Aortic intramural haematoma associated with the use of nintedanib.

We report a 74-year-old patient who developed an acute aortic syndrome (AAS) with intramural haematoma (IMH) during treatment with nintedanib, a tyrosine kinase inhibitor. As we suspected a role for nintedanib, this was immediately interrupted. Four months later, a computed tomographic angiography (CTA) showed significant regression of the IMH. Therefore, we state that, when patients use nintedanib and develop acute chest or back pain, diagnostic work-up for AAS should be considered. Furthermore, other risk factors for AAS, such as hypertension, genetic diseases and comedication should be taken into account when prescription of medication of this class is considered.

Hemocytometric characteristics of COVID-19 patients with and without cytokine storm syndrome on the sysmex XN-10 hematology analyzer.

OBJECTIVES: COVID-19 is an ongoing global pandemic. There is an urgent need for identification and understanding of clinical and laboratory parameters related to progression towards a severe and fatal form of this illness, often preceded by a so-called cytokine-storm syndrome (CSS). Therefore, we explored the hemocytometric characteristics of COVID-19 patients in relation to the deteriorating clinical condition CSS, using the Sysmex XN-10 hematology analyzer. METHODS: From March 1st till May 16th, 2020, all patients admitted to our hospital with respiratory complaints and suspected for COVID-19 were included (n=1,140 of whom n=533 COVID-19 positive). The hemocytometric parameters of immunocompetent cells in peripheral blood (neutrophils [NE], lymphocytes [LY] and monocytes [MO]) obtained upon admission to the emergency department (ED) of COVID-19 positive patients were compared with those of the COVID-19 negative ones. Moreover, patients with CSS (n=169) were compared with COVID-19 positive patients without CSS, as well as with COVID-19 negative ones. RESULTS: In addition to a significant reduction in leukocytes, thrombocytes and absolute neutrophils, it appeared that lymphocytes-forward scatter (LY-FSC), and reactive lymphocytes (RE-LYMPHO)/leukocytes were higher in COVID-19-positive than negative patients. At the moment of presentation, COVID-19 positive patients with CSS had different neutrophils-side fluorescence (NE-SFL), neutrophils-forward scatter (NE-FSC), LY-FSC, RE-LYMPHO/lymphocytes, antibody-synthesizing (AS)-LYMPHOs, high fluorescence lymphocytes (HFLC), MO-SSC, MO-SFL, and Reactive (RE)-MONOs. Finally, absolute eosinophils, basophils, lymphocytes, monocytes and MO-FSC were lower in patients with CSS. CONCLUSIONS: Hemocytometric parameters indicative of changes in immunocompetent peripheral blood cells and measured at admission to the ED were associated with COVID-19 with and without CSS.

Diagnostic criteria for initial orthostatic hypotension: a narrative review.

Abnormalities in orthostatic blood pressure changes upon active standing are associated with morbidity, mortality, and reduced quality of life. However, over the last decade, several population-based cohort studies have reported a remarkably high prevalence (between 25 and 70%) of initial orthostatic hypotension (IOH) among elderly individuals. This has raised the question as to whether the orthostatic blood pressure patterns in these community-dwelling elderly should truly be considered as pathological. If not, redefining of the systolic cutoff values for IOH (i.e., a value ≥ 40 mmHg in systolic blood pressure in the first 15 s after standing up) might be necessary to differ between normal aging and true pathology. Therefore, in this narrative review, we provide a critical analysis of the current reference values for the changes in systolic BP in the first 60 s after standing up and discuss how these values should be applied to large population studies. We will address factors that influence the magnitude of the systolic blood pressure changes following active standing and the importance of standardization of the stand-up test, which is a prerequisite for quantitative, between-subject comparisons of the postural hemodynamic response.

Angiotensin-(1-7) as a strategy in the treatment of hypertension?

PURPOSE OF REVIEW: The renin-angiotensin system plays an important role in cardiovascular disease via the production of angiotensin II. Over the past decades, however, more and more evidence has accumulated suggesting an important role for another angiotensin: Angiotensin-(1-7) [Ang-(1-7)]. In this review, we discuss the recent findings on the effects of Ang-(1-7) and the angiotensin-converting enzyme2/Ang-(1-7)/Mas axis on the cardiovascular system. RECENT FINDINGS: Recent studies demonstrated that Ang-(1-7) exerts a vasodilatory and antiproliferative effect via stimulation of the Mas receptor and inhibition of the effects of angiotensin-type 1 receptor stimulation by angiotensin II. This results in a dynamic equilibrium between Ang-(1-7) and angiotensin II. Various animal studies have demonstrated that Ang-(1-7) has beneficial effects on blood pressure, kidney function, and the prevention of cardiovascular disease. Although targeting the angiotensin-converting enzyme 2/Ang-(1-7)/Mas axis has been difficult so far, several new therapeutic strategies are being developed. Promising results of these new strategies on blood pressure and cardiovascular disease were demonstrated in animal studies. SUMMARY: The beneficial effects of the angiotensin-converting enzyme2/Ang-(1-7)/Mas axis have been widely demonstrated in animal studies and provide a promising basis for further development of drugs targeting this axis of the renin-angiotensin system. Further research in humans, however, is necessary to make a serious step forward. VIDEO ABSTRACT: http://links.lww.com/CONH/A8.

Differentiating between segmental arterial mediolysis and other arterial vasculopathies to establish an early diagnosis - a systematic literature review and proposal of new diagnostic criteria.

Segmental arterial mediolysis (SAM) is a rare vascular disease, characterized by acute but transient vulnerability of the wall of medium-sized arteries. The most characteristic feature of SAM is its biphasic course: an injurious phase marked by acute weakness of the arterial wall leading to acute dissection and/or hemorrhage, followed by a reparative phase in which granulation tissue and fibrosis restore the injured arterial wall. Residual stenosis, aneurysms, and/or arterial wall irregularities may remain visible on future imaging studies. Differentiating between SAM and other arterial vasculopathies is difficult due to its similarities with many other vascular diseases, such as vasculitis, fibromuscular dysplasia, inherited connective tissue disorders, and isolated visceral artery dissection. In this systematic review, we provide an overview on SAM, with an emphasis on the differential diagnosis and diagnostic work-up. We propose new diagnostic criteria to help establish a prompt diagnosis of SAM, illustrated by case examples from our multidisciplinary vascular clinic.

Thyroid and adrenal incidentalomas on chest CT: Prevalence, diagnostic work-up and outcomes in a cohort of COVID-19 suspected patients.

OBJECTIVE: Due to increased use of computed tomography (CT), prevalence of thyroid and adrenal incidentalomas is rising. Yet, previous studies on the outcomes of diagnostic work-up of incidentalomas are subjected to inclusion bias. Therefore, we aimed to investigate prevalence and outcomes of diagnostic work-up of thyroid and adrenal incidentalomas detected on chest CT in a less selected population of COVID-19 suspected patients. DESIGN: A retrospective, observational cohort study. METHODS: We included all COVID-19 suspected patients who underwent chest CT between March 2020 and March 2021. Radiology reports and medical records were reviewed for the presence and subsequent diagnostic work-up of thyroid and adrenal incidentalomas. RESULTS: A total of 1,992 consecutive COVID-19 patients were included (59.4% male, median age 71 years [IQR: 71-80]). Thyroid and adrenal incidentalomas were identified in 95 (4.8%) and 133 (6.7%) patients, respectively. Higher prevalence was observed with increasing age, among female patients and in patients with malignancy. Forty-four incidentalomas were further analyzed, but no malignancies were found. Only three lesions were hormonally active (1 thyrotoxicosis and 2 mild autonomous cortisol secretion). Diagnostic work-up did not lead to any change in clinical management in 97.7% of the analyzed patients. CONCLUSION: Prevalence rates of thyroid and adrenal incidentalomas on chest CT in a less selected COVID-19 cohort were 4.8% and 6.7%, respectively. Yet, as all incidentalomas turned out to be benign and only three lesions were (mildly) hormonally active, this raises the question whether intensive diagnostic work-up of incidentalomas is necessary in all patients.

Deferring diagnostic evaluation of suspected deep vein thrombosis using direct oral anticoagulant or low-molecular-weight heparin as a single dose anticoagulant: A prospective real-world study in a regionwide care pathway.

