tbuckley/cabot-search huggingface dataset:
Risk factors for rupture of intracranial aneurysm
Authors: Chengdong Wang, Peicheng Cao
Journal: BMJ (2015)

Objective
To investigate the risk factors of rupture of intracranial aneurysms.


Methods
Two hundred and seventy eight patients with cerebral aneurysms admitted from January 2000 to December 2013 were enrolled in study, including 122 cases with ruptured intracranial aneurysm (rupture group) and 156 cases without rupture (non-rupture group). The clinical data were collected from two groups, risk factors of aneurysm rupture were studied by univariate analysis and multivariate logistic regression analysis.


Results
The rates of female gender, smoking history, hypertension and atherosclerosis in rupture group were significantly higher than those in non-rupture group [70.5%(86/122) vs. 59.0% (92/156), 42.6% (52/122) vs. 29.5% (46/156), 63.9% (78/122) vs. 51.9% (81/156) and 69.7% (85/122) vs. 51.3% (80/156); χ2=3.943, 5.175, 4.034 and 4.319, respectively, all P 8 mm were 63.4%(64/101), 40.9%(38/93), 25.0%(20/84), respectively, Z=27.180, P=0.000; the rates of aneurysm rupture in patients with aneurysm neck width of <4 mm was higher than that with width ≥ 4 mm [67.3% (66/98) vs. 31.1%(56/180), χ2=33.832, P=0.000]. Multivariate logistic regression analysis showed that aneurysm diameter is an independent risk factor for rupture of intracranial aneurysm (OR=3.759, 95CI: 1.638-6.879, P=0.001).


Conclusions
The diameter of intracranial aneurysm in an independent risk factor for aneurysm rupture. Female gender, history of smoking, underlying hypertension and atherosclerosis, and the width of aneurysm neck may also related to the rupture of intracranial aneurysms.


Key words: 
Intracranial aneurysm; Rupture; Risk factors
Nanomedicine-based drug delivery towards tumor biological and immunological microenvironment
Authors: Jin Li, Diane J. Burgess
Journal: Acta Pharmaceutica Sinica B (2020)

The complex tumor microenvironment is a most important factor in cancer development. The biological microenvironment is composed of a variety of barriers including the extracellular matrix and associated cells such as endothelia cells, pericytes, and cancer-associated fibroblasts. Different strategies can be utilized to enhance nanoparticle-based drug delivery and distribution into tumor tissues addressing the extracellular matrix or cellular components. In addition to the biological microenvironment, the immunological conditions around the tumor tissue can be very complicated and cancer cells have various ways of evading immune surveillance. Nanoparticle drug delivery systems can enhance cancer immunotherapy by tuning the immunological response and memory of various immune cells such as T cells, B cells, macrophages, and dendritic cells. In this review, the main components in the tumor biological and immunological environment are discussed. The focus is on recent advances in nanoparticle-based drug delivery systems towards targets within the tumor microenvironment to improve cancer chemotherapy and immunotherapy.
Exosomal marker CD63 expression pattern using immunohistochemistry (IHC) in patients with rectal adenocarcinoma in comparison with left-sided colon cancer.
Authors: Pranitha Prodduturvar, Ben McCormick, Wadad Mneimneh, Valeria Dal Zotto, Daisy E Escobar, Ashish Manne, Leander Grimm, Paul Rider, John Hunter, Greire Iliff, Ajay Pratap Singh, Girijesh Kumar Patel, Omar Alkharabsheh, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2020)

