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BACKGROUND: Cardiovascular magnetic resonance (CMR) derived global function index (GFI) and myocardial contraction fraction (MCF) were identified as useful imaging markers to assess left ventricular (LV) cardiac performance and can provide prognostic information for several cardiac diseases. As pediatric reference values are lacking, the aim of this retrospective study was to establish these values. METHODS: 154 CMR examinations of healthy children and adolescents (4-18 years) were included. LV end-diastolic, end-systolic and stroke volumes, ejection fraction (LVEF) and myocardial mass were measured using short axis stacks. Results were used to calculate LVGFI and LVMCF. Statistically, the Lambda-Mu-Sigma (LMS)-method was applied to create percentile curves and tables. RESULTS: The mean age (standard deviation) of the subjects was 13.8 (2.8) years, 102 were male (66%). Mean LVGFI was 46.3 (6.0)% and mean LVMCF was 110.6 (19.9) %. Both, LVGFI and LVMCF decreased significantly with age (LVGFI: r = -0.30, p < 0.001; LVMCF: -0.30, p < 0.001). There was no statistical difference between girls and boys (p all >0.05). Strong correlations between LVGFI and LVMCF (r = 0.78, p < 0.001) as well as between LVGFI and LVEF (r = 0.80, p < 0.001) were documented whereas the correlation of LVMCF and LVEF was weaker (r = 0.32, p < 0.001). Univariable and multivariable regression analysis demonstrated that LVGFI was strongly associated with age whereas LVMCF was associated with weight. Percentile curves and tables were created accordingly. CONCLUSION: We provide pediatric CMR reference values for the new cardiac functional markers LVGFI and LVMCF. These may improve the interpretation of clinical CMR studies and can be used for future research studies.
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The objective of this study was to investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. We included data from 4367 patients with idiopathic PD, 159 patients with GBA1-PD, and 3090 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The association between PGS and lifestyle factors on AAO was assessed with linear and Cox proportional hazards models. The PGS showed a negative association with AAO (ß = - 1.07, p = 6 × 10-7) in patients with idiopathic PD. The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p = 0.0001), 44% (p < 2 × 10-16), and 55% (p < 2 × 10-16), compared to no use. An additive effect of aspirin (ß = 7.62, p = 9 × 10-7) and PGS (ß = - 1.58, p = 0.0149) was found for AAO without an interaction (p = 0.9993) in the linear regressions, and similar effects were seen for tobacco. In contrast, no association between aspirin intake and AAO was found in GBA1-PD (p > 0.05). In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect.
Subject(s)
Age of Onset , Life Style , Multifactorial Inheritance , Parkinson Disease , Humans , Parkinson Disease/genetics , Parkinson Disease/epidemiology , Female , Male , Middle Aged , Aged , Genetic Predisposition to Disease , Proportional Hazards Models , Glucosylceramidase/genetics , Case-Control Studies , Risk Factors , Aspirin/therapeutic useABSTRACT
BACKGROUND: Diabetic patients with coronary artery disease may benefit from elective coronary artery bypass graft (CABG) surgery. It is unknown whether this merit is transferable to patients with acute myocardial infarction (AMI) undergoing surgery. METHOD: A total of 1,427 patients underwent CABG within 48 hours of being diagnosed with AMI at the current institution between 2001 and 2019. Of these patients, 206 (14.4%) had insulin-dependent diabetes mellitus (IDDM) and 148 (10.4%) had non-insulin dependent diabetes mellitus (NIDDM). Retrospective data analysis was performed. RESULTS: Patients with NIDDM showed the highest perioperative risk profile, with a EuroScore II of 11.6 (±10.3) compared with 7.8 (±8.0) in non-diabetic patients and 8.4 (±7.8) in patients with IDDM (p<0.001). Sub-analysis demonstrated a higher proportion of non-ST-elevation myocardial infarction patients in the NIDDM cohort compared with the IDDM cohort (70.9% vs 56.8%; p=0.005). Postoperatively, NIDDM patients had more sepsis (p<0.01) and longer ventilation times (p<0.001) compared with non-DM and IDDM patients (p<0.01). Wound healing complications were rare, but almost twice as high in NIDDM patients compared with non-DM and IDDM patients (4.7% vs 0.9% vs 2.4%, respectively). The 30-day mortality was highest in the NIDDM cohort (18.3% vs 11.3% vs 7.8%; p=0.012). Analysis of survival for up to 15 years revealed a significantly reduced survival of diabetic patients compared with non-diabetic patients, with lowest survival rates in NIDDM patients (p<0.001). CONCLUSIONS: Non-insulin dependent diabetes mellitus patients undergoing CABG within 48 hours of being diagnosed with AMI are at increased risk of short-term and long-term complications. Therefore, this particular group should undergo a careful evaluation concerning the expected risks and benefits of CABG in this setting.
