Monitoring the recovery time of children after tonsillectomy using commercial activity trackers.

An observational prospective feasibility study in which children received a tracker 2 weeks before a tonsillectomy and were required to wear it until four weeks postoperatively. The parents used a diary to log the estimated steps of their child. As primary endpoint, the compliance of complete datasets was compared between the tracker and the diary. As secondary endpoints, the agreement of steps between tracker and diary, and the recovery time after tonsillectomy were analyzed.Twenty-four patients (50% male) with a median age of 6 years were recruited. The tracker had a complete dataset compliance of 91.7% in the pre-operative and 58.3% in postoperative period, whereas the diary's compliance was 62.5% in the pre-operative and 12.5% in the postoperative period. The difference of 29.2% and 45.8% in the pre-operative and postoperative periods between the tracker and the diary was significant (p < 0.005). The tracker and diary had a mean agreement difference of 1063 steps per day. Mean recovery time was 21 days after tonsillectomy.Conclusion: The results of this pilot study support the use of a tracker in terms of compliance and practicability. Consumer-level activity trackers are a viable alternative to conventional manual logging for clinical use in pediatric research.Trial registration: ClinicalTrials.gov Identifier: NCT03174496 What is known: • Consumer-level activity trackers are already used in clinical research to monitor steps and physical activity. • The use of consumer-level activity trackers in clinical studies has mostly been validated in the adult population. What is new: • This study proves the feasibility of using physical activity trackers in a pediatric population before and after a surgical intervention. • Recovery of a patient could be assessed with an activity tracker.

Supervised preoperative forearm exercise to increase blood vessel diameter in patients requiring an arteriovenous access for hemodialysis: rationale and design of the PINCH trial.

BACKGROUND: Failure of maturation occurs in 30%-60% of arteriovenous fistula (AVF) creation for hemodialysis, with highest rates in distal radiocephalic fistulas. This is partly due to initial small blood vessel size with limited blood flow capacity. Forearm exercise has shown potential as stimulus for increasing blood vessel size in patients with end-stage renal disease (ESRD) and may promote maturation of AVFs in the upper limb when applied postoperatively. However, it is unknown if forearm exercise increases blood vessel size pre-operatively, which may contribute to more distal AVF creation and raise success rates of AVF surgery. This study will investigate these issues. METHODS AND RESULTS: The PINCH trial (refers to 'pinching') is an investigator-initiated, multicenter, single-blinded, randomized controlled trial with 1:1 randomization to perform supervised forearm exercises compared to no exercise 6 weeks pre-operatively before creation of an AVF. Forty patients receiving an AVF will be included. The main study endpoints are blood vessel diameter (cephalic or basilic vein and radial and ulnar artery), AVF surgical plan (radiocephalic or brachiobasilic/cephalic), and three-month (assisted) maturation rate. The burden of the performed forearm exercises will be evaluated using Kidney Disease Quality of Life (KDQOL-SF Dutch version 1.2) and exercise specific questionnaires. The PINCH trial is planned to start in November 2017. Enrollment is expected to be completed at the end of 2019. CONCLUSIONS: The PINCH study is the first trial to evaluate the effect of pre-operative, supervised forearm exercises on vein diameter and fistula maturation in hemodialysis patients. TRIAL REGISTRATION: NTR6382.

Structural and Mechanical Comparison of Human Ear, Alar, and Septal Cartilage.

