Automatic oxygen titration versus constant oxygen flow rates during walking in COPD: a randomised controlled, double-blind, crossover trial.

RATIONALE: In patients with COPD, oxygen (O2)-supplementation via a constant flow oxygen system (CFOS) can result in insufficient oxygen saturation (SpO2 <90%) during exercise. An automatically titrating O2-system (ATOS) has been shown to be beneficial compared with an untitrated CFOS, however, it is unknown if ATOS is superior to CFOS, titrated during exercise as stipulated by guidelines. The aim was to investigate the effects of ATOS compared with titrated CFOS on walking capacity in people with hypoxaemic COPD. METHODS: Fifty participants completed this prospective randomised controlled, double-blind, crossover trial. Participants performed two endurance shuttle walk tests (ESWTs) with: (1) exercise titrated CFOS (ESWTCFOS) and (2) ATOS targeting an SpO2 of 92% (ESWTATOS). Primary outcome measure was walking time. Secondary measures were SpO2, transcutaneous-PCO2 (TcPCO2), respiratory rate (RR), heart rate (HR) at isotime (end of shortest ESWT) with blood gases and dyspnoea at rest and end exercise. RESULTS: Participants (median (IQR): age 66 (59, 70) years, FEV1 28.8 (24.8, 35.1) % predicted, PO2 54.7 (51.0, 57.7) mm Hg, PCO2 44.2 (38.2, 47.8) mm Hg) walked significantly longer with ESWTATOS in comparison to ESWTCFOS (median effect (95% CI) +144.5 (54 to 241.5) s, p<0.001). At isotime, SpO2 was significantly higher (+3 (95% CI 1 to 4) %, p<0.001) with ATOS while TcPCO2, RR and HR were comparable. End exercise, PO2 (+8.85 (95% CI 6.35 to 11.9) mm Hg) and dyspnoea (-0.5 (95% CI -1.0 to -0.5) points) differed significantly in favour of ATOS (each p<0.001) while PCO2 was comparable. CONCLUSION: In patients with hypoxaemia with severe COPD the use of ATOS leads to significant, clinically relevant improvements in walking endurance time, SpO2, PO2 and dyspnoea with no impact on PCO2. TRIAL REGISTRATION NUMBER: NCT03803384.

In 'real world' patients with COPD, exacerbation history, and not blood eosinophils, is the most reliable predictor of future exacerbations.

INTRODUCTION: There is an interest in the role of blood eosinophils for predicting inhaled corticosteroid (ICS) response in chronic obstructive pulmonary disease (COPD). Most data are from interventional clinical studies; data from unselected real-world populations may help better inform treatment decisions. DACCORD is a non-interventional real-world study. Cohort 3 recruited patients with COPD who had received triple therapy for ≥ 6 months; prior to entry patients either continued triple therapy, or switched to a long-acting muscarinic antagonist/long-acting beta2-agonist (LABA/LAMA), and were followed for 12 months. METHODS: For these post-hoc analyses, patients were divided into four groups based on exacerbation history and baseline blood eosinophil count (< 100 vs. > 300 cells/µL). Exacerbation rates were calculated overall and for the two treatments. RESULTS: Among the 430 patients in the current analyses, the largest groups had low exacerbation history with high (44.2%) or low eosinophils (36.7%). Most patients did not exacerbate during follow-up (68.8% overall; 83.2% and 63.7% with LABA/LAMA and triple therapy). The highest exacerbation rates were in groups with high exacerbation history, differing significantly in the overall analyses from those with low exacerbation history (matched by eosinophil count); rates did not differ when grouped by eosinophil count (matched by exacerbation history). CONCLUSIONS: Although most patients in these analyses did not exacerbate during follow-up, whereas exacerbation history is a predictor of future exacerbations, blood eosinophil count is not. This suggests that although eosinophil count may help to guide ICS initiation, this is less of a consideration when 'stepping-down' from triple therapy to a LABA/LAMA.

Dietary digestible carbohydrates are associated with higher prevalence of asthma in humans and with aggravated lung allergic inflammation in mice.

BACKGROUND: Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models. METHODS: Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates. RESULTS: We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH 2-TH 17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity. CONCLUSION: High consumption of digestible carbohydrates is associated with an increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related mechanisms.

Allergic disease trajectories up to adolescence: Characteristics, early-life, and genetic determinants.

BACKGROUND: Allergic diseases often develop jointly during early childhood but differ in timing of onset, remission, and progression. Their disease course over time is often difficult to predict and determinants are not well understood. OBJECTIVES: We aimed to identify trajectories of allergic diseases up to adolescence and to investigate their association with early-life and genetic determinants and clinical characteristics. METHODS: Longitudinal k-means clustering was used to derive trajectories of allergic diseases (asthma, atopic dermatitis, and rhinitis) in two German birth cohorts (GINIplus/LISA). Associations with early-life determinants, polygenic risk scores, food and aeroallergen sensitization, and lung function were estimated by multinomial models. The results were replicated in the independent Swedish BAMSE cohort. RESULTS: Seven allergic disease trajectories were identified: "Intermittently allergic," "rhinitis," "early-resolving dermatitis," "mid-persisting dermatitis," "multimorbid," "persisting dermatitis plus rhinitis," and "early-transient asthma." Family history of allergies was more prevalent in all allergic disease trajectories compared the non-allergic controls with stronger effect sizes for clusters comprising more than one allergic disease (e.g., RRR = 5.0, 95% CI = [3.1-8.0] in the multimorbid versus 1.8 [1.4-2.4] in the mild intermittently allergic cluster). Specific polygenic risk scores for single allergic diseases were significantly associated with their relevant trajectories. The derived trajectories and their association with genetic effects and clinical characteristics showed similar results in BAMSE. CONCLUSION: Seven robust allergic clusters were identified and showed associations with early life and genetic factors as well as clinical characteristics.

[Diagnosis and treatment of asthma: a guideline for respiratory specialists 2023 - published by the German Respiratory Society (DGP) e. V.] / S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023.

The management of asthma has fundamentally changed during the past decades. The present guideline for the diagnosis and treatment of asthma was developed for respiratory specialists who need detailed and evidence-based information on the new diagnostic and therapeutic options in asthma. The guideline shows the new role of biomarkers, especially blood eosinophils and fractional exhaled NO (FeNO), in diagnostic algorithms of asthma. Of note, this guideline is the first worldwide to announce symptom prevention and asthma remission as the ultimate goals of asthma treatment, which can be achieved by using individually tailored, disease-modifying anti-asthmatic drugs such as inhaled steroids, allergen immunotherapy or biologics. In addition, the central role of the treatment of comorbidities is emphasized. Finally, the document addresses several challenges in asthma management, including asthma treatment during pregnancy, treatment of severe asthma or the diagnosis and treatment of work-related asthma.

Impact of switching from triple therapy to dual bronchodilation in COPD: the DACCORD 'real world' study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) guidelines recommend reserving triple therapy of inhaled corticosteroid (ICS), long-acting ß2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) for patients with exacerbations despite dual therapy. However, many patients receive triple therapy without a clear indication. For these patients, it would be useful to know whether ICS can be withdrawn. METHODS: DACCORD was a longitudinal, non-interventional 'real-world' study in three cohorts. This manuscript describes the results of Cohort 3, which recruited patients with COPD who had received triple therapy for ≥ 6 months. Prior to entry, each patient's physician decided to continue triple therapy, or switch to a LABA/LAMA; patients were then followed for 12 months, with exacerbations and COPD Assessment Test (CAT) data recorded every 3 months. The primary endpoint was the time until COPD worsening, defined as the occurrence of a moderate/severe exacerbation or clinically relevant CAT worsening. RESULTS: Of the 1192 patients recruited into the study, 967 completed the end-of-study visit and ≥ 2 of the three interim visits, 292 and 675 receiving LABA/LAMA and triple therapy, respectively. Most baseline demographics were similar between the two groups. A lower proportion of patients in the LABA/LAMA group had COPD worsening than with triple therapy (32.5% vs 55.7% at 12 months), with the time to worsening extended in the LABA/LAMA group (hazard ratio 2.004, p < 0.001). In addition, a significantly lower proportion of patients in the LABA/LAMA group exacerbated (18.5% vs 28.7%; p < 0.001), accompanied by a greater improvement from baseline in CAT total score. Overall, fewer patients in the LABA/LAMA group reported adverse events than in the triple therapy group (12.9% vs 15.1%). CONCLUSIONS: These results suggest that in a real world setting physicians are able to identify patients who can be 'stepped down' from triple therapy to LABA/LAMA. Following step down, there was no overall decline in COPD-indeed, some patients had better outcomes.

