Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

The clinical impact of bacterial infections on bone regeneration has been incompletely quantified and documented. As a result, controversy exists about the optimal treatment strategy to maximize healing of a contaminated defect. Animal models are extremely useful in this respect, as they can elucidate how a bacterial burden influences quantitative healing of various types of defects relative to non‐infected controls. Moreover, they may demonstrate how antibacterial treatment and/or bone grafting techniques facilitate the osteogenic response in the harsh environment of a bacterial infection. Finally, it a well‐known contradiction that osteomyelitis is characterized by uncontrolled bone remodeling and bone loss, but at the same time, it can be associated with excessive new bone apposition. Animal studies can provide a better understanding of how osteolytic and osteogenic responses are related to each other during infection. This review discusses the in vivo impact of bacterial infection on osteogenesis by addressing the following questions (i) How does osteomyelitis affect the radiographic bone appearance? (ii) What is the influence of bacterial infection on histological bone healing? (iii) How do bacterial infections affect quantitative bone healing? (iv) What is the effect of antibacterial treatment on the healing outcome during infection? (v) What is the efficacy of osteoinductive proteins in infected bones? (vi) What is the balance between the osteoclastic and osteoblastic response during bacterial infections? (vii) What is the mechanism of the observed pro‐osteogenic response as observed in osteomyelitis? © 2019 The Authors. Journal of Orthopaedic Research^© published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2067–2076, 2019     

Predicting(side) effects for patients with inflammatory bowel disease: The promise of pharmacogenetics

Inflammatory bowel disease (IBD) is a chronic and heterogeneous intestinal inflammatory disorder. The medical management of IBD aims for long-lasting disease remission to prevent complications and disease progression. Early introduction of immunosuppression forms the mainstay of medical IBD management. Large inter-individual variability in drug responses, in terms of both efficacy and toxicity, leads to high rates of therapeutic failure in the management of IBD. Better patient stratification is needed to maximize patient benefit and minimize the harm caused by adverse events. Pre-treatment pharmacogenetic testing has the potential to optimize drug selection and dose, and to minimize harm caused by adverse drug reactions. In addition, optimizing the use of cheap conventional drugs, and avoiding expensive ineffective drugs, will lead to a significant reduction in costs. Genetic variation in both TPMT and NUDT15, genes involved in thiopurine metabolism, is associated to an increased risk of thiopurine-induced myelosuppression. Moreover, specific HLA haplotypes confer risk to thiopurine-induced pancreatitis and to immunogenicity to tumor necrosis factor-antagonists, respectively. Falling costs and increased availability of genetic tests allow for the incorporation of pre-treatment genetic tests into clinical IBD management guidelines. In this paper, we review clinically useful pharmacogenetic associations for individualized treatment of patients with IBD and discuss the path from identification of a predictive pharmacogenetic marker to implementation into IBD clinical care.     

Positive engagement and job resources in dental practice

Abstract – Objectives: The aim of this study is to determine the level of engagement among dentists, and subsequently, to investigate which dental job resources are positively correlated with engagement. Methods: By stratifying on gender, age, and region, a representative sample of 848 general dental practitioners was drawn at random, plus an extra group of 95 female dentists for gender comparison purposes. Engagement was assessed using the Utrecht Work Engagement Scale (UWES), consisting of three subscales: Vigor, Dedication; and Absorption. Job resources were measured using the Dentists’ Experienced Job Resources Scale (DEJRS). Results: Six hundred and thirty two dentists (67%) responded, 76% male and 25% female. Mean age: 44.6 years (SD = 9.0). Engagement: Dedication and Absorption mean scores were higher among dentists when compared with manual norm scores, based upon a variety of professions, whereas Vigor mean scores were comparable to manual norm scores. Job resources:‘Immediate results / Aesthetics’ and ‘(Long term) Patient results’ showed highest mean scores among all dentists. Gender differences were found on ‘(Long term) Patient results’ and ‘Patient care’. Engagement and job resources: All DEJRS subscales and the full scale showed statistically significant positive correlations (pmcc) with the UWES subscales. Conclusion: Dentists showed relatively high mean scores on an engagement measure when compared with manual norm scores. No gender differences in mean scores were found. Job resources most valued were ‘Immediate results / Aesthetics’. The job resources, ‘Idealism/Pride’ and ‘Patient care’, showed most predictive value with regard to engagement among dentists. In order to prevent burnout, it is recommended to raise dentists’ awareness of the importance to create sufficient time and space for stimulating aspects in their work.     

Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension

The effect of lowering sympathetic nerve activity by renal denervation (RDN) is highly variable. With the exception of office systolic blood pressure (BP), predictors of the BP‐lowering effect have not been identified. Because dietary sodium intake influences sympathetic drive, and, conversely, sympathetic activity influences salt sensitivity in hypertension, we investigated 24‐hour urinary sodium excretion in participants of the SYMPATHY trial. SYMPATHY investigated RDN in patients with resistant hypertension. Both 24‐hour ambulatory and office BP measurements were end points. No relationship was found for baseline sodium excretion and change in BP 6 months after RDN in multivariable‐adjusted regression analysis. Change in the salt intake–measured BP relationships at 6 months vs baseline was used as a measure for salt sensitivity. BP was 8 mm Hg lower with similar salt intake after RDN, suggesting a decrease in salt sensitivity. However, the change was similar in the control group, and thus not attributable to RDN.     

Analysis of tracheostoma morphology

Objectives: Existing fixation methods of automatic speaking valves (ASVs) suffer from shortcomings which partly are the result of insufficient conformity of the intratracheal fixation method’s shape to the tracheostoma anatomy. However, quantitative data are lacking and will be helpful to analyse solutions for airtight fixation. This article provides such data.

Patients and methods: The tracheostoma morphology was measured in computerized tomography scans of 20 laryngectomized patients. Measured were transverse and sagittal diameters, transition angle between skin level and tracheostoma lumen and between the tracheostoma lumen to the trachea, TE valve placement and stoma depth.

Results: The mean transverse and sagittal diameters of the stoma at the peristomal lip are 19.2?mm [standard deviation (SD 5.2?mm)] and 17.6?mm (SD 5.3?mm), respectively. The mean transition angles are 84.5° (SD 15.6°) at skin level and 153.6° (SD 11.7°) into the trachea. The mean distance between TE valve and peristomal lip is 13.5?mm (SD 7.0?mm). The mean stoma depth is 14.0?mm (SD 6.4?mm).

Conclusions: Due to the large variation, no ‘average tracheostoma morphology’, suitable for shaping a generic intratracheal fixation device, can be defined. Therefore, providing an airtight fixation in each patient would require a large range of different sizes, customization or a new approach.     

The prominent role of the liver in the elimination of asymmetric dimethylarginine (ADMA) and the consequences of impaired hepatic function

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), the enzyme which converts the amino acid arginine into nitric oxide (NO). ADMA has been identified as an important risk factor for cardiovascular diseases. Besides the role of ADMA in cardiovascular diseases, it also seems to be an important determinant in the development of critical illness, (multiple) organ failure, and the hepatorenal syndrome. ADMA is eliminated from the body by urinary excretion, but it is mainly metabolized by the dimethylarginine dimethylaminohydrolase (DDAH) enzymes that convert ADMA into citrulline and dimethylamine. DDAH is highly expressed in the liver, which makes the liver a key organ in the regulation of the plasma ADMA concentration. The prominent role of the liver in the elimination of ADMA and the consequences of impaired hepatic function on ADMA levels will be discussed in this article.