tbuckley/cabot-search huggingface dataset:
A survey on service status of rural doctors in Beijing suburb
Authors: Dongmei Jia, Li Ma, Na Li, Chen Wang, Yi Dong, Yingchun Peng, Lanqiu Liu, Shaohan Qi
Journal: BMJ (2018)

Objective
To survey the service status of rural doctors in Beijing suburb.


Methods
Twenty one village officials, 21 rural doctors and 42 local residents from 21 villages in Beijing Huairou district were selected with purposive sampling method as the objects of this qualitative study. The service status of rural doctors was assessed from four aspects: basic public health service, basic medical service, management ability, responsibility and communication ability.


Results
All the 21 village clinics provided basic public health services, including hypertension management (100.0%), diabetes management (100.0%); 11 clinics (52.4%) also provided vaccination services. Eighteen village doctors (85.7%) assisted township health center to provide signing health service, but were lack of knowledge about the types of service the general practitioners (GPs) should provide. The well performed basic medical services among 21 village clinics included diagnosis and differential diagnosis of common diseases in 19 (90.5%) clinics, home visits in 18 (85.7%) and physical examinations in 15 (71.4%), but the service like trauma management, changing dressing, subcutaneous injection, intravenous infusion were performed less well. The top three most satisfied aspects in the medical service were the service attitude (4.14 points), the quality of service (3.98 points) and service time (3.66 points), and the bottom three were equipment facilities, the types and varieties of drug, and the environment of clinics. In aspect of emergency service, 7 village doctors (33.3%) would choose self-referral by patients without preliminary on-site emergency treatment, 5(23.8%) would give on-site emergency treatment before self-referral by patients. In aspect of training needs, 18 (42.9%) local residents and 9 (42.9%) village officials considered that it was not necessary to provide training for village doctor because of relatively older age. In aspect of patient′s satisfaction, 21 village doctors (100.0%), 21 village officials (100.0%) and 34 villagers (81.0%) considered that the village doctor had a high professional sense of responsibility and medical ethics, and their doctor-patient communication skills were strong.


Conclusion
The survey reveals the current service status of village doctors in Beijing suburb, and it is necessary to take comprehensive measures to upgrade the competence of village doctors and to improve the quality of service in village clinics.


Key words: 
Rural doctors; Professional competence; Qualitative research
Genotype and phenotype correlation of common cancer predisposition syndromes in sarcoma cases.
Authors: Milita Zaheed, Kathy Tucker, Mandy L. Ballinger, David Morgan Thomas
Journal: Journal of Clinical Oncology (2020)

1524 Background: Sarcomas are rare heterogenous cancers affecting a predominantly younger population. The most recognised autosomal dominant contributor being pathogenic TP53 variants associated with Li Fraumeni Syndrome (LFS). When referred, patient eligibility for germline TP53 testing is assessed using classic or Chompret LFS criteria. Other heritable cancer syndromes which can be associated with sarcoma (breast/ovarian, colorectal) are more commonly considered in clinical practice. In some centres germline testing is offered to only those who meet established clinical criteria. Heritable cancer predisposition has several implications including therapy and clinical risk management. Here we report the concordance between clinical criteria and genotypes in sarcoma families. Methods: We included 1,664 sarcoma probands from the International Sarcoma Kindred Study. Eligibility for genetic testing was assessed using internationally accepted clinical criteria for recognised cancer syndromes. Whole genome sequencing was performed on peripheral blood DNA and variants in the ACMG cancer gene list were classified as pathogenic or likely pathogenic using established bioinformatics pipelines. Results: The median age of sarcoma diagnosis in 1664 probands (798 males, 866 Females) was 48 years (range 1-93). The median age of first cancer diagnosis was 46.5 years (0-93) with 291 probands having multiple primary cancers. Of 1504 informative pedigrees, 243 (16%) met criteria for testing; 207 (14%) TP53; 19 (1%) BRCA1/2; 2 (&lt;1%) colorectal cancer (CRC) genes and 15 (1%) familial melanoma. Of 12 TP53 PVs identified, 9 met TP53 testing criteria. Of 13 PVs identified in HR genes (7 BRCA2, 4 PALB2 and 2 BRCA1) only 1 ( PALB2) met BRCA1/2 testing criteria and 2 met Chompret criteria. Both BRCA1 cases were male with a 1st degree relative with ovarian cancer. In CRC genes (1 APC, 2 MSH2, 4 MSH6, 1 PMS2), none met CRC testing criteria but 4 met Chompret criteria. No CDKN2A PVs were identified in melanoma families. Conclusions: In probands with sarcoma, clinical criteria for eligibility for testing for common non-LFS heritable syndromes perform poorly. This should be considered when making decisions regarding germline testing.
Association of autoimmunity with survival in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Panagiota Economopoulou, Niki Gavrielatou, George Papaxoinis, Ioannis Kotsantis, Anastasios Pantazopoulos, Maria Anastasiou, George Kavourakis, Stavros Gkolfinopoulos, Amanda Psyrri
Journal: Journal of Clinical Oncology (2020)

