Anikó Szabó - Academia.edu (original) (raw)

Papers by Anikó Szabó

Circulation, Mar 13, 2012

Introduction: There continues to be an increase nationwide in hospitalizations for atrial fibrill... more Introduction: There continues to be an increase nationwide in hospitalizations for atrial fibrillation (AF). However the impact of age, race and gender on in-patient mortality and stroke events for AF hospitalizations is unknown. Methods: This is a cross-sectional study utilizing data from the 2008 Nationwide Inpatient Sample (NIS). NIS is the largest, all-payer, hospitalization database in USA. We identified all AF-related hospitalizations through the presence of the appropriate ICD-9-CM codes. We calculated the adjusted odds of in-hospital mortality and stroke events with respect to age, gender and race in AF patients using multivariate logistic regression. All analyses were adjusted for the survey design. Results: There were an estimated to 425,470 AF-related hospitalizations in 2008 with 4,041(0.95%) in-hospital deaths and 3,531(0.83%) stroke-related events associated with such hospitalizations, respectively. Table 1 shows the results related to in-hospital mortality and stroke events, adjusted for other comorbidities such as history of diabetes, hypertension, coronary artery disease, myocardial infarction, congestive heart failure and dyslipidemia. Conclusion: African Americans have the highest risk of stroke-events and in-hospital mortality with AF related hospitalizations among all racial/ethnic groups. Increasing age is associated with a large increase in the risk of in-hospital mortality, and a smaller increase in stroke events. Gender was not found to be an independent risk factor for either stroke events or in-hospital mortality for AF. Further research is needed to better characterize the natural history and treatment outcomes in this cohort. Table 1 Odds ratio and confidence limits for in-hospital mortality and stroke events adjusted for co-morbidities. Predictor Comparison In-hospital mortality In-hospital stroke events Point Estimate 95% Wald Confidence Limits p-value Point Estimate 95% Wald Confidence Limits p-value Sex Female vs Male 1.019 0.864 - 1.201 0.82 1.076 0.903 - 1.282 0.41 Race / Ethnicity Black vs White 2.123 1.625 - 2.774 0.0007 2.030 0.731 - 1.450 0.004 Hispanic vs White 1.495 1.068 - 2.093 0.28 1.479 1.061 - 2.062 0.26 Asian or Pacific Islander vs White 1.364 0.752 - 2.477 0.70 0.976 0.481 - 1.982 0.79 Native American vs White 0.732 0.227 - 2.358 0.30 0.260 0.037 - 1.856 0.14 Other vs White 1.083 0.659 - 1.779 0.60 1.282 0.807 - 2.036 0.17 Age 62 - 72 vs ≤ 61 2.454 1.723 - 3.496 0.028 1.277 0.995 - 1.640 0.75 73 - 80 vs ≤ 61 3.997 2.847 - 5.612 0.0001 1.287 0.990 - 1.674 0.69 > 80 vs ≤ 61 7.900 5.721 - 10.910

