Prognostic Value of Exercise Stress Echocardiography in Pediatric Cardiac Transplant Recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading cause of long-term morbidity and mortality in pediatric heart transplant (HTx) recipients. Exercise stress echocardiography (ESE) has been shown to be useful in the detection of angiographically confirmed coronary artery disease in children. However, the prognostic utility of ESE for prediction of cardiac events in HTx survivors is unknown. OBJECTIVES: We aim to assess whether an abnormal (positive) ESE is be associated with a higher risk of future cardiovascular (CV) outcomes in pediatric HTx recipients. METHODS: We conducted a retrospective review of CV outcomes in a cohort of 95 pediatric HTx recipients who underwent 188 ESEs over a 10-year period. A composite endpoint for CV events including myocardial infarction, hospitalization for nonrejection heart failure, coronary revascularization, need for repeat transplantation, and death was used. Based on the interpretation of the ESE results, each ESE study was classified for this study as either positive (abnormal) or negative (normal) for ischemia. Results of the coronary angiograms performed near the time of ESE were also assessed and classified for this study as positive (abnormal) or negative (normal) for CAV according to standard HTx criteria for CAV. RESULTS: Fifty-one (27%) ESEs were positive for ischemia. There was a total of 35 CV events in 23 patients. A positive ESE was associated with increased risk of any CV event (hazard ratio = 3.55; 95% CI, 1.52, 8.28), as well as an increased risk of CV death (hazard ratio = 3.19; 95% CI, 1.23, 8.28). Freedom from composite CV outcome at 1, 2, and 3 years following a positive ESE was 89.9% (95% CI = 77.3%, 95.7%), 81.5% (95% CI = 65.9%, 90.5%), and 63.2% (95% CI = 41.9%, 78.5%), respectively. Freedom from composite CV outcome at 1, 2, and 3 years following a negative ESE was 99.3% (94.8, 99.9), 98.4% (93.6, 99.6), and 97.0% (90.6, 99.1), respectively. No patient died within 1 year of a negative ESE. CONCLUSIONS: In this largest study of ESE in pediatric HTx recipients, a positive or abnormal ESE is associated with increased future CV morbidity and mortality. Conversely, a negative ESE can help predict CV event-free survival. Even in the setting of a normal coronary angiogram, our pilot data show that an abnormal ESE may still be clinically important. Use of ESE in follow-up may improve risk stratification and management of pediatric HTx recipients.

The link between non-suicidal self-injury (NSSI), body image and activity on social networking sites among female adolescents with an eating disorder.

The link between engagement in non-suicidal self-injury (NSSI)-related activities on SNS (e.g. viewing, commenting, sharing and uploading NSSI content) with body image and NSSI behaviour remains under researched in adolescents with EDs. The main aim of the current research was to examine associations between NSSI-related activities on SNS with body image and NSSI behaviour severity among female adolescents diagnosed with an ED. A total of 52 female adolescents (mean age = 15.35 years, SD = 1.49) diagnosed with an ED completed self-report questionnaires related to NSSI behaviour, SNS usage and body image. Participants were divided into two groups: low NSSI behaviour severity (from 0 to 10 NSSI behaviours; n = 28) and high NSSI behaviour severity (more than ten NSSI behaviours; n = 24). Within the high NSSI severity group, individuals that comment and share NSSI online content significantly reported higher negative body image. A hierarchical binary logistic regression showed that the frequency of NSSI online content on SNS emerged as significant predictor of NSSI behaviour severity within last year after controlling for body image and searching for ED content on SNS. Our findings suggest that not only searching for ED content, but also being daily engaged in NSSI online activities may increase the risk of NSSI behaviour severity in female adolescents with EDs.

National survey of pre-treatment HIV drug resistance in Cuban patients.

