Are large language models valid tools for patient information on lumbar disc herniation? The spine surgeons' perspective.

Introduction: Generative AI is revolutionizing patient education in healthcare, particularly through chatbots that offer personalized, clear medical information. Reliability and accuracy are vital in AI-driven patient education. Research question: How effective are Large Language Models (LLM), such as ChatGPT and Google Bard, in delivering accurate and understandable patient education on lumbar disc herniation? Material and methods: Ten Frequently Asked Questions about lumbar disc herniation were selected from 133 questions and were submitted to three LLMs. Six experienced spine surgeons rated the responses on a scale from "excellent" to "unsatisfactory," and evaluated the answers for exhaustiveness, clarity, empathy, and length. Statistical analysis involved Fleiss Kappa, Chi-square, and Friedman tests. Results: Out of the responses, 27.2% were excellent, 43.9% satisfactory with minimal clarification, 18.3% satisfactory with moderate clarification, and 10.6% unsatisfactory. There were no significant differences in overall ratings among the LLMs (p = 0.90); however, inter-rater reliability was not achieved, and large differences among raters were detected in the distribution of answer frequencies. Overall, ratings varied among the 10 answers (p = 0.043). The average ratings for exhaustiveness, clarity, empathy, and length were above 3.5/5. Discussion and conclusion: LLMs show potential in patient education for lumbar spine surgery, with generally positive feedback from evaluators. The new EU AI Act, enforcing strict regulation on AI systems, highlights the need for rigorous oversight in medical contexts. In the current study, the variability in evaluations and occasional inaccuracies underline the need for continuous improvement. Future research should involve more advanced models to enhance patient-physician communication.

Patient-reported outcomes 1 and 2 years after transforaminal thoracic interbody fusion (TTIF).

STUDY DESIGN: Retrospective Cohort Study with prospectively collected data. PURPOSE: Transforaminal interbody fusion was initially designed for the lumbar spine. A similar approach was later introduced for the thoracic spine (TTIF). Here we report the surgical technique and the Core Outcome Measures Index (COMI) at 1-year and 2-year follow-ups, as well as the sagittal radiographic kyphosis correction of TTIF, achieved at 1 year and the latest follow-up. METHODS: All TTIF procedures from 2012 to 2020 were included. COMI scores were collected preoperatively and at 1- and 2-year follow-ups. The sagittal angle between the upper and lower endplates at the segment where TTIF was performed was measured on preoperative, 1-year postoperative, and last available radiographs. RESULTS: Seventy-nine TTIF procedures were performed for 64 patients (36% males; mean age 67.5 (SD 15.3) years). COMI score reduced from a mean value of 8.1 (SD 1.4) preoperatively to 4.7 (SD 2.7) at 1-year follow-up and 4.7 (SD 2.7) at 2-year follow-up. The mean correction of segmental kyphosis was 10.8 (SD 7.3, p < 0.0001) degrees at 1-year follow-up and 9.3 (SD 7.0, p < 0.0001) degrees at the final follow-up 3.4 (SD 1.4) years after the operation. Kaplan-Meier analysis for reoperations showed a 5-year survival of 91% (95% CI 0.795-1) for primary TTIF operations and survival of 77% (95% CI 0.651-0.899) for TTIFs performed after earlier fusion operations. CONCLUSIONS: TTIF is a feasible procedure in the thoracic spine. Kyphosis correction of approximately 10° was maintained at 1-year and final follow-up. Over 69% at 1-year and 61% at 2-year follow-up achieved MCID for COMI.

Comparison Between Arthroscopic and Histological International Cartilage Repair Society Scoring Systems in Porcine Cartilage Repair Model.

OBJECTIVE: The arthroscopic and histological International Cartilage Repair Society (ICRS) scores are designed to evaluate cartilage repair quality. Arthroscopic ICRS score can give a maximum score of 12 and the histological score can give values between 0% and 100% for each of its 14 subscores. This study compares these methods in an animal cartilage repair model. This study hypothesizes that there is a significant correlation between these methods. DESIGN: A chondral defect was made in the medial femoral condyle of 18 pigs. Five weeks later, 9 pigs were treated with a novel recombinant human type III collagen/polylactide scaffold and 9 were left untreated to heal spontaneously. After 4 months, the medial condyles were evaluated with a simulated arthroscopy using the ICRS scoring system followed by a histological ICRS scoring. RESULTS: This porcine cartilage repair model produced repaired cartilage tissue ranging from good to poor repair tissue quality. The mean arthroscopic ICRS total score was 6.8 (SD = 2.2). Histological ICRS overall assessment subscore was 38.2 (SD = 31.1) and histological ICRS average points were 60.5 (SD = 19.5). Arthroscopic ICRS compared with histological ICRS average points or its overall assessment subscore showed moderate correlation (r = 0.49 and r = 0.50, respectively). The interrater reliability with the intraclass correlation coefficients for arthroscopic ICRS total scores, histological ICRS overall assessment subscore, and ICRS average points showed moderate to excellent reliability. CONCLUSIONS: Arthroscopic and histological ICRS scoring methods for repaired articular cartilage show a moderate correlation in the animal cartilage repair model.

Epidemiology, Treatment, and Treatment Quality of Overriding Distal Metaphyseal Radial Fractures in Children and Adolescents.

BACKGROUND: The incidence of completely displaced overriding distal metaphyseal radial fractures in children is unknown, and the optimal treatment is controversial. METHODS: All completely displaced distal metaphyseal radial fractures in patients <16 years old treated in our tertiary-level institution from 2014 to 2019 were identified with use of the Kids' Fracture Tool Helsinki. Etiology, fracture characteristics, management, and quality of treatment were assessed. A telephone interview with the guardian of the patient was performed for 100 (89%) of 112 patients at 1.5 to 7.2 years (median, 4.6 years) after the injury. Pain during the last month and forearm function were recorded. Treatment satisfaction was assessed with use of a 7-point Likert scale. RESULTS: A total of 113 completely displaced overriding distal metaphyseal radial fractures in 112 patients (81 of whom were residents of Helsinki) were treated during the 6-year-long study period. The mean annual incidence was 1.42 per 10,000 population. Most (73%) of these fractures occurred in children <11 years old, and most fractures were dorsally displaced and located nearly as far proximally from the distal radial physis as the maximum width of the distal metaphysis. Closed manipulation was attempted in two-thirds of cases in the emergency department, with a failure rate of 46%. Strong opioids were administered in 70 of 112 patients. None of the 26 patients whose fractures were immobilized in an overriding position had secondary interventions, pain, or functional disability. The mean satisfaction with treatment on the Likert scale was 6.2. CONCLUSIONS: The annual incidence of overriding distal metaphyseal radial fractures patients <16 years old was shown to vary between 0.72 and 2.01 per 10,000 population. Opioids, local and general anesthesia, hospital admission, and secondary interventions can be avoided in prepubescent patients by casting these fractures in an overriding position while the patient is in the emergency department. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Traumatic Rupture and Herniation of the Peroneus Tertius Muscle Leading to Compartment Syndrome and Entrapment of the Superficial Peroneal Nerve: A Case Report.

We present a patient with compartment syndrome and entrapment of the superficial peroneal nerve due to a direct hit to the lateral part of the right lower extremity. The diagnosis of evolving compartment syndrome was made without delay and the patient was quickly taken to the operating theater. Intraoperatively, the entrapment of the superficial peroneal nerve caused by rupture and herniation of the peroneus tertius muscle was surprisingly observed at the site, where the nerve pierces the anterior compartment. The nerve was successfully released in conjunction with fasciotomies of the anterior and lateral compartments. Meticulous diagnosis of compartment syndrome is critical to prevent ischemic injury to muscles and nerves. Recognition of anatomy and anatomical variations is important to prevent iatrogenic injury in unusual circumstances.

Casting in finger trap traction without reduction versus closed reduction and percutaneous pin fixation of dorsally displaced, over-riding distal metaphyseal radius fractures in children under 11 years old: a study protocol of a randomised controlled trial.

INTRODUCTION: Distal radius is the most common site of fracture in children, comprising 23%-31% of all paediatric fractures. Approximately one-fifth of these fractures are displaced. Completely displaced distal metaphyseal radius fractures in children have traditionally been treated with closed reduction. Recent evidence suggests that correcting the shortening in over-riding distal metaphyseal radius fractures is not necessary in prepubertal children. To date, no published randomised controlled trial (RCT) has compared treatment of these fractures in children by casting the fracture in bayonet position to reduction and pin fixation. METHODS AND ANALYSIS: We will conduct an RCT to compare the outcomes of casting the fracture in bayonet position in children under 11 years of age to reduction and percutaneous pin fixation. 60 patients will be randomly assigned to casting or surgery groups. We have two primary outcomes. The first is ratio (injured side/non-injured side) in the total active forearm rotation and the second is ratio (injured side/non-injured side) in total active range of motion of the wrist in the flexion-extension plane at 6 months. The secondary outcomes will include axial radiographic alignment, passive extension of the wrists, grip strength and length of forearms and hands, patient-reported outcome QuickDASH and pain questionnaire PedsQL. Patients not willing to participate in the RCT will be asked to participate in a prospective cohort. Patients not eligible for randomisation will be asked to participate in a non-eligible cohort. These cohorts are included to enhance the external validity of the results of the RCT. Our null hypothesis is that the results of the primary outcome measures in the casting group are non-inferior to surgery group. ETHICS AND DISSEMINATION: The institutional review board of the Helsinki and Uusimaa Hospital District has approved the protocol. We will disseminate the findings through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04323410. PROTOCOL: V.1.1, 29 September 2020.

Physeal Fractures of Distal Tibia: A Systematic Review and Meta-analysis.

BACKGROUND: Fractures involving the distal tibia growth plate are common in children. Injury or treatment that damages the growth plate may result in progressive angular deformity or leg length discrepancy. There is no consensus on treatment and follow-up of these injuries. This study aims to describe which factors increase the risk of premature physeal closure (PPC). MATERIAL AND METHODS: A systematic review and meta-analysis were performed. Altogether 395 articles were reviewed, and ultimately 12 of them were found eligible, comprising 1997 patients. The most usual type of fracture was Salter-Harris (SH) II (n=855, 49%) followed by SH III (n=296, 17%) and SH I (n=261, 15%). The risk of PPC according to number of reduction attempts, method of treatment, and residual displacement was the primary outcome. RESULTS: The total rate of PPC was 13% (n=245). The PPC rate varied from 0.2% to 42% across the studies. Patients with SH IV fractures were most likely to develop PPC (20%), followed by those with SH II (12%) (P<0.05) and repeated (>2) reduction maneuvers were associated with a higher risk of PPC (pooled odds ratio, 8.5; 95% confidence interval, 6.3-12.17; P<0.05). Open reduction was associated with a lower risk of PPC when analyzing only displaced fractures (odds ratio, 0.63; 95% confidence interval, 0.38-0.91; P<0.05). INTERPRETATION: This meta-analysis implies that residual displacement after reduction is the most significant factor in predicting PPC. It seems that open reduction might reduce the PPC rate among patients with dislocated fractures. In addition, there is some evidence that a higher number of reduction attempts correlates positively with the risk of PPC.

Cast immobilization in bayonet position versus reduction and pin fixation of overriding distal metaphyseal radius fractures in children under ten years of age: a case control study.

PURPOSE: Completely displaced distal radius fractures in children have been traditionally reduced and immobilized with a cast or pin fixed. Cast immobilization leaving the fracture displaced in the bayonet position has been recently suggested as a non-invasive and effective treatment alternative. This is a pilot comparative study between reduction and no reduction. METHODS: We assessed subjective, functional and radiographic outcome after a minimum 2.5-year follow-up in 12 children under ten years of age who had sustained a completely displaced metaphyseal radius fracture, which had been immobilized leaving the fracture in an overriding position (shortening 3 mm to 9 mm). A total of 12 age-matched patients, whose similar fractures were reduced and pin fixed, were chosen for controls. RESULTS: At follow-up none of the 24 patients had visible forearm deformity and the maximal angulation in radiographs was 5° Forearm and wrist movement was restored (< 10° of discrepancy) in all 24 patients. Grip strength ratio was normal in all but three surgically treated patients. All patients had returned to their previous activities. One operatively treated boy who was re-operated on reported of pain (visual analogue scale 2). CONCLUSION: The results of this study do not demonstrate the superiority of reduction and pin fixation over cast immobilization in the bayonet position of closed overriding distal metaphyseal radius fractures in children under ten years with normal neurovascular findings. LEVEL OF EVIDENCE: III.

Arthroscopic International Cartilage Repair Society Classification System Has Only Moderate Reliability in a Porcine Cartilage Repair Model.

