Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

The effects of cardiac output and pulmonary arterial hypertension on volumetric capnography derived-variables during normoxia and hypoxia

The aim of this study was to test the effect of cardiac output (CO) and pulmonary artery hypertension (PHT) on volumetric capnography (VCap) derived-variables. Nine pigs were mechanically ventilated using fixed ventilatory settings. Two steps of PHT were induced by IV infusion of a thromboxane analogue: PHT25 [mean pulmonary arterial pressure (MPAP) of 25 mmHg] and PHT40 (MPAP of 40 mmHg). CO was increased by 50 % from baseline (COup) with an infusion of dobutamine ≥5 μg kg(-1) min(-1) and decreased by 40 % from baseline (COdown) infusing sodium nitroglycerine ≥30 μg kg(-1) min(-1) plus esmolol 500 μg kg(-1) min(-1). Another state of PHT and COdown was induced by severe hypoxemia (FiO2 0.07). Invasive hemodynamic data and VCap were recorded and compared before and after each step using a mixed random effects model. Compared to baseline, the normalized slope of phase III (SnIII) increased by 32 % in PHT25 and by 22 % in PHT40. SnIII decreased non-significantly by 4 % with COdown. A combination of PHT and COdown associated with severe hypoxemia increased SnIII by 28 % compared to baseline. The elimination of CO2 per breath decreased by 7 % in PHT40 and by 12 % in COdown but increased only slightly with COup. Dead space variables did not change significantly along the protocol. At constant ventilation and body metabolism, pulmonary artery hypertension and decreases in CO had the biggest effects on the SnIII of the volumetric capnogram and on the elimination of CO2.

Arterial Hypertension Refractory to Renal Denervation, Abdominal Pain and Claudication: Any Coral’ations?

Coral reef aorta is a rare form of calcifying atherosclerosis typically involving the supra and juxtarenal aorta. P atients classically present with refractory hypertension, intermittent claudication and abdominal angina. The treatment is either surgical via transaortic endarterectomy or through transferal endovascular stentgraft placement. Here we describe the case of a 45yearold female patient infected with human immuno deficiency virus, with resistant hypertension, lower limb and abdominal claudication, who was successfully treated with endovascular stent placement. We f urther provide a brief overview of the disease characteristics and treatment options.

Spatial cognition, body representation and affective processes: the role of vestibular information beyond ocular reflexes and control of posture

A growing number of studies in humans demonstrate the involvement of vestibular information in tasks that are seemingly remote from well-known functions such as space constancy or postural control. In this review article we point out three emerging streams of research highlighting the importance of vestibular input: (1) Spatial Cognition: Modulation of vestibular signals can induce specific changes in spatial cognitive tasks like mental imagery and the processing of numbers. This has been shown in studies manipulating body orientation (changing the input from the otoliths), body rotation (changing the input from the semicircular canals), in clinical findings with vestibular patients, and in studies carried out in microgravity. There is also an effect in the reverse direction; top-down processes can affect perception of vestibular stimuli. (2) Body Representation: Numerous studies demonstrate that vestibular stimulation changes the representation of body parts, and sensitivity to tactile input or pain. Thus, the vestibular system plays an integral role in multisensory coordination of body representation. (3) Affective Processes and Disorders: Studies in psychiatric patients and patients with a vestibular disorder report a high comorbidity of vestibular dysfunctions and psychiatric symptoms. Recent studies investigated the beneficial effect of vestibular stimulation on psychiatric disorders, and how vestibular input can change mood and affect. These three emerging streams of research in vestibular science are—at least in part—associated with different neuronal core mechanisms. Spatial transformations draw on parietal areas, body representation is associated with somatosensory areas, and affective processes involve insular and cingulate cortices, all of which receive vestibular input. Even though a wide range of different vestibular cortical projection areas has been ascertained, their functionality still is scarcely understood.

Fluorescence lifetime imaging of the ocular fundus in mice

PURPOSE Fundus autofluorescence (AF) is characterized not only by its intensity or excitation and emission spectra but also by the lifetimes of the fluorophores. Fluorescence lifetime is influenced by the fluorophore's microenvironment and may provide information about the metabolic tissue state. We report quantitative and qualitative autofluorescence lifetime imaging of the ocular fundus in mice. METHODS A fluorescence lifetime imaging ophthalmoscope (FLIO) was used to measure fluorescence lifetimes of endogenous fluorophores in the murine retina. FLIO imaging was performed in 1-month-old C57BL/6, BALB/c, and C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. Measurements were repeated at monthly intervals over the course of 6 months. For correlation with structural changes, an optical coherence tomogram was acquired. RESULTS Fundus autofluorescence lifetime images were readily obtained in all mice. In the short spectral channel (498-560 nm), mean ± SEM AF lifetimes were 956 ± 15 picoseconds (ps) in C57BL/6; 801 ± 35 ps in BALB/c mice; and 882 ± 37 ps in C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. In the long spectral channel (560-720 nm), mean ± SEM AF lifetimes were 298 ± 14 ps in C57BL/6 mice, 241 ± 10 ps in BALB/c mice, and 288 ± 8 ps in C3A.Cg-Pde6b(+)Prph2(Rd2)/J mice. There was a general decrease in mean AF lifetimes with age. CONCLUSIONS Although fluorescence lifetime values differ among mouse strains, we found little variance within the groups. Fundus autofluorescence lifetime imaging in mice may provide additional information for understanding retinal disease processes and may facilitate monitoring of therapeutic effects in preclinical studies.

