tbuckley/cabot-search huggingface dataset:
Micropathological Chip Modeling the Neurovascular Unit Response to Inflammatory Bone Condition
Authors: Estrela Neto, Ana Carolina Monteiro, Catarina Leite Pereira, Miguel Simões, João Pedro Conde, Virginia Chu, Bruno Sarmento, Meriem Lamghari
Journal: Advanced Healthcare Materials (2022)

Abstract Organ‐on‐a‐chip in vitro platforms accurately mimic complex microenvironments offering the ability to recapitulate and dissect mechanisms of physiological and pathological settings, revealing their major importance to develop new therapeutic targets. Bone diseases, such as osteoarthritis, are extremely complex, comprising of the action of inflammatory mediators leading to unbalanced bone homeostasis and de‐regulation of sensory innervation and angiogenesis. Although there are models to mimic bone vascularization or innervation, in vitro platforms merging the complexity of bone, vasculature, innervation, and inflammation are missing. Therefore, in this study a microfluidic‐based neuro‐vascularized bone chip (NVB chip) is proposed to 1) model the mechanistic interactions between innervation and angiogenesis in the inflammatory bone niche, and 2) explore, as a screening tool, novel strategies targeting inflammatory diseases, using a nano‐based drug delivery system. It is possible to set the design of the platform and achieve the optimized conditions to address the neurovascular network under inflammation. Moreover, this system is validated by delivering anti‐inflammatory drug‐loaded nanoparticles to counteract the neuronal growth associated with pain perception. This reliable in vitro tool will allow understanding the bone neurovascular system, enlightening novel mechanisms behind the inflammatory bone diseases, bone destruction, and pain opening new avenues for new therapies discovery.
Tumour-associated antigens: still too fickle for population screening.
Journal: BMJ (1977)

Tumour-associated antigens: still too fickle for population screening Once in a while laboratory workers stumble!across just the conditions they are looking for to assess whether their tests may play a useful practical part in screening for cancer.In 1948 5209 residents of Framingham, Massachusetts, agreed to participate in a follow-up study designed to identify causal factors in heart disease.'As part of the programme a blood sample was taken every two years for serum cholesterol measurements; fortuitously the unused portion of the serum was stored.This has provided Williams and his colleagues2
Implementation of HIV Preexposure Prophylaxis in Diverse, Real-World Settings
Authors: Divya R. Bhamidipati, Colleen F. Kelley
Journal: JAMA Network Open (2022)

Hongyi Wang, PhD; Zixin Wang, PhD; Xiaojie Huang, PhD; Yaokai Chen, PhD; Hui Wang, PhD; Sitong Cui, MPH; Jing Zhang, PhD; Zhenxing Chu, PhD; Qinghai Hu, PhD; Haibo Ding, PhD; Hanzhu Qian, PhD; Huachun Zou, PhD; Weiming Tang, PhD; Yangyang Gao, PhD; Xia Jin, PhD; Zhaozhen Liu, MPH; Lukun Zhang, PhD; Jin Zhao, PhD; Xiaoqing He, MPH; Yongjun Jiang, PhD; Wenqing Geng, PhD; Junjie Xu, PhD; Hong Shang, PhD; China Real-World Oral Intake of PrEP (CROPrEP) Study Team; Rui Li; Qiang Kang; Shangcao Li; Zhili Hu; Rantong Bao; Hang Li; Yonghui Zhang; Zhu Mei; Yueru Jia; Zehao Ye; Yanni Ma; Xin Ma; Xiaoyun Shi; Yijun Duan; Guanghui Zhang; Fang Zhao; Yao Li
Industrial accidents.
Authors: T. C. Aw, J. M. Harrington
Journal: BMJ (1989)

surger < 50 40*.e.e ,.*BiopsyI surgery WObseration .f5 Biopsy / observation 30 1 2 3 4 5 6Nodule diameter (cm)Management strategies for solitary pulmonary nodule that produced the longest average life expectancy in smokers according to age and diameter of nodule.In a 40 year old smoker with a 2 cm nodule, for example, biopsy and observation would produce the greatest life expectancy, whereas for a 60 year old with a 4 cm nodule it would be immediate surgery. 7
Aquagenic pruritus.
Authors: M W Greaves, A K Black, R A Eady, A Coutts
Journal: BMJ (1981)

