Longitudinal Clinical Studies Research Articles

Perspectives of pregnant and breastfeeding women on longitudinal clinical studies that require non-invasive biospecimen collection \u2013 a qualitative study

BackgroundInvestigation of the microbiome during early life has stimulated an increasing number of cohort studies in pregnant and breastfeeding women that require non-invasive biospecimen collection. The objective of this study was to explore pregnant and breastfeeding women’s perspectives on longitudinal clinical studies that require non-invasive biospecimen collection and how they relate to study logistics and research participation.MethodsWe completed in-depth semi-structured interviews with 40 women who were either pregnant (n = 20) or breastfeeding (n = 20) to identify their understanding of longitudinal clinical research, the motivations and barriers to their participation in such research, and their preferences for providing non-invasive biospecimen samples.ResultsPerspectives on research participation were focused on breastfeeding and perinatal education. Participants cited direct benefits of research participation that included flexible childcare, lactation support, and incentives and compensation. Healthcare providers, physician offices, and social media were cited as credible sources and channels for recruitment. Participants viewed lengthy study visits and child protection as the primary barriers to research participation. The barriers to biospecimen collection were centered on stool sampling, inadequate instructions, and drop-off convenience.ConclusionWomen in this study were interested in participating in clinical studies that require non-invasive biospecimen collection, and motivations to participate center on breastfeeding and the potential to make a scientific contribution that helps others. Effectively recruiting pregnant or breastfeeding participants for longitudinal microbiome studies requires protocols that account for participant interests and consideration for their time.

Prenatal Cannabinoid Exposure: Emerging Evidence of Physiological and Neuropsychiatric Abnormalities.

Clinical reports of cannabis use prevalence during pregnancy vary widely from 3% to upwards of 35% in North America; this disparity likely owing to underestimates from self-reporting in many cases. The rise in cannabis use is mirrored by increasing global legalization and the overall perceptions of safety, even during pregnancy. These trends are further compounded by a lack of evidence-based policy and guidelines for prenatal cannabis use, which has led to inconsistent messaging by healthcare providers and medically licensed cannabis dispensaries regarding prenatal cannabis use for treatment of symptoms, such as nausea. Additionally, the use of cannabis to self-medicate depression and anxiety during pregnancy is a growing medical concern. This review aims to summarize recent findings of clinical and preclinical data on neonatal outcomes, as well as long-term physiological and neurodevelopmental outcomes of prenatal cannabis exposure. Although many of the outcomes under investigation have produced mixed results, we consider these data in light of the unique challenges facing cannabis research. In particular, the limited longitudinal clinical studies available have not previously accounted for the exponential increase in (-)-Δ9– tetrahydrocannabinol (Δ9–THC; the psychoactive compound in cannabis) concentrations found in cannabis over the past two decades. Polydrug use and the long-term effects of individual cannabis constituents [Δ9–THC vs. cannabidiol (CBD)] are also understudied, along with sex-dependent outcomes. Despite these limitations, prenatal cannabis exposure has been linked to low birth weight, and emerging evidence suggests that prenatal exposure to Δ9–THC, which crosses the placenta and impacts placental development, may have wide-ranging physiological and neurodevelopmental consequences. The long-term effects of these changes require more rigorous investigation, though early reports suggest Δ9–THC increases the risk of cognitive impairment and neuropsychiatric disease, including psychosis, depression, anxiety, and sleep disorders. In light of the current trends in the perception and use of cannabis during pregnancy, we emphasize the social and medical imperative for more rigorous investigation of the long-term effects of prenatal cannabis exposure.

Deep-learning based multi-modal retinal image registration for the longitudinal analysis of patients with age-related macular degeneration.

This work reports a deep-learning based registration algorithm that aligns multi-modal retinal images collected from longitudinal clinical studies to achieve accuracy and robustness required for analysis of structural changes in large-scale clinical data. Deep-learning networks that mirror the architecture of conventional feature-point-based registration were evaluated with different networks that solved for registration affine parameters, image patch displacements, and patch displacements within the region of overlap. The ground truth images for deep learning-based approaches were derived from successful conventional feature-based registration. Cross-sectional and longitudinal affine registrations were performed across color fundus photography (CFP), fundus autofluorescence (FAF), and infrared reflectance (IR) image modalities. For mono-modality longitudinal registration, the conventional feature-based registration method achieved mean errors in the range of 39-53 µm (depending on the modality) whereas the deep learning method with region overlap prediction exhibited mean errors in the range 54-59 µm. For cross-sectional multi-modality registration, the conventional method exhibited gross failures with large errors in more than 50% of the cases while the proposed deep-learning method achieved robust performance with no gross failures and mean errors in the range 66-69 µm. Thus, the deep learning-based method achieved superior overall performance across all modalities. The accuracy and robustness reported in this work provide important advances that will facilitate clinical research and enable a detailed study of the progression of retinal diseases such as age-related macular degeneration.

