tbuckley/cabot-search huggingface dataset:
Neoadjuvant therapy outcomes in nonmetastatic pancreatic cancer.
Authors: Jeanette Muniz Kovtun, Konstantin Kovtun, Koenraad Mortele, James Moser, Andrea J. Bullock
Journal: Journal of Clinical Oncology (2018)

501 Background: The optimal multidisciplinary treatment algorithm for pancreatic ductal adenocarcinoma (PDAC) is not well established. We studied outcomes in non-metastatic PDAC treated with chemotherapy and stereotactic body radiation therapy (SBRT) with or without pancreatic resection. Methods: Between August 2011 and July 2015, 73 patients with non-metastatic PDAC were treated with chemotherapy and SBRT with or without resection. Variables considered included: ECOG, CA 19-9, clinical stage, vascular involvement, pathologic stage and margin status. Resectability status was determined by an expert abdominal radiologist on initial staging imaging. Chemotherapy included FOLFIRINOX, FOLFOX, gemcitabine monotherapy (gem) or with nab-paclitaxel (gem/nab). SBRT was delivered as 30 Gy in 3 fractions over 5 days via CyberKnife. The Kaplan-Meier method and log-rank test were used to compare median overall survival (mOS), local progression free survival (LPFS) and metastasis free survival (MFS). Results: After a median follow-up of 19.3 months (mo) the mOS was 30.0 mo (95% CI, 19.4 to 36.5). The surgical group had longer mOS (36.5 vs 19.4 mo; P &lt; 0.001), LPFS (29.0 vs 16.3 mo; P = 0.03) and MFS (29.0 vs 15.1 mo; P &lt; 0.001) as compared to the nonsurgical group. FOLFIRINOX or gem/nab was associated with better mOS as compared to other chemotherapy (33.2 vs 12.8 mo; P &lt; 0.001). There was a trend towards longer mOS in pts with initial imaging deemed less resectable (36.5 vs 30.1 vs 13.0 mo in unresectable vs borderline vs resectable; P = 0.19). In a multivariate analysis significant predictors of OS were resection, ECOG and FOLFIRINOX or gem/nab chemotherapy. Conclusions: Patients who had surgery after neoadjuvant chemotherapy and SBRT had significantly longer mOS, LPFS and MFS than those without surgery. FOLFIRINOX or gem/nab and better ECOG were also associated with improved outcomes. Worse resectablity status per imaging was associated with longer OS despite less likelihood of surgery; This may reflect more intensive neoadjuvant therapy or suggest that radiologic resectability status is a poor predictor of OS. Further investigation of factors underlying this discrepancy may have implications on neoadjuvant strategy and resectability determination.
Abstract 14942: Identification of Truncation Mutations in PKP2-Encoded Plakophilin-2 in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia and Decedents With Autopsy Negative Sudden Death in the Young
Authors: Jaeger Ackerman, David Tester, John Giudicessi, Nicholas Ackerman, Marina Cerrone, Mario Delmar, Michael Ackerman
Journal: Circulation (2017)

Background:  Mutations in plakophilin-2 (PKP2) cause arrhythmogenic cardiomyopathy. Recently, a cardiomyocyte-specific PKP2 knockout mouse model revealed that loss of PKP2 markedly reduces expression of genes critical in intracellular calcium handling. The mice, with structurally normal hearts, exhibited isoproterenol-triggered polymorphic ventricular arrhythmias that mimicked catecholaminergic polymorphic ventricular tachycardia (CPVT). Therefore, we speculated that radical  PKP2  mutations might underlie some cases of CPVT and exercise-associated autopsy negative sudden death in the young (ANSDY).   Methods:  A  PKP2  gene mutational analysis was performed on DNA from 18 unrelated patients with genotype ( RYR2 ,  CASQ2,  and  KCNJ2 ) negative CPVT (9 males, average age at diagnosis 19.6 ± 12.8 years) and 19 decedents with ANSDY during exercise (13 males, average age at death, 14 ± 3 years). Only radical (i.e. frame-shift or nonsense) mutations with a minor allele frequency of ≤ 0.00005 in the genome aggregation database (gnomAD) were considered pathogenic.   Results:  Radical PKP2 mutations were identified in 5/18 (27.7%) patients with CPVT and 1/19 (5.3%) exercise-related ANSDY cases compared to 96/138,632 (0.069%) individuals in gnomAD (p=3.1 x10 -13 ). A R79X mutation was identified in both a 17-year-old female and a 12-year-old male with syncope while playing soccer. An E85fs mutation was identified in a 28-year-old female with cardiac arrest while jogging. An A418fs mutation was identified in a 19-year-old male with a history of syncope during exercise and a family history of ANSDY. An N634fs mutation was identified in a 16-year-old male that died during football drills. An H689fs mutation was identified in a 15-year-old female with exercise-induced ventricular fibrillation. Cardiac imaging or autopsy demonstrated a structurally normal heart in all patients at the time of diagnosis or sudden death.   Conclusions:  Our data suggests that the progression of the PKP2-dependent electrical disorder can be independent of structural perturbations and can precipitate sudden cardiac arrest prior to the presence of an overt cardiomyopathy akin to the PKP2 knockout out mouse model. Thus, the CPVT genetic test panel should now include  PKP2 .
Process and outcome indicators for infection control and prevention in European acute care hospitals in 2011 to 2012 – Results of the PROHIBIT study
Authors: Sonja Hansen, Frank Schwab, Walter Zingg, Petra Gastmeier
Journal: Eurosurveillance (2018)

Introduction Hospitals from 24 European countries were asked for information on infection prevention and control (IPC) indicators as part of the Prevention of Hospital Infections by Intervention and Training (PROHIBIT) survey. Methods: Leading IPC personnel of 297 hospitals with established healthcare-associated infection (HCAI) surveillance provided information on local surveillance and feedback by using a questionnaire. Results: Most hospitals focused on bloodstream infection (BSI) (n = 251) and surgical site infection (SSI) (n = 254), with a SSI post-discharge surveillance in 148 hospitals. As part of the HCAI surveillance, meticillin-resistant Staphylococcus aureus (MRSA) was the leading multidrug-resistant organism (MDRO) under surveillance. Seventy-nine per cent of hospitals (n = 236) monitored alcohol-based hand rub (ABHR) consumption. Feedback to the local IPC committees mainly included outcome data on HCAI (n = 259; 87%) and MDRO among HCAI (n = 245; 83%); whereupon a feedback of MDRO data depended on hospital size (p = 0.012). Discussion/conclusion: Objectives and methods of surveillance vary across Europe, with BSI, SSI and MRSA receiving considerably more attention than indicators such as pneumonia and urinary tract infection, which may be equally important. In order to maximise prevention and control of HCAI and MDRO in Europe, surveillance should be further improved by targeting relevant HCAI. The role of feedback should be explored in more detail.
A Young Woman With Cough and Lithoptysis
Authors: Andres de Lima, Marianne Barry, Adnan Majid
Journal: JAMA (2018)

A 28-year-old healthy woman had a 2-week history of dyspnea, cough, wheezing, and lithoptysis. She had a borderline elevated Histoplasma antigen level, and a chest computed tomography scan revealed a calcified subcarinal mass compromising the left main-stem bronchus lumen. What would you do next?
Failed Target Weight Achievement Associates with Short-Term Hospital Encounters among Individuals Receiving Maintenance Hemodialysis
Authors: Magdalene M. Assimon, Lily Wang, Jennifer E. Flythe
Journal: Journal of the American Society of Nephrology (2018)

Background Hospitalizations and 30-day readmissions are common in the hemodialysis population. Actionable clinical markers for near-term hospital encounters are needed to identify individuals who require swift intervention to avoid hospitalization. Aspects of volume management, such as failed target weight (i.e, estimated dry weight) achievement, are plausible modifiable indicators of impending adverse events. The short-term consequences of failed target weight achievement are not well established. Methods Statistically deidentified data were taken from a cohort of Medicare-enrolled, prevalent hemodialysis patients treated at a large dialysis organization from 2010 to 2012. We used a retrospective cohort design with repeated intervals, each consisting of 180-day baseline, 30-day exposure assessment, and 30-day follow-up period, to estimate the associations between failed target weight achievement and the risk of 30-day emergency department visits and hospitalizations. We estimated adjusted risk differences using inverse probability of exposure weighted Kaplan–Meier methods. Results A total of 113,561 patients on hemodialysis contributed 788,722 study intervals to analyses. Patients who had a postdialysis weight &gt;1.0 kg above the prescribed target weight in ≥30% (versus &lt;30%) of exposure period treatments had a higher absolute risk (risk difference) of 30-day: emergency department visits (2.13%; 95% confidence interval, 2.00% to 2.32%); and all-cause (1.47%; 95% confidence interval, 1.34% to 1.62%), cardiovascular (0.31%; 95% confidence interval, 0.24% to 0.40%), and volume-related (0.15%; 95% confidence interval, 0.11% to 0.21%) hospitalizations. Conclusions In the absence of objective measures of volume status, recurrent failure to achieve target weight is an easily identifiable clinical risk marker for impending hospital encounters among patients on hemodialysis.
Screening for tuberculosis in migrants and visitors from high-incidence settings: present and future perspectives
Authors: Claudia C. Dobler, Greg J. Fox, Paul Douglas, Kerri A. Viney, Faiz Ahmad Khan, Zelalem Temesgen, Ben J. Marais
Journal: European Respiratory Journal (2018)

In most settings with a low incidence of tuberculosis (TB), foreign-born people make up the majority of TB cases, but the distribution of the TB risk among different migrant populations is often poorly quantified. In addition, screening practices for TB disease and latent TB infection (LTBI) vary widely. Addressing the risk of TB in international migrants is an essential component of TB prevention and care efforts in low-incidence countries, and strategies to systematically screen for, diagnose, treat and prevent TB among this group contribute to national and global TB elimination goals. This review provides an overview and critical assessment of TB screening practices that are focused on migrants and visitors from high to low TB incidence countries, including pre-migration screening and post-migration follow-up of those deemed to be at an increased risk of developing TB. We focus mainly on migrants who enter the destination country via application for a long-stay visa, as well as asylum seekers and refugees, but briefly consider issues related to short-term visitors and those with long-duration multiple-entry visas. Issues related to the screening of children and screening for LTBI are also explored.
Medication Prescribing for Children
Authors: Gary L. Freed
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Safety and clinical activity of combining systemic ipilimumab with isolated limb infusion in patients with in-transit melanoma.
Authors: Charlotte Eielson Ariyan, Robert A Lefkowitz, Katherine Panageas, Margaret K. Callahan, Oren Misholy, Danielle Bello, Charles Fisher, Alan Kotin, Robert Siegelbaum, Daniel G. Coit, Jedd D. Wolchok, Mary Susan Brady
Journal: Journal of Clinical Oncology (2014)

9078 Background: Isolated limb infusion(ILI) for melanoma results in a limb response(CR + PR) of 50%, with 11% of patients progression free(PFS) at one year. Ipilimumab(10mg/kg) for M0 melanoma has an overall response rate of 8.3% (95% CI, 0.2-38.5). This phase II trial evaluated the safety and efficacy of ILI with melphalan and dactinomycin followed by systemic ipilimumab(IPI). Methods: Melanoma patients with regional disease (stage IIIb/c ) alone or in combination with distant disease (Stage IV) underwent ILI (melphalan + dactinomycin,7.5mg and 75 mcg/kg/limb volume). Within a median of 12 days (range 7-15) after limb infusion, patients received systemic IPI(10mg/kg) q3w x 4 doses. Patients received maintenance IPI (q3months x 2 years) if there was disease control and no limiting toxicity. The primary endpoint was PFS at one year, secondary endpoints were limb response and toxicity. Results: As of January 2014, 18 patients were enrolled; 88% of patients were stage IIIB/C and 12% were Stage IV. Weiderbink grade 2--3 limb toxicity was seen in all patients; no patient required a fasciotomy or amputation. Related adverse events(rAE) for sequential therapy occurred in 78% of patients (grade1-3). rAE included colitis (n=8, grade 2-3), hypophysitis (n=5, grade 2), and rash (n=6, grade 1-2); all were medically managed. At 3 months, 89% of patients had a limb response, 65% of which were complete (CR) and 24% were partial responses(PR). One patient had SD, and one patient had POD. With a median follow-up of 18 months, OS is 78%, 2 patients died of melanoma, one died of a pulmonary embolus 60 days after ILI, and one died of complications of pneumonia 6 months after ILI. PFS at one year is 57%. Of the 11 patients with a CR in the limb, 1 subsequently progressed in the limb and 1 progressed outside of the limb. The ALC and eosinophils increased in all patients (ALC mean of .99 after ILI to 1.8 after IPI, eosinphils mean 1.5 to 10.3 during therapy with IPI, p<0.05). Conclusions: Combination treatment with ILI and Ipilimumab is safe , with no limb threatening toxicity. The response rates and progression free survival are encouraging and support further studies of limb infusion in combination with immune checkpoint blockade. Clinical trial information: NCT01323517.
Response to Comment on Kelly et al. Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes. Diabetes Care 2018;41:120–127
Authors: Clare B. Kelly, Michelle B. Hookham, Jeremy Y. Yu, Alicia J. Jenkins, Alison J. Nankervis, Kristian F. Hanssen, Satish K. Garg, James A. Scardo, Samar M. Hammad, M. Kathryn Menard, Christopher E. Aston, Timothy J. Lyons
Journal: Diabetes Care (2018)

