Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related neuropathological conditions.

HIV in the central nervous system (CNS) mainly infects microglial cells which are known to express toll-like receptors (TLRs). This paper aimed to study the role of soluble TLR2 (sTLR2), sTLR4, and other inflammatory markers in cerebrospinal fluid (CSF) in HIV/Simian immunodeficiency virus (SIV)-related neurological sequelae. We determined sTLR2 and sTLR4 levels in CSF and serum/plasma of SIV-infected rhesus macaques with and without neurological sequelae, as well as in HIV-infected patients with and without cognitive impairments and Alzheimer's disease (AD) patients and matched controls. CSF cytokines and chemokines levels were analyzed in macaques as markers of neuroinflammation, while neopterin and S100B CSF concentrations were measured in HIV-infected patients as microglial and astrocyte marker, respectively. We found detectable levels of sTLR2 and sTLR4 in CSF of macaques and humans. Furthermore, CSF sTLR2 and sTLR4 concentrations were higher in SIV-infected macaques with neurological sequelae compared to those without neurological complications (p = 0.0003 and p = 0.0006, respectively). CSF IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels were elevated in macaques with neurological sequelae, and a positive correlation was found between CSF levels of sTLR2/4 and IL-8 and MCP-1. Also in humans, elevated CSF sTLR4 levels were found in HIV-infected patients with cognitive impairments compared to HIV-infected patients with normal cognition (p = 0.019). Unlike CSF S100B levels, neopterin correlated positively with sTLR2 and sTLR4. No difference was found in plasma and CSF sTLR2 and sTLR4 levels between AD patients and control subjects (p = 0.26). In conclusion, CSF sTLR2 and sTLR4 may play a role in HIV/SIV-related neuroinflammation and subsequent neuropathology.

Influence of cut-off value on prevalence of short cervical length.

OBJECTIVE: To assess the distribution of cervical length (CL) in a large cohort of asymptomatic low-risk women with singleton pregnancy and no previous preterm birth and to explain the low prevalence of short CL ≤ 30 mm in this cohort. METHODS: This was a secondary analysis of a multicenter cohort study with an embedded randomized controlled trial (Triple P trial; NTR-2078) on the prevention of preterm birth with progesterone. In the cohort study, CL was measured in asymptomatic low-risk women with singleton pregnancy to investigate its predictive capacity to identify those at increased risk for preterm birth. A short CL was defined by a cut-off value of ≤ 30 mm, based on existing literature. Women with a short CL were subsequently included in a randomized controlled trial evaluating the effect of progesterone, compared with placebo, on preterm birth. In total, 57 centers and 20 234 women participated in the study. Normal distributions for CL were simulated based on the mean and SD of the original data. The distribution of CL was assessed for each individual center and measurements were compared between levels of care: primary (29 ultrasound centers), secondary (21 general hospitals) and tertiary (seven university medical centers) care institutions. Comparison was also performed between centers with low, intermediate and high volume of CL measurements. CL distributions before (n = 12 284 women) and after (n = 7950 women) a national symposium, at which the prevalence of short CL measurements was addressed publicly, were analyzed. RESULTS: Between November 2009 and August 2013, 20 234 women had CL measurements, of whom 367 (1.8%) had a short CL. Mean ± SD CL was 44.2 ± 7.8 mm. A 'dip' in the distribution of CL measurements between 20 and 30 mm was observed, defined by a ratio of < 50% when comparing the number of measurements in observed and simulated normal distributions. The dip was present in 89% of participating centers. All centers showed a dip in the distribution of measurements ≤ 30 mm when analyzed according to the level of care and volume of measurements. A significant difference was found when comparing the distribution before and after publicly addressing the low prevalence of short CL (1.7% vs 2.0% of measurements were ≤ 30 mm, respectively; P < 0.001). CONCLUSIONS: A cut-off value of 30 mm for CL was used to include women in a randomized clinical trial that was embedded in a cohort study. We suggest that the use of a predefined cut-off value for a short cervix influences the distribution of the CL measurements. Since the measurement is not blinded, preference of assessors for the control or intervention arms may have introduced selection bias. This might have resulted in fewer measurements around the cut-off value. Other trials using similar designs could benefit from this observation and take precautions to avoid selection bias. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Midpregnancy Cervical Length in Nulliparous Women and its Association with Postterm Delivery and Intrapartum Cesarean Delivery.

OBJECTIVE: To evaluate the association between midpregnancy cervical length and postterm delivery and cesarean delivery during labor. STUDY DESIGN: In a multicenter cohort study, cervical length was measured in low-risk singleton pregnancies between 16 and 22 weeks of gestation. From this cohort, we identified nulliparous women who delivered beyond 34 weeks and calculated cervical length quartiles. We performed logistic regression to compare the risk of postterm delivery and intrapartum cesarean delivery to cervical length quartiles, using the lowest quartile as a reference. We adjusted for induction of labor, maternal age, ethnicity, cephalic position, preexisting hypertension, and gestational age at delivery. RESULTS: We studied 5,321 nulliparous women. Women with cervical length in the 3rd and 4th quartile were more likely to deliver at 42(+0) to 42(+6) weeks (adjusted odds ratio [aOR] 2.02, 95% confidence interval [CI] 1.07-3.79 and aOR 1.97, 95% CI 1.06-3.67, respectively). The frequency of intrapartum cesarean delivery increased with cervical length quartile from 9.4% in the 1st to 14.9% in the 4th quartile (p = 0.01). This increase was only present in intrapartum cesarean delivery because of failure to progress and not because of fetal distress. CONCLUSION: The longer the cervix at midtrimester the higher the risk of both postterm delivery and intrapartum cesarean delivery.

Effect of e-learning on quality of cervical-length measurements.

OBJECTIVES: To assess the effect of implementation of a newly developed e-learning module on the quality of cervical-length measurements. METHODS: With the introduction of cervical-length (CL) measurement in a research setting, a CL measurement e-learning module (CLEM) was developed with the purpose to enhance the knowledge and skills of experienced ultrasonographers. CLEM was designed specifically for ultrasonographers who perform ultrasound in a general obstetrical practice but who do not regularly perform CL measurements. CLEM consists of five theoretical questions and three caliper-placement tests to learn the CL measurement technique. The quality of the CL measurements of CLEM participants was compared with images of non-participants using a CL measurement image score (CIS), defined as the sum of six items which assess the quality of the image. Each CLEM participant submitted five CL images and the images of non-CLEM participants were selected randomly from an ultrasound database. RESULTS: The CIS of the CLEM participants (n = 61) were significantly higher than those of non-CLEM participants (n = 23) (164.9 vs 155.6, respectively; P = 0.03). Visualization of the internal os and positioning of the calipers on the internal and external ora were found to have significantly higher CIS among the CLEM participants than among the non-CLEM participants (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: Introducing CLEM may improve the quality of CL measurements obtained by trained and untrained sonographers.

Vitamin D status is not associated with inflammatory cytokine levels during experimental human endotoxaemia.

Vitamin D has been shown to modulate innate immune responses in vitro and ex vivo; however, human in-vivo data are lacking. At high latitudes, seasonal vitamin D deficiency is common due to alternating ultraviolet (UV)-B radiation exposure. In the present study, we investigated whether levels of 25 hydroxyvitamin D(3) [25(OH)D(3) ] and its active metabolite 1,25 dihydroxyvitamin D(3) [1,25(OH)(2) D(3) ] are subject to seasonal variation and whether plasma levels of these vitamin D metabolites correlate with the in-vivo cytokine response during experimental human endotoxaemia [administration of lipopolysaccharide (LPS) in healthy volunteers]. Plasma levels of 25(OH)D(3) and 1,25(OH)(2) D(3) were determined in samples obtained just prior to administration of an intravenous bolus of 2 ng/kg LPS (derived from Escherichia coli O:113) in 112 healthy male volunteers. In the same subjects, plasma levels of the inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were analysed serially after endotoxin administration. Plasma levels of 1,25(OH)(2) D(3) , but not 25(OH)D(3) , were subject to significant seasonal variation, with lower levels in autumn and winter. 25(OH)D(3) and 1,25(OH)(2) D(3) levels did not correlate with plasma cytokine responses. Furthermore, 25(OH)D(3) deficient subjects (< 50 nmol/l) displayed an identical cytokine response compared with sufficient subjects. In conclusion, plasma levels of vitamin D are not correlated with the LPS-induced TNF, IL-6 and IL-10 cytokine response in humans in vivo. These findings question the direct role of vitamin D in modulation of the innate immune response.

