tbuckley/cabot-search huggingface dataset:
Ca2+-binding protein NECAB2 facilitates inflammatory pain hypersensitivity
Authors: Ming-Dong Zhang, Jie Su, Csaba Adori, Valentina Cinquina, Katarzyna Malenczyk, Fatima Girach, Changgeng Peng, Patrik Ernfors, Peter Löw, Lotta Borgius, Ole Kiehn, Masahiko Watanabe, Mathias Uhlén, Nicholas Mitsios, Jan Mulder, Tibor Harkany, Tomas Hökfelt
Journal: Journal of Clinical Investigation (2018)

Pain signals are transmitted by multisynaptic glutamatergic pathways. Their first synapse between primary nociceptors and excitatory spinal interneurons gates the sensory load. In this pathway, glutamate release is orchestrated by Ca2+-sensor proteins, with N-terminal EF-hand Ca2+-binding protein 2 (NECAB2) being particular abundant. However, neither the importance of NECAB2+ neuronal contingents in dorsal root ganglia (DRGs) and spinal cord nor the function determination by NECAB2 has been defined. A combination of histochemical analyses and single-cell RNA-sequencing showed NECAB2 in small- and medium-sized C- and Aδ D-hair low-threshold mechanoreceptors in DRGs, as well as in protein kinase C γ excitatory spinal interneurons. NECAB2 was downregulated by peripheral nerve injury, leading to the hypothesis that NECAB2 loss of function could limit pain sensation. Indeed, Necab2–/– mice reached a pain-free state significantly faster after peripheral inflammation than did WT littermates. Genetic access to transiently activated neurons revealed that a mediodorsal cohort of NECAB2+ neurons mediates inflammatory pain in the mouse spinal dorsal horn. Here, besides dampening excitatory transmission in spinal interneurons, NECAB2 limited pronociceptive brain-derived neurotrophic factor (BDNF) release from sensory afferents. Hoxb8-dependent reinstatement of NECAB2 expression in Necab2–/– mice then demonstrated that spinal and DRG NECAB2 alone could control inflammation-induced sensory hypersensitivity. Overall, we identify NECAB2 as a critical component of pronociceptive pain signaling, whose inactivation offers substantial pain relief.
Cover Image: Neuroendocrine treatment of inherited keratin disorders by cannabinoids?
Authors: Y. Ramot, A. Oláh, R. Paus
Journal: British Journal of Dermatology (2018)

DEAR EDITOR, Epidermolytic ichthyosis (EI) is a rare genodermatosis caused by mutations in keratins 1 or 10.The available treatment options for this debilitating condition, such as retinoids, are highly unsatisfactory and associated with severe adverse effects. 1 A promising novel approach for the treatment of keratin disorders may be to upregulate the expression of compensatory keratins and/or to downregulate the expression of the mutated keratins by neuroendocrine mediators that profoundly modulate the expression of selected keratins. 2The current illustration underscores the potential of this as yet untapped, innovative treatment strategy for inherited human keratin disorders.Here we show that the cannabinoid receptor 1 agonist, arachidonyl-2 0 -chloroethylamide (ACEA) (1 lmol L À1 , 48 h), can upregulate the expression of keratin 10 protein in human epidermis, and decrease that of keratin 1 in human skin organ culture.Although it remains to be examined how reproducible the specific keratin-regulatory effects shown here are in skin from different patients, one wonders: can appropriate modulation of cannabinoid signalling (e.g. by topically applied agents) suppress mutated keratin 1 and upregulate the expression of functionally compensatory keratin 10 in patients with EI?
Hypoglycemia, Cardiovascular Outcomes, and Death: The LEADER Experience
Authors: Bernard Zinman, Steven P. Marso, Erik Christiansen, Salvatore Calanna, Søren Rasmussen, John B. Buse
Journal: Diabetes Care (2018)

OBJECTIVE In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) cardiovascular (CV) outcomes trial (NCT01179048), liraglutide significantly reduced the risk of CV events (by 13%) and hypoglycemia versus placebo. This post hoc analysis examines the associations between hypoglycemia and CV outcomes and death. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and high risk for CV disease (n = 9,340) were randomized 1:1 to liraglutide or placebo, both in addition to standard treatment, and followed for 3.5–5 years. The primary end point was time to first major adverse cardiovascular event (MACE) (1,302 first events recorded), and secondary end points included incidence of hypoglycemia. We used Cox regression to analyze time to first MACE, CV death, non-CV death, or all-cause death with hypoglycemia as a factor or time-dependent covariate. RESULTS A total of 267 patients experienced severe hypoglycemia (liraglutide n = 114, placebo n = 153; rate ratio 0.69; 95% CI 0.51, 0.93). These patients had longer diabetes duration, higher incidence of heart failure and kidney disease, and used insulin more frequently at baseline than those without severe hypoglycemia. In combined analysis (liraglutide and placebo), patients with severe hypoglycemia were more likely to experience MACE, CV death, and all-cause death, with higher risk shortly after hypoglycemia. The impact of liraglutide on risk of MACE was similar in patients with and without severe hypoglycemia (P-interaction = 0.90). CONCLUSIONS Patients experiencing severe hypoglycemia were at greater risk of CV events and death, particularly shortly after the hypoglycemic episode. While causality remains unclear, reducing hypoglycemia remains an important goal in diabetes management.
The incidence of vocal fold motion impairment after primary thyroid and parathyroid surgery for a single high-volume academic surgeon determined by pre- and immediate post-operative fiberoptic laryngoscopy
Authors: Vaninder K. Dhillon, Eleni Rettig, Salem I. Noureldine, Dane J. Genther, Ahmed Hassoon, Mai G. Al Khadem, Ozan B. Ozgursoy, Ralph P. Tufano
Journal: International Journal of Surgery (2018)
AB0355 The relationship between hand prehensile strength, clinical activity and functional capacity in patients with rheumatoid arthritis
Authors: I.P. Guzmán Guzmán, J.E. Navarro-Zarza, G.A. Alonso-Silverio, A. Alarcón-Paredes, D. Jerez-Mayorga, I. Parra-Rojas
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The hand is an anatomical structure with a large number of joints; its prehensile grasp capability constitutes a highly specialised biomechanical function. In rheumatoid arthritis (RA), the structures of the joint are damaged by the characteristic inflammatory process<sup>1</sup> The <i>Disease Activity Score</i> (DAS28) considers twenty hand joints in the evaluation of rheumatoid arthritis (RA). While the <i>Health Assessment Questionnaire</i> (HAQ)<i> disability index</i> (DI) (HAQ-DI) is the most frequently used instrument for measuring self-reported physical function in rheumatoid arthritis and considers the ability to dress and groom, get up, eat, hygiene, reach, grasp, situations in which the functional capability of the hand is crucial. <h3>Objectives</h3> To assess the relationship between hand prehensile strength, the DAS28 index and HAQ-DI score in patients with diagnosis of RA. <h3>Methods</h3> The prehensile strength was obtained by the dynamometry method from 105 AR patients, the maximum strength levels in the dominant and non-dominant hand were considered. The Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and HAQ-DI were recorded. <h3>Results</h3> The maximum prehensile strength, on average, was 14 kg, and the weak force category was more prevalent. The prehensile strength of both hands was negatively correlated with the HAQ-DI score and DAS28 index. In an adjusted logistic regression model, the "weak" strength category of the non-dominant hand was associated with "moderate clinical activity" in the DAS28 score (OR=8.59, p=0.02), while the category of "weak" strength of the dominant hand was associated with the presence of "some difficulty" of HAQ-DI score (OR=4.75, p=0.10). <h3>Conclusions</h3> The decrease in prehensile strength represents a marker associated with the DAS28 index and HAQ-DI score in the patient with RA, regardless of age, muscle mass, total fat or body mass. The measurement of the prehensile strength can be a useful and inexpensive tool to be considered in the clinical evaluation of the RA. <h3>Reference</h3> [1] Janet L Poole. Hand Function in Rheumatoid Arthritis. Mehmet Tuncay Duruöz A Practical Guide to Assessment. Springer. 2014. [ISBN:978–1–4614–9448–5] <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
Outcomes From a Patient-Centered, Interprofessional, Palliative Consult Team in Oncology
Authors: Andrea Feldstain, Barry D. Bultz, Janet de Groot, Amane Abdul-Razzak, Leonie Herx, Lyle Galloway, Srini Chary, Aynharan Sinnarajah
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Palliative care aims to improve suffering and quality of life for patients with life-limiting disease. This study evaluated an interdisciplinary palliative consultation team for outpatients with advanced cancer at the Tom Baker Cancer Centre. This team traditionally offered palliative medicine and recently integrated a specialized psychosocial clinician. Historic patient-reported clinical outcomes were reviewed. There were no a priori hypotheses. Methods: A total of 180 chart reviews were performed in 8 sample months in 2015 and 2016; 114 patients were included. All patients were referred for management of complex cancer symptomatology by oncology or palliative care clinicians. Patients attended initial interviews in person; palliative medicine follow-ups were largely performed by telephone, and psychosocial appointments were conducted in person for those who were interested and had psychosocial concerns. Chart review included collection of demographics, medical information, and screening for distress measures at referral, initial consult, and discharge. Results: A total of 51% of the patient sample were men, 81% were living with a partner, and 87% had an advanced cancer diagnosis. Patients were grouped based on high, moderate, or low scores for 5 symptoms (pain, fatigue, depression, anxiety, and well-being). High scores on all 5 symptoms decreased from referral to discharge. Pain and anxiety decreased in the moderate group. All 5 low scores increased significantly. Sleep, frustration/anger, sense of burdening others, and sensitivity to cold were less frequently endorsed by discharge. Conclusions: Patients who completed this interdisciplinary palliative consult service appeared to experience a reduction in their most severe symptoms. Visits to patients during existing appointments or having them attend a half-day clinic appears to have reached those referred. With interdisciplinary integration, clinicians are able to collaborate to address patient care needs. Considerations include how to further integrate palliative and psychosocial care to achieve additional benefits and ongoing monitoring of changes in symptom burden.
Azithromycin for Early <i>Pseudomonas</i> Infection in Cystic Fibrosis. The OPTIMIZE Randomized Trial
Authors: Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, AnneMarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, George Retsch-Bogart, Frank J. Accurso, Rachael Buckingham, Michelle Howenstine, Susan Jacob, Richard Kronmal, Robert Kuhn, Nicole Mayer-Hamblett, Karen McCoy, David Nichols, Bonnie W. Ramsey, Margaret Rosenfeld, Scott Sagel, Lisa Saiman, John Sheridan, Benjamin Wilfond, Edith Zemanick, Irene Bondick, Lauren Braam, Margaret Brassil, Rachael Buckingham, Missy Cianciola, Sonya Heltshe, Susan Jacob, Miya Johnson, Jean Kirihara, Margaret Kloster, Ada Kong, Shelly Ma, Sharon McNamara, Lindsey Mann, Kelly Moormann, Matthew Myers, Nicole Mayer-Hamblett, Bonnie W. Ramsey, George Retsch-Bogart, Kathy