tbuckley/cabot-search huggingface dataset:
Prevention of pneumothorax in CT-guided thoracic sympathetic nerve block
Authors: Li Zhang, Bing Huang, Ming Yao, Yong Fei, Keyue Xie
Journal: BMJ (2020)

Objective
To explore the measures for prevention of pneumothorax in CT-guided thoracic sympathetic block.


Methods
The clinical data of 769 patients with hyperhidrosis or Raynaud syndrome treated with CT-guided chemical destructive block of thoracic sympathetic nerve chain in Jiaxing First Hospital from January 2010 to December 2017 were retrospective analyzed. The CT-guided thoracic sympathetic nerve block puncture was performed with a special blunt needle outside the wall pleura above the caput costae following the principle of safe distance and advance only. After exclusion of pneumothorax by CT scan, 2.5 ml of absolute ethanol mixed with 30% iohexol 0.25 ml was injected on both sides of thoracic sympathetic nerve chain.


Results
The punctures were successfully performed in all 769 patients (1 538 nerve chain segments) and no pneumothorax occurred. After treatment with absolute ethanol injection, Horner syndrome occurred in 31 patients, which disappeared after injecting saline into the stellate ganglion; and intercostal neuralgia occurred in 188 patients after surgery, which was healed in 1 to 3 months.


Conclusion
It is suggested that pneumothorax can be avoided through CT guidance, using appropriate needles and puncture techniques during the procedure of thoracic sympathetic nerve chain block.


Key words: 
Sympathectomy, chemical; Ganglia, sympathetic, thoracic; Intraoperative complications; Pneumothorax
All-cause and cancer mortality in a private health plan in Brazil: Ten years retrospective analysis.
Authors: Joao Paulo Reis Neto, Juliana Martinho Busch, Stephen D. Stefani
Journal: Journal of Clinical Oncology (2020)

e13610 Background: Cancer is the second leading cause of death worldwide. From 2014 to 2015 Brazil estimated more than 500,000 new cases of cancer, which placed the country among those with the highest cancer incidence. This study evaluates the 10-year evolution of mortality rates due to all causes and cancer and to estimate the potential years of life lost (PYLL) in beneficiaries of health plan, according to sex, age and geographic region. Methods: Retrospective cross-sectional, descriptive study evaluated the causes of death, between 2008 and 2017, by sex and age groups, for all causes (AC) and cancer (CA) data from the health insurance system. The information on the death certificates (DC) was coded according to the ICD-10. Age was stratified into groups: up to 49 years, 50–59 years, 60–69 years, 70–79 years and 80 years or more. Data were analyzed by checking the proportions and mortality rates (MR), grouped into two five-year periods, 2008-2012 (P1) e 2013-2017 (P2). Annual MR per 100,000 population was estimated using the direct method and proportional mortality rates (PMR). To calculate the potential years of life lost (PYLL) the upper limit was 76 years old. The avoidable MR was also analyzed for individuals up to 75 years and cancer. Microsoft Excel v2010 and Qlik Sense v13.21 were used to analyze data and statistics. Results: 5,779 deaths were analyzed, 4,447 in men (77.0%, average 70.1 years) and 1,332 women (33%, 75.9 years). Cancer was the second leading cause of death (n = 953, PMR 16.5%), behind cardiovascular disease (n = 1,662 PMR 28.8%). The major crude death rate per 100,000 was due circulatory system diseases (347), followed by cancer (199) and respiratory system diseases (110). The highest cancer MR were in men, elderly and Brazilian regions with the lowest Human Development Index (HDI). Greatest number of deaths in men at P1 were from cancers of lung (CMP 19.8%), prostate (14.2%) and pancreas (8.0%). At P2, prostate (18.2%), lung (16.8%) and stomach (7.6%). In women, during P1, breast (20.2%), lung (13.1%) and pancreas (83%), and during P2, the same order, 22.5%, 14.6% and 9.3%, respectively. Cancer accounted for a total of 6,335 PYLL and 40.9% of causes of death were classified as avoidable. Conclusions: Cancer was one of the leading causes of mortality during the study. High pancreatic cancer MR differs from national statistics, requiring more analysis that involves possible occupational exposure. Although preventive actions for healthy life habits, early screening and diagnosis, Brazil presents high cancer mortality rates as showed in this analysis.
Plant-based diet trends in oncology patients.
Authors: Bradley R Webster, Matthew V Ton-That, Neda Hashemi-Sadraei, Satyan K Shah
Journal: Journal of Clinical Oncology (2020)

