Kenneth A. Myers

Classification and Grading of Chronic Venous Disease in the Lower Limbs-A Consensus Statement-

Classification and grading of chronic venous disease in the lower limbs : A consensus statement

Venous thrombosis from air travel: the LONFLIT3 study--prevention with aspirin vs low-molecular-weight heparin (LMWH) in high-risk subjects: a randomized trial.

The LONFLIT1 and 2 studies established that in high-risk subjects after long (> 10 hours) flights, the incidence of deep venous thrombosis (DVT) may be between 4% and 6%. The LONFLIT3 study aimed to evaluate methods of prevention in high-risk subjects. Of 467 subjects contacted for the study, 300 were included. These 300 subjects at high risk for DVT were randomized, after informed consent, into three groups: 1) a control group that had no prophylaxis; 2) an aspirin treatment group, in which patients were treated with 400 mg , (tablets of oral, soluble aspirin; one dose daily for 3 days, starting 12 hours before the beginning of the flight); and 3) a low-molecular-weight heparin (LMWH) group, in which one dose of enoxaparine was injected between 2 and 4 hours before the flight. The dose was weight-adjusted (1000 IU [equivalent to 0.1 mL] per 10 kg of body weight). Subjects with potential problems due to prophylaxis with aspirin or LMWH or at risk of drug interactions were excluded. Of the 100 included subjects in each group, a total of 249 subjects completed the study (dropouts due to low compliance or traveling/connections problems were 17%). Age and sex distribution were comparable in the three groups as well as risk distributions. Mean age was 47 (range, 28-75; SD, 11; 65% males). Of the 82 subjects in the control group, there were 4.82% of subjects with DVT with two superficial thromboses. In total 4.8% of limbs suffered a thrombotic event. Of 84 subjects in the aspirin treatment group, there were 3.6% of patients with DVT and three superficial thrombosis. In total 3.6% of limbs had a throm botic event. In the LMWH group (82 subjects), there were no cases of DVT. One superficial thrombosis was documented. In total only 0.6% of limbs had a thrombotic event (p < 0.002 in comparison with the other two groups). DVT was asymptomatic in 60% of subjects; 85% of DVTs were observed in passengers in non-aisle seats. Mild gastrointestinal symptoms were reported in 13% of patients taking aspirin. One dose of LMWH is an important option to consider in high-risk subjects during long-haul flights.

Venous Thromboembolism from Air Travel The LONFLIT Study

The LONFLIT study was planned to evaluate the incidence of deep venous thrombosis (DVT) occurring as a consequence of long flights. In the Lonflit 1 study 355 subjects at low-risk for DVT and 389 at high-risk were studied. Low-risk subjects had no cardiovascular disease and used no drugs. All flights were in economy class. The average flight duration was 12.4 hours (range, 10-15 hr). The mean age of the studied subjects was 46 years (range 20-80 yr, SD 11; 56% males). DVT diagnosis was made by ultrasound scans after the flights (within 24 hours). In low-risk subjects no events were recorded while in high-risk subjects 11 had DVT (2.8%) with 13 thromboses in 11 subjects and 6 superficial thromboses (total of 19 thrombotic events in 389 patients [4.9%]). In the Lonflit2 study the authors studied 833 subjects (randomized into 422 control subjects and 411 using below-knee stockings). Mean age was 44.8 years (range, 20-80 yr, SD 12; 57% males). The average flight duration was 12.4 hours. Scans were made before and after the flights. In the control group there were 4.5% of subjects with DVT while only 0.24% of subjects had DVT in the stockings group. The difference was significant. The incidence of DVT observed when subjects were wearing stockings was 18.75 times lower than in controls. Long-haul flights are associated to DVT in some 4-5% of high-risk subjects. Below-knee stockings are beneficial in reducing the incidence of DVT.

