tbuckley/cabot-search huggingface dataset:
Zika virus: management of infection and risk
Authors: Shazaad S Y Ahmad, Tejal N Amin, Andrew Ustianowski
Journal: BMJ (2016)

AMI IMAGES / SPL #### What you need to know Zika virus has caused a self limiting pyrexial illness from Africa to South-East Asia for decades. Recently it has spread across the Pacific and in 2015 caused infections for the first time in South America. Though usually asymptomatic or of little clinical significance in adults, there is concern about an apparent association between infection in pregnancy and birth defects such as microcephaly.1 2 3 We have no data to characterise the risks of abnormal fetal development and adverse pregnancy outcomes, or to guide testing strategies. In its absence, global health bodies have issued guidance for clinicians on how to minimise the risk of transmission to those who are, or may become, pregnant, and to monitor fetuses that may have been exposed. We present current management advice for healthcare professionals in non-endemic countries, who may offer advice to individuals concerned about pregnancy and conception before or after travel to an area with Zika virus. Guidance is likely to change as the clinical picture and knowledge base develop, and up to date advice can be accessed from sources such as those listed in box 1. #### Box 1: Sources of up to date advice on Zika virus and management of those exposed
Abstract 14993: Proteomic Analysis of Chylomicron Remnants Isolated by Apolipoprotein B-48 Immunoprecipitation
Authors: Daisaku Masuda, Takuya Kobayashi, Manabu Okubo, Takeshi Okada, Hajime Nakaoka, Ryota Kawase, Kazuhiro Nakatani, Tohru Ohama, Masahiro Koseki, Hiroyuki Hanada, Makoto Nishida, Yasushi Sakata, Shizuya Yamashita
Journal: Circulation (2014)

Introduction: Postprandial hypertriglyceridemia is caused by overproduction or impaired clearance of apolipoprotein (apo)B-48-containing lipoproteins, chylomicrons (CMs) and CM remnants (CM-Rs). In vitro studies have suggested that CM-Rs may lead to the formation of atherosclerotic plaques. By our ELISA and CLEIA for measuring human serum apoB-48 concentrations, we reported fasting apoB-48 concentrations are significantly higher in patients with dyslipidemia, diabetes mellitus, metabolic syndrome and chronic kidney disease than in normal subjects, and correlated with the IMT of carotid arteries and the prevalence of coronary heart disease. However, it has been technically very difficult to isolate CM-Rs and to evaluate the atherogenicity of pure CM-Rs.

Hypothesis: We tried to selectively isolate CM-Rs and analyze their lipoprotein and proteomics profiles and assessed their atherogenicity.

Methods: Fractions containing CM-Rs and VLDL (d<1.01 mg/dL) were isolated from the postprandial sera of healthy volunteers by two-step ultracentrifugation. CM-Rs were selectively eluted and isolated by immunoprecipitation using anti-human apoB-48 monoclonal antibodies conjugated with magnetic beads. Mouse peritoneal macrophages were incubated with isolated CM-Rs and stained with Oil-red O. Lipoprotein profiles of isolated human CM-Rs and mouse CMs collected from the intestinal lymph were examined by high performance liquid chromatography and proteomic analyses were performed by mass spectrometry using Synapt G2 HDMS PRO.

Results: Compared with the lipoprotein profile of postprandial serum, particle size of isolated lipoproteins varied in size from small chylomicrons to large LDL, which suggested CM-Rs. When incubated with isolated CM-Rs, foam cell formation of mouse peritoneal macrophages was observed. By proteomic analysis, isolated human CM-Rs and mouse CMs contained a variety of complements (C3, C4 and more), apolipoproteins (apoB, apoA2, apoD and apoH), paraoxonase 1 (PON-1) and many serine protease inhibitors.

Conclusions: The current study has demonstrated for the first time that human CM-Rs and CMs have an atherogenic nature and contain many types of complements, apolipoproteins, PON-1 and serine protease inhibitors.
Assessment of nutritional status and prognosis in advanced metastatic cancer (AMC)
Authors: K. Choi, H. J. Kim, S. K. Park, J. H. Yoon, S. J. Oh, S. S. Lee, K. Park
Journal: Journal of Clinical Oncology (2005)

8146 Background: Depletion of nutritional reserves and significant weight loss can lead to an increased risk of morbidity, reduced chemotherapy response, and shorter survival in patients (pts) with cancer. Numerous methodologies are used for the assessment of nutritional status. However, it remains unclear which of these tools is the most appropriate in the setting of cancer chemotherapy. The Prognostic Inflammatory Nutritional Index (PINI) is a simple scoring system that has been used to evaluate nutritional status and prognosis in critically ill pts. The PINI has been rarely evaluated in AMC. The aim of this study is to evaluate the interrelationships between the PINI and survival time (S), and performance status (PS) in pts with advanced solid malignancies following palliative chemotherapy. Methods: This study included 47 pts with PS (ECOG) 1–3 in AMC following palliative chemotherapy. PS, body mass index (BMI), alpha 1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin (ALB), prealbumin (PALB), protein, LDH, PINI ratio [PINI = (AGP x CRP)/(ALB x PALB)], and S were evaluated. We investigated the interrelationships between PS and biochemical indices, PINI, and S. Results: In 47 pts, the median age was 60 yrs (40–69 yrs). The PS was: PS 1: 19 pts, PS 2: 17 pts, PS 3: 11 pts. The mean value of PINI was: PS 1: 7.4±13.4, PS 2: 78.0±155.0, PS 3: 145.6±173.0. The mean day of S was: PS 1: 108.8±49.6, PS 2: 50.9±20.1, PS 3: 20.2±18.3. In the PS 3 group, the mean values of AGP, and CRP were significantly higher than in the PS 1 group. In the PS 3 group, the mean values of ALB, and PALB were significantly lower than in the PS 1 group. However, BMI, Protein, and LDH were not significant. The severity of PS was correlated with the PINI (p=0.004, r=0.408), AGP (p=0.001, r=0.481), CRP (p=0.003, r=0.421), ALB (p<0.001, r=-0.517), PALB (p<0.001, r=-421), and S (p<0.001, r=-0.718). The value of PINI was correlated with S (p=0.004, r=-0.418). Conclusions: The PINI may be a useful scoring system for the assessment of nutritional status and prognosis. Altered nutritional and inflammatory status correlate with PS, and S following anticancer chemotherapy. No significant financial relationships to disclose.
Diagnostic Limitation of Electrocardiogram and Phonocardiogram on the Standpoint of Operative Findings of Acquired Valvular Disease : Electrocardiogram and Phonocardiogram in Relation to Operative Findings : Symposium on Limitation of Diagnostic Value of Electrocardiography and Phonocardiography
Authors: Koshichiro Hirosawa, Minoru Shibuya
Journal: Circulation (1966)
HIV seroprevalence among homeless patients admitted to a psychiatric inpatient unit
Authors: M Empfield, F Cournos, I Meyer, K McKinnon, E Horwath, M Silver, H Schrage, R Herman
Journal: American Journal of Psychiatry (1993)

This study was conducted to determine the seroprevalence of HIV-1 antibodies among hospitalized homeless mentally ill patients.From December 1989 through May 1991 the authors collected discard blood samples from patients consecutively admitted to a psychiatric unit designated for the care of severely mentally ill persons removed from the streets of New York City. The blood samples were tested for HIV-1 antibodies, and the results were analyzed for associations with age, gender, ethnicity, male homosexual activity, and use of injected drugs.The HIV seroprevalence was 6.4% (13 of 203 samples). Patients between ages 18 and 39 accounted for 51.2% of the admissions and 84.6% of the 13 positive results, a seroprevalence of 10.6% for this subsample. Patients under age 40 were more than six times as likely to test positive for HIV antibodies as those 40 or over. Ethnicity did not predict seropositivity. Women were as likely as men to be infected. Although clinicians had noted high-risk behavior on the charts for only three (23.1%) of the 13 positive cases, a recorded history of use of injected drugs was associated with a 6.5-fold greater risk of HIV seropositivity.One in every 16 patients admitted to the special unit was HIV positive. Age under 40 and use of injected drugs were strongly associated with seropositivity. Because information on high-risk behavior was infrequent, the reasons for younger patients' greater risk are unclear. The homeless mentally ill require outreach efforts to reduce the risk of acquiring or transmitting HIV.
Clinical outcome and pathologic features associated with NRAS mutation in cutaneous melanoma.
Authors: B. A. Devitt, W. Liu, R. Salemi, R. Wolfe, J. Kelly, A. Dobrovic, G. A. McArthur
Journal: Journal of Clinical Oncology (2010)

