Somatotype and bioelectrical impedance vector analysis of Italian CrossFit® practitioners.

Objectives: CrossFit® is a high-intensity sport characterized by various workouts that require strength, speed, endurance, or agility, impacting participants' body composition. This observational study aimed to determine the morphological (anthropometrical and bioelectrical) profile of CrossFit® athletes and to compare them with other athletic populations. Methods: Anthropometrical measurements and bioelectrical vector analysis (classic and specific approaches) were performed on 145 CrossFit® practitioners (107 men aged 30.7 ± 8.4 years and 38 women aged 28.1 ± 6.7 years). Each participant's relative somatotype was calculated and compared between sexes and with a Spanish CrossFit® athletes' group. Resistance-reactance graphs and Hotelling's T2 test were applied to characterize the sample, compare them with an athletes' reference population, and identify differences between somatotype groups. Results: The most represented somatotype in both groups was the balanced mesomorph (male 3.5-5.2 - 1.7 and female 4.4-4.5 - 1.8). Compared with Spanish CrossFit® athletes, significant differences were denoted for men but not women (SAD = 2.3). The bioelectrical graphs indicated that the distribution of CrossFit® athletes is quite heterogeneous and within average values for the athlete's reference. The mesomorphic and endomorphic components were associated with a higher phase angle. Conclusions: CrossFit® practitioners predominantly present a mesomorphic component and show a body type like other power athletes, although with less pronounced characteristics. The somatotype may influence the vector's position in the RXc graphs. This study provided the bioelectrical tolerance ellipses for CrossFit® practitioners in classic and specific approaches for the first time.

Restrospective reappraisal of the prognostic classification of spitzoid melanocytic neoplasms after BRAF and NRAS mutation characterisation: a single institution experience.

AIMS: The current WHO classification of melanocytic tumours excludes neoplasms showing BRAF or NRAS mutations from the Spitz category. This study aimed to review and reclassify atypical melanocytic tumours with spitzoid morphological features diagnosed between 2009 and 2021 in our hospital after expanding the molecular profile, including BRAF and NRAS mutations in all cases. METHODS AND RESULTS: A total of 71 neoplasms showing spitzoid features (Spitz-like) and atypia were included. The risk of progression of tumours was first studied by integrating the morphology, immunohistochemistry (p16, Ki67, HMB45 and PRAME) and fluorescence in-situ hybridisation (FISH) results (melanoma multiprobe and 9p21). In a second step, after expanding the molecular study, including BRAF and NRAS mutational status, the neoplasms were finally classified into four subgroups: atypical Spitz tumour (AST, n = 45); BRAF-mutated naevus/low-grade melanocytoma with spitzoid morphology (BAMS, n = 2); Spitz melanoma (SM, n = 14); and BRAF or NRAS mutated melanoma with spitzoid features (MSF, n = 10). Follow-up of patients revealed uneventful results for AST and BAMS. Only one SM presented lymph node metastasis after 134 months. Conversely, patients with MSF showed an unfavourable outcome: three developed lymph node metastases after a mean time of 22 months, with one patient presenting distant metastasis and dying of the disease 64 months from diagnosis. The progression-free survival showed significant differences between the four groups of spitzoid tumours (P < 0.001) and between both melanoma subtypes (P = 0.012). CONCLUSIONS: The classification and prognostication of atypical neoplasms with spitzoid features requires the integration of histomorphology with the molecular investigation of tumours, which should include BRAF and NRAS mutational status.

Combined WNT-activated deep-penetrating/plexiform melanocytoma: insights into clinicopathological and molecular characterization.

BACKGROUND: A combined deep-penetrating tumour redefined as WNT-activated deep-penetrating/plexiform melanocytoma (DPM), may pose challenging clinical and histological diagnoses. OBJECTIVES: To review the clinicopathological characteristics of combined DPMs and characterize the molecular profile of atypical and malignant forms. METHODS: The study included 51 patients with combined DPMs diagnosed at the Hospital Clinic of Barcelona and the University of Florence between 2012 and 2020. Clinical data, dermoscopy images (when available) and histological characteristics were reviewed. Immunohistochemistry for ß-catenin, LEF1, HMB45, Ki67, p16 and PRAME (preferentially expressed antigen in melanoma) was performed. Atypical forms underwent next-generation sequencing (NGS) panel analysis, including driver genes implicated in DPMs, TERT-promoter (p) mutations and the investigation of the 9p21 locus via fluorescence in situ hybridization. RESULTS: Among the 51 patients (32 females and 19 males, age range 4-74 years), 68% with available clinical data (15/22) were initially suspected of having melanoma. Except for one patient, complete excision resulted in no recurrences or metastases. One patient who had an incompletely excised combined DPM developed a lymph node melanoma metastasis 10 years later. In the 51 patients, 10 samples (20%) showed atypical histological features; 7 (14%) exhibited a significant loss of p16 expression; and 2 (4%) showed a high-proliferative index (Ki67 over 5%). NGS analysis in 11 patients revealed a double mutation BRAFV600E and exon 3 CTNNB1; no TERTp mutations were detected. CONCLUSIONS: Clinical suspicion of melanoma is common in combined DPMs, but malignant progression is infrequent in tumours lacking high-grade atypia or proliferation. These findings are congruent with the consideration of these lesions as intermediate-grade tumours or melanocytomas.

Body fluids and muscle changes in trail runners of various distances.

Background: This study aims to investigate body fluids and muscle changes evoked by different trail races using anthropometric, bioelectrical, and creatine kinase (CK) measurements. Methods: A total of 92 subjects (55 men, 37 women) participating in three different races of 14, 35, and 52 km were evaluated before (PRE) and after (POST) the races. Classic bioelectrical impedance vector analysis was applied at the whole-body level (WB-BIVA). Additionally, muscle-localized bioelectrical assessments (ML-BIVA) were performed in a subgroup of 11 men (in the quadriceps, hamstrings, and calves). PRE-POST differences and correlations between bioelectrical values and CK, running time and race distance were tested. Results: Changes in whole-body vectors and phase angles disclosed an inclination towards dehydration among men in the 14, 35, and 52 km groups (p < 0.001), as well as among women in the 35 and 52 km groups (p < 0.001). PRE Z/H was negatively correlated with running time in the 35 km men group and 14 km women group (r = -0.377, p = 0.048; r = -0.751, p = 0.001; respectively). POST Z/H was negatively correlated with running time in the 14 km women group (r = -0.593, p = 0.02). CK was positively correlated with distance in men and women (p < 0.001) and negatively correlated with reactance and vector length in the 14 km men group (p < 0.05). ML-BIVA echoed the same tendency as the WB-BIVA in the 35 and 52 km runners, with the most notable changes occurring in the calves (p < 0.001). Conclusions: WB-BIVA and CK measurements underscored a conspicuous trend towards post-race dehydration and muscle damage, displaying a weak association with performance. Notably, ML-BIVA detected substantial alterations primarily in the calves. The study underscores the utility of BIVA as a technique to assess athlete's body composition changes.

In-Season Longitudinal Hydration/Body Cell Mass Ratio Changes in Elite Rugby Players.

BACKGROUND: Hydration status has a direct role in sports performance. Bioelectrical Impedance Vector Analysis (BIVA) and Urine Specific Gravity (USG) are commonly used to assess hydration. The study aims to identify the sensitivity and relationship between BIVA and USG in a field sports setting. METHODS: BIVA and USG measurements were conducted five times throughout one rugby season. 34 elite male rugby players (25.1 ± 4.4 years; 184.0 ± 7.8 cm; 99.9 ± 13.4 kg) were enrolled. Differences over time were tested using one-way repeated measures ANOVA, and Bonferroni's post-hoc test was applied in pairwise comparisons. Resistance-reactance graphs and Hotelling's T2 test were used to characterize the sample and to identify bioelectrical changes. A repeated measures correlation test was conducted for BIVA-USG associations. RESULTS: Two clear trends were seen: (1) from July to September, there was a vector shortening and an increase of the phase angle (p < 0.001); and (2) from December to April, there was a vector lengthening and a decrease of the phase angle (p < 0.001). USG reported neither changes nor correlation with BIVA longitudinally (p > 0.05). Vector variations indicated a body fluid gain (especially in the intracellular compartment) and a body cell mass increase during the preseason, suggesting a physical condition and performance improvement. During the last months of the season, the kinetic was the opposite (fluid loss and decreased body cell mass). CONCLUSIONS: Results suggested that BIVA is sensitive to physiological changes and a better option than USG for assessing hydration changes during a rugby sports season.

Correction: Cebrián-Ponce et al. Bioelectrical, Anthropometric, and Hematological Analysis to Assess Body Fluids and Muscle Changes in Elite Cyclists during the Giro d'Italia. Biology 2023, 12, 450.

In the original publication [...].

Monitoring Internal Load in Women's Basketball via Subjective and Device-Based Methods: A Systematic Review.

The monitoring of internal load in basketball can be used to understand the effects and potential physiological adaptations caused by external load. The main aim of this systematic review was to identify the methods and variables used to quantify internal load in female basketball. The studies included different populations and events: youth athletes, elite, and amateur players. Subjective methods included using the rating of perceived exertion (RPE) method, and sensor-based methods included monitoring the cardiac response to exercise, using heart rate (HR) as the primary metric. The results showed that the HRAvg exhibited a wider range of values during training than during competition, and different metrics were used to evaluate internal load, such as HRMax, HRmin, %HRMax, total time and % of time spent in different HR zones (2-8 zones), Banister's TRIMP, and summated HR zones. RPE and HR metrics were the most commonly used methods. However, the use of multiple metrics with little standardization resulted in significant heterogeneity among studies, limiting meaningful comparisons. The review provides a reference for current research on female basketball. Future research could address this limitation by adopting more consistent measurement protocols standardizing the use of metrics.

Bioelectrical, Anthropometric, and Hematological Analysis to Assess Body Fluids and Muscle Changes in Elite Cyclists during the Giro d'Italia.

This study aimed to characterize and monitor the body fluid and muscle changes during the Giro d'Italia in nine elite cyclists via bioelectrical (whole-body and muscle-localized) anthropometric and hematological analysis. There were three checkpoint assessments: at the beginning, middle, and end of the race. The Wilcoxon signed-rank test was used to compare the data at baseline and follow up. The Spearman correlation was used to explore relationships between variables. Hotelling's T2 test was used to determine bioelectrical differences in the complex vector. Bodyweight did not change during the competition, despite bioelectrical and hematological data indicating that at the first half of the race, there was a fluid gain, and in the second half a fluid loss occurred, reaching baseline values. These changes were especially prevalent in the extracellular water compartment. Significant correlations between whole-body bioelectrical vector changes and red blood cell parameter changes were reported. The muscle group most sensitive to changes were the calves. Quadriceps, hamstrings, and calves reported a PhA decrease trend during the first half of the race, and an increase during the second half. Bioelectrical impedance vector analysis appears to be sensitive enough to detect hydration and cellular integrity adaptions induced by competitions as demanding as the Giro d'Italia.

MYC and TP53 Alterations but Not MAPK Pathway Mutations Are Common Oncogenic Mechanisms in Follicular Dendritic Cell Sarcomas.

CONTEXT.­: Despite their stromal origin, follicular dendritic cells (FDCs) share many functions with hematopoietic system cells. FDC neoplasms are currently classified by the World Health Organization along with those of a histiocytic nature. However, the molecular alterations driving oncogenesis in FDC sarcomas (FDCSs) are beginning to be unveiled and do not seem to concur with those described in histiocytic neoplasms, namely MAPK pathway activation. OBJECTIVE.­: To identify molecular alterations driving tumorigenesis in FDCS. DESIGN.­: We investigated the role of MYC and TP53 in FDC-derived tumor oncogenesis and assessed comprehensively the status of the MAPK pathway in 16 FDCSs, 6 inflammatory pseudotumor (IPT)-like FDCSs, and 8 IPTs. RESULTS.­: MYC structural alterations (both amplifications and rearrangements) were identified in 5 of 14 FDCSs (35.7%), all associated with MYC overexpression. TP53 mutations were identified in 4 of 14 FDCSs (28.6%), all of which displayed intense and diffuse p53 expression. None of these alterations were identified in any IPT-like FDCSs or in IPT cases. No MAPK pathway gene alterations were identified in any of the cases studied. CONCLUSIONS.­: The presence of MYC and TP53 alterations and the lack of association with Epstein-Barr virus segregate classical FDCS from IPT-like FDCS, pointing at different oncogenic mechanisms in both entities. Our results suggest a possible oncogenic role of MYC and TP53 alterations in FDCS. The absence of MAPK pathway alterations confirms the lack of a significant role of this pathway in the oncogenesis of FDC-derived neoplasms.

