The Effect of Hygiene-Based Lymphedema Management in Lymphatic Filariasis-Endemic Areas: A Systematic Review and Meta-analysis

Background

Lymphedema of the leg and its advanced form, known as elephantiasis, are significant causes of disability and morbidity in areas endemic for lymphatic filariasis (LF), with an estimated 14 million persons affected worldwide. The twin goals of the World Health Organization’s Global Program to Eliminate Lymphatic Filariasis include interrupting transmission of the parasitic worms that cause LF and providing care to persons who suffer from its clinical manifestations, including lymphedema—so-called morbidity management and disability prevention (MMDP). Scaling up of MMDP has been slow, in part because of a lack of consensus about the effectiveness of recommended hygiene-based interventions for clinical lymphedema.

Methods and Findings

We conducted a systemic review and meta-analyses to estimate the effectiveness of hygiene-based interventions on LF-related lymphedema. We systematically searched PubMed, Embase, ISI Web of Knowledge, MedCarib, Lilacs, REPIDISCA, DESASTRES, and African Index Medicus databases through March 23, 2015 with no restriction on year of publication. Studies were eligible for inclusion if they (1) were conducted in an area endemic for LF, (2) involved hygiene-based interventions to manage lymphedema, and (3) assessed lymphedema-related morbidity. For clinical outcomes for which three or more studies assessed comparable interventions for lymphedema, we conducted random-effects meta-analyses. Twenty-two studies met the inclusion criteria and two meta-analyses were possible. To evaluate study quality, we developed a set of criteria derived from the GRADE methodology. Publication bias was assessed using funnel plots. Participation in hygiene-based lymphedema management was associated with a lower incidence of acute dermatolymphagioadenitis (ADLA), (Odds Ratio 0.32, 95% CI 0.25–0.40), as well as with a decreased percentage of patients reporting at least one episode of ADLA during follow-up (OR 0.29, 95% CI 0.12–0.47). Limitations included high heterogeneity across studies and variation in components of lymphedema management.

Conclusions

Available evidence strongly supports the effectiveness of hygiene-based lymphedema management in LF-endemic areas. Despite the aforementioned limitations, these findings highlight the potential to significantly reduce LF-associated morbidity and disability as well as the need to develop standardized approaches to MMDP in LF-endemic areas.     

Period Prevalence of Dizziness and Vertigo in Adolescents

Objectives

To assess the period prevalence and severity of dizziness and vertigo in adolescents.

Methods

In 1661 students in 8^th-10^th grade in twelve grammar schools in Munich, Germany information on vertigo/dizziness was assessed by a questionnaire in the class room setting. Three month prevalence of dizziness/vertigo was estimated; symptoms were categorized as orthostatic dizziness, spinning vertigo, swaying vertigo or unspecified dizziness. Duration of symptoms and impact on daily life activities were assessed.

Results

72.0% (95%-CI = [69.8–74.2]; N = 1196) of the students (mean age 14.5±1.1) reported to suffer from at least one episode of dizziness or vertigo in the last three months. Most adolescents ticked to have symptoms of orthostatic dizziness (52.0%, 95%-CI = [49.5–54.4], N = 863). The period prevalence for the other types of vertigo were spinning vertigo: 11.6%, 95%-CI = [10.1–13.3], N = 193; swaying vertigo: 12.2%, 95%-CI = [10.6–13.8], N = 202; and unspecified dizziness: 15.2%, 95%-CI = [13.5–17.1], N = 253. About 50% of students with spinning vertigo and swaying vertigo also report to have orthostatic dizziness. Most vertigo/dizziness types were confined to less than one minute on average. The proportion of students with any dizziness/vertigo accounting for failure attending school, leisure activities or obliging them to stay in bed were more pronounced for spinning or swaying vertigo.

Conclusion

Dizziness and vertigo in grammar school students appear to be as common as in adults. In face of the high period prevalence and clinical relevance of dizziness/vertigo in adolescents there is a need for prevention strategies. Risk factors for dizziness/vertigo need to be assessed to allow for conception of an intervention programme.     

Repeat hepatectomy justified in patients with early recurrence of colorectal cancer liver metastases: A systematic review and meta-analysis

BackgroundThe benefit of repeat hepatectomy in patients with early recurrence of colorectal cancer liver metastases (CRLM) is questioned, in particular in those suffering from recurrence within three to six months following initial hepatectomy. The aim of this review was therefore to assess whether disease-free interval was associated with overall survival in patients undergoing repeat hepatectomy for recurrent CRLM.MethodsA systematic review and meta-analysis was conducted, according to PRISMA guidelines. PubMed, Embase and Cochrane Library databases were searched from database inception to 6th June 2020. Observational studies describing results of repeat hepatectomy for recurrent CRLM, including (disease-free) interval between hepatic resections and overall survival were included. Patients undergoing repeat hepatectomy within three months or additional resection of extrahepatic disease were excluded from meta-analysis.ResultsThe initial search identified 2159 records, of which 28 were included for qualitative synthesis. A meta-analysis of 15 cohort studies was performed, comprising 1039 eligible patients. Median overall survival of 54.0 months [95 %-CI: 38.6–69.4] was observed after repeat hepatectomy in patients suffering from recurrent CRLM between three to six months compared to 53.0 months [95 %-CI: 44.3–61.6] for patients with recurrent CRLM between seven to twelve months (adjusted HR = 0.89, 95 %-CI: 0.66–1.18; p = 0.410), and 60.0 months [95 %-CI: 52.7–67.3] for patients with recurrent CRLM after twelve months (adjusted HR = 0.70, 95 %-CI: 0.53−0.92; p = 0.012).ConclusionsDisease-free interval is considered a prognostic factor for overall survival, but should not be used as selection criterion per se for repeat hepatectomy in patients suffering from recurrent CRLM.     

Long-Term Weight Change: Association with Impaired Glucose Metabolism in Young Austrian Adults

Little is known about the associations between long-term weight change and the natural history of impaired fasting glucose (IFG) in young adults. We investigated the association between long-term body mass index (BMI) change and the risk of IFG using data of 24,930 20- to 40-year-old participants from the Vorarlberg Health Monitoring and Promotion Program (VHM&PP) cohort. Poisson models were applied to estimate the 10-year risk for new development of IFG (≥5.6 mmol/L), and persistence of IFG. Over 10 years, most men (68.2%) and women (70.0%) stayed within their initial BMI category. The risk for incident IFG was highest for men and women with persisting obesity (37.4% and 24.1%) and lowest with persisting normal weight (15.7% and 9.3%). Men transitioning from normal to overweight increased their risk of incident IFG by factor 1.45 (95%-CI: 1.31, 1.62), women by 1.70 (95%-CI: 1.50, 1.93), whereas transitioning from overweight to normal weight decreased the risk in men by 0.69 (95%-CI: 0.53, 0.90) and 0.94 (95%-CI: 0.66, 1.33) in women. Relative risks for men and women transitioning from obesity to overweight were 0.58 and 0.44, respectively. In conclusion, 10 year weight increase was associated with an increased IFG risk, weight decrease with a decreased risk of IFG in young adults.     

Impact of a Community-Based Lymphedema Management Program on Episodes of Adenolymphangitis (ADLA) and Lymphedema Progression - Odisha State,India

Background

Lymphedema management programs have been shown to decrease episodes of adenolymphangitis (ADLA), but the impact on lymphedema progression and of program compliance have not been thoroughly explored. Our objectives were to determine the rate of ADLA episodes and lymphedema progression over time for patients enrolled in a community-based lymphedema management program. We explored the association between program compliance and ADLA episodes as well as lymphedema progression.

Methodology/Principal Findings

A lymphedema management program was implemented in Odisha State, India from 2007–2010 by the non-governmental organization, Church''s Auxiliary for Social Action, in consultation with the Centers for Disease Control and Prevention. A cohort of patients was followed over 24 months. The crude 30-day rate of ADLA episodes decreased from 0.35 episodes per person-month at baseline to 0.23 at 24 months. Over the study period, the percentage of patients who progressed to more severe lymphedema decreased (P-value  = 0.0004), while those whose lymphedema regressed increased over time (P-value<0.0001). Overall compliance to lymphedema management, lagged one time point, appeared to have little to no association with the frequency of ADLA episodes among those without entry lesions (RR = 0.87 (0.69, 1.10)) and was associated with an increased rate (RR = 1.44 (1.11, 1.86)) among those with entry lesions. Lagging compliance two time points, it was associated with a decrease in the rate of ADLA episodes among those with entry lesions (RR = 0.77 (95% CI: 0.59, 0.99)) and was somewhat associated among those without entry lesions (RR = 0.83 (95% CI: 0.64, 1.06)). Compliance to soap was associated with a decreased rate of ADLA episodes among those without inter-digital entry lesions.

Conclusions/Significance

These results indicate that a community-based lymphedema management program is beneficial for lymphedema patients for both ADLA episodes and lymphedema. It is one of the first studies to demonstrate an association between program compliance and rate of ADLA episodes.     

Health outcomes of road-traffic pollution among exposed roadside workers in Rawalpindi City,Pakistan

To document ill-health effects of air pollution on the local inhabitants, we analyzed the self-reported health issues associated with the inhalation of road traffic on daily basis. For this purpose, a revised version of ALS-DLD-78S questionnaire was administered, comprising the personal information and details related to the clinical history of the surveyed population (i.e. n = 580). Five dependent (outcome) variables, including chest pain, redness of eyes, shortness of breath, eye-tearing, and skin-itching were taken into account. The results revealed that ～80% of the surveyed population were directly or indirectly exposed to road traffic, and the incidence of chest pain among exposed individuals was estimated to increase with age (odds ratio (OR) = 6.49; 95% confidence interval (CI) = 1.46–28.81), especially among cardiac patients (OR = 13.87; 95%-CI = 3.28–58.61). However, the shortness of breath was predominantly observed among those who reported to have asthmatic symptoms (OR = 32.84; 95%-CI = 15.59–69.15) and cardiovascular symptoms (OR = 13.8: 95%-CI = 3.63–52.41). In case of itching, the population along the roadside were more vulnerable to exposure (OR = 5.79; 95%-CI = 2.81–11.93). While, exposure to traffic exhaust could be attributed to ～3.13% rise in the incidences of redness of eyes among general population, the outcomes of this survey show that daily exposure to traffic pollution is an important health concern for the urban population in general, as well as for various occupational groups in particular, working in outdoor environment.     

Lymphedema Prevalence and Treatment Benefits in Cancer: Impact of a Therapeutic Intervention on Health Outcomes and Costs

Background

Lymphedema is a common complication of cancer therapeutics; its prevalence, treatment outcomes, and costs have been poorly defined. The objective of this study was to examine lymphedema prevalence among cancer survivors and to characterize changes in clinical outcomes and costs associated with a defined therapeutic intervention (use of a pneumatic compression devices [PCD]) in a representative, privately insured population.

Methods and Findings

Retrospective analysis of de-identified health claims data from a large national insurer for calendar years 2007 through 2013. Patients were required to have 12 months of continuous insurance coverage prior to PCD receipt (baseline), as well as a 12-month follow-up period. Analyses were performed for individuals with cancer-related lymphedema (n = 1,065). Lymphedema prevalence was calculated: number of patients with a lymphedema claim in a calendar year divided by total number of enrollees. The impact of PCD use was evaluated by comparing rates of a pre-specified set of health outcomes and costs for the 12 months before and after, respectively, PCD receipt. Lymphedema prevalence among cancer survivors increased from 0.95% in 2007 to 1.24% in 2013. PCD use was associated with decreases in rates of hospitalizations (45% to 32%, p<0.0001), outpatient hospital visits (95% to 90%, p<0.0001), cellulitis diagnoses (28% to 22%, p = 0.003), and physical therapy use (50% to 41%, p<0.0001). The average baseline health care costs were high ($53,422) but decreased in the year after PCD acquisition (−$11,833, p<0.0001).

Conclusions

Lymphedema is a prevalent medical condition that is often a defining attribute of cancer survivorship. The problem is associated with high health care costs; Treatment (in this instance, use of PCD) is associated with significant decreases in adverse clinical outcomes and costs.     

Reliability of bioimpedance spectroscopy and tonometry after breast conserving cancer treatment

BACKGROUND: Measuring the female breast, especially after breast cancer treatment, is problematic due to breast size, texture, and patient positioning. However, being able to accurately measure changes in the breast is important, as it may help in the earlier diagnosis and treatment of early breast edema and later lymphedema. METHODS: 14 women who had undergone breast conserving surgery for breast cancer (> 12 months ago) were recruited to assess the between subject reproducibility of tonometry and bioimpedance spectroscopy (BIS). With the participant supine, two repeat measurements of the resistance of the tissues to compression (tonometry) and fluid levels (BIS) of the treated and normal breast were taken for each of the four quadrants of the breast. RESULTS: The between subject reproducibility for both measurement techniques was high, with covariance ranging from 1.29% to 3.25% for tonometry and 0.20-0.86% for BIS. CONCLUSIONS: The reliability of these two measurement techniques provides an opportunity for researchers and clinicians to easily quantify breast tissue and fluid changes which in turn may lead to the earlier diagnosis and targeted treatment of breast edema and lymphedema.     

Sensitivity of Hyperdense Basilar Artery Sign on Non-Enhanced Computed Tomography

Purpose

The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO.

Materials and Methods

102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio.

Results

Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%).

Conclusion

In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT.     

Long-Term Sequelae of Severe Acute Kidney Injury in the Critically Ill Patient without Comorbidity: A Retrospective Cohort Study

Background and Objectives

Acute kidney injury (AKI) necessitating renal replacement therapy (RRT) is associated with high mortality and increased risk for end stage renal disease. However, it is unknown if this applies to patients with a preliminary unremarkable medical history. The purpose of this study was to describe overall and renal survival in critically ill patients with AKI necessitating RRT stratified by the presence of comorbidity.

Design, Setting, Participants, and Measurements

A retrospective cohort study was performed, between 1994 and 2010, including all adult critically ill patients with AKI necessitating RRT, stratified by the presence of comorbidity. Logistic regression, survival curve and cox proportional hazards analyses were used to evaluate overall and renal survival. Standardized mortality rate (SMR) analysis was performed to compare long-term survival to the predicted survival in the Dutch population.

Results

Of the 1067 patients included only 96(9.0%) had no comorbidity. Hospital mortality was 56.6% versus 43.8% in patients with and without comorbidity, respectively. In those who survived hospitalization 10-year survival was 45.0% and 86.0%, respectively. Adjusted for age, sex and year of treatment, absence of comorbidity was not associated with hospital mortality (OR=0.74, 95%-CI=0.47-1.15), while absence of comorbidity was associated with better long-term survival (adjusted HR=0.28, 95%-CI = 0.14-0.58). Compared to the Dutch population, patients without comorbidity had a similar mortality risk (SMR=1.6, 95%-CI=0.7-3.2), while this was increased in patients with comorbidity (SMR=4.8, 95%-CI=4.1-5.5). Regarding chronic dialysis dependency, 10-year renal survival rates were 76.0% and 92.9% in patients with and without comorbidity, respectively. Absence of comorbidity was associated with better renal survival (adjusted HR=0.24, 95%-CI=0.07-0.76).

Conclusions

While hospital mortality remains excessively high, the absence of comorbidity in critically ill patients with RRT-requiring AKI is associated with a relative good long-term prognosis in those who survive hospitalization.     

Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study

Background

The role of endothelin-1 (ET-1) in the neurobiology of anxiety is unknown, therefore, we assessed in the observational multicenter DIAST-CHF study whether the C-terminal ET-1 precursor fragment (CT-proET-1) is linked to anxiety.

Methods

Plasma concentrations of CT-proET-1 were measured in a total of 1,410 patients presenting with cardiovascular risk factors (mean age 66.91±8.2 years, 49.3% males, mean left ventricular ejection fraction 60.0±8.2%) who had completed the Hospital Anxiety and Depression Scale (HADS) questionnaire.

Results

Among the total study cohort (n = 1,410), there were 118 subjects (8.4%) with an HADS anxiety score above the cut-off level of 11 suggestive of clinically relevant anxiety. Plasma CT-proET-1 levels were significantly lower in the group of anxious patients as compared to non-anxious patients (p = 0.013). In regression models adjusted for sex, age, systolic blood pressure, and diameters of left atrium and ventricle, plasma CT-proET-1 was again linked to anxiety (Exp(β) = 0.247, 95%-confidence interval [95%-CI] = 0.067–0.914, p = 0.036). Given the high prevalence of depressive disorders in anxious patients, we additionally included the HADS depression score as an independent variable in the models and found that CT-proET-1 remained a significant predictor of anxiety, independent of comorbid depression (Exp(β) = 0.114, 95%-CI = 0.023–0.566, p = 0.008).

Conclusions

Our data from a population-based study in outpatients with cardiovascular risk factors revealed that circulating CT-proET-1 levels are negatively associated with anxiety. Further investigations are required to clarify the putative anxiolytic effect of ET-1 or its precursor molecules in humans and to decipher its mechanistic pathways.     

Adipose-derived stem cell therapy shows promising results for secondary lymphedema

Lymphedema is mainly identified by progressive soft tissue swelling in impaired lymphatic system. Secondary lymphedema attributed to cancer therapy, parasite infection, and trauma remains a serious global disease. Patients with lymphedema suffer swelling, pain, and fatigue, with the dysfunction of the deformed extremities reducing the quality of life and increasing the risk of infection and lymphangiosarcoma. Adipose-derived stem cells (ADSCs) possess prominent regenerative potential to differentiate into multilineage cells, and produce various lymphangiogenic factors, making ADSC therapy a promising approach for lymphedema. The development of lymphedema consists of local inflammation, the fibrosis of lymphatic vessels, and the deposition of adipose fat. Existing animal models do not mimic the chronic inflammation environment, therefore suitable models are required in further studies. Some signal pathways and molecular mechanisms in physiological and pathological lymphagiogenesis remain unclear. In previous animal and human trials, ADSC therapy reduced edema in varying degrees. A larger number of trials with larger samples and longer follow-up periods are required to verify the efficiency and feasibility of ADSC therapy. ADSCs are of easy availability and immune exemption, making them a candidate for lymphedema treatment. Whether ADSCs enhance malignant characteristics or trigger the malignant change deserves further exploration and study before ADSC therapy can be made widely available.     

Proteomic profiling of lymphedema development in mouse model

The lymphatic vascular system plays an important role in tissue fluid homeostasis. Lymphedema is a chronic, progressive, and incurable condition that leads to lymphatic fluid retention; it may be primary (heritable) or secondary (acquired) in nature. Although there is a growing understanding of lymphedema, methods for the prevention and treatment of lymphedema are still limited. In this study, we investigated differential protein expressions in sham‐operated and lymphedema‐operated mice for 3 days, using two‐dimensional gel electrophoresis (2‐DE) and mass spectrometry analysis. Male improved methodology for culturing noninbred (ICR) mice developed lymphedema in the right hindlimb. Twenty functional proteins were found to be differentially expressed between lymphedema induced‐right leg tissue and normal left leg tissue. Out of these proteins, the protein levels of apolipoprotein A‐1 preprotein, alpha‐actinin‐3, mCG21744, parkinson disease, serum amyloid P‐component precursor, annexin A8, mKIAA0098 protein, and fibrinogen beta chain precursor were differentially upregulated in the lymphedema mice compared with the sham‐operated group. Western blotting analysis was used to validate the proteomics results. Our results showing differential up‐regulation of serum amyloid P‐component precursor, parkinson disease, and apolipoprotein A‐1 preprotein in lymphedema model over sham‐operated model suggest important insights into pathophysiological target for lymphedema. Copyright © 2016 John Wiley & Sons, Ltd.     

Adherence to Physician Recommendations for Surveillance in Opportunistic Colorectal Cancer Screening: The Necessity of Organized Surveillance

Background

Limited evidence exists on the utilization of surveillance colonoscopy in colorectal cancer (CRC) screening programs. We assessed adherence to physician recommendations for surveillance in opportunistic CRC screening in Germany.

Methods

A follow-up study of screening colonoscopy participants in 2007-2009 in Saarland, Germany, was conducted using health insurance claims data. Utilization of additional colonoscopies through to 2011 was ascertained. Adherence to surveillance intervals of 3, 6, 12 and 36 months, defined as having had colonoscopy at 2.5 to 4, 5 to 8, 10.5 to 16 and 33 to 48 months, respectively (i.e., tolerating a delay of 33% of each interval) was assessed. Potential predictors of non-adherence were investigated using logistic regression analysis.

Results

A total of 20,058 screening colonoscopy participants were included in the study. Of those with recommended surveillance intervals of 3, 6, 12 and 36 months, 46.5% (95%-confidence interval [CI]: 37.3-55.7%), 38.5% (95%-CI: 29.6-47.3%), 25.4% (95%-CI: 21.2-29.6%) and 28.0% (95%-CI: 25.5-30.5%), respectively, had a subsequent colonoscopy within the specified margins. Old age, longer recommended surveillance interval, not having had polypectomy at screening and negative colonoscopy were statistically significant predictors of non-adherence.

Conclusion

This study suggests frequent non-adherence to physician recommendations for surveillance colonoscopy in community practice. Increased efforts to improve adherence, including introduction of more elements of an organized screening program, seem necessary to assure a high-quality CRC screening process.     

Dual-task and anticipation impact lower limb biomechanics during a single-leg cut with body borne load

This study quantified how a dual cognitive task impacts lower limb biomechanics during anticipated and unanticipated single-leg cuts with body borne load. Twenty-four males performed anticipated and unanticipated cuts with and without a dual cognitive task with three load conditions: no load (∼6 kg), medium load (15% of BW), and heavy load (30% of BW). Lower limb biomechanics were submitted to a repeated measures linear mixed model to test the main and interaction effects of load, anticipation, and dual task. With body borne load, participants increased peak stance (PS) hip flexion (p = .004) and hip internal rotation (p = .001) angle, and PS hip flexion (p = .001) and internal rotation (p = .018), and knee flexion (p = .016) and abduction (p = .001) moments. With the dual task, participants decreased PS knee flexion angle (p < .001) and hip flexion moment (p = .027), and increased PS knee external rotation angle (p = .034). During the unanticipated cut, participants increased PS hip (p = .040) and knee flexion angle (p < .001), and decreased PS hip adduction (p = .001), and knee abduction (p = .005) and external rotation (p = .026) moments. Adding body borne load produces lower limb biomechanical adaptations thought to increase risk of musculoskeletal injury, but neither anticipation nor dual task exaggerated those biomechanical adaptations. With a dual task, participants adopted biomechanics known to increase injury risk; whereas, participants used lower limb biomechanics thought to decrease injury risk during unanticipated cuts.     

Staged treatment of lymphedema praecox

Lymphedema of the lower extremities poses a challenging problem in management. Gross deformities may be encountered in patients with filarial infestation. This degree of involvement is rare in native North Americans suffering from primary lymphedema.A case is presented of a patient with changes similar to those seen in filariasis, due to several episodes of acute lymphangitis over a period of years. The involved tissue was excised and the defects skin-grafted, employing a modified Charles procedure. The magnitude of the excision was such that it was carried out in three widely spaced stages. The result was satisfactory from a functional viewpoint, and also represented a marked cosmetic improvement.     

CD4+ Cells Regulate Fibrosis and Lymphangiogenesis in Response to Lymphatic Fluid Stasis

Introduction

Lymphedema is a chronic disorder that occurs commonly after lymph node removal for cancer treatment and is characterized by swelling, fibrosis, inflammation, and adipose deposition. Although previous histological studies have investigated inflammatory changes that occur in lymphedema, the precise cellular make up of the inflammatory infiltrate remains unknown. It is also unclear if this inflammatory response plays a causal role in the pathology of lymphedema. The purpose of this study was therefore to characterize the inflammatory response to lymphatic stasis and determine if these responses are necessary for the pathological changes that occur in lymphedema.

Methods

We used mouse-tail lymphedema and axillary lymph node dissection (ANLD) models in order to study tissue inflammatory changes. Single cell suspensions were created and analyzed using multi-color flow cytometry to identify individual cell types. We utilized antibody depletion techniques to analyze the causal role of CD4+, CD8+, and CD25+ cells in the regulation of inflammation, fibrosis, adipose deposition, and lymphangiogenesis.

Results

Lymphedema in the mouse-tail resulted in a mixed inflammatory cell response with significant increases in T-helper, T-regulatory, neutrophils, macrophages, and dendritic cell populations. Interestingly, we found that ALND resulted in significant increases in T-helper cells suggesting that these adaptive immune responses precede changes in macrophage and dendritic cell infiltration. In support of this we found that depletion of CD4+, but not CD8 or CD25+ cells, significantly decreased tail lymphedema, inflammation, fibrosis, and adipose deposition. In addition, depletion of CD4+ cells significantly increased lymphangiogenesis both in our tail model and also in an inflammatory lymphangiogenesis model.

Conclusions

Lymphedema and lymphatic stasis result in CD4+ cell inflammation and infiltration of mature T-helper cells. Loss of CD4+ but not CD8+ or CD25+ cell inflammation markedly decreases the pathological changes associated with lymphedema. In addition, CD4+ cells regulate lymphangiogenesis during wound repair and inflammatory lymphangiogenesis.     

Willingness to pay for prevention and treatment of lymphatic filariasis in Leogane, Haiti

BACKGROUND: Lymphatic filariasis (LF) affects more than 120 million people worldwide. Efforts to eliminate this disease require sustained community participation. This study explores community valuation of LF elimination efforts by estimating household and community willingness to pay (WTP) for the prevention of transmission and treatment of filarial lymphedema in the community of Leogane, Haiti. METHODS: A contingent valuation survey was used to assess individual WTP for specific prevention and treatment interventions. A 2-dimensional Monte Carlo simulation was developed to estimate confidence limits in mean WTP and to generate a distribution of WTP for the community, accounting for uncertainty in regression coefficients and variability within the population. RESULTS: Mean WTP was estimated to be $5.57/month/household (95% CL: $4.76, $6.72) to prevent disease transmission, and $491/yr (95% CL: $377, $662) for treatment of lymphedema for one person. Based on the estimated distributions, 7% and 39% of households were not willing to pay for prevention and treatment, respectively. CONCLUSIONS: These results suggest that the majority of the community places a positive value on both prevention and treatment of LF. Mean WTP provides a useful monetary estimate of overall societal benefit of LF prevention and treatment programs. However, for interventions which require broad and sustained community participation, the lower end of the distribution of WTP has additional implications. Cost recovery policies may result in inadequate participation and longer program duration.     

Surgical management of lymphedema of the extremity.

Lymphedema of the extremity has been managed in 14 patients by staged excisions of the edematous subcutaneous tissue beneath skin flaps. Six patients have been followed for 4 to 6 years. This method has been successful in dealing with the symptoms of this condition. No episodes of postoperative celluitis have occurred in these patients. Normal function of the extremity has been achieved, and the contour has been preserved. It appears at this time that excision of the subcutaneous tissue is the most important aspect of the surgical management of lymphedema.