Epidemiology and Risk Factors for Bloodstream Infections in a Home Parenteral Nutrition Program

Background: An increasing number of patients with intestinal failure are receiving home parenteral nutrition (HPN). Associated complications include bloodstream infections (BSIs), but data on rates and risk factors for HPN‐related BSIs are scarce. Methods: A retrospective review was conducted of patients enrolled in the regional HPN program between 2001 and 2008. Demographic information and data on indication for HPN, duration of PN therapy, type and date of insertion of central venous access device, and blood culture results were recorded. Results: In total, 155 patients (165 courses of HPN) were included for a total of 45,876 catheter days. The mean patient age was 49 years, and 105 (64%) patients were female. A total of 105 organisms were cultured from 93 distinct episodes of BSIs. The rate of BSI was found to be 2.0 per 1000 catheter days, but excluding BSIs with a single positive culture of coagulase‐negative staphylococcus and diphtheroid bacilli, the rate of infection was 1.4 per 1000 catheter days. Male sex and underlying malignancy were significant predictors of BSI, with hazard ratios of 1.69 (95% confidence interval [CI], 1.14–2.60; P = .009) and 2.38 (95% CI, 1.53–3.50; P < .001). Conclusion: In a large heterogeneous group of HPN patients, the BSI rate ranged between 1.4 and 2.0 infections per 1000 catheter days. Isolated organisms were similar to those found in hospitalized patients. Male sex and underlying malignancy were significant risk factors for BSI. These high‐risk patients are likely to benefit from interventions aimed at reducing BSIs.     

Systemic bevacizumab as salvage therapy for persistent severe bleeding and anemia in heyde syndrome following aortic valve replacement

Journal of Thrombosis and Thrombolysis - Heyde syndrome is characterized by the co-occurrence of aortic stenosis and bleeding gastrointestinal angiodysplasias, often with acquired von Willebrand...     

Overexpression of amyloid precursor protein A4 (beta-amyloid) immunoreactivity in genetically transformed cells: implications for a cellular model of Alzheimer amyloidosis.

Among the major obstacles to clarifying molecular mechanisms involved in amyloid metabolism in Alzheimer disease has been the unavailability of laboratory models for this uniquely human disorder. The present studies were aimed at establishing genetically engineered cell lines that overexpress amyloid immunoreactivity and that may be relevant to amyloid accumulation in the Alzheimer disease brain. We used cloned amyloid cDNA that contains a region encoding A4 (beta-polypeptide) amino acids along with recently developed tumor virus vectors derived from simian virus 40 to prepare transformed cells. After transient and permanent transfection, a variety of cell types overexpressed A4 immunoreactivity that was detected by highly specific monoclonal antibodies. We observed that the use of an amyloid subdomain containing the A4 region, but lacking the sequence of a Kunitz-type protease inhibitor found in amyloid precursor protein variants, was sufficient to obtain cells that overproduced an A4 epitope. The transformed cells were readily propagated in culture and may provide an experimental medium to elucidate aspects of the molecular pathogenesis of Alzheimer disease. The cellular models may also serve as tools for deriving potentially useful therapeutic agents.     

DNA Methylation Profiling Revealed Promoter Hypermethylation-induced Silencing of p16, DDAH2 and DUSP1 in Primary Oral Squamous Cell Carcinoma

