Background & aim: Propofol is commonly used in ICUs, but its long-term effects have not been thoroughly studied. In vitro studies suggest it may harm mitochondrial function, potentially... Show moreBackground & aim: Propofol is commonly used in ICUs, but its long-term effects have not been thoroughly studied. In vitro studies suggest it may harm mitochondrial function, potentially affecting clinical outcomes. This study aimed to investigate the association between substantial propofol sedation and clinical outcomes in critically ill patients.Methods: We conducted a single-centre cohort study of critically ill, mechanically ventilated (>= 7 days) adults to compare patients who received a substantial dose of propofol (cumulative >500 mg) during the first week of ICU admission with those who did not. The primary outcome was the association between substantial propofol administration and 6-month mortality, adjusted for relevant covariates. Subanalyses were performed for administration in the early (day 1-3) and late (day 4-7) acute phases of critical illness due to the metabolic changes in this period. Secondary outcomes included tracheostomy need and duration, length of ICU and hospital stay (LOS), discharge destinations, ICU, hospital, and 3-month mortality.Results: A total of 839 patients were enrolled, with 73.7 % receiving substantial propofol administration (substantial propofol dose group). Six-month all-cause mortality was 32.4 %. After adjusting for relevant variables, we found no statistically significant difference in 6-month mortality between both groups. There were also no significant differences in secondary outcomes.Conclusion: Our study suggests that substantial propofol administration during the first week of ICU stay in the least sick critically ill, mechanically ventilated adult patients is safe, with no significant associations found with 6-month mortality, ICU or hospital LOS, differences in discharge destinations or need for tracheostomy.(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Uenal, S.; Winkelman, J.A.; Heineman, D.J.; Bahce, I.; Dorp, M. van; Braun, J.A.; ... ; Dickhoff, C. 2023
Introduction: Superior sulcus tumors (SSTs) are uncom-mon, and their anatomical location can make treatment challenging. We analyzed late outcomes of patients with SST treated with concurrent... Show moreIntroduction: Superior sulcus tumors (SSTs) are uncom-mon, and their anatomical location can make treatment challenging. We analyzed late outcomes of patients with SST treated with concurrent chemoradiotherapy followed by surgical resection (trimodality) in a single tertiary institution.Methods: Patients with non-small cell SSTs, who under-went trimodality therapy between 2002 and 2017, were selected from a prospective institutional surgical database. Patients were uniformly staged with 18F-fluorodeox-yglucose-positron emission tomography, computed tomog-raphy scan of the chest and upper abdomen, and brain imaging. Patients undergoing resection of the lung plus chest wall were grouped as limited SST and those needing extensive resections (e.g., including the vertebral body) as extended SST. Kaplan-Meier survival analysis was per-formed to determine difference in survival. Multivariate Cox regression was used to identify prognostic factors.Results: A total of 123 patients were identified with a me-dian follow-up of 4.9 years (interquartile range: 1.6-8.9 y). The 90-day postoperative mortality and morbidity (Clavien-Dindo grades III-V) were 6.5% and 21.1%, respectively. Patients with a radical resection (R0: 92.7%) had better survival (p = 0.002), as did those who had major pathologic response (73%) (p = 0.001). Ten-year overall survival (OS) and disease-free survival were 48.1% and 42.6%, respec-tively. There were no differences in 90-day mortality (p = 0.31) and OS (p = 0.79) between extended SST and limited SST patients.Conclusions: In patients with SST, trimodality resulted in a 10-year estimated OS and disease-free survival of 48.1% and 42.6%, respectively, which were improved after radical resection (R0) and major pathologic response. Survival for limited and extended resections was comparable, and distant relapse was the main pattern of failure. Better sys-temic treatments are therefore needed. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Herniation of the lumbar disc can cause severe pain radiating down the leg alongside a dermatome. This pain can be caused by compression of the nerve root, but recent evidence has indicated that a... Show moreHerniation of the lumbar disc can cause severe pain radiating down the leg alongside a dermatome. This pain can be caused by compression of the nerve root, but recent evidence has indicated that a local inflammation response may also play a role. This thesis focuses on how macrophages that infiltrate the herniated disc in patients with lumbar disc herniation, influence pain and recovery after discectomy. Our data shows that for most patients, if macrophages are present, they benefit the process of healing by leading to a quicker resorption of the herniated material which results in faster recovery. However, for patients with Modic changes, which indicates a degenerated endplate (structure between disc and vertebrae), the presence of macrophages is less beneficial, for they recover more slowly after surgery. The reason for this discrepency seems to be an altered differentiation profile in macrophages. Macrophages differentiate into different types with different behaviours: the M2 macrophages are known for its anti-inflammatory properties and tissue resorption. Our study found M2 macrophages in lower numbers in patients with degenerated endplates, which can explain their slower recovery. Together the data indicates that macrophage differentiation profiles in lumbar herniated discs are promising treatment targets. Show less
Background: Evidence indicates that inflammatory processes are involved in radicular pain as well as in resorption of herniated disc tissue. Furthermore there are indications that the presence of... Show moreBackground: Evidence indicates that inflammatory processes are involved in radicular pain as well as in resorption of herniated disc tissue. Furthermore there are indications that the presence of vertebral end plate pathology (Modic changes; MC) is associated with a negative effect on inflammation. It is hypothesized that in patients with MC, the (possibly bacterial induced) inflammation will be accompanied by pro inflammatory cytokines that worsen the outcome, and that in patients without MC, the inflammation is accompanied by cytokines that induce a resorption process to accelerate recovery.Methods: This prospective cohort study will include 160 lumbar and 160 cervical patients (total of 320), which are scheduled for surgery for either a lumbar or cervical herniated disc with ages between 18 and 75. The main and interaction effects of local bacterial infection (culture), inflammatory cells in disc material (immunohistology), MC (MRI), and blood biomarkers indicating inflammation or infection (blood sample evaluation) will be evaluated. Clinical parameters to be evaluated are leg pain on the 11 point NRS pain scale, Oswestry (lumbar spine) or Neck (cervical spine) Disability Index, Global Perceived Recovery, Womac Questionnaire, and medication status, at baseline, and after 6, 16, 26 and 52 weeks.Discussion: Gaining insight in the aetiology of pain and discomfort in radiculopathy caused by a herniated disc could lead to more effective management of patients. If the type of inflammatory cells shows to be of major influence on the rate of recovery, new immunomodulating treatment strategies can be developed to decrease the duration and intensity of symptoms. Moreover, identifying a beneficial inflammatory response in the disc through a biomarker in blood could lead to early identification of patients whose herniations will resorb spontaneously versus those that require surgery. Show less
Anastasius, M.; Maggiore, P.; Huang, A.L.; Blanke, P.; Patel, M.R.; Norgaard, B.L.; ... ; Leipsic, J. 2021
Background: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFRCT) is a safe alternative to invasive coronary angiography. A negative FFRCT has been shown to have... Show moreBackground: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFRCT) is a safe alternative to invasive coronary angiography. A negative FFRCT has been shown to have low cardiac event rates compared to those with a positive FFRCT. However, the clinical utility of FFRCT according to age is not known.Methods: Patients' in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those >= 65 or <65 years of age. The impact of FFRCT on clinical decision-making, as assessed by patient age, was determined by evaluating patient management using CTA results alone, followed by site investigators submitting a report on the treatment plan based upon the newly provided FFRCT data. Outcomes at 1-year post CTA were assessed, including major adverse cardiovascular events (myocardial infarction, all-cause mortality or unplanned hospitalization for ACS leading to revascularisation) and total revascularisation. Positive FFRCT was deemed to be <= 0.8.Results: FFRCT was calculated in 1849 (40.6%) subjects aged <65 and 2704 (59.4%) >= 65 years of age. Subjects >= 65 years were more likely to have anatomic obstructive disease on CTA (>= 50% stenosis), compared to those aged <65 (69.7% and 73.2% respectively, p = 0.008). There was a similar graded increase in recommended and actual revascularisation with either CABG or PCI, with declining FFRCT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those >= or <65, regardless of FFRCT positivity or stenosis severity <50% or >= 50%. With a negative FFRCT result, and anatomical stenosis >= 50%, those >= and <65 years of age, had similar rates of MACE (0.2% for both, p = 0.1) and revascularisation (8.7% and 10.4% respectively p = 0.4).Logistic regression analysis, with age as a continuous variable, and adjustment for Diamond Forrester Risk, baseline FFRCT and treatment (CABG, PCI, medical therapy), indicated a statistically significant, but small increase in the odds of a MACE event with increasing age (OR 1.04, 95% CI 1.006-1.08, p = 0.02). Amongst patients with a FFRCT > 0.80, there was no effect of age on the odds of revascularisation.Conclusion: The findings of this study point to a low risk of MACE events or need for revascularisation in those aged >= or <65 with a FFRCT>0.80, despite the higher incidence of anatomic obstructive CAD in those >= 65 years. The findings show the clinical usefulness and outcomes of FFRCT are largely constant regardless of age. Show less
Sluijs, A.V. van der; Bonenkamp, A.A.; Dekker, F.W.; Abrahams, A.C.; Jaarsveld, B.C. van; DOMESTICO Study Grp 2019
Background More than 6200 End Stage Renal Disease patients in the Netherlands are dependent on dialysis, either performed at home or in a dialysis centre. Visiting a dialysis centre three times a... Show moreBackground More than 6200 End Stage Renal Disease patients in the Netherlands are dependent on dialysis, either performed at home or in a dialysis centre. Visiting a dialysis centre three times a week is considered a large burden by many patients. However, recent data regarding the effects of dialysis at home on quality of life, clinical outcomes, and costs compared with in-centre haemodialysis are lacking. Methods The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO) is a nationwide, prospective, observational cohort study that will include adult patients starting with a form of dialysis. Health-related quality of life, as the primary outcome, clinical outcomes and costs, as secondary outcomes, will be measured every 3-6 months in patients on home dialysis, and compared with a control group consisting of in-centre haemodialysis patients. During a 3-year period 800 home dialysis patients (600 peritoneal dialysis and 200 home haemodialysis patients) and a comparison group of 800 in-centre haemodialysis patients will be included from 53 Dutch dialysis centres (covering 96% of Dutch centres) and 1 Belgian dialysis centre (covering 4% of Flemish centres). Discussion DOMESTICO will prospectively investigate the effect of home dialysis therapies on health-related quality of life, clinical outcomes and costs, in comparison with in-centre haemodialysis. The findings of this study are expected to ameliorate the shared decision-making process and give more guidance to healthcare professionals, in particular to assess which type of patients may benefit most from home dialysis. Show less
In this thesis we focussed on so-called 'treat to target' therapy in rheumatoid arthritis (RA). Treat to target relies on repetitive measurements of disease activity using a composite score that... Show moreIn this thesis we focussed on so-called 'treat to target' therapy in rheumatoid arthritis (RA). Treat to target relies on repetitive measurements of disease activity using a composite score that incorporates signs of disease activity such as laboratory results, findings of physical joint assessments, and the opinion of the patient. It is recommended that rheumatologists intensify treatment when a predefined level of disease activity, the target, has not yet been achieved. The implementation of treatment to target in daily practice depends on the faith of the rheumatologist and the patient to rely on a disease activity composite index (for instance the DAS) rather than on some judgemental estimate of disease activity ('the patient is doing well'). It also relies on a consensual opinion that a pre-set treatment target (for instance a DAS=>1.6) meaning clinical remission) is a desirable as well as an achievable target, and especially on the willingness to intensify medication every time the treatment target has not been achieved. Several aspects of treat to target, in particular a plea for the improvement of the rheumatologists' awareness about and the implementation of treat to target recommendations in daily clinical practice, are discussed in the thesis Show less
Gvozdenovic, E.; Wolterbeek, R.; Heijde, D. van der; Huizinga, T.; Allaart, C.; Landewe, R. 2016
