Robotic alignment system Cirq (Brainlab) for navigated brain tumor biopsies in children.

INTRODUCTION: The Cirq robotic alignment system (Brainlab, Munich, Germany) is a manually adjustable electronic arm with a robotic alignment module on its distal end, enabling the neurosurgeon to automatically and accurately align surgical instruments to a preoperatively planned trajectory. In this study, we share our first experiences and results using Cirq for intracranial tumor biopsy in children. METHODS: From May 2021 until October 2022, all consecutive patients that underwent a brain tumor biopsy using Cirq were included and compared to a historical cohort of patients biopsied with the non-robotic system Varioguide (Brainlab, Munich, Germany). Patient-related data, tumor-related data, and surgery-related data were collected. Registration accuracy was calculated for different patient-to-image registration methods. Pre- and postoperative images were fused, and entry error, target error, and angulation error were calculated. RESULTS: Thirty-seven patients, aged 1-19 years, were included (14 with Cirq and 23 with Varioguide). An integrated histopathological and molecular diagnosis was acquired in all cases. Patient-to-image registration was significantly more accurate when based on bone screw fiducials combined with intraoperative CT, as compared to surface matching or skin fiducials. The target error (Euclidian distance) was 5.3 mm for Cirq as compared to 8.3 mm for Varioguide, but this was not statistically significant. Entry error and angulation error were also not significantly different between both groups. CONCLUSION: Intracranial biopsy with the Cirq robotic system is feasible and safe, and its accuracy does not differ from the Varioguide system.

Cost Analysis and Determinants of Living Donor Liver Transplantation in Taiwan.

BACKGROUND: Liver transplantation (LT) has become established therapy for end-stage liver disease and small-cell hepatocellular carcinoma (HCC), relying mainly on living donor LT (LDLT) in Taiwan. The cost of LDLT varies in different countries depending on the insurance system, the costs of the facility, and staff. In this study we aimed to investigate cost outcomes and determinants of LDLT in Taiwan. METHODS: From January 2014 to December 2015, 184 LDLT patients were enrolled in a study performed at the Kaohsiung Chang Gung Memorial Hospital. Patients' transplantation costs were defined as expense from immediately after surgery to discharge during hospitalization for LDLT. Antiviral therapy and hepatitis B immunoglobulin (HBIG) for prevention of hepatitis B virus (HBV) were included, but direct-acting antiviral (DAA) therapy for hepatitis C (HCV) was excluded. RESULTS: The median total, intensive care unit (ICU), and ward costs of LT were US$64,250, $43,357, and $16,138 (currency ratio 1:30), respectively. HBV significantly increased the total cost of LT, followed by postoperative reintubation and bile duct complications. CONCLUSION: The charges associated with anti-HBV viral therapy and HBIG increase the cost of LDLT. Disease severity of liver cirrhosis showed less importance in predicting cost. Postoperative complications such as reintubation or bile duct complications should be avoided to reduce the cost of LT.

Donor-Transmitted Bacterial Infection in Deceased Donor Liver Transplantation: Experience of Southern Taiwan Medical Center.

BACKGROUND: Bacterial Infection is the most important source of mortality and morbidity in liver transplantation recipients. Donor transmitted bacterial infection is rare but one of the most important infection sources. This kind of infection is difficult to identify, causing treatment dilemma. PATIENTS AND METHODS: In this article, we retrospectively reviewed our deceased donor liver transplants performed from January 2014 to December 2016. Forty-two recipients in Kaohsiung Chang Gung Memorial Hospital receiving liver grafts from 35 deceased liver donors were evaluated. The demography, donor transmitted infection, and outcomes were evaluated. RESULT: Two patients had probable donor transmitted bacterial infection and 1 patient died of suspected transmitted infection. CONCLUSION: Early identification of donor infection and adequate antibiotic treatment for the donor and recipient are the keys to preventing donor transmitted bacterial infection. Donor infection is not an absolute contraindication for organ donation in the area of organ shortage. Organ procurement organizations or similar authorities may establish the platform for sharing the data about donor and recipient infections.

Rising incidence of thyroid cancer in Singapore not solely due to micropapillary subtype.

Introduction The annual incidence of thyroid cancer is known to vary with geographic area, age and gender. The increasing incidence of thyroid cancer has been attributed to increase in detection of micropapillary subtype, among other factors. The aim of the study was to investigate time trends in the incidence of thyroid cancer in Singapore, an iodine-sufficient area. Materials and methods Data retrieved from the Singapore National Cancer Registry on all thyroid cancers that were diagnosed from 1974 to 2013 were reviewed. We studied the time trends of thyroid cancer based on gender, race, pathology and treatment modalities where available. Results The age-standardised incidence rate of thyroid cancer increased to 5.6/100,000 in 2013 from 2.5/100,000 in 1974. Thyroid cancer appeared to be more common in women, with a higher incidence in Chinese and Malays compared with Indians. Papillary carcinoma is the most common subtype. The percentage of papillary microcarcinoma has remained relatively stable at around 38% of all papillary cancers between 2007 and 2013. Although the incidence of thyroid cancer has increased since 1974, the mortality rate has remained stable. Conclusion This trend of increase in incidence of thyroid cancer in Singapore compares with other published series; however, the rise seen was not solely due to micropapillary type. Thyroid cancer was also more common in Chinese and Malays compared with Indians for reasons that needs to be studied further.

Fibrosis-4 index predicts cirrhosis risk and liver-related mortality in 2075 patients with chronic HBV infection.

BACKGROUND: Fibrosis-4 index (FIB-4) is a surrogate marker for hepatic fibrosis in hepatitis B virus (HBV) carriers. AIM: To investigate whether FIB-4 index stratifies the risks of adverse liver events. METHODS: A total of 2075 treatment-naïve, noncirrhotic the patients with chronic HBV infection were included. Most of them (82.1%) were HBeAg-negative patients and their baseline FIB-4 levels were explored to stratify the risks of cirrhosis, cirrhosis-related complications and liver-related mortality. RESULTS: During a mean follow-up period of 15.47 years, we found a higher baseline FIB-4 index was associated with increased incidence rates of cirrhosis in addition to the common host and viral factors. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with increased risks of cirrhosis, cirrhosis-related complications and liver-related mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76-8.05), 6.88, (3.68-12.86) and 7.79, (4.54-13.37) respectively. Within the first 3 years of follow-up, FIB-4 remained stable and its kinetics were consistently associated with the develoopment of adverse liver events. Furthermore, FIB-4 index of 1.29 was able to stratify all the risks of adverse liver events even in HBeAg-negative patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000 IU/mL and ALT <40 U/L). Only 1 patient with FIB-4 index <1.29 developed cirrhosis but not other events within 15 years of follow-up. CONCLUSIONS: In noncirrhotic patients with chronic HBV infection, a higher FIB-4 index was associated with increased risks of adverse liver events. FIB-4 index <1.29 is useful for the prediction of the lowest risks of disease progression.

Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

OBJECTIVE: To compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an "early approach" (EA), based on ventricular measurements exceeding normal (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a "late approach" (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention. METHODS: Observational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was assessed at 18-24 months. RESULTS: Forty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>-1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without (p < 0.003), with scores <-2 SD in 81%. CONCLUSION: In preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA.

Alpha galactosidase A activity in Parkinson's disease.

