ABSTRACT
Complete remission of BRAF V600E-driven ACC CUP by BRAF/MEK inhibition underscores importance of precision oncology.
Subject(s)
Proto-Oncogene Proteins B-raf , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Humans , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Mutation , Male , Female , Middle Aged , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitorsABSTRACT
INTRODUCTION: We characterize the geographic distribution of providers trained to inject Clostridium histolyticum and identify areas with low provider availability. METHODS: We utilized a publicly available search tool to identify clinical sites offering Clostridium histolyticum in the US The data gathered included the provider's name, specialty, address, and whether the site was considered high-volume (ie, administer ≥20 Clostridium histolyticum injections per year). Data were compared to the AUA Census. RESULTS: In total, 2,388 clinical sites offering Clostridium histolyticum were identified. A total of 894 sites (37%) were high-volume sites. The mean number of locations offering Clostridium histolyticum per 100,000 state residents was 0.69 (SD 0.27). Georgia (1.28), Rhode Island (1.13), and Alaska (1.10) had the highest number, whereas New Mexico (0.10), Maine (0.22), and Delaware (0.30) had the lowest. The mean proportion of urologists providing Clostridium histolyticum to total urologists was 0.17 (SD 0.07). The 3 states with the highest proportion were Georgia (0.37), Alaska (0.31), and Utah (0.30), whereas New Mexico (0.03), Maine (0.05), and Vermont (0.06) had the lowest. CONCLUSIONS: States with low numbers of clinical sites offering Clostridium histolyticum per 100,000 residents relative to other states also had a low total ratio of urologists offering Clostridium histolyticum as a treatment. There is room for urologists in these states and others to expand their practice to offer Clostridium histolyticum and improve patient access to this important nonsurgical treatment option.
Subject(s)
Penile Induration , Male , Humans , Penile Induration/drug therapy , Microbial Collagenase/therapeutic use , Treatment Outcome , Injections, Intralesional , Alaska , Clostridium histolyticumABSTRACT
BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed malignant tumor in men. The potential benefit of a healthy lifestyle contrasts sharply with the observed poor adherence to current international lifestyle guidelines. Thus, well-designed sustainable interventions of aftercare that can be translated into routine practice are highly recommended. The present pilot study aimed to evaluate the feasibility and acceptability of a multimodal lifestyle intervention program in PCa patients after radical prostatectomy (RP). METHODS: In a single-arm study, carried out at the Martini-Klinik of the University Medical Center Hamburg-Eppendorf, Germany, 59 eligible men with locally advanced PCa were recruited within 3-6 months after RP and assigned to a multimodal lifestyle program. The program consisted of 10 weekly 6-7 h course days, with a focus on dietary control, physical activity (per World Cancer Research Fund recommendations) and psychological support. Primary objectives were feasibility, acceptability, completion rate, and safety. In addition, changes in lifestyle, psychological well-being, clinical and laboratory values were assessed. The study was registered in the German Clinical Trials Register (No. DRK S00015288 [MARTINI-Lifestyle-cohort] [www.germanctr.de]). RESULTS: A high program acceptance was observed. Only three participants (5%) dropped out of the program prematurely. Personal feedback reflected appreciation for participation, personal gain through new knowledge and through the group experience. Without exception, all participants have taken part in follow-up examinations and no adverse events or incidents occurred. In addition, changes in lifestyle habits, clinical parameters and improved quality of life were detected. CONCLUSION: The MARTINI lifestyle program appears feasible and safe, and acceptance of the multimodal intervention was high among PCa patients. These encouraging results favor conducting a large multicenter trial to implement the program into routine practice and to evaluate the effectiveness of the intervention on survival and quality of life.
Subject(s)
Prostatic Neoplasms , Quality of Life , Male , Humans , Pilot Projects , Feasibility Studies , Life Style , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathologyABSTRACT
OBJECTIVES/HYPOTHESIS: Examination of tissue structures by optical coherence tomography (OCT) has been shown to be useful on mucous membranes of the vocal folds, but so far its application to the human larynx has been limited because it is technically cumbersome and usually needs to be performed with sedation. Here a newly developed, noninvasive combined laryngoscopy and OCT procedure is described and its suitability for ambulatory OCT studies evaluated. Because inhalation therapies utilizing saline solutions are commonly used as a treatment option for disorders of the airways, and vocal fold epithelium is most likely to be affected due to its superficial positioning, epithelial thickness was chosen as a relevant test parameter and evaluated before and after saline inhalation. METHODS: Seven vocally healthy participants performed a 10-minute inhalation of saline solution and underwent a combined laryngoscopy and OCT before and after the inhalation therapy. Endoscopy was performed using a newly developed combined laryngoscopy and OCT device. The OCT images were used to estimate the epithelial thickness of the vocal folds. RESULTS: Epithelial thickness measured in all participants before treatment was comparable in size reported in previous studies. Statistical differences before and after inhalation were not detected. CONCLUSION: The newly developed combined laryngoscopy and OCT procedure enables rapid investigation of the vocal fold epithelium. Inhalation of saline solution did not appear to affect the thickness of the epithelium of the vocal folds in vocally healthy subjects, as evaluated by OCT. LEVEL OF EVIDENCE: N/A. Laryngoscope, 126:E332-E336, 2016.
