Femoral neck trabecular microstructure in ovariectomized ewes treated with calcitonin: MRI microscopic evaluation.

Ovariectomy induces deterioration of the trabecular structure in the femoral neck of ewes, as depicted by MR microscopic imaging. This structural deterioration is prevented by salmon calcitonin treatment. INTRODUCTION: This study evaluated the trabecular (Tb) microarchitecture of an ovariectomy (OVX)-induced osteoporotic model in ewes and determined the effects of salmon calcitonin (sCT), an osteoclast inhibitor, on the Tb structure. This is the first report of OVX-induced changes in the Tb structure in the femoral neck in the ewes and effect of sCT on the microarchitecture. MATERIALS AND METHODS: Ewes (5-8 years old, n = 28) were equally allocated into sham (Sham), OVX injected with vehicle, or OVX injected with sCT at 50 or 100 IU, three injections per week. They were killed 6 months after OVX. The femoral neck was examined with an MR imager at 9.4 T in axial, coronal, and sagittal planes. An internal calibration procedure as a means of standardizing image analysis was used to adjust the segmentation threshold. Data from all three planes were averaged. RESULTS AND CONCLUSIONS: Compared with Sham, OVX induced significant changes (p < 0.0125) in the MRI-derived femoral neck Tb structure: Tb bone volume fraction (BV/TV), -18%; Tb number, -20%; Tb separation, +23%; number of free ends, +28%; number of nodes, -39%; number of Tb branches, -23%; mean length of Tb branches, -19%. Compared with OVX, treatment of sCT at 100 IU significantly improved all the Tb structural parameters to the Sham level (p < 0.0001 approximately p = 0.0281), whereas 50 IU significantly increased the Tb number and the mean length of the Tb branches. BV/TV explained 74% of the variation of compressive stress of the trabecular cylinder cores of the femoral neck. Combining all structural parameters in a multivariate regression analysis significantly improved the explanation to 84%, and adding BMD further improved the predictive ability of the model to 92%. We conclude that OVX induces deterioration of the MRI-derived Tb microstructure in the femoral neck of ewes. sCT treatment prevents OVX-induced changes. The femoral neck microarchitecture significantly correlates with its biomechanical properties. Combining microstructural parameters with BMD further improves the prediction of bone biomechanical properties. The effects of sCT on OVX ewes may help explain reduced fracture risk in postmenopausal osteoporotic women treated with sCT.     

High-flow via a tracheostomy tube and speaking valve during weaning from mechanical ventilation and tracheostomy

Background

Weaning from mechanical ventilation and tracheostomy after prolonged intensive care consume enormous resources with optimal management not currently well described. Restoration of respiratory flow via the upper airway is essential and early cuff-deflation using a one-way valve (OWV) is recommended. However, extended OWV use may cause dry airways and thickened secretions which challenge the weaning process. High-flow therapy via the tracheostomy tube (HFT-T) humidifies inspired air and may be connected via an in-line OWV (HFT-T-OWV) alleviating these problems. We aim to provide clinical and experimental data on the safety of HFT-T-OWV along with a practical guide to facilitate clinical use during weaning from mechanical ventilation and tracheostomy.

Methods

Data on adverse events of HFT-T-OWV were retrieved from a quality register for patients treated at an intensive care rehabilitation center between 2019 and 2022. Benchtop experiments were performed to measure maximum pressures and pressure support generated by HFT-T-OWV at 25–60 L/min flow using two different HFT-T adapters (interfaces). In simulated airway obstruction using a standard OWV (not in-line) maximum pressures were measured with oxygen delivered via the side port at 1–3 L/min.

Results

Of 128 tracheostomized patients who underwent weaning attempts, 124 were treated with HFT-T-OWV. The therapy was well tolerated, and no adverse events related to the practice were detected. The main reason for not using HFT-T-OWV was partial upper airway obstruction using a OWV. Benchtop experiments demonstrated HFT-T-OWV maximum pressures <4 cmH₂O and pressure support 0–0.6 cmH₂O. In contrast, 1–3 L/min supplemental oxygen via a standard OWV caused pressures between 84 and 148 cmH₂O during simulated airway obstruction.

Conclusions

Current study clinical data and benchtop experiments indicate that HFT-T-OWV was well tolerated and appeared safe. Pressure support was low, but humidification may enable extended use of a OWV without dry airway mucosa and thickened secretions. Results suggest the treatment could offer advantages to standard OWV use, with or without supplementary oxygen, as well as to HFT-T without a OWV, for weaning from mechanical ventilation and tracheostomy. However, for definitive treatment recommendations, randomized clinical trials are needed.     

International skeletal society outreach in Argentina

From June 28th to 29th, 2013, the Argentinian ISS Outreach Program took place in collaboration with the Centro de Diagnóstico Dr. Enrique Rossi in the city of Buenos Aires. A total of 690 participants attended. In the following report, we analyze the actual radiologic situation in this South American country. Outreach programs in a country such as Argentina are extremely valuable, as they provide a great opportunity for physicians that cannot travel overseas an attend international meetings such as RSNA, International Skeletal Society, or ARRS.     

