Assessment of paediatric exertional or peri-exertional syncope: does the story matter?

Exertional syncope has been suggested to correlate with a cardiac aetiology, particularly when occurring in mid-stride. The aim of the study is to evaluate the incidence of cardiac disease among children presenting with exertional syncope, determine the influence of timing within activity, and determine the utility of genetic testing and implantable event monitors in the evaluation of cardiac syncope. The patients ≤18 years old with exertional syncope who underwent exercise stress testing between 2008 and 2019 were retrospectively included. Patients were assessed to be in one of three groups: mid-exertion (mid-stride syncope), peri-exertion (syncope during activity but not moving), and post-exertion (within minutes of the activity). A total of 334 patients were included; 46 % were mid-exertion, 18 % were peri-exertion, and 36 % were post-exertion. Thirteen patients (3.8 %) were diagnosed with cardiac syncope; n = 9 (69 %) mid-exertion. Only mid-exertional syncope was significantly associated with a cardiac diagnosis (OR: 2.6). Cardiac diagnoses included inherited arrhythmia syndromes (n = 9), abnormal coronary origins (n = 2), and supraventricular tachycardia (n = 2). Only catecholaminergic polymorphic ventricular tachycardia (n = 5) was associated with mid-exertional syncope (OR: 1.4). The definitive diagnostic test was exercise testing (n = 8), echocardiogram (n = 2), genetic testing (n = 1), ambulatory monitor (n = 1), and EKG (n = 1). Mid-stride syncope was more likely to result in a cardiac diagnosis, and exercise testing is the most common definitive test as catecholaminergic polymorphic ventricular tachycardia was the primary aetiology of exertional syncope in our cohort. Implantable event monitors and genetic testing could be helpful in ruling out cardiac disease.

Seasonal dietary shifting in yellow-rumped warblers is unrelated to macronutrient targets.

Dietary shifting, for example from insects to fruits, is a common mechanism used in migratory songbirds to accumulate fat to fuel migratory flights. We examined a potential underlying cause of dietary shifting in yellow-rumped warblers (Setophaga coronata) by comparing energy and protein intake goals of birds during fall migration and winter. We offered captive warblers pairs of three diets differing in macronutrient composition in both the fall and winter. Using the principles of the geometric framework of nutrition we evaluated protein and energy intake to determine if consumption of the diet pairs was adjusted to meet an energy or protein intake target, and if the target differed seasonally. Regardless of season, the warblers preferred the diet with the lowest protein content and highest carbohydrate content. Total energy intake was maintained relatively constant during migration, at around 60 kJ/day, regardless of diet combination, and at about 50 kJ/day during winter. This suggests that warblers consume macronutrients available to them without protein limitations to reach their total energy intake target. When the diet combination offered allows, the warblers mixed their diet intake to consume roughly 0.5 g/day of protein, regardless of season, which suggested a constant protein target. Our findings suggest that songbirds prefer to alter non-protein energy intake proportionally to meet changing energy demand, rather than an overall increase in macronutrient intake. Additionally, they have the ability to shift their diet based on availability, resulting in high flexibility in their macronutrient intakes to maintain energy intake.

Adipocyte-Derived Adipokines and Other Obesity-Associated Molecules in Feline Mammary Cancer.

Obesity has been identified as a serious health concern in domestic cats. Feline mammary cancer (FMC) is also a concern, as it is highly prevalent and aggressive. Considering the identified connection between obesity and breast cancer, it is worthwhile to investigate the potential obesity-cancer relationship in FMC. This review investigated the association between adipokines and other obesity-associated molecules and FMC, with the aim of identifying gaps in the current literature for future research. Based on the reports to date, it was found that tissue concentrations of leptin, serum concentrations of leptin receptor, serum amyloid A, and estrogen correlate positively with FMC, and serum concentrations of leptin correlate negatively with FMC. The roles of adiponectin and prolactin in FMC development were also investigated, but the reports are either lacking or insufficient to suggest an association. Numerous research gaps were identified and could be used as opportunities for future research. These include the need for studies on additional cohorts to confirm the association of leptin/leptin receptor and serum amyloid A with FMC, and to address the role of adiponectin and prolactin in FMC. It is also important to investigate the genetic determinants of FMC, evaluate the use of molecular-targeted therapies in FMC, and exploit the enrichment of the triple-negative immunophenotype in FMC to address current clinical needs for both human triple-negative breast cancer and FMC. Finally, mechanistic studies with any of the molecules reviewed are scarce and are important to generate hypotheses and ultimately advance our knowledge and the outcome of FMC.

Implementing an integrated approach to self-management support in an acute major trauma therapy team: an improvement project.

