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"text": "\n200\nAnalyses of Premature Birth - Weight Percentiles of Extremely Premature Newborns and Prognostic-Significance of Birth-Weight and Sonographically Estimated Fetal Weight\n\nWeiss, PAM\n\nWalcher, N\n\nHuttner, U\n\nWinter, R\n\nBeiträge in Fachzeitschriften\nISI:000075822800004\nNone\n10.1055/s-2007-1022748\nNone\nPurpose: Estimated fetal weight in very-low-birth-weight infants (VLBWI) frequently serves as a prognostic factor and as an aid for planning management of delivery. However, few data are available on the normal range of birth weight prior to the 32nd gestational week. Moreover, estimated fetal weight is subject to a mean error of 15 - 20 %. Material and Method: Thus we calculated percentiles of birth weight, analyzed the prognostic significance of birth weight, and estimated fetal weight for the survival of VLBWI in 437 unselected single births. Results: The 3rd, 10th, 50th, 90th and 97th percentiles between 24 and 32 week's gestation were 514-997 g, 526-1106 g, 710-1590 g, 888-1964 g and 1106-2082 g, respectively. Thus, a 1000 g newborn could be of a gestational age of 24-32 gestational weeks (95th and 10th percentile, respectively). The estimated fetal weight had a mean error of +/-15%. The highest deviation of - 560 g corresponds to a variation of 5 gestational weeks (estimated 1100 g, acutal 1660 g). The uncorrected and corrected neonatal mortality rates were 16.5% and 7%, respectively (corrected by malformations and abortions). The uncorrected mortality rate decreased from 61 % (wk 23/24) through 29% (wk 25/26), 13% (wk 27/28), 9% (wk 29/30) to 8% (wk 31/32), respectively. The respective corrected mortality Fate decreased continuously from 25% to 3%. In contrast, the mortality rate was inconsistent between a birth weight of < 750 g and > 1500 g after weight stratification in 250 g steps (54%, 19%, 21%, 6%, 6%). While there was a significant correlation between gestational age and neonatal mortality rates (R=0, 4; p<0, 2), no correlation could be shown between birth weight and the mortality rate (R = 0.8; p = 0.11). Conclusion: Because of the lack of specificity of birth weight for gestational age and consequently fetal maturity, and because of the large systematic error in estimating fetal weight, the management of VLBWI should be based on the gestational age rather than on the estimated birth weight.\n\nWalcher, Wolfgang\n\n\n"
},
{
"text": "\n3099\nMultiple agents potentiate alpha1-adrenoceptor-induced conduction depression in canine cardiac purkinje fibers.\n\nKulier, AH\n\nTurner, LA\n\nVodanovic, S\n\nContney, S\n\nLathrop, DA\n\nBosnjak, ZJ\n\nBeiträge in Fachzeitschriften\nISI:000087389300027\n10839923.0\n10.1097%2F00000542-200006000-00031\nNone\nBACKGROUND: Halothane more so than isoflurane potentiates an alpha1-adrenoceptor (alpha1-AR)-mediated action of epinephrine that abnormally slows conduction in Purkinje fibers and may facilitate reentrant arrhythmias. This adverse drug interaction was further evaluated by examining conduction responses to epinephrine in combination with thiopental and propofol, which "sensitize" or reduce the dose of epinephrine required to induce arrhythmias in the heart, and with etomidate, which does not, and responses to epinephrine with verapamil, lidocaine, and l-palmitoyl carnitine, a potential ischemic metabolite. METHODS: Action potentials and conduction times were measured in vitro using two microelectrodes in groups of canine Purkinje fibers stimulated at 150 pulses/min. Conduction was evaluated each minute after exposure to 5 microm epinephrine (or phenylephrine) alone or with the test drugs. Changes in the rate of phase 0 depolarization (Vmax) and the electrotonic spread of intracellular current were measured during exposure to epinephrine with octanol to evaluate the role of inhibition of active and passive (intercellular coupling) membrane properties in the transient depression of conduction velocity. RESULTS: Lidocaine (20 microm) and octanol (0.2 mm) potentiated alpha1-AR-induced conduction depression like halothane (0.4 mm), with maximum depression at 3-5 min of agonist exposure, no decrease of Vmax, and little accentuation at a rapid (250 vs. 150 pulses/min) stimulation rate. Thiopental (95 microm), propofol (50 microm), and verapamil (2 microm) similarly potentiated epinephrine responses, whereas etomidate (10 microm) did not. Between groups, the decrease of velocity induced by epinephrine in the presence of (10 microm) l-palmitoyl carnitine (-18%) was significantly greater than that resulting from epinephrine alone (-6%; 0.05 = P = 0.10). Current injection experiments were consistent with marked transient inhibition of cell-to-cell coupling correlating with alpha1-AR conduction depression in fibers exposed to octanol. CONCLUSIONS: Anesthetic "sensitization" to the arrhythmogenic effects of catecholamines may be a special case of a more general phenomenon by which not only some anesthetics and antiarrhythmic drugs but also possible ischemic fatty acid metabolites potentiate conduction depression due to acute alpha1-AR-mediated cell-to-cell uncoupling.\n\n\n"
},
{
"text": "\n4121\nIntravenous zoledronic acid in postmenopausal women with low bone mineral density.\n\nReid, IR\n\nBrown, JP\n\nBurckhardt, P\n\nHorowitz, Z\n\nRichardson, P\n\nTrechsel, U\n\nWidmer, A\n\nDevogelaer, JP\n\nKaufman, JM\n\nJaeger, P\n\nBody, JJ\n\nBrandi, ML\n\nBroell, J\n\nDi Micco, R\n\nGenazzani, AR\n\nFelsenberg, D\n\nHapp, J\n\nHooper, MJ\n\nIttner, J\n\nLeb, G\n\nMallmin, H\n\nMurray, T\n\nOrtolani, S\n\nRubinacci, A\n\nSaaf, M\n\nSamsioe, G\n\nVerbruggen, L\n\nMeunier, PJ\n\nBeiträge in Fachzeitschriften\nISI:000174062800003\n11870242.0\n10.1056/NEJMoa011807\nNone\nBACKGROUND: Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored. METHODS: We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point. RESULTS: There were similar increases in bone mineral density in all the zoledronic acid groups to values for the spine that were 4.3 to 5.1 percent higher than those in the placebo group (P<0.001) and values for the femoral neck that were 3.1 to 3.5 percent higher than those in the placebo group (P<0.001). Biochemical markers of bone resorption were significantly suppressed throughout the study in all zoledronic acid groups. Myalgia and pyrexia occurred more commonly in the zoledronic acid groups, but treatment-related dropout rates were similar to that in the placebo group. CONCLUSIONS: Zoledronic acid infusions given at intervals of up to one year produce effects on bone turnover and bone density as great as those achieved with daily oral dosing with bisphosphonates with proven efficacy against fractures, suggesting that an annual infusion of zoledronic acid might be an effective treatment for postmenopausal osteoporosis.\n\n\n"
},
{
"text": "\n21924\nProstanoid therapy for pulmonary arterial hypertension.\n\nBadesch, DB\n\nMcLaughlin, VV\n\nDelcroix, M\n\nVizza, CD\n\nOlschewski, H\n\nSitbon, O\n\nBarst, RJ\n\nBeiträge in Fachzeitschriften\nISI:000222209300009\n15194179.0\n10.1016/j.jacc.2004.02.036\nNone\nProstanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients had less disease progression at six months and confirmed the results of the previous trial. However, this improvement was no longer present at 9 or 12 months. In conclusion, though treatment with prostanoids is complicated by their generally short half-lives and complicated drug delivery systems, they continue to play an important role in the treatment of PAH.\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n52381\nCell type-specific requirement of the MAPK pathway for the growth factor action of gastrin.\n\nStepan, VM\n\nDickinson, CJ\n\ndel Valle, J\n\nMatsushima, M\n\nTodisco, A\n\nBeiträge in Fachzeitschriften\nISI:000080785800007\n10362639.0\nNone\nNone\nGastrin (G17) has a CCKB receptor-mediated growth-promoting effect on the AR42J rat acinar cell line that is linked to induction of both mitogen-activated protein kinase (MAPK) and c-fos gene expression. We investigated the mechanisms that regulate the growth factor action of G17 on the rat pituitary adenoma cell line GH3. Both AR42J and GH3 cells displayed equal levels of CCKB receptor expression and similar binding kinetics of 125I-labeled G17. G17 stimulation of cell proliferation was identical in both cell lines. G17 stimulation of GH3 cell proliferation was completely blocked by the CCKB receptor antagonist D2 but not by the MEK inhibitor PD-98059 or the protein kinase C inhibitor GF-109203X, which completely inhibited G17 induction of AR42J cell proliferation. G17 induced a c-fos SRE-luciferase reporter gene plasmid more than fourfold in the AR42J cells, whereas it had no effect in the GH3 cells. In contrast to what we observed in the AR42J cells, G17 failed to stimulate MAPK activation and Shc tyrosyl phosphorylation and association with the adapter protein Grb2. Epidermal growth factor induced the MAPK pathway in the GH3 cells, demonstrating the integrity of this signaling system. G17 induced Ca2+ mobilization in both the GH3 and AR42J cells. The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited AR42J cell proliferation by 20%, whereas it completely blocked G17 induction of GH3 cell growth. The Ca2+ ionophore ionomycin stimulated GH3 cell proliferation to a level similar to that observed in response to G17, but it had no effect on AR42J cell proliferation. Thus there are cell type specific differences in the requirement of the MAPK pathway for the growth factor action of G17. Whereas in the AR42J cells G17 stimulates cell growth through activation of MAPK and c-fos gene expression, in the GH3 cells, G17 fails to activate MAPK, and it induces cell proliferation through Ca2+-dependent signaling pathways. Furthermore, induction of Ca2+ mobilization in the AR42J cells appears not to be sufficient to sustain cell proliferation.\n\nStepan, Vinzenz\n\n\n"
},
{
"text": "\n81343\nHereditary sensory neuropathy type I.\n\nAuer-Grumbach, M\n\nBeiträge in Fachzeitschriften\nISI:000255565200001\n18348718.0\n10.1186/1750-1172-3-7\nPMC2311280\nHereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease.\n\n\n"
},
{
"text": "\n113054\nTreatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial.\n\nWolf, P\n\nWeger, W\n\nLegat, FJ\n\nPosch-Fabian, T\n\nGruber-Wackernagel, A\n\nInzinger, M\n\nSalmhofer, W\n\nHofer, A\n\nBeiträge in Fachzeitschriften\nISI:000300695900051\n21910714.0\n10.1111/j.1365-2133.2011.10616.x\nNone\nTreatment with the interleukin-12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque-type psoriasis.\n To determine whether concomitant 311-nm ultraviolet (UV) B therapy can further enhance the response in patients with psoriasis treated with ustekinumab.\n Ten patients (five women and five men; mean age 58years, range 48-66) with moderate to severe plaque-type psoriasis were treated with ustekinumab at a standard dosage of 45 or 90mg subcutaneously depending on body weight (below or above 100kg) at weeks 0 and 4. Within 2days after ustekinumab initiation, the minimal erythemal dose (MED) was determined and suberythemal MED 311-nm UVB-based phototherapy was thereafter administered to one randomly selected body half (left or right, excluding the head) three times weekly for 6weeks. Treatment response was monitored weekly in terms of half-body PASI.\n Nine patients completed the study. Analysis of their data showed that 311-nm UVB significantly accelerated the therapeutic response. At baseline (i.e. start of 311-nm UVB therapy), the mean PASI was similar in both irradiated and unirradiated body halves (13·6 vs. 13·3). At week 6, however, it was lower on irradiated body halves (2·5 vs. 6·1). This difference of 3·6 (95% confidence interval 1·3-5) was statistically significant and corresponded to an overall mean PASI reduction from baseline of 82% vs. 54%, respectively. At week 6, PASI 75 was achieved significantly more often on UV-irradiated body halves than on unirradiated body halves [7/9 patients (78%) vs. 1/9 (11%)] (McNemar test, P=0·007). At week 12, this synergistic effect of 311-nm UVB was still apparent although not significantly so.\n Treatment with 311-nm UVB accelerates the clearance of psoriatic lesions in ustekinumab-treated patients.\n © 2011 The Authors. BJD © 2011 British Association of Dermatologists.\n\nGruber-Wackernagel, Alexandra\n\nHofer, Angelika\n\nLegat, Franz\n\nSalmhofer, Wolfgang\n\nWeger, Wolfgang\n\nWolf, Peter\n\n\n"
},
{
"text": "\n122888\nB vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy.\n\nCavalieri, M\n\nSchmidt, R\n\nChen, C\n\nMok, V\n\nde Freitas, GR\n\nSong, S\n\nYi, Q\n\nRopele, S\n\nGrazer, A\n\nHomayoon, N\n\nEnzinger, C\n\nLoh, K\n\nWong, KS\n\nWong, A\n\nXiong, Y\n\nChang, HM\n\nWong, MC\n\nFazekas, F\n\nEikelboom, JW\n\nHankey, GJ\n\nVITATOPS Trial Study Group\n\nBeiträge in Fachzeitschriften\nISI:000311497600029\n23093615.0\n10.1161/STROKEAHA.112.665703\nNone\nElevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B12 and B6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of B vitamins would reduce the progression of CSVD-related brain lesions.\n A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities.\n After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm3; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm3; P=0.039).\n Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD.\n http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444.\n\nCavalieri, Margherita\n\nEnzinger, Christian\n\nFazekas, Franz\n\nHomayoon, Nina\n\nRopele, Stefan\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n123822\nEfficacy of laparoscopic sleeve gastrectomy (LSG) as a stand-alone technique for children with morbid obesity\n\nTill, H\n\nBluher, S\n\nHirsch, W\n\nKiess, W\n\nBeiträge in Fachzeitschriften\nISI:000258816100315\n18459015.0\n10.1007/s11695-008-9543-6\nNone\nBackground Laparoscopic sleeve gastrectomy (LSG) is basically unknown as a stand-alone technique for bariatric surgery in children and adolescents. It may be advantageous for this age group though, since it requires neither foreign body placement nor life-long malabsorption. We present the first report about the efficacy of LSG in a small pediatric series. Methods All patients (n=4, female) had been in a multimodal weight loss program for several years without long-term success. At referral, the mean age was 14.5 years (range 8-17), mean body mass index (BMI in kg/m(2)) was 48.4 (range 40.6-56.3). All Suffered from various features of a metabolic-vascular syndrome like diabetes, dislipidemia, cholecystolithiasis, arterial hypertension. The 8-year-old girl was diagnosed Prader-Willi Syndrome at the age of 2. The decision for bariatric surgery was taken Unanimously by the parents, patient, and the obesity team. LSG was