Development of a Basic Root canal Treatment (BRT) for primary oral health care — evaluation after one year

Atraumatic Restorative Treatment (ART) was a major step forward in community dentistry but treatment options for deep carious lesions or pulp involvement still focus on tooth extraction in under-served areas worldwide. To bridge the gap between ART and extraction this pilot study aimed to develop and follow-up a basic root canal treatment for rural dental health facilities in the Republic of The Gambia (West Africa), faced with an environment lacking technical equipment and developing primary oral health care. 25 single rooted teeth with acute irreversible pulpitis were root canal treated with a standardised endodontic instrument kit and a specific procedure. A step-back technique was used with intermittent chlorhexidine 0.2% and saline irrigation. Root canal obturation was performed using a single-cone technique with gutta-percha using Grossman's root canal cement. Coronal filling was carried out by using ART. Clinical examinations were documented before treatment, one day, five days, six months and twelve months postoperatively. None of the root canal fillings had to be revised due to postoperative complications. In 9 out of 25 teeth, transitory apical pain disappeared after a few days. After six months, all ART fillings appeared clinically acceptable, two fillings had to be corrected. Four class II restorations and three class IV restorations needed replacement after 12 months. Patients' assessment of health related quality of life improved significantly, especially concerning dental pain, chewing ability and fitness for work. Preliminary clinical follow-ups showed encouraging results for the basic root canal treatment approach. Longitudinal clinical studies with greater populations are required to substantiate these results. Modifications in the coronal filling technique are preferable to improve the clinical performance of extended ART cavity restorations.

Quantitative Multi-Parameter Mapping Optimized for the Clinical Routine.

Using quantitative multi-parameter mapping (MPM), studies can investigate clinically relevant microstructural changes with high reliability over time and across subjects and sites. However, long acquisition times (20 min for the standard 1-mm isotropic protocol) limit its translational potential. This study aimed to evaluate the sensitivity gain of a fast 1.6-mm isotropic MPM protocol including post-processing optimized for longitudinal clinical studies. 6 healthy volunteers (35±7 years old; 3 female) were scanned at 3T to acquire the following whole-brain MPM maps with 1.6 mm isotropic resolution: proton density (PD), magnetization transfer saturation (MT), longitudinal relaxation rate (R1), and transverse relaxation rate (R2*). MPM maps were generated using two RF transmit field (B1+) correction methods: (1) using an acquired B1+ map and (2) using a data-driven approach. Maps were generated with and without Gibb's ringing correction. The intra-/inter-subject coefficient of variation (CoV) of all maps in the gray and white matter, as well as in all anatomical regions of a fine-grained brain atlas, were compared between the different post-processing methods using Student's t-test. The intra-subject stability of the 1.6-mm MPM protocol is 2–3 times higher than for the standard 1-mm sequence and can be achieved in less than half the scan duration. Intra-subject variability for all four maps in white matter ranged from 1.2–5.3% and in gray matter from 1.8 to 9.2%. Bias-field correction using an acquired B1+ map significantly improved intra-subject variability of PD and R1 in the gray (42%) and white matter (54%) and correcting the raw images for the effect of Gibb's ringing further improved intra-subject variability in all maps in the gray (11%) and white matter (10%). Combining Gibb's ringing correction and bias field correction using acquired B1+ maps provides excellent stability of the 7-min MPM sequence with 1.6 mm resolution suitable for the clinical routine.

