Understanding Pancreas Development for β-Cell Repair and Replacement Therapies

The lack or dysfunction of insulin-producing β-cells is the cause of all forms of diabetes. In vitro generation of β-cells from pluripotent stem cells for cell-replacement therapy or triggering endogenous mechanisms of β-cell repair have great potential in the field of regenerative medicine. Both approaches rely on a thorough understanding of β-cell development and homeostasis. Here, we briefly summarize the current knowledge of β-cell differentiation during pancreas development in the mouse. Furthermore, we describe how this knowledge is translated to instruct differentiation of both mouse and human pluripotent stem cells towards the β-cell lineage. Finally, we shortly summarize the current efforts to identify stem or progenitor cells in the adult pancreatic organ and to harness the endogenous regenerative potential. Understanding development and regeneration of β-cells already led to identification of molecular targets for therapy and informed on pathomechanisms of diabetes. In the future might lead to β-cell repair and replacement therapies.     

Comparison of revision strategies for failed C2-posterior cervical pedicle screws: a biomechanical study

Study purpose

With increasing usage within challenging biomechanical constructs, failures of C2 posterior cervical pedicle screws (C2-pCPSs) will occur. The purpose of the study was therefore to investigate the biomechanical characteristics of two revision techniques after the failure of C2-pCPSs.

Materials and methods

Twelve human C2 vertebrae were tested in vitro in a biomechanical study to compare two strategies for revision screws after failure of C2-pCPSs. C2 pedicles were instrumented using unicortical 3.5-mm CPS bilaterally (Synapse/Synthes, Switzerland). Insertion accuracy was verified by fluoroscopy. C2 vertebrae were potted and fixed in an electromechanical testing machine with the screw axis coaxial to the pullout direction. Pullout testing was conducted with load and displacement data taken continuously. The peak load to failure was measured in newtons (N) and is reported as the pullout resistance (POR). After pullout, two revision strategies were tested in each vertebra. In Group-1, revision was performed with 4.0-mm C2-pCPSs. In Group-2, revision was performed with C2-pedicle bone-plastic combined with the use of a 4-mm C2-pCPSs. For the statistical analysis, the POR between screws was compared using absolute values (N) and the POR of the revision techniques normalized to that of the primary procedures (%).

Results

The POR of primary 3.5-mm CPSs was 1,140.5 ± 539.6 N for Group-1 and 1,007.7 ± 362.5 N for Group-2; the difference was not significant. In the revision setting, the POR in Group-1 was 705.8 ± 449.1 N, representing a reduction of 38.1 ± 32.9 % compared with that of primary screw fixation. For Group-2, the POR was 875.3 ± 367.9 N, representing a reduction of 13.1 ± 23.4 %. A statistical analysis showed a significantly higher POR for Group-2 compared with Group-1 (p = 0.02). Although the statistics showed a significantly reduced POR for both revision strategies compared with primary fixation (p < 0.001/p = 0.001), the loss of POR (in %) in Group-1 was significantly higher compared with the loss in Group-2 (p = 0.04).

Conclusions

Using a larger-diameter screw combined with the application of a pedicle bone-plastic, the POR can be significantly increased compared with the use of only an increased screw diameter.     

In vivo analysis of cervical kinematics after implantation of a minimally constrained cervical artificial disc replacement

Introduction

To better understand cervical kinematics following cervical disc replacement (CDR), the in vivo behavior of a minimally constrained CDR was assessed.

Methods

Radiographic analysis of 19 patients undergoing a 1-level CDR from C4–5 to C6–7 (DISCOVER, Depuy-Spine, USA) was performed. Neutral–lateral and flexion–extension radiographs obtained at preop, postop and late follow-up were analyzed for segmental angle and global angle (GA C2–7). Flexion–extension range of motion was analyzed using validated quantitative motion analysis software (QMA®, Medical Metrics, USA). The FSU motion parameters measured at the index and adjacent levels were angular range of motion (ROM), translation and center of rotation (COR). Translation and COR were normalized to the AP dimension of the inferior endplate of the caudal vertebra. All motion parameters, including COR, were compared with normative reference data.

Results

The average patient age was 43.5 ± 7.3 years. The mean follow-up was 15.3 ± 7.2 months. C2–7 ROM was 35.9° ± 15.7° at preop and 45.4° ± 13.6° at follow-up (?p < .01). Based on the QMA at follow-up, angular ROM at the CDR level measured 9.8° ± 5.9° and translation was 10.1 ± 7.8 %. Individuals with higher ROM at the CDR level had increased translation at that level (p < .001, r = 0.97), increased translation and ROM at the supra-adjacent level (p < .001, r = .8; p = .005, r = .6). There was a strong interrelation between angular ROM and translation at the supra-adjacent level (p < .001, r = .9) and caudal-adjacent level (p < .001, r = .9). The location of the COR at the CDR- and supra-adjacent levels was significantly different for the COR-X (p < .001). Notably, the COR-Y at the CDR level was significantly correlated with the extent of CDR-level translation (p = .02, r = .6). Shell angle, which may be influenced by implant size and positioning had no impact on angular ROM but was correlated with COR-X (p = .05, r = ?.6) and COR-Y (p = .04, r = ?.5).

Conclusion

The COR is an important parameter for assessing the ability of non-constrained CDRs to replicate the normal kinematics of a FSU. CDR size and location, both of which can impact shell angle, may influence the amount of translation by affecting the location of the COR. Future research is needed to show how much translation is beneficial concerning clinical outcomes and facet loading.     

Longitudinal growth on an everolimus‐ versus an MMF‐based steroid‐free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case‐control study on longitudinal growth over 2 years in steroid‐free pediatric renal transplant recipients. Fourteen patients on a steroid‐free maintenance immunosuppressive regimen consisting of low‐dose everolimus (EVR) in conjunction with low‐dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid‐free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch‐up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid‐free pediatric patients on low‐dose EVR and CsA is not different to that of a matched steroid‐free control group on an immunosuppressive regimen with standard‐dose CNI and MMF. Hence, low‐dose EVR does not appear to negatively impact short‐term growth in pediatric renal transplant recipients.     

Individual and team training with first time users of the Pelvic C-Clamp: do they remember or will we need refresher trainings?

Background

Pelvic ring injuries with associated hemorrhage from the presacral venous plexus are major contributors to morbidity and mortality in trauma patients. The Pelvic C-Clamp is an often discussed, yet seldom used device for both skeletal and hemodynamic stabilization. In a recent study we have addressed this issue and have stressed the importance of regular training sessions with the device. This study is aimed as an extended follow up with a special focus on how trained skills are retained over time.

Materials and methods

32 participants with various levels of training were taught to use the clamp. Thirty-six hours later, a hands-on session was performed where the time needed for placement and accuracy of placement were evaluated on a model in individual and team settings. 12 months later a re-evaluation was performed.

Results

Evaluation showed that during the first session, 57/64 pins (89.15 %) were placed inside the safe area. The team training results showed reduced times for assembly and more exact pin placement. In the re-evaluation 1 year later, 75 % of all pins were safely placed and the time needed for assembly was significantly longer.

Conclusions

The majority of 57 pins were placed in the safe area within 6 min after one single training session. This reproduces the Australian data and supports the theory that adequately educated and skilled physicians should be able to handle the device properly. The data from the re-evaluation suggest that repeating the training session with the device improves performance.     

Postoperative care and rehabilitation after open carpal tunnel surgery

Background

Carpal tunnel syndrome is the most commonly diagnosed and treated entrapment neuropathy. The most frequently performed procedure in the surgical treatment is the open release of the flexor retinaculum. Regarding postoperative care, current literature is inconclusive and does not meet the necessary requirements to create a consensus on rehabilitation regimen. Although postoperative splinting is common among hand surgeons and most often applied for 1 week, none of the previous studies have especially assessed the outcome after 7 days of splinting. The aim of this study was to investigate the differences in postoperative rehabilitation following open carpal tunnel release, between a regimen of 1 week dorsal splinting and a light foam bandage for 2 days.

Methods

Sixty patients undergoing carpal tunnel surgery were enrolled in this prospective, noninterventional study. After either receiving a lightweight foam dressing or a splint, patients were followed up at 3 and 6 months, retrieving parameters of pain, two-point discrimination, grip, pinch and keypinch strength, and electrodiagnostic studies.

Results

Significant improvements were observed in both groups, regardless of the respective postoperative care. A comparison of follow-up data between the two study groups did not show any significant differences. Though, statistically significance was detected when comparing grip (5.42 ± 7.35 vs. ?0.19 ± 5.88; p = 0.001) and keypinch strength differences (2.38 ± 5.39 vs. ?0.06 ± 3.30; p = 0.035) at 6 months, favoring nonsplinted individuals.

Conclusions

The results of our research yield little benefit of unrestricted mobility in relation to 1 week postoperative splinting. Immobilization does not entail advantages and thus should be limited to certain circumstances only.     

Social media in dental education: a call for research and action

Social media are part of the fabric of today's world, from which health care is not excluded. Based on its distribution capacity, a single individual can cause an amount of damage to an institution that only a few decades ago required access to a mainstream news media outlet. Despite the obvious parallels in professional standards in the medical and dental communities, the scholarly activity and resulting collegial discourse observed among medical professionals remain unmatched in the dental education literature. As a result, a rigorous research agenda on the topic is indicated. Once these results are evaluated and thoroughly vetted, actions should be tailored to address the needs, minimize the threats, and maximize the opportunities that have been already noted by the medical profession. Regardless of input, albeit internal or external, a cadre of individuals who are willing to develop philosophy, policy, and procedure related to the use of social media policies in dental education can then be identified to evaluate the issues unique to the institution and perhaps the profession.