tbuckley/cabot-search huggingface dataset:
Abstract P229: Genetic Risk Scores are Associated with Chronic Venous Disease Prevalence and Severity in a Multi-Ethnic Cohort: The San Diego Population Study (SDPS)
Authors: Christina L Wassel, Laura J Rasmussen-Torvik, Peter W Callas, Julie O Denenberg, Peter Durda, Alexander P Reiner, Nicholas L Smith, Matthew A Allison, Michael H Criqui, Mary Cushman
Journal: Circulation (2012)

Background: Chronic venous disease is common, affecting up to 40% of the population, although estimates vary quite widely due to differing evaluation methods and definitions. Chronic venous disease shares some risk factors with venous thromboembolism (VTE). Several genetic loci have been recently discovered and replicated for VTE, mostly in populations of European descent. We tested associations of these loci, as well as a genetic risk score including these variants, with chronic venous disease prevalence and severity in a multi-ethnic cohort. Methods: The San Diego Population Study (SDPS) is a prospective cohort study that evaluated 2404 ethnically diverse men and women aged 29-91 for venous disease using duplex ultrasound. The current study includes 1229 participants from the baseline exam who were genotyped for 35 variants in 23 loci. Venous disease was defined as moderate or severe, as well as severe only. Logistic regression was used to examine the association of each variant with venous disease, stratified by ethnic group. A weighted genetic risk score, using the top 20% of variants and weighting by the beta coefficients, was generated for each ethnic group. Associations of this risk score with venous disease were examined stratified by ethnic group. Results: The mean ± standard deviation (SD) age was 60±11, with 64% female, and 62% White, 14% Hispanic, 11% African-American, and 12% Asian. The prevalence of moderate and severe venous disease was 41%, and severe venous disease alone was 25%. While some loci overlapped in the ethnic-specific genetic risk scores, others were exclusive to an ethnic group. In models adjusting for known venous disease risk factors, in Whites, Hispanics, African-Americans and Asians, respectively, each SD higher genetic risk score was associated with a 1.42-fold higher odds (95% CI (1.21, 1.66)), 2.06-fold higher odds (95% CI (1.44, 2.95)), a 2.25-fold higher odds (95% CI (1.38, 3.66)), and 2.45-fold higher odds (95% CI (1.57, 3.82)) for moderate or severe disease. The difference in c-statistics was statistically significant between the known venous risk factor model and this model adding the genetic risk factor for Hispanics, African-Americans, and Asians, with 0.67 vs. 0.75 (p=0.03), 0.69 vs. 0.77 (p=0.02), 0.63 vs. 0.74 (p=0.01), respectively. The difference was not significant for Whites, 0.64 vs. 0.66 (p=0.12). All results were similar for severe venous disease only. Conclusions: This ethnic-specific genetic risk score is strongly associated with chronic venous disease, and may be of greater importance for venous disease in those of non-European descent. Future work should focus on examining racial/ethnic group genetic architecture in relation to venous disease.
New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity
Authors: Munir Pirmohamed, David A. Ostrov, B. Kevin Park
Journal: Journal of Allergy and Clinical Immunology (2015)

Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions.
Disproportionate lethality in psychiatric patients with concurrent alcohol and cocaine abuse
Authors: I M Salloum, D C Daley, J R Cornelius, L Kirisci, M E Thase
Journal: American Journal of Psychiatry (1996)

The aim of this study was to examine the association between active, concomitant cocaine and alcohol abuse and the prevalence and severity of current suicidal and homicidal behavior among hospitalized psychiatric patients.Three groups of patients--with cocaine and alcohol abuse (N = 38), alcohol abuse only (N = 38), and cocaine abuse only (N = 25)--consecutively admitted to a psychiatric and substance abuse dual-diagnosis unit were comparatively examined for the presence of current suicidal and homicidal behavior.Logistic regression analysis revealed that the alcohol and cocaine abuse group had a higher likelihood of associated current homicidal behavior than the alcohol-only and the cocaine-only groups.
Advancing the mission
Authors: Mukesh K. Jain
Journal: Journal of Clinical Investigation (2015)

I have been honored to serve as president over the past year and as a member of the Council since 2012. The opportunity to work with my fellow Council members, distinguished colleagues across the country, and superb administrative team constitutes one of the great privileges of my professional life.

I would happily conclude my tenure by enjoying our annual meeting’s scientific sessions and then quietly returning home. But the burdensome tradition of delivering a presidential address carries on. Many past presidents have shared my consternation, perhaps best expressed by Dr. Holly Smith in his 1970 presidential address when he noted, “This rather strange custom is not embedded in the Bylaws of the American Society for Clinical Investigation. Furthermore, casual perusal of the past fails to reveal any firm mandate transmitted from a grateful membership for this form of gratuitous pontification” (1).

I would add to Dr. Smith’s trenchant remarks that the only firm mandate from the membership is that this address end in a timely fashion, and I intend to do so.

Having succumbed to the power of tradition, I set out to develop thoughtful remarks. Over the past few weeks, my children, who are both here today, watched me struggle at the keyboard. They observed with amusement but not surprise as I attempted to illuminate previously unappreciated philosophical insights. I say “without surprise” because like most young people they concluded some years ago that their father lacks a deep understanding of frankly anything, a view reaffirmed for them by my continued struggle.

I sought inspiration by reading previous presidential addresses. As I reviewed, it became clear that, while the elocutionary approach varied, recurrent themes dominated the discussion — reflective of the importance of some issues across generations. David Ginsburg, in his 2002 presidential address, provided quantitative data that the most common topics include (a) the future of the physician-scientist, (b) clinical investigation, (c) ASCI state of the union, (d) research funding, and (e) education/mentoring (2).

I found reading these previous addresses, and many, many more, to be simultaneously inspiring and disheartening. For everything I wished to say had been stated by others, more eloquently, and with more depth and insight than I could ever hope to achieve. This appreciation coupled with the recognition of myself as a utilitarian phenotype, unabashedly so, led me to abandon the well-stated, philosophical discourse as an approach. Rather, I chose to focus on three strategies that my colleagues and I have undertaken during my tenure. While each strategy may represent a modest advance, collectively they unite as a considered set of measures consonant with “Advancing the Mission” of the Society.
Doxorubicin, Vinblastine and Dacarbazine with or without Bleomycin for Older Patients with Early Stage Favorable Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 Trials
Authors: Boris Böll, Karolin Behringer, Helen Görgen, Paul Bröckelmann, Bastian von Tresckow, Dennis A. Eichenauer, Michael Fuchs, Volker Diehl, Andreas Engert, Peter Borchmann
Journal: Blood (2014)
RespiStent – A new concept for a viable stent for the treatment of endobronchial stenosis
Authors: Christian Cornelissen, Stefan Krüger, Jan Spillner, Stefan Weinandy, Stefan Jockenhoevel
Journal: European Respiratory Journal (2011)

Endobronchial stent therapy is an accepted method for the treatment of endobronchial stenosis. It is limited by a loss of physiologic surface and, thus, mucus retention. We developed a novel concept for a vitalized endobronchial stent (fig. 1 A). The concept is based on the combination of stent technologies with the principles of tissue engineering. The RespiStent provides (1) a functional respiratory epithelium on the luminal side, which allows the maintenance of the mucociliary function in the stented area and hereby will help to reduce complications of mucus retention, (2) embedded micro- or nanosphere formulations, enabling the sustained release of tissue-specific therapeutics in combination with (3) a mechanical separating layer on the external side, avoiding restenosis by a tissue ingrowth.  In addition (4) an adequate anchorage resulting from the specific stent design and the biological coating of the stent struts guarantees an adequate fixation and embedding of the construct into the surrounding tissue, thereby avoiding stent displacement during breathing and coughing. As seen in fig. 1 B and C, the stent structure embeds readily in a fibrin-gel based tissue-engineered construct.  The novel RespiStent with active mucociliary clearance will improve quality of life and increase the life expectancy of patients undergoing endobronchial stent therapy.
Abstract 3881: A distinct DNA methylation signature defines breast cancer stem cells and predict cancer outcome
Authors: Rita E. Helou, Julien Wicinski, Arnaud Guille, Jose Adelaide, Pascal Finetti, Francois Bertucci, Max Chaffanet, Daniel Birnbaum, Emmanuelle Charafe-Jauffret, Christophe Ginestier
Journal: Cancer Research (2014)

