Central-line-associated bloodstream infections and central-line-associated non-CLABSI complications among pediatric oncology patients.

OBJECTIVE: To assess central venous catheter (CVC) harm in pediatric oncology patients, we explored risks for central-line-associated bloodstream infections (CLABSIs) and central-line-associated non-CLABSI complications (CLANCs). DESIGN: Retrospective cohort study. SETTING: Midwestern US pediatric oncology program. PATIENTS: The study cohort comprised 592 pediatric oncology patients seen between 2006 and 2016. METHODS: CLABSIs were defined according to Centers for Disease Control and Prevention (CDC)/National Health Safety Network (NHSN) definitions. CLANCs were classified using a novel definition requiring CVC removal. Patient-level and central-line-level risks were calculated using a negative binomial model to adjust for correlations between total events and line numbers. RESULTS: CVCs were inserted in 62% of patients, with 175,937 total catheter days. The inpatient CLABSI and CLANC rates were 5.8 and 8.5 times higher than outpatient rates. At the patient level, shared risks included acute myeloid leukemia (AML) and age <1 year at diagnosis. At the line level, shared risks included age <1 year at diagnosis, non-mediports, and >1 lumen. AML was a CLABSI-specific risk. CLANC-specific risks included non-brain-tumor diagnosis, younger age at diagnosis or central-line placement, and age <1 year at diagnosis or line placement. Multivariable risks were for CLABSI >1 lumen and for CLANC age <1 year at placement. CONCLUSIONS: Among patients with CVCs, CLABSI and CLANC rates were similar, higher among inpatients than outpatients. For both CLABSIs and CLANCs, infants and patients with AML were at higher risk. In both univariate and multivariate models, lines with >1 lumen were associated with CLABSIs and placement during infancy with CLANCs.

Galectin-3: an emerging biomarker in stroke and cerebrovascular diseases.

The carbohydrate-binding molecule galectin-3 has garnered significant attention recently as a biomarker for various conditions ranging from cardiac disease to obesity. Although there have been several recent studies investigating its role in stroke and other cerebrovascular diseases, awareness of this emerging biomarker in the wider neurology community is limited. We performed a systematic search in PubMed, Embase, Scopus, CINAHL, Clinicaltrials.gov and the Cochrane library in November and December 2016 for articles related to galectin-3 and cerebrovascular disease. We included both human and pre-clinical studies in order to provide a comprehensive view of the state of the literature on this topic. The majority of the relevant literature focuses on stroke, cerebral ischemia and atherosclerosis, but some recent attention has also been devoted to intracranial and subarachnoid hemorrhage. Higher blood levels of galectin-3 correlate with worse outcomes in atherosclerotic disease as well as in intracranial and subarachnoid hemorrhage in human studies. However, experimental evidence supporting the role of galectin-3 in these phenotypes is not as robust. It is likely that the role of galectin-3 in the inflammatory cascade within the central nervous system following injury is responsible for many of its effects, but its varied physiological functions and multiple sites of expression mean that it may have different effects depending on the nature of the disease condition and the time since injury. In summary, experimental and human research raises the possibility that galectin-3, which is closely linked to the inflammatory cascade, could be of value as a prognostic marker and therapeutic target in cerebrovascular disease.

Galectin-3 and risk of ischaemic stroke: Reasons for Geographic and Racial Differences in Stroke cohort.

BACKGROUND AND PURPOSE: Galectin-3 is a biomarker of atherosclerotic and cardiovascular disease, and may be a useful marker for ischaemic stroke risk. METHODS: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled and examined 30 239 US participants between 2003 and 2007 (41% black, 59% white and 55% in the southeastern stroke belt). Baseline galectin-3 was measured in 526 subjects with incident ischaemic stroke over 5.4 years and in a cohort random sample (CRS) of 947 participants. Cox proportional hazards models were used to calculate hazard ratios (HRs) of ischaemic stroke by quartiles of galectin-3. RESULTS: In the CRS, galectin-3 was significantly higher with older age, black race, female sex, body mass index, hypertension, diabetes mellitus and kidney disease, and also in those who developed incident stroke. Participants with galectin-3 levels in the fourth versus first quartile had a 2.3-fold increased stroke risk [95% confidence interval (CI) 1.6, 3.4] in an unadjusted model. An interaction with age was found (P = 0.06), and therefore age-stratified analyses were performed. Amongst those younger than age 64, baseline galectin-3 in the second-fourth quartiles was associated with increased stroke risk (HR 3.0, 95% CI 1.6, 5.5) compared to the first quartile in an age-, race- and sex-adjusted model. The HR was 2.0 (95% CI 1.0, 4.0) with multivariable adjustment. There was no association amongst older participants. CONCLUSIONS: Galectin-3 was associated with incident ischaemic stroke in younger but not older individuals. Confirmation of this finding, and elucidation of its implications for stroke pathophysiology and prevention, is needed.

Cardiogenic shock from atypical Takotsubo cardiomyopathy attributed to acute disseminated encephalomyelitis lesion involving the medulla.

We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids.

Surgical management and genetic analysis of a Chinese family with the S171P mutation in the UBIAD1 gene, the gene for Schnyder corneal dystrophy.

BACKGROUND: To describe the underlying molecular genetic basis, surgical management and phenotypic variation of Schnyder corneal dystrophy (SCD) identified in a four-generation Chinese family. METHODS: This is an interventional case series of 13 members from a non-consanguineous Chinese family. All patients underwent complete ophthalmological examination and slit-lamp photography. Subsequent corneal transplantations were performed (n = 3). Blood samples were taken for DNA extraction and subsequent genetic analysis. RESULTS: Genotyping indicated linkage to the locus at chromosome 1p36. Screening of the UBIAD1 gene identified a highly conserved mutation, Ser171Pro. Phenotypic variation in this large pedigree is similar to that seen in Caucasian patients. Surgical management of patients with anterior lamellar keratoplasty and deep anterior lamellar keratoplasty showed good visual outcomes. CONCLUSIONS: The S171P mutation is described for the first time in a Chinese family. This is the largest non-Caucasian pedigree described with SCD. Visual rehabilitation may be performed successfully with lamellar surgical procedures as opposed to full-thickness corneal grafts.

Autologous transplantation for relapsed non-Hodgkin's lymphoma using intravenous busulfan and cyclophosphamide as conditioning regimen: a single center experience.

High-dose chemotherapy with autologous SCT has become standard of care for patients with relapsed aggressive non-Hodgkin's lymphoma (NHL). To improve safety and efficacy of this treatment, new conditioning regimens are being developed. We retrospectively reviewed clinical data of patients with relapsed NHL treated at our institution with i.v. BU and CY (BU/CY) as conditioning regimen for autologous SCT between January 2000 and April 2005. We identified 43 patients (24 men, 19 women, median age 50) with diffuse large B-cell lymphoma (n=28), follicular lymphoma (n=8), mantle cell lymphoma (n=4) and peripheral T-cell lymphoma (n=3). Following salvage chemotherapy, there were 26 complete responses, 13 partial responses and 4 stable diseases. Median time to neutrophil and platelet recovery was 11 and 13.5 days, respectively. Treatment-related toxicities included nausea/vomiting, diarrhea and mucositis. The 100-day mortality was 9%: sepsis (n=1), pneumonia (n=1) and hepatic veno-occlusive disease (n=2). Twenty-one patients were followed until death and twenty-one surviving patients were followed for a median of 29 months (range 0.4-76). Three-year estimates of event-free survival, progression-free survival and overall survival were 35, 39 and 43%, respectively. We conclude that i.v. BU/CY is a safe and effective conditioning regimen for autologous SCT in relapsed NHL.

Increased permeability in dextran sulphate colitis in rats: time course of development and effect of butyrate.

BACKGROUND: Increased mucosal permeability is an important factor in the genesis of mucosal inflammation in inflammatory bowel disease. This study examined the time course of increased permeability and the effect of butyrate on permeability in experimental colitis in rats. METHODS: Colitis was induced in albino rats by administration of 4% dextran sulphate sodium (DSS) orally for up to 7 days. Rats were killed sequentially after 1-7 days of DSS feeding and compared with control animals. Distal colon sheets, from normal and DSS rats, were mounted in Ussing chambers. Electric resistance and passive permeation of 14C-mannitol were measured over 90 min. In control and 5-day DSS rats additional permeability measurements were made in the presence of butyrate (25 mmol/l) in the bathing solutions. The permeability of the normal distal colon was measured after addition of DSS in vitro. Sections of colon were examined by light microscopy. The viability of colonocytes, from normal and DSS rat colon, was measured by release of lactate dehydrogenase immediately and during a 60-min incubation after isolation. RESULTS: Focal mild inflammation and shedding of epithelium were noted after 2 days of DSS administration; crypt loss with flattened epithelium in adjacent areas after 5 days; and fibrosis after 7 days. Decreased epithelial cell survival after 60 min of incubation was noted after 1 day of DSS administration, whereas decreased viability at the time of isolation was noted after 2 days of DSS administration (viability, 72.7% +/- 1.4%; mean +/- standard error) compared with control (89.3% +/- 0.8%) (P < 0.01). Increased permeability was noted after 1 day of DSS administration. Electric resistance (mu omega/cm2/h) was significantly reduced after 1 day of DSS administration to 85.9 +/- 4.6 (mean +/- standard error) compared with control animals (117.2 +/- 2.2; P < 0.001). Serosa-mucosa flux of mannitol (micromol/cm2/h) was also significantly increased after 1 day of DSS feeding (0.169 +/- 0.01) compared with control (0.061 +/- 0.08) (P < 0.01). Electric resistance and mannitol permeability were significantly returned towards normal by the presence of butyrate. DSS added directly to the bathing solution did not significantly alter the colon permeability in vitro. CONCLUSIONS: Increased mucosal permeability is a very early change in colitis induced by DSS, is accompanied by decreased cell survival, and precedes detectable changes in histology. Reversal of increased mucosal permeability by butyrate may explain its utility in the therapy of inflammatory disease of the colon.

Butyrate hastens restoration of barrier function after thermal and detergent injury to rat distal colon in vitro.

BACKGROUND: Epithelial migration restores barrier function after superficial injury to any mucosa. The present study aimed to determine whether butyrate, important to colonic epithelial physiology in diverse ways, influences restoration of barrier function in the injured rat colon. METHODS: Rat distal colon was transiently exposed in vitro to heat (55 degrees C for 10 sec) or to detergent (deoxycholic acid, 7.5 mM, for 15 min), and tissue damage was verified histologically. Epithelial barrier function was assessed, in colon tissue mounted in Ussing chambers, by measuring electric resistance and passive serosa-to-mucosa fluxes of 22Na and of 14C PEG 4000 under voltage clamp conditions. Studies were done in the absence and presence of 25 mM butyrate in the bathing solutions. RESULTS: Heat exposure induced superficial epithelial damage, and the electric resistance decreased significantly. This was accompanied by increase in flux of 14C PEG and increased passive flux of 22Na. Electric resistance was significantly higher, and PEG flux significantly lower, in tissues bathed with butyrate. Exposure to deoxycholic acid also induced superficial epithelial damage, reduced tissue electric resistance, and increased passive flux of Na and PEG. Electric resistance was significantly higher, and PEG flux significantly lower, in injured tissues bathed in butyrate, than in injured tissues bathed in butyrate-free solution. The effect of butyrate on restoration of electric resistance towards normal was seen in colon both from adult rats and from younger rats that were 2 or 6 weeks old. CONCLUSIONS: Butyrate enhanced restoration of mucosal barrier function in rat distal colon in response to heat and detergent injury.