Baseline Pressure Research Articles

The Effect of Astragalus mongholicus Water Extract on Urinary Function in Rats

This study investigated the effect of combining Astragalus mongholicus (A. mongholicus) water extract with electroacupuncture to improve bladder urinary function in rats with stress urinary incontinence (SUI). 18 SPF-grade unfertilized female SD rats were used, among which 15 rats were selected to establish the SUI model through simulated labor injury combined with bilateral oophorectomy. The 15 SUI rats were randomly divided into three groups: the model group, the Astragalus group (treated with A. mongholicus water extract), and the Astragalus+acupuncture group, with 5 rats in each group. The remaining three rats constituted the control group. After 6 weeks of treatment, the study compared bladder function parameters before and after treatment, including the positive rate of sneezing test, urethral baseline pressure (UBP), the amplitude of urethral response during sneezing (A-URS), maximum bladder capacity (MBC) indicating bladder function, leak point pressure (LPP), abdominal leak point pressure (ALPP), urine output, residual urine volume, and urination efficiency. Masson staining was used to observe changes in collagen fiber proportion in bladder tissue. Compared to the control group, the model group exhibited increased positive sneezing test, urination output, and residual urine volume, while bladder function decreased. Both the Astragalus group and Astragalus+acupuncture group demonstrated significant improvements in UBP, A-URS, MBC, LPP, ALPP, urination efficiency, collagen fiber proportion, and other indicators compared to the model group. Furthermore, the Astragalus+acupuncture group exhibited superior treatment effects compared to A. mongholicus water extract alone, suggesting the potential of this combined approach for SUI.

Abstract P137: Real-World Impact of Semaglutide on Cardiometabolic Risk Factors in Patients without Diabetes: A Multi-Center Analysis of Electronic Health Records

Introduction: In randomized controlled trials, semaglutide reduces cardiovascular risks in individuals with obesity/overweight without diabetes. However, its real-world impact on cardiometabolic risk factors remains unclear in this group. Methods: We conducted a multi-center analysis of electronic health records data from Yale New Haven Health (01/2018-12/2022) and Sentara Health (01/2018-06/2023). The study population included adults without diabetes mellitus who were prescribed semaglutide and had regular follow-ups over 24 months. The index date was the date of the first prescription of semaglutide. The percent (%) change in weight from baseline and blood pressure (BP) (mmHg) were fit in separate linear regression models. A random-effects meta-analysis was used to synthesize the results from different sites. Results: A total of 523 patients without diabetes prescribed semaglutide at Yale and Sentara were included in the analyses. The study population had a mean (SD) age of 56.6 (12.6) years, 69.6% were female, and the mean (SD) BMI was 37.9 (8.4) kg/m 2 . We observed a continuous decrease in body weight over 24 months (Figure 1). At 18-23 months, body weight among these patients was significantly reduced by 4.8 % (2.2, 7.4%). Systolic BP was significantly reduced by 2.03 mmHg (0.4, 3.7 mmHg) at 18-23 months, while there was no significant change in diastolic BP at the end of the study period. Conclusions: This multi-center analysis provided preliminary results of the impact of semaglutide on body weight and BP in real-world settings in individuals without diabetes. These findings highlight the importance of post-market surveillance of novel anti-obesity medications.

Fluidic Multichambered Actuator and Multiaxis Intrinsic Force Sensing.

Soft robots have morphological characteristics that make them preferred candidates, over their traditionally rigid counterparts, for executing physical interaction tasks with the environment. Therefore, equipping them with force sensing is essential for ensuring safety, enhancing their controllability, and adding autonomy. At the same time, it is necessary to preserve their inherent flexibility when integrating sensory units. Soft-fluidic actuators (SFAs) with hydraulic actuation address some of the challenges posed by the compressibility of pneumatic actuation while maintaining system compliance. This research further investigates the feasibility of utilizing the incompressible actuation fluid as the means of actuation and of multiaxial sensing. We have developed a hyperelastic model for the actuation pressure, acting as a baseline pressure. Any disparities from the baseline have been mapped to external forces, using the principle of pressure-based fluidic soft sensor. Computed tomography imaging has been used to examine inner deformation and validate the analytically derived actuation-pressure model. The induced stresses within the SFA are examined using COMSOL simulations, contributing to the development of a calibration algorithm, which accounts for geometric and cross-sectional nonlinearities and maps pressure variations with tip forces. Two force types (concentrated and distributed) acting on our SFA under different configurations are examined, using two experimental setups described as "Point Load" and "Distributed Force." The force sensing algorithm achieves high accuracy with a maximum absolute error of 0.32N for forces with a magnitude of up to 6N.

