Integration of molecular testing for the personalized management of patients with diffuse large B-cell lymphoma and follicular lymphoma.

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most common forms of aggressive and indolent lymphoma, respectively. The majority of patients are cured by standard R-CHOP immunochemotherapy, but 30%-40% of DLBCL and 20% of FL patients relapse or are refractory (R/R). DLBCL and FL are phenotypically and genetically hereterogenous B-cell neoplasms. To date, the diagnosis of DLBCL and FL has been based on morphology, immunophenotyping and cytogenetics. However, next-generation sequencing (NGS) is widening our understanding of the genetic basis of the B-cell lymphomas. In this review we will discuss how integrating the NGS-based characterization of somatic gene mutations with diagnostic or prognostic value in DLBCL and FL could help refine B-cell lymphoma classification as part of a multidisciplinary pathology work-up. We will also discuss how molecular testing can identify candidates for clinical trials with targeted therapies and help predict therapeutic outcome to currently available treatments, including chimeric antigen receptor T-cell, as well as explore the application of circulating cell-free DNA, a non-invasive method for patient monitoring. We conclude that molecular analyses can drive improvements in patient outcomes due to an increased understanding of the different pathogenic pathways affected by each DLBCL subtype and indolent FL vs R/R FL.

Extranodal natural killer/T-cell lymphoma nasal type in a western population: Molecular profiling identifies new therapeutic targets.

(A) Correlation matrix of unsupervised co-regulated genes, based on the 208 genes included in the NanoString platform. Some of the clusters of co-regulated genes corresponded to the following: Inflammatory cells; Epstein-Barr virus; B-cells; Cytotoxic T-cells; T-cells; and Proliferation. (B) Analysis of genomic alterations by targeted sequencing. Distribution of mutations in the 62 analyzed genes. Rows correspond to sequenced genes, columns represent individual patients. Color coding: green, missense; blue, synonymous; pink, frameshift; violet, Indel; red, stop gained; yellow, UTR.

Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B-cell lymphoma.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P<0.001, respectively). Infections in the first 6 months post-infusion were also more common in patients treated with axi-cel (38% vs. 25%, P=0.033). Non-relapse mortality was not significantly different between the axi-cel and tisa-cel groups (7% and 4%, respectively, P=0.298). With a median follow-up of 9.2 months, median PFS and OS were 5.9 and 3 months, and 13.9 and 11.2 months for axi-cel and tisa-cel, respectively. The 12-month PFS and OS for axi-cel and tisa-cel were 41% and 33% (P=0.195), 51% and 47% (P=0.191), respectively. Factors associated with lower OS in the multivariate analysis were increased lactate dehydrogenase, ECOG ≥2 and progressive disease before lymphodepletion. Safety and efficacy results in our real-world experience were comparable with those reported in the pivotal trials. Patients treated with axi-cel experienced more toxicity but similar non-relapse mortality compared with those receiving tisa-cel. Efficacy was not significantly different between both products.

Fracturas de la base del quinto metatarsiano: ¿es útil mi tornillo de esponjosa con rosca parcial? Experiencia de 10 años / Fractures of the base of the fifth metatarsal bone: is my partially-threaded cancellous screw useful? 10-year experience

