Optic nerve sheath diameter correlates with both success and failure of hydrocephalus treatment in pediatric patients with pineal region lesions.

BACKGROUND: Pineal region lesions in children are heterogenous pathologies often symptomatic due to occlusive hydrocephalus and thus elevated intracranial pressure (ICP). MRI-derived parameters to assess hydrocephalus are the optic nerve sheath diameter (ONSD) as a surrogate for ICP and the frontal occipital horn ratio (FOHR), representing ventricle volume. As elevated ICP may not always be associated with clinical signs, the adjunct of ONSD could help decision making in patients undergoing treatment. The goal of this study is to assess the available magnetic resonance imaging (MRI) of patients with pineal region lesions undergoing surgical treatment with respect to pre- and postoperative ONSD and FOHR as an indicator for hydrocephalus. METHODS: Retrospective data analysis was performed in all patients operated for pineal region lesions at a tertiary care center between 2010 and 2023. Only patients with pre- and postoperative MRI were selected for inclusion. Clinical data and ONSD at multiple time points, as well as FOHR were analyzed. Imaging parameter changes were correlated with clinical signs of hydrocephalus before and after surgical treatment. RESULTS: Thirty-three patients with forty operative cases met the inclusion criteria. Age at diagnosis was 10.9 ± 4.6 years (1-17 years). Hydrocephalus was seen in 80% of operative cases preoperatively (n = 32/40). Presence of hydrocephalus was associated with significantly elevated preoperative ONSD (p = 0.006). There was a significant decrease in ONSD immediately (p < 0.001) and at 3 months (p < 0.001) postoperatively. FOHR showed a slightly less pronounced decrease (immediately p = 0.006, 3 months p = 0.003). In patients without hydrocephalus, no significant changes in ONSD were observed (p = 0.369). In 6/6 patients with clinical hydrocephalus treatment failure, ONSD increased, but in 3/6 ONSD was the only discernible MRI change with unchanged FOHR. CONCLUSIONS: ONSD measurements may have utility in evaluating intracranial hypertension due to hydrocephalus in patients with pineal region tumors. ONSD changes appear to have value in assessing hydrocephalus treatment failure.

An Analysis of Multigenerational Issues of Generation X and Y Employees in Small- and Medium-Sized Enterprises in Thailand: The Moderation Effect of Age Groups on Person-Environment Fit and Turnover Intention.

Multigenerational employees can evidently impact human resource management practices in terms of effective employee retention. Arguably, a high turnover intention of young employees can hinder a company's human resource development, while a high volume of retirement of senior employees can create a skill deficit and even a labor management dilemma. This study explored how a supportive work environment can retain employees of different age groups in Thailand's small- and medium-sized enterprises (SMEs), particularly Generation X and Y. It modeled a supportive work environment that impacts the behaviors of Generation X and Y employees, taking into consideration the relationship among factors such as person-job fit, person-group fit, person-supervisor fit, person-organization fit, person-environment fit, and turnover intention. This paper statistically analyzed a set of data drawn from an attentive survey of a total of 400 employees of SMEs in 4 populous provinces in Thailand using structural equation modeling (SEM) and multigroup analysis (MGA) with the moderation effect of generations. This paper then found that person-job fit, person-group fit, person-supervisor fit, person-organization fit, person-environment fit, and turnover intention can influence an employee's intention to remain in his/her job. Additionally, the relationship manipulation among the aforementioned variables might influence Generation X and Y employees differently. Under the circumstances, supervisory support with less group involvement may encourage the retention of Generation Y employees, whereas a sufficient focus on job suitability could improve the retention of Generation X employees.

Long term antibody response to SARS-CoV-2 in children

Almost two years into the pandemic and with vaccination of children significantly lagging behind adults, long-term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2. We screened 6113 children <18 years by nasopharyngeal swab-PCR in a low-incidence setting after general lockdown, from May 11 to June 30, 2020. 4657 participants underwent antibody testing. Positive tests were followed up by repeated PCR and serological testing of all household contacts over 6 months. In total, the study identified 67 seropositive children (1.44 %), the median time after infection at first presentation was 83 days post-symptom onset (PSO). Follow up of household contacts showed incomplete seroconversion in most families, with higher seroconversion rates in families with adult index cases compared to pediatric index cases (OR: 1.79, P=0.047). Most importantly, children showed sustained seroconversion up to nine months PSO, and serum antibody concentrations persistently surpassed adult levels (ratio serum IgG Spike children vs. adults 90 days PSO: 1.75, P<0.001, 180 days: 1.38, P=0.01, 270 days: 1.54, P=0.001). In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroconversion rates in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.

