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.