Attributional styles and stress-related atherogenic plasma lipid reactivity in essential hypertension.

OBJECTIVE Hypertension and an atherogenic lipid profile are known risk factors for coronary heart disease (CHD). Hypertensives show greater changes in atherogenic plasma lipids to acute stress than normotensives. In this study, we investigated whether attribution of failure is associated with lipid stress reactivity in hypertensive compared with normotensive men. METHODS 18 normotensive and 17 hypertensive men (mean±SEM; 45±2.2 years) underwent an acute standardized psychosocial stress task that can be viewed as a situation of experimentally induced failure. We assessed external-stable (ES), external-variable (EV), internal-stable (IS), and internal-variable (IV) attribution of failure and psychological control variables (i.e. extent of depression and neuroticism). Moreover, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and norepinephrine were measured immediately before and several times after stress. RESULTS ES moderated TC- and LDL-C-stress reactivity in hypertensives as compared to normotensives (interaction mean arterial pressure [MAP]-by-ES for TC: F=3.71, p=.015; for LDL-C: F=3.61, p=.016). TC and LDL-C levels were highest in hypertensives with low ES immediately after stress (p≤.039). In contrast, hypertensives with high ES did not differ from normotensives in TC and LDL-C immediately after stress (p's>.28). Controlling for norepinephrine, depression, and neuroticism in addition to age and BMI did not significantly change results. There were no significant associations between lipid baseline levels or aggregated lipid secretion and IS, IV, or EV (p's>.23). CONCLUSION Our data suggest that ES may independently protect from elevated lipid stress reactivity in hypertensive individuals. ES thus might be a protective factor against CHD in hypertension.

Risk factors for colic in horses hospitalized for ocular disease

OBJECTIVE: To evaluate the incidence of colic and risk factors for colic in equids hospitalized for ocular disease. DESIGN: Retrospective observational study. Animals-337 equids (317 horses, 19 ponies, and 1 donkey) hospitalized for ocular disease. PROCEDURES: Medical records of equids hospitalized for > 24 hours for treatment of ocular disease between January 1997 and December 2008 were reviewed. Information from only the first hospitalization was used for equids that were hospitalized for ocular disease on more than 1 occasion. Information gathered included the signalment, the type of ocular lesion and the treatment administered, and any colic signs recorded during hospitalization as well as the severity, presumptive diagnosis, and treatment of the colic. Statistical analysis was used to identify any risk factors for colic in equids hospitalized for ocular disease. RESULTS: 72 of 337 (21.4%) equids hospitalized for ocular disease had signs of colic during hospitalization. Most equids (59.7% [43/72]) had mild signs of colic, and most (87.5% [63/72]) were treated medically. Ten of 72 (13.9%) equids with colic had a cecal impaction. Risk factors for colic in equids hospitalized for ocular disease were age (0 to 1 year and ≥ 21 years) and an increased duration of hospitalization (≥ 8 days). CONCLUSIONS AND CLINICAL RELEVANCE: There was a high incidence of colic in equids hospitalized with ocular disease in this study. Findings from this study may help identify equids at risk for development of colic and thereby help direct implementation of prophylactic measures.

General Practitioners' vitamin K antagonist monitoring is associated with better blood pressure control in patients with hypertension - a cross-sectional database study.