Evaluation of the CD4+ T cell response to SARS-CoV-2 infection and cross reactivity to beta variant in children of all ages

SARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group. Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response. The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN-{gamma} and Granzyme B secretion. An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.

A review of Alström syndrome: a rare monogenic ciliopathy.

Alström syndrome is a rare monogenic ciliopathy caused by a mutation to the Alström syndrome 1 (ALMS1) gene. Alström syndrome has an autosomal recessive nature of inheritance. Approximately 1,200 cases of Alström syndrome have been identified worldwide. Complications of the disease are likely caused by dysfunctional cilia with complications arising early in life. The known complications of Alström syndrome have been reported to impact multiple major organ systems, including the endocrine system, cardiac system, renal system, sensory system, and hepatic system. The symptoms of Alström syndrome have great variability in presentation and intensity but often lead to organ damage. This has resulted in a shortened lifespan for individuals affected by Alström syndrome. Individuals with the disease rare exceed the age of 50. Currently, there are no specific treatments for Alström syndrome that can cure the disease, prevent the complications, or reverse the complications. Current management involves management of symptoms with the goal of improving quality of life and lifespan. This review aims to summarize the current knowledge on the epidemiology, diagnosis, pathophysiology, complications, management, and prognosis of Alström syndrome. In addition to that, this review also aims to raise awareness and encourage research on Alström syndrome as the condition has a huge impact on affected individuals.

Financial Risk Protection for Neurosurgical Care in Indonesia and the Philippines: A Primer on Health Financing for the Global Neurosurgeon.

Which conditions treated by neurosurgeons cause the worst economic hardship in low middle-income in countries? How can public health financing be responsive to the inequities in the delivery of neurosurgical care? This review article frames the objectives of equity, quality, and efficiency in health financing to the goals of global neurosurgery. In order to glean provider perspectives on the affordability of neurosurgical care in low-resource settings, we did a survey of neurosurgeons from Indonesia and the Philippines and identified that the care of socioeconomically disadvantaged patients with malignant intracranial tumors were found to incur the highest out-of-pocket expenses. Additionally, the surveyed neurosurgeons also observed that treatment of traumatic brain injury may have to require greater financial subsidies. It is therefore imperative to frame health financing alongside the goals of equity, efficiency, and quality of neurosurgical care for the impoverished. Using principles and perspectives from managerial economics and public health, we conceptualize an implementation framework that addresses both the supply and demand sides of healthcare provision as applied to neurosurgery. For the supply side, strategic purchasing enables a systematic and contractual management of payment arrangements that provide performance-based economic incentives for providers. For the demand side, conditional cash transfers similarly leverages on financial incentives on the part of patients to reward certain health-seeking behaviors that significantly influence clinical outcomes. These health financing strategies are formulated in order to ultimately build neurosurgical capacity in LMICs, improve access to care for patients, and ensure financial risk protection.

Global Surgery Indicators and Pediatric Hydrocephalus: A Multicenter Cross-Country Comparative Study Building the Case for Health System Strengthening.

Objective: The aim of this study is to compare specific three-institution, cross-country data that are relevant to the Global Surgery indicators and the functioning of health systems. Methods: We retrospectively reviewed the clinical and socioeconomic characteristics of pediatric patients who underwent cerebrospinal fluid (CSF) diversion surgery for hydrocephalus in three different centers: the University of Tsukuba Hospital in Ibaraki, Japan (HIC), the Jose R. Reyes Memorial Medical Center in Manila, Philippines [low-to-middle-income country (LMIC)], and the Federal Neurosurgical Center in Novosibirsk, Russia (UMIC). The outcomes of interest were the timing of CSF diversion surgery and mortality. Statistical tests included descriptive statistics, Cox proportional hazards model, and logistic regression. Nation-level data were also obtained to provide the relevant socioeconomic contexts in discussing the results. Results: In total, 159 children were included, where 13 are from Japan, 99 are from the Philippines, and 47 are from the Russian Federation. The median time to surgery at the specific neurosurgical centers was 6 days in the Philippines and 1 day in both Japan and Russia. For the cohort from the Philippines, non-poor patients were more likely to receive CSF diversion surgery at an earlier time (HR = 4.74, 95% CI 2.34-9.61, p <0.001). In the same center, those with infantile or posthemorrhagic hydrocephalus (HR = 3.72, 95% CI 1.70-8.15, p = 0.001) were more likely to receive CSF diversion earlier compared to those with congenital hydrocephalus, and those with postinfectious (HR = 0.39, 95% CI 0.22-0.70, p = 0.002) or myelomeningocele-associated hydrocephalus (HR = 0.46, 95% CI 0.22-0.95, p = 0.037) were less likely to undergo surgery at an earlier time. For Russia, older patients were more likely to receive or require early CSF diversion (HR = 1.07, 95% CI 1.01-1.14, p = 0.035). External ventricular drain (EVD) insertion was found to be associated with mortality (cOR 14.45, 95% CI 1.28-162.97, p = 0.031). Conclusion: In this study, Filipino children underwent late time-interval of CSF diversion surgery and had mortality differences compared to their Japanese and Russian counterparts. These disparities may reflect on the functioning of the health systems of respective countries.