e19224 Background: Plant-based diets are beneficial in several cancers such as colorectal and prostate. However, their adoption among oncology patients is not well studied. We report trends in plant-based diet selection among medical and surgical oncology patients at a comprehensive cancer center. Methods: An IRB-approved retrospective review of all patients admitted to the University of New Mexico Hospitals between October 2009 and October 2017 was conducted. Inclusion criteria included: 1) vegetarian Ovo-Lacto (dairy and eggs ok) or vegan (no animal-derived foods) inpatient diet request and 2) age &gt;= 18 years. For each individual, the dietary orders and discharge summaries were reviewed. Patients with cancer diagnosis principally related to admission and/or admission to an oncology inpatient service were defined as oncology patients. Surgical oncology services included 8 different surgical branches. Results: A total of 181 oncology patients ordered plant-based diets. Median age was 62 years (range 18 to 90) and 69% were female. Vegetarian Ovo-Lacto (66%) was requested more than vegan diet (34%). The services on which the greatest number of these patients were treated were Medical Oncology (31%), General Surgical Oncology (23%), and Gynecology-Oncology (20%). Comparing medical and surgical oncology patients, there was no difference in terms of median age (63 vs. 62 years, p=0.62), nor in the % requesting vegan diet (30 vs. 35%, p=0.50), respectively. However, females comprised 95 of 124 (77%) surgical patients, but only 29 of 57 (51%) medical patients (p&lt;0.001). The number of patients requesting a plant-based diet grew from 81 in the first half of the study period to 100 in the second half (a 23% increase). During this time period, vegetarian diet became more popular than vegan with an increase from 48 patients (59%) in the first half to 72 (72%) in the second half (p=0.05). Conclusions: Oncology patients are increasingly requesting plant-based diets. Most are female and prefer vegetarian over vegan meals. These findings can help cancer centers improve quality of care by tailoring nutritional offerings.
以耳聋为表现的急性心肌梗死一例
Authors: 呼焕凤, 费丽萍
Journal: BMJ (2005)

患者男,62岁,因发作性耳聋20 d,加重8 h入院.20 d前无明显诱因出现耳聋,无耳鸣,持续10 min自行缓解.20 d来耳聋呈发作性,约2～3 d发作1次,每次约10 min,活动及情绪激动时加重,均可自行缓解.曾就诊于外院耳鼻喉科,诊为突发性耳聋,治疗10 d无效。
以Sweet综合征为首发症状的急性白血病一例
Authors: 周言新, 张莉
Journal: BMJ (2005)

患者男,64岁,因全身皮疹伴疼痛3 d于2003年6月首诊于皮肤科.查体见头顶部、面部、颈部、前胸及四肢皮肤散在隆起的斑丘疹,少数呈混浊样疱疹,部分轻压痛.皮肤疱疹穿刺印片可见大量中性分叶核粒细胞,少数中幼粒、晚幼粒细胞.予抗生素(不详)及皮炎平软膏治疗4 d后皮疹消失.但1周后患者再次出现全身皮疹,并伴有发热,体温38.5℃,乏力.查体:轻度贫血貌,头顶部、面部、胸背部及四肢皮肤散在隆起的斑丘疹,部分轻压痛,少数呈混浊样疱疹;颈部、锁骨上窝、腋窝及双侧腹股沟区可扪及多个花生米大小的肿大淋巴结,部分有轻压痛,质韧,活动度可,肝脾无肿大,胸骨及胫骨轻压痛。
母亲安全
Authors: 邱艳, 熊庆
Journal: BMJ (2007)

