HLA dependency and possible clinical relevance of intrathecally synthesized anti-IgLON5 IgG4 in anti-IgLON5 disease.

Background: Anti-IgLON5 disease is a rare chronic autoimmune disorder characterized by IgLON5 autoantibodies predominantly of the IgG4 subclass. Distinct pathogenic effects were described for anti-IgLON5 IgG1 and IgG4, however, with uncertain clinical relevance. Methods: IgLON5-specific IgG1-4 levels were measured in 46 sera and 20 cerebrospinal fluid (CSF) samples from 13 HLA-subtyped anti-IgLON5 disease patients (six females, seven males) using flow cytometry. Intervals between two consecutive serum or CSF samplings (31 and 10 intervals, respectively) were categorized with regard to the immunomodulatory treatment active at the end of the interval, changes of anti-IgLON5 IgG1 and IgG4 levels, and disease severity. Intrathecal anti-IgLON5 IgG4 synthesis (IS) was assessed using a quantitative method. Results: The median age at onset was 66 years (range: 54-75), disease duration 10 years (range: 15-156 months), and follow-up 25 months (range: 0-83). IgLON5-specific IgG4 predominance was observed in 38 of 46 (83%) serum and 11 of 20 (55%) CSF samples. Anti-IgLON5 IgG4 levels prior clinical improvement in CSF but not serum were significantly lower than in those prior stable/progressive disease. Compared to IgLON5 IgG4 levels in serum, CSF levels in HLA-DRB1*10:01 carriers were significantly higher than in non-carriers. Indeed, IgLON5-specific IgG4 IS was demonstrated not only in four of five HLA-DRB1*10:01 carriers but also in one non-carrier. Immunotherapy was associated with decreased anti-IgGLON5 IgG serum levels. In CSF, lower anti-IgLON5 IgG was associated with immunosuppressive treatments used in combination, that is, corticosteroids and/or azathioprine plus intravenous immunoglobulins or rituximab. Conclusion: Our findings might indicate that CSF IgLON5-specific IgG4 is frequently produced intrathecally, especially in HLA-DRB1*10:01 carriers. Intrathecally produced IgG4 may be clinically relevant. While many immunotherapies reduce serum IgLON5 IgG levels, more intense immunotherapies induce clinical improvement and may be able to target intrathecally produced anti-IgLON5 IgG. Further studies need to confirm whether anti-IgLON5 IgG4 IS is a suitable prognostic and predictive biomarker in anti-IgLON5 disease.

Poor adherence during adolescence is a risk factor for becoming lost-to-follow-up in patients with phenylketonuria.

Purpose: A high rate of lost to follow-up (LTFU) in patients with phenylketonuria (PKU) represents a main challenge. In this study, we investigated potential risk factors for becoming LTFU related to adolescence as a critical period of life. Methods: We retrospectively analyzed longitudinal data collected from 1993 to 2019 of patients diagnosed with classic PKU that were followed at our center during adolescence (14-18 y) and at least once in adulthood (>18 y). Patients who interrupted their contact with our center after the 18th birthday for at least 2 years were classified as LTFU. We performed a multivariate regression analysis to investigate following potential risk factors for becoming LTFU in adult life: sex, dietary compliance during adolescence assessed through the mean of the annual medians of phenylalanine plasma values, average number of contacts with the center during adolescence and age at first visit after the 18th birthday. Results: 93 patients (52 males, 41 females) were included in the study. 58% became LTFU during adulthood. The mean age at the last visit before becoming LTFU was 26.2 ± 5.1 years. In the multivariate Cox regression analysis we found that poor dietary compliance during adolescence was significantly associated with a higher risk of becoming LTFU during adulthood (p-value = 0.028). Discussion: Adult patients who displayed poor treatment adherence during adolescence should be identified and carefully monitored to prevent loss of contact.

A neutral comparison of algorithms to minimize L0 penalties for high-dimensional variable selection.

Variable selection methods based on L0 penalties have excellent theoretical properties to select sparse models in a high-dimensional setting. There exist modifications of the Bayesian Information Criterion (BIC) which either control the familywise error rate (mBIC) or the false discovery rate (mBIC2) in terms of which regressors are selected to enter a model. However, the minimization of L0 penalties comprises a mixed-integer problem which is known to be NP-hard and therefore becomes computationally challenging with increasing numbers of regressor variables. This is one reason why alternatives like the LASSO have become so popular, which involve convex optimization problems that are easier to solve. The last few years have seen some real progress in developing new algorithms to minimize L0 penalties. The aim of this article is to compare the performance of these algorithms in terms of minimizing L0 -based selection criteria. Simulation studies covering a wide range of scenarios that are inspired by genetic association studies are used to compare the values of selection criteria obtained with different algorithms. In addition, some statistical characteristics of the selected models and the runtime of algorithms are compared. Finally, the performance of the algorithms is illustrated in a real data example concerned with expression quantitative trait loci (eQTL) mapping.

High Rate of Passenger Lymphocyte Syndrome after ABO Minor Incompatible Lung Transplantation.

Rationale: Passenger lymphocyte syndrome (PLS) may complicate minor ABO mismatched lung transplantation (LuTX) via donor-derived red cell antibody-induced hemolysis.Objectives: To ascertain the incidence and specificity of PLS-relevant antibodies among the study population as well as the dynamics of hemolysis parameters and the transfusion requirement of patients with or without PLS.Methods: In this cohort study, 1,011 patients who received LuTX between January 2010 and June 2019 were studied retrospectively. Prospectively, 87 LuTX (July 2019 to June 2021) were analyzed. Postoperative ABO antibody and hemolytic marker determinations, transfusion requirement, and duration of postoperative hospital care were analyzed. Retrospectively, blood group A recipients of O grafts with PLS were compared with those without.Measurements and Main Results: PLS affected 18.18% (retrospective) and 30.77% (prospective) of A recipients receiving O grafts, 5.13% of B recipients of O grafts, and 20% of AB patients receiving O transplants. Anti-A and anti-A1 were the predominant PLS-inducing antibodies, followed by anti-B and anti-A,B. Significantly lower hemoglobin values (median, 7.4 vs. 8.3 g/dl; P = 0.0063) and an approximately twice as high percentage of patients requiring blood transfusions were seen in PLS. No significant differences in other laboratory markers, duration of hospital stay, or other complications after LuTX were registered.Conclusions: Minor ABO incompatible LuTX recipients are at considerable risk of developing clinically significant PLS. Post-transplant monitoring combining red cell serology and hemolysis marker determination appears advisable so as not to overlook hemolytic episodes that necessitate antigen-negative transfusion therapy.

Long-Term Care and Follow-Up in Laryngeal Cancer Patients: A Multicenter Retrospective Analysis.

PURPOSE: We conducted an outcome analysis on surgically treated laryngeal squamous cell carcinoma (LSCC) patients. METHODS: A multicenter retrospective study with 352 patients was analyzed. A new nomogram that incorporates age, T- and N-classification, and treatment was created. RESULTS: Recurrence was observed in 65 (18.5%) patients after a mean time of 16.5 months. After 60 months, 91 (25.9%) of patients developed secondary primary tumors (SPT), most commonly in the lungs (n = 29; 8.2%) followed by other head and neck cancers (n = 21; 6.0%). Notably, the mean time to occurrence of secondary head and neck cancers was twice that of lung cancer (101.1 vs. 47.5 months). CONCLUSION: Recurrent disease is less common in LSCC patients and appears much earlier than SPT. Because one in every four laryngeal cancer patients develops SPTs within 5-10 years, long-term care and follow-up, including imaging studies, are highly recommended. The nomogram was useful for estimating survival.

Durable Anti-SARS-CoV-2 Antibody Response after mRNA-1273 Booster in Peritoneal Dialysis Patients during the Omicron Wave.

