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.

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.

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.

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.

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.

Use of an algorithm based on routine blood laboratory tests to exclude COVID-19 in a screening-setting of healthcare workers.

BACKGROUND: COVID-19 is an ongoing pandemic leading to exhaustion of the hospital care system. Our health care system has to deal with a high level of sick leave of health care workers (HCWs) with COVID-19 related complaints, in whom an infection with SARS-CoV-2 has to be ruled out before they can return back to work. The aim of the present study is to investigate if the recently described CoLab-algorithm can be used to exclude COVID-19 in a screening setting of HCWs. METHODS: In the period from January 2021 till March 2021, HCWs with COVID-19-related complaints were prospectively collected and included in this study. Next to the routinely performed SARS-CoV-2 RT-PCR, using a set of naso- and oropharyngeal swab samples, two blood tubes (one EDTA- and one heparin-tube) were drawn for analysing the 10 laboratory parameters required for running the CoLab-algorithm. RESULTS: In total, 726 HCWs with a complete CoLab-laboratory panel were included in this study. In this group, 684 HCWs were tested SARS-CoV-2 RT-PCR negative and 42 cases RT-PCR positive. ROC curve analysis showed an area under the curve (AUC) of 0.853 (95% CI: 0.801-0.904). At a safe cut-off value for excluding COVID-19 of -6.525, the sensitivity was 100% with a specificity of 34% (95% CI: 21 to 49%). No SARS-CoV-2 RT-PCR cases were missed with this cut-off and COVID-19 could be safely ruled out in more than one third of HCWs. CONCLUSION: The CoLab-score is an easy and reliable algorithm that can be used for screening HCWs with COVID-19 related complaints. A major advantage of this approach is that the results of the score are available within 1 hour after collecting the samples. This results in a faster return to labour process of a large part of the COVID-19 negative HCWs (34%), next to a reduction in RT-PCR tests (reagents and labour costs) that can be saved.

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.

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.

[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.

Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial.

BACKGROUND: Therapy with elastic compression stockings has been the cornerstone for prevention of post-thrombotic syndrome for decades in patients after acute deep venous thrombosis. It is uncertain who benefits most from therapy, and what the optimum duration of therapy should be. We therefore aimed to assess the safety and efficacy of individualised duration of compression therapy versus the standard duration of 24 months following an initial treatment period of 6 months. METHODS: We did a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial at 12 hospitals in the Netherlands and two in Italy. We randomly assigned patients (1:1) with acute proximal deep vein thrombosis of the leg and without pre-existent venous insufficiency (Clinical Etiological Anatomical and Pathophysiological score

Angiotensin-(1-7)-induced renal vasodilation is reduced in human kidneys with renal artery stenosis.

BACKGROUND: Angiotensin-(1-7) modulates renal blood flow in humans with essential hypertension by inducing vasodilation and counterbalancing angiotensin II-induced vasoconstriction. Little is, however, known about the effects of angiotensin-(1-7) in kidneys with atherosclerotic renal artery stenosis. We previously demonstrated that the effect of angiotensin-(1-7) is reduced in patients with increased activity of the renin-angiotensin system. As the renin-angiotensin system is also activated in kidneys with renal artery stenosis, we hypothesized that the vasodilatory effect of angiotensin-(1-7) is also reduced in such kidneys. METHOD: Therefore, we selectively measured mean renal blood flow (¹³³Xenon washout method) before and during local infusion of angiotensin-(1-7) (0.27, 0.9, and 2.7 ng/kg per min) in hypertensive patients who were angiographically evaluated for the presence of renovascular abnormalities. Data were analyzed in three groups: stenotic kidneys, nonstenotic kidneys with renal artery stenosis of the contralateral kidney (contralateral stenotic kidneys), or essentially hypertensive controls without renovascular abnormalities (matched for urinary sodium excretion). RESULTS: Angiotensin-(1-7) infusion resulted in an increase in renal blood flow in matched controls. In stenotic kidneys however, the effect of angiotensin-(1-7) was significantly reduced as compared to controls. The angiotensin-(1-7) effect in contralateral stenotic kidneys was comparable to controls. CONCLUSION: Angiotensin-(1-7)-induced vasodilation is reduced in stenotic kidneys, but not in contralateral stenotic kidneys. This suggests that the altered blood flow regulation in kidneys with atherosclerotic renal artery stenosis is a local phenomenon and not related to generalized atherosclerotic burden. Probably, the renin-angiotensin system activation, bioavailability of nitric oxide, and structural changes in the stenotic kidney play a role in this phenomenon.

Angiotensin-(1-7)-induced renal vasodilation in hypertensive humans is attenuated by low sodium intake and angiotensin II co-infusion.

Current evidence suggests that angiotensin-(1-7) plays an important role in the regulation of tissue blood flow. This evidence, however, is restricted to studies in animals and human forearm. Therefore, we studied the effects of intrarenal angiotensin-(1-7) infusion on renal blood flow in hypertensive humans. To assess the influence of renin-angiotensin system activity, sodium intake was varied and co-infusion with angiotensin II was performed in a subgroup. In 57 hypertensive patients who were scheduled for renal angiography, renal blood flow was measured ((133)Xenon washout method) before and during intrarenal infusion of angiotensin-(1-7) (3 incremental doses: 0.27, 0.9, and 2.7 ng/kg per minute). Patients were randomized into low or high sodium intake. These 2 groups of patients received angiotensin-(1-7), with or without intrarenal co-infusion of angiotensin II (0.3 ng/kg per minute). Angiotensin-(1-7) infusion resulted in intrarenal vasodilation in patients adhering to a sodium-rich diet. This vasodilatory effect of angiotensin-(1-7) was clearly attenuated by low sodium intake, angiotensin II co-infusion, or both. Regression analyses showed that the prevailing renin concentration was the only independent predictor of angiotensin-(1-7)-induced renal vasodilation. In conclusion, angiotensin-(1-7) induces renal vasodilation in hypertensive humans, but the effect of angiotensin-(1-7) is clearly attenuated by low sodium intake and co-infusion of angiotensin II. This supports the hypothesis that angiotensin-(1-7) induced renal vasodilation depends on the degree of renin-angiotensin-system activation.

[A man with a skin lesion on his abdomen]. / Een man met een huidafwijking op zijn buik.

A 56-year-old man presented with a skin lesion 2 days after surgery for a perianal abscess. The lesion was red, swollen and very painful, with central necrosis and arose shortly after starting coumarine therapy.