OBJETIVO Evaluar el resultado quirúrgico de fracturas de las zonas 2 y 3 de la base del quinto metatarsiano usando tornillos de esponjosa de diámetro de 4,0 mm con rosca parcial. MATERIALES Y MÉTODOS Evaluación retrospectiva de pacientes operados entre 2010 a 2019. Incluimos todos los casos sintetizados con este dispositivo con seguimiento mínimo de tresmeses, y excluimos casos operados con otros dispositivos y seguimiento menor a tres meses. Evaluamos la consolidació n y la presencia de complicaciones. Determinamos el largo del tornillo, el diámetro del canal endomedular, la distancia entre el borde proximal de la tuberosidad y la fractura, y la distancia de paso de la rosca sobre el rasgo de la fractura en radiografías anteroposterior (AP) y oblicua del pie. RESULTADOS Evaluamos 39 casos, y la muestra tenía una edad promedio de 27 años, y predominio del sexo masculino. El largo de tornillo más usado fue el de 45 mm, y los diámetros promedios del canal endomedular medidos en las radiografías AP y oblicua fueron de 4,6 mm y 3,96 mm, respectivamente. La distancia del borde de la tuberosidad hasta la fractura fue de 25,8 mm, y la distancia de paso de la rosca sobre el rasgo de la fractura fue en promedio de 24 mm. Hubo 100% de consolidación, en un promedio de 9,4 semanas, y 3 casos de retardo de consolidación, 2 de retroceso de tornillo, 1 de rosca intrafoco, y 1 de fractura cortical superior. No hubo retiros de tornillos a la fecha. DISCUSION No existe consenso respecto al tornillo ideal. La literatura internacional recomienda dispositivos intramedulares de diámetro de al menos 4,5 mm. Existen pocos reportes del uso de tornillos de diámetro de 4,0 mm. CONCLUSIONES El tornillo de esponjosa de diámetro de 4,0 mm con rosca parcial es una alternativa eficaz, segura y con baja tasa de complicaciones para el manejo de estas fracturas en nuestra población.

OBJETIVE To evaluate the surgical result of zone-2 and -3 fractures of the base of the fifth metatarsal bone using partially-threaded cancellous screws with a diameter of 4.0 mm. MATERIALS AND METHODS A retrospective evaluation of patients submitted to surgery between 2010 and 2019. We included all of the cases synthesized with this device with a minimum follow-up of three months, and excluded the cases operated on with other devices and follow-up shorter than three months. We evaluated the consolidation and the presence of complications, and determined, screw length, diameter of the endomedullary canal, the distance between the proximal edge of tuberosity and the fracture, and thread pitch over the fracture line on anteroposterior (AP) and oblique radiographs. RESULTS We evaluated 39 cases, and the sample had an average age of 27 years and male predominance. The most used screw length was 45 mm, and the average diameters of the medullary canal measured on the AP and oblique radiographs were of 4.6 mm and 3.96 mm respectively. The distance from the edge of the tuberosity to the fracture was of 25.8 mm, and the thread pitch over the fracture line was on average 24 mm. The rate of consolidation was of 100%, occurring in an average of 9.4 weeks, and there were 3 cases of consolidation delay, 2 of screw recoil, 1 of intrafocus thread, and 1 of superior cortex fracture. To date, there have been no cases of screw removal. DISCUSSION There is no consensus regarding the ideal screw. The international literature recommends intramedullary devices with a diameter of at least 4.5 mm. There are few reports of the use of screws with 4.0 mm in diameter. CONCLUSIONS The partially-threaded cancellous screw with a diameter of 4.0 mm is an effective and safe option, with a low complication rate for the management of these fractures.

Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages.

Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, TP53 mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0-2/Binet A), respectively. Unmutated IGHV was associated with shorter OS and TTFT, even for early-stage patients. Lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis. Our results validate the prognostic value of IGHV mutational status at diagnosis for OS and TTFT, including for early stages. Our findings suggest a role for molecular and mutational analysis at diagnosis in future prospective studies.

Pattern analysis of a complete Achilles tendon rupture suffered during high jump preparation in an official national-level athletic competition.

Elite athletes are subject to injuries like the Achilles tendon rupture. This injury requires a long recovery process, with no guarantee of returning to the pre-injury level. When a rupture happens during natural life, movement analysis can provide useful insights concerning patterns of rupture to understand and prevent Achilles tendon injuries. Here we determined the pattern of rupture of an Achilles tendon (AT) in an elite high-jumper athlete who ruptured an AT during the straight line running phase in preparation for a high-jump attempt. This study is a novel case report regarding a national-level elite athlete. The main outcomes were kinematics parameters obtained from video analysis. The pattern of the rupture was determined by pixel intensity and outlier analysis. The rupture occurred at 44% of the single stance. The injured leg showed a higher ankle dorsal flexion and knee-ankle ratio, and a lower knee flexion compared to contralateral leg. An eccentric pattern of rupture occurred during the transition from the mid to terminal stance phases of running. The lower knee flexion and the increased ankle dorsal flexion during the stance suggest a loss of knee-ankle coordination. This might have favoured a major elongation of Achilles tendon causing the rupture.

Do the heel-rise test and isometric strength improve after Achilles tendon repair using Dresden technique?

BACKGROUND: Achilles' tendon ruptures result in impaired plantar flexion strength and endurance. It is interesting to know the plantar flexion strength, the number of heel-rise repetitions, and the maximal calf circumference following Achilles' tendon ruptures repair. METHODS: Both the injured and non-injured legs of thirty male patients with Achilles' tendon ruptures treated with the percutaneous Dresden technique were compared with the ankle function of 30 healthy participants. Rehabilitation involved partial weight-bearing for three weeks and then increased to full weight-bearing and ankle exercises. RESULTS: The injured legs had weaker plantar flexion strength (1.64 ± 0.17 Nm/kg) compared with the non-injured legs (1.91 ± 0.24 Nm/kg; p = 0.002) and the healthy participants' legs (1.93 ± 0.32 Nm/kg; p < 0.001). The non-injured leg had greater ability in doing heel-rise repetitions (39.4 ± 6.1 rep.) compared with the injured legs (37.2 ± 5.7 rep.; p < 0.023) and the healthy participants' legs (31.0 ± 13.0 rep.; p < 0.001). CONCLUSIONS: The injured leg had not recovered full isometric strength but had improved heel-rise repetition.

Tolerancia a la fatiga muscular isométrica de alta intensidad transcurrido un año de evolución de tenorrafias del tendón de Aquiles: resultados preliminares / Tolerance to high intensity isometric muscle fatigue after one year of evolution of Achilles tendon tenorrhaphies: preliminary results

Introducción: Desafortunadamente, posterior a una tenorrafia del tendón de Aquiles existe abandono de la práctica deportiva. Frente ello, son desconocidas las causas y si la capacidad de tolerancia a la fatiga muscular podría ser un factor en disfunción. Objetivo: Comparar la pendiente y tiempo de la fatiga isométrica de la musculatura plantiflexora superficial entre participantes con una tenorrafia del tendón de Aquiles posterior a 1 año y participantes sanos. Métodos: Diez hombres con tenorrafia Aquiliana y tratamiento kinésico convencional (36,7 ± 10,2 años, 172,6 ± 6,1 cm, 83,1 ± 10,9 kg, IMC 27,3 ± 2,8 kg/m2) y diez participantes sanos (29,9 ± 12,0 años, 171,8 ± 5,8 cm, 81,3 ± 12,0 peso corporal, IMC 27,5 ± 3,7 kg/m2) fueron incorporados. Los participantes realizaron una prueba plantiflexora isométrica en un dinamómetro mientras se registró una señal electromiográfica en gastrocnemio medial con un electrodo de alta densidad. La pendiente de la frecuencia peak y el tiempo hasta la fatiga fueron comprados con una prueba-t (α = 5%). Resultados: No se observaron diferencias de las pendientes entre ambos grupos (grupo sano, -0,0051 ± 0,0078 Hz/s vs grupo con tenorrafia, -0,0082 ± 0,0091 Hz/s; p = 0.513). No hubo diferencias para el tiempo hasta la fatiga entre los grupos (grupo sano, 36,1 ± 17,9 s vs grupo con tenorrafia, 32,8 ± 16,0 s; p = 0.692). Conclusión: La tolerancia a la fatiga muscular y el tiempo necesario para sostenerla en alta intensidad (90%) no es un factor de disfunción en pacientes con tenorrafia Aquiliana y terapia kinésica convencional con 1 año postquirúrgico.

Introduction: Unfortunately, after a tenorrhaphy of the Achilles tendon, there is an abandonment of sports practice. Both their causes are unknown, and if the ability to tolerate muscle fatigue may be in dysfunction. Objetive: Here, we compared the fatigue slope of the peak frequency and the time to isometric fatigue of plantar flexors between participants with an Achilles tendon tenorrhaphy after one year of evolution and healthy participants. Methods: Ten men with Achilles tenorrhaphy and traditional physical therapy (36.7 ± 10.2 years, 172.6 ± 6.1 cm, 83.1 ± 10.9 kg, BMI 27.3 ± 2.8 kg/m2) and ten healthy participants (29.9 ± 12.0 years, 171.8 ± 5.8 cm, 81.3 ± 12.0 kg, BMI 27.5 ± 3.7 kg/m2) were included. The participants performed an isometric contraction of plantar flexors on a dynamometer while high-density electromyography signals were recorded. The slope of peak frequency and time to fatigue were compared with a t-test (α = 5%). Results: For frequency slope there was not difference between groups (Healthy group = -0.0051 ± 0.0078 Hz/s vs Tenorrhaphy group = -0.0082 ± 0.0091 Hz/s; p = 0.513). For time to fatigue there was not difference between groups (Healthy group = 36.1 ± 17.9 s vs Tenorrhaphy group = 32.8 ± 16.0 s; p = 0.692). Conclusion: The tolerance to muscle isometric fatigue and the time to fatigue required to sustain it at a high intensity (90%) is not a factor of dysfunction in patients with Achilles tenorrhaphy treated with conventional physical therapy.

Changes in the ankle muscles co-activation pattern after 5 years following total ankle joint replacement.

BACKGROUND: The Hintegra® arthroplasty provides inversion-eversion stability, permits axial rotation, ankle flexion-extension, and improvements of the gait patterns are expected up to 12 months of rehabilitation. However, sensorimotor impairments are observed in ankle flexors/extensors muscles after rehabilitation, with potential negative effects on locomotion. Here we determined the timing and amplitude of co-activation of the tibialis anterior and medial gastrocnemius muscles during gait by assessing non-operated and operated legs of patients with total ankle replacement, 5 years after surgery. METHODS: Twenty-nine patients (age: 58 [5.5] years, height: 156.4 [6.5] cm, body mass: 72.9 [6.5] kg, 10 men, and 19 women) that underwent Hintegra® ankle arthroplasty were included. Inclusion criteria included 5 years prosthesis survivorship. The onset and offset of muscle activation (timing), as well as the amplitude of activation, were determined during barefoot walking at self-selected speed by surface electromyography. The timing, percentage, and index of co-activation between the tibialis anterior and medial gastrocnemius were quantified and compared between non-operated and operated legs. FINDINGS: The operated leg showed higher co-activation index and temporal overlapping between tibialis anterior and medial gastrocnemius during gait (p < 0.001). INTERPRETATION: The neuromuscular changes developed during the process of degeneration do not appear to be restored 5 years following arthroplasty. The insertion of an ankle implant may restore anatomy and alignment but neuromuscular adaptations to degeneration are not corrected by 5 years following joint replacement.

Biomechanical properties of different techniques used in vitro for suturing mid-substance Achilles tendon ruptures.

BACKGROUND: The Dresden technique preserves the paratenon during Achilles tendon repair and may improve the plantarflexor mechanism when combined with mobilization during early rehabilitation. However, the surgical repair design for Achilles tendon ruptures can affect rates of re-rupture or lengthening. Therefore, the aim of this study was to determine the biomechanical properties of the Krackow, Double-Kessler, Double-Dresden, and Triple-Dresden techniques used for repairing mid-substance Achilles tendon ruptures during cyclical and maximum traction. METHODS: Sixty mid-substance bovine tendons repaired after transverse rupturing were divided randomly into four groups by repair technique: Krackow, Double-Kessler, Double-Dresden, and Triple-Dresden. Cyclical tractions of 4.7, 5.8, 7.9, and 11.7mm (equivalent to 5°, 8°, 10°, and 15° of dorsal flexion, respectively) were applied to determine gapping, tensile strength, nominal suture stress, repair deformation, and specimens with clinical failure (gap>5mm). Maximal traction was applied to measure maximum strength and failure type (i.e. suture, knot, or tendon). FINDINGS: The Triple-Dresden technique resulted in decreased gapping, nominal suture stress, repair deformation, and quantity of specimens with clinical failure as compared to the other techniques. Furthermore, Triple-Dresden tendons showed greater comparative tensile and maximum strength. During maximal traction testing, this technique presented tendon failure, whereas the Krackow, Double-Kessler, and Double-Dresden techniques had suture failures. INTERPRETATION: Triple-Dresden repair results in better cyclical and maximum traction strengths, suggesting that this technique might be more appropriate when performing early mobilization after mid-substance Achilles tendon rupture repair.

Clinical failure after Dresden repair of mid-substance Achilles tendon rupture: human cadaveric testing.

PURPOSE: The purpose of this study was to describe the angle of clinical failure during cyclical mobilization exercises in the Achilles tendon of human cadaveric specimens that were repaired using the Dresden technique and FiberWire® No. 2. The secondary aim was to identify the secure limit of mobilization, the type of failure, and the type of apposition. METHODS: The lower limbs of eight males (mean age: 60.3 ± 6.3 years) were repaired with the Dresden technique following complete, percutaneous mid-substance Achilles tendon rupture. A basal tension of 10 N at 30° of plantarflexion was placed on each specimen. The angle of the ankle during clinical failure (tendon ends separation >5 mm) was then tested via cyclical exercises (i.e. 100 cycles between 30° and 15° of plantarflexion; 100 cycles between 15° of plantarflexion and 0°; 100 cycles between 0° and 15° of dorsiflexion; and 100 cycles between 15° of dorsiflexion and full dorsiflexion). Clinical failure was determined using the Laplacian edge detection filter, and the angle of clinical failure was obtained using a rotatory potentiometer aligned in relation to the intermalleolar axis of each foot specimen. The type of failure (knot, tendon, or suture) and apposition (termino-terminal or non-termino-terminal) were determined. Descriptive statistics were used to obtain the mean; standard deviation; 95 % confidence interval; 1st, 25th, 50th, 75th, and 100th percentiles; and the standard error of the mean for angle data. Proportions were used to describe the type of failure and apposition. RESULTS: The main results were a mean angle of clinical failure equal to 12.5° of plantarflexion, a limit of mobilization equal to 14.0° of plantarflexion, tendon failure type, and non-termino-terminal apposition in all specimens. CONCLUSIONS: While the mean angle of clinical failure in human cadaveric models was 12.5° of plantarflexion, after 14.0° of plantarflexion, the percutaneous Dresden technique was found insecure for cyclical mobilization exercises, with a 5 % range of error. These findings are clinically relevant as they provide mechanical limits for diminishing the risk of Achilles lengthening during immediate rehabilitation.

Etanercept en la enfermedad de injerto contra huésped aguda refractaria a corticoides / Etanercept on steroid-refractary acute graft-versus-host disease

Objetivo: Describir el uso y la efectividad de etanercept como terapia en la enfermedad de injerto contra huésped refractaria a corticoides tras el trasplante alogénico de progenitores hematopoyéticos. Método: Se seleccionaron los pacientes en los que se utilizó etanercept fuera de indicación para el tratamiento de la enfermedad de injerto contra huésped y se revisaron retrospectivamente sus historias clínicas para evaluar la respuesta al tratamiento. Resultados: De un total fueron cinco pacientes tratados cuatro presentaban enfermedad con afectación digestiva y otro con manifestación pulmonar y hepática. En el 80% de los casos se alcanzó alguna respuesta clínica: 60% respuesta parcial y 20% respuesta completa. En cuatro pacientes se utilizo etanecept 25mg dos veces por semana con duración variable, obteniendo una respuesta nula en uno (3 semanas), parcial en dos (4 y 8 semanas) y total en otro (8 semanas). Sólo en un caso se usó etanercept 50mg dos veces en semana durante 5 semanas con respuesta parcial. Conclusiones: Los resultados obtenidos de respuesta clínica son coherentes con los publicados previamente y vienen a incrementar la escasa bibliografía sobre la utilidad de etanercept en el tratamiento en la enfermedad de injerto contra huésped aguda y refractaria a corticoides. Dadas las limitaciones del diseño y el reducido número de pacientes, estudios controlados deberán evaluar en el futuro la eficacia y la seguridad de etanercept en estos pacientes (AU)

Objetive: To describe etanercept use and effectiveness on steroid-refractary acute graft-versus-host disease after hematopoietic cell transplantation. Method: Patients treated with etanercept as off label use for steroid-refractary acute graft-versus-host disease were selected and each patient’s medical history was reviewed to assess the clinical response. Results: The study included five patients: four presented with digestive manifestations and one presented pulmonary and liver manifestations. 80% of patients showed a clinical response: 60% a partial response and 20% a total response. In four cases etanercept 25mg was administered twice a week with variable duration of treatment, achieving no response in 1 case (3 weeks), partial response in two 2 cases (4 weeks and 8 weeks) and a complete response in 1 case (8 week period). Only one case was treated with etanercept 50mg administered twice a week for 5 weeks with a partial treatment response. Conclusions: The clinical response rate is consistent with the previously published data. This updates the scarce bibliographic information about etanecept use in steroid-refractary acute graft-versus-host disease. Due to clinical design limitations and the small patient population, future clinical studies should be conducted to assess the efficacy and security of etanercept in these patients (AU)

[Etanercept on steroid-refractary acute graft-versus-host disease]. / Etanercept en la enfermedad de injerto contra huésped aguda refractaria a corticoides.

UNLABELLED: Objetive: To describe etanercept use and effectiveness on steroid- refractary acute graft-versus-host disease after hematopoietic cell transplantation. METHOD: Patients treated with etanercept as off label use for steroid-refractary acute graft-versus-host disease were selected and each patient's medical history was reviewed to assess the clinical response. RESULTS: The study included five patients: four presented with digestive manifestations and one presented pulmonary and liver manifestations. 80% of patients showed a clinical response: 60% a partial response and 20% a total response. In four cases etanercept 25mg was administered twice a week with variable duration of treatment, achieving no response in 1 case (3 weeks), partial response in two 2 cases (4 weeks and 8 weeks) and a complete response in 1 case (8 week period). Only one case was treated with etanercept 50mg administered twice a week for 5 weeks with a partial treatment response. CONCLUSIONS: The clinical response rate is consistent with the previously published data. This updates the scarce bibliographic information about etanecept use in steroid-refractary acute graft-versus-host disease. Due to clinical design limitations and the small patient population, future clinical studies should be conducted to assess the efficacy and security of etanercept in these patients.

Objetivo: Describir el uso y la efectividad de etanercept como terapia en la enfermedad de injerto contra huésped refractaria a corticoides tras el trasplante alogénico de progenitores hematopoyéticos. Método: Se seleccionaron los pacientes en los que se utilizó etanercept fuera de indicación para el tratamiento de la enfermedad de injerto contra huésped y se revisaron retrospectivamente sus historias clínicas para evaluar la respuesta al tratamiento. Resultados: De un total fueron cinco pacientes tratados cuatro presentaban enfermedad con afectación digestiva y otro con manifestación pulmonar y hepática. En el 80% de los casos se alcanzó alguna respuesta clínica: 60% respuesta parcial y 20% respuesta completa. En cuatro pacientes se utilizo etanecept 25mg dos veces por semana con duración variable, obteniendo una respuesta nula en uno (3 semanas), parcial en dos (4 y 8 semanas) y total en otro (8 semanas). Sólo en un caso se usó etanercept 50mg dos veces en semana durante 5 semanas con respuesta parcial. Conclusiones: Los resultados obtenidos de respuesta clínica son coherentes con los publicados previamente y vienen a incrementar la escasa bibliografía sobre la utilidad de etanercept en el tratamiento en la enfermedad de injerto contra huésped aguda y refractaria a corticoides. Dadas las limitaciones del diseño y el reducido número de pacientes, estudios controlados deberán evaluar en el futuro la eficacia y la seguridad de etanercept en estos pacientes.

The influence of ethnicity on warfarin dosage requirements in the chilean population.

BACKGROUND: Vitamin K antagonists are drugs that are widely prescribed around the world and their use has helped improve the prognosis of patients with thromboembolic disease. However, a high interindividual variability has been observed in dosage requirements to reach the desired anticoagulation range that could be due to environmental and genetic factors. Studies suggest that ethnicity influences coumarin response, supporting the observed differences in dose requirements across various populations. Studies using mitochondrial DNA (mtDNA) markers have suggested that the Chilean population has a predominantly Amerindian genetic pool. OBJECTIVE: To evaluate the influence of ethnicity, defined by the presence of Amerindian mtDNA haplogroups, on the variability in therapeutic response to warfarin in the Chilean population. METHODS: A total of 191 patients treated with warfarin were included in this study. Analysis of the mitochondrial genome for detecting the presence of Amerindian mtDNA haplogroups was performed using polymerase chain reaction and polymerase chain reaction restriction fragment length polymorphism techniques. The evaluation of warfarin requirements according to each haplogroup was performed by ANOVA with a 95% CI and assuming statistical significance at P < 0.05. RESULTS: Based on the presence of an mtDNA haplogroup, 91% of the Chilean population had an Amerindian background. There were no significant differences in warfarin dosage requirements among the different Amerindian haplogroups (P = 0.083). CONCLUSIONS: The presence of Amerindian mtDNA haplogroup does not influence warfarin dosage requirements in the Chilean population.

Intratask Variability As a Correlate for DRD4 and SLC6A3 Variants: A Pilot Study in ADHD.

UNLABELLED: Behavioral variability may be an ADHD key feature. Currently used ex-Gaussian/Fast Fourier Transform analyses characterize general distribution and oscillatory/rhythmic components of performance but are unable to demonstrate slow cumulative changes over entire tasks. OBJECTIVE: To explore how performance of ADHD children and unaffected sibs gradually evolves in relation to genetic variants linked to ADHD. METHOD: A total of 40 kids (20 ADHD-discordant sib pairs) between 8 and 13 years resolved a visual Go/NoGo with 10% NoGo probability. Variable number tandem repeats (VNTRs) at DRD4 and SLC6A3 were identified following standard protocols. Performance changes were assessed by linear/logistic mixed-effect models. RESULTS: Models exploring SLC6A3 effects demonstrated less accentuated increments of response time (RT) (p = .046) and cumulative increments in the correct responses to "NoGo" (p = .00027) in 10R/10R participants. Models for DRD4 showed faster decline of correct responses to "Go" (p = .0078) in 2R/7R carriers. CONCLUSION: Dynamical analysis of attention/inhibition measures may unravel new correlates to DRD4 and SLC6A3 variants.

Are locking plates better than non-locking plates for treating distal tibial fractures?

BACKGROUND: Locking and non-locking plates has been used for distal tibia fracture osteosynthesis. Sufficient evidence to favor one implant over the other is lacking in the current literature. Our aim is to compare them in terms of fracture healing, alignment, functional outcome, complications. METHODS: Sixty-eight patients operated on using a percutaneous plate were retrospectively reviewed. They were divided into two groups: in group 1 (28 patients) a 4.5mm narrow conventional dynamic compression plate (DCP) was used. In group 2 (40 patients) a titanium locked compression plate (LCP) was used. RESULTS: Mean time to union was 16.2 and 15.4 weeks for group 1 and 2, respectively (p=0.618). 11 patients (39.3%) in group 1 and 4 patients (10%) in group 2 showed malalignment (p=0.016). AOFAS scores at follow up were 89 and 88 in groups 1 and 2, respectively. Implant removal was necessary in 9 cases (32.1%) and 4 cases (10%) in group 1 and group 2, respectively (p=0.042). Three patients (10.7%) in group 1 and three patients (7.5%) in group 2 had an infection. CONCLUSIONS: Both plating systems have similar results in terms of time to union, infection, and AOFAS scores. The LCP seems superior with respect to alignment and the need for implant removal.

Intra-Individual Response Variability Assessed by Ex-Gaussian Analysis may be a New Endophenotype for Attention-Deficit/Hyperactivity Disorder.

Intra-individual variability of response times (RTisv) is considered as potential endophenotype for attentional deficit/hyperactivity disorder (ADHD). Traditional methods for estimating RTisv lose information regarding response times (RTs) distribution along the task, with eventual effects on statistical power. Ex-Gaussian analysis captures the dynamic nature of RTisv, estimating normal and exponential components for RT distribution, with specific phenomenological correlates. Here, we applied ex-Gaussian analysis to explore whether intra-individual variability of RTs agrees with criteria proposed by Gottesman and Gould for endophenotypes. Specifically, we evaluated if normal and/or exponential components of RTs may (a) present the stair-like distribution expected for endophenotypes (ADHD > siblings > typically developing children (TD) without familiar history of ADHD) and (b) represent a phenotypic correlate for previously described genetic risk variants. This is a pilot study including 55 subjects (20 ADHD-discordant sibling-pairs and 15 TD children), all aged between 8 and 13 years. Participants resolved a visual Go/Nogo with 10% Nogo probability. Ex-Gaussian distributions were fitted to individual RT data and compared among the three samples. In order to test whether intra-individual variability may represent a correlate for previously described genetic risk variants, VNTRs at DRD4 and SLC6A3 were identified in all sibling-pairs following standard protocols. Groups were compared adjusting independent general linear models for the exponential and normal components from the ex-Gaussian analysis. Identified trends were confirmed by the non-parametric Jonckheere-Terpstra test. Stair-like distributions were observed for µ (p = 0.036) and σ (p = 0.009). An additional "DRD4-genotype" × "clinical status" interaction was present for τ (p = 0.014) reflecting a possible severity factor. Thus, normal and exponential RTisv components are suitable as ADHD endophenotypes.

Postoperative range of motion trends following total ankle arthroplasty.

BACKGROUND: It is still unknown how ankle range of motion changes following total ankle arthroplasty. This study was undertaken to more accurately address patient expectations, guide postoperative rehabilitation, and improve our understanding of how ankle range of motion changes with time. METHODS: 119 total ankle replacements of 3 different prosthetic designs from 1 surgeon were retrospectively examined and compared. Ankle dorsiflexion and plantar flexion ranges of motion were calculated and analyzed preoperatively and postoperatively at 6 weeks, 3 months, 6 months, and 1 year. The different ankle replacement systems were analyzed individually and together to determine whether trends were replicated. RESULTS: No significant increase in ankle range of motion was found 6 months postoperatively (P = .75). Mean combined postoperative range of motion did not change significantly from 24.3 degrees at 1 year versus a preoperative mean of 22.7 degrees (P = .75). Mean dorsiflexion improved significantly at the 6-week postoperative stage by 5.5 degrees (P < .001), whereas plantar flexion only improved by 2.9 degrees (P = .06). Mean dorsiflexion improved from preoperative levels by 5.4 degrees (P = .001), whereas mean plantar flexion decreased by 3.7 degrees (P = .004). CONCLUSIONS: We found no notable improvement in ankle range of motion after 6 months following total ankle arthroplasty. We also found a disproportionately higher increase in dorsiflexion compared with plantar flexion following surgery and an overall reduction in mean plantar flexion range compared with preoperative values. Notwithstanding this discrepancy, total mean ankle range of motion 1 year postoperatively was similar to preoperative values. Reasons for the discrepancy between dorsiflexion and plantar flexion are unclear. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Continuous popliteal block for postoperative analgesia in total ankle arthroplasty.

BACKGROUND: Total ankle arthroplasty is associated with severe postoperative pain. Development of analgesic techniques such as a block with continuous infusion at the popliteal level has been shown to result in good pain control, a decrease in the use of rescue analgesia and a low rate of complications. We reviewed our experience with this method of analgesia in patients who underwent total ankle arthroplasty. METHODS: A prospective study of 30 patients undergoing total ankle arthroplasty was carried out. Twenty-two of these received and maintained a block at the popliteal level with a continuous infusion of bupivacaine, while the remaining eight received no such block. RESULTS: The visual analog scale evaluation (VAS) showed a significant improvement in pain control in the group with the popliteal block after 6, 12, 18, and 24 hours postsurgery, with pain levels peaking and being most different between 6 and 12 hours postsurgery for the two groups. The group with the popliteal block also exhibited a significantly lower consumption of morphine and a greater degree of patient satisfaction. CONCLUSION: The block with continuous infusion at the popliteal fossa was a safe technique for total ankle arthroplasty postoperative analgesia, which provided good pain control, a lower requirement of opiates and a higher level of patient satisfaction.