More patients now survive multiple trauma injuries, but the level of long-term unmet needs is high. Evidence shows self-management support can improve patients ' confidence to manage these needs but traditionally this support starts post-hospital. Starting self-management support early could prepare patients and families for successful transitions from hospital. The skills and commitment of clinicians have been shown to contribute to the success or failure of self-management approaches. The aim of this project was to explore the feasibility of integrating self-management support in an acute major trauma setting by evaluating the impact of an educational intervention on clinicians' knowledge, attitudes and behaviours regarding self-management support and identifying any barriers and facilitators to integrating self-management into daily practice. Two improvement cycles were carried out over a 1-year period involving 18 allied health professionals (AHPs) in an acute major trauma centre in London, UK. An educational intervention, 'Bridges Self-Management Programme' was modified for the setting. The impact was evaluated using (1) a clinician questionnaire to evaluate knowledge and attitudes; (2) case reflection forms and (3) peer review to observe interactions to integrate self-management support. Questionnaire data were summarised and pre-training and post-training scores compared; the qualitative data from written case reflections, verbal and written feedback from training and group discussions was described and analysed thematically. The result of two improvement cycles has shown it was feasible to improve AHP's knowledge, attitudes and change behaviours regarding self-management support in the acute trauma setting, but difficult to sustain change beyond 6 months. Key barriers such as the pressure to discharge patients and support within the wider multidisciplinary team (MDT) were identified. Facilitators included the introduction of a new key-worker, to enable shared team approaches and paperwork to involve patients and families in goal setting and treatment planning. The main learning was to ensure sustainability mechanisms from the outset, engage the wider MDT in training, and integrate self-management language and principles into team processes.

A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia.

BACKGROUND: Mutations in the erythroid-specific 5-aminolevulinate-synthase gene (ALAS2) have been identified in many cases of X-linked sideroblastic anemia (XLSA). METHODS: A polymerase chain reaction-mediated restriction fragment length polymorphism (RFLP) assay was used. RESULTS: A G527T point mutation was identified. This resulted in a substitution of tyrosine for asparagine at residue 159 (D159Y). This mutation was also identified in the mother of the two probands. Mutations in all three individuals were confirmed by DNA sequencing analysis. CONCLUSIONS: We identified a missense mutation in exon 5 of the ALAS2 gene in two brothers of a consanguineous marriage, who were clinically pyridoxine-responsive.

Immunohistochemical detection of immunoglobulin light chain expression in B-cell non-Hodgkin lymphomas using formalin-fixed, paraffin-embedded tissues and a heat-induced epitope retrieval technique.

Definitive diagnosis of B-cell non-Hodgkin lymphomas often requires demonstration of B-cell monoclonality. Immunohistochemical detection of monotypic immunoglobulin light chain expression, and thereby B-cell monoclonality, may be accomplished readily using fresh cell suspensions or frozen tissue sections. However, immunohistochemical detection of immunoglobulin light chain expression in formalin-fixed, paraffin-embedded tissues is more difficult; with few exceptions, techniques suitable for formalin-fixed, paraffin-embedded tissues are not widely available. This report describes and validates a method for detecting immunoglobulin light chain expression in formalin-fixed, paraffin-embedded tissues using a heat-induced epitope retrieval technique. This method was evaluated in a series of 113 cases of B-cell non-Hodgkin lymphoma, including 73 cases with correlative flow cytometric immunophenotyping data. Monotypic light chain expression was demonstrated in 91 (81%) of 113 cases, including several small core biopsy specimens with extremely limited tissue. Compared with the reference method (flow cytometric immunophenotyping), the specificity of the assay was 100%. Interobserver reproducibility was excellent, with 87% concordance between two independent observers categorizing cases as indeterminate, suggestive or diagnostic of kappa or lambda light chain restriction (Cohen kappa statistic: 0.81). In summary, the described method permits demonstration of immunoglobulin light chain expression in formalin-fixed, paraffin-embedded tissues in approximately 80% of cases of B-cell non-Hodgkin lymphoma with a high degree of specificity and excellent interobserver reproducibility. The assay is sufficiently robust for diagnostic use in small biopsies in which fresh tissue is unavailable.

Collaborating to address infant mortality: lessons learned from the Brownsville action community for health equality.

BACKGROUND: Brownsville Action Community for Health Equality (BACHE) is a coalition-based, service system change pilot for African American and Puerto Rican women of Brownsville, a community within Brooklyn, New York, with disproportionately high rates of infant mortality. OBJECTIVES: Identify "lessons learned" from the implementation phase of a 5-year pilot project that employs a community-based participatory (CBPR) approach to reducing risk factors for infant mortality. METHODS: Nineteen semi-structured interviews were conducted with BACHE's partners throughout 2010. Sessions were audiotaped and transcribed. Data was incorporated into a framework based on grounded theory and interpreted by project partners. RESULTS: Lessons learned related to engaging partners, leveraging community resources, dealing with highly structured institutions, measuring progress, and promoting and sustaining system change. CONCLUSION: A service system change pilot like BACHE requires: social capital, capable partners, a strong coalition, flexibility of approach, internal champions, systems knowledge, awareness of policy, and strong community involvement.

Hemosiderotic fibrohistiocytic lipomatous lesion: ten cases of a previously undescribed fatty lesion of the foot/ankle.

We address the clinicopathologic features of a previously undescribed heavily-pigmented spindle cell proliferation within a circumscribed benign lipomatous lesion that occurs mainly in the ankle region of older females. Patients with "lipoma with fibrohistiocytic proliferation" were retrieved from our files. Slides and clinical information were reviewed, and immunohistochemistry was performed (n = 5). Ten patients with hemosiderotic fibrohistiocytic lipomatous lesions were identified. All cases demonstrated a well-circumscribed fatty lesion with random focal proliferations of plump, slightly pleomorphic spindled cells, scattered inflammatory cells, and abundant iron pigment. The spindled cells had vesicular nuclei with indistinct nucleoli; occasional hyperchromatism was observed. No nuclear cytoplasmic inclusions were identified. The spindled component had a reactive appearance. In most cases, the fatty component, with homogeneously sized adipocytes, predominated. The lesions occurred in the foot/ankle region (8/10, one each cheek and hand) of primarily females (8/10) with a mean age of 50.6 years (range 42-63 years), size of 7.7 cm (range 2.5-17 cm), and prior duration of 3.1 years. Seven of eight patients had a history of prior trauma. The spindled component was positive for vimentin, calponin, CD34, and occasionally KP-1 or lysozyme and negative for caldesmon, S100, and desmin. Follow-up on eight patients revealed four with recurrences or residual disease over three years, requiring re-excision. No cases metastasized or caused patient death (mean 12 years, range 1-23 years). We describe a predominantly fatty lesion that is hemosiderin rich with a "fibrohistiocytic" proliferation, composed of histiocytes, myofibroblasts, and C34-positive fibroblasts, which occurs predominantly in the ankle region of middle-aged females. We believe that this is a reactive process due to antecedent trauma, the inflammatory cells, hemosiderin, mixed spindled cells, and homogeneous non-neoplastic appearance of the fat. HFLL can be distinguished from previously described lesions. Correct identification of hemosiderotic fibrohistiocytic lipomatous lesion is important, as it may locally recur.

Fibrohistiocytic lipoma: twelve cases of a previously undescribed benign fatty tumor.

A lipoma with a spindled proliferation within it, resembling known (myo)fibroblastic lesions such as fibrous histiocytoma or dermatofibrosarcoma protuberans, (ie, fibrohistiocytic lipoma), has not been previously reported. This tumor varies from other classic lipoma variants, including spindle cell lipoma, myolipoma, angiolipoma, and fibrolipoma. We examine the clinicopathologic findings of this new lipoma variant. The Soft Tissue Pathology Registry of the Armed Forces Institute of Pathology was searched for patients with "lipoma with fibrohistiocytic proliferation." Lesions that were better classified as other entities were excluded. Patient slides and clinical history, including associated lesions, family history, duration of symptoms, history of trauma, natural progression, and treatments, were reviewed. Immunohistochemistry was performed on cases with available material (n = 6). Twelve patients with fibrohistiocytic lipoma were included. All tumors revealed a well-distributed quilt-like proliferation or solid focus of slightly plump to relatively bland spindled cells with collagenous stroma in short fascicular and storiform growth patterns. These spindled cells resembled those seen in either fibrous histiocytoma or dermatofibrosarcoma protuberans. However, the spindled proliferation was all within a well-circumscribed lipoma. The lesions lack the dermal involvement or plump pleomorphism of fibrous histiocytoma and the dermal involvement or infiltrative growth pattern of dermatofibrosarcoma protuberans. The fatty component demonstrated heterogeneously sized adipocytes, as those seen in other lipomas. Inflammation and hemosiderin were minimal. Mast cells were not identified. The tumors were typically found in the subcutis of the trunk of men (10 of 12; one each on the wrist and leg; mean age, 31 years). The average size of the lesions was 3.0 cm, and they were present for a mean duration of 10 months prior to surgical excision. One patient had two concurrent lesions; all others had solitary tumors. Another patient had a intracranial dermoid cyst removed during childhood. Four patients had a personal or family history of hypercholesterolemia, hypertension, or myocardial infarction. There was no history of antecedent trauma. Cases studied were positive for vimentin, calponin (5 of 5), CD34 (3 of 5), and occasionally KP-1 or lysozyme in the spindled component, and all cases studied were negative for the actins, caldesmon, S-100 protein, desmin, cytokeratins, and epithelial membrane antigen. Although the actins were negative in our laboratory, the more sensitive calponin positivity suggests myofibroblastic phenotype of the spindled component of this lesion. CD34-positive fibroblasts were present in three of five cases. Of eight patients with follow-up, there were no recurrences; all patients were alive and free of disease over a mean of 10 years (range, 2 months to 31 years). We have identified a lipoma variant, fibrohistiocytic lipoma, that has not been previously described. In our experience the morphology and calponin positivity suggest myofibroblastic phenotype for the spindled cells, within a lipoma. This entity can be distinguished from fibrous histiocytoma, fibromatosis, dermatofibrosarcoma protuberans, spindle cell lipoma and other lipoma, and liposarcoma variants.