Tenoscopy for the Treatment of Hand Intratendinous Ganglion: Technique Description and Case Report.

Synovial or ganglion cysts are the most common soft tissue tumors of the wrist and hand and can arise from joints or tendons. Intratendinous synovial cysts, in contrast, are rare and their pathogenesis is still a matter of debate. The treatment of synovial cysts of articular origin using arthroscopy is commonly used with good results. For cysts of tendon origin, that is, extra-articular, when located at the ankle, shoulder, knee, and wrist, endoscopic treatment has also been described in a procedure called tenoscopy. We describe the technique and the good results using tenoscopy for a patient treated for an intratendinous synovial cyst located at the extensor communis tendon of the third digit. It is a reproducible, safe technique with low morbidity, and the patient has had no complications or recurrence.

Feature-based 3D+t descriptors of hyperactivated human sperm beat patterns.

The flagellar movement of the mammalian sperm plays a crucial role in fertilization. In the female reproductive tract, human spermatozoa undergo a process called capacitation which promotes changes in their motility. Only capacitated spermatozoa may be hyperactivated and only those that transition to hyperactivated motility are capable of fertilizing the egg. Hyperactivated motility is characterized by asymmetric flagellar bends of greater amplitude and lower frequency. Historically, clinical fertilization studies have used two-dimensional analysis to classify sperm motility, despite the inherently three-dimensional (3D) nature of sperm motion. Recent research has described several 3D beating features of sperm flagella. However, the 3D motility pattern of hyperactivated spermatozoa has not yet been characterized. One of the main challenges in classifying these patterns in 3D is the lack of a ground-truth reference, as it can be difficult to visually assess differences in flagellar beat patterns. Additionally, it is worth noting that only a relatively small proportion, approximately 10-20% of sperm incubated under capacitating conditions exhibit hyperactivated motility. In this work, we used a multifocal image acquisition system that can acquire, segment, and track sperm flagella in 3D+t. We developed a feature-based vector that describes the spatio-temporal flagellar sperm motility patterns by an envelope of ellipses. The classification results obtained using our 3D feature-based descriptors can serve as potential label for future work involving deep neural networks. By using the classification results as labels, it will be possible to train a deep neural network to automatically classify spermatozoa based on their 3D flagellar beating patterns. We demonstrated the effectiveness of the descriptors by applying them to a dataset of human sperm cells and showing that they can accurately differentiate between non-hyperactivated and hyperactivated 3D motility patterns of the sperm cells. This work contributes to the understanding of 3D flagellar hyperactive motility patterns and provides a framework for research in the fields of human and animal fertility.

Scaphoid fracture non-union: a systematic review of the arthroscopic management.

BACKGROUND AND AIM: There is no consensus regarding the most appropriate treatment of scaphoid nonunion. This systematic review aimed to investigate whether wrist arthroscopy exerts a positive influence on bone union and clinical outcomes. METHODS: We searched the literature on Medline (PubMed), Web of Science, Embase and Scopus databases using the combined keywords "scaphoid" AND "arthroscopy" AND "pseudoarthrosis" OR "nonunion". Eighteen studies were finally included in our review. The quality of the studies was assessed using the Coleman Methodological Score. RESULTS: Our systematic review has shown that arthroscopic management of scaphoid nonunion achieves a high rate of union and satisfactory clinical outcomes with minimal complications. CONCLUSIONS: There is need to perform randomized controlled trials reporting on the use of arthroscopy. In addition, the different pattern of pseudoarthrosis should be better classified to manage the patients who will benefit after the management.

Human sperm rotate with a conserved direction during free swimming in four dimensions.

