tbuckley/cabot-search huggingface dataset:
Changes in cancer mortality rates after the adoption of the Affordable Care Act.
Authors: Anna Lee, Kanan Shah, Junzo P. Chino, Fumiko Chino
Journal: Journal of Clinical Oncology (2020)

2003 Background: The Affordable Care Act (ACA) was designed to improve health status in the US primarily through improving access to health insurance. As adoption of Medicaid expansion varied at the state level, this study aims to compare cancer mortality rates over time between states who did (EXP) and did not adopt (NonEXP) Medicaid expansion. Methods: Age-adjusted mortality rates per 100,000 were gathered from the National Center for Health Statistics from 1999-2017 to establish trends. Only deaths due to cancer in patients less than 65 were included. Absolute change in cancer mortality was calculated from 2011-2013 and then from 2015-2017 with 2014 as washout year. Changes within subpopulations (gender, race, ethnicity) were also assessed. Mortality changes between EXP and NonEXP groups were via “difference in differences” analysis. Results: Overall age-adjusted cancer mortality in the US fell from 1999-2017 from 66.9 to 48.8 per 100,000. EXP states had higher population (157 vs 118 million) with less black/African Americans (19.2 vs 21.8 million) and more Hispanics (33.0 vs 21.7 million) than NonEXP states (all examples from 2017). The overall age-adjusted cancer mortality was consistently worse in NonEXP states, cancer mortality fell from 64.7 to 46.0 per 100,000 in EXP states and from 69.0 to 51.9 per 100,000 in NonEXP states from 1999-2017 (both trends p &lt; 0.001, comparison p &lt; 0.001). Comparing the mortality changes in the peri-ACA years (2011-2013 vs 2015-2017) between the 2 cohorts, the difference in differences between EXP and NonEXP states was -1.1 and -0.6 per 100,000 respectively (p = 0.006 EXP, p = 0.14 NonEXP). The estimated overall cancer mortality benefit gained in EXP states after Medicaid expansion (∆∆∆) is -0.5 per 100,000 (p = NS). In EXP states, this translates to an estimated 785 less cancer deaths in 2017. Age-adjusted cancer mortality per 100,000 was worse in NonEXP states for black patients (58.5 EXP vs 63.4 NonEXP in 2017) however there was no differential mortality benefit after ACA expansion when comparing between the peri-ACA years. Of the subpopulations assessed, Hispanics in EXP states had the highest differential cancer mortality benefit at -2.1 per 100,000 (p = 0.07). Conclusions: This is the first study to show a directly measured cancer survival benefit from the ACA on a national scale using a comprehensive database. Hispanic populations appear to have the highest differential cancer mortality benefit after Medicaid expansion. Further study is needed to elucidate why other populations like black patients did not appear to reap the same mortality decrease.
Clinical characteristics of disseminated penicilliosis marneffei in non-HIV patients
Authors: Yang Jiao, Hongwei Fan, Jinjing Liu, Yue Sha, Weiguo Zhu, Xiaoming Huang
Journal: BMJ (2016)

The clinical data of 5 non-HIV patients with disseminated penicilliosis marneffei (PSM) admitted in Peking Union Medical College Hospital between January 2004 to December 2014 were analyzed retrospectively.The median age of 5 patients (4 males and 1 female) was 45 years.They had lived in or traveled to areas of high prevalence. The median duration from onset of the infection to the diagnosis was 9 months. Four of them had ostealgia. The imaging results showed that they all had osteolytic lesions. Three patients had skin multi-abscesses. Cultures of the pus from skin lesions were more sensitive than cultures of blood and sputum. Two patients were also confirmed to be co-infected with non-tuberculosis mycobacteria. Disseminated PSM was easily misdiagnosed in non-HIV patients since clinicians might be unfamiliar with the clinical characteristics of the disease. The diagnosis of disseminated PSM should be considered for patients who lived in or traveled to areas of high prevalence and presented with fever, skin multi-abscesses and osteolytic lesions. And the complication with other opportunistic infections should be considered in these patients.