BACKGROUND: In the human ear and nose, cartilage plays a key role in establishing its form and function. Interestingly, there is a noticeable paucity on biochemical, structural, and mechanical studies focused on facial cartilage. Such studies are needed to provide elementary knowledge that is fundamental to tissue engineering of cartilage. Therefore, in this study, a comparison is made of the biochemical, structural, and mechanical differences between ear, ala nasi, and septum on the extracellular matrix (ECM) level. METHODS: Cartilage samples were harvested from 10 cadaveric donors. Each sample was indented 10 times with a nanoindenter to determine the effective Young's modulus. Structural information of the cartilage was obtained by multiple-photon laser scanning microscopy capable of revealing matrix components at subcellular resolution. Biochemistry was performed to measure glycosaminoglycan (GAG), DNA, elastin, and collagen content. RESULTS: Significant differences were seen in stiffness between ear and septal cartilage (P = 0.011) and between ala nasi and septal cartilage (P = 0.005). Elastin content was significantly higher in ear cartilage. Per cartilage subtype, effective Young's modulus was not significantly correlated with cell density, GAG, or collagen content. However, in septal cartilage, low elastin content was associated with higher stiffness. Laser microscopy showed a distinct difference between ear cartilage and cartilage of nasal origin. CONCLUSION: Proposed methods to investigate cartilage on the ECM level provided good results. Significant differences were seen not only between ear and nasal cartilage but also between the ala nasi and septal cartilage. Albeit its structural similarity to septal cartilage, the ala nasi has a matrix stiffness comparable to ear cartilage.

Noninvasive Measurement of Ear Cartilage Elasticity on the Cellular Level: A New Method to Provide Biomechanical Information for Tissue Engineering.

BACKGROUND: An important feature of auricular cartilage is its stiffness. To tissue engineer new cartilage, we need objective tools to provide us with the essential biomechanical information to mimic optimal conditions for chondrogenesis and extracellular matrix (ECM) development. In this study, we used an optomechanical sensor to investigate the elasticity of auricular cartilage ECM and tested whether sensitivity and measurement reproducibility of the sensor would be sufficient to accurately detect (subtle) differences in matrix compositions in healthy, diseased, or regenerated cartilage. METHODS: As a surrogate model to different cartilage ECM compositions, goat ears (n = 9) were subjected to different degradation processes to remove the matrix components elastin and glycosaminoglycans. Individual ear samples were cut and divided into 3 groups. Group 1 served as control and was measured within 2 hours after animal death and at 24 and 48 hours, and groups 2 and 3 were measured after 24- and 48-h hyaluronidase or elastase digestion. Per sample, 9 consecutive measurements were taken ±300 µm apart. RESULTS: Good reproducibility was seen between consecutive measurements with an overall interclass correlation coefficient average of 0.9 (0.81-0.98). Although degradation led to variable results, overall, a significant difference was seen between treatment groups after 48 hours (control, 4.2 MPa [±0.5] vs hyaluronidase, 2.0 MPa [±0.3], and elastase, 3.0 MPa [±0.4]; both P < 0.001). CONCLUSIONS: The optomechanical sensor system we used provided a fast and reliable method to perform measurements of cartilage ECM in a reverse tissue-engineering model. In future applications, this method seems feasible for the monitoring of changes in stiffness during the development of tissue-engineered auricular cartilage.

Molecular imaging of bone marrow mononuclear cell survival and homing in murine peripheral artery disease.

