Elevated Pressure Research Articles

Time Interval Between Right Ventricular Early Diastolic Velocity by Tissue and Pulse Wave Doppler: An Index of Right Atrial Pressure in Pulmonary Hypertension Patients.

Background: A reversal of time difference between the onset of early diastolic velocity (e') during tissue Doppler imaging and the onset of mitral inflow (E) has been observed in cases of elevated left atrial pressure. Whether this interval (Te'-E) may be useful to assess right atrial pressure has never been investigated, neither in healthy subjects nor in pulmonary hypertension patients. Methods: Right ventricular Te'-E was assessed in patients with pre-capillary pulmonary hypertension and compared with healthy volunteers who underwent comprehensive echocardiography examination. Te'-E is the difference between the interval from R wave at the superimposed electrocardiogram to the e' wave during right ventricular tissue Doppler imaging and the interval from the R wave to transtricuspid E wave during pulsed wave Doppler imaging. Right atrial pressure was invasively measured in pulmonary hypertension patients. Results: Fifty-six patients were enrolled. Te'-E was prolonged in pulmonary hypertension subjects compared with healthy subjects (p < 0.001). Amongst the pulmonary hypertension patients, strong correlations were found between Te'-E and right atrial pressure (r = -0.885, p < 0.001), systolic pulmonary pressure (r = -0.85, p < 0.001) and the duration of tricuspid regurgitation (r = 0.72, p < 0.001). The area under the receiver operating characteristic curve of Te'-E in identifying right atrial pressure higher than 15 mm of mercury was 0.992 (sensitivity 100%, specificity 83%). Conclusions: In contrast to the left ventricle, there is a delay in the proto-diastolic filling in pulmonary hypertension patients, which correlates with the increase in systolic pulmonary arterial pressure, right atrial pressure, tricuspid regurgitation duration and restrictive diastolic pattern.

Early adoption of triamcinolone acetonide suprachoroidal injection for uveitic macular edema: a physician survey

ObjectiveTo obtain physicians’ “real-world” perspectives on early experiences with triamcinolone acetonide suprachoroidal injection (SCS-TA) for treatment of patients with uveitic macular edema (UME).ResultsTwelve retina/uveitis specialists in the United States were surveyed about SCS-TA injection procedure and patient outcomes. Survey participants administered ≥ 291 SCS-TA injections to 243 patients with UME with various disease characteristics (etiologies, chronicity, and anatomical subtypes). Commonly reported reasons for SCS-TA adoption included potential for lowering the risk of steroid-associated intraocular pressure elevations versus intravitreal injections or implants (100%), potential for longer duration of action versus intravitreal steroid injections or implants (92%), and desire to use a new delivery modality (83%). Nearly all participants (92%) found injection procedure relatively easy post-training, with most (75%) procedurally comfortable after completing 2–5 injections. 58% of participants indicated that their patients gained 2–3 lines of vision by first follow-up visit, and 92% reported having patients who experienced 100–150 μm or greater reduction in central subfield thickness. Overall, 92% of participants were satisfied with SCS-TA treatment outcomes. Findings from this survey of early adopters of SCS-TA indicate that the suprachoroidal injection technique was easy to learn and resulted in favorable patient outcomes consistent with clinical trial data.

Genetic Variants Associated with a History of Glaucoma Surgery in Japanese Patients with Primary Open-angle Glaucoma.

The genetic risk score of genetic variants associated with intraocular pressure elevation, but not those associated with optic nerve vulnerability, was associated with a history of glaucoma surgery in Japanese patients with primary open-angle glaucoma. To investigate genetic variants associated with a history of glaucoma surgery in Japanese patients with primary open-angle glaucoma (POAG). Japanese patients with POAG (n=468), including normal tension glaucoma (n=246) and high tension glaucoma (n=222), and control subjects (n=246) were genotyped for 22 genetic variants predisposing to POAG, which can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (optic nerve-related genetic variants). The unweighted and weighted genetic risk scores (GRS) of 17 IOP-related, 5 optic nerve-related and all 22 genetic variants were calculated, and the association between the GRS and a history of glaucoma surgery was evaluated. There was a significant association (odds ratio 1.13 per unweighted GRS, 95% confidence interval 1.03 to 1.24, P=0.0093) between IOP-related unweighted GRS and a history of glaucoma surgery. A significant association (odds ratio 1.09 per 0.1 weighted GRS, 95% confidence interval 1.04 to 1.14, P=0.00022) was also found between IOP-related weighted GRS and a history of glaucoma surgery. The IOP-related GRS was positively correlated with the need for glaucoma surgery. The mean of IOP-related unweighted and weighted GRS in POAG patients with a history of glaucoma surgery were significantly higher (P=0.013 and P=0.00031 respectively) than those in POAG patients without a history of glaucoma surgery. IOP-related, but not optic nerve-related, genetic variants were associated with a history of glaucoma surgery in Japanese patients with POAG. These results indicate that IOP elevation induced by IOP-related genetic variants rather than optic nerve vulnerability induced by optic nerve-related genetic variants may play an important role for requiring glaucoma surgery.

Controlled Elevation of Intraocular Pressure (CEI) Glaucoma Model in Rats.

Experimental elevation of intraocular pressure (IOP), a major glaucoma risk factor, has been a mainstay of research into mechanisms of glaucomatous optic nerve damage for decades. Methods that produce sustained IOP elevation can mimic the chronic nature of glaucoma and produce optic nerve damage. However, the pressure course for individual animals can be variable, unpredictably high at times, and difficult to monitor with current tonometry methods. All of this can complicate correlations of pressure history with axonal injury. An alternative is to control the extent and duration of IOP elevation over a period of several hour-long enough to produce axonal injury and gene expression changes within the optic nerve head that may indicate cellular mechanisms of glaucomatous optic nerve damage. The prolonged general anesthesia that this requires does have the potential to reduce systemic blood pressure, which may contribute to axonal injury in the face of elevated IOP. This chapter will describe our Controlled Elevation of IOP (CEI) model in laboratory rats. We will include methods for applying this to several animals at a time, as well as how to maintain blood pressure, oxygenation, and body temperature to ensure that the resulting injury and tissue events reflect the effects of elevated IOP on optic nerve tissues and not simply reduced ocular perfusion and ischemia.

The relationships between age, sex and exercise intensity on cerebral artery haemodynamics during isometric handgrip exercise.

Age and sex may alter the cerebral blood flow (CBF) responses to acute isometric exercise, via associated elevations in mean arterial pressure (MAP) and sympathetic activation. Our aim was to determine the relationships between age, sex and exercise intensity on cerebrovascular responses to isometric handgrip exercise. In 78 healthy adults (18-80 years, N=42 female), cerebrovascular responses were assessed during two minute isometric exercise bouts at three intensities (15, 30, 45% maximal voluntary contraction). Intracranial responses of the middle cerebral artery (MCA) and posterior cerebral artery (PCA) velocity (v) were measured using transcranial Doppler ultrasound. Extracranial responses of the internal carotid artery (ICA) and vertebral artery (VA) were assessed using Duplex ultrasound. Cardiopulmonary haemodynamic and neural parameters were measured throughout, including muscle sympathetic nerve activity, end-tidal carbon dioxide, and MAP. There were significant positive relationships between exercise intensity and the cerebral responses of the MCAv (P<0.001) and PCAv (P=0.005). There were no effects of intensity on ICA and VA responses (P>0.05), despite intensity-dependent increases in MAP (P<0.001). The increased MCAv response to exercise was blunted with advancing age (P=0.01) with no influence of sex (P=0.86). The present study provides data on age, sex and intensity specific relationships with intracranial and extracranial cerebrovascular responses to isometric exercise. Despite similar ICA, VA, and PCA responses, MCAv responses were attenuated with advancing age during handgrip exercise with no sex dependent influence. Further, intracranial responses were intensity dependent, whereas extracranial blood flow, shear-stress and velocity responses were similarly increased at all intensities during handgrip exercise.

