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101.
Beth H. Vogel Vincent Bonagura Geoffrey A. Weinberg Mark Ballow Jason Isabelle Lisa DiAntonio April Parker Allison Young Charlotte Cunningham-Rundles Chin-To Fong Jocelyn Celestin Heather Lehman Arye Rubinstein Subhadra Siegel Leonard Weiner Carlos Saavedra-Matiz Denise M. Kay Michele Caggana 《Journal of clinical immunology》2014,34(3):289-303
Purpose
To describe the process and assess outcomes for the first 2 years of newborn screening for severe combined immunodeficiency (SCID NBS) in New York State (NYS).Methods
The NYS algorithm utilizes a first-tier molecular screen for TRECs (T-cell receptor excision circles), the absence of which is indicative of increased risk of immunodeficiency.Results
During the first 2 years, 485,912 infants were screened for SCID. Repeat specimens were requested from 561 premature and 746 non-premature infants with low or borderline TRECs. A total of 531 infants were referred for diagnostic evaluation leading to identification of 10 infants with SCID and 87 with a clinically significant non-SCID abnormality based on flow cytometry or CBC results (positive predictive value 20.3 %). Nine infants were diagnosed with typical SCID and one with leaky SCID. SCID diagnoses included two patients with adenosine deaminase deficiency, three patients with typical and one with leaky IL2RG-related SCID, one patient with IL7Rα-related SCID, and three cases of typical SCID, etiology unknown. TRECs were undetectable in eight of the nine babies with typical SCID. Infants with other non-SCID conditions included 27 patients with a syndrome that included T-cell impairment, 18 of which had DiGeorge syndrome. Seventeen infants had T-cell impairment secondary to another clinically significant condition, and 13 were classified as ‘other’. Among 30 infants classified as idiopathic T-cell lymphopenia, 11 have since resolved, and the remainder continues to be followed. One infant with undetectable TRECs had normal follow-up studies. Molecular studies revealed the presence of two changes in the infant’s DNA.Conclusions
Overall, ten infants with SCID were identified during the first 2 years of screening in NYS, yielding an incidence of approximately 1 in 48,500 live births, which is consistent with the incidence observed by other states screening for SCID. The incidence of any clinically significant laboratory abnormality was approximately 1 in 5,000; both estimates are higher than estimates prior to the onset of newborn screening for SCID. Improvements to the NYS algorithm included the addition of a borderline category that reduced the proportion of infants referred for flow cytometric analysis, without decreasing sensitivity. We identified a large number of infants with abnormal TRECs and subsequent idiopathic T-cell lymphopenia. Long-term follow-up studies are needed to determine the prognosis and optimal treatment for this group of patients, some of whom may present with previously unrecognized, transient lymphopenia of infancy. 相似文献102.
103.
Camaren M.Cuenca Matthew A.Borgman Michael D.April Andrew D.Fisher Steven G.Schauer 《军事医学研究(英文)》2021,8(1):17-24
Background:Pediatric casualties account for a notable proportion of encounters in the deployed setting based on the humanitarian medical care mission.Previously published data demonstrates that an age-adjust shock index may be a useful tool in predicting massive transfusion and death in children.We seek to determine if those previous findings are applicable to the deployed,combat trauma setting.Methods:We queried the Department of Defense Trauma Registry(DODTR)for all pediatric subjects admitted to US and Coalition fixed-facility hospitals in Iraq and Afghanistan from January 2007 to January 2016.This was a secondary analysis of casualties seeking to validate previously published data using the shock index,pediatric age adjusted.We then used previously published thresholds to determine patients outcome for validation by age grouping,1-3 years(1.2),4-6 years(1.2),7-12 years(1.0),13-17 years(0.9).Results:From January 2007 through January 2016 there were 3439 pediatric casualties of which 3145 had a documented heart rate and systolic pressure.Of those 502(16.0%)underwent massive transfusion and 226(7.2%)died prior to hospital discharge.Receiver operating characteristic(ROC)thresholds were inconsistent across age groups ranging from 1.0 to 1.9 with generally limited area under the curve(AUC)values for both massive transfusion and death prediction characteristics.Using the previously defined thresholds for validation,we reported sensitivity and specificity for the massive transfusion by age-group:1-3(0.73,0.35),4-6(0.63,0.60),7-12(0.80,0.57),13-17(0.77,0.62).For death,1-3(0.75,0.34),4-6(0.66-0.59),7-12(0.64,0.52),13-17(0.70,0.57).However,negative predictive values(NPV)were generally high with all greater than 0.87.Conclusions:Within the combat setting,the age-adjusted pediatric shock index had moderate sensitivity and relatively poor specificity for predicting massive transfusion and death.Better scoring systems are needed to predict resource needs prior to arrival,that perhaps include other physiologic metrics.We were unable to validate the previously published findings within the combat trauma population. 相似文献
104.
The interval between the onset of rheumatoid arthritis (RA) and the most recent pregnancy prior to RA onset in 88 women was determined. These data were compared with data obtained from a group of 144 age-matched normal women (controls) who had been assigned a “dummy date for RA onset” for the purposes of analysis. The frequency of disease onset during 3 time intervals within the period from conception to 1 year postpartum was compared with the frequency of disease onset outside this period. There was a reduction in the incidence of disease onset during pregnancy (adjusted odds ratio [OR] 0.30, 95% confidence interval [CI] 0.04—2.6) and a numerically greater increased risk of RA onset during the first 3 months postpartum (OR 5.6, 95% CI 1.8—17.6), which persisted for the subsequent 9 months (OR 2.6, 95% CI 0.8—7.9). A reduction in the incidence of disease onset was seen during all pregnancies; in contrast, the postpartum increase was greater in those with RA onset after the first pregnancy. The reduced incidence of RA onset during pregnancy, with the increased risk postpartum, mirrors the previously described suppression of disease activity during pregnancy and the subsequent flare postpartum in women with established RA. In addition, the increased postpartum risk after the first pregnancy might suggest that in susceptible women, either the hormonal changes or the exposure to the fetus's paternal HLA might represent a risk factor for disease causation. 相似文献
105.
Amy M. Berkman MD J. A. Livingston MD Kelly Merriman PhD Michelle Hildebrandt PhD Jian Wang PhD Seyedeh Dibaj PhD Jennifer McQuade MD Nancy You MD MHSc Anita Ying MD MBA Carlos Barcenas MD MSc Diane Bodurka MD MPH April DePombo DO Hun Ju Lee MD John de Groot MD Michael Roth MD 《Cancer》2020,126(16):3708-3718
106.
Kerryn W. Reding Aaron K. Aragaki Richard K. Cheng Ana Barac Sylvia Wassertheil-Smoller Jessica Chubak Marian C. Limacher W. Gregory Hundley Ralph D'Agostino Jr. Mara Z. Vitolins Theodore M. Brasky Laurel A. Habel Eric J. Chow Rebecca D. Jackson Chu Chen April Morgenroth Wendy E. Barrington Matthew Banegas Matthew Barnhart Rowan T. Chlebowski 《The oncologist》2020,25(8):712-721
107.
April W. Armstrong Michael P. Siegel Jerry Bagel Erin E. Boh Megan Buell Kevin D. Cooper Kristina Callis Duffin Lawrence F. Eichenfield Amit Garg Joel M. Gelfand Alice B. Gottlieb John Y.M. Koo Neil J. Korman Gerald G. Krueger Mark G. Lebwohl Craig L. Leonardi Arthur M. Mandelin M. Alan Menter Abby S. Van Voorhees 《Journal of the American Academy of Dermatology》2017,76(2):290-298
108.
Jocelyn F. Burke MD Logan Schlosser BS April D. Harrison BS Muthusamy Kunnimalaiyaan PhD Herbert Chen MD FACS 《Annals of surgical oncology》2013,20(12):3862-3868
Background
Development of targeted therapies for medullary thyroid cancer (MTC) has focused on inhibition of the rearranged during transfection (RET) proto-oncogene. Akt has been demonstrated to be a downstream target of RET via the key mediator phosphoinositide-3-kinase. MK-2206 is an orally administered allosteric Akt inhibitor that has exhibited minimal toxicity in phase I trials. We explored the antitumor effects of this compound in MTC.Methods
Human MTC-TT cells were treated with MK-2206 (0–20 μM) for 8 days. Assays for cell viability were performed at multiple time points with MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). The mechanism of action, mechanism of growth inhibition, and production of neuroendocrine tumor markers were assessed with Western blot analysis.Results
MK-2206 suppressed MTC cell proliferation in a dose-dependent manner (p ≤ 0.001). Levels of Akt phosphorylated at serine 473 declined with increasing doses of MK-2206, indicating successful Akt inhibition. The apoptotic proteins cleaved poly (ADP-ribose) polymerase and cleaved caspase-3 increased in a dose-dependent manner with MK-2206, while the apoptosis inhibitor survivin was markedly reduced. Importantly, the antitumor effects of MK-2206 were independent of RET inhibition, as the levels of RET protein were not blocked.Conclusions
MK-2206 significantly suppresses MTC proliferation without RET inhibition. Given its high oral bioavailability and low toxicity profile, phase II studies with this drug alone or in combination with RET inhibitors are warranted. 相似文献109.
Richard J. Browning April T. Sanchez Stephen Mullins Daniel J. Sheehan Loretta S. Davis 《Journal of cutaneous pathology》2017,44(3):279-282
Blepharochalasis is a rare disorder of unknown etiology defined by loose, atrophic periorbital skin following recurrent episodes of eyelid edema. Characteristic histopathology shows complete absence of elastic fibers. The current case progressed after multiple episodes of crying, which may be related to matrix metalloproteinase dysregulation. This case offers further insights into the possible pathogenesis of blepharochalasis, paving the way for more targeted, disease‐modifying therapies. 相似文献
110.
Lavanya Cherukuri April Kinninger Divya Birudaraju Suvasini Lakshmanan Dong Li Ferdinand Flores Song S. Mao Matthew J. Budoff 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2021,31(6):1767-1773
Background and aimsObesity and osteoporosis are two important and growing public health problems worldwide. Body mass index (BMI) has been found to be inversely related to the risk of osteoporotic fracture. We aimed to assess the association of BMI with thoracic vertebral bone mineral density (BMD) measured from a quantitative computed tomography (QCT).Methods and resultsWe retrospectively evaluated the data from 15,758 consecutive patients (5675 females and 10,083 males) between age 20–90 years, who underwent Coronary Artery Calcium (CAC) scoring. Quantitative data analyses of thoracic trabecular BMD (mg/cm3) was performed with a phantom system or phantomless using validated software. The gender-specific subgroup was divided based on age (<45, 45–55, 55–65, >65 yrs in females; <40,40–60,>60 yrs in Males) and weight by BMI (kg/m2) as < 25 (normal or low weight), >25 - <30 (overweight) and >30 (obesity). Analysis of variance (ANOVA) and Scheffe's post hoc procedure tested the association of body weight/BMI on BMD. A significant positive association between the body weight and BMD existed in obese population in elder groups in both genders (p < 0.05). There was no significant difference in BMD in 40–60 years in men and <55 years in women with normal or low weight compared to overweight or obese cohorts.ConclusionsWe concluded that the effect of weight on BMD is age-specific and the BMD should be monitored routinely with a cardiac CT scan in the senile population. 相似文献