Duplex ultrasonography scanning for chronic venous disease : patterns of venous reflux

PURPOSE Patterns of flow in superficial and deep veins and outward flow in medial calf perforators were studied by duplex ultrasonography scanning in 1653 lower limbs in 1114 consecutive patients. This study compares results in 776 limbs with primary uncomplicated varicose veins with those in 166 limbs with the complications of lipodermatosclerosis or past venous ulceration. METHODS Duplex scanning determined whether superficial and deep veins were occluded or showed reflux and whether outward flow occurred in medial calf perforators with calf muscle contraction. RESULTS Two proximal deep veins were occluded. When limbs with primary uncomplicated varicose veins, lipodermatosclerosis, or past ulceration were compared, superficial reflux alone was seen in 55%, 39%, and 38%, deep reflux alone was seen in 2%, 7%, and 8%, and combined superficial and deep reflux was seen in 18%, 34%, and 48%, respectively. Superficial reflux affected the long saphenous system alone in 58%, 57%, and 40%, the short saphenous system alone in 18%, 18%, and 26%, and both the long and short saphenous systems in 24%, 25%, and 34%, respectively. Limbs with ulceration more frequently showed superficial reflux (p < 0.05), and all limbs with complications more frequently showed short saphenous reflux (p < 0.05) and deep reflux (p < 0.01) specifically in the posterior tibial veins (p < 0.01). Outward flow was seen in medial calf perforators in 57%, 67%, and 66%, respectively; it occurred more frequently in all limbs with complications (p < 0.05). Isolated outward flow in perforators without superficial or deep reflux was seen in 10%, 10%, and 2%, respectively. CONCLUSIONS Most limbs with complications had superficial reflux either alone or combined with deep reflux, and few had deep reflux alone. Reflux was more frequent in posterior tibial veins for limbs with complications compared with those with uncomplicated primary varicose veins. Outward flow in perforators was common in limbs with complications and with uncomplicated primary varicose veins, but isolated outward flow in perforators was uncommon. Treatment directed to the superficial veins alone may be sufficient for most patients with complications.

Hydrostatic pressure sensation in cells : integration into the tensegrity model

Hydrostatic pressure (HP) is a mechanical stimulus that has received relatively little attention in the field of the cell biology of mechanotransduction. Generalized models, such as the tensegrity model, do not provide a detailed explanation of how HP might be detected. This is significant, because HP is an important mechanical stimulus, directing cell behaviour in a variety of tissues, including cartilage, bone, airways, and the vasculature. HP sensitivity may also be an important factor in certain clinical situations, as well as under unique environmental conditions such as microgravity. While downstream cellular effects have been well characterized, the initial HP sensation mechanism remains unclear. In vitro evidence shows that HP affects cytoskeletal polymerization, an effect that may be crucial in triggering the cellular response. The balance between free monomers and cytoskeletal polymers is shifted by alterations in HP, which could initiate a cellular response by releasing and (or) activating cytoskeleton-associated proteins. This new model fits well with the basic tenets of the existing tensegrity model, including mechanisms in which cellular HP sensitivity could be tuned to accommodate variable levels of stress.

Whole‐exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation

We present a 4‐year‐old girl with profound global developmental delay and refractory epilepsy characterized by multiple seizure types (partial complex with secondary generalization, tonic, myoclonic, and atypical absence). Her seizure semiology did not fit within a specific epileptic syndrome. Despite a broad metabolic and genetic workup, a diagnosis was not forthcoming. Whole‐exome sequencing with a trio analysis (affected child compared to unaffected parents) was performed and identified a novel de novo missense mutation in GRIN2A, c.2449A>G, p.Met817Val, as the likely cause of the refractory epilepsy and global developmental delay. GRIN2A encodes a subunit of N‐methyl‐d‐aspartate (NMDA) receptor that mediates excitatory transmission in the central nervous system. A significant reduction in the frequency and the duration of her seizures was observed after the addition of topiramate over a 10‐month period. Further prospective studies in additional patients with mutations in GRIN2A will be required to optimize seizure management for this rare disorder. This report expands the current phenotype associated with GRIN2A mutations.

Hydrostatic pressure stimulation of human mesenchymal stem cells seeded on collagen-based artificial extracellular matrices.

Human mesenchymal stem cells (hMSCs) from bone marrow are considered a promising cell source for bone tissue engineering applications because of their ability to differentiate into cells of the osteoblastic lineage. Mechanical stimulation is able to promote osteogenic differentiation of hMSC; however, the use of hydrostatic pressure (HP) has not been well studied. Artificial extracellular matrices containing collagen and chondroitin sulfate (CS) have promoted the expression of an osteoblastic phenotype by hMSCs. However, there has been little research into the combined effects of biochemical stimulation by matrices and simultaneous mechanical stimulation. In this study, artificial extracellular matrices generated from collagen and/or CS were coated onto polycaprolactone-co-lactide substrates, seeded with hMSCs and subjected to cyclic HP at various time points during 21 days after cell seeding to investigate the effects of biochemical, mechanical, and combined biochemical and mechanical stimulations. Cell differentiation was assessed by analyzing the expression of alkaline phosphatase (ALP) at the protein- and mRNA levels, as well as for calcium accumulation. The timing of HP stimulation affected hMSC proliferation and expression of ALP activity. HP stimulation after 6 days was most effective at promoting ALP activity. CS-containing matrices promoted the osteogenic differentiation of hMSCs. A combination of both CS-containing matrices and cyclic HP yields optimal effects on osteogenic differentiation of hMSCs on scaffolds compared with individual responses.

Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs-UIP consensus document. Part II. Anatomy

OBJECTIVES Duplex ultrasound investigation has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this paper was an initiative of the Union Internationale de Phlébologie (UIP), The aim was to obtain a consensus of international experts on the methodology to be used for assessment of anatomy of superficial and perforating veins in the lower limb by ultrasound imaging. DESIGN Consensus conference leading to a consensus document. METHODS The authors performed a systematic review of the published literature on duplex anatomy of the superficial and perforating veins of the lower limbs; afterwards they invited a group of experts from a wide range of countries to participate in this project. Electronic submissions from the authors and the experts (text and images) were made available to all participants via the UIP website. The authors prepared a draft document for discussion at the UIP Chapter meeting held in San Diego, USA in August 2003. Following this meeting a revised manuscript was circulated to all participants and further comments were received by the authors and included in subsequent versions of the manuscript. Eventually, all participants agreed the final version of the paper. RESULTS The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination as well as the interpretation of images and measurements obtained. This document provides a detailed methodology for complete ultrasound assessment of the anatomy of the superficial and perforating veins in the lower limbs. CONCLUSIONS The authors and a large group of experts have agreed a methodology for the investigation of the lower limbs venous system by duplex ultrasonography, with specific reference to the anatomy of the main superficial veins and perforators of the lower limbs in healthy and varicose subjects.

Duplex ultrasound investigation of the veins in chronic venous disease of the lower limbs--UIP consensus document. Part I. Basic principles.

OBJECTIVES Duplex ultrasound investigation has become the reference standard in assessing the morphology and haemodynamics of the lower limb veins. The project described in this paper was an initiative of the Union Internationale de Phlébologie (UIP). The aim was to obtain a consensus of international experts on the methodology to be used for assessment of veins in the lower limbs by ultrasound imaging. DESIGN Consensus conference leading to a consensus document. METHODS The authors invited a group of experts from a wide range of countries to participate in this project. Electronic submissions from the experts were made available to all participants via the UIP website. The authors prepared a draft document for discussion at a UIP Chapter meeting held in San Diego, USA in August 2005. Following this meeting a revised manuscript was circulated to all participants and further comments were received by the authors and included in subsequent versions of the manuscript. Eventually all participants agreed to the final version of the paper. RESULTS The experts have made detailed recommendations concerning the methods to be used for duplex ultrasound examination as well as the interpretation of images and measurements obtained. This document suggests a methodology for complete assessment of the superficial and perforating veins of the lower limbs, including recommendations on reporting results and training of personnel involved in these investigations. CONCLUSIONS The authors and a large group of experts have agreed to a methodology for the investigation of the lower limbs venous system by duplex ultrasonography.

Late-onset Leclercia adecarboxylata bacteraemia in a premature infant in the NICU.

Late‐onset sepsis is a unique entity in the neonatal intensive care unit (NICU), as organisms involved are, by definition, nosocomial. As such, a limited number of microbes are characteristically involved. Leclercia adecarboxylata is a gram‐negative bacillus rarely cultured in a clinical context, with the few published cases primarily involving immunocompromised adults. We present an ex‐26‐week newborn girl who developed late‐onset sepsis with Leclercia adecarboxylata bacteraemia in the NICU. The infection was successfully treated with gentamicin and cefotaxime. This is the fifth paediatric report of Leclercia adecarboxylata infection, and the first in a neonate. The case raises the possibility that prior courses of antibiotics may have predisposed this individual to a rare infection essentially limited to immunocompromised individuals.