Test-retest reliability of the FitMáx©-questionnaire in a clinical and healthy population.

PURPOSE: The FitMáx© was developed as a questionnaire-based instrument to estimate Cardiorespiratory Fitness (CRF) expressed as oxygen uptake at peak exercise (VO2peak). Test-retest reliability is a clinometric measurement property, which defines stability over time if multiple measurements are performed (i.e. reliability). The present study aimed to assess the test-retest reliability of the FitMáx©-questionnaire in different patient groups. PATIENTS AND METHODS: A total of 127 cardiac, pulmonary and oncology patients and healthy subjects aged 19-84 years who completed the questionnaire twice within an average of 18 days were included for analysis. Participants were in a stable clinical situation (no acute disease or participating in a training program). To determine the test-retest reliability, the Intraclass Correlation Coefficient (ICC) and Standard Error of the Measurement (SEM) was calculated between the first (T0) and second (T1) administration of the questionnaires. RESULTS: An excellent agreement was found between the FitMáx©-questionnaire scores at T0 and T1, with an ICC of 0.97 (SEM 1.91) in the total study population and an ICC ranging from 0.93 to 0.98 (SEM 1.52-2.27) in the individual patient groups. CONCLUSION: The FitMáx©-questionnaire proves to be reliable and stable over time to estimate CRF of patients and healthy subjects. Trial registration NTR (Netherlands Trial Register), NL8846. Registered 25 August 2020, https://trialsearch.who.int/Trial2.aspx?TrialID=NL8846.

Estimating VO2peak in 18-90 Year-Old Adults: Development and Validation of the FitMáx©-Questionnaire.

Purpose: Cardiorespiratory fitness (CRF) plays an essential role in health outcomes and quality of life. However, it is often not assessed nor estimated. Objective CRF assessment is costly, labour intensive and not widely available. Patient-reported outcome measures estimate CRF more cost-efficiently, but current questionnaires lack accuracy. The aim of this study is to develop a new self-reported questionnaire to estimate CRF. Materials and Methods: The FitMáx©-questionnaire, consisting of only three questions assessing walking, stair climbing, and cycling capacity, was compared with the commonly used Duke Activity Status Index (DASI) and Veterans Specific Activity Questionnaire (VSAQ). These questionnaires were compared to peak oxygen uptake (VO2peak) as measured with cardiopulmonary exercise testing. This study included 759 cardiac, pulmonary and oncologic patients and healthy persons aged 18‒90. Results: FitMáx© strongly correlated (r = 0.94 (0.92‒0.95) SEE = 4.14 mL∙kg-1∙min-1) with measured VO2peak. Bias between predicted and measured VO2peak was -0.24 (-9.23‒8.75; 95% limits of agreement) mL·kg-1·min-1. The FitMáx© scored superiorly on correlation and SEE compared with the DASI and VSAQ, r = 0.75 (0.68‒0.80) SEE = 4.62 mL∙kg-1∙min-1 and r = 0.87 (0.83‒0.90) SEE = 6.75 mL∙kg-1∙min-1, respectively. Conclusion: FitMáx© is a valid and accessible questionnaire to estimate CRF expressed as VO2peak in clinical practice and shows substantial improvement compared to currently used questionnaires.

Making Patients Fit for Surgery: Introducing a Four Pillar Multimodal Prehabilitation Program in Colorectal Cancer.

BACKGROUND: Considering the relation between preoperative functional capacity and postoperative complications, enhancing patients' functional capacity before surgery with a prehabilitation program may facilitate faster recovery and improve quality of life. However, time before surgery is short, mandating a multimodal and high-intensity training approach. This study investigated feasibility and safety of a prehabilitation program for colorectal cancer. METHODS: Multimodal prehabilitation was offered to patients eligible for participation and they were assigned to an intervention or control group by program availability. The prehabilitation program consisted of the following four interventions: in-hospital high-intensity endurance and strength training, high-protein nutrition and supplements, smoking cessation, and psychological support. Program attendance, patient satisfaction, adverse events, and functional capacity were determined. RESULTS: Fifty patients participated in this study (prehabilitation 20, control 30). Program evaluation revealed a high (90%) attendance rate and high level of patient satisfaction. No adverse events occurred. Endurance and/or strength were improved. Eighty-six percent of patients with prehabilitation recovered to their baseline functional capacity 4 weeks postoperatively, 40% in the control group (P < 0.01). CONCLUSIONS: Multimodal prehabilitation including high-intensity training for colorectal cancer patients is feasible, safe, and effective. A randomized controlled trial (NTR5947) was initiated to determine whether prehabilitation may lower morbidity and mortality rates in colorectal surgery.