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Linear regression (LR) is vastly used in data analysis for continuous outcomes in biomedicine and epidemiology. Despite its popularity, LR is incompatible with missing data, which frequently occur in health sciences. For parameter estimation, this shortcoming is usually resolved by complete-case analysis or imputation. Both work-arounds, however, are inadequate for prediction, since they either fail to predict on incomplete records or ignore missingness-induced reduction in prediction accuracy and rely on (unrealistic) assumptions about the missing mechanism. Here, we derive adaptive predictor-set linear model (aps-lm), capable of making predictions for incomplete data without the need for imputation. It is derived by using a predictor-selection operation, the Moore-Penrose pseudoinverse, and the reduced QR decomposition. aps-lm is an LR generalization that inherently handles missing values. It is applied on a reference data set, where complete predictors and outcome are available, and yields a set of privacy-preserving parameters. In a second stage, these are shared for making predictions of the outcome on external data sets with missing entries for predictors without imputation. Moreover, aps-lm computes prediction errors that account for the pattern of missing values even under extreme missingness. We benchmark aps-lm in a simulation study. aps-lm showed greater prediction accuracy and reduced bias compared to popular imputation strategies under a wide range of scenarios including variation of sample size, goodness of fit, missing value type, and covariance structure. Finally, as a proof-of-principle, we apply aps-lm in the context of epigenetic aging clocks, linear models that predict a person's biological age from epigenetic data with promising clinical applications.
Subject(s)
Biometry , Linear Models , Biometry/methods , HumansABSTRACT
CONTEXT: Reliable estradiol (E2) reference intervals (RIs) are crucial in pediatric endocrinology. OBJECTIVES: This study aims to develop a sensitive ultra-performance liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method for E2 in serum, to establish graphically represented RI percentiles and annual RIs for both sexes, and to perform a systematic literature comparison. METHODS: First, a UPLC-MS/MS method for E2 was developed. Second, graphically represented RI percentiles and annual RIs covering 0-18 years were computed (cohort of healthy children [1181 girls and 543 boys]). Subsequently, RIs were compared with published data by systematic searches. RESULTS: Lower limit of quantification was 11â pmol/L, indicating high sensitivity. Estradiol first peaked during mini-puberty in both sexes (girls up to 192â pmol/L; boys up to 225â pmol/L). As could be expected, girls showed higher pubertal E2 (up to 638â pmol/L). However, boys' RIs (up to 259â pmol/L) overlapped considerably. We found 4 studies in the literature that also used LC-MS/MS to determine E2 and published RIs for the complete pediatric age range. Reference intervals varied considerably. Pre-pubertal and pubertal phases were present in all studies. Higher E2 during the time of mini-puberty in both sexes was documented in 3 studies including ours. CONCLUSIONS: Variability of RIs for E2 between studies illustrates the importance of laboratory-specific RIs despite using a LC-MS/MS reference method. In boys, the striking E2 peak during mini-puberty as well as high pubertal E2 without phenotypic estrogenization in regular male puberty indicates that the role of E2 in children and, especially in boys, requires better functional understanding.
Subject(s)
Estradiol , Puberty , Tandem Mass Spectrometry , Humans , Male , Tandem Mass Spectrometry/methods , Child , Estradiol/blood , Female , Reference Values , Child, Preschool , Adolescent , Infant , Chromatography, Liquid/methods , Chromatography, Liquid/standards , Puberty/blood , Puberty/physiology , Infant, Newborn , Sexual Maturation/physiologyABSTRACT
BACKGROUND: Cardiovascular magnetic resonance (CMR) has established itself as the gold standard for serial assessment of systemic right ventricular (RV) performance but due to the lack of standardized RV reference values for hypoplastic left heart syndrome (HLHS) patients, the interpretation of RV volumetric data in HLHS remains difficult. Therefore, this study aimed to close this gap by providing CMR reference values for the systemic RV in HLHS patients. METHODS: CMR scans of 160 children, adolescents, and young adults (age range 2.2-25.2 years, 106 males) with HLHS were retrospectively evaluated. All patients were studied following total cavopulmonary connection. Short-axis stacks were used to measure RV end-diastolic and end-systolic volumes (RVEDV, RVESV), RV stroke volume (RVSV), RV ejection fraction (RVEF), and RV end-diastolic myocardial mass (RVEDMM). Univariable and multiple linear regression analyses were performed to assess associations between RV parameters and demographic and anthropometric characteristics. Following the results of the regression analysis, reference graphs and tables were created with the Lambda-Mu-Sigma method. RESULTS: Multiple linear regression analysis showed strong associations between body height and RVEDV, RVESV as well as RVSV. Age was highly associated with RVEDMM. Therefore, percentile curves and tables were created with respect to body height (RVEDV, RVESV, RVSV) and age (RVEDMM). The influence of demographic and anthropometric parameters on RVEF was mild, thus no percentile curves and tables for RVEF are provided. CONCLUSION: We were able to define CMR reference values for RV volumetric variables for HLHS patients. These data might be useful for the assessment and interpretation of CMR scans in these patients and for research in this field.
Subject(s)
Heart Ventricles , Hypoplastic Left Heart Syndrome , Magnetic Resonance Imaging, Cine , Predictive Value of Tests , Stroke Volume , Ventricular Function, Right , Humans , Male , Female , Hypoplastic Left Heart Syndrome/diagnostic imaging , Hypoplastic Left Heart Syndrome/physiopathology , Hypoplastic Left Heart Syndrome/surgery , Retrospective Studies , Adolescent , Young Adult , Child , Adult , Child, Preschool , Reference Values , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Age Factors , Reproducibility of ResultsABSTRACT
BACKGROUND: Vulnerability to infectious diseases in refugees is dependent on country of origin, flight routes, and conditions. Information on specific medical needs of different groups of refugees is lacking. We assessed the prevalence of infectious diseases, immunity to vaccine-preventable diseases, and chronic medical conditions in children, adolescents, and adult refugees from Ukraine who arrived in Germany in 2022. METHODS: Using different media, we recruited Ukrainian refugees at 13 sites between 9-12/2022. An antigen test for acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, serologies for a range of vaccine-preventable diseases, as well as interferon gamma release assays (IGRAs) for tuberculosis (TB), and SARS-CoV-2 were performed. We assessed personal and family history of chronic medical conditions, infectious diseases, vaccination status, and conditions during migration. RESULTS: Overall, 1793 refugees (1401 adults and 392 children/adolescents) were included. Most participants were females (n = 1307; 72·3%) and from Eastern or Southern Ukraine. TB IGRA was positive in 13% (n = 184) of the adults and in 2% (n = 7) of the children. Serology-based immunological response was insufficient in approximately 21% (360/1793) of the participants for measles, 32% (572/1793) for diphtheria, and 74% (1289/1793) for hepatitis B. CONCLUSIONS: We show evidence of low serological response to vaccine-preventable infections and increased LTBI prevalence in Ukrainian refugees. These findings should be integrated into guidelines for screening and treatment of infectious diseases in migrants and refugees in Germany and Europe. Furthermore, low immunity for vaccine-preventable diseases in Ukrainians independent of their refugee status, calls for tailor-made communication efforts.