Head rotation in human spermatozoa is essential for different swimming modes and fertilisation, as it links the molecular workings of the flagellar beat with sperm motion in three-dimensional (3D) space over time. Determining the direction of head rotation has been hindered by the symmetry and translucent nature of the sperm head, and by the fast 3D motion driven by the helical flagellar beat. Analysis has been mostly restricted to two-dimensional (2D) single focal plane image analysis, which enables tracking of head centre position but not tracking of head rotation. Despite the conserved helical beating of the human sperm flagellum, human sperm head rotation has been reported to be uni- or bi-directional, and even to intermittently change direction in a given cell. Here, we directly measure the head rotation of freely swimming human sperm using multi-plane 4D (3D+t) microscopy and show that: (1) 2D microscopy is unable to distinguish head rotation direction in human spermatozoa; (2) head rotation direction in non-capacitating and capacitating solutions, for both aqueous and viscous media, is counterclockwise (CCW), as seen from head to tail, in all rotating spermatozoa, regardless of the experimental conditions; and (3) head rotation is suppressed in 36% of spermatozoa swimming in non-capacitating viscous medium, although CCW rotation is recovered after incubation in capacitating conditions within the same viscous medium, possibly unveiling an unexplored aspect of the essential need of capacitation for fertilisation. Our observations show that the CCW head rotation in human sperm is conserved. It constitutes a robust and persistent helical driving mechanism that influences sperm navigation in 3D space over time, and thus is of critical importance in cell motility, propulsion of flagellated microorganisms, sperm motility assessments, human reproduction research, and self-organisation of flagellar beating patterns and swimming in 3D space.

Quenching of oscillations via attenuated coupling for dissimilar electrochemical systems.

The coupled dynamics of two similar and disparate electrochemical cells oscillators are analyzed. For the similar case, the cells are intentionally operated at different system parameters such that they exhibit distinct oscillatory dynamics ranging from periodic to chaotic. It is observed that when such systems are subjected to an attenuated coupling, implemented bidirectionally, they undergo a mutual quenching of oscillations. The same holds true for the configuration wherein two entirely different electrochemical cells are coupled via bidirectional attenuated coupling. Therefore, the attenuated coupling protocol seems to be universally efficient in achieving oscillation suppression in coupled oscillators (similar or heterogeneous oscillators). The experimental observations were verified by numerical simulations using appropriate electrodissolution model systems. Our results indicate that quenching of oscillations via attenuated coupling is robust and therefore could be ubiquitous in coupled systems with a large spatial separation prone to transmission losses.

A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial.

BACKGROUND: An investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation. METHODS: Patients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2-4), 40-80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses. RESULTS: Of 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6-12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001). CONCLUSION: Results suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03281876.

3D+t feature-based descriptor for unsupervised flagellar human sperm beat classification.

Human spermatozoa must swim through the female reproductive tract, where they undergo a series of biochemical and biophysical reactions called capacitation, a necessary step to fertilize the egg. Capacitation promotes changes in the motility pattern. Historically, a two-dimensional analysis has been used to classify sperm motility and clinical fertilization studies. Nevertheless, in a natural environment sperm motility is three-dimensional (3D). Imaging flagella of freely swimming sperm is a difficult task due to their high beating frequency of up to 25 Hz. Very recent studies have described several sperm flagellum 3D beating features (curvature, torsion, asymmetries, etc.). However, up to date, the 3D motility pattern of hyperactivated spermatozoa has not been characterized. The main difficulty in classifying these patterns in 3D is the lack of a ground truth reference since differences in flagellar beat patterns are very difficult to assess visually. Moreover, only around 10-20% of induced to capacitate spermatozoa are truly capacitated, i.e., hyperactivated. We used an image acquisition system that can acquire, segment, and track spermatozoa flagella in 3D+t. In this work, we propose an original three-dimensional feature vector formed by ellipses describing the envelope of the 3D+t spatio-temporal flagellar sperm motility patterns. These features allowed compressing an unlabeled 3D+t dataset to separate hyperactivated cells from others (capacitated from non-capacitated cells) using unsupervised hierarchical clustering. Preliminary results show three main clusters of flagellar motility patterns. The first principal component of these 3D flagella measurements correlated with 2D OpenCASA head determinations as a first approach to validate the unsupervised classification, showing a reasonable correlation coefficient near to 0.7. Clinical relevance- The novelty of this work is defining a 3D+t feature-based descriptor consisting of a set of ellipses enveloping the flagellar motion of human sperm for its unsu-pervised classification. This is a new promising tool to determine the viability of human sperm to fertilize the egg.

Computer-Assisted Surgery Enables Beginner Surgeons, Under Expert Guidance, to Achieve Long-Term Clinical Results not Inferior to Those of a Skilled Surgeon in Knee Arthroplasty.