performed in a five-trocar technique. With a gastroscope (size 40-F) protecting the lesser curvature, the stomach was resected from the proximal antrum to the angle of His using an ENDO-GIA stapler. The stapler line was secured by a Continuous suture 3-0 vicryl. Results There were no intra- or postoperative complications. Contrast Studies confirmed a J-like gastric remnant (mean volume 76 ml) and ruled out leaks in all cases. After a mean follow-up time of 12 months (range 6-19 months), all the patients had reduced weight (mean BMI to 37.2). The girl with the longest postoperative period went from 121 to 83 kg (BMI from 40.6 to 28.4). Laboratory studies ruled Out malnutrition or vitamin deficiency. Monitoring of metabolic parameters showed gradual improvement or even resolution for most features. Conclusion At a 1-year follow-up, LSG proved a safe and effective option for bariatric surgery in children, achieving moderate weight loss and improvement of comorbidities. Thus, it may be considered as stand-alone technique. Longterm studies however must compare these results with time-tested procedures like gastric banding and Roux-en-Y gastric bypass.\n\nTill, Holger\n\n\n"
},
{
"text": "\n135952\nThe natural history of thoracic aortic aneurysms.\n\nDapunt, OE\n\nGalla, JD\n\nSadeghi, AM\n\nLansman, SL\n\nMezrow, CK\n\nde Asla, RA\n\nQuintana, C\n\nWallenstein, S\n\nErgin, AM\n\nGriepp, RB\n\nBeiträge in Fachzeitschriften\nISI:A1994NL04100019\n8176976.0\n10.1016/S0022-5223(94)70054-0\nNone\nBecause improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 +/- 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 +/- 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (> 5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter)2.1; change in volume = 0.0356 (initial aortic volume)1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)\n\n\n"
},
{
"text": "\n146913\nThe CLIF Consortium Acute Decompensation score (CLIF-C ADs) for prognosis of hospitalised cirrhotic patients without acute-on-chronic liver failure.\n\nJalan, R\n\nPavesi, M\n\nSaliba, F\n\nAmorós, A\n\nFernandez, J\n\nHolland-Fischer, P\n\nSawhney, R\n\nMookerjee, R\n\nCaraceni, P\n\nMoreau, R\n\nGinès, P\n\nDurand, F\n\nAngeli, P\n\nAlessandria, C\n\nLaleman, W\n\nTrebicka, J\n\nSamuel, D\n\nZeuzem, S\n\nGustot, T\n\nGerbes, AL\n\nWendon, J\n\nBernardi, M\n\nArroyo, V\n\nCANONIC Study Investigators\n\nEASL-CLIF Consortium\n\nBeiträge in Fachzeitschriften\nISI:000351305300013\n25463539.0\n10.1016/j.jhep.2014.11.012\nNone\nCirrhotic patients with acute decompensation frequently develop acute-on-chronic liver failure (ACLF), which is associated with high mortality rates. Recently, a specific score for these patients has been developed using the CANONIC study database. The aims of this study were to develop and validate the CLIF-C AD score, a specific prognostic score for hospitalised cirrhotic patients with acute decompensation (AD), but without ACLF, and to compare this with the Child-Pugh, MELD, and MELD-Na scores.\n The derivation set included 1016 CANONIC study patients without ACLF. Proportional hazards models considering liver transplantation as a competing risk were used to identify score parameters. Estimated coefficients were used as relative weights to compute the CLIF-C ADs. External validation was performed in 225 cirrhotic AD patients. CLIF-C ADs was also tested for sequential use.\n Age, serum sodium, white-cell count, creatinine and INR were selected as the best predictors of mortality. The C-index for prediction of mortality was better for CLIF-C ADs compared with Child-Pugh, MELD, and MELD-Nas at predicting 3- and 12-month mortality in the derivation, internal validation and the external dataset. CLIF-C ADs improved in its ability to predict 3-month mortality using data from days 2, 3-7, and 8-15 (C-index: 0.72, 0.75, and 0.77 respectively).\n The new CLIF-C ADs is more accurate than other liver scores in predicting prognosis in hospitalised cirrhotic patients without ACLF. CLIF-C ADs therefore may be used to identify a high-risk cohort for intensive management and a low-risk group that may be discharged early.\n Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.\n\nSpindelböck, Walter Johann\n\n\n"
},
{
