Autoimmunity; Atherosclerosis; Systemic Lupus Erythematosus
To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).
We performed case–cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren’s syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses.
We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls.
In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
To correlate the radiomorphometric indices obtained using digital panoramic radiography (DPR) with bone mineral densities, evaluated by the dual-energy X-ray absorptiometry test, in a population of post-menopausal females to identify patients with asymptomatic low bone mineral densities.
The morphology of the mandibular cortex was evaluated using the mandibular cortical index (MCI) and the inferior mandibular cortex width was evaluated using the mental index (MI) in 64 female patients who had undergone dual-energy X-ray absorptiometry assessment. Of these patients, 21 were diagnosed with osteopaenia and 20 with osteoporosis, and 23 were normal. Three new indices for evaluating the inferior mandibular cortex width were designed: the mental posterior index 1 (MPI1), MPI2 and MPI3. Statistical analyses were performed using the χ2 and Kruskal–Wallis tests and the receiver operating characteristic curve.
There were significant differences between the normal and lower bone mineral density groups (osteopaenia and osteoporosis) for MCI (p < 0.01). In the osteoporosis group, the MI, MPI1, MPI2 and MPI3 were significantly different from the normal and osteopaenia groups (p < 0.05). The MI, MPI1, MPI2 and MPI3 showed that there is an area in the mandibular cortex, located between the mental foramen and the antegonial region, which is valid for identifying females at high risk for osteoporosis.
The MCI, MI, MPI1, MPI2, and MPI3 radiomorphometric indices evaluated using DPR can be used to identify post-menopausal females with low bone densities and to provide adequate medical treatment for them.
bone density; osteoporosis; panoramic radiography; prevention; control
Cells use complex biochemical pathways to drive shape changes for polarization and movement. One of these pathways is the self-assembly of actin filaments and myosin motors that together produce the forces and tensions that drive cell shape changes. Whereas the role of actin and myosin motors in cell polarization is clear, the exact mechanism of how the cortex, a thin shell of actin that is underneath the plasma membrane, can drive cell shape changes is still an open question. Here, we address this issue using biomimetic systems: the actin cortex is reconstituted on liposome membranes, in an ‘outside geometry’. The actin shell is either grown from an activator of actin polymerization immobilized at the membrane by a biotin–streptavidin link, or built by simple adsorption of biotinylated actin filaments to the membrane, in the presence or absence of myosin motors. We show that tension in the actin network can be induced either by active actin polymerization on the membrane via the Arp2/3 complex or by myosin II filament pulling activity. Symmetry breaking and spontaneous polarization occur above a critical tension that opens up a crack in the actin shell. We show that this critical tension is reached by growing branched networks, nucleated by the Arp2/3 complex, in a concentration window of capping protein that limits actin filament growth and by a sufficient number of motors that pull on actin filaments. Our study provides the groundwork to understanding the physical mechanisms at work during polarization prior to cell shape modifications.
acto-myosin; cortical tension; symmetry breaking; biomimetic liposome
It is estimated that over 50 % of patients with systemic lupus erythematosus (SLE) have utilized complementary and alternative medicine (CAM) treatments to reduce symptoms and manage their health. However, there are relatively few randomized controlled trials of CAM for SLE. This review describes recent studies of vitamins and supplements, acupuncture, and mind-body interventions in SLE patients. The recent trials of CAM treatments for SLE indicate that supplements such as vitamin D, omega 3 fatty acids, N-acetyl cysteine and turmeric show some promise for reducing SLE disease activity. In addition, mind-body methods such as cognitive-behavioral therapy and other counseling interventions may improve mood and quality of life in SLE.
