Correct Clinical Interpretation Research Articles

Multiple instance learning framework can facilitate explainability in murmur detection.

Cardiovascular diseases (CVDs) account for a high fatality rate worldwide. Heart murmurs can be detected from phonocardiograms (PCGs) and may indicate CVDs. Still, they are often overlooked as their detection and correct clinical interpretation require expert skills. In this work, we aim to predict the presence of murmurs and clinical outcomes from multiple PCG recordings employing an explainable multitask model. Our approach consists of a two-stage multitask model. In the first stage, we predict the murmur presence in single PCGs using a multiple instance learning (MIL) framework. MIL also allows us to derive sample-wise classifications (i.e. murmur locations) while only needing one annotation per recording ("weak label") during training. In the second stage, we fuse explainable hand-crafted features with features from a pooling-based artificial neural network (PANN) derived from the MIL framework. Finally, we predict the presence of murmurs and the clinical outcome for a single patient based on multiple recordings using a simple feed-forward neural network. We show qualitatively and quantitatively that the MIL approach yields useful features and can be used to detect murmurs on multiple time instances and may thus guide a practitioner through PCGs. We analyze the second stage of the model in terms of murmur classification and clinical outcome. We achieved a weighted accuracy of 0.714 and an outcome cost of 13612 when using the PANN model and demographic features on the CirCor dataset (hidden test set of the George B. Moody PhysioNet challenge 2022, team "Heart2Beat", rank 12 / 40). To the best of our knowledge, we are the first to demonstrate the usefulness of MIL in PCG classification. Also, we showcase how the explainability of the model can be analyzed quantitatively, thus avoiding confirmation bias inherent to many post-hoc methods. Finally, our overall results demonstrate the merit of employing MIL combined with handcrafted features for the generation of explainable features as well as for a competitive classification performance.

Measurement uncertainty estimation of free drug concentrations in clinical laboratories using equilibrium dialysis.

Developing procedures based on equilibrium dialysis (ED) that allow measuring the free drug concentration in plasma improves therapeutic drug monitoring (TDM) in those cases where its measurement is justified. However, this procedure requires specific sample preparation and presents different pitfalls, which are not error-free. As withany result provided by a clinical laboratory, this one should be as accurate as possible to allow a correct clinical interpretation. The measurement uncertainty (MU) is a parameter that enables the accuracy of results to be known, and that is mandated by ISO 15189. Herein, this study suggests how the MU for the results of the free drug concentrations in serum could be estimated when an ED isused. A combination of the top-down and bottom-up approaches was used to estimate the MU based on the ISO/TS 20914:2019 and JCGM 100:2008 guidelines, including the concentration of free phenytoin in serum, as an example. Different scenarios were incorporated considering or not asignificant bias related to the primary drawbacks of ED: thenon-specific binding, the volume shift effect and the Gibbs-Donnan effect. The expanded uncertainties estimated ranged between 13.0 and 30.9 %. The highest MU corresponded to the free drug concentrations in serum results when significant biases related to the volume shift and Gibbs-Donnan effects exist. A detailed estimation of MU for free drug concentrations is presented using ED, considering different scenarios. This study could stimulate clinical laboratories to perform MU studies and its application in TDM.

Dynamic magnetic resonance imaging of the pelvic floor: clinical application

Dynamic magnetic resonance imaging (MRI) of the pelvic floor plays akey role in imaging complex pelvic floor dysfunction. The simultaneous detection of multiple findings in acomplex anatomic setting renders correct analysis and clinical interpretation challenging. The most important aspects (anatomy of the pelvic floor, three compartment model, morphological and functional analysis, reporting) for asuccessful clinical use of dynamic MRI of the pelvic floor are summarized. Review of the scientific literature on dynamic pelvic MR imaging with special consideration of the joint recommendations provided by the expert panel of ESUR/ESGAR in 2016. The pelvic floor is acomplex anatomic structure, mainly formed by the levator ani muscle, the urethral support system and the endopelvic fascia. Firstly, morphological changes of these structures are analysed on the static sequences. Secondly, the functional analysis using the three compartment model is performed on the dynamic sequences during squeezing, straining and defecation. Pelvic organ mobility, pelvic organ prolapse, the anorectal angle and pelvic floor relaxation are measured and graded. The diagnosis of cystoceles, enteroceles, rectoceles, the uterovaginal as well as anorectal decent, intussusceptions and dyssynergic defecation should be reported using astructured report form. Acomprehensive analysis of all morphological and functional findings during dynamic MRI of the pelvic floor can provide information missed by other imaging modalities and hence alter therapeutic strategies.

