tbuckley/cabot-search huggingface dataset:
Serial IL-6 measurements in patients with tocilizumab-treated large-vessel vasculitis detect infections and may predict early relapses
Authors: Christoph T Berger, Birke Rebholz-Chaves, Mike Recher, Tobias Manigold, Thomas Daikeler
Journal: Annals of the Rheumatic Diseases (2019)

Tocilizumab (TCZ) has been approved for giant cell arteritis (GCA). Interleukin-6 (IL-6) receptor blockade suppresses clinical disease and is steroid sparing.1 2 Since IL-6 induces the acute-phase response, the clinically used inflammation markers (C reactive protein (CRP), erythrocyte sedimentation rate (ESR)) are suppressed during TCZ treatment. Whether serum IL-6 is useful in monitoring disease activity and detecting infections in TCZ-treated GCA is unknown.

We longitudinally measured IL-6 in 23 patients with intravenous TCZ–treated GCA, two patients with polymyalgia rheumatica and one patient with Takayasu arteritis of our GCA cohort (EKBB-239/09), and in 13/26 patients additionally before TCZ treatment. Patient characteristics are shown in table 1. At each visit, clinical and laboratory parameters (white blood cell (WBC), CRP, ESR) were assessed. Relapse was defined as the need for treatment intensification following new or increasing symptoms, or rising CRP/ESR not otherwise explained.2 

View this table:

Table 1 
Patient characteristics of ‘relapser’ and ‘non-relapser’



During TCZ therapy, CRP, ESR and WBC rapidly declined and were sustainably suppressed. IL-6 levels rose and remained elevated throughout TCZ treatment (figure 1). Daily prednisone doses were successfully tapered after TCZ was initiated (figure 1C). During 23.8 patient-years of TCZ therapy, eight infections were documented with available IL-6 levels (online supplementary table S1). IL-6, but not CRP, ESR …
Royal college’s patient rep slams NHS over plans to review four hour target
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The Royal College of Emergency Medicine’s lead patient representative has written an open letter to the head of NHS England strongly criticising plans to review the target for 95% of patients presenting to emergency departments to be seen within four hours.

NHS England is expected to set out changes in March to substantially alter the current target following its review of clinical standards. This is expected to include placing more emphasis on emergency departments seeing specific patients swiftly, such as those with sepsis, stroke, or heart …
Recognition of synthetic antigenic determinants of clavulanic acid by dendritic cells in patients with immediate allergic reactions to this drug
Authors: Ruben Fernandez-Santamaria, Alba Rodriguez-Nogales, Natalia Pérez-Sanchez, Maria Salas, Adriana Ariza, Patricia Malagón, Angela Martin-Serrano Ortiz, Tahia D. Fernandez, Cristobalina Mayorga, M.J. Torres, María Isabel Montañez
Journal: Journal of Allergy and Clinical Immunology (2019)
Extreme Competence: Keystone Hosts of Infections
Authors: Lynn B. Martin, BriAnne Addison, Andrew G.D. Bean, Katherine L. Buchanan, Ondi L. Crino, Justin R. Eastwood, Andrew S. Flies, Rodrigo Hamede, Geoffrey E. Hill, Marcel Klaassen, Rebecca E. Koch, Johanne M. Martens, Constanza Napolitano, Edward J. Narayan, Lee Peacock, Alison J. Peel, Anne Peters, Nynke Raven, Alice Risely, Michael J. Roast, Lee A. Rollins, Manuel Ruiz-Aravena, Dan Selechnik, Helena S. Stokes, Beata Ujvari, Laura F. Grogan
Journal: Trends in Ecology & Evolution (2019)
Abstract 15761: Is QRS Waveform for Out-of-hospital Cardiac Arrest PEA Associated With Outcome?
Authors: Ryozo Yoshioka, Chihiro Narita, Koichi Haruta, Kyuhei Miyakawa, Akihiro Miyake, Naoki Tosaka, Yutaka Yoshida, Hiroshi Nonogi
Journal: Circulation (2017)

Introduction: In Japan, the all patients with out-of-hospital cardiac arrest received CPR are delivered to emergency hospitals and registered nation widely. Those data showed the neurological intac...
A systematic review and network meta-analysis of regorafenib and TAS-102 in refractory metastatic colorectal cancer.
Authors: Mohamad Bassam Sonbol, Raed Benkhadra, Zhen Wang, Belal Firwana, Kabir Mody, Pashtoon Murtaza Kasi, Joleen Marie Hubbard, M. Hassan Murad, Daniel H. Ahn, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2019)

619 Background: Regorafenib (at a starting dose of 160 mg/day, rego 160), regorafenib (with a weekly dose escalation, rego 80+) and TAS-102, are suggested treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these 3 strategies. Methods: We searched PubMed, Embase, and Cochrane CENTRAL, for randomized controlled trials evaluating TAS 102 or regorafenib in refractory mCRC patients who progressed on/intolerant of previous oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included OS and PFS. The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White’s multivariate meta-regression to pool evidence from direct and indirect comparisons. Results: Six trials (3 of regorafenib and 3 of TAS-102) at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS-102 as monotherapy were superior to BSC in terms of PFS (Rego 160: HR = 0.4, CI 0.26 to 0.63; TAS-102: HR = 0.46, CI 0.40 to 0.52) and OS (Rego 160: HR = 0.67, CI 0.48 to 0.93; TAS-102: HR = 0.67, CI 0.57 to 0.80). Network analysis showed that there was no difference in PFS or OS between Rego 160 and TAS-102. Rego 80+ was superior to BSC in terms of OS (HR = 0.44, CI 0.23 to 0.84) and PFS (HR = 0.37, CI 0.21 to 0.66). There was a numerical advantage for Rego 80+ compared to TAS-102 and Rego 160 (see table). Conclusions: Regorafenib 160 and TAS-102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102. [Table: see text]
Artificial intelligence outperforms pulmonologists in the interpretation of pulmonary function tests
Authors: Marko Topalovic, Nilakash Das, Pierre-Régis Burgel, Marc Daenen, Eric Derom, Christel Haenebalcke, Rob Janssen, Huib A.M. Kerstjens, Giuseppe Liistro, Renaud Louis, Vincent Ninane, Christophe Pison, Marc Schlesser, Piet Vercauter, Claus F. Vogelmeier, Emiel Wouters, Jokke Wynants, Wim Janssens
Journal: European Respiratory Journal (2019)

The interpretation of pulmonary function tests (PFTs) to diagnose respiratory diseases is built on expert opinion that relies on the recognition of patterns and the clinical context for detection of specific diseases. In this study, we aimed to explore the accuracy and interrater variability of pulmonologists when interpreting PFTs compared with artificial intelligence (AI)-based software that was developed and validated in more than 1500 historical patient cases.120 pulmonologists from 16 European hospitals evaluated 50 cases with PFT and clinical information, resulting in 6000 independent interpretations. The AI software examined the same data. American Thoracic Society/European Respiratory Society guidelines were used as the gold standard for PFT pattern interpretation. The gold standard for diagnosis was derived from clinical history, PFT and all additional tests.The pattern recognition of PFTs by pulmonologists (senior 73%, junior 27%) matched the guidelines in 74.4±5.9% of the cases (range 56-88%). The interrater variability of κ=0.67 pointed to a common agreement. Pulmonologists made correct diagnoses in 44.6±8.7% of the cases (range 24-62%) with a large interrater variability (κ=0.35). The AI-based software perfectly matched the PFT pattern interpretations (100%) and assigned a correct diagnosis in 82% of all cases (p<0.0001 for both measures).The interpretation of PFTs by pulmonologists leads to marked variations and errors. AI-based software provides more accurate interpretations and may serve as a powerful decision support tool to improve clinical practice.
The XPC-ATM-JNK-γH2AX pathway mediates UV-induced apoptosis in response to DNA replication arrest.
Authors: Sebastien de Feraudy, Luzviminda Feeney, Laura Attardi, James Cleaver
Journal: Cancer Research (2008)

