Biologic treatment sequences for plaque psoriasis: a cost-utility analysis based on 10 years of Dutch real-world evidence from BioCAPTURE.

BACKGROUND: Treatment with biologics may be indicated for patients with moderate-to-severe plaque psoriasis, but comparative evidence on cost-effectiveness is limited. Switching of biologics is common, but it is unclear what the effect is of differences in sequences of biologics. OBJECTIVES: To evaluate the cost-effectiveness of different biologic treatment sequences for psoriasis based on real-world evidence. PATIENTS AND METHODS: A sequence model was developed to evaluate the costs and health effects of three consecutive lines of biologic treatments [for example adalimumab-etanercept-ustekinumab (Ada-Eta-Ust) vs. Eta-Ust-Ada] over a 10-year time horizon in the Netherlands. The model was populated with data from the Dutch BioCAPTURE registry and scientific literature. Analyses were conducted of cost per quality-adjusted life year (QALY) and uncertainty was addressed by probabilistic as well as scenario analyses. RESULTS: Treatment of psoriasis with biologics for a 10-year period was estimated to be associated with a cost of €141 962 to €148 442 per patient depending on the treatment sequence used. Cumulative health effects ranged from 7·79 to 8·03 QALYs. Starting with Ada or Ust seems favourable concerning cost and utilities compared with strategies starting with Eta, although credible intervals were partly overlapping. CONCLUSIONS: The order in which biologics are used influences treatment cost-effectiveness, both in terms of costs and health effects. Initiation of a biologic treatment sequence for psoriasis might best be done with Ada or Ust; Eta seems less optimal from a health-economic perspective.

[Current surgical and adjuvant therapy concepts of malignant tumors of the facial skin and the pinna]. / Aktueller Stand der chirurgischen und adjuvanten Therapie der Malignome der Gesichtshaut und der Ohrmuschel.

Malignant tumors of the skin had been a rare entity 2 decades ago. Today they are spread rapidly worldwide. Malignant neoplasms of the skin, the largest human organ, may occur from all structures and layers. While previously skin cancer -occurred mainly after the age of 60, the incidence increases now in younger ages. Strong sunburns in the childhood and before the age of 20 are important risk factors for the development of malignancies of the skin. An increased exposure to UV rays is found especially in the facial skin, where basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Merkel cell carcinomas are the most common malignancies. Early diagnosis of malignancies and therapy-oriented mostly surgical approaches are crucial for the prognosis of all skin cancers. Therefore under the aspect of the increasing incidence these topics will be pointed out according to the latest findings including current multimodal therapy concepts and future treatment options.

[Cost-effectiveness in Dutch mental health care: future because of ROM?]. / Doelmatigheid in de ggz: toekomst dankzij ROM?

BACKGROUND: The document reporting Dutch mental health care negotiations for 2014-2017 calls for a cost decrease based on cost-effectiveness. Thanks to ROM, the Dutch mental health care seems well prepared for cost-effectiveness research. AIM: Evaluate how valid cost-effectiveness research should be established in mental health care and the role of rom therein. METHOD: Evaluation of requirements of cost-effectiveness research, trends, and a translation to Dutch mental health care. RESULTS: Valid cost-effectiveness research in mental health care requires the application of a societal perspective, a long time-horizon and an adequate evaluation of quality of life of patients. Healthcare consumption, outcome of care and characterisation of the patient population should be measured systematically and continuously. Currently, rom-data are not suitable to serve as a basis for cost-effectiveness research, although a proper basis is present. Further development of rom could lead to a situation in which mental health care is purchased on the basis of cost-effectiveness. However, cost-effectiveness will only really be improved if quality of care is rewarded, rather than rewarding activities that are not always related to outcome of care. CONCLUSION: Cost-effectiveness research in mental health care should focus on societal costs and benefits, quality of life and a long time-horizon. If developed further, rom has the potential to be a basis for cost-effectiveness research in the future.

Combined SPECT/CT improves detection of initial bone invasion and determination of resection margins in squamous cell carcinoma of the head and neck compared to conventional imaging modalities.

PURPOSE: Knowledge of the presence and extent of bone infiltration is crucial for planning the resection of potential bone-infiltrating squamous cell carcinomas of the head and neck (HNSCC). Routinely, plain-film radiography, multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are used for preoperative staging, but they show relatively high rates of false-positive and false-negative findings. Scintigraphy with (99m)Tc-bisphosphonate has the ability to show increased metabolic bone activity. If combined with anatomical imaging (e.g. (SPECT)/CT), it facilitates the precise localization of malignant bone lesions. The aim of this study was to analyse the indications and advantages of SPECT/CT compared with standard imaging modalities and histology with regard to specificity and sensitivity METHODS: A longitudinally evaluated group of 30 patients with biopsy-proven HNSCC adjacent to the mandible underwent (99m)Tc-bisphosphonate SPECT/CT, MRI, MSCT and conventional radiography before partial or rim resection of the mandible was performed. Bone infiltration was first evaluated with plain films, MSCT and MRI. In a second reading, SPECT/CT data were taken into account. The results (region and certainty of bone invasion) were evaluated among the different imaging modalities and finally compared with histological specimens from surgical resection as the standard of reference. For a better evaluation of the hybrid property of SPECT/CT, a retrospectively evaluated group of 20 additional patients with tumour locations similar to those of the longitudinally examined SPECT/CT group underwent SPECT, MSCT and MRI. To assess the influence of dental foci on the specificity of the imaging modalities, all patients were separated into two subgroups depending on the presence or absence of teeth in the area of potential tumour-bone contact. RESULTS: Histologically proven bone infiltration was found in 17 patients (57 %) when analysed by conventional imaging modalities. SPECT/CT data revealed bone infiltration in two additional patients (7 %), who both showed discrete cortical bone erosion not visible by MSCT or MRI. There were no false-positive or false-negative findings on SPECT/CT. The quality criteria for detecting bone involvement in HNSCC by SPECT/CT were as follows: sensitivity 100 % (lower 95 % confidence interval limit 80 %), specificity 100 % (75 %), positive predictive value 100 % (80 %) and negative predictive value 100 % (75 %). Corresponding data for MRI were 95 % (76 %), 94 % (73 %), 95 % (76 %) and 94 % (73 %), and for MSCT were 89 % (71 %), 100 % (85 %), 100 % (86 %) and 88 % (69 %). In the retrospective evaluation SPECT showed results similar to SPECT/CT. CONCLUSION: Hybrid SPECT/CT has a high specificity as it can provide additional information about the existence and local extent of malignant bone infiltration of the mandible. Although the sensitivity of conventional SPECT is similar to that of SPECT/CT, the latter provides a much better delineation of the local tumour-bone contact area. Based on this information, surgical intervention of the rim versus partial resection can be planned and performed more precisely. Patient outcome can be improved by avoiding undertreatment and unnecessary or overextended bone resections.

Anakinra in cerebral haemorrhage to target secondary injury resulting from neuroinflammation (ACTION): Study protocol of a phase II randomised clinical trial.

