tbuckley/cabot-search huggingface dataset:
Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis
Authors: Cosima Locher, Joe Kossowsky, Helen Koechlin, Thanh Lan Lam, Johannes Barthel, Charles B Berde, Jens Gaab, Guido Schwarzer, Klaus Linde, Karin Meissner
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking. <h3>Objective</h3> To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability. <h3>Data Sources</h3> Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018. <h3>Study Selection</h3> Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers. <h3>Data Extraction and Synthesis</h3> Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model. <h3>Main Outcomes and Measures</h3> Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason). <h3>Results</h3> Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (&lt;5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention. <h3>Conclusions and Relevance</h3> Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.
Single institution experience with peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET).
Authors: Heying Duan, Gaia Ninatti, Bradley Girod, Valentina Ferri, Pamela L. Kunz, George A. Fisher, Farshad Moradi, Guido Alejandro Davidzon, Benjamin Lewis Franc, Andrei Iagaru, Carina Mari
Journal: Journal of Clinical Oncology (2020)

623 Background: Neuroendocrine tumors (NETs) are rare but increasing in incidence. The only curative treatment is surgery, which in many cases is not an option due to metastatic disease at diagnosis. The NETTER-1 study showed high efficacy and low toxicity of peptide receptor radionuclide therapy (PRRT) for midgut NETs. Here, we present our initial experience with PRRT in the treatment of patients with NET. Methods: Fifty-two patients (27 males and 25 females; 37 - 81 yo, mean ± SD: 61.8 ± 10.6 years) with documented progressive NET (25 pancreas, 17 small intestine, 1 coecum, 4 unknown primary, 3 paragangliomas, and 2 pheochromocytomas) were referred to undergo PRRT at our institution from July 2018 to September 2019. Laboratory tests were obtained at baseline, 1 week before each cycle and every 3 months following treatment. Progression-free survival (PFS), objective response rate (ORR) and toxicity were assessed. An interim overall survival (OS) analysis was performed. Results, when possible, were compared with the NETTER-1 trial. Lines of therapy were documented. Results: 22/52 (42%) patients completed all 4 cycles of PRRT. 18/52 (34%) patients are currently being treated. 12/52 (23%) patients had to discontinue treatment. Hematotoxicity was the only side effect which can be related to PRRT. The 6-month and 9-month PFS rate was 82.4% and 66.8% respectively vs. 89% and 84% in the NETTER-1 trial. The ORR was 36% vs. 18% in the NETTER-1 trial. In the interim OS analysis, 6 deaths occurred. In contrast to the NETTER-1 study, PRRT in our patient cohort was performed later in the course of treatment (median lines of therapy before PRRT = 4 ±1.3 (range 1-6)). Conclusions: Our preliminary data show overall good results of PRRT in patients with NETs. However, compared to the NETTER-1 trial, PFS is shorter which is most likely due to the extensive pretreatment, but ORR was higher. [Table: see text]
Using Uniocular Visual Acuity Substantially Underestimates the Impact of Visual Impairment on Quality of Life Compared with Binocular Visual Acuity
Authors: Ryan Eyn Kidd Man, Alfred Tau Liang Gan, Eva K. Fenwick, Sahil Thakur, Preeti Gupta, Zhen Ling Teo, Ching-Yu Cheng, Tien Yin Wong, Ecosse L. Lamoureux
Journal: Ophthalmology (2020)
Prognostic implications of biopsy with tumor transection for patients with high-risk primary melanoma
Authors: Lena A. von Schuckmann, Kiarash Khosrotehrani, Maria Celia B. Hughes, Jolieke C. van der Pols, Maryrose Malt, B. Mark Smithers, Adele C. Green
Journal: Journal of the American Academy of Dermatology (2020)
Sexual health: government “should set clear targets” to tackle rising number of STIs in England
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The UK government must implement a new national strategy for tackling sexually transmitted infections (STIs) with clear targets for reducing rates, experts have urged.

In a report published on 5 February,1 the Terrence Higgins Trust and the British Association for Sexual Health & HIV said that “brutal” funding cuts and inaction by the government had led to cases of many STIs soaring in the past decade, during which time rates of gonorrhoea rose by 249% and rates of syphilis rose by 165%, reaching their highest level since the second world war.