Systemic lupus erythematosus; Complementary medicine; Alternative medicine; Integrative medicine; Supplements; Acupuncture; Vitamins; Mind–body treatments; Cognitive behavioral therapy; Meditation; Interpersonal therapy; N-acetyl cysteine; turmeric; DHEA; Vitamin D; Vitamin C; Vitamin E; Vitamin B6; Omega 3 fatty acids; Fish oil; Oxidative stress; Anti-oxidants
Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD). Traditional CVD and SLE-disease related risk factors do not fully account for this increased risk. Perivascular adipose tissue (PVAT) is a visceral adipose depot in close proximity to blood vessels possibly influencing CVD. We hypothesized that women with SLE have an increased volume of descending thoracic aortic PVAT (aPVAT) associated with increased vascular calcification.
Using electron beam computed tomography, we quantified the aPVAT in clinically CVD-free SLE women (n=135) and age-/race-matched healthy controls (HC, n=152). Coronary artery calcification (CAC) and aortic calcification (AC) were quantified using Agatston scores and the aPVAT was quantified using standard Hounsfield Units (HU) for adipose tissue.
Women with SLE had greater median aPVAT (32.2 cm3 vs. HC aPVAT 28.6 cm3, p=0.0071) and greater median AC (26.0 vs HC AC 6.0, p=0.0013) than the healthy control women. Total aPVAT (per 25 cm3) remained significantly associated with SLE after adjusting for CVD risk factors (Odds Ratio 1.74 [95% Confidence Interval: 1.04-2.9], p=0.034), but was attenuated when adjusting for circulating inflammatory markers (p=0.34). In a logistic regression analysis, SLE aPVAT (per 25 cm3) was associated with AC (6.78 [2.0-23], p=0.0019), which remained significant after adjusting for circulating inflammatory markers (p=0.0074), and CAC (2.66 [1.4-5.0], p=0.0028).
Total aPVAT is greater in clinically CVD-free SLE women than in age-/race-matched controls and is associated with calcification in different vascular beds.
atherosclerosis; adipose; systemic lupus erythematosus; calcification
Outcomes of sexual violence care programmes may vary according to the profile of survivors, type of violence suffered, and local context. Analysis of existing sexual violence care services could lead to their better adaptation to the local contexts. We therefore set out to compare the Médecins Sans Frontières sexual violence programmes in the Democratic Republic of Congo (DRC) in a zone of conflict (Masisi, North Kivu) and post-conflict (Niangara, Haut-Uélé).
A retrospective descriptive cohort study, using routine programmatic data from the MSF sexual violence programmes in Masisi and Niangara, DRC, for 2012.
In Masisi, 491 survivors of sexual violence presented for care, compared to 180 in Niangara. Niangara saw predominantly sexual violence perpetrated by civilians who were known to the victim (48%) and directed against children and adolescents (median age 15 (IQR 13–17)), while sexual violence in Masisi was more directed towards adults (median age 26 (IQR 20–35)), and was characterised by marked brutality, with higher levels of gang rape, weapon use, and associated violence; perpetrated by the military (51%). Only 60% of the patients in Masisi and 32% of those in Niangara arrived for a consultation within the critical timeframe of 72 hours, when prophylaxis for HIV and sexually transmitted infections is most effective. Survivors were predominantly referred through community programmes. Treatment at first contact was typically efficient, with high (>95%) coverage rates of prophylaxes. However, follow-up was poor, with only 49% of all patients in Masisi and 61% in Niangara returning for follow-up, and consequently low rates of treatment and/or vaccination completion.
This study has identified a number of weak and strong points in the sexual violence programmes of differing contexts, indicating gaps which need to be addressed, and strengths of both programmes that may contribute to future models of context-specific sexual violence programmes.
To describe non-lymphoma hematological malignancies in SLE.
A large SLE cohort was linked to cancer registries. We examined the types of non-lymphoma hematological cancers.