Background: Hypermethylation in promoter regions of genes might lead to altered gene functions and result in malignant cellular transformation. Thus, biomarker identification for hypermethylated genes would be very useful for early diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). The objectives of this study were to screen and validate differentially hypermethylated genes in OSCC and correlate the hypermethylation-induced genes with demographic, clinocopathological characteristics and survival rate of OSCC.Methods: DNA methylation profiling was utilized to screen the differentially hypermethylated genes in OSCC. Three selected differentially-hypermethylated genes of p16, DDAH2 and DUSP1 were further validated for methylation status and protein expression. The correlation between demographic, clinicopathological characteristics, and survival rate of OSCC patients with hypermethylation of p16, DDAH2 and DUSP1 genes were analysed in the study.Results: Methylation profiling demonstrated 33 promoter hypermethylated genes in OSCC. The differentially-hypermethylated genes of p16, DDAH2 and DUSP1 revealed positivity of 78%, 80% and 88% in methylation-specific polymerase chain reaction and 24% and 22% of immunoreactivity in DDAH2 and DUSP1 genes, respectively. Promoter hypermethylation of p16 gene was found significantly associated with tumour site of buccal, gum, tongue and lip (P=0.001). In addition, DDAH2 methylation level was correlated significantly with patients'' age (P=0.050). In this study, overall five-year survival rate was 38.1% for OSCC patients and was influenced by sex difference.Conclusions: The study has identified 33 promoter hypermethylated genes that were significantly silenced in OSCC, which might be involved in an important mechanism in oral carcinogenesis. Our approaches revealed signature candidates of differentially hypermethylated genes of DDAH2 and DUSP1 which can be further developed as potential biomarkers for OSCC as diagnostic, prognostic and therapeutic targets in the future.     

Acceptance of a COVID-19 Vaccine and Its Related Determinants among the General Adult Population in Kuwait

ObjectiveThe objective of this study was to determine the acceptance of a coronavirus disease 2019 (COVID-19) vaccine among the general adult population in Kuwait and assess its determinants.Subjects and MethodsA web-based cross-sectional study was conducted by enrolling adults living in Kuwait (n = 2,368; aged ≥21 years). Acceptance of a COVID-19 vaccine was inferred if participants indicated that they “definitely or probably will accept vaccination against COVID-19 once a vaccine is available.” Associations were explored by applying a modified Poisson regression to estimate and infer adjusted prevalence ratios (aPR) and their 95% confidence intervals (CI).ResultsIn total, 53.1% (1,257/2,368) of the participants were willing to accept a COVID-19 vaccine once available. Male subjects were more willing to accept a COVID-19 vaccine than females (58.3 vs. 50.9%, p < 0.001). Subjects who viewed vaccines in general to have health-related risks were less willing to accept vaccination (aPR = 0.39, 95% CI: 0.35–0.44). Moreover, participants who previously received an influenza vaccine were more likely to accept a COVID-19 vaccine (aPR = 1.44, 95% CI: 1.31–1.58). Willingness to get vaccinated against COVID-19 increased as the self-perceived chances of contracting the infection increased (p < 0.001).ConclusionOverall, 53.1% of the study participants demonstrated willingness to get vaccinated against COVID-19. We found several factors influencing the level of acceptance. Since vaccination appears to be an essential preventive measure that can halt the COVID-19 pandemic, factors relating to low vaccine acceptance need to be urgently addressed by public health strategies.     

Establishing and managing a periodontal biobank for research: the sharing of experience

Periodontal bio‐repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad‐based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.     

Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation

Hodgkin lymphoma (HL) relapsing after allogeneic stem cell transplantation (alloSCT) presents a major clinical challenge. In the present investigation, we evaluated brentuximab vedotin, a CD30-directed Ab-drug conjugate, in 25 HL patients (median age, 32 years; range, 20-56) with recurrent disease after alloSCT (11 unrelated donors). Patients were > 100 days after alloSCT, had no active GVHD, and received a median of 9 (range, 5-19) prior regimens. Nineteen (76%) had refractory disease immediately before enrollment. Patients received 1.2 or 1.8 mg/kg of brentuximab vedotin IV every 3 weeks (median, 8 cycles; range, 1-16). Overall and complete response rates were 50% and 38%, respectively, among 24 evaluable patients. Median time to response was 8.1 weeks, median progression-free survival was 7.8 months, and the median overall survival was not reached. Cough, fatigue, and pyrexia (52% each), nausea and peripheral sensory neuropathy (48% each), and dyspnea (40%) were the most frequent adverse events. The most common adverse events ≥ grade 3 were neutropenia (24%), anemia (20%), thrombocytopenia (16%), and hyperglycemia (12%). Cytomegalovirus was detected in 5 patients (potentially clinically significant in 1). These results support the potential utility of brentuximab vedotin for selected patients with HL relapsing after alloSCT.     

