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Background and aims: – Pseudoxanthoma elasticum (PXE) is a rare genetic disease caused by pathogenic mutations in the ABCC6 gene, resulting in low values of inorganic pyrophosphate (PPi). While low PPi is thought to contribute to arterial calcification, it remains unclear whether this fully explains premature calcification in PXE. It has been hypothesized that the ABCC6 gene could be related to dyslipidemia, which could contribute to vascular calcification seen in PXE. The aim of this study is to evaluate the relation between PXE and plasma lipid concentrations in a large cohort of PXE patients compared with reference values for the general population and compared with non-PXE controls. Methods: – The plasma concentrations of total cholesterol, HDL-cholesterol, tiglycerides, and LDL-cholesterol of 312 PXE patients were compared to age- and sex-matched modeled data of the general Dutch population. Differences in median lipid levels were compared with Mann-Whitney-U test. Secondly, plasma lipid concentrations of 44 PXE patients were compared to 44 not-genetically related relatives (spouses or friends), with linear models adjusted for age, sex and BMI. Results: – Total cholesterol in PXE patients was 5.6 [IQR 4.6–6.4] mmol/L versus 5.3 [IQR 4.7–6.0] mmol/L (p

Background: Scapular notching continues to be associated with reverse shoulder arthroplasty (RSA) and is thought to lead to fewer outcomes. Decreasing the humeral neck-shaft angle (NSA) has been associated with decreased incidence of scapular notching. Lateralizing the glenosphere center of rotation (COR) has also been proposed to decrease notching; however, its effect in lower NSA RSA is less understood. The purpose of this study was to compare the impact of the medial (0 mm) and lateral (4 mm) COR on the incidence of scapular notching and clinical outcomes after RSA with a 135° NSA humeral component. Methods: We performed a multicenter retrospective comparative cohort of 82 patients with cuff tear arthropathy (41 in each cohort) who underwent RSA with a 135° NSA humeral component and a glenosphere COR of either 0 mm (medialized COR [MCOR]) or 4 mm (lateralized COR [LCOR]) of lateralization. RSA was performed using the same 135° humeral system and baseplate design. All patients had 2-year radiographic and clinical follow-up. Postoperative radiographs were evaluated for scapular notching. Clinical outcomes included American Shoulder and Elbow Surgeons scores, visual analog pain scale, Simple Assessment Numeric Evaluation, and active range of motion. Results: The overall incidence of scapular notching was 22.0%. There was no significant difference in scapular notching between cohorts: 24.4% in the MCOR and 19.5% in the LCOR (P = .625). Both cohorts had significant improvements in American Shoulder and Elbow Surgeons scores, visual analog pain scale, Simple Assessment Numeric Evaluation, and active range of motion postoperatively (P

Background: In shoulder arthroplasty, cerclage fixation techniques are used to stabilize osteotomies, fractures, and allografts. Fixation techniques including cerclage with metal and polymer cables have been described. The purpose of this study was to evaluate suture cerclage fixation of the humeral shaft during shoulder arthroplasty. Materials and methods: Shoulder arthroplasty cases performed from 2012-2017 by 3 fellowship-trained shoulder arthroplasty surgeons were reviewed. Cases in which suture cerclage was used for osteotomy, fracture, or allograft fixation were identified. Demographic data, indications, implant types, fixation techniques, and complications were reviewed. Postoperative radiographs were analyzed for union, component loosening, and loss of fixation. American Shoulder and Elbow Surgeons and Single Assessment Numeric Evaluation scores were collected preoperatively and postoperatively. Results: A total of 27 patients (3 primary and 24 revision cases) with a mean age of 69.6 years (range, 28-88 years) were available for follow-up at a mean of 12.6 months (range, 0.8-42.3 months) postoperatively. Humeral osteotomy alone was performed in 15 cases. Allograft alone was used in 1 case. Both allograft and osteotomy were used in 6 cases. Complications occurred in 3 patients (11%), comprising 1 postoperative periprosthetic fracture and 2 prosthetic joint infections; all required further surgery. Radiographs at final follow-up showed healing of all osteotomies and fractures. No hardware failure or implant loosening occurred. The mean postoperative American Shoulder and Elbow Surgeons and Single Assessment Numeric Evaluation scores were significantly improved (α = .05) compared with preoperative scores, from 21.4 to 44.5 (P = .002) and from 26.7 to 74.1 (P < .001), respectively. Conclusion: Suture cerclage is safe and effective for humeral fixation in shoulder arthroplasty.

Tetanus antitoxin, produced in animals, has been used for the prevention and treatment of tetanus for more than 100 years. The availability of antitoxins, ethical issues around production, and risks involved in the use of animal derived serum products are a concern. We therefore developed a llama derived single-domain antibody (VHH) multimer to potentially replace the conventional veterinary product. In total, 28 different tetanus neurotoxin (TeNT) binding VHHs were isolated, 14 of which were expressed in yeast for further characterization. Four VHH monomers (T2, T6, T15 and T16) binding TeNT with high affinity (KD

Competing Interests: Conflict of interest The Department of Plastic & Reconstructive Surgery of the Erasmus MC received funding from POLYTECH Health & Aesthetics GmbH in the form of financial support for personnel costs for one PhD candidate (no grant number available) from July 2018 until July 2021. Three authors are affiliated to the Dutch Institute for Clinical Auditing (DICA), a non-profit organization, which facilitates the Dutch Breast Implant Registry (DBIR). MRDM is the data processor of data in DBIR and the Patient Access Tool described in this paper. All remaining authors have declared no conflicts of interest.

Scope: Antimicrobial stewardship teams are responsible for implementing antimicrobial stewardship programmes (ASP). However, in many countries, lack of funding challenges this obligation. A consensus procedure was performed to investigate which structural activities need to be performed by Dutch stewardship teams and how much time (and thus full-time equivalent (FTE) labor) is needed to perform these activities., Methods: In 2015, an electronic survey, based on a nonsystematic literature search and interviews with seven experienced stewardship teams, was sent to 21 stewardship teams that performed an ASP. This was followed by a semistructured face-to-face consensus meeting. Fourteen stewardship teams completed the survey (18% of Dutch acute-care hospitals), and 13 participated in the consensus meeting., Recommendations: The hours needed each year are dependent on hospital size and number of stewardship objectives monitored. If all activities are performed at a minimal base (one stewardship objective; minimal staffing standard), time investment was estimated to be 1393 to 2680 hours annually in the early phase, corresponding with 0.87 (300 beds) to 1.68 FTE (1200 beds), with a further increase to minimally 1.25 to 3.18 FTE in the following years with three stewardship objectives monitored (optimal staffing standards during the first few years of implementing an ASP). This consensus on required human resources provides a directive for structural financial support of stewardship teams in the Dutch context. Some stewardship activities (and related time investments) might be specific to the Dutch context and hospital setting. To develop standards for other settings, our methodology could be applied., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Childhood urinary tract infections (UTIs) can lead to renal scarring and ultimately to terminal renal failure, which has a high impact on quality of life, survival, and health-care costs. Variation in the treatment of UTIs between practices is high., Objective: To assess the cost-effectiveness of a maximum care model for UTIs in children, implying more testing and antibiotic treatment, compared with current practice in primary care in The Netherlands., Methods: We performed a probabilistic modeling study using Markov models. Figures used in the model were derived from a systematic review of the research literature. Multidimensional Monte Carlo simulation was used for the probabilistic analyses., Results: Maximum care gained 0.00102 (males) and 0.00219 (girls) QALYs (quality-adjusted life-years) and saved 42.70 euro (boys) and 77.81 euro (girls) in 30 years compared with current care, and was thus dominant. Net monetary benefit of maximum care ranged from 20 euro to 200 euro for a willingness to pay for a QALY ranging from 0 euro to 80,000 euro, respectively. Maximum care was also dominant over improved current care, although less dominant than to current care., Conclusions: This study suggested that maximum care for childhood UTI was dominant in the long run to current care, meaning that it delivered more quality of life at lower costs. Nevertheless, making firm conclusions is not possible, given the limitations of the input data.

Objective: To provide insight into parents' awareness of and knowledge about urinary tract infections (UTIs) in young children., Methods: Twenty interviews with parents who had a child recently diagnosed with a UTI were audiotaped, transcribed verbatim, and qualitatively analysed., Results: Most parents knew the typical symptoms related to UTI. But, according to the parents, neither they nor all general practitioners (GPs) thought of a UTI in case of atypical symptoms. The awareness that UTI can be a serious illness usually came to parents later, partly because health care workers often did not explicitly mention this. According to the parents, health care workers should be more aware of UTIs in children. Parents felt that health education or mass screening might not be desirable because it would increase anxiety or would be perceived as not relevant., Conclusion: Parents could not consistently recognise UTI in their children and were most times unaware of the possible consequences of a UTI. Nevertheless, parents were sceptical about health education and mass screening., Practice Implications: There seems little scope for health education addressed at parents or screening for UTI in young children. Instead, physicians and nurses should be alert for the possibility of UTIs in young children, and more information should be given once a UTI is diagnosed.

A blocking ELISA with specific antibodies against a synthetic sulpholipo-polysucrose (SL-Ficoll400) was developed to quantify this vaccine adjuvant component in faeces with the purpose of estimating the uptake thereof by the gastrointestinal tract after oral administration. Specific monoclonal antibodies (MABs) prepared against SL-Ficoll400 did not cross-react with components in murine faeces. SL-Ficoll400 inhibited the reactivity of the MABs in a dose-dependent fashion in the blocking ELISA and the concentration causing 50% inhibition (IC50) was about 1 microg SL-Ficoll400 per milliliter. Derivatives of Ficoll400 lacking sulphate or lipid groups or both were unable to block the MABs (IC50 > 1000 microg/ml) which confirmed the specificity of the test system. Quantification of SL-Ficoll400 in extracts of faeces of untreated mice spiked with SL-Ficoll400 revealed that more than 90% could be recovered. The blocking ELISA was used to quantify SL-Ficoll400 in the faeces of mice given this compound orally. One, two and three days after oral administration, the cumulative recovery of SL-Ficoll400 in faeces was 30, 40 and 92%, respectively. From these data, we concluded that the MABs obtained were specific for SL-Ficoll400, that SL-Ficoll400 in murine faeces could be quantified by a blocking ELISA with MABs and that SL-Ficoll400 was poorly absorbed by the gastrointestinal tract.

In this paper we compare a solid-phase enzyme immunoassay (EIA) with a neutralization-inhibition enzyme immunoassay (NI-EIA) for the determination of anti-idiotypic antibodies against Semliki Forest virus (SFV)-neutralizing monoclonal antibodies (MAs) UM 5.1 (IgG2a) and UM 1.4 (IgG2a). Against these MAs strong immune sera were induced in female BALB/c mice by two subcutaneous injections, 3 weeks apart, with keyhole limpet hemocyanin coupled MA mixed with the saponin Quil A. Rabbit immune sera were prepared by intracutaneous injections of purified MA mixed with either FCA (first immunization) or IFA (second and third immunization). In the NI-EIA serum is preincubated with neutralizing MA, in wells of 96-well plates, before SFV is added. Binding of anti-idiotypic antibodies to MA results in a diminished capacity of that MA to neutralize SFV. After 1 h incubation with SFV L cells are added and residual infectious virus is allowed to multiply for 6 h at 37 degrees C. Then the monolayers are fixed with glutaraldehyde and subsequently SFV is quantified with a horseradish peroxidase-labelled SFV-specific MA. Low absorbance values indicate that the neutralizing capacity of MA is intact and that blocking antibodies were not present in serum. In contrast high absorbance values indicate that blocking (anti-idiotypic) antibodies had abrogated the neutralizing capacity of MA. With the strongly neutralizing MA UM 5.1 as idiotypic antigen the NI-EIA proved to be at least as sensitive as the solid-phase EIA. Furthermore both normal mouse serum-absorbed rabbit immune sera and mouse immune sera were not cross-reactive in both solid-phase EIA and NI-EIA.