Biomechanical background and clinical observations of rotational malalignment in TKA: literature review and consequences

Malalignment, in particular femoral component malrotation, is a commonly accepted failure mode in total knee arthroplasty. The general objective of this paper is twofold: firstly, it accentuates clinical observations of the effects of rotational malalignment in total knee arthroplasty. Secondly, it discusses the relevant parameters of existing knee joint models with regards to rotational malalignment and its biomechanical background, thereby setting a basis for future studies. To summarise, when modelling malalignment in total knee arthroplasty, the following aspects should be considered: Friction between the implant components, ligamentous and capsular structures, deformable body to model the PE inlay, and an in vivo validation of the model. Because of the large variance in anthropometrical data between individuals, future knee joint models should also incorporate individual data.     

Comparison of diameter of ascending aorta in patients with severe aortic stenosis secondary to congenital versus degenerative versus rheumatic etiologies

Aortic root dilation has been previously reported to be associated with aortic stenosis (AS), but data to support this statement are scarce. The dimensions of the aortic root were measured at 4 levels (annulus, sinuses, sinotubular junction, and ascending aorta) in 88 patients (mean age 71.2+/-9.7 years; 56% men) with severe AS who underwent intraoperative transesophageal echocardiography immediately before aortic valve replacement. These patients were compared with 76 gender- and age-matched patients without AS who underwent transesophageal echocardiography for various indications. The etiology of aortic valve stenosis was degenerative in 62 (70.5%), bicuspid aortic valve (BAV) in 15 (17.0%), and rheumatic in 11 (12.5%). The ascending aorta was significantly wider in AS with various etiologies (BAV, rheumatic, degenerative) than in the controls (39+/-6.9, 35.0+/-4.2, 33.1+/-4.1, and 31.3+/-3.7 mm, respectively; p<0.001). The dimensions of the sinuses and sinotubular junction were significantly less in those with AS of degenerative etiology than in the controls (29.5+/-4.0 vs 32.5+/-4.3 mm and 23.6+/-3.0 vs 26.8+/-3.0 mm, respectively, p<0.001). The prevalence of a dilated aorta (>37 mm) was 3.9%, 13.1%, 36.4%, and 60% in the control group and AS patients with degenerative, rheumatic, and BAV etiology, respectively (p<0.0001). In conclusion, patients with severe AS due to BAV had significant dilation of the aortic root. Patients with degenerative and rheumatic etiology had less remarkable dilation compared with control group, and most values were within the normal range.     

Promoting informed choice: transforming health care to dispense knowledge for decision making

Ours is an era in which patients seek greater engagement in health care choices, increasing the demand for high-quality information about clinical options. Providing support for informed choice is not straightforward, however, because of challenges faced by clinicians, health systems, and consumers. Greater use of written or electronic tools can help to clarify choices for patients, but decision aids cannot replace the human element in facilitating informed choice. The ideal solution is to couple information with high-quality decision counseling to help patients understand the potential risks, benefits, and uncertainties of clinical options and to assist them in selecting the option that best accommodates their personal preferences. Decision counseling can be offered by 3 types of providers: clinicians who lack formal informed-choice training ("usual care"), clinicians with formal informed-choice training, or trained third parties who function as impartial decision counselors. Controlled studies are needed to determine which model is best, but none appears to be ideal. The health care system cannot truly support informed decision making without correcting the underlying obstacles that impede patient access to needed information. New information technology solutions, training programs, and reimbursement schemes are necessary. Patient demand for guidance will only increase as clinical options multiply and the world of information continues its rapid growth. Today's health care system is unprepared for the convergence of these 2 burgeoning domains, and the need to address systemic deficiencies will grow more urgent over time.     

Relationship of brain and skull in pre- and postoperative sagittal synostosis

Models of vertebrate skull evolution stress the coordinated developmental relationship between the skull and the brain that it houses. This study investigates the relationship between altered skull morphology and brain morphology in premature fusion of the cranial sagittal suture (isolated sagittal synostosis; ISS), a condition associated with dysmorphology of both neurocranium and brain. Although the skull displays a more normal shape following reconstructive cranial vault surgery, effects of this surgery on the brain have not been investigated. Landmark coordinate data were collected from three-dimensional magnetic resonance imaging reconstructions of the brain in a sample of ISS patients and an age-matched unaffected cohort. These data were analysed using Euclidean distance matrix analysis (EDMA). Results show that the brain in ISS is dysmorphic preoperatively, displaying a posteriorly directed neural expansion that does not 'worsen' with growth. Postoperatively, the brain in ISS displays a more globular shape overall as compared with the preoperative morphology, but differs from normal in its subcortical morphology. These results show that the ISS brain is altered following neurocranial surgery, but does not more closely approximate that of unaffected individuals. This suggests that although the brain is affected by manipulation of the skull, it retains a growth pattern that is, at least in part, independent of the skull.     

SEPT9_v4 expression induces morphological change, increased motility and disturbed polarity

Several lines of evidence indicate that altered expression of SEPT9 is seen in human neoplasia. In particular there is evidence of altered expression of the SEPT9_v4 isoform. The functional consequences of this remain unclear. We have studied the expression of wild-type- and GTP-binding mutants (G144V and S148N) of the SEPT9_v4 isoform in the MCF7 cell line as a model for its deregulation in neoplasia. We find that SEPT9_v4 expression induces dramatic actin cytoskeletal reorganization with the formation of processes around the cell periphery. Expression of the SEPT9_v4 isoform and a G144V mutant cause delocalization of endogenous SEPT9 from filamentous structures but the S148N mutant does not have this effect. In addition SEPT9_v4 isoform expression enhances cell motility and is associated with perturbation of directional movement. Expression of SEPT9_v4 GTP binding mutants also has potent effects on morphology and motility and causes loss of normal polarity, as judged by Golgi reorientation assays. The phenotypes induced by expression of the SEPT9_v4 isoform and the GTP mutants provide an insight into possible mechanisms of SEPT9_v4 function and suggest that the GTPase functions have both ras- and rab-like features. We propose a model in which overexpression of the SEPT9_v4 isoform in neoplasia is associated with perturbation of SEPT9 complexes, leading to phenotypes associated with neoplasia.     

Vascular dysfunction of venous bypass conduits is mediated by reactive oxygen species in diabetes: role of endothelin-1

Diabetes is associated with increased risk for complications following coronary bypass grafting (CABG) surgery. Augmented superoxide (*O2*) production plays an important role in diabetic complications by causing vascular dysfunction. The potent vasoconstrictor endothelin-1 (ET-1) is also elevated in diabetes and following CABG; however, the effect of ET-1 on *O2* generation and/or vascular dysfunction in bypass conduits remain unknown. Accordingly, this study investigated basal and ET-1-stimulated *O2* production in bypass conduits and determined the effect of *O2* on conduit reactivity. Saphenous vein specimens were obtained from nondiabetic (n = 24) and diabetic (n = 24) patients undergoing CABG. Dihydroethidium staining and NAD(P)H oxidase activity assays (5380 +/- 940 versus 16,362 +/- 2550 relative light units/microg) demonstrated increased basal *O2* levels in the diabetes group (p < 0.05). Plasma ET-1 levels were associated with elevated basal *O2* levels, and treatment of conduits with exogenous ET-1 further increased *O2* production and augmented vasoconstriction. Furthermore, vascular relaxation was impaired in the diabetic group (75 versus 40%), which was restored by *O2* scavenger superoxide dismutase. These findings suggest that ET-1 causes bypass conduits dysfunction via stimulation of *O2* production in diabetes. Novel therapies that attenuate *O2* generation in bypass conduits may improve acute and late outcome of CABG in diabetic patients.     

Triplet heterotopic pregnancy after gonadotropin stimulation and intrauterine insemination diagnosed at laparoscopy: a case report

Heterotopic pregnancy has been traditionally considered a rare event; however, with the use of assisted reproductive technology, the incidence of heterotopic pregnancies is increasing. Diagnosing a heterotopic pregnancy can be challenging. This report describes a 30-year-old female at 11 weeks' gestation with an intrauterine twin pregnancy after gonadotropin stimulation and intrauterine insemination who presented complaining of left lower quadrant abdominal pain with constipation and cramps. The patient was empirically treated for diverticulitis but failed to respond to therapy. A heterotopic triplet pregnancy was ultimately diagnosed at laparoscopy. Heterotopic pregnancy must be considered in the differential diagnosis of abdominal pain in the first trimester, especially in patients who conceived by means of assisted reproductive technology. Surgical treatment is the most frequently used method of treatment.