Anti-SARS-CoV-2 vaccination of dialysis patients has been proven to be safe and effective to reduce COVID-19-related morbidity and mortality. However, data on the durability of anti-SARS-CoV-2 antibodies post-vaccination in peritoneal dialysis (PD) patients are scarce. In this prospective single-center cohort study we measured anti-SARS-CoV-2 RBD antibodies 3 and 6 months after the 3rd dose of the mRNA-1273 vaccine in 27 adult PD patients and recorded breakthrough infections. Furthermore, in a mixed model analysis, we analyzed potential factors influencing the humoral response following vaccination. Anti-SARS-CoV-2 RBD antibody levels declined from 21,424 BAU/mL at 1 month to 8397 BAU/mL at 3 months and to 5120 BAU/mL at 6 months after the 3rd dose, but remained higher than pre-3rd dose levels (212 BAU/mL). Eight patients (29.6%) were infected with SARS-CoV-2 within six months from the 3rd dose during the Omicron wave. Previous high antibody levels, high glomerular filtration rate (GFR) and low Davies Comorbidity Score were associated with higher anti-SARS-CoV-2 antibody levels after the booster. In conclusion, PD patients exhibited a robust and durable humoral response after a third dose of the mRNA-1273 vaccine. A high GFR and low comorbidity as well as previous high antibody levels predicted a better humoral response to vaccination.

The Effect of Prone Positioning After Lung Transplantation.

BACKGROUND: Prone positioning has become a standard therapy in acute respiratory distress syndrome to improve oxygenation and decrease mortality. However, little is known about prone positioning in lung transplant recipients. This large, singe-center analysis investigated whether prone positioning improves gas exchange after lung transplantation. METHODS: Clinical data of 583 patients were analyzed. Prone position was considered in case of impaired gas exchange Pao2/fraction of oxygen in inhaled air (<250), signs of edema after lung transplantation, and/or evidence of reperfusion injury. Patients with hemodynamic instability or active bleeding were not proned. Impact of prone positioning (n = 165) on gas exchange, early outcome and survival were determined and compared with patients in supine positioning (n = 418). RESULTS: Patients in prone position were younger, more likely to have interstitial lung disease, and had a higher lung allocation score. Patients were proned for a median of 19 hours (interquartile range,15-26) hours). They had significantly lower Pao2/fraction of oxygen in inhaled air (227 ± 96 vs 303 ± 127 mm Hg, P = .004), and lower lung compliance (24.8 ± 9.1 mL/mbar vs 29.8 ± 9.7 mL/mbar, P < .001) immediately after lung transplantation. Both values significantly improved after prone positioning for 24 hours (Pao2/fraction of oxygen ratio: 331 ± 91 mm Hg; lung compliance: 31.7 ± 20.2 mL/mbar). Survival at 90 days was similar between the 2 groups (93% vs 96%, P = .105). CONCLUSIONS: Prone positioning led to a significant improvement in lung compliance and oxygenation after lung transplantation. Prospective studies are needed to confirm the benefit of prone positioning in lung transplantation.

The role of elective neck dissection in T1 and T2 nasal cavity squamous cell carcinomas.

PURPOSE: To evaluate the role of elective neck dissection (END) on oncological outcome in early-stage nasal cavity squamous cell carcinomas (SCCs). METHODS: In total, 87 patients with T1 (n = 59; 67.8%) and T2 (n = 28; 32.2%) SCCs were evaluated regarding performance of END, regional recurrences (RR) and its impact on cancer-specific survival (CSS). We further created a risk score based on T-classification, tumor subsite and grading to identify patients whom may benefit from END and calculated the corresponding numbers needed to treat (NNT) to prevent RR. RESULTS: Nine (10.3%) patients experienced RR of whom 3 (5.1%) were T1 and 6 (21.4%) T2 tumors (p = 0.042). All RR originated from moderately or poorly differentiated (G2-G3) SCCs of the nasal septum or vestibule. END was done in 15 (17.2%) patients and none of those experienced RR (p = 0.121). Onset of RR represented the worst prognostic factor for CSS (HR 23.3; p = 0.007) with a 5y-CSS of 44.4% vs. 97.3% (p < 0.001). RR occurred in none of the patients with no or low risk scores compared to 31.6% (6/19) in patients with high-risk scores (p = 0.006). Accordingly, three high-risk patients would need to undergo END (NNT 2.63) to prevent RR compared to a NNT of 8 for the whole cohort. CONCLUSIONS: Although rare, occurrence of RR significantly deteriorates outcome in early stage nasal cavity SCCs, which could be effectively reduced by performance of END. The importance of END is currently underestimated and our proposed risk score helps identifying those patients who will benefit from END.