Der p 23-specific IgE response throughout childhood and its association with allergic disease: A birth cohort study.

BACKGROUND: The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross-sectional studies. We longitudinally analysed the trajectory of Der p 23-specific IgE antibody (sIgE) levels throughout childhood and youth, their early-life determinants and their clinical relevance for allergic rhinitis and asthma. METHODS: We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. RESULTS: Der p 23-sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23-sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. CONCLUSIONS: Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23-sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens.

Psychopathological symptoms as precursors of depressive symptoms in adolescence: a prospective analysis of the GINIplus and LISA birth cohort studies.

INTRODUCTION: Depressive symptoms are highly prevalent in adolescence, highlighting the need for early identification of precursors. Research into psychopathological symptoms predicting depressive psychopathology in adolescents is therefore of great relevance. Moreover, given that the prevalence of depressive symptomatology in adolescence shows marked differences between girls and boys, insight into potential sex-specific differences in precursors is important. METHODS: This study examined the relationships between emotional problems, conduct problems, hyperactivity/inattention, peer problems, and difficulties in prosocial behaviour at age 10 (Strengths and Difficulties Questionnaire), and the presence of depressive symptoms at age 15 (Depression Screener for Teenagers). Using data from 2824 participants of the GINIplus and LISA birth cohorts, the association of each SDQ subscale at age 10 years with the presence of depressive symptoms at age 15 years was analyzed using sex-specific logistic regression, adjusting for potential confounders. RESULTS: Emotional problems [odds ratio (OR) 1.99, p = 0.002 for boys and OR 1.77, p < 0.001 for girls] and peer problems (OR 2.62, p < 0.001 for boys, OR 1.91, p = 0.001 for girls) at age 10 showed an increased risk for the presence of depressive symptoms at age 15. Additionally, boys with conduct problems at age 10 were at greater risk of showing depressive symptoms in adolescence (OR 2.50, p < 0.001). DISCUSSION: Based on the identified prospective relationships in our study, it might be of particular importance to tailor prevention approaches during childhood to peer and emotional problems to reduce the risk of depressive psychopathology in adolescence. Moreover, particularly in boys, it seems important to also target conduct problems in childhood as a precursor of depressive symptoms in the adolescent period.

Prevalence of overuse of short-acting beta-2 agonists (SABA) and associated factors among patients with asthma in Germany.

BACKGROUND: Overuse of short-acting beta-2 agonists (SABA), which do not treat the underlying inflammation of asthma, is linked to poor clinical outcomes such as increased exacerbation risk. This study, as part of the SABINA program, estimated the prevalence of SABA overuse and associated variables in outpatients in Germany. METHODS: This retrospective study used anonymized electronic healthcare data from the Disease Analyzer database (IQVIA). A total of 15,640 patients aged ≥ 12 years with asthma who received ≥ 1 SABA prescription(s) between July 2017 and June 2018 in 924 general physician and 22 pneumologist (PN) practices were included. SABA overuse was defined as ≥ 3 prescribed inhalers (~ 200 puffs each) during the study period. The associations between SABA overuse and physician specialty, Global Initiative for Asthma (GINA) steps (based on asthma medications), age, sex, and inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) use were estimated using multivariable regression for patients with probable moderate (GINA step 2) and probable severe (GINA steps 3-5) asthma. RESULTS: Annually, 36% of all patients (GINA steps 1-5) in general and 38% in PN practices received ≥ 3 SABA inhalers. The risk of SABA overuse was 14% higher in patients treated by a general practitioner vs. a PN; 34% and 85% higher in GINA steps 4 and 5, respectively, vs. GINA step 3; and 40% higher in male vs. female patients. CONCLUSIONS: SABA overuse is prevalent among patients with asthma across all GINA steps in Germany, which may indicate suboptimal asthma control. Further studies are needed to investigate the reasons behind SABA overuse.