Increases in Naloxone Administrations by Emergency Medical Services Providers During the COVID-19 Pandemic: Retrospective Time Series Study.

BACKGROUND: The opioid crisis in the United States may be exacerbated by the COVID-19 pandemic. Increases in opioid use, emergency medical services (EMS) runs for opioid-related overdoses, and opioid overdose deaths have been reported. No study has examined changes in multiple naloxone administrations, an indicator of overdose severity, during the COVID-19 pandemic. OBJECTIVE: This study examines changes in the occurrence of naloxone administrations and multiple naloxone administrations during EMS runs for opioid-related overdoses during the COVID-19 pandemic in Guilford County, North Carolina (NC). METHODS: Using a period-over-period approach, we compared the occurrence of opioid-related EMS runs, naloxone administrations, and multiple naloxone administrations during the 29-week period before (September 1, 2019, to March 9, 2020) and after NC's COVID-19 state of emergency declaration (ie, the COVID-19 period of March 10 to September 30, 2020). Furthermore, historical data were used to generate a quasi-control distribution of period-over-period changes to compare the occurrence of each outcome during the COVID-19 period to each 29-week period back to January 1, 2014. RESULTS: All outcomes increased during the COVID-19 period. Compared to the previous 29 weeks, the COVID-19 period experienced increases in the weekly mean number of opioid-related EMS runs (25.6, SD 5.6 vs 18.6, SD 6.6; P<.001), naloxone administrations (22.3, SD 6.2 vs 14.1, SD 6.0; P<.001), and multiple naloxone administrations (5.0, SD 1.9 vs 2.7, SD 1.9; P<.001), corresponding to proportional increases of 37.4%, 57.8%, and 84.8%, respectively. Additionally, the increases during the COVID-19 period were greater than 91% of all historical 29-week periods analyzed. CONCLUSIONS: The occurrence of EMS runs for opioid-related overdoses, naloxone administrations, and multiple naloxone administrations during EMS runs increased during the COVID-19 pandemic in Guilford County, NC. For a host of reasons that need to be explored, the COVID-19 pandemic appears to have exacerbated the opioid crisis.

Timely and conservative anticoagulation in Septic Cavernous Sinus Thrombosis: A case report

Background@#Cavernous Sinus Thrombosis (CST) is a rare and life-threatening condition with antibiotics as the mainstay of therapy for those due to infection. While controversy exists, recent retrospective reviews using anticoagulation reveal potential mortality reduction with a low risk of adverse events such as intracranial hemorrhage (ICH). The optimal timing and duration of treatment are unknown.@*The Case@#We report a 32-year-old female who presented with fever, headache, complete bilateral ophthalmoplegia, cellulitis, and a cranial MRV diagnostic of CST. She received antibiotics targeted to MRSA organisms isolated from eye and blood specimen. Further, into the course, the patient had an onset of aphasia and right-sided hemiplegia. Workup revealed multiple cranial infarcts with narrowing of the left internal carotid artery, likely representing thrombus as the source of embolism. The decision to anticoagulate was reevaluated and subsequently started. The patient was reassessed clinically after two months to have improved motor strength and speech return; thus, anticoagulation was discontinued.@*Discussion@#Although data are lacking, most recent reports favor the use of anticoagulation. Some authors recommend initiation in patients with deteriorating neurologic status despite antibiotics and hydration. The higher frequency of ICH in anticoagulated CST patients with CNS infection is a basis for some authors to withhold treatment. The treatment duration varies with different studies, generally ranging from several weeks to three months or more.@*Conclusion@#Further studies are needed to define the exact role of anticoagulation, particularly its timing and duration. Nevertheless, timely identification of the condition and constant re-evaluation are critical to early patient recovery.

Recapitulating the Bayesian framework for neurosurgical outpatient care and a cost-benefit analysis of telemedicine for socioeconomically disadvantaged patients in the Philippines during the pandemic.

OBJECTIVE: In the Philippines during recent months, a neurosurgical center that caters primarily to socioeconomically disadvantaged patients has encountered unprecedented changes in practice patterns brought about by the COVID-19 pandemic. In particular, the usual task of outpatient care has shifted to the telemedicine format, bringing along all of its attendant advantages and gargantuan challenges. The authors sought to determine the responsiveness of this telemedicine setup to the needs of their disadvantaged patients and explored the application of Bayesian inference to enhance the use of teleconsultation in daily clinical decision-making. METHODS: The authors used the following methods to assess the telemedicine setup used in a low-resource setting during the pandemic: 1) a cross-sectional survey of patients who participated in a medical consultation via telemedicine during the 16-week period from March 16, 2020, to July 15, 2020; 2) a cost-benefit analysis of the use of telemedicine by patients; and 3) a case illustration of a Bayesian approach application unique to the teleconsultation scenario. RESULTS: Of the 272 patient beneficiaries of telemedicine in a 16-week period, 57 responded to the survey. The survey responses regarding neurosurgical outpatient care through telemedicine yielded high ratings of utility for the patients and their caregivers. According to 64% of respondents, the affordability of the telemedicine setup also prevented them from borrowing money from others, among other adverse life events prevented. There were realized financial gains on the part of the patients in terms of cost savings and protection from further impoverishment. The benefit-cost ratio was 3.51 for the patients, signifying that the benefits outweighed the costs. An actual teleconsultation case vignette was reported that is meant to be instructive and contributory to the preparedness of the neurosurgeon on the provider end of the service delivery. CONCLUSIONS: Telemedicine holds promise as a viable and safe method for health service delivery during the pandemic. In the setting of a health system that is continually challenged by shortages of resources, this study shows that an effective telemedicine setup can come with high benefit-cost ratios and quality of care, along with the assurance of patient satisfaction. The potential for high-quality care can be enhanced by the inclusion of the Bayesian framework to the basic toolkit of remote clinical assessment. When confronted with choices in terms of differential diagnosis and tests, the rigor of a simple application of the Bayesian framework can minimize costs arising from uncertainties.

The state of neurosurgical training and education in East Asia: analysis and strategy development for this frontier of the world.

OBJECTIVE: The authors, who are from Indonesia, Japan, Malaysia, the Philippines, and Taiwan, sought to illustrate the processes of training neurosurgeons in their respective settings by presenting data and analyses of the current state of neurosurgical education across the East Asian region. METHODS: The authors obtained quantitative data as key indicators of the neurosurgical workforce from each country. Qualitative data analysis was also done to provide a description of the current state of neurosurgical training and education in the region. A strengths, weaknesses, opportunities, and threats (SWOT) analysis was also done to identify strategies for improvement. RESULTS: The number of neurosurgeons in each country is as follows: 370 in Indonesia, 10,014 in Japan, 152 in Malaysia, 134 in the Philippines, and 639 in Taiwan. With a large neurosurgical workforce, the high-income countries Japan and Taiwan have relatively high neurosurgeon to population ratios of 1 per 13,000 and 1 per 37,000, respectively. In contrast, the low- to middle-income countries Indonesia, Malaysia, and the Philippines have low neurosurgeon to population ratios of 1 per 731,000, 1 per 210,000, and 1 per 807,000, respectively. In terms of the number of training centers, Japan has 857, Taiwan 30, Indonesia 7, Malaysia 5, and the Philippines 10. In terms of the number of neurosurgical residents, Japan has 1000, Taiwan 170, Indonesia 199, Malaysia 53, and the Philippines 51. The average number of yearly additions to the neurosurgical workforce is as follows: Japan 180, Taiwan 27, Indonesia 10, Malaysia 4, and the Philippines 3. The different countries included in this report have many similarities and differences in their models and systems of neurosurgical education. Certain important strategies have been formulated in order for the system to be responsive to the needs of the catchment population: 1) establishment of a robust network of international collaboration for reciprocal certification, skills sharing, and subspecialty training; 2) incorporation of in-service residency and fellowship training within the framework of improving access to neurosurgical care; and 3) strengthening health systems, increasing funding, and developing related policies for infrastructure development. CONCLUSIONS: The varied situations of neurosurgical education in the East Asian region require strategies that take into account the different contexts in which programs are structured. Improving the education of current and future neurosurgeons becomes an important consideration in addressing the health inequalities in terms of access and quality of care afflicting the growing population in this region of the world.

Technique of external ventricular drainage with intraventricular administration of recombinant tissue plasminogen activator for patients with secondary intraventricular hemorrhage - Case series in a single institution

INTRODUCTION@#Intraventricular hemorrhage (IVH) as an extension of spontaneous intracerebral hemorrhage is an independent predictor of mortality. The Clot Lysis: Evaluating Accelerated Resolution of IVH phase 3 (CLEAR III) trial is a randomized, double-blinded, placebocontrolled, multiregional trial recently conducted to determine whether external ventricular drainage (EVD) plus intraventricular recombinant tissue plasminogen activator (rtPA, alteplase) improved outcome, in comparison to EVD plus saline. This study is an application of the rationale and principles of management in CLEAR III trial and related literature.@*METHODS@#There are five patients described in this case series. Report followed the PROCESS guidelines.@*RESULTS@#30-day mortality in this series is 2 out of 5 while actual allcause mortality is 4 out of 5. Modified Graeb scores and IVH scores of all subjects have decreased after the intervention. However, good functional status defined as modified Rankin scale (mRS) score of 0-3 has not been achieved with the intervention. Efficacy of completely resolving IVH and hydrocephalus has been achieved in 2 out of 5 which translated to a benefit of survival to one of the two. Shunt dependence has been avoided by the subjects except for the one with the caudate intracerebral hemorrhage. Complications related to the intervention have been noted and discussed@*CONCLUSION@#In this single-institution study, patients for which rtPA was used for intraventricular fibrinolysis of IVH clot in addition to EVD as surgical treatment for hydrocephalus resulted to a 30-day survival of 3 out of 5 in this series, while actual survival is 1 out of 5. The intervention was efficacious in decreasing the Modified Graeb scores and IVH scores of all study subjects at end of treatment. Functional status of mRS 5 is the highest score achieved among survivors.

Análisis biomecánico en la marcha deportiva entre deportistas de iniciación y alto rendimiento / Biomechanical analysis in sports walk among beginners and high performance athletes

Introducción: La relación causa / efecto entre el embarazo y la enfermedad periodontal resulta muy contradictorio en la literatura. Algunos autores niegan que exista esta relación, mientras otros la afirman. Objetivo: Identificar la presencia de Enfermedad Periodontal en gestantes del primer y tercer trimestre, teniendo en cuenta la edad y la higiene bucal de las mismas. Métodos: La muestra estuvo integrada por 106 gestantes del primer y tercer trimestre del embarazo. Las mismas fueron reunidas de acuerdo a los siguientes grupos de edades: Adolescentes, adultas jóvenes y adultas de más de 35 años. A todas las gestantes de la muestra se les efectuó un examen estomatológico para diagnosticar las pacientes portadoras de Enfermedad Periodontal, las formas clínicas presentadas, así como evaluar la calidad de la higiene bucal. Resultados: Se comprobó que 36 de las gestantes eran portadoras de Enfermedad Periodontal: 34 presentaban gingivitis y dos periodontitis. La forma clínica más abundante fue la gingivitis fibro-edematosa. De las 36 gestantes enfermas, 33 eran adultas jóvenes y tres, mayores de 35 años. Ninguna de las adolescentes presentó EP. Del total de gestantes, 20 se encontraban en el primer trimestre y 16 en el tercero. De las 36 pacientes enfermas 29 presentaron higiene bucal deficiente para un 80,55 por ciento y sólo siete mostraban una higiene bucal eficiente para un 19,44 por ciento. Conclusiones: La Enfermedad Periodontal es frecuente entre las gestantes del primer y tercer trimestre a lo cual contribuye la mala higiene bucal, la edad, como también la elevación de las hormonas durante el embarazo(AU)

