ABSTRACT
BACKGROUND: Vascular calcification is associated with increased mortality in patients with cardiovascular disease. Secondary calciprotein particles are believed to play a causal role in the pathophysiology of vascular calcification. The maturation time (T50) of calciprotein particles provides a measure of serum calcification propensity. We compared T50 between patients with ST-segment-elevated myocardial infarction and control subjects and studied the association of T50 with cardiovascular risk factors and outcome. METHODS: T50 was measured by nephelometry in 347 patients from the GIPS-III trial (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction: a Randomized Controlled Trial) and in 254 matched general population controls from PREVEND (Prevention of Renal and Vascular End-Stage Disease). We also assessed the association between T50 and left ventricular ejection fraction, as well as infarct size, the incidence of ischemia-driven reintervention during 5 years of follow-up, and serum nitrite as a marker of endothelial dysfunction. RESULTS: Patients with ST-segment-elevated myocardial infarction had a significantly lower T50 (ie, higher serum calcification propensity) compared with controls (T50: 289±63 versus 338±56 minutes; P<0.001). In patients with ST-segment-elevated myocardial infarction, lower T50 was associated with female sex, lower systolic blood pressure, lower total cholesterol, lower LDL (low-density lipoprotein) cholesterol, lower triglycerides, and higher HDL (high-density lipoprotein) cholesterol but not with circulating nitrite or nitrate. Ischemia-driven reintervention was associated with higher LDL (P=0.03) and had a significant interaction term for T50 and sex (P=0.005), indicating a correlation between ischemia-driven reintervention and T50 above the median in men and below the median in women, between 150 days and 5 years of follow-up. CONCLUSIONS: Serum calcification propensity is increased in patients with ST-segment-elevated myocardial infarction compared with the general population, and its contribution is more pronounced in women than in men. Its lack of/inverse association with nitrite and blood pressure confirms T50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T50 was associated with a more favorable serum lipid profile, suggesting the involvement of divergent pathways of calcification stress and lipid stress in the pathophysiology of myocardial infarction.
Subject(s)
ST Elevation Myocardial Infarction , Humans , Male , Female , Middle Aged , Aged , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/physiopathology , Biomarkers/blood , Heart Disease Risk Factors , Vascular Calcification/blood , Vascular Calcification/physiopathology , Risk Assessment , Risk Factors , Case-Control Studies , Time Factors , Ventricular Function, Left , Stroke VolumeABSTRACT
A potential source of novel biomarkers for mTBI is the kynurenine pathway (KP), a metabolic pathway of tryptophan (Trp), that is up-regulated by neuroinflammation and stress. Considering that metabolites of the KP (kynurenines) are implicated in various neuropsychiatric diseases, exploration of this pathway could potentially bridge the gap between physiological and psychological factors in the recovery process after mTBI. This study, therefore, set out to characterize the KP after mTBI and to examine associations with long-term outcome. Patients were prospectively recruited at the emergency department (ED), and blood samples were obtained in the acute phase (<24 h; N = 256) and at 1-month follow-up (N = 146). A comparison group of healthy controls (HC; N = 32) was studied at both timepoints. Trp, kynurenines, and interleukin (IL)-6 and IL-10 were quantified in plasma. Clinical outcome was measured at six months post-injury. Trp, xanthurenic acid (XA), and picolinic acid (PA) were significantly reduced in patients with mTBI relative to HC, corrected for age and sex. For Trp (d = -0.57 vs. d = -0.29) and XA (d = -0.98 vs. d = -0.32), larger effects sizes were observed during the acute phase compared to one-month follow-up, while for PA (d = -0.49 vs. d = -0.52) effect sizes remained consistent. Findings for other kynurenines (e.g., kynurenine, kynurenic acid, and quinolinic acid) were non-significant after correction for multiple testing. Within the mTBI group, lower acute Trp levels were significantly related to incomplete functional recovery and higher depression scores at 6 months post-injury. No significant relationships were found for Trp, XA, and PA with IL-6 or IL-10 concentrations. In conclusion, our findings indicate that perturbations of the plasma KP in the hyperacute phase of mTBI and 1 month later are limited to the precursor Trp, and glutamate system modulating kynurenines XA and PA. Correlations between acute reductions of Trp and unfavorable outcomes may suggest a potential substrate for pharmacological intervention.