Glucocerebrosidase (GCase, deficient in Gaucher disease) enzymatic activity measured in dried blood spots of Parkinson's Disease (PD) cases is within healthy range but reduced compared to controls. It is not known whether activities of additional lysosomal enzymes are reduced in dried blood spots in PD. To test whether reduction in lysosomal enzymatic activity in PD is specific to GCase, we measured GCase, acid sphingomyelinase (deficient in Niemann-Pick disease types A and B), alpha galactosidase A (deficient in Fabry), acid alpha-glucosidase (deficient in Pompe) and galactosylceramidase (deficient in Krabbe) enzymatic activities in dried blood spots of PD patients (n = 648) and controls (n = 317) recruited from Columbia University. Full sequencing of glucocerebrosidase (GBA) and the LRRK2 G2019S mutation was performed. Enzymatic activities were compared between PD cases and controls using t-test and regression models adjusted for age, gender, and GBA and LRRK2 G2019S mutation status. Alpha galactosidase A activity was lower in PD cases compared to controls both when only non-carriers were included (excluding all GBA and LRRK2 G2019S carriers and PD cases with age-at-onset below 40) [2.85 µmol/l/h versus 3.12 µmol/l/h, p = 0.018; after controlling for batch effect, p = 0.006 (468 PD cases and 296 controls)], and when including the entire cohort (2.89 µmol/l/h versus 3.10 µmol/l/h, p = 0.040; after controlling for batch effect, p = 0.011). Because the alpha galactosidase A gene is X-linked, we stratified the analyses by sex. Among women who were non-carriers of GBA and LRRK2 G2019S mutations (PD, n = 155; control, n = 194), alpha galactosidase A activity was lower in PD compared to controls (2.77 µmol/l/h versus 3.10 µmol/l/h, p = 0.044; after controlling for a batch effect, p = 0.001). The enzymatic activity of acid sphingomyelinase, acid alpha-glucosidase and galactosylceramidase was not significantly different between PD and controls. In non-carriers, most lysosomal enzyme activities were correlated, with the strongest association in GCase, acid alpha-glucosidase, and alpha galactosidase A (Pearson correlation coefficient between 0.382 and 0.532). In a regression model with all five enzymes among non-carriers (adjusted for sex and age), higher alpha galactosidase A activity was associated with lower odds of PD status (OR = 0.54; 95% CI:0.31-0.95; p = 0.032). When LRRK2 G2019S PD carriers (n = 37) were compared to non-carriers with PD, carriers had higher GCase, acid sphingomyelinase and alpha galactosidase A activity. We conclude that alpha galactosidase A may have a potential independent role in PD, in addition to GCase.

Thulium laser-assisted endoscopic third ventriculostomy: Determining safe laser settings using in vitro model and 2 year follow-up results in 106 patients.

BACKGROUND AND OBJECTIVE: Endoscopic third ventriculostomy is used to treat hydrocephalus. Different laser wavelengths have been proposed for laser-assisted endoscopic third ventriculostomies over the last decades. The aim of this study was to evaluate Thulium laser endoscopic third ventriculostomy heat penetration in the surrounding environment of the floor of the third ventricle in an in vitro setting with visualization of thermal distribution. Subsequently 106 Thulium laser endoscopic third ventriculostomy procedures were retrospectively analyzed to demonstrate safety. METHODS: The in vitro visualization was based on the color Schlieren method. The heat penetration was measured beneath a tissue phantom of the floor of the third ventricle with a fiber of 365 µm in diameter at different energy settings; 1.0W (956 J/cm2 ), 2.0W (1,912 J/cm2 ), 4.0W (3,824 J/cm2 ), and 7.0W (6,692 J/cm2 ), with a pulse duration of 1.0 second. All experiments were repeated five times. In addition, 106 Thulium laser endoscopic third ventriculostomy procedures between 2005 and 2015 were retrospectively analysed for etiology, sex, complications, and laser parameters. RESULTS: In the energy settings from 1.0 to 4.0 W, heat penetration depth beneath the phantom of the third ventricle did not exceed 1.5 mm. The heat penetration depth at 7 W, exceeded 6 mm. The clinical overall success rate was 80% at the 2-year follow-up study. Complications occurred in 5% of the procedures. In none of the 106 investigated clinical patients bleeding or damage to the basilar artery was encountered due to Thulium laser ablation. CONCLUSIONS: The in vitro experiments show that under 4.0W the situation is considered safe, due to low penetration of heat, thus the chance of accidentally damaging critical structures like the basilar artery is very small. The clinical results show that the Thulium laser did not cause any bleeding of the basilar artery, and is a safe technique for laser endoscopic third ventriculostomy. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc.

Laparoscopic Repair of Incisional Hernia Following Liver Transplantation-Early Experience of a Single Institution in Taiwan.

BACKGROUND: Ventral incisional hernia (VIH) is not uncommon following liver transplantation. Open repair was traditionally adopted for its management. Laparoscopic repair of VIH has been performed successfully in nontransplant patients with evidence of reduced recurrence rates and hospital stay. However, the application of VIH in post-transplantation patients has not been well established. Herein, we provide our initial experience with laparoscopic repair of post-transplantation VIH. METHODS: From March 2015 to March 2016, 18 cases of post-transplantation VIH were subjected to laparoscopic repair (laparoscopy group). A historical control group of 17 patients who underwent conventional open repair (open group) from January 2013 to January 2015 were identified for comparison. The demographics and clinical outcomes were retrospectively compared. RESULTS: There were no significant differences among basic demographics between the 2 groups. No conversion was recorded in the laparoscopy group. Recurrence of VIH up to the end of the study period was not noted. In the laparoscopy group, the minor complications were lower (16.7% vs 52.9%; P = .035), the length of hospital stay was shorter (3 d vs 7 d, P = .007), but the median operative time was longer (137.5 min vs 106 min; P = .003). CONCLUSIONS: Laparoscopic repair of post-transplantation VIH is a safe and feasible procedure with shorter length of hospital stay.

An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry.

Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r2>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10-8. The most significantly associated SNP, rs11720469 (ß: -0.124; P<4.5 × 10-9), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.

The diagnostic utility of preoperative breast magnetic resonance imaging (MRI) and/or intraoperative sub-nipple biopsy in nipple-sparing mastectomy.

BACKGROUND: The necessity of routine sub-nipple biopsy was uncertain, and the role of preoperative magnetic resonance imaging (MRI) in detecting nipple invasion in patients who have been selected for nipple sparing mastectomy (NSM) has not been adequately evaluated. METHODS: We retrospectively collected and analyzed the medical and surgical records of 434 patients with primary operable breast cancer who met the criteria for NSM and underwent breast surgery during the period January 2011 to December 2015. Patients were stratified into three risk groups (low, intermediate, and high) according to tumor size and tumor-to-nipple distance. RESULTS: Among the 434 patients in this study, 29 (6.7%) had occult invasion of the nipple-areola complex (NAC). Sub-nipple biopsy had a sensitivity of 84.6%, a specificity of 100%, a false negative rate of 1.2%, a false positive rate of 0%, and an overall accuracy rate of 98.8% in confirming NAC invasion. The NAC invasion rate was 0% in the low-risk group, 5.1% in the intermediate-risk group, and 19.7% in the high-risk group (P < 0.01). The overall NPV of preoperative MRI for predicting NAC invasion was 94.8%. Cost analysis revealed that the cost of NSM with sub-nipple biopsy was significantly higher than that of NSM alone, with a mean difference in cost of USD 238.5 (P < 0.01). CONCLUSION: The high negative predictive value of MRI for NAC invasion is useful for selection of patients receiving NSM. Sub-nipple biopsy is a reliable procedure to detect occult NAC invasion, however, routine use is not cost-effect for low risk patients.

Effects of Posthemorrhagic Ventricular Dilatation in the Preterm Infant on Brain Volumes and White Matter Diffusion Variables at Term-Equivalent Age.

OBJECTIVE: To evaluate the differential impact of germinal matrix-intraventricular hemorrhage (GMH-IVH) and posthemorrhagic ventricular dilatation (PHVD) on brain and cerebrospinal fluid (CSF) volumes and diffusion variables in preterm born infants at term-equivalent age (TEA). STUDY DESIGN: Nineteen infants (gestational age <31 weeks) with GMH-IVH grade II-III according to Papile et al and subsequent PHVD requiring intervention were matched against 19 controls with GMH-IVH grade II but no PHVD and 19 controls without GMH-IVH. Outcome variables on magnetic resonance imaging (MRI) including diffusion weighted imaging at TEA were volumes of white matter, cortical gray matter, deep gray matter, brainstem, cerebellum, ventricles, extracerebral CSF, total brain tissue, and intracranial volume (ICV), as well as white matter and cerebellar apparent diffusion coefficients (ADCs). Effects of GMH-IVH and PHVD on TEA-MRI measurements were evaluated using multivariable regression analysis. Brain and CSF volumes were adjusted for ICV to account for differences in bodyweight at TEA-MRI and ICV between cases and controls. RESULTS: PHVD was independently associated with volumes of deep gray matter (ß [95% CI]: -1.4 cc [-2.3; -.5]), cerebellum (-2.7 cc [-3.8; -1.6]), ventricles (+12.7 cc [7.9; 17.4]), and extracerebral CSF (-11.2 cc [-19.2; -3.3]), and with ADC values in occipital, parieto-occipital, and parietal white matter (ß: +.066-.119×10(-3) mm(2)/s) on TEA-MRI (P < .05). No associations were found between GMH-IVH grade II-III and brain and CSF volumes or ADC values at TEA. CONCLUSIONS: PHVD was negatively related to deep gray matter and cerebellar volumes and positively to white matter ADC values on TEA-MRI, despite early intervention for PHVD in the majority of the infants. These relationships were not observed for GMH-IVH.

Risk factors and outcome for colistin-resistant Acinetobacter nosocomialis bacteraemia in patients without previous colistin exposure.

The clinical characteristics of patients with colistin-resistant Acinetobacter baumannii bacteraemia have been documented, but those of patients with bacteraemia caused by other Acinetobacter species remain unknown. Previous exposure to colistin has been shown to be associated with the emergence of colistin resistance, but may be not the only predisposing factor. In the current study, we highlight the risk and outcome of patients without previous exposure to colistin who acquired colistin-resistant Acinetobacter nosocomialis (ColRAN) bacteraemia. This 11-year single-centre retrospective study analysed 58 patients with ColRAN bacteraemia and 213 patients with colistin-susceptible A. nosocomialis (ColSAN) bacteraemia. Antimicrobial susceptibilities were determined with an agar dilution method. The clonal relationship of ColRAN isolates was determined with pulsed-field gel electrophoresis. A conjugation mating-out assay was conducted to delineate the potential transfer of colistin resistance genes. Multivariable analysis was performed to evaluate the risk factors for ColRAN bacteraemia. Chronic obstructive pulmonary disease (COPD) was independently associated with ColRAN bacteraemia (OR 3.04; 95% CI 1.45-6.37; p 0.003). Patients with ColRAN bacteraemia had higher APACHE II scores, but the two groups showed no significant differences in 14-day mortality (10.3% vs. 10.3%) or 28-day mortality (15.5% vs. 15.0%). ColRAN isolates had greater resistance than ColSAN isolates to all antimicrobial agents except for ciprofloxacin (0% vs. 6.6%). There were 16 different ColRAN pulsotypes, and two major clones were found. Colistin resistance did not transfer to colistin-susceptible A. baumannii or A. nosocomialis. These results show that COPD is an independent risk factor for acquisition of ColRAN bacteraemia. The mortality rates were similar between patients with ColRAN and ColSAN bacteraemia.

Higher lifetime chance of spontaneous surface antigen loss in hepatitis B carriers with genotype C infection.

BACKGROUND: Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. METHODS: We explored the association between viral genomic factors and HBsAg loss in 2121HBeAg-negative patients. HBV pre-core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/mL (N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers. RESULTS: The cumulative lifetime (age 28-75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg-negative patients. We found that genotype C, but not pre-core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4-2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re-included HBeAg-positive, cirrhotic and treatment-experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers. CONCLUSION: Genotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers.

Cataract surgery is associated with a reduced risk of dementia: a nationwide population-based cohort study.

BACKGROUND AND PURPOSE: Our purpose was to determine the association of cataract surgery with subsequent development of dementia in older adults with newly diagnosed cataract. METHODS: By using data from Taiwan National Health Insurance Research Database (NHIRD), a population-based cohort study including 491 226 subjects aged 70 or older with first-time diagnosis of cataract coded from 2000 to 2009 was conducted. After matching cataract patients receiving cataract surgery with cataract patients without receiving cataract surgery for age, sex, index date, Charlson Comorbidity Index score, interval between first coding of cataract diagnosis and index date, hypertension and diabetes mellitus, 113 123 patients in each cohort were enrolled. The main outcome measure was newly diagnosed dementia coded by neurologists or psychiatrists more than 365 days after cataract surgery. Incidence rate and hazard ratio of dementia were compared between the cataract surgery and cataract diagnosis cohorts. RESULTS: The incidence rate of dementia was 22.40 per 1000 person-years in the cataract surgery cohort and 28.87 per 1000 person-years in the cataract diagnosis cohort. The rate of dementia was significantly lower in the cataract surgery group (hazard ratio 0.77, 95% confidence interval 0.75-0.79, P < 0.001). Female gender (P < 0.001) and a shorter interval between the date of first coding of a cataract diagnosis and the date of cataract surgery (P = 0.009) were significantly associated with a lower incidence rate of dementia. CONCLUSION: In an NHIRD cohort of Taiwanese aged 70 years and older with a diagnosis of cataract, patients undergoing cataract surgery were associated with a reduced risk of subsequent dementia compared with those without cataract surgery.

Biochemical indicators of implantation success of tissue-engineered oral mucosa.

Real-time (RT) determination of the health of in vitro tissue-engineered constructs prior to grafting is essential for prediction of success of the implanted tissue-engineered graft. In addition, the US Food and Drug Administration requires specific release criteria in RT prior to the release of tissue-engineered devices for human use. In principle, assessing the viability and functionality of the cellular component can be achieved by quantifying the secretion of growth factors and chemokines of tissue-engineered constructs. Ex vivo-produced oral mucosa equivalents (EVPOMEs) were fabricated under thermally stressed conditions at 43 °C for 24 h to create a functionally compromised EVPOME. We used microchannel enzyme-linked immunosorbent assay to evaluate the functionality of the cellular component, oral keratinocytes, of stressed and unstressed EVPOMEs by measuring the release of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), human ß-defensin 1 (hBD-1), and tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) into the spent medium, which was collected on the same day prior to graft implantation into severe combined immunodeficiency mice. Implanted EVPOMEs' histology on the seventh postimplantation day was used to correlate outcomes of grafting to secreted amounts of IL-8, hBD-1, VEGF, TIMP-1, and TIMP-2 from corresponding EVPOMEs. Our findings showed that significantly higher levels of IL-8, hBD-1, and TIMP-2 were secreted from controls than from thermally stressed EVPOMEs. We also found a direct correlation between secreted VEGF and IL-8 and blood vessel counts of implanted EVPOMEs. We concluded that measuring the constitutive release of these factors can be used as noninvasive predictors of healthy tissue-engineered EVPOMEs in RT, prior to their implantation.

Clinical evaluation of eye movements in spinocerebellar ataxias: a prospective multicenter study.

BACKGROUND: Ocular motor abnormalities reflect the varied neuropathology of spinocerebellar ataxias (SCAs) and may serve to clinically distinguish the different SCAs. We analyzed the various eye movement abnormalities detected prospectively at the baseline visit during a large multicenter natural history study of SCAs 1, 2, 3, and 6. METHODS: The data were prospectively collected from 12 centers in the United States in patients with SCAs 1, 2, 3, and 6, as part of the Clinical Research Consortium for Spinocerebellar Ataxias (NIH-CRC-SCA). Patient characteristics, ataxia rating scales, the Unified Huntington Disease Rating Scale functional examination, and clinical staging were used. Eye movement abnormalities including nystagmus, disorders of saccades and pursuit, and ophthalmoparesis were recorded, and factors influencing their occurrence were examined. RESULTS: A total of 301 patients participated in this study, including 52 patients with SCA 1, 64 with SCA 2, 117 with SCA 3, and 68 with SCA 6. Although no specific ocular motor abnormality was pathognomonic to any SCA, significant differences were noted in their occurrence among different disorders. SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades. SCA 1 and SCA 3 subjects had a more even distribution of eye movement abnormalities. CONCLUSIONS: Prospective data from a large cohort of patients with SCAs 1, 2, 3, and 6 provide statistical validation that the SCAs exhibit distinct eye movement abnormalities that are useful in identifying the genotypes. Many of the abnormalities correlate with greater disease severity measures.

Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma.

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r(2)=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4(+) T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.