In …
Survival outcomes of pancreatic intraepithelial neoplasm (PanIN) versus intraductal papillary mucinous neoplasm (IPMN) associated pancreatic adenocarcinoma.
Authors: Timothy McGinnis, Leonidas Bantis, Rashna Madan, Prasad Dandawate, Sean Kumer, Timothy Schmitt, Ravi Kumar Paluri, Anwaar Saeed, Anup Kasi
Journal: Journal of Clinical Oncology (2020)

766 Background: Pancreatic intraepithelial neoplasms (PanINs) and intraductal papillary mucinous neoplasms (IPMNs) are common pancreatic adenocarcinoma precursor lesions. However, data regarding their respective associations with prognosis is lacking. Methods: We retrospectively evaluated 72 resected pancreatic adenocarcinoma cases at the KU Cancer Center between Aug 2009 and March 2019. Patients were divided into either one of two groups, PanIN or IPMN, based on the results of the surgical path report. We compared baseline characteristics, overall and progression free survival between the two groups, as well as OS and PFS based on local or distant tumor recurrence. Results: 52 patients had PanIN and 20 patients had IPMN. Demographic and baseline characteristics are as follows (PanIN/IPMN): Median age 62.5/69; Gender (male) 63%/65%; ECOG status (0-1) 98%/85%; pancreatic head tumors 87%/70%; pancreatic body tumors 6%/15%; pancreatic tail tumors 7%/15%; Abnormal CA19-9 at diagnosis 79%/67%; Comorbidity Index 5/5 respectively. Median PFS was 26.2 months (95% CI: 21.4-31.0) for PanIN and 74.3 months (95% CI: 15.7-132.9) for IPMN [p = 0.004]. Median OS was 70.3 months (95% CI: 35.4-105.2) for PanIN and 78.8 months (95% CI: 33.2-124.4) for IPMN [p = 0.013]. Within the PanIN group, median OS after recurrence was 71.3 months (95% CI: 68.8.-73.4) for local recurrence and 46.7 months (95% CI: 39.2-54.2) for distant recurrence [p = 0.330]. Conclusions: Patients who had a IPMN associated pancreatic cancer had better PFS and OS when compared to patients with PanIN associated pancreatic cancer. In patients with PanIN associated cancer that recurred, OS was better with local recurrence compared to distant recurrence but did not meet statistical significance. The results need to be validated in a larger cohort. [Table: see text]
Molecular genetic changes in solid pseudopapillary neoplasms (SPN) of the pancreas.
Authors: Elisa M. Rodriguez-Matta, Gerardo Colon-Otero, Amanda Hemmerich, Eric Allan Severson
Journal: Journal of Clinical Oncology (2020)

749 Background: Solid Pseudopapillary Neoplasms (SPNs) of the pancreas are rare accounting for 1-2% of all pancreatic tumors. Previous studies had shown that a pathogenic mutation of the CTNNB1 gene is present in over 90% of the SPN tumors with very limited information available on the specific molecular changes present in SPN. Here we report the results of next generation genetic testing of a large series of SPN tumors from the Foundation Medicine database. Methods: Foundation Medicine database from 07/2012 to 04/2019 was reviewed. A total of 31 cases of SPN tumors were identified out of 12,892 cases of pancreatic cancers. Information collected included demographic information on the patients as well as tumor analysis for next generation genetic sequencing of 315 genes associated with cancer with FoundationOne or 324 genes associated with FoundationOneCDx. Microsatellite stability status and tumor mutation burden were determined. Results: Twenty nine out of 31 cases (93%) had a CTNNB1 mutation. Seventy percent of the CTNNB1 mutations were on position 32 (14 cases, 41%) or in position 37 (9 cases, 29%). Other sites of CTNNB1 mutations included position 34 (3 cases, 9.6%), position 2 (2 cases, 6.4%) and position 38 (1 case, 3.2%). Two cases did not have a CTNNB1 mutation, one had a CDKN2A mutation and the other had no detectable mutations. Most cases had additional mutations aside from the CTNNB1, the most common were TP53 (3 cases, 9.6%) and LRP1B (2 cases, 6.4%). Other accompanying mutations were seen just once. Twenty-five percent of these cases had actionable gene mutations, each found in one case including: MSH2, BRCA2, ATM, XRCC3, ATRX, PTEN, ESR1, CDKN2, and PIK3CA. Conclusions: Next generation genetic testing of SPN tumors is of clinical benefit since it identifies actionable mutations in 29% of the cases.
Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.
Authors: David James Pinato, Ahmed Omar Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Abdul Rafeh Naqash, ChiehJu Lee, Uqba Khan, Neil Satish Nimkar, Sonal Paul, Dominik Bettinger, Hannah Hildebrand, Tiziana Pressiani, Yehia I. Abugabal, Nicola Personeni, Yi-Hsiang Huang, Lorenza Rimassa, Celina Ang, Thomas Urban Marron
Journal: Journal of Clinical Oncology (2020)

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received &gt;10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p&gt;0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.
Executive summary: surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children
Authors: Scott L. Weiss, Mark J. Peters, Waleed Alhazzani, Michael S. D. Agus, Heidi R. Flori, David P. Inwald, Simon Nadel, Luregn J. Schlapbach, Robert C. Tasker, Andrew C. Argent, Joe Brierley, Joseph Carcillo, Enitan D. Carrol, Christopher L. Carroll, Ira M. Cheifetz, Karen Choong, Jeffry J. Cies, Andrea T. Cruz, Daniele De Luca, Akash Deep, Saul N. Faust, Claudio Flauzino De Oliveira, Mark W. Hall, Paul Ishimine, Etienne Javouhey, Koen F. M. Joosten, Poonam Joshi, Oliver Karam, Martin C. J. Kneyber, Joris Lemson, Graeme MacLaren, Nilesh M. Mehta, Morten Hylander Møller, Christopher J. L. Newth, Trung C. Nguyen, Akira Nishisaki, Mark E. Nunnally, Margaret M. Parker, Raina M. Paul, Adrienne G. Randolph, Suchitra Ranjit, Lewis H. Romer, Halden F. Scott, Lyvonne N. Tume, Judy T. Verger, Eric A. Williams, Joshua Wolf, Hector R. Wong, Jerry J. Zimmerman, Niranjan Kissoon, Pierre Tissieres
Journal: Intensive Care Medicine (2020)
A new laboratory test to help diagnose a specific type of pemphigoid
Authors: F. Giurdanella, A.M. Nijenhuis, G.F.H. Diercks, M.F. Jonkman, H.H. Pas
Journal: British Journal of Dermatology (2020)

An autoimmune disease is a condition where the body sees one of its own proteins as foreign and will try to destroy it. There are various types of autoimmune diseases and one rare form is anti-laminin-332 mucous membrane pemphigoid, a severe chronic disease which causes blistering of the mucous membranes in the mouth, eyes, nose and airways, the oesophagus and the genital region. The disease is characterized by IgG (antibodies) which attack a protein called laminin-332 that is essential for an intact skin. Binding of IgG to laminin-332 results in inflammation, forming erosions and blisters. There are other forms of mucous membrane pemphigoid that look similar and diagnosis is therefore difficult. A commercial laboratory test that can find the antibodies in the blood is not available. In this study from the Netherlands, the authors developed a simple and specific method to detect the IgG against laminin-332, called keratinocyte footprint assay. They cultured (meaning grew in a lab) keratinocytes, which are the main cells of skin, on small glass disks. In culture, cells move over the glass and thereby, like slugs, leave behind a trail. These trails contain laminin-332. After culture the glass disks are air dried and stored in a freezer. When a diagnosis of anti-laminin-332 is suspected a disk is taken out and serum (part of the blood) of the patient is brought onto the disk. If IgG to laminin-332 is present this will bind to the trails. After an hour the disks are rinsed and a fluorescent substance that binds to IgG is put onto the disk. The disks are then investigated under a fluorescent microscope and if the trails are fluorescent, that is proof that the patient has anti-laminin-332 antibodies. Comparing blood samples of healthy persons and patients with other autoimmune diseases showed that this method is very specific and sensitive, meaning it is accurate. This summary relates to the study: Keratinocyte footprint assay discriminates antilaminin-332 pemphigoid from all other forms of pemphigoid diseases
Pasireotide and Corticosteroids for Prevention of Pancreatic Fistula—Over-HYPed?
Authors: Fabio Casciani, Charles M. Vollmer
Journal: JAMA Surgery (2020)

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Efficacy of chemotherapy for patients with unresectable or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.
Authors: Yukio Yoshida, Akira Fukutomi, Makoto Ueno, Keita Mori, Kazuo Watanabe, Akihiro Ohba, Satoshi Kobayashi, Mitsuhiro Furuta, Akiko Tsujimoto, Masato Osaka, Naohiro Okano, Kei Yane, Kumiko Umemoto, Yasuyuki Kawamoto, Takeshi Terashima, Hidetaka Tsumura, Keitaro Doi, Kazuhiko Shioji, Akinori Asagi, Junji Furuse
Journal: Journal of Clinical Oncology (2020)