Immunophenotype of tumor-infiltrating lymphocytes in atypical Spitzoid tumors according to the risk of progression.

The aims of the study were to investigate and compare the immunophenotype of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in a series of benign, intermediate and malignant Spitzoid lesions showing marked inflammatory lymphoid component, to find out its possible relation with the prognosis of these lesions. Six out of 97 Spitz nevus (SN) (6 %), five out of 26 atypical Spitz tumors (AST) (16 %) and seven out of 37 Spitzoid melanomas (SM) (19 %) showed diffuse, intense inflammatory component and were included in the study. The biological risk of the tumors was assessed in all AST through the melanoma 4 probe-FISH assay and the 9p21 locus exploration. TILs were quantitatively immunophenotyped using CD3, CD4, CD8, CD20, TIA1, FOXP3 and PD1 antibodies. PD-L1 was assessed in tumoral cells and inflammatory cells adjacent to the tumor. No significant differences of TILs immunophenotype were found between SN, AST and SM. However, the classification of tumors according to the biological risk showed that grouped SN plus low-risk AST had a significantly higher number of T-cells CD8+ and TIA-1+, as well as a lower CD4/CD8 relation and B- lymphocyte number than high-risk of progression tumors (grouped high-risk AST plus SM). Immunoregulatory T-cell markers PD1 and FOXP3 only correlated with each other and with PD-L1 expression. In conclusion, The TILs immunoprofile differences between low-risk and high-risk of progression Spitzoid tumors, especially regarding CD8 and the cytotoxic immune response, can add prognostic information about these challenging tumors and impact the clinical management of patients.

Physical Fitness and Performance in Talented & Untalented Young Chinese Soccer Players.

Sports performance is a complex process that involves many factors, including ethnic and racial differences. China's youth soccer is in a process of constant development, although information about the characteristics of its players and their methodological systems is scarce. The aim of this retrospective study was to characterize the physical fitness and the competitive performance of 722 Chinese players of three sports categories (8.0-9.9, 10.0-11.9 and 12.0-13.9 years), who were classified by their coaches as talented (n = 204) or untalented (n = 518). Players were assessed for anthropometry (body height, body mass, body mass index), lung capacity (Forced Vital Capacity), jumping performance (Squat Jump, Countermovement Jump and Abalakov tests), sprinting performance (10 m and 30 m Sprint tests), agility performance (Repeated Side-Step test) and flexibility (Sit & Reach test). A descriptive, comparative, correlational and multivariate analysis was performed. Competitive ranking was created in order to act as dependent variable in multiple linear regression analysis. Results indicate that Chinese players classified as talented have better motor performance than untalented ones. However, these differences are neither related nor determine the competitive performance of one group or the other.

Electrical Impedance Myography in Health and Physical Exercise: A Systematic Review and Future Perspectives.

Background: Electrical impedance myography (EIM) is a non-invasive method that provides information about muscle health and changes that occur within it. EIM is based on the analysis of three impedance variables: resistance, reactance, and the phase angle. This systematic review of the literature provides a deeper insight into the scope and range of applications of EIM in health and physical exercise. The main goal of this work was to systematically review the studies on the applications of EIM in health and physical exercise in order to summarize the current knowledge on this method and outline future perspectives in this growing area, including a proposal for a research agenda. Furthermore, some basic assessment principles are provided. Methods: Systematic literature searches on PubMed, Scopus, SPORTDiscus and Web of Science up to September 2020 were conducted on any empirical investigations using localized bioimpedance devices to perform EIM within health and physical exercise contexts. The search included healthy individuals, elite soccer players with skeletal muscle injury, and subjects with primary sarcopenia. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used to develop the systematic review protocol. The quality and risk of bias of the studies included were assessed with the AQUA tool. Results: Nineteen eligible original articles were included in this review, which were separated into three tables according to the nature of the study. The first table includes six studies on the bioelectrical characterization of muscle. The second table includes five studies analyzing muscle changes in injured elite soccer players. The third table includes studies on the short-, medium-, and long-term bioelectrical adaptations to physical exercise. Conclusions: EIM has been used for the evaluation of the muscle condition in the clinical field over the last few years, especially in different neuromuscular diseases. It can also play an important role in other contexts as an alternative to complex and expensive methods such as magnetic resonance imaging. However, further research is needed. The main step in establishing EIM as a valid tool in the scientific field is to standardize the protocol for performing impedance assessments.

PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain.

Anti-programmed cell death (PD1)/ligand-1 (PD-L1) checkpoint inhibitors have improved the survival of non-small cell lung cancer (NSCLC) patients. Additionally, PD-L1 has emerged as a predictive biomarker of response. Our goal was to examine the histological features of all PD-L1 cases of NSCLC analyzed in our center between 2017 and 2020, as well as to correlate the expression values of the same patient in different tested samples. PD-L1 immunohistochemistry (IHC) was carried out on 1279 external and internal samples: 482 negative (tumor proportion score, TPS < 1%; 37.7%), 444 low-expression (TPS 1-49%; 34.7%) and 353 high-expression (TPS ≥ 50%; 27.6%). Similar results were observed with samples from our institution (N = 816). Significant differences were observed with respect to tumor histological type (p = 0.004); squamous carcinoma was positive in a higher proportion of cases than other histological types. There were also differences between PD-L1 expression and the type of sample analyzed (surgical, biopsy, cytology; p < 0.001), with a higher frequency of negative cytology. In addition, there were cases with more than one PD-L1 determination, showing heterogeneity. Our results show strong correlation with the literature data and reveal heterogeneity between tumors and samples from the same patient, which could affect eligibility for treatment with immunotherapy.

Segmental body composition estimated by specific BIVA and dual-energy X-ray absorptiometry.

AIMS: The aim of this study was to analyse the association between specific bioelectric impedance vector analysis (BIVA) and dual-energy X-ray absorptiometry (DXA) to assess segmental body composition using DXA as the reference technique. METHODS: The sample comprised 50 young active students who practised or played different sports (25 men, age: 24.37 ± 4.79 y; 25 women, age: 24.32 ± 4.43 y) from the National Institute of Physical Education of Catalonia (INEFC). Anthropometric data (height, weight, arm, waist, and calf circumferences) and bioelectrical measurements (R, ohm; Xc, ohm) were recorded. Body composition was analysed with specific BIVA. DXA was used as the reference method to assess body composition of the whole-body, the trunk, and the limbs. The percentage of fat mass (%FMDXA) and fat-free mass index (FFMIDXA = FFM/length2) were calculated. The agreement between specific BIVA and DXA was evaluated by a depth-depth analysis, two-way ANOVA, and Pearson's correlations. RESULTS: The depth-depth analysis showed a good agreement between DXA and BIVA (F = 14.89, p < 0.001) in both sexes and all body segments. Specific vector length (Zsp; i.e. indicative of %FM) was correlated with %FMDXA in the whole body and all body segments, and the phase angle was correlated with FFMIDXA, with he trunk in women as the only exception. Specific BIVA demonstrated to balance the effect of body size on bioelectrical measurements in both whole and segmental approaches. CONCLUSIONS: Segmental specific BIVA and DXA provided a consistent evaluation of body composition in both sexes, of the whole body and each body segment. The indices %FM and FFMI obtained with DXA were correlated to vector length and phase angle in each segment, respectively. Specific BIVA represents a promising technique for monitoring segmental body composition changes in sport science and clinical applications.

TP53 mutation and tumoral PD-L1 expression are associated with depth of invasion in desmoplastic melanomas.

