Locking versus nonlocking plates in mandibular reconstruction with fibular graft—a biomechanical ex vivo study

Objectives

The main goal of the present study was to compare the biomechanical stability of locking plates and conventional miniplate combinations in human mandibles reconstructed with fibular grafts.

Materials and methods

A specially developed and well-proven testing device reproduced the in vivo loading conditions on the mandible. Cadaveric human mandibles (n?=?12) reconstructed with harvested human fibular bone grafts were divided into two groups, and different osteosynthesis systems were applied using two lines of plates per osteotomy. On the test apparatus, the specimens were stressed to failure, and interfragmentary movement was monitored and quantified with a contact-free optical measurement system.

Results

The relevant interfragmentary movement results from a Euclidean summary calculation which considered all three spatial angles around the axes. Using values up to a maximum load of 300 N, the conventional six-hole miniplates (profile 1.0) had an average value of 7.45°?±?1.46°, and the locking six-hole plates (profile 1.3) had an average value of 12.16°?±?2.37° for rotational interfragmentary movement. The miniplate system exhibited a significantly superior performance in fixation compared to the fixed-angle system (p?<?0.05).

Conclusion

According to these biomechanical experiments, both osteosynthesis devices provided sufficient stabilization at loads of up to 300 N. The six-hole miniplate system provided better stabilization of the osteotomy gap for mandibles reconstructed with fibular grafts.

Clinical relevance

The osteosynthesis system is essential for primary stability and the avoidance of pseudarthrosis formation. This study demonstrates that the miniplates provide sufficient stabilization and offers a method to improve fixation in reconstructed mandibles.     

Global structural changes of an ion channel during its gating are followed by ion mobility mass spectrometry

Mechanosensitive ion channels are sensors probing membrane tension in all species; despite their importance and vital role in many cell functions, their gating mechanism remains to be elucidated. Here, we determined the conditions for releasing intact mechanosensitive channel of large conductance (MscL) proteins from their detergents in the gas phase using native ion mobility–mass spectrometry (IM-MS). By using IM-MS, we could detect the native mass of MscL from Escherichia coli, determine various global structural changes during its gating by measuring the rotationally averaged collision cross-sections, and show that it can function in the absence of a lipid bilayer. We could detect global conformational changes during MscL gating as small as 3%. Our findings will allow studying native structure of many other membrane proteins.One of the best candidates to explore the gating of mechanosensitive channels is the mechanosensitive channel of large conductance (MscL) from Escherichia coli. The crystal structure of MscL in its closed/nearly closed state from Mycobacterium tuberculosis revealed this channel as a homopentamer (1). Each subunit has a cytoplasmic N- and C-terminal domain as well as two α-helical transmembrane (TM) domains, TM1 and TM2, which are connected by a periplasmic loop. The five TM1 helices form the pore and the more peripheral TM2 helices interact with the lipid bilayer.MscL detects changes in membrane tension invoked by a hypoosmotic shock and couples the tension sensing directly to large conformational changes (1, 2). On the basis of a large body of structural and theoretical data, numerous gating models of MscL have been proposed (3–9). These models agree upon (i) the hydrophobic pore constriction of the channel and (ii) the channel opens by an iris-like rotation—i.e., a tilting and outward movement of transmembrane helices that make the channel wider and shorter (5). This mechanism is supported by patch-clamp (10), disulfide cross-linking (11), FRET spectroscopy (12), and site-directed spin labeling EPR experiments (6, 7), as well as computational studies (13–15). So far, direct experimental results have only been observed for short-range local structural changes, and no measure of the overall global structural changes during channel gating have been reported. Because there is no crystal structure available for the open MscL channel, elucidating overall global structural changes from the onset of channel activation is of utmost importance for our understanding of the gating mechanism of mechanosensitive channels. Here, we provide direct experimental evidence for the key areal changes occurring during channel gating by combining our ability to activate MscL in a controlled manner to different subopen states (16) with a native ion mobility-mass spectrometry (IM-MS) approach.     

Rectal carcinoids: a systematic review

Background

Rectal carcinoids are increasing in incidence worldwide. Frequently thought of as a relatively benign condition, there are limited data regarding optimal treatment strategies for both localized and more advanced disease. The aim of this study was to summarize published experiences with rectal carcinoids and to present the most current data.

Methods

Following PRISMA guidelines, an electronic literature search performed of PubMed, Medline, Embase, and the Cochrane Library using the terms “rectum” or “rectal” AND “carcinoid” over a 20-year study period from January 1993 to May 2013. Non-English-language studies, animal studies, and studies of fewer than 100 patients were excluded. Study end points included demographic information, tumor features, intervention and outcomes. All included articles were quality assessed.

Results

Using the search parameters and exclusions as outlined above, a total of 14 articles were identified for detailed analysis. The quality of articles was low/moderate for all included scoring 9 to 17 of 27. The articles included 4,575 patients diagnosed with a rectal carcinoid. Approximately 80 % of tumors were <10 mm, 15 % 11–20 mm, and 5 % >20 mm. Eight percent of patients presented with regional lymph node metastases, and 4 % presented with distant metastases. Tumor size >10 mm, and muscular and lymphovascular invasion are independently associated with an increased risk of metastases. The 5-year survival was 93 % in patients presenting with localized disease and 86 % overall.

Conclusions

Small tumors up to 10 mm without any adverse features can be treated with endoscopic or local excision. The treatment of carcinoids between 10 and 20 mm is still contentious, but those up to 16 mm without adverse feature are suitable for local/endoscopic excision followed by careful histopathological assessment. Those >20 mm or with adverse features require radical surgery with mesorectal clearance in suitable patients.     

Sensitization,pathologic, and imaging findings comparing symptomatic and quiescent failed renal allografts

Late allograft failure (LAF) is a common cause of end stage renal disease. These patients face interrelated challenges regarding immunosuppression management, risk of graft intolerance syndrome (GIS), and sensitization. This retrospective study analyzes sensitization, pathology, imaging, and transfusion requirements in 33 LAFs presenting either with GIS (22) or grafts remaining quiescent (11). All patients underwent immunosuppression weaning to discontinuation at LAF. Profound increases in sensitization were noted for all groups and occurred in the GIS group prior to transplant nephrectomy (TxN). Patients with GIS experienced a major upswing in sensitization at, or before the time of their symptomatic presentation. For both GIS and quiescent grafts, sensitization appeared to be closely linked to immunosuppression withdrawal. Most transfusion naïve patients became highly sensitized. Fourteen patients in the GIS group underwent TxN which revealed grade II acute cellular rejection or worse, with grade 3 chronic active T‐cell‐mediated rejection. Blinded comparisons of computed tomography scan of GIS group revealed swollen allografts with fluid collections compared with the quiescent allografts (QAs), which were shrunken and atrophic. The renal volume on imaging and weight of explants nearly matched. Future studies should focus on interventions to avoid sensitization and GIS.     

The joint impact of donor and recipient parameters on the outcome of heart transplantation in Germany after graft allocation

Organ shortage in heart transplantation (HTx) results in increased use of grafts from donors with substantial risk factors. It is discussed controversially which donor characteristics may be detrimental. Therefore, we evaluated the joint impact of donor‐ and patient‐related risk factors in HTx on patient survival by multiple analysis in a nationwide multicentre study after donor selection was carried out. The research database consists of data concerning hearts donated and transplanted in Germany between 2006 and 2008 as provided by Deutsche Stiftung Organtransplantation and the BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (n = 774, recipient age ≥ 18 years). Survival was significantly decreased by donor age (1.021 [1.008–1.035] per year), nontraumatic cause of death (1.481 [1.079–2.034]), troponin >0.1 ng/ml (2.075 [1.473–2.921]), ischaemia time (1.197 [1.041–1.373] per hour), recipient age (1.017 [1.002–1.031] per year) and in recipients with pulmonary vascular resistance ≥320 dyn*s*cm^?5 (1.761 [1.115–2.781]), with ventilator dependency (3.174 [2.211–6.340]) or complex previous heart surgery (1.763 [1.270–2.449]). After donor selection had been conducted, multiple Cox regression revealed donor age, nontraumatic cause of death, troponin and ischaemia time as well as recipient age, pulmonary hypertension, ventilator dependency and previous complex heart surgery as limiting risk factors concerning patient survival.     

Factors influencing long‐term outcome after kidney transplantation

Many factors influence the long‐term outcome of kidney transplantation, which is defined very schematically by patient death or renal dysfunction leading to graft loss. The most important of these factors is most likely the quality of the transplant itself, with kidneys from living donors showing a positive impact, while kidneys from expanded criteria donors show deleterious impacts. Various clinicopathological scores exist to predict mid‐ to long‐term outcomes and avoid the transplantation of kidneys displaying inferior results. The key factors related to the recipient include their age as well as disease recurrence, HLA matching, HLA immunization, ethnic background, time on dialysis, and cardiovascular comorbidities. Renal function, defined based on estimated GFR and/or proteinuria values, is a result of all these factors. Delayed graft function has a detrimental long‐term impact, as does the level of renal function impairment either in stable condition or in case of progressing dysfunction. Finally, although current immunosuppression regimes are highly efficient in preventing acute rejection, the burden of specific (diabetes, nephrotoxicity) and nonspecific (infection and cancer) side effects has significant negative long‐term consequences that may well be worse in the future because of the increasing ages of both donors and recipients. The development of safer immunosuppression strategies is therefore crucial to improve long‐term outcomes.