Skin-Related complications of Klippel-Trenaunay Syndrome: a retrospective review of 410 patients.

BACKGROUND: Little is known about skin-related complications in Klippel-Trenaunay syndrome (KTS), a complex vascular anomaly defined by capillary malformation (CM), venous malformation (VM) ± lymphatic malformation (LM) and limb overgrowth. Reported skin-related complications of KTS include ulceration, vascular ectasias (blebs), bleeding and infection. OBJECTIVE: To determine the spectrum, prevalence and predictors of skin-related complications in KTS. METHODS: A retrospective review of 410 patients fulfilling KTS criteria was performed to assess for the presence of skin-related complications. RESULTS: Skin-related complications were present in 45% of patients. Most prevalent were CM-related complications including blebs, bleeding, thickening (25%), cellulitis (22%) and ulceration (21%). Features positively associated with skin-related complications were presence of LM (OR 17.17; P < 0.001), VM on the buttocks/perineum/genitalia (OR 1.92; P = 0.009), CM on the feet (OR 1.77; P = 0.039) and male sex (OR 1.63; P = 0.034). Features negatively associated with skin-related complications were CM on the trunk (OR 0.59; P = 0.029) and tissue hypertrophy of the hands (OR 0.27; P = 0.025). CONCLUSION: Skin-related complications affect nearly half of patients with KTS. Those with lymphatic involvement or malformation presence in the undergarment area or feet are most at risk.

The cascading origin of the 2018 Kilauea eruption and implications for future forecasting.

The 2018 summit and flank eruption of Kilauea Volcano was one of the largest volcanic events in Hawai'i in 200 years. Data suggest that a backup in the magma plumbing system at the long-lived Pu'u 'O'o eruption site caused widespread pressurization in the volcano, driving magma into the lower flank. The eruption evolved, and its impact expanded, as a sequence of cascading events, allowing relatively minor changes at Pu'u 'O'o to cause major destruction and historic changes across the volcano. Eruption forecasting is inherently challenging in cascading scenarios where magmatic systems may prime gradually and trigger on small events.

Cyclic lava effusion during the 2018 eruption of Kilauea Volcano.

Lava flows present a recurring threat to communities on active volcanoes, and volumetric eruption rate is one of the primary factors controlling flow behavior and hazard. The time scales and driving forces of eruption rate variability, however, remain poorly understood. In 2018, a highly destructive eruption occurred on the lower flank of Kilauea Volcano, Hawai'i, where the primary vent exhibited substantial cyclic eruption rates on both short (minutes) and long (tens of hours) time scales. We used multiparameter data to show that the short cycles were driven by shallow outgassing, whereas longer cycles were pressure-driven surges in magma supply triggered by summit caldera collapse events 40 kilometers upslope. The results provide a clear link between eruption rate fluctuations and their driving processes in the magmatic system.

Orthopaedic diagnoses in patients with Klippel-Trenaunay syndrome.

PURPOSE: Klippel-Trenaunay syndrome (KTS) is a rare combined vascular malformation composed of capillary malformation, lymphatic and/or venous malformation and limb overgrowth, which commonly affects the extremities. Due to limb involvement, it is not uncommon for these patients to require referral to an orthopaedic surgeon. Herein we reviewed the prevalence of orthopaedic diagnoses in a large cohort of KTS patients and described the associated surgical interventions. METHODS: Between 1976 and 2012, 410 patients fulfilling strict criteria for KTS were evaluated at a single institution. Patient charts were reviewed for demographic information, details of the clinical evaluation, orthopaedic consultation and surgical interventions. RESULTS: A total of 264 of 410 patients (64%) with confirmed KTS required orthopaedic evaluation. Of these 264 patients, 84% had documented limb-length discrepancy. Other common diagnoses included: angular deformities (10%), scoliosis (9%), osteopenia/osteoporosis (7%), pathological fractures (6%), joint contracture (5%), degenerative joint disease (4%) and limb/joint pain (4%). Of the 264 patients evaluated by orthopaedic surgery, 133 patients (50.4%) underwent 169 surgeries. Surgery was most commonly performed for limb-length discrepancy (62%). Multivariable analysis confirmed an orthopaedic condition was more likely in patients with lymphatic malformation (odds ratio (OR) 3.78; p < 0.001), as well as in those with bone and/or soft-tissue hypertrophy of the lower extremity (OR 7.51; p < 0.001) or foot (OR 3.23; p < 0.001). CONCLUSION: Orthopaedic conditions are common in patients with KTS and approximately 50% require surgical intervention. Those with a lymphatic malformation and/or soft-tissue hypertrophy of the lower extremity are more likely to need surgery. LEVEL OF EVIDENCE: Level IV, Descriptive Case Series.

The 2018 rift eruption and summit collapse of Kilauea Volcano.

In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.

Juvenile idiopathic arthritis and future risk for cardiovascular disease: a multicenter study.

OBJECTIVES: To evaluate the frequency of cardiovascular disease (CVD) and CVD risk factor development in adult patients previously diagnosed with juvenile idiopathic arthritis (JIA). METHOD: A cohort study was conducted utilizing patients at two academic institutions (cohorts 1 and 2). Each institution evaluated the common endpoint of CVD outcomes and CVD risk factor development in adults aged ≥ 30 years and at the 29-year follow-up from disease onset in cohorts 1 and 2, respectively, with comparison to control groups of similar age and sex. RESULTS: Cohort 1 included 41 patients with JIA and follow-up ≥ 30 years of age with comparison to 41 controls. Three patients (7%) had CVD, compared to one control (2%; p = 0.31). Cohort 2 included 170 patients with JIA and a median of 29 years of follow-up from disease onset with comparison to 91 controls. Two patients (2%) had CVD, compared to none of the controls (p = 0.29). The presence of CVD risk factors was found to be increased in the JIA group compared to the controls in three categories: family history of CVD (cohort 1), hypertension (cohort 2), and ever smokers (cohorts 2). CONCLUSIONS: There is no increase in CVD events in patients with JIA 29 years following disease onset when compared to the general population. As these cohorts age, it will be informative to evaluate whether this baseline risk remains present or a trend towards increasing CVD emerges. Continued longitudinal follow-up of these cohorts and larger population-based studies are needed to establish a definitive relationship between JIA and CVD.

Variability in coefficient of restitution in human facial skin.

BACKGROUND: If particles rebound on human facial skin, they can be re-entrained into the airflow and subsequently inhaled, increasing aspiration efficiency estimates. A realistic estimate of facial skin coefficient of restitution (CoR) is necessary to accurately model particle bounce. This study investigated the effects of sampling location, temperature, humidity levels, age, gender, and BMI on facial skin CoR. METHODS: A torsional ballistometer was used to measure facial CoR for 30 participants divided into three age groups (18-30, 31-40, and 41-65 years), at three temperatures and three humidity levels. The study was repeated twice: once in the late winter and once in the early summer to capture the seasonal variability. RESULTS: The CoR significantly varied across five facial locations, with values ranging from 0.55 to 0.75. Gender, sampling season and the interaction between sampling location and age were found to be significant, but changes in values were relatively small (0.05 at most) and are not considered practically significant. CONCLUSION: CoR was non-uniform across the face. The use of uniform CoR value as modeling input parameters or for mannequin facial surfaces in experimental wind tunnel studies may not be accurate due to the high variability in CoR between facial sampling locations.

Influence of secondary aspiration on human aspiration efficiency.

Computational fluid dynamics (CFD) was used to evaluate the contribution of secondary aspiration to human aspiration efficiency estimates using a humanoid model with realistic facial features. This study applied coefficient of restitution (CoR) values for working-aged human facial skin to the facial regions on the humanoid CFD model. Aspiration efficiencies for particles ranging from 7 to 116 µm were estimated for bounce (allowing for secondary aspiration) and no-bounce (CoR=0) simulations. Fluid simulations used the standard k-epsilon turbulence model over a range of test conditions: three freestream velocities, two breathing modes (mouth and nose breathing, using constant inhalation), three breathing velocities, and five orientations relative to the oncoming wind. Laminar particle trajectory simulations were used to examine inhaled particle transport and estimate aspiration efficiencies. Aspiration efficiency for the realistic CoR simulations, for both mouth- and nose-breathing, decreased with increasing particle size, with aspiration around 50% for 116 µm particles. For the CoR=0 simulations, aspiration decreased more rapidly with increasing particle size and approached zero for 116 µm compared to realistic CoR models (differences ranged from 0% to 80% over the particle sizes and velocity conditions). Differences in aspiration efficiency were larger with increasing particle size (>52 µm) and increased with decreasing freestream velocity and decreasing breathing rate. Secondary aspiration was more important when the humanoid faced the wind, but these contributions to overall aspiration estimates decreased as the humanoid rotated through 90°. There were minimal differences in aspiration between uniform CoR values of 0.5, 0.8, 1.0 and realistic regionally-applied CoR values, indicating differences between mannequin surfaces and between mannequin and human skin will have negligible effect on aspiration for facing-the-wind orientation.

Biomechanical activation of vascular endothelium as a determinant of its functional phenotype.