Establishment of transfusion-relevant bacteria reference strains for red blood cells.

BACKGROUND AND OBJECTIVES: Red blood cell concentrates (RBCC) are susceptible to bacterial contamination despite cold storage. A reliable evaluation of strategies to minimize the risk of RBCC-associated bacterial transmission requires the use of suitable reference bacteria. Already existing Transfusion-Relevant Bacteria Reference Strains (TRBRS) for platelet concentrates fail to grow in RBCC. Consequently, the ISBT TTID, Working Party, Bacterial Subgroup, conducted an international study on TRBRS for RBCC. MATERIALS AND METHODS: Six bacterial strains (Listeria monocytogenes PEI-A-199, Serratia liquefaciens PEI-A-184, Serratia marcescens PEI-B-P-56, Pseudomonas fluorescens PEI-B-P-77, Yersinia enterocolitica PEI-A-105, Yersinia enterocolitica PEI-A-176) were distributed to 15 laboratories worldwide for enumeration, identification, and determination of growth kinetics in RBCC at days 7, 14, 21, 28, 35 and 42 of storage after low-count spiking (10-25 CFU/RBCC). RESULTS: Bacterial proliferation in RBCC was obtained for most strains, except for S. marcescens, which grew only at 4 of 15 laboratories. S. liquefaciens, S. marcescens, P. fluorescens and the two Y. enterocolitica strains reached the stationary phase between days 14 and 21 of RBCC storage with a bacterial concentration of approximately 109  CFU/ml. L. monocytogenes displayed slower growth kinetics reaching 106 -107  CFU/ml after 42 days. CONCLUSION: The results illustrate the importance of conducting comprehensive studies to establish well-characterized reference strains, which can be a tool to assess strategies and methods used to ameliorate blood safety. The WHO Expert Committee on Biological Standardization adopted the five successful strains as official RBCC reference strains. Our study also highlights the relevance of visual inspection to interdict contaminated RBC units.

Clinical Course and Treatment Paradigms for JIA-related Uveitis and Pars Planitis Uveitis Using Precise Ocular Investigational Methods.

PURPOSE: The aim of this study was to report on the disease course and management modalities in patients with juvenile idiopathic arthritis-related uveitis (JIA uveitis) or intermediate uveitis of the pars planitis type (PP) who were followed up using precise ocular investigational techniques. METHODS: This is a retrospective single-centre study. All charts of patients seen in our centre over 15 years (2005 - 2019) with a diagnosis of JIA uveitis or PP were retrieved and analysed for clinical course, severity of inflammation, type of management, and the role played by precise investigational techniques (laser flare photometry [LFP], optical coherence tomography [OCT] and fluorescein angiography [FA]) in therapeutic decisions. RESULTS: 26 out of a total of 64 patients with sufficient data could be included in the study. Mean age was 11.2 years (SD ± 5.4). 13/26 (50%) patients presented with JIA uveitis and 13/26 (50%) with PP. PP patients had a more benign course (mean LFP values at presentation 9.9 ± 3.2 ph/ms), and at the end of follow-up, only 2/13 PP patients (15%) still needed systemic treatment. In contrast, JIA uveitis as a whole was more severe, although benign forms were present (LFP values at presentation 105.9 ± 19.5 ph/ms), and at the end of follow-up, 5/13 patients (38%) still needed systemic treatment. Complications were also more severe and frequent in JIA uveitis patients. In 6/26 patients (24%, 3 JIA and 3 PP patients), the precise monitoring methods allowed unjustified systemic treatment to be discontinued, and to avoid such a treatment, it was recommended that it should be replaced by topical treatment or observation. CONCLUSION: Nowadays, new investigational techniques have made precise follow-up of uveitis possible. We determined the precise inflammatory pattern of JIA uveitis and PP, which is crucial information to determine the therapeutic intervention. As these two entities are common in young and paediatric patients, such precise monitoring is essential to determine adequate treatment paradigms and avoid unnecessary systemic treatment, especially corticosteroids. When the ophthalmic status requires it, multidisciplinary collaboration between the ophthalmologist, the paediatrician and the rheumatologist may be needed to offer optimal management to the patient. In cases of purely ocular involvement, it is the ophthalmologist who should determine the management.