ABSTRACT
OBJECTIVE: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis. BACKGROUND: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention. METHODS: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications. RESULTS: Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33-2.28; P =0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56-7.37; P =0.34). The median number of additional interventions was 0 (IQR 0-0) in both groups ( P =0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P =0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar. CONCLUSIONS: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach. TRIAL REGISTRATION: ISRCTN33682933.
Subject(s)
Pancreatitis, Acute Necrotizing , Quality of Life , Humans , Treatment Outcome , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/surgery , Anti-Bacterial Agents/therapeutic use , Drainage/methodsABSTRACT
BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).
Subject(s)
Anti-Bacterial Agents/therapeutic use , Drainage , Pancreas/pathology , Pancreatitis, Acute Necrotizing/therapy , Time-to-Treatment , Aged , Combined Modality Therapy , Female , Humans , Length of Stay , Male , Middle Aged , Pancreas/surgery , Pancreatitis, Acute Necrotizing/drug therapy , Pancreatitis, Acute Necrotizing/pathology , Pancreatitis, Acute Necrotizing/surgeryABSTRACT
BACKGROUND AND AIMS: Individuals with type 2 diabetes (T2D) have a higher risk of cardiovascular disease, compared with those without T2D. The serum T50 test captures the transformation time of calciprotein particles in serum. We aimed to assess whether serum T50 predicts cardiovascular mortality in T2D patients, independent of traditional risk factors. METHODS: We analyzed 621 individuals with T2D in this prospective cohort study. Cox regression models were performed to test the association between serum T50 and cardiovascular and all-cause mortality. Causes of death were categorized according to ICD-10 codes. Risk prediction improvement was assessed by comparing Harrell's C for models without and with T50. RESULTS: The mean age was 64.2 ± 9.8 years, and 61% were male. The average serum T50 time was 323 ± 63 min. Higher age, alcohol use, high-sensitive C-reactive protein, and plasma phosphate were associated with lower serum T50 levels. Higher plasma triglycerides, venous bicarbonate, sodium, magnesium, and alanine aminotransferase were associated with higher serum T50 levels. After a follow-up of 7.5[5.4-10.7] years, each 60 min decrease in serum T50 was associated with an increased risk of cardiovascular (fully adjusted HR 1.32, 95% CI 1.08-1.50, and p = 0.01) and all-cause mortality (HR 1.15, 95%CI 1.00-1.38, and p = 0.04). Results were consistent in sensitivity analyses after exclusion of individuals with estimated glomerular filtration rate <45 or <60 mL/min/1.73 m2 and higher plasma phosphate levels. CONCLUSIONS: Serum T50 improves prediction of cardiovascular and all-cause mortality risk in individuals with T2D. Serum T50 may be useful for risk stratification and to guide therapeutic strategies aiming to reduce cardiovascular mortality in T2D.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Male , Middle Aged , Female , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Prospective Studies , Aged , Risk Factors , Predictive Value of Tests , Biomarkers/blood , Risk AssessmentABSTRACT
OBJECTIVE: Systemic sclerosis-interstitial lung disease (SSc-ILD) is the leading cause of death in SSc, affecting around 50 % of the patients. Lung tissue of patients with early-stage SSc-ILD is characterized by a predominant inflammatory response with inconspicuous fibrosis, which may progress to honeycombing fibrosis. Hence, a better understanding of the molecular mechanisms underpinning SSc-ILD pathogenesis is needed to improve treatment options and progression prediction. This transcriptomic study aims to reveal the differential gene expression between control (ctrl) lung tissue and inflammatory, prefibrotic and fibrotic lung tissue to capture progression of early to late phase SSc-ILD. METHODS: Twelve explanted lungs from patients with SSc-ILD were used to analyze gene expression from formalin-fixed paraffin-embedded lung tissues with varying stages of ILD (n = 18) and control lung tissue (n = 6). The SSc-ILD tissues were stratified into three ROIs: inflammatory, prefibrotic, and fibrotic using histological assessments to define a longitudinal simulation of early to late phases of SSc-ILD. The nanoString (nS) nCounter Human Fibrosis Panel was used to profile the transcriptome in the regions of interest. Validation of potential targetswas performed with immunohistochemistry in the same tissues that were used for transcriptome analysis. RESULTS: To validate our simulation model, we performed subgroup analysis that showed an incremental increase in pathway scores related to the severity of fibrosis. Ctrl vs SSc-ILD comparison demonstrated 24 differentially expressed genes, two of which had the most pronounced p-values. Cyclin-dependent kinase inhibitor (cdkn2c) was overexpressed (P = 0.00052) in SSc-ILD compared to ctrl, while expression of Pellino E3 ubiquitin-protein ligase 1 (peli1) showed lower expression (P = 0.0012). Additionally, in all four groups, cdkn2c and peli1 gene expression showed an incremental increase and decrease, respectively. Immunohistochemistry of cdkn2c showed consistent results with the nS analysis. CONCLUSION: More cdkn2c and less peli1 expression were associated with more advanced stages of SSc-ILD on histologic assessment. We report the potential of the cell cycle inhibitor and senescence marker, cdkn2c (p18) to be associated with fibrosis progression.