BACKGROUND: The International Cartilage Repair Society (ICRS) score was designed for arthroscopic use to evaluate the quality of cartilage repair. PURPOSE: To evaluate the reliability of the ICRS scoring system using an animal cartilage repair model. STUDY DESIGN: Controlled laboratory study. METHODS: A chondral defect with an area of 1.5 cm2 was made in the medial femoral condyle of 18 domestic pigs. Five weeks later, 9 pigs were treated using a novel recombinant human type III collagen/polylactide scaffold, and 9 were left to heal spontaneously. After 4 months, the pigs were sacrificed, then 3 arthroscopic surgeons evaluated the medial femoral condyles via video-recorded simulated arthroscopy using the ICRS scoring system. The surgeons repeated the evaluation twice within a 9-month period using their recorded arthroscopy. RESULTS: The porcine cartilage repair model produced cartilage repair tissue of poor to good quality. The mean ICRS total scores for all observations were 6.6 (SD, 2.6) in arthroscopy, 5.9 (SD, 2.7) in the first reevaluation, and 6.2 (SD, 2.8) in the second reevaluation. The interrater reliability with the intraclass correlation coefficient (ICC) for the ICRS total scores (ICC, 0.46-0.60) and for each individual subscore (ICC, 0.26-0.71) showed poor to moderate reliability. The intrarater reliability with the ICC also showed poor to moderate reliability for ICRS total scores (ICC, 0.52-0.59) and for each individual subscore (ICC, 0.29-0.58). A modified Bland-Altman plot for the initial arthroscopy and for the 2 reevaluations showed an evident disagreement among the observers. CONCLUSION: In an animal cartilage repair model, the ICRS scoring system seems to have poor to moderate reliability. CLINICAL RELEVANCE: Arthroscopic assessment of cartilage repair using the ICRS scoring method has limited reliability. We need more objective methods with acceptable reliability to evaluate cartilage repair outcomes.

Appearance of congenital hand anomalies.

BACKGROUND AND OBJECTIVE: Impact of appearance of congenital hand anomalies has not previously been reported. The purpose of this study was to describe the common perception about how different congenitally malformed hands look. METHODS: We developed a questionnaire in a game format to evaluate the appearance of different hands. Altogether 1450 (954 females) 4- to 84-year-old residents (296 children) of two European and one Asian (n = 102) country were asked to rate the appearance of different looking hands on a five-point pictorial Likert-type scale. Standardized photographs of the dorsal aspect of 17 different congenitally malformed non-operated hands and a normal hand were presented to respondents. Significance of age, gender, nationality, and profession of the respondents was assessed. RESULTS: The respondents' ranking order of the hands was nearly consistent. The normal hand (mean = 4.43, standard deviation = 0.85, Md = 5) and clinodactyly (mean = 4.37, standard deviation = 0.86, Md = 5) were perceived to have the best appearance. Symbrachydactyly (mean = 1.42, standard deviation = 0.68, Md = 1) and radial club hand (mean = 1.40, standard deviation = 0.68, Md = 1) received the lowest scores. Adults rated the appearance of hands higher than children regarding 14 hands, females higher than men regarding 15 hands, and Europeans higher than Asians in 4 hands (p < 0.05, respectively). Europeans rated four-finger hand (mean = 3.21, standard deviation = 1.18, Md = 3) better looking than six-finger hand (mean = 2.92, standard deviation = 1.18, Md = 3, p < 0.005), whereas Asians gave higher scores to six-finger hand (mean = 2.66, standard deviation = 1.26, Md = 3) compared to four-finger hand (mean = 2.51, standard deviation = 1.14, Md = 2). Medical doctors and nurses gave higher scores compared to the other profession groups, school children, and high school students in five hands (p < 0.05). CONCLUSIONS: A normal hand is perceived distinctly better looking than most congenitally different hands. Different malformations' appearance was ranked very coherently in the same order despite of participants' age, gender, nationality, or profession. Asians seem to prefer an additional digit to a four-finger hand.

Risk of premature physeal closure in fractures of distal tibia.

The reported incidence of premature physeal closure (PPC) in fractures of the distal tibia has varied between 5 and 36%, but there is no consensus on the cause. We wanted to determine incidence and predictors of PPC in distal tibia physeal fractures in a population-based patient cohort. Two hundred forty-one patients (195 Peterson type I-V fractures and 46 transitional fractures) treated for a physeal fracture of the distal tibia during a 5-year period in two tertiary-level teaching hospitals. Odds ratios (OR) for developing PPC for different parameters (Peterson fracture type, associated fibula fracture, primary and postreduction displacement, number of reductions and the method of treatment) were calculated by binary logistic regression analysis. In 195 children with Peterson type I-V fractures PPC was diagnosed in 21 children (11%), of which 11 (6%) had surgery at mean 14 months from the fracture to correct either angular deformity or leg length discrepancy. The incidence of distal tibia PPC is at least 0.05/1000 children. More than one reduction attempt was the most significant risk factor (OR 7.0) for PPC. Peterson fracture type, associated fibula fracture, initial or post-reduction displacement or type of treatment did not correlate with PPC. The incidence of distal tibia PPC is at least 0.05/1000 children. The number of reductions correlates positively with the risk of PPC.

Most surgeons still prefer to reduce overriding distal radius fractures in children.

Background and purpose - Traditionally, overriding distal radius fractures in children have been reduced and immobilized with a cast or treated with percutaneous pin fixation. There is recent evidence that these fractures heal well if immobilized in the bayonet position without reduction. We evaluated the present treatment of these fractures.Methods - A questionnaire including AP and lateral radiographs of overriding distal radius fractures in 3 pre-pubertal children was answered by 213 surgeons from 28 countries. The surgeons were asked to choose their preferred method of treatment (no reduction, reduction, reduction and osteosynthesis), type and length of cast immobilization, and the number of clinical and radiographic follow-ups.Results - Of the 213 participating surgeons, 176 (83%) would have reduced all 3 presented fractures, whereas 4 (2%) would have treated all 3 children with cast immobilization without reduction. Most reductions (77%) would have been done under general anesthesia. Over half (54%) of the surgeons who preferred anesthesia would have fixed (pins 99%, plate 1%) the fractures. An above-elbow splint or circular cast was chosen in 84% of responses, and the most popular (44%) length of immobilization was 4 weeks. Surgeons from the Nordic countries were more eager to fix the fractures (54% vs. 31%, p < 0.001) and preferred shorter immobilization and follow-up times and less frequent clinical and radiological follow-ups compared with their colleagues from the USA.Interpretation - Most of the participating surgeons prefer to reduce overriding distal radius fractures in children under anesthesia. There is substantial lack of agreement on the indications for osteosynthesis, type of cast, length of immobilization, and follow-up protocol.

Retraction: Complementary Cast Immobilization Is Not Necessary after Intramedullary Fixation of Unstable Tibial Shaft Fractures in Pediatric Patients.

The above article published in European Journal of Pediatric Surgery on April 15, 2020 (DOI: 10.1055/s-0040-1703010) has been retracted as per authors' request.

Treatment of Closed Tibia Shaft Fractures in Children: A Systematic Review and Meta-Analysis.

Tibia fractures are among the most common long-bone fractures in children. Despite this, there is no current consensus on the optimal treatment strategy for closed displaced tibia shaft fractures in the pediatric patient population. The aim of this study is to compare the reported complications and outcomes of reduction and cast immobilization versus flexible intramedullary nailing in the treatment of pediatric tibia shaft fractures. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement when conducting and reporting this prospectively registered systematic review. Eleven studies were included. Quality of the studies was assessed using the Coleman methodology score. Mantel-Haenszel cumulative odds ratios were used to compare the risk of complication between different methods of treatment. Eleven studies including 1,083 patients with diaphyseal fractures of the tibia met the inclusion criteria. The most common fracture type was simple 42-A (782; 91%). Majority (75%) of the patients were treated nonoperatively. The total complication rate was higher among operatively treated patients (24 vs. 9%; p < 0.05). Satisfactory fracture alignment had to be restored surgically in 5% of the primarily nonoperatively treated patients. The evidence levels of the included studies were II (1), III (2), and IV (7). Three-fourths of closed diaphyseal fractures of the tibia in children are still treated with reduction and cast immobilization. Flexible intramedullary nailing is associated with significantly higher complication rate than nonoperative treatment.

Routine radiographic follow-up is not necessary after physeal fractures of the distal tibia in children.