Relationships between lower urinary tract symptoms and bladder outlet obstruction: Results from the ICS-“BPH” Study

Despite the lack of evidence in the literature for close relationships between lower urinary tract symptoms and bladder outlet obstruction, the majority of urologists rely on symptomatology when selecting patients for prostatic surgery. We investigated the relationships between a wide range of lower urinary tract symptoms from the ICSmale questionnaire and the results of urodynamic pressure and flow studies. We evaluated 933 patients with lower urinary tract symptoms suggestive for bladder outlet obstruction from 12 countries who participated in the ICS-“BPH” study with the ICSmale questionnaire and urodynamic pressure and flow studies. Spearman rank correlation coefficients were obtained between symptoms and measures of bladder outlet obstruction. There was little or no correlation between a wide range of symptoms and the results of free uroflowmetry and pressure and flow studies. From symptoms alone, it is not possible to diagnose bladder outlet obstruction. Pressure and flow studies and symptom profiles measure different aspects of the clinical condition that should be viewed separately in the evaluation and treatment decision of the patient presenting with lower urinary tract symptoms. Neurourol. Urodynam. 17:99–108, 1998. © 1998 Wiley-Liss, Inc.     

Patient-based decision for resuming activity after ACL reconstruction: a single-centre experience

Purpose

The purpose of the study was to report the functional outcome following anterior cruciate ligament (ACL) reconstruction in patients who decide when to resume work and normal sporting activity post-operatively. The hypothesis tested was that patient-based decision to return to work and sport was possible without compromising functional outcome and increased the rate of repeat rupture in comparison with the existing literature.

Methods

This was a monocentric, retrospective study. Seventy-two patients requiring primary ACL reconstruction were included. All patients were followed up for a mean period of 4.3 years. Return to work and to sporting activity was allowed based on patient’s decision. No restriction was suggested by the physician. Delays to return to work and sports and occurrence of graft failure were documented.

Results

Sixty-six patients (92 %) returned to any sporting activity. The mean delay was 4.1 months for running, 6.1 months for pivoting sports, and 6.6 months for contact sports. Return to competitive sport was possible in 82 % of patients after a mean delay of 7.1 months. Return to work was possible for 96 % of patients after a mean delay of 2.3 months. Index Tegner score normalized in 71 % of patients. Four repeat ruptures (6 %) were observed, all of them following a significant knee injury.

Conclusions

Patient-based decision to return to work and sport was possible without compromising functional outcome. The post-operative restrictions implemented by orthopaedic surgeons following ACL reconstructions may be relaxed and more patient based.

     

Treatment Resistance in Stem Cells and Breast Cancer

Cancer stem cells are resistant to current chemotherapy and radiation regimens available for breast cancer, making it imperative to study the mechanisms of resistance and development of therapeutic strategies that targets the tumor initiating cell population. One of the difficulties in identifying new drug targets has been that our current high throughput drug screens look for tumor shrinkage and do not incorporate the impact of compounds on the cancer stem cell population. In this review we discuss the literature on treatment resistance in breast cancer and the design of new clinical trials for test compounds which will allow us to determine both the reduction in tumor size and decrease in cancer stem cell population. In order to detect the effect of target compounds on cancer stem cells in a clinical setting, we will need to do multiple assays which include high throughput flow sorting analysis to determine the total number of CD44⁺/CD24^−/low/Lin⁻ and ALDH1 positive cells, as well as in-vitro mammosphere formation assay which is a functional assay dependent on the self renewal and anchorage independent growth properties of these cells.     

Vitamin C improves resistance but not conduit artery endothelial function in patients with chronic renal failure

BACKGROUND: Chronic renal failure is associated with impaired endothelium-dependent vasodilation and accelerated atherogenesis. To examine whether endogenous reactive oxygen species (ROS) modify endothelial function in renal failure, we evaluated the effect of the antioxidant vitamin C on endothelium-dependent responses in both the conduit and resistance vasculature of subjects with severe renal impairment. METHODS: Endothelial function of the forearm resistance vasculature was assessed using plethysmography to measure the dilator response to intra-arterial acetylcholine (Ach) (25 to 100 nmol/min). Endothelial function of radial and brachial arteries was assessed using vascular ultrasound to measure the dilator response to flow during reactive hyperemia [flow-mediated dilatation (FMD)]. Studies were performed before and after administration of vitamin C by intra-arterial infusion (25 mg/min) in 33 predialysis patients or by intravenous infusion (3 g) in 17 hemodialysis patients. RESULTS: Parenteral administration of vitamin C resulted in a 100-fold increase (intra-arterial studies) and a 4.5-fold increase (intravenous studies) in serum antioxidant activity. Vitamin C administration increased the dilator response to ACh in resistance vessels (P = 0.01), but did not alter the dilator response to flow in conduit vessels of either dialysis (P = 0.3) or predialysis subjects (P = 0.8). In the presence of the nitric oxide (NO) synthase inhibitor NGmonomethyl-L-arginine (L-NMMA), there was no effect of vitamin C on resistance vessel endothelial function. In all cases the dilator response to the endothelium-independent dilators was unaffected by vitamin C. CONCLUSION: Acute administration of vitamin C reduces oxidant stress in renal failure and improves NO-mediated resistance vessel dilatation.