Screening for Delirium During Pediatric Brain Injury Rehabilitation.

OBJECTIVE: To assess feasibility of routine delirium screening using the Cornell Assessment of Pediatric Delirium (CAPD) in children admitted for rehabilitation with acquired brain injury (ABI), report on the prevalence of positive delirium screens in this population, and explore longitudinal trends in CAPD scores and their association with rehabilitation outcomes. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation unit. PARTICIPANTS: 144 children (median 10.8 years) with ABI (N=144). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Percent compliance with twice daily delirium screening; prevalence of positive delirium screens; trajectories in CAPD scores and their relation with FIM for Children (WeeFIM) scores. RESULTS: Screening was feasible (mean 75% compliance for each of 144 children). Of 16,136 delirium screens, 29% were positive. 62% of children had ≥1 positive screen. Four primary patterns of CAPD trajectories were identified: Static Encephalopathy (10%), Episodic Delirium (10%), Improving (32%), and No Delirium (48%). Validity of these trajectories was demonstrated through association with WeeFIM and CALS outcomes. Younger age at admission was associated with positive delirium screens, and rehabilitation length of stay was significantly longer for the Improving group. CONCLUSIONS: Delirium occurs frequently in children with ABI during inpatient rehabilitation. Routine delirium screening provides clinically relevant information including the potential to facilitate early detection and intervention for medical complications. Longitudinal ratings of delirium symptoms may also have a role in developing a standardized definition for Post Traumatic Confusional State (PTCS) stage of recovery in children.

CFD Study of the Effect of the Angle Pattern on Iliac Vein Compression Syndrome.

Iliac vein compression syndrome (IVCS, or May-Thurner syndrome) occurs due to the compression of the left common iliac vein between the lumbar spine and right common iliac artery. Because most patients with compression are asymptomatic, the syndrome is difficult to diagnose based on the degree of anatomical compression. In this study, we investigated how the tilt angle of the left common iliac vein affects the flow patterns in the compressed blood vessel using three-dimensional computational fluid dynamic (CFD) simulations to determine the flow fields generated after compression sites. A patient-specific iliac venous CFD model was created to verify the boundary conditions and hemodynamic parameter set in this study. Thirty-one patient-specific CFD models with various iliac venous angles were developed using computed tomography (CT) angiograms. The angles between the right or left common iliac vein and inferior vena cava at the confluence level of the common iliac vein were defined as α1 and α2. Flow fields and vortex locations after compression were calculated and compared according to the tilt angle of the veins. Our results showed that α2 affected the incidence of flow field disturbance. At α2 angles greater than 60 degrees, the incidence rate of blood flow disturbance was 90%. In addition, when α2 and α1 + α2 angles were used as indicators, significant differences in tilt angle were found between veins with laminar, transitional, and turbulent flow (p < 0.05). Using this mathematical simulation, we concluded that the tilt angle of the left common iliac vein can be used as an auxiliary indicator to determine IVCS and its severity, and as a reference for clinical decision making.

Association of Hepatitis B and C Virus with the Risk of Coronary Artery Disease and Cerebrovascular Disease in Patients with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma accounts for approximately 90% of primary liver cancers and hepatitis virus was believed to have the potential for altering the pathogenesis of arteriosclerosis. However, the influence of the hepatitis virus on coronary artery disease or cerebral vascular disease remains unclear. This study used the Taiwan National Health Insurance Research Database to clarify the virus-associated risk of coronary artery disease and cerebral vascular disease in patients with hepatocellular carcinoma (HCC). METHODS: A total of 188,039 HCC individuals, age 20 years or older, were enrolled from the Longitudinal Health Insurance Database between 2000 and 2017 for cohort analysis. A total of 109,348 with hepatitis B virus (HBV) infection, 37,506 with hepatitis C virus (HCV) infection, 34,110 without HBV or HCV, and 7075 with both HBV and HCV were recorded. Statistically, propensity score matched by sex, age, and index year at a ratio of 15:5:5:1 and a sensitivity test using multivariable Cox regression were used. RESULTS: The risk of coronary artery disease in the HCV-related HCC group was 1.516-fold (95% CI: 1.328-2.034, p < 0.001) higher than in the HBV-related HCC group, followed by the HBV/HCV-related HCC group and the non-B/C HCC group; the cerebral vascular disease risk in the HCV-related HCC group was 1.467-fold higher than in the HBV-related HCC group (95% CI: 1.335 to 1.786, p < 0.001), followed by the HBV/HCV-related HCC group and the non-B/C HCC group. CONCLUSION: Hepatitis C virus infection was found to have a higher risk of developing coronary artery disease or cerebral vascular disease in patients with hepatocellular carcinoma. For patients with hepatocellular carcinoma, our findings warrant the importance in preventing artherosclerotic disease in the setting of hepatitis C virus infection.

