Elastographic parameters of liver steatosis and fibrosis predict independently the risk of incident chronic kidney disease and acute myocardial infarction in patients with type 2 diabetes mellitus.

AIMS: The aim of this prospective study was to examine the relationship between controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) with the risk of developing a composite endpoint inclusive of incident acute myocardial infarction (AMI), cerebrovascular insult (CVI) or chronic kidney disease (CKD) in people with type 2 diabetes mellitus (T2DM). METHODS: This study included 238 T2DM outpatients without chronic liver diseases. RESULTS: The patient population was followed for a median period of 7.6 years. Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the aforementioned composite outcome (P < 0.001 by the log-rank test), as well as CKD (P < 0.001) or AMI alone (P = 0.014) among those with elevated CAP values (≥238 dB/m) at baseline. Similarly, Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the composite outcome (P < 0.001), as well as CKD (P < 0.001), or AMI alone (P < 0.001) among those with elevated LSM values (≥7.0/6.2 kPa). In multivariable regression analyses, the presence of elevated CAP (adjusted-hazard ratio 2.34, 95% CI 1.32-4.15) and elevated LSM (adjusted-hazard ratio 2.84, 95% CI 1.92-4.21), independently of each other, were associated with a higher risk of developing the composite outcome, as well as incident AMI or CKD alone after adjusting for traditional cardiovascular risk factors and diabetes-related variables. CONCLUSIONS: Our study shows that the elastographic parameters of liver steatosis and fibrosis independently predict the long-term risk of developing chronic vascular complications in T2DM patients.

Significant liver fibrosis, as assessed by fibroscan, is independently associated with chronic vascular complications of type 2 diabetes: A multicenter study.

AIMS: The aim of this study was to investigate whether controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as assessed by vibration-controlled transient elastography (VCTE), are associated with chronic vascular complications of diabetes mellitus type 2 (T2DM). METHODS: We studied 442 outpatients with established T2DM, and who underwent VCTE and extensive assessment of chronic vascular complications of diabetes. RESULTS: A quarter of analyzed patients had a previous history of myocardial infarction and/or ischemic stroke, and about half of them had at least one microvascular complication (chronic kidney disease (CKD), retinopathy or polyneuropathy). The prevalence of liver steatosis (i.e., CAP ≥ 238 dB/m) and significant liver fibrosis (i.e., LSM ≥ 7.0/6.2 kPa) was 84.2% and 46.6%, respectively. Significant liver fibrosis was associated with an increased likelihood of having myocardial infarction (adjusted-odds ratio 6.61, 95%CI 1.66-37.4), peripheral polyneuropathy (adjusted-OR 4.55, 95%CI 1.25-16.6), CKD (adjusted-OR 4.54, 95%CI 1.24-16.6) or retinopathy (adjusted-OR 1.81, 95%CI 1.62-1.97), independently of cardiometabolic risk factors, diabetes-related variables, and other potential confounders. Liver steatosis was not independently associated with any macro-/microvascular diabetic complications. CONCLUSIONS: Significant liver fibrosis is strongly associated with the presence of macro-/microvascular complications in patients with T2DM. These results offer a new perspective on the follow-up of people with T2DM.

Early nasojejunal tube feeding versus nil-by-mouth in acute pancreatitis: A randomized clinical trial.