Seidel, Michelle Skalland, Carmen Ufret-Vincenty, Jill VanDalfsen, Christopher H. Goss, David J. Horne, Erin K. Kross, Peter J. Leary, Kathleen J. Ramos, Patricia Roush, Jack C. Salerno, Gregory Omlor, Deborah Ouellette, Deanna Green, Kathy Hosler, Adrienne Savant, Zainub Ashrafi, Ariel Berlinski, Andrea Ross, Gregory Sawicki, Robert Fowler, Monica Ulles, Gary Albers, Freda Branch, Kevin Kirchner, Kerry DiBenardo, Gwendolyn Kerby, Meg Anthony, Thomas Keens, Alejandra Franquez, Carmen Reyes, Ibrahim Abdulhamid, Catherine Van Wagnen, David Orenstein, Elizabeth Hartigan, Carley Mihlo, Ronald Williams, Margaret Lessard, Laura Sass, Erin McAndrews, Jennifer Parrott, Julie Noe, Patricia Hastings, Theresa Kump, John Clancy, Stacey Niehaus, Lisa Saiman, Juyan Zhou, Gary Mueller, Sandy Bartosik, Jason Fullmer, Colleen Millian, Arlene Stecenko, Joy Dangerfield, Gavin Graff, Diane Kitch, AnneMarie Cairns, Carrie Milliard, Robert Zanni, Bridget Marra, Karen McCoy, Patsy Guittar, Melinda Smith, David Schaeffer, Elizabeth DeLuca, John Welter, Meighan Gallagher, Armando Ramirez, Alexandra Cornell, Erika Simeon, Dion Roberts, Katherine Nelson, James Chmiel, Cindy Schaefer, Stephanie D. Davis, Lori Shively, James Wallace, Allisa Richter, Bonnie Ramsey, Sharon McNamara, Jessica Pittman, Tina Hicks, Perry Brown, Dixie Durham, Carlos Milla, Jacquelyn Zirbes, Christopher Fortner, Valoree Suttmore, Philip Black, Rose Thompson, Cori Daines, Monica Varela, Timothy Starner, Mary Teresi, Samya Nasr, Dawn Kruse, Heather Thomas, Lisa Houdesheldt, George Retsch-Bogart, Carol Barlow, Rose Cunnion, Saumini Srinivasan, Catherine Horobetz, Fadi Asfour, Jessica Francis, Michael Rock, Linda Makholm, Marie Egan, Catalina Guzman
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.
Circulating tumor cells (CTC) as a biomarker of response in patients with extensive-stage small cell lung cancer (EX-SCLC).
Authors: Chao H. Huang, Apar Kishor Ganti, Prakash Neupane, G. Sitta Sittampalam, Sarah Schmitt, Sanjit Nirmalanandhan, Stephen K. Williamson, Jo Wick, Janie Smart, Sarah Ellen Spencer, Andrew K. Godwin, Peter J. Van Veldhuizen
Journal: Journal of Clinical Oncology (2013)

e22048 Background: SCLC, a variant of lung cancer marked by early metastases, accounts for 13% of all lung cancers diagnosed in US. Despite high response rates to treatment, it is an aggressive disease with a median survival of 9-11 months for patients with EX-SCLC. Detection of CTCs is a novel laboratory technique currently in use to determine response to therapy and to predict prognosis in breast, colorectal and prostate cancer. We initiated a study to study the role of CTC as a biomarker of response and relapse in patients with EX-SCLC. Methods: We collected blood sample from chemotherapy naïve patients with EX-SCLC prior to initiation of therapy, following completion of systemic therapy, follow up every 6-8 weeks and at relapse. The CTC was determined using the Cell Search system in a central laboratory. The study was conducted in 4 different sites and it was reviewed and approved by respective Research Review Committee and IRBs. Results: We enrolled 27 patients with EX-SCLC, 1 was excluded due ineligibility, all patients were treated with platinum and etoposide. We observed partial response in 16 patients (61%), stable disease in 3 patients, 1 with progression of disease and not assessed in 7 patients (5 deceased, 2 not available); the baseline CTC of 2 patient were not measured (one due instrument failure and one due insufficient blood). The overall median number of CTCs in 24 patients measured at baseline and post-tx was 75 (range 0 to 3430) and 2 (range 0 to 526), respectively. A significant reduction in CTCs from baseline to post-tx was identified; for the 14 subjects with pre and post treatment CTC, the median reduction was 51.5% (51.5% decrease, range -2904% to +5%, p&lt; 0.001). Conclusions: We were able to demonstrate feasibility of using CTC as a biomarker of response in patients with EX-SCLC in clinical setting. CTC could be a useful biomarker in the management of SCLC to predict response to therapy.