Purpose: The purpose of this study is to determine whether the use of a surgical navigation system in total knee replacement (TKR) enables beginner and intermediate surgeons to achieve clinical PROM outcomes as good as those conducted by expert surgeons in the long term. Methods: We enrolled 100 consecutive patients whose total navigated knee arthroplasty (TKA) was performed in our institution from 2008 to 2010. According to the principal surgeon's surgical experience, the patients were divided into three groups: (1) beginner surgeons, with no more than 30 previous knee replacement performances, (2) intermediate surgeons, with more than 30 but not more than 300, and (3) expert surgeons, with more than 300 knee replacements. Demographic data collected on the cohort included gender, laterality, age, and body mass index (BMI). The outcome measures assessed were Forgotten Joint Score (FJS), implant positioning, limb alignment, and prosthesis survival rate. A margin of equivalence of ± 18.5 points in the FJS scale was prespecified in terms of the minimal clinically important difference (MCID) to compare the FJS results obtained in the long period between the groups of interest. Results: The mean follow-up was 11.10 ± 0.78, 10.86 ± 0.66, and 11.30 ± 0.74 years, respectively, for each of the groups. The long-term FJS mean score was 80.86 ± 21.88, 81.36 ± 23.87, and 90.48 ± 14.65 for each group. The statistical analysis proved noninferiority and equivalence in terms of the FJS results reported in the long term by patients in Groups 1 or 2 compared to those in Group 3. More specifically, it has been proved that the mean difference between groups is within the interval of equivalence defined in terms of the MCID. The overall prostheses survival rate was 93.7%. Conclusion: Navigated assisted TKA, under expert guidance, can be as effective when performed by beginner or intermediate surgeons as performed by senior surgeons regarding the accuracy of implant positioning, limb alignment, and long-term clinical outcome.

Mechanical Alignment in Knee Replacement Homogenizes Postoperative Coronal Hip-Knee-Ankle Angle in Varus Knees: A Navigation-Based Study.

After knee replacement, postoperative lower limb alignment is influenced by the geometry of the prosthesis position and surrounding soft tissue that contributes to the hip-knee-ankle (HKA) angle. The purpose of this study is to determine the dynamic coronal HKA angle after mechanical alignment in total knee replacement using computer navigation. We conducted a pre-post design study of 71 patients with varus osteoarthritic knees on which total knee arthroplasty was performed. The HKA was measured before and at the end of the surgical procedure with the patient in the supine position using a navigation system at 30, 60, and 90 degrees of knee flexion. Postoperative implant position and flexion and extension gaps were assessed. HKA was clustered in three preoperative dynamic patterns (PDPs; Varus-Neutral, Varus-Valgus, and Varus-Varus). There were statistically significant differences in the dynamic coronal HKA between the preoperative and postoperative statuses after mechanically aligned knee replacement (with p < 0.0001) Before the surgical procedure, statistically significant differences were found between patterns at any angle of flexion confirming a well-differentiated preoperative dynamic behavior between the three groups. Postoperatively, 98.6% (71 out of 72) of the knees were within ± 3 degrees of the HKA at full extension. Fifty-eight knees (80.6%) were assessed to a "within-range" postoperative dynamic alignment at any grade of flexion considered. There are differences between the preoperative and postoperative status of the dynamic coronal HKA angle after mechanically aligned knee replacement. We proposed that an excellent dynamic HKA alignment is achieved not only at full extension within the range of 0 ± 3 degrees but also when this alignment is maintained at 30, 60, and 90 degrees.

Role of calcium oscillations in sperm physiology.

Intracellular Ca2+ is a key regulator of cell signaling and sperm are not the exception. Cells often use cytoplasmic Ca2+ concentration ([Ca2+]i) oscillations as a means to decodify external and internal information. [Ca2+]i oscillations faster than those usually found in other cells and correlated with flagellar beat were the first to be described in sperm in 1993 by Susan Suarez, in the boar. More than 20 years passed before similar [Ca2+]i oscillations were documented in human sperm, simultaneously examining their flagellar beat in three dimensions by Corkidi et al. 2017. On the other hand, 10 years after the discovery of the fast boar [Ca2+]i oscillations, slower ones triggered by compounds from the egg external envelope were found to regulate cell motility and chemotaxis in sperm from marine organisms. Today it is known that sperm display fast and slow spontaneous and agonist triggered [Ca2+]i oscillations. In mammalian sperm these Ca2+ transients may act like a multifaceted tool that regulates fundamental functions such as motility and acrosome reaction. This review covers the main sperm species and experimental conditions where [Ca2+]i oscillations have been described and discusses what is known about the transporters involved, their regulation and the physiological purpose of these oscillations. There is a lot to be learned regarding the origin, regulation and physiological relevance of these Ca2+ oscillations.

Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection.

RTS,S/AS01 is an advanced pre-erythrocytic malaria vaccine candidate with demonstrated vaccine efficacy up to 86.7% in controlled human malaria infection (CHMI) studies; however, reproducible immune correlates of protection (CoP) are elusive. To identify candidates of humoral correlates of vaccine mediated protection, we measured antibody magnitude, subclass, and avidity for Plasmodium falciparum (Pf) circumsporozoite protein (CSP) by multiplex assays in two CHMI studies with varying RTS,S/AS01B vaccine dose and timing regimens. Central repeat (NANP6) IgG1 magnitude correlated best with protection status in univariate analyses and was the most predictive for protection in a multivariate model. NANP6 IgG3 magnitude, CSP IgG1 magnitude, and total serum antibody dissociation phase area-under-the-curve for NANP6, CSP, NPNA3, and N-interface binding were also associated with protection status in the regimen adjusted univariate analysis. Identification of multiple immune response features that associate with protection status, such as antibody subclasses, fine specificity and avidity reported here may accelerate development of highly efficacious vaccines against P. falciparum.

Comprehensive Data Integration Approach to Assess Immune Responses and Correlates of RTS,S/AS01-Mediated Protection From Malaria Infection in Controlled Human Malaria Infection Trials.

RTS,S/AS01 (GSK) is the world's first malaria vaccine. However, despite initial efficacy of almost 70% over the first 6 months of follow-up, efficacy waned over time. A deeper understanding of the immune features that contribute to RTS,S/AS01-mediated protection could be beneficial for further vaccine development. In two recent controlled human malaria infection (CHMI) trials of the RTS,S/AS01 vaccine in malaria-naïve adults, MAL068 and MAL071, vaccine efficacy against patent parasitemia ranged from 44% to 87% across studies and arms (each study included a standard RTS,S/AS01 arm with three vaccine doses delivered in four-week-intervals, as well as an alternative arm with a modified version of this regimen). In each trial, RTS,S/AS01 immunogenicity was interrogated using a broad range of immunological assays, assessing cellular and humoral immune parameters as well as gene expression. Here, we used a predictive modeling framework to identify immune biomarkers measured at day-of-challenge that could predict sterile protection against malaria infection. Using cross-validation on MAL068 data (either the standard RTS,S/AS01 arm alone, or across both the standard RTS,S/AS01 arm and the alternative arm), top-performing univariate models identified variables related to Fc effector functions and titer of antibodies that bind to the central repeat region (NANP6) of CSP as the most predictive variables; all NANP6-related variables consistently associated with protection. In cross-study prediction analyses of MAL071 outcomes (the standard RTS,S/AS01 arm), top-performing univariate models again identified variables related to Fc effector functions of NANP6-targeting antibodies as highly predictive. We found little benefit-with this dataset-in terms of improved prediction accuracy in bivariate models vs. univariate models. These findings await validation in children living in malaria-endemic regions, and in vaccinees administered a fourth RTS,S/AS01 dose. Our findings support a "quality as well as quantity" hypothesis for RTS,S/AS01-elicited antibodies against NANP6, implying that malaria vaccine clinical trials should assess both titer and Fc effector functions of anti-NANP6 antibodies.

Long-term segmentation-free assessment of head-flagellum movement and intracellular calcium in swimming human sperm.

Human spermatozoa are the archetype of long-term self-organizing transport in nature and are critical for reproductive success. They utilize coordinated head and flagellar movements to swim long distances within the female reproductive tract in order to find and fertilize the egg. However, to date, long-term analysis of the sperm head-flagellar movements, or indeed those of other flagellated microorganisms, remains elusive due to limitations in microscopy and flagellar-tracking techniques. Here, we present a novel methodology based on local orientation and isotropy of bio-images to obtain long-term kinematic and physiological parameters of individual free-swimming spermatozoa without requiring image segmentation (thresholding). This computer-assisted segmentation-free method evaluates, for the first time, characteristics of the head movement and flagellar beating for up to 9.2 min. We demonstrate its powerful use by showing how releasing Ca2+ from internal stores significantly alters long-term sperm behavior. The method allows for straightforward generalization to other bio-imaging applications, such as studies of bull sperm and Trypanosoma, or indeed of other flagellated microorganisms - appealing to communities other than those investigating sperm biology.

Transcriptional profiles of adjuvanted hepatitis B vaccines display variable interindividual homogeneity but a shared core signature.

The current routine use of adjuvants in human vaccines provides a strong incentive to increase our understanding of how adjuvants differ in their ability to stimulate innate immunity and consequently enhance vaccine immunogenicity. Here, we evaluated gene expression profiles in cells from whole blood elicited in naive subjects receiving the hepatitis B surface antigen formulated with different adjuvants. We identified a core innate gene signature emerging 1 day after the second vaccination and that was shared by the recipients of vaccines formulated with adjuvant systems AS01B, AS01E, or AS03. This core signature associated with the magnitude of the hepatitis B surface-specific antibody response and was characterized by positive regulation of genes associated with interferon-related responses or the innate cell compartment and by negative regulation of natural killer cell-associated genes. Analysis at the individual subject level revealed that the higher immunogenicity of AS01B-adjuvanted vaccine was linked to its ability to induce this signature in most vaccinees even after the first vaccination. Therefore, our data suggest that adjuvanticity is not strictly defined by the nature of the receptors or signaling pathways it activates but by the ability of the adjuvant to consistently induce a core inflammatory signature across individuals.

Human sperm uses asymmetric and anisotropic flagellar controls to regulate swimming symmetry and cell steering.

Flagellar beating drives sperm through the female reproductive tract and is vital for reproduction. Flagellar waves are generated by thousands of asymmetric molecular components; yet, paradoxically, forward swimming arises via symmetric side-to-side flagellar movement. This led to the preponderance of symmetric flagellar control hypotheses. However, molecular asymmetries must still dictate the flagellum and be manifested in the beat. Here, we reconcile molecular and microscopic observations, reconnecting structure to function, by showing that human sperm uses asymmetric and anisotropic controls to swim. High-speed three-dimensional (3D) microscopy revealed two coactive transversal controls: An asymmetric traveling wave creates a one-sided stroke, and a pulsating standing wave rotates the sperm to move equally on all sides. Symmetry is thus achieved through asymmetry, creating the optical illusion of bilateral symmetry in 2D microscopy. This shows that the sperm flagellum is asymmetrically controlled and anisotropically regularized by fast-signal transduction. This enables the sperm to swim forward.

Descripción y análisis del patrón de normalidad de flujo dinámico y morfológico de las arterias principales de la muñeca y mano en población sana española / Description and analysis of the dynamic and morphological flow pattern of the main arteries of the wrist and hand in a healthy spanish population

ANTECEDENTES Y OBJETIVO: La anatomía vascular de la mano ya ha sido ampliamente descrita a nivel macroscópico. Sin embargo, existen muy pocos trabajos que estudien el patrón de normalidad de la vascularización in vivo y describan y analicen las arterias principales de la mano. El objetivo de este trabajo es realizar un estudio que sirva de referencia para los valores normales de tamaño y flujo de la arteria radial y ulnar a nivel de la muñeca y de las arterias digitales radiales y ulnares a nivel de los dedos. MATERIAL Y MÉTODO: Estudio descriptivo observacional de corte trasversal sobre 200 manos en 100 voluntarios sanos entre 20-30 años. Se realizó ecografía Doppler-color de las arterias ulnar y radial en la muñeca, así como de las arterias digitales radial y ulnar de cada dedo. Una vez tomadas las medidas se llevó a cabo un análisis comparativo de forma general y también teniendo en cuenta la lateralidad, la dominancia y el género. RESULTADOS: Se observó que existe un mayor tamaño de la arteria radial sobre la ulnar a nivel de la muñeca; sin embargo, es la arteria ulnar la que presentó dominancia de flujo a este nivel. A nivel de los dedos, en los tres primeros fue la arteria digital ulnar la que presentó un mayor tamaño y mayor flujo. No obstante, en el cuarto y quinto dedos fue la arteria digital radial la que presentó un mayor tamaño y dominancia de flujo. CONCLUSIÓN: Ha quedado confirmado que la dominancia de flujo, pero no de tamaño, a nivel de la muñeca es de la arteria ulnar. A nivel de los dedos, existe un mayor tamaño y flujo de las arterias en las zonas de los dedos más protegidas de las lesiones (arteria digital ulnar en los tres primeros y radial en el cuarto y quinto)