BACKGROUND/OBJECTIVES: There is substantial evidence of superiority of enteral nutrition (EN) to parenteral nutrition in acute pancreatitis (AP) treatment, but few studies evaluated its effectiveness compared to no intervention. The objective of our trial was to compare the effects of EN to a nil-by-mouth (NBM) regimen in patients with AP. METHODS: Patients with AP were randomized to receive either EN via a nasojejunal tube initiated within 24 h of admission or no nutritional support. Systemic inflammatory response syndrome (SIRS) was assessed as the primary outcome. Secondary outcomes included mortality, organ failure, local complications, infected pancreatic necrosis, surgical interventions, length of hospital stay, adverse events and inflammatory response intensity. Outcomes were compared using Student's t-test and Mann-Whitney U test as appropriate. RESULTS: 214 patients were randomized in total, 107 to each group. SIRS occurrence was similar between groups, with 48 (45%) versus 51 (48%), respectively (RR 0.94; 95% CI 0.71-1.26). No significant reduction of persistent organ failure (RR 0.81; 95% CI 0.52-1.27) and mortality (RR 0.59; 95% CI 0.28-1.23) was present in the EN group. There were no significant differences in other outcomes between the groups. When analyzing the occurrence of SIRS and mortality in subgroup of patients with severe disease no significant differences were noted. CONCLUSION: Our results showed no significant reduction of persistent organ failure and mortality in patients with AP receiving early EN compared to patients treated with no nutritional support (NCT01965873).

Nanoscale spin reversal by non-local angular momentum transfer following ultrafast laser excitation in ferrimagnetic GdFeCo.

Ultrafast laser techniques have revealed extraordinary spin dynamics in magnetic materials that equilibrium descriptions of magnetism cannot explain. Particularly important for future applications is understanding non-equilibrium spin dynamics following laser excitation on the nanoscale, yet the limited spatial resolution of optical laser techniques has impeded such nanoscale studies. Here we present ultrafast diffraction experiments with an X-ray laser that probes the nanoscale spin dynamics following optical laser excitation in the ferrimagnetic alloy GdFeCo, which exhibits macroscopic all-optical switching. Our study reveals that GdFeCo displays nanoscale chemical and magnetic inhomogeneities that affect the spin dynamics. In particular, we observe Gd spin reversal in Gd-rich nanoregions within the first picosecond driven by the non-local transfer of angular momentum from larger adjacent Fe-rich nanoregions. These results suggest that a magnetic material's microstructure can be engineered to control transient laser-excited spins, potentially allowing faster (~ 1 ps) spin reversal than in present technologies.

Nanoplasma dynamics of single large xenon clusters irradiated with superintense x-ray pulses from the linac coherent light source free-electron laser.

The plasma dynamics of single mesoscopic Xe particles irradiated with intense femtosecond x-ray pulses exceeding 10(16) W/cm2 from the Linac Coherent Light Source free-electron laser are investigated. Simultaneous recording of diffraction patterns and ion spectra allows eliminating the influence of the laser focal volume intensity and particle size distribution. The data show that for clusters illuminated with intense x-ray pulses, highly charged ionization fragments in a narrow distribution are created and that the nanoplasma recombination is efficiently suppressed.

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight.

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.

Femtosecond dark-field imaging with an X-ray free electron laser.

The emergence of femtosecond diffractive imaging with X-ray lasers has enabled pioneering structural studies of isolated particles, such as viruses, at nanometer length scales. However, the issue of missing low frequency data significantly limits the potential of X-ray lasers to reveal sub-nanometer details of micrometer-sized samples. We have developed a new technique of dark-field coherent diffractive imaging to simultaneously overcome the missing data issue and enable us to harness the unique contrast mechanisms available in dark-field microscopy. Images of airborne particulate matter (soot) up to two microns in length were obtained using single-shot diffraction patterns obtained at the Linac Coherent Light Source, four times the size of objects previously imaged in similar experiments. This technique opens the door to femtosecond diffractive imaging of a wide range of micrometer-sized materials that exhibit irreproducible complexity down to the nanoscale, including airborne particulate matter, small cells, bacteria and gold-labeled biological samples.

Toxic epidermal necrolysis associated with carvedilol treatment.

