tbuckley/cabot-search huggingface dataset:
Drug Shortages and Group Purchasing Organizations—Reply
Authors: Julie M. Donohue, Inmaculada Hernandez, Tina Batra Hershey
Journal: JAMA (2020)

In Reply We agree with Ms Calleja that GPOs play an important role in the supply of health care products, including pharmaceuticals. The need for a high-functioning supply chain for health care products has never been more salient than now, during the coronavirus disease 2019 (COVID-19) pandemic.
Making ordinary decisions in extraordinary times
Authors: Rachel Burman, Ruth Cairns, Sergio Canestrini, Robert Elias, Victoria Metaxa, Gareth Owen, Hazel Polat, Alex Ruck Keene, Emer Sutherland
Journal: BMJ (2020)

<b>Members of a covid-19 ethics working group</b> at a large London teaching hospital argue that a lack of detail in national decision support guidelines led to fear driven anticipatory triage during the first wave of the pandemic
Authors’ response: importance of a careful investigation to avoid attributing Legionnaires’ disease cases to an incorrect source of infection
Authors: Claudia Palazzolo, Gaetano Maffongelli, Alessandra D’Abramo, Luciana Lepore, Andrea Mariano, Antonella Vulcano, Tommaso Ascoli Bartoli, Nazario Bevilacqua, Maria Letizia Giancola, Enrico Di Rosa, Emanuele Nicastri
Journal: Eurosurveillance (2020)

Preview this article: Authors’ response: importance of a careful investigation to avoid attributing Legionnaires’ disease cases to an incorrect source of infection, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/25/34/eurosurv-25-34-5-1.gif
Case 27-2020: A 53-Year-Old Woman with Headache and Gait Imbalance
Authors: Geoffrey S. Gottlieb, Jacob M. Rosenberg, R. Gilberto Gonzalez, Rajesh T. Gandhi
Journal: New England Journal of Medicine (2020)

A 53-year-old woman presented with progressive headache and gait instability. MRI showed an enhancing intraaxial lesion (2.0 cm by 1.8 cm by 1.7 cm) in the right cerebellar hemisphere. An HIV screening assay was reactive, but plasma HIV-1 RNA was not detected; the CD4+ T-cell count was 39 per microliter. Diagnostic tests were performed.
Janus kinase (JAK) inhibition with baricitinib in refractory juvenile dermatomyositis
Authors: Hanna Kim, Samantha Dill, Michelle O'Brien, Laura Vian, Xiaobai Li, Manuk Manukyan, Minal Jain, Lilian W Adeojo, Jomy George, Maria Perez, Alexei A Grom, Michelle Sutter, Brian M Feldman, Lawrence Yao, Michelle Millwood, April Brundidge, Dominique C Pichard, Edward W Cowen, Yinghui Shi, Shajia Lu, Wanxia Li Tsai, Massimo Gadina, Lisa G Rider, Robert A Colbert
Journal: Annals of the Rheumatic Diseases (2020)

Juvenile dermatomyositis (JDM) is a systemic vasculopathy with weakness and rash, frequently exhibiting a chronic/polycyclic course, and treated with broad immunosuppression. An interferon (IFN) signature correlates with disease activity.1 Interferonopathies have been successfully targeted by janus kinase (JAK) inhibitors.2 3 We report the first comprehensive prospective evaluation of JAK inhibition (baricitinib) in JDM.

Four patients (5.8–20.7 years old), with chronically active JDM (≥3/6 core set measures)4 who had failed three to six immunomodulatory medications, were enroled on compassionate use study NCT01724580 (online supplementary methods, online supplementary table 1). Biologics other than intravenous immunoglobulin were washed out and other medications continued.### Supplementary data

[annrheumdis-2020-218690supp001.pdf]