Abstract Pluripotency of stem cells depends on epigenetic programs that regulate self-renewal and differentiation. During oncogenesis, dysregulation of these two programs leads to the development of cancer stem cells (CSCs). Recent evidence suggests that CSCs are relatively resistant to conventional therapies and responsible for metastasis formation. Deciphering these processes will help gain insight into oncogenesis and allow the development of new targeted therapies. We used a whole-genomic promoter microarray to establish the DNA methylation portrait of breast cancer stem cells (bCSC) and compared it to non-bCSC. bCSC from five breast cancer cell lines were isolated using the ALDEFLUOR assay. We identified a DNA methylation signature with 68 differentially methylated regions (DMRs) that were hypomethylated in bCSCs as compared to non-bCSCs. Using a differentiation assay we demonstrated that DMRs are rapidly hypermethylated within the first six hours following induction of CSC differentiation whereas the cells reached the steady-state within 6 days, suggesting that these DMRs are linked to early CSC epigenetic regulation. DMRs were enriched in genes coding for TGFβ signaling-related proteins. Interestingly, overexpression of TGFβ signaling genes was correlated to DMRs hypomethylation in a series of 109 breast tumors. Moreover, the tumors harboring the bCSC DMRs signature had a worse evolution than the ones with the non-bCSC DMRs signature. Our results provide evidence that bCSCs harbor a distinct DNA methylation landscape with TGFβ signaling as a key epigenetic regulator of bCSCs differentiation. Note: This abstract was not presented at the meeting. Citation Format: Rita El Helou, Julien Wicinski, Arnaud Guille, Jose Adelaide, Pascal Finetti, Francois Bertucci, Max Chaffanet, Daniel Birnbaum, Emmanuelle Charafe-Jauffret, Christophe Ginestier. A distinct DNA methylation signature defines breast cancer stem cells and predict cancer outcome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3881. doi:10.1158/1538-7445.AM2014-3881
転移性結腸直腸癌患者におけるベバシズマブを基本とした併用レジメンの有効性と安全性:ベバシズマブ+FOLFIR対ベバシズマブ+XELIRIのランダム化第二相試験(FNCLCC ACCORD 13/0503研究)の予備結果
Authors: Ducreux M, Adenis A, Pignon J, Francois E, Boucher E, Chauffert B, Ychou M, Pierga J, Montoto-Grillot C, Conroy T
Journal: Annals of Oncology (2009)
Abstract 11291: Visualization of Intra-QRS Fragmented Activation in Patients with Hypertrophic Cardiomyopathy and Life-Threatening Ventricular Tachyarrhythmias Using Magnetocardiography
Authors: Kazushi Sakane, Hiroshi Takaki, Shuji Hashimoto, Yuko Yamada, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Takeshi Aiba, Wataru Shimizu, Naohiko Aihara, Shiro Kamakura, Masaru Sugimachi
Journal: Circulation (2011)