Key words: 
Penicilliosis marneffei; Opportunistic infection
Correlation of serum PIVKA-II and AFP level with portal vein tumor thrombus and BCLC stage in newly diagnosed hepatocellular carcinoma patients.
Authors: Goutham Gandham, Hridya Jayamohanan, Bharadwaj Ponnada, Anil Kumar, Sudhindran S, Pavithran Keechilat
Journal: Journal of Clinical Oncology (2020)

e16608 Background: Protein Induced by Vitamin K Absence-II (PIVKA-II) is a tumor marker specific for hepatocellular carcinoma (HCC). PIVKA-II levels correspond with HCC oncogenesis and disease progression. Portal vein tumor thrombus (PVTT) in patients with HCC is a significant factor that affect treatment and prognosis. In this study we assessed the predictive value of PIVKA-II and AFP for vascular invasion and BCLC stage in newly diagnosed HCC patients. Methods: We retrospectively reviewed records of newly diagnosed HCC patients at a tertiary hospital in India between January 2019 to December 2019. Clinical details, BCLC stage, radiological imaging records, serum levels of PIVKA-II and AFP at the time of diagnosis were obtained from medical records. Diagnostic accuracy and cut-off value of PIVKA-II in patients with portal invasion were calculated using receiver operator curve (ROC) analysis. Multiple pairwise comparisions between BCLC stage with PIVKA-II and AFP levels were analysed using Kruskal-Wallis test. Results: Out of 162 newly diagnosed HCC patients 42(25.9%) were detected with PVTT on imaging such as contrast-enhanced computed tomography or magnetic resonance imaging at the time of diagnosis.120(74.1%) patients without PVTT were taken as controls for the analysis. Serum level of PIVKA-II in HCC patients with PVTT was significantly higher than in HCC patients without PVTT (1152.57 mAU/ml vs 146.39 mAU/ml; p = 0.001). AUROC of PIVKA-II was 0.796 (95%CI 0.70-0.892, p = 0.000).The optimal cut-off value of PIVKA-II was 271.81 mAU/ml with a sensitivity of 78.6% and specificity of 52.4%, and the diagnostic accuracy was 59.98%. AUROC of AFP was 0.619 (95%CI 0.59-0.72, p = 0.001). Median PIVKA-II value increased from BCLC stage A to D. Kruskal-Wallis test showed a significant difference of PIVKA-II levels between all stages except stage A and B (p values for stage A-B (0.297), A-C (0.000), A-D(0.000),whereas for AFP results were significant only between stages A and C (p values for stage A-B (0.348), A-C (0.003), A-D(0.206). Conclusions: Serum PIVKA-II level appears as a good predictive marker for PVTT and BCLC stage when compared to AFP which may guide therapeutic strategy and assessment of prognosis in newly diagnosed HCC patients.
Advanced imaging to assess longitudinal vascular changes in brain metastases treated with immune checkpoint inhibition.
Authors: Albert Eusik Kim, Ken Chang, Andrew Beers, Kyrre E. Emblem, Jayashree Kalpathy-Cramer, Eudocia Quant Lee, Nancy U. Lin, Lakshmi Nayak, Ugonma Nnenna Chukwueke, Kevin S. Oh, Helen Alice Shih, Michael White, Donald P. Lawrence, Beverly Moy, Justine Vanessa Cohen, Anita Giobbie-Hurder, Daniel P. Cahill, Ryan J. Sullivan, Priscilla Kaliopi Brastianos, Elizabeth Robins Gerstner
Journal: Journal of Clinical Oncology (2020)

2529 Background: Immune checkpoint inhibitors (ICI) have recently been shown to be effective for brain metastases (BM) for melanoma and lung cancer. This breakthrough has prompted interest in evaluating ICI in BM of other histologies. However, accurately assessing intracranial response in patients undergoing ICI is a challenge, as current measures cannot distinguish pseudoprogression from true tumor progression. To shed light on potential biomarkers of response, we prospectively use perfusion MRI to identify characteristic vascular signatures in a BM-specific trial of ICI. Methods: As part of an ongoing phase II study of pembrolizumab for patients with untreated or progressive, previously treated BM from any histology, patients underwent advanced MRI that includes tumor volume measurements and perfusion imaging with dynamic susceptibility contrast MRI. To calculate volumetric radiographic response, all enhancing voxels were summated. A volumetric increase of &gt;40% was categorized as progressive disease (PD), a decrease of &gt;60% as partial response (PR), and stable disease (SD) as between -60% and +40%. Results: 53 patients have been enrolled, of whom 44 have received at least baseline advanced MR imaging. Histologies include 21 with breast cancer, 5 with non-small cell lung cancer, 4 with melanoma, and 13 with other cancers. At baseline, the total number of BM was 1-50+ per patient. Based on summing the entire enhancing intracranial disease burden, best volumetric responses for the 33 evaluable patients include 4 PR, 10 SD, and 19 PD. On preliminary analysis, there was a correlation between increased tumor cerebral blood volume/flow with tumor progression. Correlation of additional vascular physiologic parameters (e.g. vessel caliber, tissue oxygenation) and volumetric response to patient outcome and standardized response criteria (iRANO) are ongoing. Conclusions: Pembrolizumab likely has anti-tumor efficacy in BM. Our data provides potential evidence that effective ICI is associated with a decrease in perfusion. Ongoing analyses to uncover additional vascular changes – specifically longitudinal metrics reflecting vascular structure and function - within BM to ICI are pending. These findings have potential to illustrate mechanisms of efficacy for ICI and biomarkers of response in this patient population.
抗结核药物研究进展
Authors: 唐神结, 肖和平
Journal: BMJ (2011)

1944年,链霉素的问世开创了抗结核药物治疗新时代,1946年对氨基水杨酸开发成功,1950年乙胺丁醇的研制,到了1951年异烟肼顺利应用于临床,宣告了结核病从此进入了化学治疗(化疗)时代.链霉素、异烟肼和对氨基水杨酸组合被称为结核病的“老三化”,一个又一个的结核患者获得治愈.1952年吡嗪酰胺、1955年环丝氨酸以及1956年乙硫异烟胺和卡那霉素的先后问世为结核病的治疗添砖加瓦.1965年利福平问世被认为是结核病化疗具有里程碑意义的重大事件[1].随后结核病的治疗进入了“短程化疗时代”,结核病也因此迎来了“防有办法,治有措施”的好时机,那时人们普遍相信消灭结核病指日可待了.然而,由于全球结核病防治被严重忽视,对结核病的投人大为削弱等原因,20世纪90年代后期全球结核病全面回潮,死亡人数达300万。
Informed consent in phase I clinical trials: Implications for trends in design.
Authors: Paul Henry Frankel, Susan G. Groshen
Journal: Journal of Clinical Oncology (2020)

e14077 Background: Informed Consent (IC) is a critical aspect of human subjects protection. Institutional Review Boards are tasked with insuring proper IC as one aspect of protecting participants in clinical trials. Phase I trials in oncology present special issues with IC, as often neither the risks nor the benefits are well-known. This has resulted in carefully worded IC templates for Phase I studies based on the traditional use of dose-finding designs that are geared towards finding the “Maximum Tolerated Dose (MTD)”. As the definition of this term varies by study, the implication for patient risk and informed consent are rarely discussed. Methods: We reviewed Phase I designs to present options for improving the informed consent process for Phase I oncology trials. Results: Phase I studies have seen an increase in designs based on work from the early 1990s seeking a dose that results in a targeted percent of patients experiencing a “Dose Limiting Toxicity (DLT)” to define the MTD. The most common definition of a DLT is a treatment-related toxicity that results in a particularly concerning severe toxicity (grade 3 or higher) in the first cycle of therapy and the most common rate targeted (in designs that define toxicity as a goal) is 25%. In that setting, while lower doses may have a lower likelihood of DLT, higher doses or the expansion cohort are likely to have a 25% chance of DLT if the target is pursued. This information is rarely quantitatively communicated in the informed consent. Conclusions: IRBs and investigators should consider communicating through informed consent the quantitative summary of goals of the study and related risk. For example, transparency suggests conveying when the goal (target) of the study is to find the dose where there is a one in four chance of experiencing a severe adverse event in the first cycle.
Epidemiological profile of patients diagnosed with prostate cancer at Muriaé Cancer Hospital, Minas Gerais, Brazil.
Authors: Carla Simone Moreira de Freitas, Aleida Nazareth Soares
Journal: Journal of Clinical Oncology (2020)