妊娠和分娩是一个正常的生理过程,但在这一过程中每个母亲和儿童的健康甚至生命都面临着危险,母亲安全即是帮助母亲克服、战胜这些危险,安全幸福地将一个新生命带到这个世界上来.保障母亲安全是社会的责任,是基本人权的体现,更是广大医务人员的神圣职责。
Clinical features of different subtypes of esophageal achalasia
Authors: Ying Xu, Yurong Tang
Journal: BMJ (2020)

Esophageal achalasia is a rare digestive disease. The pathogenesis of achalasia is still elusive. The main symptoms of achalasia are dysphagia, regurgitation, chest pain and weight loss. Three subtypes are defined in the Chicago Classification 3.0, and each subtype has unique clinical features and treatment consideration. This article will review the clinical features of three subtypes of esophageal achalasia.


Key words: 
Esophageal achalasia; Esophagogastric junction; Diagnosis; Therapy
Targeting HER2 in combination with anti-PD-1 and chemotherapy confers a significant tumor shrinkage of gastric cancer: A multi-institutional phase Ib/II trial of first-line triplet regimen (pembrolizumab, trastuzumab, chemotherapy) for HER2-positive advanced gastric cancer (AGC).
Authors: Sun Young Rha, Choong-Kun Lee, Hyo Song Kim, Beodeul Kang, Minkyu Jung, Woo Kyun Bae, Dong-Hoe Koo, Su-Jin Shin, Hei-Cheul Jeung, Dae Young Zang, Hyun Cheol Chung
Journal: Journal of Clinical Oncology (2020)

3081 Background: Combining anti-PD-1 agent and trastuzumab has shown synergy in HER2 positive preclinical cancer models. We first report the result of a multi-institutional phase Ib/II trial of triple combination (pembrolizumab, trastuzumab, and chempotherapy) as first line therapy for HER2 positive AGC. (PANTHERA trial; NCT02901301). Methods: Pembrolizumab 200mg IV D1, Trastuzumab 6mg/kg (after 8mg/kg load) D1, Capecitabine 1000mg/m 2 bid D1-14, and Cisplatin 80mg/m 2 D1 every 3 weeks was selected as recommended phase II dose. The primary endpoint for phase II was ORR per RECIST v1.1. Secondary endpoints included PFS, OS, DoR, safety, and molecular analysis by targeted NGS. Results: Total of 43 patients were treated with median follow up of 16.1 months, and 11 pts remained on the treatment (treatment duration range: 1.4 to 24 months). There was significant tumor shrinkage of 95.3% with 54.6% median depth of response, with 76.7% ORR (CR 16.3%, PR 60.5%, conversion surgery 4.6%), and 97.7% DCR. Median PFS was 8.6 months (95% CI 7.2-22.0) and median OS was 18.4 months (95% CI 17.9-NA). Subsequent chemotherapy was given to 83.3% of 30 progressed pts. There were no MSI-H/dMMR or EBV-positive pts. PD-L1 status (57.1% of pts ≥ CPS 1 and 14.3% of pts ≥ CPS 10 among 35 pts), metastatic organ or baseline tumor burden was not related to the survival. Treatment-related AE (≥G3) occurred in 32 pts (74.4%) including 17 pts (39.5%) with neutropenia G3-4. Immune-related AEs (≥G3) occurred in 4 pts (10%). Ninety-six tumor tissues from 32 pts (paired tumor tissues from 25 pts) were analyzed with targeted NGS. TMB (median 12.7 mut/MB with range of 9.45-16.71) was not related to the PD-L1 expression or survival. Conclusions: First-line triplet regimen (Pembrolizumab, Trastuzumab, and Chemotherapy) confers a significant tumor shrinkage for HER2 positive AGC, regardless of PD-L1 status. Phase III Keynote-811 study (NCT03615326) is ongoing based on the protocol of this study. Clinical trial information: NCT02901301 . [Table: see text]
A phase II trial of atezolizumab (anti-PD-L1) with carboplatin in patients with metastatic triple-negative breast cancer (mTNBC).
Authors: Eric Michael Lander, Brian David Lehmann, Payal D Shah, Elizabeth Claire Dees, Tarah Jean Ballinger, Paula Raffin Pohlmann, Cesar Augusto Santa-Maria, Yu Shyr, Ingrid A. Mayer, Ben Ho Park, Jennifer A. Pietenpol, Vandana G Abramson
Journal: Journal of Clinical Oncology (2020)