We thank Foussard et al. (1) for their interest in our study (2). We agree that caution is required when identifying predictive markers of clinical interest in pregnant women with diabetes with regard to preeclampsia (PE). Accurate estimation of renal function is critical for the care of pregnant patients. Alper et al. (3) highlighted the limitations of currently available formulas for accurately predicting the glomerular filtration rate (GFR) in patients with PE. Our study focused on markers of renal function early in pregnancy prior to the clinical onset of PE.

We studied a population with type 1 diabetes, thus at high risk of …
Neutral Theory and Phenotypic Evolution
Authors: Jianzhi Zhang
Journal: Molecular Biology and Evolution (2018)

Although the neutral theory of molecular evolution was proposed to explain DNA and protein sequence evolution, in principle it could also explain phenotypic evolution. Nevertheless, overall, phenotypes should be less likely than genotypes to evolve neutrally. I propose that, when phenotypic traits are stratified according to a hierarchy of biological organization, the fraction of evolutionary changes in phenotype that are adaptive rises with the phenotypic level considered. Consistently, molecular traits are frequently found to evolve neutrally whereas a large, random set of organismal traits were recently reported to vary largely adaptively. Many more studies of unbiased samples of phenotypic traits are needed to test the general validity of this hypothesis.
Abstract 17302: Long-Term Association of Low-Risk Profile and White Blood Cell Count - The Chicago Healthy Aging Study (CHAS)
Authors: Thanh Huyen T Vu, Kiang Liu, Donald M Lloyd-Jones, Amber Pirzada, Daniel B Garside, Jeremiah Stamler, Martha L Daviglus
Journal: Circulation (2011)

Background: Low CVD risk factor (RF) burden at younger ages is associated with substantially lower risk of future clinical CVD events. White blood cell (WBC) count, a measure of systemic inflammation, also predicts CVD morbidity and mortality, and is cross-sectionally associated with CVD risk factors. No data exist on long-term associations of risk status at younger ages and WBC at older ages. Methods: Using data from CHAS, we assessed the association of baseline low risk (LR) status (1967-73) with follow-up WBC count (2007-10). Participants were classified as baseline LR, 0 RF high, only 1 RF high, and 2+RF high (see table footnote for definitions). WBC counts in the 5th quintile (≥7.5x10 9 cells/L) were classified as "high" compared to all others (&lt;7.5x10 9 cells/L). Results: The sample consisted of 1389 participants (28% women, 9% African American, and 20% LR) baseline ages 25-45 (follow-up mean age 71), free of baseline major ECG abnormalities or myocardial infarction. With average follow-up 39 years, multivariate adjusted mean WBC count was higher in a linear fashion across baseline RF categories (P-trend &lt;0.001) (see table footnote for adjustments). Greater number of baseline RFs was also associated with greater likelihood of high WBC count (P-trend= 0.001). Thus, for persons with baseline 0 RF high, 1 only RF high, and ≥2 RFs high, the odds of high WBC count were higher by 57%, 74%, and 81%, respectively, compared to those with baseline LR (see Table). Analyses with individual RFs instead of LR status showed that the above association was mostly due to baseline smoking status and BMI. The association was stronger in women compared to men: coefficient/p-trend was 0.30/&lt;0.001 in women and 0.11/0.049 in men (results not shown). Conclusion: Low risk profile at younger ages is associated with lower WBC count in older age. A low risk profile early in life apparently leads to long-term decreased inflammation, as well as reduced risk of CVD events later in life.
Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment
Authors: Xu‐Feng Huang, Xueqin Song
Journal: Medicinal Research Reviews (2018)

Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia. Neurite deficits contribute to altered brain development, neural networking and connectivity as well as symptoms including psychosis and altered cognitive function. This review revealed that (1) antipsychotic drugs could have profound effects on neurites, synaptic spines and synapse, by which they may influence and regulate neural networking and plasticity; (2) antipsychotic drugs target not only neurotransmitter receptors but also intracellular signaling molecules regulating the signaling pathways responsible for neurite outgrowth and maintenance; (3) high doses and chronic administration of antipsychotic drugs may cause some loss of neurites, synaptic spines, or synapsis in the cortical structures. In addition, confounding effects causing neurite deficits may include elevated inflammatory cytokines and antipsychotic drug-induced metabolic side effects in patients on chronic antipsychotic therapy. Unraveling how antipsychotic drugs affect neurites and neural connectivity is essential for improving therapeutic outcomes and preventing aversive effects for patients on antipsychotic drug treatment.
Empowering the digital therapeutic relationship: virtual clinics for digital health interventions
Authors: John Torous, Honor Hsin
Journal: npj Digital Medicine (2018)

As "digital phenotyping" and monitoring technologies begin to unleash the potential of data insights for mental health care, we propose here a complementary concept of the "digital therapeutic relationship" to unleash the power of the patient-provider alliance in clinical care. In millions of clinics today, care decisions are made on a daily basis in the context of a relationship honed through professional training to be respectful, protective, and empowering of patients. Now as clinical care evolves toward online and especially mobile platforms, it is critical to not ignore the digital therapeutic relationship and instead to realize that supporting it will require new and innovative means of care delivery. Here, we propose that technology can be harnessed to facilitate, augment, and expand these relationships directly, and identify virtual clinics as the currently missing but necessary environment to unleash the true potential of digital medicine.
Abstract 15548: Heart Transplantation in Heterotaxy Syndrome is Associated With Reduced Survival and Increased Cost of Care: A Multicenter Linked Registry Analysis
Authors: Son Q Duong, Justin Godown, Jonathan H Soslow, Cary Thurm, Matt Hall, Debra A Dodd, Brian Feingold
Journal: Circulation (2017)

Introduction:  Outcomes after heart transplantation (HT) in children with visceral heterotaxy (VH) are not well described. Anomalies of cardiac position and venous return may complicate HT for patients with VH. We hypothesized that patients with VH have inferior survival and increased resource use after HT.   Methods:  Using linked data from the Pediatric Health Information System (PHIS) and Scientific Registry of Transplant Recipients (SRTR) we identified VH patients who received primary HT from 2001-2016. VH was defined as SRTR diagnosis of CHD plus ≥1 of the following ICD-9/10 codes: situs inversus (759.3, Q89.3), poly/asplenia (759.0, Q89.01, Q89.09), or dextrocardia (746.87, Q24.0). Data were compared by Fisher exact, Mann-Whitney, or Kaplan Meier method with log rank test.   Results:  A total of 177 primary HT recipients (6% of all HT) with VH were identified. Compared to non-VH recipients with CHD (non-VH CHD), VH recipients were older (median age 5.1 vs 1.6 yr, p   Conclusions:  In this first, multicenter analysis of children and young adults with visceral heterotaxy who receive HT we found increased risk of reoperation, longer ICU and total LOS after HT, greater post-operative costs, and inferior early and late post HT survival. While increased surgical complexity may account for many of these differences, inferior late survival is less well explained and deserves further study to improve outcomes for VH patients.