Pharmacokinetics of the combination raltegravir/atazanavir in HIV-1-infected patients.

OBJECTIVES: To evaluate the use of raltegravir with unboosted atazanavir in combination with one nucleoside reverse transcriptase inhibitor (NRTI) (lamivudine or emtricitabine) as a potentially well-tolerated once-daily (qd) maintenance regimen. METHODS: We compared the pharmacokinetics of raltegravir 400 mg twice daily (bid) with raltegravir 800 mg qd in HIV-infected patients (n=17) on unboosted atazanavir (600 mg qd) in combination with lamivudine or emtricitabine. RESULTS: The area under the plasma concentration vs. time curve for a dose interval t (AUC0 -t ) of 800 mg qd divided by 2 was not significantly different from the AUC0 -t of 400 mg bid (P=0.664) but the minimum concentration (C min ) was 72% lower with the qd regimen (P=0.002). The regimen was well tolerated and the viral load remained undetectable in all patients during the 6 weeks of the study follow-up. CONCLUSIONS: A qd regimen of raltegravir 800 mg, atazanavir 600 mg and lamivudine or emtricitabine resulted in favourable pharmacokinetic profiles and good short-term safety and efficacy data. Larger phase IIb studies are needed to explore this novel regimen.

Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals.

The immune modulating capacity of vitamin D(3) is well-recognized. Ultra-violet (UV) exposure determines production of vitamin D(3) in vivo and varies through the course of the year, especially in temperate regions. However, it is not known whether the human innate immune response differs due to seasonality. To validate the seasonal effects of vitamin D(3) , the effect of 1,25(OH)(2) D(3) on peripheral blood mononuclear cells (PBMC) cytokine response was first determined in vitro. 1,25(OH)(2) D(3) decreased interleukin (IL)-6 and tumour necrosis factor (TNF)-α release by PBMC stimulated with tripalmitoyl-S-glycerylcysteine (Pam3Cys) or lipopolysaccharide (LPS). Subsequently, ex-vivo stimulation studies were performed in 15 healthy volunteers through the course of the four seasons of the year. PBMC were isolated and stimulated with Toll-like receptor (TLR)-2 and TLR-4 ligands Pam3Cys and LPS, respectively. Circulating concentrations of 25(OH)D(3) and 1,25(OH)(2) D(3) were higher during summer (P<0·05) and a down-regulation of TLR-4-mediated IL-1ß, IL-6, TNF-α, interferon (IFN)-γ and IL-10 production in summer was observed compared to winter (P<0·05). The variation in cytokine response upon TLR-2 (Pam3Cys) stimulation was moderate throughout the four seasons. The repressed cytokine production during the summer months could be explained partly by the reduced cell-membrane expression of TLRs. Physiological variation in vitamin D(3) status through the four seasons of the year can lead to alteration in the innate immune responses. Elevated vitamin D(3) level in vivo is associated with down-regulation of cytokine response through diminished surface expression of pattern recognition receptors.

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa.

OBJECTIVES: Areas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. METHODS: In a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. RESULTS: A total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. CONCLUSIONS: Viral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.

Perinatal exposure of rats to the HIV drug efavirenz affects medial prefrontal cortex cytoarchitecture.

Efavirenz (EFV) is used for antiretroviral treatment of HIV infection, and successfully inhibits viral replication and mother-to-child transmission of HIV during pregnancy and childbirth. Unfortunately, the drug induces neuropsychiatric symptoms such as anxiety and depressed mood and potentially affects cognitive performance. EFV acts on, among others, the serotonin transporter and serotonin receptors that are expressed in the developing brain. Yet, how perinatal EFV exposure affects brain cytoarchitecture remains unclear. Here, we exposed pregnant and lactating rats to EFV, and examined in the medial prefrontal cortex (mPFC) of their adult offspring the effects of the maternal EFV exposure on cortical architecture. We observed a significant decrease in the number of cells, mainly mature neurons, in the infra/prelimbic and cingulate cortices of adult offspring. Next, we found an altered cortical cytoarchitecture characterized by a significant reduction in deep- and superficial-layer cells. This was accompanied by a sharp increase in programmed cell death, as we identified a significantly higher number of cleaved Caspase-3-positive cells. Finally, the serotonergic and dopaminergic innervation of the mPFC subdomains was increased. Thus, the perinatal exposure to EFV provoked in the mPFC of adult offspring cell death, significant changes in cytoarchitecture, and disturbances in serotonergic and dopaminergic innervation. Our results are important in the light of EFV treatment of HIV-positive pregnant women, and its effect on brain development and cognitive behavior.

