tbuckley/cabot-search huggingface dataset:
Dupilumab improves health‐related quality of life in patients with chronic rhinosinusitis with nasal polyposis
Authors: Claus Bachert, Peter W. Hellings, Joaquim Mullol, Daniel L. Hamilos, Philippe Gevaert, Robert M. Naclerio, Vijay N. Joish, Jingdong Chao, Leda P. Mannent, Nikhil Amin, Adeline Abbe, Christine Taniou, Chunpeng Fan, Gianluca Pirozzi, Neil M. H. Graham, Puneet Mahajan, Heribert Staudinger, Asif Khan
Journal: Allergy (2019)

Abstract Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) negatively affects health‐related quality of life (HRQoL). In a previously reported randomized clinical trial (NCT01920893), addition of dupilumab to mometasone furoate in patients with CRSwNP refractory to intranasal corticosteroids (INCS) significantly improved endoscopic, radiographic, and clinical endpoints and patient‐reported outcomes. The objective of this analysis was to examine the impact of dupilumab treatment on HRQoL and productivity using secondary outcome data from this trial. Methods Following a 4‐week mometasone furoate nasal spray run‐in, patients were randomized to commence subcutaneous dupilumab (600 mg loading dose, then 300 mg once weekly for 15 weeks [n = 30], or matched placebo [n = 30]). Outcomes included scores on the CRS disease severity visual analog scale (VAS), 22‐item Sino‐Nasal Outcome Test (SNOT‐22), 5‐dimension EuroQoL (EQ‐5D) general health status VAS, and 36‐item Short‐Form Health Survey (SF‐36) for HRQoL and nasal polyp‐related healthcare resource use questionnaires. Results Following 16 weeks of treatment, the proportion of patients with moderate‐to‐severe CRSwNP (VAS &gt; 3‐10) decreased from 86.2% to 21.4% with dupilumab and 88.0% to 84.2% with placebo. Dupilumab (vs placebo) resulted in significantly greater improvement in HRQoL, based on SNOT‐22, SF‐36, and EQ‐5D VAS scores. The dupilumab group had a significantly lower adjusted annualized mean number of sick leave days (0.09, vs 4.18 with placebo, P = .015) and significantly greater improvement (vs placebo) in the SNOT‐22 item “reduced productivity.” Conclusions In adults with CRSwNP refractory to treatment with INCS alone, the addition of dupilumab reduced disease severity, significantly improved HRQoL, and improved productivity.
Crizotinib versus pemetrexed-based chemotherapy in patients with advanced ROS1-rearranged non-small cell lung cancer.
Authors: Lan Shen, Shun Lu
Journal: Journal of Clinical Oncology (2019)

9101 Background: ROS1 rearrangement is an important therapeutic target that occurs in approximately 1-2% of patients with non-small cell lung cancer (NSCLC). It has been shown that ROS1-rearranged patients could benefit from crizotinib treatment. However, the efficacy of crizotinib as compared with pemetrexed-based chemotherapy in such patients is unknown. Methods: Advanced ROS1-rearranged NSCLC patients receiving crizotinib or pemetrexed-based chemotherapy as first-line treatment in Shanghai Chest Hospital between August 2010 and December 2017 were retrospectively reviewed. Clinical characteristics, treatments and survival outcomes data were abstracted. Results: Of 77 patients included, 30 patients (39.0%) received crizotinib and 47 patients (61.0%) received pemetrexed-based chemotherapy as their first-line treatment. The median follow-up was 26.8 months. The objective response rate was significantly better with crizotinib than with pemetrexed-based therapy (86.7% vs 44.7%, P &lt; 0.001). The disease control rate wasc 96.7% with crizotinib, as compared with 85.1% with pemetrexed-based therapy (P = 0.140). The median progression-free survival was significantly longer with crizotinib versus pemetrexed-based therapy (18.4 months [95% confidence interval [CI]: 6.8-30.0] vs 8.6 months [95% CI:7.1-10.2], P &lt; 0.001). No significant difference in overall survival (OS) was observed between the two groups (Not reach vs 28.1 months [95% CI:18.7-38.5], P = 0.173). Six patients (20%) in the crizotinib group switched to pemetrexed-based therapy in subsequent lines, while twenty-nine patients (61.7%) in the chemotherapy group crossed over to receive crizotinib after progression. There was no significant difference in median OS between patients who received crizotinib first and those who received pemetrexed-based treatment prior to crizotinib (38.6 months [95% CI: 0-81.0] vs 32.7 months [95% CI:14.3-51.1], P = 0.890). Conclusions: Crizotinib is superior to pemetrexed-based chemotherapy as an initial treatment for advanced ROS1-rearranged NSCLC patients. The sequence of crizotinib treatment and pemetrexed-based chemotherapy does not influence OS.
Oral diseases: a global public health challenge
Authors: Marco A Peres, Lorna M D Macpherson, Robert J Weyant, Blánaid Daly, Renato Venturelli, Manu R Mathur, Stefan Listl, Roger Keller Celeste, Carol C Guarnizo-Herreño, Cristin Kearns, Habib Benzian, Paul Allison, Richard G Watt
Journal: The Lancet (2019)
In vivo ultrasound-activated delivery of recombinant tissue plasminogen activator from the cavity of sub-micrometric capsules
Authors: Clara Correa-Paz, María F. Navarro Poupard, Ester Polo, Manuel Rodríguez-Pérez, Pablo Taboada, Ramón Iglesias-Rey, Pablo Hervella, Tomás Sobrino, Denis Vivien, José Castillo, Pablo del Pino, Francisco Campos, Beatriz Pelaz
Journal: Journal of Controlled Release (2019)
A randomized pilot phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF-vaccine (CEA-vac) in patients (pts) with pancreatic adenocarcinoma (PC).
Authors: Daniel M. Geynisman, Yuanyuan Zha, Rangesh Kunnavakkam, Mebea Aklilu, Daniel Virgil Thomas Catenacci, Blase N. Polite, Cara Ann Rosenbaum, Azadeh Namakydoust, Theodore Karrison, Thomas Gajewski, Hedy Lee Kindler
Journal: Journal of Clinical Oncology (2012)

2561 Background: CEA is expressed in &gt;90% of PC and may be an appropriate immunotherapy target. CEA is poorly immunogenic due to immune tolerance; CAP1-6D, an altered peptide ligand can help bypass tolerance. We conducted a pilot randomized phase I trial in PC pts to determine the appropriate CEA-vac peptide dose required to induce an optimal cytotoxic T lymphocyte (CTL) response. Methods: Eligible pts, PS 0-1, expressed HLA-A2 and had CEA-expressing, histologically-confirmed, previously-treated PC. Randomization: 10 μg (arm A), 100 μg (arm B) or 1000 μg (arm C). CEA-vac was given Q 2 weeks until disease progression (amended 4/09 to a 24 dose maximum). Results: From 2/06-9/09 66 pts were screened for HLA-A2; 19 pts randomized to Arms A/B/C 5/8/6 are evaluable for toxicity; 14 pts (5/5/4) who received at least 3 doses of CEA-vac are evaluable for the primary immunologic endpoint. Median age: 60 (range 27-86), female: 68%, PS 0: 58%. Disease stage: metastatic (M) 74%, locally advanced (LA) 5%, resected (R) 21%. Cycles: median 4 (range 1-81). Mean CTL response by ELISPOT (spots per 10 4 CD8 + cells, Arm A/B/C): 37/126/248. (A vs. C, p=0.037). CTL responses developed in 20%/60%/100% of pts in Arms A/B/C. 1 LA pt in Arm C had a complete radiologic response, a strong CTL response, and remains alive at 71 mo. 1 M pt in Arm B had SD for 11 mo, a strong CTL response, and is alive at 39 mo. Toxicity: no grade 3/4 toxicities, 58% grade 1/2 skin toxicity. Conclusions: CTL response was dose-dependent in this randomized phase I trial; the 1 mg peptide dose elicited the most robust CTL response. Clinical activity was demonstrated at the higher doses. Further evaluation of 1 mg CEA-vac with stronger adjuvants, combined with agents to overcome immune inhibitory pathways, may be warranted in PC pts. Supported by UCCCSG P30CA14599.
Characterisation of infectious Ebola virus from the ongoing outbreak to guide response activities in the Democratic Republic of the Congo: a phylogenetic and in vitro analysis
Authors: Laura K McMullan, Mike Flint, Ayan Chakrabarti, Lisa Guerrero, Michael K Lo, Danielle Porter, Stuart T Nichol, Christina F Spiropoulou, César Albariño
Journal: The Lancet Infectious Diseases (2019)
Patient reported toxicities: Development and validation of patient-reported symptom measure for lung cancer patients receiving immunotherapy.
Authors: Sandra S. Shaw, Heather S.L. Jim, Sarah Eisel, Aasha Hoogland, David LeDuc, Adam P. Dicker
Journal: Journal of Clinical Oncology (2019)

93 Background: There is increasing clinical and research interest in patient-reported outcomes (PROs) which provide unique and complementary information to provider-rated adverse events. While several studies have been published of PROs in lung cancer patients receiving immune checkpoint blockade, to our knowledge all have focused on PROs collected as part of a clinical trial. This interim analysis describes PROs outside the context of a clinical trial. Methods: The Addario Lung Cancer Foundation (ALCF) international patient registry was used to collect patient-reported clinical and PRO information. Patients who reported current or past treatment with an FDA-approved immune checkpoint inhibitor were asked to complete a second survey of symptomatic toxicities of these therapies. Patients rated 40 symptoms on a five-point scale. The Charlson Comorbidity Index and Functional Assessment of Cancer Therapy General (FACT-G) were administered to assess comorbidities and quality of life, respectively. Results: A total of 116 patients (mean age 61, 75% female) who reported treatment with nivolumab (52%) or pembrolizumab (47%) were included in analyses. The majority of patients (70%) had been treated for 6 months or less. The most commonly reported symptoms were fatigue (72%), aching joints (52%), aching muscles (35%), insomnia (34%), back pain (30%), itching (27%), bone pain (26%), and skin dryness (25%). A total of 26% of patients had experienced a treatment delay, 10% had been to the emergency room, and 6% had been hospitalized due to toxicity. Participants reported a mean score of 75.88 (SD=17.59) on the FACT-G, significantly lower than previously-published normative data for cancer patients. Conclusions: This study is among the first to evaluate patient-reported toxicities of immune checkpoint inhibitor outside the context of a clinical trial. Results from this interim analysis indicate patient reported toxicities of immune checkpoint inhibitors are common in lung cancer patients. Additional research is needed to better understand the longitudinal course of symptomatic toxicities. Acknowledgements: ALCF, IASLC, American Lung Association.
Dynactin1 depletion leads to neuromuscular synapse instability and functional abnormalities
Authors: Valérie Bercier, Jeffrey M. Hubbard, Kevin Fidelin, Karine Duroure, Thomas O. Auer, Céline Revenu, Claire Wyart, Filippo Del Bene
Journal: Molecular Neurodegeneration (2019)

Dynactin subunit 1 is the largest subunit of the dynactin complex, an activator of the molecular motor protein complex dynein. Reduced levels of DCTN1 mRNA and protein have been found in sporadic amyotrophic lateral sclerosis (ALS) patients, and mutations have been associated with disease, but the role of this protein in disease pathogenesis is still unknown.We characterized a Dynactin1a depletion model in the zebrafish embryo and combined in vivo molecular analysis of primary motor neuron development with live in vivo axonal transport assays in single cells to investigate ALS-related defects. To probe neuromuscular junction (NMJ) function and organization we performed paired motor neuron-muscle electrophysiological recordings and GCaMP calcium imaging in live, intact larvae, and the synapse structure was investigated by electron microscopy.Here we show that Dynactin1a depletion is sufficient to induce defects in the development of spinal cord motor neurons and in the function of the NMJ. We observe synapse instability, impaired growth of primary motor neurons, and higher failure rates of action potentials at the NMJ. In addition, the embryos display locomotion defects consistent with NMJ dysfunction. Rescue of the observed phenotype by overexpression of wild-type human DCTN1-GFP indicates a cell-autonomous mechanism. Synaptic accumulation of DCTN1-GFP, as well as ultrastructural analysis of NMJ synapses exhibiting wider synaptic clefts, support a local role for Dynactin1a in synaptic function. Furthermore, live in vivo analysis of axonal transport and cytoskeleton dynamics in primary motor neurons show that the phenotype reported here is independent of modulation of these processes.Our study reveals a novel role for Dynactin1 in ALS pathogenesis, where it acts cell-autonomously to promote motor neuron synapse stability independently of dynein-mediated axonal transport.
Controlling faecal incontinence in women by performing anal exercises with biofeedback or loperamide: a randomised clinical trial
Authors: J Eric Jelovsek, Alayne D Markland, William E Whitehead, Matthew D Barber, Diane K Newman, Rebecca G Rogers, Keisha Dyer, Anthony G Visco, Gary Sutkin, Halina M Zyczynski, Benjamin Carper, Susan F Meikle, Vivian W Sung, Marie G Gantz, John Eric Jelovsek, Mathew D. Barber, Marie Fidela R. Paraiso, Mark D. Walters, Beri Ridgeway, Brooke Gurland, Massarat Zutshi, Geetha Krishnan, Ly Pung, Annette Graham, Vivian W. Sung, Deborah L. Myers, Charles R. Rardin, Cassandra Carberry, B. Star Hampton, Kyle Wohlrab, Ann S. Meers, Anthony Visco, Cindy Amundsen, Alison Weidner, Nazema Siddiqui, Amie Kawasaki, Shantae McLean, Nicole Longoria, Jessica Carrington, Niti Mehta, Ingrid Harm-Ernandes, Jennifer Maddocks, Amy Pannullo, Alayne Markland, Holly E. Richter, R. Edward Varner, Robert Holley, L. Keith Lloyd, Tracy S. Wilson, Alicia Ballard, Jeannine McCormick, Velria Willis, Nancy Saxon, Kathy Carter, Susan Meikle, Charles Nager, Michael Albo, Emily Lukacz, Cindy Furey, Patricia Riley, JoAnn Columbo, Sherella Johnson, Shawn Menefee, Karl Luber, Keisha Dyer, Gouri Diwadkar, Jasmine Tan-Kim, Rebecca G. Rogers, Yuko Komesu, Gena Dunivan, Peter Jeppson, Sara Cichowski, Christy Miller, Erin Yane, Julia Middendorf, Risela Nava, Marie G. Gantz, Dennis Wallace, Amanda Shaffer, Poonam Pande, Kelly Roney, Benjamin Carper, Ryan E. Whitworth, Lauren Klein Warren, Kevin A. Wilson, Brenda Hair, Kendra Glass, Daryl Matthews, James W. Pickett, Yan Tang, Tamara L. Terry, Lynda Tatum, Barbara Bibb, Jutta Thornberry, Kristin Zaterka-Baxter, Lindsay Morris, Lily Arya, Ariana Smith, Heidi Harve, Uduak Umoh Andy, Pamela Levin, Diane K. Newman, Mary Wang, Donna Thompson, Teresa Carney, Michelle Kingslee, Lorraine Flick, Halina M. Zyczynski, Pam Moalli, Gary Sutkin, Jonathan Shepherd, Michael Bonidie, Steven Abo, Janet Harrison, Christopher Chermansky, Lori Geraci, Judy Gruss, Karen Mislanovich, Ellen Eline, Beth Klump, Susan E. George, William E. Whitehead, Kay Dickersin, Luohua Jiang, Missy Lavender, Kate O'Dell, Kate Ryan, Paul Tulikangas, Lan Kong, Donna McClish, Leslie Rickey, David Shade, Ashok Tuteja, Susan Yount
Journal: The Lancet. Gastroenterology & hepatology (2019)
Does facility birth reduce maternal and perinatal mortality in Brong Ahafo, Ghana? A secondary analysis using data on 119 244 pregnancies from two cluster-randomised controlled trials
Authors: Sabine Gabrysch, Robin C Nesbitt, Anja Schoeps, Lisa Hurt, Seyi Soremekun, Karen Edmond, Alexander Manu, Terhi J Lohela, Samuel Danso, Keith Tomlin, Betty Kirkwood, Oona M R Campbell
Journal: The Lancet Global Health (2019)