"text": "\n152365\nTrends in the use of partial nephrectomy for cT1 renal tumors: Analysis of a 10-yr European multicenter dataset.\n\nSimone, G\n\nDe Nunzio, C\n\nFerriero, M\n\nCindolo, L\n\nBrookman-May, S\n\nPapalia, R\n\nSperduti, I\n\nCollura, D\n\nLeonardo, C\n\nAnceschi, U\n\nTuderti, G\n\nMisuraca, L\n\nDalpiaz, O\n\nHatzl, S\n\nLodde, M\n\nTrenti, E\n\nPastore, AL\n\nPalleschi, G\n\nLotrecchiano, G\n\nSalzano, L\n\nCarbone, A\n\nDe Cobelli, O\n\nTubaro, A\n\nSchips, L\n\nZigeuner, R\n\nTostain, J\n\nMay, M\n\nGuaglianone, S\n\nMuto, G\n\nGallucci, M\n\nBeiträge in Fachzeitschriften\nISI:000387524400017\n27106494.0\n10.1016/j.ejso.2016.03.022\nNone\nAlthough extensively addressed in US registries, the utilization rate of Partial Nephrectomy has been poorly addressed in European settings. Our aim is to evaluate the impact of hospital volume on the use of PN for cT1 renal tumors.\n 2526 patients with cT1N0M0 renal tumors treated with either PN or radical nephrectomy at 10 European centres in the last decade were included in the analysis. Joinpoint regression analysis was used to identify significant changes over time in linear slope of the trend for each center. The correlation between yearly caseload and the slopes was assessed with the non-parametric Spearman test. Coincident pairwise tests and regression analyses were used to generate and compare the trends of high-volume (HV), mid-volume (MV) and low-volume (LV) groups.\n Yearly caseload was significantly associated with increased use of PN (R = 0.69, p = 0.028). The utilization rate of PN was stable at LV centres (p = 0.67, p = 0.7, p = 0.76, for cT1, cT1a, and cT1b tumors, respectively), while increased significantly at MV (p = 0.002, 0.0005 and 0.007, respectively) and HV centers (all p < 0.0001). Regression analysis confirmed the trends for HV and MV as significantly different from those observed in LV centres (all p ≤ 0.002) and highlighted significant differences also between MV and HV centres (all p ≤ 0.03).\n We confirmed the association between caseload and the use of PN for cT1 tumors. Our findings suggest that a minimum caseload might turn the tide also in LV centres while a selective referral to HV centers for cT1b tumors should be considered.\n Copyright © 2016 Elsevier Ltd. All rights reserved.\n\nDalpiaz, Orietta\n\nHatzl, Stefan\n\nZigeuner, Richard\n\n\n"
},
{
"text": "\n163342\nNon-linear Heart Rate and Blood Pressure Interaction in Response to Lower-Body Negative Pressure.\n\nVerma, AK\n\nXu, D\n\nGarg, A\n\nCote, AT\n\nGoswami, N\n\nBlaber, AP\n\nTavakolian, K\n\nBeiträge in Fachzeitschriften\nISI:000413544300001\n29114227.0\n10.3389/fphys.2017.00767\nPMC5660688\nEarly detection of hemorrhage remains an open problem. In this regard, blood pressure has been an ineffective measure of blood loss due to numerous compensatory mechanisms sustaining arterial blood pressure homeostasis. Here, we investigate the feasibility of causality detection in the heart rate and blood pressure interaction, a closed-loop control system, for early detection of hemorrhage. The hemorrhage was simulated via graded lower-body negative pressure (LBNP) from 0 to -40 mmHg. The research hypothesis was that a significant elevation of causal control in the direction of blood pressure to heart rate (i.e., baroreflex response) is an early indicator of central hypovolemia. Five minutes of continuous blood pressure and electrocardiogram (ECG) signals were acquired simultaneously from young, healthy participants (27 ± 1 years, N = 27) during each LBNP stage, from which heart rate (represented by RR interval), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were derived. The heart rate and blood pressure causal interaction (RR↔SBP and RR↔MAP) was studied during the last 3 min of each LBNP stage. At supine rest, the non-baroreflex arm (RR→SBP and RR→MAP) showed a significantly (p < 0.001) higher causal drive toward blood pressure regulation compared to the baroreflex arm (SBP→RR and MAP→RR). In response to moderate category hemorrhage (-30 mmHg LBNP), no change was observed in the traditional marker of blood loss i.e., pulse pressure (p = 0.10) along with the RR→SBP (p = 0.76), RR→MAP (p = 0.60), and SBP→RR (p = 0.07) causality compared to the resting stage. Contrarily, a significant elevation in the MAP→RR (p = 0.004) causality was observed. In accordance with our hypothesis, the outcomes of the research underscored the potential of compensatory baroreflex arm (MAP→RR) of the heart rate and blood pressure interaction toward differentiating a simulated moderate category hemorrhage from the resting stage. Therefore, monitoring baroreflex causality can have a clinical utility in making triage decisions to impede hemorrhage progression.\n\nGoswami, Nandu\n\n\n"
},
{
"text": "\n164123\nSoluble CD163 and soluble mannose receptor predict survival and decompensation in patients with liver cirrhosis, and correlate with gut permeability and bacterial translocation.\n\nRainer, F\n\nHorvath, A\n\nSandahl, TD\n\nLeber, B\n\nSchmerboeck, B\n\nBlesl, A\n\nGroselj-Strele, A\n\nStauber, RE\n\nFickert, P\n\nStiegler, P\n\nMøller, HJ\n\nGrønbaek, H\n\nStadlbauer, V\n\nBeiträge in Fachzeitschriften\nISI:000424486300012\n29266346.0\n10.1111/apt.14474\nPMC6333289\nActivated hepatic macrophages play a key role in inflammation and fibrosis progression in chronic liver disease.\n To assess the prognostic value of soluble (s)CD163 and mannose receptor (sMR) in cirrhotic patients and explore associations with markers of intestinal permeability (lactulose-mannitol ratio, diamine oxidase), bacterial translocation (endotoxin, lipopolysaccharide-binding protein) and markers of systemic immune activation (interleukin-6, interleukin-8, sCD14).\n We prospectively investigated 101 cirrhotic patients (Child-Pugh class A: n = 72, Child-Pugh classes B and C: n = 29) and 31 healthy controls. Patients were observed for a median follow-up of 37 months.\n Median plasma levels of sCD163 and soluble mannose receptor were significantly elevated in cirrhotic patients (P < .001) and increased with disease severity (sCD163 in healthy controls = 1.3, Child-Pugh class A = 4.2, Child-Pugh classes B and C = 8.4 mg/L; sMR in healthy controls = 15.8, Child-Pugh class A = 36.5, Child-Pugh classes B and C = 66.3 μg/dL). A total of 21 patients died during the observation period. Patients with sCD163 levels above 5.9 mg/L showed significantly reduced survival (survival rate after 36 months: 71% versus 98%, P < .001). Patients with soluble mannose receptor levels above 45.5 μg/dL developed significantly more complications of cirrhosis within 12 months (73% versus 9%, P < .001). Furthermore, both variables correlated with the lactulose-mannitol ratio, diamine oxidase, lipopolysaccharide and interleukin-8.\n Our data demonstrate the prognostic value of sCD163 in predicting long-term survival in patients with liver cirrhosis and identify soluble mannose receptor as a prognostic marker for occurrence of cirrhosis-associated complications. The correlation between gut barrier dysfunction and activation of macrophages points towards a link between them.\n © 2017 John Wiley & Sons Ltd.\n\nBlesl, Andreas\n\nFickert, Peter\n\nGroselj-Strele, Andrea\n\nHorvath, Angela\n\nLeber, Bettina\n\nRainer, Florian\n\nStadlbauer-Köllner, Vanessa\n\nStauber, Rudolf\n\nStiegler, Philipp\n\n\n"
},
{
"text": "\n164647\nModulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice.\n\nHartmann, P\n\nHochrath, K\n\nHorvath, A\n\nChen, P\n\nSeebauer, CT\n\nLlorente, C\n\nWang, L\n\nAlnouti, Y\n\nFouts, DE\n\nStärkel, P\n\nLoomba, R\n\nCoulter, S\n\nLiddle, C\n\nYu, RT\n\nLing, L\n\nRossi, SJ\n\nDePaoli, AM\n\nDownes, M\n\nEvans, RM\n\nBrenner, DA\n\nSchnabl, B\n\nBeiträge in Fachzeitschriften\nISI:000434113900012\n29159825.0\n10.1002/hep.29676\nPMC5962369\nAlcoholic liver disease (ALD) is associated with changes in the intestinal microbiota. Functional consequences of alcohol-associated dysbiosis are largely unknown. The aim of this study was to identify a mechanism of how changes in the intestinal microbiota contribute to ALD. Metagenomic sequencing of intestinal contents demonstrated that chronic ethanol feeding in mice is associated with an over-representation of bacterial genomic DNA encoding choloylglycine hydrolase, which deconjugates bile acids in the intestine. Bile acid analysis confirmed an increased amount of unconjugated bile acids in the small intestine after ethanol administration. Mediated by a lower farnesoid X receptor (FXR) activity in enterocytes, lower fibroblast growth factor (FGF)-15 protein secretion was associated with increased hepatic cytochrome P450 enzyme (Cyp)-7a1 protein expression and circulating bile acid levels. Depletion of the commensal microbiota with nonabsorbable antibiotics attenuated hepatic Cyp7a1 expression and reduced ALD in mice, suggesting that increased bile acid synthesis is dependent on gut bacteria. To restore intestinal FXR activity, we used a pharmacological intervention with the intestine-restricted FXR agonist fexaramine, which protected mice from ethanol-induced liver injury. Whereas bile acid metabolism was only minimally altered, fexaramine treatment stabilized the gut barrier and significantly modulated hepatic genes involved in lipid metabolism. To link the beneficial metabolic effect to FGF15, a nontumorigenic FGF19 variant-a human FGF15 ortholog-was overexpressed in mice using adeno-associated viruses. FGF19 treatment showed similarly beneficial metabolic effects and ameliorated alcoholic steatohepatitis.\n Taken together, alcohol-associated metagenomic changes result in alterations of bile acid profiles. Targeted interventions improve bile acid-FXR-FGF15 signaling by modulation of hepatic Cyp7a1 and lipid metabolism, and reduce ethanol-induced liver disease in mice. (Hepatology 2018;67:2150-2166).\n © 2017 by the American Association for the Study of Liver Diseases.\n\nHorvath, Angela\n\n\n"
},
{
"text": "\n164888\nThe urgent need for a harmonized severity scoring system for acute allergic reactions.\n\nMuraro, A\n\nFernandez-Rivas, M\n\nBeyer, K\n\nCardona, V\n\nClark, A\n\nEller, E\n\nHourihane, JO\n\nJutel, M\n\nSheikh, A\n\nAgache, I\n\nAllen, KJ\n\nAngier, E\n\nBallmer-Weber, B\n\nBilò, MB\n\nBindslev-Jensen, C\n\nCamargo, CA\n\nCianferoni, A\n\nDunnGalvin, A\n\nEigenmann, PA\n\nHalken, S\n\nHoffmann-Sommergruber, K\n\nLau, S\n\nNilsson, C\n\nPoulsen, LK\n\nRueff, F\n\nSpergel, J\n\nSturm, G\n\nTimmermans, F\n\nTorres, MJ\n\nTurner, P\n\nvan Ree, R\n\nWickman, M\n\nWorm, M\n\nMills, ENC\n\nRoberts, G\n\nBeiträge in Fachzeitschriften\nISI:000443222400004\n29331045.0\n10.1111/all.13408\nNone\nThe accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.\n © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.\n\nSturm, Gunter\n\n\n"
