Presentation outside office hours does not negatively influence treatment times for reperfusion therapy for acute ischemic stroke.

BACKGROUND: Treatment outside office hours has been associated with increased workflow times for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Limited data suggest that this "off-hours effect" also exists for endovascular treatment (EVT). We investigated this phenomenon in a well-organized acute stroke care region in the Netherlands. METHODS: Retrospective, observational cohort study of consecutive patients with AIS who received reperfusion therapy in the Greater Amsterdam Area, consisting of 14 primary stroke centers and 1 comprehensive stroke center (IVT: 2009-2015, EVT: 2014-2017). Office hours were defined as presentation during weekdays between 8 AM and 5 PM, excluding National Festive days. Primary outcome was door-to-treatment time (door-to-needle [DNT] for IVT, door-to-groin [DGT] for EVT). For DGT, we used the door time of the first hospital. Other outcomes were in-hospital mortality, modified Rankin Scale (mRS) score at 90 days and symptomatic intracranial hemorrhage (sICH). We performed multivariable linear and logistic regression analyses and used multiple imputation to account for missing values. RESULTS: In total, 59% (2450/4161) and 61% (239/395) of patients treated with IVT and EVT, respectively, presented outside office hours. Median DNT was minimally longer outside office hours (32 vs. 30 min, p = 0.024, adjusted difference 2.5 min, 95% CI 0.7-4.2). Presentation outside office hours was not associated with a longer DGT (median 130 min for both groups, adjusted difference 7.0 min, 95% CI - 4.2 to 18.1). Clinical outcome and sICH rate also did not differ. CONCLUSION: Presentation outside office hours did not lead to clinically relevant treatment delays for reperfusion therapy in patients with AIS.

Intra-nodal nevi in sentinel node-negative patients with cutaneous melanoma does not influence survival.

BACKGROUND: Melanoma patients with intra-nodal nevi (INN) and without melanoma metastasis in the sentinel lymph node biopsy (SLNB) are generally treated as patients with negative SLNB. However, diagnosis of INN may be difficult and nodal melanoma metastases may falsely be regarded as INN. OBJECTIVES: Our aim was to evaluate the clinical significance of INN in the SLNB in patients with primary cutaneous melanoma on a nationwide level in The Netherlands by comparing survival between three groups: patients with INN and without nodal melanoma metastasis (INN group), patients without INN and without nodal melanoma metastasis (negative SLNB group) and patients with nodal melanoma metastasis irrespective of INN (positive SLNB group). METHODS: Data were obtained from 'PALGA', the Dutch Nationwide Network and Registry of Histopathology and Cytopathology, yielding a cohort of adults with histologically proven, primary, invasive cutaneous melanoma patients in The Netherlands diagnosed between 2000 and 2014 who underwent SLNB. Clinical and pathological variables were extracted from the pathology text files. Differences between patients with INN, negative SLNB and positive SLNB were analysed using Kaplan-Meier analysis. RESULTS: A total of 11 274 patients were eligible for inclusion. The prevalence of INN in the SLNB was 5.0%. Melanomas with INN had similar median Breslow thickness compared to melanomas with negative SLNB and were more frequently located on trunk and upper limbs and observed in younger patients compared to melanomas with negative and positive SLNB. Overall survival of patients with INN showed no significant difference compared with negative SLNB (median follow-up of 5.7 years of all patients). CONCLUSIONS: As there seems to be no difference in overall survival between patients with INN and negative SLNB, the diagnosis of INN seems to be reliable. Current practice to treat patients with INN as patients with negative SLNB appears to be appropriate.

The treatment of ocular hypotony after trabeculectomy with a scleral lens: A case series.

PURPOSE: Ocular hypotony after trabeculectomy may be treated medically, surgically and with a tamponade. Three cases are reported in which a scleral lens was applied to treat ocular hypotony after mitomycin C (MMC) augmented trabeculectomy. METHODS: In this retrospective case series the records of three eyes of three patients who developed ocular hypotony after they had undergone trabeculectomy augmented with MMC were evaluated. The patients were between 11 and 69 years of age and the intraocular pressure (IOP) after surgery ranged between 3 and 6 mmHg. All three patients showed a negative Seidel test; one had suspected hypotonic maculopathy and one had a collapsed anterior chamber. After unsuccessful treatment with large bandage lenses all three patients were subsequently fitted with a scleral lens. The scleral lens was fitted to fully cover and compress the bleb. Scleral lenses were worn continuously with a check-up after one night of wear and subsequent check-ups when needed. One patient continued to wear the scleral lens for a further 6.5 months on a daily wear basis. RESULTS: In all three eyes the IOP was higher after wearing the scleral lens. Two patients stopped wearing the scleral lens after the IOP was stable. One patient developed a cataract; the cataract surgery was combined with a bleb revision and scleral lens wear was therefore discontinued. DISCUSSION: The scleral lens might be a useful tool in the treatment of ocular hypotony after trabeculectomy augmented MMC surgery. The effect of the scleral lens on the ocular pressure is unpredictable. Caution is advised in vulnerable corneas due to risk factors such as hypoxia and infection. Further research is warranted to establish the safety of the procedure, the patient selection and the overall success in a larger patient group.

Disproportionate Cochlear Length in Genus Homo Shows a High Phylogenetic Signal during Apes' Hearing Evolution.

Changes in lifestyles and body weight affected mammal life-history evolution but little is known about how they shaped species' sensory systems. Since auditory sensitivity impacts communication tasks and environmental acoustic awareness, it may have represented a deciding factor during mammal evolution, including apes. Here, we statistically measure the influence of phylogeny and allometry on the variation of five cochlear morphological features associated with hearing capacities across 22 living and 5 fossil catarrhine species. We find high phylogenetic signals for absolute and relative cochlear length only. Comparisons between fossil cochleae and reconstructed ape ancestral morphotypes show that Australopithecus absolute and relative cochlear lengths are explicable by phylogeny and concordant with the hypothetized ((Pan,Homo),Gorilla) and (Pan,Homo) most recent common ancestors. Conversely, deviations of the Paranthropus oval window area from these most recent common ancestors are not explicable by phylogeny and body weight alone, but suggest instead rapid evolutionary changes (directional selection) of its hearing organ. Premodern (Homo erectus) and modern human cochleae set apart from living non-human catarrhines and australopiths. They show cochlear relative lengths and oval window areas larger than expected for their body mass, two features corresponding to increased low-frequency sensitivity more recent than 2 million years ago. The uniqueness of the "hypertrophied" cochlea in the genus Homo (as opposed to the australopiths) and the significantly high phylogenetic signal of this organ among apes indicate its usefulness to identify homologies and monophyletic groups in the hominid fossil record.

Plasma-derived human C1-esterase inhibitor does not prevent mechanical ventilation-induced pulmonary complement activation in a rat model of Streptococcus pneumoniae pneumonia.

Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury.

The influence of water/air cooling on collateral tissue damage using a diode laser with an innovative pulse design (micropulsed mode)-an in vitro study.

Since the diode laser is a good compromise for the daily use in dental offices, finding usage in numerous dental indications (e.g., surgery, periodontics, and endodontics), the minimization of the collateral damage in laser surgery is important to improve the therapeutical outcome. The aim of this study was to investigate the effect of water/air cooling on the collateral thermal soft tissue damage of 980-nm diode laser incisions. A total of 36 mechanically executed laser cuts in pork liver were made with a 980-nm diode laser in micropulsed mode with three different settings of water/air cooling and examined by histological assessment to determine the area and size of carbonization, necrosis, and reversible tissue damage as well as incision depth and width. In our study, clearly the incision depth increased significantly under water/air cooling (270.9 versus 502.3 µm-test group 3) without significant changes of incision width. In test group 2, the total area of damage was significantly smaller than in the control group (in this group, the incision depth increases by 65 %). In test group 3, the total area of damage was significantly higher (incision depth increased by 85 %), but the bigger part of it represented a reversible tissue alteration leaving the amount of irreversible damage almost the same as in the control group. This first pilot study clearly shows that water/air cooling in vitro has an effect on collateral tissue damage. Further studies will have to verify, if the reduced collateral damage we have proved in this study can lead to accelerated wound healing. Reduction of collateral thermal damage after diode laser incisions is clinically relevant for promoted wound healing.

Reduction of collateral thermal impact of diode laser irradiation on soft tissue due to modified application parameters.

The aim of this study was to investigate the effect of different working modes (pulsed and micropulsed) and power settings of a standardized 980-nm diode laser on collateral thermal soft-tissue damage. A total of 108 bovine liver samples were cut with a diode laser at various settings in pulsed and micropulsed mode and histologically assessed to determine the area and depth of carbonization, necrosis and reversible tissue damage, as well as incision depth and width. Incision depth and width and the area and depth of carbonization, necrosis and reversible damage were correlated strongly with cutting speed. The area and depth of reversible damage were correlated with average power. The micropulsed mode produced a smaller zone of carbonization and necrosis and a smaller incision width. Setting the laser parameters in accordance with the absorption characteristics of the tissue reduced collateral thermal tissue damage while maintaining an acceptable cutting ability. Reducing collateral thermal damage from diode laser incisions is clinically relevant for promoting wound healing.

Surgical and prosthetic reconsiderations in patients with maxillectomy.

The purpose of this study was to establish and evaluate new possibilities for rehabilitation of patients with obturator prosthesis who had undergone partial or total maxillectomy because of tumour ablation surgery. Eleven patients with maxillary defects were reconstructed with a computer-aided design/computer-aided manufacturing designed prosthesis. Missing retention was gained by inserting implants in the remaining bone, so that an expansion of the surgical defect to gain further retention could be avoided. All patients were treated successfully according to the previously described treatment plan. The Obturator Functioning Scale (OFS) of the Memorial Sloan-Kettering Cancer Centre was applied to evaluate the functional quality of the obturator prosthesis and patient's satisfaction. It showed good results in all fields of functional outcome and social acceptance.

The impact of an erbium, chromium:yttrium-scandium-gallium-garnet laser with radial-firing tips on endodontic treatment.

Radial-firing tips should allow a more homogeneous laser irradiation of root canal walls. The aim of the study was to assess the effects of erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser irradiation in conjunction with those newly designed tips. The investigation comprised bacteriology, morphological evaluations and temperature measurements. Root canals were inoculated with two test strains and laser irradiated with power settings of 0.6 W and 0.9 W and a repetition rate of 20 Hz. Subsequently, the samples were subjected to microbiological evaluation. The morphological changes of the canal walls were assessed by scanning electron microscopy. To reveal possible thermal side effects, we carried out temperature measurements. The bacteriological evaluation revealed a decisive disinfectant effect. Scanning electron microscopy showed the homogeneous removal of smear layer from the root canal walls. The temperature rise at the root surface during the irradiation was moderate, yielding 1.3 degrees C for the 0.6 W setting and 1.6 degrees C for the 0.9 W setting. The investigations indicated that the Er,Cr:YSGG laser, in conjunction with radial-firing tips, is a suitable tool for the elimination of bacteria in root canals and for the removal of smear layer.

CYP3A5 genotype is associated with longer patient survival after kidney transplantation and long-term treatment with cyclosporine.

The CYP3A5*1 allele has been linked to high expression of CYP3A5 and metabolism of cyclosporine. We evaluated the role of CYP3A5*1 for long-term survival in renal transplant patients in a cohort of 399 patients who underwent cadaveric or living donor kidney allograft transplantation. All patients were treated with a similar cyclosporine-based immunosuppressive maintenance therapy protocol. The mean duration of follow-up was 8.6+/-3.7 years. In univariate survival analysis, the presence of the CYP3A5*1 allele in recipients significantly increased patient survival P=0.028 (log-rank), resulting in a hazard ratio (HR) of 0.52 (95% CI=0.29-0.94). When the presence of the CYP3A5*1 allele was included in multivariate Cox regression analyses accounting for major risk factors for patient death, CYP3A5*1 still conferred a protective effect. Further, haplotype analysis at the CYP3A5 locus confirmed that CYP3A5*1 might indeed be responsible for this survival benefit.

Neutron radiography and other NDE tests of main rotor helicopter blades.

A few nondestructive examination (NDE) techniques are extensively being used worldwide to investigate aircraft structures for all types of defects. The detection of corrosion and delaminations, which are believed to be the major initiators of defects leading to aircraft structural failures, are addressed by various NDE techniques. In a combined investigation by means of visual inspection, X-ray radiography and shearography on helicopter main rotor blades, neutron radiography (NRad) at SAFARI-1 research reactor operated by Necsa, was performed to introduce this form of NDE testing to the South African aviation industry to be evaluated for applicability. The results of the shearography, visual inspection and NRad techniques are compared in this paper. The main features and advantages of neutron radiography, within the framework of these investigations, will be highlighted.

The drying process of concrete: a neutron radiography study.

The natural drying process of concrete, which has a significant effect on its characteristics, for example durability, was studied at the neutron radiography facility at SAFARI-1 nuclear research reactor, operated by Necsa. Monitoring of the movement of the water in concrete samples, which were wet cured for one day and covered on all the sides but one, was done by means of a CCD camera system. In this paper the methodology in observing the drying process will be described together with results obtained from this investigation. The measured water content and porosity results were quantified and compared reasonably well with conventional gravimetrical measurements.

Apolipoprotein E and familial dysbetalipoproteinemia: clinical, biochemical, and genetic aspects.

In humans, apolipoprotein E (apoE) is a polymorphic protein of which three common isoforms can be distinguished, designated apoE2, apoE3, and apoE4. This genetic variation is associated with different plasma lipoprotein levels, different response to diet and lipid-lowering therapy, and a variable risk for cardiovascular disease and Alzheimer's disease. An example of an apoE-mediated, autosomal recessive, lipid disorder is familial dysbetalipoproteinemia (FD), caused by mutations in the apolipoprotein E gene. Homozygosity for APOE*2 (1 in 170 persons) causes FD or type III hyperlipoproteinemia in less than 20% of the adult APOE*2 homozygotes. Less common, dominant negative mutations may also cause the disorder. The patients may present with typical skin lesions and elevated plasma levels of cholesterol and triglycerides, mainly in very-low-density lipoprotein remnants and intermediate-density lipoproteins. The disorder is associated with peripheral and coronary artery disease. Additional gene and environmental factors are necessary for the expression of this hyperlipoproteinemia. Hyperinsulinemia and defects in genes involved in the hydrolysis of triglycerides are associated with this lipid disorder. Diet and weight reduction are effective but usually not sufficient to normalize the lipid levels. Additional therapy with statins or fibrates is necessary and effective in most patients.

Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies.

BACKGROUND: While chromosomal abnormalities are often the cause of missed abortions, other defects could be involved, which might be screened for by transcervical embryoscopy. METHODS: A total of 272 patients with missed abortion underwent transcervical embryoscopy prior to dilatation and curettage, together with cytogenetic analysis of chorionic villi, using either standard G-banding cytogenetic techniques or comparative genomic hybridization in combination with flow cytometry analysis. RESULTS: Visualization of the embryo or early fetus (12 cases) was successful in 233 patients, and karyotyping in 221. Among 233 examined cases, 33 had normal external features, 71 were classified as growth-disorganized and 129 had either isolated or multiple defects, including holoprosencephaly, anencephaly, encephalocele, spina bifida, microcephaly, facial dysplasia, limb reduction defect, cleft hand, syndactyly, pseudosyndactly, polydactyly, various forms of cleft lip and an amniotic adhesion. Of the 165 cases with an abnormal karyotype, there were 46 grossly disorganized embryos, 98 multiple defects, six single defects and 15 morphologically normal cases. Of the 56 cases with a normal karyotype, there were 20 grossly disorganized embryos, 16 multiple defects, four single defects and 16 morphologically normal cases. CONCLUSIONS: A total of 75% of the cases with missed abortion had an abnormal karyotype, 18% had a morphological defect with a normal karyotype, while no embryonic or chromosomal abnormality could be diagnosed in 7% of the cases. Correlation of morphological and cytogenetic findings in spontaneous abortion specimens could provide valuable information for genetic counselling and prenatal care in future pregnancies in couples with a history of repeated pregnancy loss.

Long term efficacy and safety of atorvastatin in the treatment of severe type III and combined dyslipidaemia.

BACKGROUND: Fibric acid derivatives and HMG-CoA reductase inhibitors are effective in combination for treating patients with familial dysbetalipoproteinaemia and severe combined dyslipidaemia, but combination therapy affects compliance and increases the risk of side effects. AIM: To evaluate the efficacy and safety of monotherapy with atorvastatin, an HMG-CoA reductase inhibitor with superior efficacy in lowering low density lipoprotein cholesterol and triglyceride concentrations, in patients with dysbetalipoproteinaemia and severe combined dyslipidaemia. METHODS: Atorvastatin was tested as single drug treatment in 36 patients with familial dysbetalipoproteinaemia and 23 patients with severe combined dyslipidaemia. RESULTS: After 40 weeks of 40 mg atorvastatin treatment decreases in total cholesterol, triglycerides, and apolipoprotein B of 40%, 43%, and 41%, respectively, were observed in the combined dyslipidaemia group, and of 46%, 40%, and 43% in the dysbetalipoproteinaemic patients. Target concentrations of total cholesterol (< 5 mmol/l) were reached by 63% of the patients, and target concentrations of triglycerides (< 3.0 mmol/l) by 66%. Treatment with atorvastatin was well tolerated and no serious side effects were reported. CONCLUSIONS: Atorvastatin is very effective as monotherapy in the treatment of familial dysbetalipoproteinaemia and severe combined dyslipidaemia.