tbuckley/cabot-search huggingface dataset:
Abstract 16325: Short-Term Changes in Carotid Artery Inflammation Measured by Positron Emission Tomography are Associated With Long Term Atherosclerosis Progression Measured by Magnetic Resonance Imaging
Authors: Amorina Ishai, Philip Joseph, Venkatesh Mani, David Kallend, James Rudd, Zahi Fayad, Ahmed Tawakol
Journal: Circulation (2015)

Introduction: It is unknown whether short-term changes arterial wall inflammation are associated with changes in the rate of structural progression of atherosclerosis. Hypothesis: We assessed arterial inflammation, using positron emission tomography (PET) imaging and 18F-fluorodeoxyglucose (FDG) to test the hypothesis that short term changes in arterial inflammation predict long term atherosclerosis progression, measured by magnetic resonance imaging( MRI). Methods: Forty-two participants enrolled in the dal-PLAQUE study , who underwent both PET and MRI imaging of the carotid arteries were evaluated. Short-term change in arterial inflammation was measured as change in the carotid FDG target to background ratio [TBR] by PET between baseline and 6 months. The long-term rate of atherosclerotic plaque progression was assessed using MRI, as percent change in carotid mean wall area [MWA] and mean wall thickness [MWT] between baseline and 24 months. Results: The mean age of the population was 62.5 years, and 12 (28.6 %) were male. In participants with (vs. without) any increase in arterial inflammation over 6 months, long-term rate of change in MWT was significantly higher (% change MWT: 17.49% vs. 1.74%, p=0.038) and long-term rate of change in MWA was significantly higher (% change MWA: 25.50% vs. 3.59%, p = 0.027). Results remained significant after adjusting for clinical and biochemical covariates. Individuals with no increase in arterial inflammation over 6 months had no significant structural progression of atherosclerosis over 24 months, measured as MWT (p=0.616) or MWA (p=0.373). Conclusions: Short-term changes in arterial inflammation predict long-term atherosclerosis progression. In those with no increase in arterial inflammation, no significant changes in atherosclerosis progression were observed.
Unmasking the hidden tuberculosis mortality burden in a large <i>post mortem</i> study in Maputo Central Hospital, Mozambique
Authors: Alberto L. Garcia-Basteiro, Juan Carlos Hurtado, Paola Castillo, Fabiola Fernandes, Mireia Navarro, Lucilia Lovane, Isaac Casas, Llorenç Quintó, Dercio Jordao, Mamudo R. Ismail, Cesaltina Lorenzoni, Carla Carrilho, Ariadna Sanz, Natalia Rakislova, Aurea Mira, Miriam J. Alvarez-Martínez, Anélsio Cossa, Frank Cobelens, Inácio Mandomando, Jordi Vila, Quique Bassat, Clara Menendez, Jaume Ordi, Miguel J. Martínez
Journal: European Respiratory Journal (2019)

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI 7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, Mycobacterium tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 (27.8%) cases had TB disease at death and 80 (35.9%) had TB findings.The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death.