Subjects were assessed before and 4, 8, 12 and 24 weeks after starting baricitinib (4–8 mg/day divided two times per day) dosed by weight and renal function.3 Significant improvement was noted by week 4 in Physician Global Activity, Patient/Parent Global Activity, and Extramuscular Global Activity, and Cutaneous Dermatomyositis Disease Area and Severity Index (figure 1, online supplementary table 2). Two patients with baseline weakness improved by week 4 (ACR/EULAR Myositis Response Criteria) and showed clinically relevant improvement in Manual Muscle Testing-8 by week 8, confirmed by blinded MRI assessment (online supplementary figures 1 and 2). There was no significant change in muscle enzymes (online supplementary table 3), though some had variable elevations with stable/improved strength. Daily corticosteroids were decreased (0.28 to 0.18 mg/kg/day); other immunosuppressive medications were decreased/discontinued (online supplementary table 1). There were no flares/worsening requiring increased immunosuppression. There was no notable change in calcinosis (n=2).



Figure 1 
Change in disease activity and pharmacodynamic markers on baricitinib treatment. (A–D) Multiple clinical assessments are shown at …
Abstract 11236: Vascular Endothelial Growth Factor Enhances Profibrotic Activities Through Modulation of Calcium Homeostasis in Human Atrial Fibroblasts
Authors: Cheng Chih Chung, Yung-Kuo Lin, Yao-Chang Chen, Yu Kao, TingI Lee, Yi-Jen Chen
Journal: Circulation (2019)

Background/Aims: Vascular endothelial growth factor (VEGF), a pivotal activator of angiogenesis and calcium (Ca2+) signaling in endothelial cells, was shown to increase collagen production in atria...
Nivolumab Induced Hepatocanalicular Cholestasis and Liver Rejection in a Patient With Lung Cancer and Liver Transplant
Authors: Marius Braun, Vered Fuchs, Waleed Kian, Laila Roisman, Nir Peled, Eli Rosenberg, Ludmila Friedel
Journal: Journal of Thoracic Oncology (2020)
Urine PGE-M to assess prostaglandin E2 (PGE<sub>2</sub>) levels in non-small cell lung cancer (NSCLC)
Authors: L. Horn, G. Milne, A. Sandler, J. Morrow, D. Carbone, Y. Shyr, A. Hayes, N. Campbell, D. H. Johnson
Journal: Journal of Clinical Oncology (2009)

e19026 Background: COX-2 is often overexpressed in NSCLC leading to high systemic PGE 2 levels that in turn play a role in NSCLC pathogenesis. Changes in urine PGE-M (the major PGE 2 metabolite) reflect changes in systemic &amp; intratumoral PGE 2 [Csiki et al. Clin Cancer Res 11:6634, 2005]. A ≥70% decline in PGE-M in NSCLC patients (pts) treated with celecoxib (C) (400 mg bid) + docetaxel (D) was associated with an apparent survival benefit [Ibid]. To effect maximum COX-2 inhibition we tested a higher C dose in a subsequent phase II trial. Methods: Eligibility: previously treated NSCLC, PS 0–2, evaluable/measurable disease, adequate marrow, renal &amp; hepatic function, no current NSAID or sulfa allergy. Urine PGE-M measured prior to &amp; 5–10 days after C 600 mg PO bid. Pts with ≥70% decline in PGE-M continued on C + D 75 mg/m 2 or pemetrexed 500 mg/m 2 q3wk x 4 cycles followed by maintenance C 400 mg PO bid until PD or drug intolerance. Results: 21 pts enrolled; F=7, M=14; 2 ineligible (1 carcinoid; 1 elevated LFT); 2 stopped C early (1 ARF; 1 pruritus). Mean PGE-M levels decreased from 38.9 to 7.8 ng/mg Cr pre- &amp; post-C (mean change = 80%; P=0.002). The mean decline was greater in current &amp; former smokers (81%; P=0.002) compared to never smokers (46%; P=0.19). Males had higher pre- treatment PGE-M (44 vs. 28.8 ng/mg Cr; P=0.21). Males had a significant decrease in mean PGE-M levels after C (78%; P=0.011); a similar albeit not significant change occurred in females (P=0.12). 12 screened pts (57%) had a ≥70% decline in PGE-M &amp; received treatment with C + chemotherapy; 8 pts are evaluable for response; SD = 6; PD = 2. Treatment was well tolerated with no cardiac toxicities noted. Conclusions: These preliminary data indicate C 600 mg bid effectively inhibits intratumoral COX-2 in &gt;50% NSCLC pts, a higher percentage than our previous trial using C 400 mg bid. The effect is greatest in former &amp; current smokers &amp; males compared to never smokers &amp; females. Toxicities are acceptable. Accrual is ongoing. [Funding: VICC Lung Cancer SPORE CA90949]. No significant financial relationships to disclose.
External Evaluation of 3 Commercial Artificial Intelligence Algorithms for Independent Assessment of Screening Mammograms
Authors: Mattie Salim, Erik Wåhlin, Karin Dembrower, Edward Azavedo, Theodoros Foukakis, Yue Liu, Kevin Smith, Martin Eklund, Fredrik Strand
Journal: JAMA Oncology (2020)