Three patients were studied in whom brief contact of the skin with water at any temperature evoked intense itching without visible changes in the skin. The patients were otherwise apparently healthy, and this chronic and disabling disorder tended to attract a "psychogenic" label. Pharmacological studies showed that the condition was associated with local release of acetyl choline in the skin, mast-cell degranulation, and raised blood histamine concentrations. It responded well to antihistamines in two of the three patients. Aquagenic pruritus is probably common, but it is generally unrecognised and may be misdiagnosed. Antihistamines may induce a good therapeutic response.
Association of changing bone metastatic (mets) patterns with dynamics of circulating tumor DNA (ctDNA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Vincenza Conteduca, Emanuela Scarpi, Alice Rossi, Fabio Ferroni, Giorgia Gurioli, Sara Bleve, Caterina Gianni, Giuseppe Schepisi, Nicole Brighi, Cristian Lolli, Maria Concetta Cursano, Alessandra Virga, Chiara Casadei, Amelia Altavilla, Alberto Farolfi, Paola Ulivi, Domenico Barone, Federica Matteucci, Giovanni Paganelli, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2022)

152 Background: Accurate monitoring response of bone mets to treatment is an active need for mCRPC patients (pts). Recently, ctDNA has been showed as an early biomarker efficacy of androgen receptor signaling inhibitor (ARSI) therapy for mCRPC ( Conteduca, Br J Cancer 2020). In this study, we aimed to reveal if ctDNA analysis can permit more reliable prediction of bone mets burden and radiographic progression disease (PD). Methods: In a biomarker study (REC 2192/2013), targeted next generation sequencing was performed to assess ctDNA fraction. Radiographic evidence of bone disease was documented by conventional imaging according to PCWG3 criteria ( Scher, J Clin Oncol 2018), and was classified on the basis of mets number (≤5, 6 -19, ≥20) in oligometastatic (O), diffuse (D), and widespread (W), respectively. Associations were explored both through uni/multivariate logistic regressions. Results: Serial plasma samples and radiographic scans on ARSI treatment were prospectively collected from 73 CRPC with bone mets. Median age was 74 years [interquartile range (IQR) 69-79]. Bone mets patterns were significantly associated with median baseline ctDNA level (O = 0.16, D = 0.33, and W = 0.46, p 0.0003). Similar results were reported on treatment and at PD (p 0.0003 and p 0.0007, respectively). In 24 pts with a progressive worsening of bone mets pattern (O→D→W) compared to pts with no change in bone mets pattern on ARSI, we observed an early meaningful ctDNA rise with a % ctDNA variation from baseline to 3 month therapy of 150.6% (IQR 104.9-210.7) vs 11.1% (IQR 0-36.6), p &lt; 0.0001. Univariate analysis showed that early ctDNA rise was significantly associated with radiographic progression free/overall survival (rPFS/OS): hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.30-3.27, p 0.002, and HR 1.82, 95% CI 1.15-2.88, p 0.01, respectively]. In multivariable analyses including ctDNA variation, changing bone mets pattern, age, performance status, and presence of concomitant visceral mets, ctDNA change at 3 month ARSI resulted the only independent predictor of both rPFS/OS (HR 2.27, 95% CI 1.04-4.94, p 0.027 and HR 2.98, 95% CI 1.31-6.81, p 0.033, respectively). Visceral mets were associated with only OS (HR 3.87, 95% CI 1.76-8.51, p 0.0008). Conclusions: Early ctDNA variation may reflect changes in bone mets pattern on ARSI allowing to track pattern of bone progression and predict outcome. Further studies to validate these findings are warranted.
Abstract 17269: Incidence of Atrial Fibrillation in Patients With Cobalt and Chromium Containing Hip Arthroplasty
Authors: Sunita Sharma, Shiva Ponamgi, Christopher Desimone, Cody Wyles, Philip Sun, Vidushei Yogeswaran, Deepak Padmanabhan, Majd El-Harasis, David Hodge, Joshua Slusser, Matthew Abdel, Samuel Asirvatham
Journal: Circulation (2018)

