The bovine paranasal sinuses: Bacterial flora, epithelial expression of nitric oxide and potential role in the in-herd persistence of respiratory disease pathogens

peer-reviewedThe bovine paranasal sinuses are a group of complex cavernous air-filled spaces, lined by respiratory epithelium, the exact function of which is unclear. While lesions affecting these sinuses are occasionally reported in cattle, their microbial flora has not been defined. Furthermore, given that the various bacterial and viral pathogens causing bovine respiratory disease (BRD) persist within herds, we speculated that the paranasal sinuses may serve as a refuge for such infectious agents. The paranasal sinuses of clinically normal cattle (n = 99) and of cattle submitted for post-mortem examination (PME: n = 34) were examined by microbial culture, PCR and serology to include bacterial and viral pathogens typically associated with BRD: Mycoplasma bovis, Histophilus somni, Mannheimia haemolytica and Pasteurella multocida, bovine respiratory syncytial virus (BRSV) and bovine parainfluenza-3 virus (BPIV-3). Overall, the paranasal sinuses were either predominantly sterile or did not contain detectable microbes (83.5%: 94.9% of clinically normal and 50.0% of cattle submitted for PME). Bacteria, including BRD causing pathogens, were identified in relatively small numbers of cattle (<10%). While serology indicated widespread exposure of both clinically normal and cattle submitted for PME to BPIV-3 and BRSV (seroprevalences of 91.6% and 84.7%, respectively), PCR identified BPIV-3 in only one animal. To further explore these findings we investigated the potential role of the antimicrobial molecule nitric oxide (NO) within paranasal sinus epithelium using immunohistochemistry. Expression of the enzyme responsible for NO synthesis, inducible nitric oxide synthase (iNOS), was detected to varying degrees in 76.5% of a sub-sample of animals suggesting production of this compound plays a similar protective role in the bovine sinus as it does in humans

GI Bleeding in the Elderly

Purpose: To determine the risk factors contributing to and etiologies of gastrointestinal bleeding in an elderly patient population seen by Southwest Gastroenterology (SWGA) providers. Methods: This study reviews charts of patients with GI bleeding from documented sources between 1/1999 and 3/2006. The cases are gathered retrospectively from the clinical records of SWGA, a 12-person private, single specialty gastroenterology group serving community hospitals. Etiology and risk factors for GI hemorrhages are recorded in an elderly population, defined as patients age 55 and older. Results: GI hemorrhages are identified in 105 patients. The majority (83, 79%) of hemorrhages are upper GI bleeds (UGIB) comparing to 22 (21%) lower GI bleeds (LGIB). In the UGIB group, the most common etiology of bleed is gastric ulcer (29%). We also found 72% of UGIB patients on prescribed anticoagulation medications, including anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs). 20% of these patients are also positive for H. Pylori. Thirty patients in the UGIB group smoke or consume alcohol heavily (consuming more than 3 drinks per day for men and two drinks per day for women) while 2 patients smoke or consume alcohol in the LGIB group. Previous bleeds are common in both groups with 39 (41%) in UGIB and 9 (47%) in LGIB. Co-morbidity is the most common risk factor with 20 (91%) in LGIB and 73 (88%) in UGIB. In the peptic ulcer disease (PUD) bleeds, the majority (77%) are taking NSAIDs, while in the non-PUD bleeds, only 38% are currently on NSAIDs. Overall, there are 2 mortalities resulting from cardiovascular complications of GI bleeding. Conclusion: The etiologies of GI bleeds in this population are comparable to other studies in the literature. The ratio of UGIB to LGIB in this elderly population is also similar to that reported in the literature. The risk factors shown to be most correlated to bleeding are co-morbidities, previous episodes of bleeding, anticoagulation, NSAID use, smoking and alcohol use. NSAID use is significant in PUD bleed patients. This study reinforces that increased knowledge of etiology, incidence and contributing factors of GI bleeding are necessary for physicians to efficiently treat GI bleeds in the elderly population

Risk of venous thromboembolism in children after general surgery

Background/purpose: The purpose of the study was to determine absolute and relative rates of venous thromboembolism (VTE) following general surgical procedures in children compared to the general population. Methods: We analyzed data from all patients under the age of 18 years in the Clinical Practice Research Datalink, linked to Hospital Episode Statistics from England (2001–2011) undergoing a general surgical procedure and population controls. Crude rates of VTE and adjusted hazard ratios were calculated using Cox regression. Results We identified 15,637 children who had a surgical procedure with 161,594 controls. Six children undergoing surgery had a VTE diagnosed in the year after compared to five children in the population cohort. The overall rate of VTE following surgery was 0.4 per 1000 person years (pyrs) (95% confidence interval [CI] 0.15–0.88) compared to 0.04 per 1000 pyrs (95% CI 0.02–0.09) in the population cohort. This represented a 9 fold increase in risk compared to the population cohort (adjusted hazard ratio [HR] 8.80; 95% CI 2.59–29.94). Conclusions Children are at increased risk for VTE following general surgical procedures compared to the general population however the absolute risk is small and given this the benefits of thromboprophylaxis need to be balanced against the risk of complications following its use