Achalasia: diagnostic delay and manometric characteristics with high-resolution solid-state and perfusion equipment.

The early diagnosis of achalasia requires a high degree of clinical suspicion, and delays in diagnosis are frequent. High-resolution oesophageal manometry (HRM) is the gold standard for its diagnostic confirmation. There are two HRM systems, perfusion and solid-state, which allow its classification into three subtypes: I, or classical; II, or with pan-oesophageal pressurization; and III, or spastic. To determine the clinical and manometric characteristics of the three subtypes with high-resolution perfusion and solid-state equipment and the time of evolution until diagnosis. This was a multicentre, observational, retrospective study of patients from the INTEGRA database of the Spanish Association of Neurogastroenterology and Motility who were diagnosed with primary achalasia confirmed by HRM, who fell under the Chicago Classification v3.0, and who had not been treated. The study included 110 patients (subtype I, N = 14; subtype II, N = 73; subtype III, N = 23). The HRM equipment was perfusion for 49 and solid-state for 61. The mean age was 61.8 ± 14 years (age range 44-81), the age was lower in subtype II, and the sex distribution was similar. The time of clinical evolution until diagnosis was > 12 months (51.6%), subtype II being the one that was diagnosed earlier and the most often (66.3%). Dysphagia was the most frequent symptom (90.5%). According to the comparative analysis by high-resolution perfusion and solid-state oesophageal manometry equipment, the baseline pressure of the lower oesophageal sphincter was higher in the solid-state oesophagus, but the difference was not statistically significant. The median integrated relaxation pressure at 4 seconds (IRP4) was similar (21 mmHg) between the perfusion and solid-state measurements. We describe the ranges of IRP4 in achalasia patients with both systems and confirm the possibility of achalasia even when IRP4 is within the normal range. Achalasia in our environment has a significant diagnostic delay. No significant differences were observed in the oesophagogastric junction between the two groups diagnosed with perfusion and solid-state equipment.

Sex-Related Differences in Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation.

Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long-term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long-term mortality in patients with HCM undergoing ASA based on sex. This is a single-center retrospective study evaluating hemodynamic changes and long-term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P=0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P=0.011). On Cox multivariable regression, predictors of mortality were age (per group change <60 years, 61-70 years, 71-80 years, and >80 years; hazard ratio [HR], 1.45 [95% CI, 1.10-1.91], P=0.008), female sex (HR, 0.59 [95% CI, 0.35-0.99], P=0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06-3.33], P=0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14-3.19], P=0.014). Women with HCM undergoing ASA are older and have higher left-sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Comparison of the effects of two concentrations of adrenaline (0.33 mg/l versus 1 mg/l) in the irrigation serum for arthroscopic shoulder surgery: protocol of a randomized controlled trial

Background: Controlling bleeding during arthroscopic shoulder surgery helps improve the clarity of the arthroscopic visual field. Adrenaline is considered an effective and safe method to reduce bleeding. Two doses of adrenaline (0.33 mg/l and 1 mg/l) have been evaluated in the literature, but never against each other. Methods: This prospective, double-blind, randomized controlled trial will study the clarity of the visual field using a numerical scale (NS) during rotator cuff surgery on 180 patients across 5 centres. The secondary objectives include: the duration of the operation, volume of saline used, increase in baseline pressure, number of arthropump hyperpressures, mean systolic blood pressure and heart rate, as well as sudden variability. Results: Among the 154 patients in the Clinical Trial Group, 70/154 (45%) continued to have proteinuria, while 84/154 (55%) had no proteinuria (remission) compared to 41 (28%) in remission and 104 (72%) with continued proteinuria in the Usual Care group (p&lt;0.001). Conclusions: This study aims to determine which of the two dosages previously studied in the literature (0.33 mg/l versus 1 mg/l) provides better clarity. Trial Registration Number: 2021-A02773-38.