6537 Background: ICIs are associated with immune-related adverse events (irAEs) that occur as a consequence of enhanced immune response due to T-cell activation. The objective of this observational cohort study was to investigate the association between irAEs and disease outcome in pts with R/M HNSCC. Methods: 110 pts treated with ICIs were reviewed. Overall survival (OS) was calculated from the date of initiation of ICI to the date of death. To overcome guarantee-time bias, we calculated post-irAEs survival from the date of first irAE presentation in patients who developed irAEs or from the date of ICI initiation in pts without irAEs. Results: Primary site was the oral cavity (N = 51), oropharynx (N = 20), larynx (N = 29), hypopharynx (N = 1), paranasal sinuses (N = 5) and nasopharynx (N = 4). 41 (37.3%) had metastatic and 69 (62.7%) recurrent disease. 32 pts (29.1%) developed irAEs, with more common thyroiditis (N = 15, 13.6%). Of 100 pts with evaluable disease, 14 (14%) responded. 6/31 (19.4%) with irAEs vs. 8/69 (11.6%) without irAEs responded to ICI (p = 0.354). After a median follow-up of 16.4 months, 69 pts died. Median OS was 10 mo (95%CI, 6.7-13.4), 10 mo (95%CI, 5.6-14.5) for pts with recurrent and 10 mo (95%CI, 7.7-12.3) for pts with metastatic HNSCC (p = 0.966). Median OS was 17.9 mo (95%CI, 7.9-27.9) for pts with irAEs and 6.6 mo (95%CI, 3.3-9.9) for pts without irAEs (p = 0.001). Median post-irAEs survival was 16.3 (95%CI, 7.1-25.5) for pts with irAEs vs. 6.6 mo (95%CI, 3.3-9.9) for pts without irAEs (p = 0.020). Responders to ICI did not differ in median post-irAEs survival irrespective of whether they developed irAEs (p = 0.561), while among non-responders, those who developed irAEs had significantly longer median post-irAEs survival compared to those who did not (10 vs. 6 mo, respectively, p = 0.044). Multiviariate Cox proportional hazard models showed that independent favorable prognostic factors for post-irAEs survival were the development of irAEs (HR 0.54, 95%CI 0.30-0.97, p = 0.039) and response to ICI (HR 0.16, 95%CI 0.05-0.50, p = 0.002). Conclusions: The development of irAEs is a strong predictor of improved survival in patients with advanced HNSCC treated with ICIs.
Magentic Resonance Imaging Evaluation of Regional Lung V<scp>t</scp>s in Severe Neonatal Bronchopulmonary Dysplasia
Authors: Kara R. Gouwens, Nara S. Higano, Kaitlyn T. Marks, Julia N. Stimpfl, Erik B. Hysinger, Jason C. Woods, Paul S. Kingma
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Bronchopulmonary dysplasia is a heterogeneous lung disease characterized by regions of cysts and fibrosis, but methods for evaluating lung function are limited to whole lung rather than specific regions of interest.Objectives: Respiratory-gated, ultrashort echo time magnetic resonance imaging was used to test the hypothesis that cystic regions of the lung will exhibit a quantifiable Vt that will correlate with ventilator settings and clinical outcomes.Methods: Magnetic resonance images of 17 nonsedated, quiet-breathing infants with severe bronchopulmonary dysplasia were reconstructed into end-inspiration and end-expiration images. Cysts were identified and measured by using density threshold combined with manual identification and segmentation. Regional Vts were calculated by subtracting end-expiration from end-inspiration volumes in total lung, noncystic lung, total-cystic lung, and individual large cysts.Measurements and Main Results: Cystic lung areas averaged larger Vts than noncystic lung when normalized by volume (0.8 ml Vt/ml lung vs. 0.1 ml Vt/ml lung, P < 0.002). Cyst Vt correlates with cyst size (P = 0.012 for total lung cyst and P < 0.002 for large cysts), although there was variability between individual cyst Vt, with 22% of cysts demonstrating negative Vt. Peak inspiratory pressure positively correlated with total lung Vt (P = 0.027) and noncystic Vt (P = 0.015) but not total lung cyst Vt (P = 0.8). Inspiratory time and respiratory rate did not improve Vt of any analyzed lung region.Conclusions: Cystic lung has greater normalized Vt when compared with noncystic lung. Ventilator pressure increases noncystic lung Vt, but inspiratory time does not correlate with Vt of normal or cystic lung.
Association of detectable levels of circulating tumor DNA (ctDNA) with disease burden in prostate cancer (PC).
Authors: Gerhardt Attard, Michael Gormley, Karen Urtishak, Jason S. Simon, Deborah S. Ricci, Trilok V. Parekh, Shinta Cheng, Kim N. Chi, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2020)

5562 Background: PC is characterized by a relatively low prevalence of recurrent somatic point mutations. ctDNA is shed from PC and can be analyzed to profile somatic point mutations and copy number changes. We evaluated a computational approach to detect ctDNA (ie. ctDNA+) in PC based on allele frequencies of polymorphisms and mutations. We then sought to confirm the association of this biomarker with disease burden and clinical outcome. Methods: Customized, hybrid capture, high-depth next-generation sequencing was performed on pre-treatment (PT) plasma samples from a phase 2 line 3+ metastatic castration-resistant PC (mCRPC) study (NCT02854436, GALAHAD) and PT and end of treatment (EOT) samples from randomized Phase 3 study in non-metastatic (nm) CRPC (NCT01946204, SPARTAN) and from metastatic castration-sensitive PC (mCSPC) (NCT02489318, TITAN). Associations of ctDNA+ with bone lesions (number), visceral metastases (+/-), circulating tumor cells count (CTCc), and serum prostate specific antigen (PSA), alkaline phosphatase (AP) and lactate dehydrogenase (LD) were tested. Also, associations of ctDNA+ with overall survival (OS) and second progression free survival (PFS2) were evaluated in randomized studies using Cox regression. Results: ctDNA+ at PT was 7.5% in nmCRPC, 23.7% in mCSPC and 66% in heavily pre-treated mCRPC. ctDNA+ increased from PT to EOT in nmCRPC (7.5% to 27%) and mCSPC (23.7% to 63.6%). Disease burden metrics were evaluated in ctDNA+ vs ctDNA- patients. ctDNA+ was associated with higher disease burden in mCRPC (Table), nmCRPC and mCSPC. At EOT, ctDNA+ patients had shorter OS and PFS2 in nmCRPC (HR [95% CI] OS: 2.73 [1.83, 4.08], p &lt; 0.0001; PFS2: 2.00 [1.38, 2.90], p = 0.0002) and mCSPC (HR [95% CI] OS: 7.59 [3.22, 17.91], p &lt; 0.0001; PFS2: 4.84 [2.47, 9.47], p &lt; 0.0001). Conclusions: ctDNA+ assessed using our novel, composite biomarker increases with advanced disease state and disease progression, is significantly associated with disease burden and poor clinical outcome in PC and could be a clinically relevant metric for monitoring response to therapy. Clinical trial information: NCT02854436 . [Table: see text]
MCM4 as a prognostic biomarker of early-stage lung cancer.
Authors: Virote Sriuranpong, Sutima Luangdilok, Poonchavist Chantranuwatana, Nussara Leeladejkul, Nopporn Pornpatanarak, Vichai Benjacholamas, Piyada Sitthideatphaiboon, Chanida - Vinayanuwattikun, Trairak Pisitkun
Journal: Journal of Clinical Oncology (2020)