Higher eGFR at Dialysis Initiation Is Not Associated with a Survival Benefit in Children
Authors: Erica Winnicki, Kirsten L. Johansen, Michael D. Cabana, Bradley A. Warady, Charles E. McCulloch, Barbara Grimes, Elaine Ku
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Although observational studies suggest that dialysis initiation at higher levels of eGFR is not associated with survival benefit in adults with ESRD, the issue is not well studied in children. In a retrospective cohort study of the timing of dialysis initiation and survival in children who (according to the US Renal Data System) began dialysis in 1995–2015, the authors found a trend toward increased initiation of dialysis at higher eGFR over that period. Higher eGFR at dialysis initiation was associated with an increased risk of death, particularly for children who initiated treatment with hemodialysis rather than peritoneal dialysis. These findings may have important implications for the care of children with ESRD; a more concerted effort to delay dialysis initiation in asymptomatic children may reduce exposure to dialysis. Background Study findings suggest that initiating dialysis at a higher eGFR level in adults with ESRD does not improve survival. It is less clear whether starting dialysis at a higher eGFR is associated with a survival benefit in children with CKD. Methods To investigate this issue, we performed a retrospective cohort study of pediatric patients aged 1–18 years who, according to the US Renal Data System, started dialysis between 1995 and 2015. The primary predictor was eGFR at the time of dialysis initiation, categorized as higher (eGFR&gt;10 ml/min per 1.73 m 2 ) versus lower eGFR (eGFR≤10 ml/min per 1.73 m 2 ). Results Of 15,170 children, 4327 (29%) had a higher eGFR (median eGFR, 12.8 ml/min per 1.73 m 2 ) at dialysis initiation. Compared with children with a lower eGFR (median eGFR, 6.5 ml/min per 1.73 m 2 ), those with a higher eGFR at dialysis initiation were more often white, girls, underweight or obese, and more likely to have GN as the cause of ESRD. The risk of death was 1.36 times higher (95% confidence interval, 1.24 to 1.50) among children with a higher (versus lower) eGFR at dialysis initiation. The association between timing of dialysis and survival differed by treatment modality—hemodialysis versus peritoneal dialysis ( P &lt;0.001 for interaction)—and was stronger among children initially treated with hemodialysis (hazard ratio, 1.56, 95% confidence interval, 1.39 to 1.75; versus hazard ratio, 1.07, 95% confidence interval, 0.91 to 1.25; respectively). Conclusions In children with ESRD, a higher eGFR at dialysis initiation is associated with lower survival, particularly among children whose initial treatment modality is hemodialysis.
A phase II study of AMN107, a novel tyrosine kinase inhibitor, administered to patients (pts) with systemic mastocytosis (SM)
Authors: M. Schatz, G. Verhoef, N. Gattermann, O. G. Ottmann, T. Schimansky, L. Alland, T. Rafferty, A. Gratwohl, G. Follows, A. Hochhaus
Journal: Journal of Clinical Oncology (2006)

6588 Background: SM is a clonal hematologic disorder associated with a constitutive activation of c-kit based on point mutations of this tyrosine kinase and is characterized by mast cell infiltration of extracutaneous organs. AMN107 is a novel aminopyrimidine which potently inhibits Bcr-Abl, as well as the PDGFR and c-kit kinases. Methods: This phase II, open-label study was designed to evaluate the safety and efficacy of AMN107 (400 mg bid). SM pts meeting specific disease criteria and with a clinical indication for treatment were enrolled. Preliminary data are presented for the first 23 pts accrued prior to September 1, 2005. Results: The median age was 49 (range 33–78) yrs and the median time from diagnosis of SM was 27 (range 1 to 292) months. For those with data available, 13/17 pts had a c-kit D816V mutation in bone marrow cells. The median exposure to AMN107 was 144 days. Treatment is ongoing for 18 (78%) pts; 5 (22%) discontinued, 3 (13%) for adverse events and 2 (9%) withdrew consent. Three (13%) responses were reported (2 incomplete remissions and 1 minor response), based on serum tryptase, bone marrow mast cell infiltration and improvement of clinical symptoms. Baseline mutation data are available for 2 of the 3 responding pts and revealed the c-kit D816V mutation. Anemia was reported in 2 (9%) pts. Non-hematologic toxicities in ≥10% of pts were headache in 12 (52%) pts (Gr 3/4 in 2; 9%), fatigue in 9 (39%) pts (Gr 3/4 in 1; 4%), nausea in 8 (35%) pts, vomiting in 7 (30%) pts, pruritus in 7 (30%) pts (Gr 3/4 in 2; 9%), muscle spasms in 6 (26%) pts (Gr 3/4 in 1; 4%), diarrhea in 5 (22%) pts (Gr 3/4 in 1; 4%), upper abdominal pain, rash in 5 (22%) pts each, dizziness, pain in extremities in 4 (17%) pts each (Gr 3/4 in 1; 4% each), dyspnea, myalgia, in 4 (17%) pts each, increased ALAT in 4 (17%) pts (Gr 3/4 in 2; 9%), bone pain, abdominal pain, cough, hard feces, pustular rash in 3 (13%) pts each, and hypotension in 3 (13%) pts (Gr 3/4 in 2; 9%). There were no deaths. Conclusions: These data suggest that AMN107 has clinical activity and an acceptable safety and tolerability profile in pts with SM. [Table: see text]
Effect of a Community Health Worker–Delivered Parental Education and Counseling Intervention on Anemia Cure Rates in Rural Indian Children
Authors: Arun S. Shet, Merrick Zwarenstein, Abha Rao, Paul Jebaraj, Karthika Arumugam, Salla Atkins, Maya Mascarenhas, Neil Klar, Maria Rosaria Galanti
Journal: JAMA Pediatrics (2019)

Iron deficiency anemia, the largest cause of anemia worldwide, adversely affects cognitive development in children. Moreover, the imperceptible childhood anemia prevalence reduction in response to anemia control measures is associated with tremendous social and economic cost.To evaluate the effects of community-based parental education/counseling when combined with usual treatment on children's anemia cure rate.A pragmatic cluster randomized clinical trial in children aged 12 to 59 months from 55 villages from the rural Chamrajnagar district in southern India was conducted between November 2014 and July 2015; 6-month follow-up ended in January 2016. Villages were randomly assigned to either usual treatment (n = 27) or to the intervention (n = 28). Among 1144 participating children, 534 were diagnosed as having anemia (hemoglobin levels <11 g/dL and >7.9 g/dL; to convert to grams per liter, multiply by 10) and constituted the study sample in this analysis. Data were analyzed between July 2016 and September 2017.Iron and folic acid (IFA), 20 mg/d, 5 times daily per week, for 5 months (usual treatment) or health worker-delivered education/counseling combined with usual treatment (intervention).The primary outcome was anemia cure rate defined as hemoglobin level at or greater than 11 g/dL during follow-up.Of the children included in the study, the mean age was 30 months, with a slightly higher ratio of boys to girls. Of 534 children with anemia (intervention n = 303; usual treatment n = 231), 517 were reassessed after 6 months (intervention n = 298; usual treatment n = 219) while 17 were lost to follow-up (intervention n = 5 and usual treatment n = 12). Anemia cure rate was higher in children in the intervention group compared with children receiving usual treatment (55.7% [n = 166 of 298] vs 41.4% [n = 90 of 219]). The risk ratio derived through multilevel logistic regression was 1.37 (95% CI, 1.04-1.70); the model-estimated risk difference was 15.1% (95% CI, 3.9-26.3). Intervention-group children demonstrated larger mean hemoglobin increments (difference, intervention vs control: 0.25 g/dL; 95% CI, 0.07-0.44 g/dL) and improved IFA adherence (61.7%; 95% CI, 56.2-67.3 vs 48.4%; 95% CI, 41.7-55.1 consumed >75% of tablets provided). Adverse events were mild (intervention: 26.8%; 95% CI, 21.8-31.9 vs usual treatment: 21%; 95% CI, 15.6-26.4). To cure 1 child with anemia, 7 mothers needed to be counseled (number needed to treat: 7; 95% CI, 4-26).Parental education and counseling by a community health worker achieved perceivable gains in curing childhood anemia. Policy makers should consider this approach to enhance population level anemia control.ISRCTN identifier: ISRCTN68413407.