Rethinking recovery in adolescent concussions: Network-level functional connectivity alterations associated with motor deficits.

Adolescents who are clinically recovered from concussion continue to show subtle motor impairment on neurophysiological and behavioral measures. However, there is limited information on brain-behavior relationships of persistent motor impairment following clinical recovery from concussion. We examined the relationship between subtle motor performance and functional connectivity of the brain in adolescents with a history of concussion, status post-symptom resolution, and subjective return to baseline. Participants included 27 adolescents who were clinically recovered from concussion and 29 never-concussed, typically developing controls (10-17 years); all participants were examined using the Physical and Neurologic Examination of Subtle Signs (PANESS). Functional connectivity between the default mode network (DMN) or dorsal attention network (DAN) and regions of interest within the motor network was assessed using resting-state functional magnetic resonance imaging (rsfMRI). Compared to controls, adolescents clinically recovered from concussion showed greater subtle motor deficits as evaluated by the PANESS and increased connectivity between the DMN and left lateral premotor cortex. DMN to left lateral premotor cortex connectivity was significantly correlated with the total PANESS score, with more atypical connectivity associated with more motor abnormalities. This suggests that altered functional connectivity of the brain may underlie subtle motor deficits in adolescents who have clinically recovered from concussion. More investigation is required to understand the persistence and longer-term clinical relevance of altered functional connectivity and associated subtle motor deficits to inform whether functional connectivity may serve as an important biomarker related to longer-term outcomes after clinical recovery from concussion.

Association of protein disulfide isomerase family A, member 4, and inflammation in people living with HIV.

OBJECTIVES: Protein disulfide isomerase (PDI) family members are specific endoplasmic reticulum proteins associated with inflammation, obesity, and cancer. In HIV infection, the role of PDI family A, member 4 (PDIA4), is unclear. This study aimed to clarify the association between plasma PDIA4 levels and inflammation in people living with HIV (PLWH). METHODS: In this study, 287 PLWH and 74 healthy participants were enrolled. The plasma PDIA4 values, demographic data, laboratory data, and other inflammatory markers were recorded. The association between PDIA4 level and inflammatory extent was analyzed using logistic regression and Spearman rank-order correlations. Other results were analyzed using Student's t-test or chi-square test. RESULTS: In PLWH, the PDIA4 levels were positively associated with the inflammatory markers, interleukin 6 (r = 0.209, p = 0.001), and tumor necrosis factor-α (r = 0.162, p = 0.01) levels, but not with high-sensitivity C-reactive protein levels. Moreover, the plasma PDIA4 level of PLWH decreased after anti-viral treatment (p = 0.0001). CONCLUSION: Plasma PDIA4 levels are closely associated with inflammation in PLWH and have a positive correlation with the viral load during anti-viral therapy.

Inter-rater Reliability of the Revised Physical and Neurological Examination of Subtle Signs (PANESS) scored using video review.

The Physical and Neurological Examination of Subtle Signs (PANESS) is a brief neuromotor exam designed for use in children. This study examined the inter-rater reliability of PANESS scoring using video review in 23 typically developing youth, aged 10-18 years, who were either never-concussed or evaluated following clinical recovery from concussion. Moderate to excellent inter-rater reliability was identified across PANESS subscores and total score. The strongest inter-rater reliability was observed for the Timed Motor portion of the PANESS (ICCs >.90) suggesting that this section in particular may be a strong candidate for video-based scoring or telehealth administration.

New insights into sex differences in primary biliary cholangitis. Gender difference in primary biliary cholangitis.