8500 Background: Mutations in NRAS and BRAF are common in cutaneous melanoma leading to constitutive activation of the MAPK pathway controlling cell proliferation. We examined the effect of NRAS mutations on the pathologic features and clinical outcomes in patients with cutaneous melanoma when compared to tumors containing BRAF mutations and those wild-type (WT) for both. Methods: Clinical outcome data was obtained from a prospective cohort study of 251 patients with cutaneous melanoma from Australian melanoma centers. Mutations in exon 2 of NRAS (N61R) and exon 15 of BRAF were detected by high resolution melting and sequence verified. Cox proportional hazards regression was performed to examine the significance of NRAS and BRAF mutations on pathologic features, overall survival (OS), melanoma specific survival (MSS) and disease free survival. Results: 249 patients with a median follow-up of 47 months were available. NRAS mutations were found in 36 (14%) patients, BRAF mutations in 112 (45%) and 101 (41%) were WT. 39 deaths occurred, 28 due to melanoma. Overall survival was similar in the three groups. Compared to WT in univariate analysis, there was shorter MSS in patients with NRAS mutations (HR 2.51; p = 0.05) but no difference in those with mutations in BRAF (HR 0.98; p = 0.96). NRAS mutations were associated with thicker tumors with 75% of tumors > 1 mm thick having mutations in NRAS compared to 40% for BRAF and 34% for WT. NRAS mutations were also associated with increased proliferation rates with 75% of tumors having > 1 mitosis/mm2 containing mutations in NRAS (BRAF 40% WT 55%). Multivariate analysis of MSS identified NRAS mutations as an independent adverse prognostic factor (HR 3.22; p = 0.03) along with site, Breslow thickness and presence of mitosis (p < 0.03). BRAF mutations had no effect on MSS (HR 1.68; p = 0.26). Conclusions: NRAS mutation in cutaneous melanoma is associated with higher rates of tumour proliferation when compared to BRAF and WT melanoma and independently of this, associated with shorter melanoma specific survival. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Novartis, Pfizer
The frequency and impact on cachexia of secondary causes of impaired oral nutritional intake in advanced cancer patients: A systematic review of the literature
Authors: A. G. Omlin, D. Blum, J. Walker, F. Strasser
Journal: Journal of Clinical Oncology (2008)

20658 Background: Secondary causes (SecC) of impaired oral nutritional intake (O-NI) - a common and devastating complication of advanced cancer - remain poorly recognised in daily practice. They may be classified as O-NI with impaired (e.g. mucositis) or normal (e.g. dyspnea, body-pain) gastrointestinal function/integrity. To evaluate systematically the frequency and the impact on cancer cachexia of SecC of impaired O-NI. Methods: A systematic review of the literature (MedLine, Cochrane, Embase, PsycINFO, CinAhl; 1995–2007) applied 3 combined search strings ([MeSH], free text): 1. cachexia/anorexia/wasting/malnutrition, 2. cancer and 3. classification/staging. Inclusion criteria of citations, then abstracts and finally papers were advanced cancer, original work, and either A) O-NI correlated with SecC or B) twenty-one predefined factors (SecC) know to be associated with O-NI correlated with weight loss. (O-NI had to be objectively assessed by any method, SecC were based on checklists used by experts in daily clinical practice in 3 independent clinics). Results: Of 7,655 citations, 1,409 abstracts and 130 full-papers were reviewed, 7 papers (A: 4, B: 3) were included. From A, two studies (75 & 59 HNO patients [pts]) report impaired O-NI by radiation induced symptoms (oral dryness, swallowing discomfort), depression and taste disturbances. Of 66 pts (solid tumors), those with severe (n=16), moderate (18), and mild (15) chemosensory complaints had lower O-NI (900, 350, 250 kcal/day) than those without. In 40 pts (colorectal cancer) with or without GI-symptoms (lack of appetite, nausea, vomiting) O-NI was not different. From B, only for muscositis and dysphagia (from the list of 21 SecC) significant correlations with weight loss are reported from 481 pts (HNO, esophageal cancer). 18 descriptive and 2 qualitative (n=39, HNO) studies did not fulfil the inclusion criteria but support the observations of SecC as a frequent problem in clinical care. Conclusions: The concept of Sec-C of cachexia seems to be well known but so far only little data have been systematically collected. The awareness for SecC may help in palliating the causes and effects of cachexia and may be of value when identifying patients for therapy studies. No significant financial relationships to disclose.
Initial Combination Therapy With Canagliflozin Plus Metformin Versus Each Component as Monotherapy for Drug-Naïve Type 2 Diabetes
Authors: Julio Rosenstock, Leonard Chuck, Manuel González-Ortiz, Kate Merton, Jagriti Craig, George Capuano, Rong Qiu
Journal: Diabetes Care (2016)

