Prognostic impact of inter-metastatic heterogeneity of viable tumour cells in colorectal liver metastases.

BACKGROUND: Heterogenous response to neoadjuvant chemotherapy in patients with multiple colorectal liver metastases (CRLM) has been associated with an acquired resistance to systemic therapy. This study evaluated the occurrence of a heterogenous inter-metastatic tumour response with regards to the proportion of viable tumour cells, and its prognostic impact. METHODS: A retrospective cohort study was conducted, including all patients with CRLM surgically treated at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with the proportion of viable tumour cells and inter-metastatic heterogeneity were analysed with regression and survival analyses. RESULTS: Out of 640 surgically treated patients, 405 patients (1357 CRLM), received neoadjuvant chemotherapy. Multiple CRLM were present in 314 patients (78%), out of whom 72 patients (23%) presented with a heterogenous tumour response. The median overall survival (OS) for patients with a heterogenous inter-metastatic tumour response was 36 months, compared to 57 months for patients with a homogenous inter-metastatic tumour response (p < .001). Poor OS in patients receiving preoperative chemotherapy was significantly associated with a heterogenous inter-metastatic tumour response (hazard ratio (HR) 1.68 (1.02-2.78)), right-sided primary tumour (HR 2.01 (1.29-3.43)) and CRLM diameter >5 cm (HR 1.83 (1.06-3.17)). CONCLUSION: Outcome in patients with a heterogenous inter-metastatic tumour response, illustrated by the proportion of viable tumour cells, is inferior to that of patients with a homogenous response. These results suggest that heterogeneity in treatment response is an important marker of aggressive disease and could be of clinical value for decisions on post-operative therapy.

Towards a Large-Scale Assessment of the Relationship between Biological and Chronological Aging: The INSPIRE Mouse Cohort.

Aging is the major risk factor for the development of chronic diseases. After decades of research focused on extending lifespan, current efforts seek primarily to promote healthy aging. Recent advances suggest that biological processes linked to aging are more reliable than chronological age to account for an individual's functional status, i.e. frail or robust. It is becoming increasingly apparent that biological aging may be detectable as a progressive loss of resilience much earlier than the appearance of clinical signs of frailty. In this context, the INSPIRE program was built to identify the mechanisms of accelerated aging and the early biological signs predicting frailty and pathological aging. To address this issue, we designed a cohort of outbred Swiss mice (1576 male and female mice) in which we will continuously monitor spontaneous and voluntary physical activity from 6 to 24 months of age under either normal or high fat/high sucrose diet. At different age points (6, 12, 18, 24 months), multiorgan functional phenotyping will be carried out to identify early signs of organ dysfunction and generate a large biological fluids/feces/organs biobank (100,000 samples). A comprehensive correlation between functional and biological phenotypes will be assessed to determine: 1) the early signs of biological aging and their relationship with chronological age; 2) the role of dietary and exercise interventions on accelerating or decelerating the rate of biological aging; and 3) novel targets for the promotion of healthy aging. All the functional and omics data, as well as the biobank generated in the framework of the INSPIRE cohort will be available to the aging scientific community. The present article describes the scientific background and the strategies employed for the design of the INSPIRE Mouse cohort.

A novel pancreatic tumour and stellate cell 3D co-culture spheroid model.