Prehabilitation, making patients fit for surgery - a new frontier in perioperative care.

Optimizing a patients' condition before surgery to improve the postoperative outcome can be achieved by using prehabilitation; preoperative interventions focusing on modifiable risk factors to improve the physical, nutritional, and mental status of the patient. A multimodal, multidisciplinary approach induces a synergistic effect between the various interventions and affects the outcome postoperatively. While awaiting higher-quality evidence, the worldwide implementation of prehabilitation programs has started, resulting in a true revolution in perioperative care.

MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): study protocol of a multicenter randomised controlled trial.

BACKGROUND: In case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy. METHODS/DESIGN: This study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates 'bulky N2-N3' disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment. DISCUSSION: Results of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice. TRIAL REGISTRATION: The trial is registered at the Netherlands Trial Register on July 6th, 2017 ( NTR 6528 ).

Lateral Cutaneous Nerve Entrapment Syndrome (LACNES): A previously unrecognized cause of intractable flank pain.

BACKGROUND AND AIMS: Chronic abdominal pain may occasionally be due to terminal endings of intercostal nerves (ACNES, abdominal cutaneous nerve entrapment syndrome) that are entrapped in the abdominal wall. Spontaneous neuropathic flank pain may also be caused by involvement of branches of these intercostal nerves. Aim is to describe a series of patients with flank pain due to nerve entrapment and to increase awareness for an unknown condition coined Lateral Cutaneous Nerve Entrapment Syndrome (LACNES). METHODS: Patients possibly having LACNES (constant area of flank tenderness, small point of maximal pain with neuropathic characteristics, locoregional altered skin sensation) presenting between January 2007 and May 2016 received a diagnostic 5-10mL 1% lidocaine injection. Pain levels were recorded using a numerical rating scale (0, no pain to 10, worst possible). A >50% pain reduction was defined as success. Long term effect of injections and alternative therapies were determined using a satisfaction scale (1, very satisfied, no pain - 5, pain worse). RESULTS: 30 patients (21 women, median age 52, range 13-78) were diagnosed with LACNES. Pain following one injection dropped from 6.9±1.4 to 2.4±1.9 (mean, p<0.001) leading to an 83% immediate success rate. Repeated injection therapy was successful in 16 (pain free n=7, pain acceptable, n=9; median 42 months follow-up). The remaining 14 patients received (minimally invasive) surgery (n=5) or other treatments (medication, manual therapy or pulsed radiofrequency, n=9). Overall treatment satisfaction (scale 1 or 2) was attained in 79%. CONCLUSIONS AND IMPLICATIONS: LACNES should be considered in patients with chronic flank pain. Injection therapy is long term effective in more than half of the population.

Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model.

INTRODUCTION: Chronic low back pain due to intervertebral disc (IVD) degeneration is associated with increased levels of inflammatory mediators. Current medical treatment consists of oral anti-inflammatory drugs to alleviate pain. In this study, the efficacy and safety of a novel thermoreversible poly-N-isopropylacrylamide MgFe-layered double hydroxide (pNIPAAM MgFe-LDH) hydrogel was evaluated for intradiscal controlled delivery of the selective cyclooxygenase (COX) 2 inhibitor and anti-inflammatory drug celecoxib (CXB). METHODS: Degradation, release behavior, and the ability of a CXB-loaded pNIPAAM MgFe-LDH hydrogel to suppress prostaglandin E2 (PGE2) levels in a controlled manner in the presence of a proinflammatory stimulus (TNF-α) were evaluated in vitro. Biocompatibility was evaluated histologically after subcutaneous injection in mice. Safety of intradiscal application of the loaded and unloaded hydrogels was studied in a canine model of spontaneous mild IVD degeneration by histological, biomolecular, and biochemical evaluation. After the hydrogel was shown to be biocompatible and safe, an in vivo dose-response study was performed in order to determine safety and efficacy of the pNIPAAM MgFe-LDH hydrogel for intradiscal controlled delivery of CXB. RESULTS: CXB release correlated to hydrogel degradation in vitro. Furthermore, controlled release from CXB-loaded hydrogels was demonstrated to suppress PGE2 levels in the presence of TNF-α. The hydrogel was shown to exhibit a good biocompatibility upon subcutaneous injection in mice. Upon intradiscal injection in a canine model, the hydrogel exhibited excellent biocompatibility based on histological evaluation of the treated IVDs. Gene expression and biochemical analyses supported the finding that no substantial negative effects of the hydrogel were observed. Safety of application was further confirmed by the absence of clinical symptoms, IVD herniation or progression of degeneration. Controlled release of CXB resulted in a nonsignificant maximal inhibition (approximately 35 %) of PGE2 levels in the mildly degenerated canine IVDs. CONCLUSIONS: In conclusion, this study showed biocompatibility and safe intradiscal application of an MgFe LDH-pNIPAAM hydrogel. Controlled release of CXB resulted in only limited inhibition of PGE2 in this model with mild IVD degeneration, and further studies should concentrate on application of controlled release from this type of hydrogel in animal models with more severe IVD degeneration.

A novel injectable thermoresponsive and cytocompatible gel of poly(N-isopropylacrylamide) with layered double hydroxides facilitates siRNA delivery into chondrocytes in 3D culture.

Hybrid hydrogels composed of poly(N-isopropylacrylamide) (pNIPAAM) and layered double hydroxides (LDHs) are presented in this study as novel injectable and thermoresponsive materials for siRNA delivery, which could specifically target several negative regulators of tissue homeostasis in cartilaginous tissues. Effectiveness of siRNA transfection using pNIPAAM formulated with either MgAl-LDH or MgFe-LDH platelets was investigated using osteoarthritic chondrocytes. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an endogenous model gene to evaluate the extent of silencing. No significant adverse effects of pNIPAAM/LDH hydrogels on cell viability were noticed. Cellular uptake of fluorescently labeled siRNA was greatly enhanced (>75%) in pNIPAAM/LDH hydrogel constructs compared to alginate, hyaluronan and fibrin gels, and was absent in pNIPAAM hydrogel without LDH platelets. When using siRNA against GAPDH, 82-98% reduction of gene expression was found in both types of pNIPAAM/LDH hydrogel constructs after 6 days of culturing. In the pNIPAAM/MgAl-LDH hybrid hydrogel, 80-95% of GAPDH enzyme activity was reduced in parallel with gene. Our findings show that the combination of a cytocompatible hydrogel and therapeutic RNA oligonucleotides is feasible. Thus it might hold promise in treating degeneration of cartilaginous tissues by providing supporting scaffolds for cells and interference with locally produced degenerative factors.

Novel protease-based diagnostic devices for detection of wound infection.

A gelatinase-based device for fast detection of wound infection was developed. Collective gelatinolytic activity in infected wounds was 23 times higher (p ≤ 0.001) than in noninfected wounds and blisters according to the clinical and microbiological description of the wounds. Enzyme activities of critical wounds showed 12-fold elevated enzyme activities compared with noninfected wounds and blisters. Upon incubation of gelatin-based devices with infected wound fluids, an incubation time of 30 minutes led to a clearly visible dye release. A 32-fold color increase was measured after 60 minutes. Both matrix metalloproteinases and elastases contributed to collective gelatinolytic enzyme activity as shown by zymography and inhibition experiments. The metalloproteinase inhibitor 1,10-phenanthroline (targeting matrix metalloproteinases) and the serine protease inhibitor phenylmethlysulfonyl fluoride (targeting human neutrophil elastase) inhibited gelatinolytic activity in infected wound fluid samples by 11-37% and 60-95%, respectively. Staphylococcus aureus and Pseudomonas aeruginosa, both known for gelatinase production, were isolated in infected wound samples.