OBJECTIVES: This study aims to provide insight into cellular kinetics using molecular imaging after different transplantation methods of bone marrow-derived mononuclear cells (MNCs) in a mouse model of peripheral artery disease (PAD). BACKGROUND: MNC therapy is a promising treatment for PAD. Although clinical translation has already been established, there is a lack of knowledge about cell behavior after transplantation and about the mechanism whereby MNC therapy might ameliorate complaints of PAD. METHODS: MNCs were isolated from F6 transgenic mice (FVB background) that express firefly luciferase (Fluc) and green fluorescence protein (GFP). Male FVB and C57Bl6 mice (n = 50) underwent femoral artery ligation and were randomized into 4 groups receiving the following: 1) single intramuscular (IM) injection of 2 × 10(6) MNCs; 2) 4 weekly IM injections of 5 × 10(5) MNCs; 3) 2 × 10(6) MNCs intravenously; and 4) phosphate-buffered saline as control. Cells were characterized by flow cytometry and in vitro bioluminescence imaging (BLI). Cell survival, proliferation, and migration were monitored by in vivo BLI, which was validated by ex vivo BLI, post-mortem immunohistochemistry, and flow cytometry. Paw perfusion and neovascularization was measured with laser Doppler perfusion imaging (LDPI) and histology, respectively. RESULTS: In vivo BLI revealed near-complete donor cell death 4 weeks after IM transplantation. After intravenous transplantation, BLI revealed that cells migrated to the injured area in the limb, as well as to the liver, spleen, and bone marrow. Ex vivo BLI showed presence of MNCs in the scar tissue and adductor muscle. However, no significant effects on neovascularization were observed, as monitored by LDPI and histology. CONCLUSIONS: This is one of the first studies to assess kinetics of transplanted MNCs in PAD using in vivo molecular imaging. MNC survival is short-lived, MNCs do not preferentially home to injured areas, and MNCs do not significantly stimulate perfusion in this particular model.

Interleukin-16 deficiency suppresses the development of chronic rejection in murine cardiac transplantation model.

BACKGROUND: IL-16 promotes the recruitment of various cells expressing CD4, a receptor for IL-16. The precise role of IL-16 in transplant rejection remains unknown; therefore, the present study investigated the contribution of IL-16 to the development of chronic rejection in heart transplants. METHODS: C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into (1) IL-16-deficient (IL-16(-/-)) C57BL/6J or (b) wild type (WT) control recipients (MHC class II mismatch). Grafts were harvested at 52 days, parenchymal rejection was assessed by the ISHLT grading system, and CAV was examined morphometrically. Graft infiltrating cells were detected 10 and 52 days after transplantation. Intragraft cytokine and chemokine profiles were assessed. To confirm the role of IL-16 in CAV development, C-H-2(bm12)KhEg (H-2(bm12)) donor hearts were transplanted into C57BL/6J WT recipients treated with (1) anti-IL-16-neutralization monoclonal antibody or (b) control immunoglobulin G. Grafts were harvested at 52 days, and CAV was quantified morphometrically. Graft-infiltrating cells were examined histologically. RESULTS: Parenchymal rejection and CAV was significantly attenuated in donor hearts transplanted into IL-16(-/-) recipient mice compared with WT controls. Donor hearts transplanted into IL-16(-/-) recipients had a significant reduction in coronary artery luminal occlusion, intima-to-media ratio, and percentage of diseased vessels. CAV was associated with decreased donor organ inflammation, as well as donor organ cytokine (IL-1ß and IL-6) and chemokine (MCP-1 and KC) protein expression. Intimal proliferation and inflammatory cell infiltration were significantly reduced in hearts transplanted into recipients treated with an IL-16-neutralization antibody. CONCLUSIONS: IL-16-deficiency reduced graft inflammatory cell recruitment, and allograft inflammatory cytokine and chemokine production. Therefore, IL-16 neutralization may provide a potential target for novel therapeutic treatment for cardiac allograft rejection.

Role of molecular imaging in stem cell therapy for myocardial restoration.

During the past two decades, stem cells have created enthusiasm as a regenerative therapy for ischemic heart disease. Transplantation of bone marrow stem cells, skeletal myoblasts, and endothelial progenitor cells has shown to improve myocardial function after infarction. Recently, attention has focused on the potential use of embryonic stem cells and induced pluripotent stem cells because they possess the capacity to differentiate into various cell types, including cardiac and endothelial cells. Clinical trials have shown positive effects on the functional recovery of heart after myocardial infarction and have answered questions on timing, dosage, and cell delivery route of stem cells such as those derived from bone marrow. Despite the current advances in stem cell research, one main hurdle remains the lack of reliable information about the fate of cell engraftment, survival, and proliferation after transplantation. This review discusses the different cell types used in cardiac cell therapy as well as molecular imaging modalities relevant to survival issues.