TPS1112 Background: Patients with metastatic triple negative breast cancer (mTNBC) have limited treatment options. Recent studies with a PD-L1 inhibitor and taxane based chemotherapy have demonstrated an increase in median progression free survival (PFS) in mTNBC. While taxanes target microtubules, platinum agents directly alkylate DNA and may generate additional neoantigens to enhance anti-tumor immunity via immune checkpoint inhibition. In this study, we are evaluating the combination of carboplatin with and without atezolizumab in patients with mTNBC. Serial biopsies are poised to help elucidate biological differences in responders and nonresponders. As optimal timing of adding checkpoint inhibition to chemotherapy is debatable, the randomized, crossover design will give insight into whether priming mTNBCs with DNA damaging chemotherapy results in cellular and immune changes that lead to a greater likelihood of response. Methods: This is a randomized phase II multicenter study at seven sites within the Translational Breast Cancer Research Consortium (TBCRC). Patients with mTNBC, ECOG 0-1, and 0-1 prior regimens for mTNBC are eligible. 106 patients will be randomized 1:1 to receive atezolizumab 1200 mg plus carboplatin AUC 6 (n = 53; Arm A) or carboplatin AUC 6 alone (n = 53; Arm B) every 3 weeks until intolerable toxicity or disease progression occurs. Patients receiving carboplatin alone have the option to cross over to atezolizumab upon progression (Arm Bx). Patients will undergo clinical assessment every cycle, and tumor assessment every 3 cycles with CT scan of the chest, abdomen, and pelvis and bone scan. Core biopsies of a metastatic lesion are performed at baseline and at progression. The primary endpoint is median progression free survival (PFS) with 95% confidence intervals based on RECIST 1.1. The sample size of 106 with 1:1 randomization is powered to detect a 1.5-month difference in PFS between arms (α = 0.10, β = 0.20). Secondary endpoints include overall response rate (ORR), duration of response (DOR), clinical benefit rate, and overall survival. The PFS, ORR, and DOR will also be measured by irRECIST to account for delayed effects of atezolizumab on tumor burden. The quantification of tumor infiltrating lymphocytes (TILs) will study the prognostic effects of TILs on PFS in patients receiving atezolizumab. Biopsy-derived PD-L1 expression by IHC and RNA-seq will assess treatment-induced changes, define triple-negative subtypes, and evaluate for resistance mechanisms. To date, 89 of 106 patients are enrolled. Clinical trial information: NCT03206203 .
女性尿失禁的手术治疗
Authors: 马乐, 赵丽红
Journal: BMJ (2005)

女性尿失禁的手术治疗主要是针对压力性尿失禁患者.尽管临床对压力性尿失禁的保守治疗方法很多,但其共同缺点是必须坚持,而且对部分患者的效果不明显,仅手术治疗是根本性治疗方法,尽管各种手术方法均存在一定复发的机会。
A novel CSF-1R neutralizing antibody, DCB-AB21, as a potential therapeutics for tumors.
Authors: Chen-Hsuan HO, Chu-Bin Liao, Yu Kai, Tze-Ping Yang, Sze-Liang Lai, Yin-Chieh Chien
Journal: Journal of Clinical Oncology (2020)