Clinical Nephrology, Oct 1, 2010

The review concluded that evidence from this systematic review favoured hydration with sodium bic... more The review concluded that evidence from this systematic review favoured hydration with sodium bicarbonate (as compared with sodium chloride) for prevention of contrast nephropathy. The review was generally well conducted, but the poor quality of some of the included trials limits the reliability of the authors' conclusions. Authors' objectives To evaluate the benefit of sodium bicarbonate-based hydration for the prevention of contrast-induced nephropathy. Searching MEDLINE was searched from 1950 to October 2008 for articles published in English. Search terms were reported. Cochrane Central Register of Controlled Trials (CENTRAL) was also searched. Abstracts from seven scientific meetings were searched manually between 2005 and 2008. An update search of MEDLINE was conducted in May 2009. A further update search was conducted in July 2009. Study selection Randomised controlled trials (RCTs) of adult patients randomised to receive a bicarbonate-containing intravenous solution versus an alternate solution were eligible for inclusion. Trials had to report the incidence of contrast-induced nephropathy based on serum creatinine criterion and had to use a uniform contrast agent (unless randomisation was stratified according to type of contrast). Abstracts were included. Trials permitted cointerventions if both arms were administered similarly. Trials were excluded if they used differing rates of infusion, significantly different osmolarity and if they used prophylactic agents that were administered in a non-standardised or non-stratified manner. The included trials compared sodium bicarbonate with sodium chloride in seven countries (China, USA, South Korea, Japan, Turkey and Germany were included). Trials generally used a non-ionic low osmolar contrast agent. Most patients underwent cardiac angiography. Contrast-induced nephropathy was defined by either relative increase in serum creatinine (≥25%) or absolute increase in serum creatinine (≥0.05mg/dL). Two authors independently performed study selection. Disagreements were resolved by discussion. Assessment of study quality Two reviewers independently assessed trial quality using the Jadad scale and Delphi criteria. Quality items such as blinding, randomisation, intention-to-treat, similarity of baseline groups, withdrawals and allocation concealment were assessed. The Jadad scale was used to give a quantitative estimate of quality: trials were scored from 1 (poor quality) to a maximum of 5 (high quality). Disagreements between reviewers were resolved by discussion. Data extraction Two reviewers extracted data on contrast-induced nephropathy using a pre-defined sheet and used these data to calculate odds ratios (OR) and 95% confidence intervals (CI). Trial authors were contacted for missing data. Methods of synthesis Fixed-effect meta-analysis was undertaken to obtain pooled odds ratios and 95% CIs. Statistical heterogeneity was assessed using I 2 and Woolf's test. Subgroup analysis excluded studies that allowed N-acetylcysteine co-therapy. Sensitivity analysis was undertaken using random-effects meta-analysis. Publication bias was assessed with funnel plots and Macaskill's test. Results of the review Ten RCTs were included in the review (n=1,090 patients), five of which were abstracts. Trial sample sizes ranged from

Neurobiology of Stress, 2015

Objective: Hematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical proc... more Objective: Hematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical procedure involving significant emotional and immune challenges. The endocannabinoid (eCB) signaling system is involved in regulation of both the immune system and emotional reactivity, yet little is known about its function during HCT. We investigated the role of the eCB signaling system in a group of HCT recipients. Methods: A total of 19 HCT recipients were enrolled and provided psychosocial data and blood samples at three peri-transplant time points: prior to transplant, hospital discharge, and approximately 100 days post-transplant. Psychosocial factors, inflammatory molecules, and the eCBs were determined and assessed for changes over this period and association with each other. Results: HCT recipients demonstrated significant changes over the peri-transplant period in inflammatory molecules and psychosocial functioning, but not in circulating concentrations of the eCBs. Associations among these variables were most likely to be present pre-transplant and least likely to be present immediately post-transplant, with depressive symptoms and inflammation most significantly associated. The eCB 2-arachidonoylglycerol (2-AG) was significantly, positively associated with both interleukin (IL)-6 and C-reactive protein (CRP) and negatively associated with depressive symptoms. Conclusions: The eCB signaling system may have alternative sources and regulatory mechanisms in addition to the immune system. Given the significant associations with inflammatory molecules and depressive symptoms in the peri-transplant period, it is important to better understand this system and its potential implications in the setting of complex and stressful medical procedures such as HCT.

Breast cancer research : BCR, 2006

Predicting the clinical course of breast cancer is often difficult because it is a diverse diseas... more Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation. Gene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive carcinomas, one fibroadenoma and five normal tissues) and three breast cancer cell lines were prospectively analyzed using a microarray (Agilent) and a qRT-PCR assay comprised of 53 genes. Biological subtypes were assigned from the microarray and...

Stroke; a journal of cerebral circulation, 2015

Journal of Nephrology, 2014

Optometry and vision science : official publication of the American Academy of Optometry, 2014

Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relativ... more Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD). Forty asymptomatic subjects were recruited (9 men, 31 women; age range, 51 to 69 years; mean age, 61.4 years). Comprehensive eye examination, fundus photography, and high-resolution retinal imaging using spectral domain optical coherence tomography and adaptive optics were performed on each patient. Genetic RR scores were developed using an age-independent algorithm. Adaptive optics scanning light ophthalmoscope images were acquired in the macula extending to 10 degrees temporal and superior from fixation and were used to calculate cone density in up to 35 locations for each subject. Relative risk was not significantly predictive of fundus grade (p = 0.98). Only patients with a high RR displayed drusen on Cirrus or Bioptigen OCT. Compared to an eye with a grade of 0, an eye with a fundus grade equal to or greater than 1 h...

