How to treat venous thromboembolism (TVE) in cancer patients: ten years of multidisciplinary team meetings (MDTM) at Saint-Louis Hospital.

BACKGROUND: - The management of venous thromboembolism (VTE) is particularly challenging in patients with cancer who undergo complex treatment protocols. Cancer patients often have comorbidities which may affect the efficacy and safety of anticoagulant treatments. Coordinated multidisciplinary management of these complex cases can help optimize delivery of individualized anticoagulant treatment. AIMS: - To describe the multidisciplinary team meeting (MDTM) for the management of VTE in cancer patients at our institution and to document outcomes in these patients. METHODS: - Bi-monthly MDTMs attended by different physicians and nurses were established at Saint-Louis Hospital in 2008. We performed a retrospective analysis of all cases discussed between September 2008 and January 2018. RESULTS: - Over a 10-year period, 520 patients were discussed a total of 551 times. Their mean age was 63 years with 278 (53%) women. The most frequent primary cancer sites were breast (23%), genitourinary (21 %), hematological (20%), digestive (15%), and lung (9%). Fifty-two percent of patients had metastatic cancer, and 54% of them were receiving chemotherapy. The optimal treatment for pulmonary embolism (17%), deep vein thrombosis (16%), catheter-related thrombosis (20%) or combined events (46%) was discussed. Twenty-three patients (4.4%) were discussed for one VTE recurrence and 4 (0.8%) for 2 recurrences. CONCLUSIONS: - A dedicated MDTM for the management of VTE in cancer patients allows to discuss a wide range of clinical scenarios and contributes to optimal adherence to evidence-based clinical practices guidelines. The MDTM evaluation was successfully carried out within a short time-frame of VTE diagnosis and helped optimize individualized treatment plans.

Management of cancer-related thrombosis in the era of direct oral anticoagulants: A comprehensive review of the 2019 ITAC-CME clinical practice guidelines. On behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of death after cancer progression. VTE management and prophylaxis are critical in cancer patients, but effective therapy can be challenging because these patients are at higher risk of VTE recurrence and bleeding under anticoagulant treatment. Numerous published studies report inconsistent implementation of existing evidence-based clinical practice guidelines (CPG), including underutilization of thromboprophylaxis, and wide variability in clinical practice patterns across different countries and various practitioners. This review aims to summarize the 2019 ITAC-CME evidence-based CPGs for treatment and prophylaxis of cancer-related VTE, which include recommendations on the use of direct oral anticoagulants specifically in cancer patients. The guidelines underscore the gravity of developing VTE in cancer and recommend the best approaches for treating and preventing cancer-associated VTE, while minimizing unnecessary or over-treatment. Greater adherence to the 2019 ITAC guidelines could substantially decrease the burden of VTE and improve survival of cancer patients.

Quantification of microfibre levels in South Africa's beach sediments, and evaluation of spatial and temporal variability from 2016 to 2017.

The microfibre content of beach sediment samples was established at 175 sampling sites along over 2700 km of South Africa's coastline in 2016 and again in 2017. The average microfibre content was 80 ±â€¯102 F/dm3 in Feb/March 2017 (n = 161), and 87 ±â€¯84 F/dm3 in May/June 2016 (n = 128). These average values, and the observed ranges of 0 to 797 F/dm3 in 2017 and 4 to 772 F/dm3 in 2016, are consistent with global observations. The highest microfibre levels were observed at sampling sites close to large coastal waste water treatment work discharge points. Several instances of temporal variability are observed, only some of which can be associated with seasonal changes in river runoff. This baseline data set is a valuable reference point for identification of priority study sites for more detailed study of marine ecosystem response to microfibre pollution.

Major bleeding complications in patients treated with direct oral anticoagulants: One-year observational study in a Paris Hospital.

Direct oral anticoagulants (DAOC) are indicated for the treatment of venous thromboembolism and the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Given their advantages and friendly use for patient, the prescription of long term DOAC therapy has rapidly increased both as first line treatment while initiating anticoagulation and as a substitute to vitamins K antagonist (VKA) in poorly controlled patients. However, DOAC therapy can also be associated with significant bleeding complications, and in the absence of specific antidote at disposal, treatment of serious hemorrhagic complications under DOAC remains complex. We report and discuss herein five cases of major hemorrhagic complications under DOAC, which were reported to the pharmacological surveillance department over one year at Saint-Louis University Hospital (Paris, France). We further discuss the need for careful assessment of the risk/benefit ratio at time of starting DOAC therapy in daily clinical practice.

Correlation between veno-venous anastomoses, TTTS and perinatal mortality in monochorionic twin pregnancies.

INTRODUCTION: The clinical significance of veno-venous (VV) anastomoses in monochorionic (MC) placentas remains inconclusive and controversial. The purpose of this study was to investigate the correlation between the presence of VV anastomoses and clinical outcome in a large cohort of MC twin pregnancies. METHODS: All MC placentas injected with colored dye from 2002 to 2014 were included in the study. We excluded MC pregnancies managed with fetoscopic laser surgery. RESULTS AND DISCUSSION: A total of 384 MC placentas were analyzed. VV anastomoses were detected in 27% (104/384) of MC placentas. The prevalence of twin-twin transfusion syndrome (TTTS) in MC placentas with VV anastomoses was significantly higher compared to MC placentas without VV anastomoses, 20% (21/104) versus 10% (29/280), respectively (P = .01). The overall perinatal mortality in MC twins with and without VV anastomoses was 16% versus 10%, respectively (P = .02). Risk factor analysis showed the presence of VV anastomoses was associated with perinatal mortality (P = .02; odds ratio (OR): 1.76; 95% confidence interval (CI): 1.11-2.79), but was not an independent risk factor for perinatal mortality (P = .26, OR: .66; 95% CI: .33-1.35) in MC twin pregnancies. However, VV anastomoses was associated with and was an independent risk factor for TTTS (P = .00, OR: 3.59; 95% CI: 1.72-7.47). VV anastomoses-related perinatal mortality may be due to the high rate of TTTS in MC twins with VV anastomoses. CONCLUSION: The presence of VV anastomoses is correlated with TTTS and perinatal mortality, but is not an independent risk factor for perinatal mortality in MC twin pregnancies.

Velamentous cord insertion in monochorionic twins with or without twin-twin transfusion syndrome: Does it matter?

OBJECTIVE: To study the association between velamentous cord insertion (VCI) and different outcomes in monochorionic twins with and without twin-twin transfusion syndrome (TTTS). METHODS: We recorded the cord insertion type in all consecutive monochorionic placentas examined in two tertiary medical centers. The association between VCI and several outcomes was estimated. RESULTS: A total of 630 monochorionic placentas with TTTS (n = 304) and without TTTS (n = 326) were studied. The incidence of VCI in the TTTS and non-TTTS group was 36.8% and 35.9%, respectively (P = 0.886). The presence of VCI in one twin was significantly associated with small for gestational age (SGA) status (odds ratio [OR] 1.45, 95% CI 1.13, 1.87) and severe birth weight discordance (OR 3.09, 95% CI 1.93, 4.96). Our results also showed significant interaction between TTTS and VCI when we considered intrauterine fetal demise (IUFD) and gestational age (GA) at birth. The prevalence of IUFD in monochorionic pregnancies without TTTS increased from 4.6% to 14.1% in the presence of VCI (P = 0.027). In the TTTS group, the prevalence of IUFD was comparable in the absence or presence of VCI. Similarly, GA at birth was significantly lower in the presence of VCI only in the non-TTTS group. CONCLUSION: Our findings suggest that VCI is not associated with the development of TTTS but increases the risk of adverse outcomes. Both VCI and TTTS independently increase the prevalence of IUFD and lower GA at birth in a similar way, showing that VCI is an important indicator of adverse perinatal outcome in monochorionic twins.

Prevalence, size, number and localization of vascular anastomoses in monochorionic placentas.

INTRODUCTION: Most monochorionic (MC) twin pregnancies have an uncomplicated course, but some develop severe complications including selective intrauterine growth restriction (sIUGR), twintwin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). The underlying pathogenesis of these various complications is associated with the ubiquitous presence of vascular anastomoses in MC placentas. METHODS: The aim of this study was to estimate the prevalence, number, size and localization of the anastomoses in sIUGR, TTTS and TAPS placentas compared to normal MC placentas using color dye injection. We excluded MC twin pregnancies treated with fetoscopic laser surgery or selective feticide. RESULTS: A total of 235 placentas fulfilled the inclusion criteria: 126 normal MC, 47 TTTS, 46 sIUGR and 16 spontaneous TAPS. Median number of anastomoses in normal MC, sIUGR, TTTS and TAPS placentas was 8 (IQR: 4-12), 8 (IQR: 5-14), 7 (IQR: 5-11) and 4 (IQR: 3-5), respectively. The prevalence of arterio-arterial (AA) anastomoses in normal MC, sIUGR, TTTS and TAPS placentas was 96%, 98%, 47% and 19%, respectively. We found AV anastomoses to be evenly distributed along the vascular equator in all MC placentas except in TAPS cases, where anastomoses were mostly localized near the margin. We also found that, in sIUGR and TTTS placentas, AA anastomoses tended to be at the center of the placenta. CONCLUSION: The present study shows that the prevalence, size, number and localization of the various types of anastomoses differ between normal MC, sIUGR, TTTS and TAPS placentas.

Placental characteristics in monochorionic twins with spontaneous versus post-laser twin anemia-polycythemia sequence.

INTRODUCTION: Twin anemia-polycythemia sequence (TAPS) may occur in monochorionic twins either spontaneously or after laser surgery for twin-twin transfusion syndrome. Our aim was to analyze the placental angioarchitecture in spontaneous versus post-laser TAPS. METHODS: We included all monochorionic twin placentas with spontaneous or post-laser TAPS injected at our center between 2002 and 2012. Placental angioarchitecture was evaluated using colored dye injection. RESULTS: A total of 600 monochorionic placentas were injected during the study period of which 43 (7.2%) with TAPS (spontaneous TAPS, n = 16; post-laser TAPS, n = 27). Almost all anastomoses (96%; 119/124) were very small (diameter <1 mm) and the majority was localized near the placental margin. The median number of anastomoses per placenta was 4 (interquartile range (IQR): 3-5) in the spontaneous TAPS group and 2 (IQR: 1-3) in the post-laser TAPS group (p = 0.003). Arterio-arterial (AA) anastomoses were detected in 14.0% (6/43) of TAPS placentas and were all minuscule (diameter <1 mm). The rate of AA anastomoses in the spontaneous TAPS group and post-laser TAPS group was 18.8% (3/16) and 11.1% (3/27), respectively (p = 0.184). DISCUSSION: Spontaneous TAPS placentas have a significantly higher total number of anastomoses compared to post-laser TAPS placentas. Most anastomoses were localized near the margins of the placenta. Minuscule AA anastomoses were detected sporadically in both groups and the rate of AA anastomoses is slightly higher in the spontaneous TAPS group than in the post-laser group. CONCLUSION: Spontaneous TAPS placentas have a different placental angioarchitecture than post-laser TAPS placentas in terms of number and type of vascular anastomoses.

Arterio-arterial vascular anastomoses in monochorionic placentas with and without twin-twin transfusion syndrome.

We performed a matched case-control study to analyze the placental angioarchitecture, in particular the diameter of arterio-arterial (AA) anastomoses in monochorionic placentas from pregnancies with twin-twin transfusion syndrome (TTTS) compared to a control group of uncomplicated monochorionic placentas. Placental angioarchitecture was analyzed using colored dye injection. AA anastomoses were detected in 37% (14/38) of TTTS placentas versus 91% (209/228) in control placentas (p < 0.001). The median diameter of AA anastomoses in the group with and without TTTS was 1.9 mm and 2 mm, respectively (p = 0.711). In conclusion, our findings show that AA anastomosis occur less frequently in TTTS placentas, supporting the concept of the protective role of AA anastomoses in TTTS. However, the size of the AA anastomosis, when present, does not appear to influence the pathophysiology of the disease.

Arterio-arterial vascular anastomoses in monochorionic twin placentas with and without twin anemia-polycythemia sequence.

We performed a matched case-control study to analyze the placental angioarchitecture, in particular the diameter of arterio-arterial (AA) anastomoses in monochorionic placentas from pregnancies with spontaneous twin anemia-polycythemia sequence (TAPS) compared to a control group of uncomplicated monochorionic placentas. Placental angioarchitecture was analyzed using colored dye injection. AA anastomoses were detected in 20% (3/15) of spontaneous TAPS placentas. The median diameter of AA anastomoses in the group with and without TAPS was 0.4 mm and 2.2 mm, respectively (p = 0.01). In conclusion, AA anastomoses are rarely detected in TAPS placentas. When present, the AA anastomosis is very small, preventing equilibration of hemoglobin levels between both twins.

Genetic structure and relationships within and between cultivated and wild sorghum (Sorghum bicolor (L.) Moench) in Kenya as revealed by microsatellite markers.

Understanding the extent and partitioning of diversity within and among crop landraces and their wild/weedy relatives constitutes the first step in conserving and unlocking their genetic potential. This study aimed to characterize the genetic structure and relationships within and between cultivated and wild sorghum at country scale in Kenya, and to elucidate some of the underlying evolutionary mechanisms. We analyzed at total of 439 individuals comprising 329 cultivated and 110 wild sorghums using 24 microsatellite markers. We observed a total of 295 alleles across all loci and individuals, with 257 different alleles being detected in the cultivated sorghum gene pool and 238 alleles in the wild sorghum gene pool. We found that the wild sorghum gene pool harbored significantly more genetic diversity than its domesticated counterpart, a reflection that domestication of sorghum was accompanied by a genetic bottleneck. Overall, our study found close genetic proximity between cultivated sorghum and its wild progenitor, with the extent of crop-wild divergence varying among cultivation regions. The observed genetic proximity may have arisen primarily due to historical and/or contemporary gene flow between the two congeners, with differences in farmers' practices explaining inter-regional gene flow differences. This suggests that deployment of transgenic sorghum in Kenya may lead to escape of transgenes into wild-weedy sorghum relatives. In both cultivated and wild sorghum, genetic diversity was found to be structured more along geographical level than agro-climatic level. This indicated that gene flow and genetic drift contributed to shaping the contemporary genetic structure in the two congeners. Spatial autocorrelation analysis revealed a strong spatial genetic structure in both cultivated and wild sorghums at the country scale, which could be explained by medium- to long-distance seed movement.

Pattern formation in draining thin film suspensions.

We demonstrate the emergence of complexity from remarkably simple and ubiquitous systems: draining thin-film suspensions exhibiting a striking transition between two classes of self-organizing patterns. Vertical channels form when attractive forces lead to transient gelation, while horizontal bands result from granular mixtures. We propose an explanation whereby the generic physical mechanisms require only the existence of viscous and excluded-volume couplings among the particles, solvent, and substrate. System-specific, small inhomogeneities trigger large-scale pattern formation, through collective dynamics, where jamming plays a crucial role. Our results shed light on emergent complexity in bio- and geophysical processes and have implications for coatings and food industries.

Active immunization against nicotine suppresses nicotine-induced dopamine release in the rat nucleus accumbens shell.

BACKGROUND: Tobacco smoking is the largest preventable cause of morbidity and premature mortality in the world. Although its medical consequences are well documented, 20-50% of the population even in developed countries remain tobacco smokers. The drugs presently used in smoking cessation have limited efficiency and, therefore, there is a need for alternative and improved treatments. One novel approach in this regard may be provided by immunization against nicotine. OBJECTIVE: The present study in male Wistar rats investigated if active immunization with a novel nicotine immunogen, IP18-KLH, may generate nicotine-selective antibodies and, furthermore, whether this treatment might prevent nicotine from exerting its stimulating effect on the mesolimbic, dopaminergic reward system in the brain. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to determine the titer of nicotine antibodies in plasma after immunization with IP18-KLH in Freund's adjuvant. Competitive ELISA was used to assess the selectivity of the antibodies. Finally, we used in vivo voltammetry to investigate whether active immunization with IP18-KLH could prevent nicotine-induced dopamine release in the shell of nucleus accumbens (NAC(shell)). RESULTS: The present study shows that active immunization with IP18-KLH generates antibodies that are highly selective for nicotine. Furthermore, immunization with IP18-KLH prevented the nicotine-induced increase in dopamine release in the NAC(shell), a biochemical correlate to the rewarding properties of nicotine. CONCLUSIONS: Active immunization with IP18-KLH prevents a central effect of nicotine that is considered critical for the induction of nicotine dependence. Consequently, active immunization may provide long-term protection against initiation of tobacco dependence, an effect that may prove particularly advantageous in relapse prevention.

Active immunization against nicotine prevents reinstatement of nicotine-seeking behavior in rats.

BACKGROUND: The presently available pharmaceutical aids in smoking cessation possess a rather limited effectiveness. Therefore, we have synthesized a series of immunoconjugates that stimulate the induction of antibodies which may bind nicotine in the blood, thereby preventing it from passing the blood-brain barrier. Thus, the reinforcing action of nicotine in the brain, which is the driving force in tobacco smoking, should be abolished. OBJECTIVE: The present study was undertaken to test this notion in a long-term relapse model in rats, measuring the reinstatement of nicotine-seeking behavior, following active immunization with IP18-KLH, one of our immunoconjugates. METHODS: Male Wistar rats were immunized with a nicotine-KLH conjugate (nicotine immunogen) and Freund's adjuvant after having been trained to meet the criteria of stable nicotine self-administration on a fixed ratio (FR3) schedule. The rats were subsequently extinguished from nicotine self-administration behavior and finally, as extinction was completed, they were exposed to small, priming doses of nicotine, which previously have been shown to reinstate the nicotine-seeking behavior. The antibody titers were measured by ELISA. RESULTS: It was found that rats with high titers (>1:10,000) of antibodies against nicotine, in contrast to those with low/no nicotine selective antibodies, do not reinstate nicotine self-administration behavior when they are exposed to nicotine. CONCLUSIONS: Our findings indicate that active immunization against nicotine may effectively abolish the reinforcing action of nicotine in brain, an effect which is critical for relapse in nicotine dependence. These data suggest the potential utility of active immunization in smoking cessation programs.

Nicotine-induced Fos expression in the nucleus accumbens and the medial prefrontal cortex of the rat: role of nicotinic and NMDA receptors in the ventral tegmental area.

We have previously shown that the nicotine-induced dopamine release in the nucleus accumbens can be attenuated by local administration into the ventral tegmental area (VTA), of antagonists at nicotinic and N-methyl-D-aspartate (NMDA), but not alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. In the present study, we investigated the role of nicotinic and NMDA receptors in the VTA for the expression of Fos-like immunoreactivity (FLI) in the shell and core of the nucleus accumbens and in the medial prefrontal cortex (mPFC) of the rat after acute nicotine administration. Systemically administered nicotine increased FLI in both the mPFC and the nucleus accumbens when compared to saline controls, although this effect was more pronounced, and reached statistical significance in the nucleus accumbens, especially in the core region. When mecamylamine was delivered by reverse dialysis into the VTA, the systemic nicotine-induced FLI was significantly attenuated in the nucleus accumbens. Similarly, the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5), infused locally in the VTA, also antagonized the nicotine-induced FLI in the nucleus accumbens. Neither mecamylamine nor AP-5 alone affected basal FLI levels in any of the structures studied. Local administration of nicotine in the VTA increased FLI in the nucleus accumbens but not in the mPFC. Since the nicotine-induced FLI is probably due to an increased dopamine release in both the nucleus accumbens and the mPFC, we conclude that FLI in the nucleus accumbens is mediated, to a large extent, through the activation of dopamine neurons via nicotinic and NMDA receptors in the VTA, whereas the nicotine-induced FLI in the mPFC is subjected to a differential control mechanism, tentatively involving nicotinic receptors at the terminal level of the mPFC-projecting dopamine neurons.

Detection of low-temperature hydrothermal fluxes by seawater Mg and Ca anomalies

Geochemical fluxes into and out of the ocean control its chemical composition. Measurements of the magnesium (Mg) content of seawater, an assumed "conservative" element in the ocean, reveal mid-depth Mg depletions in the vicinity of the East Pacific Rise. The magnitude of the anomalies suggests that fluxes associated with the low-temperature circulation of seawater through axial mid-ocean ridge systems are much larger than the high-temperature axial component. A higher total axial hydrothermal flux provides a mechanism that simultaneously satisfies the mass balance requirement of several major seawater constituents.

Secondary carriage with multi-resistant Acinetobacter baumannii and Klebsiella pneumoniae in an adult ICU population: relationship with nosocomial infections and mortality.

A one year prospective, observational survey was performed to evaluate the abnormal carriage of multi-resistant Klebsiella pneumoniae and/ or Acinetobacter baumannii, to determine associated risk factors for carriage, and to correlate the abnormal carriage with infectious morbidity and mortality in the intensive care unit (ICU) of a University Hospital. Two hundred and ninety-eight patients who stayed in the ICU > 48h, and were not neutropenic, were studied. Salivary and rectal samples were obtained on admission and weekly until discharge. Out of 265 evaluable patients, 88 (33%) developed oropharyngeal and/or rectal carriage within a median of nine days. Three factors were significantly associated with abnormal carriage: higher 'severity of illness' score on admission, a threefold increase in ICU stay, and the need for mechanical ventilation. K. pneumoniae or A. baumannii accounted for 57/158 (36%) of all ICU-acquired infections (in 46 patients). They were considered as secondary endogenous infections (SEI) in 42 patients who were previously colonized with the same strains, and developed infection within a median of three days (range 0-68 days). Prolonged stay in ICU was the only factor associated with SEI in the carrier population. Mortality was significantly greater in the carrier group (43 vs 25%, P = 0.0006). Post hoc stratification suggested that abnormal carriage only influenced mortality in patients showing a low severity of illness score on admission to ICU. Abnormal carriage was found in the most severely ill patients, predisposed to secondary nosocomial infections, and could influence mortality in the less severely ill.

Biological Controls on Coral Sr/Ca and dgr18O Reconstructions of Sea Surface Temperatures.

Coral strontium/calcium ratios have been used to infer that the tropical sea surface temperature (SST) cooled by as much as 6 degrees C during the last glacial maximum. In contrast, little or no change has been inferred from other marine-based proxy records. Experimental studies of the effect of growth rate and the magnitude of intraspecific differences indicate that biological controls on coral skeletal strontium/calcium uptake have been underestimated. These results call into question the reliability of strontium/calcium-based SST reconstructions.