In 16, 409 patients, 115 hematological cancers (including myelodysplastic syndrome) occurred. Among these, 33 were non-lymphoma. Of the 33 non-lymphoma cases, 13 were of lymphoid lineage: multiple myeloma (N=5), plasmacytoma (N=3), B-cell chronic lymphocytic leukemia, B-CLL (N=3), precursor cell lymphoblastic leukemia (N=1), and unspecified lymphoid leukemia (N=1). The remaining 20 cases were of myeloid lineage: myelodysplastic syndrome, MDS (N=7), acute myeloid leukemia, AML (N=7), chronic myeloid leukemia, CML (N=2), and 4 unspecified leukemias. Most of these malignancies occurred in female Caucasians, except for plasma cell neoplasms (4/5 multiple myeloma and 1/3 plasmacytoma cases occurred in blacks).
In this large SLE cohort, the most common non-lymphoma hematological malignancies were myeloid types (MDS and AML). This contrasts to the general population, where lymphoid types are 1.7 times more common than myeloid non-lymphoma hematological malignancies. Most (80%) multiple myeloma cases occurred in blacks, which requires further investigation.
Systemic lupus erythematosus; malignancy; cancer
Patients with systemic lupus erythematosus (SLE) are at increased risk for cardiovascular (CV) disease. The aim of this study was to investigate the association between subclinical CV disease as measured by carotid intima-media thickness (IMT) and plaque using B-mode carotid ultrasound and incident CV events in a combined cohort of female patients with SLE. This was a prospective, 2-center observational study of 392 adult women with SLE and no previous CV events with a mean 8 years of follow-up. Incident CV events confirmed by clinicians were defined as angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, fatal cardiac arrest, transient ischemic attack, and cerebrovascular accident. Incident hard CV events excluded angina and transient ischemic attack. The mean age was 43.5 years, and most patients were Caucasian (77.3%). During follow-up, 38 patients had incident CV events, and 17 had incident hard CV events. Patients with incident hard CV events had higher mean carotid IMT (0.80 vs 0.64 mm, p <0.01) and presence of carotid plaque (76.5% vs 30.4%, p <0.01) compared with those without incident hard CV events. Baseline carotid IMT and presence of plaque were predictive of any incident hard CV event (hazard ratio 1.35, 95% confidence interval 1.12 to 1.64, and hazard ratio 4.26, 95% confidence interval 1.23 to 14.83, respectively), independent of traditional CV risk factors and medication use. In conclusion, in women with SLE without previous CV events, carotid IMT and plaque are predictive of future CV events. This suggests that carotid ultrasound may provide an additional tool for CV risk stratification in patients with SLE.
To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE).
The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity.
AUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03).
CBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.
Autoimmune Diseases; Systemic Lupus Erythematosus; Autoantibodies
Alcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis.
Pre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies.
Our study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.
Alcohol; 5-mehtyltetrahydrofolate; Neural crest; FASD; Xenopus
Early initiation of antenatal care (ANC) can reduce common maternal complications and maternal and perinatal mortality. Though Rwanda demonstrated a remarkable decline in maternal mortality and 98% of Rwandan women receive antenatal care from a skilled provider, only 38% of women have an ANC visit in their first three months of pregnancy. This study assessed factors associated with delayed ANC in Rwanda.
This is a cross-sectional study using data collected during the 2010 Rwanda DHS from 6,325 women age 15–49 that had at least one birth in the last five years. Factors associated with delayed ANC were identified using a multivariable logistic regression model using manual backward stepwise regression. Analysis was conducted in Stata v12 applying survey commands to account for the complex sample design.
Several factors were significantly associated with delayed ANC including having many children (4–6 children, OR = 1.42, 95% CI: 1.22, 1.65; or more than six children, OR = 1.57, 95% CI: 1.24, 1.99); feeling that distance to health facility is a problem (OR = 1.20, 95% CI: 1.04, 1.38); and unwanted pregnancy (OR = 1.41, 95% CI: 1.26, 1.58). The following were protective against delayed ANC: having an ANC at a private hospital or clinic (OR = 0.29, 95% CI: 0.15, 0.56); being married (OR = 0.85, 95% CI: 0.75, 0.96), and having public mutuelle health insurance (OR = 0.81, 95% CI: 0.71, 0.92) or another type of insurance (OR = 0.33, 95% CI: 0.23, 0.46).
This analysis revealed potential barriers to ANC service utilization. Distance to health facility remains a major constraint which suggests a great need of infrastructure and decentralization of maternal ANC to health posts and dispensaries. Interventions such as universal health insurance coverage, family planning, and community maternal health system are underway and could be part of effective strategies to address delays in ANC.
Antenatal care; Delayed; Demographic survey; Rwanda; Predictors
The lack of high quality timely data for evidence-informed decision making at the district level presents a challenge to improving maternal and newborn survival in low income settings. To address this problem, the EQUIP project (Expanded Quality Management using Information Power) implemented a continuous household and health facility survey for continuous feedback of data in two districts each in Tanzania and Uganda as part of a quality improvement innovation for mothers and newborns.
Within EQUIP, continuous survey data were used for quality improvement (intervention districts) and for effect evaluation (intervention and comparison districts). Over 30 months of intervention (November 2011 to April 2014), EQUIP conducted continuous cross-sectional household and health facility surveys using 24 independent probability samples of household clusters to represent each district each month, and repeat censuses of all government health facilities. Using repeat samples in this way allowed data to be aggregated at six four-monthly intervals to track progress over time for evaluation, and for continuous feedback to quality improvement teams in intervention districts.
In both countries, one continuous survey team of eight people was employed to complete approximately 7,200 household and 200 facility interviews in year one. Data were collected using personal digital assistants. After every four months, routine tabulations of indicators were produced and synthesized to report cards for use by the quality improvement teams.
The first 12 months were implemented as planned. Completion of household interviews was 96% in Tanzania and 91% in Uganda. Indicators across the continuum of care were tabulated every four months, results discussed by quality improvement teams, and report cards generated to support their work.
The EQUIP continuous surveys were feasible to implement as a method to continuously generate and report on demand and supply side indicators for maternal and newborn health; they have potential to be expanded to include other health topics. Documenting the design and implementation of a continuous data collection and feedback mechanism for prospective description, quality improvement, and evaluation in a low-income setting potentially represents a new paradigm that places equal weight on data systems for course correction, as well as evaluation.
Electronic supplementary material
The online version of this article (doi:10.1186/s13012-014-0112-1) contains supplementary material, which is available to authorized users.
Continuous survey; Quality improvement; Maternal and newborn health; Tanzania; Uganda
Low birthweight babies need extra care, and families need to know whether their newborn is low birthweight in settings where many births are at home and weighing scales are largely absent. In the context of a trial to improve newborn health in southern Tanzania, a counselling card was developed that incorporated a newborn foot length measurement tool to screen newborns for low birth weight and prematurity. This was used by community volunteers at home visits and shows a scale picture of a newborn foot with markers for a ‘short foot’ (<8 cm). The tool built on previous hospital based research that found newborn foot length <8 cm to have sensitivity and specificity to identify low birthweight (<2500 g) of 87% and 60% respectively.
Reliability of the tool used by community volunteers to identify newborns with short feet was tested. Between July-December 2010 a researcher accompanied volunteers to the homes of babies younger than seven days and conducted paired measures of newborn foot length using the counselling card tool and using a plastic ruler. Intra-method reliability of foot length measures was assessed using kappa scores, and differences between measurers were analysed using Bland and Altman plots.
142 paired measures were conducted. The kappa statistic for the foot length tool to classify newborns as having small feet indicated that it was moderately reliable when applied by volunteers, with a kappa score of 0.53 (95% confidence interval 0.40 – 0.66) . Examination of differences revealed that community volunteers systematically underestimated the length of newborn feet compared to the researcher (mean difference −0.26 cm (95% confidence interval −0.31—0.22), thus overestimating the number of newborns needing extra care.
The newborn foot length tool used by community volunteers to identify small babies born at home was moderately reliable in southern Tanzania where a large number of births occur at home and scales are not available. Newborn foot length is not the best anthropometric proxy for birthweight but was simple to implement at home in the first days of life when the risk of newborn death is highest.
In Sub-Saharan Africa over one million newborns die annually. We developed a sustainable and scalable home-based counselling intervention for delivery by community volunteers in rural southern Tanzania to improve newborn care practices and survival. Here we report the effect on newborn care practices one year after full implementation.
All 132 wards in the 6-district study area were randomised to intervention or comparison groups. Starting in 2010, in intervention areas trained volunteers made home visits during pregnancy and after childbirth to promote recommended newborn care practices including hygiene, breastfeeding and identification and extra care for low birth weight babies. In 2011, in a representative sample of 5,240 households, we asked women who had given birth in the previous year both about counselling visits and their childbirth and newborn care practices.
Four of 14 newborn care practices were more commonly reported in intervention than comparison areas: delaying the baby’s first bath by at least six hours (81% versus 68%, OR 2.0 (95% CI 1.2-3.4)), exclusive breastfeeding in the three days after birth (83% versus 71%, OR 1.9 (95% CI 1.3-2.9)), putting nothing on the cord (87% versus 70%, OR 2.8 (95% CI 1.7-4.6)), and, for home births, tying the cord with a clean thread (69% versus 39%, OR 3.4 (95% CI 1.5-7.5)). For other behaviours there was little evidence of differences in reported practices between intervention and comparison areas including childbirth in a health facility or with a skilled attendant, thermal care practices, breastfeeding within an hour of birth and, for home births, the birth attendant having clean hands, cutting the cord with a clean blade and birth preparedness activities.
A home-based counselling strategy using volunteers and designed for scale-up can improve newborn care behaviours in rural communities of southern Tanzania. Further research is needed to evaluate if, and at what cost, these gains will lead to improved newborn survival.
Trial Registration Number NCT01022788 (http://www.clinicaltrials.gov, 2009)
Newborn; Delivery of health care; Community health workers; Tanzania; Evaluation studies
There is controversy in medical literature regarding the use of electromagnetic fields to promote bone healing.
After designing and building devices capable of generating an electromagnetic field for this study, their safety was confirmed and the electromagnetic therapy was randomly allocated and compared to placebo in patients with fracture of the femoral diaphysis. Treatment began six weeks after the fracture and it was administered once a day, during 1 h, for eight consecutive weeks. Twenty device were built, 10 of which were placebo-devices. Between June 2008 and October 2009, 64 patients were randomized in two different hospitals and were followed for 24 weeks. The mean age was 30 years (18-59) and 81% were males.
Healing observed at week 12 was 75% vs. 58% (p =0.1); at week 18 it was 94% vs. 80% (p= 0.15); and at week 24 it was 94% vs. 87% (p= 0.43) for the device group and the placebo group, respectively.
This study suggests that an electromagnetic field stimulus can promote earlier bone healing compared to placebo in femoral diaphyseal fractures. Faster bone healing translates into sooner weight bearing, which -in turn- permits quicker return to normal daily activities.
Femur fracture; non-union; electromagnetic stimuli; bone healing
Despite evidence supporting Integrated Management of Childhood Illness (IMCI) as a strategy to improve pediatric care in countries with high child mortality, its implementation faces challenges related to lack of or poor post-didactic training supervision and gaps in necessary supporting systems. These constraints lead to health care workers’ inability to consistently translate IMCI knowledge and skills into practice. A program providing mentoring and enhanced supervision at health centers (MESH), focusing on clinical and systems improvement was implemented in rural Rwanda as a strategy to address these issues, with the ultimate goal of improving the quality of pediatric care at rural health centers. We explored perceptions of MESH from the perspective of IMCI clinical mentors, mentees, and district clinical leadership.
We conducted focus group discussions with 40 health care workers from 21 MESH-supported health centers. Two FGDs in each district were carried out, including one for nurses and one for director of health centers. District medical directors and clinical mentors had individual in-depth interviews. We performed a hermeneutic analysis using Atlas.ti v5.2.
Study participants highlighted program components in five key areas that contributed to acceptability and impact, including: 1) Interactive, collaborative capacity-building, 2) active listening and relationships, 3) supporting not policing, 4) systems improvement, and 5) real-time feedback. Staff turn-over, stock-outs, and other facility/systems gaps were identified as barriers to MESH and IMCI implementation.
Health care workers reported high acceptance and positive perceptions of the MESH model as an effective strategy to build their capacity, bridge the gap between knowledge and practice in pediatric care, and address facility and systems issues. This approach also improved relationships between the district supervisory team and health center-based care providers. Despite some challenges, many perceived a strong benefit on clinical performance and outcomes. This study can inform program implementers and policy makers of key components needed for developing similar health facility-based mentorship interventions and potential barriers and resistance which can be proactively addressed to ensure success.
Clinical mentorship; Quality improvement; Pediatrics; Health centers; Perceptions; Acceptability; IMCI; Rwanda
To assess the impact on stent implantation rate and mid-term outcomes of prolonged high pressure angioplasty of femoropopliteal lesions.
We retrospectively enrolled 620 consecutive patients from January 2011 to December 2011 (75.6 ± 12.3 years, 355 males, 76.5% in Rutherford class 5–6), referred for critical limb ischemia and submitted to prolonged high-pressure angioplasty of femoropopliteal lesions. The definition of prolonged high-pressure angioplasty includes dilation to at least 18 atm for at least 120 s. Procedural data, and clinical and instrumental follow-up were analyzed to assess stent implantation rate and mid-term outcomes.
The preferred approach was ipsilateral femoral antegrade in 433/620 patients (69.7%) and contralateral cross-over in 164/620 (26.4%) and popliteal retrograde + femoral antegrade in 23/620 (3.7%). Techniques included subintimal angioplasty in 427/620 patients (68.8%) and endoluminal angioplasty in 193/620 patients (31.2%). The prolonged high pressure balloon angioplasty procedure was successful in 86.2% (minor intra-procedural complications rate 15.7 %), stent implantation was performed in 74 patients (11.9%), with a significant improvement of ankle-brachial index (0.29 ± 0.6 vs. 0.88 ± 0.3, P < 00.1) and Rutherford class (5.3 ± 0.8 vs. 0.7 ± 1.9, P < 0.01), a primary patency rate of 86.7%, restenosis of 18.6 % on Doppler ultrasound and a target lesion revascularization of 14.8% at a mean follow-up of 18.1 ± 6.4 months (range 1–24 months). Secondary patency rate was 87.7%.
Prolonged high pressure angioplasty of femoropopliteal lesions appears to be safe and effective allowing for an acceptable patency and restenosis rates on mid-term.
Peripheral artery disease; Angioplasty; Balloon; Stent
Few conventional cytotoxic anticancer therapeutics induce immunogenic cell death (ICD). This means that they induce tumor cells to undergo apoptosis while eliciting the emission of a spatiotemporal-defined combination of damage-associated molecular patterns (DAMPs) decoded by the immune system to activate antitumor immunity effective for long-term therapeutic success. The neurotoxin capsaicin (CPS) can induce both cancer cell apoptosis and immune-mediated tumor regression. In the present study, we investigated whether CPS is capable of eliciting the emission of ICD hallmarks in human bladder cancer cell lines undergoing apoptosis. We demonstrated that CPS induces pre- and early apoptotic cell surface exposure of calreticulin (CRT), HSP90, and HSP70 as well as ATP release. Moreover, CRT exposure was prevented by inhibition of endoplasmic reticulum–Golgi traffic by brefeldin A. Furthermore, high-mobility group box 1, HSP90, and HSP70 were passively released at late apoptotic stages. We provide the first evidence that CPS is an inducer of ICD hallmarks, suggesting CPS as a novel potential immunogenic cytotoxic agent.