[Role of Non-Invasive Strategies in the Treatment of Acute Hypoxemic Respiratory Failure Related to COVID-19]. / Bedeutung nicht-invasiver Verfahren in der Therapie des akuten hypoxämischen Versagens bei COVID-19.

Non-invasive strategies such as HFOT (high-flow oxygen therapy), CPAP (continuous positive airway pressure) and NIV (non-invasive ventilation) are increasingly being used during the COVID-19 pandemics in order to treat acute hypoxemic respiratory failure related to COVID-19, and this is aimed at avoiding intubation. This review article summarizes the current evidence by also emphasizing its heterogeneity. Importantly, current evidence suggests that these non-invasive strategies can be successfully used even in case of severe respiratory failure and are, thus, indeed capable of avoiding intubation, and consequently, tube-related complications. In contrast, it also remains to be emphasized that prolonged spontaneous breathing supported by non-invasive treatment strategies is also prone to complications. In particular, late NIV failure is associated with substantially deteriorated outcome, which is suggested to be meaningful in view of NIV failure rates still being high in Germany. Finally, the current article also refers to a parallel article that addresses the discussion being held in the public media in Germany concerning this topic. Here, its textual questionability, but also its negative consequences for both the research community and the general society are elaborated. In this context, the importance of national and regularly updated guidelines is emphasized.

COPD Assessment Test Changes from Baseline Correlate with COPD Exacerbations: A Longitudinal Analysis of the DACCORD Observational Study.

PURPOSE: A number of analyses have shown the immediate impact of COPD exacerbations on health status. However, none evaluated the long-term correlation between health status and the occurrence of exacerbations. METHODS: DACCORD is an observational study in patients with COPD recruited across Germany following initiation or change in COPD maintenance medication. Data collected include COPD Assessment Test (CAT) total score on entry and after 1 and 2 years, and the occurrence of exacerbations. We analysed the correlation between change from baseline in CAT total score and exacerbations, after excluding patients who exacerbated during the quarter immediately prior to the CAT assessment of interest. RESULTS: The initial correlation analysis was performed in 6075 patients, 28% with ≥ 1 exacerbation over the 2-year follow-up, and 58% with a clinically relevant CAT improvement. There was a significant correlation between exacerbations over 2 years and CAT change from baseline at Year 2 (p = 0.0041). The Spearman's correlation coefficient was 0.03711, indicating very weak correlation-potentially driven by the high proportion of non-exacerbating patients. In a subsequent logistic regression, the probability of experiencing frequent (≥ 2 per year) or severe exacerbations was higher in patients with worsening in CAT total score (p < 0.001). However, the probability of a patient exacerbating in Year 1 or Year 2 did not correlate with CAT change. CONCLUSIONS: In this population (initiating or changing maintenance COPD medication), patients with frequent or severe exacerbations had a long-term worsening in health status (beyond the acute effect of an exacerbation) compared with patients who do not exacerbate.

Training improves the handling of inhaler devices and reduces the severity of symptoms in geriatric patients suffering from chronic-obstructive pulmonary disease.

PURPOSE: Elderly patients with impaired vision, cognitive decline or motor/sensory disturbances of their fingers suffering from chronic-obstructive pulmonary disease (COPD) encounter difficulties in handling inhaler devices used as the cornerstones of treatment of pulmonary obstruction. Many elderly patients make severe mistakes which impede adequate drug delivery to the bronchioles. This multimodal training program was designed to reduce the number of handling mistakes of inhaler devices. METHODS: From October 1, 2016 to September 30, 2017, a prospective intervention study was conducted in 38 in-patients > 65 years (median age 79 years) with previously diagnosed COPD. The effect of an 8-day intervention comprising daily counselling and video demonstration according to the recommendations of the German Airway League on the frequency of mistakes during handling of inhaler devices, the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC) and the perception of symptoms (COPD Assessment Test, CAT) were studied. Measurements on days 1 and 8 were compared by Wilcoxon signed rank test. RESULTS: The number of handling mistakes per patient decreased as a consequence of the intervention from 3.0 (0-7) to 0.5 (0-6) [median (minimum-maximum; p < 0.0001)]. The CAT Score decreased from 19.5 (14/24) to 14.5 (10.75/21) [median (25./75. percentile; p < 0.0001) indicating a substantial reduction of clinical symptoms. Conversely, FEV1 and FVC only slightly increased (difference statistically not significant). At study entry, the number of handling mistakes was inversely correlated with the Mini Mental Status Test (MMST) score (p = 0.01). The reduction of the number of handling mistakes during the intervention was not correlated with the MMST. CONCLUSION: In COPD, intensive training for 8 days improved the handling of inhalers and reduced clinical symptoms in geriatric patients. Patients with cognitive abnormalities also benefitted from this intervention. TRIAL REGISTRATION: German Clinical Trials Registry DRKS00023196 , date of registration September 29, 2020 (retrospectively registered).

Open Reduction and Internal Fixation of Unilateral Mandibular Condylar Base and Neck Fractures Using a Lambda Plate: Selection Criteria for Application.

PURPOSE: The aim of this study was to evaluate the clinical, radiologic, and functional outcomes in a retrospective cohort study of patients with condylar base and neck fractures treated with open reduction and internal fixation via lambda plates to define selection criteria for their application. PATIENTS AND METHODS: Eleven patients underwent open reduction and internal fixation using lambda plates for osteosynthesis of condylar base and neck fractures. The mean follow-up period was 8 months. All kinds of complications were recorded. Postoperative maximum jaw opening and occlusion were determined. Pain on palpation of the joint area, pain on movement, and muscle pain were examined. The criteria for the intraoperative selection of a lambda plate were recorded. RESULTS: Positioning and fixation of lambda plates were feasible in all cases. A condylar neck fracture with limited bone surface on the proximal fragment for internal fixation prevailed as the primary indication for the selection of a lambda plate. Avoiding extensive soft tissue stripping at the proximal fragment when using a transoral endoscopically assisted approach in cases of condylar base fractures also was a selection criterion. The overall complication rate was low. CONCLUSIONS: The indications for lambda plates for internal fixation of condylar fractures are neck fractures with limited bone surface along the proximal fragment for internal fixation. Application of the plate through a transoral endoscopic approach to avoid extensive soft tissue stripping at the proximal fragment is favorable in high condylar base fractures.

Combination of Rigid and Nonrigid Fixation Versus Nonrigid Fixation for Bilateral Mandibular Fractures: A Multicenter Randomized Controlled Trial.

PURPOSE: We aimed to compare complication rates and functional outcomes in patients with bilateral mandibular fractures treated with different degrees of internal fixation rigidity. PATIENTS AND METHODS: This international, multicenter randomized controlled trial included adults with bilateral mandibular fractures located at either the angle and body, angle and symphysis, or body and symphysis. Patients were treated with either a combination of rigid fixation for the anterior fracture and nonrigid fixation for the posterior fracture (mixed fixation) or nonrigid fixation for both fractures. The primary outcome was complications within 6 weeks after surgery. Secondary outcomes were complications within 3 months, Helkimo dysfunction index, and mandibular mobility at 6 weeks and 3 months after surgery. RESULTS: Of the 315 patients enrolled, 158 were randomized to the mixed fixation group and 157 to the nonrigid fixation group. The overall complication rate at 6 weeks in the intention-to-treat population was 9.6% (95% confidence interval [CI], 5.3% to 15.6%) in the mixed fixation group and 7.8% (95% CI, 4.0% to 13.5%) in the nonrigid fixation group. With an unadjusted odds ratio of 1.25 (95% CI, 0.51 to 3.17), there were no statistically significant differences in complication rates between the 2 groups (P = .591). A multivariable model for complication risk at 6 weeks found no significant differences between treatment groups, but patients with moderate or severe displacement had a higher complication rate than those with no or minimal displacement (adjusted odds ratio, 4.58; 95% CI, 1.16 to 18.06; P = .030). There were no significant between-group differences in complication rates at 3 months. Moreover, no significant differences in Helkimo dysfunction index and mandibular mobility index at 6 weeks and 3 months were found between groups according to treatment allocated and treatment received. CONCLUSIONS: A combination of rigid and nonrigid fixation in patients with bilateral mandibular fracture has similar complication rates and functional outcomes to nonrigid fixation for both fractures.

MRI of the inferior alveolar nerve and lingual nerve-anatomical variation and morphometric benchmark values of nerve diameters in healthy subjects.

OBJECTIVE: Since MRI using dedicated imaging sequences has recently shown promising results in direct visualization of the inferior alveolar nerve (IAN) and the lingual nerve (LN) with high spatial resolution, the aim of this study was to generate suitable standard specifications to reliably depict the IAN and LN in MRI and to delineate the anatomy and its variants of these nerves in healthy subjects. METHODS: Thirty healthy volunteers were examined on a 3-T scanner (Elition, Philips Healthcare, Best, the Netherlands). The sequence protocol consisted of 3D STIR, 3D DESS, and 3D T1 FFE "black bone" sequences. RESULTS: The study reconfirmed a good feasibility of direct visualization of proximal and peripheral portions of the IAN and of the proximal course of the LN. The STIR sequence showed the highest apparent signal to noise ratio (aSNR) and best apparent nerve-muscle contrast to noise ratio (aNMCNR) for IAN and for the LN. The applied MRI sequences allowed to differentiate the tissue composition of the neurovascular bundle inside the mandibular canal. CONCLUSION: Dedicated MRI sequence protocols proved effectively to detect the IAN and LN and their course in healthy volunteers. The tissue composition of the mandibular neurovascular bundle was conclusively distinguishable as was the varying topography inside multiple bony channels. CLINICAL RELEVANCE: The presented data on the precise and valid visualization of the IAN and LN have clinical implications in respect to local anesthesia prior to dental treatments in the mandible but also regarding surgical procedures and implant insertion in the molar region.

Evaluation of Complications After Open Reduction and Internal Fixation of Mandibular Condylar Base and Neck Fractures Using Trapezoidal Plates.

The purpose of the study was to evaluate the different fracture pattern of patients being treated with trapezoidal plate fixation of condylar base and neck fractures using the AOCMF Classification System to determine specific fracture pattern that are associated with failure of trapezoidal plate fixation. Ten patients with mandibular condylar base and neck fractures underwent internal fixation using trapezoidal plates. Fractures of the condylar process were classified according to the AOCMF Classification System using computed tomography data. The fracture pattern was compared to complications according to hardware failure such as plate or screw loosening and plate fracture. Plate and screw loosening of trapezoidal plates for fixation of condylar base and neck fractures was associated with fracture location in the neck region and major fragment displacement with contact loss between the proximal and distal fragment of the fracture. Further investigations such as finite-element analysis of different plating systems for fixation of condylar neck fractures are necessary to establish the optimal fixation technique for condylar neck fractures.