Subject(s)
Laryngeal Mucosa/diagnostic imaging , Laryngoscopy/methods , Sodium Chloride/administration & dosage , Tomography, Optical Coherence/methods , Vocal Cords/diagnostic imaging , Administration, Inhalation , Adult , Female , Healthy Volunteers , Humans , Laryngeal Mucosa/anatomy & histology , Male , Vocal Cords/anatomy & histology , Young AdultABSTRACT
Optical coherence tomography (OCT) provides structural information of laryngeal tissue which is comparable to histopathological analysis of biopsies taken under general anesthesia. In awake patients, movements impede clinically useful OCT acquisition. Therefore, an automatic compensation of movements was implemented into a swept source OCT-laryngoscope. Video and OCT beam path were combined in one tube of 10-mm diameter. Segmented OCT images served as distance sensor and a feedback control adjusted the working distance between 33 and 70 mm by synchronously translating the reference mirror and focusing lens. With this motion compensation, the tissue was properly visible in up to 88% of the acquisition time. During quiet respiration, OCT contrasted epithelium and lamina propria. Mean epithelial thickness was measured to be 109 and [Formula: see text] in female and male, respectively. Furthermore, OCT of mucosal wave movements during phonation enabled estimation of the oscillation frequency and amplitude. Regarding clinical issues, the OCT-laryngoscope with automated working distance adjustment may support the estimation of the depth extent of epithelial lesions and contribute to establish an indication for a biopsy. Moreover, OCT of the vibrating vocal folds provides functional information, possibly giving further insight into mucosal behavior during the vibratory cycle.
ABSTRACT
BACKGROUND: The diagnosis of hip pain after total hip replacement (THR) represents a highly challenging question that is of increasing concern to orthopedic surgeons. This retrospective study assesses bone scintigraphy with Hybrid SPECT/CT for the diagnosis of painful THR in a selected cohort of patients. METHODS: Bone SPECT/CT datasets of 23 patients (mean age 68.9 years) with a painful hip after THR were evaluated. Selection of the patients required an inconclusive radiograph, normal serum levels of inflammatory parameters (CRP and ESR) or a negative aspiration of the hip joint prior to the examination. The standard of reference was established by an interdisciplinary adjudication-panel using all imaging data and clinical follow-up data (>12 month). Pathological and physiological uptake patterns were defined and applied. RESULTS: The cause of pain in this study group could be determined in 18 out of 23 cases. Reasons were aseptic loosening (n = 5), spine-related (n = 5), heterotopic ossification (n = 5), neuronal (n = 1), septic loosening (n = 1) and periprosthetic stress fracture (n = 1). In (n = 5) cases the cause of hip pain could not be identified. SPECT/CT imaging correctly identified the cause of pain in (n = 13) cases, in which the integrated CT-information led to the correct diagnosis in (n = 4) cases, mainly through superior anatomic correlation. Loosening was correctly assessed in all cases with a definite diagnosis. CONCLUSIONS: SPECT/CT of THA reliably detects or rules out loosening and provides valuable information about heterotopic ossifications. Furthermore differential diagnoses may be detected with a whole-body scan and mechanical or osseous failure is covered by CT-imaging. SPECT/CT holds great potential for imaging-based assessment of painful prostheses.
Subject(s)
Arthralgia/diagnosis , Arthralgia/etiology , Arthroplasty, Replacement, Hip/adverse effects , Hip Joint/diagnostic imaging , Tomography, Emission-Computed, Single-Photon/methods , Aged , Bone Cements , Female , Humans , Male , Multimodal Imaging/methods , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
Ceramic components in total knee arthroplasty (TKA) are evolving. We analyze the first case of BIOLOX delta ceramic femoral component fracture. A longitudinal midline fracture in the patellar groove was present, with an intact cement mantle and no bony defects. Fractographic analysis with laser scanning microscopy and white light interferometry showed no evidence of arrest lines, hackles, wake hackles, material flaws, fatigue or crack propagation. Analysis of periprosthetic tissues with Fourier-transform infrared (FT-IR) microscopy, contact radiography, histology, and subsequent digestion and high-speed centrifugation did not show ceramic debris. A macrophage-dominated response was present around polyethylene debris. We conclude that ceramic femoral component failure in this case was related to a traumatic event. Further research is needed to determine the suitability of ceramic components in TKA.
Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Equipment Failure Analysis/methods , Knee Prosthesis/adverse effects , Osteoarthritis, Knee/surgery , Prosthesis Failure , Biocompatible Materials , Ceramics , Female , Humans , Middle AgedABSTRACT
Water-filtered infrared-A (wIRA) radiation has been described as supportive for tissue regeneration. We sought to investigate in detail the wIRA effect at different temperatures in 3T3 fibroblasts that were treated with glyoxal to induce formation of advanced glycation end products (AGEs). Nonirradiated and nonglyoxal-treated cells served as controls. Experiments were carried out over a range of 37°-45°C with exact temperature monitoring to distinguish between temperature and wIRA effects. Metabolic activity was assessed by resazurin assay. Mitochondrial membrane potential was assessed by JC-1 vital staining. Apoptotic changes were determined by vital staining with annexin V and YO-PRO-1 and determination of subG1 DNA content. Temperature had a dominant effect overriding effects exerted by wIRA or glyoxal treatment. The number of apoptotic cells was significantly higher at 45°C, while the percentage of healthy cells was significantly lower at 45°C. WIRA irradiation itself or in combination with glyoxal treatment exerted no damaging effects on the fibroblasts at physiological (37°-40°C) or higher (42°-45°C) temperatures compared to untreated controls. Temperatures of 45°C, which can occur during inappropriate application of infrared irradiation, damage cells even in the absence of wIRA or glyoxal application.
Subject(s)
Fibroblasts/drug effects , Fibroblasts/radiation effects , Glyoxal/pharmacology , Infrared Rays , Stress, Physiological/drug effects , Stress, Physiological/radiation effects , Temperature , 3T3 Cells , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Cells, Cultured , Fibroblasts/cytology , Fibroblasts/metabolism , Filtration , Health , Membrane Potential, Mitochondrial/drug effects , Mice , Necrosis , WaterABSTRACT
There is a growing interest in analyzing lung mechanics at the level of the alveoli in order to understand stress-related pathogenesis and possibly avoid ventilator associated lung injury. Emerging quantitative models to simulate fluid mechanics and the associated stresses and strains on delicate alveolar walls require realistic quantitative input on alveolar geometry and its dynamics during ventilation. Here, three-dimensional optical coherence tomography (OCT) and conventional intravital microscopy are joined in one setup to investigate the geometric changes of subpleural alveoli during stepwise pressure increase and release in an isolated and perfused rabbit lung model. We describe good qualitative agreement and quantitative correlation between the OCT data and video micrographs. Our main finding is the inflation and deflation of individual alveoli with noticeable hysteresis. Importantly, this three-dimensional geometry data can be extracted and converted into input data for numerical simulations.
Subject(s)
Imaging, Three-Dimensional/methods , Pulmonary Alveoli/cytology , Subtraction Technique , Tomography, Optical Coherence/methods , Animals , In Vitro Techniques , Microscopy, Video , Rabbits , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
OBJECTIVES: : To analyze alveolar dynamics in healthy and acid-injured lungs of ventilated mice. Protective ventilation is potentially lifesaving in patients with acute lung injury. However, optimization of ventilation strategies is hampered by an incomplete understanding of the effects of mechanical ventilation at the alveolar level. DESIGN: : In anesthetized and ventilated Balb/c mice, subpleural alveoli were visualized by darkfield intravital microscopy and optical coherence tomography. SETTING: : Animal research laboratory. SUBJECTS: : Male Balb/c mice. INTERVENTIONS: : Lung injury was induced by intratracheal instillation of hydrochloric acid. In control animals and mice with lung injury, ventilation pressures were varied between 0 and 24 cm H2O at baseline, 60 mins, and 120 mins, and alveolar distension and cyclic opening and collapse of alveolar clusters were analyzed. MEASUREMENTS AND MAIN RESULTS: : In normal lungs, alveolar clusters distend with increasing ventilation pressure in a sigmoid relationship. Although an increase in ventilation pressure from 0 to 24 cm H2O increases alveolar size by 41.5 +/- 2.3% in normal lungs, alveolar distension is reduced to 20.6 +/- 2.2% 120 mins after induction of lung injury by acid aspiration. Cyclic opening and collapse of alveolar clusters are neither observed in normal nor acid-injured lungs. Alveolar compliance is highest in small and distensible alveolar clusters, which are also most prone to acid-induced injury. CONCLUSIONS: : Over the applied pressure range, volume changes in control and acid-injured mouse lungs result predominantly from alveolar distension rather than cyclic opening and collapse of alveolar clusters. Preferential loss of compliance in small alveolar clusters redistributes tidal volume to larger alveoli, which increases spatial heterogeneity in alveolar inflation and may promote alveolar overdistension.