OBJECTIVE This study assessed the efficacy/safety of canagliflozin (CANA), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, plus metformin extended-release (MET) initial therapy in drug-naïve type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, double-blind, phase 3 study randomized 1,186 patients to CANA 100 mg (CANA100)/MET, CANA 300 mg (CANA300)/MET, CANA100, CANA300, or MET. Primary end point was change in HbA1c at week 26 for combinations versus monotherapies. Secondary end points included noninferiority in HbA1c lowering with CANA monotherapy versus MET; changes in fasting plasma glucose, body weight, and blood pressure; and proportion of patients achieving HbA1c &amp;lt;7.0% (&amp;lt;53 mmol/mol). RESULTS From mean baseline HbA1c of 8.8% (73 mmol/mol), CANA100/MET and CANA300/MET significantly lowered HbA1c versus MET (median dose, 2,000 mg/day) by –1.77%, –1.78%, and –1.30% (–19.3, –19.5, and –14.2 mmol/mol; differences of −0.46% and –0.48% [–5.0 and –5.2 mmol/mol]; P = 0.001) and versus CANA100 and CANA300 by –1.37% and –1.42% (–15.0 and –15.5 mmol/mol; differences of –0.40% and –0.36% [–4.4 and –3.9 mmol/mol]; P = 0.001). CANA100 and CANA300 monotherapy met noninferiority for HbA1c lowering and had significantly more weight loss versus MET (–2.8, –3.7, and –1.9 kg [–3.0%, –3.9%, and –2.1%]; P = 0.016 and P = 0.002). Greater attainment of HbA1c &amp;lt;7.0% (50%, 57%, and 43%) and significantly more weight loss (–3.2, –3.9, and –1.9 kg [–3.5%, –4.2%, and –2.1%]; P = 0.001) occurred with CANA100/MET and CANA300/MET versus MET. The incidence of adverse events (AEs) related to SGLT2 inhibition (genital mycotic infections, osmotic diuresis– and volume depletion–related AEs) was higher in the CANA arms (0.4–4.4%) versus MET (0–0.8%). AE-related discontinuation rates were 1.3–3.0% across groups. The incidence of hypoglycemia was 3.0–5.5% in the CANA arms and 4.6% with MET. CONCLUSIONS Initial therapy with CANA plus MET was more effective and generally well tolerated versus each monotherapy in drug-naïve type 2 diabetes. CANA monotherapy demonstrated noninferior HbA1c lowering versus MET.
Invasive melanoma of the face: Patterns of local and regional disease in 261 patients managed at a single institution
Authors: A. J. Chambers, T. Murynka, J. P. Arlette, J. G. Mckinnon
Journal: Journal of Clinical Oncology (2009)

e20015 Background: The face is a common site of melanoma occurrence, and lesions in this location present specific management challenges. The purpose of this study was to examine outcomes associated with invasive melanoma of the face, with respect to local, regional and distant recurrence. Methods: Patients with invasive melanoma of the face managed from 1997–2008 were identified from a large population-based tumor registry and retrospectively reviewed. Details of lesion histopathology, initial management, sentinel node biopsy (SNB), and local, regional or distant recurrences were recorded. Results: 261 patients were reviewed, mean age 68 and median tumor thickness 0.87mm. Three patients (1.1%) had clinically involved nodes at presentation and underwent nodal dissection. Of 108 patients who were eligible for SNB (with tumor thickness &gt;1mm, Clark level ≥IV or ulceration) this was performed in only 29 (27%). SNB was successfully identified in 28 (97%). No facial nerve injuries occurred. A mean of 1.5 nodes were removed; from parotid region in 24, cervical chain in 12, submandibular in 5, submental in 1 and retroauricular in 1. SNB was positive in 3 (11%) who subsequently underwent neck dissection/parotidectomy. Mean follow-up duration was 37 months. Local recurrence occurred in 13 (5%), in-transit recurrence in 4 (1.5%) and distant recurrence in 20 (7.7%). Regional nodal recurrence occurred in 10 (3.8%); after negative SNB in 1 (SNB failure rate 3.7%), after unsuccessful SNB in 1, following neck dissection for nodal disease at presentation in 1, and in 7 who did not undergo SNB (including 6 patients who were eligible). During the study period there were 60 deaths (crude mortality 23%); due to melanoma in 16, unrelated causes in 41, and indeterminate in 3. Conclusions: Facial melanoma is associated with low rates of regional recurrence despite a low rate of SNB for eligible lesions. Sentinel nodes were most commonly found in the parotid region and could be safely removed without nerve injury. Most regional recurrences occurred in patients eligible for SNB not undergoing this procedure. Due to the older age of patients with facial melanoma, most deaths occurring are from unrelated conditions, and distant metastatic disease was seen in only a small percentage of cases. No significant financial relationships to disclose.
Desmoid Tumor Showing Intense Uptake on 68Ga PSMA-HBED-CC PET/CT
Authors: Gowri L. Kanthan, Edward Hsiao, Andrew Kneebone, Thomas Eade, Geoffrey Paul Schembri
Journal: Clinical Nuclear Medicine (2016)