Contribution of Inflammation and Bone Destruction to Pain in Arthritis: A Study in Murine Glucose‐6‐Phosphate Isomerase–Induced Arthritis
Authors: Matthias Ebbinghaus, Sylvia Müller, Gisela Segond von Banchet, Annett Eitner, Isabel Wank, Andreas Hess, Ingrid Hilger, Thomas Kamradt, Hans‐Georg Schaible
Journal: Arthritis & Rheumatology (2019)

Objective Arthritis is often characterized by inflammation and bone destruction. This study was undertaken to investigate the contribution of inflammation and bone destruction to pain. Methods Inflammation, bone resorption, pain‐related behaviors, and molecular markers (activating transcription factor 3 [ ATF ‐3], p‐ CREB , and transient receptor potential vanilloid channel 1) in sensory neurons were measured in murine glucose‐6‐phosphate isomerase (G6 PI )–induced arthritis, a model of rheumatoid arthritis. Depletion of Treg cells before immunization changed self‐limiting arthritis into nonremitting arthritis with pronounced bone destruction. Zoledronic acid ( ZA ) was administered to reduce bone resorption. Results Compared to nondepleted mice, Treg cell–depleted mice exhibited arthritis with more severe bone destruction and higher guarding scores ( P &lt; 0.05; n = 10 mice per group) as well as more persistent thermal hyperalgesia ( P &lt; 0.05), but displayed similar mechanical hyperalgesia at the hindpaws (n = 18–26 mice per group). These pain‐related behaviors, as well as an up‐regulation of the neuronal injury marker ATF ‐3 in sensory neurons (studied in 39 mice), appeared before the clinical score (inflammation) became positive and persisted in Treg cell–depleted and nondepleted mice. In the late stage of arthritis, Treg cell–depleted mice treated with ZA showed less bone resorption (&lt;50%; P &lt; 0.01) and less thermal hyperalgesia ( P &lt; 0.01) than Treg cell–depleted mice without ZA treatment (n = 15 mice per group), but ZA treatment did not reduce the clinical score and local mechanical hyperalgesia. Conclusion Pain‐related behaviors precede and outlast self‐limiting arthritis. In nonremitting arthritis with enhanced bone destruction, mainly local thermal, but not local mechanical, hyperalgesia was aggravated. The up‐regulation of ATF ‐3 indicates an early and persisting affection of sensory neurons by G6 PI ‐induced arthritis.
Posttraumatic Stress Disorder and Cognitive Processing Therapy in Youth–Reply
Authors: Rita Rosner, Ulrich Frick, Regina Steil
Journal: JAMA Psychiatry (2019)

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Robust Health Utility Assessment Among Long-term Survivors of Prostate Cancer: Results from the Cancer of the Prostate Strategic Urologic Research Endeavor Registry
Authors: Chang Wook Jeong, Janet E. Cowan, Jeanette M. Broering, Renske M.T. ten Ham, Leslie S. Wilson, Peter R. Carroll, Matthew R. Cooperberg
Journal: European Urology (2019)
Tissue-Resident Macrophages Promote Renal Cystic Disease
Authors: Kurt A. Zimmerman, Cheng J. Song, Zhang Li, Jeremie M. Lever, David K. Crossman, Addison Rains, Ernald J. Aloria, Nancy M. Gonzalez, John R. Bassler, Juling Zhou, Michael R. Crowley, Dustin Z. Revell, Zhaoqi Yan, Dan Shan, Etty N. Benveniste, James F. George, Michal Mrug, Bradley K. Yoder
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Disruption of cilia function before postnatal day 12–14 in mice or renal injury in adult mice with cilia dysfunction results in accelerated renal cyst formation. Macrophages have been implicated in promoting cyst formation; however, it is unclear whether infiltrating bone marrow-derived or kidney resident macrophages are responsible. The authors show that a specific population of juvenile-like resident macrophages are present during periods of accelerated cyst formation. Inhibition of juvenile-like resident macrophage accumulation using a colony-stimulating factor 1 receptor kinase inhibitor reduced the severity of cystic disease in two different animal models of cystic disease. These results suggest resident renal macrophages contribute to cystic disease. Background Mutations affecting cilia proteins have an established role in renal cyst formation. In mice, the rate of cystogenesis is influenced by the age at which cilia dysfunction occurs and whether the kidney has been injured. Disruption of cilia function