Predictors of Seizure Outcomes in Children with Tuberous Sclerosis Complex and Intractable Epilepsy Undergoing Resective Epilepsy Surgery: An Individual Participant Data Meta-Analysis

Objective

To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery.

Data Sources

Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions.

Study Selection

We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion.

Data Extraction

One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes.

Data Synthesis

To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable.

Results

Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2–8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1–24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4–7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8–13.5, p = 0.002) were associated with a good postoperative seizure outcome.

Conclusions

Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review.     

A Frequent PNPLA3 Variant Is a Sex Specific Disease Modifier in PSC Patients with Bile Duct Stenosis

Background & Aims

Primary sclerosing cholangitis predominantly affects males and is an important indication for liver transplantation. The rs738409 variant (I148M) of the PNPLA3 gene is associated with alcoholic and non-alcoholic liver disease and we evaluated its impact on the disease course of PSC.

Methods

The I148M polymorphism was genotyped in 121 German PSC patients of a long-term prospective cohort and 347 Norwegian PSC patients.

Results

In the prospective German cohort, actuarial survival free of liver transplantation was significantly reduced for I148M carriers (p = 0.011) compared to wildtype patients. This effect was restricted to patients with severe disease, as defined by development of dominant stenosis (DS) requiring endoscopic intervention. DS patients showed markedly decreased survival (p = 0.004) when carrying the I148M variant (I148M: mean 13.8 years; 95% confidence interval: 11.6–16.0 vs. wildtype: mean 18.6 years; 95% confidence interval: 16.3–20.9) while there was no impact on survival in patients without a DS (p = 0.87). In line with previous observations of sex specific effects of the I148M polymorphism, the effect on survival was further restricted to male patients (mean survival 11.9 years; 95% confidence interval: 10.0–14.0 in I148M carriers vs. 18.8 years; 95% confidence interval: 16.2–21.5 in wildtype; p<0.001) while female patients were unaffected by the polymorphism (p = 0.65). These sex specific findings were validated in the Norwegian cohort (p = 0.013).

Conclusions

In male PSC patients with severe disease with bile duct stenosis requiring intervention, the common I148M variant of the PNPLA3 gene is a risk factor for reduced survival.     

Lower Prevalence of Carotid Plaque Hemorrhage in Women,and Its Mediator Effect on Sex Differences in Recurrent Cerebrovascular Events

Background and Purpose

Women are at lower risk of stroke, and appear to benefit less from carotid endarterectomy (CEA) than men. We hypothesised that this is due to more benign carotid disease in women mediating a lower risk of recurrent cerebrovascular events. To test this, we investigated sex differences in the prevalence of MRI detectable plaque hemorrhage (MRI PH) as an index of plaque instability, and secondly whether MRI PH mediates sex differences in the rate of cerebrovascular recurrence.

Methods

Prevalence of PH between sexes was analysed in a single centre pooled cohort of 176 patients with recently symptomatic, significant carotid stenosis (106 severe [≥70%], 70 moderate [50–69%]) who underwent prospective carotid MRI scanning for identification of MRI PH. Further, a meta-analysis of published evidence was undertaken. Recurrent events were noted during clinical follow up for survival analysis.

Results

Women with symptomatic carotid stenosis (50%≥) were less likely to have plaque hemorrhage (PH) than men (46% vs. 70%) with an adjusted OR of 0.23 [95% CI 0.10–0.50, P<0.0001] controlling for other known vascular risk factors. This negative association was only significant for the severe stenosis subgroup (adjusted OR 0.18, 95% CI 0.067–0.50) not the moderate degree stenosis. Female sex in this subgroup also predicted a longer time to recurrent cerebral ischemic events (HR 0.38 95% CI 0.15–0.98, P = 0.045). Further addition of MRI PH or smoking abolished the sex effects with only MRI PH exerting a direct effect.Meta-analysis confirmed a protective effect of female sex on development of PH: unadjusted OR for presence of PH = 0.54 (95% CI 0.45–0.67, p<0.00001).

Conclusions

MRI PH is significantly less prevalent in women. Women with MRI PH and severe stenosis have a similar risk as men for recurrent cerebrovascular events. MRI PH thus allows overcoming the sex bias in selection for CEA.     

Higher Fibrinogen Level is Independently Linked with the Presence and Severity of New-Onset Coronary Atherosclerosis among Han Chinese Population

Background

Fibrinogen is a coagulation/inflammatory biomarker strongly associated with atherogenesis. However, no data is currently available regarding the association of fibrinogen level with the presence and severity of new-onset coronary atherosclerosis assessed by Gensini score (GS), particularly in Han Chinese with a large sample size.

Methods and Results

We studied 2288 consecutive, new-onset subjects undergoing coronary angiography with angina-like chest pain. Clinical and laboratory data were collected. Coronary stenotic lesions were considered to be the incidence of coronary atherosclerosis. The severity of coronary stenosis was determined by the GS system. Data indicated that patients with high GS had significantly elevated fibrinogen level (p<0.001). The prevalence and severity of coronary atherosclerosis were dramatically increased according to fibrinogen tertiles. Spearman correlation analysis revealed a positive association between fibrinogen level and GS (r = 0.138, p<0.001). Multivariate logistic regression analysis demonstrated that plasma fibrinogen level was independently associated with high GS (OR = 1.275, 95% CI 1.082–1.502, p = 0.004) after adjusting for potential confounders. Moreover, fibrinogen level was also independently related to the presence of coronary atherosclerosis (fibrinogen tertile 2: OR = 1.192, 95% CI 0.889–1.598, p = 0.241; tertile 3: OR = 2.003, 95% CI 1.383–2.903, p <0.001) and high GS (fibrinogen tertile 2: OR = 1.079, 95% CI 0.833–1.397, p = 0.565; tertile 3: OR = 1.524, 95% CI 1.155–2.011, p = 0.003) in a dose-dependent manner. Receiver-operating characteristic curve analysis showed that the best fibrinogen cut-off value for predicting the severity of coronary stenosis was 3.21 g/L.

Conclusions

Higher fibrinogen level is independently linked with the presence and severity of new-onset coronary atherosclerosis in Han Chinese population.     

A Comprehensive Expression Analysis of Mucins in Appendiceal Carcinoma in a Multicenter Study: MUC3 Is a Novel Prognostic Factor

Background

Mucins are implicated in survival in various cancers, but there have been no report addressed on survival in appendiceal carcinoma, an uncommon disease with different clinical and pathological features from those of other colon cancers. We aimed to investigate the clinical implications of expression of mucins in appendiceal carcinoma.

Methods

Expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6, MUC16 and MUC17 in cancer tissue were examined by immunohistochemistry in 108 cases of surgically resected appendiceal carcinoma.

Results

The following relationships of mucins with clinicopathologic factors were identified: MUC1 with positive lymphatic invasion (p = 0.036); MUC2 with histological type (mucinous carcinoma, p<0.001), superficial invasion depth (p = 0.007), negative venous invasion (p = 0.003), and curative resection (p = 0.019); MUC3 with non-curative resection (p = 0.017); MUC5AC with histological type (mucinous carcinoma, p = 0.002), negative lymphatic invasion (p = 0.021), and negative venous invasion (p = 0.022); and MUC16 with positive lymph node metastasis (p = 0.035), positive venous invasion (p<0.05), and non-curative resection (p = 0.035). A poor prognosis was related to positive lymph node metastasis (p = 0.04), positive lymphatic invasion (p = 0.02), positive venous invasion (p<0.001), non-curative resection (p<0.001), and positive expression of MUC3 (p = 0.004). In multivariate analysis, positive venous invasion (HR: 6.93, 95% CI: 1.93–24.96, p = 0.003), non-curative resection (HR: 10.19, 95% CI: 3.05–34.07, p<0.001) and positive MUC3 expression (HR: 3.37, 95% CI: 1.13–10.03, p = 0.03) were identified as significant independent prognostic factors in patients with appendiceal carcinoma.

Conclusions

Expression of MUC3 in appendiceal carcinoma is an independent factor for poor prognosis and a useful predictor of outcome in patients with appendiceal carcinoma after surgery.     

Significantly Reducing Post-Tonsillectomy Haemorrhage Requiring Surgery by Suturing the Faucial Pillars: A Retrospective Analysis

Background

The tonsillectomy is one of the most frequently performed surgical procedures. Given the comparatively frequent postsurgical bleeding associated with this procedure, particular attention has been paid to reduction of the postoperative bleeding rate. In 2006, we introduced routine suturing of the faucial pillars at our clinic to reduce postoperative haemorrhage.

Methods

Two groups from the years 2003–2005 (n = 1000) and 2007–2009 (n = 1000) have been compared. We included all patients who had an elective tonsillectomy due to a benign, non-acute inflammatory tonsil illness. In the years 2007–2009, we additionally sutured the faucial pillars after completing haemostasis. For primary haemostasis we used suture ligation and bipolar diathermy.

Results

The rate of bleeding requiring second surgery for haemostasis was 3.6% in 2003–2005 but only 2.0% in 2007–2009 (absolute risk reduction 1.6% (95% CI 0.22%–2.45%, p = 0.04)). The median surgery time—including adenoidectomy and paracentesis surgery—increased from 25 to 31 minutes (p<0.01).

Conclusions

We have been able to substantiate that suturing of the faucial pillars nearly halves the rate of postoperative haemorrhage. Surgery takes 8 minutes longer on average. Bleeding occurs later, mostly after 24 h. The limitations of this study relate to its retrospective character and all the potential biases related to observational studies.     

Prognostic Value of TNF-Related Apoptosis Inducing Ligand (TRAIL) in Acute Coronary Syndrome Patients

Background

Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes.

Methods

The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone.

Results

During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03–0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1–54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05–0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004–0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02–1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56–145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters.

Conclusions

Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.     

Abdominal Regional Fat Distribution on MRI Correlates with Cholecystolithiasis

Aims

To determine whether abdominal regional fat distribution pattern on MRI is correlated with cholecystolithiasis.

Methods

Magnetic resonance imaging (MRI) of 163 patients with cholecystolithiasis and 163 non-cholecystolithiasis control subjects admitted to our institution between March 2011 and September 2013 were included in this cross-sectional evaluation. There were 98 women and 65 men in cholecystolithiasis group with an average age of 57±16 years (range 25–86 years). There were 87 women and 76 men in the control group with an average age of 41±16 years (range 14–77 years). Visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT) and total abdominal adipose tissue (TAT) of all the subjects at navel level were measured on abdominal MRI. According to the visceral adipose area (cut-off point VAT = 100 cm²), study subjects were divided into 1) increased accumulation of intra-abdominal fat and 2) normal distribution of intra-abdominal fat. Logistic regression was used to assess the association of fat with the presence of cholecystolithiasis, adjusted for age and sex.

Results

The incidence of increased intra-abdominal fat accumulation in the cholecystolithiasis group was significantly higher than that of the control group (P = 0.000). After adjusting for age and sex, cholecystolithiasis was associated with a one standard deviation increment in the waist circumference (WC) (OR = 1.44; 95%CI: 1.01,1.93; p = 0.00), VAT (OR = 4.26; 95%CI: 1.85,5.29; p = 0.00), VAT/SAT (OR = 8.66; 95%CI: 1.60,12.63; p = 0.00), and VAT/TAT (OR = 6.73; 95%CI: 4.24,12.18; p = 0.00), but not with fat content in the abdominal subcutaneous fat (p = 0.19).

Conclusions

The visceral adipose tissue and distribution proportion of abdominal adipose tissue are correlates of cholecystolithiasis.     

Comparison of Transverse Island Flap Onlay and Tubularized Incised-Plate Urethroplasties for Primary Proximal Hypospadias: A Systematic Review and Meta-Analysis

Purpose

This meta-analysis was conducted to compare postoperative outcomes between transverse island flap (TVIF) onlay and tubularized incised-plate (TIP) urethroplasties for primary proximal hypospadias.

Materials and Methods

A comprehensive literature search updated to 21^st May 2014 was carried out for relevant studies. After literature identification and data extraction, odds ratio (OR) with 95% confidential interval (CI) was calculated to compare postoperative complication rate between TVIF onlay and TIP. Meta-regression and subgroup analyses were applied to find potential affective factors.

Results

A total of 6 studies including 309 patients receiving TVIF onlay and 262 individuals subjected to TIP met inclusion criteria. The synthetic data suggested that TVIF onlay and TIP were comparable in terms of total complication rate (OR 0.85, 95% CI 0.56–1.30, p = 0.461), fistula (OR 0.68, 95% CI 0.38–1.21, p = 0.194), recurrent curvature (OR 1.16, 95% CI 0.43–3.12, p = 0.766), dehiscence (OR 0.95, 95% CI 0.33–2.74, p = 0.920), diverticulum (OR 1.90, 95% CI 0.53–6.78, p = 0.321), meatal stenosis (OR 0.74, 95% CI 0.20–2.77, p = 0.651) and urethral stricture (OR 1.49, 95% CI 0.41–5.50, p = 0.545), without significant heterogeneity for each comparison group. Meta-regression and subgroup analyses revealed no significant findings. One-way sensitivity analysis indicated that the results were stable. No publication bias was detected using both funnel plot and Egger’s test. Also, there were no obvious differences observed in cosmetic and functional outcomes.

Conclusions

This meta-analysis suggests that TVIF onlay and TIP urethroplasties are clinically equivalent. Given the inherent limitations of included studies, this conclusion should be interpreted with caution and wait to be confirmed by more well-designed randomized controlled trials with high quality in the future.     

Increased Risk of Ischemic Stroke in Young Patients with Ankylosing Spondylitis: A Population-Based Longitudinal Follow-Up Study

Background

Prospective data on the association between ischemic stroke and ankylosing spondylitis (AS) in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS.

Methods

A total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates.

Results

During follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021). The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20–3.29; p = 0.0079) and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16–3.20; p = 0.0110).

Conclusion

Our study showed an increased risk of developing ischemic stroke in young patients with AS.     

Mitochondrial DNA (mtDNA) Haplogroups Influence the Progression of Knee Osteoarthritis. Data from the Osteoarthritis Initiative (OAI)

Objective

To evaluate the influence of the mtDNA haplogroups on knee osteoarthritis progression in Osteoarthritis Initiative (OAI) participants through longitudinal data from radiographs and magnetic resonance imaging (MRI).

Methods

Four-year knee osteoarthritis progression was analyzed as increase in Kellgren and Lawrence (KL) grade, in addition to increase in OARSI atlas grade for joint space narrowing (JSN), osteophytes and subchondral sclerosis in the tibia medial compartment of 891 Caucasian individuals from the progression subcohort. The influence of the haplogroups on the rate of structural progression was also assessed as the four-year change in minimum joint space width (mJSW in millimetres) in both knees of (n = 216) patients with baseline unilateral medial-tibiofemoral JSN. Quantitative cartilage measures from longitudinal MRI data were those related to cartilage thickness and volume with a 24 month follow-up period (n = 381).

Results

During the four-year follow-up period, knee OA patients with the haplogroup T showed the lowest increase in KL grade (Hazard Risk [HR] = 0.499; 95% Confidence Interval [CI]: 0.261–0.819; p<0.05) as well as the lowest cumulative probability of progression for JSN (HR = 0.547; 95% CI: 0.280–0.900; p<0.05), osteophytes (HR = 0.573; 95% CI: 0.304–0.893; p<0.05) and subchondral sclerosis (HR = 0.549; 95% CI: 0.295–0.884; p<0.05). They also showed the lowest decline in mJSW (standardized response means (SRM) = −0.39; p = 0.037) in those knees without baseline medial JSN (no-JSN knees). Normalized cartilage volume loss was significantly lower in patients carrying the haplogroup T at medial tibia femoral (SRM = −0.33; p = 0.023) and central medial femoral (SRM = −0.27; p = 0.031) compartments. Cartilage thickness loss was significantly lower in carriers of haplogroup T at central medial tibia-femoral (SRM = −0.42; p = 0.011), medial tibia femoral (SRM = −0.32; p = 0.018), medial tibia anterior (SRM = +0.31; p = 0.013) and central medial femoral (SRM = −0.19; p = 0.013) compartments.

Conclusions

Mitochondrial genome seems to play a role in the progression of knee osteoarthritis. mtDNA variation could improve identification of patients predisposed to faster or severe progression of the disease.     

Genetic Variation in the Interleukin-28B Gene Is Associated with Spontaneous Clearance and Progression of Hepatitis C Virus in Moroccan Patients

Background

Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population.

Methods

We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5′ allelic discrimination assay.

Results

The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99–11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19–66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99–3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08–8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40–3.93; p = 0.0100).

Conclusions

In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection.     

Coexistence of Low Vitamin D and High Fibroblast Growth Factor-23 Plasma Levels Predicts an Adverse Outcome in Patients with Coronary Artery Disease

Objective

Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease.

Methods

Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6–12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed.

Results

Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m². After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48–0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04–1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31–0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62–1.71; p = 0.904).

Conclusions

Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036     

Prediction of Long-Term Mortality by Preoperative Health-Related Quality-of-Life in Elderly Onco-Surgical Patients

Objective

Aim of this study was to evaluate the association between preoperative health-related quality of life (HRQoL) and mortality in a cohort of elderly patients (>65 years) with gastrointestinal, gynecological and genitourinary carcinomas.

Design

Prospective cohort pilot study.

Setting

Tertiary university hospital in Germany.

Patients

Between June 2008 and July 2010 and after ethical committee approval and written informed consent, 126 patients scheduled for onco-surgery were included. Prior to surgery as well as 3 and 12 months postoperatively all participants completed the EORTC-QLQ-C30 questionnaire (measuring self-reported health-related quality of life). Additionally, demographic and clinical data including the Mini Mental State Examination (MMSE) were collected. Surgery and anesthesia were conducted according to the standard operating procedures. Primary endpoint was the cumulative mortality rate over 12 months after one year. Changes in Quality of life were considered as secondary outcome.

Results

Mortality after one year was 28%. In univariable and multivariable logistic regression analysis baseline HRQoL self-reported cognitive function (OR per point: 0.98; CI 95% 0.96–0.99; p = 0.024) and higher symptom burden for appetite loss (per point: OR 1.02; CI 95% 1.00–1.03; p = 0.014) were predictive for long-term mortality. Additionally the MMSE as an objective measure of cognitive impairment (per point: OR 0.69; CI 95% 0.51–0.96; p = 0.026) as well as severity of surgery (OR 0.31; CI 95% 0.11–0.93; p = 0.036) were predictive for long-term mortality. Global health status 12 months after surgery was comparable to the baseline levels in survivors despite moderate impairments in other domains.

Conclusion

This study showed that objective and self-reported cognitive functioning together with appetite loss were prognostic for mortality in elderly cancer patients. In addition, impaired cognitive dysfunction and severity of surgery were predictive for one-year mortality whereas in this selected population scheduled for surgery age, gender, cancer site and metastases were not.     

Coronary Collateral Circulation in Patients of Coronary Ectasia with Significant Coronary Artery Disease

Objectives

Patients with coronary ectasia (CE) usually have coexisting coronary stenosis resulting in myoischemia. Coronary collateral plays an important role in protecting myocardium from ischemia and reducing cardiovascular events. However, limited studies investigate the role of CE in coronary collaterals development.

Methods

We evaluated 1020 consecutive patients undergoing coronary angiography and 552 patients with significant coronary artery disease (SCAD), defined as diameter stenosis more than 70%, were finally analyzed. CE is defined as the ectatic diameter 1.5 times larger than adjacent reference segment. Rentrop collateral score was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.

Results

73 patients (13.2%) had CE lesions which were most located in the right coronary artery (53.4%). Patients with CE had a lower incidence of diabetes (43.8% vs 30.1%, p = 0.03), higher body mass index (25.4±3.5 vs 26.7±4.6, p = 0.027) and poorer coronary collateral (58.2% vs 71.2%, p = 0.040). Patients with poor collateral (n = 331) had a higher incidence of CE (15.7% vs 9.5%, p = 0.040) and fewer diseased vessels numbers (1.96±0.84 vs 2.48±0.69, p<0.001). Multivariate analysis showed diabetes (odd ratio (OR) 0.630, p = 0.026), CE (OR = 0.544, p = 0.048), and number of diseased vessels (OR = 2.488, p<0.001) were significant predictors of coronary collaterals development.

Conclusion

The presence of CE was associated with poorer coronary collateral development in patients with SCAD.     

Fetal Eye Movements on Magnetic Resonance Imaging

Objectives

Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed.

Methods

Dynamic SSFP sequences were acquired in 72 singleton fetuses (17–40 GW, three age groups [17–23 GW, 24–32 GW, 33–40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid.

Results

In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded.Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3–45%.

Conclusions

In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations.     

Mitral Tissue Inhibitor of Metalloproteinase 2 Is Associated with Mitral Valve Surgery Outcome

Background

Matrix metalloproteinases play a role in regulating cardiac remodeling. We previously reported an association between tissue inhibitor of metalloproteinase 2 (TIMP-2) expression and mitral valve (MV) disease. However, the determinants and prognostic value of mitral TIMP2 after MV surgery are unknown.

Methods

This retrospective study of 164 patients after MV surgery in a tertiary medical center in Taiwan assessed mitral TIMP2 on a semiquantitative scale (0–2) by immunohistochemical staining. The primary endpoints were the composite of cardiovascular death and heart failure admission.

Results

Mean age was 50.4±13.7 years. After a mean follow-up period of 101±59 months, primary endpoints had occurred in 25 (15.2%) subjects. Patients with and without primary endpoint events significantly differed in terms of age (56.6±14.4 vs. 49.2±13.4 years, respectively; p = 0.013) and left ventricular end-systolic diameter (LVESD) (39.7±8.2 vs. 35.5±7.5 mm, p = 0.010) at surgery. The TIMP2 had a significant dose-dependent association with development of a primary endpoint (p = 0.002). Kaplan–Meier analysis showed that TIMP2 expression has a significant positive association with primary endpoint-free survival (log-rank test; p = 0.004). Cox regression analysis showed that independent predictors of primary endpoints were TIMP2 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.12–0.65; p = 0.003), age (HR 1.05; 95% CI 1.02–1.09; p = 0.003) and LVESD (HR 1.05; 95% CI 1.01–1.10; p = 0.020).

Conclusions

The lack of mitral TIMP2 expression is associated with increases in cardiovascular death and heart failure following MV surgery.     

Surgically Acquired Deficits and Diffusion Weighted MRI Changes after Glioma Resection - A Matched Case-Control Study with Blinded Neuroradiological Assessment

Background

Acquired deficits following glioma resection may not only occur due to accidental resection of normal brain tissue. The possible importance of ischemic injuries in causing neurological deficits after brain tumor surgery is not much studied. We aimed to study the volume and frequency of early postoperative circulatory changes (i.e. infarctions) detected by diffusion weighted resonance imaging (DWI) in patients with surgically acquired neurological deficits compared to controls.

Methods

We designed a 1∶1 matched case-control study in patients with diffuse gliomas (WHO grade II–IV) operated with 3D ultrasound guided resection. 42 consecutive patients with acquired postoperative dysphasia and/or new motor deficits were compared to 42 matched controls without acquired deficits. Controls were matched with respect to histopathology, preoperative tumor volumes, and eloquence of location. Two independent radiologists blinded for clinical status assessed the postoperative DWI findings.

Results

Postoperative peri-tumoral infarctions were more often seen in patients with acquired deficits (63% versus 41%, p = 0.046) and volumes of DWI abnormalities were larger in cases than in controls with median 1.08 cm³ (IQR 0–2.39) versus median 0 cm³ (IQR 0–1.67), p = 0.047. Inter-rater agreement was substantial (67/82, κ = 0.64, p<0.001) for diagnosing radiological significant DWI abnormalities.

Conclusion

Peri-tumoral infarctions were more common and were larger in patients with acquired deficits after glioma surgery compared to glioma patients without deficits when assessed by early postoperative DWI. Infarctions may be a frequent and underestimated cause of acquired deficits after glioma resection. DWI changes may be an attractive endpoint in brain tumor surgery with both good inter-rater reliability among radiologists and clinical relevance.