Background: Worldwide, approximately one million patients have had total hip arthroplasty with 35% being cobalt and chromium Metal-on-Metal (MoM) or Metal-on-Polythelene (MoP) implants. Animal models have suggested that cobalt and chromium can affect all chambers, but there seems to be an atrial predilection. There are several case reports of metal containing hip arthroplasty causing atrial arrhythmias but the true incidence of atrial fibrillation associated with metal hip arthroplasty remains undefined. Objective: We sought to determine the incidence of atrial fibrillation in patients with metal containing hip arthroplasty. We also examined the association between serum cobalt and chromium levels and arrhythmias in this cohort and all cause mortality. Methods: We retrospectively examined the records of patients from the Mayo Clinic total hip arthroplasty registry (Metal group - Metal-on-Metal: MoM and Metal-on-Polyethylene: MoP, Non-Metal group - Ceramic-on-Ceramic: CoC and Ceramic-on-Polyethylne: CoP) to obtain demographic data, comorbidities, laboratory, ECG, and echocardiographic data. Out of a total of 1756 patients, Cobalt and Chromium levels were available in 138 patients. Results: The mean age of patients with metal containing hip replacement was 50 years and were predominantly male. During a follow up period of 10 years, the incidence of atrial fibrillation in our study population was 8% in metal group compared to 2% (p=0.11) in non-metal group. There was no association between cobalt or chromium levels with the incidence of atrial fibrillation. All-cause mortality was significantly higher in metal group versus non-metal group (p=0.005). Conclusion: The incidence of atrial fibrillation was relatively more in patients with metal versus non-metal hip arthroplasty but there was no association of serum cobalt or chromium levels with incidence of atrial fibrillation in the subset of patients. In addition, all-cause mortality was significantly higher in the metal group suggesting potential toxic effects of metal containing hip arthroplasty.
The role of cytoreductive nephrectomy and systemic therapy in the management of tumor thrombus in patients with metastatic renal cell carcinoma.
Authors: Abhenil Mittal, Esmail Mutahar Al-Ezzi, Xuan Li, Brooke Wilson, Pavlina Spiliopoulou, Srikala S. Sridhar, Nazanin Fallah-Rad, Peter W. M. Chung, Robert James Hamilton, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2022)

345 Background: Patients (pts) with metastatic renal cell carcinoma (mRCC) and tumor thrombus have historically been treated with cytoreductive nephrectomy (CN), however, their outcomes remain poor. Recent phase III data suggest the role for cytoreductive nephrectomy (CN) in mRCC is limited. To date, only case-reports have described thrombus response to systemic therapy. Here, we describe response and survival outcomes of de novo mRCC patients with thrombi treated with systemic therapy with or without CN. Methods: Pts with de novo mRCC at the Princess Margaret Cancer Centre were identified. Demographics, disease characteristics (including the presence of thrombus) and survival outcomes were collected. Progression free survival (PFS) and overall survival (OS) in months (m) was calculated using the Kaplan-Meier method (log-rank). Results: We identified 226 pts with de novo mRCC between 2002 and 2019. Pt demographics are listed in the table. In total, 157 pts underwent a CN and 69 received only systemic therapy. Of the total cohort, 64 pts (28%) had tumor thrombus at presentation (46 CN, 18 no CN). Of the 18 patients with tumor thrombus treated with only systemic therapy, 17 received first-line angiogenesis inhibitors and 1 had chemotherapy (medullary histology). Six (33%) had thrombus progression, 8 (44%) had stable disease and four (22%) had an objective response. Median PFS and OS for patients with and without tumor thrombus treated with systemic therapy only was not significantly different [5.3m (95% CI 3.6-11.7) vs 4.1m (95% CI 3.1-5.9)), p=0.33; OS: 12.1m (95% CI 8.8-27.7) vs 13.9m (95% CI 7.9-21.5), p=0.87). PFS for patients with tumor thrombus who had CN was similar to those treated with systemic therapy alone [8.4m (95% CI: 5.7-13.4) vs 5.3m (95% CI 3.6-11.7), p=0.57] but OS was significantly better favoring CN [29.4m (95% CI: 17.4-48.9) vs 12.1m (95% CI 8.8-27.7), p=0.01). Conclusions: In this largest series of patients with mRCC and thrombus treated with systemic therapy +/- CN, CN appears to plays an important role. More data is needed for patients with tumor thrombus treated with immunotherapy to confirm these findings and elucidate the role of surgery in those cohorts. Bias due to the retrospective study design is an important limitation.[Table: see text]
Sequential endoscopic balloon dilations using a calibrated small-caliber-tip transparent hood for a patient with 10 ileal strictures secondary to Crohn’s disease
Authors: Kunihiko Oguro, Tomonori Yano, Hirotsugu Sakamoto, Manabu Nagayama, Yoshikazu Hayashi, Alan Kawarai Lefor, Hironori Yamamoto
Journal: Endoscopy (2022)

