Factores que Afectan la Percepción de Dolor ¿Cómo Influyen en la Toma de Decisiones Clínicas durante el Proceso de Rehabilitación Kinesiológica? / Factors That Affect Pain Perception: How Do They Influence Clinical Decision Making During the Kinesiological Rehabilitation Process?

Introducción. La percepción del dolor es un fenómeno complejo y subjetivo. Comprender los factores que afectan en la percepción del dolor es crucial en el contexto de la toma de decisiones clínicas durante el proceso de rehabilitación kinesiológica. Objetivo. Exponer los factores que afectan la percepción del dolor, desde la perspectiva del modelo biopsicosocial y discutir sus implicancias para la toma de decisiones clínicas. Métodos. Se describen factores que afectan la percepción de dolor, separados en biológicos como la injuria, sexo, genética y edad, psicológicos como creencias, catastrofismo, kinesiofobia, afectividad negativa, calidad de sueño, atención, afrontamiento y autoeficacia; y socio-culturales como soporte social, rol de género, etnia, aculturación y estatus socioeconómico. Luego se discute cómo estos factores impactan en las decisiones clínicas del profesional kinesiólogo. Finalmente, se entregará un análisis de las barreras y facilitadores descritos por la literatura científica respecto al uso del modelo biopsicosocial.

Background. The perception of pain is a complex and subjective phenomenon. Thus, understanding the factors that influence pain perception is crucial in the context of clinical decision-making during the kinesic rehabilitation process. The objective of this article is to expose the factors that affect the perception of pain, from the perspective of the biopsychosocial model and discuss its implications for clinical decision making during this process. Initially, the biological, psychological and sociocultural factors that affect the perception of pain with the greatest presence in the scientific literature are described. It is discussed how these factors impact the clinical decisions of the kinesiologist professional. Finally, an analysis of the barriers and facilitators described by the scientific literature regarding the use of the biopsychosocial model will be provided.

Calidad de vida, nivel de actividad física y pruebas funcionales en personas adultas y mayores laboralmente activas / Quality of life, level of physical activity and functional tests in actively working adults and older people

BACKGROUND: The population of actively working older people is growing rapidly. The relationship between quality of life, levels of physical activity and functionality in this population is not entirely clear. AIM: To determine the association between quality of life, levels of physical activity and functional tests in actively working adults and older people. MATERIAL AND METHODS: Cross sectional assessment of 138 adults aged 40 to 50 years (53% women) and 119 older people aged 60 to 75 years (53% women) who were actively working in two public services. Quality of life was measured with the SF-36 questionnaire and usual physical activity was assessed with the International Physical Activity Questionnaire (IPAQ-short). Handgrip strength, the timed up and go (TUG) and chair stand test (CST) were used as functional tests. RESULTS: Compared to older people, adults had better physical functional tests (P < 0.01). Older people had better scores in the mental health component (MHC) of quality of life (p < 0.05). In adults, the physical health component of quality of life (CSF) had a positive association with physical activity (Spearman Rho (rs)= 0.270; p = 0.01), grip strength (rs = 0.330; p < 0.01) and the TUG (rs = −0.229; p < 0.01). In older patients, CSM and CST were positively correlated (rs = 0.201; P = 0.029). In both groups, a correlation was observed between CSM, grip strength (adults rs = 0.283; p < 0.01; older people rs = 0.211; P = 0.02) and with TUG (adults rs = −0.197; P = 0.021; older people rs = - 0.212; p = 0.02). CONCLUSIONS: There is a positive correlation between quality of life and level of physical activity in working adults, which is not observed in older people. Adequate performance in physical functional tests is positively correlated with better quality of life (CSF and CSM) in adults and only with the mental health component in older people.

Influencia de Factores Psicológicos en el Pronóstico de Individuos con Artroplastia de Cadera por Artrosis: una Revisión de la Literatura / Influence of Psychological Factors on the Prognosis of Individuals with Hip Arthroplasty for Osteoarthritis: A Review of the Literature

Introducción. Los factores psicológicos preoperatorios pueden influir en los resultados de la rehabilitación de la artroplastia de cadera por artrosis. No existe consenso de cuáles serían estos factores, ni sobre en qué medidas de resultados influirían. Objetivo. Sintetizar la evidencia respecto a los factores psicológicos que pronostican los resultados de la artroplastía de cadera en términos de función física y dolor en individuos con artrosis de cadera. Métodos. Se efectuó una búsqueda en PUBMED, EMBASE, SCOPUS y CINAHL. Los términos incluyeron artroplastia de cadera, artrosis, factores psicológicos, función física y dolor. Se incorporaron estudios observacionales prospectivos. Los resultados se agruparon por factor psicológico en periodos menor a un año e igual o mayor a un año. Resultados. La búsqueda arrojó 895 artículos, dos cumplieron los criterios de elegibilidad. Los resultados descritos fueron: 1) un mayor nivel de expectativas preoperatorias genera un efecto positivo en la disminución de la intensidad de dolor y 2) tiene un efecto positivo en la función física, ambas a menos de un año, y 3) la depresión preoperatoria genera un efecto negativo en la disminución de intensidad de dolor a un año o más. Conclusiones. La presencia de depresión preoperatoria se asoció a una menor reducción de dolor, y las altas expectativas preoperatorias se asociaron con una mejor función física y una menor intensidad de dolor. Sin embargo, se hace necesaria la generación de nueva evidencia científica que profundice en la asociación factores psicológicos preoperatorios y dolor crónico en esta población.

Background. Preoperative psychological factors may influence the results of hip arthroplasty rehabilitation for osteoarthritis. There is no consensus on what these factors would be, nor on what outcome measures they would influence. Objetive. To review was to synthesize the evidence regarding psychological factors that predict hip arthroplasty outcomes in terms of physical function and pain in individuals with hip osteoarthritis. Methods. A search was carried out in PUBMED, EMBASE, SCOPUS and CINAHL. Terms included hip arthroplasty, osteoarthritis, psychological factors, physical function, and pain. Prospective observational studies were incorporated. The results were grouped by psychological factor in periods of less than one year and equal to or greater than one year. Results. The search yielded 895 articles, two met the eligibility criteria. The results described were: 1) a higher level of preoperative expectations generates a positive effect in the reduction of pain intensity and 2) has a positive effect on physical function, both at less than one year, and 3) preoperative depression generates a negative effect in the reduction of pain intensity at one year or more. Conclusions. The presence of preoperative depression was associated with less pain reduction, and high preoperative expectations were associated with better physical function and less pain intensity. However, it is necessary to generate new scientific evidence that deepens the association of preoperative psychological factors and chronic pain in this population.

Análisis del Modelo de Miedo-Evitación (Fear-avoidance model) del Dolor Crónico / Analysis of the Fear-avoidance model of Chronic Pain

Se han propuesto diversos modelos para entender la experiencia dolorosa, dentro de los que destaca el "fear-avoidance model" o modelo de miedo-evitación. Este ensayo presenta y discute los principales postulados de los artículos más relevantes para entender el desarrollo y evolución de este modelo. Esta evolución nos permite comprender nuestra propia evolución como kinesiólogos musculoesqueléticos, visualizando una concepción fenomenológica del dolor, comprendiendo su complejidad y multidimensionalidad.

Several models have been proposed to understand the painful experience, among which the "fear-avoidance model" stands out. This essay presents and discusses the main postulates of the most relevant articles to understand the development and evolution of this model. This evolution allows us to understand our own evolution as musculoskeletal physical therapists, visualizing a phenomenological conception of pain, understanding its complexity and multidimensionality.