BACKGROUND: Patients with suspected deep vein thrombosis (DVT) are typically referred to the emergency department for immediate evaluation. To enhance efficiency, our hospital implemented a regional, general practitioner (GP)-driven DVT care pathway, deferring diagnostic evaluation to a scheduled outpatient DVT clinic appointment the following day. Patients receive a single dose anticoagulant from their GP to prevent thrombosis progression while awaiting diagnostic workup. This prospective study aimed to evaluate the safety and patient preferences regarding the DVT care pathway and the type of single dose anticoagulant (low-molecular-weight heparin (LMWH) vs. direct oral anticoagulant (DOAC)). METHODS: Patients enrolled in the DVT care pathway between June 2021 and July 2023 were eligible. Until July 2022, LMWH was administered, and thereafter, the protocol recommended DOAC as the single dose anticoagulant. Patients completed questionnaires, incorporating patient-reported outcome and experience measures (PROMs/PREMs), during their DVT clinic visit and after five days. The primary endpoint was bleeding events within 72 h of receiving the single dose anticoagulant. RESULTS: Of 460 included patients, 229 received LMWH and 231 received DOAC as the single dose anticoagulant. DVT was confirmed in 24.8 % of patients. No major or clinically relevant non-major bleeding were reported. LMWH was associated with more minor bleedings (22.3 % vs. DOAC 13.4 %), primarily attributed to injection site hematomas. Patients reported high satisfaction with the DVT care pathway (96.5 %) and generally preferred DOAC over LMWH. CONCLUSION: Deferring diagnostic evaluation for DVT using a single dose of either LMWH or DOAC in a real-world population is deemed safe. Considering practical advantages, patient preferences, and fewer skin hematomas, we favor DOACs as the single dose anticoagulant in this care pathway.

Deferring diagnostic evaluation for suspected deep venous thrombosis using a single dose of anticoagulant: Real-world data from a regionwide care pathway.

BACKGROUND: Patients with suspected deep venous thrombosis (DVT) are typically referred to the emergency department (ED) for immediate evaluation. However, this often contributes to ED overcrowding and necessitates round-the-clock sonographic examinations. Therefore, we implemented a regionwide care pathway for deferring diagnostic workup of suspected DVT until the following day. Patients receive a single anticoagulant dose from their general practitioner (GP) to prevent progression of DVT in the interval between referral and diagnostic evaluation. The next day, patients undergo comprehensive evaluation at our outpatient DVT clinic, including venous ultrasound. This retrospective study aims to provide real-world data on the safety of this care pathway regarding the occurrence of bleeding complications and pulmonary embolism (PE). METHODS: We included all GP-referred patients with suspected DVT in 2018 and 2019. Patients with absolute contraindications to deferred evaluation or anticoagulation were excluded. The primary endpoint was the occurrence of bleeding complications. Secondary endpoints included PE events and all-cause mortality within seven days following DVT evaluation. RESULTS: Among 1,024 included patients, DVT was confirmed in 238 patients (23.2%) and superficial thrombophlebitis in 98 patients (9.6%). No bleeding events were recorded in patients in whom DVT was ruled out. PE was confirmed in eight patients on the same day as DVT evaluation (0.8%, 95%CI 0.4-1.6) and in six patients within seven days following DVT evaluation (0.6%, 0.2-1.3%). No deaths occurred during this timeframe. CONCLUSION: This real-world study observed a very low incidence of bleeding complications and PE events, indicating that this care pathway of deferred DVT workup is safe and may offer a more streamlined diagnostic approach for patients with suspected DVT.

Stress-Induced Graves Disease: Spontaneous Recovery After Stress Relief.

Purpose: Emotional stress is a precipitating factor for Graves disease (GD). However, the influence of stress relief on the course of GD is unknown. Here, we present a series of patients diagnosed with stress-induced GD in whom stress relief alone led to remission of GD. Cases: We report on 11 patients in whom hyperthyroid symptoms started just after severe emotional stress. All patients had suppressed thyroid-stimulating hormone (TSH) levels and elevated free thyroxine (FT4; 22.2-49.5 pmol/L) and TSH-receptor antibody (TRAb; 0.57-40 U/L) levels and were subsequently diagnosed with stress-induced GD. However, all patients declined antithyroid drug treatment. Surprisingly, clinical and biochemical remission was observed in 9 out of 11 patients after 1 to 3 and 2 to 7 months of self-reported stress relief, respectively. Five patients showed long-lasting remission (median follow-up 2.3 years). In 4 patients, remission was initially achieved, but GD relapsed 1 to 4 years afterwards. In 2 patients, treatment with antithyroid drugs was initiated because of rapidly increasing FT4 levels. Baseline FT4 and TRAb levels tended to be higher in patients who did not achieve remission. Furthermore, patients without long-lasting remission were more frequently known to have prior thyroid disease. Conclusion: We report on a series of patients with stress-induced GD in whom stress relief alone led to remission of GD (thus without antithyroid drugs). This may indicate that clinicians could consider stopping antithyroid drug treatment or at least shortening the treatment period after stress relief in patients with stress-induced GD.

Pulmonary embolism in hospitalized COVID-19 patients: Short- and long-term clinical outcomes.

Introduction: Pulmonary embolism (PE) is a frequent complication in COVID-19. However, the influence of PE on the prognosis of COVID-19 remains unclear as previous studies were affected by misclassification bias. Therefore, we evaluated a cohort of COVID-19 patients whom all underwent systematic screening for PE (thereby avoiding misclassification) and compared clinical outcomes between patients with and without PE. Materials and methods: We included all COVID-19 patients who were admitted through the ED between April 2020 and February 2021. All patients underwent systematic work-up for PE in the ED using the YEARS-algorithm. The primary outcome was a composite of in-hospital mortality and ICU admission. We also evaluated long-term outcomes including PE occurrence within 90 days after discharge and one-year all-cause mortality. Results: 637 ED patients were included in the analysis. PE was diagnosed in 46 of them (7.2%). The occurrence of the primary outcome did not differ between patients with PE and those without (28.3% vs. 26.9%, p = 0.68). The overall rate of PE diagnosed in-hospital (after an initial negative PE screening in the ED) and in the first 90 days after discharge was 3.9% and 1.2% respectively. One-year all-cause mortality was similar between patients with and without PE (26.1% vs. 24.4%, p = 0.83). Conclusions: In a cohort of COVID-19 patients who underwent systematic PE screening in the ED, we found no differences in mortality rate and ICU admissions between patients with and without PE. This may indicate that proactive PE screening, and thus timely diagnosis and treatment of PE, may limit further clinical deterioration and associated mortality in COVID-19 patients.

Systematic screening versus clinical gestalt in the diagnosis of pulmonary embolism in COVID-19 patients in the emergency department.

BACKGROUND: Diagnosing concomitant pulmonary embolism (PE) in COVID-19 patients remains challenging. As such, PE may be overlooked. We compared the diagnostic yield of systematic PE-screening based on the YEARS-algorithm to PE-screening based on clinical gestalt in emergency department (ED) patients with COVID-19. METHODS: We included all ED patients who were admitted because of COVID-19 between March 2020 and February 2021. Patients already receiving anticoagulant treatment were excluded. Up to April 7, 2020, the decision to perform CT-pulmonary angiography (CTPA) was based on physician's clinical gestalt (clinical gestalt cohort). From April 7 onwards, systematic PE-screening was performed by CTPA if D-dimer level was ≥1000 ug/L, or ≥500 ug/L in case of ≥1 YEARS-item (systematic screening cohort). RESULTS: 1095 ED patients with COVID-19 were admitted. After applying exclusion criteria, 289 were included in the clinical gestalt and 574 in the systematic screening cohort. The number of PE diagnoses was significantly higher in the systematic screening cohort compared to the clinical gestalt cohort: 8.2% vs. 1.0% (3/289 vs. 47/574; p<0.001), even after adjustment for differences in patient characteristics (adjusted OR 8.45 (95%CI 2.61-27.42, p<0.001) for PE diagnosis). In multivariate analysis, D-dimer (OR 1.09 per 1000 µg/L increase, 95%CI 1.06-1.13, p<0.001) and CRP >100 mg/L (OR 2.78, 95%CI 1.37-5.66, p = 0.005) were independently associated with PE. CONCLUSION: In ED patients with COVID-19, the number of PE diagnosis was significantly higher in the cohort that underwent systematic PE screening based on the YEARS-algorithm in comparison with the clinical gestalt cohort, with a number needed to test of 7.1 CTPAs to detect one PE.

