Translation, cross-cultural adaptation, and validation of the sino-nasal outcome test (snot)-22 for Finnish patients

Purpose The Sino-Nasal Outcome Test-22 (SNOT-22) is the most commonly used disease-specific quality of life questionnaire in rhinology. The purpose of this prospective study was to translate and validate SNOT-22 into Finnish. Methods The validation process followed the guidelines proposed for cross-cultural adaptation of health-related measures of quality of life. The study consisted of three groups: rhinologic out-patients (N = 96), FESS patients (N = 49) and healthy controls (N = 79). Out-patient and FESS groups completed the questionnaire twice (answers A and B), out-patients after two weeks and FESS patients after 3 months. Validity, reliability and responsiveness were evaluated. Results The mean SNOT-22 sum score of the out-patient questionnaires were 35.3 points (answer A) and 32.4 points (answer B). ICC in out-patient group was 0.879. For the FESS patients, the mean pre- and postoperative (answer A and B) SNOT-22 sum scores were 46.8 and 21.9 points, respectively (p <0.0001). The mean SNOT-22 of healthy controls was 8.9 points. The out-patients (answer A) and healthy controls had statistically significant difference in SNOT-22 scores (p <0.0001). Conclusions The results of our study show that the validated Finnish version of the SNOT-22 questionnaire demonstrates good validity, reliability and responsiveness.Peer reviewe

A Comprehensive Panel of Three-Dimensional Models for Studies of Prostate Cancer Growth, Invasion and Drug Responses

Peer reviewe

Tautikohtaisen elämänlaatumittarin validointi - esimerkkinä nenä- ja sivuontelotautikohtainen SNOT-22-mittari

English summar

Visible and Near-Infrared Spectroscopy Enables Differentiation of Normal and Early Osteoarthritic Human Knee Joint Articular Cartilage

Osteoarthritis degenerates cartilage and impairs joint function. Early intervention opportunities are missed as current diagnostic methods are insensitive to early tissue degeneration. We investigated the capability of visible light-near-infrared spectroscopy (Vis-NIRS) to differentiate normal human cartilage from early osteoarthritic one. Vis-NIRS spectra, biomechanical properties and the state of osteoarthritis (OARSI grade) were quantified from osteochondral samples harvested from different anatomical sites of human cadaver knees. Two support vector machines (SVM) classifiers were developed based on the Vis-NIRS spectra and OARSI scores. The first classifier was designed to distinguish normal (OARSI: 0–1) from general osteoarthritic cartilage (OARSI: 2–5) to check the general suitability of the approach yielding an average accuracy of 75% (AUC = 0.77). Then, the second classifier was designed to distinguish normal from early osteoarthritic cartilage (OARSI: 2–3) yielding an average accuracy of 71% (AUC = 0.73). Important wavelength regions for differentiating normal from early osteoarthritic cartilage were related to collagen organization (wavelength region: 400–600 nm), collagen content (1000–1300 nm) and proteoglycan content (1600–1850 nm). The findings suggest that Vis-NIRS allows objective differentiation of normal and early osteoarthritic tissue, e.g., during arthroscopic repair surgeries.Peer reviewe

Site- and Zone-Dependent Changes in Proteoglycan Content and Biomechanical Properties of Bluntly and Sharply Grooved Equine Articular Cartilage

In this study, we mapped and quantified changes of proteoglycan (PG) content and biomechanical properties in articular cartilage in which either blunt or sharp grooves had been made, both close to the groove and more remote of it, and at the opposing joint surface (kissing site) in equine carpal joints. In nine adult Shetland ponies, standardized blunt and sharp grooves were surgically made in the radiocarpal and middle carpal joints of a randomly chosen front limb. The contralateral control limb was sham-operated. At 39 weeks after surgery, ponies were euthanized. In 10 regions of interest (ROIs) (six remote from the grooves and four directly around the grooves), PG content as a function of tissue-depth and distance-to-groove was estimated using digital densitometry. Biomechanical properties of the cartilage were evaluated in the six ROIs remote from the grooves. Compared to control joints, whole tissue depth PG loss was found in sites adjacent to sharp and, to a larger extent, blunt grooves. Also, superficial PG loss of the surgically untouched kissing cartilage layers was observed. Significant PG loss was observed up to 300 µm (sharp) and at 500 µm (blunt) from the groove into the surrounding tissue. Equilibrium modulus was lower in grooved cartilage than in controls. Grooves, in particular blunt grooves, gave rise to severe PG loss close to the grooved sites and to mild degeneration more remote from the grooves in both sharply and bluntly grooved cartilage and at the kissing sites, resulting in loss of mechanical strength over the 9-month period

Translation, cross-cultural adaptation, and validation of the sino-nasal outcome test (snot)-22 for Finnish patients

Purpose The Sino-Nasal Outcome Test-22 (SNOT-22) is the most commonly used disease-specific quality of life questionnaire in rhinology. The purpose of this prospective study was to translate and validate SNOT-22 into Finnish. Methods The validation process followed the guidelines proposed for cross-cultural adaptation of health-related measures of quality of life. The study consisted of three groups: rhinologic out-patients (N = 96), FESS patients (N = 49) and healthy controls (N = 79). Out-patient and FESS groups completed the questionnaire twice (answers A and B), out-patients after two weeks and FESS patients after 3 months. Validity, reliability and responsiveness were evaluated. Results The mean SNOT-22 sum score of the out-patient questionnaires were 35.3 points (answer A) and 32.4 points (answer B). ICC in out-patient group was 0.879. For the FESS patients, the mean pre- and postoperative (answer A and B) SNOT-22 sum scores were 46.8 and 21.9 points, respectively (p p Conclusions The results of our study show that the validated Finnish version of the SNOT-22 questionnaire demonstrates good validity, reliability and responsiveness.</p

Ex vivo assessment of targeted therapies in a rare metastatic epithelial–myoepithelial carcinoma

Epithelial–myoepithelial carcinoma (EMC) is a rare subtype of salivary gland neoplasms. Since the initial description of the cancer, just over 300 cases have been reported. EMCs occupy a biphasic cellular differentiation-state defined by the constitution of two cell types representing epithelial and myoepithelial lineages, yet the functional consequence of the differentiation-state heterogeneity with respect to therapy resistance of the tumors remains unclear. The reported local recurrence rate of the cases is approximately 30%, and while distant metastases are rare, a significant fraction of these cases are reported to receive no survival benefit from radio- or chemotherapy given in addition to surgery. Moreover, no targeted therapies have been reported for these neoplasms. We report here the first use and application of ex vivo drug screening together with next generation sequencing to assess targeted treatment strategies for a rare metastatic epithelial–myoepithelial carcinoma. Results of the ex vivo drug screen demonstrate significant differential therapeutic sensitivity between the epithelial and myoepithelial intra-tumor cell lineages suggesting that differentiation-state heterogeneity within epithelial–myoepithelial carcinomas may present an outlet to partial therapeutic responses to targeted therapies including MEK and mTOR inhibitors. These results suggest that the intra-tumor lineage composition of EMC could be an important factor to be assessed when novel treatments are being evaluated for management of metastatic EMC

Ex vivo drug screening informed targeted therapy for metastatic parotid squamous cell carcinoma

The purpose of ex vivo drug screening in the context of precision oncology is to serve as a functional diagnostic method for therapy efficacy modeling directly on patient-derived tumor cells. Here, we report a case study using integrated multiomics ex vivo drug screening approach to assess therapy efficacy in a rare metastatic squamous cell carcinoma of the parotid gland. Tumor cells isolated from lymph node metastasis and distal subcutaneous metastasis were used for imaging-based single-cell resolution drug screening and reverse-phase protein array-based drug screening assays to inform the treatment strategy after standard therapeutic options had been exhausted. The drug targets discovered on the basis of the ex vivo measured drug efficacy were validated with histopathology, genomic profiling, and in vitro cell biology methods, and targeted treatments with durable clinical responses were achieved. These results demonstrate the use of serial ex vivo drug screening to inform adjuvant therapy options prior to and during treatment and highlight HER2 as a potential therapy target also in metastatic squamous cell carcinoma of the salivary glands

Machine learning augmented near-infrared spectroscopy: In vivo follow-up of cartilage defects

OBJECTIVE: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. METHOD: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up time points (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. RESULTS: For the independent test, the trained networks yielded significant correlations for cartilage thickness (ρ=0.473) and instantaneous modulus (ρ=0.498). These networks were used to predict the reference properties at baseline and follow-ups. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. CONCLUSION: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints demonstrated more vulnerability to cartilage degeneration after damage than intercarpal joints

Dual-contrast micro-CT enables cartilage lesion detection and tissue condition evaluation ex vivo

Background: Post-traumatic osteoarthritis is a frequent joint disease in the horse. Currently, equine medicine lacks effective methods to diagnose the severity of chondral defects after an injury. Objectives: To investigate the capability of dual-contrast-enhanced computed tomography (dual-CECT) for detection of chondral lesions and evaluation of the severity of articular cartilage degeneration in the equine carpus ex vivo. Study design: Pre-clinical experimental study. Methods: In nine Shetland ponies, blunt and sharp grooves were randomly created (in vivo) in the cartilage of radiocarpal and middle carpal joints. The contralateral joint served as control. The ponies were subjected to an 8-week exercise protocol and euthanised 39 weeks after surgery. CECT scanning (ex vivo) of the joints was performed using a micro-CT scanner 1 hour after an intra-articular injection of a dual-contrast agent. The dual-contrast agent consisted of ioxaglate (negatively charged, q = −1) and bismuth nanoparticles (BiNPs, q = 0, diameter ≈ 0.2 µm). CECT results were compared to histological cartilage proteoglycan content maps acquired using digital densitometry. Results: BiNPs enabled prolonged visual detection of both groove types as they are too large to diffuse into the cartilage. Furthermore, proportional ioxaglate diffusion inside the tissue allowed differentiation between the lesion and ungrooved articular cartilage (3 mm from the lesion and contralateral joint). The mean ioxaglate partition in the lesion was 19 percentage points higher (P < 0.001) when compared with the contralateral joint. The digital densitometry and the dual-contrast CECT findings showed good subjective visual agreement. Main limitations: Ex vivo study protocol and a low number of investigated joints. Conclusions: The dual-CECT methodology, used in this study for the first time to image whole equine joints, is capable of effective lesion detection and simultaneous evaluation of the condition of the articular cartilage