Protective effect of curcumin on N-nitrosodiethylamine and carbon tetrachloride-induced hepatocarcinogenesis in Sprague–Dawley rats

Curcumin, the yellow spice derived from the roots (rhizomes) of the plant Curcuma longa, has been reported to have a chemoprotective effect against several neoplasms. The protective effect of curcumin during N-nitrosodiethylamine- and carbon tetrachloride-induced hepatocarcinogenesis in Sprague–Dawley rats and its effect on the expression of IkappaB-alpha mRNA were evaluated. Sixty male rats were randomly assigned into four experimental groups. Group A animals received a single i.p. injection of N-nitrosodiethylamine (200 mg/kg b.w.). After 1 week, the animals received weekly s.c. injections of carbon tetrachloride (3 ml/kg b.w./week) for 6 weeks. Group B was given diet containing 0.2 % curcumin 2 weeks before the injection of N-nitrosodiethylamine and continued throughout the experimental period (20 weeks). Group C was given only a diet containing 0.2 % curcumin for the whole period of the experiment. Group D animals served as control. The level of IkappaB-alpha (IкB-α) mRNA was determined by semiquantitative PCR. Administration of diet containing 0.2 % curcumin, 2 weeks before the injection of N-nitrosodiethylamine and throughout the period of experiment, decreased percentage of preneoplastic foci in hepatic parenchyma and inhibited the development of hepatocellular carcinoma, cholangiofibrosis, and cystic cholangioma in rat liver. Moreover, curcumin administration decreased the number and size of the preneoplastic foci induced by N-nitrosodiethylamine and carbon tetrachloride in the liver. The densitometric analysis of the IкB-α mRNA bands revealed that curcumin administration blocked the decrease of IкB-α mRNA induced by N-nitrosodiethylamine and carbon tetrachloride. These results concluded that curcumin inhibited hepatocarcinogenesis induced by N-nitrosodiethylamine and carbon tetrachloride through blocking IкB-α degradation.     

Increased risk of pneumonia among ventilated patients with traumatic brain injury: every day counts!

Background

Patients with traumatic brain injury (TBI) frequently require mechanical ventilation (MV). The objective of this study was to examine the association between time spent on MV and the development of pneumonia among patients with TBI.

Materials and methods

Patients older than 18 y with head abbreviated injury scale (AIS) scores coded 1–6 requiring MV in the National Trauma Data Bank 2007–2010 data set were included. The study was limited to hospitals reporting pneumonia cases. AIS scores were calculated using ICDMAP-90 software. Patients with injuries in any other region with AIS score >3, significant burns, or a hospital length of stay >30 d were excluded. A generalized linear model was used to determine the approximate relative risk of developing all-cause pneumonia (aspiration pneumonia, ventilator-associated pneumonia [VAP], and infectious pneumonia identified by the International Classification of Disease, Ninth Revision, diagnosis code) for each day of MV, controlling for age, gender, Glasgow coma scale motor score, comorbidity (Charlson comorbidity index) score, insurance status, and injury type and severity.

Results

Among the 24,525 patients with TBI who required MV included in this study, 1593 (6.5%) developed all-cause pneumonia. After controlling for demographic and injury factors, each additional day on the ventilator was associated with a 7% increase in the risk of pneumonia (risk ratio 1.07, 95% confidence interval 1.07–1.08).

Conclusions

Patients who have sustained TBIs and require MV are at higher risk for VAP than individuals extubated earlier; therefore, shortening MV exposure will likely reduce the risk of VAP. As patients with TBI frequently require MV because of neurologic impairment, it is key to develop aggressive strategies to expedite ventilator independence.