Background and purpose - Unnecessary radiographic and clinical follow-ups are common in treatment of pediatric fractures. We hypothesized that follow-up radiographs are unnecessary to monitor union of physeal fractures of the distal tibia.Patients and methods - All 224 (147 boys) children under 16 years old treated for a physeal fracture of the distal tibia during a 5-year period (2010-14) in Helsinki Children's Hospital were included in this study. Peterson type II fractures comprised 55% and transitional fractures (Tillaux and Triplane) 20% of all injuries. Fracture displacement and alignment was measured. Type and place of treatment was recorded. Number of follow-up radiographs and outpatient visits was calculated and their clinical significance was assessed.Results - 109 children had fractures with < 2 mm displacement and no angulation. The other 115 children's mean fracture displacement was 6 mm (2-28). 54% of all children were treated by casting in situ in the emergency room, 20% with manipulation under anesthesia and 26% with surgery (internal 57, external fixation 2). Median 3 (1-7) follow-up appointments and median 3 (0-6) radiographs were taken. Follow-up radiographs at or before cast removal did not alter treatment in any of the patients. 223 patients' fractures healed within 4-9 weeks in good alignment (≤ 5° angulation).Interpretation - Routine radiographic follow-up is unnecessary to monitor alignment and union of physeal fractures of the distal tibia.

In Vivo Evaluation of the Potential of High-Frequency Ultrasound for Arthroscopic Examination of the Shoulder Joint.

OBJECTIVE: Accurate arthroscopic evaluation of cartilage lesions could significantly improve the outcome of repair surgery. In this study, we investigated for the first time the potential of intra-articular ultrasound as an arthroscopic tool for grading cartilage defects in the human shoulder joint in vivo and compared the outcome to results from arthroscopic evaluation and magnetic resonance imaging findings. DESIGN: A total of 26 sites from 9 patients undergoing routine shoulder arthroscopy were quantitatively evaluated with a clinical intravascular (40MHz) ultrasound imaging system, using the regular arthroscopy portals. Reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB), and ultrasound roughness index (URI) were calculated, and high-resolution ultrasound images were obtained per site. Each site was visually graded according to the International Cartilage Repair Society (ICRS) system. "Ultrasound scores" corresponding to the ICRS system were determined from the ultrasound images. Magnetic resonance imaging was conducted and cartilage integrity at each site was classified into 5 grades (0 = normal, 4 = severely abnormal) by a radiologist. RESULTS: R and IRC were lower at sites with damaged cartilage surface (P = 0.033 and P = 0.043, respectively) and correlated with arthroscopic ICRS grades (r s = -0.444, P = 0.023 and r s = -0.426, P = 0.03, respectively). Arthroscopic ICRS grades and ultrasound scores were significantly correlated (rs = 0.472, P = 0.015), but no significant correlation was found between magnetic resonance imaging data and other parameters. CONCLUSION: The results suggest that ultrasound arthroscopy could facilitate quantitative clinical appraisal of articular cartilage integrity in the shoulder joint and provide information on cartilage lesion depth and severity for quantitative diagnostics in surgery.

Cell-tissue interactions in osteoarthritic human hip joint articular cartilage.

Volume and morphology of chondrocytes in osteoarthritic human hip joint articular cartilage were characterized, and their relationship to tissue structure and function was determined. Human osteochondral articular cartilage samples (n=16) were obtained from the femoral heads of nine patients undergoing total hip arthroplasty due to osteoarthritis (OA). Superficial chondrocytes (N=65) were imaged in situ with a confocal laser scanning microscope at 37 °C. This was followed by the determination of the mechanical properties of the tissue samples, depth-wise characterization of cell morphology (height, width; N=385) as well as structure and composition of the tissues using light microscopy, digital densitometry, Fourier transform infrared microspectroscopy and polarized light microscopy. Significant correlations were found between the cell volume and the orientation angle associated with the collagen fibers (r=0.320, p=0.009) as well as between the cell volume and the initial dynamic modulus of the tissue (r=-0.305, p=0.013). Furthermore, the depth-dependent chondrocyte aspect ratio (height/width) correlated significantly with the orientation angle of the collagen fibers and with the tissue's proteoglycan content (r=0.261 and r=0.228, respectively, p<0.001). Our findings suggest that the orientation angle of the collagen fibers primarily controls chondrocyte volume and shape in osteoarthritic human hip joint articular cartilage.

Candidate driver genes in microsatellite-unstable colorectal cancer.

Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in ∼ 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI cancers. Here, we evaluated somatic mutations in microsatellite repeats of 790 genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat of 6-10 bp in length. All the repeats were initially sequenced in 30 primary MSI CRC samples and whenever frameshift mutations were identified in >20%, additional 70 samples were sequenced. To distinguish driver mutations from passengers, we similarly analyzed the occurrence of frameshift mutations in 121 intronic control repeats and utilized a statistical regression model to determine cut-off mutation frequencies for repeats of all types (A/T and C/G, 6-10 bp). Along with several know target genes, including TGFBR2, ACVR2, and MSH3, six novel candidate driver genes emerged that harbored significantly more mutations than identical control repeats. The mutation frequencies in 100 MSI CRC samples were 51% in G8 of GLYR1, 47% in T9 of ABCC5, 43% in G8 of WDTC1, 33% in A8 of ROCK1, 30% in T8 of OR51E2, and 28% in A8 of TCEB3. Immunohistochemical staining of GLYR1 revealed defective protein expression in tumors carrying biallelic mutations, supporting a loss of function hypothesis. This is a large scale, unbiased effort to identify genes that when mutated are likely to contribute to MSI CRC development.

Ultrasound evaluation of mechanical injury of bovine knee articular cartilage under arthroscopic control.

A local cartilage injury can trigger development of posttraumatic osteoarthritis (OA). Surgical methods have been developed for repairing cartilage injuries. Objective and sensitive methods are needed for planning an optimal surgery as well as for monitoring the surgical outcome. In this laboratory study, the feasibility of an arthroscopic ultrasound technique for diagnosing cartilage injuries was investigated. In bovine knees (n = 7) articular cartilage in the central patella and femoral sulcus was mechanically degraded with a steel brush modified for use under arthroscopic control. Subsequently, mechanically degraded and intact adjacent tissue was imaged with a high frequency (40 MHz) intravascular ultrasound device operated under arthroscopic guidance. After opening the knee joint, mechanical indentation measurements were also conducted with an arthroscopic device at each predefined anatomical site. Finally, cylindrical osteochondral samples were extracted from the measurement sites and prepared for histological analysis. Quantitative parameters, i.e., reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB), and ultrasound roughness index (URI) were calculated from the ultrasound signals. The reproducibilities (sCV %) of the measurements of ultrasound parameters were variable (3.7% to 26.1%). Reflection and roughness parameters were significantly different between mechanically degraded and adjacent intact tissue (p < 0.05). Surface fibrillation of mechanically degraded tissue could be visualized in ultrasound images. Furthermore, R and IRC correlated significantly with the indentation stiffness. The present results are encouraging; however, further technical development of the arthroscopic ultrasound technique is needed for evaluation of the integrity of human articular cartilage in vivo.

Arthroscopic Ultrasound Assessment of Articular Cartilage in the Human Knee Joint: A Potential Diagnostic Method.

OBJECTIVE: We tested whether an intra-articular ultrasound (IAUS) method could be used to evaluate cartilage status arthroscopically in human knee joints in vivo. DESIGN: Seven patients undergoing arthroscopic surgery of the knee were enrolled in this study. An ultrasonic examination was conducted using the same portals as in the arthroscopic surgery. A high-frequency (40-MHz) ultrasound transducer (diameter = 1 mm) was directed to the desired location on the articular surface under arthroscopic control. In addition to ultrasound data, an IAUS video and optical video through the arthroscope were recorded. Classification of cartilage injuries according to International Cartilage Repair Society, as conducted by the orthopedic surgeon, provided reference data for comparison with the IAUS. RESULTS: The IAUS method was successful in imaging different characteristics of the articular surfaces (e.g., intact surface, surface fibrillation, and lesions of varying depth). In some cases, also the subchondral bone and abnormal internal cartilage structure were visible in the IAUS images. Specifically, using the IAUS, a local cartilage lesion of 1 patient was found to be deeper than estimated arthroscopically. CONCLUSIONS: The IAUS method provided a novel arthroscopic method for quantitative imaging of articular cartilage lesions. The IAUS provided quantitative information about the cartilage integrity and thickness, which are not available in conventional arthroscopy. The present equipment is already approved by the Food and Drug Administration for intravascular use and might be transferred to intra-articular use. The invasiveness of the IAUS method might restrict its wider clinical use but combined with arthroscopy, ultrasonic assessment may enlarge the diagnostic potential of arthroscopic surgery.