e15006 Background: Tumor-associated macrophages (TAMs) represent the major cell components of immune infiltrate in solid tumors, and it has been reported that high TAMs density is associated with poor clinical prognosis. Within the tumor microenvironment, TAMs rely on signaling through colony stimulating factor 1 receptor (CSF-1R)/CSF-1 axis for various tumor promoting processes such as tumor growth, drug resistance, angiogenesis, and metastasis. Therefore, decrease of TAMs density in tumors through CSF-1R inhibition is considered an attractive therapeutic target for drug development. Methods: DCB-AB21 was screened from immunized mouse hybridoma clones. ELISA-based and flow cytometry-based affinity screening is performed and then the growth inhibition test by cell-based CSF-1-dependent cell line were further used as antibody screening assay. Results: A novel anti-CSF-1R monoclonal antibody DCB-AB21 which specifically binds to CSF-1R and inhibits CSF-1R downstream signaling. Our results showed DCB-AB21 can block the CSF-1 and IL-34-induced cell proliferation. Potent inhibition of CSF-1R-dependent signaling was observed in the Ba/F3 CSF-1R driven model cells, and in human THP-1 leukemia monocytic cell lines. Humanization engineering further improves this antibody’s affinity and anti-proliferative efficacy. The discovery of novel binding epitope of DCB-AB21 differentiates itself from the current CSF-1R targeting antibodies testing in clinical trials. In vivo efficacy of DCB-AB21 showed AB21 alone has moderate anti-cancer activity and it further potentiate anti-PD-1’s efficacy. Conclusions: These data demonstrate that DCB-AB21 can potently inhibit CSF-1R in cellular contexts and in vivo model, and has the potential to induce a phenotypic effect on macrophages. These data suggest that DCB-AB21 is a promising new agent with possibility to combine with immune checkpoint inhibitors to relief macrophage-dependent immune suppression and would yield clinical benefit.
COVID-19 human challenge studies: ethical issues
Authors: Euzebiusz Jamrozik, Michael J Selgelid
Journal: The Lancet Infectious Diseases (2020)

COVID-19 poses an extraordinary threat to global public health and an effective vaccine could provide a key means of overcoming this crisis. Human challenge studies involve the intentional infection of research participants and can accelerate or improve vaccine development by rapidly providing estimates of vaccine safety and efficacy. Human challenge studies of low virulence coronaviruses have been done in the past and human challenge studies with severe acute respiratory syndrome coronavirus 2 have been proposed. These studies of coronaviruses could provide considerable benefits to public health; for instance, by improving and accelerating vaccine development. However, human challenge studies of severe acute respiratory syndrome coronavirus 2 in particular might be controversial, in part, for ethical reasons. The ethical issues raised by such studies thus warrant early consideration involving, for example, broad consultation with the community. This Personal View provides preliminary analyses of relevant ethical considerations regarding human challenge studies of severe acute respiratory syndrome coronavirus 2, including the potential benefits to public health and to participants, the risks and uncertainty for participants, and the third-party risks (ie, to research staff and the wider community). We argue that these human challenge studies can reasonably be considered ethically acceptable insofar as such studies are accepted internationally and by the communities in which they are done, can realistically be expected to accelerate or improve vaccine development, have considerable potential to directly benefit participants, are designed to limit and minimise risks to participants, and are done with strict infection control measures to limit and reduce third-party risks.
Benefits of an early mobility program for hospitalized cancer patients: A pilot study.
Authors: Cardinale B. Smith, Melissa Gunning, Margie Hubman, Christine Conklin, Nicole Wells, Haley Hines Theroux, Mark Liu, Jennifer Wolfe
Journal: Journal of Clinical Oncology (2020)