Small molecule modulation of the p75 neurotrophin receptor inhibits multiple amyloid beta-induced tau pathologies

Longitudinal preclinical and clinical studies suggest that Aβ drives neurite and synapse degeneration through an array of tau-dependent and independent mechanisms. The intracellular signaling networks regulated by the p75 neurotrophin receptor (p75NTR) substantially overlap with those linked to Aβ and to tau. Here we examine the hypothesis that modulation of p75NTR will suppress the generation of multiple potentially pathogenic tau species and related signaling to protect dendritic spines and processes from Aβ-induced injury. In neurons exposed to oligomeric Aβ in vitro and APP mutant mouse models, modulation of p75NTR signaling using the small-molecule LM11A-31 was found to inhibit Aβ-associated degeneration of neurites and spines; and tau phosphorylation, cleavage, oligomerization and missorting. In line with these effects on tau, LM11A-31 inhibited excess activation of Fyn kinase and its targets, tau and NMDA-NR2B, and decreased Rho kinase signaling changes and downstream aberrant cofilin phosphorylation. In vitro studies with pseudohyperphosphorylated tau and constitutively active RhoA revealed that LM11A-31 likely acts principally upstream of tau phosphorylation, and has effects preventing spine loss both up and downstream of RhoA activation. These findings support the hypothesis that modulation of p75NTR signaling inhibits a broad spectrum of Aβ-triggered, tau-related molecular pathology thereby contributing to synaptic resilience.

Updating exposure assessment for skin sensitization quantitative risk assessment for fragrance materials

In 2008, a proposal for assessing the risk of induction of skin sensitization to fragrance materials Quantitative Risk Assessment 1 (QRA1) was published. This was implemented for setting maximum limits for fragrance materials in consumer products. However, there was no formal validation or empirical verification after implementation. Additionally, concerns remained that QRA1 did not incorporate aggregate exposure from multiple product use and included assumptions, e.g. safety assessment factors (SAFs), that had not been critically reviewed. Accordingly, a review was undertaken, including detailed re-evaluation of each SAF together with development of an approach for estimating aggregate exposure of the skin to a potential fragrance allergen. This revision of QRA1, termed QRA2, provides an improved method for establishing safe levels for sensitizing fragrance materials in multiple products to limit the risk of induction of contact allergy. The use of alternative non-animal methods is not within the scope of this paper. Ultimately, only longitudinal clinical studies can verify the utility of QRA2 as a tool for the prevention of contact allergy to fragrance materials.

A Bayesian natural cubic B-spline varying coefficient method for non-ignorable dropout

BackgroundDropout is a common problem in longitudinal clinical trials and cohort studies, and is of particular concern when dropout occurs for reasons that may be related to the outcome of interest. This paper reviews common parametric models to account for dropout and introduces a Bayesian semi-parametric varying coefficient model for exponential family longitudinal data with non-ignorable dropout.MethodsTo demonstrate these methods, we present results from a simulation study and estimate the impact of drug use on longitudinal CD4 + T cell count and viral load suppression in the Women’s Interagency HIV Study. Sensitivity analyses are performed to consider the impact of model assumptions on inference. We compare results between our semi-parametric method and parametric models to account for dropout, including the conditional linear model and a parametric frailty model. We also compare results to analyses that fail to account for dropout.ResultsIn simulation studies, we show that semi-parametric methods reduce bias and mean squared error when parametric model assumptions are violated. In analyses of the Women’s Interagency HIV Study data, we find important differences in estimates of changes in CD4 + T cell count over time in untreated subjects that report drug use between different models used to account for dropout. We find steeper declines over time using our semi-parametric model, which makes fewer assumptions, compared to parametric models. Failing to account for dropout or to meet parametric assumptions of models to account for dropout could lead to underestimation of the impact of hard drug use on CD4 + cell count decline in untreated subjects. In analyses of subjects that initiated highly active anti-retroviral treatment, we find that the estimated probability of viral load suppression is lower in models that account for dropout.ConclusionsNon-ignorable dropout is an important consideration when analyzing data from longitudinal clinical trials and cohort studies. While methods that account for non-ignorable dropout must make some unavoidable assumptions that cannot be verified from the observed data, many methods make additional parametric assumptions. If these assumptions are not met, inferences can be biased, making more flexible methods with minimal assumptions important.

Salivary IgA as a Useful Biomarker for Dental Caries in Down's Syndrome Patients: A Systematic Review and Meta-analysis.

The objective of this systematic review and meta-analysis is to critically analyze and summarize studies reporting association of salivary immunoglobulin A (IgA) levels as a biomarker for dental caries in Down syndrome (DS) patients. Using the keywords salivary [All Fields] AND IgA [All Fields] AND (“down syndrome” [MeSH Terms] OR (“down”[All Fields] AND “syndrome” [All Fields]) OR “down syndrome” [All Fields]), an electronic search was conducted via PubMed and Scopus databases by two authors, H. H. and Z. K. independently. Retrieved studies were screened against the predefined exclusion and inclusion criteria. To estimate the risk of bias, quality assessment of included studies was carried using the Newcastle–Ottawa quality assessment scale for observational studies. Primary search resulted in 10 articles from PubMed and 13 articles from Scopus. Ten studies fulfilled the defined selection criteria and evaluated the salivary IgA (sIgA) level in DS patients with dental caries. Five articles were further analyzed in a quantitative synthesis presented in the meta-analysis. Due to a modified lifestyle and compromised oral hygiene in DS patients, understandably, it is still postulated in the literature that the presence of sIgA can have a protective effect on the occurrence of dental caries as compared with healthy counterparts. As indicated by the present meta-analysis, no conclusions can be drawn as to definitively label sIgA as a biomarker for dental caries. Further, well-designed longitudinal clinical studies and translational research are therefore required before the benchmarking of sIgA as a useful biomarker for dental caries in DS patients with preferable molecular insights.

The fate of donor cells in intestinal transplantation: friend or foe?

Intestinal transplantation (ITx) has become an established therapy for a selected group of patients with irreversible intestinal failure. Unique for ITx are surgical and immunological challenges. Outcomes have improved over time with patient and graft survival of 77% and 71%, respectively by 1 year and 47 and 41% by 10 years, yet, remaining below those of other solid organ transplants. Indeed, ITx is linked high numbers of perioperative complications, rejections, infections infectious, and cardiovascular complications [1]. A particular challenge in addressing the complex interplay of immune responses following ITx has been the lack of longitudinal clinical studies.

Retrospective clinical evaluation of implant-assisted removable partial dentures combined with implant surveyed prostheses

Statement of problemImplant-assisted removable partial dentures (IARPDs) have been proposed as a treatment option for partially edentulous patients. However, evidence regarding the outcome of implant-assisted removable partial dentures with implant surveyed prostheses is limited. PurposeThe purpose of this retrospective clinical study was to evaluate the clinical status and complications of IARPDs combined with implant surveyed prostheses in terms of clinical tissue condition, marginal bone resorption, and prosthetic complications. Material and methodsPatients treated with IARPDs combined with implant surveyed prostheses who had worn an IARPD for at least 12 months were included. Twenty-four participants (25 prostheses, 12 maxillary, and 13 mandibular) were evaluated, with 80 implants used as abutments for IARPDs. The average follow-up period was 27.6 months, and the maximum follow-up was 78 months. Implant cumulative survival rate, marginal bone resorption, probing depth, peri-implant inflammation, bleeding, plaque, calculus, and complications were evaluated. ResultsNo implant failure occurred, and all implants functioned without clinical mobility. Mean marginal bone resorption of implants at 1 year after loading was 0.77 ±0.63 mm, and mean probing depth was 3.4 ±0.1 mm. No patient developed peri-implantitis, and no implant failed. Two clasp fractures, 1 rest fracture, 1 decementation, and 1 fracture of porcelain on an implant surveyed prosthesis were detected at 12 months after loading. ConclusionsWell-planned IARPDs using implant surveyed prostheses were clinically successful. Longitudinal and systematic clinical studies are necessary to confirm these results.

Association between cardiovascular diseases and apical periodontitis: an umbrella review.

The existence of an association between cardiovascular diseases (CVDs) and apical periodontitis (AP) remains unclear because results obtained from previous clinical studies and reviews are inconsistent or inconclusive. To conduct an umbrella review to determine whether there is an association between CVDs and the prevalence of AP in adults. The protocol of the review was registered in the PROSPERO database (CRD42020185753). The literature search was conducted using the following electronic databases: Clarivate Analytics' Web of Science Scopus, PubMed and Cochrane Database of Systematic Reviews, from inception to May, 2020, with no language restrictions. Systematic reviews with or without meta-analysis that evaluated the association between CVDs and AP were included. Other types of studies, including narrative reviews, were excluded. Two reviewers independently performed a literature search, data extraction and quality assessment of included studies. Any disagreements or doubts were resolved by a third reviewer. The quality of the reviews was assessed using the AMSTAR 2 tool (A measurement tool to assess systematic reviews), with 16 items. A final categorization of the systematic reviews classified each as of 'high', 'moderate', 'low' or 'critically low' quality. Four systematic reviews were included in the current review. Three reviews were graded by AMSTAR 2 as 'moderate' quality, whereas one review was graded as 'critically low' quality. Only one systematic review included a meta-analysis. Substantial heterogeneity amongst the primary studies included within each systematic review was notable in preventing a pooled analysis. From the limited 'moderate' to 'critically low' quality evidence available, the current umbrella review concluded that a weak association exists between CVDs and AP. In the future, well-designed, longitudinal clinical studies with long-term follow-up are required.