Skin disorders in HIV-infected patients from West Java.

AIM: to describe the spectrum of HIV-related skin disorders as well as their prevalence and relation to CD4-cell counts among HIV-seropositive patients from West Java, Indonesia. METHODS: all HIV-positive patients presenting in 2008 at the HIV-clinic, Hasan Sadikin Hospital, were included in a cross-sectional study. Patients who had a skin complaint were examined by a dermatologist. Skin diseases were classified based on ICD 10. RESULTS: among 843 patients, 121 (14.4%) had a skin complaint, consisting of skin manifestations (73.3%), drug eruptions (30.5%), and sexually transmitted infections (15.7%), some of them had more than one diseases. The most common skin manifestations were drug eruptions, pruritic papular eruptions, seborrhoeic dermatitis, herpes zoster, dermatophytosis, and bacterial skin infections. Among patients who started nevirapine, 6.4% (95%CI: 3.9% - 8.9%) developed any kind of drug eruption, and 1.4% (95%CI 0.2%-2.6%) developed a severe drug eruption. No cases of Kaposi sarcoma, penicilliosis, eosinophilic folliculitis were seen, however one case of histoplasmosis was diagnosed. CONCLUSION: this is the first report describing the prevalence and characteristic of skin manifestation in HIV-positive in Indonesia. Indonesian physicians should be alert about HIV when patient presents with certain skin manifestations. The rate of severe drug eruptions following treatment with nevirapine is a cause of concern that needs further study.

Prevention and treatment of HIV addicted patients: a biopsychosocial approach.

Injecting drug use is the main route of HIV transmission in many parts of Indonesia. Efforts to prevent HIV-transmission through injecting drug use mostly focus on subjects who actively inject. In scientific publications, the term 'injecting drug users' tends to be used without a clear definition and without specifying the pattern of drug use as current or former drug use, frequency, duration, type of injected drug(s) or context (e.g. imprisonment). Actually, injecting drug users (IDUs) have different drug use patterns, risk behavior, somatic co-morbidity, psychiatric co-morbidity, and psychosocial problems. In fact, these patients are suffering from addiction as a chronic brain disease in co-occurrence with somatic and psychiatric disorder and many social problems. Failing in addressing the problems comprehensively will lead to the failure of drug treatment. This is why addiction can be best studied and treated from a biopsychosocial perspective. Accordingly, treatment goals can be differentiated in crisis intervention, cure or recovery (detoxification, relapse prevention), and care or partial remission (stabilization and harm reduction). In summary, injecting drug use in Indonesia is not a single entity and patient oriented prevention and care for IDUs, especially focusing on their addiction, should be addressed to prevent the transmission of HIV/AIDS.

The effect of cholecalciferol supplementation on vitamin D levels and insulin sensitivity is dose related in vitamin D-deficient HIV-1-infected patients.

OBJECTIVE: The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, bone mineral density (BMD), body fat distribution and insulin sensitivity in vitamin D-deficient HIV-1-infected patients. METHODS: Twenty vitamin D-deficient HIV-1-infected patients were prospectively treated with 2000 IU cholecalciferol/day for 14 weeks, whereafter treatment was continued with half this dosage until 48 weeks. BMD, body fat distribution, 1,25-dihydroxy vitamin D(3) (1,25(OH)2D3), fasting glucose, insulin, adiponectin, leptin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were measured at baseline, and at 24 and 48 weeks. Parathyroid hormone (PTH), 25-hydroxy vitamin D(3) [25(OH)D(3)], cholesterol and triglycerides were measured at baseline, and at 12, 24 and 48 weeks. RESULTS: After 24 weeks, cholecalciferol supplementation significantly increased 25(OH)D3 and 1,25(OH)2D3 levels and decreased PTH and insulin sensitivity. After 48 weeks, however, only 25(OH)D3 levels remained significantly different from baseline, while the other parameter levels returned to baseline, suggesting a dose-response effect. Cholecalciferol had no effect on BMD, adipokines and triglycerides. CONCLUSIONS: The effect of cholecalciferol treatment in this cohort appears to be dose dependent. Cholecalciferol dosages of > or =2000 IU are necessary to achieve 1,25(OH)2D3 levels that significantly decrease PTH, but also negatively affect insulin sensitivity. The results of this hypothesis-driven explorative study need to be confirmed in larger clinical trials.

