Sleep disturbance in adults with chronic pruritic dermatoses is associated with increased C-reactive protein levels.

BACKGROUND: Pruritus is a common symptom that can significantly reduce quality of life through sleep disruption. OBJECTIVE: To examine features of disturbed sleep in patients with chronic pruritic dermatoses and test the hypothesis that systemic inflammation may serve as a biomarker for impaired sleep in these patients. METHODS: Cross-sectional analysis of the National Health and Nutrition Examination Survey investigating systemic inflammation using C-reactive protein (CRP) levels. Logistic regression was used to compare patients with and without sleep disturbances, adjusting for demographics (model 1) and medical comorbidities (model 2). RESULTS: Chronic pruritic dermatoses were associated with multiple sleep disturbances, including nighttime awakenings (model 1: odds ratio [OR], 1.646; 95% confidence interval [CI], 1.031-2.627; model 2: OR, 1.329; 95% CI, 0.888-1.989) and early morning awakening (model 1: OR, 1.669, 95% CI, 1.118-2.493; model 2: OR, 1.582; 95% CI, 1.008-2.481). Mean CRP levels were 52.8% higher among patients with pruritic dermatoses reporting trouble sleeping compared with those who did not (0.663 vs 0.434 mg/dL; P = .034). Trouble sleeping was also positively correlated with CRP levels (ß = 0.142, P = .025). LIMITATIONS: Potential recall bias among participants. CONCLUSIONS: In addition to confirming sleep disturbances with pruritic dermatoses, we found these disturbances are more likely to present with elevated CRP levels. Clinicians should consider the potential risk for sleep-related and cardiac comorbidities in patients diagnosed with itchy skin conditions.

Comorbidities in Mycosis Fungoides and Racial Differences in Co-Existent Lymphomatoid Papulosis: A Cross-Sectional Study of 580 Patients in an Urban Tertiary Care Center.

Background: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma. Previous reports have suggested MF is associated with inflammatory conditions such as psoriasis, increased cardiovascular risk factors as well as secondary neoplasms. Methods: A cross-sectional study of MF patients seen from 2013 to 2019 was performed. Comorbidities were selected based on the 2015 Medicare report highlighting the most common chronic medical illnesses in the United States. Lifetime comorbidity occurrence in patients with MF were compared with that in patients with atopic dermatitis, psoriasis and patients without MF. Additional analyses were performed with patients sub-stratified by race. Results: Compared to control groups, MF was strongly associated with lymphomatoid papulosis and Hodgkin's disease, but not significantly associated with lung, breast or colon cancer. Interestingly, the association with lymphomatoid papulosis was observed in Caucasians (CI 1062-4338; p < 0.001) and not African Americans (p = 0.9). Patients with MF had a greater association with congestive heart failure, hypertension (HT) and hyperlipidemia (HLD) compared with the general population. However, they were significantly less likely to have HT and HLD when compared with psoriasis patients (HT CI: 0.6-0.9; p < 0.001, and HLD CI: 0.05-0.07; p < 0.001). MF patients were also significantly less likely to have concomitant vitamin D deficiency compared with atopic dermatitis (AD) and psoriasis (p < 0.001). Conclusions: Our results suggest that the association of MF with lymphomatoid papulosis varies by race. Compared to the general population, hypertension and hyperlipidemia were positively associated with MF, however, these were significantly less likely on comparison to psoriasis. Unlike previously described, vitamin D deficiency was found to be significantly less in patients with MF.

Preexisting smooth muscle cells contribute to neointimal cell repopulation at an incidence varying widely among individual lesions.

BACKGROUND: With the diverse origin of neointimal cells, previous studies have documented differences of neointimal cell lineage composition across models, but the animal-to-animal difference has not attracted much attention, although the cellular heterogeneity may impact neointimal growth and its response to therapeutic interventions. METHODS: R26R(+);Myh11-CreER(+), and R26R(+);Scl-CreER(+) mice were used to attach LacZ tags to the preexisting smooth muscle cells (SMCs) and endothelial cells (ECs), respectively. Neointimal lesions were created via complete ligation of the common carotid artery (CCA) and transluminal injury to the femoral artery (FA). RESULTS: LacZ-tagged SMCs were physically relocated from media to neointima and changed to a dedifferentiated phenotype in both CCA and FA lesions. The content of SMCs in the neointimal tissue, however, varied widely among specimens, ranging from 5 to 70% and 0 to 85%, with an average at low levels of 27% and 29% in CCA (n = 15) and FA (n = 15) lesions, respectively. Bone marrow cells, although able to home to the injured arteries, did not differentiate fully into SMCs after either type of injury. Preexisting ECs were located in the subendothelial region and produced mesenchymal marker α-actin, indicating endothelial-mesenchymal transition (EndoMT); however, EC-derived cells represented only 7% and 3% of the total neointimal cell pool of CCA (n = 7) and FA (n = 7) lesions, respectively. ECs located on the luminal surface exhibited little evidence of EndoMT. CONCLUSION: Neointimal hyperplasia proceeds with a wide range of variation in its cellular composition between individual lesions. Relative to ECs, SMCs are major contributors to the lesion-to-lesion heterogeneity in neointimal cell lineage composition.

The advent of thoracic endovascular aortic repair is associated with broadened treatment eligibility and decreased overall mortality in traumatic thoracic aortic injury.

BACKGROUND: Aortic injury is the second leading cause of death in trauma. Thoracic endovascular aortic repair (TEVAR) has recently been applied to traumatic thoracic aortic injuries (TTAIs) as a minimally invasive alternative to open surgery. We sought to determine the impact of TEVAR on national trends in the management of TTAI. METHODS: We queried the Nationwide Inpatient Sample from the years 2001 to 2007 to select patients diagnosed with TTAI (International Classification of Disease-9 code 901.0). Patients were evaluated based on open surgical repair, TEVAR, or nonoperative management, before and after widespread adoption of TEVAR (2001-2005 and 2006-2007). Outcomes of interest were inpatient mortality, length of stay (LOS), and major complications. RESULTS: An estimated 1180 annual admissions occurred for TTAI in the United States. Comparing the two time periods, there was an increase in TEVAR (P < .001) with a simultaneous decrease in open repair (P < .001) in 2006 to 2007. The overall number of interventions also increased (P < .001). Overall mortality decreased (25.0% vs 19.0%;P < .001), corresponding to improved survival in the nonoperative group (28.0% vs 23.2%; P < .001). There was no improvement in open repair mortality rates between the two time periods. Comparing intervention types, the TEVAR group had a higher percentage of patients with brain injury (26.1% vs 20.6%; P = .008), lung injury (25.0% vs 17.7%; P < .001), and hemothorax (32.5% vs 21.7%; P < .001) than the open surgery group. There were no differences in the number of intra-abdominal injuries or major orthopedic fractures. The open surgery group had more respiratory complications (43.9% vs 54.2%; P < .001), whereas TEVAR had a higher stroke rate (1.9% vs 0.7%; P = .021). There were no differences in paraplegia or renal failure. Overall in-hospital mortality was 23.2% (nonoperative group 26.7%, open repair 12.4%, and TEVAR 10.6%). Mortality between open repair and TEVAR groups were not significantly different. LOS was shorter among the TEVAR group vs open (15.7 vs 22.9 days; P < .001). CONCLUSION: TEVAR has replaced open repair as the primary operative treatment for TTAI and has extended operative treatment to those patients not previously considered candidates for repair. Increased utilization of TEVAR is associated with improved overall mortality. There is no difference in mortality between TEVAR and open repair groups in our study, which likely reflects the multisystem nature of injury and greater preoperative risk in the TEVAR group.

Emerging national trends in the management and outcomes of lower extremity peripheral arterial disease.

BACKGROUND: In this study, we sought to analyze emerging national trends in the treatment of lower extremity peripheral arterial disease and associated outcomes. METHODS: The Nationwide Inpatient Sample was queried between 2001 and 2007. Patients diagnosed with lower extremity atherosclerosis were selected by using the International Classification of Diseases, 9th Revision codes 440.20-440.24, resulting in an average of 307,000 annual hospitalizations. Within this group, we determined the annual number of lower extremity bypasses, endovascular interventions, and major and/or minor amputations (below-the- and/or above-the-knee amputation versus toe and/or foot amputation). Chi-square analysis was performed on discharge-weighted data to compare two periods (2001-2003 and 2004-2007) to determine changes in management and differences in outcome. Multivariate logistic regression was used to identify predictors of amputation. RESULTS: Comparing the two periods, it was found that the average annual number of endovascular interventions increased by 78% (37,692 vs. 67,248, p < 0.001), and open lower extremity bypasses decreased by 20% (68,326 vs. 54,348, p < 0.001). Annually, the total number of interventions increased by 15% (106,018 vs. 121,596, p < 0.001), whereas the number of total amputations (59,693 vs. 50,254, p < 0.001), major amputations (39,543 vs. 31,043, p < 0.001), and minor amputations (20,150 vs. 19,211, p < 0.001) performed all significantly decreased. Diabetes was the leading predictor of amputation, especially those involving the toe and forefoot. After adjusting for age and comorbidities, African Americans were found to have a 2.4 times odds of amputation as compared with Caucasians, whereas those with Medicare or Medicaid had a 1.5 times odds as compared with those having private insurance or Health Maintenance Organization. CONCLUSIONS: Between the periods examined, we observed that the treatment of lower extremity peripheral arterial disease has evolved with increased use of lesser invasive endovascular techniques and fewer open lower extremity bypasses. These trends are associated with fewer major lower extremity amputations. Significant socioeconomic disparities persist in amputation rates, with racial minorities and those with Medicare or Medicaid having higher odds of amputation.

Heparin-induced thrombocytopenia: a practical review.

Heparin-induced thrombocytopenia (HIT) remains under-recognized despite its potentially devastating outcomes. It begins when heparin exposure stimulates the formation of heparin-platelet factor 4 antibodies, which in turn triggers the release of procoagulant platelet particles. Thrombosis and thrombocytopenia that follow comprise the 2 hallmark traits of HIT, with the former largely responsible for significant vascular complications. The prevalence of HIT varies among several subgroups, with greater incidence in surgical as compared with medical populations. HIT must be acknowledged for its intense predilection for thrombosis and suspected whenever thrombosis occurs after heparin exposure. Early recognition that incorporates the clinical and serologic clues is paramount to timely institution of treatment, as its delay may result in catastrophic outcomes. The treatment of HIT mandates an immediate cessation of all heparin exposure and the institution of an antithrombotic therapy, most commonly using a direct thrombin inhibitor. Current "diagnostic" tests, which primarily include functional and antigenic assays, have more of a confirmatory than diagnostic role in the management of HIT. Special attention must be paid to cardiac patients who are often exposed to heparin multiple times during their course of treatment. Direct thrombin inhibitors are appropriate, evidence-based alternatives to heparin in patients with a history of HIT, who need to undergo percutaneous coronary intervention. As heparin remains one of the most frequently used medications today with potential for HIT with every heparin exposure, a close vigilance of platelet counts must be practiced whenever heparin is initiated.

Time-lapse mapping of cortical changes in schizophrenia with different treatments.

Using time-lapse maps, we visualized the dynamics of schizophrenia progression, revealing spreading cortical changes that depend on the type of antipsychotic treatment. Dynamic, 4-dimensional models of disease progression were created from 4 repeated high-resolution brain magnetic resonance imaging scans of 36 first-episode schizophrenia patients (30 men/6 women; mean age: 24.2 +/- 5.1 SD years) randomized to haloperidol (HAL) (n = 15) or olanzapine (OLZ) treatment (n = 21), imaged at baseline, 3, 6, and 12 months (144 scans). Based on surface-based cortical models and point-by-point measures of gray matter volume, we generated time-lapse maps for each treatment. Disease trajectories differed for atypical versus typical neuroleptic drugs. A rapidly advancing parietal-to-frontal deficit trajectory, in HAL-treated patients, mirrored normal cortical maturation but greatly intensified. The disease trajectory advanced even after symptom normalization, involving the frontal cortex within 12 months with typical drug treatment. Areas with fastest tissue loss shifted anteriorly in the first year of psychosis. This trajectory was not seen with OLZ. Whether this association reflects either reduced neurotoxicity or neuroprotection cannot be addressed with neuroimaging; changes may relate to glial rather than neural components. These maps revise current models of schizophrenia progression; due to power limitations, the findings require confirmation in a sample large enough to model group x time interactions.

Review of the best case series methodology: best case series results of East-West Cancer Center.

PURPOSE: To assess the efficacy of the best case series program methodology as a preliminary evaluation of complementary and alternative programs. SETTING: East-West Cancer Center (EWCC) is a traditional oriental cancer center located in Daejeon, Korea. Cancer patients received Wheel balance therapy (WBT), which focuses on rediscovering homeostatic harmony with dietary therapy, metabolism-activating therapy, antiangiogenesis and immune system therapy, and controlled breathing and psychotherapy. METHODS: Summaries of 6 cases in which patients showed longer survival without progression and were treated with WBT without conventional treatments were submitted for review to the National Cancer Institute (NCI) Office of Cancer Complementary and Alternative Medicine. Each case was then classified by the NCI review panel with pathologic confirmation of disease and radiologic confirmation of complete response or partial response not attributable to conventional treatments. RESULTS: Two of 6 cases were classified as evaluable NCI best cases; the other 4 cases were classified as unevaluable. Except for a patient with squamous cell lung carcinoma, no patient showed further progression as of July 2007. CONCLUSION: The best case series program provides a preliminary evaluation of complementary and alternative medicine programs. But the method will only find treatments that have effects similar to those of conventional methods such as surgery, chemotherapy, and radiation therapy. Therefore, in future studies, BCSP reviewers should additionally consider assessing tumor dormancy and efficacy of combination therapies for Best Case qualification.

Cerebral metabolic dysfunction and impaired vigilance in recently abstinent methamphetamine abusers.

BACKGROUND: Methamphetamine (MA) abusers have cognitive deficits, abnormal metabolic activity and structural deficits in limbic and paralimbic cortices, and reduced hippocampal volume. The links between cognitive impairment and these cerebral abnormalities are not established. METHODS: We assessed cerebral glucose metabolism with [F-18]fluorodeoxyglucose positron emission tomography in 17 abstinent (4 to 7 days) methamphetamine users and 16 control subjects performing an auditory vigilance task and obtained structural magnetic resonance brain scans. Regional brain radioactivity served as a marker for relative glucose metabolism. Error rates on the task were related to regional radioactivity and hippocampal morphology. RESULTS: Methamphetamine users had higher error rates than control subjects on the vigilance task. The groups showed different relationships between error rates and relative activity in the anterior and middle cingulate gyrus and the insula. Whereas the MA user group showed negative correlations involving these regions, the control group showed positive correlations involving the cingulate cortex. Across groups, hippocampal metabolic and structural measures were negatively correlated with error rates. CONCLUSIONS: Dysfunction in the cingulate and insular cortices of recently abstinent MA abusers contribute to impaired vigilance and other cognitive functions requiring sustained attention. Hippocampal integrity predicts task performance in methamphetamine users as well as control subjects.

Mapping hippocampal and ventricular change in Alzheimer disease.

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Sixty-two [corrected] high-resolution MRI scans were acquired from 12 AD patients (mean [corrected] age +/- SE at first scan: 68.7 +/- 1.7 [corrected] years) and 14 matched controls (age: 71.4 +/- 0.9 years) [corrected] each scanned twice (1.9 +/- 0.2 [corrected] years apart, when all subjects are pooled [corrected] 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials.

Structural abnormalities in the brains of human subjects who use methamphetamine.

We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.

Dynamics of gray matter loss in Alzheimer's disease.

We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer's disease (AD). The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions, sparing sensorimotor cortices. The shifting deficits were asymmetric (left hemisphere > right hemisphere) and correlated with progressively declining cognitive status (p < 0.0006). Novel brain mapping methods allowed us to visualize dynamic patterns of atrophy in 52 high-resolution magnetic resonance image scans of 12 patients with AD (age 68.4 +/- 1.9 years) and 14 elderly matched controls (age 71.4 +/- 0.9 years) scanned longitudinally (two scans; interscan interval 2.1 +/- 0.4 years). A cortical pattern matching technique encoded changes in brain shape and tissue distribution across subjects and time. Cortical atrophy occurred in a well defined sequence as the disease progressed, mirroring the sequence of neurofibrillary tangle accumulation observed in cross sections at autopsy. Advancing deficits were visualized as dynamic maps that change over time. Frontal regions, spared early in the disease, showed pervasive deficits later (>15% loss). The maps distinguished different phases of AD and differentiated AD from normal aging. Local gray matter loss rates (5.3 +/- 2.3% per year in AD v 0.9 +/- 0.9% per year in controls) were faster in the left hemisphere (p < 0.029) than the right. Transient barriers to disease progression appeared at limbic/frontal boundaries. This degenerative sequence, observed in vivo as it developed, provides the first quantitative, dynamic visualization of cortical atrophic rates in normal elderly populations and in those with dementia.