A computer algorithm that performs at or above the level of radiologists in mammography screening assessment could improve the effectiveness of breast cancer screening.
Gemcitabine-oxaliplatin combination (SEGEMOX) in anthracycline (A) and taxanes (T) pretreated metastatic breast cancer (MBC): Results from the GERCOR-SEGEMOX phase II trial
Authors: J. Gligorov, L. Cals, C. Tournigand, Z. Merad, J. Dutel, F. Selle, N. Zeghib, B. Chibaudel, F. Cvitkovic
Journal: Journal of Clinical Oncology (2009)

1108 Objectives: To evaluate efficacy and safety of SEGEMOX regimen for previously A and T pre-treated MBC patients. Methods: Forty-five women with MBC not eligible for A and/or T chemotherapy were enrolled on SEGEMOX study. SEGEMOX was delivered as follows: Gemcitabine was given at 1000 mg/m 2 /100min on day 1, followed by oxaliplatin at 100 mg/m 2 /120min iv on day 2 every 2 weeks. Efficacy results were analyzed and are presented in an intention to treat analysis and toxicity according to the total number of cycles regimen. Results: Forty-four of the 45 patients received at least 1 cycle of SEGEMOX. Fifty-eight perccent of the patients have received previous adjuvant chemo, 36% 1st line and 42% 2nd line for MBC before the protocol inclusion. Visceral metastases were dominant site of disease (44% liver; 36% lung; 44% bone). Median age of the population was 55.8 years (36–73). After a median of 7.7 cycles (3.5 months of treatment); the overall response rate (ORR) is 38% [95%CI; 23%-51%] [1 CR (2.2%) and 16 PR (35.6%)]; 33% of stable disease [95%CI; 17%-43%], 24.4% progressive disease with a clinical benefit (CB) of 71% [95%CI; 57%-85%]. The median progression free survival (PFS) is 7.1 months for responders and 4.8 months for patients with stable disease. The all population median overall survival (OS) is 21.4 months with 22.7 months MOS for responders. Concerning toxicity analysis: 339 cycles of gemcitabine and 312 of oxaliplatinum were delivered. Respectively, grade 3–4 neutropenia occurred in 43% of patients (febrile neutropenia in 7%), grade 3–4 thrombocytopenia in 41%, and anemia in 2.3%. The most frequent non hematologic toxicities were represented by grade 3 peripheral neuropathy (Levi Scale) in 11.4% of the patients and grade 2 alopecia in 11.4%. For the subgroup of hormone receptor negative MBC (n = 12) the ORR is 33% [95%CI; 2%-64%], CB 50% [95%CI; 16%-73%], PFS of 2.8 months and MOS of 12 months. Conclusions: The SEGEMOX combination has relevant activity in A and T not eligible MBC patients, with a manageable toxicity profile. In the limited number of patients with HRN MBC even if the response rate is close to the overall population the prognosis seems still worse. No significant financial relationships to disclose.
Prevention and management of periodontal diseases and dental caries in the older adults
Authors: Lubna Al‐Nasser, Ira B. Lamster
Journal: Periodontology 2000 (2020)