BACKGROUND: Desmoplastic melanoma (DM) is a rare subtype of spindle cell malignant melanoma characterized by frequent local recurrences and hematogenous spread, but without molecular classification. The aim of the study was to investigate in a DM series the incidence of relevant gene alterations in cancer, the programmed death-ligand 1 (PD-L1) expression status and the association with clinicopathological features and melanoma progression. METHODS: A total of 38 patients were included. Clinical follow-up and the histopathological features of all cases were retrospectively collected. PD-L1 expression by immunohistochemistry (IHC) and BRAF genomic alterations by real-time PCR were determined in 34 samples. Additionally, a molecular analysis by next-generation sequencing was performed in 25 DMs. RESULTS: Tumors occurred predominantly in men (76%) and in the head and neck region (50%). Most tumors were pure DMs (66%), containing less than 10% of conventional melanoma. Overall, 48% of our cohort harbored TP53 mutations, most of them showing a molecular signature associated with ultraviolet (UV)-oncogenesis, and 29%, BRAF mutations. A positive correlation between TP53 with depth of invasion (P=0.005) and presence of elastosis (P=0.002) was found. High-expression of PD-L1 in tumor cells was observed in 38% of cases and correlated with depth of tumoral infiltration (P=0.003), TP53 (P=0.016), PD-1 (P<0.001) and tumor-infiltrating lymphocytes (TILS) (P<0.001). PD-L1 expression in immune cells correlated with PD-1 (P=0.006), tumoral PD-L1 expression (P=0.029) and TP53 mutation (P=0.002). Survival correlated with depth of invasion (P=0.003), stage of tumors (P=0.015), positive sentinel lymph node (P=0.004), lymph node metastasis (P=0.024) and distant metastasis (P<0.001). CONCLUSIONS: Our results suggest that progressed DMs with deep tumoral infiltration frequently harbor TP53 mutations, PD-L1 expression and present a high inflammatory response, probably related to adaptive immune resistance in this tumor-type.

HHV8-positive, EBV-positive Hodgkin lymphoma-like large B cell lymphoma: expanding the spectrum of HHV8 and EBV-associated lymphoproliferative disorders.

Human herpesvirus type 8 (HHV8) is a gamma herpesvirus known for its role in lymphoid neoplasms, especially in immunosuppressed patients. We describe the case of a 64-year-old male, without known immunodeficiency, with 1-year-long clinical history of mediastinal and abdominal lymphadenopathies and recurrent pulmonary infections. Histopathological evaluation of a mediastinal lymph node revealed the presence of scattered atypical large cells with Hodgkin and Reed-Sternberg morphology in a background of lymphocytes and extensive areas of fibrosis. The large cells were positive for HHV8 and Epstein-Barr virus (EBV), with a clonal pattern of IGH gene rearrangement. A descriptive diagnosis of "HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma" was rendered. Interestingly, the retrospective evaluation of a previous biopsy, diagnosed as reactive lymphadenitis, revealed the presence of HHV8- and EBV-positive cells, with a polyclonal pattern and a small peak corresponding to that of the most recent biopsy. This case presents diagnostic challenges due to the presence of particular features not clearly related to current HHV8-associated entities, and also suggests the possibility for disease progression in the spectrum of HHV8- and EBV-associated lymphoproliferative disorders.

Implementation of an NGS panel for clinical practice in paraffin-embedded tissue samples from locally advanced and metastatic melanoma patients.