Peripapillary Retinal Nerve Fiber Layer Thickness and its Ocular and Systemic Determinants in an Elderly Population: A Population-Based Study.

To determine the distribution, ocular, and systemic determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) using spectral-domain optical coherence tomography (SD-OCT) in an elderly population. This report is a part of the Tehran Geriatric Eye Study, a population-based cross-sectional study conducted in Tehran, the capital of Iran. The study population was all residents aged 60 years and above in Tehran. The sampling was performed using a multi-stage stratified random cluster sampling method. All study participants underwent ocular examination (including measurement of visual acuity, objective and subjective refraction, and slit-lamp biomicroscopy), anterior segment imaging using Pentacam HR, and ocular biometry using IOLMaster 500. The OCT imaging was performed for a random subsample (1307 individuals) using Spectralis SD-OCT. Two thousand two hundred and forty-six eyes of 1189 individuals were analyzed for this report. Of these, 691 (58.1%) were female, and the mean age of the participants was 67.3 ± 5.9 years (60-94 years). The mean overall pRNFLT was 98.6 μ (95% confidence interval [CI]: 98.0-99.3). There was a statistically significant difference in pRNFLT between different quadrants; the highest and lowest mean pRNFLT was related to inferior and temporal quadrants, respectively (P < 0.001). The multiple generalized estimating equation model showed that older age (coefficient: -0.15 [95% CI: -0.24 to -0.06], P = 0.001), diabetes (coefficient: -1.69 [95% CI: -2.82 to -0.55], P = 0.004), and longer axial length (coefficient: -0.52 [95% CI: -0.83 to -0.22], P < 0.001) were significantly associated with a decreased overall pRNFLT. Higher body mass index was significantly related to an increased overall pRNFLT (coefficient: 0.19 [95% CI: 0.07 to 0.30], P = 0.002). The results of the present study can be used as a reference database for pRNFLT in the elderly population. Considering ocular and systemic determinants of pRNFLT is necessary for correct clinical interpretation of this parameter.

Lynch syndrome, molecular mechanisms and variant classification.

Patients with the heritable cancer disease, Lynch syndrome, carry germline variants in the MLH1, MSH2, MSH6 and PMS2 genes, encoding the central components of the DNA mismatch repair system. Loss-of-function variants disrupt the DNA mismatch repair system and give rise to a detrimental increase in the cellular mutational burden and cancer development. The treatment prospects for Lynch syndrome rely heavily on early diagnosis; however, accurate diagnosis is inextricably linked to correct clinical interpretation of individual variants. Protein variant classification traditionally relies on cumulative information from occurrence in patients, as well as experimental testing of the individual variants. The complexity of variant classification is due to (1) that variants of unknown significance are rare in the population and phenotypic information on the specific variants is missing, and (2) that individual variant testing is challenging, costly and slow. Here, we summarise recent developments in high-throughput technologies and computational prediction tools for the assessment of variants of unknown significance in Lynch syndrome. These approaches may vastly increase the number of interpretable variants and could also provide important mechanistic insights into the disease. These insights may in turn pave the road towards developing personalised treatment approaches for Lynch syndrome.

Multivariate classification techniques and mass spectrometry as a tool in the screening of patients with fibromyalgia

Fibromyalgia is a rheumatological disorder that causes chronic pain and other symptomatic conditions such as depression and anxiety. Despite its relevance, the disease still presents a complex diagnosis where the doctor needs to have a correct clinical interpretation of the symptoms. In this context, it is valid to study tools that assist in the screening of this disease, using chemical work techniques such as mass spectroscopy. In this study, an analytical method is proposed to detect individuals with fibromyalgia (n = 20, 10 control samples and 10 samples with fibromyalgia) from blood plasma samples analyzed by mass spectrometry with paper spray ionization and subsequent multivariate classification of the spectral data (unsupervised and supervised), in addition to the treatment of selected variables with possible associations with metabolomics. Exploratory analysis with principal component analysis (PCA) and supervised analysis with successive projections algorithm with linear discriminant analysis (SPA-LDA) showed satisfactory results with 100% accuracy for sample prediction in both groups. This demonstrates that this combination of techniques can be used as a simple, reliable and fast tool in the development of clinical diagnosis of Fibromyalgia.

Cardiorespiratory Fitness, Workload, and the Blood Pressure Response to Exercise Testing

We propose that for correct clinical interpretation of exaggerated exercise blood pressure (EEBP), both cardiorespiratory fitness and exercise workload must be considered. A key recommendation toward achieving the correct clinical interpretation of EEBP is that exercise BP should be measured during submaximal exercise with a fixed external workload.

Intractable lateral epicondilytis: A differential diagnosis algorithm for a correct clinical interpretation

Abstract The epicondylalgia is the most frequent upper extremity pathology in adults and it can become an “intractable lateral epicondylitis” when patients do not improve with the treatment received. This is a complex entity that includes several musculo-tendinous, articular and neural syndromes than can coexist and they can also be confused with each other. For this reason, it is necessary to do a systematized and exhaustive evaluation where all the dysfunctions capable of generating the symptoms are precisely and independently analyzed. On this basis, a 7 steps assessment algorithm is proposed on this paper to enable the clinician to perform a complete and organized evaluation of these patients, to achieve a correct clinical interpretation.

Spotlight on the Developmental Eye Movement (DEM) Test.

The developmental eye movement (DEM) test is a practical and simple method for assessing and quantifying ocular motor skills in children. In this review, a summary of the literature relevant to the DEM test has been made, its psychometric properties and its pros and cons have also been considered. The DEM test provides clinicians with a simple method of measuring eye movement using a psychometric test. Over the years, many studies have enabled the identification of the strengthens and weaknesses of this test apart from outlining the psychometric properties. The validity of the test has been checked and expanded over time and studies have shown that the DEM test measures an aspect of eye movement related to reading, rather than purely parameters associated with eye-movement. Some reservations have emerged regarding the repeatability of the test because a degree of learning effect emerges over multiple sessions. Being aware of this point allows correct clinical application and interpretation of the test. Normative data in children were available for nine languages and countries. So far, DEM test could be applied clinically in each case when a rapid test of eye movement was required, such as in testing for vision-related visual problems.

A Comprehensive Review of Radiohumeral Synovial Plicae for a Correct Clinical Interpretation in Intractable Lateral Epicondylitis

Radiohumeral synovial plicae (RHSP) have been studied by different authors in different ways; in spite of this, the evidence is poor and the results are controversial and inconclusive even when it comes to referring to this elbow structure. The aim of this article is to review the embryologic development, anatomy and histology, pathophysiologic features, clinical manifestations, physical examination, imaging findings, and treatment of radiohumeral synovial plicae, for their correct clinical interpretation in patients with intractable lateral epicondylitis. Radiohumeral synovial plicae syndrome (RHSPS) can cause intractable lateral epicondylitis and can be easily confused with other clinical conditions affecting the elbow. Many clinicians are not familiar with radiohumeral synovial plica syndrome since there are not many studies about it and previous reports do not seem to reach a consensus. Although its role in elbow injuries and epicondylitis is accepted and its surgical treatment is effective, there is no clear consensus about clinically relevant aspects. RHSP are remnants of normal embryo development of the articular synovial membrane with different anatomical locations, size and shape. Traumatism or overuse can turn RHSP into symptomatic structures at any age and can be compressed between the radial and humeral heads during movement. This compression can cause pain and other symptoms such as snapping, catching, mobility restriction, pitching, clicking, locking, blockage, popping and swelling. Radiohumeral synovial plica syndrome (RHSPS) may be an isolated condition or it can be associated with other elbow abnormalities. The findings on physical examination and imaging diagnosis are multiple and variable. Nowadays, RHSPS are quite unknown and previous reports do not seem to agree, leading to misdiagnoses as epicondylitis and making this structure the main cause of some cases of "intractable lateral epicondylitis". The outcomes of surgical treatments are quite promising although more, higher quality research is needed. Taking this into account, this review is meant to be a starting point for new anatomical and clinical studies.

Chapter 15 - Neurologic assessment

Despite rapidly evolving technologies, an accurate and thorough clinical neurologic assessment is still crucial to understanding presenting symptoms and signs. It is the most exciting but also challenging part of the diagnostic puzzle, essential to establishing a rational working hypothesis and a consistent management plan. Flexibility, creativity, and social skills are needed to elicit the child's participation. History taking is of the utmost importance, requiring not only time and perseverance, but also knowledge and effective communication to obtain relevant and precise information. Understanding what is being tested and distinguishing the normal from the abnormal are indispensable in reaching a correct clinical interpretation. The clinician needs to tailor an individualized approach for each patient according to the chief complaint, clinical context, and the child's chronologic and developmental age. The questions about the nature, localization, and etiology must be addressed first and then summarized and developed into a reasonable diagnostic hypothesis and differential diagnosis. This chapter aims to guide the reader through a situation-related approach from history taking and neurologic examination to a systematic, step-by-step interpretation of the information and findings. It also provides some practical advice on how to avoid common pitfalls.

The rare Alus element-mediated chimerism of multiple de novo complex rearrangement sequences in GAN result in giant axonal neuropathy

Giant axonal neuropathy (GAN) is a rare and grievous autosomal recessive neurodegenerative disease due to loss-of-function mutation in GAN. However, the chimerism of complex rearrangement sequences of GAN has not been reported so far, and the mechanism for its complex rearrangements remains to be determined. We identified a family with clinical symptoms of GAN and aimed to reveal a genetic cause underlying this disease. By whole-exome sequencing in the patient we identified a novel homozygous frameshift mutation with 1 bp deletion (c.27delC) in GAN. However, when analyzed the patient’s genomic DNA (gDNA) by quantitative real-time PCR and breakpoint DNA sequencing, we found the chimerism of multiple complex rearrangement sequences encompassing exon 1 of GAN in the patient's genome. The microhomology and localization of the breakpoint indicated that they may be caused by Alu repeat elements. We also found that the mRNA expression level of GAN in patient’s lymphocyte was decreased, confirming the pathogenicity of these mutations. Our study is the first reported on many complex rearrangement sequences mosaic in GAN mediated by Alu element. The patient here is not a simple homozygous frameshift mutation, but a compound heterozygous paternal c.27delC mutation and the chimerism of multiple de novo complex rearrangement sequences in GAN. Our results may also provide new insights into the formation and pathogenicity of complex rearrangement in GAN, and may be helpful to genetic counseling and genetic testing. It also enriches the Alu-mediated disease-associated database which are important for correct clinical interpretation.

A Novel Pathogenic Variant in the CABP2 Gene Causes Severe Nonsyndromic Hearing Loss in a Consanguineous Iranian Family

Background and Objectives: Hereditary hearing loss (HL) can originate from mutations in one of many genes involved in the complex process of hearing. CABP2 mutations have been reported to cause moderate HL. Here, we report the whole exome sequencing (WES) of a proband presenting with prelingual, severe HL in an Iranian family. Methods: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 2 affected members. After excluding mutations in the GJB2 gene and 7 other most common autosomal recessive nonsyndromic HL (ARNSHL) genes via Sanger sequencing and genetic linkage analysis in the family, WES was utilized to find the possible etiology of the disease. Results: WES results showed a novel rare variant (c.311G>A) in the CABP2gene.This missense variant in the exon 4 of the CABP2gene meets the criteria of being pathogenic according to the American College of Medical Genetics and Genomics (ACMG) interpretation guidelines. Conclusions: Up to now, 3 mutations have been reported for the CABP2gene to cause moderate ARNSHL in different populations. Our results show that CABP2variantsalso cause severe ARNSHL, adding CABP2to the growing list of genes that exhibit phenotypic heterogeneity. Expanding our understanding of the mutational spectrum of HL genes is an important step in providing the correct clinical molecular interpretation and diagnosis for patients.

A Rare Case of Absence of the Lateral Cutaneous Nerve of Forearm: Case Report

Introduction Variations in the formation and in the branching pattern of the brachial plexus are common. Numerous anastomotic variations between the musculocutaneous nerve (MCN) and the median nerve (MN) have been reported and could be implicated in a wide range of sensory and motor dysfunctions. Objective To report an uncommon case of an anastomotic variation between the MN and the MCN with a rare absence of the lateral cutaneous nerve of forearm (LCNF). Material and Methods A dissection of a male cadaver was performed at the Morphology Department of the Universidade Federal do Ceará, Fortaleza, state of Ceará, Brazil. The brachial plexus was exposed. Results It was observed that the MCN, after its origin in the lateral fasciculus of the brachial plexus, anastomoses with the MN in the middle third of the arm. It diverges from the most prevalent anatomical pattern, in which the MCN continues to pass distally beneath the brachii biceps, originating the LCNF. In this case, the MCN does not emit its main terminal branch, the LCNF, which innervates the lateral portion of the skin of the forearm. In the present case, the innervation of the lateral portion of the skin of the forearm is provided by radial nerve branches. The reported case has practical implications, since the absence of the LCNF could cause hypoesthesia in the skin of the forearm. Conclusion Thus, the knowledge of the formation and of the branching pattern of the brachial plexus is clinically important for the correct clinical interpretation of the sensory and motor disorders of the upper limbs caused by peripheral nerve injuries, as well as for planning surgical procedures to correct upper limb traumas.