OBJECTIVE: To report a case of fatal toxic epidermal necrolysis associated with carvedilol treatment. CASE SUMMARY: Two days after the initiation of carvedilol treatment, a 70-year old woman presented with skin eruptions in the form of maculous rash with blisters that rapidly progressed to epidermal necrolysis. Although the suspected drug was withdrawn, the reaction was extremely rapid in its development with fatal outcome. DISCUSSION: Carvedilol is not a drug commonly associated with TEN. To our knowledge there are no cases of carvedilol related TEN reported in the literature. CONCLUSION: Because of the close temporal relationship between the initiation of carvedilol treatment and the appearance of skin eruptions, and because carvedilol was the only new medication the patient had taken, the etiology of TEN was most likely a reaction to this drug. Physicians should be aware of this extremely rare but serious ADR.

Systematic evaluation of FRAP experiments performed in a confocal laser scanning microscope--part II: Multiple diffusion processes.

A procedure for a systematic evaluation of fluorescence recovery after photo-bleaching (FRAP) data is presented that allows one to determine distributions of diffusion coefficients. The method provides a straightforward and calibration-free way to quantify multiple diffusion processes when FRAP is measured as a function of time and space by means of confocal laser scanning microscopy. It is verified utilizing FRAP experiments on mixtures of differently sized fluorescent micro-spheres as realizations of discrete D distributions.

Biosocial and nutritional effects on body composition in young adults from Wroclaw, Poland.

This work concerns the questions if and to what extent social variables past and present, and actual sports activity and nutritional and smoking habits, have an influence on body compartment indices, and how this differs between female and male medical students from Wroclaw, Poland. Backward stepwise regression was applied to four dependent variables, i.e. Body Mass Index (BMI), %Fat Mass (%FM), Extracellular Water/Intracellular Water Index (100 x ECW/ICW) and Body Cell Mass Index (BCMI=BCM/height2), and for eighteen independent variables including nutrition, parents' social status, smoking and sports activity. Females ate meat less frequently and fruit and vegetables more often, and drank beer less frequently but milk more often than did male students. It seems that there exists some effect on fat accumulation resulting from difference in nutrition between females and males. The results may be interpreted in terms of a parental gender effect on body composition of children associated with different conditions of life and nutrition in childhood and youth for female and male students in Wroclaw.

Aging with quality of life--a challenge for society.

This article focus on biological, nutritional, psychological, medical and social variables which have proven useful indicators for assessing wellbeing of individuals. Such objective data (measured by the two investigators) and subjective information (self-reported by the participants) were collected between 2002-2003 from samples of healthy, free living females and males aged between 59 and 92 years from Vienna and surroundings. In both these groups some habitual practices (habit variables) were observed of elderly and old which have a negative influence on health i.e low daily liquid uptake and smoking. There is also a fair amount of overweight and obesity (BMI>or=30) and also of hypertension, particularly in males, There is also malnourishment, predominantly in females, as reflected by the Body Cell Mass Index. Several participants either were not aware of being hypertensive or admitted that they deliberately ignored medical advice. With respect to social variables there are greater percentages of married males and widowed females. Possibly partially resulting from this loss of the partner a greater number of females report feelings of loneliness than do males. Positive results relate to the overall high percentages of family contacts, positive feelings towards life and physical activity as reported by the large majority of the participants. These findings stress the need for further information of living habits of the elderly and old as a possible guide of helping improve their quality of life.

[Significance of body weight status for bone density in the elderly and very old]. / Zur Bedeutung des Gewichtsstatus für die Knochendichte bei Betagten und Hochbetagten.

Reduced bone density and osteoporosis are significant health problems and contributors to disability and mortality among older women and men. Therefore the decline of bone mineral content (BMC) and bone mineral density (BMD) are aspects of ageing with great medical and social significance. In recent years a low body weight was declared to be an important risk factor for the development of osteoporosis. In the present study the impact of weight status, defined by the categories of the WHO, on BMC of the whole body and BMD of the proximal femur end, determined by dual energy x-ray absorptiometry (DEXA), were studied in 77 female and 62 male probands aged between 60 and 92 years (x = 71.7 yrs). With increasing weight status (BMI categories), BMC and BMD increased significantly (p < 0.001). This was true of both sexes. Even moderate overweight women and men (BMI 25.0-29.99) showed a significantly higher bone density than their normal weight counterparts (BMI < 25.0). In the present study a marked positive impact of body weight on bone density of old-aged women and men could be shown.

Body composition characteristics are associated with the bone density of the proximal femur end in middle- and old-aged women and men.

OBJECTIVES: In the present study the associations between bone density of the proximal femur end and weight status, fat distribution patterns (FDI) and body composition parameters i.e. amount of body fat and lean body mass were tested in a sample of old aged women and men. METHODS: In 77 healthy women ranging in age from 60 to 92 years (x=71.8 years) and 62 healthy men ranging in age from 60 to 86 years (x=71.5 years) the bone mineral density (BMD of the proximal femur end and the body composition parameters absolute fat mass, relative fat mass, lean body mass and bone mineral content were estimated by dual energy X-ray absorptiometry. Additionally, the weight status (body mass index, BMI) and the FDI were calculated. The bone density of the proximal femur end was correlated with the absolute fat mass and the lean body mass as well as with the BMI and the FDI. RESULTS: BMD correlated in females significantly positively with parameters of body composition, in males no significant correlations between fat mass (absolute and relative) and BMD as well as BMD/stature was found. Furthermore, it was shown that the weight status (BMI; r(2)=0.13, P<0.0003 in males and r(2)=0.27, P<0.000 in females), and the lean body mass (r(2)=0.21, P<0.001 in males, r(2)=0.36, P<0.004 in females) were associated significantly positively with the BMD of the proximal femur end in both sexes. The absolute fat mass had a significant impact on BMD in the female subsample only (r(2)=0.24, P<0.000). CONCLUSIONS: A lower weight status and a low amount of lean body mass, indicating not only lack of biomechanical forces of the proximal femur end, but also a lack of physical activity can be assumed to be associated increased bone loss and the development of osteoporosis in both sexes. An association between low amount of fat tissue and decreased BMD was especially found in women and may be due to the reduced conversion rates from androgens to estrogens in a low amount of fat tissue.

Clinical outcome of microsurgical subinguinal varicocelectomy in infertile men.

The present study assesses the clinical outcome of microsurgical subinguinal varicocelectomy in infertile men, especially with regard to sperm count, motility and fertility. Between June 1990 and October 1998, 272 patients had subinguinal microsurgical varicocelectomy operations for clinical varicoceles, and their long-term results were assessed. In nearly all the patients there was a significant improvement in sperm count and sperm motility after 3 and 6 months. Very few complications arose from this procedure. We concluded that microsurgical subinguinal varicocelectomy is an effective treatment for clinical varicoceles in infertile men. The significant improvement in the quality of spermatozoa, the low complication rates and the remarkably high pregnancy rates make this a valuable alternative to in vitro reproduction techniques.

Misplacement of a femoral venous catheter into the ascending lumbar vein: repositioning using ultrasonographic guidance.

A 5-week-old infant with congenital chylothorax required long-term intravenous access for parenteral nutrition. Cannulation of the inferior vena cava via the left femoral vein was attempted, but the catheter was misplaced into the left ascending lumbar vein. Catheter removal is advised when such malposition is identified. We were able successfully to redirect the catheter into the inferior vena cava using ultrasonographic guidance. This procedure has not been described previously in children. We propose that repositioning of incorrectly placed vascular catheters can be achieved using ultrasound guidance at the bedside.

Effect of sodium arsenite on iNOS expression and vascular hyporeactivity associated with cecal ligation and puncture in the rat.

Induction of the heat shock response protects animals from either endotoxemia or peritonitis. In endotoxemia, heat shock protein (HSP) induction is associated with reversal of vascular hyporeactivity and inhibition of iNOS expression. Recent studies suggest differences in the inflammatory mechanisms during endotoxemia and peritonitis animal models and their response to therapeutic interventions. We therefore studied the effect of the HSP inducer sodium arsenite (SA) on vascular reactivity and iNOS expression in rats undergoing cecal ligation and puncture (CLP). CLP resulted in suppression of the pressor effect of norepinephrine (NE) in vivo (measured by changes in blood pressure in response to NE boluses) and ex vivo (changes in contraction force in isolated mesenteric arteries in response to NE concentrations), and in the expression of iNOS protein. Pretreatment of the rats with SA resulted in reversal of CLP-induced vascular hyporeactivity in vivo and ex vivo, and inhibition of iNOS expression after 22 h. SA pretreatment improved 7-day survival after CLP from 18.2% to 70% (P < 0.005). Glucocorticoid receptor inhibition did not affect the effect of HSP induction on iNOS expression. The similarity of the effect of HSP on vascular reactivity and iNOS expression in two distinct sepsis models suggests that this effect may be clinically important and that a causative relationship between HSP induction, iNOS inhibition, and reversal of vascular reactivity is likely.

Use of acetazolamide to decrease cerebrospinal fluid production in chronically ventilated patients with ventriculopleural shunts.

Acetazolamide (ACTZ), a carbonic anhydrase inhibitor, has been shown to decrease cerebrospinal fluid (CSF) production in both in vivo and in vitro animal models. We report two children with hydrocephalus who experienced multiple shunt failures, and who had externalised ventriculostomy drains (EVD) prior to ventriculopleural shunt placement. The effects of increasing doses of ACTZ on CSF production and subsequent tolerance to ventriculopleural shunts were evaluated. The patients had a 48% and a 39% decrease in their EVD CSF output when compared to baseline with maximum ACTZ dose of 75 mg/kg/day and 50 mg/kg/day, respectively (p < 0.05). This is the first report of change in CSF volume in children after extended treatment with ACTZ. ACTZ treatment in mechanically ventilated paediatric patients with hydrocephalus may improve tolerance of ventriculopleural shunts and minimise respiratory compromise. Potassium and bicarbonate supplements are required to correct metabolic disturbances.

The use of a mobile computed tomography scanner in the pediatric intensive care unit to evaluate airway stenting and lung volumes with varying levels of positive end-expiratory pressure.

OBJECTIVE: Presentation of a case report describing the use of a mobile computed tomography (CT) scanner in the pediatric intensive care unit (PICU) to radiographically evaluate tracheobronchial stenting and lung volumes while using different levels of positive end-expiratory pressure (PEEP) and positioning in a critically ill infant. DESIGN: Case report of a single patient. SETTING: Pediatric intensive care unit in a University Hospital. PATIENT: A 6-month-old premature infant with bronchopulmonary dysplasia, tracheobronchomalacia, and progressive respiratory failure. INTERVENTIONS: CT scans of the chest were performed by using a mobile CT scanner in the PICU. Serial CT scans were performed at PEEP levels of 5, 10, 15, and 20 cm H(2)O in both the supine and prone position. Scheduled medical care and standard monitoring were continued during the course of the CT scans. MEASUREMENTS AND MAIN RESULTS: Identical anatomic levels demonstrating the trachea, bronchi, and lung parenchyma were compared while different levels of PEEP and supine or prone positioning were used. From these comparisons, the level of PEEP in which lung volumes were optimized was radiographically determined. No significant changes in large airway caliber were observed. There was no difference noted between prone and supine positioning. CT scans were completed with minimal disruption to the patient's care. CONCLUSIONS: Mobile CT scanners can be used in the PICU for the diagnostic evaluation of critically ill children. This option allows for the continuation of medical therapies and monitoring in the intensive care setting while avoiding the potential complications of transporting a critically ill child to the radiology department. The use of mobile CT scanners may disrupt PICU routine and is more expensive than use of fixed CT scanners. Mobile CT scanners may be useful in radiographically determining the optimal level of PEEP in infants with tracheobronchomalacia and bronchopulmonary dysplasia.

Effect of tyrosine kinase inhibition on sepsis-induced vascular hyporesponsiveness, inos mrna expression and NF-kappaB nuclear translocation in rats.

The dependence of the critical steps in the sepsis cascade on the transcription factor NF-kappaB andation to nitric oxide (NO) production are controversial. Tyrosine kinase (TK) is involved in several of the steps, and TK inhibitors (TKI) inhibit lipopolysaccharide (LPS)-induced vascular hyporesponsiveness in septic animals. We studied the relationship of TK inhibition, hemodynamics, vascular contraction, iNOS mRNA expression and NF-kappaB translocation in anesthetized endotoxic rats. The TKI AG556 (2.5 mg/kg i.p.), given 1 h before i.v. endotoxin (LPS) resulted in attenuation of early (<60 min) and late (60-120 min) hypotension, improved contraction of mesenteric arteries to norepinephrine 4 h after LPS, and attenuated tissue iNOS mRNA expression. LPS-induced NF-kappaB translocation was unaffected. The observed dissociation between NF-kappaB translocation and the salutary effect of TKI in vivo and ex vivo and its effect on iNOS mRNA expression suggest that although NF-kappaB may be involved in the sepsis cascade, it may not be essential for some of the molecular and vascular consequences of septic shock.

Prospective evaluation of propofol anesthesia in the pediatric intensive care unit for elective oncology procedures in ambulatory and hospitalized children.

OBJECTIVES: To evaluate our experience with propofol anesthesia delivered by pediatric intensivists in the pediatric intensive care unit (PICU) to facilitate elective oncology procedures in children performed by pediatric oncologists. METHODS: Elective oncology procedures performed with propofol anesthesia in our multidisciplinary, university-affiliated PICU were prospectively evaluated over a 7-month period. Ambulatory and hospitalized children were prescheduled for their procedure, underwent a medical evaluation, and met fasting requirements before the start of anesthesia. Continuous cardiorespiratory and neurologic monitoring was performed by a pediatric intensivist and a PICU nurse, while the procedure was performed by a pediatric oncologist. Propofol was delivered in intermittent boluses to achieve the desired level of anesthesia. Information studied included patient demographics, procedures performed, induction and total doses of propofol used, the duration of the different phases of the patient's PICU stay, the occurrence of side effects, the need for therapeutic interventions, and the incidence of recall of the procedure. RESULTS: Fifty procedures in 28 children (mean age: 7.5 +/- 4.3 years) were evaluated. Sixty-one percent of patients had established diagnoses. Fifty-four percent of procedures were lumbar puncture with intrathecal chemotherapy administration and 26% of procedures were bone marrow aspirations with biopsy. Induction propofol doses were 2. 0 +/-.8 mg/kg for ambulatory and hospitalized patients, while total propofol doses were 6.6 +/- 2.3 mg/kg and 7.9 +/- 2.4 mg/kg for ambulatory and hospitalized patients, respectively. Induction time was 1.5 +/-.7 minutes, recovery time was 23.4 +/- 11.5 minutes, and total PICU time was 88.8 +/- 27.7 minutes. Transient decreases in systolic blood pressure less than the fifth percentile for age occurred in 64% of procedures, with a mean decrease of 25% +/- 10%. Intravenous fluids were administered in 31% of these cases. Hypotension was more common in ambulatory patients but was not predicted by propofol dose, anesthesia time, or age. Partial airway obstruction was noted in 12% of procedures while apnea requiring bag-valve-mask ventilation occurred in 2% of procedures. Neither was associated with age, propofol dose, or the duration of anesthesia. All procedures were successfully completed and there were no incidences of recall of the procedure. CONCLUSIONS: Propofol anesthesia is effective in achieving patient comfort and amnesia, while optimizing conditions for elective oncology procedures in children. Although transient hypotension and respiratory depression may occur, propofol anesthesia seems to be safe to use for these procedures in the PICU setting. Recovery from anesthesia was rapid and total stay was brief. Under the proper conditions, propofol anesthesia delivered by pediatric intensivists in the PICU is a reasonable option available to facilitate invasive oncology procedures in children.