A new nomogram to predict oncological outcome in laryngeal and hypopharyngeal carcinoma patients after laryngopharyngectomy.

BACKGROUND: To create nomograms for better prediction of the oncological outcome in advanced laryngeal (LxCAs) or hypopharyngeal (HpxCAs) cancer after laryngopharyngectomy. MATERIALS: 239 patients who underwent total laryngectomy or laryngopharyngectomy due to LxCA (52.7%) or HpxCA (47.3%) were included in this study. Based on clinical risk factors (tumor site, lymph node involvement, salvage setting), we created nomograms for prediction of disease-specific survival (DSS) and disease-free survival (DFS). RESULTS: HpxCAs showed a higher rate of lymph node involvement (p < 0.001), a 2.47-fold higher risk of a 2nd head and neck cancer (p = 0.009) and significantly worse loco-regional control rates (p = 0.003) compared to LxCAs. Positive neck nodes and salvage procedures were associated with significantly worse outcome. Nomograms demonstrated that hypopharyngeal tumors with positive neck nodes in salvage situations had the worst oncological outcome with a 5-year DSS of 15-20%. CONCLUSIONS: The oncological outcome is worse in hypopharyngeal carcinomas and could be easily quantified by our nomograms that are based on tumor site, lymph node involvement and salvage situation.

Heart failure with preserved ejection fraction: Calculating the risk of future heart failure events and death.

Objective: We sought to develop a clinical model to identify heart failure patients with preserved ejection fraction (HFpEF) at highest risk for acute HF events or death. Methods and results: Between 2010 and 2019, 422 patients with HFpEF were followed. Acute HF events occurred in 190 patients (45%), including 110 (58%) with recurrent hospitalizations. Those with recurrent events had worse 6-min walk test (p < 0.001), higher brain N-terminal prohormone natriuretic peptide (NT-proBNP, p < 0.001), and higher New York Heart Association functional class (NYHA, p < 0.001). Overall survival rates in patients with 1 HF event vs > 1 HF events were: at 1-year 91.6 vs. 91.8%, at 3-years 84.7 vs. 68.3% and at 5-years 67.4 vs. 42.7%, respectively (p < 0.04). The Hfpef survivAL hOspitalization (HALO) score revealed best predictive capability for all-cause mortality combining the variables age (p = 0.08), BMI (p = 0.124), NYHA class (p = 0.004), need for diuretic therapy (p = 0.06), left atrial volume index (p = 0.048), systolic pulmonary artery pressure (p = 0.013), NT-proBNP (p = 0.076), and number of prior hospitalizations (p = 0.006). HALO score predicted future HF hospitalizations in an ordinal logistic regression model (OR 3.24, 95% CI: 2.45-4.37, p < 0.001). The score performance was externally validated in 75 HFpEF patients, confirming a strong survival prediction (HR 2.13, 95% CI: 1.30-3.47, p = 0.002). Conclusions: We developed a model to identify HFpEF patients at increased risk of death and HF hospitalization. NYHA class and recurrent HF hospitalizations were the strongest drivers of outcome.

Identification of apple cultivars hypoallergenic for birch pollen-allergic individuals by a multidisciplinary in vitro and in vivo approach.

BACKGROUND: Birch pollen-related apple allergy is the most frequent IgE-mediated food allergy in Central-Northern Europe with Mal d 1 as major allergen. Its concentration in apples varies with the cultivar and storage time. Year-round appealing, hypoallergenic cultivars still are needed to satisfy the nutritional needs of affected individuals. We characterized three promising cultivars by multidisciplinary in vitro assays including long-term storage and by clinical challenges of allergic individuals before and after the birch pollen season. METHODS: Proteins were extracted from fruits of 'Santana', 'Golden Delicious' (GD), and three genuine cultivars in November 2018 and April 2019. Mal d 1-levels were analysed by mass spectrometry, SDS-PAGE, immunoblotting, competitive ELISA, and basophil activation tests. Twenty-eight allergic individuals underwent single-blinded open food challenges and skin testing with the cultivars and birch pollen in November 2018 and May 2019. Allergen-specific IgE-levels were determined. RESULTS: After storage all cultivars except 'Santana' were of appealing appearance and taste. Their Mal d 1 content had increased, also reflected by significantly amplified basophil activation and stronger reactions in clinical challenges. Besides, individuals showed boosted reactivity after pollen exposure indicated by enhanced allergen-specific IgE-levels and skin reactions to birch pollen. Still, all cultivars remained significantly less allergenic than GD and comparable to Santana in November 2018 in all assessments except for skin testing. CONCLUSIONS: Combined expertise in pomology and allergology identified promising new cultivars for allergic consumers. The evaluation of hypoallergenic apples should incorporate long-term storage and birch pollen exposure. Basophil activation tests may be suitable in the selection of promising cultivars for oral challenges.

Humoral Response to mRNA-1273 SARS-CoV-2 Vaccine in Peritoneal Dialysis Patients: Is Boostering After Six Months Adequate?

In dialysis patients the humoral response to anti-SARS-CoV-2 vaccines is attenuated and rapidly declines over time. However, data on the persistence of the immune response in peritoneal dialysis (PD) patients are scarce, particularly after a third (booster) dose with mRNA-1273 vaccine. In this prospective cohort study, we report anti-SARS-CoV-2 antibody levels in PD patients before and after the third dose of mRNA-1273 vaccine. Six months after the second dose, anti-SARS-CoV-2 antibodies were detected in all patients (n = 34). However, within this time period antibodies substantially declined in 31 of 34 patients (4.5-fold, median = 192 BAU/mL, p = 1.27 × 10-9) and increased in three patients. In accordance with government regulations, a third dose of mRNA-1273 vaccine (50 µg) was given to 27 PD patients 6 months after the second dose which induced a significant increase of anti-SARS-CoV-2 antibody titers (58.6-fold, median = 19405 BAU/mL, p = 1.24 × 10-29). A mixed model analysis showed that a lower Davies Comorbidity Score and a higher GFR were associated with higher antibody titers (p = 0.03 and p = 0.02). The most common adverse events after the third dose were pain at the injection site (77.8%) and fatigue (51.9%). No hospitalizations were reported. In conclusion, 6 months after the second dose of mRNA-1273 vaccine, anti-SARS-CoV-2 antibodies substantially decreased in PD patients, whereas a well-tolerated third dose induced a robust humoral response. Our data suggest that the administration of a booster dose within a shorter interval than 6 months should be considered in PD patients in order to maintain high anti-SARS-CoV-2 antibody levels and assure protection from severe COVID-19 disease.

A systematic review and meta-analysis of HLA class II associations in patients with IgG4 autoimmunity.

Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001/OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.

Selecting predictive biomarkers from genomic data.

Recently there have been tremendous efforts to develop statistical procedures which allow to determine subgroups of patients for which certain treatments are effective. This article focuses on the selection of prognostic and predictive genetic biomarkers based on a relatively large number of candidate Single Nucleotide Polymorphisms (SNPs). We consider models which include prognostic markers as main effects and predictive markers as interaction effects with treatment. We compare different high-dimensional selection approaches including adaptive lasso, a Bayesian adaptive version of the Sorted L-One Penalized Estimator (SLOBE) and a modified version of the Bayesian Information Criterion (mBIC2). These are compared with classical multiple testing procedures for individual markers. Having identified predictive markers we consider several different approaches how to specify subgroups susceptible to treatment. Our main conclusion is that selection based on mBIC2 and SLOBE has similar predictive performance as the adaptive lasso while including substantially fewer biomarkers.

Preoperative buccal bone volume predicts long-term graft retention following augmentation in the esthetic zone: A retrospective case series.

OBJECTIVES: Buccal bone augmentation in the esthetic zone is routinely used to achieve optimal clinical outcomes. Nonetheless, long-term data are sparse, and it is unknown how baseline buccal bone volume affects the retention of the augmented volume over time. MATERIAL AND METHODS: This is a long-term follow-up retrospective case series. After a preoperative computed tomography scan, implants were placed in the anterior maxilla following guided bone regeneration, autogenous block grafting, or both. At the follow-up, patients received a computed tomography scan and a clinical examination. Buccal bone volume was the primary outcome. Buccal bone thickness, peri-implant, and esthetic parameters were secondary outcomes. RESULTS: After a median follow-up of 6.7 years (interquartile range: 4.9-9.4), 28 implants in 19 patients (median age at augmentation: 43.3 years, interquartile range: 34.4-56.7, 53% female) were followed up. Preoperative buccal bone volume at baseline (V0 ) showed a moderate correlation to final buccal bone volume (Vt , rs  = .43) but a strong correlation to the absolute volumetric change (ΔV = Vt -V0 , rs  = -.80). A linear mixed model for Vt had a large intercept of 91.39 (p < .001) and a rather small slope of .11 for V0 (p = .11). Observed differences between treatments were not statistically significant in the mixed model. V0 above 105 mm3 predicted a negative volume change (ΔV < 0) with a specificity of 100% and a sensitivity of 96%. CONCLUSIONS: The results suggest higher gains in sites with lower V0 and point to a cutoff V0 above which the augmented volume is not retained long-term.

Influence of antenatal corticosteroid lung maturation on maternal inflammatory parameters.

The aim of this prospective study (Clinical Trials Identifier: NCT02993744) was to detect the effect of fetal lung maturation with betamethasone on the maternal inflammatory parameters C-reactive protein (CRP) and leukocytes. The blood results of 75 patients in the week of gestation (WOG) 23/0 to 34/6 under threat of preterm delivery and treated with betamethasone were analyzed. Sixty-five pregnant women without complications served as control group. Leukocyte numbers increased significantly about 2.4 thsd./µL (±3.3 standard deviation), with a confidence interval of 95% from 1.5 to 3.2 (p < .001). Calculations for CRP were done with logarithmized values. CRP decreased significantly (p < .001) by the factor 0.465, with a 95% confidence interval from 0.376 to 0.576. The results of this study can be used in clinical routine as a decision support, to come to conclusions about inflammatory processes during lung maturation.

Lungs from polytrauma donors with significant chest trauma can be safely used for transplantation.

BACKGROUND: The use of organs from polytrauma donors for lung transplantation is controversial in the literature. For many centers, the radiologic manifestation of lung contusions is a clear reason to reject an organ offer. This results in the loss of potentially viable organs for the donor pool. METHODS: We analyzed 1152 donor lungs procured by our transplant center between January 2010 and June 2018. These included 118 lungs with a history of polytrauma involving the chest. Sixteen polytrauma donor lungs were rejected after procurement. A total of 102 lungs were transplanted, divided into 2 groups: the polytrauma contusion group (n = 44), comprising polytrauma donors with radiologic signs of lung contusion at the time of offer, and the polytrauma clear group (n = 58), comprising polytrauma donors without lung contusion. Nontrauma donor lungs transplanted during the study period were assigned to a polytrauma control group (n = 650). Short- and long-term outcomes of the 3 groups were compared. RESULTS: Basic demographic data and preoperative factors were similar in the 3 groups. Rates of primary graft dysfunction grade 3 at 72 hours did not differ among the 3 groups (0.0% vs 3.4% vs 3.9%; P = .409). The duration of ventilation was similar the 3 groups: 45 hours (interquartile range [IQR], 28-94 hours), 37 hours (IQR, 22-71 hours), and 42 hours (IQR, 22-96 hours), respectively (P = .674). Long-term graft survival was not impaired in the trauma groups compared with controls. One-year survival rates were 84.1% for the polytrauma contusion group, 93.1% for the polytrauma clear group, and 83.1% for the no polytrauma group. Five-year graft survival in the 3 groups was 74.7%, 87.2%, and 70.0%, respectively. CONCLUSIONS: Lung transplantation using organs from polytrauma donors is associated with similar short- and long-term results as transplantation from nontrauma donors. The presence or absence of radiologic signs of lung contusion at the time of offer has no impact on primary graft function and long-term survival.

Optical coherence tomography-measured retinal nerve fiber layer thickness values compensated with a multivariate model and discrimination between stable and progressing glaucoma suspects.

