The evolution of radiological measurements and the association with clinician and patient reported outcome following distal radius fractures in non-osteoporotic patients:what is clinically relevant?

Introduction: Following distal radius fractures in young non-osteoporotic patients, clinical relevancy of outcome has been scarcely reported. Outcome can be put in perspective by using measurement errors of radiological measurements and Minimal Important Change when reporting on clinician and patient reported outcome. Aim of this study was to assess the clinical relevance of radiological measurements, clinician and patient reported outcomes following distal radius fractures in young non-osteoporotic patients.Methods: Retrospective cohort study. Non-osteoporotic patients following a distal radius fracture were selected. Radiographs of both wrists were obtained at baseline, 6 weeks and at follow-up. Active range of motion and grip strength measurements were obtained at the follow-up visit and 4 questionnaires were answered to assess pain, upper extremity functioning, and health status.Results: Seventy-three patients (32 women, 41 men) with a mean age of 33.5 (SD 9.2) years at the time of injury were included. Median follow up was 62 months (IQR 53.0-84.5). Several radiological measurements evolved statistically significantly over time, however none exceeded measurement errors. Flexion/extension difference of injured compared to uninjured wrist (mean difference 11.2°, t = -7.5, df = 72, p < 0.001), exceeded Minimal Important Change, while grip strength differences did not. When comparing patients with DRFs to healthy controls, only the differences on Patient Reported Wrist Evaluation subscales "pain", "function" and total scores exceeded minimal important change (8, 10 and 13 points, respectively). Multivariable regression analysis revealed statistically significant relationships between residual step-off and respectively diminished flexion/extension (B = -36.8, 95% CI -62; -11.1, p  =  0.006), diminished radial/ulnar deviation (B = -17.9, 95% CI -32.0; -3.9, p  =  0.013) and worse ShortForm-36 "mental component score" (B = -15.4, 95% CI -26.6; -4.2, p < 0.001).Conclusion: Radiological measurements following distal radius fractures seem to evolve over time, but differences were small and were probably not clinically relevant. Range of motion, in particular flexion/extension, was impaired to such extend that it was noticeable for a patient, whereas grip strength was not impaired. The Patient Reported Wrist Evaluation was clinically relevantly diminished. Residual articular incongruency seems to influence range of motion.Implications for rehabilitationReporting Minimal Important Change regarding clinician and patient reported outcome following distal radius fractures is of more clinical value than reporting on statistical significance.Following distal radius fractures, the changes in radiological measurements do not seem to reflect a clinical relevant change.Range of motion, in particular flexion/extension, should be measured following distal radius fractures, as this might be impaired in a clinically relevant way.Measuring grip strength is of less importance following distal radius fractures, because grip strength does not seem to be affected.Residual articular incongruency seems to influence range of motion and therefore should be reduced to a minimum when treating non-osteoporotic patients

Structural validity and construct validity of the Dutch-Flemish PROMIS® physical function-upper extremity version 2.0 item bank in Dutch patients with upper extremity injuries

