Management in Advanced Chronic Kidney Disease
Authors: Rodolfo J Galindo, Roy W Beck, Maria F Scioscia, Guillermo E Umpierrez, Katherine R Tuttle
Journal: Endocrine Reviews (2020)

Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.
Lessons on humanity: The voice of cancer patients through a literary contest.
Authors: Darío Niewiadomski, Ernesto Gil Deza, Daniela Gercovich, Lourdes Gil Deza, Claudia Lorena Acuna, Leonel Smolje, Sandra L. Ares, Natasha Gercovich, Alba Marin Ordoñez, Marcelo Muino, Inés Danussi, Flavio Tognelli, Marta Dragosky, Eduardo L. Morgenfeld, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2020)

e24189 Background: Most cancer narratives are provided by skilled American and British writers (Broyard, Hitchens, Jobs, Kalanithi, Pausch, Sacks, Sontag or Wishart). This paper highlights the voice of ordinary Latin American patients who wrote about their experience. Methods: Between February 2, 2019 and March 3, 2019, the first author encouraged cancer patients to narrate their experience with the disease for an online literary contest (“ www.oncologiaesperanzadora.com ”). After studying all submissions, we grouped attitudes, feelings, metaphors and descriptions used in different domains related to the course of the disease. A text-mining study was conducted to identify the context of keywords in each of the domains. Results: In total, 224 literary works were submitted to the contest. Characteristics of the population: sex F/M: 184/40; age at time of contest: 53 yo (18-82); time between diagnosis and submission to contest: 8 y (1-73); country of origin: Argentina (201), other countries (23); diagnosis: breast (130), hematological (15), colorectal (13), melanoma (6), lung (5), head and neck (5), kidney (3), other (47). The table shows keywords found in each of the domains. Conclusions: 1) Cancer patients are willing to share their story if they are given the opportunity. 2) Through the narratives of the disease, it is possible to study its impact on patients’ lives and the different coping strategies. 3) Reading the experience of patients with the disease in their own voice is a valuable instrument for medical education. [Table: see text]
Compliance rate of clinic appointments among residents contracting family doctor service and its influencing factors
Authors: Jie Chen
Journal: BMJ (2016)

Objective
To investigate compliance rate of clinic appointments among residents contracting family doctor  and its influencing factors.


Methods
Total 1 442 clinic appointments among residents contracting family doctor  in Yuetan community were investigated by face to face questionnaire.


Results
Among 1 442 clinic appointments in Yuetan community health  center in June 2015, 563 were kept with a compliance rate of 37.2%. There were significant difference in compliance rate among the residents with difference degree of education(OR=1.461, 95%CI: 1.296-1.646, P=0.000), between those with and without chronic diseases(OR=2.009, 95%CI: 1.136-3.550, P=0.016), with and without receiving first contact care at community(OR=1.360, 95%CI: 1.036-1.785, P=0.027), with and without satisfying with family doctor service(OR=1.315, 95%CI: 1.060-1.630, P=0.013), with and without recognizing clinic  system(OR=2.765, 95%CI: 2.142-3.569, P=0.000). Among the 906 failed appointments, the reasons were forgetting the appointment in 525 (57.9%), missing the date in 124 (13.7%), time conflict in 92 (10.2%), not bring reservation form in 85 (9.4%), being hospitalized or engaging in other medical service in 41 (4.5%) and neglecting  system in 39 (4.3%).


Conclusion
Compliance rate of clinic appointments among residents contracting family doctor  is lower, and necessary measures should be taken to increase the compliance rate.


Key words: 
Appointments and schedules; Questionnaires; Family doctor service; Compliance rate
SAF-189s in previously treated patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC): Results from the dose-finding portion in a single-arm, first-in-human phase I/II study.
Authors: Jin-Ji Yang, Jianying Zhou, Nong Yang, Zhuli Wu, Juan Sun, Ai-Min Hui, Yi-Long Wu
Journal: Journal of Clinical Oncology (2020)

e21689 Background: Patients(pts) with ALK-rearranged non-small cell lung cancer (NSCLC) are sensitive but progress in 8–11 months with treatment of ALK inhibitor crizotinib, with leading progression in brain metastasis. SAF-189s is a novel and selective ALK inhibitor, can penetrate through blood brain barrier, and overcome multiple resistance mutation. This study aimed to explore the safety, efficacy, and pharmacokinetic properties of SAF-189s in patients with advanced ALK-rearranged NSCLC. Methods: In this multicenter I/II study, SAF-189s was orally administered under fasting condition at doses ranging from 20–210 mg once daily in a 21-day cycle to 36 pts with advanced ALK-positive NSCLC who had failed to prior systemic therapy. In this analysis report, anti-tumor activity of SAF-189s was evaluated in 34 pts received 40(n = 6), 80(n = 8), 120(n = 8), 160(n = 9) and 210(n = 3) mg doses daily. Safety was evaluated in all 36 pts who received ≥1 treatment. This study is registered with clinicaltrials.gov, NCT04237805. Results: 36 pts were enrolled in total, 22 pts had CNS metastases at baseline and 26 pts had progressed to prior TKIs therapy. There was no treatment-related SAE among the 36 pts. The most common drug-related events were nausea (14 [38.9%] of 36 pts), vomiting (10[27.8%] of 36 pts), QT prolongation (9 [25.0%] of 36 pts), sinus bradycardia (7 [19.4%] of 36 pts), ALT increase (10 [27.8%] of 36 pts), diarrhea (6 [16.7%] of 36 pts). Only one DLT of grade 3 blood glucose increase occurred at 210 mg out of the first 3 pts, so another 3 pts will be enrolled to determine RP2D/MTD. SAF-189s had shown response in the starting dose of 20mg, with 1of 2 pts achieving partial response (PR) over 43 cycles until clinical data cut off. All 34 pts in efficacy analysis set had achieved tumor shrinkage, with 17 confirmed PR (50%) (95% CI, 32.4–67.6%) and 4 unconfirmed PR (11.7%). 11 (45.8%) pts had confirmed PR among 24 pts who had failed to Crizotinib or Ceritinib and 10 (47.6%) pts had confirmed PR among 21pts who had CNS metastases. PFS data is pre-mature, with only median PFS of the 80 mg cohort being inferred as 19.42 months. Conclusions: In the dose-escalation portion of this study, SAF-189s was safe, very tolerable, and demonstrated both systemic and intracranial activity in pts with advanced ALK-positive NSCLC who had failed to at least 1 prior systemic therapy. Therefore, this study warrants further investigation to prove SAF-189s as an effective therapeutic option for pts who have ALK+ NSCLC. Clinical trial information: NCT04237805.
Prognostic biomarker potential of quantifying endotrophin in serum from pancreas cancer patients.
Authors: Nicholas Willumsen, Inna Chen, Neel Ingemann Nissen, Astrid Zedlitz Johansen, Julia S. Johansen, Morten A. Karsdal
Journal: Journal of Clinical Oncology (2020)

e16804 Background: Pancreas cancer (PC) is the most stroma rich tumor type defined by increased collagen deposition and remodeling (desmoplasia/tumor fibrosis), which result in poor prognosis and lack of treatment response. The cleavage product of the type VI collagen alpha 3 (COL6a3) chain, also knowns as endothrophin, has been shown to signaling properties and affect several pro-tumorigenic events by augmenting desmoplasia, angiogenesis, inflammation and tumor growth. Here we evaluate the clinical utility of a biomarker (PRO-C6) quantifying endothrophin in serum from patients with PC. Methods: Serum PRO-C6 was measured by ELISA (Nordic Bioscience) in 814 PC patients (n = 15, 201, 164 and 434 for stage 1-4, respectively) and 87 patients with benign conditions from the clinical study BIOPAC (NCT03311776, Denmark). PC was histologically confirmed, and patients received standard of treatment (surgical resection or palliative chemotherapy). PRO-C6 was compared between PC and benign conditions and correlated to stage. Association between OS and PRO-C6 in PC patients was analyzed by Kaplan-Meyer curves and Cox regression analysis alone, and after adjusting for age, gender, BMI, diabetes, smoking, performance status, cachexia, CA19-9, stage and metastatic sites. Results: PRO-C6 was elevated in PC compared to benign disease (p = 0.009) and increased with tumor stage (p = 0.0006). When dividing PRO-C6 into quartiles (Q1-Q4) a stepwise decrease was detected in median OS time (Q1:380 days, Q2:264 days, Q3:236 days, Q4:176 days, p &lt; 0.0001). Patients in Q4 had 85% increased risk of dying compared to Q1 (HR:1.85, p &lt; 0.0001). High PRO-C6 (Q4) remained associated with poor OS after adjusting for co-variates (HR: 1.66, p = 0.0018). Conclusions: Pretreatment serum PRO-C6 (a measure of the COL6a3 chain/endothrophin) is associated with PC and has independent prognostic value. This suggests that endothrophin, and the desmoplastic reaction, plays a key role in PC and indicate that PRO-C6 may provide means for a theragnostic approach for stratifying and treating PC patients in the future. Clinical trial information: NCT03311776 .
Bone scintigraphy and PET-CT: A necessary alliance for bone metastasis detection in breast cancer?
Authors: Joana Cristo Santos, Miguel Henriques Abreu, Miriam Seoane Santos, Hugo Duarte, Tiago Alpoim, Susana Sousa, Pedro Henriques Abreu
Journal: Journal of Clinical Oncology (2020)

e13070 Background: Bone is one of the main sites of breast cancer metastasis. Staging of this kind of disease spread can be performed in locally advanced cases with PET-CT in conjunction with Bone Scintigraphy. The purpose of this work is to compare the efficiency of bone metastasis detection between PET-CT and bone scintigraphy. Methods: Prospective analysis of locally advanced breast cancer patients treated in a Comprehensive Cancer Center between 2014 and 2019 that performed PET-CT and Bone Scintigraphy in the staging. Interval between the two exams could not exceed 2 months. Clinical and pathological characteristics of the disease were collected from electronic files and independently clinical images reports were considered to evaluate the ability of each imaging modalities to identify bone disease. In discrepancy cases a re-analysis of the images by two independent nuclear physicians was performed to validate the findings. Results: We analyzed 204 cases. The majority of them had ductal carcinomas (72.5%), cT2/3 (70%), cN1/2(61.8%) and G2/3 (94.6%), luminal B- like, HER2 positive disease (49.2%). In this cohort, bone metastasis was documented in 52 (25.5%) patients. PET-CT presented 97.0% of accuracy, surpassing the 94.1% presented by Bone Scintigraphy. The latter failed to correctly detect bone metastasis in 11 (5.4%) patients and only outperformed PET-CT in 3 (1.5%) patients. The main difference between the two modalities was the non-detection of cranium lesions in PET-CT images. Conclusions: PET-CT showed higher efficiency in bone metastasis detection than Bone Scintigraphy, probably because it detects lytic lesions. The non-detection of cranium ones can be harmful and so modifications in the image acquisition are required to improve the quality of PET-CT, avoiding other exams in bone staging.
Assessment of Maternal Glycemia and Newborn Size Among Pregnant Women Who Use Wood Stoves in Northern New England
Authors: Abby F. Fleisch, Shravanthi M. Seshasayee, Eric Garshick, Jonathan W. Chipman, Petros Koutrakis, Emily R. Baker, Margaret R. Karagas
Journal: JAMA Network Open (2020)

This cohort study uses data from the New Hampshire Birth Cohort Study to assess maternal glycemia and newborn size among pregnant women who use wood-burning stoves in their New England homes.
Relative dose intensity and pathologic response rates in HIV-infected and HIV-uninfected breast cancer patients who received neoadjuvant chemotherapy.
Authors: Yehoda M. Martei, Surbhi Grover, Mohan Narasimhamurthy, Dipho Irene I Setlhako, Gezahen N Ayane, Tlotlo Bathethi Ralefala, Sebathu Phillip Chiyapo, Robert Gross, Angela DeMichele, Lawrence N. Shulman
Journal: Journal of Clinical Oncology (2020)

e19140 Background: HIV-infected (HIV+) breast cancer patients may have significantly worse survival compared to HIV-uninfected (HIV-). If so, identifying the underlying mechanism might lead to effective interventions to reduce the disparity. Relative dose intensity (RDI) &lt; 0.85 has been associated with worse survival outcomes in non-metastatic breast cancer patients. We aimed to determine if RDI of chemotherapy and pathologic complete response (pCR) rates were lower for HIV+ patients who received neoadjuvant chemotherapy (NAC) compared with HIV-. Methods: We conducted a prospective cohort study in newly diagnosed breast cancer patients with locally advanced disease who initiated NAC at Princess Marina Hospital in Botswana between 2/2017 and 9/2019. Clinical and treatment data were collected at baseline and at every treatment visit. Surgical pathology post-NAC was graded as pCR if there was no invasive disease in the breast or lymph nodes. RDI was calculated for each patient, with optimal RDI ≥ 0.85. Dichotomous variables were compared using Fisher’s exact and chi-squared tests; and continuous variables using rank sum tests. Results: 111 patients were enrolled, of whom 84 (75.7%) were HIV-, 26 (23.4%) HIV+ and 1 (0.9%) with unknown status who was excluded from final analysis. HIV+ patients were less likely to receive optimal RDI (0.74 vs. 0.88; p = 0.03). Of the 110 patients 15 (13.6%) were still receiving chemotherapy; 22 (20%) prematurely discontinued chemotherapy of whom 11 (10%) received surgery; 7 (6.4%) completed chemotherapy but had no surgery. 77 (70%) completed surgery which included 11 (10%) with no pathology reports available, 3 (2.7%) inadequate surgical specimens and 63 (57.3%) complete pathology results included in pCR analysis: 1/13 (7.7%) HIV+ patients had a pCR compared to 12/50 (24%) in HIV-(p = 0.27). Conclusions: HIV+ patients were significantly more likely to receive inadequate neoadjuvant chemotherapy dose intensity, and trended towards a lower pCR in this small cohort, which may contribute to adverse treatment outcomes. Further study needed to validate high rate of treatment discontinuation and specific risk factors to inform targeted interventions to improve therapy delivery.
Long-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.
Authors: Laura Alder, Matthew Nguyen, James Qu, Hannah Lee, Leroy R. Thacker, Sean Dougherty, Andrew Stewart Poklepovic
Journal: Journal of Clinical Oncology (2020)

e16633 Background: Yttrium-90 (Y90) radioembolization is a catheter-based therapy utilized in the treatment of hepatic tumors such as hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; few have assessed long term hepatic function. These studies reported PFS ranging from 7.9 to 18 months (m), and median OS of 17.2 to 18 m for Child-Pugh (CP) Class A and 6.0 to 7.7 m for CP Class B. This study aimed to evaluate a clinical real-world experience of Y90 therapeutic effectiveness and long-term impact on hepatic function. Methods: A single-center retrospective chart review was performed for patients with a CP score of A or B who received Y90 for primary HCC between 2008 and 2016. Model for end stage liver disease (MELD) and CP scores were calculated for the day of treatment and at 1, 3, 6, 12, and 24 m post procedure. OS and PFS were characterized using a Kaplan-Meier survival analysis and a multivariate model. Results: 134 patients were included. Mean age was 60 years old, ranging from 44-90. Underlying liver disease included HCV – 66%, ETOH cirrhosis – 23%, NAFLD – 19%, HBV – 5%. CP Class A patients (79%) had a median OS of 16.59 m (95% CI: 8.90 to 23.10m) from date of Y90 treatment compared to a median of 7.90 m (95% CI: 4.60 to 15.64 m) for CP Class B. CP Class A patients had a median PFS of 3.45 m (95% CI: 2.99 to 5.55 m) from date of Y90 treatment compared to a median of 3.71 m (95% CI: 2.07 to 8.28 m) for CP Class B patients. These differences were not statistically significant. Median OS from date of diagnosis for the entire study population was 29.37 m (95% CI: 23.00 to 38.77 m). MELD scores were statistically significantly higher at 1, 3, 6 and 12 m post-treatment than on Day 0, with significant recovery at 24 vs 3 m. Older age, higher T stage, higher MELD and CP scores, and patients with a history of portal vein thrombosis (PVT) had significantly lower OS. PFS was significantly shorter in those with advanced stage at diagnosis and higher CP score. Conclusions: While our study supports the literature for OS in Y90 patients, we found a shorter PFS in this population. This may reflect the utilization of RECIST in clinical trials vs clinical radiology practice in determining progression. Over time, the most significant factors associated with OS were age, MELD and CP scores and PVT. For PFS, CP score and stage at diagnosis were significant. The increasing MELD and CP scores over time reflect a possible mix of radio embolization‐induced liver disease and progression of HCC. The downtrend at 24 m is likely due to durable survivors with significant benefit from therapy and no long-term complications from Y90.
Cadmium, Smoking, and Human Blood DNA Methylation Profiles in Adults from the Strong Heart Study
Authors: Arce Domingo-Relloso, Angela L. Riffo-Campos, Karin Haack, Pilar Rentero-Garrido, Christine Ladd-Acosta, Daniele M. Fallin, Wan Yee Tang, Miguel Herreros-Martinez, Juan R. Gonzalez, Anne K. Bozack, Shelley A. Cole, Ana Navas-Acien, Maria Tellez-Plaza
Journal: Environmental Health Perspectives (2020)

The epigenetic effects of individual environmental toxicants in tobacco remain largely unexplored. Cadmium (Cd) has been associated with smoking-related health effects, and its concentration in tobacco smoke is higher in comparison with other metals.
风湿病的基本检查
Authors: 张卓莉
Journal: BMJ (2006)

风湿病泛指影响骨关节及其周围软组织,如肌腱、滑囊、筋膜等的一组疾病,包括弥漫性结缔组织病、脊柱关节病、骨关节炎、代谢性骨关节病及感染性关节炎等.风湿病是全身性疾病,可以累及全身各个系统和脏器,表现形式多样,涵盖了10大类200多种疾病.风湿病学和免疫学紧密相关,为了区别于传统的以腰腿痛和(或)关节痛为主的风湿病概念,又称其为风湿免疫病.现对其关节检查法、实验室检查及影像学检查概述如下。