Aim: Single biomarker diagnostic test of BRAFV600 locus in metastatic melanoma is mandatory for treatment decision; however, multiple-gene based techniques, such as targeted next-generation sequencing (NGS) are being used to maximize the number of patients that can benefit from a targeted therapy. The main objective of this study is to investigate whether an NGS panel could be adopted in routine clinical care for advanced melanoma. Methods: Patients diagnosed with advanced melanoma at our center from 2017 to 2019 were included. Presence of genetic alterations was performed using two methods: real-time polymerase chain reaction-based Idylla test (Biocartis) and NGS with the oncomine solid tumor DNA kit (Thermo Fisher Scientific). Total genomic DNA was extracted from formalin-fixed and paraffin embedded samples for sequencing. Results: A total of 155 samples were evaluated for molecular analysis but 40 samples (25.8%) were inadequate for sequencing. The clinical utility of BRAFV600 real-time polymerase chain reaction and targeted-NGS was compared in 29 samples and a very good concordance was observed (Kappa = 0.89, 95% confidence interval 0.68 ± 1.05). An oncogenic mutation by NGS was found in 75 samples (65%)-53% of whom were candidates for personalized therapies. The most prevalent mutated genes were BRAF (39%), TP53 (23%), and NRAS (14%). Other genes identified at lower incidence (< 5%) were: PIK3CA, ERBB4, CTNNB1, STK11, FGFR1, SMAD4, KRAS, FGFR3, PTEN and AKT. Co-occurrence of oncogenic mutations was detected in 40% of the samples. Among the mutations identified, TP53 was significantly more prevalent in men (men 31.8% versus women 12.2%, P = 0.03) and NRAS in women (men 9.1% versus women 24.4%, P = 0.03). Conclusions: Targeted-NGS testing is a feasible technique to implement in the routine clinical practice. Based on our results, NGS has provided more information on target-genes than RT-PCR technique, maximizing the benefit for patients with advanced melanoma.

Clinicopathological evaluation of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in post-transplant lymphoproliferative disorders: association with Epstein-Barr virus, PD-L1 copy number alterations, and outcome.

AIMS: The clinical implications of the programmed cell death 1 (PD1)/programmed cell death-ligand 1 (PD-L1) axis in patients with post-transplant lymphoproliferative disorders are largely unknown, and its association with Epstein-Barr virus (EBV) status and PD-L1 copy number alterations (CNAs) has not been thoroughly studied. METHODS AND RESULTS: PD1/PD-L1 expression was studied in 50 adult post-transplant lymphoproliferative disorders, and the correlations with PD-L1 CNAs, EBV, clinicopathological features and outcome were evaluated. Thirty-seven (74%) cases were classified as diffuse large B-cell lymphoma (DLBCL), nine (18%) cases were classified as polymorphic, and four (8%) cases were classified as classic Hodgkin lymphoma. Thirty-four cases were EBV-positive, with 29 of 34 (85%) having latency II or III, and 15 of 34 (44%) having viral replication. PD-L1 expression in tumour cells and tumour-associated macrophages was observed in 30 (60%) and 37 (74%) cases, respectively. PD1 positivity was seen in 16 (32%) cases. PD-L1 expression was associated with EBV with latency II or III (P = 0.001) and organ rejection (P = 0.04), and, in DLBCL, with non-germinal centre type DLBCL (P < 0.001). Cases with PD-L1-positive tumour cells showed a higher number of PD-L1 CNAs than PD-L1-negative cases (P = 0.001). Patients with EBV/latency III/replication and simultaneous PD-L1 expression showed the worst overall survival (P < 0.001). CONCLUSIONS: The PD1/PD-L1 axis is deregulated in post-transplant lymphoproliferative disorders, with frequent PD-L1 expression and PD1 negativity. PD-L1 expression is associated with EBV latency II or III and PD-L1 CNAs, and probably reflects a proinflammatory tumour microenvironment. The combined analysis of EBV status and PD-L1 expression may help to identify deeply immunosuppressed patients who can benefit from immune reconstitution approaches.

Bioelectrical Impedance Vector Analysis (BIVA) and Body Mass Changes in an Ultra-Endurance Triathlon Event.