Patients with Crohnʼs disease may have multiple strictures of the small intestine, and surgical resection can lead to short-bowel syndrome. Endoscopic balloon dilation (EBD) is an alternative treatment to avoid surgical resection [1]; however, it is considered challenging to perform EBDs of multiple strictures. The calibrated small-caliber-tip transparent (CAST) hood (TOP Corporation, Tokyo, Japan) ([Fig. 1]) [2] makes it easier to insert a guidewire and a balloon catheter through a stricture. The CAST hood enables measurement of the strictureʼs inner diameter ([Fig. 2]), which is an important factor in choosing the appropriate size of balloon catheter for EBD. Although the passage through dilated strictures is frequently difficult, the CAST hood makes it easier to pass through post-EBD strictures. Therefore, the CAST hood makes it easier to perform EBDs of multiple strictures.
Evolution and development: engine-driven endodontic rotary nickel-titanium instruments
Authors: Yuhong Liang, Lin Yue
Journal: International Journal of Oral Science (2022)

Abstract Various engine-driven NiTi endodontic files have been indispensable and efficient tools in cleaning and shaping of root canals for practitioners. In this review, we introduce the relative terms and conceptions of NiTi file, including crystal phase composition, the design of the cutting part, types of separation. This review also analysis the main improvement and evolution of different generations of engine-driven nickel-titanium instruments in the past 20 years in the geometric design, manufacturing surface treatment such as electropolishing, thermal treatment, metallurgy. And the variety of motion modes of NiTi files to improve resistance to torsional failure were also discussed. Continuous advancements by the designers, provide better balance between shaping efficiency and resistance to of NiTi systems. In clinical practice an appropriate system should be selected based on the anatomy of the root canal, instrument characteristics, and operators’ experience.
Treatment (tx) patterns among men with metastatic castration resistant prostate cancer (mCRPC) in the United States (US).
Authors: Pedro C. Barata, Andrea Leith, Amanda Ribbands, Rachel Montgomery, Matthew Last, Bhakti Arondekar, Alexander Niyazov, Jasmina Ivanova
Journal: Journal of Clinical Oncology (2022)