Calidad de Sueño y Dolor en Individuos con Trastornos Musculoesqueléticos: un Estudio de Corte Transversal / Sleep Quality and Pain in Individuals with Musculoskeletal Disorders: a Cross-sectional Study

Introducción. Los trastornos musculoesqueléticos (TME) y una calidad de sueño (CS) deficiente tienen una alta comorbilidad y una relación recíproca. Son varios los factores capaces de influir esta relación, como el sexo, la duración del dolor y posiblemente el contexto socioeconómico. La información proviene principalmente de países de alto ingreso económico. Así, ampliar el estudio de esta relación a distintos escenarios sociales, como Hispanoamérica, resulta relevante. Objetivo. Analizar la relación entre CS y dolor en individuos chilenos con TME. Método. Estudio transversal, cuantitativo-analítico. Participaron 286 individuos con diagnóstico de TME (edad promedio 49,11±18,27 años). Se evaluó la CS con el índice de calidad de sueño de Pittsburgh (PSQI). Asimismo, se midió la intensidad e interferencia de dolor con escala visual análoga (EVA) y la duración del dolor en meses. Se comparó intensidad e interferencia del dolor según CS y se correlacionó el puntaje de PSQI con intensidad e interferencia del dolor. Resultados. Los individuos con CS deficiente presentaron mayores niveles de interferencia e intensidad de dolor. Un mayor puntaje total PSQI (es decir, menor CS) se correlacionó con mayor intensidad e interferencia de dolor. Conclusión. Una CS deficiente se relacionó con la percepción de mayor intensidad dolor y mayor interferencia de dolor. El manejo integral de pacientes con dolor musculoesquelético debe considerar abordar factores modificables que influyan en él, como la CS.

Background. Musculoskeletal disorders (MSD) and poor sleep quality (SQ) have been reported to have a high comorbidity and a reciprocal relationship. Several factors can influence this relationship, such as gender, duration of pain, and possibly socioeconomic background. This, added to the fact that the information comes mainly from countries with high economic income, highlights the importance of expanding its study to different social scenarios, such as Latin America. Objective. To analyse the relationship between SQ and pain in Chilean individuals with MSD. Methods. Cross-sectional, quantitative-analytical study. 286 individuals with a diagnosis of MSD participated (mean age 49.11±18.27 years). SQ was assessed with the Pittsburgh Sleep Quality Index (PSQI). Likewise, the intensity and interference of pain with a visual analogue scale (VAS) and the duration of the pain in months were measured. Pain intensity and interference were compared according to SQ and PSQI score was correlated with pain intensity and interference. Results. The frequency of poor SQ was 81.1%. Individuals with poor SQ presented higher levels of interference and pain intensity. A higher PSQI total score (i.e., lower SQ) correlated significantly with higher pain intensity and interference. Conclusion. A poor SQ was directly related to the perception of greater pain intensity and greater pain interference. Comprehensive management of patients with musculoskeletal pain should consider addressing modifiable factors that influence it, such as SQ.

Factores de Riesgo relacionados al Síndrome de Estrés Medial Tibial en Corredores Competitivos: Una Revisión Sistemática / Risk Factors related to Medial Tibial Stress Syndrome in Competitive Runners: A Systematic Review

Introducción. El síndrome de estrés tibial medial (SEMT) tiene una alta prevalencia entre corredores y genera un negativo impacto funcional. Un gran número de factores de riesgo se asocian con el desarrollo de SEMT, sin embargo, no existe claridad de cuales factores desencadenan la lesión en esta población. Objetivo. Identificar los factores de riesgo relacionados al SEMT en corredores sintetizando la información en una revisión sistemática. Métodos. Se realizó una búsqueda de estudios de cohorte y, casos y controles, en idioma inglés y español, en distintas bases de datos tales como Pubmed, EMBASE, EBSCO, SPORTDiscus, Scopus y Web of Science. Se incluyeron estudios con población de corredores de cross-country y track and field. Se analizaron factores de riesgo asociados a SEMT. Además, Se extrajeron datos como diseño y duración del estudio, definición del SEMT utilizada, características de la población y método diagnóstico. Se evaluó la calidad metodológica con el "NIH Quality Assessment Tool". Resultados. Cinco estudios y 43 factores de riesgo fueron analizados. 18 factores de riesgo presentaron una asociación significativa con SEMT. Los estudios tuvieron entre 64,3-85,7% de calidad metodológica. Los factores de riesgo más analizados fueron sexo, caída del navicular, índice de masa corporal, talla, peso, rango de dorsiflexión de tobillo y rotación de cadera en el plano transverso. Conclusión. Nuestra revisión no permitió determinar un factor de riesgo de SEMT, ya que los resultados entre los estudios fueron contradictorios o solo un estudio mostraba resultados significativos.

Background. Medial tibial stress syndrome (MTSS) has a high prevalence among runners and creates a major functional impact. A large number of risk factors are associated with the development of MTSS, which are not conclusive in this population. Objective: To identify the risk factors associated with MTSS in runners summarizing the gathered data through a systematic review. Methods. A search for cohort and case-control studies retrieved from different databases was conducted in English and Spanish. Studies with cross-country, track, and field runners were covered, in which risk factors associated with MTSS will be analyzed. The extracted data included: the design and duration of the study, the definition of MTSS currently used, the characteristics of the population, the analyzed risk factors, and the diagnostic method. The methodological quality was screened through the use of the "NIH Quality Assessment Tool". Results. Five studies and 43 risk factors were analyzed. Eighteen risk factors had a significant association with MTSS. The studies had a methodological quality of 64.3 -85.7%. The most analyzed risk factors were gender, navicular drop, body mass index, height, weight, range of ankle dorsiflexion and hip rotation in the transverse plane. Conclusion. Our review did not allow us to determine a risk factor for SEMT, since the results between the studies were contradictory or only one study showed significant results.

Effect of adduction during glenohumeral external rotation exercises in the scapulohumeral muscles / Efecto de la adducción durante ejercicios de rotación externa glenohumeral en los músculos escapulohumerales

SUMMARY: The effect of adduction during glenohumeral external rotation (ER) exercises on the scapulohumeral muscles is controversial. The aim of this study was to evaluate the effect of carrying out adduction during external rotation exercises in low and high shoulder positions on the electromyographic (EMG) activity of the infraspinatus (IS), middle deltoid (MD), and posterior deltoid (PD) muscles. EMG activity of the IS, MD, and PD muscles of 20 healthy participants was evaluated. Subjects performed 6 ER exercises that combined two factors: i) different adduction pressures according to biofeedback unit (0, 5 and 10 mmHg), and ii) low and high shoulder position. The pressure was controlled using a biofeedback unit. The low and high shoulder positions were 20? and 90? of abduction. In the low shoulder position, the activity of the IS muscle increased as the pressure on the biofeedback unit increased and the MD and PD muscles presented the highest activity at 10 mmHg. In the high shoulder position, the activity of the IS muscle was higher at 0 and 10 mmHg, the MD muscle presented higher activity at 5 mmHg, and PD muscle activity did not vary with the pressure. The addition of adduction at a pressure of 5 mmHg in the low shoulder position promotes is activity. Likewise, adduction at a pressure of 10 mmHg will promote activity of the IS, MD, and PD.

RESUMEN: El efecto de la aducción durante los ejercicios de rotación externa (RE) glenohumeral sobre los músculos escapulohumerales es controversial. El objetivo de este estudio fue evaluar el efecto de la realización de la aducción durante los ejercicios de rotación externa en posiciones bajas y altas del hombro sobre la actividad electromiográfica (EMG) delos músculos infraespinoso (IS), deltoides medio (DM) y deltoides posterior (DP). Se evaluó la actividad EMG de los músculos IS, MD y PD de 20 participantes sanos. Los sujetos realizaron 6 ejercicios de RE que combinaron dos factores: i) diferentes presiones de aducción de acuerdo con la unidad de biorretroalimentación (0, 5 y 10 mmHg), y ii) posición del hombro baja y alta. La presión se controló mediante una unidad de biorretroalimentación. Las posiciones del hombro baja y alta fueron de 20? y 90? de abducción. En la posición del hombro bajo, la actividad del músculo IS aumentó a medida que aumentaba la presión sobre la unidad de biorretroalimentación y los músculos MD y PD presentaron la actividad más alta a 10 mmHg. En la posición del hombro alto, la actividad del músculo IS fue mayor a 0 y 10 mmHg, el músculo MD presentó mayor actividad a 5 mmHg y la actividad del músculo PD no varió con la presión. La adición de aducción a una presión de 5 mmHg en la posición baja del hombro promueve la actividad del músculo IS. Asimismo, la aducción a una presión de 10 mmHg promoverá la actividad del IS, MD y PD.

Association between sleep quality and pain in young amateur athletes / Asociación entre calidad del sueño y dolor en jóvenes atletas amateurs / Associação entre qualidade do sono e dor em jovens atletas amadores

ABSTRACT Introduction: It has been shown that there is a close association between sleep quality and pain. In young athletes, sleep disorders and pain have a particularly high prevalence; however, the relationship between them has not been widely studied. Objective: To study the association between sleep quality and pain in young athletes. Methods: A cross-sectional study was conducted in which 71 young amateur athletes (39 males) were included. The mean age was 16.9 ± 1.2 years, with 6.5 ± 3.2 years of sports practice and 5.2 ± 1.2 hours of training per week. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). The participants were classified according to sleep quality, as PSQI-I = without sleep disorders, PSQI-II = requiring medical assistance and PSQI-III = requiring medical assistance and treatment. Also, pain intensity was assessed on the Numerical Rating Scale, both at rest (NRSr) and during sports activity (NRSs), along with pain duration. Results: The individuals classified as PSQI-III presented higher NRSr (Mdn = 2.0; IQR = 4.0 vs. Mdn = 0.0; IQR = 2.0; p = 0.04) and higher NRSs (Mdn = 4.0; IQR = 5.0 vs. Mdn = 0.0; IQR = 2.0; p = 0.03) than the individuals classified as PSQI-I. No differences were observed in relation to pain duration. The PSQI score was positively but weakly associated with NRSr (rs = 0.24, p=0.046) and NRSs (rs = 0.27, p = 0.03) but not with pain duration. Conclusion: Young athletes with lower levels of sleep quality show higher levels of pain at rest and during sports practice. Therefore, sleep quality and pain should be considered in the routine assessment of young athletes, by technical and health teams. Level of evidence III; type of study: Cross-sectional .

RESUMEN Introducción: Se demostró que existe estrecha relación entre calidad del sueño y dolor. En atletas jóvenes, los disturbios del sueño y dolor tienen prevalencia bastante alta, sin embargo, la relación entre ellos no fue ampliamente estudiada. Objetivo: Estudiar la asociación entre calidad del sueño y dolor en atletas jóvenes. Métodos: Fue realizado un estudio transversal, en el cual fueron incluidos 71 atletas jóvenes amateurs (39 hombres). El promedio de edad fue de 16,9 ± 1,2 años, con 6,5 ± 3,2 años de práctica deportiva y 5,2 ± 1,2 horas de entrenamiento por semana. La calidad del sueño fue evaluada por medio del Índice de Calidad del Sueño de Pittsburgh (PSQI). Los participantes fueron clasificados de acuerdo con la calidad del sueño, PSQI-I= sin disturbios del sueño, PSQI-II= requiere atención médica y PSQI-III= requiere atención médica y tratamiento. Además, la intensidad del dolor fue evaluada en la Escala de Evaluación Numérica en reposo (EANr) y durante la actividad deportiva (EANe), juntamente con la duración del dolor. Resultados: Los individuos clasificados como PSQI-III presentaron mayor valor en el EANr (Mdn = 2,0; IQR = 4,0 vs. Mdn = 0,0; IQR = 2,0; p = 0,04) y EANe mayores (Mdn = 4,0; IQR = 5,0 vs. Mdn = 0,0; IQR = 2,0; p = 0,03) que los individuos clasificados con PSQI-I. No fue observada ninguna diferencia con relación a la duración del dolor. El puntaje del PSQI fue positivo y con débil asociación a EANr (rs = 0,24, p=0.046) y EANe (rs = 0,27, p = 0,03), pero no con la duración del dolor. Conclusión: Los atletas jóvenes con niveles más bajos de calidad del sueño tienen niveles más elevados de dolor en reposo y durante la práctica deportiva. Por lo tanto, la calidad del sueño y el dolor deben ser considerados por los equipos técnicos y de salud en la evaluación rutinaria de atletas jóvenes. Nivel de evidencia III;Tipo de estudio: Transversal.

RESUMO Introdução: Demonstrou-se que existe estreita associação entre qualidade do sono e dor. Em atletas jovens, distúrbios do sono e dor têm prevalência bastante alta, no entanto, a relação entre eles não foi amplamente estudada. Objetivo: Estudar a associação entre qualidade do sono e dor em atletas jovens. Métodos: Foi realizado um estudo transversal, no qual foram incluídos 71 atletas jovens amadores (39 homens). A média de idade foi de 16,9 ± 1,2 anos, com 6,5 ± 3,2 anos de prática esportiva e 5,2 ± 1,2 horas de treinamento por semana. A qualidade do sono foi avaliada por meio do Índice de Qualidade do Sono de Pittsburgh (PSQI). Os participantes foram classificados de acordo com a qualidade do sono, PSQI-I = sem distúrbios do sono, PSQI-II = requer atendimento médico e PSQI-III = requer atendimento médico e tratamento. Além disso, intensidade da dor foi avaliada na Escala de Avaliação Numérica em repouso (EANr) e durante a atividade esportiva (EANe), juntamente com a duração da dor. Resultados: Os indivíduos classificados como PSQI-III apresentaram maior valor no EANr (Mdn = 2,0; IQR = 4,0 vs. Mdn = 0,0; IQR = 2,0; p = 0,04) e EANe maiores (Mdn = 4,0; IQR = 5,0 vs. Mdn = 0,0; IQR = 2,0; p = 0,03) do que os indivíduos classificados com PSQI-I. Nenhuma diferença foi observada com relação à duração da dor. O escore do PSQI foi positivo e com fraca associação a EANr (rs= 0,24, p=0.046) e EANe (rs= 0,27, p = 0,03), mas não com a duração da dor. Conclusão: Atletas jovens com níveis mais baixos de qualidade do sono têm níveis mais elevados de dor em repouso e durante a prática esportiva. Portanto, a qualidade do sono e a dor devem ser consideradas pelas equipes técnicas e de saúde na avaliação rotineira de atletas jovens. Nível de evidência III; Tipo de estudo: Transversal.

Tubulosine selectively inhibits JAK3 signalling by binding to the ATP-binding site of the kinase of JAK3.

Gain- or loss-of-function mutations in Janus kinase 3 (JAK3) contribute to the pathogenesis of various haematopoietic malignancies and immune disorders, suggesting that aberrant JAK3 signalling is an attractive therapeutic target to treat these disorders. In this study, we performed structure-based computational database screening using the 3D structure of the JAK3 kinase domain and the National Cancer Institute diversity set and identified tubulosine as a novel JAK3 inhibitor. Tubulosine directly blocked the catalytic activity of JAK3 by selective interacting with the JAK3 kinase domain. Consistently, tubulosine potently inhibited persistently activated and interleukin-2-dependent JAK3, and JAK3-mediated downstream targets. Importantly, it did not affect the activity of other JAK family members, particularly prolactin-induced JAK2/signal transducer and activator of transcription 5 and interferon alpha-induced JAK1-TYK2/STAT1. Tubulosine specifically decreased survival and proliferation of cancer cells, in which persistently active JAK3 is expressed, by inducing apoptotic and necrotic/autophagic cell death without affecting other oncogenic signalling. Collectively, tubulosine is a potential small-molecule compound that selectively inhibits JAK3 activity, suggesting that it may serve as a promising therapeutic candidate for treating disorders caused by aberrant activation of JAK3 signalling.

High-sensitivity sequencing reveals multi-organ somatic mosaicism causing DICER1 syndrome.

