tbuckley/cabot-search huggingface dataset:
Abstract O.28: Macrophage Activation Syndrome Associated with Kawasaki Disease
Authors: Giuseppe A Latino, Cedric Manlhiot, Brian W McCrindle, Nita Chahal, Rae S Yeung
Journal: Circulation (2015)

Introduction: Macrophage activation syndrome (MAS) is a life threatening disease that is increasingly recognized in children with inflammatory conditions including Kawasaki disease (KD). We describe the prevalence, clinical features and outcomes of patients with MAS secondary to KD. Methods: All patients diagnosed and treated for KD at The Hospital for Sick Children between 2001 and 2013 were included and reviewed for features of MAS. A diagnosis of MAS required 4 out of the following clinical findings: fever, hepatosplenomegaly, cytopenia in at least 2 cell lines, hyperferritinemia, hypofibrinogenemia and/or hypertriglyceridemia, and presence of biopsy-proven hemophagocytosis. Results: Of 1,020 patients included in this study, 21 met MAS diagnostic criteria for an incidence of 2.1% (95% CI: 1.4-3.1%). All patients had fever, 9 (43%) hepatosplenomegaly, 10 (47%) hypofibrinogenemia and/or hypertriglyceridemia, 19 (90%) hyperferritinemia, 19 (90%) cytopenia, and 7 (33%) biopsy-confirmed hemophagocytosis. MAS was associated with: older age at KD diagnosis (median 5.7 vs. 3.0 years, p=0.06), longer fever duration prior to diagnosis (median 10 vs. 6 days, p=0.01), and higher incidence of incomplete KD (57% vs. 32%, p=0.04) and confirmed infection during acute phase (48% vs. 19%, p=0.02). Treatment included multiple IVIGs for 12 patients (57%), methylprednisolone for 15 (71%), oral prednisone for 13 (62%) and cyclosporine for 2 (10%). Median total duration of fever was 13 days (vs. 7 days, p=0.001), duration of fever after first IVIG treatment was 4 days, and median duration of hospital stay was 6 days (vs. 3 days, p=0.01). 5 patients received pRBC transfusions, 3 required ICU care, 1 had severe CNS involvement, and 1 developed multisystem organ failure dying 28 days after admission. Mild transient coronary dilatation was seen in 3 patients Conclusions: The clinical presentation of KD and MAS are quite similar. Both entities are syndrome complexes defined by massive immune activation and share pro-inflammatory cytokine signatures. MAS is a rare but important complication with KD. Further research is needed to optimize diagnosis and management.
Molecular High-Grade B-Cell Lymphoma: Defining a Poor-Risk Group That Requires Different Approaches to Therapy
Authors: Chulin Sha, Sharon Barrans, Francesco Cucco, Michael A. Bentley, Matthew A. Care, Thomas Cummin, Hannah Kennedy, Joe S. Thompson, Rahman Uddin, Lisa Worrillow, Rebecca Chalkley, Moniek van Hoppe, Sophia Ahmed, Tom Maishman, Josh Caddy, Anna Schuh, Christoph Mamot, Catherine Burton, Reuben Tooze, Andrew Davies, Ming-Qing Du, Peter W.M. Johnson, David R. Westhead
Journal: Journal of Clinical Oncology (2018)

Purpose Biologic heterogeneity is a feature of diffuse large B-cell lymphoma (DLBCL), and the existence of a subgroup with poor prognosis and phenotypic proximity to Burkitt lymphoma is well known. Conventional cytogenetics identifies some patients with rearrangements of MYC and BCL2 and/or BCL6 (double-hit lymphomas) who are increasingly treated with more intensive chemotherapy, but a more biologically coherent and clinically useful definition of this group is required. Patients and Methods We defined a molecular high-grade (MHG) group by applying a gene expression–based classifier to 928 patients with DLBCL from a clinical trial that investigated the addition of bortezomib to standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The prognostic significance of MHG was compared with existing biomarkers. We performed targeted sequencing of 70 genes in 400 patients and explored molecular pathology using gene expression signature databases. Findings were validated in an independent data set. Results The MHG group comprised 83 patients (9%), with 75 in the cell-of-origin germinal center B-cell-like group. MYC rearranged and double-hit groups were strongly over-represented in MHG but comprised only one half of the total. Gene expression analysis revealed a proliferative phenotype with a relationship to centroblasts. Progression-free survival rate at 36 months after R-CHOP in the MHG group was 37% (95% CI, 24% to 55%) compared with 72% (95% CI, 68% to 77%) for others, and an analysis of treatment effects suggested a possible positive effect of bortezomib. Double-hit lymphomas lacking the MHG signature showed no evidence of worse outcome than other germinal center B-cell-like cases. Conclusion MHG defines a biologically coherent high-grade B-cell lymphoma group with distinct molecular features and clinical outcomes that effectively doubles the size of the poor-prognosis, double-hit group. Patients with MHG may benefit from intensified chemotherapy or novel targeted therapies.