7008 Background: Cancer patients are often hospitalized with complications from cancer and cancer treatment. Many experience a decline in physical functioning which likely contributes to increased length of stay (LOS) and excess days, increased readmissions and decreased patient experience. We aimed to determine whether a mobility program project would improve quality of care and decrease healthcare utilization. Methods: We implemented a mobility aide program on an oncology unit in a large academic medical center between April 2, 2019 to December 31, 2019. The program consisted of nursing evaluation using the Activity Measure for Postacute Care (AMPAC), an ordinal scale ranging from bed rest to ambulating ≥250 feet, was used to quantify mobility. Plan of care was determined in a multidisciplinary manner with physical therapy (PT), nursing and a mobility aide, a medical assistant with enhanced rehabilitation training. Patients were then mobilized two times per day seven days a week. Using descriptive statistics we evaluated the programs impact on excess days, readmissions, changes in mobility and patient experience as measured by Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) during this time period compared to the 6 month interval prior to implementation. Results: During the study interval, 988 patients were admitted and received the mobility program. There was a 6% reduction in excess days (p = 0.04). Similarly, readmission rates decreased from 25% to 19% (p = 0.03). Overall 76% of patients wither maintained or improved their mobility score. During this time period HCAHPS scores (willingness to recommend hospital) increased from 63% at baseline to 91% (p = 0.01). Conclusions: Use of this mobility program resulted in a significant decrease in healthcare utilization and improvement in patient experience. This demonstrates that non-PT professionals can mobilize hospitalized cancer patients decreasing the burden of PT and nursing resources. Future work will evaluate the sustainability of the program and evaluate association with healthcare costs.
Publisher Correction: A clonal expression biomarker associates with lung cancer mortality
Authors: Dhruva Biswas, Nicolai J. Birkbak, Rachel Rosenthal, Crispin T. Hiley, Emilia L. Lim, Krisztian Papp, Stefan Boeing, Marcin Krzystanek, Dijana Djureinovic, Linnea La Fleur, Maria Greco, Balázs Döme, János Fillinger, Hans Brunnström, Yin Wu, David A. Moore, Marcin Skrzypski, Christopher Abbosh, Kevin Litchfield, Maise Al Bakir, Thomas B. K. Watkins, Selvaraju Veeriah, Gareth A. Wilson, Mariam Jamal-Hanjani, Judit Moldvay, Johan Botling, Arul M. Chinnaiyan, Patrick Micke, Allan Hackshaw, Jiri Bartek, Istvan Csabai, Zoltan Szallasi, Javier Herrero, Nicholas McGranahan, Charles Swanton
Journal: Nature Medicine (2020)
First-in-human phase I/Ib multicenter, open-label dose escalation study to assess safety and tolerability of PMD-026 in patients with metastatic breast cancer with expansion in metastatic triple negative breast cancer.
Authors: Muralidhar Beeram, Judy Sing-Zan Wang, Lida A. Mina, Amita Patnaik, Mary Rose Pambid, Aarthi Jayanthan, My-my Huynh, Sandra Elaine Dunn, Gerrit Los, Andrew Dorr
Journal: Journal of Clinical Oncology (2020)

TPS1110 Background: Metastatic triple negative breast cancer (mTNBC) has a poor prognosis with limited durable treatment options. RSK (P90 ribosomal S6 kinase) is a signaling protein at the convergence point of PDK-1 and MAPK signaling pathways. RSK1-3 phosphorylates transcription factors, including Y-box binding protein-1 (YB-1), thereby inducing drug resistance and cancer growth genes. Phosphorylated YB-1 is involved in tumor cell survival, proliferation, and drug resistance. In human breast tumor samples, RSK2 protein is expressed across all breast cancer subtypes (TNBC, ER+ and HER2+) and is associated with poor overall survival. Expression of RSK2 is found in approximately 87% of mTNBC tumors and of those tumors approximately 41% have very high expression of RSK2. PMD-026 is a potent, oral, small molecule RSK inhibitor with high selectivity for RSK2. Preclinical in vivo studies have demonstrated activity both as a single agent and in combination with standard of care therapies. Further, a CAP/CLIA certified IHC method has been developed with Roche to determine tumor expression of RSK2. Methods: This single-arm, open-label, first-in-human, phase I/Ib study evaluates the safety and efficacy of single agent PMD-026 in patients with metastatic breast cancer for whom standard therapies are no longer effective. During dose escalation, the study utilizes an accelerated titration design with single patient cohorts until the occurrence of DLT or Grade 2+ toxicity; then reverts to 3+3 design to define the maximally tolerated dose (MTD) and recommended phase II dose (RP2D). The dose expansion portion will enroll approximately 20 patients with mTNBC. Patients are dosed orally once daily in 21-day cycles with measures to adapt the dosing schedule based on the pharmacokinetic (PK) data, as needed. Tumor tissue is required for all enrolled patients; RSK2 expression will be retrospectively correlated with clinical outcomes. The primary objectives are to determine safety and tolerability of PMD-026, determine the MTD, define a RP2D, and assess anti-tumor activity of PMD-026 in patients with TNBC. Secondary objectives are to evaluate PK, time to response, mTNBC subtyping using NanoString, and duration of response of PMD-026. To date, cohorts 1 and 2 have been completed without DLT. Enrollment to cohort 3 began in January 2020. Clinical trial information: NCT04115306 .