52 Background: Novel hormonal therapies (NHTs) and docetaxel were initially approved for the tx of men with mCRPC. Over time, these agents moved earlier in the disease continuum and are now also used in metastatic castration sensitive prostate cancer (mCSPC). Little is known about first-line (1L) mCRPC tx patterns for men with prior taxane-based chemotherapy (CT) or NHT exposure. This study evaluated the impact of taxane CT or NHT use in mCSPC on recent 1L tx patterns among men with mCRPC in the US. Methods: Participating physicians collected information from medical charts for the next consecutive 4 adult men with mCRPC during January-August 2020. A subset of men had prior mCSPC tx information available. 1L mCRPC txs were described overall and stratified by previous tx with taxane CT or NHT during mCSPC. No statistical comparisons were performed. Results: 116 adult men with mCRPC and known mCSPC tx history were included. Mean age was 70 years; 15% had known family history of prostate cancer; 70% had bone metastases and 33% had visceral metastases at data collection. Overall, 10% (12/116) of men had been previously treated with taxane CT and 28% (32/116) were treated with NHT during mCSPC. 1L mCRPC tx was initiated on average 35 days after mCRPC diagnosis. NHT was the most common 1L mCRPC tx regardless of prior taxane CT or NHT use. Men pre-treated with taxane CT were more likely to initiate mCRPC tx with NHT than taxane naïve men. NHT pre-treated men were less likely to initiate 1L mCRPC tx with NHT and more likely to initiate tx with docetaxel than NHT naïve men. 53% of men with prior NHT tx were rechallenged with NHTs in 1L mCRPC. (Table). Conclusions: Findings from this US real-world study among men with mCRPC suggest physicians most commonly initiate 1L mCRPC life-prolonging tx with NHT regardless of prior taxane CT or NHT exposure. Additional studies with larger sample sizes are needed to confirm these findings and better understand optimal tx sequencing, especially as new tx options become available.[Table: see text]
Neuraxial Labor Analgesia for Vaginal Delivery and Severe Maternal Morbidity
Authors: Evelina Pankiv, Alan Yang, Kazuyoshi Aoyama
Journal: JAMA Network Open (2022)

Jean Guglielminotti, MD, PhD; Ruth Landau, MD; Jamie Daw, PhD; Alexander M. Friedman, MD, MPH; Stanford Chihuri, MPH; Guohua Li, MD, DrPH
Abstract 246: The Relationship Between Favorable Neurological Outcome in Patients With Out-of-Hospital Cardiac Arrest Due to Cardiac Etiology and Regional Disparity of the Number of Physicians
Authors: Tsukasa Yagi, Ken Nagao, Shigemasa Tani, Eizo Tachibana, Nobutaka Chiba, Tadashi Ashida, Naohiro Yonemoto, Morimasa Takayama, Hiroshi Nonogi, Naoya Matsumoto, Yasuo Okumura
Journal: Circulation (2018)

Background: Cardiac arrest is a major public health issue worldwide. In Japan, the regional disparity of the number of physicians per 100000 population is also a major public health problem. However, it is unknown whether there is the relationship between favorable neurological outcome in patients with out-of-hospital cardiac arrest (OHCA) due to cardiac etiology and this regional disparity. The aim of the present study was to clarify this relationship using the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of OHCA. Methods: From the data of the All-Japan Utstein Registry between 2011 and 2015, we included adult patients who had OHCA due to cardiac etiology. 47 prefectures of Japan were divided into quartiles on the basis of the number of physicians in each prefecture, reported by Ministry of Health, Labor and Welfare in Japan. In addition, study patients were divided into four groups based on these quartiles. We compared favorable neurological outcome at 30 days after OHCA in each group, using the multivariable logistic-regression analysis. Results: Four quartile ranges of the number of physicians were set for this study (Figure). Moreover, of the 629,471 OHCA victims between 2011 and 2015, 358,993 met the inclusion criteria. Figure represented favorable neurological outcome at 30 days after OHCA in each quartile. In the multivariable analysis, the adjusted odds ratios for Quartile 2, Quartile 3 and Quartile 4 compared with Quartile 1 for favorable neurological outcome at 30 days after OHCA was 0.971 (95%CI 0.918- 1.027; P=0.307), 1.011 (95%CI 0.956- 1.069; P=0.703) and 0.850 (95%CI 0.809- 0.893; P&lt;0.001), respectively. Conclusion: The regions in which the number of physicians per 100000 population was larger were inferior to the regions in which the number of these was smaller, in terms of neurological benefits in patients with OHCA due to cardiac etiology.
Highlights
Journal: JAMA Cardiology (2019)