Pharmacokinetics (PK) of Subcutaneous Daratumumab in Patients with Relapsed or Refractory (RR) Multiple Myeloma (MM): Primary Clinical Pharmacology Analysis of the Open-Label, Multicenter, Phase 1b Study (PAVO)
Authors: Pamela L Clemens, Steven Xu, Melody Luo, Ajai Chari, Saad Z. Usmani, Maria-Victoria Mateos, Niels WCJ van de Donk, Jonathan L Kaufman, Philippe Moreau, Albert Oriol, Torben Plesner, Lotfi Benboubker, Jesus F San-Miguel, X. Yu-Nien Sun, Andrew Farnsworth, Tara Masterson, Peter Hellemans, Ming Qi, Hareth Nahi
Journal: Blood (2018)
Comparability of the Cancer Supportive Care Clinical Studies Collaborative (CSCCSC) study population to national referrals to other specialist palliative care services.
Authors: David Christopher Currow, Hiromichi Matsuoka, Samuel Allingham, Belinda Fazekas, Linda Brown, Zac Vandersman, Katherine Clark, Meera Agar
Journal: Journal of Clinical Oncology (2018)

63 Background: There are no agreed national nor international criteria for referral to palliative care. Key population characteristics have been defined to aid the generalizability of research findings in palliative care clinical studies. To codify differences in key demographic factors between patients with cancer participating in the Australian national Cancer Supportive Care Clinical Studies Collaborative (CSCCSC) phase III symptom control studies and the population referred to other Australian palliative care services. Methods: This study compares two contemporaneous consecutive cohorts generated through clinical trial participation and the national palliative care clinical quality improvement registry in Australia. Age, sex, cancer diagnosis, language, and socio-economic status were compared. Results: Cohorts were people with cancer: enrolled in CSCCSC phase III clinical studies (n=902; 17 sites); and registered by the Australian national Palliative Care Outcomes Collaboration (PCOC; n=75,240; 117 sites). Participants in CSCCSC studies were younger than those of PCOC (median 71 (IQR 62, 79) versus median 73 (IQR 63, 81); p=0.003 respectively). There was no significant difference in sex (p=0.483). Patients who spoke English accounted 95.0% of enrollees in the CSCCSC group and 92.2% in the PCOC group (p = 0.004). Clinical study participants had higher socioeconomic status that the PCOC group (p=0.022). Conclusions: Overall, the slightly different demographic patterns are reflective of the differences often seen between phase III trials and the populations to whom the results will be applied. Age differences particularly need to be taken into account when considering the best way to apply each study’s findings.
Whole Genome Sequencing detects Inter-Facility Transmission of Carbapenem-resistant Klebsiella pneumoniae
Authors: Melanie D. Spencer, Kathryn Winglee, Catherine Passaretti, Ashlee M. Earl, Abigail L. Manson, Holly P. Mulder, Robert L. Sautter, Anthony A. Fodor
Journal: Journal of Infection (2018)

To identify transmission patterns of Carbapenem-resistant Klebsiella pneumoniae infection during an outbreak at a large, tertiary care hospital and to detect whether the outbreak organisms spread to other facilities in the integrated healthcare network.We analyzed 71 K. pneumoniae whole genome sequences collected from clinical specimens before, during and after the outbreak and reviewed corresponding patient medical records. Sequence and patient data were used to model probable transmissions and assess factors associated with the outbreak.We identified close genetic relationships among carbapenem-resistant K. pneumoniae isolates sampled during the study period. Transmission tree analysis combined with patient records uncovered extended periods of silent colonization in many study patients and transmission routes that were likely the result of asymptomatic patients transitioning between facilities.Detecting how and where Carbapenem-resistant K. pneumoniae infections spread is challenging in an environment of rising prevalence, asymptomatic carriage and mobility of patients. Whole genome sequencing improved the precision of investigating inter-facility transmissions. Our results emphasize that containment of Carbapenem-resistant K. pneumoniae infections requires coordinated efforts between healthcare networks and settings of care that acknowledge and mitigate transmission risk conferred by undetected carriage and by patient transfers between facilities.