Backgrounds:  Previous studies indicated that intra-QRS fragmentation (QRSf) on ECG is a possible marker of lethal ventricular arrhythmias in ischemic and other heart diseases, the origin of QRSf remains unclarified, however. We hypothesized that patients with hypertrophic cardiomyopathy (HCM) who had experienced ventricular tachycardia (VT) or fibrillation (Vf) exhibit similar abnormalities, which can be visualized by high-resolution multi-channel (64-Ch) magnetocardiography (MCG).   Methods:  In 21 HCM patients with narrow QRS (   Results:  In 19 of 21 patients, QRSf was recognized on ECG. MCG analysis revealed that LV conduction time in HCM patients was markedly prolonged compared with Controls (73±17 vs 51±5 ms, p   Conclusions:  Patients with HCM and a history of life-threatening ventricular tachyarrhythmias often showed intra-QRS fragmentation on ECG. This depolarization abnormalities, possibly associated with the occurrence of lethal arrhythmias, can be noninvasively visualized on the MCG 2-D current mapping.
Interleukin-13 induces the production of interleukin-1 receptor antagonist (IL-1ra) and the expression of the mRNA for the intracellular (keratinocyte) form of IL-1ra in human myelomonocytic cells
Authors: M Muzio, F Re, M Sironi, N Polentarutti, A Minty, D Caput, P Ferrara, A Mantovani, F Colotta
Journal: Blood (1994)
Abstract 103: Rib and Sternum Fractures After Cardiopulmonary Resuscitation: An Autopsy Study
Authors: Niklas Friberg, Charles Walther, Elisabet Englund
Journal: Circulation (2014)

Introduction: Chest compression during cardiopulmonary resuscitation (CPR) is associated with skeletal chest injury. The aim of this study was to investigate the incidence of rib and sternum fractures after mechanical active compression-decompression CPR (aCPR) and standard manual CPR (mCPR). Method: This prospective study was conducted from January 1 2005 through December 31 2013. We included adult patients (age ≥18 years) who did not survive after CPR and were referred for clinical autopsy. The patients had been treated with either the aCPR device Lund University Cardiac Arrest System (LUCAS) or mCPR only. Patient and CPR data was drawn from autopsy referral documents or the patient medical records. Out of many referred cases, inclusion required examination by one of two pathologists with experience of CPR-related injuries. Autopsy was performed with special attention given to skeletal chest injuries and a standardized written protocol was used. Results: In the period 2005-2013 we included 362 cases treated with aCPR and 52 cases treated with mCPR. Sternum fracture was found in 291/362 cases (80 %) in the aCPR group and in 20/52 cases (38 %; p&lt;0.001) in the mCPR group. Rib fracture was found in 349/362 cases (96 %) in the aCPR group and in 40/52 cases (77 %; p&lt;0.001) in the mCPR group. Fracture on ≥ three ribs was present in 334/362 cases (92 %) in the aCPR group and in 36/52 cases (69 %; p&lt;0.001) in the mCPR group. In the majority of cases there were multiple bilateral rib fractures, with a median of 10 fractures per case (interquartile range 7 to 13 fractures) in the aCPR group and 7 fractures per case (interquartile range 1 to 9.75 fractures; p&lt;0.001) in the mCPR group. There was no fracture in 6/362 cases (1.7 %) in the aCPR group and in 10/52 cases (19 %; p&lt;0.001) in the mCPR group. Conclusion: The incidence of rib and sternum fracture was significantly higher after aCPR than after mCPR, sternum fractures being twice as common and rib fractures being markedly more numerous after aCPR. These findings should be considered in the light of emerging survival data.
Abstract 15661: Low Awareness of Atrial Fibrillation in a Nationally Representative Sample of Older Adults
Authors: Ciaran Finucane, John Frewen, Hilary Cronin, Patricia Kearney, Ciara Rice, Claire O Regan, Joe Harbison, Rose Anne Kenny
Journal: Circulation (2011)

Introduction Atrial Fibrillation (AF) is the most common cardiac arrhythmia worldwide and strongly increases risk of stroke. Information on its prevalence, levels of awareness and diagnosis is seve...
Propanolol treatment in pulmonary capillary hemangiomatosis
Authors: Francesco Paolo Rossi, Paola Francalanci, May Chebl El Hachem, Teresa Salerno, Maria Giovanna Paglietti, Laura Menchini, Renato Cutrera
Journal: European Respiratory Journal (2011)

