Risk factors for reperfusion injury after lung transplantation

Objective: To assess the influence of recipient's and donor's factors as well as surgical events on the occurrence of reperfusion injury after lung transplantation. Design and setting: Retrospective study in the surgical intensive care unit (ICU) of auniversity hospital. Methods: We collected data on 60 lung transplantation donor/recipient pairs from June1993 to May2001, and compared the demographic, peri- and postoperative variables of patients who experienced reperfusion injury (35%) and those who did not. Results: The occurrence of high systolic pulmonary pressure immediately after transplantation and/or its persistence during the first 48 h after surgery was associated with reperfusion injury, independently of preoperative values. Reperfusion injury was associated with difficult hemostasis during transplantation (p = 0.03). Patients with reperfusion injury were more likely to require the administration of catecholamine during the first 48 h after surgery (p = 0.014). The extubation was delayed (p = 0.03) and the relative odds of ICU mortality were significantly greater (OR 4.8, 95% CI: 1.06, 21.8) in patients with reperfusion injury. Our analysis confirmed that preexisting pulmonary hypertension increased the incidence of reperfusion injury (p < 0.01). Conclusions: Difficulties in perioperative hemostasis were associated with reperfusion injury. Occurrence of reperfusion injury was associated with postoperative systolic pulmonary hypertension, longer mechanical ventilation and higher mortality. Whether early recognition and treatment of pulmonary hypertension during transplantation can prevent the occurrence of reperfusion injury needs to be investigate

Three-Dimensional Magnetic Resonance Imaging Bone Models of the Hip Joint Using Deep Learning: Dynamic Simulation of Hip Impingement for Diagnosis of Intra- and Extra-articular Hip Impingement

Background: Dynamic 3-dimensional (3D) simulation of hip impingement enables better understanding of complex hip deformities in young adult patients with femoroacetabular impingement (FAI). Deep learning algorithms may improve magnetic resonance imaging (MRI) segmentation. Purpose: (1) To evaluate the accuracy of 3D models created using convolutional neural networks (CNNs) for fully automatic MRI bone segmentation of the hip joint, (2) to correlate hip range of motion (ROM) between manual and automatic segmentation, and (3) to compare location of hip impingement in 3D models created using automatic bone segmentation in patients with FAI. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The authors retrospectively reviewed 31 hip MRI scans from 26 symptomatic patients (mean age, 27 years) with hip pain due to FAI. All patients had matched computed tomography (CT) and MRI scans of the pelvis and the knee. CT- and MRI-based osseous 3D models of the hip joint of the same patients were compared (MRI: T1 volumetric interpolated breath-hold examination high-resolution sequence; 0.8 mm3 isovoxel). CNNs were used to develop fully automatic bone segmentation of the hip joint, and the 3D models created using this method were compared with manual segmentation of CT- and MRI-based 3D models. Impingement-free ROM and location of hip impingement were calculated using previously validated collision detection software. Results: The difference between the CT- and MRI-based 3D models was <1 mm, and the difference between fully automatic and manual segmentation of MRI-based 3D models was <1 mm. The correlation of automatic and manual MRI-based 3D models was excellent and significant for impingement-free ROM (r = 0.995; P < .001), flexion (r = 0.953; P < .001), and internal rotation at 90° of flexion (r = 0.982; P < .001). The correlation for impingement-free flexion between automatic MRI-based 3D models and CT-based 3D models was 0.953 (P < .001). The location of impingement was not significantly different between manual and automatic segmentation of MRI-based 3D models, and the location of extra-articular hip impingement was not different between CT- and MRI-based 3D models. Conclusion: CNN can potentially be used in clinical practice to provide rapid and accurate 3D MRI hip joint models for young patients. The created models can be used for simulation of impingement during diagnosis of intra- and extra-articular hip impingement to enable radiation-free and patient-specific surgical planning for hip arthroscopy and open hip preservation surgery

Automated quantification of cartilage quality for hip treatment decision support

Purpose Preservation surgery can halt the progress of joint degradation, preserving the life of the hip; however, outcome depends on the existing cartilage quality. Biochemical analysis of the hip cartilage utilizing MRI sequences such as delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), in addition to morphological analysis, can be used to detect early signs of cartilage degradation. However, a complete, accurate 3D analysis of the cartilage regions and layers is currently not possible due to a lack of diagnostic tools. Methods A system for the efficient automatic parametrization of the 3D hip cartilage was developed. 2D U-nets were trained on manually annotated dual-flip angle (DFA) dGEMRIC for femoral head localization and cartilage segmentation. A fully automated cartilage sectioning pipeline for analysis of central and peripheral regions, femoral-acetabular layers, and a variable number of section slices, was developed along with functionality for the automatic calculation of dGEMRIC index, thickness, surface area, and volume. Results The trained networks locate the femoral head and segment the cartilage with a Dice similarity coefficient of 88 ± 3 and 83 ± 4% on DFA and magnetization-prepared 2 rapid gradient-echo (MP2RAGE) dGEMRIC, respectively. A completely automatic cartilage analysis was performed in 18s, and no significant difference for average dGEMRIC index, volume, surface area, and thickness calculated on manual and automatic segmentation was observed. Conclusion An application for the 3D analysis of hip cartilage was developed for the automated detection of subtle morphological and biochemical signs of cartilage degradation in prognostic studies and clinical diagnosis. The segmentation network achieved a 4-time increase in processing speed without loss of segmentation accuracy on both normal and deformed anatomy, enabling accurate parametrization. Retraining of the networks with the promising MP2RAGE protocol would enable analysis without the need for B1 inhomogeneity correction in the future