BACKGROUND: The World Health Organization (WHO) recommends a method to estimate nationally representative pretreatment HIV drug resistance (PDR) in order to evaluate the effectiveness of first -line treatments. The objective of the present study was to determine the prevalence of PDR in Cuban adults infected with HIV-1. MATERIALS AND METHODS: A cross-sectional study in Cuban adults infected with HIV-1 over 18 years was conducted. The probability proportional to size method for the selection of municipalities and patients without a prior history of antiretroviral treatment during the period from January 2017 to June 2017 was used. The plasma from 141 patients from 15 municipalities for the determination of viral subtype and HIV drug resistance was collected. Some clinical and epidemiological variables were evaluated. RESULTS: 80. 9% of the patients corresponded to the male sex and 76.3% were men who have sex with other men (MSM). The median CD4 count was 371 cells / mm3 and the median viral load was 68000 copies / mL. The predominant genetic variants were subtype B (26.9%), CRF19_cpx (24.1%), CRF 20, 23, 24_BG (23.4%) and CRF18_cpx (12%). Overall, the prevalence of PDR was 29.8% (95%, CI 22.3-38.1). The prevalence was 12.8% (95%, CI 6.07-16.9) for any nucleoside reverse transcriptase inhibitor (NRTI), 23.4% (95%, CI 16.7-31.3) for any non-reverse transcriptase inhibitor (NNRTI) and 1.4% (95%, CI 0.17-5.03) for any protease inhibitor (PI). The most frequent mutations detected were K103N (12.9%), G190A (6.4%) and Y181C (4.8%). CONCLUSIONS: The NNRTI prevalence above 10% in our study indicates that the first-line antiretroviral therapy in Cuba may be less effective and supports the need to look for new treatment options that contribute to therapeutic success and help the country achieve the global goals 90-90-90 set forth by UNAIDS.

Clinical Progress in the Management of Tetralogy of Fallot in the Dominican Republic: A Case Series.

BACKGROUND: Definitive surgical interventions for Dominican children with congenital heart disease, like those of other low- and middle-income countries, have been historically limited. METHODS: We undertook review of a case series focusing on the surgical correction of complex forms of tetralogy of Fallot at a single center, CEDIMAT Centro Cardiovascular, in the Dominican Republic, over a 30-month period. RESULTS: According to our criteria, 43 cases were determined to be complex tetralogy of Fallot repairs from the two-year period. Besides tetralogy of Fallot, the cohort had an additional 55 anatomic anomalies that had to be addressed at the time of surgery. Median age at the time of surgery was notably 30 months, and an average of 42 months elapsed from the time of diagnosis to the time of surgery for this group. Only 33% of the cases reviewed had no hypercyanotic crises before repair. Median time to extubation for this group of patients was one day, with a three-day median length of stay in the intensive care setting. CONCLUSIONS: Our study importantly captures the present experience of a surgical congenital heart program that has recently transitioned from a traditional "mission model" to a now self-sustaining local practice. Both the number and the complexity of the lesions corrected in this caseload represent an advance from the level of care previously provided to children in the Dominican Republic.

The evaluation of adolescent chest pain: a screening ECG or PSC-17?

PURPOSE OF REVIEW: The present review offers an update on entities presenting as chest pain in the adolescent population. It discusses recently proposed tools and shared mental models used in primary and urgent care settings to evaluate chest pain, and their focus on identifying life-threatening processes. We consider whether the current practice may be improved by accounting for the increasingly recognized non-life-threatening causes of adolescent chest pain. RECENT FINDINGS: The present experiences and behaviors of adolescents have added new causes of chest pain to the work-up of this disquieting chief complaint. The initial approach to adolescent chest pain has classically focused on ruling out life-threatening entities, and current diagnostic algorithms offer systematic approaches with similar emphases. A growing body of literature on the nonlife-threatening causes of adolescent chest pain, often categorized as idiopathic, suggests a need to reevaluate our practice. SUMMARY: Adolescent chest pain is most often noncardiac and non-life threatening in nature, yet current diagnostic algorithms and evaluations emphasize identifying the exceptional case of cardiac chest pain. Familiarizing ourselves with the more common causes of chest pain and with our present approach to the evaluation of this particular chief complaint, may help us to better counsel our patients and avoid unnecessary use of valuable resources.

AIDS-Associated Cardiac Lymphoma-A Review: Apropos a Case Report.

Despite treatment with potent and effective combination antiretroviral medications, the incidence of non-Hodgkin lymphoma (NHL) in the population living with HIV/AIDS remains significantly higher than that in noninfected individuals. The majority of the HIV-infected patients with NHL present with advanced stage extranodal disease of the B-cell phenotype. Lymphomas are the second most common tumors involving the heart in HIV-infected patients. Although the heart may serve as the primary focus of the lymphoma, in most HIV-related cases, cardiac lymphomatous involvement is part of a metastatic process that originated elsewhere.

In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer.

BACKGROUND: Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining. METHODS: TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods. RESULTS: A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also over-expressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining. CONCLUSIONS: Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage.

Development and validation of a Spanish translation of the Yale activity questionnaire.

BACKGROUND: Valid measures of physical activity are critical research tools. The objective of this study was to develop a Spanish translation of the Yale Physical Activity Survey, and to provide preliminary evidence of its validity in a population of Dominican patients with lower extremity arthritis. METHODS: A Dominican bilingual health care professional translated the Yale Physical Activity Survey (YPAS) from English to Spanish. Several Dominican adults reviewed the translation to ensure it was linguistically and culturally appropriate. The questionnaire was back-translated to English by a North American researcher who is fluent in Spanish. Discrepancies between the original and back-translated versions were resolved by the translator and back-translator. The Spanish translation was administered to 108 Dominican subjects with advanced hip or knee arthritis prior to (N = 44) or one to four years following (N = 64) total joint replacement. We assessed construct validity by examining the association of YPAS scores and measures of functional status and pain (WOMAC), quality of life (EQ-5D) and the number of painful lower extremity joints. RESULTS: A higher YPAS Part II Activity Dimensions Summary Index score had weak to modest correlations with worse function and quality of life as measured with the WOMAC function scale (r = 0.21, p = 0.03), SF-36 Physical Activity Scale (r = 0.29, p = 0.004) and EQ-5D (r = 0.34, p = 0.0007). Total minutes of vigorous activity and walking had weak to modest correlation with these measures (WOMAC Function Scale (r = 0.15, p = 0.15), SF-36 Physical Activity Scale (r = 0.21, p = 0.04) and EQ-5D utility (r = 0.24, p = 0.02)). Correlations between the YPAS Part I energy expenditure score and these measures were lower (WOMAC Function Scale (r = 0.07, p = 0.49), SF-36 Physical Activity Scale (r = 0.03, p = 0.74) and EQ-5D utility (r = 0.18, p = 0.07)). CONCLUSIONS: We have developed a new Spanish translation of the Yale Physical Activity Survey and provided evidence of convergent validity in a sample of Dominican patients prior to or 1-4 years following total joint replacement.

The anthrax attacks 10 years later.

Ten years ago, just weeks after the September 11 attacks, the United States experienced a deliberate act of bioterrorism. Through use of the postal service, anthrax spores were widely disseminated, including to homes, the Senate, and major newsrooms, resulting in morbidity and mortality and effectively disrupting our way of life and revealing our vulnerability. Even though such attacks had been the subject of much writing and had been planned for, detection of and the appropriate response to an attack with an agent from the so-called "Category 'A' List" had only been considered in theoretical terms. What transpired during the following difficult weeks, including how public health and federal government agencies performed, has been both praised and criticized. An intertwined epidemiologic and criminal investigation of such magnitude was unprecedented in U.S. history. To address the question of whether we as a nation are now better prepared for future threats involving biologic agents, it is important to learn from the lessons of the 2001 anthrax attacks, including the critical role of clinicians in surveillance. As physicians involved in diagnosing anthrax in the index case and alerting authorities, we offer our perspective on these events a decade after their occurrence.

Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis.

BACKGROUND: Chronic intestinal inflammation culminates in cancer and a link to Toll-like receptor-4 (TLR4) has been suggested by our observation that TLR4 deficiency prevents colitis-associated neoplasia. In the current study we address the effect of the aberrant activation of epithelial TLR4 on induction of colitis and colitis-associated tumor development. We take a translational approach to address the consequences of increased TLR signaling in the intestinal mucosa. METHODS: Mice transgenic for a constitutively active TLR4 under the intestine-specific villin promoter (villin-TLR4 mice) were treated with dextran sodium sulfate (DSS) for acute colitis and azoxymethane (AOM)-DSS TLR4 expression was analyzed by immunohistochemistry in colonic tissue from patients with ulcerative colitis (UC) and UC-associated cancer. The effect of an antagonist TLR4 antibody (Ab) was tested in prevention of colitis-associated neoplasia in the AOM-DSS model. RESULTS: Villin-TLR4 mice were highly susceptible to both acute colitis and colitis-associated neoplasia. Villin-TLR4 mice had increased epithelial expression of COX-2 and mucosal PGE2 production at baseline. Increased severity of colitis in villin-TLR4 mice was characterized by enhanced expression of inflammatory mediators and increased neutrophilic infiltration. In human UC samples, TLR4 expression was upregulated in almost all colitis-associated cancer and progressively increased with grade of dysplasia. As a proof of principle, a TLR4/MD-2 antagonist antibody inhibited colitis-associated neoplasia in the mouse model. CONCLUSIONS: Our results show that regulation of TLRs can affect the outcome of both acute colitis and its consequences, cancer. Targeting TLR4 and other TLRs may ultimately play a role in prevention or treatment of colitis-associated cancer.