This study aimed to provide the first description of the whole-body bioimpedance vector of nine non-professional triathletes, and to assess body mass (BM) and vector variations evoked by an ultra-endurance triathlon event. Anthropometric and bioelectrical assessments were performed before (PRE), after (POST), and 48 hours following the race (POST48h). Bioimpedance vector analysis (BIVA) showed triathletes' vectors placed to the left of the major axis and mostly outside the 50% tolerance ellipse of the reference population. Vector migration in POST indicated dehydration, paralleled by a decrease in BM (p = 0.0001). Increased hydration status from POST to POST48h was suggested by a reversed vector migration and increased BM (p = 0.0001). Compared to PRE, POST48h values reflected fluid retention by changes in BIVA, while BM was still lower (p = 0.0001). Racing time was positively related to basal resistance -R/h- (r = 0.68; p = 0.04) and bioimpedance -Z/h- (r = 0.68; p = 0.045). Besides, basal R/h and Z/h were positively related to PRE-to-POST changes of R/h and Z/h (r = 0.80; p = 0.009). PRE-to-POST changes of R/h and Z/h were positively related to racing time (r = 0.80, p = 0.01) and internal workload (r = 0.80, p ≤ 0.02). Notwithstanding the lack of significant correlation between BM and bioelectrical parameters, the vector's behavior was explained from a multifactorial perspective (including BM variations) by using multiple regression analysis. On the other hand, BM changes were not related to racing time, internal workload or energy deficit (ranges: r = - 0.46 to 0.65; p = 0.06 to 0.98). In conclusion, these triathletes exhibit a specific bioelectrical distribution. Furthermore, vector migration was consistent with fluid loss induced by the event. Finally, vector analysis seems to provide additional information about hydration changes 48h after the event in comparison with BM alone.

Assessing subcutaneous adipose tissue by simple and portable field instruments: Skinfolds versus A-mode ultrasound measurements.

PURPOSE: This study compared subcutaneous adipose tissue (SAT) measurements using a skinfold caliper and Renco Lean-Meater Series 12 A-mode portable ultrasound scanner (A-US). It aimed to assess their inter- and intra-rater reliability and measure the agreement between both methods. METHODS: Eighty-four volunteers of different fitness levels were divided into three groups by Æ©6 skinfolds: G1 ≤ 55 mm (n = 33 males); G2 > 55 mm (n = 32 males); G3 = 98.0 ± 52.3 mm (n = 19 females). Triceps, subscapular, biceps, iliac crest, supraspinal, abdominal, front thigh and medial calf were assessed by ultrasound and skinfolds. Two technicians for both tools performed triplicate measures. Intraclass correlation (ICC), technical error of measurement (TEM) and coefficients of variation (CVs) were applied for test-retest and inter-rater reliability. Non-Parametric statistics were used in order to establish possible statistical differences and correlation between skinfolds thickness and uncompressed subcutaneous adipose tissue thickness from ultrasound. The amount of agreement between both methods was assessed with Lin's coefficient and a scatterplot of all site locations. A Bland-Altman plot was constructed to establish limits of agreement between groups and regression analysis was employed to assess the ability of skinfolds to explain the variance of ultrasound. RESULTS: Test-retest ICC for skinfolds and ultrasound were higher than 0.989 and 0.793, respectively. Inter-rater ICC for skinfolds was 0.999 with a 95% CI of 0.995 to 0.999 and for ultrasound was 0.755 with a much larger 95% CI of 0.622 to 0.841. TEMs (> 8.50%) and CVs (> 6.72%) compromised ultrasound reliability. Statistical differences were found in most of the analysed anatomical sites (p < 0.001) except in biceps G2 (Z = -1.150, p = 0.25) and G3 (Z = -1.309, p = 0.19). Good correlations (r > 0.7, p ≤ 0.05) were reported at almost all anatomical sites and groups except for biceps (G1: Rho = 0.26, p = 0.140) and abdominal (G2: Rho = -0.16, p = 0.38; G3: Rho = 0.43, p = 0.068). Lin's concordance correlation coefficient registered low values of agreement between skinfolds and A-mode ultrasound (ranged from-0.009-0.646). The scatterplot and the estimated regression line drawn through the midst of all anatomical sites of the whole sample had a slope of 0.51 and R2 adjusted = 0.62 was obtained. The combined analysis between the Bland-Altman plot and the linear regression showed that specifically in the G2 and G3 groups, as the SAT increases the differences between skinfolds and ultrasounds measurements also increases. CONCLUSIONS: The Renco Lean-Meater ultrasound is not interchangeable with skinfold measures. Its utility is questionable, particularly for assessing SAT in active adult populations. Its poor test-retest and inter-rater reliability as well as the lack of agreement when compared to the skinfolds would exclude the free use of the A-mode ultrasound scanner in its hypothetical replacing of the classical calipers.