The Transdiaphragmatic Pressure Gradient and the Lower Esophageal Sphincter in the Pathophysiology of Gastroesophageal Reflux Disease: an Analysis of 500 Esophageal Function Tests.

BACKGROUND: Gastroesophageal reflux disease (GERD) pathophysiology is multifactorial. Greater importance has been attributed to a defective lower esophageal sphincter (LES) in comparison to an altered transdiaphragmatic pressure gradient (TPG). This study aims to evaluate the role of the TPG and LES disfunction in GERD pathogenesis. METHODS: Five hundred consecutive esophageal function tests from patients with clinically suspected GERD were reviewed. Patients were classified according to the pH monitoring in GERD positive or GERD negative. Abdominal pressure, thoracic pressure, TPG (abdominal-thoracic pressures), LES resting pressure (mid-respiratory, expiratory, and EGJ-CI), and LES retention pressure (LES resting pressure-TPG) were determined. RESULTS: GERD was present in 296 (59%) individuals. GERD-positive patients were mostly males. LES resting pressure (by all parameters) and thoracic pressure were not different between groups. Abdominal pressure and TPG were higher in GERD-positive patients. LES retention pressure (by all parameters) was lower in GERD-positive patients. DeMeester score had a positive correlation with LES resting pressure, TPG, and LES retention pressure (by all parameters) but not with abdominal pressure and thoracic pressure. CONCLUSIONS: LES valvular competency as measured by absolute resting pressure was not reliable to predict GERD; however, it was associated with GERD severity. Relative LES pressure (LES retention pressure) predicted GERD presence and severity, but no parameter showed superiority. TPG plays an important role in the pathophysiology of GERD since it is related to GERD presence and severity; still TPG is altered mostly based on a higher abdominal pressure.

The Role of the Transdiaphragmatic Pressure Gradient (TGP) in the Pathophysiology of Proximal Reflux.

INTRODUCTION: An increased transdiaphragmatic pressure gradient (TGP) is a main element for distal gastroesophageal reflux disease (GERD). The role of TGP for proximal reflux is still unclear. This study aims to evaluate the presence, severity, and importance of proximal reflux in relationship to the TGP, comparing healthy volunteers, obese individuals, and patients with chronic obstructive pulmonary disease (COPD). METHODS: We studied 114 individuals comprising 19 healthy lean volunteers, 47 obese individuals (mean body mass index 45 ± 7 kg/m2), and 48 patients with COPD. All patients underwent high-resolution manometry and dual-channel esophageal pH monitoring. Esophageal motility, thoracic pressure (TP), abdominal pressure (AP), TGP, DeMeester score, and % of proximal acid exposure time (pAET) were recorded. RESULTS: Pathologic distal GERD was found in 0, 44, and 57% of the volunteers, obese, and COPD groups, respectively. pAET was similar among groups, only higher for obese individuals GERD + as compared to obese individuals GERD - and COPD GERD -. pAET did not correlate with any parameter in healthy individuals, but it correlated with AP in the obese, TP in the COPD individuals, and TGP and DeMeester score in both groups. When all individuals were analyzed as a total, pAET correlated with AP, TGP, and DeMeester score. DeMeester score was the only independent variable that correlated with pAET. CONCLUSIONS: Our results show that (a) TGP is an important mechanism associated with distal esophageal acid exposure and this fact is linked with proximal acid exposure and (b) obesity and COPD both seem to be primary causes for GERD but not directly for proximal reflux.

Correlation between ocular perfusion pressure and translaminar pressure difference in glaucoma: Evidence for a three-pressure disease?

AIM: To evaluate the correlation between the translaminar pressure difference (TLPD) and the ocular perfusion pressure (OPP) in glaucoma patients. METHODS: This was a cross-sectional study. Primary open-angle glaucoma (POAG) patients and normal individuals underwent an ophthalmic evaluation as well as blood pressure, height, and weight measurements. Intracranial pressure (ICP) and OPP were calculated using proxy mathematical formulas to attain indirect surrogate parameter values. The TLPD was calculated as intraocular pressure minus ICP. The association between the variables was evaluated using linear and non-linear regression analysis and the correlation estimated with Pearson's correlation coefficient. RESULTS: The sample included 50 POAG patients and 25 normal subjects. The mean OPP for all 75 subjects (75 eyes) was 53.1 ± 9.3 mmHg and the calculated TLPG was 3.1 ± 4.2 mmHg. TLPG showed a negative correlation with OPP (r = -0.580; 95% CI, -0.690 to -0.366; p < 0.0001). CONCLUSION: The negative correlation between OPP and TLPD observed in the study substantiates the concept of glaucoma as a three-pressure disease.

Aperfeiçoamento de modelo de estimativa da eficiência de remoção de turbidez da água em floculadores tubulares helicoidais / Model improvement for estimating of water turbidity removal efficiency in helical tubular flocculators

RESUMO Estudos científicos têm demonstrado que os floculadores tubulares helicoidais (FTHs) têm alta eficiência na formação de flocos e baixo tempo de retenção hidráulica, quando comparados aos floculadores comumente usados em tratamento de água e esgoto. No entanto, sua aplicação prática é limitada, pois ainda existe demanda significativa por avanços na compreensão da relação entre a hidrodinâmica da unidade e o processo de floculação, bem como critérios e metodologias para auxiliar em projeto racionais de FTH. Nesse contexto, este estudo teve por objetivo propor um aperfeiçoamento no modelo de estimativa de eficiência de remoção de turbidez apresentado por Oliveira (2014), o qual leva em conta um conjunto de parâmetros geométricos, hidráulicos e hidrodinâmicos relevantes ao processo de floculação nesse tipo de reator, pela incorporação de um dos parâmetros mais representativos de processos de floculação, o gradiente de pressão normal (GPp), como uma de suas variáveis independentes. O desenvolvimento do trabalho empregou dinâmica dos fluidos computacional (CFD) no estudo de 84 configurações de FTH, contemplando regimes de escoamento laminar e turbulento. Como resultado, chegou-se a uma nova versão de modelo de estimativa da eficiência de remoção de turbidez da água que, em relação à versão original: tem menor número de variáveis independentes; apresenta melhor ajuste aos dados experimentais; e é mais simples do ponto de vista operacional.

ABSTRACT Scientific studies have been demonstrating that helical tubular flocculators (HTFs) have high efficiency in floc formation and low hydraulic retention time when compared to flocculators commonly used in water and wastewater treatment. However, its practical application is still limited because there is still a significant demand for advances in the understanding of the relationship between the hydrodynamics of the unit and the flocculation process, as well as for criteria and methodologies in support to the rational design of HTF. In this context, the objective of this study was to propose an improvement in the model of turbidity removal efficiency developed by Oliveira (2014), which takes into account a set of geometric, hydraulic and hydrodynamic parameters relevant to the flocculation process in this type of reactor, by incorporating one of the most representative parameters of flocculation processes, the normal pressure gradient, as one of its independent variables. The development of the work employs computational fluid dynamics (CFD) in the study of 84 HTFs configurations, considering laminar and turbulent flow regimes. As a result, a new model version for estimating water turbidity removal's efficiency in helical tubular flocculators was obtained, which, in relation to the original version, has a smaller number of independent variables, presents better fit to the experimental data and is simpler from the operational point of view.

Predictors of Early Extubation after Patent Ductus Arteriosus Ligation among Infants Born Extremely Preterm Dependent on Mechanical Ventilation.

We conducted a retrospective study of 166 ventilator-dependent neonates born extremely preterm in whom patent ductus arteriosus was surgically ligated and evaluated the association of preoperative characteristics and time-to-successful postoperative extubation. Larger patent ductus arteriosus diameter ([>2.5 mm], adjusted hazard ratio 0.51, 95% CI 0.36-0.72) and left-ventricular dilatation (z score ≥2, adjusted hazard ratio 0.61, 95% CI 0.42-0.87) were associated with earlier extubation.

Inhaled Beta Agonist Bronchodilator Does Not Affect Trans-diaphragmatic Pressure Gradient but Decreases Lower Esophageal Sphincter Retention Pressure in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Gastroesophageal Reflux Disease (GERD).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients have a high incidence of gastroesophageal reflux disease (GERD) whose pathophysiology seems to be linked to an increased trans-diaphragmatic pressure gradient and not to a defective esophagogastric barrier. Inhaled beta agonist bronchodilators are a common therapy used by patients with COPD. This drug knowingly not only leads to a decrease in the lower esophageal sphincter (LES) resting pressure, favoring GERD, but also may improve ventilatory parameters, therefore preventing GERD. AIMS: This study aims to evaluate the effect of inhaled beta agonist bronchodilators on the trans-diaphragmatic pressure gradient and the esophagogastric barrier. METHODS: We studied 21 patients (mean age 67 years, 57 % males) with COPD and GERD. All patients underwent high-resolution manometry and esophageal pH monitoring. Abdominal and thoracic pressure, trans-diaphragmatic pressure gradient (abdominal-thoracic pressure), and the LES retention pressure (LES basal pressure-transdiaphragmatic gradient) were measured before and 5 min after inhaling beta agonist bronchodilators. RESULTS: The administration of inhaled beta agonist bronchodilators leads to the following: (a) a simultaneous increase in abdominal and thoracic pressure not affecting the trans-diaphragmatic pressure gradient and (b) a decrease in the LES resting pressure with a reduction of the LES retention pressure. CONCLUSION: In conclusion, inhaled beta agonist bronchodilators not only increase the thoracic pressure but also lead to an increased abdominal pressure favoring GERD by affecting the esophagogastric barrier.

Métodos diagnósticos en hipertensión portal / Diagnostic Methods in Portal Hypertension

La hipertensión portal en el curso natural de las enfermedades hepáticas es una de las complicaciones más frecuentes resultado del aumento de la resistencia vascular hepática que determina el desarrollo de otros sucesos responsables de la mayor mortalidad en pacientes con hepatopatías. En consecuencia, el conocimiento de la fisiopatología de la hipertensión portal y de sus causas representa un factor importante para su adecuado manejo y el de las demás complicaciones relacionadas. Es así como se cuentan con métodos diagnósticos de diferentes tipos para la detección temprana y adecuada de dicha entidad; lo cual, además, corresponde al objetivo de la presente revisión: dar una mirada a los métodos diagnósticos utilizados para la detección de hipertensión portal, disponibles en la actualidad.

Portal hypertension is one of the most frequent complications in the natural course of liver disease. It results from increased hepatic vascular resistance and determines the development of other events responsible for increased mortality in patients with liver disease. Consequently, knowledge of the pathophysiology of portal hypertension and its causes is an important factor for handling it and related complications proper. Explanation of the various diagnostic methods for early and appropriate detection is one of the objectives of this review which will take a look at diagnostic methods available and in use for the detection of portal hypertension.

Patogénesis de la hipertensión portal / Pathogenesis of portal hypertension

It is now well established that portal hypertension is not a purely mechanical phenomenon. Primary hemodynamic alterations develop in the hepatic and systemic circulatory systems; these alterations in combination with mechanical factors contribute to the development of portal hypertension. In the hepatic circulation, these hemodynamic alterations are characterized by vasoconstriction and impaired hepatic vasodilatory responses, whereas in the systemic circulation, particularly in the splanchnic bed, vessels are hyperemic with increased flow. Thus, an increase in intrahepatic resistance in conjunction with increased portal venous inflow, mediated through splanchnic dilation, contributes to the development of portal hypertension. The ensuing development of elevated flow and transmural pressure through collateral vessels from the hypertensive portal vasculature into the lower pressure systemic venous circulation accounts for many of the complications, such as bleeding esophageal varices, observed with portal hypertension. The importance of the primary vascular origin of portal hypertension is emphasized by the utility of current therapies aimed at reversing these hemodynamic alterations, such as nitrates, which reduce portal pressure through direct intrahepatic vasodilatation, and fi blockers and octreotide, which reduce splanchnic vasodilatation and portal venous inflow. New evidence concerning relevant molecular mechanisms of contractile signaling pathways in hepatic stellate cells and the complex regulatory pathways of vasoactive molecules in liver endothelial cells makes a better understanding of these processes essential for developing further experimental therapies for portal hypertension. This article examines the current concepts relating to cellular mechanism that underlie the hemodynamic alterations that characterize and account for the development of portal hypertension.

Actualmente está bien establecido que la hipertensión portal no es un fenómeno puramente mecánico. En esta entidad se presentan alteraciones hemodinámicas primarias en los sistemas circulatorios hepático y sistémico; estas alteraciones en combinación con factores mecánicos, contribuyen al desarrollo de la hipertensión portal. En la circulación hepática, las alteraciones hemodinámicas se caracterizan por vasoconstricción y una respuesta anómala a la vasodilatación, mientras que en la circulación sistémica, especialmente en el lecho esplácnico, los vasos están congestivos y con un flujo aumentado. Por lo tanto un incremento en las resistencias intrahepáticas asociado a un aumento del flujo venoso portal, mediado a través de la dilatación esplácnica, contribuyen al desarrollo de la hipertensión portal. La consecuencia del flujo y la presión transmural elevada a través de los vasos colaterales a partir de una vasculatura portal hipertensa hacia la circulación venosa sistémica con menor presión, conlleva a muchas de las complicaciones observadas en la hipertensión portal, como la hemorragia por várices esofágicas. La importancia del origen vascular primario de la hipertensión portal se basa en la utilidad de terapias actuales orientadas a revertir estas alteraciones hemodinámicas, como los nitratos que reducen la presión portal, a través de vasodilatación intrahepática directa y los P bloqueadores y octreótida, que reducen la vasodilatación esplácnica y el flujo venoso portal. Además, existen nuevas evidencias en relación con los mecanismos moleculares de vías de señalización contráctil de las células estelares hepáticas y complejas vías de regulación de sustancias vasoactivas en las células endoteliales hepáticas que han ayudado a entender mejor estos procesos esenciales para el desarrollo de terapias experimentales para la hipertensión portal. Este artículo revisa los conceptos actuales relacionados con los mecanismos celulares causales de las alteraciones hemodinámicas que caracterizan y condicionan el desarrollo de la hipertensión portal.