PURPOSE: Our previously introduced multivariate model, compensating for intersubject variability, was applied to circumpapillary retinal nerve fiber layer (RNFL) values measured with optical coherence tomography in glaucoma suspects with or without prior progressive optic disc (OD) change in a series of confocal scanning laser tomography (CSLT, HRT III) measurements. METHODS: In this prospective study, OD change during CSLT follow-up was determined with strict, moderate, and liberal criteria of the topographic change analysis (TCA). Model compensation (MC) as well as age compensation (AC) was applied to RNFL sectors (RNFLMC vs. RNFLAC). Diagnostic performance of RNFLMC vs. RNFLAC was tested with an area under the receiver operating characteristic (AUROC) and was compared between methods. RESULTS: Forty-two glaucoma suspects were included. Patients without prior progressive OD change during the CSLT follow-up (= stable) had thicker RNFL thickness values in most areas and for all progression criteria. RNFLMC AUROC for the global RNFL (0.719) and the inferior quadrant (0.711) performed significantly better compared with RNFLAC AUROC (0.594 and 0.631) to discriminate between stable and progressive glaucoma suspects as defined by the moderate criteria of CSLT progression analysis (p = 0.028; p = 0.024). CONCLUSION: MC showed a slight but significant improvement in detection of subjects with prior progressive OD change among a group of glaucoma suspects, when compared to AC, which is the compensation method commonly used during OCT data evaluation in daily routine. Further studies are warranted to validate the present results.

Engagement in purposeful activities and social interactions amongst persons with dementia in special care units compared to traditional nursing homes: An observational study.

BACKGROUND: Persons with dementia spend most time of their day not engaging in activities or social interactions. A care concept of a dementia special care unit that promotes activities and social interaction through a household-like design and individualised stimuli is studied. AIM: To evaluate the main outcomes of the care concept of a dementia special care unit, namely, engagement in activities and social interactions. METHODS: We conducted an observational study as part of a theory-driven evaluation. The Maastricht Daily Life Observation Tool was used to collect momentary assessments multiple times per participant, including engagement in activity, type of activity, engagement in social interaction, interaction partners, location, agitation and mood. Thirty-three residents of the dementia special care units that implemented the care concept and 54 residents with dementia of two traditional nursing homes participated in the study, resulting in 2989 momentary assessments. RESULTS: Residents of both settings did not engage in activities or social interaction in approximately half of the observations. Compared to residents of traditional nursing homes, residents of special care units had a significantly higher chance for engagement in activities and social interaction in the afternoon but not in the morning or evening. CONCLUSION: The care concept of the special care unit facilitated engagement but had its limitations. Further research is needed to develop and evaluate appropriate interventions to enhance engagement of persons with dementia.

Multi-omics profiling predicts allograft function after lung transplantation.

RATIONALE: Lung transplantation is the ultimate treatment option for patients with end-stage respiratory diseases but bears the highest mortality rate among all solid organ transplantations due to chronic lung allograft dysfunction (CLAD). The mechanisms leading to CLAD remain elusive due to an insufficient understanding of the complex post-transplant adaptation processes. OBJECTIVES: To better understand these lung adaptation processes after transplantation and to investigate their association with future changes in allograft function. METHODS: We performed an exploratory cohort study of bronchoalveolar lavage samples from 78 lung recipients and donors. We analysed the alveolar microbiome using 16S rRNA sequencing, the cellular composition using flow cytometry, as well as metabolome and lipidome profiling. MEASUREMENTS AND MAIN RESULTS: We established distinct temporal dynamics for each of the analysed data sets. Comparing matched donor and recipient samples, we revealed that recipient-specific as well as environmental factors, rather than the donor microbiome, shape the long-term lung microbiome. We further discovered that the abundance of certain bacterial strains correlated with underlying lung diseases even after transplantation. A decline in forced expiratory volume during the first second (FEV1) is a major characteristic of lung allograft dysfunction in transplant recipients. By using a machine learning approach, we could accurately predict future changes in FEV1 from our multi-omics data, whereby microbial profiles showed a particularly high predictive power. CONCLUSION: Bronchoalveolar microbiome, cellular composition, metabolome and lipidome show specific temporal dynamics after lung transplantation. The lung microbiome can predict future changes in lung function with high precision.