A Tracheostomy Support Device to Reduce Tracheostomy-Related Pressure Injury.

Tracheostomies provide many advantages for the care of patients who are critically ill but may also result in complications, including tracheostomy-related pressure injuries. Research efforts into the prevention of these pressure injuries has resulted in specialized clinical care teams and pathways. These solutions are expensive and labor intensive, and fail to target the root cause of these injuries; namely, pressure at the device-skin interface. Here we measure that pressure directly and introduce a medical device, the tracheostomy support system, to reduce it. This was a cross-sectional study of 21 subjects in the ICU, each with a tracheostomy tube connected to a ventilator. A force-sensing resistor was used to measure baseline pressures at the device-skin interface along the inferior flange. This pressure was then measured again with the use of the tracheostomy support system in the inactive and active states. Resultant pressures and demographics were compared. Fifteen male and 6 female subjects, with an average age of 47 ± 14 (mean ± SD) years, were included in this study. Average pressures at the tracheostomy-skin interface at baseline in these 21 ICU subjects were 273 ± 115 (mean ± SD) mm Hg. Average pressures were reduced by 59% (median 62%, maximum 98%) with the active tracheostomy support system to 115 ± 83 mm Hg (P < .001). All the subjects tolerated the tracheostomy support system without issue. Despite best clinical practice, pressure at the tracheostomy-skin interface can remain quite high. Here we provide measures of this pressure directly and show that a tracheostomy support system can be effective at minimizing that pressure.

Changes in intraocular pressure following intravitreal dexamethasone implant in patients with history of glaucoma filtration surgery.

This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery. The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6months post-injection. A subgroup analysis was performed for pressure > 35mmHg, > 30mmHg, > 25mmHg, and a difference > 10mmHg between the peak and baseline pressure. Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09mmHg vs. 18.10mmHg, P = 0.042 and 13.91mg vs. 17.25mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25mmHg, > 30mmHg, and a difference > 10mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25mmHg, 24.0%; > 30mmHg, 20.0%; > 10mmHg difference, 28.0%). Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma.

Pressure Dynamics on Intervertebral Disc Cages in Transforaminal Lumbar Interbody Fusion: A Cadaver Study

This study aimed to quantify the change in pressure on the cage during compression manipulation in lumbar interbody fusion. While the procedure involves applying compression between pedicle screws to press the cage against the endplate, the exact compression force remains elusive. We hypothesize that an intact facet joint might serve as a fulcrum, potentially reducing cage pressure. Pressure on the intervertebral disc cage was measured during compression manipulation in 4 donor cadavers undergoing lumbar interbody fusion. Unilateral facetectomy models with both normal and parallel compression and bilateral facetectomy models were included. A transforaminal lumbar interbody fusion cage with a built-in load cell measured the compression force. Pressure data from 14 discs indicated a consistent precompression pressure average of 68.16N. Following compression, pressures increased to 125.99N and 140.84N for normal and parallel compression postunilateral facetectomy, respectively, and to 154.58N and 150.46N for bilateral models. A strong linear correlation (correlation coefficient: 0.967, P<0.0001) between precompression and postcompression pressures emphasized the necessity of sufficient precompression pressure for achieving desired postcompression outcomes. None of the data showed a decrease in compression force to the cage with the compression maneuver. Both normal and parallel compression maneuvers effectively increased the pressure on the cage, irrespective of the facet joint resection status. Compression manipulation consistently enhanced compressive force on the cage. However, when baseline pressure is low, the manipulation might not yield significant increases in compression force. This underlines the essential role of meticulous precompression preparation in enhancing surgical outcomes.

Assessment of intraocular pressure changes following intravitreal injections of three anti-VEGF agents

PurposeIntravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents has emerged as the primary treatment for prevalent retinal diseases. Despite its efficacy, IVI may induce intraocular pressure elevation due to vitreous fluid shifts. This study aims to compare the effects of three distinct anti-VEGF agents on intraocular pressure (IOP) elevation within a single clinic setting. DesignA prospective study, conducted at a single retinal clinic in a tertiary medical center (Tel Aviv Sourasky Medical Centre, Tel-Aviv, Israel). MethodsPatients receiving 3 different anti VEGF medications; bevacizumab, aflibercept, and ranibizumab, were examined. IOP was measured pre- and post-injection using an iCare Pro-tonometer. Demographic parameters and ocular characteristics were collected. ResultsThe study included 195 patients (average age 76.13 years; 100 males, 95 females). The medications administered were aflibercept (N = 70, 35 %), bevacizumab (N = 73, 37.4 %), and ranibizumab (N = 52, 26.7 %). In patients with a normal baseline intraocular pressure, no significant variance was observed in the post-injection versus pre-injection pressure change (delta) across medications. Conversely, in patients with higher pressure (>20 mmHg), aflibercept incited a more substantial increase than bevacizumab or ranibizumab. No correlation emerged between the pressure rise and age or lens status. ConclusionsNo significant difference was found in the increase of intraocular pressure following injection among different medications in patients with low-normal intraocular pressure. However, for patients prone to higher baseline pressure, caution is recommended with aflibercept due to a more pronounced increase. Further research is essential to comprehend the factors influencing pressure increase and their associated clinical implications.

Alteraciones de la motilidad esofágica

Esophageal motility disorders (EMD) manifest clinically with the presence of dysphagia and/or chest pain related to swallowing. In order to diagnose it, it is necessary to first rule out organic causes that would explain these symptoms. In recent decades, the development of high-resolution manometry and its use in routine clinical practice has allowed for better characterization of esophageal motility disorders. The diagnostic criteria have been updated in recent years in the Chicago Classification v4.0, which establishes two large groups of motor disorders: those with esophagogastric junction outflow obstruction (EGJOO) and those with abnormal esophageal body contractility. The treatment of EMDs with EGJOO (the various presentations of achalasia and esophagogastric junction outflow obstruction) is aimed at reducing the baseline pressure in this area. Various techniques are available for this, such as pneumatic balloon dilatation, endoscopic (POEM) and surgical myotomy (Heller myotomy), and, less frequently, the use of oral drugs and botulinum toxin injection. In the case of esophageal peristalsis disorders, the goal of treatment is to control symptoms. To do so, proton pump inhibitors (PPIs) are used in patients with associated gastroesophageal reflux disease (GERD) and, in the case of disorders associated with hypercontractility, other drugs such as nitrates or calcium channel blockers and, occasionally, low-dose tricyclic antidepressants may be used.

PRESERFLO MicroShunt implantation versus trabeculectomy for primary open-angle glaucoma: a two-year follow-up study

BackgroundTo compare the intermediate-term efficacy of PRESERFLO (PF) MicroShunt implantation with trabeculectomy (TE) in patients with primary open-angle glaucoma, focusing on longitudinal changes of functional and structural parameters.MethodsThis retrospective comparative study included 104 eyes of 104 patients who underwent TE and 83 eyes of 83 patients that underwent PF implantation between January 2019 and December 2020, with a minimum follow-up of two years. Baseline and postoperative intraocular pressure (IOP), number of IOP-lowering medications, visual field mean defect (MD) and peripapillary retinal nerve fibre layer (RNFL) thickness measured using optical coherence tomography were assessed and compared between groups.ResultsBaseline characteristics (age, sex, IOP, number of IOP-lowering medications, MD, RNFL thickness) were comparable between the two groups (all P > 0.05). During the two-year of follow-up, mean IOP decreased from 24.09 ± 1.15 mmHg and 21.67 ± 0.77 mmHg to 11.37 ± 1.13 mmHg (P < 0.001) and 15.50 ± 1.54 mmHg (P = 0.028), and the mean number of IOP-lowering medications decreased from 3.25 ± 0.14 and 3.51 ± 0.14 to 0.53 ± 0.14 (P < 0.001) and 1.06 ± 0.43 (P < 0.001) in the TE and PF groups, respectively. MD remained stable [− 11.54 ± 0.93 dB and − 11.17 ± 1.66 to − 10.67 ± 0.91 dB (P = 0.226) and − 10.40 ± 4.75 dB (P = 0.628) in the TE and PF groups, respectively] but RNFL thickness decreased continuously during follow-up [62.79 ± 1.94 µm and 62.62 ± 2.05 µm to 57.41 ± 1.81 µm (P < 0.001) and 60.22 ± 1.98 µm (P = 0.182) in the TE and PF groups, respectively].ConclusionPF implantation is comparably effective in the intermediate term in lowering IOP and reducing the use of IOP-lowering medications over a two-year follow-up period. Although visual field defects were stable, RNFL continued to decrease during postoperative follow-up.

Papillomacular bundle defect (PMBD) in glaucoma patients with high myopia: frequency and risk factors

Little is known about the papillomacular bundle defect (PMBD) in glaucoma. As such, we investigated the frequency of PMBD in glaucoma patients with high myopia, and its risk factors. In this retrospective, cross-sectional study, retinal nerve fiber layer (RNFL) defect was analyzed in 92 glaucomatous eyes with high myopia (axial length of 26.0 mm or more or an average spherical value of − 6.0 diopters or less). After dividing them into two groups with and without PMBD, the clinical characteristics of the groups were compared and analyzed. The mean age of the patients was 52.1 ± 10.5 years, and there were 53 males and 39 females. PMBD were observed in 55 eyes (59.8%). There was no significant intergroup difference in baseline or follow-up intraocular pressure (IOP). Parapapillary atrophy (PPA)-to-disc-area ratio (OR 3.83, CI: 1.58–10.27, p = 0.010), lamina cribrosa defect (LCD; OR 2.92, CI: 1.14–8.13, p = 0.031) and central visual field defect (CVFD; OR 3.56, CI: 1.38–9.58, p = 0.010) were significantly associated with the PMBD..

Abstract 18906: Post-COVID Hemodynamic Pathophysiology: Prevalence of Dysfunctional Breathing and Preload Insufficiency Using Novel Invasive Cardiopulmonary Exercise Testing

Introduction: The pathophysiologic mechanisms underlying persistent post-COVID cardiorespiratory symptoms remain understudied, despite the significant worldwide prevalence. Invasive cardiopulmonary exercise testing (iCPET) is a novel investigation that can inform our understanding of underlying hemodynamic abnormalities. Research Question: What is the prevalence of dysfunctional breathing (DB) and preload insufficiency (PI) in post-COVID patients who undergo iCPET? Methods: We studied hemodynamic characteristics in a cohort of 52 post-COVID patients who underwent iCPET in a sitting bicycle. The protocol augments CPET with continuous hemodynamic and laboratory data from pulmonary artery catheterization and arterial line. PI is defined as abnormally low right atrial pressure during exercise and reduced peak cardiac output percentage of predicted. DB is characterized by exercise-induced oscillatory ventilation. Results: The study cohort had a mean age of 40.8 years, and 36 of the 52 patients (69.2%) were female. iCPET revealed the prevalence of only DB as 15.4%, only PI as 34.6%, both DB and PI as 34.6%, and neither DB nor PI as 15.4%. These 4 sub-groups were subsequently compared for analysis. Notably, the cardiac output percentage of predicted at peak exercise was significantly different between the 4 groups (95.4%, 81.2%, 85.1%, 102.9%; p=0.007). The differential between baseline (sitting) and peak (maximal exercise) right atrial pressure was also significantly different between the 4 groups (0.00, 0.056, 0.333, 4.875; p=0.026). Our study suggests that PI and DB are common entities noted in symptomatic post-COVID patients, and may co-occur. Conclusion: This study is a first step towards understanding the altered hemodynamics that drive common symptoms in post-COVID patients. iCPET yields physiologic mechanistic information that could inform targeted interventions.

Transient Pressure Interference during CO2 Injection in Saline Aquifers

Summary CO2 injection in subsurface geological formations (e.g., deep saline aquifers) causes pressure perturbations over a large area surrounding the injection well. Observation wells are widely considered in geologic CO2 storage (GCS) projects where the pressure perturbation induced by CO2 injection is measured. In this work, we use analytical and numerical modeling tools along with field data to examine the pressure behavior in GCS projects before and after CO2 arrival at an observation well. Before CO2 arrival, a baseline pressure trend is established which corresponds to single-phase brine flow across the observation well (approximated by the Theis solution). Therefore, analysis of early time pressure data is straightforward, provides the single-phase flow characteristics (mobility and storativity), and helps in establishing a baseline pressure change that can be extended beyond the single-phase flow period at the observation well. Upon CO2 arrival, a departure from this baseline trend is expected. For the pressure to detect the CO2 arrival at an observation well, the departure from baseline pressure behavior must be significant and well above the background noise levels. We use existing analytical models to determine the strength of the expected pressure departure signal from the baseline trend upon CO2 arrival. The strength of the expected pressure departure is found to be directly proportional to the change in the mobility upon CO2 arrival. Larger change in the flow mobility—compared with single-phase brine mobility—results in a stronger pressure departure signal. In addition, the departure is found to be upward (downward) from the baseline pressure trend when the mobility ratio is less (more) than unity. We present a pressure analysis approach through application to synthetic and field data and show the characteristic pressure behavior before and after CO2 arrival. We show that while generally the pressure can be either above or below the expected baseline pressure trend, it would be likely above the baseline upon CO2 arrival. This is because the mobility ratio becomes less than unity after CO2 arrival. We show that depending on the reservoir characteristics, changes in the pressure trend may or may not be sufficient to detect the CO2 arrival.

"Inspiratory muscle weakness in acutely hospitalized patients 75years and over": a secondary analysis of a randomized controlled trial on the effectiveness of multicomponent exercise and inspiratory muscle training.

The impact of hospitalization for acute illness on inspiratory muscle strength in oldest-old patients is largely unknown, as are the potential benefits of exercise and inspiratory muscle training (IMT) during in-hospital stay. This was a sub-study of a randomized clinical trial that evaluated the efficiency of a multicomponent exercise program in preventing hospitalization-associated disability. Patients were randomized into control (CG) and intervention (IG) groups. The intervention included two daily sessions of supervised walking, squat, balance, and IMT. Baseline and discharge maximal inspiratory pressure (MIP) and inspiratory muscle weakness (IMW) were determined. The effect of the intervention on inspiratory muscle strength was assessed by analyzing (1) the differences between groups in baseline and discharge MIP and IMW, (2) the association, patient by patient, between baseline and discharge MIP, and the improvement index (MIP discharge/baseline) in patients with or without IMW. In total, 174 patients were assessed (mean age of 87), 57 in CG and 117 in IG. Baseline MIP was lower than predicted in both sexes (women 29.7 vs 44.3; men 36.7 vs 62.5 cmH2O, P < 0.001, baseline vs predicted, respectively). More than 65% of patients showed IMW at admission. In women in IG, the mean MIP was higher at discharge than at admission (P = 0.003) and was the only variable that reached expected reference levels at discharge (Measured MIP 39.2 vs predicted MIP 45 cmH2O, P = 0.883). Patients with IMW on admission showed a statistically significant improvement in MIP after the intervention. IMW is very prevalent in oldest-old hospitalized with acute illness. Patients might benefit from a multicomponent exercise program including IMT, even during short-stay hospitalization. ClinicalTrials.gov; No.: NTC03604640. May 3, 2018.

Mechanism of spirometry associated gastro-esophageal reflux in individuals undergoing esophageal assessment.

Persistent variability observed during spirometry, even when technical and personal factors are controlled, has prompted interest in uncovering its underlying mechanisms. Notably, our prior investigations have unveiled that spirometry has the potential to trigger gastro-esophageal reflux in a susceptible population. This current study embarks on elucidating the intricate mechanisms orchestrating reflux induced by spirometry. To achieve this, we enlisted twenty-four (24) participants exhibiting reflux symptoms for esophageal assessment. These participants underwent two sets of spirometry sessions, interspersed with a 10-minute intermission, during which we closely scrutinized fluid flow dynamics and esophageal function through high-resolution impedance esophageal manometry. Our comprehensive evaluation juxtaposed baseline manometric parameters against their equivalents during the initial spirometry session, the intervening rest period, and the subsequent spirometry session. Remarkably, impedance values, serving as a metric for fluid quantity, exhibited a substantial elevation during each spirometry session and the ensuing recovery interval in the pan-esophageal and hypopharyngeal regions when compared to baseline levels. Additionally, the resting pressure of the lower esophageal sphincter experienced a noteworthy reduction subsequent to the first bout of spirometry (13.6 ± 8.8 mmHg) in comparison to the baseline pressure (22.5 ± 13.3 mmHg). Furthermore, our observations unveiled a decline in spirometric parameters-FEV1 (0.14 ± 0.24 L, P = 0.042) and PEFR (0.67 L/s, P = 0.34)-during the second spirometry session when contrasted with the first session. Collectively, our study underscores the compelling evidence that spirometry maneuvers can elicit gastro-esophageal reflux by eliciting intra-esophageal pressure differentials and inducing temporary relaxation of the lower esophageal sphincter.

Investigating the variability in pressure-volume relationships during hemorrhage and aortic occlusion.

The pressure-volume (P-V) relationships of the left ventricle are the classical benchmark for studying cardiac mechanics and pumping function. Perturbations in the P-V relationship (or P-V loop) can be informative and guide the management of heart failure, hypovolemia, and aortic occlusion. Traditionally, P-V loop analyses have been limited to a single-beat P-V loop or an average of consecutive P-V loops (e.g., 10 cardiac cycles). While there are several algorithms to obtain single-beat estimations of the end-systolic and end-diastolic pressure-volume relations (i.e., ESPVR and EDPVR, respectively), there remains a need to better evaluate the variations in P-V relationships longitudinally over time. This is particularly important when studying acute and transient hemodynamic and cardiac events, such as active hemorrhage or aortic occlusion. In this study, we aim to investigate the variability in P-V relationships during hemorrhagic shock and aortic occlusion, by leveraging on a previously published porcine hemorrhage model. Briefly, swine were instrumented with a P-V catheter in the left ventricle of the heart and underwent a 25% total blood volume hemorrhage over 30 min, followed by either Zone 1 complete aortic occlusion (i.e., REBOA), Zone 1 endovascular variable aortic control (EVAC), or no occlusion as a control, for 45 min. Preload-independent metrics of cardiac performance were obtained at predetermined time points by performing inferior vena cava occlusion during a ventilatory pause. Continuous P-V loop data and other hemodynamic flow and pressure measurements were collected in real-time using a multi-channel data acquisition system. We developed a custom algorithm to quantify the time-dependent variance in both load-dependent and independent cardiac parameters from each P-V loop. As expected, all pigs displayed a significant decrease in the end-systolic pressures and volumes (i.e., ESP, ESV) after hemorrhage. The variability in response to hemorrhage was consistent across all three groups. However, upon introduction of REBOA, we observed significantly high levels of variability in both load-dependent and independent cardiac metrics such as ESP, ESV, and the slope of ESPVR (Ees). For instance, pigs receiving REBOA experienced a 342% increase in ESP from hemorrhage, while pigs receiving EVAC experienced only a 188% increase. The level of variability within the EVAC group was consistently less than that of the REBOA group, which suggests that the EVAC group may be more supportive of maintaining healthier cardiac performance than complete occlusion with REBOA. In conclusion, we successfully developed a novel algorithm to reliably quantify the single-beat and longitudinal P-V relations during hemorrhage and aortic occlusion. As expected, hemorrhage resulted in smaller P-V loops, reflective of decreased preload and afterload conditions; however, the cardiac output and heart rate were preserved. The use of REBOA and EVAC for 44 min resulted in the restoration of baseline afterload and preload conditions, but often REBOA exceeded baseline pressure conditions to an alarming level. The level of variability in response to REBOA was significant and could be potentially associated to cardiac injury. By quantifying each P-V loop, we were able to capture the variability in all P-V loops, including those that were irregular in shape and believe that this can help us identify critical time points associated with declining cardiac performance during hemorrhage and REBOA use.

Ultrasound-assisted intravesical botulinum toxin A delivery attenuates acetic acid-induced bladder hyperactivity in rats.

Background: Intradetrusor injection of botulinum toxin A (BTX-A) is an effective treatment for overactive bladder (OAB). However, the occurrence of adverse events associated with BTX-A injection therapy hinders its acceptance among patients and its clinical promotion. Intravesical instillation of BTX-A offers a promising alternative to injection therapy for treating OAB. Nevertheless, due to the presence of the bladder permeability barrier (BPB) and the high molecular weight of BTX-A, direct instillation is unable to penetrate the bladder urothelium. Purpose: This study aims to investigate the safety and feasibility of ultrasound-assisted intravesical delivery of BTX-A and its potential benefits in a rat model of bladder hyperactivity induced by acetic acid instillation. Methods: Hengli BTX-A and microbubbles (MB) were mixed and prepared as a novel complex. The size distribution and zeta potentials of the complex were measured. On day 1, rats' bladders were instilled with 1mL of saline, BTX-A (20U in 1mL), MB, or MB-BTX-A (20U in 1mL) complex with or without ultrasound (US) exposure (1MHz, 1.5W/cm2, 50% duty cycle, sonication for 10s with a 10-s pause for a total of 10min). The instillations were maintained for 30min. After 7days, cystometry was performed by filling the bladder with saline and 0.3% acetic acid (AA). Bladders were collected, weighed, and processed for immunoblotting, enzyme-linked immunosorbent assay (ELISA), histologic, and immunofluorescence analyses. Expression and distribution of SNAP-25 and SNAP-23 were assessed using Western blot and immunofluorescence. Calcitonin gene-related peptide (CGRP) in the bladder was detected using ELISA. Results: Intercontraction intervals (ICI) decreased by 72.99%, 76.16%, and 73.96% in rats pretreated with saline, BTX-A, and US + MB, respectively. However, rats treated with US + MB + BTX-A showed a significantly reduced response to AA instillation (57.31% decrease in ICI) without affecting amplitude, baseline pressure, or threshold pressure. Rats treated with US + MB + BTX-A exhibited increased cleavage of SNAP-25 and CGRP expression compared to the control group. Conclusion: Ultrasound-assisted intravesical delivery of BTX-A, with the assistance of MB cavitation, led to cleavage of SNAP-25, inhibition of calcitonin gene-related peptide release from afferent nerve terminals, and amelioration of acetic acid-induced bladder hyperactivity. These results support ultrasound-assisted intravesical delivery as an efficient non-injection method for administering BTX-A.

Digestive, anorectal, and urogenital functions in patients with type 2 diabetes mellitus, impaired glucose tolerance and normal glucose tolerance: Association with autonomic neuropathy.

Gastrointestinal disorders including constipation and fecal incontinence are common in type 2 diabetes and may derive from diabetic autonomous neuropathy, severe intestinal bacterial overgrowth, or a dysfunctional anorectal sphincter. The present study aims to characterize the correlation between these conditions. Patients with type 2 diabetes, prediabetes and normal glucose tolerance were included. Anorectal function was assessed with high-resolution anorectal manometry. Patients were screened for autonomous neuropathy by measuring olfactory, sweat, and erectile dysfunction as well as heart rate variability. Constipation and fecal (in-)continence were evaluated using validated questionnaires. Breath tests were used to assess severe intestinal bacterial overgrowth. We included 59 participants (32 (54.2%) type 2 diabetes, 9 (15.3%) prediabetes and 18 (30.5%) normal glucose tolerance). Presence of autonomous neuropathy, severe bacterial overgrowth and symptoms of constipation and incontinence was comparable. HbA1c was correlated with an increased anorectal resting sphincter pressure (r = 0.31, P = 0.019) and constipation symptoms (r = 0.30, P = 0.031). In patients with long- standing diagnosis of type 2 diabetes significantly higher values for maximum anorectal resting pressure (∆ = +27.81 ± 7.84 mmHg, P = 0.0015) and baseline pressure (∆ = 20.50 ± 9.74 mmHg, P = 0.046) were found compared with normal glucose tolerance, but not with prediabetes. Long-standing type 2 diabetes increases anorectal sphincter activity, and constipation symptoms are associated with higher HbA1c levels. The lack of an association of symptoms with autonomous neuropathy suggests glucotoxicity as the primary mechanism.