Introduction: The cause / effect relationship between pregnancy and periodontal disease is very contradictory in the literature. Some authors deny that this relationship exists, while others affirm it. Objective: To identify the presence of Periodontal Disease in first and third trimester pregnant women, taking into account their age and oral hygiene. Methods: The sample consisted of 106 pregnant women from the first and third trimesters of pregnancy. They were collected according to the following age groups: Adolescents, young adults and adults over 35 years of age. All the pregnant women in the sample underwent a stomatological examination to diagnose the patients carrying Periodontal Disease, the presented clinical forms, as well as to evaluate the quality of the oral hygiene. Results: It was found that 36 of the pregnant women were carriers of Periodontal Disease: 34 had gingivitis and two periodontitis. The most abundant clinical form was fibro-edematous gingivitis. Of the 36 pregnant women, 33 were young adults and three were over 35 years old. None of the adolescents presented EP. Of the total of pregnant women, 20 were in the first quarter and 16 in the third. Of the 36 sick patients, 29 had poor oral hygiene for 80.55 percent and only seven showed efficient oral hygiene for 19.44 percent. Conclusions: Periodontal disease is common among pregnant the first and third quarter which contributes to poor oral hygiene, age, as well as elevated hormones during pregnancy(AU)

Attenuation of Blood-Brain Barrier Breakdown and Hyperpermeability by Calpain Inhibition.

Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability followed by brain edema are hallmark features of several brain pathologies, including traumatic brain injuries (TBI). Recent studies indicate that pro-inflammatory cytokine interleukin-1ß (IL-1ß) that is up-regulated following traumatic injuries also promotes BBB dysfunction and hyperpermeability, but the underlying mechanisms are not clearly known. The objective of this study was to determine the role of calpains in mediating BBB dysfunction and hyperpermeability and to test the effect of calpain inhibition on the BBB following traumatic insults to the brain. In these studies, rat brain microvascular endothelial cell monolayers exposed to calpain inhibitors (calpain inhibitor III and calpastatin) or transfected with calpain-1 siRNA demonstrated attenuation of IL-1ß-induced monolayer hyperpermeability. Calpain inhibition led to protection against IL-1ß-induced loss of zonula occludens-1 (ZO-1) at the tight junctions and alterations in F-actin cytoskeletal assembly. IL-1ß treatment had no effect on ZO-1 gene (tjp1) or protein expression. Calpain inhibition via calpain inhibitor III and calpastatin decreased IL-1ß-induced calpain activity significantly (p < 0.05). IL-1ß had no detectable effect on intracellular calcium mobilization or endothelial cell viability. Furthermore, calpain inhibition preserved BBB integrity/permeability in a mouse controlled cortical impact model of TBI when studied using Evans blue assay and intravital microscopy. These studies demonstrate that calpain-1 acts as a mediator of IL-1ß-induced loss of BBB integrity and permeability by altering tight junction integrity, promoting the displacement of ZO-1, and disorganization of cytoskeletal assembly. IL-1ß-mediated alterations in permeability are neither due to the changes in ZO-1 expression nor cell viability. Calpain inhibition has beneficial effects against TBI-induced BBB hyperpermeability.

Experience of Circuit Survival in Extracorporeal Continuous Renal Replacement Therapy Using Small-Calibre Venous Cannulae.

OBJECTIVES: To describe an experience of circuit survival in extracorporeal continuous renal replacement therapy using small-calibre (< 7 French gauge [F]) venous cannulae. DESIGN: An observational study. SETTING: A multidisciplinary, university-affiliated PICU. SUBJECTS: Case note review of all continuous renal replacement therapy episodes (1998-2010), which used vascular access cannulae of an external diameter less than 7F, was performed. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients underwent continuous renal replacement therapy treatment during which circuit blood flow was delivered using either 5F or 6.5F double-lumen cannulae. One hundred thirty-nine circuits were employed (median per patient, 2; interquartile range, 1-3) in providing 4,903 hours of therapy (median duration of therapy, 43 hr; interquartile range, 22-86 hr); allowing for censoring, the median circuit survival time was 40 hours (95% CI, 28-66). Eighty-one circuits (58%) failed because of clotting/technical problems, equating to a circuit failure rate of 16.5 (95% CI, 13.3-20.5) per 1,000 hours of continuous renal replacement therapy. The probability of a circuit surviving 40 hours or greater was 50% with 43% (95% CI, 34-53%) expected to survive 60 hours or more. No significant relationship between circuit survival and the calibre of the cannula deployed was identified; however, placement of venous access in an internal jugular vein was associated with improved circuit survival. CONCLUSIONS: Contrary to previous reports, vascular access cannulae of a caliber less than 7F can support sufficiently prolonged continuous renal replacement therapy to make them a useful means of delivering renal support in neonates and small infants.