Advanced oxidation technologies for chemical demilitarization

This is the final report of a one-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory. The main project objective was to establish a technical basis for future program development in the area of chemical warfare agent destruction using a Los Alamos-developed advanced oxidation process: a two-stage device consisting of thermal packed-bed reactor (PBR) and a nonthermal plasma (NTP) reactor. Various compounds were evaluated as potential surrogates for chemical warfare (CW) agents. Representative effluent mass balances were projected for future comparisons with incinerators. The design and construction of lab-scale PBR/NTP reactors (consisting of a liquid injection and metering system, electric furnace, condensers, chemical traps, plasma reactors, power supplies, and chemical diagnostics) has been completed. This equipment, the experience gained from chemical-processing experiments, process modeling, and an initial demonstration of the feasibility of closed-loop operation, have provided a technical basis for further demonstrations and program development efforts

Venous thromboembolism in children with cancer – a population-based cohort study

Introduction: Cancer is a known risk factor for venous thromboembolism (VTE) in adults, but population-based data in children are scarce. Materials and methods: We conducted a cohort study utilising linkage of the Clinical Practice Research Database (primary care), Hospital Episodes Statistics (secondary care), UK Cancer Registry data and Office for National Statistics cause of death data. From these databases, we selected 498 children with cancer diagnosed between 1997 and 2006 and 20,810 controls without cancer. We calculated VTE incidence rates in children with cancer vs. controls, and hazard ratios (HRs) using Cox regression. Results: We identified four VTE events in children with cancer compared with four events in the larger control population corresponding to absolute risks of 1.52 and 0.06 per 1000 person-years respectively. The four children with VTE and cancer were diagnosed with hematological, bone or non-specified cancer. Childhood cancer was hence associated with a highly increased risk of VTE (HR adjusted for age and sex: 28.3; 95%CI = 7.0-114.5). Conclusions: Children with cancer are at increased relative risk of VTE compared to those without cancer. Physicians could consider thromboprophylaxis in children with cancer to reduce their excess risk of VTE however the absolute risk is extremely small and the benefit gained therefore would need to be balanced against the risk invoked of implementing such a strategy. Novelty & Impact Statements: While there is a reasonable level of knowledge about the risk of VTE in adult populations, it is not well known whether this risk is reflected in paediatric patients. We found a substantial increase in risk of VTE in children with cancer compared to a child population without cancer. While this finding is important, the absolute risk of VTE is still low and must be balanced with the risks of anticoagulation

Clinical practice: The bleeding child. Part II: Disorders of secondary hemostasis and fibrinolysis

Bleeding complications in children may be caused by disorders of secondary hemostasis or fibrinolysis. Characteristic features in medical history and physical examination, especially of hemophilia, are palpable deep hematomas, bleeding in joints and muscles, and recurrent bleedings. A detailed medical and family history combined with a thorough physical examination is essential to distinguish abnormal from normal bleeding and to decide whether it is necessary to perform diagnostic laboratory evaluation. Initial laboratory tests include prothrombin time and activated partial thromboplastin time. Knowledge of the classical coagulation cascade with its intrinsic, extrinsic, and common pathways, is useful to identify potential defects in the coagulation in order to decide which additional coagulation tests should be performed

Recent Advances in Childhood Arterial Ischemic Stroke

Although many underlying diseases have been reported in the setting of childhood arterial ischemic stroke, emerging research demonstrates that non-atherosclerotic intracerebral arteriopathies in otherwise healthy children are prevalent. Minor infections may play a role in arteriopathies that have no other apparent underlying cause. Although stroke in childhood differs in many aspects from adult stroke, few systematic studies specific to pediatrics are available to inform stroke management. Treatment trials of pediatric stroke are required to determine the best strategies for acute treatment and secondary stroke prevention. The high cost of pediatric stroke to children, families, and society demands further study of its risk factors, management, and outcomes. This review focuses on the recent findings in childhood arterial ischemic stroke

Rivaroxaban Compared with Standard Anticoagulants for the Treatment of Acute Venous Thromboembolism in Children: a Randomised, Controlled, Phase 3 Trial

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0–17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. Findings: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87–95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29–35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11–1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51–6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. Interpretation: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. Funding: Bayer AG and Janssen Research & Development. © 2020 Elsevier Ltd