e21033 Background: Prognostic biomarker in early-stage lung cancer is less well defined. Despite early detection, one-third of patients with completely resected early-stage lung cancer without lymph node involvement have a recurrence. Our main objective is to investigate potential biomarkers useful in classification and predicting prognosis of this early-stage lung cancer, particularly in lymph node-negative subgroup. Methods: In discovery phase, we performed proteomic profiling on 60 lung cancer tissues to distinguish solid versus non-solid adenocarcinoma. Relative protein quantification was analyzed using Tandem Mass Tag mass spectrometry. In validation phase, tumor tissues from an additional cohort were analyzed by immunohistochemistry in conjunction with quantitative image analysis to confirm the differential expression of significantly altered proteins, including MCM2, MCM4, MCM6, SCAMP3, DPP4 and MYH11. Prognostic potentials of each biomarker were analyzed with univariate and multivariate analyses. Results: Quantitative proteomic analysis of predominantly solid versus non-solid adenocarcinoma tissues showed 30 differentially expressed proteins consisting of 13 increased and 17 decreased proteins found in solid compared with non-solid adenocarcinoma. Four most increased proteins (MCM2, MCM4, MCM6, and SCAMP3) and two most decreased proteins (DPP4 and MYH11) were selected for immunostaining in the validation cohort of 204 patients with resected adenocarcinoma without lymph node involvement. 57 out of 204 (27.9%) patients had recurrent disease. The high expression level of MCM4 was the strongest signature for disease recurrence (HR 4.85, 95%CI 2.78-8.47, p &lt; 0.0001) and remained significant under multivariate analyses adjusted for TNM stage, histologic subtypes, lymphovascular invasion, tumor necrosis, and adjuvant chemotherapy. Recurrence-free survival (RFS) was significantly shorter in patients with high MCM4 compared with low MCM4 (5-y RFS 50% vs 84%, p &lt; 0.0001) and remained highly significant within stage IA (5-y RFS 69% vs 93%, p &lt; 0.0001), or stage IB and II (5-y RFS 36% vs 69%, p = 0.001). High expression of MCM4 correlated with other poor prognosis factors including smoking (p = 0.001), stage (p = 0.003), lymphovascular invasion (p = 0.036), visceral pleural invasion (p = 0.005), tumor necrosis (p &lt; 0.0001) and solid histology (p &lt; 0.0001). Conclusions: High MCM4 expression serves as an important prognostic biomarker predicting recurrence in early-stage node-negative lung adenocarcinoma.
Complications and solutions related to home enteral nutrition for patients with acute pancreatitis
Authors: Huijie Deng
Journal: BMJ (2019)

Acute pancreatitis is a common disease, the mortality of severe acute pancreatitis (SAP) is high and early enteral nutrition can effectively reduce the complications and mortality of SAP. However, it is difficult to complete the whole course of enteral nutrition in the hospital, so that home enteral nutrition(HEN) becomes necessary. The main limitation of HEN is the occurrence of various problems in the procedure. This article is intended to explore and summarize the problems related to HEN, including mechanical complications, gastrointestinal side effects, metabolic problems, infection, and psychologic problems, expense, quality of life and others. In consideration of these problems, we also give feasible suggestions for HEN.


Key words: 
Pancreatitis, acute necrotizing; Home enteral nutrition; Complication; Prevention
Locoregional recurrence following pathologic complete response in patients with T1-3 N0 breast cancer treated with neoadjuvant chemotherapy, breast conserving surgery and whole breast radiation: Is a trial of omission of radiation warranted?
Authors: Elena Parvez, Thierry Muanza
Journal: Journal of Clinical Oncology (2020)