Introduction: Aim of this study was to validate the Dutch–Flemish Patient-Reported Outcomes Measurement Information System Physical Function–Upper Extremity version 2.0 item bank in patients with upper extremity injuries. Materials and methods: Cross-sectional study. Structural validity was assessed using Confirmatory Factor Analysis examining unidimensionality. In addition, a bi-factor model was fitted. Internal consistency was assessed by Cronbach’s alpha. Construct validity was examined by assessing correlations with legacy instruments Disability of Arm Shoulder and Hand, Patient Reported Wrist Evaluation and Michigan Hand Questionnaire subscale Activities in Daily Life. Results: A total of 303 patients (144 female) with mean age of 50 years (standard deviation 18) were included. Confirmatory Factor Analysis showed Comparative Fit Index of 0.94, a Tucker Lewis Index of 0.93, a Root Mean Square Error of Approximation of 0.12 and a Standardized Root Mean Residual of 0.09. Factor loadings were all above 0.70. Bifactor analysis showed an omega-H of 0.79 and Explained Common Variance of 0.67. The correlations with the legacy instruments were as expected or higher than expected. Conclusion: The Dutch-Flemish Patient-Reported Outcomes Measurement Information System Physical Function–Upper Extremity version 2.0 item bank measures a unidimensional trait and sufficient construct validity was found.IMPLICATIONS FOR REHABILITATION Completing Patient Reported Outcomes is time-consuming for patients and interpretability of outcomes is sometimes unclear due to some variation in psychometric properties. Computerized Adaptive Testing reduces the burden for patients by using an algorithm which decreases the amount of questions that need to be answered to 4 to 7 items. The Dutch-Flemish Patient-Reported Outcomes Measurement Information System Physical Function–Upper Extremity version 2.0 item bank measures a unidimensional trait and has sufficient structural validity, internal consistency and construct validity. After calibration of the Patient-Reported Outcomes Measurement Information System Physical Function–Upper Extremity version 2.0, the item bank is operable to use with Computerized Adaptive Testing

Pain, impaired functioning, poor satisfaction and diminished health status eight years following perilunate (fracture) dislocations

Purpose: Perilunate (fracture) dislocations are rare injuries and diminished functional outcomes are reported. However, Patient Reported Outcomes (PROs) following these injuries are rarely described. The aim of this study was to investigate the long-term impact of perilunate (fracture) dislocations using a range of measures, including pain, function, and quality of life. Materials and Methods: This cross-sectional study was conducted from January 2016 until March 2016. Eleven patients who had suffered from perilunate (fracture) dislocations between August 1996 and January 2014 were matched on age and gender with 22 healthy controls. Functional outcome included range of motion and grip strength measurements. The Patient Reported Outcomes included: Patient Reported Wrist Evaluation, Disability of Arm, Shoulder and Hand questionnaire, Michigan Hand Questionnaire and the Short Form-36. Results: The 11 patients that were included (9 males) had a median age at injury of 38 years (IQR 33; 54) and median follow up of 97 months (IQR 84-193). Flexion/extension (mean difference −60°, 95% CI −76, −43, p < 0.001) and ulnar/radial deviation (mean difference −28°, 95% CI −38, −18, p < 0.001) were significantly diminished in patients following perilunate (fracture) dislocations. Grip strength was not affected. The patients experienced significantly more pain as assessed on all pain subscales. Physical functioning was significantly worse in the group with perilunate (fracture) dislocations as assessed on all function subscales, except the PRWE function score and the subscale physical functioning of the Short Form-36. Satisfaction as measured with the Michigan Hand Questionnaire satisfaction subscale (mean difference −36, 95% CI −57, −16, p = 0.002) was also reported poorer. No difference was found regarding work participation. Conclusions: A perilunate (fracture) dislocation has a significant impact on everyday life, as patients experience diminished range of motion, pain, diminished physical functioning, diminished satisfaction and report lower general health status than healthy controls. However, no consequences for work participation were found in this study. Level of evidence 3.Implications for rehabilitation Flexion/extension and ulnar/radial deviation remains limited following perilunate (fracture) dislocations. Grip strength is not diminished in patients with perilunate (fracture) dislocations. Pain, restrictions in physical functioning, diminished satisfaction and lower general health status are likely to be present following perilunate (fracture) dislocations. If conservative treatment including pain medication and rehabilitation strategies do not relief pain following perilunate (fracture) dislocations, surgical treatment options such as wrist denervation or arthrodesis should be considered