ABSTRACT
INTRODUCTION: Intraoperative blood loss and postoperative hemorrhage affect outcomes after liver resection. GATT-Patch is a new flexible, pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with N-hydroxy-succinimide polyoxazoline. We evaluated safety and performance of the GATT-Patch for hemostasis at the liver resection plane. METHODS: Adult patients undergoing elective open liver surgery were recruited in three centers. GATT-Patch was used for minimal to moderate bleeding at the liver resection plane. The primary endpoint was hemostasis of the first-treated bleeding site at 3 min versus a prespecified performance goal of 65.4%. RESULTS: Two trial stages were performed: I (n = 8) for initial safety and II (n = 39) as the primary outcome cohort. GATT-Patch was applied in 47 patients on 63 bleeding sites. Median age was 60.0 (range 25-80) years and 70% were male. Most (66%) surgeries were for colorectal cancer metastases. The primary endpoint was met in 38 out of 39 patients (97.4%; 95% confidence interval: 84.6%-99.9%) versus 65.4% (P < 0.001). Of all the 63 bleeding sites, hemostasis was 82.7% at 30, 93.7% at 60, and 96.8% at 180 s. No reoperations for rebleeding or device-related issues occurred. CONCLUSIONS: When compared to a performance goal derived from state-of-the-art hemostatic agents, GATT-Patch for the treatment of minimal to moderate bleeding during liver surgery successfully and quickly achieved hemostasis with acceptable safety outcomes. (ClinicalTrials.gov Identifier: NCT04819945).
Subject(s)
Blood Loss, Surgical , Hepatectomy , Humans , Male , Middle Aged , Female , Aged , Adult , Hepatectomy/adverse effects , Hepatectomy/methods , Aged, 80 and over , Blood Loss, Surgical/statistics & numerical data , Blood Loss, Surgical/prevention & control , Hemostasis, Surgical/methods , Hemostasis, Surgical/instrumentation , Hemostatics/administration & dosage , Hemostatics/therapeutic use , Hemostatics/adverse effects , Treatment Outcome , Gelatin/adverse effects , Gelatin/administration & dosage , Prospective Studies , Liver Neoplasms/surgery , Liver Neoplasms/secondaryABSTRACT
BACKGROUND: Chronic pain is a disabling condition which is prevalent in about 20% of the adult population. Physiotherapy is the most common non-pharmacological treatment option for chronic pain, but often demonstrates unsatisfactory outcomes. Virtual Reality (VR) may offer the opportunity to complement physiotherapy treatment. As VR has only recently been introduced in physiotherapy care, it is unknown to what extent VR is used and how it is valued by physiotherapists. The aim of this study was to analyse physiotherapists' current usage of, experiences with and physiotherapist characteristics associated with applying therapeutic VR for chronic pain rehabilitation in Dutch primary care physiotherapy. METHODS: This online survey applied two rounds of recruitment: a random sampling round (873 physiotherapists invited, of which 245 (28%) were included) and a purposive sampling round (20 physiotherapists using VR included). Survey results were reported descriptively and physiotherapist characteristics associated with VR use were examined using multivariable logistic regression analysis. RESULTS: In total, 265 physiotherapists participated in this survey study. Approximately 7% of physiotherapists reported using therapeutic VR for patients with chronic pain. On average, physiotherapists rated their overall experience with therapeutic VR at 7.0 and "whether they would recommend it" at 7.2, both on a 0-10 scale. Most physiotherapists (71%) who use therapeutic VR started using it less than two years ago and use it for a small proportion of their patients with chronic pain. Physiotherapists use therapeutic VR for a variety of conditions, including generalized (55%), neck (45%) and lumbar (37%) chronic pain. Physiotherapists use therapeutic VR mostly to reduce pain (68%), improve coordination (50%) and increase physical mobility (45%). Use of therapeutic VR was associated with a larger physiotherapy practice (OR = 2.38, 95% CI [1.14-4.98]). Unfamiliarity with VR seemed to be the primary reason for not using VR. DISCUSSION: Therapeutic VR for patients with chronic pain is in its infancy in Dutch primary care physiotherapy practice as only a small minority uses VR. Physiotherapists that use therapeutic VR are modestly positive about the technology, with large heterogeneity between treatment goals, methods of administering VR, proposed working mechanisms and chronic pain conditions to treat.
Subject(s)
Chronic Pain , Physical Therapists , Adult , Humans , Chronic Pain/diagnosis , Chronic Pain/therapy , Physical Therapy Modalities , Research Design , Primary Health CareABSTRACT
BACKGROUND: During the first lockdown of the COVID-19 pandemic, an exponential increase in video consultations replacing in-person outpatient visits was observed in hospitals. Insight into patients' experiences with this type of consultation is helpful for a broad, sustainable, and patient-centered implementation of video consultation. OBJECTIVE: This study aims to examine patients' experiences with video consultation during the COVID-19 pandemic and identify discriminative patient and consultation characteristics to determine when video consultation is most feasible. METHODS: A cross-sectional survey study was conducted. Patients aged ≥18 years and scheduled for a video consultation at the outpatient clinic of a Dutch university medical center from August 2020 to December 2020 for all medical specialties were eligible. Patients' experiences were explored through a study-specific survey using descriptive quantitative statistics. Open-ended questions were qualitatively analyzed and thematically categorized into appreciated aspects and aspects for improvement. Discriminative patient and consultation characteristics were identified using 3 distinctive survey items. Characteristics of patients who scored and those who did not score all 3 items positively were analyzed using binary logistic regression. RESULTS: A total of 1054 patients were included in the analysis. Most patients (964/1054, 91.46%) were satisfied with their video consultation, with a mean overall grade of 8.6 (SD 1.3) of 10. In the qualitative analyses, 70.02% (738/1054) of the patients cited aspects they appreciated and 44.97% (474/1054) mentioned aspects for improvement during their consultation. Patients with better self-rated health reported a positive evaluation significantly more often (P=.001), which also held true for other medical specialties (vs surgical and nonsurgical specialties; P<.001). CONCLUSIONS: Video consultation was perceived as highly satisfactory by patients during the COVID-19 pandemic, with the best experience reported by healthy participants and those undergoing their first consultation. Appreciated aspects are mainly at the individual professional level, organizational level, and innovation level itself. The aspects that were mentioned for improvement can be changed for the better.
Subject(s)
COVID-19 , Outpatients , Humans , Adolescent , Adult , Cross-Sectional Studies , Pandemics , Communicable Disease ControlABSTRACT
BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571.
Subject(s)
Exocrine Pancreatic Insufficiency , Pancreatitis, Acute Necrotizing , Drainage , Endoscopy, Gastrointestinal , Follow-Up Studies , Humans , Pancreatitis, Acute Necrotizing/complications , Pancreatitis, Acute Necrotizing/diagnosis , Pancreatitis, Acute Necrotizing/surgery , Quality of Life , Treatment OutcomeABSTRACT
SSc is a multiphase autoimmune disease with a well-known triad of clinical manifestations including vasculopathy, inflammation and fibrosis. Although a plethora of drugs has been suggested as potential candidates to halt SSc progression, nothing has proven clinically efficient. In SSc, both innate and adaptive immune systems are abnormally activated fuelling fibrosis of the skin and other vital organs. Macrophages have been implicated in the pathogenesis of SSc and are thought to be a major source of immune dysregulation. Due to their plasticity, macrophages can initiate and sustain chronic inflammation when classically activated while, simultaneously or parallelly, when alternatively activated they are also capable of secreting fibrotic factors. Here, we briefly explain the polarization process of macrophages. Subsequently, we link the activation of macrophages and monocytes to the molecular pathology of SSc, and illustrate the interplay between macrophages and fibroblasts. Finally, we present recent/near-future clinical trials and discuss novel targets related to macrophages/monocytes activation in SSc.
Subject(s)
Scleroderma, Systemic , Humans , Fibrosis , Macrophages/pathology , Monocytes , Inflammation , Skin/pathologyABSTRACT
BACKGROUND: Triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL) are associated positively whereas high-density lipoproteins (HDL) are associated inversely with the development of new-onset type 2 diabetes (T2D). Here we studied potential associations between these lipoprotein particle concentrations and the risk of developing microvascular complications in patients with established T2D. METHODS: Lipoprotein particle concentrations (TRLP, LDLP, and HDLP) were determined in 278 patients with T2D participating in a primary care-based longitudinal cohort study (Zwolle Outpatient Diabetes project Integrating Available Care [ZODIAC] study) leveraging the Vantera nuclear magnetic resonance (NMR) platform using the LP4 algorithm. Associations between lipoprotein particles and incident microvascular complications (nephropathy, neuropathy, and retinopathy) were assessed using Cox proportional hazards regression models. RESULTS: In total, 136 patients had microvascular complications at baseline. During a median follow-up of 3.2 years, 49 (34.5%) of 142 patients without microvascular complications at baseline developed new-onset microvascular complications. In multivariable Cox proportional hazards regression analyses, both total LDLP and HDLP concentrations, but not total TRLP concentrations, were positively associated with an increased risk of developing any microvascular complications after adjustment for potential confounding factors, including age, sex, disease duration, HbA1c levels, history of macrovascular complications, and statin use (adjusted hazard ratio [HR] per 1 SD increment: 1.70 [95% CI 1.24-2.34], P < 0.001 and 1.63 [95% CI 1.19-2.23], P = 0.002, respectively). When analyzing each microvascular complication individually, total LDLP concentrations were positively associated with retinopathy (adjusted HR 3.35, 95% CI 1.35-8.30, P = 0.009) and nephropathy (adjusted HR 2.13, 95% CI 1.27-3.35, P = 0.004), and total HDLP concentrations with neuropathy (adjusted HR 1.77, 95% CI 1.15-2.70, P = 0.009). No significant associations were observed for lipoprotein particle subfractions. CONCLUSIONS: Total lipoprotein particle concentrations of both LDL and HDL associate positively with an increased risk of developing microvascular complications in T2D. We propose that the protective role of HDL on the development of microvascular complications may be lost in established T2D.
Subject(s)
Diabetes Mellitus, Type 2 , Lipoproteins, HDL , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Longitudinal Studies , Cholesterol, HDL , Lipoproteins , Lipoproteins, LDLABSTRACT
BACKGROUND: The epidermal growth factor receptor (EGFR) pathway is involved in kidney tissue repair and growth. Preclinical interventional data and scarce human data have suggested a role for this pathway in the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD), while other data have suggested that its activation is causally linked to repair of damaged kidney tissue. We hypothesize that urinary EGFR ligands, as a reflection of EGFR activity, are associated with kidney function decline in ADPKD in the context of tissue repair following injury, and as the disease progresses as a sign of insufficient repair. METHODS: In the present study, we measured the EGFR ligands, EGF and heparin binding-EGF (HB-EGF), in 24-h urine samples of 301 ADPKD patients and 72 age- and sex-matched living kidney donors to dissect the role of the EGFR pathway in ADPKD. During a median follow-up of 2.5 years, the association of urinary EGFR ligand excretion with annual change in estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume in ADPKD patients was analyzed using mixed-models methods, and the expression of three closely related EGFR family receptors in ADPKD kidney tissue was investigated by immunohistochemistry. Additionally, the effect of reducing renal mass (after kidney donation), was assessed to investigate whether urinary EGF matches this reduction and thus reflects the amount of remaining healthy kidney tissue. RESULTS: At baseline, urinary HB-EGF did not differ between ADPKD patients and healthy controls (P = .6), whereas a lower urinary EGF excretion was observed in ADPKD patients [18.6 (11.8-27.8)] compared with healthy controls [51.0 (34.9-65.4) µg/24 h, P < .001]. Urinary EGF was positively associated with baseline eGFR (R = 0.54, P < .001) and a lower EGF was strongly associated with a more rapid GFR decline, even when adjusted for ADPKD severity markers (ß = 1.96, P < .001), whereas HB-EGF was not. Expression of the EGFR, but not other EGFR-related receptors, was observed in renal cysts but was absent in non-ADPKD kidney tissue. Finally, unilateral nephrectomy resulted in a decrease of 46.4 (-63.3 to -17.6) % in urinary EGF excretion, alongside a decrease of 35.2 ± 7.2% in eGFR and 36.8 ± 6.9% in measured GFR (mGFR), whereas maximal mGFR (measured after dopamine induced hyperperfusion) decreased by 46.1 ± 7.8% (all P < .001). CONCLUSIONS: Our data suggest that lower urinary EGF excretion may be a valuable novel predictor for kidney function decline in patients with ADPKD.
Subject(s)
Polycystic Kidney, Autosomal Dominant , Humans , Polycystic Kidney, Autosomal Dominant/complications , Heparin-binding EGF-like Growth Factor , Epidermal Growth Factor , Disease Progression , Kidney , Glomerular Filtration Rate , Patient AcuityABSTRACT
PURPOSE: Knowledge of clinical pharmacotherapy is essential for all who prescribe medication. The aims of this study were to investigate differences in the pharmacotherapy and polypharmacy knowledge of medical and surgical residents and consultants and whether this knowledge can be improved by following an online course. METHODS: Design: A before-and-after-measurement. SETTING: An online course available for Dutch residents and consultants working in hospitals. STUDY POPULATION: Dutch residents and consultants from different disciplines who voluntarily followed an online course on geriatric care. INTERVENTION: An online 6-week course on geriatric care, with 1 week dedicated to clinical pharmacotherapy and polypharmacy. Variables, such as medical vs surgical specialty, consultant vs resident, age, and sex, that could predict the level of knowledge. The effects of the online course were studied using repeated measures ANOVA. The study was approved by the National Ethics Review Board of Medical Education (NERB dossier number 996). RESULTS: A total of 394 residents and 270 consultants, 220 from surgical and 444 from medical specialties, completed the online course in 2016 and 2017. Residents had higher test scores than consultants for pharmacotherapy (73% vs 70%, p < 0.02) and polypharmacy (75% vs 72%, p < 0.02). The learning effect did not differ. Medical residents/consultants had a better knowledge of pharmacotherapy (74% vs 68%, p < 0.001) and polypharmacy (77% vs 66%, p < 0.001) than surgical residents/consultants, but the learning effect was the same. CONCLUSIONS: Residents and consultants had a similar learning curve for acquiring knowledge, but residents outperformed consultants on all measures. In addition, surgical and medical residents/consultants had similar learning curves, but medical residents/consultants had higher test scores on all measures.
Subject(s)
Internship and Residency , Humans , Aged , Consultants , Polypharmacy , Clinical CompetenceABSTRACT
AIM: Colorectal anastomotic leakage (AL) is a serious complication. Studies on the impact of AL on health-related quality of life (HRQoL) are scarce. We aimed to investigate the association between AL and HRQoL in colorectal cancer patients up to 2 years after diagnosis, and to evaluate whether AL is associated with a clinically relevant decrease in HRQoL over time. METHODS: Patients diagnosed with Stage I-III colorectal cancer undergoing elective surgical resection with primary anastomosis between 2010 and 2017 were included. HRQoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, represented by the summary score, and analysed at diagnosis and at 6 months and 2 years post-diagnosis. Multivariable linear regression was performed to assess the association between AL and HRQoL, while multivariable logistic regression was used to investigate the association between AL and a clinically relevant HRQoL decrease (≥10 points) during follow-up compared to the time of diagnosis. RESULTS: In total, 1197 patients were included of whom 63 (5%) developed AL. AL was not associated with HRQoL at 6 months post-diagnosis nor at 2 years post-diagnosis. However, having AL was associated with an increased risk of a clinically relevant decrease in HRQoL at 6 months post-diagnosis (OR 3.65, 95% CI 1.62-8.21) but not at 2 years after diagnosis (OR 1.91, 95% CI 0.62-5.93). CONCLUSION: Although AL was not associated with HRQoL at 6 months or 2 years post-diagnosis, AL was a determinant of a clinically relevant decrease in HRQoL at 6 months after diagnosis. Future work should identify feasible and effective strategies to prevent declines in QoL in this patient population.