BACKGROUND AND AIM: The vascular anatomy of the hand has already been widely described macroscopically. However, there are very few papers that study the pattern of normality of in vivo vascularisation that describe and analyse the main arteries of the hand. The aim of this paper was to carry out a study to serve as a reference for the normal values of size and flow of the radial and ulnar artery at the level of the wrist, and the digital radial and ulnar arteries at the level of the fingers. MATERIAL AND METHOD: A descriptive observational cross-sectional study on 200 hands in 100 healthy volunteers aged between 20-30 years. Doppler-colour ultrasound was performed on the ulnar and radial arteries in the wrist, as well as on the radial and ulnar digital arteries in each finger. Once the measurements had been taken, a general comparative analysis was performed also taking laterality, dominance and gender into account. RESULTS: It was observed that the radial artery is larger in size than the ulnar at wrist level, however, it was the ulnar artery that showed flow dominance at this level. At finger level, the arteries are greater in size and flow in the areas of the fingers more protected from injury (digital ulnar artery in the first three and radial artery in the fourth and fifth digits)

Description and analysis of the dynamic and morphological flow pattern of the main arteries of the wrist and hand in a healthy spanish population. / Descripción y análisis del patrón de normalidad de flujo dinámico y morfológico de las arterias principales de la muñeca y mano en población sana española.

BACKGROUND AND AIM: The vascular anatomy of the hand has already been widely described macroscopically. However, there are very few papers that study the pattern of normality of in vivo vascularisation that describe and analyse the main arteries of the hand. The aim of this paper was to carry out a study to serve as a reference for the normal values of size and flow of the radial and ulnar artery at the level of the wrist, and the digital radial and ulnar arteries at the level of the fingers. MATERIAL AND METHOD: A descriptive observational cross-sectional study on 200 hands in 100 healthy volunteers aged between 20-30years. Doppler-colour ultrasound was performed on the ulnar and radial arteries in the wrist, as well as on the radial and ulnar digital arteries in each finger. Once the measurements had been taken, a general comparative analysis was performed also taking laterality, dominance and gender into account. RESULTS: It was observed that the radial artery is larger in size than the ulnar at wrist level, however, it was the ulnar artery that showed flow dominance at this level. At finger level, the arteries are greater in size and flow in the areas of the fingers more protected from injury (digital ulnar artery in the first three and radial artery in the fourth and fifth digits).

A Th1/IFNγ Gene Signature Is Prognostic in the Adjuvant Setting of Resectable High-Risk Melanoma but Not in Non-Small Cell Lung Cancer.

PURPOSE: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non-small cell lung cancer (NSCLC) tumor samples from two phase III studies. EXPERIMENTAL DESIGN: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies. One-third of the samples were used as "training set"; the remaining two thirds, constituting the "test set," were used for the prospective validation of the GS. RESULTS: In the melanoma training set, the expression level of eight Th1/IFNγ-related genes in tumor-positive lymph node tissue predicted the duration of disease-free survival (DFS) and overall survival (OS) in the placebo arm. This GS was prospectively and independently validated as prognostic in the test set. Building a multivariate Cox model in the test set placebo patients from clinical covariates and the GS score, an increased number of melanoma-involved lymph nodes and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFNγ-related genes was associated with the presence of lymphocytes in tumor samples in both indications. CONCLUSIONS: These findings provide evidence that expression of Th1/IFNγ genes in the TME, as measured by this GS, is associated with clinical outcome in melanoma. This suggests that, using this GS, patients with stage IIIB/C melanoma can be classified into different risk groups.