LDL-C-Guided Statin Treatment in Borderline CVD Risk 969Among individuals with the same 10-year absolute risk (AR 10 ) of atherosclerotic cardiovascular disease (CVD), those with higher levels of low-density lipoprotein cholesterol (LDL-C) experience greater absolute risk reduction from statin therapy.Kohli-Lynch and coauthors estimated the cost-effectiveness of statin treatment across ranges of age, sex, AR 10 , and LDL-C levels using data from the 1999-2014 US National Health and Nutrition Examination Surveys.Prescribing statins to individuals aged 40 years at baseline with borderline AR 10 (5.0% to 7.4%) and LDL-C levels of 130 to 189 mg/dL would be cost-saving, and treating all individuals with AR 10 of at least 5.0% would be highly cost-effective ($33 558 per qualityadjusted life-year) and would prevent the most atherosclerotic CVD events.Within age, AR 10 , and sex categories, individuals with higher baseline LDL-C levels gained more qualityadjusted life-years from statin therapy.
Address in Surgery
Authors: G. Y. Heath
Journal: BMJ (1870)

TSHE BRITISH MEDICAL 5 OURNAL.163e pondering over it much and often, and weighing in the scale every theory that I could think of, that my inference is supported by the small number of these cases of acute rheumatism that presented pericard- itis, and the happy results in those who were threatened and affected with endocarditis, so large a number of whom left the hospital with valves faultless, so far as we could detect.But the inference is, that we do own to a marked extent, the small proportion of cases of peri.carditis, especially in the young patients, and the happy result of those threatened and affected with endocarditis to the care which is taken to keep the inflamed joints at rest, to shield them from external pressure, and to give them ease.
Immune system and intestinal microbiota determine efficacy of androgen depletion therapy against prostate cancer.
Authors: Safae Terrisse, Anne-Gaëlle Goubet, Kosuke Ueda, Andrew M. Thomas, Valentin Quiniou, Cassandra Thelemaque, Garett Dunsmore, Emmanuel Clave, Melissa Gamat-Huber, Satoru Yonekura, Lisa Derosa, Stephane Culine, Paule Opolon, Florent Ginhoux, Antoine Toubert, Nicola Segata, Douglas G. McNeel, Karim Fizazi, Guido Kroemer, Laurence Zitvogel
Journal: Journal of Clinical Oncology (2022)

168 Background: Prostate cancer (PC) responds to androgen deprivation therapy (ADT) usually in a transient fashion, progressing from hormone-sensitive PC (HSPC) to castration-resistant PC (CRPC). While it is recognized that ADT has an immunomodulatory effect, little is known about the intestinal microbiome effect on therapeutic outcome of ADT. Methods: We investigated a mouse model of PC as well as specimens from PC patients to unravel an unsuspected contribution of thymus-derived T lymphocytes and the intestinal microbiota in the efficacy of ADT. Preclinical experiments were performed in PC-bearing mice, immunocompetent or immunodeficient. In parallel, we prospectively included 65 HSPC and CRPC patients to analyze their feces and blood specimen. Results: In PC-bearing mice, ADT increased thymic cellularity and output. PC implanted in T lymphocyte-depleted or athymic mice responded less efficiently to ADT than in immunocompetent mice. Moreover, depletion of the intestinal microbiota by oral antibiotics reduced the efficacy of ADT. PC reduced the relative abundance of Akkermansia muciniphila in the gut, and this effect was reversed by ADT. Moreover, cohousing of PC-bearing mice with tumor-free mice, or oral gavage with Akkermansia improved the efficacy of ADT. This appear to be applicable to PC patients because long-term ADT resulted in an increase of thymic output, as demonstrated by an increase in circulating recent thymic emigrant cells (sjTRECs). Moreover, as compared to HSPC controls, CRPC patients demonstrated a shift in their intestinal microbiota that significantly correlated with sjTRECs. While feces from healthy volunteers restored ADT efficacy. Conclusions: These findings suggest that reversing the intestinal dysbiosis and repairing acquired immune defects in PC patients have a potential impact on the therapeutic outcome of ADT.