Subject(s)
Anastomotic Leak , Colorectal Neoplasms , Humans , Anastomotic Leak/epidemiology , Quality of Life , Colorectal Neoplasms/etiology , Anastomosis, Surgical/adverse effects , Colectomy/adverse effectsABSTRACT
BACKGROUND: Chronic low back pain (CLBP) is the most common chronic pain condition worldwide. Currently, primary care physiotherapy is one of the main treatment options, but effects of this treatment are small. Virtual Reality (VR) could be an adjunct to physiotherapy care, due to its multimodal features. The primary aim of this study is to assess the (cost-)effectiveness of physiotherapy with integrated multimodal VR for patients with complex CLBP, compared to usual primary physiotherapy care. METHODS: A multicenter, two-arm, cluster randomized controlled trial (RCT) including 120 patients with CLBP from 20 physiotherapists will be conducted. Patients in the control group will receive 12 weeks of usual primary physiotherapy care for CLBP. Patients in the experimental group will receive treatment consisting of 12 weeks of physiotherapy with integrated, immersive, multimodal, therapeutic VR. The therapeutic VR consists of the following modules: pain education, activation, relaxation and distraction. The primary outcome measure is physical functioning. Secondary outcome measures include pain intensity, pain-related fears, pain self-efficacy and economic measures. Effectiveness of the experimental intervention compared to the control intervention on primary and secondary outcome measures will be analyzed on an intention-to-treat principle, using linear mixed-model analyses. DISCUSSION: This pragmatic, multicenter cluster randomized controlled trial, will determine the clinical and cost-effectiveness of physiotherapy with integrated, personalized, multimodal, immersive VR in favor of usual physiotherapy care for patients with CLBP. TRIAL REGISTRATION: This study is prospectively registered at ClinicalTrials.gov (identifier: NCT05701891).
Subject(s)
Chronic Pain , Low Back Pain , Virtual Reality , Humans , Low Back Pain/diagnosis , Low Back Pain/therapy , Treatment Outcome , Physical Therapy Modalities , Chronic Pain/diagnosis , Chronic Pain/therapy , Chronic Disease , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
BACKGROUND: Deviated optical angles create visuospatial and psychomotor challenges during laparoscopic procedures, resulting in delayed operative time and possibly adverse events. If it is possible to train the skills needed to work under these deviated optical angles, this could benefit procedure time and patient safety. This study investigates the influence of the optical angle on development of basic laparoscopic surgical skills. METHODS: A total of 58 medical students performed a four-session laparoscopic training course on a Virtual Reality Simulator. During each session, they performed an identical task under optical angles of 0°, 45° and - 45°. Performance parameters of task duration and damage were compared between the optical angles to investigate the effect of optical angle on performance development. The 4th session performance was compared to the 2nd session performance for each angle to determine improvement. RESULTS: Participants performed the task significantly faster under the 0° optical angle compared to the plus and minus 45° optical angles during the last three sessions (z between - 2.95 and - 2.09, p < .05). Participants improved significantly and similarly for task duration during the training course under all optical angles. At the end of the training course however significant performance differences between the zero and plus/minus 45 optical angles remained. Performance for damage did not improve and was not affected by optical angle throughout the course. CONCLUSION: Dedicated virtual reality training improves laparoscopic basic skills performance under deviated optical angles as it leads to shorter task duration, however a lasting performance impairment compared to the 0° optical angle remained. Training for performing under deviating optical angles can potentially shorter the learning curve in the operating room.
