Reliability of mechanical and phased-array designs for serial intravascular ultrasound examinations

Background: Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials. Methods: We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients. Results: Both systems correlated well for areas (r 0.90, p < 0.0001) and diameters (r 0.84, p < 0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: –0.24 and 0.96 mm², p < 0.055) and diameter (–0.08 and 0.16 mm, p < 0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (r 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small. Conclusions: Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials.     

Importance of planning ovulation induction therapy in systemic lupus erythematosus and antiphospholipid syndrome: a single center retrospective study of 21 cases and 114 cycles

OBJECTIVE: To analyze the results and complications of ovulation induction therapy (OIT) in women with systemic lupus erythematosus (SLE) and/or the antiphospholipid syndrome (APS). METHODS: A retrospective study of 21 women followed in a single tertiary-referral French center who underwent 114 OIT cycles with or without in vitro fertilization and embryo transfer (IVFET). RESULTS: Before OIT, SLE was present in 6 women, APS in 3, SLE-related APS in 3, and discoid lupus in 1. Eight women had no identified disease and underwent 36 cycles of OIT. Diagnosis (SLE, n = 3; primary APS, n = 5) was made after OIT complication: spontaneous abortion (n = 5), SLE flare (n = 2), and thrombophlebitis (n = 1). Five women with known disease intentionally concealed their history from their gynecologists and underwent 34 cycles. Forty-four cycles were planned in 11 women, in 3 of them after complications of prior OIT performed without particular therapy and monitoring. Eighteen pregnancies occurred, which ended in 9 live births, 4 fetal deaths, and 5 embryonic losses. The pregnancy rate was higher with gonadotropin and/or gonadotropin-releasing hormone analog (GnRHa) (25% of cycles) than with clomiphene (4% of cycles, P <.0001). When the gynecologists did not know the underlying disease, three-quarters of pregnancies induced by OIT with IVFET ended in embryonic losses or fetal deaths. In contrast, 6 of 7 pregnancies induced by planned OIT with IVFET ended in live births (P <.0001). Phlebothromboses were observed only with gonadotropin treatment. The SLE flare rate was higher with gonadotropin and/or GnRHa (27% of cycle) than with clomiphene (6%, NS). It also was higher (30%) when the gynecologists did not know the underlying disease than in the planned procedures (10%, NS). CONCLUSIONS: The OIT may precipitate SLE or APS. A careful review of the patient's history and appropriate laboratory tests should be undertaken before OIT. Clomiphene complications are rare. When gonadotropins are prescribed, preventive anti-inflammatory therapy should be considered in women with SLE, in addition to heparin and/or anti-aggregant therapy in patients with asymptomatic anti-phospholipid antibodies or prior thrombotic events.     

Treatment of diffuse large B-cell lymphoma

A review of new or emerging ideas concerning diffuse large B-cell lymphomas (DLBCL) is presented with particular emphasis on histologic classification, genetic prognostic factors, and first-line treatments. This lymphoma rests the most heterogeneous of all lymphomas for its clinical characteristics and outcome. This heterogeneity is probably secondary to the fact that a large proportion seems to occur from a transformation of an unknown indolent lymphoma. Current treatment is based on the combination of chemotherapy including cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) or dose-intense CHOP-like regimen, and rituximab (R-CHOP).     

Digital ischaemia aetiologies and mid-term follow-up: A cohort study of 323 patients

Upper extremity digital ischaemia (UEDI) is a rare heterogeneous condition whose frequency is 40 times less than that of toe ischaemia. Using a large cohort, the aim of this study was to evaluate aetiologies, prognosis and midterm clinical outcomes of UEDI.All patients with UEDI with or without cutaneous necrosis in a university hospital setting between January 2000 to December 2016 were included. Aetiologies, recurrence of UEDI, digital amputation and survival were analyzed retrospectively.Three hundred twenty three patients were included. UEDI due to cardio-embolic disease (DICE) was the highest occurring aetiology with 59 patients (18.3%), followed by DI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromboangiitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%), and cancer (6.2%). DICE patients tended to be older and featured more cases with arterial hypertension whereas TAO patients smoked more tobacco and cannabis. During follow-up, recurrences were significantly more frequent in SSc than in all other tested groups (P < .0001 vs idiopathic and DICE, P = .003 vs TAO) and among TAO patients when compared to DICE patients (P = .005). The cumulated rate of digital amputation was higher in the SSc group (n = 18) (P = .02) and the TAO group (n = 7) (P = .03) than in DICE (n = 2).This retrospective study suggests that main aetiologies of UEDI are DICE, SSc and idiopathic. This study highlights higher frequency of iatrogenic UEDI than previous studies. UEDI associated with SSc has a poor local prognosis (amputations and recurrences) and DICE a poor survival. UEDI with SSc and TAO are frequently recurrent.     

Model-Based Determination of Effective Blood Concentrations of Cyclosporine for Neutrophil Response in the Treatment of Severe Aplastic Anemia in Children

Optimal immunosuppressive therapy in acquired severe aplastic anemia (SAA) remains to be refined, especially cyclosporine (CsA) use. Current recommendations state that CsA trough blood concentrations (TBC) should be maintained between 200 and 400 ng/mL despite the lack of supporting data. This study aimed at quantifying relationships between CsA exposure and neutrophil response and determining an effective range for CsA TBC. Twenty-three SAA patients treated with CsA were retrospectively analyzed. Nonlinear mixed effect modeling approaches were used to develop a pharmacokinetic-pharmacodynamic model. The pharmacokinetic model described the relationships between CsA doses and TBC. The pharmacodynamic model allowed to estimate boundaries for optimal CsA effects, neutrophils being used as biomarker of response. A time-to-event model linked effective concentration to time-to-therapeutic success. CsA TBC were adequately described by a two-compartment model with first-order absorption, a lag time, and a linear elimination. The efficient range of CsA TBC was estimated between 87 and 120 ng/mL. Model-based simulations and external validation in three additional patients confirmed these results. This original modeling approach was successful in describing the relationship between CsA TBC and neutrophil response in SAA patients. Although further evaluation of the model is necessary, this work suggests that an optimal CsA TBC target of 100 ng/mL would be associated with a better neutrophil response in children with SAA.KEY WORDS: aplastic anemia, cyclosporine, modeling, pharmacokinetics, regulatory T lymphocytes     

Genomic aberrations of the CACNA2D1 gene in three patients with epilepsy and intellectual disability

Voltage-gated calcium channels have an important role in neurotransmission. Aberrations affecting genes encoding the alpha subunit of these channels have been associated with epilepsy and neuropsychiatric disorders such as autism or schizophrenia. Here we report three patients with a genomic aberration affecting the CACNA2D1 gene encoding the α₂δ subunit of these voltage-gated calcium channels. All three patients present with epilepsy and intellectual disability pinpointing the CACNA2D1 gene as an interesting candidate gene for these clinical features. Besides these characteristics, patient 2 also presents with obesity with hyperinsulinism, which is very likely to be caused by deletion of the CD36 gene.     

From the Cover: Bumblebees perceive the spatial layout of their environment in relation to their body size and form to minimize inflight collisions

Animals that move through complex habitats must frequently contend with obstacles in their path. Humans and other highly cognitive vertebrates avoid collisions by perceiving the relationship between the layout of their surroundings and the properties of their own body profile and action capacity. It is unknown whether insects, which have much smaller brains, possess such abilities. We used bumblebees, which vary widely in body size and regularly forage in dense vegetation, to investigate whether flying insects consider their own size when interacting with their surroundings. Bumblebees trained to fly in a tunnel were sporadically presented with an obstructing wall containing a gap that varied in width. Bees successfully flew through narrow gaps, even those that were much smaller than their wingspans, by first performing lateral scanning (side-to-side flights) to visually assess the aperture. Bees then reoriented their in-flight posture (i.e., yaw or heading angle) while passing through, minimizing their projected frontal width and mitigating collisions; in extreme cases, bees flew entirely sideways through the gap. Both the time that bees spent scanning during their approach and the extent to which they reoriented themselves to pass through the gap were determined not by the absolute size of the gap, but by the size of the gap relative to each bee’s own wingspan. Our findings suggest that, similar to humans and other vertebrates, flying bumblebees perceive the affordance of their surroundings relative their body size and form to navigate safely through complex environments.

Avoiding collisions with obstacles is a requirement for successful locomotion through most natural habitats, where the physical environment is often cluttered and complex. At the most elemental level, animals moving through their environments need to identify gaps between obstacles and assess their passability. In this context, whether a gap between obstacles “affords” passing is determined by the fit between the spatial layout of the environment and the properties of the organism’s form and action system, as described in classical theses on affordances (1–3). In humans and other highly cognitive vertebrates, the perception of affordances for performing visually guided actions such as grasping, passing through apertures, and climbing is actively shaped throughout ontogeny, as body size, configuration, and experience change (2, 4–7). However, the strategies used by animals with much smaller brains, such as insects, to contend with the challenges of navigating environmental clutter and spatial heterogeneity are unclear.We used bumblebees to investigate whether flying insects take into account their own size during interactions with their surroundings. Bumblebees and other volant insects that travel long distances (8) and frequently encounter regions of dense clutter can be expected to exhibit strategies to avoid collisions, because damage to sensitive structures such as the wings is irreparable and adversely impacts flight performance and lifespan (9, 10). For an animal attempting to navigate through tight spaces, perceiving the relationship between the layout of the environment and its own size can help inform the animal of its potential for collision-free passage. Bumblebee workers naturally display large variation in body size within a given colony (11, 12), and thus are particularly suitable models for testing the effects of insect body size on aerial navigation and for determining whether insects perceive the external environment in relation to their own spatial dimensions.To elicit repeatable flight behavior, we trained foraging bumblebees to fly within a 1.6 × 0.3 × 0.3 m (l × w × h) flight tunnel that separated the hive from a foraging arena (Materials and Methods, SI Appendix, Fig. S1, and Movie S1). After bees were habituated to the setup and began foraging normally, we placed an unexpected obstacle within the tunnel, consisting of a thin vertical wall (5-mm thickness) spanning the tunnel’s width and height. The obstructing wall contained a rectangular gap starting midway up and extending to the top of the wall (Materials and Methods, SI Appendix, Fig. S1, and Movie S1). The width of the gap was varied between 20 and 60 mm over different trials, with the presenting order of gap sizes chosen randomly. A high-speed camera placed above the tunnel was used to record bees’ instantaneous positions, heading/yaw orientations (Fig. 1A), and trajectories as they approached the obstructing wall and passed through the gap. To prevent bees from becoming familiar with the experimental paradigm, the obstructing wall was removed after each flight recording. In total, we recorded and analyzed over 400 flights of bees of varying body sizes flying through seven different gap sizes (SI Appendix, Table S1). For the population of bees recorded, wingspan was the longest dimension of the body and it varied linearly by a factor of 1.9 compared to their longitudinal body length while in flight (SI Appendix, Fig. S2A).Open in a separate windowFig. 1.Bumblebees can safely fly through gaps that are smaller than their wingspan. (A and B) Illustrations indicating the wingspan of bees (Ws), the size of the gap (Gs), and the positive and negative yaw (heading) angles for bees flying in the tunnel, respectively. (C) Schematic illustration of the flight of a bee flying through a gap that is much wider than its wingspan. (D) The instantaneous yaw angle of bee shown in C. (E) Schematic illustrationof the flightofabeeflying through a gap that is smaller than its wingspan. (F) The instantaneous yaw angle of bee shown in E. Flights, in both cases (C and E), consisted of approach, lateral peering, and—for the smaller gap size (E)—body reorientation (an increase in yaw angle) while passing through the gap. The differences in reorientation behavior can be noted at x = 0 (location of the gap), whereas in F the bee displays a large increase in yaw angle that reorients its body to pass through the small gap, and body reorientation in D is minimal. For the flight shown in C and D, Ws = 27.5 mm and Gs = 50 mm, while for the flight shown in E and F, Ws = 27 mm and Gs = 25 mm.     

All-cause and cardiovascular mortality using the different definitions of metabolic syndrome

The aim of the present study was to assess the risk of all-cause and cardiovascular disease (CVD) mortality in subjects identified as having metabolic syndrome (MS) using either the recent International Diabetes Federation (IDF) definition or the revised National Cholesterol Educational Program (NCEP-R) definition, but not the original NCEP (2001) definition. The study population was composed of 84,730 men and women without CVD aged > or =40 years who had a health checkup at the IPC Center. Follow-up for mortality was 4.7 +/-1.7 years. Prevalences of MS were 9.6%, 21.6%, and 16.5% according to the NCEP, IDF, and NCEP-R definitions, respectively. Compared with subjects without MS, risks of all-cause mortality associated with MS were 1.63 (95% confidence interval [CI] 1.38 to 1.93) with the NCEP, 1.25 (95% CI 1.09 to 1.45) with the IDF, and 1.32 (95% CI 1.13 to 1.53) with the NCEP-R, and risks of CVD mortality were 2.05 (95% CI 1.28 to 3.28), 1.77 (95% CI 1.18 to 2.64), and 1.64 (95% CI 1.08 to 2.50), respectively. In subjects with MS detected using the IDF and NCEP-R definitions, but not the NCEP definition, risks of all-cause mortality were 1.07 (95% CI 0.89 to 1.28) and 0.92 (95% CI 0.73 to 1.18) and 1.42 (95% CI 0.86 to 2.34) and 1.07 (95% CI 0.55 to 2.09) for CVD mortality, respectively. In conclusion, in a large French population, the recent definitions of MS almost double the prevalence compared with the original definition. Subjects identified as having MS using only the recent definitions and not the original definition did not have higher rates of all-cause and CVD mortality compared with subjects without MS during follow-up.     

A prospective national study on colonoscopy and sigmoidoscopy in 2000 in France

AIM: The aim of this study was to evaluate the practice of colonoscopy and sigmoidoscopy in France in 2000. METHODS: A prospective study was conducted in November 2000 using questionnaires sent to all gastroenterologists practicing in France (N=2858) who were asked to reply to items concerning colonoscopies and sigmoidoscopies performed on two workdays chosen in advance. The response rate was 32.8%. Data were extrapolated to establish estimates for the entire year. RESULTS: An estimated 894000 colonoscopies and 115320 sigmoidoscopies were performed in 2000. Single-use material was used in 22.1% of the procedures. Indications for endoscopy were mainly hematochezia (21.6%), gastrointestinal symptoms (35%) and surveillance of patients with a history of previous polypectomy (15%). Colorectal cancer screening was the indication for 20% of colonoscopies. Abnormal findings were reported for 54.8% of the endoscopies (polyps for 287218 procedures and cancer for 32799). Failure was noted in 4.9% of colonoscopies. The complication rate was 0.48%. Most polyps were adenomas (64.4%) or hyperplasic polyps (28.1%). The overall estimated number of colonoscopies with polypectomy was 224133. CONCLUSION: In 2000 there was an increased rate of colonoscopy for colorectal cancer screening (20%) but an overall decrease (2.5%) in the total number of colonoscopies compared to 1999. Abnormal findings were disclosed by 54.8% of the procedures. Extrapolation from these data indicates that colonoscopic screening enabled the diagnosis of 32799 colorectal cancers.