Abstract As a result of aging populations, in the future, dental practitioners will be caring for more older adults than ever before. These older adults, especially in developed countries, will demand a greater number of dental services, driven by increased tooth retention and an expectation of excellent oral healthcare throughout the life course. Further, the global rise in the prevalence and incidence of chronic diseases will increase the risk and/or severity of oral diseases and add a layer of complexity to the management of oral diseases in older adults. More older adults will be at a higher risk of periodontal disease and root caries as a result of reduced tooth loss and edentulism. This article reviews information on periodontitis and root caries, oral diseases which reflect the cumulative risk of the individual, and which are best addressed through prevention. Oral healthcare providers must embrace the concept of lifelong emphasis on prevention, as well as participation as active members of a healthcare team which provides healthcare for older adults in various settings (eg, hospital/clinic‐based care, community‐based settings, and long‐term care facilities). National guidelines that address oral health are being considered by some countries, and if these are implemented they will increase the accessibility to oral health for older adults. In parallel to this, revisions of existing older adult insurance schemes (eg, the inclusion of routine oral healthcare in the US Medicare program) would promote the maintenance of a functional dentition that is pain‐free and conducive to general health. The opportunity exists to implement a holistic approach to oral health that will align oral health with general health and emphasize that true health can only be achieved with the inclusion of oral health.
AB0042 Structure of renal damage in rheumatoid arthritis
Authors: RM Balabanova, IB Vinogradova, VI Mukhorin, VE Briginevich
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Renal damage is one of most unfavourable prognostic factors in rheumatoid arthritis (RA). Most frequent pathology is renal amyloidosis. Rheumatic glomerulonephritis as a systemic manifestation of RA is infrequent. Important place belongs to renal exacerbations due to NSAIDs treatment and basic drugs. <h3>Objectives</h3> To determine the character of renal damage in RA by the data of biopsy material. <h3>Methods</h3> In the period from 1998 to 2000 in Rheumatological department of Ulianovsk Regional Hospital 10 RA pts with nephropathy symptoms were examined: proteinuria, azotemia, nephrotic syndrome with median disease duration of 17.7 ± 5.1 years. Appearing of symptoms of renal pathology was in 10.7 ± 3.5 years from RA onset. Pts did not have basic therapy; according to their condition – only NSAIDs (Diclofenac, Indomethacin). All pts had closed renal biopsy. <h3>Results</h3> According to data of hystological analysis 4 pts demonstrated amyloid lesion, 4 – interstitial nephritis, 1 – mesangioproliferative glomerulonephritis, 1 – combination of amyloidosis and interstitial nephritis. In two cases renal damage was the reason for lethal outcome. <h3>Conclusion</h3> Absence of basic therapy for a long period of time of the disease results in the development of extraarticular manifestations and RA complication – amyloid renal damage.
Abstract 2605: Cytokeratin 5 promotes endocytosis to remodel cell adhesions in breast cancer
Authors: Olivia Frances McGinn, Ashley V. Ward, Jessica Finlay-Schultz, Kiran Vinod Paul, Peter Kabos, Carol Sartorius
Journal: Cancer Research (2020)