Exaggerated natriuresis after renal artery balloon angioplasty for flash pulmonary oedema: a potential complication in one-kidney renovascular hypertension.

Flash pulmonary oedema is a life-threatening complication of renal artery stenosis. We report a very rare complication in a patient with bilateral atherosclerotic renal artery stenosis who underwent unilateral renal artery angioplasty because of recurrent flash pulmonary oedema. Shortly after the procedure, she developed extreme polyuria (over 201 in the first 48 h) with massive natriuresis (>1000 mmol urinary sodium excretion in the first 24 h). Most likely, the occurrence of this phenomenon is related to the fact that her contralateral kidney was atrophic and no longer functioning due to total renal artery occlusion. We provide an overview of the literature and discuss several mechanisms that may contribute to the occurrence of this exaggerated natriuretic response in patients with one-kidney renovascular hypertension who undergo renovascular revascularization. We recommend close monitoring of natriuresis in such patients and - if needed - administration of intravenous isotonic saline (0.9% NaCl) to prevent hypovolemia.

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.

Validating the RISE UP score for predicting prognosis in patients with COVID-19 in the emergency department: a retrospective study.

OBJECTIVE: To mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed Risk Stratification in the Emergency Department in Acutely ill Older Patients (RISE UP) score has very good discriminatory value for short-term mortality in older patients in the emergency department (ED). It consists of six readily available items. We hypothesised that the RISE UP score could have discriminatory value for 30-day mortality in ED patients with COVID-19. DESIGN: Retrospective analysis. SETTING: Two EDs of the Zuyderland Medical Centre, secondary care hospital in the Netherlands. PARTICIPANTS: The study sample consisted of 642 adult ED patients diagnosed with COVID-19 between 3 March and until 25 May 2020. Inclusion criteria were (1) admission to the hospital with symptoms suggestive of COVID-19 and (2) positive result of the PCR or (very) high suspicion of COVID-19 according to the chest CT scan. OUTCOME: Primary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU). RESULTS: Within 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value for 30-day mortality (area under the receiver operating characteristic curve (AUC) 0.77, 95% CI 0.73 to 0.81) and for the composite outcome (AUC 0.72, 95% CI 0.68 to 0.76). Patients with RISE UP scores below 10% (n=121) had favourable outcome (zero deaths and six ICU admissions), while those with scores above 30% (n=221) were at high risk of adverse outcome (46.6% mortality and 19.0% ICU admissions). CONCLUSION: The RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome and may help guide decision-making and allocating healthcare resources.

[Mortality and re-admission after hospitalization with COVID-19]. / Sterfte en heropname na ziekenhuisopname met covid-19.

OBJECTIVE: Hospitalization for corona virus disease 2019 (COVID-19) may be followed by complications after discharge. We aimed to evaluate mortality, readmission rate, and readmission characteristics after hospitalization with COVID-19. DESIGN: A retrospective cohort study METHODS: Inclusion of all patients hospitalized for COVID-19 between March 1, 2020, and June 1, 2020 in Zuyderland Medical Centre, The Netherlands. Main outcome measures were mortality and readmission after hospitalization. Univariate and multivariate regression analysis were performed to identify risk factors for death and readmission. RESULTS: A total of 769 patients hospitalized with COVID-19 (mean age 70 ± 14 years; 39% female) were included in the study. In-hospital mortality was 22.4% , as such 596 patients were discharged alive and followed after discharge with a median of 80 days (IQR 66-91). Total mortality after discharge was 6.4% (n=38) and readmission rate was 11.7% (n=70). Main reasons for readmission were respiratory insufficiency (31%), arterial and venous thrombotic events (16%) or related to a chronic comorbidity (14%). Mortality rates were higher in older patients and patients who experienced delirium during hospital stay. Risk factors for readmission were male sex, discharge to a long-term care facility and COPD. CONCLUSION: 1 out of 6 COVID-19 positive patients died or was readmitted after discharge. This shows an ongoing vulnerability of COVID-19 patients. Physicians and policy makers should consider this high rate when making decisions on discharge, hospital-capacity planning, and patient monitoring after discharge.