Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP‐1, IL‐8, IL‐18 and IL‐23 levels have a strong correlation with HS (P < .010‐0.004; AUC = 0.790‐0.883). Notably, combinations of two or three cytokines (TNF‐a, MCP‐1 and IL‐23; AUC: 0.942, Nagelkerke R²: 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.     

One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients

Objectives

Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.

Intratemporal facial nerve transfer with direct coaptation to the hypoglossal nerve.

OBJECTIVE: To evaluate functional recovery after facial-hypoglossal nerve transfer with direct coaptation of the intratemporal part of the facial nerve. STUDY DESIGN: Retrospective study. SETTING: University-based tertiary referral center. PATIENTS: Nine patients who underwent facial-hypoglossal transfer surgery between 2001 and 2006 to treat a unilateral complete facial nerve palsy. INTERVENTION: The facial nerve is mobilized in the temporal bone, transsected at the second genu, transferred and directly coaptated to a partially incised hypoglossal nerve. MAIN OUTCOME MEASURES: The House-Brackmann grading system was used to evaluate facial nerve reinnervation. Tongue atrophy and movements were documented. Quality of life related to facial function was assessed using the validated Facial Disability Index. RESULTS: A House-Brackmann Grade III (86%) was achieved in six patients, and Grade IV (14%) in one patient with an average follow-up of 22 months (range, 12-48 mo). Two patients had a follow-up of less than 12 months after surgery, and reinnervation was still in progress. In none of the patients who were operated on was tongue atrophy or impaired movement observed. Postoperative Facial Disability Index scores (mean, 71.8 +/- standard deviation [SD] 10.6) for physical functioning and social functioning (mean, 85.7 +/- SD 9.8) were increased for all patients when compared with preoperative scores (mean, 28.6 +/- SD 9.0; mean, 37.7 +/- SD 14.4, respectively). CONCLUSION: The facial-hypoglossal nerve transfer with direct coaptation of the intratemporal part of the facial nerve offers good functional results with low lingual morbidity and improved quality of life. The technique is straightforward, relatively simple, and should be considered as first option for reanimation of traumatic facial nerve lesions.     

Three new families with arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is a rare condition with autosomal recessive inheritance characterized by connective tissue abnormalities. The most specific clinical findings are cardiovascular anomalies including tortuosity, lengthening, aneurysm, and stenosis formation of major arteries. Also ventricular hypertrophy is frequently present. Other anomalies are skin hyperextensibility and cutis laxa, joint laxity or contractures of the joints, and inguinal herniae. Histology shows disruption of elastic fibers of the media. These features suggest that ATS is a connective tissue disorder. A biochemical or molecular defect has not yet been identified. We describe here nine additional ATS patients from three consanguineous Moroccan families and review a total of 35 patients with this uncommon condition.     

The radial depth-dose distribution of a 188W/188Re beta line source measured with novel,ultra-thin TLDs in a PMMA phantom: comparison with Monte Carlo simulations

The radial depth-dose distribution of a prototype 188W/188Re beta particle line source of known activity has been measured in a PMMA phantom, using a novel, ultra-thin type of LiF:Mg,Cu,P thermoluminescent detector (TLD). The measured radial dose function of this intravascular brachytherapy source agrees well with MCNP4C Monte Carlo simulations, which indicate that 188Re accounts for > or = 99% of the dose between 1 mm and 5 mm radial distance from the source axis. The TLDs were calibrated using a 90Sr/90Y beta secondary standard. Several correction factors are calculated using analytical and Monte Carlo methods. An analysis of the measurement uncertainty is made. Since it is partly determined by components of uncertainty arising from random effects, repeated measurements yield a lower uncertainty. The expanded uncertainty in the absolute dose at 2 mm radial distance equals 11%, 10%, 9% and 8% for 1, 2, 3 and 5 measurements, respectively. After a correction for source non-uniformity, the measured dose rate per unit source activity at 2 mm radial distance equals (1.53 +/- 0.16) Gy min(-1) GBq(-1) (2sigma), in agreement with the value of (1.45 +/- 0.01) Gy min(-1) GBq(-1) (2sigma) predicted by the MCNP4C simulations.     

Large deletions in the polycystic kidney disease 1 (PKD1) gene

Since identification of the genes mutated in patients with Autosomal Dominant Polycystic Kidney Disease, PKD1 and PKD2, a large number of different germ line mutations in both genes have been found by conventional PCR-based mutation detection methods. Nevertheless, in approximately 40% of the PKD1 families the disease-causing mutation remains to be elucidated. Complex germ line rearrangements are often not detectable by these standard diagnostic techniques. To detect large deletions in the PKD1 gene we performed Field Inversion Gel Electrophoresis (FIGE) followed by Southern blot analysis with probes selected in the unique and in the reiterated region of this gene. Our analysis revealed 4 deletions in 125 patients, indicating that large deletions in PKD1 are rare. Likely, patients with a deletion that also affects the neighbouring Tuberous Sclerosis Complex 2 (TSC2) gene will be diagnosed as patients with tuberous sclerosis. It was speculated that the exceptional polypyrimidine tract located in intron 21 and the small tract in intron 22, might play a role in the pathogenesis of ADPKD. Since this region is extremely difficult to amplify by PCR, we analysed the 5.8 kb BamHI fragment that contains the polypyrimidine tracts. We did not observe a disease-linked alteration although we detected two different rare variants either in PKD1 or in one of its homologues.     

Variable selection under multiple imputation using the bootstrap in a prognostic study

Background  

Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection.     

Immune activation modulates hematopoiesis through interactions between CD27 and CD70

The differentiation of hematopoietic stem cells into mature blood cell lineages is tightly regulated. Here we report that CD27, which is expressed on stem and early progenitor cells in bone marrow, can be important in this process. Deletion of CD27 increased the myeloid colony-forming potential of stem and early progenitor cells and enhanced B lymphoid reconstitutive capacity in competitive transplantation experiments. Conversely, stimulation of CD27(+) progenitor cells with CD70, the unique ligand for CD27, inhibited colony-forming potential in vitro and lymphocyte outgrowth in vivo. As CD70 is expressed only on activated immune cells, we suggest that CD27 triggering on early progenitor cells provides a negative feedback signal to leukocyte differentiation during immune activation.     

Who contextualises clinical epidemiological evidence? A political analysis of the problem of evidence-based medicine in the layered Dutch healthcare system

We critically examine the discussion on the role of evidence-based medicine (EBM) in healthcare governance. We take the institutionally layered Dutch healthcare system as our case study. Here, different actors are involved in the regulation, provision and financing of healthcare services. Over the last decades, these actors have related to EBM to inform their actor specific roles. At the same time, EBM has increasingly been problematised. To better understand this problematisation, we organised focus groups and interviews. We noticed that particularly EBM’s reductionist epistemology and its uncritical use by ‘professional others’ are considered problematic. However, our analysis also reveals that something else seems to be at stake. In fact, all the actors involved underwrite EBM’s reductionist epistemology and emphasise that evidence should be contextualised. They however do so in different ways and with different contexts in mind. Moreover, the ways in which some actors contextualise evidence has consequences for the ways in which others can do the same. We therefore emphasise that behind EBM’s scientific problematisation lurks a political issue. A dispute over who should contextualise evidence how, in a layered healthcare system with interdependent actors that cater to both individual patients and the public. We urge public administration scholars and policymakers to open-up the political confrontation between healthcare actors and their sometimes irreconcilable, yet evidence-informed perspectives.