Video Head Impulse Test in Darkness, Without Visual Fixation: A Study on Healthy Subjects.

OBJECTIVE: The head impulse test (HIT) is triggered by the vestibulo-ocular reflex (VOR), complemented by the optokinetic and pursuit systems. This study aimed to evaluate the possibility of individualizing the VOR contribution to the HIT. DESIGN: Thirty-six healthy individuals (19 males, 17 females; age 21-64 years, mean 39 years) underwent horizontal video HIT (vHIT). This was first conducted in darkness, without visual fixation, and then visually tracked. RESULTS: Seventy percent of the impulses delivered ocular responses opposite to the direction of the head, matching its velocity to a point where quick anticompensatory eye movements (SQEM) stopped the response (SQEM mean latency 58.21 ms, interquartile range 50-67 ms). Of these, 75% recaptured the head velocity after culmination. Thirty percent of the responses completed a bell-shaped curve. The completed bell-shaped curve gains and instantaneous gains (at 40, 60, and 80 ms) before SQEM were equivalent for both paradigms. Females completed more bell-shaped traces (42%) than males (15%); p = 0.01. The SQEM latency was longer (62.81 versus 55.71 ms, p < 0.01), and the time to recapture the bell-shaped curve was shorter (77.51 versus 92.52 ms, p < 0.01) in females than in males. The gains were comparable between sexes in both paradigms. CONCLUSIONS: The VOR effect can be localized in the first 70 ms of the vHIT response. In addition, other influences may take place in estimating the vHIT responses. The study of these influences might provide useful information that can be applied to patient management.

Does patient environment have any influence on balance?

BACKGROUND: Although patient environment is a factor to consider when planning a vestibular rehabilitation program, there are no studies correlating this factor to outcomes of balance assessment. AIM: To evaluate whether there are differences in objective evaluation of balance in elderly patients at risk of falls according to the environment in which they live (urban or rural) and their lifestyle (considering cardiovascular risk factors). METHODS: Cross-sectional study of a sample of 139 elderly patients with high risk of falls assessed with objective outcome measures: Computer Dynamic Posturography (CDP), and the modified Timed Up-and-Go (TUG) test; and subjective outcome measures: Dizziness Handicap Inventory (DHI) and short Falls Efficacy Scale-International (short FES-I). Rural or urban environment was defined according to administrative and legal criteria. RESULTS: Elderly patients at risk of fall living in rural environment show better composite results in SOT with better scores in Condition 6 and fewer falls during the CDP. They also require fewer steps to perform the TUG test. DISCUSSION: The present study provides evidence that patient environment has an influence in balance. CONCLUSION: Patient environment should be considered when analyze tests evaluating static and dynamic balance.

Addison's Disease Secondary to Bilateral Adrenal Gland Metastatic Mammary Carcinoma in a Dog.

A 12 yr old intact female Siberian husky was referred with a 2 wk history of progressive weakness, paraparesis, anorexia, and panting. A 4 cm diameter grade 3 mammary solid carcinoma involving the fifth right mammary gland had been removed 2 days prior to the current visit. While hospitalized, the dog was diagnosed with Addison's disease based on electrolyte disturbances and low serum cortisol levels following adrenocorticotropic hormone stimulation test. An abdominal ultrasound revealed adrenal glands at the upper limit of normal size. Despite treatment, the dog deteriorated and died 4 days after presentation. A postmortem examination revealed a neoplastic infiltrate of epithelial malignant cells in both adrenal glands, popliteal lymph nodes, vertebral bodies, and paralumbar musculature, compatible with metastasis from mammary carcinoma. To our knowledge, this is the first reported case of Addison's disease secondary to metastatic mammary carcinoma in a dog.

Usefulness of carotid ultrasonography in the assessment of coronary artery disease extension in patients undergoing exercise echocardiography.

OBJECTIVES: To evaluate whether carotid disease is associated with coronary artery disease (CAD) extension in patients undergoing treadmill exercise stress echocardiography (EE). METHODS: We retrospectively studied 156 patients without previous vascular disease who underwent EE, carotid ultrasonography, and coronary angiography between 2002 and 2013. Low-, intermediate-, and high-risk EE were defined as negative, localized ischemia, and multivessel/extensive ischemia EE respectively; carotid disease according to Mannheim and American Society of Echocardiography Consensus and CAD extension from zero to three vessel disease as stenosis ≥50% by visual assessment. RESULTS: Of the 156 patients, 67 (42.9%), 43 (27.6%), 22 (14.1%), and 24 (15.4%) had zero, one, two, and three vessel disease respectively. Age (P = 0.047), male sex (P = 0.010), diabetes mellitus (P = 0.039), smoking habit (P = 0.015), fasting plasma glucose (P = 0.021), European Systematic COronary Risk Evaluation (P = 0.003), pretest CAD probability (P = 0.003), high-risk EE (P < 0.001), and carotid plaque presence (CP) (P < 0.001) were associated in univariate analysis with more extensive CAD. Predictors of CAD extension in multivariate analysis were high-risk EE (odds ratio [OR] 2.42, P < 0.001), CP presence (OR 1.75, P = 0.004), and pretest CAD probability >65% (OR 1.49, P = 0.023). CP was also associated with multivessel CAD in the 53 patients with low- or intermediate-risk EE (P = 0.001). CONCLUSIONS: CP is associated with CAD extension in patients with ischemic heart disease suspicion undergoing EE. Patients with CP could benefit from a more aggressive therapeutic strategy regarding patients without carotid disease and similar risk EE, especially in intermediate- and/or low-risk test where guidelines recommend initially optimal medical treatment.

Usefulness of carotid ultrasonography in the diagnosis of coronary artery disease in patients undergoing exercise echocardiography.

BACKGROUND: Relationship between carotid and coronary artery disease (CAD) in patients undergoing invasive and non-invasive test is unclear. The aim of the study is to evaluate whether carotid disease is associated with CAD in patients submitted to exercise echocardiography (EE) and if it improves the EE ability to predict CAD. METHODS: We retrospectively studied 156 subjects without previous vascular disease who underwent EE, carotid ultrasonography and coronary angiography between 2002 and 2013. Positive EE was defined as exercise induced wall motion abnormalities, carotid disease according to Manheim and American Society of Echocardiography Consensus and significant CAD as stenosis ≥50%. RESULTS: Eighty-nine (57.1%) subjects had significant CAD. Factors associated with CAD in multivariate analysis were fasting plasma glucose (odds ratio [OR] 1.02, p = 0.031), pre-test probability of CAD > 65% (OR 3.71, p < 0.001), positive EE (OR 10.51, p < 0.001) and carotid plaque (CP) presence (OR 2.95, p = 0.013). There was neither statistical significant difference in area under the curve after addition of CP to EE results (0.77 versus 0.81, p = 0.525) nor sensitivity, specificity, predictive values or efficiency. CP presence reclassified as very high-risk according to Systematic COronary Risk Evaluation 13 patients (34.2%) with negative EE and 22 (33.3%) without CAD. CONCLUSION: CP is associated with CAD in patients undergoing EE, however its addition to EE does not improve CAD prediction, probably due to insufficient statistical power. CP reclassified one third of patients to very high-risk category despite negative EE or CAD absence, these subjects benefit from aggressive primary prevention interventions.

Histone deacetylase 4 promotes cholestatic liver injury in the absence of prohibitin-1.

UNLABELLED: Prohibitin-1 (PHB1) is an evolutionarily conserved pleiotropic protein that participates in diverse processes depending on its subcellular localization and interactome. Recent data have indicated a diverse role for PHB1 in the pathogenesis of obesity, cancer, and inflammatory bowel disease, among others. Data presented here suggest that PHB1 is also linked to cholestatic liver disease. Expression of PHB1 is markedly reduced in patients with primary biliary cirrhosis and biliary atresia or with Alagille syndrome, two major pediatric cholestatic conditions. In the experimental model of bile duct ligation, silencing of PHB1 induced liver fibrosis, reduced animal survival, and induced bile duct proliferation. Importantly, the modulatory effect of PHB1 is not dependent on its known mitochondrial function. Also, PHB1 interacts with histone deacetylase 4 (HDAC4) in the presence of bile acids. Hence, PHB1 depletion leads to increased nuclear HDAC4 content and its associated epigenetic changes. Remarkably, HDAC4 silencing and the administration of the HDAC inhibitor parthenolide during obstructive cholestasis in vivo promote genomic reprogramming, leading to regression of the fibrotic phenotype in liver-specific Phb1 knockout mice. CONCLUSION: PHB1 is an important mediator of cholestatic liver injury that regulates the activity of HDAC4, which controls specific epigenetic markers; these results identify potential novel strategies to treat liver injury and fibrosis, particularly as a consequence of chronic cholestasis.

Analysis of methods to determine the sediment retained by check dams and to estimate erosion rates in badlands.

Check dams are useful structures at a catchment scale to determine erosion rates using the sediment retained in their wedges. Several studies employ different complex, accurate methods to estimate them. We likewise evaluate which catchment variables affect these erosion rate values. Our study aims to compare five frequently used methods (two prismatic and three topographic) to evaluate how they estimate total sediment yield (TSY) at two locations in Central Spain. For this purpose, we determine the sediment trapped in each area by 25 check dams built during the twentieth century. We also evaluate the catchment variables influencing TSY rates. Results show differences between methods in TSY determinations at the 90 % confidence level, although there are no differences between locations or the location-method iteration. We found that the natural logarithm of the drainage area was the factor that best explained TSY, presenting a negative trend (partial correlation coefficient, 0.83). Vegetation cover factor had no influence in estimating TSY for the two locations. We conclude that the determination of TSY rates depends on the chosen method and four related variables: check dam length, check dam height, wedge length and check dam drainage area. Furthermore, it is important to analyse and select the best method to estimate erosion rates based on the sediment retained by check dams depending on the characteristics of the study area (channel and sediment wedge shape), method accuracy and field effort. A more accurate estimation of erosion rates will allow researchers to determine the role of check dams in controlling sediment in each specific restoration project.

Right ventricular dysfunction in the critically ill. Echocardiographic evaluation.

Right ventricular dysfunction is common in critically ill patients, and is associated with increased mortality. Its diagnosis moreover remains challenging. In this review, we aim to outline the potential mechanisms underlying abnormal biomechanics of the right ventricle and the different injury phenotypes. A comprehensive understanding of the pathophysiology and natural history of right ventricular injury can be informative for the intensivist in the diagnosis and management of this condition, and may serve to guide individualized treatment strategies. We describe the main recommended parameters for assessing right ventricular systolic and diastolic function. We also define how to evaluate cardiac output and pulmonary circulation pressures with echocardiography, with a focus on the diagnosis of acute cor pulmonale and relevant applications in critical disorders such as distress, septic shock, and right ventricular infarction.

Thrombotic microangiopathy (TMA) associated with pregnancy: role of the clinical laboratory in differential diagnosis.

Objectives: Thrombotic microangiopathy (TMA) is characterized by thrombocytopenia, microangiopathic hemolytic anemia and target organ damage. Pregnancy is associated with several forms of TMA, including preeclampsia (PE), HELLP syndrome, thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). When HUS is secondary to a deregulation of the alternative complement pathway, it is known as atypical HUS (aHUS). Differential diagnosis is challenging, as these forms share clinical characteristics. However, early diagnosis is crucial for a specific treatment to be established and improve prognosis. Case presentation: We present the case of a 43 year-old primiparous woman admitted to hospital for an urgent C-section at 33 gestational weeks due to a diagnosis of severe preeclampsia and fetal distress. In the immediate postpartum, the patient developed acute liver failure and anuric renal failure in the context of the HELLP syndrome, anemia, thrombocytopenia, arterial hypertension (HTN) and neurological deficit. TMA study and differential diagnosis confirmed pregnancy-associated aHUS. Treatment with eculizumab was initiated, with good response and progressive improvement of clinical and analytical parameters. Conclusions: aHUS is a rare multifactorial disease that used to be associated with high mortality rates before the advent of eculizumab. Due to challenging diagnosis, the clinical laboratory plays a major role in the differential diagnosis and management of the disease.

Hepatoma cells from mice deficient in glycine N-methyltransferase have increased RAS signaling and activation of liver kinase B1.

BACKGROUND & AIMS: Patients with cirrhosis are at high risk for developing hepatocellular carcinoma (HCC), and their liver tissues have abnormal levels of S-adenosylmethionine (SAMe). Glycine N-methyltransferase (GNMT) catabolizes SAMe, but its expression is down-regulated in HCC cells. Mice that lack GNMT develop fibrosis and hepatomas and have alterations in signaling pathways involved in carcinogenesis. We investigated the role of GNMT in human HCC cell lines and in liver carcinogenesis in mice. METHODS: We studied hepatoma cells from GNMT knockout mice and analyzed the roles of liver kinase B1 (LKB1, STK11) signaling via 5'-adenosine monophosphate-activated protein kinase (AMPK) and Ras in regulating proliferation and transformation. RESULTS: Hepatoma cells from GNMT mice had defects in LKB1 signaling to AMPK, making them resistant to induction of apoptosis by adenosine 3',5'-cyclic monophosphate activation of protein kinase A and calcium/calmodulin-dependent protein kinase kinase 2. Ras-mediated hyperactivation of LKB1 promoted proliferation of GNMT-deficient hepatoma cells and required mitogen-activated protein kinase 2 (ERK) and ribosomal protein S6 kinase polypeptide 2 (p90RSK). Ras activation of LKB1 required expression of RAS guanyl releasing protein 3 (RASGRP3). Reduced levels of GNMT and phosphorylation of AMPKα at Thr172 and increased levels of Ras, LKB1, and RASGRP3 in HCC samples from patients were associated with shorter survival times. CONCLUSIONS: Reduced expression of GNMT in mouse hepatoma cells and human HCC cells appears to increase activity of LKB1 and RAS; activation of RAS signaling to LKB1 and RASGRP3, via ERK and p90RSK, might be involved in liver carcinogenesis and be used as a prognostic marker. Reagents that disrupt this pathway might be developed to treat patients with HCC.

Ultrasonography and procedures in intensive care medicine.

The use of point-of-care ultrasonography (POCUS) is not limited to the diagnosis and/or monitoring of critically ill patients. Further, ultrasound guidance is of paramount relevance to aid in successfully and safely performing several procedures in the intensive care unit (ICU). In this article, we review the role of POCUS as a procedural guidance in the ICU. Core procedures include, but are not limited to, vascular cannulation, pericardiocentesis, thoracentesis, paracentesis, aspiration of soft-tissue collections/arthrocentesis and lumbar puncture. With time, the procedures performed by intensivists may extend beyond the core competencies depicted in this review. Ultrasound guidance should be part of the intensivist's competencies, for which appropriate training should be achieved.

Design of a new mortality indicator in acute coronary syndrome on admission to the Intensive Care Unit.

OBJECTIVE: To design a mortality indicator in acute coronary syndrome (ACS) in the intensive care unit (ICU). DESIGN: A multicenter, observational descriptive study was carried out. PARTICIPANTS: Patients with ACS admitted to the ICUs included in the ARIAM-SEMICYUC registry between January 2013 and April 2019. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Demographic parameters, time of access to the healthcare system, and clinical condition. Revascularization therapy, drugs and mortality were analyzed. Cox regression analysis was performed, followed by the design of a neural network. A receiver operating characteristic curve (ROC) was plotted to calculate the power of the new score. Lastly, the clinical utility or relevance of the ARIAM indicator (ARIAM's) was assessed using a Fagan test. RESULTS: A total of 17,258 patients were included in the study, with a mortality rate of 3.5% (n = 605) at discharge from the ICU. The variables showing statistical significance (P < .001) were entered into the supervised predictive model, an artificial neural network. The new ARIAM's yielded a mean of 0.0257 (95%CI: 0.0245-0.0267) in patients discharged from the ICU versus 0.27085 (95%CI: 0.2533-0.2886) in those who died (P < .001). The area under the ROC curve of the model was 0.918 (95%CI: 0.907-0.930). Based on the Fagan test, the ARIAM's showed the mortality risk to be 19% (95%CI: 18%-20%) when positive and 0.9% (95%CI: 0.8%-1.01%) when negative. CONCLUSIONS: A new mortality indicator for ACS in the ICU can be established that is more accurate and reproducible, and periodically updated.

Audiovestibular Manifestations in Patients with Primary Raynaud's Phenomenon and Raynaud's Phenomenon Secondary to Systemic Sclerosis.

OBJECTIVES: To address the prevalence of audiovestibular disorders in patients with primary Raynaud's Phenomenon (RP). A series of patients with primary RP and secondary RP in the context of systemic sclerosis (SSc) were compared with healthy controls. METHODS: A prospective multicenter observational cross-sectional study was conducted in several Otolaryngology and Rheumatology Divisions of tertiary referral hospitals, recruiting 57 patients with RP and 57 age- and gender-matched controls. Twenty patients were classified as primary RP when unrelated to any other conditions and 37 patients who met the 2013 ACR/EULAR classification criteria for SSc were classified as having secondary RP associated with SSc. Audiometric and vestibular testing (vHIT), clinical sensory integration and balance testing (CTSIB), and Computerized Dynamic Posturography (CDP) were performed. RESULTS: As significant differences were found in the age of the two study groups, primary and secondary RP, no comparisons were made between both groups of RP but only with their control groups. No sensorineural hearing loss (SNHL) was recorded in any of our patients with primary RP and no differences were found in the voice audiometry tests with respect to controls. Four of 37 (10.8%) secondary RP patients presented SNHL. Those with SNHL were 7.03 times more likely to have a secondary RP than controls (p < 0.001). The audiometric curve revealed high-frequency hearing loss in 4 patients with RP secondary to SSc, and statistically significant differences were achieved when RP secondary was compared to controls in vHIT gain, caloric test, CTSIB, and CDP. CONCLUSIONS: Unlike patients with RP secondary to SSc, patients with primary RP do not show audiovestibular abnormalities. Regarding audiovestibular manifestations, primary RP can be considered a different condition than secondary RP.

Successful Treatment of 3 Dogs With Fluoroquinolone-Resistant Escherichia coli Associated Granulomatous Colitis.

Successful resolution of Escherichia coli associated granulomatous colitis (ECGC) is becoming a challenge due to the development of fluoroquinolone resistant E coli, which is associated with poor prognosis. Three dogs presented with signs of chronic colitis and were diagnosed with ECGC. All 3 were initially treated with enrofloxacin and trimethoprim-sulfamethoxazole, without clinical improvement. Despite the fact that culture and susceptibility testing results demonstrate resistance to fluoroquinolone and trimethoprim-sulfamethoxazole, the addition of amikacin fully resolved the clinical signs in all 3 cases. This case series describes the clinical presentation, diagnostic findings, and successful treatment of 3 dogs with fluoroquinolone-resistant ECGC. It suggests an alternative strategy for multidrug-resistance ECGC patients. Further investigations are required to confirm the efficacy of and to determine the molecular mechanisms underpinning the apparent success of aminoglycoside antibiotic combinations for treatment of ECGC.

Comparative Analysis of the Efficiency of Two Treatment Protocols for Posterior Canal Benign Paroxysmal Positional Vertigo.

BACKGROUND AND OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is the most common vertigo of labyrinthine origin, its social and healthcare impact is remarkable. It has recently been shown that single session treatment is as safe and effective as weekly treatment, which could have impact on direct and indirect costs related to the disease. The objective of this study is to determine whether single session treatment of unilateral posterior canal BPPV canalolithiasis is more efficient than conventional treatment. MATERIALS AND METHODS: A prospective randomized controlled trial was performed in 53 consecutive patients diagnosed with unilateral posterior canal BPPV canalolithiasis previously untreated: 26 patients were assigned to single session treatment and 27 patients to weekly treatment. Average and total cost of care, consultation time and the impact in terms of temporary disability and loss of productivity for the company due to patients' medical visits were compared. RESULTS: Average and total cost of care and loss of productivity for the company due to patients' medical visits were significantly lower in the single session group. Consultation time was also better in this group when travelling time was considered. CONCLUSIONS: The single session protocol is fast, effective and reduces direct and indirect cost of care related to disease justifying high resolution consultations.

What could posturography tell us about balance in essential tremor?

BACKGROUND: Essential tremor (ET) is a neurological disorder characterized primarily by action tremor. Balance impairments in ET patients were formerly considered to be uncommon and simply age-related. However quantitative assessment with posturography has revealed impairments in control of both static and dynamic balance. RESEARCH QUESTION: The aim of the present study is to assess postural stability with different posturographic techniques in ET patients. METHODS: A prospective cross-sectional study conducted in two University Hospitals. Eleven patients diagnosed with essential tremor and twelve healthy controls were included. Balance assessment were performed with: sensory organization test (SOT) and limits of stability (LOS) of the computer dynamic posturography (CDP), results of free-field body sway analysis with mobile posturography (Vertiguard®), modified timed up and go test (TUG), Dizziness handicap inventory (DHI) and activities-specific balance confidence scale (ABC). RESULTS: Patients with ET showed poorer scores in the SOT than controls for composite balance and somatosensory input. They also performed worse in LOS tests and Vertiguard® device indicated a higher risk of falling. There were no differences in the modified TUG. The mean score of DHI was 15.64 and 85.16 for ABC. SIGNIFICANCE: Posturography assessment (CDP and Vertiguard®) is more accurate in showing balance impairment in ET patients than clinical evaluation (modified TUG). Balance impairment involves deteriorated processing of somatosensory input which could be explained by cerebellar dysfunction. Balance deficits could be included into future diagnostic criteria.

Comparative analysis of the efficiency of two treatment protocols for posterior canal benign paroxysmal positional vertigo. / Análisis comparativo de la eficiencia de dos protocolos de tratamiento del vértigo posicional paroxístico benigno del conducto semicircular posterior.

BACKGROUND AND OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is the most common vertigo of labyrinthine origin, its social and healthcare impact is remarkable. It has recently been shown that single session treatment is as safe and effective as weekly treatment, which could have impact on direct and indirect costs related to the disease. The objective of this study is to determine whether single session treatment of unilateral posterior canal BPPV canalolithiasis is more efficient than conventional treatment. MATERIALS AND METHODS: A prospective randomized controlled trial was performed in 53 consecutive patients diagnosed with unilateral posterior canal BPPV canalolithiasis previously untreated: 26 patients were assigned to single session treatment and 27 patients to weekly treatment. Average and total cost of care, consultation time and the impact in terms of temporary disability and loss of productivity for the company due to patients' medical visits were compared. RESULTS: Average and total cost of care and loss of productivity for the company due to patients' medical visits were significantly lower in the single session group. Consultation time was also better in this group when travelling time was considered. CONCLUSIONS: The single session protocol is fast, effective and reduces direct and indirect cost of care related to disease justifying high resolution consultations.

Can Benign Paroxysmal Positional Vertigo Be Treated in a One Session?

OBJECTIVE: To determine the reliability and safety of posterior canal BPPV (pc-BPPV) treatment with subsequent assessment of the effectiveness of the maneuver in a single session, compared to the classic weekly procedure. METHOD: A prospective study of two randomized groups of unilateral pc-BPPV was performed: a weekly management group (27 patients) and single-session treatment group (26 patients). The number of maneuvers required to clear pc-BPPV, incidence of side effects (re-entries and canal conversions), and recurrence rates were compared. RESULTS: There were no statistically significant differences in the number of maneuvers needed to resolve pc-BPPV, the incidence of side effects, or the recurrence rate between the two groups. Two re-entries were diagnosed in the single-session group, and both were easily and successfully treated. Three early recurrences were found in the single-session group and one spontaneous recovery was encountered in the weekly group. Time required to discharge patients to follow-up was significantly reduced in the single-session group. CONCLUSION: Managing pc-BPPV in one session is safe and reliable, resulting in fewer visits to outpatient clinics and optimization of treatment strategies.