Chronic thromboembolic pulmonary hypertension suspicion after pulmonary embolism in cancer patients.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe condition which should be screened in patient with persistent dyspnea after pulmonary embolism (PE). After PE, CTEPH incidence was estimated between 0.1 and 9.1% in overall patients. Although cancer is associated with an increased risk of CTEPH, CTEPH incidence is still unknown in cancer patients with PE. We aimed to estimate the frequency CTEPH-likely patients after PE, in cancer patients. MATERIALS: We individualized cancer patients of a monocentric prospective registry including consecutive patients with symptomatic PE. The primary outcome was the frequency of "CTEPH-likely" patients defined by the European Respiratory Society (ERS) guidelines (an accelerated tricuspid regurgitation more than 2.8m/s and at least 1-2 segmental or larger-sized defects, after more than 3 months of therapeutic anticoagulation). RESULTS: We included 129 cancer patients with PE. Colorectal cancer (19%), breast cancer (17%) and prostate cancer (15%) were the most frequent cancers. PE occurred after surgery or medical immobilization in 17% of patients, while 26% of patients had history of venous thromboembolism. During the follow-up, 2 patients (1.5%) had a clinical suspicion of CTEPH and only 1 patient with ovarian cancer (0.75% 95%CI [0.0%-2.2%]) was classified as "CTEPH-likely", 6 months after PE. CONCLUSION: The frequency of screening for CTEPH seems negligible in PE patients with cancer. Concomitant cancer may affect the clinical suspicion of CTEPH.

Surgical repair of propagating condylar fractures of the third metacarpal/metatarsal bones with cortical screws placed in lag fashion in 26 racehorses (2007-2015).

BACKGROUND: Despite the recommendation of plate fixation for propagating condylar fractures of the third metacarpal (McIII) or third metatarsal bone (MtIII), lag screw fixation can be a viable surgical option. OBJECTIVES: To evaluate short-term outcome and long-term racing performance of horses that underwent lag screw fixation of long condylar fractures of the McIII/MtIII. STUDY DESIGN: Retrospective case series. METHODS: Medical records, post-surgical racing performance and outcome of 26 horses with propagating fractures of the medial and/or lateral condyle of McIII/MtIII were reviewed. Medical information included were age, breed, sex, physical examination at admission, circumstances of fracture, radiographic evaluation, anaesthesia and recovery records, surgical and post-operative management, as well as complications. Outcome included racing data and information from telephone interviews. RESULTS: Twenty-six horses (9 Standardbreds and 17 Thoroughbreds) were admitted with a long condylar fracture of the McIII/MtIII. Fore- and hindlimbs were equally represented with the left hindlimb being more frequently involved. Most of the fractures had a spiralling component (76%) and four (15%) were comminuted. Fifteen (58%) horses raced post-surgery including nine Standardbreds (100%) and six Thoroughbreds (35%). Twelve of them were placed in at least one race and 11 won at least once. One horse sustained a severe complication in recovery. No significant difference was observed in the racing performances before and after surgery. MAIN LIMITATIONS: Follow-up method and duration were not standardised and there is a low number of cases with six surgeons. CONCLUSIONS: Long condylar fractures can be repaired using lag fashion technique combined with a half-limb or full-limb tight cast for recovery as a good surgical alternative. Similar results to plate fixation can be expected, with a return to racing of more than 50%, and the prognosis being even better for pacers.

Individual patient data meta-analysis of enoxaparin vs. unfractionated heparin for venous thromboembolism prevention in medical patients.

BACKGROUND: Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are both recommended for venous thromboembolism (VTE) prophylaxis in hospitalized medical patients. OBJECTIVE: To perform an individual patient data meta-analysis to evaluate the relative efficacy and safety of the LMWH enoxaparin and UFH in preventing VTE in hospitalized medical patients. METHODS: Randomized clinical trials comparing subcutaneous enoxaparin (4000 IU once-daily) and UFH (5000 IU subcutaneous two- or three-times daily) for VTE prevention were identified by a systematic search. Individual patient data were obtained from each eligible trial. RESULTS: Overall, four trials were eligible, including 3600 patients randomized to receive enoxaparin (n = 1799) or UFH (n = 1801). Median patient age was 71 years, and 49.3% were female. Compared with UFH, enoxaparin was associated with risk reductions of 37% for total VTE [relative risk (RR) 0.63, 95% confidence interval (CI) 0.51-0.77] and 62% for symptomatic VTE (RR 0.38, 95% CI 0.17-0.85) at day 15. RR for total VTE in stroke and non-stroke patients was 0.59 (95% CI 0.47-0.74) and 0.87 (95% CI 0.51-1.50), respectively. Major bleeding rates were consistently low and similar between treatment groups at day 15 (RR 1.13, 95% CI 0.53-2.44). There was a trend towards reduced risk for mortality in patients receiving enoxaparin (RR 0.83, 95% CI 0.64-1.08), compared with UFH. CONCLUSIONS: Enoxaparin significantly reduces VTE in hospitalized medical patients, compared with UFH, without increasing the risk for major bleeding, and was associated with a trend towards reduced all-cause mortality.

[Vena cava filters and treatment of venous thromboembolism in cancer patients]. / Place des filtres caves dans le traitement de la maladie thromboembolique veineuse chez les patients cancéreux.

Despite numerous publications, there is still only one randomised clinical trial with vena cava filter in the treatment of venous thromboembolism (VTE). This study has shown a potential and early benefit on the risk of pulmonary embolism (PE) (the first three months) but a late negative effect on the risk of deep vein thrombosis (DVT) recurrences (beyond the sixth month) especially on the risk of filter thrombosis. Consequently, the international recommendations are against a systematic use of vena cava filter to treat VTE (grade 1A) and they suggest to use them in case of a recurrence despite adequate treatment or in case of a contra-indication to anticoagulants (grade 2C). But these two conditions are frequent with VTE associated with cancer since, the risk of VTE recurrences is about 5 to 10% despite prolonged low-molecular-weight heparins (LMWH) treatment and the major bleeding risk is also about 5 to 10% in this case. These VTE recurrences are frequently early (first month of treatment) and contra-indications to anticoagulants due to major bleeding are mostly temporary. In this way, retrievable vena cava filters (possible retrieval until six months after placement) could be useful in order, to prevent recurrences during the thromboembolic risk period without any prolonged increasing risk of vena cava thrombosis. However, vena cava filters could be associated with some complications (tilt, migration sepsis...). So without any strong validation, they have still to be considered as a therapeutic strategy needing to be evaluated especially in cancer patient.

Structure of worldwide populations of Lasioderma serricorne (Coleoptera: Anobiidae) as revealed by amplified fragment length polymorphism profiles.

The cigarette beetle Lasioderma serricorne (Fabricius) is the most widespread and destructive pest of stored tobacco. The capability to differentiate between populations from different geographic origins would enable researchers to better understand how insect dispersal through transportation affects the infestation of stored tobacco. Using amplified fragment length polymorphism (AFLP), DNA polymorphisms were assessed in 16 populations of L. serricorne collected from 15 countries. The dendrograms constructed from profile distance matrices revealed well-supported colony clusters. There was no clear clustering as a function of the geographic origin of the samples. The results suggest extensive insect dispersal among geographical regions due to movement of infested commodities worldwide. This first AFLP population study of a stored-product insect demonstrates the potential of AFLP for distinguishing L. serricorne populations.

Alps, genes, and chromosomes: their role in the formation of species in the Sorex araneus group (Mammalia, Insectivora), as inferred from two hybrid zones.

During the Pleistocene glaciations, the Alps were an efficient barrier to gene flow between isolated populations, often leading to allopatric speciation. Afterwards, the Alps strongly influenced the post-glacial recolonization of Europe and represent a major suture zone between differentiated populations. Two hybrid zones in the Swiss and French Alps between genetically and chromosomally well-differentiated species-the Valais shrew, Sorex antinorii, and the common shrew, S. araneus-were studied karyotypically and by analyzing the distribution of seven microsatellite loci. In the center of the Haslital hybrid zone the two species coexist over a distance of 900 m. Hybrid karyotypes, among them the most complex known in Sorex, are rare. F-statistics based on microsatellite data revealed a strong heterozygote deficit only in the center of the zone, due to the sympatric distribution of the two species with little hybridization between them. Structuring within the species (both F(IS) and F(ST)) was low. An hierarchical analysis showed a high level of interspecific differentiation. Results were compared with those previously reported in another hybrid zone located at Les Houches in the French Alps. Genetic structuring within and between species was comparable in both hybrid zones, although chromosomal incompatibilities are more important in Haslital, where a linkage block of the race-specific chromosomes should additionally impede gene flow. Evidence for a more restricted gene flow in Haslital comes from the genetically intermediate hybrid karyotypes, whereas in Les Houches, hybrid karyotypes are genetically identical to individuals of the pure karyotypic races. Genic and chromosomal introgression was observed in Les Houches, but not in Haslital. The possible influence of a river, separating the two species at Les Houches, on gene flow is discussed.

Phylogeographical structure, postglacial recolonization and barriers to gene flow in the distinctive Valais chromosome race of the common shrew (Sorex araneus).

Using one male-inherited and eight biparentally inherited microsatellite markers, we investigate the population genetic structure of the Valais chromosome race of the common shrew (Sorex araneus) in the Central Alps of Europe. Unexpectedly, the Y-chromosome microsatellite suggests nearly complete absence of male gene flow among populations from the St-Bernard and Simplon regions (Switzerland). Autosomal markers also show significant genetic structuring among these two geographical areas. Isolation by distance is significant and possible barriers to gene flow exist in the study area. Two different approaches are used to better understand the geographical patterns and the causes of this structuring. Using a principal component analysis for which testing procedure exists, and partial Mantel tests, we show that the St-Bernard pass does not represent a significant barrier to gene flow although it culminates at 2469 m, close to the highest altitudinal record for this species. Similar results are found for the Simplon pass, indicating that both passes represented potential postglacial recolonization routes into Switzerland from Italian refugia after the last Pleistocene glaciations. In contrast with the weak effect of these mountain passes, the Rhône valley lowlands significantly reduce gene flow in this species. Natural obstacles (the large Rhône river) and unsuitable habitats (dry slopes) are both present in the valley. Moreover, anthropogenic changes to landscape structures are likely to have strongly reduced available habitats for this shrew in the lowlands, thereby promoting genetic differentiation of populations found on opposite sides of the Rhône valley.

Microsatellites can be misleading: an empirical and simulation study.

It has been long recognized that highly polymorphic genetic markers can lead to underestimation of divergence between populations when migration is low. Microsatellite loci, which are characterized by extremely high mutation rates, are particularly likely to be affected. Here, we report genetic differentiation estimates in a contact zone between two chromosome races of the common shrew (Sorex araneus), based on 10 autosomal microsatellites, a newly developed Y-chromosome microsatellite, and mitochondrial DNA. These results are compared to previous data on proteins and karyotypes. Estimates of genetic differentiation based on F- and R-statistics are much lower for autosomal microsatellites than for all other genetic markers. We show by simulations that this discrepancy stems mainly from the high mutation rate of microsatellite markers for F-statistics and from deviations from a single-step mutation model for R-statistics. The sex-linked genetic markers show that all gene exchange between races is mediated by females. The absence of male-mediated gene flow most likely results from male hybrid sterility.

Do riverine barriers, history or introgression shape the genetic structuring of a common shrew (Sorex araneus) population?

The common shrew (Sorex araneus) is subdivided into numerous chromosome races. The Valais and Cordon chromosome races meet and hybridize at a mountain river in Les Houches (French Alps). Significant genetic structuring was recently reported among populations found on the Valais side of this hybrid zone. In this paper, a phylogenetic analysis and partial Mantel tests are used to investigate the patterns and causes of this structuring. A total of 185 shrews were trapped at 12 localities. All individuals were typed for nine microsatellite loci. Although several mountain rivers are found in the study area, riverine barriers do not have a significant influence on gene flow. Partial Mantel tests show that our result is caused by the influence of the hybrid zone with the Cordon race. The geographical patterns of this structuring are discussed in the context of the contact zone, which appears to extend up to a group of two rivers. The glacier they originate from is known to have cut the Arve valley as recently as 1818. The recent history of this glacier, its moraine and possibly rivers, may therefore be linked to the history of this hybrid zone.

Weight and metabolic changes induced by low carbohydrate-high fat diets in man and in rat.

Weight loss and potential toxicity of low carbohydrate-high fat diets were examined in 8 volunteer medical students given either a high fat diet or a high carbohydrate diet for 15 days, as well as in 36 Sprague-Dawley rats fed for 5 weeks a series of low carbohydrate diets (less than 1%), varying in protein and lipid proportions. A weight loss occurred with the low carbohydrate-high fat diets; serum cholesterol level increased in both man and rat; plasma triglycerides rose in man. In rat, we found an increase in hepatic lipid levels as in plasma ketone and non-esterified fatty acid concentrations. These effects seemed to be related to the increase in lipid intake rather than the lack of carbohydrates.