OBJECTIVE: To highlight the clinical characteristics of primary biliary cholangitis on the basis of gender in terms of the extent of liver injury and extra-liver autoimmune expressions. METHODS: The retrospective study was conducted at the Tri-Service General Hospital, Taiwan, and comprised data of patients aged >20 years diagnosed with primary biliary cholangitis between January 2000 and December 2018. Patients in the control group were randomly selected from the health examination centre. Liver injury manifestations and susceptibilities were analysed along gender lines. The gene expression microarray data from the National Centre for Biotechnology Information Gene Expression Omnibus database was also used to explore the relationship between autoimmune-induced inflammation and androgen response expression. Statistical analysis was done using Graph-Pad Prism 7.0. RESULTS: Of the 75 cases, 63(84%) were females with a mean age of 64.6±1.78 years, and 12(16%%) were males with a mean age of 46.6±5.6 years. Of the 66 controls, 55(83.3%) were females with a mean age of 51.67 years, and 11(16.6%) were males with a mean age of 45.9 years. There were no significant differences in terms of liver profiles related to gender in the control group (p>0.05). Among the cases, male patients showed fewer extrahepatic autoimmune disorders and more severe liver injuries before or after ursodeoxycholic acid treatment (p<0.05). There was a positive correlation between androgen receptor response and the extent of systemic inflammation (p<0.05). Conclusion: The association between androgen receptor responses and inflammation was linked to gender-related hepatic injuries, which may explain why liver inflammation in male patients is generally more severe compared to the female patients. Conclusion: The association between androgen receptor responses and inflammation was linked to gender-related hepatic injuries, which may explain why liver inflammation in male patients is generally more severe compared to the female patients.

Altered white matter diffusivity and subtle motor function in a pilot cohort of adolescents with sports-related concussion.

BACKGROUND AND OBJECTIVE: Adolescents with sports-related concussion (SRC) demonstrate acute and persistent deficits in subtle motor function. However, there is limited research examining related neurological underpinnings. This pilot study examined changes in motor-associated white matter pathways using diffusion tensor imaging (DTI) and their relationship with subtle motor function. METHODS: Twelve adolescents with SRC (12-17 years) within two-weeks post-injury and 13 never-injured neurotypical peers completed DTI scanning. A subset of 6 adolescents with SRC returned for a follow-up visit post-medical clearance from concussion. Subtle motor function was evaluated using the Physical and Neurological Examination of Subtle Signs (PANESS). RESULTS: Adolescents with SRC showed higher mean diffusivity (MD) of the superior corona radiata and greater subtle motor deficits compared to controls. Across all participants, greater subtle motor deficits were associated with higher (more atypical) MD of the superior corona radiata. Preliminary longitudinal analysis indicated reduction in fractional anisotropy of the corpus callosum but no change in the MD of the superior corona radiata from the initial visit to the follow-up visit post-medical clearance. CONCLUSIONS: These findings support preliminary evidence for a brain-behavior relationship between superior corona radiata microstructure and subtle motor deficits in adolescents with SRC that merits further investigation.

Rasch Properties of the Cognitive and Linguistic Scale and Optimization for Outcome Trajectory Modeling in Pediatric Acquired Brain Injury.

OBJECTIVES: To (1) determine if items on the Cognitive and Linguistic Scale (CALS) follow a Rasch distribution and (2) explore the relationship between Rasch-derived Cognitive Ability Estimates and outcome trajectory parameters using a nonlinear mixed-effects modeling approach. DESIGN: Retrospective study. SETTING: Pediatric inpatient rehabilitation hospital. PARTICIPANTS: A total of 252 children (N=252) aged of 2-21 years (median, 11.8 [IQR, 6.4-15.9] years) consecutively admitted to an inpatient rehabilitation brain injury unit (2008-2014) for a first inpatient admission after acquired brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch-derived Cognitive Ability Estimates from the CALS and associated outcome trajectory parameters. RESULTS: The CALS demonstrates adequate interval-scale properties with removal of scores from the arousal and responsivity items. Rasch-derived Cognitive Ability Estimates were associated with age (ß=0.025, P<.001) such that older age was associated with a faster rate of recovery and more complete ultimate recovery. Slower recovery initiation was associated with a less complete overall cognitive recovery (Spearman ρ=-0.31; P<.001). CONCLUSIONS: The Cognitive Ability Estimates derived from the CALS and associated outcome parameters (eg, rate of recovery) may serve as an ideal outcome measure for clinical trials evaluating interventions for acquired brain injury in a pediatric rehabilitation setting.

Risk of Non-Alcoholic Fatty Liver Disease in Xanthelasma Palpebrarum.