Limbic-predominant age-related TDP-43 encephalopathy in Black and White decedents.

The association of limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathologic change (LATE-NC) with cognition and dementia was assessed in community-dwelling Black elders, and racial differences in these associations were tested. Black (n = 76) and White (n = 152) decedents from 4 longitudinal clinical pathologic studies of aging were matched 2 to 1 by age at death, sex, years of education, dementia status, and follow-up time. LATE-NC detected by immunohistochemistry was dichotomized into none/mild and moderate/severe groups. Distribution and clinical and pathologic characteristics of LATE-NC and its association with cognitive profiles and odds of dementia were determined in Black decedents, and racial differences in these associations were assessed. The overall frequency of LATE-NC in Black and White decedents was similar (40.8% vs 45.4%). Black decedents with moderate/severe LATE-NC were older, had significantly lower global cognition scores, particularly in memory domains, and had higher frequency of Alzheimer disease, hippocampal sclerosis, and cerebral amyloid angiopathy than the LATE-NC none/mild group. LATE-NC in Black decents was independently associated with impaired global cognition, episodic and semantic memory, and visuospatial abilities. There were no racial differences in clinical features or pathologic distribution of LATE-NC except for a significant increase in the mean cytoplasmic inclusions in the entorhinal and mid temporal cortices in White compared to Black decedents. In addition, no racial differences in the cognitive profiles or the odds of dementia were observed in Black vs White decedents. Consistent with findings in White decedents, LATE-NC in Black decedents is associated with impaired cognition, including memory domains.

An Autonomous Diurnal Sweat Sampling Patch for Biomarker Data Analytics

Wearable sweat analysis possesses significant potential for transforming personalized and precision medicine, by capturing the longitudinal profiles of a broad spectrum of biomarker molecules that are informative of our body’s dynamic chemistry. However, the lack of established physiological criteria to provide personalized feedback, based on sweat biomarker readings, has prevented the translation of wearable sweat-based bioanalytical technologies into health and wellness monitoring applications. Accordingly, scalable sweat sampling tools are required to facilitate large-scale and longitudinal clinical studies focusing on interpreting sweat biomarker readings. However, conventional sweat induction-collection tools are bulky and require multi-step and manual operations. Accordingly, here, we devise a sweat sampling patch, which can be deployed for autonomous diurnal sweat induction-collection. The core of this patch is an addressable array of miniaturized and coupled iontophoresis/microfluidic interfaces that can be activated on-demand or at scheduled time-points to induce/collect sufficient sweat samples for analysis. The iontophoresis interface was designed following an introduced design space centering on sufficient sweat secretory agonist delivery at safe current levels. The microfluidic interface was fabricated following a simple, rapid, and low-cost fabrication scheme. To achieve autonomous operation, these interfaces were extended into an array format and coupled with a custom-developed flexible and wireless circuit board. To inform utility, periodically induced/collected sweat samples of an individual were analyzed in relation to meal intake. [2020-0194]

Report of the Skin Research Workgroups from the GRAPPA 2019 Annual Meeting.

The International Dermatology Outcome Measures (IDEOM) initiative is a nonprofit organization dedicated to enhancing clinical care and research in dermatology by developing evidence-based, patient-centered outcome measures. At the 2019 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the IDEOM psoriasis working group presented an overview of its selected deliverables and discussed its efforts to agree on meaningful, valid, and feasible outcome measures for quality measurement in psoriasis. The psoriatic arthritis (PsA) workgroup focused on the measurement of PsA symptoms in psoriasis clinical trials, and the measurement of nonspecific musculoskeletal symptoms among patients with psoriasis in psoriasis longitudinal clinical trials and cohort studies.

Immediate Effects of High-frequency Diathermy on Muscle Architecture and Flexibility in Subjects With Gastrocnemius Tightness

Background: The gastrocnemius (GCM) is one of the lower extremity muscles that tend to tighten easily. GCM tightness results in limited ankle dorsi-flexion (DF), especially when the knee joint is fully extended. Joint flexibility is determined by the morphological and physiological characteristics of joints, muscles, tendons, and ligaments. Impaired joint flexibility can be attributed to increased susceptibility to muscle injury. High-frequency diathermy is clinically used to reduce pain and muscle tightness and to improve limited range of motion. Objects: This study aimed to investigate the immediate effects of high-frequency therapy in subjects with GCM tightness. Methods: The study was designed as a one-group before–after trial. The subjects included 28 volunteers with GCM tightness (an active ankle DF angle of less than 12°) without any known neurological and musculoskeletal pathologies in the ankle and calf areas. WINBACK Transfer Electrode Capacitive and Resistive Therapy equipment was used to apply high-frequency therapy to the subjects’ GCMs for 10–15 minutes. The pennation angle and the fascicle length of the GCM were measured using ultrasonography. The flexibility of the ankle joint, peak torque to the passive ankle DF (Biodex), and soft tissue stiffness (MyotonPRO) were also measured. Results: The pennation angle was significantly decreased following the treatment; however, no significant difference in the fascicle length was found (p < 0.05). The flexibility was significantly increased and both the passive peak torque to passive ankle DF and the soft tissue stiffness significantly decreased (p < 0.05). Conclusion: High-frequency therapy is immediately effective for improving the muscle’s architectural properties and functional factors in subjects with GCM tightness. Further longitudinal clinical studies are required to investigate the long-term effects of high-frequency therapy on subjects with GCM tightness from various causes.

Personalized treatment selection via the covariate-specific treatment effect curve for longitudinal data

Treatment selection based on patient characteristics has been widely recognised in modern medicine. In this paper, we propose a generalised partially linear single-index mixed-effects modelling strategy for treatment selection and heterogeneous treatment effect estimation in longitudinal clinical and observational studies. We model the treatment effect as an unknown functional curve of a weighted linear combination of time-dependent covariates. This method enables us to investigate covariate-specific treatment effects and make personalised treatment selection in a flexible fashion. We develop a method that combines local linear regression and penalised quasi-likelihood to estimate the weight for each covariate, the unknown treatment effect curve and the parameters for mixed-effects. Based on pointwise confidence intervals for the treatment effect curve, we can make individualised treatment decisions from the information of patient characteristics. A simulation study is conducted to evaluate finite sample performance of the proposed method. We also illustrate the method via analysis of a real data example.

Microvasculopathy and biomarkers in sickle cell disease: the promise of non‐invasive real‐time in vivo tools

Microvasculopathy and biomarkers in sickle cell disease: the promise of non‐invasive real‐time <i>in vivo</i> tools

Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.

Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures. Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma. Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, Aβ40, and Aβ42 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery. Tau increased during surgery (1752%, p = 0.0001) and NFL rose seven days post-surgery (1090%, p < 0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for Aβ40 and Aβ42. Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.

Neurophysiological Markers of Alzheimer's Disease: Quantitative EEG Approach.

Currently established and employed biomarkers of Alzheimer's disease (AD) predominantly mirror AD-associated molecular and structural brain changes. While they are necessary for identifying disease-specific neuropathology, they lack a clear and robust relationship with the clinical presentation of dementia; they can be altered in healthy individuals, while they often inadequately mirror the degree of cognitive and functional deficits in affected subjects. There is growing evidence that synaptic loss and dysfunction are early events during the trajectory of AD pathogenesis that best correlate with the clinical symptoms, suggesting measures of brain functional deficits as candidate early markers of AD. Resting-state electroencephalography (EEG) is a widely available and noninvasive diagnostic method that provides direct insight into brain synaptic activity in real time. Quantitative EEG (qEEG) analysis additionally provides information on physiologically meaningful frequency components, dynamic alterations and topography of EEG signal generators, i.e. neuronal signaling. Numerous studies have shown that qEEG measures can detect disruptions in activity, topographical distribution and synchronization of neuronal (synaptic) activity such as generalized EEG slowing, reduced global synchronization and anteriorization of neuronal generators of fast-frequency resting-state EEG activity in patients along the AD continuum. Moreover, qEEG measures appear to correlate well with surrogate markers of AD neuropathology and discriminate between different types of dementia, making them promising low-cost and noninvasive markers of AD. Future large-scale longitudinal clinical studies are needed to elucidate the diagnostic and prognostic potential of qEEG measures as early functional markers of AD on an individual subject level.