Delineation of a new fibrillin-2-opathy with evidence for a role of FBN2 in the pathogenesis of carpal tunnel syndrome.

BACKGROUND: Although carpal tunnel syndrome (CTS) is the most common form of peripheral entrapment neuropathy, its pathogenesis remains largely unknown. An estimated heritability index of 0.46 and an increased familial occurrence indicate that genetic factors must play a role in the pathogenesis. METHODS AND RESULTS: We report on a family in which CTS occurred in subsequent generations at an unusually young age. Additional clinical features included brachydactyly and short Achilles tendons resulting in toe walking in childhood. Using exome sequencing, we identified a heterozygous variant (c.5009T>G; p.Phe1670Cys) in the fibrillin-2 (FBN2) gene that co-segregated with the phenotype in the family. Functional assays showed that the missense variant impaired integrin-mediated cell adhesion and migration. Moreover, we observed an increased transforming growth factor-ß signalling and fibrosis in the carpal tissues of affected individuals. A variant burden test in a large cohort of patients with CTS revealed a significantly increased frequency of rare (6.7% vs 2.5%-3.4%, p<0.001) and high-impact (6.9% vs 2.7%, p<0.001) FBN2 variants in patient alleles compared with controls. CONCLUSION: The identification of a novel FBN2 variant (p.Phe1670Cys) in a unique family with early onset CTS, together with the observed increased frequency of rare and high-impact FBN2 variants in patients with sporadic CTS, strongly suggest a role of FBN2 in the pathogenesis of CTS.

Bilateral breast implant associated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A case report.

INTRODUCTION: An estimated 30.000 breast implants are placed in the Netherlands annually. An increasing amount of reports have linked implants to the rare anaplastic large cell lymphoma (ALCL). Other implant-related lymphomas, such as those of B-cell lineage, are much rarer. PRESENTATION OF CASE: A 62-year-old female presented with pain and Baker grade III capsular contraction of the right breast. Subpectorally placed textured anatomical implants had been in situ for 26 years after cosmetic augmentation. Magnetic Resonance Imaging (MRI) showed bilateral implant leakage. Explantation of both implants confirmed bilateral leakage after which symptoms went into remission. Three months later our patient noticed an erythematous area, scar swelling and serous fluid leakage on the lateral side of the inframammary fold of the right breast. Siliconomas were excised bilaterally together with a partial capsulectomy on the left. Histopathology and immunohistochemical analysis showed monotonous small cell B-lymphocytic infiltration (CD20+, CD5+, CD23+, ALK-) in both capsules, highly suggestive for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). DISCUSSION: CLL/SLL are classified as nearly the same disease. The primary difference is the localization; CLL is found the bone marrow and blood whereas SLL is predominantly in the lymph nodes and spleen. There are no previous descriptions of bilateral CLL/SLL found in periprosthetic capsules. CONCLUSION: Breast implants are increasingly linked to various malignancies. In most cases, including our patient, implant explantation together with long-term follow-up suffices. MRI yields additional value in early stage diagnosis. More research is required to further optimize multidisciplinary care and improve patient outcomes.

Arm sling after carpal tunnel surgery: myth or evidence based?

Arm sling elevation is widely used after hand surgery to prevent swelling and pain. This prospective cohort study investigated whether arm sling elevation has any value after carpal tunnel release surgery. Patients were assigned to one of two groups after carpal tunnel release: with or without arm sling elevation. The primary outcome was postoperative swelling. Secondary outcomes were pain and symptom relief and functional outcome. Volumetric analysis showed no significant difference between the sling and non-sling group. Pain scores and improvement of symptom severity and functional status scores were similar for both groups. Thirty-eight per cent found the sling uncomfortable. These results do not support routine use of arm sling elevation after carpal tunnel release. Level of evidence: III.

Prognostic factors for return to work and resumption of other daily activities after traumatic hand injury.

The purpose of this study was to investigate prognostic factors for the time off work, the time to resumption of activities of daily living and hobbies, and duration of complaints in patients with a traumatic hand or wrist injury. In a 10-month longitudinal prospective cohort study, 383 patients were included and interviewed in person every 2 to 3 months. Several sociodemographic, psychological and work-related prognostic factors were investigated. For the time off work, job type, diagnosis, complication, blaming someone else for the trauma and gender were all found to be individual prognostic factors in Cox regression. For the time to resumption of activities of daily living and hobbies, and duration of complaints, gender, diagnosis, treatment and complications were found to be prognostic factors in univariate analysis. Age was solely correlated with resumption of activities of daily living and the duration of complaints. Considering these prognostic factors can help predict a patient's recovery more accurately. Level of evidence: II.

Bi-allelic Loss-of-Function Mutations in the NPR-C Receptor Result in Enhanced Growth and Connective Tissue Abnormalities.

The natriuretic peptide signaling pathway has been implicated in many cellular processes, including endochondral ossification and bone growth. More precisely, different mutations in the NPR-B receptor and the CNP ligand have been identified in individuals with either short or tall stature. In this study we show that the NPR-C receptor (encoded by NPR3) is also important for the regulation of linear bone growth. We report four individuals, originating from three different families, with a phenotype characterized by tall stature, long digits, and extra epiphyses in the hands and feet. In addition, aortic dilatation was observed in two of these families. In each affected individual, we identified a bi-allelic loss-of-function mutation in NPR3. The missense mutations (c.442T>C [p.Ser148Pro] and c.1088A>T [p.Asp363Val]) resulted in intracellular retention of the NPR-C receptor and absent localization on the plasma membrane, whereas the nonsense mutation (c.1524delC [p.Tyr508∗]) resulted in nonsense-mediated mRNA decay. Biochemical analysis of plasma from two affected and unrelated individuals revealed a reduced NTproNP/NP ratio for all ligands and also high cGMP levels. These data strongly suggest a reduced clearance of natriuretic peptides by the defective NPR-C receptor and consequently increased activity of the NPR-A/B receptors. In conclusion, this study demonstrates that loss-of-function mutations in NPR3 result in increased NPR-A/B signaling activity and cause a phenotype marked by enhanced bone growth and cardiovascular abnormalities.

Prognostic factors for outcome after median, ulnar, and combined median-ulnar nerve injuries: a prospective study.

BACKGROUND: A major problem in the surgical treatment of peripheral nerve injuries of the upper extremities is the unpredictable final outcome. More insight and understanding of the prognostic factors is necessary to improve functional outcome after repair of the peripheral nerves. The objective of this study was to identify prognostic factors for the functional recovery of peripheral nerve injury of the forearm and their independent contribution in the outcome in the first year after reconstruction. METHODS: A multicentered prospective study in the Netherlands resulted in the inclusion of 61 patients with a median, ulnar, or combined median-ulnar nerve injury. The age, level of injury, type of nerve injury, number of damaged structures, number of damaged arteries, education, smoking, and posttraumatic stress were analyzed as prognostic factors for functional outcome after repair of the peripheral nerves. The outcome parameters were sensory recovery (Semmes-Weinstein monofilament test) and motor recovery (Medical Research Council (MRC) score, power grip, and pinch grip) and the ability to perform daily activities. RESULTS: Gender, age, level of education, number of injured arteries and structures, damaged nerve, location of the injury, type of the nerve injury, and posttraumatic stress at 1 and 3 months after repair of the peripheral nerve injury were found to be predictors of functional recovery. CONCLUSIONS: Our prospective analysis of prognostic factors shows several factors to be predictive for the functional recovery after peripheral nerve injuries of the median and/or ulnar nerve of the forearm. Sensibility of the hand, power grip, and DASH score (DASH, Disabilities of Arm, Shoulder and Hand) have proven to be the three best prognostic factors in this study. Of these prognostic factors, only posttraumatic stress can be influenced to optimize functional outcome.

Type 2 diabetes seems not to be a risk factor for the carpal tunnel syndrome: a case control study.

