Approach to lymphoma diagnosis and management in South Africa

Lymphoma is a cancer of the lymphoid cells, with a hugely variable mode of clinical presentation, which includes constitutional symptoms, lymphadenopathy, superficial or deep-seated masses, effusions, and full blood count abnormalities such as anaemia and lymphocytosis. Lymphoma can infiltrate any organ of the body, although it typically involves lymphoid tissue or bone marrow, or both. In this article an overview is given of the diagnostic pathway and clinical diagnostic subsets that determine treatment. The treatment approach according to these subsets is best understood as: indolent lymphoma, where treatment is not urgent and the disease is not curable; aggressive lymphoma, where rapid diagnosis and treatment are of the utmost importance, with the majority of cases curable; and very aggressive lymphoma, where patients are at high risk of death at presentation, but with rapid diagnosis and treatment there is an excellent chance of long-term cure. The past decade has seen an explosion of targeted (as opposed to classic chemotherapeutic) treatments for lymphoma. These drugs target certain molecules or receptors in the tumour pathway, often with spectacularly beneficial effects that open up new horizons for cure

Identifying relevant determinants of in-hospital time to diagnosis for ANCA-associated vasculitis patients

OBJECTIVES: Diagnosing patients with ANCA-associated vasculitis (AAV) can be challenging owing to its rarity and complexity. Diagnostic delay can have severe consequences, such as chronic organ damage or even death. Given that few studies have addressed diagnostic pathways to identify opportunities to improve, we performed a clinical audit to evaluate the diagnostic phase. METHODS: This retrospective, observational study of electronic medical records data in hospitals focused on diagnostic procedures during the first assessment until diagnosis. RESULTS: We included 230 AAV patients from nine hospitals. First assessments were mainly performed by a specialist in internal medicine (52%), pulmonology (14%), ENT (13%) or rheumatology (10%). The overall median time to diagnosis was 13 [interquartile range: 2–49] days, and in patients primarily examined by a specialist in internal medicine it was 6 [1–25] days, rheumatology 14 [4–45] days, pulmonology 15 [5–70] days and ENT 57 [16–176] days (P = 0.004). Twenty-two of 31 (71%) patients primarily assessed by a specialist in ENT had non-generalized disease, of whom 14 (64%) had ENT-limited activity. Two hundred and nineteen biopsies were performed in 187 patients (81%). Histopathological support for AAV was observed in 86% of kidney biopsies, 64% of lung biopsies and 34% of ENT biopsies. CONCLUSION: In The Netherlands, AAV is diagnosed and managed predominantly by internal medicine specialists. Diagnostic delay was associated with non-generalized disease and ENT involvement at presentation. Additionally, ENT biopsies had a low diagnostic yield, in contrast to kidney and lung biopsies. Awareness of this should lead to more frequent consideration of AAV and early referral for a multidisciplinary approach when AAV is suspected

The Undergraduate–Postgraduate–Faculty Triad: Unique Functions and Tensions Associated with Undergraduate Research Experiences at Research Universities

We present an exploratory study of how undergraduates' involvement in research influences postgraduates (i.e., graduate and postdoctoral researchers) and faculty. We used a qualitative approach to examine the relationships among undergraduates, postgraduates, and the faculty head in a research group. In this group, undergraduates viewed postgraduates as more approachable than the faculty head both literally and figuratively. Mentorship by postgraduates presented unique challenges for undergraduates, including unrealistic expectations and varying abilities to mentor. The postgraduates and faculty head concurred that undergraduates contributed to the group's success and served as a source of frustration. Postgraduates appreciated the opportunity to observe multiple approaches to mentoring as they saw the faculty head and other postgraduates interact with undergraduates. The faculty head viewed undergraduate research as important for propagating the research community and for gaining insights into undergraduates and their postgraduate mentors. These results highlight how the involvement of undergraduates and postgraduates in research can limit and enhance the research experiences of members of the undergraduate–postgraduate–faculty triad. A number of tensions emerge that we hypothesize are intrinsic to undergraduate research experiences at research universities. Future studies can focus on determining the generalizability of these findings to other groups and disciplines

Guideline for the treatment of myelodysplastic syndromes (MDS) in South Africa

The original publication is available at http://www.samj.org.zaIntroduction. Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal haematopoietic disorders characterised by chronic and progressive cytopenias resulting from ineffective haematopoiesis. Treatment is complicated by differences in disease mechanisms in different subgroups, variable clinical phenotypes and risk of progression to acute myeloid leukaemia. Rationale. Changes in disease classification, prognostic scoring systems, the availability of novel treatment options and the absence of South African guidelines for the diagnosis and management of these complex disorders underpinned the need for the development of these recommendations. Methods. These recommendations are based on the opinion of a number of experts in the field from the laboratory as well as clinical settings and came from both the private and institutional academic environments. The most recent literature as well as available guidelines from other countries were discussed and debated at a number of different meetings held over a 2-year period. Results. A comprehensive set of recommendations was developed focusing on risk stratification, supportive management and specific treatment. Novel agents and their indications are discussed and recommendations are made based on best available evidence and taking into account the availability of treatments in South Africa. Conclusion. Correct diagnosis, risk stratification and appropriate therapeutic choices are the cornerstones of success in the management of patients with MDS.Publishers' Versio

How baseline, new-onset, and persistent depressive symptoms are associated with cardiovascular and non-cardiovascular mortality in incident patients on chronic dialysis

AbstractObjectiveDepressive symptoms are associated with mortality among patients on chronic dialysis therapy. It is currently unknown how different courses of depressive symptoms are associated with both cardiovascular and non-cardiovascular mortality.MethodsIn a Dutch prospective nation-wide cohort study among incident patients on chronic dialysis, 1077 patients completed the Mental Health Inventory, both at 3 and 12months after starting dialysis. Cox regression models were used to calculate crude and adjusted hazard ratios (HRs) for mortality for patients with depressive symptoms at 3months only (baseline only), at 12months only (new-onset), and both at 3 and 12months (persistent), using patients without depressive symptoms at 3 and 12months as reference group.ResultsDepressive symptoms at baseline only seemed to be a strong marker for non-cardiovascular mortality (HRadj 1.91, 95% CI 1.26–2.90), whereas cardiovascular mortality was only moderately increased (HRadj 1.41, 95% CI 0.85–2.33). In contrast, new-onset depressive symptoms were moderately associated with both cardiovascular (HRadj 1.66, 95% CI 1.06–2.58) and non-cardiovascular mortality (HRadj 1.46, 95% CI 0.97–2.20). Among patients with persistent depressive symptoms, a poor survival was observed due to both cardiovascular (HRadj 2.14, 95% CI 1.42–3.24) and non-cardiovascular related mortality (HRadj 1.76, 95% CI 1.20–2.59).ConclusionThis study showed that different courses of depressive symptoms were associated with a poor survival after the start of dialysis. In particular, temporary depressive symptoms at the start of dialysis may be a strong marker for non-cardiovascular mortality, whereas persistent depressive symptoms were associated with both cardiovascular and non-cardiovascular mortality

The Relationship between Regular Sports Participation and Vigilance in Male and Female Adolescents

The present study investigated the relationship between regular sport participation (soccer) and vigilance performance. Two groups of male and female adolescents differentiated in terms of their sport participation (athletes, n = 39, and non-athletes, n = 36) took part in the study. In one session, participants performed the Leger Multi-stage fitness test to estimate their aerobic fitness level. In the other session, participants completed the Psychomotor Vigilance Task (PVT) to evaluate their vigilance performance. Perceived arousal prior to the task and motivation toward the task were also measured in the PVT session. The results revealed that athletes had better cardiovascular fitness and showed better performance in the PVT. However, correlation analyses did not show any significant relationship between cardiovascular fitness and performance in the PVT. Athletes showed larger scores in motivation and perceived arousal measures with respect to non-athletes, although, once again, these variables were not correlated with PVT performance. Gender differences were observed only in the Leger test, with males showing greater fitness level than females. The major outcome of this research points to a positive relationship between regular sport participation and vigilance during adolescence. This relationship did not seem to be influenced by gender, perceived arousal, motivation toward the task or cardiovascular fitness. We discuss our results in terms of the different hypotheses put forward in the literature to explain the relationship between physical activity and cognitive functioning.This research was supported by a Spanish Ministerio de Educación y Cultura (https://sede. educacion.gob.es) predoctoral grant (FPU13-05605) to the first author, and project research grants: Junta de Andalucia Proyecto de Excelencia SEJ-6414 (http://www.juntadeandalucia.es) and Ministerio de Economía y Competitividad PSI2013-46385 (http://www.mineco.gob.es) to DS and FH

Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection

Needle-free measles virus vaccination by aerosol inhalation has many potential benefits. The current standard route of vaccination is subcutaneous injection, whereas measles virus is an airborne pathogen. However, the target cells that support replication of live-attenuated measles virus vaccines in the respiratory tract are largely unknown. The aims of this study were to assess the in vivo tropism of live-attenuated measles virus and determine whether respiratory measles virus vaccination should target the upper or lower respiratory tract. Four groups of twelve cynomolgus macaques were immunized with 104 TCID50 of recombinant measles virus vaccine strain Edmonston-Zagreb expressing enhanced green fluorescent protein. The vaccine virus was grown in MRC-5 cells and formulated with identical stabilizers and excipients as used in the commercial MVEZ vaccine produced by the Serum Institute of India. Animals were immunized by hypodermic injection, intra-tracheal inoculation, intra-nasal instillation, or aerosol inhalation. In each group six animals were euthanized at early time points post-vaccination, whereas the other six were followed for 14 months to assess immunogenicity and protection from challenge infection with wild-type measles virus. At early time-points, enhanced green fluorescent protein-positive measles virus-infected cells were detected locally in the muscle, nasal tissues, lungs, and draining lymph nodes. Systemic vaccine virus replication and viremia were virtually absent. Infected macrophages, dendritic cells and tissue-resident lymphocytes predominated. Exclusive delivery of vaccine virus to the lower respiratory tract resulted in highest immunogenicity and protection. This study sheds light on the tropism of a live-attenuated measles virus vaccine and identifies the alveolar spaces as the optimal site for respiratory delivery of measles virus vaccine