tbuckley/cabot-search huggingface dataset:
Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons
Authors: Michael C. Donohue, Reisa A. Sperling, Ronald Petersen, Chung-Kai Sun, Michael W. Weiner, Paul S. Aisen
Journal: JAMA (2017)

<h3>Importance</h3> Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline. <h3>Objective</h3> To characterize and quantify the risk for Alzheimer-related cognitive decline among cognitively normal individuals with elevated brain amyloid. <h3>Design, Setting, and Participants</h3> Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal individuals in the United States and Canada. Participants were observed from August 23, 2005, to June 7, 2016, for a median of 3.1 years (interquartile range, 2.0-4.2 years; maximum follow-up, 10.3 years) as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). <h3>Exposures</h3> Individuals were classified at baseline as having normal (n = 243) or elevated (n = 202) brain amyloid using positron emission tomography amyloid imaging or a cerebrospinal fluid assay of amyloid β. <h3>Main Outcomes and Measures</h3> Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC; a sum of 4 baseline standardized<i>z</i>scores, which decreases with worse performance), Mini-Mental State Examination (MMSE; 0 [worst] to 30 [best] points), Clinical Dementia Rating Sum of Boxes (CDR–Sum of Boxes; 0 [best] to 18 [worst] points), and Logical Memory Delayed Recall (0 [worst] to 25 [best] story units). <h3>Results</h3> Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women. The mean score for PACC at baseline was 0.00 (2.60); for MMSE, 29.0 (1.2); for CDR–Sum of Boxes, 0.04 (0.14); and for Logical Memory Delayed Recall, 13.1 (3.3). Compared with the group with normal amyloid, those with elevated amyloid had worse mean scores at 4 years on the PACC (mean difference, 1.51 points [95% CI, 0.94-2.10];<i>P</i> &lt; .001), MMSE (mean difference, 0.56 points [95% CI, 0.32-0.80];<i>P</i> &lt; .001), and CDR–Sum of Boxes (mean difference, 0.23 points [95% CI, 0.08-0.38];<i>P</i> = .002). For Logical Memory Delayed Recall, between-group score was not statistically significant at 4 years (mean difference, 0.73 story units [95% CI, −0.02 to 1.48];<i>P</i> = .056). <h3>Conclusions and Relevance</h3> Exploratory analyses of a cognitively normal cohort followed up for a median of 3.1 years suggest that elevation in baseline brain amyloid level, compared with normal brain amyloid level, was associated with higher likelihood of cognitive decline, although the findings are of uncertain clinical significance. Further research is needed to assess the clinical importance of these differences and measure longer-term associations.
“Focus on…” Session: PET use in lymphoma
Authors: A Khan, S Barrington, R Carr, H Lanic, S Mareschal, F Mechken, J Picquenot, M Cornic, C Maingonnat, P Bertrand, F Clatot, P Ruminy, C Bastard, H Tilly, S Becker, P Vera, F Jardin, C Tychyj-Pinel, F Ricard, M Meignan, T Lamy, J Estell, O Shpilberg, E Gyan, D Decaudin, C Forsyth, E Garin, M Fulham, G Salles, J Trotman
Journal: Annals of Oncology (2011)
Phase III trial of tumor-treating fields (TTFields) together with temozolomide compared with temozolomide (TMZ) alone in patients with newly diagnosed glioblastoma multiforme (NCT00916409).
Authors: Santosh Kesari, Sophie Taillibert, Andrew Kanner, Uri Weinberg
Journal: Journal of Clinical Oncology (2012)

TPS2106 Background: TTFields therapy is a novel, non-invasive, anti-mitotic treatment, inhibiting tumor growth by interfering with the metaphase to anaphase transition during mitosis (Lee et al., 2011). TTF therapy was recently approved by the FDA for recurrent GBM following a prospective, randomized trial. Preclinical studies have shown TTFields and TMZ to have an additive inhibitory effect on glioma cell proliferation. The design for the current study was supported by results from a pilot study with TTFields therapy and TMZ in patients with newly diagnosed GBM demonstrating favorable safety, tolerability and promising efficacy (Kirson et al., 2009). Methods: The hypothesis of the current study is that the addition of TTFields therapy to maintenance TMZ will increase progression free survival (PFS) of newly diagnosed GBM patients. Secondary endpoints include overall survival (OS), radiological response, quality of life and safety. Eligible patients will be randomized (2:1) to continuous TTFields therapy (200 kHz) in combination with maintenance TMZ versus maintenance TMZ alone. Maintenance TMZ will be administered as per the Stupp Protocol for 6 courses (Stupp et al., 2005). TTFields therapy may be administered for up to 24 months. Patients will be stratified based on: extent of resection and MGMT methylation status. Eligibility criteria include: pathological diagnosis of GBM; Karnofsky ≥ 70; previous chemoradiotherapy per Stupp Protocol; no progressive disease at baseline. Patients with infratentorial tumor or implanted electronic devices are excluded. The sample size of 700 patients will have 80% power to detect a 2 month (9 vs 7 months) improvement in PFS using log-rank test with an overall 5% 2-sided type I error. The trial is also powered to detect a 4.5 month increase in median OS in NovoTTF-100A/TMZ patients. Patients will be followed clinically monthly and with bimonthly MRI to assess tumor progression and additional endpoints. 221 patients have been enrolled at the time of abstract submission. The DMC last reviewed the trial in October 2010 and recommended that the trial continue as designed.
Improved Outcome and Decreased Morbidity and Mortality Rates of B-Cell Malignancies with Less Intensive Chemotherapy Induction: Experience in a Single Institution
Authors: Cristian G Sanchez La Rosa, Myriam Guitter, Alfaro Elizabeth, Natalia Millan, Jorge Gabriel Rossi, Andrea Bernasconi, Laura Galuzzo, Andrea Montanari, Edgardo Baialardo, Pedro Zubizarreta, Guillermo Chantada, Maria Sara Felice
Journal: Blood (2016)
Cinical Outcome of Surgery for Fulminant Clostridium Difficile Colitis
Authors: K Koss, DSA Sanders, MRB Keighley, D Morton, M Clark, J Goh
Journal: Endoscopy (2004)

The clinical presentation of C difficile infection ranges from asymptomatic carriage, colitis with or without pseudomembranes and fulminant colitis. Although not common, fulminant C difficile colitis can result in bowel perforation and peritonitis and mortality of up to 80% has been reported. We retrospectively analyzed the outcome of 13 patients who underwent surgery for fulminant C difficile colitis in the period 1996–2002 in our Unit. The indications for surgery were systemic toxicity and peritonitis (n=9) and radiologic and clinical evidence of progressive toxic colonic dilatation (n=4). C difficile infection as the cause of colitis was diagnosed pre-operatively in only 6 patients (46.2%), five of whom underwent a subtotal colectomy and one right hemicolectomy. Overall mortality in our series was 38%. Subtotal colectomy was associated with a mortality rate (MR) of 12.5% (n=8) while the MR for left hemicolectomy was 100% (n=4). One patient underwent a right hemicolectomy survived after prolonged hospital stay. Hemicolectomy was undertaken on the basis of deceptively normal external appearance of the rest of the colon intraoperatively. All patients received appropriate treatment at time of diagnosis of C difficile.
Effect of community health clubs on child diarrhoea in western Rwanda: cluster-randomised controlled trial
Authors: Sheela S Sinharoy, Wolf-Peter Schmidt, Ronald Wendt, Leodomir Mfura, Erin Crossett, Karen A. Grépin, William Jack, Bernard Ngabo Rwabufigiri, James Habyarimana, Thomas Clasen
Journal: The Lancet Global Health (2017)