BACKGROUND: Previous studies have shown that the carpal tunnel syndrome seems to occur more frequently in patients with diabetes mellitus and might be associated with the duration of diabetes mellitus, microvascular complications and degree of glycaemic control. Primary aim was to determine if type 2 diabetes can be identified as a risk factor for carpal tunnel syndrome after adjusting for possible confounders. Furthermore, the influence of duration of diabetes mellitus, microvascular complications and glycaemic control on the development of carpal tunnel syndrome was investigated. METHODS: Retrospective, case-control study using data from electronic patient charts from the Isala (Zwolle, the Netherlands). All patients diagnosed with carpal tunnel syndrome in the period from January 2011 to July 2012 were included and compared with a control group of herniated nucleus pulposus patients. RESULTS: A total of 997 patients with carpal tunnel syndrome and 594 controls were included. Prevalence of type 2 diabetes was 11.5% in the carpal tunnel syndrome group versus 7.2% in the control group (Odds Ratio 1.67 (95% confidence interval 1.16-2.41)). In multivariate analyses adjusting for gender, age and body mass index, type 2 diabetes was not associated with carpal tunnel syndrome (OR 0.99 (95% CI 0.66-1.47)). No differences in duration of diabetes mellitus, microvascular complications or glycaemic control between groups were detected. CONCLUSION: Although type 2 diabetes was more frequently diagnosed among patients with carpal tunnel syndrome, it could not be identified as an independent risk factor.

Complete pseudoepiphyses with associated enhanced growth in hands and feet: a report of 2 siblings--case report.

We present 2 siblings with multiple complete pseudoepiphyses in their hands and feet with associated symptomatic enhanced growth. Physical examination of the 6-year-old boy revealed long slender fingers and hyperplastic great toes. Radiography showed complete pseudoepiphyses in the first metacarpals, proximal and middle phalanges of the hands, and proximal phalanges of the feet. The patient's younger brother had a similar phenotype with slightly milder functional complaints. Genetic analysis did not reveal an underlying syndrome in these siblings.

Nerve decompression surgery as treatment for peripheral diabetic neuropathy: literature overview and awareness among medical professionals.

Peripheral diabetic neuropathy (PDN) is one of the major complications arising in patients with diabetes. Since PDN is traditionally considered an irreversible disorder, treatment has been aimed to prevent the development of complications. In a novel concept, however, it is postulated that decompression surgery of the affected nerve may reverse the natural course of PDN. In this review, we will discuss experimental and human studies that addressed the value of nerve decompression surgery in PDN. Furthermore, we report on the awareness of this novel treatment strategy among medical professionals that are primarily involved in diabetes care.

Can face-to-face patient education be replaced by computer-based patient education? A randomised trial.

OBJECTIVE: Computer-based patient education is an effective (therapeutic) tool. More and more studies prove that it can be an effective additive for face-to-face education, but it is still unclear if it is possible to educate patients by only using a computer. Our objective was to compare knowledge levels and satisfaction scores after computer-based patient education versus doctor-based patient education. METHODS: We started a randomised and stratified trial in a large plastic surgery clinic in the Netherlands. One hundred thirteen patients with carpal tunnel syndrome (CTS), scheduled for operation were included. One group received CTS education by a doctor using a checklist (group A). The other group received the same CTS education by specially designed interactive computer program (group B). After 2 weeks, knowledge levels and satisfaction scores were tested by using a questionnaire. RESULTS: One hundred thirteen patients were included, 96 patients finished the questionnaire. With respect to knowledge levels the doctor group (A) scored 20.2 points (max 40 points), and the computer group (B) scored 23.5 points. After correction the difference was 2.8 points (p=0.001). The total satisfaction score in group A was 7.6 and in group B 7.5; a difference of -0.16 (p=0.585). CONCLUSIONS: The results suggest that educating patients can result in a higher knowledge levels by using a computer than by using a doctor. Satisfaction seems equal after both methods of education. PRACTICE IMPLICATIONS: Knowing that you can educate patients without seeing a doctor or nurse seems promising. Patient can be educated by computer-based education programs leaving more time in a consultation for asking questions and discussing treatment options. The discussion will be at a more equal level of knowledge. Possibly it can save time and money resulting in a more efficient patient care, without dissatisfying our patients.