Abstract Breast cancer (BC) is clinically classified according to expression of estrogen receptor, progesterone receptor (ER+ BC), HER2 (HER2+), or absence of these markers (triple negative BC). While TNBC has the inferior prognosis in the short term, ER+ breast cancer has an extended risk of recurrence that lasts up to 20 years and accounts for the most deaths overall. Cytokeratin 5 (CK5) is an intermediate filament protein that is expressed in the majority of TNBC cases and 10-50% of ER+ BC. In CK5+/ER+ BC, there is widespread heterogeneity in the amount of CK5+ tumor cells (~1-50%). The mere presence of CK5+ cells is an indicator of poor prognosis across both subtypes of BC; the reasons for this are poorly understood. We have shown that CK5+ cells within ER+ and TNBC cell lines, and heterogeneous PDX tumor models lose membrane localization of adherens junction proteins β-catenin and E-cadherin. Loss of membrane β-catenin and E-cadherin is associated with poor prognosis in breast cancer and is a precursor to cell invasion. CK5+ cells have been reported to have increased invasive potential by us and others. Thus, identifying the mechanism of CK5-dependent loss of adherens proteins at the membrane could lead to development of therapies targeting this process. β-catenin and E-cadherin localization have been reported to be regulated through endocytosis which is mediated through the small GTPase family of Rab proteins. We performed a screen to identify potential CK5 interacting proteins in breast cancer cells and identified several Rab proteins. Thus, we hypothesize that CK5 acts as a scaffold for Rabs to promote endocytosis of β-catenin and E-cadherin to increase invasive potential.To investigate this, we treated CK5 overexpressing ER+ and TNBC cells with the endocytosis inhibitor Dyngo4a and found membrane β-catenin and E-cadherin localization were restored, suggesting that CK5 may be mediating endocytosis of β-catenin and E-cadherin. Rab5 is responsible for trafficking vesicles from the plasma membrane to the early endosomes. CK5 was confirmed to interact with Rab5 by co-IP in TNBC and CK5 overexpressing ER+ cell lines. In ongoing studies, we are testing whether Rab5 knockdown prevents loss of membrane β-catenin and E-cadherin and decreases cell invasiveness. These experiments will collectively determine whether CK5 regulated endocytosis is a targetable feature in breast cancer cells. Citation Format: Olivia Frances McGinn, Ashley V. Ward, Jessica Finlay-Schultz, Kiran Vinod Paul, Peter Kabos, Carol Sartorius. Cytokeratin 5 promotes endocytosis to remodel cell adhesions in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2605.
Persistent, refractory, and biphasic anaphylaxis: A multidisciplinary Delphi study
Authors: Timothy E. Dribin, Hugh A. Sampson, Carlos A. Camargo, David C. Brousseau, Jonathan M. Spergel, Mark I. Neuman, Marcus Shaker, Ronna L. Campbell, Kenneth A. Michelson, Susan A. Rudders, Amal H. Assa’ad, Kimberly A. Risma, Mariana Castells, Lynda C. Schneider, Julie Wang, Juhee Lee, Rakesh D. Mistry, David Vyles, Lisa M. Vaughn, Daniel J. Schumacher, John K. Witry, Shiv Viswanathan, Erica M. Page, David Schnadower
Journal: Journal of Allergy and Clinical Immunology (2020)
Flowcytometric evaluation of cerebrospinal fluid in childhood ALL identifies CNS involvement better then conventional cytomorphology
Authors: Valérie de Haas, Rob Pieters, Alita J. van der Sluijs-Gelling, C. Michel Zwaan, Hester A. de Groot-Kruseman, Edwin Sonneveld, Rolinda L. Stigter, Vincent H. J. van der Velden
Journal: Leukemia (2020)
AB0010 Increased collagen production by human lung fibroblasts in the response to tumour necrosis factor-related apoptosis-inducing ligand
Authors: VV Yurovsky
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), also called Apo-2 ligand, is a member of the TNF family that has been reported to induce apoptosis in a variety of transformed cell lines, as well as in normal human hepatocytes <i>in vitro</i>. Among the family members, TRAIL displays highest homology to CD95 ligand, receptor of which may not only mediate apoptosis of T cells, but also mediate the proliferation of normal human fibroblasts. Considering structural and functional similarities between TRAIL and CD95 ligand, we examined the effects of soluble TRAIL on normal human lung fibroblasts. Collagen a2(I) mRNA expression in fibroblasts was measured by RT-PCR, with ribosomal protein S9 as an internal standard. Normalised collagen mRNA expression was increased in fibroblasts stimulated with TRAIL for 1 or 7 days, with peak response (&gt; 5-fold increase) at 10 ng/ml TRAIL. The increased expression of collagen a2(I) gene was confirmed by cDNA microarray that also revealed 72 other genes with expression level increased and 108 genes with expression level decreased ª 2.2-fold in comparison with quiescent fibroblasts. There was little, if any, effect of TRAIL on fibroblast proliferation. The expression of TRAIL was also found in CD8<sup>+</sup> T cell clones that had undergone oligoclonal expansion in the lungs of patients with systemic sclerosis (scleroderma) and were able to stimulate collagen production in lung fibroblasts <i>in vitro</i>. These data suggest that TRAIL can enhance collagen production by fibroblasts that are resistant to TRAIL-induced apoptosis. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3>
Ethically Allocating COVID-19 Drugs Via Pre-approval Access and Emergency Use Authorization
Authors: Jamie Webb, Lesha D. Shah, Holly Fernandez Lynch
Journal: The American Journal of Bioethics (2020)

Allocating access to unapproved COVID-19 drugs available via Pre-Approval Access pathways or Emergency Use Authorization raises unique challenges at the intersection of clinical care and research. In conditions of scarcity, prioritization approaches should minimize harm, maximize benefit, and promote fairness. To promote continued data collection, patients seeking access to unproven COVID-19 drugs should receive lower priority for allocation when they decline to participate in clinical trials, either of the requested drug or other investigational products, offering a comparable balance of risks and benefits; special attention should be paid to concerns of voluntariness and distrust. In addition, institutional treatment protocols that can contribute more robust real world data should be preferred to single patient requests for access, with priority for inclusion based on traditional clinical allocation criteria relying on available evidence. Fairness demands distribution of these protocols across a diverse range of sites, particularly those serving marginalized populations, among other protections.
FRI0216 Antibodies to recombinant 60-kd ro, 52-kd ro and 48-kd la proteins in primary sjÖgren’s syndrome. usefulness of combination of analytical methods for detecting anti-ro and anti la antibodies
Authors: S Aguilera, D Castillo, J González
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To determine the reactivity and specificity of sera from primary Sjögren's syndrome (SS) patients to recombinant 60-Kd Ro, 52-Kd Ro and 48-Kd La proteins, and to correlate the results with clinical and laboratory findings. <h3>Methods</h3> Sera from 46 patients with primary SS diagnosed according to modified 1997 European criteria, were classified in 2 groups based on the presence of anti- Ro and anti-La detected by commercial enzyme linked immunobsorbent assay (ELISA). Group A (n = 32) had anti-Ro positive sera, and group B (n = 14) had anti-Ro and anti-La negative sera, but positive antinuclear antibodies and/or rheumatoid factors. Autoantibody reactivity and specificity to recombinant 60-Kd Ro, 52-Kd Ro and 48-Kd La were analysed by ELISA and Western blot. <h3>Results</h3> Forty-two out of 46 primary SS sera (91.30%), had reactivity to either natural or recombinant antigens or both. Anti-60-Kd Ro was found in 27 (58.69%) of all sera, of these, 22 (68.75%) sera were of group A, and 5 sera (35.71%) of group B. Anti-52-Kd Ro was highly prevalent since 38 out of 46 sera (62.60%) were positive. Among group A, 31 out of 32 (96.87%) sera were positive for 52-Kd Ro, and 7 out of 14 (50%) in group B. Anti-recombinant 48-Kd La was also highly prevalent, 38 (82.60%) of all sera were positive. In group A, 31 (96.87%) of sera were positive, while 5 (35.71%) of sera of group B, were positive. Ten (71.42%) of 14 patients of group B had antibodies for at least 1 of 3 recombinant antigens: 52-Kd Ro, 60-Kd Ro or 48-Kd La. Comparison of ELISA and Western blot produced a good intermethod agreement coefficient when anti-recombinant antibodies from sera in group A were tested: 60-Kd Ro (k = 0.563) and 52-Kd Ro (k = 0.652). Both groups were similar regarding of baseline characteristics, except that patients in group A who were younger at the time of diagnosis than those of group B (mean 39.9 v/s 63.7 years), and hipergammaglobulinemia was more frequent in group A than B. Extraglandular manifestations were similar in both groups. <h3>Conclusion</h3> The detection of antibodies to recombinant 60-Kd Ro, 52-Kd Ro and 48-Kd La proteins, might be a new research tool as well as an aid for the diagnosis of SS, mainly in cases who are seronegative for anti-Ro or La by conventional techniques.