Community health clubs are multi-session village-level gatherings led by trained facilitators and designed to promote healthy behaviours mainly related to water, sanitation, and hygiene. They have been implemented in several African and Asian countries but have never been evaluated rigorously. We aimed to evaluate the effect of two versions of the community health club model on child health and nutrition outcomes.We did a cluster-randomised trial in Rusizi district, western Rwanda. We defined villages as clusters. We assessed villages for eligibility then randomly selected 150 for the study using a simple random sampling routine in Stata. We stratified villages by wealth index and by the proportion of children younger than 2 years with caregiver-reported diarrhoea within the past 7 days. We randomly allocated these villages to three study groups: no intervention (control; n=50), eight community health club sessions (Lite intervention; n=50), or 20 community health club sessions (Classic intervention; n=50). Households in these villages were enrolled in 2013 for a baseline survey, then re-enrolled in 2015 for an endline survey. The primary outcome was caregiver-reported diarrhoea within the previous 7 days in children younger than 5 years. Analysis was by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT01836731.At the baseline survey undertaken between May, 2013, and August, 2013, 8734 households with children younger than 5 years of age were enrolled. At the endline survey undertaken between Sept 21, 2015, and Dec 22, 2015, 7934 (91%) of the households were re-enrolled. Among children younger than 5 years, the prevalence of caregiver-reported diarrhoea in the previous 7 days was 514 (14%) of 3616 assigned the control, 453 (14%) of 3196 allocated the Lite intervention (prevalence ratio compared with control 0·97, 95% CI 0·81-1·16; p=0·74), and 495 (14%) of 3464 assigned the Classic intervention (prevalence ratio compared with control 0·99, 0·85-1·15; p=0·87).Community health clubs, in this setting in western Rwanda, had no effect on caregiver-reported diarrhoea among children younger than 5 years. Our results question the value of implementing this intervention at scale for the aim of achieving health gains.Bill & Melinda Gates Foundation.
Adjuvant or neoadjuvant chemotherapy in early stage triple negative breast cancer (TNBC) comparison of outcomes in both BRCA positive and BRCA negative patients.
Authors: Katherine Clifton, Angelica Gutierrez Barrera, Junsheng Ma, Roland L. Bassett, Jennifer Keating Litton, Banu Arun
Journal: Journal of Clinical Oncology (2017)

576 Background: NSABP Protocol B-18 was a randomized trial which found no statistically significant difference in overall survival (OS) in patients (pts) receiving neoadjuvant (NAC) or adjuvant chemotherapy (AC), however outcome was not analyzed by breast cancer subtypes. Subsequent retrospective studies in TNBC reported conflicting results with an initial study showing a significant OS benefit with AC and later studies showing a trend toward improved survival with NAC. Furthermore, studies have not included a significant number of pts with BRCA mutations. This study aims to analyze outcomes of AC versus NAC in pts with early stage TNBC with and without BRCA germline mutations. Methods: Pts with stage I or II TNBC who had BRCA testing were identified from a prospective cohort study of 4027 pts at MD Anderson Cancer Center. Clinical, demographic, genetic test results, chemotherapy, recurrence, survival data were collected. OS and disease free survival (DFS) were estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Results: 305 pts with stage I and II TNBC who met eligibility criteria were included in the analysis. Pts who received both NAC and AC or no chemotherapy were excluded. 181 received AC (59.3%) and 124 received NAC (40.7%). The majority of the pts were less than 50 years old (236, 77.4%) and white (194, 63.8%). 134 were BRCA positive (44.1%) and 170 were BRCA negative (55.9%). The majority of the pts received an anthracycline and taxane regimen (223, 73.1%). There was no significant association between OS or DFS and treatment with NAC versus AC in the overall cohort. Furthermore, there were no significant differences between pt subgroups (NAC BRCA positive, NAC BRCA negative, AC BRCA positive, and AC BRCA negative) with respect to either OS or DFS. Conclusions: NAC versus AC with standard anthracycline and taxane containing regimens results in similar DFS and OS survival amongst pts with stage I and II TNBC regardless of BRCA status. Further studies are needed to evaluate whether similar results are observed with newer agents, such as platinums, PARP inhibitors and other targeted agents.
Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy
Authors: Jose D. Sandoval-Sus, Francis Mogollon-Duffo, Ankita Patel, Nathan Visweshwar, Damian A. Laber, Richard Kim, Michael V. Jagal
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control. <h3>Case presentation</h3> In December 2015, at the time of the patient's progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient's wishes before admission, and after agreement with the family, nivolumab (3&nbsp;mg/kg every 2&nbsp;weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5&nbsp;months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response. <h3>Conclusions</h3> We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options. Unlike classic cytotoxic chemotherapy, which relies on preserved organ function to ameliorate potential severe side effects (i.e. myelosuppression), elimination of monoclonal antibodies is fairly independent of baseline renal and hepatic function since they are usually metabolized by circulating phagocytes and/or by their target antigen-expressing cell.
OC-068 Albumin is central in mediating the cardio-renal dysfunction of cirrhosis: a study in analbuminaemic rats: Abstract OC-068 Figure 1
Authors: R Garcia Martinez, A Habtesion, G Tritto, M Jover, R Jalan, N Davies
Journal: Gut (2012)