e12625 Background: Pathologic complete response(pCR) after neoadjuvant chemotherapy(NAC) in patients with breast cancer(BC) is associated with decreased recurrence and improved survival. In NSABP B18 and B27, 10-yr locoregional recurrence(LRR) after pCR in patients with Stage I-III BC undergoing breast conserving surgery(BCS) and whole breast RT(WBRT) was 5.2-6.9%. However, LRR may be overestimated as Her2 therapy was not used and only some eligible patients received endocrine therapy. A retrospective study using modern protocols found a 5-yr LRR of up to 2.6%. We hypothesize that LRR in N0 patients is even lower, and de-escalation of therapy should be examined. The study objective is to assess if a prospective trial of omission of WBRT after BCS in patients with N0 BC and pCR after NAC is warranted and to assess feasibility. Methods: Patients with T1-T3 N0 invasive BC diagnosed between Dec 2011-2017 treated with NAC and BCS were identified from a hospital BC registry. Health records were retrospectively reviewed to identify patients with pCR, defined as absence of residual invasive or in-situ disease(ypT0N0). Incidents of locoregional and distant recurrence were recorded. Results: Of 89 patients with T1-3 N0 invasive BC treated with NAC and BCS, 29(32.6%) had pCR. Median follow-up was 61.1 months. Median age was 55 yrs and median tumour size was 2.4cm. Receptor status was 16(55.2%) HR-Her2-, 4(13.8%) HR-Her2+, 7(24.1%) HR+Her2+ and 2(6.9%) HR+Her2-. NAC protocols consisted of an anthracycline and/or a taxane in 27(90%) patients, and 6 patients were treated on NAC trials. All patients with Her2+ disease received Her2 targeted therapy. Adjuvant endocrine therapy was taken by 8 of 9 patients with HR+ disease. All patients received WBRT without nodal RT. RT plan was available for 26(86.7%) patients. RT dose ranged from 40-50Gy, and all but 4 received tumour bed boost. There were no local or regional recurrence events at last follow-up. One patient developed brain metastases at 15.7 months. Conclusions: Over 6 years, 29 patients were identified that would be eligible for a prospective trial evaluating omission of WBRT after pCR in N0 patients treated with NAC and BCS. At median 5-yr follow-up, there were no locoregional recurrences in our cohort, demonstrating that the absolute benefit provided by WBRT is likely small. Our results indicate a prospective trial is warranted and will require multi-institution participation to accrue.
Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response
Authors: Hyun Young Woo, Jun Yong Park, Si Hyun Bae, Chang Wook Kim, Jae Young Jang, Won Young Tak, Dong Joon Kim, In Hee Kim, Jeong Heo, Sang Hoon Ahn
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV.Methods: This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded.Results: Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], &lt;i&gt;P&lt;/i&gt;&lt;0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, &lt;i&gt;P&lt;/i&gt;&lt;0.001). Multivariate analysis indicated that high baseline HBV DNA level (&lt;i&gt;P&lt;/i&gt;=0.005) and LAM/LdT+ADV maintenance therapy (&lt;i&gt;P&lt;/i&gt;=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events.Conclusions: ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).
Phase II study of nivolumab (anti-PD1), tadalafil, and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers.
Authors: M. Cecilia Monge B., Changqing Xie, Donna Mabry-Hrones, Bradford J. Wood, Seth M. Steinberg, David E Kleiner, Tim F. Greten
Journal: Journal of Clinical Oncology (2020)

TPS4656 Background: Treatment options for advanced hepatocellular carcinoma (HCC) and liver dominant metastatic disease from colorectal or pancreatic cancers are limited with poor overall survival. Tadalafil has shown to increase anti-tumor immunity by decreasing myeloid derived suppressor cells (MDSC) and impair tumor growth in preclinical HCC models. Oral vancomycin affects bile acid metabolizing gut commensal bacteria leading to increased CXCL16 expression in the liver resulting in NKT mediated liver-selective anti-tumor effects. This study combines immune checkpoint inhibition (ICI) treatment with nivolumab in combination with tadalafil and oral vancomycin. We aim to evaluate the synergy of the antitumor effect induced by the change in gut microbiome with oral vancomycin and the immunomodulatory effect of PDE5 inhibition combined with ICI with nivolumab in advanced liver cancer or liver metastasis. Correlative Studies: Paired liver tumor biopsies are analyzed for genomic analysis (WES, RNA-seq), immune cell infiltration, proteomics and metabolomic studies (bile acids) and chemokine expression. Stool samples are analyzed for microbiota. Blood samples are analyzed for immune monitoring, cytokine profiles and pharmacokinetics of study drugs. Serum bile acid levels are determined in blood in the 2 hour period after test meal ingestion. Methods: This is a single-arm study of nivolumab, oral vancomycin and tadalafil. Treatment is delivered in 4-week cycles (C) and continues until off treatment. Imaging is done every 8 weeks. Biopsies are done at baseline and during week 3 of C2. Nivolumab is administered on day (D)1 of each C at a dose of 480 mg IV. Tadalafil is administered orally (PO); 10 mg daily starting on D1 of C1 and continues daily until off study. Vancomycin administration starts on D1 of C1 at 125 mg PO every 6 hours for a total daily dose of 500 mg. Patients will be on vancomycin 3 weeks on, 1 week off per regimen. The study is currently enrolling without DLT. Clinical trial information: NCT03785210 .