Omega-3 poly-unsaturated fatty acids for the prevention of severe neutropenic enterocolitis in patients with acute myeloid leukemia

Neutropenic enterocolitis is a potentially fatal complication of myeloablative chemotherapy in patients with acute myeloid leukemia. Omega-3 polyunsaturated fatty acids (PUFA) are precursors of potent anti-inflammatory prostaglandins. Our aim was to explore the safety and effectiveness of omega-3 PUFA added to parenteral nutrition in protecting leukemia patients from severe enterocolitis. Fourteen patients with acute myeloid leukemia who received omega-3 PUFA in a Phase II trial were compared with 66 consecutive control patients not getting this intervention. We performed crude and adjusted comparisons, using inverse probability of treatment weighting for adjusted analysis, and blind outcome assessment to minimize assessor bias. Primary outcome was severe enterocolitis (≥Grade 3). The crude odds ratio of Grade 3 colitis or higher was 1.36 (95% CI 0.37 to 4.96, P = 0.64), and the adjusted odds ratio was 0.79 (95% CI 0.35 to 1.78, P = 0.57). There was little evidence to suggest differences between groups in serious adverse events and overall mortality. Our results provide little evidence that addition of omega-3 PUFA is beneficial in this condition. Routine treatment with omega-3 PUFA is currently not warranted.

Case and partnership reproduction numbers for a curable sexually transmitted infection

Sexually transmitted infections (STIs) are, by definition, transmitted between sexual partners. For curable STIs an infected index case can potentially re-infect the same partner multiple times. Thus, R0, the average number of secondary infections one typical infected individual will produce during his or her infectious period is not necessarily the same as the average number of secondary cases (infected persons). Here we introduce the new concept of the case reproduction number (Rc). In addition, we define the partnership reproduction number (Rp) as the average number of secondary partnerships consisting of two infected individuals one typical infected individual will produce over his or her infectious lifetime. Rp takes into account clearance and re-infection within partnerships, which results in a prolongation of the duration of the infectious period. The two new reproduction numbers were derived for a deterministic pair model with serial monogamous partnerships using infection parameters for Chlamydia trachomatis, an example of a curable STI. We showed that re-infection within partnerships means that curable STIs can be sustained endemically even when the average number of secondary cases a person produces during his or her infectious period is below one.

Arthroscopic versus open cam resection in the treatment of femoroacetabular impingement

PURPOSE The purpose of this study was to evaluate if osseous correction of the femoral neck achieved arthroscopically is comparable to that achieved by surgical dislocation. METHODS We retrospectively analyzed all patients who were treated with hip arthroscopy or surgical dislocation for cam or mixed type femoroacetabular impingement (FAI) in our institution between 2006 and 2009. Inclusion criteria were complete clinical and radiologic documentation with standardized radiographs. Group 1 consisted of 66 patients (49 female patients, mean age 33.8 years) treated with hip arthroscopy. Group 2 consisted of 135 patients (91 male patients, mean age 31.2 years) treated with surgical hip dislocation. We compared the preoperative and postoperative alpha and gamma angles, as well as the triangular index. Mean follow-up was 16.7 months (range, 2 to 79 months). RESULTS In group 1, the mean alpha angle improved from 60.7° preoperatively to 47.8° postoperatively (P < .001) and the mean gamma angle improved from 47.3° to 44.5° (P < .001). Over time, the preoperative mean alpha angle increased from 56.3° in 2006 to 67.5° in 2009, whereas the postoperative mean alpha angle decreased from 51.2° in 2006 to 47.5° in 2009. In group 2, the mean alpha angle improved from 75.3° preoperatively to 44.8° postoperatively (P < .001), and the mean gamma angle improved from 65.1° to 52.2° (P < .001). Arthroscopic revision of intra-articular adhesions was performed in 4 patients (6.1%) in group 1 and 16 patients (12%) in group 2. Three patients (2.2%) in group 2 underwent revision for nonunion of the greater trochanter. CONCLUSIONS Osseous correction of cam-type FAI with hip arthroscopy is comparable to the correction achieved by surgical hip dislocation. There is a significant learning curve for hip arthroscopy, with postoperative osseous correction showing improved results with increasing surgical experience. LEVEL OF EVIDENCE Level III, retrospective comparative study.

The importance of partnership factors and individual factors associated with absent or inconsistent condom use in heterosexuals: a cross-sectional study.

OBJECTIVES Decisions to use condoms are made within partnerships. We examined the associations between inconsistent or no condom use and individual and partnership characteristics. We also examined the relative importance of individual versus partnership factors. METHODS Cross-sectional study of heterosexual individuals enrolled from the sexually transmitted infections (STI) outpatient clinic in Amsterdam, the Netherlands, from May to August 2010. Participants completed a questionnaire about sexual behaviour with the last four partners in the preceding year. Participant and partnership factors associated with inconsistent or no condom use in steady and casual partnerships were identified. RESULTS 2144 individuals were included, reporting 6401 partnerships; 54.7% were female, the median age was 25 (IQR 22-30) years and 79.9% were Dutch. Inconsistent or no condom use occurred in 13.9% of 2387 steady partnerships and in 33.5% of 4014 casual partnerships. There was statistical evidence of associations between inconsistent condom use in steady partnerships and ethnic concordance, longer duration, higher number of sex acts, practising anal sex, and sex-related drug use. In casual partnerships, associations were found with having an older partner, ethnic concordance, longer duration, higher number of sex acts, anal sex, sex-related drug use, ongoing partnerships and concurrency. In multivariable models, partnership factors explained 50.9% of the variance in steady partnerships and 70.1% in casual partnerships compared with 10.5% and 15.4% respectively for individual factors. CONCLUSIONS Among heterosexual STI clinic attendees in Amsterdam, partnership factors are more important factors related with inconsistent condom use than characteristics of the individual.

Epidemic of Salmonellosis in Passerine Birds in Switzerland With Spillover to Domestic Cats

A die-off of passerine birds, mostly Eurasian siskins (Carduelis spinus), occurred in multiple areas of Switzerland between February and March 2010. Several of the dead birds were submitted for full necropsy. Bacteriological examination was carried out on multiple tissues of each bird. At gross examination, common findings were light-tan nodules, 1 to 4 mm in diameter, scattered through the esophagus/crop. Histologically, a necroulcerative transmural esophagitis/ingluvitis was observed. Bacterial cultures yielded Salmonella enterica subsp. enterica serovar Typhimurium. At the same time, 2 pet clinics reported an unusual increase of domestic cats presented with fever, anorexia, occasionally dolent abdomen, and history of presumed consumption of passerine birds. Analysis of rectal swabs revealed the presence of S. Typhimurium in all tested cats. PFGE (pulsed field electrophoresis) analysis was performed to characterize and compare the bacterial isolates, and it revealed an indistinguishable pattern between all the avian and all but 1 of the feline isolates. Cloacal swabs collected from clinically healthy migrating Eurasian siskins (during autumn 2010) did not yield S. Typhimurium. The histological and bacteriological findings were consistent with a systemic infection caused by S. Typhimurium. Isolation of the same serovar from the dead birds and ill cats, along with the overlapping results of the PFGE analysis for all the animal species, confirmed a spillover from birds to cats through predation. The sudden increase of the number of siskins over the Swiss territory and their persistency during the whole winter of 2009-2010 is considered the most likely predisposing factor for the onset of the epidemic.

A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

Surveillance of bovine tuberculosis and risk estimation of a future reservoir formation in wildlife in Switzerland and Liechtenstein.

Bovine tuberculosis (bTB) caused by Mycobacterium bovis or M. caprae has recently (re-) emerged in livestock and wildlife in all countries bordering Switzerland (CH) and the Principality of Liechtenstein (FL). Comprehensive data for Swiss and Liechtenstein wildlife are not available so far, although two native species, wild boar (Sus scrofa) and red deer (Cervus elaphus elaphus), act as bTB reservoirs elsewhere in continental Europe. Our aims were (1) to assess the occurrence of bTB in these wild ungulates in CH/FL and to reinforce scanning surveillance in all wild mammals; (2) to evaluate the risk of a future bTB reservoir formation in wild boar and red deer in CH/FL. Tissue samples collected from 2009 to 2011 from 434 hunted red deer and wild boar and from eight diseased ungulates with tuberculosis-like lesions were tested by direct real-time PCR and culture to detect mycobacteria of the Mycobacterium tuberculosis complex (MTBC). Identification of suspicious colonies was attempted by real-time PCR, genotyping and spoligotyping. Information on risk factors for bTB maintenance within wildlife populations was retrieved from the literature and the situation regarding identified factors was assessed for our study areas. Mycobacteria of the MTBC were detected in six out of 165 wild boar (3.6%; 95% CI: 1.4-7.8) but none of the 269 red deer (0%; 0-1.4). M. microti was identified in two MTBC-positive wild boar, while species identification remained unsuccessful in four cases. Main risk factors for bTB maintenance worldwide, including different causes of aggregation often resulting from intensive wildlife management, are largely absent in CH and FL. In conclusion, M. bovis and M. caprae were not detected but we report for the first time MTBC mycobacteria in Swiss wild boar. Present conditions seem unfavorable for a reservoir emergence, nevertheless increasing population numbers of wild ungulates and offal consumption may represent a risk.

Concomitant lipopolysaccharide-induced transfer of blood-derived components including immunoglobulins into milk

During a mammary immune response, the integrity of the blood-milk barrier is negatively affected and becomes leaky. The aim of the present study was to demonstrate the blood origin, and to investigate changes in the concentration, of various constituents including immunoglobulins in blood and milk during the early phase of lipopolysaccharide (LPS)-induced mastitis. Five lactating dairy cows received continuous β-hydroxybutyrate (BHBA) clamp infusions to maintain elevated BHBA blood concentrations (1.5 to 2.0 mmol/L) from 48 h before and 8h after LPS administration. One udder quarter was infused with 200 μg of Escherichia coli LPS. A second quarter served as control. Milk and blood samples were taken hourly for 8h postchallenge (PC). The somatic cell count in LPS-challenged quarters was increased from 4h PC to the end of the experiment compared with control quarters. In LPS-challenged quarters, l-lactate, BHBA, lactate dehydrogenase (LDH), IgG(1), and IgG(2) were increased at 3h PC and remained elevated until the end of experiment (8h PC) compared with control quarters. In addition, the optical density values in milk in a nonquantitative ELISA for antibodies directed against bluetongue virus (used as a measure of nonspecific antibody transfer; all animals were vaccinated) increased and, thus, indicates an increase in these antibodies in response to LPS treatment. l-Lactate concentration also increased in blood 2h PC and in the milk of control quarters during the experiment from 3h PC. A second experiment was conducted in vitro to investigate a possible contribution from destructed milk cells to l-lactate concentration and activity of LDH in milk. Aliquots of milk samples (n=8) were frozen (-20°C) or disrupted with ultrasound, respectively. Freeze thawing and ultrasound treatment increased LDH in milk samples, but had no effect on l-lactate concentrations. Results suggest that intramammary infusion of LPS induces a systemic response, as evidenced by an elevation of blood l-lactate concentration. The concomitant changes of all investigated components suggest that they were blood derived. However, the increase in blood components in the milk is not necessarily supportive of the mammary immune system, and likely a side effect of reduced blood-milk barrier integrity.

Short communication: differential immunoglobulin transfer during mastitis challenge by pathogen-specific components

Mastitis induced by Escherichia coli is often characterized by severe clinical signs, indicating a more powerful combat of the immune system against the pathogen compared with Staphylococcus aureus infections, which are often represented by chronic and subclinical diseases. The aim of this study was to test the major pathogenic component lipopolysaccharide (LPS) from E. coli and lipoteichoic acid (LTA) from Staph. aureus for their effects on blood-milk barrier integrity and the related transfer of immunoglobulins and lactate from blood into milk. A similar somatic cell count (SCC) increase was achieved by intramammary challenge of 1 quarter of 5 cows with 20 µg of LTA, and 8 cows with 0.2 µg of LPS (maximum log SCC/mL: 7). Milk IgG(1) concentrations increased in LPS- but not in LTA-challenged quarters. Milk IgG(2) concentrations were increased in treated quarters at 3h after LPS, and 6h after LTA challenge. Higher maximum levels of IgG(2) were reached in milk of LPS-treated quarters (173 ± 58 μg/mL) than of LTA-challenged quarters (62 ± 13 μg/mL). Immunoglobulin G(1) and IgG(2) levels did not change in control quarters. l-Lactate concentrations in milk increased 4h after LPS and 5h after LTA challenge and reached higher maximum levels in LPS- (221 ± 48 mg/L) than in LTA-treated quarters (77 ± 18 mg/L). In conclusion, a mammary inflammation on a quantitatively similar level based on SCC increase achieves a more efficient transfer of blood components such as IgG(2) via the blood-milk barrier if induced by LPS from E. coli than by LTA from Staph. aureus. This pathogen-specific difference may play an important role in the cure rate of the respective intramammary infection, which is usually lower in Staph. aureus- than in E. coli-induced mastitis.

Identification of erosional mechanisms during past glaciations based on a bedrock surface model of the central European Alps

The bedrock topography beneath the Quaternary cover provides an important archive for the identification of erosional processes during past glaciations. Here, we combined stratigraphic investigations of more than 40,000 boreholes with published data to generate a bedrock topography model for the entire plateau north of the Swiss Alps including the valleys within the mountain belt. We compared the bedrock map with data about the pattern of the erosional resistance of Alpine rocks to identify the controls of the lithologic architecture on the location of overdeepenings. We additionally used the bedrock topography map as a basis to calculate the erosional potential of the Alpine glaciers, which was related to the thickness of the LGM ice. We used these calculations to interpret how glaciers, with support by subglacial meltwater under pressure, might have shaped the bedrock topography of the Alps. We found that the erosional resistance of the bedrock lithology mainly explains where overdeepenings in the Alpine valleys and the plateau occur. In particular, in the Alpine valleys, the locations of overdeepenings largely overlap with areas where the underlying bedrock has a low erosional resistance, or where it was shattered by faults. We also found that the assignment of two end-member scenarios of erosion, related to glacial abrasion/plucking in the Alpine valleys, and dissection by subglacial meltwater in the plateau, may be adequate to explain the pattern of overdeepenings in the Alpine realm. This most likely points to the topographic controls on glacial scouring. In the Alps, the flow of LGM and previous glaciers were constrained by valley flanks, while ice flow was mostly divergent on the plateau where valley borders are absent. We suggest that these differences in landscape conditioning might have contributed to the contrasts in the formation of overdeepenings in the Alpine valleys and the plateau.

Outcome of standard and high-risk patients with acute anterior circulation stroke after stent retriever thrombectomy.

BACKGROUND AND PURPOSE Stent retrievers have become an important tool for the treatment of acute ischemic stroke. The aim of this study was to analyze outcome and complications in a large cohort of patients with stroke treated with the Solitaire stent retriever. The study also included patients who did not meet standard inclusion criteria for endovascular treatment: low or high baseline National Institutes of Health Stroke Scale score, ≥80 years of age, extensive ischemic signs in middle cerebral artery territory, and time from symptom onset to endovascular intervention>8 hours. METHODS Consecutive patients with acute anterior circulation stroke treated with the Solitaire FR were analyzed. Data on characteristics of endovascular interventions, complications, and clinical outcome were collected prospectively. Patients who met standard inclusion criteria were compared with those who did not. RESULTS A total of 227 patients were included. Mean age was 68.2±14.7 years, and median National Institutes of Health Stroke Scale score on admission was 16 (range, 2-36). Reperfusion was successful (thrombolysis in cerebral infarction, 2b-3) in 70.9%. Outcome was favorable (modified Rankin Scale, 0-2) in 57.7% of patients who met standard inclusion criteria and 30.3% of those who did not. The rates for symptomatic intracranial hemorrhage were 3.7% and 13.1%, for death 11.4% and 33.8%, and for symptomatic intraprocedural complications 2.5% and 4.8%, respectively. CONCLUSIONS Patients<80 years of age, without extensive pretreatment ischemic signs, and baseline National Institutes of Health Stroke Scale score≤30 had high rates of favorable outcome and low periprocedural complication rates after Solitaire thrombectomy. Successful reperfusion was also common in patients not fulfilling standard inclusion criteria, but worse clinical outcomes warrant further research with a special focus on optimal patient selection.

Characterization of microcirculation in multiple sclerosis lesions by dynamic texture parameter analysis (DTPA)

OBJECTIVE Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA), a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL), non-enhancing lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis (MS). METHODS We investigated 18 patients with MS and clinical isolated syndrome (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. RESULTS Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant differences in the DTPA texture maps were found during inflow (52 parameters), outflow (40 parameters) and reperfusion (62 parameters). The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. CONCLUSION DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2-hypersignal, on a numeric scale allowing for a more subtle grading of MS-lesions.

Factors that determine penumbral tissue loss in acute ischaemic stroke

The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. Among these factors collaterals as seen on angiography were of special interest. Forty-four patients were included in this analysis. They had all received endovascular therapy and at least minimal reperfusion was achieved. Their penumbra was assessed with perfusion- and diffusion-weighted imaging. Perfusion-weighted imaging volumes were defined by circular singular value decomposition deconvolution maps (Tmax > 6 s) and results were compared with volumes obtained with non-deconvolved maps (time to peak > 4 s). Loss of penumbral volume was defined as difference of post- minus pretreatment diffusion-weighted imaging volumes and calculated in per cent of pretreatment penumbral volume. Correlations between baseline characteristics, reperfusion, collaterals, time to reperfusion and penumbral volume loss were assessed using analysis of covariance. Collaterals (P = 0.021), reperfusion (P = 0.003) and their interaction (P = 0.031) independently influenced penumbral tissue loss, but not time from magnetic resonance (P = 0.254) or from symptom onset (P = 0.360) to reperfusion. Good collaterals markedly slowed down and reduced the penumbra loss: in patients with thrombolysis in cerebral infarction 2 b-3 reperfusion and without any haemorrhage, 27% of the penumbra was lost with 8.9 ml/h with grade 0 collaterals, whereas 11% with 3.4 ml/h were lost with grade 1 collaterals. With grade 2 collaterals the penumbral volume change was -2% with -1.5 ml/h, indicating an overall diffusion-weighted imaging lesion reversal. We conclude that collaterals and reperfusion are the main factors determining loss of penumbral tissue in patients with middle cerebral artery occlusions. Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatment.