Impact of Unilateral Alveolar Bone Grafting on Nasal Volume and Nasolabial Surface: A 3D Analysis.

OBJECTIVE: To determine possible effects of unilateral alveolar cleft closure on internal nasal volume and external nasolabial surface. DESIGN: Retrospective, single-arm, cohort study. SETTING: Institutional, tertiary care. PATIENTS: Patients with complete unilateral cleft lip, alveolus, and palate (CUCLAP), who underwent closure of the alveolar cleft with autologous bone graft (ABG) at the age of 9-11 years, with cone beam computed tomography (CBCT) and/or three-dimensional (3D) stereophotogrammetry images taken before and one year after the ABG procedure. INTERVENTIONS: ABG-pocedure in patients with CUCLAP. MAIN OUTCOME MEASURES: The influence of ABG on the internal and external nasal morphology. RESULTS: A total of 28 patients (21M/7F, 14R/14L) were divided into internal (CBCT) and external (3D-stereophotogrammetry) measurement subgroups. The external nasolabial surface showed a significant decrease of the angle alar curvature right-subnasale-alar curvature left (-1.99°; P = .02; 95% CI -2.61, -0.36) and an increase of the linear measurement between these points (+1.01 mm; P = .03; 95% CI: 0.11, 1.91). No significant differences were found when comparing the distance maps of the affected side with the non-affected side (P = .50, 95% CI: -0.20, 0.29). CONCLUSIONS: Closure of the alveolar cleft in CUCLAP patients with ABG did not affect the internal nasal volume, but significantly affected the external nasal surface. The procedure resulted in the nose becoming wider because both alar curvatures moved caudally and laterally relative to the subnasale.

Effects of ileocolonic delivered vitamin B2, B3 and C (ColoVit) or the Groningen anti-inflammatory diet on disease course and microbiome of patients with Crohn's disease (VITA-GrAID study): a protocol for a randomised and partially blinded trial.

BACKGROUND: Diet plays a pivotal role in the onset and progression of Crohn's disease (CD). Nutritional interventions revealed effects on intestinal inflammation and gut microbial composition. However, data from well-designed and controlled dietary trials are lacking. Therefore, evidence-based dietary recommendations are still unavailable to patients and physicians. Here, we aim to investigate the effects of an evidence-based anti-inflammatory diet, and an ileocolonic-targeted capsule containing vitamin B2, B3 and C (ColoVit) on patients with CD and their healthy household members. METHODS AND ANALYSIS: In this multicentre, randomised, placebo-controlled, partially blinded nutritional intervention trial, we aim to recruit 255 CD patients with Harvey-Bradshaw Index <8 and a faecal calprotectin (FCal) cut-off of ≥100 µg/g at baseline. Participants will be randomised into two experimental intervention groups and one placebo group. In the experimental groups, participants will either adhere to the Groningen anti-inflammatory diet (GrAID) or ingest an ileocolonic-delivered oral vitamin B2/B3/C capsule (ColoVit). The study consists of a 12-week controlled interventional phase, which proceeds to a 9-month observational follow-up phase in which patients allocated to the GrAID group will be requested to continue the intervention on their own accord. Household members of participating patients will be asked to participate in the trial as healthy subjects and are allocated to the same group as their peer. The primary study outcome for patients is the change in FCal level from baseline. The primary outcome for household members is the change in gut microbial composition, which is set as secondary outcome for patients. ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board of the Stichting Beoordeling Ethiek Biomedisch Onderzoek in Assen, the Netherlands. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT04913467.

The effect of Bruton's tyrosine kinase inhibitor ibrutinib on atherothrombus formation under stenotic flow conditions.

BACKGROUND: Bruton's kinase (Btk) is critical for collagen-triggered platelet signal transduction. The Btk inhibitor ibrutinib has been shown to selectively block platelet adhesion to atherosclerotic plaque material under laminar arterial flow. However, this has not been studied under a shear gradient, which is characteristic for atherothrombosis. OBJECTIVE: To determine the effect of ibrutinib treatment on in vitro thrombus formation on collagen and atherosclerotic plaque material in the absence or presence of a shear gradient. METHODS: Blood was obtained from patients with chronic lymphocytic leukemia, mantle-cell lymphoma and Waldenström macroglobulinemia with and without ibrutinib treatment and perfused through a microfluidic channel with(out) 60% stenosis over Horm type I collagen or human atherosclerotic plaque homogenate. RESULTS: At a constant shear rate of 1500 s-1, platelet deposition was significantly decreased in blood from haematological malignancy patients treated with ibrutinib as compared to untreated patients, on atherosclerotic plaque material but not on collagen. However, thrombus size, stability, and height, were reduced on both plaque material and collagen. An increase in shear rate up to 3900 s-1, as induced by 60% stenosis, resulted in decreased platelet deposition and thrombus parameters on plaque material but not on collagen when compared to a laminar shear of 1500 s-1. Ibrutinib treatment decreased platelet deposition and thrombus parameters even further around the stenosis. CONCLUSION: Treatment of patients with haematological disorders with the Btk inhibitor ibrutinib reduces in vitro platelet deposition, thrombus size and contraction on human atherosclerotic plaque around a stenosis when compared to patients not receiving ibrutinib.

Oxidative Stress Predicts Post-Surgery Complications in Gastrointestinal Cancer Patients.

INTRODUCTION: An excessive perioperative inflammatory reaction can lead to more postoperative complications in patients treated for gastrointestinal cancers. It has been suggested that this inflammatory reaction leads to oxidative stress. The most important nonenzymatic antioxidants are serum free thiols. The purpose of this study was to evaluate whether high preoperative serum free thiol levels are associated with short-term clinical outcomes. METHODS: Blood samples were drawn before, at the end of, and 1 and 2 days after surgery of a consecutive series of patients with gastrointestinal cancer. Serum free thiols were detected using a colorimetric detection method using Ellman's reagent. Short-term clinical outcomes were defined as 30-day complications (Clavien-Dindo ≥2) and length of hospital stay. Logistic regression was applied to examine the association between serum free thiol levels and short-term patient outcomes. RESULTS: Eighty-one patients surgically treated for gastrointestinal cancer were included in the study. Median age was 68 (range 26-87) years, and 28% were female. Patients in the lowest tertile of preoperative serum free thiols had a threefold higher risk to develop postoperative complications (odds ratio [OR]: 3.4; 95% confidence interval [CI]:1.1-10.7) and a fourfold higher risk to have an increased length of stay in the hospital (OR 4.0; 95% CI 1.3-12.9) compared with patients in the highest tertile. CONCLUSIONS: Patients with lower preoperative serum free thiol levels, indicating a decrease in extracellular antioxidant capacity and therefore an increase in systemic oxidative stress, are more likely to develop postoperative complications and show a longer in hospital stay than patients with higher serum free thiol levels.

Listing criteria for heart transplantation in the Netherlands.

The updated listing criteria for heart transplantation are presented on behalf of the three heart transplant centres in the Netherlands. Given the shortage of donor hearts, selection of those patients who may expect to have the greatest benefit from a scarce societal resource in terms of life expectancy and quality of life is inevitable. The indication for heart transplantation includes end-stage heart disease not remediable by more conservative measures, accompanied by severe physical limitation while on optimal medical therapy, including ICD/CRT­D. Assessment of this condition requires cardiopulmonary stress testing, prognostic stratification and invasive haemodynamic measurements. Timely referral to a tertiary centre is essential for an optimal outcome. Chronic mechanical circulatory support is being used more and more as an alternative to heart transplantation and to bridge the progressively longer waiting time for heart transplantation and, thus, has become an important treatment option for patients with advanced heart failure.

Nasolabial shape and aesthetics in unilateral cleft lip and palate: an analysis of nasolabial shape using a mean 3D facial template.

The aim of this study was to determine the amount of deviation in nasolabial shape in patients with a cleft compared with an average non-cleft face, and to assess whether this difference is related to nasolabial aesthetics. Three-dimensional stereophotogrammetric images of 60 patients with a unilateral cleft were used. To quantify shape differences, four average non-cleft faces were constructed from stereophotogrammetric images of 141 girls and 60 boys. Three-dimensional shape differences were calculated between superimposed cleft faces and the average non-cleft face for the same sex and age group. Nasolabial aesthetics were rated with the modified Asher-McDade Aesthetic Index using a visual analogue scale (VAS). Mean VAS scores ranged from 51.44 to 60.21 for clefts, with lower aesthetic ratings associated with increasing cleft severity. Shape differences were found between cleft faces and the average non-cleft face. No relationship was found for the VAS, age, and sex, except that a lower VAS was related to a higher nose and lip distance between the superimposed cleft and average non-cleft faces for nasal profile (P= 0.02), but the explained variance was low (R2=0.066). In conclusion, except for nasal profile, nasolabial aesthetics were not influenced by the extent of shape differences from the average non-cleft face.

Vascular protective effect of aspirin and rivaroxaban upon endothelial denudation of the mouse carotid artery.

While in recent trials the dual pathway inhibition with aspirin plus rivaroxaban has shown to be efficacious in patients with atherosclerotic cardiovascular disease, little is known about the effects of this combination treatment on thrombus formation and vascular remodelling upon vascular damage. The aim of this study was to examine the effects of aspirin and/or rivaroxaban on injury-induced murine arterial thrombus formation in vivo and in vitro, vessel-wall remodelling, and platelet-leukocyte aggregates. Temporary ligation of the carotid artery of C57BL/6 mice, fed a western type diet, led to endothelial denudation and sub-occlusive thrombus formation. At the site of ligation, the vessel wall stiffened and the intima-media thickened. Aspirin treatment antagonized vascular stiffening and rivaroxaban treatment led to a positive trend towards reduced stiffening. Local intima-media thickening was antagonized by both aspirin or rivaroxaban treatment. Platelet-leukocyte aggregates and the number of platelets per leukocyte were reduced in aspirin and/or rivaroxaban treatment groups. Furthermore, rivaroxaban restricted thrombus growth and height in vitro. In sum, this study shows vascular protective effects of aspirin and rivaroxaban, upon vascular injury of the mouse artery.

The role of long-term mechanical circulatory support in patients with advanced heart failure.

In patients with end-stage heart failure, advanced therapies such as heart transplantation and long-term mechanical circulatory support (MCS) with a left ventricular assist device (LVAD) have to be considered. LVADs can be implanted as a bridge to transplantation or as an alternative to heart transplantation: destination therapy. In the Netherlands, long-term LVAD therapy is gaining importance as a result of increased prevalence of heart failure together with a low number of heart transplantations due to shortage of donor hearts. As a result, the difference between bridge to transplantation and destination therapy is becoming more artificial since, at present, most patients initially implanted as bridge to transplantation end up receiving extended LVAD therapy. Following LVAD implantation, survival after 1, 2 and 3 years is 83%, 76% and 70%, respectively. Quality of life improves substantially despite important adverse events such as device-related infection, stroke, major bleeding and right heart failure. Early referral of potential candidates for long-term MCS is of utmost importance and positively influences outcome. In this review, an overview of the indications, contraindications, patient selection, clinical outcome and optimal time of referral for long-term MCS is given.

The risk of revision after total hip arthroplasty in young patients depends on surgical approach, femoral head size and bearing type; an analysis of 19,682 operations in the Dutch arthroplasty register.

BACKGROUND: Total hip arthroplasty (THA) is used increasingly in younger patients. There is little knowledge about the effect of THA characteristics on risk of revision, especially in young patients. Therefore, we studied the influence of both patient-related and surgical factors on the risk of revision using data from the Dutch Arthroplasty Registry (LROI). METHODS: All patients younger than 55 years with a primary THA implanted in the Netherlands between 2007 and 2017 were selected (n = 19,682). The covariates age, sex, primary diagnosis, ASA-classification, surgical approach, fixation method, bearing type, head size and year of surgery were entered into Cox proportional hazards models to calculate hazard ratios for the risk of revision. RESULTS: The overall 5-year survival of primary THA was 95.3% (95% CI, 94.9-95.6). Use of the anterior approach resulted in a lower risk of revision than the use of the posterolateral approach (HR: 0.66, 95% CI: 0.47-0.92). THAs with a head diameter ≥ 38 mm had a higher risk of revision (HR: 1.90, 95% CI: 1.33-2.72) than THAs with 32 mm heads. Use of MoM bearings resulted in an increased risk when compared to C-PE (HR: 1.76, 95% CI: 1.27-2.43). CONCLUSION: The risk of revision in patients younger than 55 years depends on surgical approach, head size and bearing type. The anterior approach resulted in a decreased risk of revision, whereas use of ≥38 mm heads and MoM bearings resulted in an increased risk of revision for any reason.

A Sensory Update to the Chaîne Opératoire in Order to Study Skill: Perceptive Categories for Copper-Compositions in Archaeometallurgy.

This paper introduces the methodology of perceptive categories through which an empirical analysis of skill is achievable, taking European Bronze Age metalworking as a case study. Based on scientific data provided by the material sciences, in this case compositional and metallographic analyses of Late Copper Age and Early Bronze Age axes, the thresholds to categorise and interpret these data, and organise them in a chaîne opératoire, are centred on the human senses-and thus on metalworking as a craft. This is a pragmatic approach that appreciates scientific measurements of metal objects as essential empirical evidence whilst recognising that a considerable share of these archaeometric data are inapt or too detailed for an understanding of skill. This empirical approach towards skill is relevant to our knowledge of the role of crafts and materials in the past. After all, skill is a fundamental asset for the production of material culture, and a distinct human-material relationship characterised by an intimate form of material engagement.

Acquired platelet antagonism: off-target antiplatelet effects of malignancy treatment with tyrosine kinase inhibitors.

Platelets can contribute to tumor progression and metastasis. Cancer patients are at increased risk of thrombosis, and advanced stages of cancer are associated with thrombocytosis or increased platelet reactivity. Tyrosine kinase inhibitors (TKIs) are widely used as a targeted strategy for cancer treatment, with the aim of prolonging progression-free survival of the patients. Because of their broad kinase target spectrum, most TKIs inevitably have off-target effects. Platelets rely on tyrosine kinase activity for their activation. Frequently observed side effects are lowering of platelet count and inhibition of platelet functions, whether or not accompanied by an increased bleeding risk. In this review, we aim to give insights into: (i) 38 TKIs that are currently used for the treatment of different types of cancer, either on the market or in clinical trials; (ii) how distinct TKIs can inhibit activation mechanisms in platelets; and (iii) the clinical consequences of the antiplatelet effects of TKI treatment. For several TKIs, the knowledge on affinity for their targets does not align with the published effects on platelets and reported bleeding events. This review should raise awareness of the potential antiplatelet effects of several TKIs, which will be enhanced in the presence of antithrombotic drugs.

Disturbances of dental development distinguish patients with oligodontia-ectodermal dysplasia from isolated oligodontia.

OBJECTIVE: To investigate phenotypic differences in dental development between isolated oligodontia and oligodontia-ectodermal dysplasia (ED). SETTING AND SAMPLE POPULATION: A total of 129 patients diagnosed with isolated oligodontia and 22 patients with oligodontia as part of ED were eligible. METHODS: The phenotype of dental development was assessed for the frequency of missing a certain tooth, dental age, development of each tooth present, abnormal size and abnormal shape of teeth. The data were analysed building linear, ordinal and logistic regression models. RESULTS: Compared to patients with isolated oligodontia, patients with oligodontia-ED missed more frequently central incisors and second molars in both jaws, and lateral incisors in the mandible (P < .05). Oligodontia-ED was associated with delayed development of the permanent dentition (ß = -0.10; 95% CI: -0.17, -0.03). Specifically, the maxillary teeth: right central incisor, right lateral incisor, right second premolar and left second premolar were delayed approximately from 2 to 4 developmental stages. In addition, the left mandibular second premolar was 3 developmental stages delayed. Abnormal shape of teeth was 7 times more evident in patients with oligodontia-ED compared to patients with isolated oligodontia (OR = 6.54; 95% CI: 2.34, 18.28). The abnormal size of teeth was not a distinctive characteristic for oligodontia-ED. CONCLUSIONS: Oligodontia-ED distinguishes from isolated oligodontia by more disturbances in dental development. The abnormal shape of incisors and canines in a patient with oligodontia can raise suspicions for accompanying ectodermal abnormalities.

Dentition Patterns in Different Unilateral Cleft Lip Subphenotypes.

Oral clefts play an essential role in disturbed odontogenesis of the deciduous and permanent dentition, yet little is known about this relationship. We investigated, within the categories cleft lip with or without alveolus (CL ± A) and cleft lip, alveolus and palate (CLAP), whether different CL subphenotypes based on morphological severity of the cleft show different dentition patterns and whether a more detailed subdivision of the incomplete CL has clinical relevance. In this retrospective study, 345 children with nonsyndromic unilateral CL ± A and CLAP from the Dutch Association for Cleft Palate and Craniofacial Anomalies (NVSCA) registry were included to assess the association between the CL subphenotypes and lateral incisor patterns. Five different deciduous and permanent patterns of the lateral incisor were distinguished: located in normal position (pattern z/Z), in the anterior segment (pattern x/X) or in the posterior segment of the cleft (pattern y/Y), one in each segment of the cleft (pattern xy/XY), and agenesis of the lateral incisor (pattern ab/AB). Analyses were performed by using multinomial logistic regression models. Children born with a vermillion notch or a one-third to two-thirds CL were most likely to have a deciduous pattern x and a permanent pattern X, while children born with a two-thirds to subtotal CL were most likely to have deciduous pattern xy and a permanent pattern X compared to children with a complete CL that predominantly had deciduous pattern y and a permanent pattern AB. Based on the relationship of the CL morphology with the deciduous dentition, subdivision of the CL morphology into vermillion notch to two-thirds CL, two-thirds to subtotal CL, and complete CL appears to be an optimal subdivision. Our results indicate that a more detailed subdivision of the CL has clinical relevance and that critical factors in the pathogenesis of the CL are also critical for the odontogenesis.

Undernutrition in nursing home rehabilitation patients.

OBJECTIVE: To examine the prevalence of undernutrition, received dietetic treatment and self-perception of nutritional status in older patients admitted to Dutch nursing home rehabilitation wards. METHODS: Between December 2012-February 2014, we included 190 patients (≥65 y) admitted to seven nursing home rehabilitation wards. Nutritional status in the first week of admission was characterized as: severely undernourished (>10% unintentional weight loss in the past six months and/or >5% unintentional weight loss in the past month and/or BMI < 20 kg/m2), moderately undernourished (5-10% unintentional weight loss in the past 6 months and/or BMI 20-22 kg/m2), well-nourished (<5% unintentional weight loss in the past 6 months and BMI 22-28 kg/m2) and overweight (BMI>28 kg/m2). Primary diagnosis was categorized as: trauma, elective orthopaedics, stroke and other. Perceived nutritional status was determined with the question: 'Do you currently consider yourself undernourished?' (yes/no). Information regarding dietetic treatment was obtained from medical records. RESULTS: A complete dataset was obtained from 179 patients (70% female, age 81 ± 8 y). 26% of the patients was found to be severely undernourished and 14% moderately undernourished. Prevalence of undernutrition did not differ by sex or age. Of all undernourished patients, 56% had been treated by a dietitian. Only one out of five of undernourished patients considered themselves undernourished. Elective orthopaedics patients had the lowest prevalence of undernutrition (19%) while patients categorised as 'other' had the highest prevalence (51%). CONCLUSION: More than one in three older patients in Dutch nursing home rehabilitation wards are moderately to severely undernourished. Out of these patients the majority does not consider themselves undernourished and almost half has not received dietetic treatment. More attention to undernutrition in nursing home rehabilitation patients seems necessary.

Level of agreement between cardiac output measurements using Nexfin® and thermodilution in morbidly obese patients undergoing laparoscopic surgery.

Morbidly obese patients are at increased risk of intra-operative haemodynamic instability, which may necessitate intensive monitoring. Non-invasive monitoring is increasingly used to measure cardiac output; however, it is unknown whether the weight-based algorithm utilised in these devices is applicable to patients with morbid obesity. We compared the level of agreement and trending ability of non-invasive cardiac output measurements (Nexfin® ) with the gold-standard thermodilution technique in 30 morbidly obese patients undergoing laparoscopic surgery. Bland-Altman analysis revealed a mean (SD) bias of 0.60 (1.62) l.min-1 (limits of agreement -2.67 to 3.86 l.min-1 ) and the precision error was 46%. Polar plot analysis resulted in an angular bias of 2.61°, radial limits of agreement of -60.08° to 49.82° and angular concordance rate was 77%. Both agreement and trending were outside the Critchley criteria for the comparison of cardiac output devices with a gold-standard. Nexfin has an unacceptable level of agreement compared with thermodilution for cardiac output measurement in morbidly obese patients.

[Combined orthodontic and restorative treatment]. / De gecombineerde orthodontisch restauratieve behandeling.

In patients with agenesis or enamel anomalies in anterior teeth combined orthodontic and restorative treatment is often necessary to achieve an optimal aesthetic result. How both can best be achieved, but also how to maintain the result, requires communication between the dentist and the orthodontist. The orthodontic treatment plan needs to be established in cooperation with the dentist who will carry out the restorative treatment while the patient is at a young age. Since with these young patients, who are still growing craniofacially and whose teeth are still developing, possible future restorative and/or orthodontic treatment, as well as the means of orthodontic retention, need to be included in the treatment plan. In cleft palate patients, it is also important that methods of orthodontic retention of maxillary arch width are given timely attention in the restorative treatment plan because it is especially vulnerable to relapse.