International Journal of Radiation Biology, 2014

Purpose-To develop mitigators for combined irradiation to the lung and skin. Methods-Rats were tr... more Purpose-To develop mitigators for combined irradiation to the lung and skin. Methods-Rats were treated with X-rays as follows: (1) 12.5 or 13 Gy whole thorax irradiation (WTI) (2) 30 Gy soft X-rays to 10% area of the skin only (3) 12.5 or 13 Gy WTI+30 Gy skin irradiation after 3 hours (4) 12.5 Gy WTI+skin irradiation and treated with captopril (160 mg/m 2 / day) started after 7 days. Our end points were survival (primary) based on IACUC euthanization criteria and secondary measurements of breathing intervals and skin injury. Lung collagen at 210 days was measured in rats surviving 13 Gy WTI. Results-After 12.5 Gy WTI with or without skin irradiation, one rat (12.5 Gy WTI) was euthanized. Survival was less than 10% in rats receiving 13 Gy WTI, but was enhanced when combined with skin irradiation (p<0.0001). Collagen content increased at 210 days after 13 Gy WTI vs 13 Gy WTI+30 Gy skin irradiation (p<0.05). Captopril improved radiation-dermatitis after 12.5 Gy WTI+30 Gy skin irradiation (p=0.008).

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 24, 2014

The optimal chemotherapy regimen to use with radiotherapy in stage III non-small-cell lung cancer... more The optimal chemotherapy regimen to use with radiotherapy in stage III non-small-cell lung cancer is unknown. Here, we compare the outcome of patents treated within the Veterans Health Administration with either etoposide-cisplatin (EP) or carboplatin-paclitaxel (CP). We identified patients treated with EP and CP with concurrent radiotherapy from 2001 to 2010. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and an instrumental variables analysis. Comorbidities and treatment complications were identified through administrative data. A total of 1,842 patients were included; EP was used in 27% (n = 499). Treatment with EP was not associated with a survival advantage in a Cox proportional hazards model (hazard ratio [HR], 0.97; 95% CI, 0.85 to 1.10), a propensity score matched cohort (HR, 1.07; 95% CI, 0.91 to 1.24), or a propensity score adjusted model (HR, 0.97; 95% CI, 0.85 to 1.10). I...

Journal of Nephrology, 2014

Background-The epidemiology of gastrointestinal bleeding (GIB) in end-stage renal disease (ESRD) ... more Background-The epidemiology of gastrointestinal bleeding (GIB) in end-stage renal disease (ESRD) has not been adequately characterized. Using United States Renal Data System data we investigated the epidemiology of GIB in hospitalized patients receiving long-term dialysis. Methods-Medicare ESRD patients who began dialysis between 1996 and 2005 were followed from 90 days after starting dialysis to death, transplant, loss of Medicare, or December 31, 2006. GIB events were identified using claims data. Predictors of GIB incidence were analyzed using over-dispersed Poisson regression and Cox regression was used to evaluate the effect on survival. Repeat episodes were modeled using a partially conditional Cox regression model. Results-406,836 patients were followed for 832,131 person-years, during which 133,967 events were identified. The incidence of GIB was stable through year 2000 but steadily increased thereafter. Chronic gastric ulcer and colonic diverticulosis were the commonest defined causes of upper and lower GIB respectively. Age >49 years, female gender, hypertension as the cause of ESRD, and initiation on hemodialysis was associated with a greater risk of GIB. An episode of GIB conferred a increased hazard of death (hazard ratio 1.9, 95 % CI 1.86-1.93). A previous episode of GIB was associated with greater hazard of another episode (hazard ratio 3.93, 95 % CI 3.82-4.05). Conclusions-In ESRD patients incident to long-term dialysis the incidence of hospitalassociated GIB is increasing, is associated with a greater hazard of death, and carries a great hazard of repeat episodes.