e16096 Background: Adenocarcinomas arising from the distal one third of the transverse colon, splenic flexure, descending colon, sigmoid colon and rectum are often grouped together due to their hindgut embryologic origin and referred to as left-sided colorectal cancer (CRC). Rectal cancer represents a subset of CRC that has distinct differences in anatomical location, clinical behavior, prognosis and molecular background. In patients with left sided colon cancer (LSCC), the expression of exosomal marker CD63 was reported to be higher in the adjacent normal mucosa (ANM) compared to the tumor (224 vs 154, p = 0.0001). Here, we explored the pattern of CD63 expression using immunohistochemistry in patients with rectal cancer in comparison with patients with LSCC. Methods: Between 2015 and 2018, 53 patients underwent rectal cancer biopsy/resection and had available tissues for CD63 IHC staining. Two pathologists independently scored CD63 expression in the tumor and ANM. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Paired t test was used for statistical analysis. Results: Median age was 60 (range 34-80). Females represented 26%. Caucasians and African Americans represented 74% and 26%, respectively. In patients with rectal cancer, the mean CD63 expression was higher in ANM compared to their expression in the tumor (147 vs 113, p = 0.0012). Compared to patients with LSCC (N = 30), the mean CD63 expression in patients with rectal cancer was lower in the ANM (224 vs 147, p &lt; 0.0001) and in the tumor (154 vs 113, p = 0.01). Conclusions: In our cohort of patients with rectal cancer, exosomal marker CD63 expression was lower in tumor compared to ANM. This observation was similar to our previously reported findings in patients with LSCC. Compared to patients with LSCC, patients with rectal cancer had lower expression of CD63 in the tumor and ANM. To our knowledge, this is the first study to explore exosomal marker CD63 expression using IHC in patients with rectal cancer.
Using GIS Mapping to Track Hot Spots of Kidney Disease in California
Authors: Shuchi Anand, Allison Staniec, Maria Montez-Rath, Penny Vlahos
Journal: New England Journal of Medicine (2020)

To the Editor: Chronic kidney disease of unknown origin is a leading cause of death in adults living in dry, lowland farming regions of Sri Lanka, Nicaragua, El Salvador, and India.The Central Valley of California has a high annual incidence of end-stage renal disease (ESRD) of 545 cases per million population, as compared with 382 cases per million population in the United States. 1 The climate, topography, and agricultural activity in this region overlap substantially with international regions where chronic kidney disease of unknown origin is endemic, but it remains unclear whether agricultural activity is linked to the incidence of ESRD in California.We mapped the nitrate level in groundwater -a proxy for agricultural activity, fertilizer use, and pesticide application 2 -and superimposed hot spots of unexplained ESRD in California.We first obtained groundwater nitrate levels from wells sampled statewide and annually by the California Water Board during a 5-year period (2010-2014) and restricted our analysis to ZIP Code tabulation areas (ZCTAs) that had more than 10 samples, which resulted in the inclusion of 1066 ZCTAs with 134,901 samples from 13,666 wells.On the basis of consensus recommendations 3,4 and using data obtained from all adults with incident ESRD in the U.S. Renal Data System from 2015 through 2017, we identified cases of unexplained ESRD in California.We defined unexplained ESRD as interstitial nephritis, ESRD of unknown cause, or ESRD that was attributed to hypertension in patients between the ages of 18 and 60 years.We then calculated the percentage of ESRD cases that were classified as unexplained in each ZCTA.To determine
Oncotherad immunotherapy elicits promising responses in Bacillus Calmette-Guérin-unresponsive non–muscle invasive bladder cancer: Results from phase I/ II study.
Authors: João Carlos Cardoso Alonso, Ianny Brum Reis, Juliana Mattoso Gonçalves, Bianca Ribeiro de Souza Sasaki, Adriano Angelo Cintra, Nelson Duran, Athanase Billis, Wagner José Fávaro
Journal: Journal of Clinical Oncology (2020)

