Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study.

BACKGROUND: Clinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population. AIM: To determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. METHODS: Two large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument. RESULTS: Between 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis. CONCLUSIONS: High-risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

Measurement of Dynamic Hyperinflation During the 6-Minute Walk Test Using a Mobile Device.

BACKGROUND: Dynamic hyperinflation is a major cause of dyspnea in patients with COPD. Dynamic hyperinflation is usually measured with cardiopulmonary exercise testing, but this test requires maximal effort from the patient, and inspiratory capacity (IC) measurements may influence test results. This study investigated another approach by measuring dynamic hyperinflation during the more natural and better-tolerated 6-min walk test (6MWT), using a mobile system for IC measurements. METHODS: Twenty subjects were studied, including 10 healthy subjects and 10 subjects with COPD. Each subject performed a pair of 6MWTs. RESULTS: The study showed that test-retest reliability in healthy subjects was excellent (intraclass correlation coefficient 0.995). In addition, mean resting IC in healthy subjects (3.27 ± 0.77 L) was not affected at the end of the 6MWT, whereas mean resting IC in subjects with COPD (2.45 ± 0.90 L) decreased to 1.93 L ± 0.68 L at the end of the 6MWT (P = .004). The tolerability of the device for subjects with COPD appeared to be only slightly hampered by an increased sense of dyspnea attributed to wearing a mask. CONCLUSIONS: This study provides a proof of principle for mobile IC measurements during the 6MWT, demonstrating good test performance, reasonable tolerability, and a power to differentiate normal from pathologic conditions.

Current perspective: Osimertinib-induced QT prolongation: new drugs with new side-effects need careful patient monitoring.

An increasing number of tyrosine kinase inhibitors (TKIs) are available for the treatment of non-small cell lung cancer (NSCLC). QT prolongation is one of the known, but relatively rare, adverse events of several TKIs (e.g. osimertinib, crizotinib, ceritinib). Screening for QT prolongation in (high risk) patients is advised for these TKIs. When a QT prolongation develops, the physician is challenged with the question whether to (permanently) discontinue the TKI. In this perspective, we report on a patient who developed a grade III QT prolongation during osimertinib (a third-generation epidermal growth factor receptor [EGFR]-TKI) treatment. On discontinuation of osimertinib, she developed a symptomatic disease flare, not responding to subsequent systemic treatment. The main aim of this perspective is to describe the management of QT prolongation in stage IV EGFR driver mutation NSCLC patients. We also discuss the ethical question of how to weigh the risk of a disease flare due to therapy cessation against the risk of sudden cardiac death. A family history of sudden death and a prolonged QT interval might indicate a familiar long QT syndrome. We have summarised the current monitoring advice for TKIs used in the treatment of lung cancer and the most common drug-TKI interactions to consider and to optimise TKI treatment in lung cancer patients.

Predictive validity of the Glasgow Blatchford Bleeding Score in an unselected emergency department population in continental Europe.

BACKGROUND AND AIM: Glasgow Blatchford Bleeding Score stratifies patients presenting with acute upper gastrointestinal haemorrhage at the emergency department according to the likelihood of the need for treatment. The objective of this study was to validate the Glasgow Blatchford Bleeding Score for use in an emergency department in the Netherlands. Furthermore, we assessed its clinical usefulness for safe discharge of low-risk acute upper gastrointestinal haemorrhage patients and compared its test validity to that of other scoring systems. METHODS: This multicentre historic cohort study was conducted in two hospitals in the Netherlands. All 478 patients presenting with a suspicion of acute upper gastrointestinal haemorrhage at our emergency departments during a 1-year period were included. For each patient we calculated Glasgow Blatchford Bleeding Score and other commonly used scores. Test validity was assessed using the receiver operated characteristics curve analysis; calibration plots were used to assess the probability of the need for treatment of different levels of the scores. RESULTS: Glasgow Blatchford Bleeding Score had a good discriminative ability in predicting the need for treatment, receiver operated characteristics curve analysis showed an area under the curve of 0.879. Counting a score of 2 or less as low risk (negative), 104 patients (21.7%) were classified as low-risk, with a negative predictive value of 98.1%. These results were superior to those of the other scoring systems. CONCLUSION: Patients presenting at an emergency department in continental Europe with acute upper gastrointestinal haemorrhage and a Glasgow Blatchford Bleeding Score of 2 or less can be safely discharged. The Glasgow Blatchford Bleeding Score performed better than the other commonly used scoring systems.