Subject(s)
Communicable Diseases , Eastern European People , Refugees , Tuberculosis , Vaccine-Preventable Diseases , Adolescent , Adult , Child , Female , Humans , Male , Communicable Diseases/epidemiology , Cross-Sectional Studies , Germany/epidemiology , Prevalence , Tuberculosis/epidemiology , Tuberculosis/prevention & control , UniversitiesABSTRACT
Background: The design of appropriate consent procedures for the secondary use of personal health data is a key concern of current medical research. In Germany, the concept of 'data donation' has recently come into focus, defined as a legal entitlement to the research use of personal medical data without prior consent, combined with an easy-to-exercise right of the data subjects to opt-out. Methods: Standardized online interviews of 3,013 individuals, representative of the German online population, were conducted in August 2022 to determine their attitude towards data donation for medical research. Results: A majority of participants supported a consent-free data donation regulation, both for publicly funded (85.1%) and for private medical research (66.4%). Major predictors of a positive attitude towards data donation included (i) sufficient appreciation of the respective kind of research (i.e. public or private), (ii) a reciprocity attitude that patients who benefit from research have a duty to support research, and (iii) sufficient trust in data protection and data control. Conclusion: People's attitude towards data donation to medical research is generally positive in Germany and depends upon factors that can be curbed by legislation and internal rules of procedure. Worthy of note, designing data donation in the form of an opt-out regulation does not necessarily mean that the paradigm of informedness has to be abandoned. Rather the process of information provision must be shifted towards the creation of basic knowledge in the general population about the risks and benefits of data-intensive medical research ('health data literacy').
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In forensics investigations, it is common to encounter biological mixtures consisting of homogeneous or heterogeneous components from multiple individuals and with different genetic contributions. One promising mixture deconvolution strategy is the DEPArray™ technology, which enables the separation of cell populations before genetic analysis. While technological advances are fundamental, their reliable validation is crucial for successful implementation and use for casework. Thus, this study aimed to 1) systematically validate the DEPArray™ system concerning specificity, sensitivity, repeatability, and contamination occurrences for blood, epithelial, and sperm cells, and 2) evaluate its potential for single-cell analysis in the field of forensic science. Our findings confirmed the effective identification of different cell types and the correct assignment of successfully genotyped single cells to their respective donor(s). Using the NGM Detect™ Amplification Kit, the average profile completeness for diploid cells was approximately 80%, with â¼ 290 RFUs. In contrast, haploid sperm analysis yielded an average completeness of 51% referring to the haploid reference profile, accompanied by mean peak heights of â¼ 176 RFUs. Although certain alleles of heterozygous loci in diploid cells showed strong imbalances, the overall peak balances yielded acceptable values above ≥ 60% with a mean value of 72% ± 0.21, a median of 77%, but with a maximum imbalance of 9% between heterozygous peaks. Locus dropouts were considered stochastic events, exhibiting variations among donors and cell types, with a notable failure incidence observed for TH01. Within the wet-lab experimentation with >500 single cells for the validation, profiling was performed using the consensus approach, where profiles were selected randomly from all data to better mirror real casework results. Nevertheless, complete profiles could be achieved with as few as three diploid cells, while the average success rate increased to 100% when using profiles of 6-10 cells. For sperms, however, a consensus profile with completeness >90% of the autosomal diploid genotype could be attained using ≥15 cells. In addition, the robustness of the consensus approach was evaluated in the absence of the respective reference profile without severe deterioration. Here, increased stutter peaks (≥ 15%) were found as the main artifact in single-cell profiles, while contamination and drop-ins were ascertained as rare events. Lastly, the technique's potential and limitations are discussed, and practical guidance is provided, particularly valuable for cold cases, multiple perpetrator rapes, and analyses of homogeneous mixed evidence.
Subject(s)
DNA Fingerprinting , Semen , Humans , Male , DNA Fingerprinting/methods , Microsatellite Repeats , Polymerase Chain Reaction/methods , SpermatozoaABSTRACT
Objective: To investigate the association between a Parkinson's disease (PD)-specific polygenic score (PGS) and protective lifestyle factors on age at onset (AAO) in PD. Methods: We included data from 4375 patients with idiopathic PD, 167 patients with GBA1-PD, and 3091 healthy controls of European ancestry from AMP-PD, PPMI, and Fox Insight cohorts. The PGS was calculated based on a previously proposed composition of 1805 variants. The association between PGS and lifestyle factors (i.e., coffee, tobacco, and aspirin) on AAO was assessed with linear and Cox proportional hazards models. Results: The PGS showed a negative association with AAO (ß=-1.07, p=6×10-7). The use of one, two, or three of the protective lifestyle factors showed a reduction in the hazard ratio by 21% (p=0.0001), 45% (p<2×10-16), and 55% (p<2×10-16), respectively, compared to no use. An additive effect of aspirin (ß=7.61, p=8×10-7) and PGS (ß=-1.63, p=0.0112) was found for AAO without an interaction (p=0.9789) in the linear regressions, and similar effects were seen for tobacco. Aspirin is shown to be a better predictor of AAO (R2=0.1740) compared to coffee and tobacco use (R2=0.0243, R2=0.0295) or the PGS (R2=0.0141). In contrast, no association between aspirin and AAO was found in GBA1-PD (p>0.05). Interpretation: In our cohort, coffee, tobacco, aspirin, and PGS are independent predictors of PD AAO. Additionally, lifestyle factors seem to have a greater influence on AAO than common genetic risk variants with aspirin presenting the largest effect. External validation of our findings is needed.
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BACKGROUND: Convexity meningiomas (CM) can be successfully treated with neurosurgery. However, clinical complications due to CM have been reported. Moreover, systematic investigations of CM with respect to all relevant clinical factors are currently lacking. METHODS: We performed a systematic investigation in 210 patients with supratentorial CM considering all relevant clinical and radiological factors, with a follow-up time of 19.5 years. RESULTS: Among 812 patients with intracranial meningiomas treated in our department (2003-2020), 28.2 % of intracranial meningiomas were located over the supratentorial convexity, and the patients had a median age of 62 years (95 % CI:59-64). The median follow-up was 30.4 months (95 % CI:21.6-37.1). Tumor-related symptoms were observed in 88.1 % of patients. The most common preoperative symptom was headache (28.1 %), followed by seizure (19.5 %). Symptomatic patients had significantly higher tumor volumes than asymptomatic patients (p = 0.0003; 24.5 cm3 and 6.98 cm3, respectively). Complete tumor resection was achieved in 92.9 % of patients. The most common postoperative complication was bleeding (7.1 %) in the approach area. Of all bleedings, only three were intracerebral hemorrhages and did not require surgical intervention. The second most common complication was postoperative seizure (4.7 %). The multiple logistic regression analyses showed that tumor volume (OR:1.007; 95 % CI:1.001-1.013; p = 0.02) and brain infiltration by the tumor (OR:1.961; 95 % CI:1.028-3.741; p = 0.04) had a significant impact on postoperative complications. The postoperative and final KPS scores significantly improved (p < 0.001). The tumor recurrence rate was 6.2 %, with a median time of 38 months. No surgery-related deaths occurred. CONCLUSION: A large tumor volume and brain infiltration by the tumor were significant factors for postoperative complications. The clinical conditions significantly improved postoperatively and further during the follow-up period.
Subject(s)
Meningeal Neoplasms , Meningioma , Humans , Middle Aged , Meningioma/diagnostic imaging , Meningioma/surgery , Meningioma/complications , Neoplasm Recurrence, Local , Seizures/complications , Postoperative Complications/epidemiology , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/surgery , Meningeal Neoplasms/complications , Treatment Outcome , Retrospective StudiesABSTRACT
BACKGROUND: A mitochondrial polygenic score (MGS) is composed of genes related to mitochondrial function and found to be associated with Parkinson's disease (PD) risk. OBJECTIVE: To investigate the impact of the MGS and lifestyle/environment on age at onset (AAO) in LRRK2 p.Gly2019Ser parkinsonism (LRRK2-PD) and idiopathic PD (iPD). METHODS: We included N = 486 patients with LRRK2-PD and N = 9259 with iPD from the Accelerating Medicines Partnership® Parkinson's Disease Knowledge Platform (AMP-PD), Fox Insight, and a Tunisian Arab-Berber founder population. Genotyping data were used to perform the MGS analysis. Additionally, lifestyle/environmental data were obtained from the PD Risk Factor Questionnaire (PD-RFQ). Linear regression models were used to assess the relationship between MGS, lifestyle/environment, and AAO. RESULTS: Our derived MGS was significantly higher in PD cases compared with controls (P = 1.1 × 10-8 ). We observed that higher MGS was significantly associated with earlier AAO in LRRK2-PD (P = 0.047, ß = -1.40) and there was the same trend with a smaller effect size in iPD (P = 0.231, ß = 0.22). There was a correlation between MGS and AAO in LRRK2-PD patients of European descent (P = 0.049, r = -0.12) that was visibly less pronounced in Tunisians (P = 0.449, r = -0.05). We found that the MGS interacted with caffeinated soda consumption (P = 0.003, ß = -5.65) in LRRK2-PD and with tobacco use (P = 0.010, ß = 1.32) in iPD. Thus, patients with a high MGS had an earlier AAO only if they consumed caffeinated soda or were non-smokers. CONCLUSIONS: The MGS was more strongly associated with earlier AAO in LRRK2-PD compared with iPD. Caffeinated soda consumption or tobacco use interacted with MGS to predict AAO. Our study suggests gene-environment interactions as modifiers of AAO in LRRK2-PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Subject(s)
Parkinson Disease , Protein Serine-Threonine Kinases , Humans , Protein Serine-Threonine Kinases/genetics , Parkinson Disease/complications , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Age of Onset , Risk Factors , Life Style , MutationABSTRACT
BACKGROUND: The outcome of cochlear implantation has improved over the last decades, but there are still patients with less benefit. Despite numerous studies examining the cochlear implant (CI) outcome, variations in speech comprehension with CI remains incompletely explained. The aim of this study was therefore to examine preoperative pure-tone audiogram and speech comprehension as well as aetiology, to investigate their relationship with postoperative speech comprehension in CI recipients. METHODS: A retrospective study with 664 ears of 530 adult patients was conducted. Correlations between the target variable postoperative word comprehension with the preoperative speech and sound comprehension as well as aetiology were investigated. Significant correlations were inserted into multivariate models. Speech comprehension measured as word recognition score at 70 dB with CI was analyzed as (i) a continuous and (ii) a dichotomous variable. RESULTS: All variables that tested preoperative hearing were significantly correlated with the dichotomous target; with the continuous target, all except word comprehension at 65 dB with hearing aid. The strongest correlation with postoperative speech comprehension was seen for monosyllabic words with hearing aid at 80 dB. The preoperative maximum word comprehension was reached or surpassed by 97.3% of CI patients. Meningitis and congenital diseases were strongly negatively associated with postoperative word comprehension. The multivariate model was able to explain 40% of postoperative variability. CONCLUSION: Speech comprehension with hearing aid at 80 dB can be used as a supplementary preoperative indicator of CI-aided speech comprehension and should be measured regularly in the clinical routine. Combining audiological and aetiological variables provides more insights into the variability of the CI outcome, allowing for better patient counselling.
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Since their first appearance in the context of schizophrenia and bipolar disorder in 2009, polygenic risk scores (PRSs) have been described for a large number of common complex diseases. However, the clinical utility of PRSs in disease risk assessment or therapeutic decision making is likely limited because PRSs usually only account for the heritable component of a trait and ignore the etiological role of environment and lifestyle. We surveyed the current state of PRSs for various diseases, including breast cancer, diabetes, prostate cancer, coronary artery disease, and Parkinson disease, with an extra focus upon the potential improvement of clinical scores by their combination with PRSs. We observed that the diagnostic and prognostic performance of PRSs alone is consistently low, as expected. Moreover, combining a PRS with a clinical score at best led to moderate improvement of the power of either risk marker. Despite the large number of PRSs reported in the scientific literature, prospective studies of their clinical utility, particularly of the PRS-associated improvement of standard screening or therapeutic procedures, are still rare. In conclusion, the benefit to individual patients or the health care system in general of PRS-based extensions of existing diagnostic or treatment regimens is still difficult to judge.
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PURPOSE: The role of positive endexpiratory pressure (PEEP) for successful cannulation of the subclavian vein (SCV) remains inconclusive. The aim of our study was to assess the effect of different levels of PEEP on distance from SCV to parietal pleura (DVP) and on the cross-sectional area (CSA) of the SCV. METHODS: Invasive mechanically ventilated adult patients with a clinical indication for a stepwise PEEP-trial (0, 5, 10, and 15 cm H2O) were included in this prospective observational single-center study. Ultrasound examinations of SCV were performed with a linear ultrasound probe using the infraclavicular view. DVP and CSA were measured on the right and left bodyside. Examinations were repeated at each PEEP step. RESULTS: 27 patients were enrolled (12 female; 60±21 years; BMI 24.6±4.9 kg/m2; 20 patients on controlled, 7 on assisted ventilation). A statistically significant increase of DVP in the in-plane view was found on the left side which was not clinically relevant. No significant differences of DVP were observed in all other views. PEEP induced changes in CSAs were statistically significant but clinically not relevant on both sides. The largest change in CSA (2mm2) was observed when comparing PEEP 10 with PEEP 0 cm H2O. CONCLUSION: A stepwise PEEP increase was not associated with clinically relevant changes of the DVP and CSA. Thus, a PEEP-optimization for the cannulation of the subclavian vein is not indicated.