BACKGROUND: Pancreatic ductal adenocarcinoma is a devastating disease with poor outcome, generally characterized by an excessive stroma component. The purpose of this study was to develop a simple and reproducible in vitro 3D-assay employing the main constituents of pancreatic ductal adenocarcinoma, namely pancreatic stellate and cancer cells. METHOD: A spheroid assay, directly co-culturing human pancreatic stellate cells with human pancreatic tumour cells in 3D was established and characterized by electron microscopy, immunohistochemistry and real-time RT-PCR. In order to facilitate the cell type-specific crosstalk analysis by real-time RT-PCR, we developed a novel in vitro 3D co-culture model, where the participating cell types were from different species, human and mouse, respectively. Using species-specific PCR primers, we were able to investigate the crosstalk between stromal and cancer cells without previous cell separation and sorting. RESULTS: We found clear evidence for mutual influence, such as increased proliferation and a shift towards a more mesenchymal phenotype in cancer cells and an activation of pancreatic stellate cells towards the myofibroblast phenotype. Using a heterospecies approach, which we coined virtual sorting, confirmed the findings we made initially in the human-human spheroids. CONCLUSIONS: We developed and characterized different easy to set up 3D models to investigate the crosstalk between cancer and stroma cells for pancreatic cancer.

The 'brick diet' and postprandial insulin: a practical method to balance carbohydrates ingested and prandial insulin to prevent hypoglycaemia in hospitalized persons with diabetes.

AIM: Insulin is the preferred treatment for the control of diabetes in hospital, but it raises the risk of hypoglycaemia, often because oral intake of carbohydrates in hospitalized persons is lower than planned. Our aim was to assess the effect on the incidence of hypoglycaemia of giving prandial insulin immediately after a meal depending on the amount of carbohydrate ingested. METHODS: A prospective pre-post intervention study in hospitalized persons with diabetes eating meals with stable doses of carbohydrates present in a few fixed foods. Foods were easily identifiable on the tray and contained fixed doses of carbohydrates that were easily quantifiable by nurses as multiples of 10 g (a 'brick'). Prandial insulin was given immediately after meals in proportion to the amount of carbohydrates eaten. RESULTS: In 83 of the first 100 people treated with the 'brick diet', the oral carbohydrate intake was lower than planned on at least one occasion (median: 3 times; Q1-Q3: 2-6 times) over a median of 5 days. Compared with the last 100 people treated with standard procedures, postprandial insulin given on the basis of ingested carbohydrate significantly reduced the incidence of hypoglycaemic events per day, from 0.11 ± 0.03 to 0.04 ± 0.02 (P < 0.001) with an adjusted incidence rate ratio of 0.70 (95% confidence interval 0.54-0.92; P = 0.011). CONCLUSIONS: In hospitalized persons with diabetes treated with subcutaneous insulin, the 'brick diet' offers a practical method to count the amount of carbohydrates ingested, which is often less than planned. Prandial insulin given immediately after a meal, in doses balanced with actual carbohydrate intake reduces the risk of hypoglycaemia.

A randomized, phase 2 study of cetuximab plus cisplatin with or without paclitaxel for the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: B490 (EudraCT# 2011-002564-24) is a randomized, phase 2b, noninferiority study investigating the efficacy and safety of first-line cetuximab plus cisplatin with/without paclitaxel (CetCis versus CetCisPac) in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: Eligible patients had confirmed R/M SCCHN (oral cavity/oropharynx/larynx/hypopharynx/paranasal sinus) and no prior therapy for R/M disease. Cetuximab was administered on day 1 (2-h infusion, 400 mg/m2), then weekly (1-h infusions, 250 mg/m2). Cisplatin was given as a 1-h infusion (CetCis arm: 100 mg/m2; CetCisPac arm: 75 mg/m2) on day 1 of each cycle for a maximum of six cycles. Paclitaxel was administered as a 3-h infusion (175 mg/m2) on day 1 of each cycle. After six cycles, maintenance cetuximab was administered until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). We assumed a noninferiority margin of 1.40 as compatible with efficacy. RESULTS: A total of 201 patients were randomized 1 : 1 to each regimen; 191 were assessable. PFS with CetCis (median, 6 months) was noninferior to PFS with CetCisPac (median, 7 months) [HR for CetCis versus CetCisPac 0.99; 95% CI: 0.72-1.36, P = 0.906; margin of noninferiority (90% CI of 1.4) not reached]. Median overall survival was 13 versus 11 months (HR = 0.77; 95% CI: 0.53-1.11, P = 0.117). The overall response rates were 41.8% versus 51.7%, respectively (OR = 0.69; 95% CI: 0.38-1.20, P = 0.181). Grade ≥3 adverse event rates were 76% and 73% for CetCis versus CetCisPac, respectively, while grade 4 toxicities were lower in the two-drug versus three-drug arm (14% versus 33%, P = 0.015). No toxic death or sepsis were reported and cardiac events were negligible (1%). CONCLUSION: The two-drug CetCis regimen proved to be noninferior in PFS to a three-drug combination with CetCisPac. The median OS of both regimens is comparable with that observed in EXTREME, while the life-threatening toxicity rate appeared reduced. CLINICAL TRIAL NUMBER: EudraCT# 2011-002564-24.

White-to-brite conversion in human adipocytes promotes metabolic reprogramming towards fatty acid anabolic and catabolic pathways.

OBJECTIVE: Fat depots with thermogenic activity have been identified in humans. In mice, the appearance of thermogenic adipocytes within white adipose depots (so-called brown-in-white i.e., brite or beige adipocytes) protects from obesity and insulin resistance. Brite adipocytes may originate from direct conversion of white adipocytes. The purpose of this work was to characterize the metabolism of human brite adipocytes. METHODS: Human multipotent adipose-derived stem cells were differentiated into white adipocytes and then treated with peroxisome proliferator-activated receptor (PPAR)γ or PPARα agonists between day 14 and day 18. Gene expression profiling was determined using DNA microarrays and RT-qPCR. Variations of mRNA levels were confirmed in differentiated human preadipocytes from primary cultures. Fatty acid and glucose metabolism was investigated using radiolabelled tracers, Western blot analyses and assessment of oxygen consumption. Pyruvate dehydrogenase kinase 4 (PDK4) knockdown was achieved using siRNA. In vivo, wild type and PPARα-null mice were treated with a ß3-adrenergic receptor agonist (CL316,243) to induce appearance of brite adipocytes in white fat depot. Determination of mRNA and protein levels was performed on inguinal white adipose tissue. RESULTS: PPAR agonists promote a conversion of white adipocytes into cells displaying a brite molecular pattern. This conversion is associated with transcriptional changes leading to major metabolic adaptations. Fatty acid anabolism i.e., fatty acid esterification into triglycerides, and catabolism i.e., lipolysis and fatty acid oxidation, are increased. Glucose utilization is redirected from oxidation towards glycerol-3-phophate production for triglyceride synthesis. This metabolic shift is dependent on the activation of PDK4 through inactivation of the pyruvate dehydrogenase complex. In vivo, PDK4 expression is markedly induced in wild-type mice in response to CL316,243, while this increase is blunted in PPARα-null mice displaying an impaired britening response. CONCLUSIONS: Conversion of human white fat cells into brite adipocytes results in a major metabolic reprogramming inducing fatty acid anabolic and catabolic pathways. PDK4 redirects glucose from oxidation towards triglyceride synthesis and favors the use of fatty acids as energy source for uncoupling mitochondria.

Impaired atrial natriuretic peptide-mediated lipolysis in obesity.

BACKGROUND: Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered. METHODS: Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis. RESULTS: In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men. CONCLUSIONS: ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.

Adipogenic progenitors from obese human skeletal muscle give rise to functional white adipocytes that contribute to insulin resistance.

BACKGROUND/OBJECTIVES: Recent reports indicate that inter/intramuscular adipose tissue (IMAT), composed by adipocytes underneath the deep fascia of the muscles, is positively correlated with aging, obesity and insulin resistance in humans. However, no molecular/cellular evidence is available to support these interactions. The current study aimed to better characterize human skeletal muscle-derived adipogenic progenitors obtained from obese volunteers and investigate the impact of derived adipocytes on insulin action in primary skeletal muscle cells. METHODS: Primary cultured stroma-vascular fraction (SVF) obtained from vastus lateralis muscle biopsies of middle-aged obese subjects was immunoseparated (magnetic beads or flow cytometry). The characteristics and/or metabolic phenotype of CD56(+), CD56(-) and CD56(-)CD15(+) cellular fractions were investigated by complementary approaches (flow cytometry, cytology, quantitative PCR and metabolic assays). The effects of conditioned media from CD56(-)CD15(+) cells differentiated into adipocytes on insulin action and signaling in human primary myotubes was also examined. RESULTS: Our data indicate that CD56(+) and CD56(-) cellular fractions isolated from cultured SVF of human muscle contain two distinct committed progenitors: CD56(+) cells (that is, satellite cells) as myogenic progenitors and CD15(+) cells as adipogenic progenitors, respectively. CD56(-)CD15(+)-derived adipocytes display the phenotype and metabolic properties of white adipocytes. Secretions of CD56(-)CD15(+) cells differentiated into functional white adipocytes reduced insulin-mediated non-oxidative glucose disposal (P=0.0002) and insulin signaling. CONCLUSIONS: Using in-vitro models, we show for the first time that secretions of skeletal muscle adipocytes are able to impair insulin action and signaling of muscle fibers. This paracrine effect could explain, at least in part, the negative association between high levels of IMAT and insulin sensitivity in obesity and aging.

FERTILITY PATTERN AND FITNESS OF THE SPANISH-MEXICAN COLONISTS OF CALIFORNIA (1742-1876).

The analysis of fertility in colonizing populations is of great interest, since its individuals experience a major environmental change, and fertility rates can reflect the level of adaptation of the population to its new conditions. Using Northrop's genealogical compilations, this paper examines the fertility pattern of California's early Spanish-Mexican colonists between 1742 and 1876, their fitness levels and their trend across time throughout the colonizing period. A total of 197 women from 599 compiled families who had completed their reproductive period and had at least one child were analysed. The correlations among variables were also analysed in order to infer the relationship between longevity and fertility, and the influence of fertility determinants. The results show a natural fertility pattern, with a very young age at marriage and birth of first child (17.2 and 19.1 years respectively), and also a young age at last childbirth (38.8 years). The population's fitness showed greater values than for contemporary European populations, with 8 of 9.2 children surviving to adulthood, in comparison with 55% of newborns in Finland for the same period, suggesting a good adaptation of the population to their new environmental conditions. No relationship between fertility and lifespan was observed, as has been reported by other authors and in opposition to classical theories. A temporal trend in the number of children, consisting of three different phases, was observed, in accordance with the stability of living conditions in the region.

French invasive Asian tiger mosquito populations harbor reduced bacterial microbiota and genetic diversity compared to Vietnamese autochthonous relatives.

The Asian tiger mosquito Aedes albopictus is one of the most significant pathogen vectors of the twenty-first century. Originating from Asia, it has invaded a wide range of eco-climatic regions worldwide. The insect-associated microbiota is now recognized to play a significant role in host biology. While genetic diversity bottlenecks are known to result from biological invasions, the resulting shifts in host-associated microbiota diversity has not been thoroughly investigated. To address this subject, we compared four autochthonous Ae. albopictus populations in Vietnam, the native area of Ae. albopictus, and three populations recently introduced to Metropolitan France, with the aim of documenting whether these populations display differences in host genotype and bacterial microbiota. Population-level genetic diversity (microsatellite markers and COI haplotype) and bacterial diversity (16S rDNA metabarcoding) were compared between field-caught mosquitoes. Bacterial microbiota from the whole insect bodies were largely dominated by Wolbachia pipientis. Targeted analysis of the gut microbiota revealed a greater bacterial diversity in which a fraction was common between French and Vietnamese populations. The genus Dysgonomonas was the most prevalent and abundant across all studied populations. Overall genetic diversities of both hosts and bacterial microbiota were significantly reduced in recently established populations of France compared to the autochthonous populations of Vietnam. These results open up many important avenues of investigation in order to link the process of geographical invasion to shifts in commensal and symbiotic microbiome communities, as such shifts may have dramatic impacts on the biology and/or vector competence of invading hematophagous insects.

Indirect application of near infrared light induces neuroprotection in a mouse model of parkinsonism - an abscopal neuroprotective effect.

We have previously shown near infrared light (NIr), directed transcranially, mitigates the loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr treatment is that unilateral exposure can lead to a bilateral healing response, suggesting NIr may have 'indirect' protective effects. We investigated whether remote NIr treatment is neuroprotective by administering different MPTP doses (50-, 75-, 100-mg/kg) to mice and treating with 670-nm light directed specifically at either the head or body. Our results show that, despite no direct irradiation of the damaged tissue, remote NIr treatment produces a significant rescue of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta at the milder MPTP dose of 50-mg/kg (∼30% increase vs sham-treated MPTP mice, p<0.05). However this protection did not appear as robust as that achieved by direct irradiation of the head (∼50% increase vs sham-treated MPTP mice, p<0.001). There was no quantifiable protective effect of NIr at higher MPTP doses, irrespective of the delivery mode. Astrocyte and microglia cell numbers in substantia nigra pars compacta were not influenced by either mode of NIr treatment. In summary, the findings suggest that treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the 'abscopal effect' sometimes observed in radiation treatment of metastatic cancer. This discovery has implications for the clinical translation of light-based therapies, providing an improved mode of delivery over transcranial irradiation.

Effect of endurance training on skeletal muscle myokine expression in obese men: identification of apelin as a novel myokine.

BACKGROUND: It has been suggested that the metabolic benefits of physical exercise could be mediated by myokines. We examined here the effect of exercise training on skeletal muscle expression of a panel of myokines in humans. Pathways regulating myokine expression were investigated in human myotubes. METHODS: Eleven obese non-diabetic male subjects were enrolled in an 8-week endurance training program. Insulin sensitivity was assessed by an oral glucose tolerance test. Subcutaneous adipose tissue and Vastus lateralis muscle biopsy samples were collected before and after training. RNAs were prepared from adipose tissue and skeletal muscle. Primary culture of myoblasts was established. RESULTS: As expected, exercise training improved aerobic capacity and decreased fat mass. No significant change in interleukin 6, fibroblast growth factor 21, myostatin (MSTN) or irisin mRNA level was found in muscle after training. A twofold increase in apelin mRNA level was found in muscle but not in adipose tissue. No change in circulating myokine and adipokine plasma levels was observed in the resting state in response to training. Interestingly, apelin was significantly expressed and secreted in primary human myotubes. Apelin gene expression was upregulated by cyclic AMP and calcium, unlike the other myokines investigated. Importantly, changes in muscle apelin mRNA levels were positively related to whole-body insulin sensitivity improvement. CONCLUSION: Collectively, our data show that exercise training upregulates muscle apelin expression in obese subjects. Apelin expression is induced by exercise signaling pathways and secreted in vitro in human primary myotubes, and may behave as a novel exercise-regulated myokine with autocrine/paracrine action.

Impact of intrapancreatic or extrapancreatic bile duct involvement on survival following pancreatoduodenectomy for common bile duct cancer.

BACKGROUND: The clinicopathological factors that influence survival following pancreatoduodenectomy (PD) for common bile duct (CBD) cancer are not well known. This study aimed to investigate the effect of tumour involvement of the intrapancreatic versus extrapancreatic CBD on margin status, overall (OS) and disease-free (DFS) survival. METHODS: This was a retrospective study of patients who underwent PD for CBD cancer between 2001 and 2009. Pathological examination was performed according to a previously described standardized protocol based on axial slicing. Clinicopathological data and outcome in terms of margin status, DFS and OS were compared between cancers involving exclusively the intrapancreatic CBD (CBDin) and those involving the extrapancreatic CBD, in isolation or combined with invasion of the intrapancreatic part of the duct (CBDex). RESULTS: A total of 66 patients were enrolled. Most CBD cancers were locally advanced (97 per cent pathological (p) T3, 76 per cent pN1). Microscopic margin involvement (R1) was more frequent in CBDex than in CBDin cancers (34 of 39 versus 13 of 27; P = 0.001), more often multifocal (P < 0.001) and more frequently affected the periductal margin (P = 0.005). Venous resection was more often required for CBDex cancers (P = 0.009). CBDex cancers were associated with worse OS (median 21 versus 28 months; P = 0.020) and DFS (14 versus 31 months; P = 0.015), but the rate and site of recurrence did not differ. Metastasis to more than two lymph nodes was an independent predictor of OS and DFS. CONCLUSION: CBDex cancer is associated with a higher rate of R1 resection and venous resection after PD, and has a worse outcome than CBDin cancer.

Non-adrenergic, non-cholinergic, non-purinergic contractions of the urothelium/lamina propria of the pig bladder.

Acetylcholine, and to a lesser extent ATP, mediates neurogenic contractions of bladder smooth muscle. Recently, the urothelium and lamina propria have also been shown to have contractile properties, but the neurotransmitters involved in mediating responses to nerve stimulation have not been investigated. Isolated strips of porcine urothelium with lamina propria were electrically field stimulated and contractions recorded. Drugs interfering with neurotransmission were then employed to identify which neurotransmitters mediated responses. Strips of urothelium/lamina propria developed spontaneous contractions with a frequency of 3.5±0.1 cycles min⁻¹ and amplitude of 0.84±0.06 g. Electrical field stimulation at 5, 10, and 20 Hz resulted in frequency-related contractions (1.13±0.36 g, 1.59±0.46 g and 2.20±0.53 g, respectively, n=13), and these were reduced in the presence of tetrodotoxin (1 µm) by 77±20% at 5 Hz, 79±7% at 10 Hz and 74±12% at 20 Hz (all P<0.01), indicating they were predominantly neurogenic in nature. Neither the muscarinic antagonist atropine (10 µm), the adrenergic neurone blocker guanethidine (10 µm) nor desensitization of the purinergic receptors with α,ß-methylene ATP (10 µm) affected the contractile amplitude. Similarly, responses were not affected by the nitric oxide synthase inhibitor L-NNA (100 µm) or drugs that interfere with peptide neurotransmission (capsaicin, NK2 antagonist GR159897, protease inhibitors). In conclusion, electrical depolarization of the nerves present in the porcine urothelium/lamina propria results in frequency-dependent contractions, which are predominantly neurogenic in nature. These contractions are resistant to drugs that inhibit the adrenergic, cholinergic and purinergic systems. The neurotransmitter involved in the responses of this tissue is therefore unknown but does not appear to be a peptide.

First evidence and molecular characterization of Babesia vogeli in naturally infected dogs and Rhipicephalus sanguineus ticks in southern France.

Babesiosis is an emerging tick-borne disease of animals and humans caused by intraerythrocytic protozoa of the genera Babesia and Theileria. In France canine babesiosis has a high prevalence with Babesia canis thought to be the main aetiological agent of the disease. Babesia vogeli has already been reported to occur in Europe and in other countries around the Mediterranean Sea. The tick Rhipicephalus sanguineus, the main known vector of B. vogeli, occurs in southern France. However, only one case of a B. vogeli infected dog has been reported to date in France. To gain further insight into the prevalence of Babesia and Theileria infections in dogs and ticks of the R. sanguineus complex, a study was conducted in a veterinary practice in the south of France from January to September 2010. Twelve bloods from dogs and 36 R. sanguineus ticks were analyzed using PCR and sequencing. For the analysis of ticks, a new primer was designed to specifically amplify the B. vogeli 18S rRNA gene. Four dogs (33.3%) and 8 ticks (22.2%) were found to be infected with B. vogeli. This approach has thus revealed for the first time a cluster of cases of canine babesiosis caused by B. vogeli in France and highlights the need to systematically screen for pathogens potentially responsible for canine babesiosis at the species level using suitable molecular tools.

[Complete popliteal artery rupture one month after arthroscopic partial meniscectomy]. / Rotura completa de arteria poplítea de un mes de evolución, tras meniscectomía parcial artroscópica.

A patient suffered a complete popliteal artery injury one month after a partial arthroscopic meniscectomy. The patient complained of progressive and severe distal pain. A complete lesion of the popliteal artery was found. Distal vascular flow was barely supported by two geniculate arteries. Vascular repair was performed using open vascular surgery. Although the popliteal neurovascular bundle is close to the posterior capsule of the knee and is obviously potentially vulnerable, injuries in arthroscopy of the knee are very rare. To avoid catastrophic consequences, the possibility of vascular injuries following arthroscopy of the knee, even several weeks after the surgery must not be ruled out.

[Intraosseous access for fluid therapy in combat situations: use by Spanish military medical staff in Afghanistan]. / El acceso intraóseo para fluidoterapia en situación de combate. Experiencia de la sanidad militar española en Afganistán.

OBJECTIVES: To describe the Spanish military medical staff's experience with the use of intraosseous lines for fluid therapy in a combat zone. PATIENTS AND METHODS: Descriptive study of 25 patients (30 needles). The patients were injured by firearms or explosive devices, or had multiple injuries, and were attended by Spanish military physicians in western Afghanistan (Herat) between March 2007 and June 2008. RESULTS: The bone puncture was performed on 19 patients in prehospital settings. The remaining 6 patients underwent the procedure in the Spanish military hospital. All patients were men; the mean (SD) age was 26 (2.3) years. Most belonged to the Afghan National Army (64%) and had injuries caused by explosive devices (68%). The largest percentage of injuries involved the lower limbs (56%). A line could be inserted in 76% of the cases (100% at the military hospital). The first-choice site of puncture was the anterior tibial tuberosity. Fluids and medications were successfully administered through the intraosseous lines. No complications occurred during needle insertion, but 5 patients reported pain. CONCLUSION: Our experience suggests that intraosseous access can provide an alternative to venous access for treating trauma patients in combat zones.

Association of ß-2 adrenergic agonist and corticosteroid injection in the treatment of lipomas.

AIM: The aim of this study was to evaluate the efficacy of isoproterenol and prednisolone in the treatment of subcutaneous lipomas. METHODS: The first experiment evaluated in vitro lipolysis induced by isoproterenol 10(-6) M alone and across a range of prednisolone concentrations to determine the optimal dose to maximize lipolysis. The second experiment evaluated lipolysis in a lipoma and subcutaneous fat by in vivo microdialysis in five subjects to isoproterenol 10(-6) M with and without prednisolone 10(-6) M. These five subjects and five additional subjects had a lipoma treated five times a week for 4 weeks in a 4-cm grid with 0.2 ml injections of 10(-6) M isoproterenol and 10(-6) M prednisolone. Lipoma size was followed monthly for 1 year or until surgical removal. RESULTS: Prednisolone increased in vitro lipolysis to isoproterenol and 10(-6) M was the optimal concentration of both drugs. Lipomas responded with less lipolysis to isoproterenol than subcutaneous fat during microdialysis, and prednisolone treatment increased lipolysis in both lipomas and subcutaneous fat. Injection treatment of the lipomas decreased their volume 50%. All but one lipoma grew after treatment. Eight of the 10 subjects elected for surgical treatment, and the histology of the lipomas was normal fat tissue. CONCLUSIONS: Prednisolone and isoproterenol in combination increased lipolysis, and injections of the combination into lipomas decreased their volume 50% over 4 weeks. Eight of the 10 subjects elected for surgical removal.