<h3>Introduction</h3> Albumin is a multifunctional protein which is reduced in concentration and function in liver disease. Albumin infusion prevents and improves renal dysfunction in patients with advanced liver failure but the mechanisms of its beneficial properties are unclear. We hypothesised that albumin is central in the maintenance of cardio-renal function in cirrhosis and albumin impairment worsens outcome. In order to answer this question we investigated analbuminaemic rats, characterised by lack of albumin but with normal protein concentration, following induction of cirrhosis with bile duct ligation (BDL). <h3>Methods</h3> Male Sprague-Dawley (SD) and Nagase analbuminaemic (NAR) rats were studied 6 weeks after BDL or sham surgery (n=6 sham-SD, 8 sham-NAR, 7 SD-BDL, 7 NAR-BDL). Rats underwent systemic mean arterial pressure (MAP) and portal pressure (PP) assessment under terminal anaesthesia. Plasma and urine were collected for measurements of renal function and protein profile. Plasma renin activity (PRA) was measured as a marker of cardio-renal dysfunction. Urinary neopterin, a marker of macrophage activation was assessed. <h3>Results</h3> NARs showed plasma total protein concentration similar to SD despite lack of albumin before (72±15 vs 82±8) and after BDL (67±7 vs 75±22). After BDL both groups of animals showed histological evidence of severe liver damage, though the NARs showed a significantly worse systemic haemodynamics with lower MAP (p=0.01), evidence of renal dysfunction indicated by higher plasma creatinine and higher PRA (p&lt;0.05) compared with SD (Abstract OC-068 figure 1). There was a significant inflammatory response following BDL in both groups showed by an increase in urinary neopterin which was found to correlate with PRA (r=0.59, p&lt;0.01). <h3>Conclusion</h3> A lack of albumin was associated with a raised PRA and a marked deterioration in systemic haemodynamics and renal function after liver injury (BDL), despite normal total plasma protein concentration. This worsened outcome in the absence of albumin strongly supports the central role of albumin in maintenance of cardio-renal function in liver failure and may indicate that albumin plays a crucial role in moderating inflammation. <h3>Competing interests</h3> None declared.
MRCP does not Significantly Reduce ERCP Workload
Authors: AR Aftab, A Coss, R Curtin, G Courtney
Journal: Endoscopy (2004)

Magnetic resonance cholangio-pancreatography (MRCP) is increasingly used as a non-invasive method of imaging the biliary and pancreatic ducts, representing an acceptable alternative to diagnostic endoscopic retrograde cholangio-pancreatography (ERCP) in many cases. However, access to MRCP is often limited.
Abdominal Ultrasound for Pediatric Blunt Trauma
Authors: David O. Kessler
Journal: JAMA (2017)

