Utilization and Complications of Central Venous Access Devices in Oncology Patients

Purpose: To describe how central venous access devices (CVADs) are utilized for ambulatory oncology patients and to evaluate the rate of complications. Method: Single institution retrospective study of oncology patients with CVADs who received systemic treatment at the Walker Family Cancer Centre (WFCC) between 1 January and 31 December 2018. Results: A total of 480 CVADS were placed in 305 patients, of which 408 (85%) were peripherally inserted central catheters (PICCs) and 72 (15%) were implanted vascular access devices (PORTs). The incidence of early and late complications was 9% and 24%, respectively. For the entire cohort, the rate of venous thromboembolism (VTE) was 16%, of which 9% were CVAD-related thrombosis (CRTs) and 7% were distant VTE. The CRT rates were similar for PICCs and PORTs (9% vs. 7%). A total of 6% of CVADs were complicated by infection (i.e., localized infections and bacteremia), with a total infection rate of 0.43 and 0.26 per 1000 indwelling days for PICCs and PORTs, respectively. The incidence of central line associated bloodstream infections (CLABSI) was greater for PICCs than PORTs, at a rate of 0.22 compared with 0.08 per 1000 indwelling days, respectively. The premature catheter removal rate was 26% for PICCs and 18% for PORTs. PORTs required more additional hospital visits. Conclusions: PICCs were utilized more frequently than PORTs and had a higher rate of premature removal. The rates of VTE and CRT were similar for both CVAD types. PORTs had a lower rate of infection per 1000 indwelling days. However, the management of PORT related complications required more visits to the hospital and oncology clinic.     

Heterogeneity in amount of growth factors secreted by platelets in platelet-rich plasma samples from alopecia patients

Platelet α-granules release growth factors (GFs) that promote healing and tissue regeneration. Platelet-rich plasma (PRP) is shown to be beneficial in treating alopecia, and however, clinical response can be inconsistent. Due to several fold enrichment of platelets secreting large quantities of GFs following PRP injections, heterogeneity in amounts of GFs secreted by platelets may contribute to inconsistent clinical responses. Herein, we evaluated factors that could potentially contribute to heterogeneous secretion of GFs by platelets. We measured platelet secretion of transforming growth factor beta1 (TGFβ1), platelet-derived growth factor (PDGF-BB), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF2) in aliquots of de-identified PRP samples from female patients undergoing therapy in the hair disease clinic. Although secretion of GFs by platelets was comparable in PRP samples of patients with non-cicatricial and cicatricial alopecia, a Shapiro-Wilk test for normal distribution indicated significant variability across all patient samples. The amount of GF secreted by platelets was comparable when PRP prepared from two FDA-cleared devices with distinct techniques were compared. We provide evidence of platelets secreting heterogeneous amounts of GFs within each sample as high and low secretion of random factors could be simultaneously detected. These results suggest inherent heterogeneity in secretion of GFs by platelets in patient samples that are not influenced by the device used to prepare PRP. Since some GFs could have antagonistic effects on hair growth, a balance between amounts of growth promoting and inhibiting factors may be crucial in determining clinical response to PRP therapy.     

Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.     

Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease.

For patients who receive a liver transplant (LTX) for alcoholic liver disease (ALD), investigators are focusing beyond survival to determine specific alcohol use outcomes. Studies suggest the use of alcohol ranges from 8 to 22% for the first post-transplant year with cumulative rates reaching 30 to 40% by 5 years following transplantation. Yet while investigators are interested in determining specific rates of alcohol use and predictors of use, only three studies since 1990 have been prospective. In 1998, we began a prospective study of post-LTX alcohol consumption in ALD recipients using multiple repeated measures of alcohol use. After 5 years of follow-up, we found that 22% had used any alcohol by the first year and 42% had a drink by 5 years. By 5 years, 26% drank at a heavier use (binge) pattern and 20% drank in a frequent pattern. In a univariate model, predictors of alcohol use included pre-transplant length of sobriety, a diagnosis of alcohol dependence, a history of other substance use, and prior alcohol rehabilitation.     

Biologic effects of parathyroid hormone metabolites: implications for renal bone disease.

PTH fragments consisting of the C-terminal portion of the molecule may have biologic effects and may modify the actions of PTH. Evidence for the presence of a C-terminal PTH receptor further supports a biologic role for such fragments. Because C-PTH fragments accumulate in patients with renal insufficiency, it is possible that they may contribute to renal bone disease. The precise role of circulating C-PTH fragments in the pathogenesis, diagnosis, and management of renal osteodystrophy, however, remains to be determined. Future studies of the biologic effects and regulation of these fragments may lead to better understanding of skeletal biology and may also improve our approach to the diagnosis and treatment of renal bone disease.     

Familial hemiplegic migraine and autosomal dominant arteriopathy with leukoencephalopathy (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.     

Improved Cellular Delivery of Antisense Oligonucleotides Using Transferrin Receptor Antibody-Oligonucleotide Conjugates

This work is dedicated to the memory of the late Dr Ian Walker.     

Study on the pathogenicity of Campylobacter jejuni by modifying the medium

Campylobacter jejuni has been documented as one of the major aetiological agents of diarrhoeal illness all over the world. Studies revealed its pathogenicity by different assay methods, but none could be strongly recommended as a tool for differentiating toxigenic strains of C. jejuni. This study was an attempt to demonstrate better its pathogenicity by media modification. Fifteen isolates of C. jejuni recovered from diarrhoeal patients at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka Hospital were included in this study. The standard medium for C. jejuni was modified by the incorporation of FeCl3 at different concentrations. The pathogenicity of the test isolates were studied by rabbit ileal loop assay; Chinese hamster ovary (CHO), human epithelial cervical carcinoma (HeLa); Y-1 adrenal cell lines and suckling mouse assay. Sonicated extracts of the test organisms, grown with FeCl3 supplement, were also assayed. An enhanced growth of C. jejuni was obtained with the increasing concentration of FeCl3 supplementation in the medium. Only five isolates of C. jejuni produced cytotoxic effect on HeLa cell monolayer. Other cell lines were not affected by the test specimens or sonicates. Rabbit ileal loop assay did not reveal any fluid accumulation but on dissection, the test loops were found highly haemorrhagic. No heat-stable (ST) toxin could be detected. Cell-free culture supernatant of patients' isolates of C. jejuni had an effect on HeLa cell monolayer. Sonicated extracts of patients' extracts had a greater effect on HeLa cell monolayer. Pathogenic strains of C. jejuni might be distinguished on HeLa cell monolayer using its sonicated extracts.