1868  After UV irradiation, H2AX phosphorylation (γH2AX) by JNK is associated with induction of apoptosis. Here, we show that the XPC-ATM-JNK-γH2AX pathway mediates UV-induced apoptosis in response to DNA replication arrest. We found that inhibition of JNK prevents UV-induced apoptosis. After UV irradiation, that does not directly induce DSB, phosphorylation of H2AX serine 139 is required for cell survival. UV light generates a range of γH2AX intensities in all phases of the cell cycle. During DNA replication arrest, UV irradiation induces in a sub-population of cells a super intense homogenous nuclear-wide γH2AX signal that does not co-localize with markers of DSB, 53BP1. This S phase super-intense γH2AX is mediated by JNK, ATM and XPC. Super-intense γH2AX represents an early apoptotic signal that might correspond to genome-wide chromatin modifications preceding caspase-induced DNA fragmentation and other markers of apoptosis. We propose that during UV-induced DNA replication arrest, the DNA Damage Response (DDR) involves at least 2 competing pathways that determine cell fate: a NER-ATM-JNK pathway that leads to a super-intense γH2AX and eventually apoptosis, and an RPA/ATRIP/ATR pathway that leads to lower γH2AX levels, repair and survival.
Abstract 12386: A Conservative Treatment Strategy for Fulminant Right Sided Infective Endocarditis: Long Term Outcomes
Authors: Robin Cherian, Lieng Hsei Ling, Tiong Cheng Yeo, Raymond Ching Chiew Wong, Wern Miin Soo, William Kok Fai Kong, Kian Keong Poh, Edgar Lik Wui Tay
Journal: Circulation (2017)

Introduction: Right sided infective endocarditis (IE) related to intravenous drug use (IVDU) can result in valve destruction, severe tricuspid regurgitation (TR) and septic pulmonary embolism (SPE). In patients at high risk of IE recurrence from resumption of IVDU, management poses ethical dilemmas. We examined the impact of conservative management on long term outcomes. Methods: We studied patients with IVDU related right sided IE and severe TR at presentation. Surgery was considered indicated if there was a) anticipated poor response to antibiotics (persistent septicemia, vegetation size >20 mm, multi-resistant organism, recurrent SPE) b) abscess formation c) left sided IE and d) refractory right heart failure (HF). Patients were stratified based on surgical indication and eventual management. Results: From 2005 through 2016, there were 33 patients (24 males, mean age 35±8 years) with severe TR due to IVDU related IE. Median follow up was 6.4 years. Past history included IE (n=7), HF (n=1) and left side...
Astrocytic mitochondrial ROS modulate brain metabolism and mouse behaviour
Authors: Carlos Vicente-Gutierrez, Nicoló Bonora, Veronica Bobo-Jimenez, Daniel Jimenez-Blasco, Irene Lopez-Fabuel, Emilio Fernandez, Charlene Josephine, Gilles Bonvento, Jose A. Enriquez, Angeles Almeida, Juan P. Bolaños
Journal: Nature Metabolism (2019)
Comparing Automated Office Blood Pressure Readings With Other Methods of Blood Pressure Measurement for Identifying Patients With Possible Hypertension
Authors: Michael Roerecke, Janusz Kaczorowski, Martin G. Myers
Journal: JAMA Internal Medicine (2019)