},
{
"text": "\n168248\nInfectious Complications After Laparoscopic Appendectomy in Pediatric Patients with Perforated Appendicitis: Is There a Difference in the Outcome Using Irrigation and Suction Versus Suction Only? Results of a Multicentric International Retrospective Study.\n\nEscolino, M\n\nBecmeur, F\n\nSaxena, A\n\nTill, H\n\nMasieri, L\n\nCortese, G\n\nHolcomb, GW\n\nEsposito, C\n\nBeiträge in Fachzeitschriften\nISI:000447150300019\n29906215.0\n10.1089/lap.2018.0061\nNone\nAnalyzing the recent literature, it seems that the use of irrigation increases the incidence of intra-abdominal abscesses (IAAs) and infectious complications in perforated appendicitis. The aim of this study was to compare peritoneal irrigation and suction versus suction only during laparoscopic appendectomy (LA) for perforated appendicitis in children.\n We retrospectively reviewed the records of 699 patients (460 boys and 239 girls, average age 9.8 years) who underwent LA for complicated appendicitis in six international centers of pediatric surgery over a 5-year period. The appendix was perforated with localized peritonitis in 465 cases and diffuse peritonitis in 234 patients. Irrigation + suction was used in 488 cases (group 1 [G1]), whereas suction only was used in 211 cases (group 2 [G2]).\n No significant difference between the two groups was found in regard to average operative time (P = .23), average time of resumption of oral diet (P = .55), average reprise of gastrointestinal transit (P = .55), and average length of hospital stay (P = .41). As for postoperative complications, the incidence of IAAs was significantly higher in G2 (41/211; 19.4%) compared with G1 (38/488; 7.7%) (P = .0000), whereas no significant difference was found between the two groups in regard to wound infection (G1: n = 2 or 0.4%; G2: n = 4 or 1.8%; P = .05) and small bowel obstruction rates (G1: n = 8 or 1.6%; G2: n = 2 or 0.9%; P = .47).\n In contrast with the most recent literature on this topic, our results demonstrated that peritoneal irrigation and suction were associated with a lower rate of postoperative IAA formation compared with the suction-only approach in children with perforated appendicitis. In such cases, peritoneal irrigation and abdominal drainage should be the preferred methods for peritoneal toilette, with no increase in operative time and postoperative morbidity.\n\nTill, Holger\n\n\n"
},
{
"text": "\n168873\nEfficacy and safety of a new low-volume PEG with citrate and simethicone bowel preparation for colonoscopy (Clensia): a multicenter randomized observer-blind clinical trial vs. a low-volume PEG with ascorbic acid (PEG-ASC).\n\nKump, P\n\nHassan, C\n\nSpada, C\n\nBrownstone, E\n\nDatz, C\n\nHaefner, M\n\nRenner, F\n\nSchoefl, R\n\nSchreiber, F\n\nBeiträge in Fachzeitschriften\nISI:000440444800001\n30083580.0\n10.1055/a-0624-2266\nPMC6070370\nQuality of inspection during colonoscopy is strictly related to the level of cleansing. High-volume (PEG-based) solutions are highly effective and safe, but their high volume affects tolerability and compliance. The aim of this study was to compare a new low-volume PEG with citrate and simethicone solution (PMF 104, lensia) with a low-volume PEG with ascorbic acid solution (PEG-ASC; Moviprep).\n This was a multicenter, randomized, observer-blind, parallel-group, phase 3 clinical trial, where patients were randomized between PMF 104 and PEG-ASC. In both groups, patients were instructed to take a full-dose regimen the evening before if colonoscopy was scheduled before 11 am to 12 pm, or to take a split regimen if colonoscopy was scheduled after 11 am to 12 pm. The primary end-point was an equivalence between PMF104 and PEG-ASC in the rate of adequate level of cleansing (Ottawa scale ≤ 6), with safety, mucosal visibility, tolerability, acceptance and compliance being also assessed.\n Of the 403 enrolled, 367 patients (Mean age [SD]: 55.6 (14.4) years; male:166 [45.2 %]) were included in the per protocol (PP) analysis: 184 being randomized in the PMF 104 group and 183 in the PEG-ASC group. Successful bowel cleansing was 78.3 % and 74.3 % in PMF104 and in PEG-ASC, respectively ( P = 0.37). Both preparations were equally safe (mild adverse events were observed in 9.2 % and 9.3 % of patients in the PMF104 and in the PEG-ASC group, respectively) and acceptable (no or mild distress during the intake in 81.4 % and 80.8 % in the PMF104 in the PEG-ASC, respectively [ P = 0.74]).\n The new low-volume product Clensia is equivalent to the reference low-volume PEG-ASC in terms of bowel cleansing, safety and acceptance.\n\nKump, Patrizia\n\n\n"
},
{
"text": "\n175488\nTesting the feasibility of augmented digital skin imaging to objectively compare the efficacy of topical treatments for radiodermatitis.\n\nPartl, R\n\nLehner, J\n\nWinkler, P\n\nKapp, KS\n\nBeiträge in Fachzeitschriften\nISI:000470854200036\n31181091.0\n10.1371/journal.pone.0218018\nPMC6557505\nRadiation-induced dermatitis (RID) is routinely graded by visual inspection. Inter-observer variability makes this approach inadequate for an objective assessment of the efficacy of different topical treatments. In this study we report on the first clinical application of a new image-analysis tool developed to measure the relevant effects quantitatively and to compare the effects of two different topical preparations used to treat RID.\n After completion of radiotherapy, RID was retrospectively assessed in 100 white female breast cancer patients who had received adjuvant breast irradiation. Of these patients, 34 were treated with R1&R2, a Lactokine-fluid derived from milk proteins, and 66 were treated with Bepanthen. In addition RID was graded independently by two experienced radiation oncologists in accordance with the Common Terminology Criteria for Adverse Events (CTCAE). For quantitative evaluation, the irradiated breast and the non-irradiated contralateral breast were photographed in a standardized manner including a color reference card. For analysis, all images were converted into the color space L*a*b* and mean values were calculated for each of the color parameters.\n The CTCAE-based grading revealed statistically significant inter-observer variability in the scoring of RID Grades 1, 2 and 3 (p<0.001). A difference between the two topical products could not be observed with visual inspection. By using augmented image analysis methods a statistically significant increase in a*-values (mean 4.15; 95%CI: 5.97-2.33, p<0.001) in patients treated with R1&R2 indicated more intense reddening. Digital subtraction was used to eliminate differences in individual baseline skin tone to generate a new, low-scatter parameter (ΔSEV).\n Visual CTCAE-based evaluation of RID was not suitable for assessing the efficacy of the skin treatment products. In contrast, the novel image analysis enabled a quantitative evaluation independent of skin type and baseline skin tone in our cohort suggesting that augmented image analysis may be a suitable tool for this type of investigation. Prospective studies are needed to validate our findings.\n\nPartl, Richard\n\nWinkler, Peter\n\n\n"
},
{
"text": "\n184065\nMeal replacement by formula diet reduces weight more than a lifestyle intervention alone in patients with overweight or obesity and accompanied cardiovascular risk factors-the ACOORH trial.\n\nHalle, M\n\nRöhling, M\n\nBanzer, W\n\nBraumann, KM\n\nKempf, K\n\nMcCarthy, D\n\nSchaller, N\n\nPredel, HG\n\nScholze, J\n\nFührer-Sakel, D\n\nToplak, H\n\nBerg, A\n\nACOORH study group\n\nBeiträge in Fachzeitschriften\nISI:000586347800001\n33128036.0\n10.1038/s41430-020-00783-4\nNone\nAs formula diets have demonstrated to be effective in reducing weight, we hypothesised that in patients with overweight or obesity and accompanied cardiovascular risk factors, combining a liquid formula diet with a lifestyle intervention is superior in reducing weight and improving cardiovascular risk factors than lifestyle intervention alone.\n In this multicenter RCT 463 participants with overweight or obesity (BMI: 27-35 kg/m²; at least one additional co-morbidity of the metabolic syndrome) were randomised (1:2) into either a control group with lifestyle intervention only (CON, n = 155) or a lifestyle intervention group including a liquid meal replacement (INT, n = 308). Both groups used telemonitoring devices (scales and pedometers), received information on healthy diet and were instructed to increase physical activity. Telemonitoring devices automatically transferred data into a personalised online portal and acquired data were discussed. INT obtained a liquid meal replacement substituting three meals/day (~1200 kcal) within the first week. During weeks 2-4, participants replaced two meals/day and during weeks 5-26 only one meal/day was substituted (1300-1500 kcal/day). Follow-up was conducted after 52 weeks. Intention-to-treat analyses were performed. Primary outcome was weight change. Secondary outcomes comprised changes in cardiometabolic risk factors including body composition and laboratory parameters.\n From the starting cohort 360 (78%, INT: n = 244; CON: n = 116) and 317 (68%, INT: n = 216; CON: n = 101) participants completed the 26-weeks intervention phase and the 52-weeks follow-up. The estimated treatment difference (ETD) between both groups was -3.2 kg [-4.0; -2.5] (P < 0.001) after 12 weeks and -1.8 kg [-2.8; -0.8] (P < 0.001) after 52 weeks.\n A low-intensity lifestyle intervention combined with a liquid meal replacement is superior regarding weight reduction and improvement of cardiovascular risk factors than lifestyle intervention alone.\n\nToplak, Hermann\n\n\n"
}
]
}