Ultrasonographic placental edematous changes as predictive markers of unplanned preterm birth in post-Fontan pregnancies: A single-center observational study.

Fontan surgery is a palliative procedure commonly performed for functional single-ventricle heart diseases. Fontan circulation is characterized by elevated central venous pressure and low cardiac output. It causes placental hypoxia, which could lead to poor obstetric outcomes. During post-Fontan pregnancies, ultrasonography may detect abnormal appearance of the placenta. We have focused on higher incidences of unexpected onset of labor when this ultrasonographic finding is present. In this study, we aimed to investigate whether this finding could be an indicator of premature delivery before pre-scheduled dates in post-Fontan pregnancies. During post-Fontan pregnancies, the placenta exhibits a mosaic pattern with areas of low and high echogenicity and unusually thick on ultrasonography. We refer to these changes as "ultrasonographic placental edematous changes." We retrospectively analyzed clinical charts and ultrasonograms for post-Fontan pregnancies between 2015 and 2022. Fifteen patients were included in this study. Ultrasonographic placental edematous changes in the placenta during pregnancy were detected in eight cases (53%). Six (75%) of these patients experienced unexpected premature labor. Two patients underwent vaginal delivery because of sudden onset of labor. Four patients underwent emergency cesarean sections. Two patients underwent planned preterm cesarean sections. In the seven pregnancies without placental edematous changes, all deliveries occurred on the pre-scheduled dates determined based on the maternal heart condition. Pregnancies with ultrasonographic placental edematous changes have a higher risk of unexpected preterm delivery than those without these changes. Ultrasonographic placental edematous changes may serve as predictive markers for unplanned preterm births in post-Fontan pregnancies.

Evaluation of Cross-Linked Actin Networks (CLANs) in Human Trabecular Meshwork Cells and Tissues.

Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of glaucoma, the leading cause of irreversible vision loss and blindness. An overall increase in resistance to aqueous humor outflow causes sustained elevation in IOP. Glaucomatous insults in the aqueous humor outflow pathway, including the trabecular meshwork (TM), precede such chronic physiological changes in IOP. These insults include ultrastructural changes with excessive extracellular matrix deposition and actin cytoskeletal reorganization that leads to pathological stiffening of the ocular tissues. One of the most common cytoskeletal changes associated with TM tissue stiffness in glaucoma is the increased prevalence of cross-linked actin networks (CLANs) in cells of the trabecular meshwork (TM) and lamina cribrosa (LC). In glaucomatous cells, rearrangement of linear actin stress fibers leads to formation of polygonal arrays within the cytoplasm, resembling a geodesic dome-like structure, that we identified as CLANs. In addition to increased amounts of CLANs in POAG TM cells and tissues, we also discovered that glucocorticoid (GC) and TGFβ2 signaling pathways associated with the development of ocular hypertension (OHT) and glaucoma also induced CLANs in the TM. Despite a clear association, we are yet to completely understand the mechanisms involved in CLAN formation and their direct relevance to disease pathology. In this chapter, we will describe methods to identify and characterize CLANs using fluorescent microscopy in primary TM cell cultures, ex vivo perfusion cultured human anterior segments, and in situ in human donor eyes.

A Comprehensive Protocol for Microbead-Induced Ocular Hypertension in Mice.

Glaucoma is a common optic neuropathy characterized by degeneration of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP), that is, ocular hypertension, is the primary modifiable risk factor for glaucoma and the primary characteristic of most preclinical glaucoma models. Extensive genotype and phenotype diversity at relatively low cost and high accessibility makes laboratory mice an excellent preclinical model for glaucoma. The microbead occlusion model was introduced in 2010 as an inducible model of ocular hypertension in mice and is now one of the most extensively utilized models of rodent glaucoma. Subsequent modifications of the microbead model increased the magnitude and duration of IOP elevation, primarily through modification of injection materials. Despite its popularity, accessibility of the model is hindered by procedural consistency between users. Here we outline an updated and comprehensive protocol for execution of the microbead model that is focused on improving surgical and outcome measure consistency and on enabling single experimenter execution.

Autophagy activation ameliorates the fibrosis of trabecular meshwork cells induced by TGFβ2 through the promotion of fibrotic proteins degradation.

The level of transforming growth factor-beta2 (TGFβ2) is elevated in aqueous humor of partial glaucoma patients, and induced trabecular meshwork (TM) fibrosis, which could cause TM cells dysfunction and lead to intraocular pressure (IOP) elevation. Autophagy is a dynamic process of bulk degradation of organelles and proteins under stress condition, while its functions in fibrotic development remain controversial. Meanwhile, it is still unclear if activation of autophagy could ameliorate TGFβ2-induced fibrosis in TM cells. In this study, we demonstrated that autophagy activation with Rapamycin or Everolimus could ameliorate TM fibrosis induced by TGFβ2. We also proved that activation of autophagy may decrease TM cells fibrosis and reduce elevated IOP induced by TGFβ2 in vivo, while Rapamycin or Everolimus has no effect on TGFβ/Smad3 pathway activity and fibrotic genes expression. However, when Chloroquine phosphate blocks autophagy-lysosome pathway, the protective effect of Rapamycin or Everolimus on fibrosis was weakened. We established that autophagy activation ameliorates TM fibrosis through promoting fibrotic proteins degradation.

Nanotubules and Cellular Communication in Trabecular Meshwork Cells.

Glaucoma causes dysfunction to tissues located in the anterior and posterior eye. In the anterior eye, the trabecular meshwork (TM) is the site of pathogenesis, where decreased TM cell numbers and alterations to the amount and composition of extracellular matrix hinder outflow of aqueous humor fluid from the anterior chamber. This causes intraocular pressure (IOP) elevation. Elevated IOP, a main risk factor for primary open-angle glaucoma, damages the axons of retinal ganglion cells in the posterior eye, which ultimately leads to blindness. Thus, clinical treatment paradigms for glaucoma are focused on reducing IOP. Normotensive IOPs are established by balancing the production of aqueous fluid from the ciliary body with drainage through the TM to Schlemm's canal. When IOP becomes elevated, TM cells coordinate a homeostatic response to lower IOP, which requires effective and efficient cellular communication. Tunneling nanotubes (TNTs) are transient specialized structures that allow cells to communicate with one another. Actin-rich tubes allow direct transmission of signals and cargoes between cells. This is important to overcome limitations of diffusion-based signaling in aqueous environments such as the anterior eye. Here, we describe a live-cell imaging method for monitoring TNTs in primary TM cells.

Mouse Model of Glucocorticoid-Induced Glaucoma.

Extended glucocorticoid (GC) treatment can lead to ocular hypertension and induce iatrogenic open-angle glaucoma. GC-induced glaucoma mimics many clinical and pathological features of primary open-angle glaucoma (POAG), and therefore mouse models of GC-induced glaucoma are utilized to study pathophysiology of glaucoma. We have recently demonstrated that weekly periocular injections of dexamethasone-21-acetate (Dex-Ac) lead to robust and significant intraocular pressure (IOP) elevation, retinal ganglion cell (RGC) loss, and optic nerve degeneration in mice. Our mouse model exhibits signature features of POAG including significant IOP elevation due to reduced outflow facility, progressive optic nerve degeneration, and structural and functional loss of RGCs. Dex-induced IOP elevation is associated with increased aqueous outflow resistance due to trabecular meshwork (TM) dysfunction including excessive extracellular matrix deposition and induction of endoplasmic reticulum stress. Mouse model of Dex-induced glaucoma represents an ideal animal model to investigate both glaucomatous damage to the TM and RGC axons and to develop novel therapies. Here, we present a detailed protocol for developing this model in laboratory settings.

Comprehensive analysis of VEGF/VEGFR inhibitor-induced immune-mediated hypertension: integrating pharmacovigilance, clinical data, and preclinical models.

This study aimed to elucidate the differential immunological mechanisms and characteristics of hypertension induced by VEGF inhibitors (VEGFi) and VEGF receptor inhibitors (VEGFRi), with the goal of optimizing monitoring strategies and treatment protocols. We investigated the risk of immune-related adverse events associated with VEGFi/VEGFRi-induced hypertension by analyzing the FDA Adverse Event Reporting System (FAERS) database. Findings were corroborated with blood pressure characteristics observed in clinical patients and preclinical models exposed to various VEGF/VEGFRi. Clinical and preclinical studies were conducted to compare immunological responses and hypertension profiles between inhibitor classes. An integrative analysis across cancer types and species was performed, focusing on key signaling pathways. Analysis of FAERS data, in conjunction with clinical observations, revealed that both VEGFi and VEGFRi significantly elevated the risk of immune-mediated, blood pressure-related adverse events (ROR=7.75, 95% CI: 7.76-7.95). Subsequent clinical and preclinical studies demonstrated differential immunological responses and hypertension profiles between inhibitor classes. VEGFRi exhibited a more rapid onset, greater blood pressure elevation, and higher incidence of immune-mediated adverse events compared to VEGFi (Systolic BP: ROR=0 for VEGFi vs. ROR=12.25, 95% CI: 6.54-22.96 for VEGFRi; Diastolic BP: ROR=5.09, 95% CI: 0.60-43.61 for VEGFi vs. ROR=12.90, 95% CI: 3.73-44.55 for VEGFRi). Integrative analysis across cancer types and species, focusing on key signaling pathways, revealed that VEGF/VEGFRi-induced blood pressure elevation was associated with immunomodulation of the mitogen activated protein kinase (MAPK) pathway (R=-0.379, P=0.0435), alterations in triglyceride metabolism (R=-0.664, P=0.0001), modulation of myo-inositol 1,4,5-trisphosphate-sensitive calcium release channel activity (R=0.389, P=0.0378), and dysregulation of nitric oxide eNOS activation and metabolism (R=-0.439, P=0.0179). The temporal dynamics of these effects demonstrated greater significance than dose-dependent responses. Both VEGFi and VEGFRi significantly augmented the risk of immune-mediated, blood pressure-related adverse events, with VEGFRi inducing a more rapid and pronounced onset of blood pressure elevation and a higher incidence of immune-related, blood pressure-associated adverse events compared to VEGFi.

Cardiovascular handgrip responses during treadmill exercise: randomized pilot trial.

The isometric exercise performed using the handgrip (HG) acutely promotes elevation of systolic blood pressure (SBP) and diastolic blood pressure (DBP), and in a non-consensual manner among articles elevation or maintenance of heart rate (HR). Currently, although there is a vast literature on the hemodynamic effects of interval training and isometric exercise with HG alone, there is still no consistent evidence of such adjustments occurring in the association between the two. Therefore, the objective of this study was to describe the acute hemodynamic responses found only during interval training and when combined with isometric contraction with HG. This is a pilot study of a crossover clinical trial. Seven male volunteers, aged 24±3.9 years, underwent three protocols on an ergometric treadmill, with a 3-minute warm-up at 30% of heart rate reserve (HRR), four sprints 2 minutes at 50% HRR and active intervals at the same speed as the warm-up. Randomization was carried out in a simple random manner. The protocols were classified according to the use of HG during sprints, as follows: PI = without HG; PII = HG 30% of handgrip strength (HGS) and PIII = 60% of HGS). Variations (Δ) in HR, double product (DP), SBP and DBP were evaluated. The presence of HG did not change HR behavior, but it increased DP (PI: 10,472±2,539 vs. PII: 12,217±1,933 vs. PIII: 13,369±3,089) through SBP, which in PI had a plateau behavior of 15±22.2 mmHg, while PII varied with an average of 41±12.2 mmHg and PIII 47±11.1 mmHg, in the 4th sprint. DBP fell in PI with 12±13.2 mmHg, while PII and PIII showed an drop of 0±19.6 and 6±13.0 mmHg in the last sprint, respectively. The use of HG during interval training directly modulates hemodynamic variables, promoting an increase in SBP elevation, attenuation of the drop in DBP and an increase in DP, without an increase in HR. RBR-78fhyrf. Available in https://ensaiosclinicos.gov.br/rg/RBR-78fhyrf.

Phacolytic Glaucoma Diagnosed by Cytopathology: A Clinicopathologic Case Series

ABSTRACT Purpose The aim of this study was to describe the clinical presentation, histopathologic characteristics, and management of phacolytic glaucoma. Patients and Methods The database at the Florida Lions Ocular Pathology Laboratory was searched for surgical specimens at the Bascom Palmer Eye Institute. Patients with a diagnosis of “phacolytic glaucoma” on cytopathology between the years of 1997 and 2023 were included (n = 15). Patient demographics, anatomic site, laterality, clinical features, and ocular examination findings were obtained from available medical records. Results The diagnosis of phacolytic glaucoma was established by light microscopic examination of cytology specimens in 15 eyes (Right = 8, Left = 6, not specified = 1). Between 1997 and 2023, there were 32 cytopathology cases with a preoperative diagnosis of phacolytic glaucoma. From this group of 15 cases, there were nine males and six females. Mean age was 64.2 years (Range: 39–87). Thirteen samples were from the anterior chamber and two were obtained from the vitreous. All 15 cases (100%) demonstrated histiocytes with engulfed foamy and/or granular presumed lenticular material. CD68 immunohistochemistry was positive within histiocytes in four cases that were stained (100%). Of the available medical records, clinical features, and ocular examination findings included: eye redness, decreased vision, eye pain, anterior chamber inflammation, dislocated or subluxed crystalline lens, cataract, and elevated intraocular pressure (average = 41.3 ± 8.67 mm Hg). Conclusions Phacolytic glaucoma is a rare complication of mature/hypermature cataracts that presents with ocular pain, decreased vision, and anterior chamber inflammation. AC paracentesis with cytopathologic evaluation is a minimally invasive, rapid technique that can aid in the diagnosis and management of this disease.

Compressibility effects in microchannel flows between two-parallel plates at low reynolds and mach numbers: Numerical analysis

Under certain circumstances, flow in microchannels can exhibit compressibility effects even at Reynolds numbers (Re) around (below 2,300) and low Mach numbers (below 0.3). This is particularly true for gases, especially when the flow undergoes significant pressure changes or acceleration within the microchannel. This study investigates the compressibility effects encountered in two-parallel plates microchannels at these low Reynolds and Mach numbers, due to the high-pressure drop associated with the small scale of the microchannels. This uncommon flow is characterized by an exceptionally small channel diameter-to-length aspect ratio (∼10–3), resulting in a friction coefficient that deviates from the typical value for laminar flow between parallel plates (f = 96/Re). Both steady and transient effects on the flow field are examined under low Re subsonic flow, assuming continuum behavior. The ideal gas equation is used to model gas density, while the isothermal Tait-Murnaghan equation models liquid density. For gases, compressibility effects are observed primarily when the inlet pressure ratio exceeds 0.1. The results show that these effects are less pronounced for liquids, even at elevated inlet pressure ratios. Additionally, a flow delay across the channel exhibits a first-order transient response. For liquid flow, this effect depends on the channel resistance, the total fluid volume within the channel, and the liquid's bulk properties, rather than the inlet pressure ratio.

A cross-sectional study of factors associated with carotid atherosclerosis.

The aim of this work was to study the relationship between carotid atherosclerosis (CAS) and several indexes and provide a basis for the prevention and treatment of cardiovascular and cerebrovascular diseases. There were 11,028 adults who underwent physical examination at the Guangzhou Cadre and Talent Health Management Center from January 2023 to December 2023 and were selected as research subjects. Retrospective analysis was used to understand the carotid atherosclerosis of the examined population and analyze its relationship with sex, age, blood pressure, blood glucose, blood lipids, renal function, 25-hydroxyvitamin D, neutrophil to lymphocyte count ratio (NLR), platelet to lymphocyte count ratio (PLR), systemic immune inflammation index (SII), monocyte count to high-density lipoprotein cholesterol ratio (MHR), triglyceride glucose body mass index (TyG-BMI), insulin resistance metabolic index (METS-IR), and other indicators. Among 11,028 subjects, the detection rate of carotid atherosclerotic thickening (CAT) was 12.00% and carotid atherosclerotic plaque (CAP) was 25.11%. The CAT and CAP detection rates in men were 13.32% and 28.78%, respectively, which were higher than the CAT detection rate of 8.28% and CAP detection rate of 14.80% in women, and the differences were statistically significant (both p < 0.001). Multivariate logistic regression analysis using TyG-BMI and METS-IR as two indicators was modeled separately, and the results showed that CAS was associated with men, increasing age, and systolic blood pressure. The area under the curve (AUC) was analyzed using the subject's work characteristic (ROC) curve in the descending order of METS-IR, TyG-BMI, and MHR. The combination of the three indexes of sex, age, and METS-IR predicted atherosclerosis with the highest AUC values. Carotid atherosclerosis is highly prevalent in men. Elevation of systolic blood pressure, fasting glucose, MHR, and TyG-BMI (or METS-IR) with age are independent influences on carotid atherosclerosis. The three indexes of MHR, TyG-BMI, and METS-IR, respectively, in combination with sex and age, can be used as a new and effective index to predict CAS.

Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion.

To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment. This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT). The best corrected visual acuity (BCVA) and CRT were measured at baseline, and at 1, 3, 4 and 6mo post-DEX implant injection. Adverse events such as elevated intraocular pressure (IOP) and cataract were recorded. For RVO cases (n=22), there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection (P<0.05) and CRT decreased from 472.1±90.6 to 240.5±39.0 µm at 6mo (P<0.0001). DME cases (n=15) experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection (P=0.0098), with CRT reducing from 445.7±55.7 to 271.7±34.1 µm at 6mo (P<0.0001). Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications. No cases of cataract or other adverse events were reported. DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

Impact and mechanisms of drag-reducing polymers on shear stress regulation in pulmonary hypertension.

Pulmonary hypertension (PH) is a refractory disease characterized by elevated pulmonary artery pressure and resistance. Drag-reducing polymers (DRPs) are blood-soluble macromolecules that reduce vascular resistance by altering the blood dynamics and rheology. Our previous work indicated that polyethylene oxide (PEO) can significantly reduce the medial wall thickness and vascular resistance of the pulmonary arteries, but the specific mechanism is still unclear. This study was designed to investigate the role and mechanism of PEO on intracellular calcium [Ca2+] i and cytoskeletal proteins of endothelial cells (ECs) induced by low shear stress (LSS) in PH. Primary Pulmonary Artery Endothelial Cells (PAECs) were subjected to steady LSS (1 dyn/cm2) or physiological shear stress (SS) (10 dyn/cm2) for 20 h in a BioFlux 200 flow system. Calcium influx assays were conducted to evaluate the mechanisms of PEO on [Ca2+] i. Subsequently, taking the key protein that induces cytoskeletal remodeling, the regulatory light chain (RLC) phosphorylation, as the breakthrough point, this study focused on the two key pathways of PEO that regulate phosphorylation of RLC: Myosin light chain kinase (MLCK) and Rho-associated kinase (ROCK) pathways. Our current research revealed that PEO at LSS (1 dyn/cm2) significantly suppressed LSS-induced [Ca2+] i and the expression level of transient receptor potential channel 1(TRPC1). In addition, ECs convert LSS stimuli into the upregulation of cytoskeletal proteins, including filamentous actin (F-actin), MLCK, ROCK, p-RLC, and pp-RLC. Further experiments using pharmacological inhibitors demonstrated that PEO at the LSS downregulated cytoskeleton-related proteins mainly through the ROCK and MLCK pathways. This study considered intracellular calcium and cytoskeleton rearrangement as entry points to study the application of PEO in the biomedical field, which has important theoretical significance and practical application value for the treatment of PH.

Electrocardiographic Findings in Patients with Severe COVID-19: Characterisation and Clinical Correlations

In a prospective study of 200 COVID-19 patients, categorised into mild symptoms (category A; n=39), mild symptoms with cardiopulmonary comorbidities (category B; n=68) and severe symptoms with haemodynamic compromise (category C), category C showed higher incidences of left axis deviations, left atrial enlargement, prolonged QRS, elevated left ventricular amplitude, poor R wave progression and T inversion in V1–V6. A novel marker, rS complex – R/S ratio &gt;1 in lead III, was noted. Univariate analysis revealed left atrial enlargement, left axis deviation, left ventricular amplitude and poor R wave progression as mortality predictors. Multivariate analysis identified age and left atrial enlargement as independent predictors. These findings suggest possible elevated left ventricular end-diastolic pressure, which will help in categorising disease severity and predicting outcomes.

Prognostic Significance of Right Ventricular Free Wall Longitudinal Strain and Angiographic Correlation in Acute Inferior Wall ST-elevation MI

Background: In this study, we assessed the prognostic significance of right ventricular free wall longitudinal strain (RVfwLS) in patients with acute inferior wall MI and investigated its association with angiographic characteristics and adverse outcomes. Methods: A prospective observational study was conducted with 200 patients admitted with acute inferior wall MI who underwent primary angioplasty. 2D speckle tracking echocardiography was used to measure the RVfwLS at the time of admission. Angiographic characteristics were collected, and patients were followed up for adverse outcomes until discharge. Categorical data were compared using the χ2 test or Fisher’s exact test. Logistic regression analysis was used to identify adverse cardiovascular outcomes independently associated with RVfwLS. A p-value of &lt;0.05 was considered statistically significant for all analyses. Results: Compared with patients with normal strain (n=88, 44%), patients with diminished strain (n=116, 56%) had significantly lower blood pressure (56.52% versus 43.58%; p=0.03), reduced tissue velocities (93.3% versus 6.7%; p&lt;0.01), elevated jugular venous pressure (58.93% versus 41.07%; p=0.04), and higher right ventricular systolic pressure (52.04% versus 47.96%; p=0.04). Additionally, patients with diminished strain had a higher incidence of triple vessel disease (80% versus 20%; p=0.026) and arrhythmias necessitating inotropic support (66.67% versus 37.33%; p=0.02), as well as a longer hospital stay (78.7% versus 21.3%; p&lt;0.01) compared with patients with normal strain. In multivariate analysis, arrhythmias (p=0.046; OR 2.05; 95% CI [0.93–8.10]) and right heart failure (p=0.035; OR 3.64; 95% CI [1.35–11.53]) were independently associated with RVfwLS. The optimal RVfwLS cut-off value for predicting adverse outcomes was −14.8% (AUC=0.915; 95% CI [0.876–0.954]; p&lt;0.001), with a sensitivity of 81.3% and specificity of 86.8%. Conclusion: RVfwLS can be used to categorise the severity of infarction and predict adverse outcomes.