BACKGROUND: Inflammation plays a vital role in the development of secondary brain injury after spontaneous intracerebral haemorrhage (ICH). Interleukin-1 beta is an early pro-inflammatory cytokine and a potential therapeutic target. AIM: To determine the effect of treatment with recombinant human interleukin-1 receptor antagonist anakinra on perihematomal oedema (PHO) formation in patients with spontaneous ICH compared to standard medical management, and investigate whether this effect is dose-dependent. METHODS: ACTION is a phase-II, prospective, randomised, three-armed (1:1:1) trial with open-label treatment and blinded end-point assessment (PROBE) at three hospitals in The Netherlands. We will include 75 patients with a supratentorial spontaneous ICH admitted within 8 h after symptom onset. Participants will receive anakinra in a high dose (loading dose 500 mg intravenously, followed by infusion with 2 mg/kg/h over 72 h; n = 25) or in a low dose (loading dose 100 mg subcutaneously, followed by 100 mg subcutaneous twice daily for 72 h; n = 25), plus standard care. The control group (n = 25) will receive standard medical management. OUTCOMES: Primary outcome is PHO, measured as oedema extension distance on MRI at day 7 ± 1. Secondary outcomes include the safety profile of anakinra, the effect of anakinra on serum inflammation markers, MRI measures of blood brain barrier integrity, and functional outcome at 90 ± 7 days. DISCUSSION: The ACTION trial will provide insight into whether targeting interleukin-1 beta in the early time window after ICH onset could ameliorate secondary brain injury. This may contribute to the development of new treatment options to improve clinical outcome after ICH.

Hypersensitivity pneumonitis due to metalworking fluids: how to find the antigens.

Most surveys of outbreaks of hypersensitivity pneumonitis (HP) in subjects with occupational exposure to water-based metalworking fluids (MWFs) were unable to detect a clear link between symptoms and the precise causative agents. We studied the case of a male 41-year-old industrial knife grinder with exposure to water-based MWFs since 12 years. The diagnosis of HP was made by typical work-related symptoms, the demonstration of high lymphocyte numbers in bronchoalveolar lavage and elevated IgG antibody concentrations to various molds in the patient's serum, and complete recovery after early exposure cessation. Whereas an environmental survey showed only low numbers of mold contamination in one sump sample, high antigenic activity was demonstrated in the same sample by antigen-specific IgG inhibition tests. We conclude that the detection of antigenic molds in water-based MWFs by culture methods may be limited. The link between occupational exposure to specific molds in MWFs and hypersensitivity pneumonitis can be established by the demonstration of antigenic activity by antigen-specific IgG inhibition tests.

Changes in intra- and extracranial carotid plaque calcification: a 2-year follow-up study.

Extra- and intracranial carotid plaque calcification might have plaque-stabilizing effects, yet information on changes in plaque calcification remains scarce. We evaluated changes in carotid plaque calcification over 2 years follow-up in patients with symptomatic carotid artery disease. This study is based on the PARISK-study, a multicenter cohort study, with TIA/minor stroke patients with ipsilateral mild-to-moderate carotid artery stenosis (< 70%). We included 79 patients (25% female, mean age 66 years) who underwent CTA imaging with 2 year interval. We assessed the volume of extra- and intracranial carotid artery calcification (ECAC and ICAC) and calculated the difference between baseline and follow-up ECAC and ICAC volume. We performed multivariable regression analyses to investigate the association between change of ECAC or ICAC with cardiovascular determinants. ECAC. We found increase (46.2%) and decrease (34%) in ECAC volume during 2 year follow-up, both significantly correlation with baseline ECAC volume (OR = 0.72, 95% CI 0.58-0.90 respectively OR = 2.24, 95% CI 1.60-3.13).We found significant correlation for change in ECAC volume with diabetes (ß = 0.46, 95% CI 0.03-0.89) and baseline ECAC volume (ß = 0.81, 95% CI 0.73-0.88). ICAC. We found increase (45.0%) and decrease (25.0%) in ICAC volume. The ICAC decrease was significantly correlated with baseline ICAC volume (OR = 2.17, 95% CI 1.48-3.16), age (OR = 2.00, 95% CI 1.19-3.38) and use of antihypertensive drugs (OR = 3.79, 95% CI 1.20-11.96]).The overall change of ICAC volume was also significantly correlated with diabetes (ß = 0.92, 95% CI 1.59-7.02), use of oral hypoglycemic drugs (ß = 0.86, 95% CI 0.12-1.59) and baseline ICAC volume (ß = 0.71, 95% CI 0.55-0.87). We provide novel insights into the dynamics of carotid plaque calcification in symptomatic stroke patients.

Potential biomarkers for identification of mycobacterial cultures by proton transfer reaction mass spectrometry analysis.

RATIONALE: Several mycobacterial species can produce serious infections in humans, and the treatment required depends on the infecting species. Fast identification, ideally with minimal manipulation of the infecting species, is therefore critical; here, we propose a method potentially allowing cultures to be identified by headspace analysis and use it to screen for differences between mycobacterial species based on the volatiles released during growth. METHODS: Short-chain volatile organic compound emissions from two non-tuberculosis slow growing mycobacterial species, Mycobacterium avium and Mycobacterium kansasii, and a non-pathogenic fast growing species, Mycobacterium smegmatis, in Middlebrook M7H9 culturing media were followed online with a proton transfer reaction quadrupole mass spectrometer. RESULTS: Measurable differences between the headspace of the two slow growing mycobacteria M. kansasii and M. avium were found, as well as differences with respect to the faster growing mycobacteria M. smegmatis. Three compounds, attributed to sulfur-containing volatiles--dimethyl sulfide, propanethiol and dimethyl disulfide--were found to be specific to M. avium. CONCLUSIONS: Clear differences were detected in the low molecular weight volatile emissions compounds of the mycobacterial species under study, without the need for sample manipulation. Further studies with other mycobacterial species will reveal if the differences observed are specific to the species studied here. Furthermore, the use of an ion trap as a mass analyzer with the same ionization technique, allowing molecular detection over a wider molecular range, could allow the detection of additional biomarkers thus capturing a wider molecular range.

Early-onset LBSL: how severe does it get?

AIM: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is known as a relatively mild leukoencephalopathy. We investigated the occurrence of severe variants of LBSL with extensive brain magnetic resonance imaging (MRI) abnormalities. METHOD: MRIs of approximately 3,000 patients with an unknown leukoencephalopathy were retrospectively reviewed for extensive signal abnormalities of the cerebral and cerebellar white matter, posterior limb of the internal capsule, cerebellar peduncles, pyramids, and medial lemniscus. Clinical data were retrospectively collected. RESULTS: Eleven patients fulfilled the MRI criteria (six males); six had DARS2 mutations. Clinical and laboratory findings did not distinguish between patients with and without DARS2 mutations, but MRI did. Patients with DARS2 mutations more often had involvement of structures typically affected in LBSL, including decussatio of the medial lemniscus, anterior spinocerebellar tracts, and superior and inferior cerebellar peduncles. Also, involvement of the globus pallidus was associated with DARS2 mutations. Earliest disease onset was neonatal; earliest death at 20 months. INTERPRETATION: This study confirms the occurrence of early infantile, severe LBSL, extending the known phenotypic range of LBSL. Abnormality of specific brainstem tracts and cerebellar peduncles are MRI findings that point to the correct diagnosis.

'Give me something meaningful': GPs perspectives on how to improve an audit and feedback report provided by health insurers - an exploratory qualitative study.

BACKGROUND: Audit and feedback (A&F) is a valuable quality improvement strategy, which can contribute to de-implementation of low-value care. In the Netherlands, all health insurers collaboratively provide A&F to general practitioners (GPs), the 'Primary Care Practice Report' (PCPR). Unfortunately, the use of this report by GPs is limited. This study examined the thoughts of GPs on the usability of the PCPR and GPs recommendations for improving the PCPR. METHOD: We used an interpretative qualitative design, with think-aloud tasks to uncover thoughts of GPs on the usability of the PCPR and semistructured interview questions to ask GPs' recommendations for improvement of the PCPR. Interviews were audiorecorded and transcribed ad verbatim. Data were analysed using thematic content analysis. RESULTS: We identified two main themes: 'poor usability of the PCPR', and 'minimal motivation to change based on the PCPR'. The GPs found the usability of the PCPR poor due to the feedback not being clinically meaningful, the data not being recent, individual and reliable, the performance comparators offer insufficient guidance to assess clinical performance, the results are not discussed with peers and the definitions and visuals are unclear. The GPs recommended improving these issues. The GPs motivation to change based on the PCPR was minimal. CONCLUSIONS: The GPs evaluated the PCPR as poorly usable and were minimally motivated to change. The PCPR seems developed from the perspective of the reports' commissioners, health insurers, and does not meet known criteria for effective A&F design and user-centred design. Importantly, the GPs did state that well-designed feedback could contribute to their motivation to improve clinical performance.Furthermore, the GPs stated that they receive a multitude of A&F reports, which they hardly use. Thus, we see a need for policy makers to invest in less, but more usable A&F reports.

Expression of Y-box-binding protein YB-1 allows stratification into long- and short-term survivors of head and neck cancer patients.

BACKGROUND: Histology-based classifications and clinical parameters of head and neck squamous cell carcinoma (HNSCC) are limited in their clinical capacity to provide information on prognosis and treatment choice of HNSCC. The primary aim of this study was to analyse Y-box-binding protein-1 (YB-1) protein expression in different grading groups of HNSCC patients, and to correlate these findings with the disease-specific survival (DSS). METHODS: We investigated the expression and cellular localisation of the oncogenic transcription/translation factor YB-1 by immunohistochemistry on tissue micro arrays in a total of 365 HNSCC specimens and correlated expression data with clinico-pathological parameters including DSS. RESULTS: Compared with control tissue from healthy individuals, a significantly (P<0.01) increased YB-1 protein expression was observed in high-grade HNSCC patients. By univariate survival data analysis, HNSCC patients with elevated YB-1 protein expression had a significantly (P<0.01) decreased DSS. By multivariate Cox regression analysis, high YB-1 expression and nuclear localisation retained its significance as a statistically independent (P<0.002) prognostic marker for DSS. Within grade 2 group of HNSCC patients, a subgroup defined by high nuclear and cytoplasmic YB-1 levels (co-expression pattern) in the cells of the tumour invasion front had a significantly poorer 5-year DSS rate of only 38% compared with overall 55% for grade 2 patients. Vice versa, the DSS rate was markedly increased to 74% for grade 2 cancer patients with low YB-1 protein expression at the same localisation. CONCLUSION: Our findings point to the fact that YB-1 expression in combination with histological classification in a double stratification strategy is superior to classical grading in the prediction of tumour progression in HNSCC.

Prevalence and clinical consequences of carotid artery residual defects following endarterectomy: a prospective CT angiography evaluation study.

OBJECTIVES: It is still unclear whether residual defects seen after carotid endarterectomy (CEA) have clinical consequences. We investigated prevalence of residual defects in the carotid artery and their possible impact on clinical and Duplex ultrasound (DUS) follow-up. MATERIALS AND METHODS: Sixty-five patients who had undergone CEA were prospectively examined with 1-3 month postoperative computed tomographic angiography (CTA), clinical and DUS follow-up. Defects in common (CCA), external (ECA) and internal carotid artery (ICA) were scored as clamp marks, intimal step or flap, mural thrombus, kink, microdehiscence suture or residual stenosis. RESULTS: Fifty-eight patients (89.2%) had residual defects in CCA, ECA or ICA (143 defects). Intimal steps (n = 39) and residual stenosis (n = 17) were most noted defects. Only residual defects in ECA were significantly associated with significant higher PSV values both at short-term and long-term follow-up (1990 vs. 1400 mm s(-1) at 1 year and 2000 vs. 1230 mm s(-1) at 2 years, P-values 0.031 and 0.016). CONCLUSION: Carotid artery residual defects on CTA after CEA are very common, simple fingerprints of the operative procedure, have no clear consequence. When CTA is performed clinically after CEA, knowledge of high prevalence and type of defects detected on CTA may be of importance for radiologists and clinicians.

Factor V Leiden and prothrombin 20210G>A [corrected] mutation and paediatric ischaemic stroke: a case-control study and two meta-analyses.

AIM: To determine whether factor V Leiden (FVL) and prothrombin (PT) 20210G>A mutation are associated with paediatric ischaemic stroke. METHODS: The study consisted of two parts. Case-control study included neuroradiologically confirmed paediatric ischaemic stroke patients from two tertiary children's hospitals in Estonia. For control group, DNA was obtained from 400 anonymous screening test cards of newborns born consecutively in all delivery departments of Estonia in January 2005. Meta-analyses was performed to assess the association between paediatric sinovenous thrombosis and FVL and PT 20210G>A. RESULTS: A total of 75 children (45 boys, 30 girls) were included into the case-control study: 19 with childhood arterial ischaemic stroke, 49 with perinatal arterial ischaemic stroke and seven with cerebral venous thrombosis. Both FVL and PT 20210G>A occurred significantly more frequently among patients with sinovenous thrombosis compared with controls (OR = 12.9; 95% CI: 2.3-73.0 and OR = 11.9; 95% CI: 2.1-67.2, respectively). The difference was not significant between childhood/perinatal arterial ischaemic stroke and controls. Meta-analyses (including our study) revealed that both FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis (OR = 3.1; 95% CI: 1.8-5.5 and OR = 3.1; 95% CI: 1.4-6.8, respectively). CONCLUSION: FVL and PT 20210G>A are associated with paediatric sinovenous thrombosis.

Lesions of the lateral pterygoid muscle-an overestimated reason for temporomandibular dysfunction: a 3T magnetic resonance imaging study.

The aim of this study was to examine the lateral pterygoid muscle (LPM) parenchyma, myotendinous junction, and tendon in temporomandibular disorder (TMD) patients using 3T magnetic resonance imaging (MRI). Results were compared with findings reported in the literature, in which the LPM has been attributed a major role in triggering TMD. 3T MRI was used for temporomandibular joint (TMJ) imaging. The MRI images of 63 patients were analysed for muscle contracture and atrophy, tendon rupture, signal alterations of the tendon, tendon contrast enhancement, and peritendinous fluid collection. Descriptive statistics and the coefficient estimate method were used for statistical analysis. Focus was placed on the association between LPM tendon pathology and TMJ lesions like osteoarthritis and disc displacement. Severe lesions of the LPM tendon and muscle parenchyma, like rupture or fibrosis, were detected in very few cases. Only moderate signs of tendinosis were found in TMD patients. In contrast, there was a clear correlation between tendon lesions and osteoarthritis or anterior disc displacement. These results indicate the need to discuss and question the role of the LPM and its tendon in TMD. Data suggest that LPM and tendon lesions are part of complex degenerative changes of the TMJ, and it seems less likely that a LPM disorder is causative in TMD.

MRI Vessel Wall Imaging after Intra-Arterial Treatment for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Vessel wall imaging is increasingly performed in the diagnostic work-up of patients with ischemic stroke. The aim of this study was to compare vessel wall enhancement after intra-arterial thrombosuction with that in patients not treated with thrombosuction. MATERIALS AND METHODS: From 2009 to 2017, forty-nine patients with an ischemic stroke underwent 7T MR imaging within 3 months after symptom onset as part of a prospective intracranial vessel wall imaging study. Fourteen of these patients underwent intra-arterial treatment using thrombosuction (intra-arterial treatment group). In the intra-arterial treatment group, vessel walls were evaluated for major vessel wall changes. All patients underwent pre- and postcontrast vessel wall imaging to assess enhancing foci of the vessel wall using coregistered subtraction images. A Wilcoxon signed rank test was performed to test for differences. RESULTS: In the intra-arterial treatment group, 11 of 14 patients (79%) showed vessel wall enhancement compared with 17 of 35 patients without intra-arterial treatment (49%). In the intra-arterial treatment group, more enhancing foci were detected on the ipsilateral side (n = 18.5) compared with the contralateral side (n = 3, P = .005). Enhancement was more often concentric on the ipsilateral side (n = 8) compared with contralateral side (n = 0, P = .01). No differences were found in the group without intra-arterial treatment between the number and configuration of ipsilateral and contralateral enhancing foci. CONCLUSIONS: Patients with intra-arterial treatment by means of thrombosuction showed more (concentric) enhancing foci of the vessel wall ipsilateral compared with contralateral to the treated artery than the patients without intra-arterial treatment, suggesting reactive changes of the vessel wall. This finding should be taken into account when assessing vessel wall MR images in patients with stroke.

Monoclonal antibodies directed against the sexual binding site of Chlamydomonas eugametos gametes.

Monoclonal antibodies were raised against the mt- sexual agglutinin of Chlamydomonas eugametos gametes. Those that blocked the agglutination site were selected. They were divided into two classes dependent upon whether they gave a weak (class A) or clear positive (class B) reaction with mt- flagellar membranes in an ELISA and an indirect immunofluorescence test using glutaraldehyde-fixed mt- gametes. Class A antibodies were shown to be specific for the agglutinin in an extract of mt- gametes, based on results from immunoblotting, immunoprecipitation, affinity chromatography, and the absence of a reaction with nonagglutinable cells. Surprisingly, class A mAbs also recognized two mt+ glycoproteins, one of which is the mt+ agglutinin. Class B antibodies were shown to bind to several glycoproteins in both mt- and mt+ gametes, including the mt- agglutinin. Fab fragments from class A mAbs blocked the sexual agglutination process, but those from class B did not, even though the parent antibody did. We conclude that the class A epitope lies in or close to the agglutination site of the mt- agglutinin, whereas the class B epitope lies elsewhere on the molecule. We also conclude that the mt- agglutinin is the only component on the mt- flagellar surface directly involved in agglutination. Class A mAbs were found to elicit several reactions displayed by the mt+ agglutinin. They bound to the mt- agglutinin on gamete flagella and induced most of the reactions typical of sexual agglutination, with the exception of flagellar tip activation. None of these reactions was induced by Fab fragments. High concentrations of class A mAbs completely repressed the sexual competence of live mt- gametes, but low concentrations stimulated cell fusion.

Intracranial Atherosclerotic Burden on 7T MRI Is Associated with Markers of Extracranial Atherosclerosis: The SMART-MR Study.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis, a major risk factor for ischemic stroke, is thought to have different atherogenic mechanisms than extracranial atherosclerosis. Studies investigating their relationship in vivo are sparse and report inconsistent results. We studied the relationship between intracranial atherosclerosis and extracranial atherosclerosis in a cohort of patients with a history of vascular disease. MATERIALS AND METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART) study, cross-sectional analyses were performed in 130 patients (mean age, 68 ± 9 years) with a history of vascular disease and with assessable 7T intracranial vessel wall MR imaging data. Intracranial atherosclerosis burden was defined as the number of intracranial vessel wall lesions in the circle of Willis and its major branches. Age- and sex-adjusted unstandardized regression coefficients (b-value) were calculated with intracranial atherosclerosis burden as the dependent variable and extracranial atherosclerosis markers as independent variables. RESULTS: Ninety-six percent of patients had ≥1 vessel wall lesion, with a mean intracranial atherosclerosis burden of 8.5 ± 5.7 lesions. Significant associations were observed between higher intracranial atherosclerosis burden and carotid intima-media thickness (b = 0.53 lesions per +0.1 mm; 95% CI, 0.1-1.0 lesions), 50%-100% carotid stenosis versus no stenosis (b = 6.6 lesions; 95% CI, 2.3-10.9 lesions), ankle-brachial index ≤ 0.9 versus >0.9 (b = 4.9 lesions; 95% CI, 1.7-8.0 lesions), and estimated glomerular filtration rate (b = -0.77 lesions per +10 mL/min; 95% CI, -1.50 to -0.03 lesions). No significant differences in intracranial atherosclerosis burden were found among different categories of vascular disease. CONCLUSIONS: Intracranial atherosclerosis was associated with various extracranial markers of atherosclerosis, not supporting a different etiology.

Teres major tendon transfer in the treatment of irreparable posterosuperior rotator cuff tears: long-term improvement of shoulder function and pain reduction at eight to 12 years' follow-up.

Aims: Since long-term outcome of teres major tendon transfer surgery for irreparable posterosuperior rotator cuff (RC) tears is largely unknown, the primary aim of this study was to evaluate the long-term outcome of the teres major transfer. We also aimed to report on the results of a cohort of patients with a similar indication for surgery that underwent a latissimus dorsi tendon transfer. Patients and Methods: Patients and Methods In this prospective cohort study, we reported on the long-term results of 20 consecutive patients with a teres major tendon transfer for irreparable massive posterosuperior RC tears. Additionally, we reported on the results of the latissimus dorsi tendon transfer (n = 19). The mean age was 60 years (47 to 77). Outcomes included the Constant score (CS), and pain at rest and during movement using the Visual Analogue Scale (VAS). Results: At a mean of ten years (8 to 12) following teres major transfer, the CS was still 23 points (95% confidence interval (CI) 14.6 to 30.9, p < 0.001) higher than preoperatively. VAS for pain at rest (21 mm, 95% CI 4.0 to 38.9, p = 0.016) and movement (31 mm, 95% CI 16.0 to 45.1, p < 0.001) were lower than preoperatively. We also found an increase in CS (32 points, 95% CI 23.4 to 40.2, p < 0.001) and reduction of pain (26 mm, 95% CI 9.9 to 41.8, p = 0.001) six years after latissimus dorsi transfer. Conclusion: Teres major tendon transfer is a treatment option to gain shoulder function and reduce pain in patients with an irreparable posterosuperior RC tear at a mean follow-up of ten years. The teres major tendon might be a valuable alternative to the commonly performed latissimus dorsi tendon transfer in the treatment of irreparable posterosuperior RC tears. Cite this article: Bone Joint J 2018;100-B:309-17.

Intraoperative cell isolation for a cytological assessment of bone resection margins in patients with head and neck cancer.

The intraoperative cytological assessment of bony resection margins (ICAB) is a feasible diagnostic approach to support frozen section for assessment of invasion of margins of soft and hard tissue. However, complex resection margins could challenge both diagnostic approaches. Our objective here was to identify the limitations of intraoperative diagnostic methods for assessing margins. We present an advanced cytological approach to assess complex margins that may solve the problem. Data from 119 patients in whom frozen section was supported by ICAB, were reviewed and the reasons for false results analysed. In 35 patients with squamous cell carcinoma infiltrating bone, specimens (n=100) from the resection margin went through an intraoperative cell isolation process for the cytological assessment of bony margins (ICAB). The results were compared with the histological results of the corresponding margins of bone as a reference. Limitations to the assessment of operative bony margins intraoperatively included an infiltrative histological pattern of growth of the carcinoma, with carcinoma cells disseminated within the cancellous bone, complex and uneven resection margins with soft and bony tissue, inflammation, and signs of previous radiotherapy. Intraoperative cell isolation plus (ICICAB) allowed the microscopic assessment of up to 1cm3 of bony tissue to detect disseminated carcinoma cells within the cancellous bone with a sensitivity of 92.3% (95% CI 74.9% to 99.1%), and a specificity of 100% (95% CI 95.1% to 100%), and positive and negative predictive values of 100% (95% CI 85.8% to 100%) and 97.4% (95%CI 90.8% to 99.7%), respectively. Intraoperative cell isolation is a feasible new technique to support ICAB and frozen section in the assessment of bony and soft tissue margins.