BACKGROUND: Xanthelasma palpebrarum (XP) is a sign of hyperlipidemia and is closely linked to atherosclerosis. Since fatty liver shares similar risk factors with atherosclerosis, we hypothesized that patients with XP are also at risk of non-alcoholic fatty liver disease (NAFLD). METHODS: In this retrospective cohort study, 37 patients with XP were compared with sex- and age-matched controls undergoing general health examination. Moreover, demographic information and lipid profiles were compared. The risk of NAFLD was evaluated using the hepatic steatosis and ZJU indices. In addition, we analyzed publicly available RNA sequencing data from the GSE48452 and GSE61260 datasets in the Gene Expression Omnibus database. FINDINGS: Patients with XP had higher scores of hepatic steatosis index (37 ± 1.13 vs 32 ± 0.82, p=0.0006) and ZJU index (38.77 ± 1.0 vs 33.88 ± 0.74, p=0.0002). In addition, they had higher levels of lipid parameters, including total cholesterol, low-density lipoprotein (LDL), and fasting glucose. Among patients with fatty liver, individuals presenting with XP showed higher serum levels of total cholesterol (216 ± 10.4 vs 188.9 ± 7.6, p=0.04), fasting glucose (117.1 ± 6.4 vs 98.3 ± 2.4, p=0.002), and low-density lipoprotein (145.1 ± 8.7 vs 115.6 ± 6.4, p=0.009) than those without XP. In gene expression analysis, individuals presenting with non-alcoholic steatohepatitis showed higher Z scores of xanthelasma than those without non-alcoholic steatohepatitis. CONCLUSION: Our results suggest that individuals with XP have a higher risk of progression to NAFLD and develop a more severe dyslipidemia.

Relationships Between Vitamin D Status and Cytokine: Results from Interferon-Based Therapy in Non-Cirrhotic, Treatment-Naïve Patients with Chronic Hepatitis C Infection.

BACKGROUND: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans. METHODS: A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25[OH]D) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus. FINDINGS: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders. CONCLUSION: In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.

Is a bleeding scan prior to single-balloon enteroscopy necessary in patients with obscure gastrointestinal bleeding?

BACKGROUND/PURPOSE: To evaluate the efficacy and accuracy of bleeder localization in a pre-enteroscopic bleeding scan in patients with obscure gastrointestinal bleeding (OGIB). METHODS: From January 2009 to December 2014, 98 patients with OGIB undergoing single-balloon enteroscopy (SBE) were enrolled. These patients were classified based on their history of a previous bleeding scan; 56 patients had undergone a previous bleeding scan, whereas 42 had not. The clinical characteristics, endoscopic findings, and rebleeding rate were compared between these two groups. The ability of the bleeding scan to localize the bleeding site was analyzed. RESULTS: The mean age of patients was 56 ± 22 years; final diagnostic yield, 65.3%; and the most common etiology of OGIB, angiodysplasia (29.6%). There was no significant difference in demographic characteristics, OGIB etiologies, and final diagnostic yields (67.9% vs. 61.2%, bleeding scan vs. control group) between groups. In the bleeding scan group, the rate of positive detection was approximately 80.4%. However, only 26.7% patients with a positive bleeding scan showed correct localization of bleeding. Moreover, the bleeding scan delayed SBE (8.9 days vs. 3.0 days, p < 0.001). During the 24 months of follow-up, 15 patients (15.3%) exhibited rebleeding and needed to be hospitalized, but there was no significant difference between the groups. CONCLUSION: In our study, bleeding scans in patients with OGIB revealed poor localization of the bleeder and delay in performing SBE. Thus, a bleeding scan prior to SBE showed a limited role for patients with OGIB.

Pre-medication to improve esophagogastroduodenoscopic visibility: a meta-analysis and systemic review.

BACKGROUND/AIMS: The use of pre-medication to improve visibility in gastrointestinal endoscopy has not been well addressed and remains controversial. The aim is to evaluate the effects of current pre-medication on endoscopic visualization. METHODOLOGY: We made the overall strategies to search the different databases and assessed the quality of included studies according to the included and excluded standard. 1541 patients were treated with pre-medication. RESULT: Ten prospective studies involving 1541 patients were included. There was improved visibility in patients treated with Simethicone (weighted mean difference -4.3; 95% confidence interval (CI), -4.94 to -3.67), compared to those who did not use Simethicone. In the Simethicone based regiment, administration of Pronase was noted with significantly improved visibility in the location of antrum and fundus, compared to those who did not use; however, administration of N-acetyl-L-cysteine could not lead to significantly improved visibility. Simethicone offered better visibility than N-acetyl-L-cysteine and Pronase alone. CONCLUSIONS: There is improved visibility with pre-medication using Simethicone before esophagogastroduodenoscopy. In the Simethicone based regimen, administration of Pronase or N-acetyl-Lcysteine may be of little use in improving visibility. Based on the literature review, Simethicone dissolved in the water with the acceptably lowest ratio of 0.7 can still offer the good visibility but 30 mL of water should be avoided.