e17530 Background: Prostate cancer (CP) is one of the most common malignant neoplasms among men with high prevalence worldwide. In Brazil, in 2019, 582,000 new cases of cancer were estimated, 282,000 in women and 300,000 in men, 75% are prostate cancer in individuals over 65 years of age (BRASIL, 2019). The occurrence of CP has specific risk factors, such as advanced age (over 65 years), genetic predisposition (patients with a family history of prostate cancer, between 35 and 40 years of age) and ethnicity (mostly blacks). Mortality due to this neoplasm is considered relatively low compared to other types of cancers, which partly reflects a good prognosis.The objective of this study is to describe the epidemiological profile of prostate cancer patients treated in an Muriae Cancer hospital in Minas Gerais - Brazil. Methods: Descriptive cross-sectional study conducted between 1997 and 2019 with 4,395 patients diagnosed with CP, living in the region and adjacencies, 4,175 (95%) assisted by the Unified Health System (SUS). Results: Patients from Minas Gerais-Brazil, cities of microregions and rural areas, the most prevalent age group was between 61-70 years of age with 1769 cases (40.25%), 3476 (79.1%) with low schooling, 3156 (71.82%) with per capita family income less than 0.5 minimum wages, and in regarding profession, the majority 541 (58.05%) is retired and rural workers 148 (15.88%); 1933 (44%) alcohol users, 2021 (46%) smokers and 1626 (37%) with a report of a family history of cancer. As for ethnicity, 1943 (44.23%) were black. Nutritional status 3845 (87.49) were eutrophic. The mean time between diagnosis and treatment was 51 months. PSA levels were 1ng/ml to 10 ng/ml (39%), from 10 ng/ml to 28 ng/ml (21%), from 28 ng/ml to 70 ng/ml (9%) and from 70 ng/ml to 200 ng/ml (6%) and &gt; 200 ng/ml (5%); altered tests 1845 (42%), PSA elevation 1538 (35%), obstructive symptoms 965 (5%), dysuria 579 (3%) and pain 579 (3%). The majority (50.41%) with stage II, stage III (18.10%) and IV (9%), highlighting that in 1997 the percentage of advanced stages (III and IV) was 47% and in 2019 it decreased to 18%, due to earlier diagnoses. Conclusions: The analyzed data allowed to characterize the epidemiological and sociodemographic profile of patients treated in Muriaé Cancer hospital, Brazil, contributing to decision-making regarding the treatment provided to this population.
Reconstructive operation with transpositional colon behind sternum for esophageal stricture after corrosive burns
Authors: 马旭晨, 区颂雷, 张志泰, 胡燕生, 宋飞强, 张韶岩
Journal: BMJ (2007)