e17048 Background: Standard treatment for high-grade non-muscle-invasive bladder cancer (HGNMIBC) is transurethral resection of the bladder tumor followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. Up to 40% of patients with HGNMIBC will fail intravesical BCG therapy. A promising therapeutic perspective is represented by OncoTherad immunotherapy. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein developed by University of Campinas/Brazil that exhibits antitumor properties. The aims of this study were to evaluate the efficacy and safety of OncoTherad immunotherapy for BCG-refractory or relapsed HGNMIBC. Methods: We conducted a prospective, single-center (Municipal Hospital of Paulinia, São Paulo, Brazil), single-arm phase I/ II study of OncoTherad immunotherapy in 29 (18 male, 11 female) patients with BCG-unresponsive HGNMIBC (≥ 1 previous course of BCG intravesical therapy). The schedule was initiated with weekly intravesical (120 mg/mL) and intramuscular (25 mg/mL) OncoTherad treatment for 6 weeks, followed by one every other week application for 3 months and, one monthly application until the end of the treatment (24 months). Follow-up was performed with systematic mapping biopsies of the bladder, cystoscopy and ultrasound. The primary endpoint was pathological complete response (pCR) and recurrence-free survival (RFS). The recurrence was defined as histology proven tumor recurrence (any grade) and monitored at 3-month intervals. Secondary endpoints were time to disease recurrence and safety response. Results: The median age of the 29 patients was 64 years (range 34-94). At baseline pTis, pTaG2-3, pT1G2-3 occurred in 10%, 59% and 31% of patients respectively. OncoTherad treatment showed pCR rates (95% CI) of 100% at 3, 6 and 9 months, 89,6% (26/29) at 12 months and, 89,6% (26/29) at 24 months. A 24-months RFS rate in all patients was 79,3%. Also, the median time to disease recurrence for patients was 459 days (15,3 months; 95% CI) at 24-months follow-up. 95% of adverse events were Grade 1 or 2. The most commonly reported treatment-related adverse events were dysuria (51,7%), cystitis (34,5%), pruritus (44,8%), rash (27,6%), arthralgia (27,6%) and fatigue (27,6%). Conclusions: In conclusion, OncoTherad seems a safe and effective treatment option for BCG-unresponsive HGNMIBC patients and may provide benefit for preventing tumor recurrence. Clinical trial information: RBR-6swqd2.
The impact of patients’ and physicians’ characteristics on surgery decision for head and neck cancer: Results of a national survey.
Authors: Agnès Dupret-Bories, Pascale Grosclaude, Sebastien Lamy, Antoine Nebout, Pierre Bories, Fanny Cros
Journal: Journal of Clinical Oncology (2020)

e14151 Background: The choice between surgical or medical treatments in head and neck cancer is a function of many patient-related and disease-related factors. We investigated how physicians' behavioral characteristics and patients’ socioeconomic status could affect medical decision-making. Methods: A nationwide cross-sectional online survey of surgeons and (radiation) oncologists specialized in head and neck oncology collected data on medical decision-making for 7 clinical vignettes involving head and neck squamous cell carcinoma patients that were representative of routine practice. Questionnaires elicited physicians' demographic and occupational characteristics along with their individual behavioral characteristics according to the decision theory framework. Patients’ gender and socioeconomic position were distributed across vignettes using a Latin square design. Results: We obtained 206 assessable answers. A multivariate analysis shows that surgeons suggested surgery more often than other professionals, which is mostly related to vignettes corresponding to clinical cases for which there is no consensus, so oncologists are 68% less likely than surgeons to choose surgery. For clinical vignette with an absence of consensus, physicians with lower risk aversion recommend more often surgery compared to those with higher risk aversion (OR = 1.88, p = 0.052). When the vignette corresponds to a clinical case for which there is a surgical consensus decision the isolated male blue-collar worker has a 75% lower chance of being offered surgery compared to the married male small business owner (OR = 0.25, p = 0.024). We did not observe any differences based on the patient's gender. Conclusions: Patients’ socioeconomic status did affect our clinical management decisions in head and neck oncology. The significant association between medical decision and individual behavioral characteristics of the physician documented still understudied mechanisms that involved nonbiological factor to explain clinical practices variations.
Comprehensive genomic profiling in malignant myoepithelioma to suggest potential alternative diagnosis.
Authors: Brittany Siontis, Jonathan B. McHugh, Alexa Betzig Schrock, Dean Pavlick, Jeffrey S. Ross, Siraj Mahamed Ali, Vincent A. Miller, Dan R. Robinson, Jyoti Athanikar, Yi-Mi Wu, Arul Chinnaiyan, Laurence H. Baker, Scott Schuetze, Rashmi Chugh
Journal: Journal of Clinical Oncology (2020)

e23530 Background: Malignant myoepithelioma of soft tissue (MM) is a rare tumor affecting patients (pts) of any age without sex predilection. MM has varied histopathologic findings, with epithelioid and spindle components and differentiation along osseous, chondroid or other lineages. Morphologic features suggest MM, however histologic overlap with other lesions exists. Diagnosis requires ancillary immunohistochemical &amp;/or molecular studies; EWSR1 rearrangement with various fusion partners has been reported. Clinical behavior is varied and poorly understood due to disease rarity. Here, we undertook comprehensive genomic profiling (CGP) of MM to evaluate for potential targetable molecular alterations and report clinical outcomes. Methods: We identified pts with MM treated at University of Michigan (UM) from 2000-2017, obtained clinical data and reviewed pathology on 10 available samples and performed integrative sequencing through Michigan Oncology Sequencing Program (MI-ONCOSEQ) on 6. For 31 additional FFPE samples, hybrid capture-based DNA CGP (n = 16) or DNA+RNA CGP (n = 15) was performed (Foundation Medicine, FM). Results: 13 pts were treated at UM; median age at diagnosis was 52 (22-88) with male predominance (9/13). Primary tumor size was 3 cm (2-9.5) and most common location was trunk (4/13) and extremity (3/13). Four pts with metastatic disease (mets) underwent systemic chemotherapy with 0 responses. Median progression free and overall survival in mets was 20 (5-75) and 57 (12-91) months, respectively. CGP analyses of all samples (Table) revealed EWSR1 rearrangement in 8.1% (3/37) and presence of PHF1-TFE3 and CIC:DUX4 rearrangements in 16% (6/37). Independent blinded histopathology review of whole slides and tissue is underway. Conclusions: MM is a rare malignancy with variable clinical course. In our series, pts with mets derived little benefit from systemic therapy. CGP revealed CDKN2A/B alteration as the most prevalent with few harboring EWSR1 rearrangement. PHF1-TFE3 was recently described in ossifying fibromyxoid tumor (OFMT) that may represent a subset of OFMT not yet expressing bone markers. The presence of hypermutation and CIC:DUX4 fusions also suggests potential alternate diagnosis. These results indicate that CGP could complement histopathologic evaluation to aid in diagnoses and treatment of this entity. [Table: see text]
Care homes after covid-19: the government needs a plan
Authors: Finbarr C Martin
Journal: BMJ (2020)

<h3>Background</h3> An accentuated Quadriceps (Q) angle, genu valgum, flat feet, femoral anteversion, lumbar hyperlordosis and lower limb dysmetria can be factors favouring the occurrence of injuries. <h3>Objective</h3> To determine what degrees of Q angle can be tolerated by and what corrector guidelines can be established for volleyball players. <h3>Design</h3> A Q angle analysis was performed on 36 female and 41 male volleyball players from a Spanish honour division team for 5 years, as well as a measurement of weight distribution on a balance platform. We determined the injuries suffered during each season and their relation to the physical activity. <h3>Setting and participants</h3> 44 females and 46 males (females: mean age 22±3.4 years; height: 182.3±5.7 cm; weight: 71.9±4.1 kg; males: 23±3.3 and; 188.2±3.8 cm; 84.8±6.9 kg) who were on the team during the 5-year period of study. Eight females and five males did not complete the study. <h3>Interventions</h3> A logistic regression analysis was performed to determine the influence of anthropometric factors on the occurrence of injuries. Independent Variables: Anthropometric measures, balance, minutes of training. Dependent: Injuries. <h3>Results</h3> Females: In the right lower limb, the Q angle average is 14.14°±1.8 degrees, while in the left lower limb it is 14.97°±1.1 (p&lt;0.01). Males: Right Q angle: 13.1°±2.2; Left: 13.75°±1.7 (p&lt;0.01). Sharp Left Q angle favours the occurrence of lower limb and back injuries. There is no connection to practical exposure. <h3>Conclusions</h3> We formulated a logistic regression equation that predicts the occurrence of injuries. Degree of satisfaction: 75% (females), 85% (males). 1/1+e-(0.757•LQA−0.647•DTT)2. (e: Natural Logarithm e; LQA: Left Q angle; DTT: Differences in thigh thickness).
以惊厥为首发症状的小儿一氧化碳中毒六例
Authors: 商晓红, 罗焕华, 刘玉, 陈焕芝
Journal: BMJ (2006)