Subject(s)
Laparoscopy , Learning Curve , Humans , Operating Rooms , Operative Time , Patient SafetyABSTRACT
To evaluate a minute-by-minute monitoring algorithm against a periodic early warning score (EWS) in detecting clinical deterioration and workload. Periodic EWSs suffer from large measurement intervals, causing late detection of deterioration. This might be prevented by continuous vital sign monitoring with a real-time algorithm such as the Visensia Safety Index (VSI). This prospective comparative data modeling cohort study (NCT04189653) compares continuous algorithmic alerts against periodic EWS in continuous monitored medical and surgical inpatients. We evaluated sensitivity, frequency, number of warnings needed to evaluate (NNE) and time of initial alert till escalation of care (EOC): Rapid Response Team activation, unplanned ICU admission, emergency surgery, or death. Also, the percentage of VSI alerting minutes was compared between patients with or without EOC. In 1529 admissions continuous VSI warned for 55% of EOC (95% CI: 45-64%) versus 51% (95% CI: 41-61%) by periodic EWS. NNE for VSI was 152 alerts per detected EOC (95% CI: 114-190) compared to 21 (95% CI: 17-28). It generated 0.99 warnings per day per patient compared to 0.13. Time from detection score till escalation was 8.3 hours (IQR: 2.6-24.8) with VSI versus 5.2 (IQR: 2.7-12.3) hours with EWS (P=0.074). The percentage of warning VSI minutes was higher in patients with EOC than in stable patients (2.36% vs 0.81%, P<0.001). Although sensitivity of detection was not significantly improved continuous vital sign monitoring shows potential for earlier alerts for deterioration compared to periodic EWS. A higher percentage of alerting minutes may indicate risk for deterioration.
Subject(s)
Clinical Deterioration , Humans , Cohort Studies , Hospitalization , Monitoring, Physiologic , Prospective Studies , Vital SignsABSTRACT
Continuous vital sign monitoring (CM) may detect ward patient's deterioration earlier than periodic monitoring. This could result in timely ICU transfers or in a transfer delay due to misperceived higher level of care on the ward. The primary objective of this study was to compare patient's disease severity upon unplanned ICU transfer, before and after CM implementation. We included a one-year period before and after CM implementation between August 1, 2017 - July 31, 2019. Before implementation, surgical and internal medicine patients' vital signs were periodically monitored, compared to continuous monitoring with wireless linkage to hospital systems after implementation. In both periods the same early warning score (EWS) protocol was in place. Primary outcome was disease severity scores upon ICU transfer. Secondary outcomes were ICU and hospital length of stay, incidence of mechanical ventilation and ICU mortality. In the two one-year periods 93 and 59 unplanned ICU transfer episodes were included, respectively. Median SOFA (3 (2-6) vs 4 (2-7), p = .574), APACHE II (17 (14-20) vs 16 (14-21), p = .824) and APACHE IV (59 (46-67) vs 50 (36-65), p = .187) were comparable between both periods, as were the median ICU LOS (3.0 (1.7-5.8) vs 3.1 (1.6-6.1), p.962), hospital LOS (23.6 (11.5-38.0) vs 19 (13.9-39.2), p = .880), incidence of mechanical ventilation (28 (47%) vs 22 (54%), p.490), and ICU mortality (11 (13%) vs 10 (19%), p.420). This study shows no difference in disease severity upon unplanned ICU transfer after CM implementation for patients who have deteriorated on the ward.
Subject(s)
Hospitals , Intensive Care Units , Humans , APACHE , Monitoring, Physiologic , Vital Signs , Hospital Mortality , Retrospective Studies , Length of StayABSTRACT
BACKGROUND: A translational ex vivo perfusion-based mandibular pig model was developed as an alternative to animal experiments, for initial assessment of biomaterials in dental and maxillofacial surgery and training. This study aimed to assess the face and content validity of the novel perfusion-based model. METHODS: Cadaveric porcine heads were connected to an organ assist perfusion device for blood circulation and tissue oxygenation. Dental professionals and dental trainees performed a surgical procedure on the mandibula resembling a submandibular extraoral incision to create bone defects. The bone defects were filled and covered with a commercial barrier membrane. All participants completed a questionnaire using a 5-point Likert scale to assess the face and content validity of the model. Validation data between the two groups of participants were compared with Mann-Whitney U test. RESULTS: Ten dental professionals and seven trainees evaluated the model for face and content validity. Participants reported model realism, with a mean face validity score of 3.9 ± 1.0 and a content validity of 4.1 ± 0.8. No significant differences were found for overall face and content validity between experts and trainees. CONCLUSION: We established face and content validity in a novel perfusion-based mandibular surgery model. This model can be used as an alternative for animal studies evaluating new biomaterials and related dental and maxillofacial surgical procedural training.