Soft tissue anaplastic large T-cell lymphoma associated with a metallic orthopedic implant: case report and review of the current literature.

On occasion, the placement of orthopedic prosthetic components or stabilization hardware leads to surgical site infections, in some cases presenting at a point in time distant from the surgical procedure. Although infectious complications are the most common etiology for surgical site pain and inflammation, malignancies can also develop around prosthetic devices and metallic implants. When encountered, such malignancies are most often sarcoma, but rarely B-cell non-Hodgkin's lymphoma has also been described. In this article, we describe what we believe to be the first published case of anaplastic large T-cell lymphoma associated with a stainless steel fixation plate that was implanted several years earlier for repair of a tibial fracture. Appropriate to this case, we review the medical literature on the association of orthopedic implants with the development of neoplasm, along with the theorized pathogenic mechanisms leading to such an association.

Mycobacterial prosthetic valve endocarditis.

Prosthetic valve endocarditis (PVE) due to mycobacteria is a rare but frequently fatal complication that may occur early after the surgical procedure, or even years later. Infection has been described with both mechanical and biologic valvular prosthesis. The most commonly implicated mycobacterial species belong to the rapid-grower group (M. chelonei, M. fortuitum, and M. abscessus) of nontuberculous mycobacteria (NTM). The source of infection in this context is thought to be nosocomial, likely related to preoperative or intraoperative contamination of the prosthesis by contact with aqueous solutions containing the organisms. These infections are difficult to diagnose because blood cultures are often negative. Clinically, it is important to recognize the possibility of NTM-PVE in the differential diagnosis of culture-negative patients who develop signs and symptoms of endocarditis, whether they present early or late in onset after the surgical procedure. These patients should be treated with surgical removal of the infected valve, followed by adequate antimicrobial therapy based on the susceptibility of the species isolated from the valve or perivalvular tissue culture. In a significant number of patients, however, an unstable hemodynamic condition ensues, precluding surgical intervention, and therefore leading to a high mortality rate.

Comportamiento de la TSH y la T4 en una cohorte de pacientes con arritmia cardiaca tratados con amiodarona u otros antiarrítmicos / Behavior of TSH and T4 in a cohort of patients with cardiac arrhythmia treated with amiodarone or other antiarrhythmics

La amiodarona es uno de los antiarrítmicos de uso más extendido, pero de la misma forma es un medicamento con efectos adversos bien conocidos y a múltiples niveles; uno de los más importantes es el que se describe para el tejido tiroideo. Cerca de 80 porciento de los pacientes que la toman de forma indefinida, presentarán algún efecto adverso; sin embargo, menos de 15 porciento la suspenderán. En la glándula tiroides, los mecanismos de lesión se relacionan, por su semejanza estructural, con la levotiroxina, la liberación de altas concentraciones de yodo y la inducción de reactividad inmune, entre otras. No obstante, la mayoría de los pacientes permanece eutiroideos.Este estudio describe la variación de la función tiroidea a corto plazo, en 77 pacientes que recibieron diferentes tipos de antiarrítmicos, que no tenían factores de riesgo asociados a disfunción tiroidea, y que se reclutaron en el servicio de hospitalización. Se tomaron muestras de TSH al inicio y al cabo de tres meses de seguimiento. Se observaron niveles de TSH normales en 26 porciento (43 pacientes) y tendencia a valores más altos en el control al tercer mes en el grupo medicado con amiodarona. De manera adicional, se describió una proporción mayor de trastornos de la función de la glándula tiroides en la población masculina.

Fatal amebic encephalitis caused by Balamuthia mandrillaris in an immunocompetent host: a clinicopathological review of pathogenic free-living amebae in human hosts.

Encephalitis caused by Balamuthia amebic species is an increasingly recognized chronic granulomatous infectious process that may affect both immunocompetent and immunocompromised individuals. The course of the disease is insidious but fatal in most cases, mainly because of delayed diagnosis, difficulty in isolation and/or identification of the organism, and lack of well-established therapeutic regimens. We report a fatal case of Balamuthia mandrillaris chronic granulomatous encephalitis in an immunocompromised host and review the clinicopathologic characteristics of infections caused by this and other pathogenic free-living amebae.

Balamuthia mandrillaris amebic encephalitis.

Amebic encephalitis caused by Balamuthia spp is an increasingly recognized chronic granulomatous central nervous system infectious process, which may affect both immunocompetent and immunocompromised individuals. The course of the disease is insidious and fatal in most cases, mainly due to delayed diagnosis, difficulty in isolation and/or identification of the organism, and lack of well-established amebicidal therapeutic regimens. This article reviews the clinicopathologic characteristics of infections caused by Balamuthia mandrillaris compared to other pathogenic free-living amebae and summarizes the latest diagnostic and therapeutic advances in infections caused by Balamuthia spp.

Intrasellar and parasellar cellular schwannoma.

The complexity of the anatomy of the sella turcica and its surroundings accounts for the large number of pathologic entities that may involve this critical area. Intrasellar and parasellar schwannomas are exceedingly rare; only a handful of true sellar tumors of this nature have been reported in the English literature. These lesions may simulate nonsecretory pituitary adenomas clinically and neuroradiologically. Although benign, complete surgical resection of these tumors is usually difficult because of their size, invasiveness, and rich vascularity. From the histopathologic stand point, those cases lacking typical schwannoma histomorphologic features may pose a diagnostic challenge to the pathologist, especially at the time of frozen section examination, because they may resemble other spindle cell neoplasms more common to that location, such as fibrous meningothelial tumors. We report a case of intrasellar and parasellar cellular schwannoma lacking common and reliable neurilemmomatous features, such as the coexistence of cellular Antoni A and loose Antoni B areas, Verocay bodies, and hyalinized thickened vessels. In addition, features infrequently seen in schwannomas were identified in the specimen, including the presence of psammoma bodies, nuclear optically clear pseudoinclusions, and fine intracytoplasmic melanin-like pigment. Ultimately, the use of immunohistochemistry was necessary to achieve a definitive pathologic diagnosis. Cellular schwannoma expands the pathologic differential diagnosis of spindle cell neoplasms of sellar location that the pathologist should have in mind, especially at the time of frozen section examination. The clinical, histopathologic, and neurosurgical aspects of primary cellular schwannomas of the sella turcica are reviewed.

Primary gastroesophageal-ileal hodgkin lymphoma.

Primary Hodgkin lymphoma of the gastrointestinal tract is exceedingly rare to the point that some authors regard with skepticism the existence of this entity. Cases of gastrointestinal Hodgkin lymphoma have been reported previously; however, most of these cases represented secondary involvement of the digestive tract in the context of systemic disease. Other cases have been reclassified in retrospective studies as non-Hodgkin lymphomas after the application of immunohistochemical techniques. We report a case of primary Hodgkin lymphoma of the gastrointestinal tract in a patient who presented with obstructive symptoms at the site of a gastroileal bypass; the bypass had been performed years earlier because of morbid obesity. Some non-Hodgkin lymphomas may morphologically mimic Hodgkin lymphoma and vice versa; therefore, an accurate pathologic diagnosis is important, since the therapeutic approach and prognostic implications differ significantly for these diseases. In this context, immunohistochemistry should be used to confirm or to exclude the histologic diagnosis of Hodgkin lymphoma.

Temporal relationships between acute cellular rejection features and increased mucosal fibrosis in the early posttransplant period of human small intestinal allografts.

BACKGROUND: Intestinal allograft biopsies limit histopathological analysis to the superficial layers of the bowel. These biopsies allow a reasonable assessment of the histological features of acute rejection, but characteristics of chronic injury in mucosal layers remain poorly defined because of the limitations posed by endoscopic sampling. Experimental work has inferred that intestinal mucosal fibrosis may be indicative of chronic rejection; however, a temporal, graded study of mucosal fibrosis has not been performed. METHODS: A total of 79 endoscopic intestinal allograft biopsies from 12 patients obtained at 3 to 120 days posttransplantation were evaluated. Fibrosis and individual parameters of acute cellular rejection were graded according to a semiquantitative scoring system and were evaluated for potential relationships with each other. RESULTS: We found that while acute rejection tends to occur early in the posttransplant period, fibrosis of the lamina propria increases at a later time, particularly in the third and fourth month. Several individual graded parameters of acute rejection had an association with fibrosis at the same time points. CONCLUSIONS: Fibrous replacement of the lamina propria in human endoscopic allograft biopsies occurs with advancing time after transplantation. Acute rejection precedes and may have some eventual impact upon the amount of fibrosis present. A measurement of the connective tissue component of bowel transplant tissue may serve as a harbinger of long-term enteral allograft dysfunction.