一氧化碳(CO)中毒在我国北方冬季常见.小儿CO中毒多与家人同时发病而被发现.我院儿科于2004年11月至2005年2月救治6例以惊厥发作就诊的CO中毒患儿,经治疗无任何后遗症,现报告如下。
Association of HLA class 1 homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer (NSCLC) treated with PD-1 inhibitor as first-line therapy.
Authors: Young Kwang Chae, Dongyup Lee, Jonghanne Park, Horyun Choi, Gahyun Gim, Sukjoo Cho, Leeseul Kim, Youjin Oh, Cyra Y Kang, Pedro Antonio Hermida de Viveiros
Journal: Journal of Clinical Oncology (2020)

e21519 Background: Homozygosity at human leukocyte antigen class I (HLA-I) locus has been reported to be an unfavorable predictive biomarker of second line or beyond immunotherapy in patients with different types of cancer including melanoma and NSCLC. The linkage between HLA-I homozygosity and survival outcomes in NSCLC patients treated with first-line immunotherapy has not been reported. Methods: Next generation sequencing with HLA genotyping was performed for patients with unresectable stage III or IV NSCLC treated with pembrolizumab plus chemotherapy as first line (N = 25). Progression free survival (PFS) was compared between HLA-I homozygous (defined as homozygosity in at least one locus A, B, or C) and heterozygous patients. Kaplan-Meier curves were built and Log-rank test was used to compare unadjusted survival statistics between the groups. Cox Proportional Hazards were then used to adjust for potential confounders; age, sex, and tumor mutation burden status (TMB, above vs. below median). Results: The median follow up time was 259 days [interquartile range,163 to 350]. Among 25 enrollees, 21 patients (84%) were HLA-I heterozygous and 4 patients (16%) were HLA-I homozygous. Treatment response was not available in 6 patients with HLA-I homozygosity. Among 15 patients with HLA-I homozygosity, 4 patients (26.7%) had partial response (PR), 7 patients (46.7%) had stable disease(SD), and 4 patients (26.7%) had progressive disease (PD). Among 4 patients with HLA-I heterozygosity, 1 patient (25%) had PR, 1 patient (25%) had SD, and 2 patients (50%) had PD. The disease control rates (PR and SD) were 73.4% in heterozygous group and 50% in homozygous group. The heterozygous group showed longer median PFS than the homozygous group (19 vs. 9.4 months, Log-rank p = 0.14). Patients with HLA-I homozygosity demonstrated shorter PFS (HR = 2.35, 95% CI = 0.56-9.9, p = 0.25). Adjusted HRs controlled for age, sex, and TMB were 3.6[0.65-20], 2.3[0.55-9.9] and 1.7[0.34-8.6] respectively. Conclusions: We observed a trend toward an inverse association between HLA-I homozygosity and survival outcomes in patients with NSCLC treated with first-line immunotherapy. Further perspective studies to validate such relationship are warranted.
Management of tinnitus and its relation to non-auditory disease
Authors: Jianning Zhang
Journal: BMJ (2016)

耳鸣是一种常见的临床症状，表现为耳内或颅内有声音的一种主观感觉。耳鸣病因复杂，多与听觉系统疾病相关，但研究发现听觉系统外的很多疾病也与耳鸣发病有关，需要引起全科医生的重视。由于耳鸣的发病率逐渐增高，治愈困难，患者痛苦，临床上需要全科医生了解耳鸣与全身各系统疾病的关系并尽快掌握规范的耳鸣诊治要求。通过全面阐述耳鸣综合疗法三步曲的核心思想及耳鸣诊治的操作规范，指导全科医生正确、合理地应用耳鸣综合疗法开展耳鸣诊治的临床实践。
阻塞性睡眠呼吸暂停低通气综合征肥胖患者血清瘦素和胰岛素的变化
Authors: 王曾, 杜黎明, 李京合
Journal: BMJ (2006)