Pulmonary Capillary Haemangiomatosis (PCH) is a rare disease with broad symptoms, from dyspnoea to pulmonary hypertension. Oral steroids are considered the first line treatment for severe haemangioma. Other therapeutic options are less used for side effects and toxicity. Propanolol has been discovered by chance in 2 children who showed rapid regression of skin haemangiomas when treated for cardiopulmonary conditions.  We describe a case of a 8 year old boy with persistent respiratory failure, in whom open lung biopsy demonstrated diffuse proliferation of capillary vessels consistent with PCH. L. began propanolol, with increasing dose up to 2 mg/kg/day. Respiratory symptoms and general conditions immediately improved without side effects and steroid treatment discontinuation was achieved uneventfully. Propanolol therapy was effective in resolving respiratory symptoms and avoiding new lesions growth without any observed side effect. In our patient we achieved lesions stability, excellent general and respiratory conditions, satisfactory growth; the future most likely therapeutic approach may be surgical to completely remove the lesion.  A control MRI, performed after 6 months, showed that no new lesions appeared after the treatment, due to the anti-neoangiogenic effect of propranolol, which avoids new vessels growth.  The patient is still on propranolol and in regular follow up. The lesions are stable, his general and respiratory conditions excellent, growth is satisfactory; the future most likely therapeutic approach may be surgically to completely remove the lesion.  The excellent results that we reached with lack of adverse effects confirm propanolol a promising therapy for difficult haemangiomas, including PCH.
Paradoxical lithium neurotoxicity: a report of five cases and a hypothesis about risk for neurotoxicity
Authors: A P West, H Y Meltzer
Journal: American Journal of Psychiatry (1979)

There have been many reports of probable lithium-induced organic brain syndromes occurring when serum lithium levels are within or close to the therapeutic range. The authors report on five patients who developed clinical syndromes suggestive of severe neurotoxicity during lithium treatment. In all cases lithium levels were between .75 and 1.7 mEq/liter. The patients who developed neurotoxicity had markedly higher global ratings of psychotic symptomatology and anxiety in the pretoxic period than did patients who never deveoped neurotoxicity. When the acute manic state is characterized by marked psychotic symptoms and intense anxiety, it may be associated with increased vulnerability to the development of severe lithium neurotoxicity.
Hydrogen peroxide in exhaled air: A source of error, a paradox and its resolution
Authors: Stefan Peters, Angelika Kronseder, Stefan Karrasch, Petra Neff, Matz Haaks, Rembert Koczulla, Dennis Nowak, Rudolf Jörres
Journal: European Respiratory Journal (2012)

Background: The concentration of hydrogen peroxide (H2O2) in exhaled air has been reported to be elevated in asthma and COPD, but the data are inconsistent and difficult to reproduce. Notably, a relevant concentration of H2O2 can be found in ambient air. Therefore, we examined the association between H2O2 in ambient and exhaled air.

Methods: Exhaled breath condensate (EBC) of 12 COPD patients and 9 healthy subjects was collected with an inhalation filter (F; efficiency 81%) or without (nF). Ambient air condensate (AAC) was collected in parallel and all samples were analysed for H2O2. Additionally, ambient H2O2 concentration was recorded by an analyser for atmospheric H2O2.

Results: H2O2 concentration in AAC (3.60±1.40µM, mean±SD) was higher (p<0.01) than in EBC (Table). It showed meteorological variations concordant with atmospheric measurements. In both groups studied, the inhalation filter caused a reduction of H2O2 values (p<0.01). Despite the comparatively low levels in exhaled air, analysis by means of a mathematical model revealed an endogenous H2O2 contribution which was more pronounced when using the inhalation filter.

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Conclusion: The paradox of low H2O2 values in exhaled air assessed by EBC dissolves when taking into account the reconditioning of inhaled air containing H2O2. This may partially explain the heterogeneity of study results and their limited reproducibility. Still, there seems to be endogenous H2O2 production but its valid determination requires inhalation filters. This suggests a reanalysis of studies from the literature.