SP0171 Sleep disturbances in primary sjÖgren’s syndrome: evidence from the literature, patient sleep diaries and a qualitative focus group study
Authors: K.L. Hackett
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Primary Sjögren's syndrome is a systemic autoimmune disease which targets secretory glands resulting in dryness. Extra-glandular features include fatigue, pain and sleep disturbances. There are few studies exploring the specific sleep disturbances experienced by PSS patients; the impact of these disturbances or the potential acceptability of interventions to address some of these problems. In this talk, I will present work which begins to map the landscape of sleep disturbances in PSS: Firstly, a systematic review of the literature explores sleep disturbances in PSS patients and identifies particular sleep symptoms which are problematic in these patients.<sup><sup>1</sup></sup> Secondly, I will explore the relationship between daytime sleepiness (hyper-somnolence) and other clinical parameters in patients recruited to the UK Primary Sjogren's Syndrome Registry. Thirdly, I will report on sleep diary data from 30 patients attending a multidisciplinary fatigue clinic in the North East of England. Finally, I will present findings from focus groups conducted with PSS patients and their partners. In this qualitative study, we explored the impact of sleep disturbances on patients and their families and potential acceptability of a non-pharmacological intervention (cognitive behavioural therapy for insomnia) to address specific sleep disturbances.<sup><sup>2</sup></sup> <h3>References</h3> [1] Hackett KL, Gotts ZM, Ellis J, Deary V, Rapley T, Ng W-F, Newton JL, Deane KHO. An investigation into the prevalence of sleep disturbances in primary Sjögren's syndrome: a systematic review of the literature. Rheumatology (Oxford). 2017;56(4):570–80. [2] Hackett KL, Deary V, Deane KHO, Newton JL, Ng W-F, Rapley T. Experience of sleep disruption in primary Sjögren's syndrome: A focus group study. British Journal of Occupational Therapy. 2018;0(0):0308022617745006. <h3>Disclosure of Interest</h3> None declared
AB0515 Spanish society of rheumatology (SER) recommendations on primary antiphospholipid syndrome (APS). in a patient with obstetric aps, which treatments are more effective? systematic review
Authors: H. Sánchez Pérez, M. Nishishinya Aquino, C. Pereda, P. Díaz del Campo Fontecha, M. Martínez Zamora
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Pregnancy complications and poor obstetric prognosis are part of the manifestations of APS. The obstetric APS (O-APS) includes 3 or more early miscarriages, 1 or more intrauterine foetal deaths, prematurity secondary to preeclampsia or placental insufficiency, intrauterine growth retardation and HELLP syndrome among others. There is disagreement among different published studies regarding the need of preconceptional or primary thromboprophylaxis (treating with anticoagulant/antiaggregant drugs in the presence of specific autoantibodies but without previous clinical events) and the most effective and safest drug to use, as well as which treatment should be chosen in the case of secondary thromboprophylaxis (treating in the presence of autoantibodies and recurrent miscarriages or previous obstetric complications). <h3>Objectives</h3> To evaluate the available scientific evidence on which treatments are the most effective and safest in O-APS. <h3>Methods</h3> A systematic review (SR) was performed to evaluate the efficacy and safety of different interventions (Aspirin (ASA), Heparin, Antimalarials, Immunoglobulin IV (IVIG), others) in pregnant women with O-APS. We included SR, randomised clinical trials (RCTs) and comparative cohort studies. Result measures on morbidity (prematurity, low birth weight, need for intensive care, impaired cognitive development, preeclampsia, eclampsia, HELLP, abruptio placentae) and mortality included both the newborn and the pregnant woman. A peer review selection and analysis of the studies was carried out (SP,H; NA, MB). <h3>Results</h3> 788 citations were identified (Medline, EMBASE, CENTRAL. May 2017). We included 17 studies: 5 SR, 5 RCTs and 7 cohort studies. Results are shown on the table 1 below: <h3>Conclusions</h3> In women with O-APS: <b>Secondary thromboprophylaxis:</b> The combination of ASA +Heparin is more effective than ASA monotherapy. With regards to the use of IVIG, corticosteroids and statins: NO representative conclusions can be drawn from published studies <b>Pre-conceptional thromboprophylaxis, primary thromboprophylaxis:</b> NO representative conclusions can be drawn from published studies. <h3>Acknowledgements</h3> <i>This review is part of the preparation of SER Recommendations on Primary APS treatment.</i> <h3>Disclosure of Interest</h3> None declared