Advanced Cases of Birdshot HLA-A29 Retinochoroiditis: Prevalence and Characteristics.

PURPOSE: To establish the prevalence, morphological, and functional characteristics and evolution of advanced cases of birdshot retinochoroiditis (BRC). METHODS: A retrospective review of all BRC cases seen at the Centre for Ophthalmic Specialized Care, Lausanne, Switzerland, with at least 3 years of follow-up since the onset of symptoms. The following parameters were evaluated: demographic characteristics, best-corrected visual acuity (BCVA), fundus photographs, fluorescein (FA) and indocyanine green (ICGA) angiography frames, and visual field evaluation from initial visit to last follow-up. RESULTS: Out of the 1920 patients with uveitis who were followed from 1995 until 2018, 32 (1.67%) were diagnosed with BRC; 20 of these 32 patients had sufficient data to be included. Three of these twenty patients (15.0%) had severe forms of the disease. Two patients had received insufficient treatment and one progressed despite attempted maximal therapy. The mean BCVA was 0.62 (± 0.42) at presentation, which was already at an advanced stage of the disease, and 0.51 (± 0.37) at last follow-up. The average visual field mean defect (VFMD) was 19.65 (± 4.71 dB) at presentation and 21.40 (± 2.45 dB) at last follow-up. Choroidal inflammatory activity monitored by ICGA decreased from 10.67 (± 9.18) at presentation to 6.67 (± 5.61) at last follow-up. FA revealed mild retinal vasculitis at 6.50 (± 4.76), which remained stable to 4.67 (± 3.20). EDI-OCT estimated choroidal thickness (EDI-OCT-CT) measurements were 246.36 (± 116.93 µm) at presentation and 231.30 (± 120.70 µm) at the last follow-up. CONCLUSIONS: In our setting, 15% of BRC cases had a severe course and suffered extensive irreversible chorioretinal damage, obviously due to insufficient treatment in two cases. This underlines the importance of correctly diagnosing BRC and initiating therapy as promptly as possible to avoid such outcomes in an otherwise possibly controllable disease.

Wash-Free Multiplexed Mix-and-Read Suspension Array Fluorescence Immunoassay for Anthropogenic Markers in Wastewater.

Pharmaceuticals, certain food ingredients, and mammalian endogenous metabolic products in wastewater are mostly of human origin. They are anthropogenic markers. Proper knowledge of their levels in wastewater helps to track sources of pollutants in natural waters and allows for calculation of removal efficiencies in wastewater treatment plants. Here, we describe the development and application of an indirect competitive, multiplexing suspension array fluorescence immunoassay (SAFIA) for the detection of carbamazepine (CBZ), diclofenac (DCF), caffeine (CAF), and isolithocholic acid (ILA) in wastewater, covering those classes of anthropogenic markers. The assay consists of haptens covalently conjugated to fluorescence-encoded polystyrene core/silica shell microparticles to create a site for competitive binding of the antibodies (Abs). Bound Abs are then stained with fluorophore-labeled Abs. Encoding and signaling fluorescence of the particles are determined by an automated flow cytometer. For compatibility of the immunoassay with the 96-well microtiter plate format, a stop reagent, containing formaldehyde, is used. This enables a wash-free procedure while decreasing time-to-result. Detection limits of 140 ± 40 ng/L for CBZ, 180 ± 110 ng/L for CAF, 4 ± 3 ng/L for DCF, and 310 ± 70 ng/L for ILA are achieved, which meet the sensitivity criteria of wastewater analysis. We demonstrate the applicability of SAFIA to real wastewater samples from three different wastewater treatment plants, finding the results in good agreement with LC-MS/MS. Moreover, the accuracy in general exceeded that from classical ELISAs. We therefore propose SAFIA as a quick and reliable approach for wastewater analysis meeting the requirements for process analytical technology.