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Allogeneic Hematopoietic Cell Transplantation for Elderly Patients: Prognosis Determined By Disease Risk Index
Authors: Fiona C. He, Aleksandr Lazaryan, Qing Cao, Claudio G Brunstein, Shernan G. Holtan, Erica D. Warlick, Celalettin Ustun, Brian McClune, Mukta Arora, Daniel J. Weisdorf, Nelli Bejanyan
Journal: Blood (2016)
Ultrasound imaging for identification of cerebral damage in congenital Zika virus syndrome: a case series
Authors: Bruno Schaub, Michèle Gueneret, Eugénie Jolivet, Valérie Decatrelle, Soraya Yazza, Henriette Gueye, Alice Monthieux, Marie-Laure Juve, Manuella Gautier, Fatiha Najioullah, Manon Vouga, Jean-Luc Voluménie, David Baud
Journal: The Lancet Child & Adolescent Health (2017)
Unexpected consequences: exon skipping caused by CRISPR-generated mutations
Authors: Joshua J. Sharpe, Thomas A. Cooper
Journal: Genome biology (2017)

A new study finds that splicing disruption is a frequent consequence of mutations generated by CRISPR/Cas9 gene-editing technology, and alleles designed to be null can express aberrant proteins. This new information allows enhanced quality control procedures to select the best mutant alleles generated by CRISPR/Cas9. Please see related Method article: https://www.doi.org/10.1186/s13059-017-1237-8
Abstract P143: Activation of GPR30 Attenuates Diastolic Dysfunction and LV Remodeling in Oophorectomized mRen2.Lewis Rats
Authors: Hao Wang, Jewell A Jessup, Sarah Lindsey, Marina S Lin, Clarissa Chagas, Leanne Groban
Journal: Circulation Research (2011)

The incidence of diastolic dysfunction increases in women after menopause but the mechanisms involved are not completely understood. GPR30 is a novel estrogen receptor expressed in various tissues including the heart. Studies have shown that activation of GPR30 by its agonist G1, improves contractile function and reduces infarct size in isolated rat and mouse hearts subjected to ischemia/reperfusion injury and attenuates diastolic dysfunction in a salt-sensitive rat model of hypertension. We hypothesized that the activation of GPR30 by G1 protects against the development of diastolic dysfunction and cardiac hypertrophy in oophorectomized mRen2.Lewis rats, an established model that emulates the cardiac phenotype of the postmenopausal woman. Surgical bilateral oophorectomy (OVX) was performed in female mRen2.Lewis rats at 4 weeks of age, and G1 (50 or 100 µg/kg/day) was given subcutaneously via minipump starting at 13 weeks of age for 2 weeks. Both doses of G1 significantly improved lusitropic function and structure, independent of changes in blood pressure. Compared to vehicle-treated OVX rats, G1 reduced the tissue Doppler-derived index of left ventricular filling pressure (E/e’), left ventricle mass, wall thickness, and the biomarkers of hypertrophy, ANF and BNP mRNA levels. Using cultured H9c2 cardiomyocytes, in vitro studies further showed that 1) G1 inhibited angiotensin (ANG) II-induced hypertrophy, evidenced by reductions in cell size, and ANF and BNP gene expression; 2) the antagonist of GPR30, G15, inhibited estrogen’s protective effects on ANG II-induced hypertrophy; and 3) G1 induced phosphorylation of Erk and Akt. These data demonstrate the protective role of GPR30 in a model of diastolic dysfunction and cardiac hypertrophy, and provide insight into the underlying mechanisms.
Use weak government to push for local NHS change, says MP
Authors: Abi Rimmer
Journal: BMJ (2017)

Doctors’ and patients’ groups should use the current government’s weak position to push for improvements in their local NHS, a Scottish National Party MP has said.

The UK general election ended in a hung parliament after the Conservative Party won 318 seats, eight short of the 326 seats needed for a majority.

Philippa Whitford, a consultant breast cancer surgeon, was re-elected as the Scottish National Party MP for Central Ayrshire. She said that now was a good time for doctors’ and patients’ groups, charities, and representative bodies to propose detailed and thought-out plans for changes to their local NHS.

“I think there is a lot that local areas can do to put their MPs under pressure. But I think that a very simplistic ‘Save Hospital X’ [campaign] won’t do it because it becomes a chant . . . you might get that MP under pressure, but it …