Quantity and quality of image artifacts in optical coherence tomography angiography.

ObjectiveTo analyze quality and frequency of OCTA artifacts and to evaluate their impact on the interpretability of OCTA images.Design75 patients with diabetic retinopathy (DR), retinal artery occlusion (RAO), retinal vein occlusion (RVO), or neovascular age-related macular degeneration (nAMD) and healthy controls were enrolled in this cross-sectional study in the outpatient department of a tertiary eye care center.MethodsAll participants underwent an OCTA examination (spectral domain OCT Cirrus 5000 equipped with the AngioPlex module). OCTA scans were analyzed independently by two experienced ophthalmologists. Frequency of various artifacts for the entire OCTA scan and for different segmentation layers and the grading of OCTA interpretability were investigated.ResultsThe analysis of 75 eyes of 38 women and 37 men between 24 and 94 years were included. Six eyes had no retinal disease, 19 eyes had nAMD, 16 had DR, 19 eyes had RVO, and 15 eyes showed RAO. A macular edema (ME) was present in 40 of the diseased eyes. Projection artifacts occurred in all eyes in any structure below the superficial retinal vessel layer, segmentation and motion artifacts were found in 55% (41/75) and 49% (37/75) of eyes, respectively. Other artifacts occurred less frequently. Segmentation artifacts were significantly more frequent in diseased than in healthy eyes (p<0.01). Qualitative assessment of OCTA images was graded as excellent in 65% and sufficient in 25% of cases, adding up to 91% images deemed acceptable for examination. Presence of ME was associated with a significantly poorer interpretability (p<0.01).Conclusion and RelevanceVarious artifacts appear at different frequencies in OCTA images. Nevertheless, a qualitative assessment of the OCTA images is almost always possible. Good knowledge of possible artifacts and critical analysis of the complete OCTA dataset are essential for correct clinical interpretation and determining a precise clinical diagnosis.

Replicative and non-replicative mechanisms in the formation of clustered CNVs are indicated by whole genome characterization.

Clustered copy number variants (CNVs) as detected by chromosomal microarray analysis (CMA) are often reported as germline chromothripsis. However, such cases might need further investigations by massive parallel whole genome sequencing (WGS) in order to accurately define the underlying complex rearrangement, predict the occurrence mechanisms and identify additional complexities. Here, we utilized WGS to delineate the rearrangement structure of 21 clustered CNV carriers first investigated by CMA and identified a total of 83 breakpoint junctions (BPJs). The rearrangements were further sub-classified depending on the patterns observed: I) Cases with only deletions (n = 8) often had additional structural rearrangements, such as insertions and inversions typical to chromothripsis; II) cases with only duplications (n = 7) or III) combinations of deletions and duplications (n = 6) demonstrated mostly interspersed duplications and BPJs enriched with microhomology. In two cases the rearrangement mutational signatures indicated both a breakage-fusion-bridge cycle process and haltered formation of a ring chromosome. Finally, we observed two cases with Alu- and LINE-mediated rearrangements as well as two unrelated individuals with seemingly identical clustered CNVs on 2p25.3, possibly a rare European founder rearrangement.In conclusion, through detailed characterization of the derivative chromosomes we show that multiple mechanisms are likely involved in the formation of clustered CNVs and add further evidence for chromoanagenesis mechanisms in both “simple” and highly complex chromosomal rearrangements. Finally, WGS characterization adds positional information, important for a correct clinical interpretation and deciphering mechanisms involved in the formation of these rearrangements.

Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation.

Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results. Time will tell whether new molecular and flow cytometric high-throughput technologies can overcome the limitations of current standard methods and eventually bring additional benefits. MRD during standard ALL chemotherapy is the strongest overall prognostic indicator and has therefore been used for refining initial treatment stratification. Moreover, MRD positivity after the maintenance phase of treatment may point to an impending relapse and thus enable salvage treatment to be initiated earlier, which could possibly improve treatment results. The prognostic relevance of pretransplantation MRD was shown by several studies, and MRD high-risk patients were shown to benefit from stem cell transplantation (SCT). Also, MRD positivity after SCT correlates with worse outcomes. In addition, MRD information is very instructive in current clinical trials that test novel agents to evaluate their treatment efficacy. Although conventional clinical risk factors lose their independent prognostic significance when combined with MRD information, recently identified genetic markers may further improve the treatment stratification in ALL.

Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation.

Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results. Time will tell whether new molecular and flow cytometric high-throughput technologies can overcome the limitations of current standard methods and eventually bring additional benefits. MRD during standard ALL chemotherapy is the strongest overall prognostic indicator and has therefore been used for refining initial treatment stratification. Moreover, MRD positivity after the maintenance phase of treatment may point to an impending relapse and thus enable salvage treatment to be initiated earlier, which could possibly improve treatment results. The prognostic relevance of pretransplantation MRD was shown by several studies, and MRD high-risk patients were shown to benefit from stem cell transplantation (SCT). Also, MRD positivity after SCT correlates with worse outcomes. In addition, MRD information is very instructive in current clinical trials that test novel agents to evaluate their treatment efficacy. Although conventional clinical risk factors lose their independent prognostic significance when combined with MRD information, recently identified genetic markers may further improve the treatment stratification in ALL.

Biological variation of platelet parameters determined by the Sysmex XN hematology analyzer

BackgroundThis study was aimed to define the short- and medium-term biological variation (BV) estimates, the index of individuality and the reference change value (RCV) of platelet count, platelet distribution width, mean platelet volume, platelet larger cell ratio, plateletcrit and immature platelet fraction. MethodsThe study population consisted of 43 health subjects, who participated to the assessment of medium-term (21 subjects; blood sampling once a week for 5 consecutive weeks) and short-term (22 subjects; blood sampling once a day for 5 consecutive days) BV study, using Sysmex XN-module. Eight subjects were also scheduled to participate to both phases. The data were subject to outlier analysis prior to CV-ANOVA, to determine the BV estimates with the relative confidence intervals. ResultsThe medium-term and short-term within-subject BV (CVI) was comprised between 2.3 and 7.0% and 1.1–8.6%, whereas the medium-term and short-term between-subjects BV (CVG) was comprised between 7.1 and 20.7% and 6.8–48.6%. The index of individuality and index of heterogeneity were always respectively <0.6 and >0.63 for all the parameters, in both arms of the study. The RCVs were similar for all parameters, in both arms of the study. ConclusionThis study allowed to define the BV estimates of many platelet parameters, some of them unavailable in literature. The kinetics of platelet turnover suggests the use of short-term BV data for calculating analytical goals and RCV. The correct clinical interpretation of platelet parameters also necessitates that each laboratory estimates local RCV values.

Heart rate variability to monitor performance in elite athletes: Criticalities and avoidable pitfalls

BackgroundSpectral analysis of Heart Rate Variability (HRV) is a simple, non-invasive technique that is widely used in sport to assess sympatho-vagal regulation of the heart. Its employment is increasing partly due to the rising usage of wearable devices. However data acquisition using these devices may be suboptimal because they cannot discriminate between sinus and non-sinus beats and do not record any data regarding respiratory frequency. This information is mandatory for a correct clinical interpretation. MethodsThis study involved 974 elite athletes, all of them underwent a complete autonomic assessment, by way of Autoregressive HRV analysis. ResultsIn 91 subjects (9% of the total population) we observed criticalities of either cardiac rhythm or respiration. Through perusal of one-lead ECG analysis we observed that 77 subjects had atrial or ventricular ectopy, i.e. conditions which impair stationarity and sinus rhythm. Running anyway autonomic nervous system analysis in this population, we observed that RR variance and raw values of LF and HF regions are significantly higher in arrhythmic subjects. In addition 14 subjects had slow (about 6 breath/min, 0.1Hz) respiration. This condition clouds the separation between LF from HF spectral regions of RR interval variability, respectively markers of the prevalent sympathetic and vagal modulation of SA node and of their synergistic interaction. ConclusionsCaution must be payed when assessing HRV with non-ECG wearable devices. Recording ECG signal and ensuring that respiratory rate is higher than 10 breath/min are both prerequisites for a more reliable analysis of HRV particularly in athletes.