Macrophage Activation and Hemophagocytic Syndrome in Langerhans Cell Histiocytosis: Report of 30 Cases

Macrophage activation and secondary hemophagocytic syndrome are rarely reported in association with Langerhans cell histiocytosis (LCH). The authors reviewed their pathology files for cases of LCH in which evidence of macrophage activation coexisted and report 30 such cases indicating that the association is not that rare and may even be underdiagnosed unless specifically sought. Available clinical data were collected and correlated with pathological findings. Of the 30 cases of LCH with varying degrees of macrophage activation, 29 had multisystem disease. The cases were graded from I to V on the basis of evidence for, and severity of, macrophage activation; cases in category I had evidence of fully developed hemophagocytic syndrome whereas those in category V had limited evidence of macrophage activation. There were seven cases with fully developed hemophagocytic syndrome (category I) and an additional five with hemophagocytosis and some but not all of the features of hemophagocytic syndrome (category II). Most of these 12 cases were young children with high-risk LCH and poor prognosis; 4 are known to have died. Coexisting hemophagocytic syndrome in these cases of LCH may have contributed to their poor prognosis. The association of LCH with macrophage activation, though more than coincidental, is of unknown pathogenesis, but the role of T lymphocytes and cytokines is prominent in both disorders and is presumed to link the two. Received September 25, 2001; accepted October 2, 2001.     

Progress Towards Optimal Trial End-Points in Rheumatoid Arthritis

Trials in rheumatoid arthritis have been difficult to perform and interpret due to disagreement over what to measure. This paper reviews the most frequently used measures and their validity against the background of the Outcome Measures in Rheumatology (OMERACT) consensus conferences. These conferences have resulted in the adoption of a core set of end-points to be used as a minimum in all clinical trials in rheumatoid arthritis. These are known as the World Health Organization/International League of Associations for Rheumatology (WHO/ILAR) core set. This set of measures comprises: pain;patient global assessmentphysical disability;swollen joints;tender joints;acute phase reactants;physician (assessor) global assessment; and, in studies of 1 or more years duration,radiographs of joints. Other developments include a renewed interest in aggregate end-points (indices) such as response criteria, and in the measurement of adverse effects and economic costs. In sum, measurement methodology in rheumatoid arthritis has been improved in time to take advantage of expected important advances in treatment.     

Mesh Removal and Selective Neurectomy for Persistent Groin Pain Following Lichtenstein Repair

Background

Some patients with persistent inguinodynia following a Lichtenstein hernia repair fail all non-surgical treatments. Characteristics of mesh-related pain are not well described whereas a meshectomy is controversial. Aims were to define mesh-related pain symptoms, to investigate long-term effects of a meshectomy and to provide recommendations on meshectomy.

Methods

Consecutive patients undergoing open meshectomy with/without selective neurectomy for chronic inguinodynia following Lichtenstein repair were analysed including a follow-up questionnaire. Outcome measures were complications, satisfaction (excellent, good, moderate, poor) and hernia recurrence rate. Recommendations for meshectomy are proposed based on a literature review.

Results

Seventy-four patients (67 males, median age 56 years) underwent mesh removal (exclusively mesh, 26%; combined with tailored neurectomy, 74%) between June 2006 and March 2015 in a single centre. Complications were intraoperatively recognized small bowel injury (n = 1) and testicular atrophy (n = 2). A 64% excellent/good long-term result was attained (median 18 months). Success rates of a meshectomy (63%) or combined with a neurectomy (64%) were similar. Five hernia recurrences occurred during follow-up (7%). A patient with a pure mesh-related groin pain characteristically reports a ‘foreign body feeling’. Pain intensifies during hip flexion (car driving) and is attenuated following hip extension or supine position. Palpation is painful along the inguinal ligament whereas neuropathic characteristics (hyperpathic skin, trigger points) are lacking.