Maternal and perinatal mortality are still unacceptably high in many countries despite steep increases in facility birth. The evidence that childbirth in facilities reduces mortality is weak, mainly because of the scarcity of robust study designs and data. We aimed to assess this link by quantifying the influence of major determinants of facility birth (cluster-level facility birth, wealth, education, and distance to childbirth care) on several mortality outcomes, while also considering quality of care.
Leonard L Bailey: in 1984 he transplanted a baboon heart into a human infant known as “Baby Fae”
Authors: Ned Stafford
Journal: BMJ (2019)

Credit: Loma Linda-PR

On the morning of 26 October 1984, Leonard L Bailey and his heart transplantation team were gathered around an operating table at Loma Linda University Medical Center in California. They were operating on Stephanie Fae Beauclair, a baby girl who had been born prematurely only 12 days before with hypoplastic left heart syndrome, a fatal defect.

Shortly after 9 am—around an hour and 45 minutes into the operation, with Stephanie’ s body temperature lowered to 68°F—Bailey went to the hospital’ s research laboratory, where an anaesthetised 7 month old female baboon awaited. Bailey removed the baboon’s walnut sized heart, placed it in a container of icy saline slush, and returned to the surgical suite.1

“I arrived with the heart,” Bailey recalled in a 2007 interview. “We made the incision, and went to work.”2 Bailey removed Stephanie’s defective heart. After inserting the new heart and connecting it, Stephanie’s chest cavity was closed and her body temperature slowly increased. “We were blessed,” Bailey said. “It just turned out beautifully. Her response to the surgery was just perfect.”2

At 1135 am, Stephanie’s new heart began to beat.

“There was absolute awe,” Sandra Nehlsen-Cannarella, an immunologist on Bailey’s team, said at the time. “I don’t think there was a dry eye in the room.”

The heart transplantation turned out to be one of the most controversial procedures in the history of medicine. News of the transplantation triggered headlines around the world. Animal rights groups were outraged at the “ghoulish tinkering” with human and animal life. Bailey received threatening hate mail. Around 275 journalists, including TV news crews, converged on Loma Linda University.

To protect Stephanie’s privacy, the university identified her only as Baby Fae and declined to name her parents. Only years later were they publicly identified.

The medical community was …
Mortality has improved in RA, but we must remain vigilant. Response to: ‘Early intensive treatment normalises excess mortality in ACPA-negative RA but not in ACPA-positive RA’ by Matthijssen <i>et al</i>
Authors: Pomme B M Poppelaars, Lilian H D van Tuyl, Maarten Boers
Journal: Annals of the Rheumatic Diseases (2019)

We compliment Matthijssen et al with this highly interesting analysis and results from the Leiden Early Arthritis Clinic. Their mortality results strongly support our findings1 and again emphasise that the focus should be on the excess mortality that emerges after 10 years. Their data also suggest anti-CCP antibody (ACPA) is a strongly predictive factor for mortality.

The COBRA trial was performed before ACPA testing became available; however, we did run exploratory analyses on several prognostic factors, including rheumatoid factor which can be seen as a partial proxy for ACPA, and …
Multiparametric MRI for prostate cancer diagnosis: current status and future directions
Authors: Armando Stabile, Francesco Giganti, Andrew B. Rosenkrantz, Samir S. Taneja, Geert Villeirs, Inderbir S. Gill, Clare Allen, Mark Emberton, Caroline M. Moore, Veeru Kasivisvanathan
Journal: Nature Reviews Urology (2019)
The Gamma Globulins
Authors: Charles A. Janeway, Fred S. Rosen
Journal: New England Journal of Medicine (1966)

THE work of Cohn and his colleagues in the 1940's made feasible large-scale fractionation of serum proteins by precipitation with ethanol under carefully controlled conditions in the cold. Cohn Fraction II contains principally the serum γG globulin and only trace amounts of γA and γM globulins. It is commercially available as a 16.5 per cent slightly opalescent, colorless solution when prepared from ordinary plasma and with a brownish color when prepared from placental blood. The solution contains glycine and merthiolate as stabilizer and preservative. Gamma globulin is also distributed by the American Red Cross and is available through many state . . .
Reducing childhood respiratory morbidity and mortality in low and middle income countries: a current challenge
Authors: Cristina Ardura-Garcia, Claudia E. Kuehni
Journal: European Respiratory Journal (2019)

Pneumonia is a major cause of death of children in low and middle income countries (LMICs). In this issue of the European Respiratory Journal , Nguyen et al . [1] examine pneumonia care in a large secondary care hospital in Vietnam and compare it to World Health Organization (WHO) case management guidelines. This carefully conducted prospective study highlights the weaknesses of the WHO approach, which leads to overdiagnosis of pneumonia with unnecessary hospitalisations and antibiotic use, and underdiagnosis of obstructive airway diseases. Pneumonia overdiagnosis and asthma underdiagnosis in children should be addressed together in low resource settings <http://bit.ly/2XPvega> We thank Christopher Ritter (Institute of Social and Preventive Medicine, University of Bern, Switzerland) for his editorial assistance.
Early Effects of an Accountable Care Organization Model for Underserved Areas
Authors: Matthew J. Trombley, Betty Fout, Sasha Brodsky, J. Michael McWilliams, David J. Nyweide, Brant Morefield
Journal: New England Journal of Medicine (2019)

The Centers for Medicare and Medicaid Services (CMS) developed the Accountable Care Organization (ACO) Investment Model (AIM) to encourage the growth of Medicare Shared Savings Program (MSSP) ACOs in rural and underserved areas. AIM provides financial support to eligible MSSP ACOs by means of prepayment of shared savings. Estimation of the performance of AIM ACOs on measures of spending and utilization in their first performance year would be useful for understanding the viability of ACOs located in these areas.We analyzed Medicare claims and enrollment data for a group of fee-for-service beneficiaries who had been attributed to 41 AIM ACOs and for a comparable group of beneficiaries who resided in the ACO markets but were served primarily by non-ACO providers. We used a difference-in-differences study design to compare changes in outcomes from the baseline period (2013 through 2015) to the performance period (2016) among beneficiaries attributed to AIM ACOs with concurrent changes among beneficiaries in the comparison group. The primary outcome of interest was total Medicare Part A and B spending.Provider participation in AIM was associated with a differential reduction in total Medicare spending of $28.21 per beneficiary per month relative to the comparison group, which amounted to an aggregate decrease of $131.0 million. Over the same period, CMS made $76.2 million in prepayments and paid an additional $6.2 million in shared savings to ACOs in which shared savings exceeded the prepayments. After we accounted for this $82.4 million in CMS spending, the aggregate net reduction was $48.6 million, which corresponded to a net reduction of $10.46 per beneficiary per month. Decreases in the number of hospitalizations and use of institutional post-acute care contributed to the observed reduction in overall spending.With up-front investments, participation in ACO shared savings contracts by providers serving rural and underserved areas was associated with lower Medicare spending than that among non-ACO providers. (Funded by the Centers for Medicare and Medicaid Services.).
Hidradenitis Suppurativa Area and Severity Index ( <scp>HASI</scp> ): a pilot study to develop a novel instrument to measure the physical signs of hidradenitis suppurativa
Authors: N. Goldfarb, J.R. Ingram, G.B.E. Jemec, H.B. Naik, V. Piguet, M.J. Hyde, R. Freese, M.A. Lowes, A. Alavi
Journal: British Journal of Dermatology (2019)

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The potential of genomics for restoring ecosystems and biodiversity
Authors: Martin F. Breed, Peter A. Harrison, Colette Blyth, Margaret Byrne, Virginie Gaget, Nicholas J. C. Gellie, Scott V. C. Groom, Riley Hodgson, Jacob G. Mills, Thomas A. A. Prowse, Dorothy A. Steane, Jakki J. Mohr
Journal: Nature Reviews Genetics (2019)