目的 探讨经胸骨后隧道间置结肠替代食管术式治疗腐蚀性食管烧伤后瘢痕狭窄的临床经验及并发症的治疗.方法 对65例食管腐蚀性烧伤后瘢痕狭窄患者,分别行顺蠕动结肠代食管经胸骨后至颈部与食管端端吻合(56例)、顺蠕动结肠代食管经胸骨后至咽底吻合(7例)、逆蠕动结肠代食管经胸骨后至颈部与食管端端吻合(2例)治疗,总结上述病例术前、术中、术后治疗经验.结果 术后51例患者恢复顺利痊愈出院.12例术后出现颈部吻合口瘘,其中2例经再次颈部手术治愈,10例保守治疗痊愈.2例术后发生结肠坏死,再次手术死亡1例,痊愈1例.结论 治疗腐蚀性食管烧伤可以旷置瘢痕食管,在良好术前准备、准确的外科操作、正确的术后处理前提下,经胸骨后隧道间置结肠替代食管术式效果满意。
CIMAC-CIDC CyTOF harmonization.
Authors: Adeeb Rahman, Bita Sahaf, Melanie Davila, Nicholas Fernandez, Emily McWilliams, Karen Millerchip, Salah E Bentebibel, Cara L. Haymaker, Natalia Sigal, Caroline Duault, Emily Thrash, Diane Del Valle, Beatriz Sanchez Espiridion, Mina Pichavant, Chantale Bernatchez, Ignacio Ivan Wistuba, Sacha Gnjatic, Sean Bendall, Holden Maecker
Journal: Journal of Clinical Oncology (2020)

e15242 Background: The Cancer Immune Monitoring and Analysis Centers – Cancer Immunology Data Commons (CIMAC-CIDC) network is a National Cancer Institute-funded initiative to identify biomarkers of mechanisms and response to cancer immunotherapy clinical trials, using state-of-the-art assay technologies. A primary platform for CIMAC-CIDC biomarker studies is CyTOF mass cytometry, which is performed at all four CIMAC laboratories. Methods: To test the ability to generate comparable data across labs, a cross-site harmonization effort was undertaken. We first harmonized SOPs between centers. Because of a new acquisition protocol introduced by the vendor (Fluidigm), we also tested this protocol across sites before finalizing the harmonized SOP. We then performed a cross-site assay harmonization experiment, using 5 shared cryopreserved PBMC samples and one lyophilized control cell preparation, along with a shared lyophilized antibody cocktail consisting of 14 markers, as validated in the HIPC consortium, plus CD45. These reagents and samples were distributed to the four sites, and FCS files were centrally analyzed by both manual gating and automated methods (Astrolabe). Results: Average CVs across sites for each cell population were reported and compared to a previous multisite CyTOF study. Once a cell recovery issue at two sites was resolved, this experiment resulted in inter-site reproducibility of under 20% CV for most cell subsets, very similar to the previous study. Conclusions: These results emphasize the ability to reproduce CyTOF across sites, and also highlights procedures, such as use of spike-in control samples, useful for tracking variability in this assay.
HELLP综合征12例
Authors: 苟安栓, 王琳, 李晓英, 徐文仪, 康焰
Journal: BMJ (2006)

HELLP综合征是一组表现为溶血、肝酶升高及血小板减少的综合征,是妊娠期高血压病的严重并发症,母婴病死率较高.1996年1月至2004年1月,我院收治重度子痫前期患者176例,出现HELLP综合征12例,报告如下。
A phase II study of BP1001 (liposomal Grb2 antisense oligonucleotide) in patients with hematologic malignancies.
Authors: Maro Ohanian, Tara L. Lin, Michael Craig, Apurv Agrawal, Kathleen Halka, Ana Tari Ashizawa, Jorge E. Cortes, Gail J. Roboz
Journal: Journal of Clinical Oncology (2020)

TPS7561 Background: The growth factor receptor bound protein-2 (Grb2) is vital to oncogene signaling and tumor progression. BP1001 is a liposome-incorporated Grb2 antisense oligonucleotide that inhibits Grb2 expression. Grb2 inhibition suppresses cancer growth and survival. A Phase I/Ib single center study in patients with refractory/relapsed leukemias demonstrated the safety of BP1001 up to 90 mg/m 2 dose and the efficacy of BP1001 in combination with low dose cytarabine (LDAC) in refractory/relapsed acute myeloid leukemia (AML) patients (Ohanian, Lancet Haematol 2018). Based on pharmacokinetic (PK) considerations, the recommended Phase II dose was 60 mg/m 2 . A phase II study was initiated to explore the clinical impact of BP1001 in combination with LDAC in untreated AML patients. Interim safety and efficacy of BP1001 + LDAC in untreated AML patients was presented at the 2018 Annual ASH Meeting. BP1001 was safely administered to 25 patients with untreated AML, who were considered unfit for standard chemotherapy. Efficacy data compared favorably to what has been reported with available options for unfit patients largely with secondary AML or adverse-risk AML. Since the Interim Data presentation, the study was amended to investigate BP1001 + decitabine combination and include myelodysplastic syndrome (MDS) patients. This is because BP1001 enhanced decitabine anti-leukemic effects in preclinical studies. Methods: This is a multi-center, open-label study with 2 parallel cohorts of BP1001 + decitabine treatment in untreated AML/high risk MDS patients and refractory/relapsed AML/high risk MDS patients who are considered by the investigator unsuitable for or refused intensive chemotherapy. BP1001 is given intravenously (IV) at 60 mg/m 2 twice weekly. Decitabine is given 20 mg/m 2 IV daily for 5 consecutive days. Each cycle is 28 days. Each cohort can enroll 19 patients, with a decision to stop or proceed to 54 patients. The primary objective of this study is to assess whether BP1001 + decitabine provides higher complete remission rates than decitabine alone (by historical comparison) in AML/high risk MDS patients. The secondary objectives of this study are to assess: Safety of BP1001 + decitabine; partial remissions and blast count reductions; overall survival, time to response and duration of response; minimal residual disease status in patients who achieve complete remission; and plasma PK profile of BP1001. The exploratory objective of this study is to evaluate the association of treatment response with cytogenetic and molecular characteristics. Clinical trial information: NCT02781883 .
Management of lung cancer in elderly population: A mono-centric retrospective study at University Hospital of Caen, Normandy, France.
Authors: Youssef Oulkhouir, Emmanuel Bergot, Jeannick Madelaine, Boris Stchepinsky
Journal: Journal of Clinical Oncology (2020)

e21573 Background: Lung cancer is one of the leading causes of death worldwide and its incidence is increasing in the elderly patient population. Management of these population is not as well codified as that of younger patients due to their under-representation in clinical trials. The objective of this study is to assess the clinical characteristics, diagnostics and treatments in our population at the University Hospital of Caen (CHU). Methods: It was a retrospective monocentric study including all patients over 75 years old who were diagnosed with a lung cancer between January 1, 2014 and December 31, 2017 in our center of Caen. We analyzed epidemiological, clinical and therapeutic criteria. We evaluated the overall survival and according to the type of treatment used, the identification of factors of poor prognosis. Adverse events in that specific population of patients were analyzed. We also looked at the correlation between length of hospitalization and survival data. Results: 132 patients aged 75 to 95 years were included, with a large predominance of men. Almost 90% of our patients had comorbidities. The median survival of the entire population was 7 months. Factors identified as significantly influencing survival are the initiation of a specific cancer treatment, performans status, undernutrition, presence of comorbidities, age, stage of disease, and hospitalization at diagnosis. 58.9% of our patients received treatment including 60% chemotherapy and 17.7% surgery. 52% of patients treated with chemotherapy had Grade 3-4 toxicities. None of the patients treated with targeted therapy had any major side effects. 67.4% of our patients were hospitalized for diagnosis. The percentage of survival time spent in hospital is also significantly higher in the best supportive care group with a rate of 69% versus 25%. 14 patients had a diagnosis of early stage lung cancer. Surgery and radiotherapy were performed and were well tolerated. Conclusions: The elderly population with lung cancer managed in our center is highly diagnosed at an advanced stage and has many associated comorbidities affecting survival. Performans status, nutritional condition and inaugural hospitalization are factors of poor prognosis leading to exclusive palliative care. However, in early stages disease radical treatment good be performed and be well tolerated.