STAT3 is required for IL-21-induced secretion of IgE from human naive B cells

The production of immunoglobulin E (IgE) is tightly regulated. This is evidenced by the fact that it comprises less than 0.0001% of serum Ig, and aberrant production causes atopic conditions, including allergy, rhinitis, and anaphylaxis. Interleukin-4 (IL-4) is a well-characterized inducer of IgE by human and murine B cells, whereas interferon-gamma can antagonize this effect. IL-21 has also been recognized for its ability to suppress IL-4-induced IgE production by murine B cells. Here, we identified IL-21 as an inducer of IgE production by CD40L-stimulated human naive B cells. Furthermore, there was a striking synergy between IL-4 and IL-21 on inducing IgE secretion by CD40L-stimulated human B cells, such that the levels detected under these conditions exceeded those induced by IL-4 or IL-21 alone by more than 10-fold. IL-21 induced activation of STAT3 and analysis of B cells from patients with loss-of-function STAT3 mutations revealed that the ability of IL-21 to induce IgE secretion, and augment that driven by IL-4, was STAT3-dependent. These findings highlight a fundamental difference between the regulation of IgE production by human and murine B cells and have implications for the dysregulated production of IgE in conditions characterized by extremely high levels of serum IgE.     

Feeding sources and trypanosome infection index of Rhodnius pallescens in a Chagas disease endemic area of Amador County, Panama

The sylvatic triatomine Rhodnius pallescens is considered to be the most important and widespread vector of Trypanosoma cruzi and Trypanosoma rangeli in Panama. However, its behavior and biological characteristics have only been partially investigated. Thus, to achieve sustainable and efficient control over Chagas disease in Panama, a better understanding of the ecology and biology of R. pallescens is essential. In this study we evaluated R. pallescens host feeding sources using a dot-blot assay, and the trypanosome infection index by PCR analysis in a Chagas disease endemic area of central Panama. It was found that in peridomestic palm trees, 20.3% of the examined bugs had fed on opossums (Didelphis marsupialis). However, we observed an increased anthropophagy (25.4%) for those bugs collected inside houses. Considering the domestic and peridomestic habitats as a whole, the proportion of collected R. pallescens infected with trypanosomes was 87.4%. In the two habitats the predominant infection was with T. cruzi (80-90%). Between 47-51% of the analyzed triatomines were infected with T. rangeli. Mixed infections (40-51%) were also detected. These findings provide a better basis for the implementation of a rational control and surveillance program for Chagas disease in regions where R. pallescens is endemic.     

Comparison of the grading of esophageal varices by transnasal endoluminal ultrasound and esophagogastroduodenoscopy.

BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is the current standard for evaluating esophageal varices, yet there is no universally accepted system of grading varices endoscopically and several studies have shown interobserver variability of endoscopic grading. High-resolution endoluminal ultrasound 20 MHz (HRES) has been shown to detect varices accurately and can be performed without sedation. Our aim was to compare the detection of esophageal varices by transnasal HRES and EGD. METHODS: We prospectively studied 37 cirrhotic patients being evaluated for esophageal varices. HRES was used to measure the largest esophageal variceal diameter and then EGD was performed. Photographs were taken for both procedures. Three blinded investigators graded the EGD photographs at 2 periods. End points were as follows: (1) the correlation of HRES variceal diameter and EGD grading of varices, and (2) the assessment of interobserver and intraobserver variation in varix grading by EGD. RESULTS: The correlation between the transnasal HRES and EGD was .63, with a 95% confidence interval of .37-.80. The HRES detected early varices that were not seen by EGD. The interobserver correlation for EGD scoring was .87 or greater in all comparisons and the intraobserver correlation was .91 or greater. CONCLUSIONS: In conclusion, there is a significant correlation between transnasal HRES size measurement of esophageal varices and EGD. HRES is much more sensitive in detecting early esophageal varices and may not require sedation, suggesting that it may be more tolerable to patients and is worth further study.     

Comparison of biodegradable and newer generation durable polymer drug-eluting stents with short-term dual antiplatelet therapy: a systematic review and Bayesian network meta-analysis of randomized trials comprising of 43,875 patients

Journal of Thrombosis and Thrombolysis - Newer generation durable polymer drug-eluting stents (DP-DES) and biodegradable polymer DES (BP-DES) have similar efficacy with dual-antiplatelet therapy...     