根据睡眠呼吸暂停低通气指数和体重指数将56例研究对象分为4组,测定血瘦素和胰岛素水平.结果显示,阻塞性睡眠呼吸暂停低通气综合征(OSAHS)肥胖组、非肥胖组及单纯肥胖组空腹胰岛素、瘦素水平较正常对照组显著升高,且OSAHS肥胖组胰岛素、瘦素显著高于OSAHS非肥胖组及单纯肥胖组.提示OSAHS肥胖患者体内存在瘦素抵抗和胰岛素抵抗,瘦素和胰岛素与OSAHS有独立的相关性。
肾病综合征患者脂类代谢指标的临床分析
Authors: 朱振远, 孙文阁, 瑞云, 潘运刚
Journal: BMJ (2005)

各型肾病综合征(nephritic syndrome,NS)患者体内均存在不同的脂类代谢紊乱,而传统的血脂检查项目因干扰和影响因素较多,不同患者其变化程度差别很大,有许多不足之处,给临床诊治带来不便.为此我们开展一些在NS时能准确反映患者体内脂类代谢真实状况的较理想的实验室检查项目,并对其进行比较评价。
Association of reinvigoration of circulating anti-telomerase CD4 Th1 response in cancer patients with anti-PD-1 response.
Authors: Emeline Orillard, Laura Boullerot, Caroline Laheurte, Amandine Martin, Marion Jacquin, Diane Berthod, Mélanie Ramseyer, Pascale Jacoulet, Jean Lahourcade, Marie Gainet Brun, Hamadi Almotlak, Eve Puzenat, Charlee Nardin, Guillaume Eberst, Marc Guion-Dusserre, Laura Mansi, Francois Aubin, Virginie Westeel, Christophe Borg, Olivier Adotevi
Journal: Journal of Clinical Oncology (2020)

3044 Background: Increasing evidence highlights the crucial roles played by CD4+ Th1 cells in cancer immunity and immunotherapy (Spitzer et al., Cell 2017, Borst et al., Nat rev Immunol 2018). Here, we investigate the relevance of circulating CD4 Th1 response against shared tumor-associated antigens (TAA) in cancer patients treated by anti-PD-1 immunotherapy. Methods: A total of 46 advanced cancer patients (pts) including 32 pts with non-small cell lung cancer (NSCLC), 14 pts with melanoma, were enrolled (ITHER trial NCT02840058). Patients were treated with anti-PD-1 therapy as standard of care (26 pts with nivolumab and 20 pts with pembrolizumab). Peripheral blood mononuclear cells were collected before and after treatment at 1 and 3 months. The presence of circulating TAA-specific Th1 response was measured by IFNy ELISPOT assay using a mixture of 15mer peptides derived from telomerase (TERT) (Laheurte et al., Oncoimmunology 2016 and Br J C 2019). Results: At the baseline, the anti-TERT Th1 response was observed in 37% of pts. After anti-PD-1 therapy, de novo induction and/or amplification of pre-existing anti-TERT Th1 response was found in 26 % of pts (12/46). Whereas, a decrease of this response was documented in 15% of pts (7/46).The presence of anti-TERT Th1 response in peripheral blood during anti-PD-1 treatment was associated with a prolonged progression free-survival (PFS) as compared to the immune non responder pts (14.4 vs 2.6 months respectively, p = 0.006, HR 0.39 [0.2;0.76]). Similar observation was made for the overall survival (OS) (22.3 vs 12.3 months respectively, p = 0.04 HR 0.45 [0.21;0.96]). Notably, de novo reinvigoration of peripheral anti-TERT Th1 response after anti-PD-1 therapy was associated with a better clinical outcome as compared to the group of pts with decreased immune response after treatment (Median OS not reached vs 5.8 months). In contrast, no association with anti-PD-1 response was observed neither with circulating anti-NY-ESO-1 or with anti-viral Th1 response, concurrently measured in these patients. Conclusions: The reinvigoration of circulating CD4 Th1 against telomerase in patients treated by anti-PD-1 is associated with a better clinical outcome. These results underline the potential interest of monitoring circulating antitumor CD4 Th1 response for immune checkpoint inhibitors management.