Subject(s)
Catheterization, Central Venous , Subclavian Vein , Adult , Humans , Female , Subclavian Vein/diagnostic imaging , Respiration, Artificial , Positive-Pressure Respiration , PleuraABSTRACT
Variation in apolipoprotein E (APOE) has been shown to have the strongest genetic effect on human longevity. The aim of this study was to unravel the evolutionary history of the three major APOE alleles in Europe by analysing ancient samples up to 12,000 years old. We detected significant allele frequency shifts between populations and over time. Our analyses indicated that selection led to large frequency differences between the earliest European populations (i.e., hunter-gatherers vs. first farmers), possibly due to changes in diet/lifestyle. In contrast, the allele distributions in populations from ~4000 BCE onward can mainly be explained by admixture, suggesting that it also played an important role in shaping current APOE variation. In any case, the resulting allele frequencies strongly influence the predisposition for longevity today, likely as a consequence of past adaptations and demographic processes.
Subject(s)
Apolipoproteins E , Longevity , Humans , Infant, Newborn , Alleles , Gene Frequency/genetics , Longevity/genetics , Apolipoproteins E/genetics , EuropeABSTRACT
BACKGROUND: Peritumoral brain edema (PTBE) is a common complication related to intracranial meningiomas. In several studies, researchers have investigated the pathogenesis of PTBE, and the factors involved in its development in patients with intracranial meningiomas have been reported. However, very little is known about the clinical effect of PTBE on patients with intracranial meningiomas; therefore, a systematic examination of this matter is necessary. METHODS: In this study, we performed a systematic examination of 696 patients with primary intracranial meningiomas to assess the effect of preoperative PTBE on preoperative symptoms, neurological deficits and postoperative complications, and long-term outcomes with a follow-up period of 16.8 years. We performed a univariate analysis and multiple regression for specific outcomes and adjusted for other relevant clinical factors. RESULTS: A total of 627 (90.1%) patients were symptomatic preoperatively. One hundred eighty-eight (90.8%) patients with small to moderate PTBE and 125 (98.4%) patients with severe PTBE presented with symptoms significantly more often than the 314 (86.7%) patients without PTBE (p < 0.001, univariate analysis). Cognitive deficits, palsy and seizure were significantly more present, preoperatively, in patients with PTBE than in patients without PTBE (p < 0.001, univariate analysis). Two hundred fifty-five (36.6%) patients experienced surgical and systemic complications postoperatively. The complication rate was significantly higher in patients with PTBE; 41.5% for patients with small to moderate PTBE and 52.8% for patients with severe PTBE, compared to 28.2% of patients without PTBE (p < 0.001, univariate analysis). Furthermore, pre- and postoperative KPS scores were significantly lower in patients with PTBE (p < 0.001). Patients with PTBE required additional medical support significantly more often (p < 0.001) and had a significantly longer hospital stay (p < 0.001). The mortality rate was higher in patients with PTBE immediately after surgery and in the follow-up period; however, the difference was not significant. The neurological condition of all patients improved in the follow-up and did not show significant differences between patients with and without preoperative PTBE (p = 0.6361). Multiple logistic regression analyses revealed a significant association between PTBE and the presence of preoperative cognitive deficits, the incidences of seizure and postoperative complications, and low pre- and postoperative KPS scores. CONCLUSIONS: Preoperative PTBE significantly increased the incidences of specific preoperative symptoms, neurological deficits and postoperative complications in patients with intracranial meningiomas. After surgery, patients with preoperative PTBE required medical support significantly more often than patients without PTBE. However, all patients had favorable outcomes after surgery.
Subject(s)
Brain Edema , Meningeal Neoplasms , Meningioma , Humans , Meningioma/complications , Meningioma/surgery , Meningioma/pathology , Meningeal Neoplasms/complications , Meningeal Neoplasms/surgery , Meningeal Neoplasms/pathology , Brain Edema/complications , Seizures/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective StudiesABSTRACT
BACKGROUND: Measurement of atrial volumes by MRI is becoming increasingly important in pediatric cardiac disorders. However, MRI normal values for atrial volumes in children are lacking. PURPOSE: To establish pediatric reference values for atrial volumes. STUDY TYPE: Retrospective. SUBJECTS: A total of 155 healthy children from two large institutions (103 male, age 13.9 ± 2.8 years, range 4-18 years). FIELD STRENGTH/SEQUENCE: A 1.5 T; balanced steady-state free precession (bSSFP) sequence. ASSESSMENT: The monoplane and biplane area-length methods were used to measure minimal and maximal left and right atrial volumes (LAmin , LAmax , RAmin , and RAmax ) from four-chamber (4ch) and two-chamber (2ch) MR cine images. Centile charts and tables for atrial volumes were created. STATISTICAL TESTS: Descriptive statistics, lambda-mu-sigma (LMS)-method of Cole and Green, univariable and multivariable linear regression models. A P value < 0.05 was considered to be statistically significant. RESULTS: In the multivariable linear model, body surface area was significantly associated with all atrial volumes and sex was significantly associated with RA volumes, LA volumes measured in the 2ch-view as well as biplane LAmax. Average atrial volumes measured: monoplane 4ch: LAmin 13.1 ± 4.8 mL/m2 , LAmax 33.4 ± 8.8 mL/m2 , RAmin 18.5 ± 6.8 mL/m2 , RAmax 33.2 ± 9.6 mL/m2 ; monoplane 2ch: LAmin 12.7 ± 4.9 mL/m2 , LAmax 30.5 ± 9.5 mL/m2 ; biplane: LAmin 12.3 ± 4.5 mL/m2 , LAmax 30.9 ± 8.7 mL/m2 . DATA CONCLUSION: Pediatric MRI reference values for atrial volumes have been provided. TECHNICAL EFFICACY: 2 EVIDENCE LEVEL: 4.
Subject(s)
Heart Diseases , Magnetic Resonance Imaging , Humans , Child , Male , Child, Preschool , Adolescent , Reference Values , Retrospective Studies , Magnetic Resonance Imaging/methods , Heart Atria/diagnostic imaging , Magnetic Resonance Imaging, Cine/methodsABSTRACT
BACKGROUND: Measurement of ventricular volumes and function using MRI is an important tool in pediatric congenital heart disease. However, normal values for children are sparce and analysis methods are inconsistent. PURPOSE: To propose biventricular reference values in children for two MRI postprocessing (contouring) techniques. STUDY TYPE: Retrospective. SUBJECTS: A total of 154 children from two institutions (13.9 ± 2.8 years; 101 male) that were referred for a clinical MRI study. FIELD STRENGTH/SEQUENCE: 1.5 T; balanced steady-state free precession (bSSFP) sequence. ASSESSMENT: Left ventricular (LV) and right ventricular (RV) end-diastolic and end-systolic volumes (LVEDV, LVESV, RVEDV, RVESV) and end-diastolic and end-systolic myocardial mass (LVEDMM, LVESMM, RVEDMM, RVESMM) were measured from short-axis images using two contouring techniques: 1) papillary muscles, trabeculations and the moderator band were included in the ventricular blood volume and excluded from the myocardial mass, 2) papillary muscles, trabeculations and the moderator band were excluded from the ventricular volume and included in the ventricular mass. STATISTICAL TESTS: Univariable and multivariable linear regression models were used to evaluate relationships between sex, weight, height, body surface area (BSA) and age and volumetric results. Reference graphs and tables were created with the LMS-method. Contouring techniques were compared by intraclass correlation, regression analysis and Bland-Altman plots. A P value < 0.05 was considered statistically significant. RESULTS: Height and BSA were significantly associated with LVESV (method 1) and with LVEDV and RVEDV (method 2). LVESV (method 2), RVESV (both methods), RVEDV (method 1), and LVEDMM and RVEDMM (both methods), showed significant associations with height and weight. LVSV and RVSV (both methods) were significantly associated with BSA and weight. RVESV (method 1) was significantly associated with age. Gender showed significant associations for all parameters. DATA CONCLUSION: The proposed pediatric reference values can be used in the diagnosis and follow-up of congenital or acquired heart disease and for research purposes. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.