Gut-brain axis metabolic pathway regulates antidepressant efficacy of albiflorin
Authors: Zhen-Xiong Zhao, Jie Fu, Shu-Rong Ma, Ran Peng, Jin-Bo Yu, Lin Cong, Li-Bin Pan, Zuo-Guang Zhang, Hui Tian, Chun-Tao Che, Yan Wang, Jian-Dong Jiang
Journal: Theranostics (2018)

The gut microbiota is increasingly recognized to influence brain function through the gut-brain axis.Albiflorin, an antidepressant natural drug in China with a good safety profile, is difficult to absorb and cannot be detected in the brain after oral administration.Accordingly, the antidepressant mechanism of albiflorin in vivo has not been elucidated clearly.Methods: We identified benzoic acid as the characteristic metabolite of albiflorin in vivo and in vitro, then discovered the roles of gut microbiota in the conversion of albiflorin by carboxylesterase.Pharmacodynamic and pharmacokinetic studies were performed for the antidepressant activities of albiflorin in animals, and the efficacy of benzoic acid in inhibiting D-amino acid oxidase (DAAO) in brain was further investigated.Results: We validated that gut microbiota transformed albiflorin to benzoic acid, a key metabolite in the intestine that could cross the blood-brain barrier and, as an inhibitor of DAAO in the brain, improved brain function and exerted antidepressant activity in vivo.Intestinal carboxylesterase was the crucial enzyme that generated benzoic acid from albiflorin.Additionally, the regulatory effect of albiflorin on the gut microbiota composition was beneficial to alleviate depression.Conclusion: Our findings suggest a novel gut-brain dialogue through intestinal benzoic acid for the treatment of depression and reveal that the gut microbiota may play a causal role in the pathogenesis and treatment of the central nervous system disease.
A framework for the development of effective anti-metastatic agents
Authors: Robin L. Anderson, Theo Balasas, Juliana Callaghan, R. Charles Coombes, Jeff Evans, Jacqueline A. Hall, Sally Kinrade, David Jones, Paul S. Jones, Rob Jones, John F. Marshall, Maria Beatrice Panico, Jacqui A. Shaw, Patricia S. Steeg, Mark Sullivan, Warwick Tong, Andrew D. Westwell, James W. A. Ritchie
Journal: Nature Reviews Clinical Oncology (2018)

Abstract Most cancer-related deaths are a result of metastasis, and thus the importance of this process as a target of therapy cannot be understated. By asking ‘how can we effectively treat cancer?’, we do not capture the complexity of a disease encompassing &gt;200 different cancer types — many consisting of multiple subtypes — with considerable intratumoural heterogeneity, which can result in variable responses to a specific therapy. Moreover, we have much less information on the pathophysiological characteristics of metastases than is available for the primary tumour. Most disseminated tumour cells that arrive in distant tissues, surrounded by unfamiliar cells and a foreign microenvironment, are likely to die; however, those that survive can generate metastatic tumours with a markedly different biology from that of the primary tumour. To treat metastasis effectively, we must inhibit fundamental metastatic processes and develop specific preclinical and clinical strategies that do not rely on primary tumour responses. To address this crucial issue, Cancer Research UK and Cancer Therapeutics CRC Australia formed a Metastasis Working Group with representatives from not-for-profit, academic, government, industry and regulatory bodies in order to develop recommendations on how to tackle the challenges associated with treating (micro)metastatic disease. Herein, we describe the challenges identified as well as the proposed approaches for discovering and developing anticancer agents designed specifically to prevent or delay the metastatic outgrowth of cancer.
How long do patients with advanced cancer survive after discharge to sub-acute rehabilitation?
Authors: Muhammad Azeem Khan, Diana Stewart, Clint S. Pettit, Hunter Groninger
Journal: Journal of Clinical Oncology (2018)

67 Background: Patients with advanced cancer inevitably experience a functional decline diminishing quality of life. Many are admitted to the hospital due to progression of disease and become further deconditioned. Discharge to sub-acute rehabilitation (SAR) to "gain strength" for future anti-cancer therapy is common as participation in more intensive rehab therapy is rarely possible. In this study, we wished to determine the length of survival after discharge to SAR and if factors such as pre-hospitalization ECOG correlated with increased length of survival. Methods: At our 926-bed urban academic center, we performed a retrospective chart review from June 2015 to January 2017 of hospitalized patients with solid cancers who were subsequently discharged to SAR. Patients were excluded if they had surgery, a cerebrovascular event during their hospitalization or no post-hospital oncology follow-up plan. The primary outcome was death. Results: Fifty-six patients were identified (median age 69, range 28-95; 87% African American; 72% female). Forty-seven (86%) had metastatic disease. Forty-seven patients (86%) were deceased as of June 2017. The mean survival from date of discharge was 114 days (SD 122.89, range 1-447). Twenty-eight patients (51%) had a pre-hospitalization ECOG of 1 or 2 and twenty-seven patients (49%) had an ECOG of 3 or 4. Mann-Whitney U correlation was used to test the correlation between ECOG and survival. Patients with an ECOG of 1 or 2 trended to survive longer (156 vs 75 days, p=0.06). Self identified white patients had a statistically significant longer survival post discharge to SAR compared to African Americans (204 vs 104 days, p=0.03). Conclusions: Compared to patients with ECOG 1 or 2, patients with ECOG of 3 or 4 survived for a fewer number of days. The identification of additional markers of poor prognosis through larger prospective multi-institutional studies will help to delineate which patients are more likely to benefit from discharge to SAR.
A US National Study of the Association Between Income and Ambulance Response Time in Cardiac Arrest
Authors: Renee Y. Hsia, Delphine Huang, N. Clay Mann, Christopher Colwell, Mary P. Mercer, Mengtao Dai, Matthew J. Niedzwiecki
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Emergency medical services (EMS) provide critical prehospital care, and disparities in response times to time-sensitive conditions, such as cardiac arrest, may contribute to disparities in patient outcomes. <h3>Objectives</h3> To investigate whether ambulance 9-1-1 times were longer in low-income vs high-income areas and to compare response times with national benchmarks of 4, 8, or 15 minutes across income quartiles. <h3>Design, Setting, and Participants</h3> A retrospective cross-sectional study was performed of the 2014 National Emergency Medical Services Information System data in June 2017 using negative binomial and logistic regressions to examine the association between zip code–level income and EMS response times. The study used ambulance 9-1-1 response data for out-of-hospital cardiac arrest from 46 of 50 state repositories (92.0%) in the United States. The sample included 63 600 cardiac arrest encounters of patients who did not die on scene and were transported to the hospital. <h3>Main Outcomes and Measures</h3> Four time measures were examined, including response time, on-scene time, transport time, and total EMS time. The study compared response times with EMS response time benchmarks for responding to cardiac arrest calls within 4, 8, and 15 minutes. <h3>Results</h3> The study sample included 63 600 cardiac arrest encounters of patients (mean [SD] age, 60.6 [19.0] years; 57.9% male), with 37 550 patients (59.0%) from high-income areas and 8192 patients (12.9%) from low-income areas. High-income areas had greater proportions of white patients (70.1% vs 62.2%), male patients (58.8% vs 54.1%), privately insured patients (29.4% vs 15.9%), and uninsured patients (15.3% vs 7.9%), while low-income areas had a greater proportion of Medicaid-insured patients (38.3% vs 15.8%). The mean (SD) total EMS time was 37.5 (13.6) minutes in the highest zip code income quartile and 43.0 (18.8) minutes in the lowest. After controlling for urban zip code, weekday, and time of day in regression analyses, total EMS time remained 10% longer (95% CI, 9%-11%;<i>P</i> &lt; .001), translating to 3.8 minutes longer in the poorest zip codes. The EMS response time to patients in high-income zip codes was more likely to meet 8-minute and 15-minute cutoffs compared with low-income zip codes. <h3>Conclusions and Relevance</h3> Patients with cardiac arrest from the poorest neighborhoods had longer EMS times compared with those from the wealthiest, and response times were less likely to meet national benchmarks in low-income areas, which may lead to increased disparities in prehospital delivery of care over time.
Outbreak of Dengue Virus Type 2 — American Samoa, November 2016–October 2018
Authors: Caitlin J. Cotter, A. John Tufa, Stephanie Johnson, Mary Matai’a, Rebecca Sciulli, Kyle R. Ryff, W. Thane Hancock, Christian Whelen, Tyler M. Sharp, Magele Scott Anesi
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The U.S. territory of American Samoa has experienced recent outbreaks of illnesses caused by viruses transmitted by Aedes species mosquitoes, including dengue, chikungunya, and Zika virus. In November 2016, a traveler from the Solomon Islands tested positive for infection with dengue virus type 2 (DENV-2). Additional dengue cases were identified in the subsequent weeks through passive and active surveillance. Suspected dengue cases were tested locally with a dengue rapid diagnostic test (RDT) for DENV nonstructural protein 1 (NS1). Specimens from RDT-positive cases and patients meeting the dengue case definition were tested by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) at Hawaii State Laboratories. During November 2016-October 2018, a total of 3,240 patients were tested for evidence of DENV infection (118 by RDT-NS1 alone, 1,089 by real-time RT-PCR alone, and 2,033 by both methods), 1,081 (33.4%) of whom tested positive for dengue (19.5 per 1,000 population). All 941 real-time RT-PCR-positive specimens were positive for DENV-2. The monthly number of laboratory-confirmed cases peaked at 120 during December 2017. Among laboratory-confirmed dengue cases, 380 (35.2%) patients were hospitalized; one patient, who was transferred to American Samoa for care late in his illness, died. The public health response to this outbreak included disposal of solid waste to remove mosquito breeding sites, indoor residual spraying of pesticides in schools, reinforcement of dengue patient management education, and public education on mosquito avoidance and seeking medical care for symptoms of dengue.
AB1348 Prevalence, gender-predominance and clinical presentation of behÇet’s disease in egypt: preliminary findings from a multicenter nationwide study
Authors: E.M. Abd El-Latif, I.I. El-Gazzar, N. Samy, N.H. Hammam, A.R. E-Najjar, M.N. Salem, D.F. El-Essawi, H.M. Fathi, R.R. El-Shereef, M.I. Abd Elazeem, N.M. Khalil, S.I. Nasef, S.E. Ibrahim, H.M. Khalil
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Behçet’s disease is a chronic, relapsing multisystemic vasculitis that is common in the Mediterranean basin region with a diverse spectrum of clinical manifestations. A previous single-centre study from Alexandria conducted 20 years ago reported a prevalence of 7.6/100.000 population and a M:F ratio of 5.4:1. <h3>Objectives</h3> The aim of this multicenter study was to present the prevalence and pattern of Behcet’s disease (BD) in adult Egyptian patients. <h3>Methods</h3> This study included 1098 BD patients from 14 highly specialised centres over .<sup>Egypt during 2017</sup> The demographic, clinical characteristics, laboratory findings, BD current activity form (BDCAF) and medications received were reported. <h3>Results</h3> The mean age of the patients was 36.3±10.2 years (16–73 years), disease duration was 6.7±5.2 years and they were 776 males and 322 females (2.4:1) and was 1.9:1 from Alexandria. Their mean age at disease onset was 29.8±8.7 years. 24.9% were diabetic and 30.7% hypertensive. The frequency of presenting cases was highest from Alexandria (41.3%) followed by Cairo (35.3%), Beni-Suef (6.4%), Assuit (6.1%), Sharkia (3.9%), Fayoum (3.2%), Minia (2.7%) and 1.1% from Ismailia. The total prevalence from those 8 major cities after adjusting for adults according to the 2017 population consensus was 4.35/100.000 inhabitants; 13.76 for Alexandria, 6.3 for Cairo and the highest prevalence in upper Egypt from Beni-Suef was 3.48 and the least from Minia (0.85). The prevalence from Sharkia was 0.93, Fayoum 1.51 and was 1.41 from Ismailia. All patients had oral ulcers while genital ulcers were present in 80%. The eyes were involved in 78.9%, cutaneous manifestations were present in 59.8%, arthritis in 34.7%, neuropsychiatric manifestations in 13.9%, gastrointestinal tract involvement in 11.5% and deep venous thrombosis in 23.1%. Their mean BDCAF was 4.6±4.6. The mean erythrocyte sedimentation rate was 29.1±19.9 mm/1sthr, C-reactive protein 11.3±15.2 mg/dl, haemoglobin content 13.3±6 g/dl, total leucocytic count 8.6±14.5 × 10<sup>3</sup>/mm<sup>3</sup>, platelets 262.6±76.9 × 10<sup>3</sup>/mm<sup>3</sup> and serum uric acid 4.8±1.6 mg/dl. 90.7% were receiving steroids, 81.1% were receiving colchicine, while only 8.1% were receiving biologic therapy. <h3>Conclusions</h3> The prevalence of BD in Egypt is high and higher in Alexandria than previously reported. The male-to-female ratio is lower than previously found being more in harmony with the globally reported ratios. The pattern of clinical presentation is unique for this country yet comparable to the universally stated frequencies. <h3>Disclosure of Interest</h3> None declared