BACKGROUND Patients requiring anticoagulation suffer from comorbidities such as hypertension. On the occasion of INR monitoring, general practitioners (GPs) have the opportunity to control for blood pressure (BP). We aimed to evaluate the impact of Vitamin-K Antagonist (VKA) monitoring by GPs on BP control in patients with hypertension. METHODS We cross-sectionally analyzed the database of the Swiss Family Medicine ICPC Research using Electronic Medical Records (FIRE) of 60 general practices in a primary care setting in Switzerland. This database includes 113,335 patients who visited their GP between 2009 and 2013. We identified patients with hypertension based on antihypertensive medication prescribed for ≥6 months. We compared patients with VKA for ≥3 months and patients without such treatment regarding BP control. We adjusted for age, sex, observation period, number of consultations and comorbidity. RESULTS We identified 4,412 patients with hypertension and blood pressure recordings in the FIRE database. Among these, 569 (12.9 %) were on Phenprocoumon (VKA) and 3,843 (87.1 %) had no anticoagulation. Mean systolic and diastolic BP was significantly lower in the VKA group (130.6 ± 14.9 vs 139.8 ± 15.8 and 76.6 ± 7.9 vs 81.3 ± 9.3 mm Hg) (p < 0.001 for both). The difference remained after adjusting for possible confounders. Systolic and diastolic BP were significantly lower in the VKA group, reaching a mean difference of -8.4 mm Hg (95 % CI -9.8 to -7.0 mm Hg) and -1.5 mm Hg (95 % CI -2.3 to -0.7 mm Hg), respectively (p < 0.001 for both). CONCLUSIONS In a large sample of hypertensive patients in Switzerland, VKA treatment was independently associated with better systolic and diastolic BP control. The observed effect could be due to better compliance with antihypertensive medication in patients treated with VKA. Therefore, we conclude to be aware of this possible benefit especially in patients with lower expected compliance and with multimorbidity.

Determinants of renal tissue oxygenation as measured with BOLD-MRI in chronic kidney disease and hypertension in humans.

Experimentally renal tissue hypoxia appears to play an important role in the pathogenesis of chronic kidney disease (CKD) and arterial hypertension (AHT). In this study we measured renal tissue oxygenation and its determinants in humans using blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) under standardized hydration conditions. Four coronal slices were selected, and a multi gradient echo sequence was used to acquire T2* weighted images. The mean cortical and medullary R2* values ( = 1/T2*) were calculated before and after administration of IV furosemide, a low R2* indicating a high tissue oxygenation. We studied 195 subjects (95 CKD, 58 treated AHT, and 42 healthy controls). Mean cortical R2 and medullary R2* were not significantly different between the groups at baseline. In stimulated conditions (furosemide injection), the decrease in R2* was significantly blunted in patients with CKD and AHT. In multivariate linear regression analyses, neither cortical nor medullary R2* were associated with eGFR or blood pressure, but cortical R2* correlated positively with male gender, blood glucose and uric acid levels. In conclusion, our data show that kidney oxygenation is tightly regulated in CKD and hypertensive patients at rest. However, the metabolic response to acute changes in sodium transport is altered in CKD and in AHT, despite preserved renal function in the latter group. This suggests the presence of early renal metabolic alterations in hypertension. The correlations between cortical R2* values, male gender, glycemia and uric acid levels suggest that these factors interfere with the regulation of renal tissue oxygenation.

Arterial hypertension in elderly patients

Why do we need a review specifically addressing arterial hypertension in elderly patients? First, a rterial hypertension prevalence increases with age and, therefore, a large proportion of hypertensive patients are elderly patients. Despite this fact, the specific issues of arterial hypertension in elderly patients are only marginally debated in current guidelines. Second, there are physiological changes (e.g., i ncreasing arterial stiffness, reduced body water content, decreased function of several organ systems) and pathophysiological changes (e.g. increasing prevalence of comorbidities) with increasing age, making diagnosis and therapy of arterial hypertension in elderly patients more demanding. Third, f or some recommendations (e.g., a ppropriate target blood pressure) levels of evidence are lower than in younger hypertensive patients, leading to conflicting recommendations between guidelines. This review intends to discuss some of the specific issues in elderly patients with arterial hypertension. Key words: hypertension; elderly; guidelines; geriatric assessment

First report of the Global SYMPLICITY Registry on the effect of renal artery denervation in patients with uncontrolled hypertension.

UNLABELLED This study aimed to assess the safety and effectiveness of renal denervation using the Symplicity system in real-world patients with uncontrolled hypertension (NCT01534299). The Global SYMPLICITY Registry is a prospective, open-label, multicenter registry. Office and 24-hour ambulatory blood pressures (BPs) were measured. Change from baseline to 6 months was analyzed for all patients and for subgroups based on baseline office systolic BP, diabetic status, and renal function; a cohort with severe hypertension (office systolic pressure, ≥160 mm Hg; 24-hour systolic pressure, ≥135 mm Hg; and ≥3 antihypertensive medication classes) was also included. The analysis included protocol-defined safety events. Six-month outcomes for 998 patients, including 323 in the severe hypertension cohort, are reported. Mean baseline office systolic BP was 163.5±24.0 mm Hg for all patients and 179.3±16.5 mm Hg for the severe cohort; the corresponding baseline 24-hour mean systolic BPs were 151.5±17.0 and 159.0±15.6 mm Hg. At 6 months, the changes in office and 24-hour systolic BPs were -11.6±25.3 and -6.6±18.0 mm Hg for all patients (P<0.001 for both) and -20.3±22.8 and -8.9±16.9 mm Hg for those with severe hypertension (P<0.001 for both). Renal denervation was associated with low rates of adverse events. After the procedure through 6 months, there was 1 new renal artery stenosis >70% and 5 cases of hospitalization for a hypertensive emergency. In clinical practice, renal denervation resulted in significant reductions in office and 24-hour BPs with a favorable safety profile. Greater BP-lowering effects occurred in patients with higher baseline pressures. CLINICAL TRIAL REGISTRATION URL: www.clinicaltrials.gov. Unique identifier: NCT01534299.

Effect of Pulmonary Hypertension Hemodynamic Presentation on Clinical Outcomes in Patients With Severe Symptomatic Aortic Valve Stenosis Undergoing Transcatheter Aortic Valve Implantation: Insights From the New Proposed Pulmonary Hypertension Classification.

BACKGROUND Pulmonary hypertension (PH) frequently coexists with severe aortic stenosis, and PH severity has been shown to predict outcomes after transcatheter aortic valve implantation (TAVI). The effect of PH hemodynamic presentation on clinical outcomes after TAVI is unknown. METHODS AND RESULTS Of 606 consecutive patients undergoing TAVI, 433 (71.4%) patients with severe aortic stenosis and a preprocedural right heart catheterization were assessed. Patients were dichotomized according to whether PH was present (mean pulmonary artery pressure, ≥25 mm Hg; n=325) or not (n=108). Patients with PH were further dichotomized by left ventricular end-diastolic pressure into postcapillary (left ventricular end-diastolic pressure, >15 mm Hg; n=269) and precapillary groups (left ventricular end-diastolic pressure, ≤15 mm Hg; n=56). Finally, patients with postcapillary PH were divided into isolated (n=220) and combined (n=49) subgroups according to whether the diastolic pressure difference (diastolic pulmonary artery pressure-left ventricular end-diastolic pressure) was normal (<7 mm Hg) or elevated (≥7 mm Hg). Primary end point was mortality at 1 year. PH was present in 325 of 433 (75%) patients and was predominantly postcapillary (n=269/325; 82%). Compared with baseline, systolic pulmonary artery pressure immediately improved after TAVI in patients with postcapillary combined (57.8±14.1 versus 50.4±17.3 mm Hg; P=0.015) but not in those with precapillary (49.0±12.6 versus 51.6±14.3; P=0.36). When compared with no PH, a higher 1-year mortality rate was observed in both precapillary (hazard ratio, 2.30; 95% confidence interval, 1.02-5.22; P=0.046) and combined (hazard ratio, 3.15; 95% confidence interval, 1.43-6.93; P=0.004) but not isolated PH patients (P=0.11). After adjustment, combined PH remained a strong predictor of 1-year mortality after TAVI (hazard ratio, 3.28; P=0.005). CONCLUSIONS Invasive stratification of PH according to hemodynamic presentation predicts acute response to treatment and 1-year mortality after TAVI.

A RAB3GAP1 SINE Insertion in Alaskan Huskies with Polyneuropathy, Ocular Abnormalities and Neuronal Vacuolation (POANV) Resembling Human Warburg Micro Syndrome 1 (WARBM1)

We observed a hereditary phenotype in Alaskan Huskies, which was characterized by polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV). The affected dogs developed a progressive severe ataxia, which led to euthanasia between 8 and 16 months of age. The pedigrees were consistent with a monogenic autosomal recessive inheritance. We localized the causative genetic defect to a 4 Mb interval on chromosome 19 by a combined linkage and homozygosity mapping approach. Whole genome sequencing of one affected dog, an obligate carrier and an unrelated control revealed a 218 bp SINE insertion into exon 7 of the RAB3GAP1 gene. The SINE insertion was perfectly associated with the disease phenotype in a cohort of 43 Alaskan Huskies and it was absent from 541 control dogs of diverse other breeds. The SINE insertion induced aberrant splicing and led to a transcript with a greatly altered exon 7. RAB3GAP1 loss-of-function variants in humans cause Warburg Micro Syndrome 1 (WARBM1), which is characterized by additional developmental defects compared to canine POANV, whereas Rab3gap1 deficient mice have a much milder phenotype than either humans or dogs. Thus the RAB3GAP1 mutant Alaskan Huskies provide an interesting intermediate phenotype that may help to better understand the function of RAB3GAP1 in development. Furthermore, the identification of the presumed causative genetic variant will enable genetic testing to avoid the non-intentional breeding of affected dogs.