Conclusions

Mesh removal either or not combined with tailored neurectomy is beneficial in two of three patients with characteristics of mesh-related inguinodynia following Lichtenstein hernia repair who are refractory to alternative pain treatments.

     

The silent overall burden of foot disease in a representative hospitalised population

The aims of this study were to investigate the point prevalence, and associated independent factors, for foot disease (ulcers, infections and ischaemia) in a representative hospitalised population. We included 733 (83%) of 883 eligible adult inpatients across five representative Australian hospitals on one day. We collected an extensive range of self‐reported characteristics from participants. We examined all participants to clinically diagnose foot disease (ulcers, infections and ischaemia) and amputation procedures. Overall, 72 participants (9·8%) [95% confidence interval (CI):7·2–11·3%] had foot disease. Foot ulcers, in 49 participants (6·7%), were independently associated with peripheral neuropathy, peripheral arterial disease, previous foot ulcers, trauma and past surgeon treatment (P < 0·05). Foot infections, in 24 (3·3%), were independently associated with previous foot ulcers, trauma and past surgeon treatment (P < 0·01). Ischaemia, in 33 (4·5%), was independently associated with older age, smokers and past surgeon treatment (P < 0·01). Amputation procedures, in 14 (1·9%), were independently associated with foot infections (P < 0·01). We found that one in every ten inpatients had foot disease, and less than half of those had diabetes. After adjusting for diabetes, factors linked with foot disease were similar to those identified in diabetes‐related literature. The overall inpatient foot disease burden is similar in size to well‐known medical conditions and should receive similar attention.     

How do patients choose between active surveillance,radical prostatectomy,and radiotherapy? The effect of a preference-sensitive decision aid on treatment decision making for localized prostate cancer

Purpose

To determine the effect of a decision aid (DA) on treatment preferences and to investigate which patient preferences are important for final treatment preferences. We also determined if the patient?s treatment decision was influenced by the urologist?s treatment preference.

Factor analyses for the Örebro Musculoskeletal Pain Questionnaire for working and nonworking patients with chronic low back pain

Background Context

The Örebro Musculoskeletal Pain Questionnaire (ÖMPQ) has good psychometric properties to predict return to work in patients with acute low back pain. Although it is used in patients with chronic back pain and nonworkers, there is no evidence on the factor structure of the ÖMPQ in these populations. This is deemed an important prerequisite for future prediction studies.

Towards fair and effective North–South collaboration: realising a programme for demand-driven and locally led research

Background

At the turn of the 90s, studies showed that health research contributed little to health and development in low- and middle-income countries because it was oriented towards international priorities and dominated by researchers from the North. A new approach to North–South collaboration was required that would support demand-driven and locally led research in the South. The aim of this study was to analyse the development and functioning of a programme for demand-driven and locally led research in Ghana that was supported by a North–South collaboration.

Methods

For this mixed-method case study, we combined document analysis, key informant interviews and observation of programme events.

Results

The development of the research programme started with constructing a sponsorship constellation in the Netherlands. After highlighting the problems with traditional research collaboration, an advisory council formulated a vision for a more equal and effective approach to North–South collaboration. Together with Ghanaian partners, this vision was turned into a proposal for a Ghanaian-led programme for demand-driven and locally led research, which was funded by the Netherlands government. Research priority setting showed that the Ghanaian research needs were very different from the priorities of foreign funders and researchers. After a slow start, the number of locally submitted proposals increased from 13 in 2001 to 94 in 2005, revealing the existence of a substantial, but partly latent reservoir of research capacity. In total, 79 studies were funded. An impact evaluation showed that the results of the majority of the studies were used to contribute to action. Despite its success, the research programme came to an end in 2008 after the sponsorship constellation in the Netherlands fell apart.

Conclusion

Our study shows that realising a programme for demand-driven and locally led research in the South provides an effective approach to North–South collaboration in which results are used and local capacities and institutions are strengthened.

     

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

Introduction: The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization.

Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development.

Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.