before postnatal day 12–14 results in rapid cyst formation; however, cyst formation is slower when cilia dysfunction is induced after postnatal day 14. Rapid cyst formation can also be induced in conditional adult cilia mutant mice by introducing renal injury. Previous studies indicate that macrophages are involved in cyst formation, however the specific role and type of macrophages responsible has not been clarified. Methods We analyzed resident macrophage number and subtypes during postnatal renal maturation and after renal injury in control and conditional Ift88 cilia mutant mice. We also used a pharmacological inhibitor of resident macrophage proliferation and accumulation to determine the importance of these cells during rapid cyst formation. Results Our data show that renal resident macrophages undergo a phenotypic switch from R2b (CD11c lo ) to R2a (CD11c hi ) during postnatal renal maturation. The timing of this switch correlates with the period in which cyst formation transitions from rapid to slow following induction of cilia dysfunction. Renal injury induces the reaccumulation of juvenile-like R2b resident macrophages in cilia mutant mice and restores rapid cystogenesis. Loss of primary cilia in injured conditional Ift88 mice results in enhanced epithelial production of membrane-bound CSF1, a cytokine that promotes resident macrophage proliferation. Inhibiting CSF1/CSF1-receptor signaling with a CSF1R kinase inhibitor reduces resident macrophage proliferation, R2b resident macrophage accumulation, and renal cyst formation in two mouse models of cystic disease. Conclusions These data uncover an important pathogenic role for resident macrophages during rapid cyst progression.
Interleukin-2 (IL-2) with 13-cis retinoic acid (RA) is more effective than IL-2 alone as maintenance therapy in advanced cancer responsive to chemotherapy. Final result of a Phase-II randomized trial
Authors: Francesco Recchia, Sandro De Filippis, Gaetano Saggio, Edoardo Alesse, Rita Gallo, Silvio Rea
Journal: Cancer Research (2004)

4684  In a phase 1B study we established that low-dose IL-2 and 13-cis retinoic acid was not toxic and could be administered safely as maintenance therapy for patients (PTS) exhibiting response or disease stabilization to chemotherapy (CT), but at a high risk of relapse (Clin Cancer Res 7: 1251-1257, 2001). A phase II study (Int J Oncol 20: 1275-82, 2002) showed the efficacy of such regimen in improving immunological parameters and in prolonging response in the same category of PTS.With the objective of verifying the role of RA in this drug combination, 112 PTS with histologically proven, locally advanced or metastatic tumors, were enrolled in this phase II randomized study. After standard CT, PTS were randomized to receive IL-2, 1.8 x 106 I.U. for 5 days/week for 2 consecutive cycles of 3 weeks, with 1 week’s rest, for up to 3 years (arm A, 56 PTS) or the same regimen plus RA, 0.5 mg/Kg administered according to the same schedule (arm B, 56 PTS). PTS were monitored every 2 months by determination of vascular endothelial growth factor (VEGF), CD4/CD8 ratio, NK and tumor markers, with response assessed every 4 months. PTS were homogeneous in both arms for age, performance status, type of disease, amount of previous chemotherapy received and baseline values of all parameters. Toxicity was slight in both arms. After a median follow-up of 31 months (minimum 23 months), even if all parameters improved in both arms, arm B had better results (lymphocyte p=0.001, NK p=0.001, CD4/CD8 p=0.001). There was a trend for a reduction of VEGF in both arms. Time to progression was 11.7 and 40.3 months in arm A and B respectively (P
Beyond autism: Challenging unexamined assumptions about social motivation in typical development
Authors: Karen Bartsch, David Estes
Journal: Behavioral and Brain Sciences (2019)

Abstract In challenging the assumption of autistic social uninterest, Jaswal &amp; Akhtar have opened the door to scrutinizing similar unexamined assumptions embedded in other literatures, such as those on children's typically developing behaviors regarding others’ minds and morals. Extending skeptical analysis to other areas may reveal new approaches for evaluating competing claims regarding social interest in autistic individuals.