Gingival Crevicular Fluid Biomarkers During Periodontitis Progression and After Periodontal Treatment.

OBJECTIVE: To identify gingival crevicular fluid (GCF)-derived inflammatory markers of periodontitis progression and periodontal treatment impact. METHODS: Periodontally healthy (H; n = 112) and periodontitis (P; n = 302) patients were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Levels of 64 biomarkers were measured in the GCF samples collected at each visit from progressing (n = 12 sites in H; n = 76 in P) and stable (n = 100 in H, n = 225 in P) sites. Clinical parameters and log-transformed analyte levels were averaged within clinical groups at each time point and analysed using linear mixed models. RESULTS: During monitoring, progressing sites had significantly higher levels of IL-1ß, MMP-8, IL-12p40, EGF and VEGF. MMP-9 and Periostin were significantly more elevated in stable sites. Distinct cytokine profiles were observed based on baseline PD. Treatment led to significant reductions in Eotaxin, Flt-3L, GDF-15, GM-CSF, IL-1ß, IL-17, MIP-1d, RANTES and sCD40L, and increases in IP-10 and MMP-9. CONCLUSION: Distinct cytokine signatures observed in stable and progressing sites were maintained over time in the absence of treatment and significantly affected by NSPT.

Salivary and serum inflammatory biomarkers during periodontitis progression and after treatment.

AIM: To identify serum- and salivary-derived inflammatory biomarkers of periodontitis progression and determine their response to non-surgical treatment. MATERIALS AND METHODS: Periodontally healthy (H; n = 113) and periodontitis patients (P; n = 302) were monitored bi-monthly for 1 year without therapy. Periodontitis patients were re-examined 6 months after non-surgical periodontal therapy (NSPT). Participants were classified according to disease progression: P0 (no sites progressed; P1: 1-2 sites progressed; P2: 3 or more sites progressed). Ten salivary and five serum biomarkers were measured using Luminex. Log-transformed levels were compared over time according to baseline diagnosis, progression trajectory and after NSPT. Significant differences were sought using linear mixed models. RESULTS: P2 presented higher levels (p < .05) of salivary IFNγ, IL-6, VEGF, IL-1ß, MMP-8, IL-10 and OPG over time. Serum analytes were not associated with progression. NSPT led to clinical improvement and significant reduction of IFNγ, IL-6, IL-8, IL-1ß, MMP-8, IL-10, OPG and MMP-9 in saliva and of CRP, MMP-8, MMP-9 and MPO in serum. CONCLUSIONS: Periodontitis progression results from a sustained pro-inflammatory milieu that is reflected in salivary biomarkers, but less so in serum, likely because of the limited amount of progression per patient. NSPT can significantly decrease the levels of several salivary analytes.

Renal Histologic Analysis Provides Complementary Information to Kidney Function Measurement for Patients with Early Diabetic or Hypertensive Disease.

BACKGROUND: Patients with diabetic or hypertensive kidney disease rarely undergo kidney biopsy because nephrologists commonly believe that biopsy-related risk outweighs the potential benefits of obtaining histologic information to guide clinical decisions. Although kidney function is acutely regulated, histologic changes such as interstitial fibrosis, tubular atrophy, and glomerulosclerosis may represent chronic kidney damage, and thus might provide additional information about disease severity. However, whether histologic analysis provides information complementary to clinically used kidney function measurements, such as eGFR and proteinuria, is unclear. METHODS: We performed a standardized semiquantitative histologic analysis of 859 nephrectomies obtained from individuals with or without diabetes mellitus or hypertension and varying degrees of kidney dysfunction. Changes in glomeruli, tubules, interstitium, and the vasculature were scored using 17 descriptive parameters in a standardized manner. We used multivariable linear and logistic regression analyses and unbiased, hierarchical clustering to assess associations between histologic alterations and clinical variables. RESULTS: At CKD stages 3-5, eGFR correlates reasonably well with the degree of glomerulosclerosis and interstitial fibrosis and tubular atrophy (IFTA). In patients with CKD stages 1-2, the degree of histologic damage was highly variable and eGFR poorly estimated the degree of damage. Individuals with diabetes mellitus, hypertension, or Black race had significantly more glomerulosclerosis and IFTA, at the same eGFR level. Inclusion of glomerulosclerosis improved the kidney function decline estimation, even at early disease stages. CONCLUSIONS: Histologic analysis is an important complementary method for kidney disease evaluation, especially at early disease stages. Some individuals present with relatively severe structural damage despite preserved eGFR.

Transplantation of Center for Disease Control "High-Risk" Donor Hearts Does Not Adversely Impact Long-Term Outcomes in Adults.

BACKGROUND: The "high-risk donor" (HRD) label was applied to donors who met the Centers for Disease Control and Prevention criteria for high-risk behavior in 2004. The number of potential recipients who die awaiting orthotopic heart transplantation (OHT) has increased. Despite organ shortages, HRD grafts are often declined given infectious concerns. We hypothesized that recipients would have equivalent outcomes. METHODS: We retrospectively analyzed the United Network of Organ Sharing adult heart transplant data from June 2004 to December 2013. OHT recipients were divided into 2 cohorts by donor status. RESULTS: During the study period, 37,408 OHTs were performed and 3196 (8.5%) patients received HRD grafts. Recipients of HRD were significantly older (P < .0001) and had a higher body mass index (P < .0001) compared with standard-risk donor recipients. No significant difference in waitlist time (P = .69) or blood type (P = .07) was noted. A higher number of HRD recipients were on mechanical circulatory support (35.6%) compared with standard-risk donor (33.3%, P = .009). Both grafts manifested similar, low rates of rejection before discharge (P = .88). One1 (84.3 vs 83%) and 5-year (71.2 vs 65.5%) survival was similar in the cohorts (log-rank P = .7571). CONCLUSIONS: HRD status does not significantly affect recipient outcomes after OHT. Increased use of HRD grafts could augment donor pool and decrease the mortality associated with long waitlist times.

How Short is Too Short According to Parents of Primary Care Patients.

OBJECTIVE: Height is a physical trait on a continuum. The threshold between normal and abnormal is arbitrarily set but can potentially influence medical decision-making. We sought to examine parents' perceptions of adult heights and associated demographic factors. METHODS: Parents of pediatric primary care patients of various heights completed a one-time survey. Parents answered the question "How short is too short?" for adult males and females. The results were summarized as median [interquartile range]. Factors significantly associated with height threshold by simple linear regression were included in a multivariable mixed effects analysis of covariance model. RESULTS: A total of 1,820 surveys were completed (83% response rate; 1,587 females, 231 males). The median threshold height deemed too short for adult females was 56 inches [48, 59] among male respondents and 57 inches [50, 60] among females (P<.05). The median threshold height for adult males was 61 inches among males [60, 64] and females [59, 66] (P<.05). The median of male minus female heights per respondent (delta heights) was 5 [2, 7] inches. Factors found to be significant main effects in a parsimonious model were sex of the adult considered, height of respondent, sex of respondent, respondent race, primary care practice, income, and having concerns about their child's height. CONCLUSION: Taller acceptable height thresholds were perceived by respondents who were taller, wealthier, white, female, from nonurban practices, or who had a personal concern about their child's height. Male heights were expected to be taller than female heights. Such traits may influence who is concerned and more likely to seek medical treatment for their children.

Intravenous GLP-1 (7-36) amide for prevention of hyperglycemia during cardiac surgery: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The authors sought to evaluate the efficacy of an intravenous glucagon-like peptide-1 (GLP-1) infusion, compared with placebo, to mitigate intraoperative hyperglycemia. DESIGN: Prospective, double-blinded, randomized, placebo-controlled. SETTING: University hospital. PARTICIPANTS: Diabetic (non-insulin dependent) and non-diabetic patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 fashion to GLP-1 (7-36) amide infusion (1.5 pmol/kg/min) or placebo. Insulin was administered intraoperatively to both groups per a standardized protocol. MEASUREMENTS AND MAIN RESULTS: A total of 77 patients were included for analysis (GLP-1, n = 37; placebo, n = 40). Mean blood glucose during cardiopulmonary bypass was 127.5 mg/dL and 142.5 mg/dL (p = 0.002) in the GLP-1 and placebo groups, respectively. Mean blood glucose values during the entire intraoperative course were 12.2 mg/dL lower for subjects given GLP-1 (95% CI 2.3, 22, p = 0.015), independent of time. During the period of cardiopulmonary bypass, mean blood glucose values in subjects given GLP-1 were 14.1 mg/dL lower than those who received placebo (95% CI 3.5, 24.8, p = 0.009), independent of time. The incidence of hypoglycemia did not differ significantly between the 2 groups. CONCLUSIONS: Administration of intravenous GLP-1 (7-36) amide to patients undergoing cardiac surgery significantly reduced their plasma glucose levels intraoperatively and may represent a novel therapeutic strategy to prevent perioperative hyperglycemia.

Characterization of clinical photosensitivity in cutaneous 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.

Prevalence of self-report 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.

Effectiveness of Oral Antibiotic Therapy in Prevention of Postoperative Wound Infection Requiring Surgical Washout In Spine Surgery.

BACKGROUND: Surgical site infections (SSIs) after spine surgery are a significant cause of morbidity. Surgeons often prescribe oral antibiotics in the postoperative setting for infected-appearing wounds to prevent reoperation for infection; however, the efficacy of this practice has not been well studied. METHODS: Neurosurgical spine patients with clinical concerns for SSI at the University of Pennsylvania were retrospectively studied from 2014 to 2018. Clinical predictors of 90-day reoperation for infection despite antibiotic treatment and variables that influenced antibiotic prescription were analyzed. RESULTS: Three hundred and ninety-two patients were included in the study. Preoperative albumin level, days elapsed to antibiotic prescription from index surgery, preoperative hemoglobin level, surgical location, gender, discharge disposition, and level of wound concern were significant predictors of reoperation for infection on bivariate analysis. Days elapsed to antibiotic prescription, surgical location, and level of wound concern remained significant after multivariable logistic regression. Variables that significantly predicted prescription of an antibiotic include length of stay, cerebrospinal fluid leak, race, and level of wound concern. Length of stay, race, and level of wound concern remained significant after multivariable analysis. CONCLUSIONS: Wound infection remains a challenging problem in spine surgery and it is reasonable to perform early reoperation in patients with high clinical concerns for infection, because bacterial isolates are often resistant to common oral antibiotics. Patients with wounds with low clinical concerns for infection may undergo a trial of oral antibiotics; however, duration of treatment should not be prolonged.

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.

Correlation Between Plasma Catecholamines, Weight, and Diabetes in Pheochromocytoma and Paraganglioma.

CONTEXT: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. OBJECTIVE: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. DESIGN: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1]. SETTING: Tertiary academic hospital. PATIENTS: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female. MAIN OUTCOME MEASURES: The primary and secondary outcomes were weight and HbA1c, respectively. RESULTS: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c. CONCLUSION: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.

Catecholamines, adiponectin, and insulin resistance as measured by HOMA in children with obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) has been implicated in the pathophysiology of metabolic syndrome. Its contribution to insulin resistance is complicated by obesity and puberty. We hypothesized that OSA is associated with worse insulin resistance and lower adiponectin after adjustment for obesity and puberty and that catecholamines might mediate these changes. METHODS: Normal controls and children with suspected OSA were recruited and categorized as pubertal or prepubertal. Overnight polysomnography (PSG) was performed. Subjects were categorized as OSA for total apnea hypopnea index (Total-AHI) > or = 1.5 events/h. Fasting blood glucose, insulin, adiponectin, and 24-hour urinary catecholamines were obtained. Homeostatic model assessment of insulin resistance (HOMA) was calculated. The independent effects of OSA upon HOMA, adiponectin, and urinary catecholamines following adjustment for body mass index (BMI) were determined. RESULTS (median; min, max): Subjects (n = 98, 42F; 11 +/- 4 years, 37 prepubertal) were generally overweight (BMI-Z = 2.1; -3, 4.1) and had wide-ranging insulin sensitivities (HOMA = 2.7; 0.5, 27) and PSG parameters (Total-AHI = 1.6; 0, 185). The risks of elevated insulin (P = 0.04) and HOMA (P = 0.05) were higher in OSA vs non OSA obese pubertal children. Polysomnographic markers of OSA, including Total-AHI (P = 0.001, R2 = 0.32), were negatively associated with adiponectin in pubertal children. Total-AHI and oxygen desaturation were associated with higher urinary normetanephrine and norepinephrine. CONCLUSIONS: In obese pubertal children, OSA was associated with worse insulin resistance. Worsening OSA was associated with lower adiponectin and increasing urinary catecholamines. Whether OSA directly lowers adiponectin and aggravates a predisposition to insulin resistance is unknown, but these preliminary findings highlight the importance of further studying pediatric OSA.

Prostate-Specific Antigen Concentrations in Response to Testosterone Treatment of Severely Hypogonadal Men.

CONTEXT: Clinical guidelines recommend measurement of the serum prostate-specific antigen (PSA) concentration during testosterone treatment of hypogonadal men to determine whether the increase is sufficiently high to warrant urologic referral. Prior studies of the effect of testosterone treatment on PSA concentrations have been conducted in men who were mildly to moderately hypogonadal. OBJECTIVE: The objective of this work is to determine the PSA response to testosterone treatment of men who are severely hypogonadal. DESIGN AND SETTING: This retrospective cohort study was conducted at a single academic medical center. PARTICIPANTS: Eighty-five men participated who were severely hypogonadal as a result hypothalamic-pituitary or testicular disease. MAIN OUTCOME MEASURE: Changes in serum PSA concentrations were measured during testosterone treatment for up to 18 months. RESULTS: Testosterone treatment increased the median serum testosterone concentration from 36 ng/dL (interquartile range [IQR], 20-91 ng/dL) at baseline to 395 ng/dL (IQR, 266-542 ng/dL) at 6 to 18 months. This treatment resulted in a median increment in PSA above baseline of 0.70 ng/mL (IQR, 0.10-1.85 ng/mL) at 6 to 18 months. Apropos current Endocrine Society clinical guidelines, 31% of the men experienced a PSA increase above baseline greater than 1.4 ng/mL, and 13% reached an absolute PSA concentration of greater than 4.0 ng/mL. Four men were diagnosed with prostate cancer. CONCLUSIONS: The PSA response to testosterone replacement in men who are severely hypogonadal as a result of pituitary or testicular disease is greater than that previously reported in men with mild to moderate hypogonadism. These results suggest the magnitude of the PSA response to testosterone replacement is related to the degree of hypogonadism.

Clinical Utility of Plasma Cell-Free DNA in Adult Patients with Newly Diagnosed Glioblastoma: A Pilot Prospective Study.

PURPOSE: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). EXPERIMENTAL DESIGN: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. RESULTS: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). CONCLUSIONS: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.

Sex-based prevalence of growth faltering in an urban pediatric population.

OBJECTIVE: To determine the sex-based prevalence of growth faltering in a pediatric primary care setting. STUDY DESIGN: A total of 33 476 children attending 4 urban pediatric primary care practices affiliated with a tertiary pediatric hospital between July 2002 and June 2005 were studied. Growth faltering was defined as height <5th percentile or a drop in height z-score by >or= 1.5 standard deviations (SD) before age 18 months or by >or= 1 SD thereafter. The growth-faltering and nonfaltering groups were compared in terms of sex, race, age, number of clinic visits, and insurance, and by US census tract, socioeconomic status and parental education. Similar comparisons were made for children with height z-scores below -2.25 SD. RESULTS: Growth faltering was present in 3007 of the children studied (9%). Univariate and multivariate logistic regression analyses identified significant associations between growth faltering and younger age (P< .0001), Caucasian race (P< .0001), fewer clinic visits (P< .0001), and Medicaid insurance (P< .005), but not with sex nor by residential census tract, median income or proportion with less than high school education. Height below -2.25 SD was associated with male sex (P< .01), Medicaid insurance (P< .01), and more primary care visits (P< .0005). CONCLUSIONS: The sex disparity in subspecialty growth center referrals (2:1 male:female) is not due to male predominance in growth faltering among children in the urban primary care setting.

Concerns and Expectations of Parents Seeking Subspecialist Care for Their Child's Short Stature.

INTRODUCTION: Parents (PP) of children in primary care clinics previously reported factors influencing their height-related medical decision making. However, patients seeking height-related care in endocrine subspecialty clinics and their parents (EP) differ demographically from the general population. OBJECTIVE: To determine EP height-related medical concerns and expectations, and to compare between EP and PP. METHODS: EP completed a survey assessing their concerns in seeking medical care for their child's height with identical questions previously asked of PP and two additional questions about growth hormone (GH) treatment. RESULTS: A greater proportion of the 166 EP (80% response rate) than the 1,820 PP (83% response rate) previously surveyed was Caucasian (75% EP, 41% PP) and privately insured (80% EP, 58% PP). Both groups rated treatment efficacy and risks most as having a bigor extreme impact on decision making (65% EP, 58% PP). The second most rated concern for EP was comparison of child's height to peers or growth chart (60% EP, 32% PP) versus child's health for PP (54% EP, 56% PP). Of the 166 EP surveyed, 76% rated GH treatment as potentially improving quality of life (QoL), with 88% reporting a minimum 3-inch height increase as necessary to improve QoL. CONCLUSIONS: Height comparisons were more likely to impact EP than PP in seeking height-related medical care for their children. EP had high expectations of QoL improvement with GH treatment, which are unlikely to be met with treatment of idiopathic short stature. Thus, clinicians should be prepared to support families in other ways that promote positive development in children with short stature.

Racial/Ethnic Disparities in US Pediatric Growth Hormone Treatment.

BACKGROUND/AIMS: To compare racial/ethnic proportions of subjects receiving growth hormone (GH) treatment to the expected proportions, and secondarily, to assess racial/ethnic differences in subject characteristics at GH treatment initiation. METHODS: Race/ethnicity-based expected frequencies of height <-2.25 SD were determined by applying relative risks for short stature, calculated from a regional population of 189,280 pediatric primary care patients, to US census data, and compared to racial/ethnic proportions of US subjects enrolled in the Pfizer International Growth Study (KIGS) using the χ2 test. Characteristics of white and black subjects at GH treatment initiation were presented as medians and compared by the Wilcoxon rank sum test (significant p < 0.01). RESULTS: White subjects exceeded the expected frequency (63%) for all indications (83%) and each separately, ranging from 73% for congenital GH deficiency (GHD) to 85% for idiopathic short stature (p < 0.001). Compared to white subjects, black subjects treated for idiopathic GHD had greater height deficits relative both to the population (-2.97 vs. -2.56 SD) and to their mid-parental heights (-2.47 vs. -1.89 SD), lower stimulated GH peak levels (4.9 vs. 6.0 ng/mL), and lower birth weights (-0.86 vs. -0.48 SD). Black subjects with congenital GHD had lower stimulated GH peaks (2.1 vs. 3.2 ng/mL) and started GH treatment at younger ages (2.9 vs. 4.8 years), while those with acquired GHD had lower birth weights (-1.12 vs. -0.08 SD). Male predominance did not differ by race for any or all indications. CONCLUSION: Overrepresentation of white children among those receiving GH treatment in the US KIGS registry reflects racial/ethnic treatment biases, not just differences in growth rates.

Phylogroup and virulence gene association with clinical characteristics of Escherichia coli urinary tract infections from dogs and cats.

Escherichia coli isolates from infections outside the gastrointestinal tract are termed extra-intestinal pathogenic E. coli (ExPEC) and can be divided into different subpathotypes; one of these is uropathogenic E. coli (UPEC). The frequency with which UPEC strains cause urinary tract infections in dogs and cats is not well documented. We used an oligonucleotide microarray to characterize 60 E. coli isolates associated with the urinary tract of dogs ( n = 45) and cats ( n = 15), collected from 2004 to 2007, into ExPEC and UPEC and to correlate results with patient clinical characteristics. Microarray analysis was performed, and phylogroup was determined by a quadruplex PCR assay. Isolates that were missing 1 or 2 of the gene determinants representative of a function (capsule, iron uptake related genes, or specific adhesins) were designated as "non-classifiable" by microarray. Phylogroup B2 was positively associated with the UPEC subpathotype ( p < 0.0005) and negatively associated with "non-classifiable" isolates ( p < 0.0005). Phylogroup D was positively associated with ExPEC pathotype ( p = 0.025) and negatively associated with UPEC subpathotype ( p = 0.014). The ExPEC pathotype was positively associated with hospitalization for one or more days ( p = 0.031). The UPEC subpathotype was negatively associated with previous antimicrobial therapy ( p = 0.045) and previous hospitalization within the 3 mo prior to the positive culture ( p = 0.041). The UPEC subpathotype was positively associated with prostatitis ( p = 0.073) and negatively associated with current immunosuppressive therapy ( p = 0.090). Our results indicate that the case history observations may be critically important during the interpretation of laboratory results to encourage judicious use of antimicrobials.

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

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.

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 28,195 dollars; 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.