Posterior Extra-articular Ischiofemoral Impingement Can Be Caused by the Lesser and Greater Trochanter in Patients With Increased Femoral Version: Dynamic 3D CT–Based Hip Impingement Simulation of a Modified FABER Test

Background: Posterior extra-articular hip impingement has been described for valgus hips with increased femoral version (FV). These patients can present clinically with lack of external rotation (ER) and extension and with a positive posterior impingement test. But we do not know the effect of the combination of deformities, and the impingement location in early flexion is unknown. Purpose: To evaluate patient-specific 3-dimensional computed tomography (3D CT) scans of hips with increased FV and control hips for differences in range of motion, location and prevalence of osseous posterior intra- and extra-articular hip impingement. Study Design: Case series; Level of evidence, 4. Methods: Osseous 3D models based on segmentation of 3D CT scans were analyzed for 52 hips (38 symptomatic patients) with positive posterior impingement test and increased FV (>35°). There were 26 hips with an increased McKibbin instability index >70 (unstable hips). Patients were mainly female (96%), with an age range of 18 to 45 years. Of them, 21 hips had isolated increased FV (>35°); 22 hips had increased FV and increased acetabular version (AV; >25°); and 9 valgus hips (caput-collum-diaphyseal angle >139°) had increased FV and increased AV. The control group consisted of 20 hips with normal FV, normal AV, and no valgus (caput-collum-diaphyseal angle <139°). Validated 3D CT–based collision detection software for impingement simulation was used to calculate impingement-free range of motion and location of hip impingement. Surgical treatment was performed after the 3D CT–based impingement simulation in 27 hips (52%). Results: Hips with increased FV had significantly (P < .001) decreased extension and ER at 90° of flexion as compared with the control group. Posterior impingement was extra-articular (92%) in hips with increased FV. Valgus hips with increased FV and AV had combined intra- and extra-articular impingement. Posterior hip impingement occurred between the ischium and the lesser trochanter at 20° of extension and 20° of ER. Impingement was located between the ischium and the greater trochanter or intertrochanteric area at 20° of flexion and 40° of ER, with a modification of the flexion-abduction-ER (FABER) test. Conclusion: Posterior extra-articular ischiofemoral hip impingement can be caused by the lesser and greater trochanter or the intertrochanteric region. We recommend performing the modified FABER test during clinical examination in addition to the posterior impingement test for female patients with high FV. In addition, 3D CT can help for surgical planning, such as femoral derotation osteotomy and/or hip arthroscopy or resection of the lesser trochanter

Holocene landscape evolution, palaeoclimate and human impact in the Fotsch Valley, Stubai Alps, Austria: Interrogating biomarkers, stable isotopes, macrofossils and palynological indicators from a subalpine mire archive

Peatlands are receiving increasing attention in palaeoenvironmental research and represent very useful terrestrial archives for reconstructing vegetation, climate and human history. Previous palaeoenvironmental studies in the Fotsch Valley, Stubai Alps, Austria, focused on geoarchaeological investigations on the Ullafelsen representing a very important prehistorical encampment site used by Mesolithic hunter-gatherers (10.9–9.5 cal. kyr BP). In order to contribute to a better understanding of the landscape evolution of the Fotsch Valley, we here studied the close-by subalpine ‘Potsdamer Hütte Mire’ by applying radiocarbon dating as well as elemental, biomarker, compound-specific stable isotope, palynological and macrofossil analyses on bulk peat samples. The calculated age-depth model using R Bacon indicates the beginning of peat formation during the Early Holocene and shows a strongly reduced peat accumulation rate (PAR) from 170 to 121 cm depth (8.5–2.1 cal. kyr BP) and/or a striking hiatus. Results of leaf wax-derived n-alkane biomarkers as well as macrofossils and palynological indicators reflect the local presence of coniferous trees and the synchronous expansion of deciduous trees during the Early Holocene. The above-mentioned strongly reduced PAR and/or hiatus coincides with the Neolithic, the Bronze and the Iron Age, and goes hand in hand with strong changes in vegetation and an increase of micro-charcoal and black carbon. Despite age uncertainties, these changes can be explained with strongly increasing human and livestock activities in form of deforestation, domestic fires and the beginning of Alpine pastoralism. The latter is confirmed by the finding of pasture and cultural indicator pollen (Cerealia-type, Rumex, Plantago lanceolata, Poaceae) occurring since the Middle to Late Bronze Age. The oxygen isotope composition of sugar biomarkers (δ18Osugars) likely reflects the dry versus humid climatic variability associated with the Holocene climatic optimum during the Mesolithic, the Roman Age, the Late Antique Little Ice Age, the Middle Ages and the Little Ice Age

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease