Andrew J. Cucchiara

In vivo magnetic resonance detects rapid remodeling changes in the topology of the trabecular bone network after menopause and the protective effect of estradiol.

Introduction: Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the μMRI‐based virtual bone biopsy can capture the temporal changes of scale and topology of the trabecular network and that estrogen supplementation preserves the integrity of the trabecular network.

Frequency, Risk Factors, and Clinical Outcomes of Left Ventricular Assist Device-Associated Ventricular Thrombus

A retrospective, transesophageal study of 51 consecutive patients receiving a left ventricular (LV) assist device (AD) over a 2-year period showed that LVAD-associated LV thrombosis (16%) was predicted by acute myocardial infarction, atrial cannulation, and postimplantation bleeding, and was associated with a fourfold increased risk of stroke compared with patients without thrombosis. LV cannulation, when using short-term LVADs, may decrease the incidence of LV thrombosis, and early transition to Heartmate-LVAD support may improve outcome.

Hemorrhagic Transformation of Childhood Arterial Ischemic Stroke

Background and Purpose— The objective of this study was to describe the occurrence of hemorrhagic transformation (HT) among children with arterial ischemic stroke within 30 days after symptom onset and to describe clinical factors associated with HT. Methods— Sixty-three children aged 1 month to 18 years with arterial ischemic stroke between January 2005 and November 2008 were identified from a single-center prospective pediatric stroke registry. All neuroimaging studies within 30 days of stroke were reviewed by a study neuroradiologist. Hemorrhage was classified according to the European Cooperative Acute Stroke Study-1 definitions. Association of HT with clinical factors, systemic anticoagulation, stroke volume, and outcome was analyzed. Results— HT occurred in 19 of 63 children (30%; 95% CI, 19% to 43%), only 2 (3%) of whom were symptomatic. Hemorrhage classification was hemorrhagic infarction (HI)1 in 14, HI2 in 2, parenchymal hematoma (PH)1 in 2, and PH2 in 1. HT was less common in children with vasculopathy (relative risk, 0.27; 95% CI, 0.07 to 1.06; P=0.04) than in those with other stroke mechanisms. HT was not significantly associated with anticoagulation versus antiplatelet therapy (relative risk, 0.6; 95% CI, 0.2 to 1.5; P=0.26) but was associated with larger infarct volumes (P=0.0084). In multivariable analysis, worse Pediatric Stroke Outcome Measure scores were associated with infarct volume ≥5% of total supratentorial brain volume (OR, 4.0; 95% CI, 1.1 to 15; P=0.04), and a trend existed toward association of worse Pediatric Stroke Outcome Measure scores with HT (OR, 4.0; 95% CI, 0.9 to 18; P=0.07). Conclusions— HT occurred in 30% of children with arterial ischemic stroke within 30 days. Most hemorrhages were petechial and asymptomatic. Infarct volume was associated with HT and worse outcome.

Resistin Levels in Lupus and Associations with Disease-specific Measures, Insulin Resistance, and Coronary Calcification

Objective. To evaluate levels of resistin in female subjects with systemic lupus erythematosus (SLE) compared to age and race-matched controls and to determine the relationship between resistin and systemic inflammation, disease measures, and coronary artery calcification (CAC). Methods. Resistin levels were measured on stored samples from 159 women with SLE and 70 controls as an extension of a previous cross-sectional study. Spearman correlations and multivariable regressions were used to examine whether resistin levels were associated with SLE, disease-specific and inflammatory markers, insulin resistance, and CAC. Results. In a multivariable linear regression model, a diagnosis of SLE was significantly associated with higher resistin levels independent of age, race, renal function, body mass index (BMI), high-sensitivity CRP (hsCRP), hypertension, diabetes, and steroid use. In SLE, resistin levels correlated positively with Systemic Lupus International Collaborating Clinics Damage Index, glomerular filtration rate (GFR), hsCRP, erythrocyte sedimentation rate, homocysteine, and disease duration (all p < 0.03). Resistin level did not correlate with markers of insulin resistance or body adiposity, including homeostatic model assessment or BMI. Resistin levels were significantly elevated in SLE cases with CAC compared to cases without CAC (16.58 vs 13.10 ng/ml, respectively; p = 0.04). In multivariate logistic regression, the association was not present after adjustment for age, race, and GFR. Conclusion. SLE was independently associated with higher resistin levels. Among subjects with SLE, higher resistin level correlated positively with renal dysfunction, inflammatory markers, and disease damage but not with insulin resistance or BMI. SLE cases with CAC had higher resistin levels than cases without CAC; however, this relationship was dependent on other established risk factors.

The impact of continuous pulse oximetry monitoring on intensive care unit admissions from a postsurgical care floor.

Continuous pulse oximetry (CPOX) has the potential to increase vigilance and decrease pulmonary complications and thus decrease intensive care unit (ICU) admissions. In a randomized nonblinded study of 1219 subjects we compared the effects of CPOX and standard monitoring on the rate of transfer to an ICU from a 33-bed postcardiothoracic surgery care floor. There was no difference in the rate of ICU readmission between the CPOX and standard monitor groups. Despite older age and comorbidity, estimated cost to time of censoring (enrollment to completion of the study) was less in the monitored patients who required ICU transfer than in the unmonitored patients who required ICU transfer (mean estimated cost difference of

Prevalence of self-report photosensitivity in cutaneous lupus erythematosus

28,195; P = 0.04). Use of CPOX altered the reasons that patients were transferred to an ICU but did not affect the rate of transfer. The duration, and thus estimated cost, of ICU stay was significantly less in the CPOX-monitored group. The potential for CPOX to allow for early intervention, or perhaps prevention of pulmonary complications, needs to be explored. Routine CPOX monitoring did not reduce transfer to ICU, mortality, or overall estimated cost of hospitalization, and it is unclear if there is any real benefit from the application of this technology in patients on a general care floor who are recovering from cardiothoracic surgery.

Characterization of clinical photosensitivity in cutaneous lupus erythematosus

BACKGROUND Little is known about the prevalence of self-reported photosensitivity (PS) and its effects on quality of life in a US cutaneous lupus population. OBJECTIVE We sought to determine the prevalence of self-reported PS among a cutaneous lupus population and to examine its impact on quality of life. METHODS A total of 169 patients with lupus were interviewed about PS symptoms and completed the modified Skindex-29+3, a quality-of-life survey. A complete skin examination was conducted and the Cutaneous Lupus Erythematosus Disease Area and Severity Index was completed. RESULTS In all, 68% of patients reported some symptoms of PS. The PS group (those who reported a history of and current PS) scored worse on PS-related items of the modified Skindex-29+3 and had higher cutaneous disease activity as determined by the Cutaneous Lupus Erythematosus Disease Area and Severity Index. Patients with PS had worse symptoms and emotions and experienced significant functional impairments compared with patients who had cutaneous lupus without PS. LIMITATIONS This study was done at a single referral center. CONCLUSIONS Self-reported PS is very common among patients with cutaneous lupus and is associated with significant impairments related to symptoms, emotions, and daily functioning.

Functional Polymorphisms of Folate-Metabolizing Enzymes in Relation to Homocysteine Concentrations in Systemic Lupus Erythematosus

BACKGROUND Photosensitivity (PS) in lupus erythematosus (LE) is frequently determined by patient report. OBJECTIVE We sought to characterize self-reported PS in cutaneous LE (CLE). METHODS The PS survey was used to classify subject responses into 5 phenotypes: direct sun-induced CLE flare (directCLE); general exacerbation of CLE (genCLE); polymorphic light eruption-like reactions (genSkin); general pruritus/paresthesias (genRxn); and sun-induced systemic symptoms (genSys). In all, 91 subjects with CLE alone or with CLE and systemic LE were interviewed. RESULTS In all, 81% ascribed to 1 or more PS phenotypes. CLE-specific reactions (direct sun-induced CLE flare or general exacerbation of CLE) were reported by 86% of photosensitive subjects. Higher CLE disease activity (measured by CLE Disease Area and Severity Index activity scores) was suggestive of direct sun-induced CLE flare reactions (P = .09). In all, 60% of photosensitive subjects described CLE-nonspecific reactions: polymorphic light eruption-like rash and general pruritus/paresthesias. These phenotypes often co-occurred with CLE-specific reactions and were predicted by more systemic disease activity as measured by Physicians Global Assessment (PGA) scores in regression analyses (genSkin, P = .02) and (genRxn, P = .05). In all, 36% of subjects reported systemic reactions and higher PGA scores were predictive of the sun-induced systemic symptoms phenotype (P = .02); a diagnosis of systemic LE was not (P = .14). LIMITATIONS PS was inferred from patient report and not directly observed. CONCLUSIONS Characterization of self-reported PS in LE reveals that patients experience combinations of CLE-specific, CLE-nonspecific, and systemic reactions to sunlight. Sun-induced CLE flares are associated with more active CLE disease. Polymorphic light eruption-like, generalized pruritus/paresthesias, and systemic reactions are associated with more active systemic disease. Recognition of PS phenotypes will permit improved definitions of clinical PS and allow for more precise investigation into its pathophysiology.

A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study.

Objective To determine if functional polymorphisms of folate/homocysteine pathway enzymes are associated with homocysteine concentrations and/or coronary artery calcification (CAC) scores in patients with systemic lupus erythematosus (SLE) and controls. Methods We investigated 163 SLE patients and 160 controls. Functional polymorphisms in 6 genes in the folate/homocysteine pathway were genotyped: 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, cystathionine β-synthase (CBS) 844ins68, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G, thymidylate synthase (TYMS) 1494del6, and dihydrofolate reductase (DHFR) c.86+60_78. Results Homocysteine levels were higher in African American SLE patients than Caucasian patients and African American controls. Genotype distributions were significantly different in African American and Caucasian controls for 6 of the 7 polymorphisms. Genotype distributions for each polymorphism did not differ significantly between SLE patients and controls even after stratification by race. Glomerular filtration rate was strongly negatively correlated to homocysteine levels, and was therefore adjusted for as a covariate in the models of the effects of the polymorphisms on homocysteine levels. In SLE patients none of the 7 polymorphisms was associated with homocysteine concentrations. In Caucasian controls only MTHFR 677C>T and 1298A>C showed effects on homocysteine similar to what would be expected from the literature. There were no genotypic associations with median CAC scores in SLE patients or controls with and without stratification by race. Conclusion Polymorphisms in folate/homocysteine metabolizing enzymes do not predict higher homocysteine levels or CAC scores in patients with SLE.

Hemiparesis and epilepsy are associated with worse reported health status following unilateral stroke in children.

OBJECTIVE To evaluate feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. METHODS Patients with MDD (defined by DSM-IV-TR) who were depressed despite ≥ 8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015. RESULTS In the ITT sample (n = 25), the SKY arm (n = 13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n = 12) (-9.77 vs 0.50, P = .0032). SKY also showed greater reduction in BDI total score versus waitlist control (-17.23 vs -1.75, P = .0101). Mean changes in BAI total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: -5.19; 95% CI, -0.93 to -9.34; P = .0097; completer mean difference: -6.23; 95% CI, -1.39 to -11.07; P = .0005). No adverse events were reported. CONCLUSIONS Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02616549.