Benefits of the povidone-iodine: simultaneously decrease risk of infection and tumor seeding after percutaneous endoscopic gastrostomy.

Percutaneous endoscopic gastrostomy (PEG) is a well-established enteral feeding modality in patients with oropharyngeal/esophageal cancer; however, these patients are at risk for two possible PEG-related complications. First, oropharyngeal organisms may be transported to the PEG stoma and thus increase the risk of peristomal infection. Second, oropharyngeal/esophageal cancer cells may adhere to the PEG tube and thus increase the risk of tumor seeding along the PEG tract. Because of its microbicidal and tumoricidal effects, povidone-iodine pretreatment of the PEG tube may decrease the risk of peristomal infection and tumor seeding associated with PEG insertion in patients with oropharyngeal/esophageal cancer. To test this hypothesis, we brushed povidone-iodine onto the outer surface of PEG tubes prior to insertion.

Efficacy of simethicone and N-acetylcysteine as premedication in improving visibility during upper endoscopy.

BACKGROUND: Simethicone and N-acetylcysteine have been widely used in improving endoscopic visibility. However, the optimal dose, volume, and dosing time for the premedication regimen are still unclear. AIM: Our aim was to assess the efficacy of premedication in improving endoscopic visibility and determine the contributions of dose, volume, and premedication time. METHODS: A total of 1849 patients were prospectively treated in three groups: group A: 100-mg simethicone suspension in 5 mL water; group B: 100-mg simethicone suspension in 100 mL water; and group C: 100-mg simethicone suspension in 100 mL water containing 200 mg N-acetylcysteine. Mucosa visibility was assessed at seven sites of upper gastrointestinal tract. The sum of scores was considered as total mucosal visibility score (TMVS). RESULTS: The upper body of stomach had the worst visibility score for all groups. TMVS of groups B and C were significantly lower than those of group A. Group C had a significantly fewer patients requiring endoscopic flushing than groups A and B. The TMVS for groups B and C were significantly lower than for group A within 30 min of beginning premedication. Beyond 30 min of premedication, there was no significant difference in the TMVS among groups. CONCLUSIONS: Premedication using 100 mg simethicone in 100 mL of water improves endoscopic visibility. Addition of N-acetylcysteine to simethicone in 100 mL of water reduces the need for endoscopic flushing. For patients unable to tolerate a large fluid volume, a 5-mL simethicone suspension administered more than 30 min prior to upper endoscopy is suggested.

Hepatitis C virus infection in patients with primary biliary cirrhosis.

BACKGROUND AND AIM: The aim of this study is to evaluate the role of hepatitis C virus (HCV) infection in patients with primary biliary cirrhosis (PBC). MATERIAL AND METHODS: On the basis of a retrospective review of medical records, all patients consecutively diagnosed with PBC or HCV infection between 1999 and 2011 and who had a regular follow-up of at least 3 years were included in the study. Clinical characteristics, especially the severity of cirrhosis, were analyzed in PBC patients with HCV infection (PBC-HCV), PBC patients without HCV infection (PBC-only), and patients with only HCV infection (HCV-only). RESULTS: A total of 76 patients with PBC, including 9 patients with HCV infection, were analyzed. Of the PBC-HCV patients, 7 (7/9, 77.8%) were women with a mean age of 55.11 ± 14.29 years. Age- and sex-matched PBC-only patients (n = 36) and HCV-only patients (n = 36) were used as control groups. In comparison to the PBC-only controls, PBC-HCV patients had a greater severity of cirrhosis based on Child-Pugh (p = 0.019) and Model for End-Stage Liver Disease (MELD) (p = 0.01) scores. However, no significant difference in the severity of cirrhosis was found between the PBC-HCV and HCV-only control patients (p = 0.94 in Child-Pugh scores; p = 0.64 in MELD scores). CONCLUSIONS: In PBC patients with concomitant HCV infection, aggressive management may be warranted in view of the associated more severe liver cirrhosis.