A decrease of plasma macrophage migration inhibitory factor concentration is associated with lower numbers of circulating lymphocytes in experimental Plasmodium falciparum malaria.

Macrophage migration inhibitory factor (MIF) has recently been implicated in the pathogenesis of malarial anaemia. However, field studies have reported contradictory results on circulating MIF concentrations in patients with clinically overt Plasmodium falciparum malaria. We determined plasma MIF levels over time in 10 healthy volunteers during experimental P. falciparum infection. Under fully controlled conditions, MIF levels decreased significantly during early blood-stage infection and reached a nadir at day 8 post-infection. A decrease in the number of circulating lymphocytes, which are an important source of MIF production, paralleled the decrease in MIF levels. Monocyte/macrophage counts remained unchanged. At MIF nadir, the anti-inflammatory cytokine interleukin (IL)-10, which is an inhibitor of T-cell MIF production, was detectable in only 2 of 10 volunteers. Plasma concentrations of the pro-inflammatory cytokines IL-8 and IL-1beta were only marginally elevated. We conclude that circulating MIF levels decrease early in blood-stage malaria as a result of the decline in circulating lymphocytes.

[Less ventilator-associated pneumonia after oral decontamination with chlorhexidine; a randomised trial]. / Minder beademingspneumonieën door orale decontaminatie met chloorhexidine; gerandomiseerde trial.

OBJECTIVE: To determine the effect of oral decontamination with either chlorhexidine (CHX, 2%) or the combination chlorhexidine-colistin (CHX-COL, 2%-2%) on the frequency and the time to onset of ventilator-associated pneumonia in Intensive Care patients. DESIGN: Double blind, placebo-controlled, multicentre, randomised trial. METHODS: Consecutive ICU patients needing at least 48 h of mechanical ventilation were enrolled in a randomized trial with 3 arms: CHX, CHX-COL, and placebo (PLAC). The trial medication was administered in the oral cavity every 6 h. Oropharyngeal swabs were obtained daily and analysed quantitatively for Gram-positive and Gram-negative microorganisms. Endotracheal colonisation was monitored twice weekly. Ventilator-associated pneumonia was diagnosed on the basis of a combination of clinical, radiological and microbiological criteria. RESULTS: Of 385 patients included, 130 received PLAC, 127 CHX and 128 CHX-COL. Baseline characteristics in the three groups were comparable. The daily risk of ventilator-associated pneumonia was reduced in both treatment groups compared to PLAC: 65% (HR= 0.352; 95% CI: 0.160-0.791; p = 0.012) for CHX and 55% (HR= 0.454; 95%/ CI: 0.224-0.925; p = 0.030) for CHX-COL. CHX-COL provided a significant reduction in oropharyngeal colonisation with both Gram-negative and Gram-positive microorganisms, whereas CHX significantly affected only colonisation with Gram-positive microorganisms. There were no differences in the duration of mechanical ventilation, ICU-stay or ICU-survival. CONCLUSION: Oral decontamination of the oropharyngeal cavity with chlorhexidine or the combination chlorhexidine-colistin reduced the incidence and the time to onset ofventilator-associated pneumonia.

The Asp299Gly Toll-like receptor 4 polymorphism in advanced aortic atherosclerosis.

BACKGROUND: Recently, the common Asp299Gly polymorphism of the Toll-like receptor 4 (TLR-4) was found to be associated with a reduced incidence of acute myocardial infarction and carotid atherosclerosis. As TLR-4 signalling is causally involved in atherogenesis, the polymorphism was postulated to impart protection from atherosclerosis. To explore a potential atheroprotective effect, we studied the association between the Asp299Gly polymorphism and atherosclerosis in hypertensive patients undergoing angiography for suspected renovascular disease. METHODS: 140 hypertensive subjects underwent intraarterial digital subtraction angiography, during which the presence of atherosclerotic lesions was assessed at the level of the abdominal aorta and renal arteries. Extensiveness of disease was classified as follows: atherosclerosis confined to the abdominal aorta, unilateral renal artery stenosis or bilateral renal artery stenosis. Subsequently, genotyping for the +896 A>G (Asp299Gly) single nucleotide polymorphism was performed in all patients. In statistical analyses 17 patients were excluded because of incomplete data (n=3) or a diagnosis of fibromuscular disease (n=14). RESULTS: 21 patients were found heterozygous for the 299Gly allele, whereas none of the subjects were 299Gly homozygous (299Gly allele frequency 7.8%). The prevalence of the 299Gly allele in atherosclerotic patients was not different from the prevalence observed in subjects without atherosclerotic lesions (16.9 vs 15.5%, p=0.83). Moreover, 299Gly carriership was not associated with the extensiveness of (advanced) aortic atherosclerosis (p=0.64). CONCLUSION: Our results suggest that the Asp299Gly TLR-4 receptor polymorphism is not associated with the prevalence nor extensiveness of (advanced) aortic atherosclerosis.

Aetiology and presentation of HIV/AIDS-associated pulmonary infections in patients presenting for bronchoscopy at a referral hospital in northern Tanzania.

OBJECTIVES: To determine the aetiological agents of pulmonary infections in HIV-infected Tanzanians and to correlate the causative agents with clinical, radiographic features, and mortality. DESIGN: A prospective study. SETTING: Kilimanjaro Christian Medical Centre (KCMC), Tanzania. SUBJECTS: Bronchoalveolar lavage fluid (BAL) were obtained from 120 HIV infected patients with pulmonary infections. BAL for causative agents was analysed and correlated with clinical and radiographic features, and one-month outcome. RESULTS: Causative agents were identified in 71 (59.2%) patients and in 16 of these patients, multiple agents were found. Common bacteria were identified in 35 (29.2%) patients, Mycobacterium tuberculosis in 28 (23.3%), Human Herpes Virus 8 (HHV8) in 12 (10%), Pneumocystis jiroveci in nine (7.5%) and fungi in five (4.2%) patients. Median CD4 T cell count of the patients with identified causes was 47 cells/microl (IQR 14-91) and in the 49 patients with undetermined aetiology was 100 cells/ microl (IQR 36-188; p = 0.01). Micronodular chest radiographic lesions were associated with presence of M. tuberculosis (p = 0.002). The one-month mortality was 20 (16.7%). The highest mortality was associated with HHV8 (41.7%) and M. tuberculosis (32.1%). Mortality in patients with undetermined aetiology was 11.3%. No death occurred in patients with PCP. CONCLUSION: In this population of severely immunosuppressed HIV-infected patients with pulmonary infection a variety of causative agents was identified. Micronodular radiographic lesions were indicative of TB. High mortality was associated with M. tuberculosis or HHV8. No death occurred in patients with P. jiroveci infection.

[Splenomegaly in an Eritrean refugee: the hyper-reactive malaria splenomegaly syndrome.] / Splenomegalie bij een Eritrese vluchteling.

BACKGROUND: Hyper-reactive malaria splenomegaly (HMS) is a rare and potentially severe complication of malaria. It is likely that the incidence of patients with HMS will rise in the Netherlands due to the recent increase in asylum-seekers from Sub-Saharan Africa. It can be difficult to diagnose this disease, as this case shows. CASE DESCRIPTION: A 31-year-old male from Eritrea was admitted with fever and dyspnea, caused by an influenza A-infection. The patient also presented with cachexia, pronounced hepatosplenomegaly and pancytopenia. Microscopic diagnostic analysis for malaria was negative. HMS was eventually diagnosed through high-sensitivity qPCR for malaria, which showed the presence of a very low level of Plasmodium falciparum parasitemia; furthermore, IgM levels were high and malaria serology was strongly positive. CONCLUSION: HMS should be considered in patients from malaria-endemic areas presenting with splenomegaly and pancytopenia. Because standard diagnostics for malaria are often negative in this population, malaria serology and sensitive qPCR play an important diagnostic role.

C-reactive protein, atherosclerosis and kidney function in hypertensive patients.

Previous studies have shown a relationship between coronary or carotid atherosclerosis and C-reactive protein (CRP) concentrations. In the present investigation, we evaluated the relationship between high-sensitivity CRP (hsCRP) concentrations and the presence of atherosclerotic lesions in the renal arteries and/or abdominal aorta. In 95 hypertensive patients who underwent intra-arterial DSA on suspicion of renovascular disease, blood was sampled during the procedure for measurement of hsCRP. The presence of atherosclerotic lesions was assessed at the level of the renal arteries and the abdominal aorta. Haemodynamically significant renal artery stenosis was diagnosed when 50% or more stenosis was observed. Patients with fibromuscular disease (n = 8) or incomplete data (n = 4) were excluded from analysis. The results revealed that the median hsCRP concentrations were significantly higher among the 57 patients with atherosclerosis of the aorta and/or renal arteries compared to those in the 26 patients without any angiographic lesions (4.6 vs 1.7 mg/l; P < 0.005). Moreover, in patients with renal artery stenosis, levels of hsCRP were higher when the degree of stenosis exceeded 50%. However, the association between hsCRP and the presence of atherosclerosis appeared to be confounded by serum creatinine, creatinine clearance, age and gender. In the whole group a significant inverse relationship was found between creatinine clearance and hsCRP (P < 0.05). In conclusion, hsCRP concentrations are related to atherosclerotic lesions in the renal arteries and the abdominal aorta. While this supports the view that atherosclerotic renal artery stenosis is part of a systemic inflammatory vascular disease, increased concentrations of CRP may also coincide with decreased renal function.

New parameters available on Sysmex XE-5000 hematology analyzers contribute to differentiating dengue from leptospirosis and enteric fever.

INTRODUCTION: Distinguishing dengue virus infection from other febrile thrombocytopenic illnesses such as leptospirosis or enteric fever is important but difficult, due to the unavailability of reliable diagnostic tests. Sysmex XE-5000 hematology analyzers use fluorescence flow cytometry to quantitate new parameters including cells in the atypical lymphocyte area (AL), high-fluorescent lymphocyte counts (HFLC), immature granulocytes (IG), and immature platelets (IPF). This study aimed to investigate whether these parameters can help to discriminate between the diseases. MATERIAL AND METHODS: We compared hematocytometry performed by a Sysmex XE-5000 analyzer in Indonesian adults with dengue (n = 93), leptospirosis (n = 11), and enteric fever (n = 6) infection, and in healthy controls (n = 28). RESULTS: Receiver operating characteristic curves comparing dengue and leptospirosis showed that dengue was characterized by increased %AL (AUC 0.87; 95% CI 0.70-1.03), %HFLC (AUC 0.89; 95% CI 0.78-0.99), and %IPF (AUC 0.81; 95% CI 0.65-0.97), while patients with leptospirosis had increased %IG (AUC 0.86; 95% CI 0.71-1.02). Low %AL, %HFLC, and %IG supported a diagnosis of enteric fever. CONCLUSIONS: The detection of AL, HFLC, IG, and IPF by Sysmex XE-5000 hematology analyzers can help to differentiate between common causes of febrile illnesses with thrombocytopenia in dengue endemic areas. We recommend further investigating the discriminatory value of these parameters in clinical practice.

Is cervical length associated with maternal characteristics?

OBJECTIVE: Women with a mid-trimester short cervical length (CL) are at increased risk for preterm delivery. Consequently, CL measurement is a potential screening tool to identify women at risk for preterm birth. Our objective was to assess possible associations between CL and maternal characteristics. STUDY DESIGN: A nationwide screening study was performed in which CL was measured during the standard anomaly scan among low risk women with a singleton pregnancy. Data on maternal height, pre-pregnancy weight, ethnicity, parity and gestational age at the time of the CL measurement were collected from January 2010 to December 2012. Univariable and multivariable linear regression analyses were performed to assess the relationship between CL and maternal characteristics. RESULTS: We included 5092 women. The mean CL was 44.3mm. No association was found between CL and maternal height or gestational age of the measurement. Maternal weight was associated with CL (p=0.007, adjusted R(2) 0.03). Separate analysis for BMI did not change these results. Ethnicity, known in 2702 out of 5092 women, was associated with CL (mean CL in Caucasian women 45.0mm, Asian 43.9mm, Mediterranean 43.1mm, and African 41.8mm, p=0.003), as well as parity (mean CL multiparous 45.3mm, nulliparous 43.5mm, p<0.0001). CONCLUSION: Shorter mid-trimester cervical length is associated with higher maternal weight, younger maternal age, nulliparity and non-Caucasian ethnicity, but not with maternal height.