One of the striking features of vascular endothelium, the single-cell-thick lining of the cardiovascular system, is its phenotypic plasticity. Various pathophysiologic factors, such as cytokines, growth factors, hormones, and metabolic products, can modulate its functional phenotype in health and disease. In addition to these humoral stimuli, endothelial cells respond to their biomechanical environment, although the functional implications of this biomechanical paradigm of activation have not been fully explored. Here we describe a high-throughput genomic analysis of modulation of gene expression observed in cultured human endothelial cells exposed to two well defined biomechanical stimuli-a steady laminar shear stress and a turbulent shear stress of equivalent spatial and temporal average intensity. Comparison of the transcriptional activity of 11,397 unique genes revealed distinctive patterns of up- and down-regulation associated with each type of stimulus. Cluster analyses of transcriptional profiling data were coupled with other molecular and cell biological techniques to examine whether these global patterns of biomechanical activation are translated into distinct functional phenotypes. Confocal immunofluorescence microscopy of structural and contractile proteins revealed the formation of a complex apical cytoskeleton in response to laminar shear stress. Cell cycle analysis documented different effects of laminar and turbulent shear stresses on cell proliferation. Thus, endothelial cells have the capacity to discriminate among specific biomechanical forces and to translate these input stimuli into distinctive phenotypes. The demonstration that hemodynamically derived stimuli can be strong modulators of endothelial gene expression has important implications for our understanding of the mechanisms of vascular homeostasis and atherogenesis.

CT for the evaluation of flank pain.

Unenhanced helical CT allows rapid and accurate determination of whether a stone is present anywhere in the urinary tract. There is a learning curve for both radiologist and urologist, but a number of signs are highly predictive of stone. Helical CT scans should always be accompanied by a "scoutogram" to convey an idea of what the stone might look like. The scan requires no contrast medium and takes only 5 to 10 minutes of imaging time, making it cost effective. It behooves both urologists and radiologists to familiarize themselves with the techniques for reading these scans.

Anti-inflammatory and lung function effects of montelukast in asthmatic volunteers exposed to sulfur dioxide.

BACKGROUND: Sulfur dioxide (SO(2)) gas may induce acute asthmatic responses when inhaled by individuals in the setting of community or occupational air pollution during exercise. Some asthma medications mitigate the SO(2) response, which is not fully understood but appears to involve multiple mechanisms. OBJECTIVE: We tested the hypothesis that pretreatment with the cysteinyl-leukotriene inhibitor montelukast sodium protects against the inflammatory and bronchoconstrictive effects of SO(2) in the airways of asthmatic subjects. METHODS: Asthmatic volunteers (enrolled, 12 subjects; completed study, 11 subjects) were exposed to 0.75 ppm SO(2) for 10-min periods during exercise (mean ventilation, 35 L/min) and were exposed similarly to filtered air (control condition) after double-blinded pretreatments with montelukast (10 mg/d for 3 days) and placebo. RESULTS: After montelukast pretreatment, specific airways resistance, FEV(1), symptoms, and eosinophil counts in induced sputum showed statistically and clinically significant improvements in preexposure measurements and/or decreased responses to SO(2) exposure or exercise. The mean FEV(1) immediately after exposure was 95% of baseline FEV(1) with montelukast pretreatment vs 82% with placebo. CONCLUSION: Montelukast significantly protects against airways eosinophilic inflammation and bronchoconstriction from SO(2) exposure during exercise. This implies a role for leukotrienes in SO(2)-induced lung effects.

Mechanosensitive endothelial gene expression profiles: scripts for the role of hemodynamics in atherogenesis?

The possibility that hemodynamic forces can act as a "local risk factor" for endothelial dysfunction provides a conceptual framework for the longstanding observation that the earliest lesions of atherosclerosis develop in a nonrandom pattern, the geometries of which correlate with branch points and other regions of altered blood flow. This has led us to hypothesize that hemodynamic forces, in particular wall shear stresses generated by complex patterns of blood flow, can function as both positive and negative stimuli in atherogenesis via effects on endothelial cell gene expression. To understand how endothelial cells in different regions of the arterial tree acquire both functional and dysfunctional phenotypes due to regional hemodynamics, it was important to begin to delineate, in a comprehensive fashion, the mechanoresponsiveness of endothelial cells. To address this fundamental question, we undertook high-throughput transcriptional profiling to assess the global patterns of gene expression in cultured endothelial cells exposed to two defined biomechanical stimuli. Analyses of the transcriptional activity of thousands of genes have revealed unique patterns of gene expression associated with certain types of stimuli. These unique gene expression programs and their associated functional phenotypes constitute the strongest evidence to date that vascular endothelial cells can discriminate among different types of biomechanical stimuli. The results of these studies and the working hypotheses inspired by detailed molecular analyses of biomechanically activated vascular endothelium promise to provide new insights into the role of hemodynamics in the pathogenesis of atherosclerosis.

Laparoscopic lower urinary tract reconstruction.

In the past decade laparoscopy has been successfully utilized for both the obliterative and reconstructive management of urologic disease. We have seen not only an advance in the technology available to perform these procedures, but also an effort on the part of laparoscopic urologists to refine their techniques to allow them to perform more complicated procedures. In the lower urinary tract, the development of reconstructive procedures has been slow. While early interest in laparoscopy prompted several pioneers to perform the initial reconstructive procedures, the difficulties associated with these procedures at that time largely precluded their widespread application or adoption. Recently, improvements in the skills of laparoscopic urologists and the advent of instruments to facilitate suturing (e.g. EndoStitch semi-automatic suturing device, Lapra-Ty clips to replace intracorporeal knotting, and advances in staple and clip technology) have facilitated a renewed interest in laparoscopic reconstructive surgery of the lower urinary tract. At present, almost all types of urologic open reconstructive procedures have been accomplished laparoscopically: urinary diversion (e.g. ureteroileal loop urinary diversion and continent diversion), bladder reconstruction (e.g. ureterovesicostomy, bladder augmentation, bladder diverticulectomy, partial cystectomy), ureteral reimplantation, and, most recently, urethrovesical anastomosis following radical prostatectomy. This article will review the development of these procedures.

From paper to electron: how an STM journal can survive the disruptive technology of the Internet.

The Internet represents a different type of technology for publishers of scientific, technical, and medical journals. It is not a technology that sustains current markets and creates new efficiencies but is, rather, a disruptive technology that could radically alter market forces, profit expectations, and business models. This paper is a translation and amplification of the research done in this area, applied to a large-circulation new science journal, Pediatrics. The findings suggest that the journal of the future will be electronic, have a less volatile cost structure, be supported more by services than by content, be less able to rely on subscription revenues, and abandon certain elements of current value networks. It also provides a possible framework for other publishers to use to evaluate their own journals relative to this disruptive technology.

Endothelial dysfunction, hemodynamic forces, and atherogenesis.

Phenotypic modulation of endothelium to a dysfunctional state contributes to the pathogenesis of cardiovascular diseases such as atherosclerosis. The localization of atherosclerotic lesions to arterial geometries associated with disturbed flow patterns suggests an important role for local hemodynamic forces in atherogenesis. There is increasing evidence that the vascular endothelium, which is directly exposed to various fluid mechanical forces generated by pulsatile blood flow, can discriminate among these stimuli and transduce them into genetic regulatory events. At the level of individual genes, this regulation is accomplished via the binding of certain transcription factors, such as NF kappa B and Egr-1, to shear-stress response elements (SSREs) that are present in the promoters of biomechanically inducible genes. At the level of multiple genes, distinct patterns of up- and downregulation appear to be elicited by exposure to steady laminar shear stresses versus comparable levels of non-laminar (e.g., turbulent) shear stresses or cytokine stimulation (e.g., IL-1 beta). Certain genes upregulated by steady laminar shear stress stimulation (such as eNOS, COX-2, and Mn-SOD) support vasoprotective (i.e., anti-inflammatory, anti-thrombotic, anti-oxidant) functions in the endothelium. We hypothesize that the selective and sustained expression of these and related "atheroprotective genes" in the endothelial lining of lesion-protected areas represents a mechanism whereby hemodynamic forces can influence lesion formation and progression.

A new mathematical approach predicts individual cell growth behavior using bacterial population information.

A theoretical methodology has been developed for studying the growth kinetics of bacterial cells. It utilizes the steady-state cell length distribution in a bacterial population to predict the dependency of growth and division rates on cell length and age. The mathematical model has been applied to the analysis of two bacterial populations, a wild-type strain of Bacillus subtilis, and a minicell-producing strain that carries the divIVB1 mutation. The results show that our model describes the wild-type population very well and that the assumptions typically used in traditional methods are unrealistic. In the case of the minicell-producing mutant we find evidence that the rate of cell division must be a function not only of cell size but also of cell age.

Simple nephrectomy: managing the difficult case: xanthogranulomatous pyelonephritis and autosomal dominant polycystic kidney disease.

Laparoscopic surgery for kidneys with xanthogranulomatous pyelonephritis or autosomal dominant polycystic disease has proved to be technically difficult but is possible. The Harmonic Scalpel facilitates the dissection of inflammatory tissues and does not inflict burns. Hand-assisted laparoscopy may be useful. Pain relief is obtained by most patients undergoing cyst drainage, although recurrence after a year or two is common. A specific and detailed preoperative diagnosis and treatment plan are essential to a successful outcome.