Effects on upper airway collapsibility of presence of a pharyngeal catheter

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol‐anaesthetized subjects (14 men) with and without a multi‐sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)‐defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow‐limited breaths defined Rus. Pcrit was similar with the catheter in and out (?1.5 ± 5.4 cmH₂O and ?2.1 ± 5.6 cmH₂O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG‐defined OSA (3.9 ± 2.2 cmH₂O and 2.6 ± 1.4 cmH₂O, n = 6) and those at low risk/without OSA (?3.3 ± 4.9 cmH₂O and ‐3.7 ± 5.6 cmH₂O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH₂O mL^?1 s^?1 and 16.8 ± 10.1 cmH₂O mL^?1 s^?1, P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.     

Mortality and causes of death in Crohn's disease: follow-up of a population-based cohort in Copenhagen County,Denmark

BACKGROUND & AIMS: A population-based cohort comprising 374 patients with Crohn's disease diagnosed in Copenhagen County between 1962 and 1987 was observed until 1997 for mortality and causes of death. METHODS: Observed deaths were compared with expected deaths calculated by using individually computed person-years at risk and 1995 rates for Copenhagen County. Cumulative survival curves were calculated. RESULTS: A total of 84 deaths occurred vs. 67 expected (standardized mortality ratio [SMR], 1.3; 95% confidence interval [CI], 1.01-1.56): 45 women vs. 31.8 expected (SMR, 1.4; 95% CI, 1.03-1.89) and 39 men vs. 35.2 expected (SMR, 1.1; 95% CI, 0.79-1.51). An excess mortality was observed among women observed for 21-25 years after diagnosis. Among women aged <50 years at diagnosis, 25 deaths were observed vs. 7.3 expected (SMR, 3.42; 95% CI, 2.21-5.04). Fourteen (31%) of the observed deaths among women and 8 (21%) among men had a certain or possible connection to Crohn's disease. Among causes of death unrelated to Crohn's disease, an overrepresentation of gastrointestinal diseases, infections, and diseases of the urinary organs was observed. CONCLUSIONS: An increased mortality was observed late in the disease course that was most pronounced among women younger than 50 years at diagnosis and was attributed to death associated with severe Crohn's disease.     

Development and Validation of the Athlete Fear Avoidance Questionnaire

Context

The fear-avoidance model was developed in an attempt to explain the process by which “pain experience” and “pain behavior” become dissociated from the actual pain sensation in individuals who manifest the phenomenon of exaggerated pain perception. High levels of fear avoidance can lead to chronic pain and disability and have successfully predicted rehabilitation time in the work-related–injury population. Existing fear-avoidance questionnaires have all been developed for the general population, but these questionnaires may not be specific enough to fully assess fear avoidance in an athletic population that copes with pain differently than the general population.

Objective

To develop and validate the Athlete Fear Avoidance Questionnaire (AFAQ).

Design

Qualitative research to develop the AFAQ and a cross-sectional study to validate the scale.

Patients or Other Participants

For questionnaire development, a total of 8 experts in the fields of athletic therapy, sport psychology, and fear avoidance were called upon to generate and rate items for the AFAQ. For determining concurrent validity, 99 varsity athletes from various sports participated.

Data Collection and Analysis

A total of 99 varsity athletes completed the AFAQ, the Fear-Avoidance Beliefs Questionnaire, and the Pain Catastrophizing Scale. We used Pearson correlations to establish concurrent validity.

Results

Concurrent validity was established with significant correlations between the AFAQ and the Fear Avoidance Beliefs Questionnaire-Physical Activity (r = 0.352, P > .001) as well as with the Pain Catastrophizing Scale (r = 0.587, P > .001). High internal consistency of our questionnaire was established with a Cronbach α coefficient of 0.805. The final version of the questionnaire includes 10 items with good internal validity (P < .05).

Conclusions

We developed a questionnaire with good internal and external validity. The AFAQ is a scale that measures sport-injury–related fear avoidance in athletes and could be used to identify potential psychological barriers to rehabilitation.Key Words: fear-avoidance model, scale, sports, athletic injuries, rehabilitation, psychology

Key Points

• We developed and validated the Athlete Fear Avoidance Questionnaire to assess pain-related fear in athletes.
• Pain-related fear or fear avoidance plays a critical role in the rehabilitation of patients with low back pain and work-related injuries. High levels of fear avoidance in athletes may affect rehabilitation times.

Most health professionals who work with injured athletes have encountered situations in which an athlete was struggling psychologically to return to play or the duration of rehabilitation was disproportionate to the athlete''s initial physical dysfunction. To date, a few scales measure athletes'' readiness to return to play, such as the Sports Inventory for Pain and the Injury–Psychological Readiness to Return to Sport Scale.^1,2 The Sports Inventory for Pain was developed specifically to identify beneficial and detrimental pain-coping strategies among the athletic population, but the authors worked with a student population to generate the items on the questionnaire, rather than a panel of experts in the field, and they did not establish concurrent validity. The Injury–Psychological Readiness to Return to Sport Scale was developed as a tool to assess an athlete''s confidence and psychological readiness to go back to play; however, it was designed to be administered at the end of an athlete''s rehabilitation process and, therefore, cannot be used to address psychological barriers at the beginning of rehabilitation that may lengthen the time to return to play.² Neither scale has been used extensively, but the fear-avoidance model (FAM), a psychological model well established in the general population, has been used extensively for its predictive value. For example, Sullivan et al³ noted that the Pain Catastrophizing Scale (PCS) has been cited more than 900 times on Web of Science since 1995.The FAM is based on the emotional reaction of pain perception and high levels of fear avoidance that can lead to dysfunction.⁴ The FAM was created in an attempt to explain the development of chronic pain from acute pain. The model comprises 4 components: fear of pain, kinesiophobia, fear-avoidance belief, and catastrophizing. According to the FAM, exaggerated pain perception could lead to the development of chronic pain,⁴ and fear of pain is a main focus. There are 2 possible coping reactions to fear of pain: confrontation and avoidance. Individuals who experience elevated levels of fear of pain with signs of fear avoidance in response to acute pain are more likely to develop chronic pain than those who confront their fear of pain.⁴ The FAM assessment tools were all developed for the general population or patients with chronic low back pain. The main questionnaires used to assess the 4 components of the FAM are the Fear of Pain Questionnaire-III, the PCS, the Tampa Scale for Kinesophobia, and the Fear-Avoidance Beliefs Questionnaire (FABQ). The FABQ was developed in part for patients with work-related injuries.⁵ Injured varsity athletes may not relate to work-specific items on the FABQ, such as “My pain was caused by my work or by an accident at work.” Although some of the questionnaires, such as the PCS, have been validated on athletes, they were not developed specifically for the athletic population.⁶ In fact, the FAM questionnaires can be used to predict outcomes.^7,8 Klenerman et al⁷ conducted a study to determine whether chronic pain could be predicted from acute low back pain in the general population. Results indicated that patients with acute low back pain either will improve within 2 months or will develop chronic pain and that the FAM appears to be the best predictor of the course of low back pain within the first 2 months.⁷ In another study, Fritz and George⁸ aimed to identify psychosocial factors that could predict return to work in patients with acute work-related back pain. The results revealed that the FABQ-Work (FABQ-W) was the strongest predictor of work status and may be used to predict return to work in patients with acute work-related low back pain.⁸ The authors of the PCS also established that people who catastrophize have higher levels of pain and disability than people who do not.⁹Some studies have indicated that parts of the FAM can influence athletes'' rehabilitation.^6,10,11 Kvist et al¹⁰ also reported on the psychological effect an injury can have on a player. Of the 47% who did not return to their sport, 24% did not return to play because of their fear of reinjury.¹⁰ People who returned to their preinjury levels of activity had the lowest levels of fear of reinjury, whereas people who did not return to their preinjury levels of activity had a higher fear of reinjury.¹⁰ The results of these studies might have been stronger using a scale that was developed specifically for athletes. To date, no questionnaire or scale has been specifically developed to assess fear avoidance or pain-related fear in athletes, who differ from the general population in their mentality and reality (ie, the role of sports or activity in their lives). Furthermore, athletes are exposed to pain and sports injuries relatively often, so knowing whether fear avoidance is a major concern among that population is important. Therefore, taking fear avoidance into account might be useful to establish the most appropriate and effective rehabilitation plan and, consequently, to reduce the time for return to play. A questionnaire specific to athletes might help establish how the FAM or pain-related fear can influence the athletic population, specifically regarding rehabilitation.Therefore, the aims of our study were to develop and validate the Athlete Fear Avoidance Questionnaire (AFAQ). We used a qualitative study design, a modified Delphi technique, to develop the scale and then a cross-sectional study to establish its validity.