Automated office blood pressure (AOBP) measurement involves recording several blood pressure (BP) readings using a fully automated oscillometric sphygmomanometer with the patient resting alone in a quiet place. Although several studies have shown AOBP measurement to be more accurate than routine office BP measurement and not subject to a "white coat effect," the cumulative evidence has not yet been systematically reviewed.To perform a systematic review and meta-analysis to examine the association between AOBP and office BP readings measured in routine clinical practice and in research studies, and ambulatory BP recorded during awake hours, as the latter is a standard for predicting future cardiovascular events.The MEDLINE, Embase, and Cochrane Library were searched from 2003 to April 25, 2018.Studies on systolic and diastolic BP measurement by AOBP in comparison with awake ambulatory BP, routine office BP, and research BP measurements were included if they contained 30 patients or more.Study characteristics were abstracted independently and random effects meta-analyses and meta-regressions were conducted.Pooled mean differences (95% CI) of systolic and diastolic BP between types of BP measurement.Data were compiled from 31 articles comprising 9279 participants (4736 men and 4543 women). In samples with systolic AOBP of 130 mm Hg or more, routine office and research systolic BP readings were substantially higher than AOBP readings, with a pooled mean difference of 14.5 mm Hg (95% CI, 11.8-17.2 mm Hg; n = 9; I2 = 94.3%; P < .001) for routine office systolic BP readings and 7.0 mm Hg (95% CI, 4.9-9.1 mm Hg; n = 9; I2 = 85.7%; P < .001) for research systolic BP readings. Systolic awake ambulatory BP and AOBP readings were similar, with a pooled mean difference of 0.3 mm Hg (95% CI, -1.1 to 1.7 mm Hg; n = 19; I2 = 90%; P < .001).Automated office blood pressure readings, only when recorded properly with the patient sitting alone in a quiet place, are more accurate than office BP readings in routine clinical practice and are similar to awake ambulatory BP readings, with mean AOBP being devoid of any white coat effect. There has been some reluctance among physicians to adopt this technique because of uncertainty about its advantages compared with more traditional methods of recording BP during an office visit. Based on the evidence, AOBP should now be the preferred method for recording BP in routine clinical practice.
Racial disparity in gastrointestinal cancer: Insight from national cancer database.
Authors: Maharaj Singh, Samit Kumar Datta, Wesley Allan Papenfuss, Geoffrey Belini, Aaron Chevinsky, James L. Weese
Journal: Journal of Clinical Oncology (2019)

607 Background: The number of cases of cancers originating from the gastrointestinal (GI) tract and from other associated GI organs has increased 28% between the years 2004-2014. The incidence and overall survival for GI tract related cancers shows systematic racial disparity. Our goal was evaluate racial disparity for overall survival and mortality among patients with GI tract cancers. Methods: We used the national cancer database to evaluate data from 12 types of GI tract cancers (esophagus, stomach, gallbladder, intrahepatic bile duct, extrahepatic bile duct, liver, pancreas, small intestine, colon, rectosigmoid, rectum, and anal) between the years 2004-2014. The racial categories included non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and Other (All other races were combined into an ‘Other’ category). We used Kaplan-Meier estimator with log-rank test for comparing the survival probability among the four race categories. We also used Cox regression to find out the hazard ratio for mortality adjusting for the age, sex, and Charlson index. Results: The study population included a total of 2,044,565 patients diagnosed with one of the GI tract cancers. Of the total 55% were male, 72% NHW 12% NHB, 0.4% Hispanic, and the rest were classified as ‘other’ race (16%) which includes majority of white or black Hispanic and Asian (82%), The mean age at diagnosis of the patients was 66.8 ± 11.3 years. Overall survival was better for the Hispanic group, followed by the ‘Other’ group, NHW and NHB (P &lt; 0.001). Adjusted for age, sex, and for Charlson index, the hazards ratio was 0.93 (95% CI, 0.90-096, p &lt; 0.001) for Hispanic vs other, 1.15 (95% CI, 1.14-1.16, p &lt; 0.001) for NHB vs other, 0.98 (95% CI, 0.97-0.98, p &lt; 0.001) for NHW vs others. Mortality rate among Hispanic, NHW, NHB, and other was 46.4%, 59.4%, 59.6%, 56.7%. Conclusions: With a very large study population the survival for Hispanic patient population as well as the ‘Other’ (majority of patients were Asian) category had higher overall survival probability and low rate mortality compared to other race categories. Possible hypotheses include dietary preferences, underlying genetic profile and environmental factors. Further studies are needed to confirm the hypotheses.
Studies on the Effect of Exercise on Cardiovascular Function
Authors: ROBERT S. FRASER, CARLETON B. CHAPMAN
Journal: Circulation (1954)

Attempts to follow changes in blood pressure induced by exercise, using indirect sphygmomanometry, have yielded conflicting results. In the following study, blood pressure measurements were made at rest (standing), during a standard treadmill work load, and during a six-minute recovery period, using a direct method and a suitably damped recording system. It was found that during exercise systolic pressure rises and that diastolic pressure falls, the net result being very little change in the mean pressure. In some subjects there is a secondary rise in all three items between 10 and 30 seconds after cessation of exercise. Changes in pulse rate during exercise and recovery are also discussed.
Assessment of topical bakuchiol and retinol for facial photoageing
Authors: S. Dhaliwal, I. Rybak, S.R. Ellis, M. Notay, M. Trivedi, W. Burney, A.R. Vaughn, M. Nguyen, P. Reiter, S. Bosanac, H. Yan, N. Foolad, R.K. Sivamani
Journal: British Journal of Dermatology (2019)

Bakuchiol is found mainly in the seeds of the Indian plant Psoralea corylifolia (babchi) and has recently been shown to have a number of antioxidant and anti‐inflammatory properties. The goal of this study, by researchers from universities in California, Michigan, Florida and Pennsylvania in the US, was to compare the efficacy and side effects of bakuchiol with the commonly‐used anti‐ageing ingredient retinol. 44 volunteers were asked to apply either bakuchiol 0.5% cream twice daily, or retinol 0.5% cream daily, to facial skin for 12 weeks. Retinol 0.5% has previously been shown to be effective at preventing and addressing signs of skin ageing but can have side effects including stinging, scaling and redness. A facial photograph and analytical system was used to take and analyse high‐resolution photographs of patients at 0, 4, 8 and 12 weeks of the study. Patients also answered questions about side‐effects. During study visits, a dermatologist graded pigmentation (skin colouring) and redness. To avoid bias, this dermatologist was not made aware of which treatment each participant was using. The study found that bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the two compounds. However, the retinol users reported more skin scaling and stinging. The results were most marked after the full 12 weeks, with a 20 percent reduction in wrinkle severity. 59 percent of the participants in the bakuchiol group showed improvement in their hyperpigmentation at week 12, compared to 44 percent of those in the retinol group. The improvements related both to the intensity of the colour and to the size of the area affected. The findings of this study are promising for bakuchiol as an effective anti‐ageing treatment with minimal side effects, however this would need to be confirmed in larger studies.
Separation of Craniopagus Twins by a Multidisciplinary Team
Authors: Gregory G. Heuer, Peter J. Madsen, Tracy M. Flanders, Benjamin C. Kennedy, Phillip B. Storm, Jesse A. Taylor
Journal: New England Journal of Medicine (2019)

Conjoined twins who are classified as craniopagus (joined at the cranium) have a rare congenital anomaly. Despite advances in surgical techniques and critical care, the rate of complications and death is still high among twins with total fusion in which the superior sagittal sinus is shared. Here, we describe total-fusion craniopagus twins who at 10 months of age underwent successful surgical separation performed by a multidisciplinary team. Computer-aided design and modeling with a three-dimensional printer, custom-designed cranial distraction and constriction devices, and intraoperative navigation techniques were used. These techniques allowed for separation of the twins at an early age and harnessed the regenerative capacity of their young brains.
PANOVA-3: A phase III study of tumor treating fields with nabpaclitaxel and gemcitabine for front-line treatment of locally advanced pancreatic adenocarcinoma (LAPC).
Authors: Uri Weinberg, Moshe Giladi, Zeev Bomzon, Eilon David Kirson
Journal: Journal of Clinical Oncology (2019)

TPS469 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of patients with glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The Phase 2 PANOVA study was the first trial testing TTFields in pancreatic cancer patients, and demonstrated the safety of TTFields when combined with nab-paclitaxel and gemcitabine in both metastatic and LAPC. The Phase 3 PANOVA-3 trial (NCT03377491) is designed to test the efficacy of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Methods: Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m 2 once weekly). TTFields (150kHz) will be deilvered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q8w, including a CT scan of the chest and abdomen. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint and progression-free survival, objective response rate, rate of resectability, quality of life and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Clinical trial information: NCT03377491.