Serum tests, liver stiffness and artificial neural networks for diagnosing cirrhosis and portal hypertension

BACKGROUND The diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established. AIMS To assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices. METHODS 202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created. RESULTS The best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness (C-statistics=0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy>80%), but were not statistically superior to liver stiffness alone. CONCLUSIONS Liver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone.

Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension

BACKGROUND & AIMS Vascular hyporeactivity to vasoconstrictors contributes to splanchnic arterial vasodilatation and hemodynamic dysregulation in portal hypertension. Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to improve adrenergic vascular contractility in portal hypertensive rats and markedly attenuate hyperdynamic circulation. To further characterize the NPY-effects in portal hypertension, we investigated its role for non-receptor-mediated vasoconstriction in the superior mesenteric artery (SMA) of portal vein ligated (PVL) and sham-operated rats. METHODS Ex vivo SMA perfusion of PVL and sham rats was used to analyse the effects of NPY on pressure response to non-receptor-mediated vasoconstriction. Dose-response curves to KCl (30-300 mM) were used to bypass G protein-coupled receptor mechanisms. Potential involvement of the cyclooxygenase-pathway was tested by non-selective cyclooxygenase-inhibition using indomethacin. RESULTS KCl-induced vascular contractility but not vascular sensitivity was significantly attenuated in PVL rats as compared with sham rats. Administration of NPY resulted in an augmentation of KCl-evoked vascular sensitivity being not different between study groups. However, KCl-induced vascular contractility was markedly more enhanced in PVL rats, thus, vascular response was no more significantly different between PVL and sham rats after addition of NPY. Administration of indomethacin abolished the NPY-induced enhancement of vasoconstriction. CONCLUSIONS Receptor-independent vascular contractility is impaired in mesenteric arteries in portal hypertension. NPY improves non-receptor mediated mesenteric vasoconstriction more effective in portal hypertension than in healthy conditions correcting splanchnic vascular hyporesponsiveness. This beneficial vasoactive action of NPY adds to its well known more pronounced effects on adrenergic vasoconstriction in portal hypertension making it a promising therapeutic agent in portal hypertension.

Hypertension in pregnancy

PURPOSE OF REVIEW Hypertension in pregnancy contributes substantially to perinatal mortality and morbidity of both the mother and her child. High blood pressure is mainly responsible for this adverse outcome, in particular when associated with preeclampsia. Although preeclampsia is nowadays a well-known clinical-obstetrical entity, and screening for this complication has been part of routine care during pregnancy for nearly 100 years, its cause is still enigmatic. RECENT FINDINGS Profound changes of the demographic development of our society, the worldwide rising prevalence of obesity and metabolic disorders, and progress in reproductive medicine will inevitably modify the prevalence of many medical problems in pregnancy. Complications such as gestational diabetes mellitus, chronic hypertension, and preeclampsia will rise and an interdisciplinary approach is necessary to handle these women during pregnancy and also after delivery. Indeed, it is now well established that these women and their offspring born large or small-for-gestational age are at increased risk for severe cardiovascular and metabolic complications later in life. SUMMARY Knowledge of the pregnancy course is not only important for an obstetrician but also increasingly inevitable for the general practitioner. Recognition, classification, and adequate management of hypertensive pregnancy disorders and associated complications may considerably reduce perinatal death and morbidity.

Long-term data from the Swiss pulmonary hypertension registry.

BACKGROUND Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE To provide long-term data of the Swiss PH registry of 1998-2012. METHODS PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.

Risk Factors for Intracranial Haemorrhage in Accidents Associated with the Shower or Bathtub

BACKGROUND There has been little research on bathroom accidents. It is unknown whether the shower or bathtub are connected with special dangers in different age groups or whether there are specific risk factors for adverse outcomes. METHODS This cross-sectional analysis included all direct admissions to the Emergency Department at the Inselspital Bern, Switzerland from 1 January 2000 to 28 February 2014 after accidents associated with the bathtub or shower. Time, age, location, mechanism and diagnosis were assessed and special risk factors were examined. Patient groups with and without intracranial bleeding were compared with the Mann-Whitney U test.The association of risk factors with intracranial bleeding was investigated using univariate analysis with Fisher's exact test or logistic regression. The effects of different variables on cerebral bleeding were analysed by multivariate logistic regression. RESULTS Two hundred and eighty (280) patients with accidents associated with the bathtub or shower were included in our study. Two hundred and thirty-five (235) patients suffered direct trauma by hitting an object (83.9%) and traumatic brain injury (TBI) was detected in 28 patients (10%). Eight (8) of the 27 patients with mild traumatic brain injuries (GCS 13-15), (29.6%) exhibited intracranial haemorrhage. All patients with intracranial haemorrhage were older than 48 years and needed in-hospital treatment. Patients with intracranial haemorrhage were significantly older and had higher haemoglobin levels than the control group with TBI but without intracranial bleeding (p<0.05 for both).In univariate analysis, we found that intracranial haemorrhage in patients with TBI was associated with direct trauma in general and with age (both p<0.05), but not with the mechanism of the fall, its location (shower or bathtub) or the gender of the patient. Multivariate logistic regression analysis identified only age as a risk factor for cerebral bleeding (p<0.05; OR 1.09 (CI 1.01;1.171)). CONCLUSION In patients with ED admissions associated with the bathtub or shower direct trauma and age are risk factors for intracranial haemorrhage. Additional effort in prevention should be considered, especially in the elderly.

The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus.

OBJECTIVE We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

The Risk of Seizure After Surgery for Unruptured Intracranial Aneurysms: A Prospective Cohort Study.

BACKGROUND We aimed to identify a group of patients with a low risk of seizure after surgery for unruptured intracranial aneurysms (UIA). OBJECTIVE To determine the risk of seizure after discharge from surgery for UIA. METHODS A consecutive prospectively collected cohort database was interrogated for all surgical UIA cases. There were 726 cases of UIA (excluding cases proximal to the superior cerebellar artery on the vertebrobasilar system) identified and analyzed. Cox proportional hazards regression models and Kaplan-Meier life table analyses were generated assessing risk factors. RESULTS Preoperative seizure history and complication of aneurysm repair were the only risk factors found to be significant. The risk of first seizure after discharge from hospital following surgery for patients with neither preoperative seizure, treated middle cerebral artery aneurysm, nor postoperative complications (leading to a modified Rankin Scale score >1) was <0.1% and 1.1% at 12 months and 7 years, respectively. The risk for those with preoperative seizures was 17.3% and 66% at 12 months and 7 years, respectively. The risk for seizures with either complications (leading to a modified Rankin Scale score >1) from surgery or treated middle cerebral artery aneurysm was 1.4% and 6.8% at 12 months and 7 years, respectively. These differences in the 3 Kaplan-Meier curves were significant (log-rank P < .001). CONCLUSION The risk of seizures after discharge from hospital following surgery for UIA is very low when there is no preexisting history of seizures. If this result can be supported by other series, guidelines that restrict returning to driving because of the risk of postoperative seizures should be reconsidered. ABBREVIATIONS MCA, middle cerebral arterymRS, modified Rankin ScaleUIA, unruptured intracranial aneurysms.

The Effect of Increasing Intracranial Pressure on Ocular Vestibular-Evoked Myogenic Potential Frequency Tuning.

OBJECTIVE Ocular vestibular-evoked myogenic potentials (oVEMPs) represent extraocular muscle activity in response to vestibular stimulation. The authors sought to investigate whether posture-induced increase of the intracranial pressure (ICP) modulated oVEMP frequency tuning, that is, the amplitude ratio between 500-Hz and 1000-Hz stimuli. DESIGN Ten healthy subjects were enrolled in this study. The subjects were positioned in the horizontal plane (0 degree) and in a 30-degree head-downwards position to elevate the ICP. In both positions, oVEMPs were recorded using 500-Hz and 1000-Hz air-conducted tone bursts. RESULTS When tilting the subject from the horizontal plane to the 30-degree head-down position, oVEMP amplitudes in response to 500-Hz tone bursts distinctly decreased (3.40 μV versus 2.06 μV; p < 0.001), whereas amplitudes to 1000 Hz were only slightly diminished (2.74 μV versus 2.48 μV; p = 0.251). Correspondingly, the 500/1000-Hz amplitude ratio significantly decreased when tilting the subjects from 0- to 30-degree inclination (1.59 versus 1.05; p = 0.029). Latencies were not modulated by head-down position. CONCLUSIONS Increasing ICP systematically alters oVEMPs in terms of absolute amplitudes and frequency tuning characteristics. oVEMPs are therefore in principle suited for noninvasive ICP monitoring.

Intracranial EEG correlates of implicit relational inference within the hippocampus

Drawing inferences from past experiences enables adaptive behavior in future situations. Inference has been shown to depend on hippocampal processes. Usually, inference is considered a deliberate and effortful mental act which happens during retrieval, and requires the focus of our awareness. Recent fMRI studies hint at the possibility that some forms of hippocampus-dependent inference can also occur during encoding and possibly also outside of awareness. Here, we sought to further explore the feasibility of hippocampal implicit inference, and specifically address the temporal evolution of implicit inference using intracranial EEG. Presurgical epilepsy patients with hippocampal depth electrodes viewed a sequence of word pairs, and judged the semantic fit between two words in each pair. Some of the word pairs entailed a common word (e.g.,‘winter - red’, ‘red - cat’) such that an indirect relation was established in following word pairs (e.g, ‘winter - cat’). The behavioral results suggested that drawing inference implicitly from past experience is feasible because indirect relations seemed to foster ‘fit’ judgments while the absence of indirect relations fostered 'do not fit' judgments, even though the participants were unaware of the indirect relations. A event-related potential (ERP) difference emerging 400 ms post-stimulus was evident in the hippocampus during encoding, suggesting that indirect relations were already established automatically during encoding of the overlapping word pairs. Further ERP differences emerged later post-stimulus (1500 ms), were modulated by the participants' responses and were evident during encoding and test. Furthermore, response-locked ERP effects were evident at test. These ERP effects could hence be a correlate of the interaction of implicit memory with decision-making. Together, the data map out a time-course in which the hippocampus automatically integrates memories from discrete but related episodes to implicitly influence future decision making.