BACKGROUND: Somatic mosaicism is being increasingly recognised as an important cause of non-Mendelian presentations of hereditary syndromes. A previous whole-exome sequencing study using DNA derived from peripheral blood identified mosaic mutations in DICER1 in two children with overgrowth and developmental delay as well as more typical phenotypes of germline DICER1 mutation. However, very-low-frequency mosaicism is difficult to detect, and thus, causal mutations can go unnoticed. Highly sensitive, cost-effective approaches are needed to molecularly diagnose these persons. We studied four children with multiple primary tumours known to be associated with the DICER1 syndrome, but in whom germline DICER1 mutations were not detected by conventional mutation detection techniques. METHODS AND RESULTS: We observed the same missense mutation within the DICER1 RNase IIIb domain in multiple tumours from different sites in each patient, raising suspicion of somatic mosaicism. We implemented three different targeted-capture technologies, including the novel HaloPlex(HS) (Agilent Technologies), followed by deep sequencing, and confirmed that the identified mutations are mosaic in origin in three patients, detectable in 0.24-31% of sequencing reads in constitutional DNA. The mosaic origin of patient 4's mutation remains to be unequivocally established. We also discovered likely pathogenic second somatic mutations or loss of heterozygosity (LOH) in tumours from all four patients. CONCLUSIONS: Mosaic DICER1 mutations are an important cause of the DICER1 syndrome in patients with severe phenotypes and often appear to be accompanied by second somatic truncating mutations or LOH in the associated tumours. Furthermore, the molecular barcode-containing HaloPlex(HS) provides the sensitivity required for detection of such low-level mosaic mutations and could have general applicability.

Laparoscopic Surgery for Acute Appendicitis in Children With Cancer.

INTRODUCTION: Abdominal pain during cancer chemotherapy may be caused by medical or surgical conditions. A retrospective review of 5 children with cancer who had appendicitis while receiving chemotherapy was performed. CASE DESCRIPTIONS: Three had acute lymphoblastic leukemia,and 1 each had T-cell lymphoblastic lymphoma and rhabdomyosarcoma. Two of the patients had a Pediatric Appendectomy Score of 6, and 1 each had a score of 7, 5, and 2. All had evidence of appendicitis on computed tomography. Laparoscopic appendectomy was performed without any perioperative complication. DISCUSSION: Appendicitis is an important diagnosis in children with cancer, and laparoscopic appendectomy is safe and the procedure of choice.

Identification of mutant alleles of JAK3 in pediatric patients with acute lymphoblastic leukemia.

Children with acute lymphoblastic leukemia (ALL) have an 80% chance of long-term survival. Despite the high rate of cure, children relapse, and recurrent ALL is difficult to cure with chemotherapeutic regimens. Therefore, improved biological understanding of ALL and the development of rationally designed therapeutics targeting molecules associated with the pathogenesis of ALL are essential. We identified missense and synonymous JAK3 mutations in 16 of 91 pediatric patients with ALL. The expression of JAK3(V722I) mutant caused the cytokine-independent activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and conferred the factor-independent growth of murine interleukin-3 (IL-3)-dependent pro-B Ba/F3 cells. Importantly, inhibition of JAK3 by the known JAK3 inhibitor CP-690 550 converted the Ba/F3-JAK3(V722I) cells back to factor-dependent growth. These observations suggest that JAK3 may contribute to the pathogenesis of pediatric ALL and serve as an important therapeutic target which can be leveraged to improve outcomes for pediatric patients with ALL.

Iron deficiency in infants and toddlers in the United States.

Iron deficiency anemia (IDA) continues to be overwhelmingly the leading cause of anemia in early childhood and a global public health challenge. Although there has been a significant decrease in the frequency of IDA and iron deficiency (ID) in infants and toddlers in recent years in the United States, ID and IDA persist and the adverse effects of ID are long-lasting if not permanent. Moreover, ID can result in lead toxicity, and this toxic exposure, even with low levels, can impair neurocognitive function as well. This review describes the major steps that have taken place to decrease the frequency of ID and IDA.

Urinary tract infections in pediatric oncology patients with fever and neutropenia.

The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia.

Prospective evaluation of 2009 H1N1 influenza A in patients admitted with fever to an oncology unit.

We prospectively evaluated all oncology inpatients for 2009 H1N1 influenza virus. All patients recovered completely. Evaluating all oncology patients with fever for influenza involved overtreatment of influenza-negative patients and involved a significant infection control burden. However, early antiviral intervention could have contributed to a favorable outcome.

Inhibition of the signalling kinase JAK3 alleviates inflammation in monoarthritic rats.

BACKGROUND AND PURPOSE: Many cytokines associated with autoimmune disorders and inflammation have been shown to activate the signalling kinase JAK3, implying that JAK3 plays key roles in the pathogenesis of these diseases. Therefore, investigating the alterations of JAK3 activity and the efficacy of selective JAK3 antagonists in animal models of such disorders is essential to a better understanding of the biology of JAK3 and to assess the potential clinical benefits of JAK3 inhibitors. EXPERIMENTAL APPROACH: Through high-throughput cell-based screening using the NCI compound library, we identified NSC163088 (berberine chloride) as a novel inhibitor of JAK3. Specificity and efficacy of this compound were investigated in both cellular and animal models. KEY RESULTS: We show that berberine chloride has selectivity for JAK3 over other JAK kinase members, as well as over other oncogenic kinases such as Src, in various cellular assays. Biochemical and modelling studies strongly suggested that berberine chloride bound directly to the kinase domain of JAK3. Also phospho-JAK3 levels were significantly increased in the synovial tissues of rat joints with acute inflammation, and the treatment of these rats with berberine chloride decreased JAK3 phosphorylation and suppressed the inflammatory responses. CONCLUSIONS AND IMPLICATIONS: The up-regulation of JAK3/STATs was closely correlated with acute arthritic inflammation and that inhibition of JAK3 activity by JAK3 antagonists, such as berberine chloride, alleviated the inflammation in vivo.

Rituximab therapy to prevent relapse in chronic relapsing thrombotic thrombocytopenic purpura (TTP) in a child.

Our patient first developed thrombotic thrombocytopenic purpura (TTP) at age 10 years with an initial platelet count of 10,000/microL. She achieved remission with plasmapheresis (PE), but suffered 2 relapses in the next 2 years, each approximately 1 year from PE, with ADAMTS13 levels of <5%. Early in her third remission, with vincristine (weekly x 4 doses) and prednisone (for 2 weeks) her ADAMTS13 increased to 99% in 24 weeks, but decreased to <4% in the next 38 weeks. After 4 weekly doses of rituximab (375 mg/m(2)), her ADAMTS13 level reached 101% in 9 weeks and has remained consistently above 97% on bimonthly monitoring for more than a year. She remains in continuous clinical and hematologic remission with an ADAMTS13 level of 108% at 60 weeks from rituximab therapy and 124 weeks from her second relapse. This case report suggests that monitoring ADAMTS13 level at regular intervals in recurrent TTP may help us identify patients at risk for further relapse; and such a relapse may be prevented, or at least delayed with timely rituximab therapy, thus reducing morbidity from relapsed TTP and its treatment.

Immunosuppressant-induced endothelial damage and pulmonary arterial hypertension.

Cyclosporine A, used to prevent graft-versus-host-disease, is known to induce endothelial injury. Endothelial dysfunction is an important feature of pulmonary arterial hypertension (PAH). In this article, we describe 2 children who developed cyclosporine-induced acute respiratory distress syndrome. Lung biopsy showed patchy loss of endothelial caveolin-1 and von Willebrand factor to occur early. Significant loss of endothelial caveolin-1 was associated with robust expression of caveolin-1 in smooth muscle cells with subsequent neointima formation leading to fatal PAH. Thus, patients who develop acute respiratory distress syndrome after immunosuppressive therapy are at risk of developing PAH.