Capsaicin; Immunogenic cell death; Calreticulin; Heat shock proteins; Adenosine triphosphate; High-mobility group box 1
To update estimates of cancer risk in SLE relative to the general population.
A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers.
Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin’s lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61–0.88), endometrial (SIR 0.44, 95% CI 0.23–0.77), and possibly ovarian cancers (0.64, 95% CI 0.34–1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23).
These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
Systemic Lupus Erythematosus; Epidemiology; Treatment; Disease Activity
Maternal and newborn mortality remain unacceptably high in sub-Saharan Africa. Tanzania and Uganda are committed to reduce maternal and newborn mortality, but progress has been limited and many essential interventions are unavailable in primary and referral facilities. Quality management has the potential to overcome low implementation levels by assisting teams of health workers and others finding local solutions to problems in delivering quality care and the underutilization of health services by the community. Existing evidence of the effect of quality management on health worker performance in these contexts has important limitations, and the feasibility of expanding quality management to the community level is unknown. We aim to assess quality management at the district, facility, and community levels, supported by information from high-quality, continuous surveys, and report effects of the quality management intervention on the utilization and quality of services in Tanzania and Uganda.
In Uganda and Tanzania, the Expanded Quality Management Using Information Power (EQUIP) intervention is implemented in one intervention district and evaluated using a plausibility design with one non-randomly selected comparison district. The quality management approach is based on the collaborative model for improvement, in which groups of quality improvement teams test new implementation strategies (change ideas) and periodically meet to share results and identify the best strategies. The teams use locally-generated community and health facility data to monitor improvements. In addition, data from continuous health facility and household surveys are used to guide prioritization and decision making by quality improvement teams as well as for evaluation of the intervention. These data include input, process, output, coverage, implementation practice, and client satisfaction indicators in both intervention and comparison districts. Thus, intervention districts receive quality management and continuous surveys, and comparison districts-only continuous surveys.
EQUIP is a district-scale, proof-of-concept study that evaluates a quality management approach for maternal and newborn health including communities, health facilities, and district health managers, supported by high-quality data from independent continuous household and health facility surveys. The study will generate robust evidence about the effectiveness of quality management and will inform future nationwide implementation approaches for health system strengthening in low-resource settings.
Quality management; Quality improvement; Maternal and child health; Health system strengthening; Community empowerment; Tanzania; Uganda
Previous work has demonstrated that northern and southern European ancestries are associated with specific systemic lupus erythematosus (SLE) manifestations. Here, 1855 SLE cases of European descent were genotyped for 4965 single nucleotide polymorphisms and principal components analysis of genotype information was used to define population substructure. The first principal component (PC1) distinguished northern from southern European ancestry, PC2 differentiated eastern from western European ancestry, and PC3 delineated Ashkenazi Jewish ancestry. Compared to northern European ancestry, southern European ancestry was associated with autoantibody production (OR=1.40, 95% CI 1.07-1.83) and renal involvement (OR 1.41, 95% CI 1.06-1.87), and was protective for discoid rash (OR=0.51, 95% CI 0.32-0.82) and photosensitivity (OR=0.74, 95% CI 0.56-0.97). Both serositis (OR=1.46, 95% CI 1.12-1.89) and autoantibody production (OR=1.38, 95% CI 1.06-1.80) were associated with Western compared to Eastern European ancestry. Ashkenazi Jewish ancestry was protective against neurologic manifestations of SLE (OR=0.62, 95% CI 0.40-0.94). Homogeneous clusters of cases defined by multiple PCs demonstrated stronger phenotypic associations. Genetic ancestry may contribute to the development of SLE endophenotypes and should be accounted for in genetic studies of disease characteristics.
Systemic lupus erythematosus; epidemiology; population substructure; genetics