Ga-PSMA PET/CT is a new imaging technique that is highly sensitive to metastatic prostate cancer lesions compared with other conventional imaging modalities. We report a case of a 77-year-old man with newly diagnosed prostate carcinoma who had a PSMA PET/CT scan for staging of his disease. An intensely PSMA-avid right pelvic mass was identified abutting the cecum and terminal ileum. Surgical removal and histopathologic examination of this lesion revealed the diagnosis of a desmoid tumor. It is important to be aware that many tumors other than prostate carcinoma may also show avid uptake on PSMA PET/CT scan.
Childhood sexual abuse and bulimia nervosa: a comparison of American, Austrian, and Brazilian women
Authors: H G Pope, B Mangweth, A B Negrão, J I Hudson, T A Cordás
Journal: American Journal of Psychiatry (1994)

This study was designed to assess the prevalence of childhood sexual abuse among women with bulimia nervosa in three countries: the United States, Austria, and Brazil. In addition, it assessed whether bulimic subjects might have experienced more severe sexual abuse than women in the general population and whether bulimic subjects who report abuse might display greater psychopathology than those who do not report abuse.Thirty-three university students in Innsbruck, Austria, 33 university students in Boston, and 25 women in São Paulo, Brazil, all meeting DSM-III-R criteria for bulimia nervosa, were recruited by advertisement. Detailed histories of sexual abuse, obtained at the conclusion of a comprehensive evaluation interview, were prepared, translated into English, and rated by an investigator who was blind to the nationality of the subject. Subjects were compared on frequency of eating binges, history of major depression, body mass index, and satisfaction with body image.Narrowly defined childhood sexual abuse was reported by 24%-36% of women in the three countries, although only 15%-32% of women reported abuse before the onset of bulimia nervosa. There were no significant differences between countries in rates of abuse. Overall, these rates appear no greater than those reported in comparable studies of women in the general population. The data also did not support the hypothesis that bulimic subjects had endured more severe sexual abuse than other women, nor was there a significant association between history of childhood sexual abuse and severity of bulimic symptoms.These findings add to the weight of evidence suggesting that childhood sexual abuse is not a risk factor for bulimia nervosa.
Abstract P365: The Beneficial Effect of Moderate Alcohol Consumption on Type 2 Diabetes Risk is Modified by Smoking Status and BMI in The French E3n Cohort
Authors: Guy Fagherazzi, Laura Tondeur, Martin Lajous, FranÇoise Clavel-Chapelon
Journal: Circulation (2012)

Background - A U-shape relationship between alcohol consumption and risk of type 2 diabetes (T2D) has already been suggested. While smoking has been shown to act synergically with alcohol, with improvement of insulin sensitivity in ex-smokers, little is known about a possible interaction between alcohol and body mass index (BMI) on T2D risk. Material &amp; Methods - We investigated the relationship between alcohol consumption (categorized as non-consumers, 2 drinks/day, 1 drink=10g of ethanol) and T2D among 66,118 women from the French prospective E3N cohort, the French component of EPIC. Multivariate Cox models were performed to estimate hazard ratios (HR) and 95% confidence intervals (CI) and were then stratified by BMI and smoking status (non-, former and current smokers). Between 1992 and 2007, 1,369 cases of incident diabetes were identified and validated using a drug reimbursement dataset and a supplementary questionnaire. Results - The median alcohol intake among consumers was 0.8 drink/day. Compared to non-consumers, women in the [1-2 drinks/day] category had a significantly lower rate of T2D (HR=0.81 [0.66-0.99]). Higher or lower intakes were not significantly associated with risk of T2D but the pattern of HRs was U-shaped across categories (HR=1, 0.98, 0.94, 0.81 and 0.95 respectively; P=0.04 for the quadratic term). The inverse association between moderate drinking and T2D risk was restricted to overweight or obese women (HR=0.73 [0.57-0.94]). The association was strongest among former smokers (HR=0.60 [0.41-0.87]). Conclusion - The observed decrease in T2D risk associated with moderate alcohol consumption may be limited to overweight or obese women. Our findings also support the hypothesis of a combined beneficial effect of moderate alcohol consumption and smoking cessation on T2D risk.