Type B Aortic Dissection After the Use of Tadalafil

A 63-year-old male patient with a type B aortic dissection after the use of tadalafil, a phosphodiesterase type 5 inhibitor, is presented. The possible role of a novel predisposing factor-sexual activity combined with tadalafil-is reviewed. This report and three other cases add a new dimension to the known predisposing factors such as chronic systemic hypertension, hereditary connective tissue diseases-and congenital aortic valve diseases. However, the precise role of phosphodiesterase type 5 inhibitors in the pathophysiology of aortic dissection remains unknown. (Ann Thorac Surg 2012;93:651-3) (C) 2012 by The Society of Thoracic Surgeon

Surgical learning curve in reverse shoulder arthroplasty for proximal humerus fractures

Background: Fracture reverse shoulder arthroplasty (fRSA) in geriatric, complex dislocated proximal humerus fractures is becoming the standard treatment next to conservative treatment. fRSA is a multifaceted, reasonably challenging procedure of which functional outcomes and complication rates are likely to depend on the experience of the surgeon. The goal of this study was to determine whether there is a learning curve for fRSA. Methods: All patients with a dislocated multipart proximal humerus fracture that were treated with an fRSA between 2013 and 2019 in a specialized institution were included. The functional outcomes (Constant Shoulder Score, Oxford Shoulder Score, and range of motion), complications, and operation time of fRSA were assessed with linear regression plots and cumulative summation analysis to establish whether a learning curve was present. Results: In this cohort study, 50 patients were included. They had a mean age of 77.1 years and were treated with an fRSA by one trauma surgeon. Learning curves were distinguished for functional outcomes, complications, and operation time based on learning targets for daily activity and the mean complications and operation time. Results indicated that an optimal treatment is achieved after performing 20 fRSAs. Conclusion: The results show that functional outcomes of PHFs treated with an fRSA improve with surgical experience. Also, outcomes are getting less variable after about 20 procedures. Surgeons starting this procedure should be aware of the learning curve and, therefore, should consider guidance from an experienced surgeon to swiftly optimize functional outcomes and prevent unnecessary complications

Integrated clinical and omics approach to rare diseases : Novel genes and oligogenic inheritance in holoprosencephaly

Holoprosencephaly is a pathology of forebrain development characterized by high phenotypic heterogeneity. The disease presents with various clinical manifestations at the cerebral or facial levels. Several genes have been implicated in holoprosencephaly but its genetic basis remains unclear: different transmission patterns have been described including autosomal dominant, recessive and digenic inheritance. Conventional molecular testing approaches result in a very low diagnostic yield and most cases remain unsolved. In our study, we address the possibility that genetically unsolved cases of holoprosencephaly present an oligogenic origin and result from combined inherited mutations in several genes. Twenty-six unrelated families, for whom no genetic cause of holoprosencephaly could be identified in clinical settings [whole exome sequencing and comparative genomic hybridization (CGH)-array analyses], were reanalysed under the hypothesis of oligogenic inheritance. Standard variant analysis was improved with a gene prioritization strategy based on clinical ontologies and gene co-expression networks. Clinical phenotyping and exploration of cross-species similarities were further performed on a family-by-family basis. Statistical validation was performed on 248 ancestrally similar control trios provided by the Genome of the Netherlands project and on 574 ancestrally matched controls provided by the French Exome Project. Variants of clinical interest were identified in 180 genes significantly associated with key pathways of forebrain development including sonic hedgehog (SHH) and primary cilia. Oligogenic events were observed in 10 families and involved both known and novel holoprosencephaly genes including recurrently mutated FAT1, NDST1, COL2A1 and SCUBE2. The incidence of oligogenic combinations was significantly higher in holoprosencephaly patients compared to two control populations (P < 10 -9). We also show that depending on the affected genes, patients present with particular clinical features. This study reports novel disease genes and supports oligogenicity as clinically relevant model in holoprosencephaly. It also highlights key roles of SHH signalling and primary cilia in forebrain development. We hypothesize that distinction between different clinical manifestations of holoprosencephaly lies in the degree of overall functional impact on SHH signalling. Finally, we underline that integrating clinical phenotyping in genetic studies is a powerful tool to specify the clinical relevance of certain mutations