Transfusion, 2013

Background-Twenty-four low frequency platelet antigens (HPAs) have been implicated as immunogens ... more Background-Twenty-four low frequency platelet antigens (HPAs) have been implicated as immunogens in neonatal alloimmune thrombocytopenia (NAIT). We performed studies to define more fully how often these antigens trigger maternal immunization leading to NAIT. Study design and methods-In a Phase 1 study, fathers of selected NAIT cases not resolved by serologic testing but thought to have a high likelihood of NAIT on clinical and serologic grounds were typed for low frequency HPAs (LFHPAs) by DNA sequencing. In a Phase 2 study, high-throughput methods were used to type fathers of 1067 consecutive unresolved NAIT cases for LFHPAs. Mothers of 1338 unresolved cases were also typed to assess the prevalence of LFHPAs in a population racially/ethnically similar to the fathers. Results-In Phase 1, LFHPAs were identified in 16 of 244 fathers (6.55%). In Phase 2, LFPAs were found in only 28 of 1067 fathers (2.62%). LFHPAs were identified in 27 of 1338 maternal samples (2.01%). HPA-9bw was by far the most common LFHPA identified in the populations

Transfusion, 2012

We and others have identified more than 20 low-frequency human platelet (PLT) antigens (HPAs) tha... more We and others have identified more than 20 low-frequency human platelet (PLT) antigens (HPAs) that can induce antibodies capable of causing neonatal alloimmune thrombocytopenia (NAIT). 1-4 Like HPA-1a and HPA-4b, the antigens that most often trigger NAIT in Caucasian and Asian populations, respectively, the incidence of lowfrequency antigens is likely to vary significantly in different ethnic and racial populations. We recently described HPA-21bw, a low-frequency antigen, responsible for a single case of severe NAIT in a presumed Caucasian family. 1 The HPA-21bw antigen results from a G>A1960 mutation (RS70940817), in ITGB3, encoding PLT glycoprotein (GP) β3 subunit (GPIIIa) and creates a Glu>Lys substitution at Residue 628 in mature β3. No examples of HPA-21bw were identified in 100 unrelated Caucasian individuals. 1 We recently encountered a second case of NAIT apparently caused by HPA-21bw in an Asian family (unpublished). The mutation encoding HPA-21bw was also identified in two of 38 Asian individuals tested in a hypertension and insulin resistance study according to the human SNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; ss95216694). CONFLICT OF INTEREST There are no conflicts of interest.

The Thoracic and Cardiovascular Surgeon, 2007

The Thoracic and Cardiovascular Surgeon, 2007

The Thoracic and Cardiovascular Surgeon, 2007

Radiation Research, 2013

The goal of our study was to identify a histological marker for testing countermeasures for mitig... more The goal of our study was to identify a histological marker for testing countermeasures for mitigation of late radiation injury to the lung. Pulmonary fibrosis is currently the best described "late effect" in survivors of acute radiation pneumonitis. However, robust fibrosis does not develop in some rodent strains for years after a single dose of radiation to the whole thorax. We observed radiation-associated focal alveolar lesions that were rich in giant cells and macrophages containing cholesterol clefts in the lungs of irradiated WAG/ RijCmcr rats. These lesions were first observed after pneumonitis, around 21 weeks after receiving a radiation dose of 13 Gy to the thorax but not until 71 weeks in unirradiated rats. The number of cholesterol clefts increased with time after irradiation through 64 weeks of observation, and at 30 weeks after 13 Gy, cholesterol clefts were associated with several indices of deterioration in lung function. The number of cholesterol clefts in irradiated lung sections were reduced by the angiotensin converting enzyme (ACE) inhibitor enalapril (25-42 mg/m 2 /day) from 18.7 ± 4.2/lung section to 6.8 ± 2.4 (P = 0.029), 5.2 ± 1.9 (P = 0.0051) and 6.7 ± 1.9 (P = 0.029) when the drug was started at 1 week, 5 or 15 weeks after irradiation, respectively, and continued. Similar lesions have been previously observed in the lungs of one strain of irradiated mice and in patients following radiotherapy. We propose that alveolar lesions with cholesterol clefts may be used as a histological marker of the severity of radiation lung injury and to study its mitigation in WAG/

PM&R, 2011

Objective. To determine if folic acid supplementation improves vascular function (brachial artery... more Objective. To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design. Prospective cross-sectional study. Setting. Academic institution in the Midwestern United States. Subjects. Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures. Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flowinduced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results. Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions. This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention.

Circulation, Mar 13, 2012

Introduction: There continues to be an increase nationwide in hospitalizations for atrial fibrill... more Introduction: There continues to be an increase nationwide in hospitalizations for atrial fibrillation (AF). However the impact of age, race and gender on in-patient mortality and stroke events for AF hospitalizations is unknown. Methods: This is a cross-sectional study utilizing data from the 2008 Nationwide Inpatient Sample (NIS). NIS is the largest, all-payer, hospitalization database in USA. We identified all AF-related hospitalizations through the presence of the appropriate ICD-9-CM codes. We calculated the adjusted odds of in-hospital mortality and stroke events with respect to age, gender and race in AF patients using multivariate logistic regression. All analyses were adjusted for the survey design. Results: There were an estimated to 425,470 AF-related hospitalizations in 2008 with 4,041(0.95%) in-hospital deaths and 3,531(0.83%) stroke-related events associated with such hospitalizations, respectively. Table 1 shows the results related to in-hospital mortality and stroke events, adjusted for other comorbidities such as history of diabetes, hypertension, coronary artery disease, myocardial infarction, congestive heart failure and dyslipidemia. Conclusion: African Americans have the highest risk of stroke-events and in-hospital mortality with AF related hospitalizations among all racial/ethnic groups. Increasing age is associated with a large increase in the risk of in-hospital mortality, and a smaller increase in stroke events. Gender was not found to be an independent risk factor for either stroke events or in-hospital mortality for AF. Further research is needed to better characterize the natural history and treatment outcomes in this cohort. Table 1 Odds ratio and confidence limits for in-hospital mortality and stroke events adjusted for co-morbidities. Predictor Comparison In-hospital mortality In-hospital stroke events Point Estimate 95% Wald Confidence Limits p-value Point Estimate 95% Wald Confidence Limits p-value Sex Female vs Male 1.019 0.864 - 1.201 0.82 1.076 0.903 - 1.282 0.41 Race / Ethnicity Black vs White 2.123 1.625 - 2.774 0.0007 2.030 0.731 - 1.450 0.004 Hispanic vs White 1.495 1.068 - 2.093 0.28 1.479 1.061 - 2.062 0.26 Asian or Pacific Islander vs White 1.364 0.752 - 2.477 0.70 0.976 0.481 - 1.982 0.79 Native American vs White 0.732 0.227 - 2.358 0.30 0.260 0.037 - 1.856 0.14 Other vs White 1.083 0.659 - 1.779 0.60 1.282 0.807 - 2.036 0.17 Age 62 - 72 vs ≤ 61 2.454 1.723 - 3.496 0.028 1.277 0.995 - 1.640 0.75 73 - 80 vs ≤ 61 3.997 2.847 - 5.612 0.0001 1.287 0.990 - 1.674 0.69 &amp;amp;gt; 80 vs ≤ 61 7.900 5.721 - 10.910

Clinical Nephrology, Oct 1, 2010

The review concluded that evidence from this systematic review favoured hydration with sodium bic... more The review concluded that evidence from this systematic review favoured hydration with sodium bicarbonate (as compared with sodium chloride) for prevention of contrast nephropathy. The review was generally well conducted, but the poor quality of some of the included trials limits the reliability of the authors' conclusions. Authors' objectives To evaluate the benefit of sodium bicarbonate-based hydration for the prevention of contrast-induced nephropathy. Searching MEDLINE was searched from 1950 to October 2008 for articles published in English. Search terms were reported. Cochrane Central Register of Controlled Trials (CENTRAL) was also searched. Abstracts from seven scientific meetings were searched manually between 2005 and 2008. An update search of MEDLINE was conducted in May 2009. A further update search was conducted in July 2009. Study selection Randomised controlled trials (RCTs) of adult patients randomised to receive a bicarbonate-containing intravenous solution versus an alternate solution were eligible for inclusion. Trials had to report the incidence of contrast-induced nephropathy based on serum creatinine criterion and had to use a uniform contrast agent (unless randomisation was stratified according to type of contrast). Abstracts were included. Trials permitted cointerventions if both arms were administered similarly. Trials were excluded if they used differing rates of infusion, significantly different osmolarity and if they used prophylactic agents that were administered in a non-standardised or non-stratified manner. The included trials compared sodium bicarbonate with sodium chloride in seven countries (China, USA, South Korea, Japan, Turkey and Germany were included). Trials generally used a non-ionic low osmolar contrast agent. Most patients underwent cardiac angiography. Contrast-induced nephropathy was defined by either relative increase in serum creatinine (≥25%) or absolute increase in serum creatinine (≥0.05mg/dL). Two authors independently performed study selection. Disagreements were resolved by discussion. Assessment of study quality Two reviewers independently assessed trial quality using the Jadad scale and Delphi criteria. Quality items such as blinding, randomisation, intention-to-treat, similarity of baseline groups, withdrawals and allocation concealment were assessed. The Jadad scale was used to give a quantitative estimate of quality: trials were scored from 1 (poor quality) to a maximum of 5 (high quality). Disagreements between reviewers were resolved by discussion. Data extraction Two reviewers extracted data on contrast-induced nephropathy using a pre-defined sheet and used these data to calculate odds ratios (OR) and 95% confidence intervals (CI). Trial authors were contacted for missing data. Methods of synthesis Fixed-effect meta-analysis was undertaken to obtain pooled odds ratios and 95% CIs. Statistical heterogeneity was assessed using I 2 and Woolf's test. Subgroup analysis excluded studies that allowed N-acetylcysteine co-therapy. Sensitivity analysis was undertaken using random-effects meta-analysis. Publication bias was assessed with funnel plots and Macaskill's test. Results of the review Ten RCTs were included in the review (n=1,090 patients), five of which were abstracts. Trial sample sizes ranged from

Neurobiology of Stress, 2015

Objective: Hematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical proc... more Objective: Hematopoietic stem cell transplantation (HCT) is a stressful and rigorous medical procedure involving significant emotional and immune challenges. The endocannabinoid (eCB) signaling system is involved in regulation of both the immune system and emotional reactivity, yet little is known about its function during HCT. We investigated the role of the eCB signaling system in a group of HCT recipients. Methods: A total of 19 HCT recipients were enrolled and provided psychosocial data and blood samples at three peri-transplant time points: prior to transplant, hospital discharge, and approximately 100 days post-transplant. Psychosocial factors, inflammatory molecules, and the eCBs were determined and assessed for changes over this period and association with each other. Results: HCT recipients demonstrated significant changes over the peri-transplant period in inflammatory molecules and psychosocial functioning, but not in circulating concentrations of the eCBs. Associations among these variables were most likely to be present pre-transplant and least likely to be present immediately post-transplant, with depressive symptoms and inflammation most significantly associated. The eCB 2-arachidonoylglycerol (2-AG) was significantly, positively associated with both interleukin (IL)-6 and C-reactive protein (CRP) and negatively associated with depressive symptoms. Conclusions: The eCB signaling system may have alternative sources and regulatory mechanisms in addition to the immune system. Given the significant associations with inflammatory molecules and depressive symptoms in the peri-transplant period, it is important to better understand this system and its potential implications in the setting of complex and stressful medical procedures such as HCT.

Breast cancer research : BCR, 2006

Predicting the clinical course of breast cancer is often difficult because it is a diverse diseas... more Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation. Gene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive carcinomas, one fibroadenoma and five normal tissues) and three breast cancer cell lines were prospectively analyzed using a microarray (Agilent) and a qRT-PCR assay comprised of 53 genes. Biological subtypes were assigned from the microarray and...

Stroke; a journal of cerebral circulation, 2015

Journal of Nephrology, 2014

Optometry and vision science : official publication of the American Academy of Optometry, 2014

Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relativ... more Utilize high-resolution imaging to examine retinal anatomy in patients with known genetic relative risk (RR) for developing age-related macular degeneration (AMD). Forty asymptomatic subjects were recruited (9 men, 31 women; age range, 51 to 69 years; mean age, 61.4 years). Comprehensive eye examination, fundus photography, and high-resolution retinal imaging using spectral domain optical coherence tomography and adaptive optics were performed on each patient. Genetic RR scores were developed using an age-independent algorithm. Adaptive optics scanning light ophthalmoscope images were acquired in the macula extending to 10 degrees temporal and superior from fixation and were used to calculate cone density in up to 35 locations for each subject. Relative risk was not significantly predictive of fundus grade (p = 0.98). Only patients with a high RR displayed drusen on Cirrus or Bioptigen OCT. Compared to an eye with a grade of 0, an eye with a fundus grade equal to or greater than 1 h...

International Journal of Radiation Biology, 2014

Purpose-To develop mitigators for combined irradiation to the lung and skin. Methods-Rats were tr... more Purpose-To develop mitigators for combined irradiation to the lung and skin. Methods-Rats were treated with X-rays as follows: (1) 12.5 or 13 Gy whole thorax irradiation (WTI) (2) 30 Gy soft X-rays to 10% area of the skin only (3) 12.5 or 13 Gy WTI+30 Gy skin irradiation after 3 hours (4) 12.5 Gy WTI+skin irradiation and treated with captopril (160 mg/m 2 / day) started after 7 days. Our end points were survival (primary) based on IACUC euthanization criteria and secondary measurements of breathing intervals and skin injury. Lung collagen at 210 days was measured in rats surviving 13 Gy WTI. Results-After 12.5 Gy WTI with or without skin irradiation, one rat (12.5 Gy WTI) was euthanized. Survival was less than 10% in rats receiving 13 Gy WTI, but was enhanced when combined with skin irradiation (p<0.0001). Collagen content increased at 210 days after 13 Gy WTI vs 13 Gy WTI+30 Gy skin irradiation (p<0.05). Captopril improved radiation-dermatitis after 12.5 Gy WTI+30 Gy skin irradiation (p=0.008).

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 24, 2014

The optimal chemotherapy regimen to use with radiotherapy in stage III non-small-cell lung cancer... more The optimal chemotherapy regimen to use with radiotherapy in stage III non-small-cell lung cancer is unknown. Here, we compare the outcome of patents treated within the Veterans Health Administration with either etoposide-cisplatin (EP) or carboplatin-paclitaxel (CP). We identified patients treated with EP and CP with concurrent radiotherapy from 2001 to 2010. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding provided by propensity score methods and an instrumental variables analysis. Comorbidities and treatment complications were identified through administrative data. A total of 1,842 patients were included; EP was used in 27% (n = 499). Treatment with EP was not associated with a survival advantage in a Cox proportional hazards model (hazard ratio [HR], 0.97; 95% CI, 0.85 to 1.10), a propensity score matched cohort (HR, 1.07; 95% CI, 0.91 to 1.24), or a propensity score adjusted model (HR, 0.97; 95% CI, 0.85 to 1.10). I...

Journal of Nephrology, 2014

Background-The epidemiology of gastrointestinal bleeding (GIB) in end-stage renal disease (ESRD) ... more Background-The epidemiology of gastrointestinal bleeding (GIB) in end-stage renal disease (ESRD) has not been adequately characterized. Using United States Renal Data System data we investigated the epidemiology of GIB in hospitalized patients receiving long-term dialysis. Methods-Medicare ESRD patients who began dialysis between 1996 and 2005 were followed from 90 days after starting dialysis to death, transplant, loss of Medicare, or December 31, 2006. GIB events were identified using claims data. Predictors of GIB incidence were analyzed using over-dispersed Poisson regression and Cox regression was used to evaluate the effect on survival. Repeat episodes were modeled using a partially conditional Cox regression model. Results-406,836 patients were followed for 832,131 person-years, during which 133,967 events were identified. The incidence of GIB was stable through year 2000 but steadily increased thereafter. Chronic gastric ulcer and colonic diverticulosis were the commonest defined causes of upper and lower GIB respectively. Age >49 years, female gender, hypertension as the cause of ESRD, and initiation on hemodialysis was associated with a greater risk of GIB. An episode of GIB conferred a increased hazard of death (hazard ratio 1.9, 95 % CI 1.86-1.93). A previous episode of GIB was associated with greater hazard of another episode (hazard ratio 3.93, 95 % CI 3.82-4.05). Conclusions-In ESRD patients incident to long-term dialysis the incidence of hospitalassociated GIB is increasing, is associated with a greater hazard of death, and carries a great hazard of repeat episodes.

Transfusion, 2013

Background-Twenty-four low frequency platelet antigens (HPAs) have been implicated as immunogens ... more Background-Twenty-four low frequency platelet antigens (HPAs) have been implicated as immunogens in neonatal alloimmune thrombocytopenia (NAIT). We performed studies to define more fully how often these antigens trigger maternal immunization leading to NAIT. Study design and methods-In a Phase 1 study, fathers of selected NAIT cases not resolved by serologic testing but thought to have a high likelihood of NAIT on clinical and serologic grounds were typed for low frequency HPAs (LFHPAs) by DNA sequencing. In a Phase 2 study, high-throughput methods were used to type fathers of 1067 consecutive unresolved NAIT cases for LFHPAs. Mothers of 1338 unresolved cases were also typed to assess the prevalence of LFHPAs in a population racially/ethnically similar to the fathers. Results-In Phase 1, LFHPAs were identified in 16 of 244 fathers (6.55%). In Phase 2, LFPAs were found in only 28 of 1067 fathers (2.62%). LFHPAs were identified in 27 of 1338 maternal samples (2.01%). HPA-9bw was by far the most common LFHPA identified in the populations

Transfusion, 2012

We and others have identified more than 20 low-frequency human platelet (PLT) antigens (HPAs) tha... more We and others have identified more than 20 low-frequency human platelet (PLT) antigens (HPAs) that can induce antibodies capable of causing neonatal alloimmune thrombocytopenia (NAIT). 1-4 Like HPA-1a and HPA-4b, the antigens that most often trigger NAIT in Caucasian and Asian populations, respectively, the incidence of lowfrequency antigens is likely to vary significantly in different ethnic and racial populations. We recently described HPA-21bw, a low-frequency antigen, responsible for a single case of severe NAIT in a presumed Caucasian family. 1 The HPA-21bw antigen results from a G>A1960 mutation (RS70940817), in ITGB3, encoding PLT glycoprotein (GP) β3 subunit (GPIIIa) and creates a Glu>Lys substitution at Residue 628 in mature β3. No examples of HPA-21bw were identified in 100 unrelated Caucasian individuals. 1 We recently encountered a second case of NAIT apparently caused by HPA-21bw in an Asian family (unpublished). The mutation encoding HPA-21bw was also identified in two of 38 Asian individuals tested in a hypertension and insulin resistance study according to the human SNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; ss95216694). CONFLICT OF INTEREST There are no conflicts of interest.

The Thoracic and Cardiovascular Surgeon, 2007

The Thoracic and Cardiovascular Surgeon, 2007

The Thoracic and Cardiovascular Surgeon, 2007

Radiation Research, 2013

The goal of our study was to identify a histological marker for testing countermeasures for mitig... more The goal of our study was to identify a histological marker for testing countermeasures for mitigation of late radiation injury to the lung. Pulmonary fibrosis is currently the best described "late effect" in survivors of acute radiation pneumonitis. However, robust fibrosis does not develop in some rodent strains for years after a single dose of radiation to the whole thorax. We observed radiation-associated focal alveolar lesions that were rich in giant cells and macrophages containing cholesterol clefts in the lungs of irradiated WAG/ RijCmcr rats. These lesions were first observed after pneumonitis, around 21 weeks after receiving a radiation dose of 13 Gy to the thorax but not until 71 weeks in unirradiated rats. The number of cholesterol clefts increased with time after irradiation through 64 weeks of observation, and at 30 weeks after 13 Gy, cholesterol clefts were associated with several indices of deterioration in lung function. The number of cholesterol clefts in irradiated lung sections were reduced by the angiotensin converting enzyme (ACE) inhibitor enalapril (25-42 mg/m 2 /day) from 18.7 ± 4.2/lung section to 6.8 ± 2.4 (P = 0.029), 5.2 ± 1.9 (P = 0.0051) and 6.7 ± 1.9 (P = 0.029) when the drug was started at 1 week, 5 or 15 weeks after irradiation, respectively, and continued. Similar lesions have been previously observed in the lungs of one strain of irradiated mice and in patients following radiotherapy. We propose that alveolar lesions with cholesterol clefts may be used as a histological marker of the severity of radiation lung injury and to study its mitigation in WAG/

PM&R, 2011

Objective. To determine if folic acid supplementation improves vascular function (brachial artery... more Objective. To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design. Prospective cross-sectional study. Setting. Academic institution in the Midwestern United States. Subjects. Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures. Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flowinduced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results. Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions. This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention.