A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Infantile fibrosarcoma with an EGFR kinase domain duplication: Underlining a close relationship with congenital mesoblastic nephroma and highlighting a similar morphological spectrum.

Infantile fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) are locally aggressive tumors primarily occurring in infants. Both IFS and the cellular subtype of CMN show overlapping morphological features and an ETV6-NTRK3 fusion, suggesting a close relationship. An activating alteration of EGFR, based on an EGFR kinase domain duplication (KDD), occurs in a subset of CMNs lacking an NTRK3 rearrangement, especially in the classic and mixed type. So far no EGFR-KDDs have been detected in IFS. We describe four pediatric tumors at the extremities (leg, n = 2; foot and arm n = 1) with histological features of IFS/CMN. Two cases showed classic IFS morphology while two were similar to classic/mixed type CMN. In all cases, an EGFR-KDD was identified without detection of a fusion gene. There were no abnormalities of the kidneys in any of the patients. This is the first description of IFS with an EGFR-KDD as driver mutation, supporting that IFS and CMN are similar lesions with the same morphological and genetic spectrum. Pathologists should be aware of the more fibrous variant of IFS, similar to classic/mixed type CMN. Molecular analyses are crucial to treat these lesions adequately, especially with regard to the administration of tyrosine kinase inhibitors.

Predicting poor outcome in patients with suspected COVID-19 presenting to the Emergency Department (COVERED) - Development, internal and external validation of a prediction model.

BACKGROUND: A recent systematic review recommends against the use of any of the current COVID-19 prediction models in clinical practice. To enable clinicians to appropriately profile and treat suspected COVID-19 patients at the emergency department (ED), externally validated models that predict poor outcome are desperately needed. OBJECTIVE: Our aims were to identify predictors of poor outcome, defined as mortality or ICU admission within 30 days, in patients presenting to the ED with a clinical suspicion of COVID-19, and to develop and externally validate a prediction model for poor outcome. METHODS: In this prospective, multi-center study, we enrolled suspected COVID-19 patients presenting at the EDs of two hospitals in the Netherlands. We used backward logistic regression to develop a prediction model. We used the area under the curve (AUC), Brier score and pseudo-R2 to assess model performance. The model was externally validated in an Italian cohort. RESULTS: We included 1193 patients between March 12 and May 27 2020, of whom 196 (16.4%) had a poor outcome. We identified 10 predictors of poor outcome: current malignancy (OR 2.774; 95%CI 1.682-4.576), systolic blood pressure (OR 0.981; 95%CI 0.964-0.998), heart rate (OR 1.001; 95%CI 0.97-1.028), respiratory rate (OR 1.078; 95%CI 1.046-1.111), oxygen saturation (OR 0.899; 95%CI 0.850-0.952), body temperature (OR 0.505; 95%CI 0.359-0.710), serum urea (OR 1.404; 95%CI 1.198-1.645), C-reactive protein (OR 1.013; 95%CI 1.001-1.024), lactate dehydrogenase (OR 1.007; 95%CI 1.002-1.013) and SARS-CoV-2 PCR result (OR 2.456; 95%CI 1.526-3.953). The AUC was 0.86 (95%CI 0.83-0.89), with a Brier score of 0.32 and, and R2 of 0.41. The AUC in the external validation in 500 patients was 0.70 (95%CI 0.65-0.75). CONCLUSION: The COVERED risk score showed excellent discriminatory ability, also in an external validation. It may aid clinical decision making, and improve triage at the ED in health care environments with high patient throughputs.

Association between pain phenotype and disease activity in rheumatoid arthritis patients: a non-interventional, longitudinal cohort study.

BACKGROUND: In well-controlled rheumatoid arthritis (RA) without significant joint damage, a substantial proportion of patients complain of persistent pain. Previous studies have identified different pain phenotypes in RA, in which non-nociceptive pain phenotypes are associated with higher concurrent disease activity scores. In this longitudinal study, we explored associations between pain phenotypes and long-term disease activity outcome in RA patients. Secondly, we explored whether pain phenotype is associated with comorbid conditions. METHODS: One hundred eighty established RA patients were classified with a nociceptive (61%) or a non-nociceptive (39%) pain phenotype, based on their responses to the painDETECT-questionnaire. Two years of clinical follow-up data on disease activity outcomes were collected. Information on comorbid diseases was derived from electronic patient files. RESULTS: Patients with a non-nociceptive pain phenotype showed higher mean disease activity scores (DAS28, 2.57; 95% CI, 2.37-2.77 vs. 2.11; 95% CI, 1.94-2.27; p < 0.001) and a twofold lower chance of achieving sustained DAS28 remission (OR = 0.49; 95% CI, 0.26-0.92; p = 0.020). Only the tender joint count and patient global health significantly differed between the pain phenotype groups. Patients with a non-nociceptive pain phenotype had more often been diagnosed with concurrent fibromyalgia (9.9% vs. 0.9%; p = 0.007) and other pain-associated comorbid diseases (52.1% vs. 35.8%; p = 0.030) compared with patients with a nociceptive pain phenotype. CONCLUSION: This longitudinal study showed consistently worse long-term disease activity outcomes in RA patients with a non-nociceptive pain phenotype which appeared to be mainly due to differences in the subjective components of the disease activity score. TRIAL REGISTRATION: The DREAM cohort study is registered in the Netherlands Trial Register: NTR578.

Glucagon-like peptide-1 receptor agonist treatment reduces beta cell mass in normoglycaemic mice.

AIMS/HYPOTHESIS: Incretin-based therapies improve glycaemic control in patients with type 2 diabetes. In animal models of diabetes, glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase beta cell mass. GLP-1RAs are also evaluated in non-diabetic individuals with obesity and cardiovascular disease. However, their effect on beta cell mass in normoglycaemic conditions is not clear. Here, we investigate the effects of the GLP-1RA liraglutide on beta cell mass and function in normoglycaemic mice. METHODS: C57BL/6J mice were treated with the GLP-1RA liraglutide or PBS and fed a control or high-fat diet (HFD) for 1 or 6 weeks. Glucose and insulin tolerance tests were performed after 6 weeks. BrdU was given to label proliferating cells 1 week before the animals were killed. The pancreas was taken for either histology or islet isolation followed by a glucose-induced insulin-secretion test. RESULTS: Treatment with liraglutide for 6 weeks led to increased insulin sensitivity and attenuation of HFD-induced insulin resistance. A reduction in beta cell mass was observed in liraglutide-treated control and HFD-fed mice at 6 weeks, and was associated with a lower beta cell proliferation rate after 1 week of treatment. A similar reduction in alpha cell mass occurred, resulting in an unchanged alpha to beta cell ratio. In contrast, acinar cell proliferation was increased. Finally, islets isolated from liraglutide-treated control mice had enhanced glucose-induced insulin secretion. CONCLUSIONS/INTERPRETATION: Our data show that GLP-1RA treatment in normoglycaemic mice leads to increases in insulin sensitivity and beta cell function that are associated with reduced beta cell mass to maintain normoglycaemia.

Married women's economic dependency in The Netherlands, 1979-1991.

The present paper offers a replication of an analysis by Sørensen and McLanahan (1987) of 1940-1980 USA data on trends in married women's economic dependency, this time using Dutch income data for 1979-1991. The results show that in the Netherlands, as opposed to the USA, a vast majority of the wives are still completely or strongly dependent on their husband's income. Yet, also Dutch wives' economic dependency is decreasing at a significant rate. Despite clear life course differences that yet seem to persist, we observe declining levels of dependency within each age group. This declining trend seems to reflect mostly changes in married women's employment status over time. An implication of the reported trend, however, is that it becomes increasingly important to study the influence of the social position of both partners.