647 Background: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). Although unresectable or recurrent PASC is usually treated by systemic chemotherapy, there are few reports which show the efficacy of chemotherapy. The aim of this study was to evaluate the efficacy of chemotherapy for patients (pts) with unresectable or recurrent PASC. Methods: We collected data retrospectively from 24 Japanese institutions. The selection criteria were as follows: 1) histologically or cytologically proven PASC (non-surgical specimens were eligible if squamous cell carcinoma (SCC) was detected), 2) unresectable or recurrent disease treated with 1st line chemotherapy between April 2001 and December 2017. Results: This study included 138 pts with median age of 66 years (range: 36-85). About 60% of pts were diagnosed with biopsy and only SCC was detected in 13.0% of pts. Median overall survival (mOS) was 6.7 months (M), median progression free survival (mPFS) was 2.8 M, and the 1-year survival rate (1YSR) was 26.7%. For the 102 metastatic or distal recurrent pts with PS of 0-1, patient characteristics were as follows: ≥76 years old, 9 (8.8%); PS of 0, 39 (38.2%); number of metastatic sites ≥2, 25 (24.5%). The treatment efficacies (The objective response rates(%)/mPFS(M)/mOS(M)/1YSR(%)) of the 5 major regimens were Gemcitabine(GEM) (n=45, 4.4%/2.2M/4.8M/28.1%), GEM+nab-PTX (n=24, 29.2%/2.9M/7.6M/23.1%), GEM+S-1 (n=9, 11.1%/5.1M/9.9M/25.4%), FOLFIRINOX (n=7, 14.3%/2.5M/7.5M/14.3%), and S-1 (n=7; 28.6%/2.6M/5.0M/28.6%), respectively. One patient with liver metastasis underwent conversion surgery after GEM+nab-PTX and achieved long survival. CRP ≥3.0mg/dl, CA19-9 ≥1000 U/ml, residual primary site, and monotherapy had a significant correlation with poor survival in multivariate analysis. Conclusions: Although combination chemotherapy regimens such as FOLFIRINOX and GEM+nab-PTX are now available, the prognosis of metastatic PASC remains poor. Development of more effective treatment options is required.
Implementation of an EMR integrated pathway for the management of malignant bowel obstruction.
Authors: Darryl Schuitevoerder, Charles Christian Vining, Michael White, Claire Hoppenot, Isabel Lazo, Scott K. Sherman, Alaine Kamm, Luz Chavez, Pujitha Kallakuri, Emily Fenton, Joshua Male, Sandy Tun, Osmanuddin Ahmed, Carol Semrad, Dragana Radovanovic, Oliver Eng, Dejan Micic, Nita Karnik Lee, Blase N. Polite, Kiran Turaga
Journal: Journal of Clinical Oncology (2020)

813 Background: Despite published evidence based interventions for malignant bowel obstruction (MBO), implementation of a standard pathway is challenging. We hypothesized that using industrial engineering techniques and a modified dynamic sustainability framework for implementation, we can implement an electronic medical record (EMR) based pathway in the management of MBO. Methods: A workflow in the management of MBO was developed using iterative meetings from 8/2018 to 4/2019 including gateway stakeholders (surgical oncology, gynecological oncology and medical oncology), interventional stakeholders (gastroenterology, interventional radiology) and supportive stakeholders (hospital medicine, palliative care, nutrition, nursing). Industrial engineers were utilized to study human factors, and perform a method study. EMR integration was performed using EPIC systems Agile MD pathway and educational materials were created. Interventions such as early placement of gastrostomy tubes, total parenteral nutrition and medications were protocolized. Results: Since implementation, over 6 months the pathway and order set has been activated 56 times. Orders have been employed 21 times through the AgileMD pathway demonstrating a pathway drift of 62.5%. Educational materials have been accessed routinely during this time. Conclusions: Feasibility of implementing an EMR integrated MBO pathway is demonstrated with early suggestion of pathway drift. Utilizing tools of implementation science are necessary to facilitate widespread adoption of evidence based interventions in the management of patients with MBO.
Temporomandibular joint damage in K/BxN arthritic mice
Authors: Sabine Kuchler-Bopp, Alexandre Mariotte, Marion Strub, Chrystelle Po, Aurore De Cauwer, Georg Schulz, Xavier Van Bellinghen, Florence Fioretti, François Clauss, Philippe Georgel, Nadia Benkirane-Jessel, Fabien Bornert
Journal: International Journal of Oral Science (2020)

Abstract Rheumatoid arthritis (RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/BxN mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint (TMJ) inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging (μMRI) and micro-computed tomography (μCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/BxN animals, which was also evidenced by μCT but was less pronounced than that seen in the knee joints. μMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes (FLSs) isolated from the TMJ of K/BxN mice secreted inflammatory cytokines (IL-6 and IL-1β) and expressed degradative mediators such as matrix metalloproteinases (MMPs). K/BxN mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.