Occurrence Of Edema Research Articles

Explainable machine learning prediction of edema adverse events in patients treated with tepotinib.

Tepotinib is approved for the treatment of patients with non-small-cell lung cancer harboring MET exon 14 skipping alterations. While edema is the most prevalent adverse event (AE) and a known class effect of MET inhibitors including tepotinib, there is still limited understanding about the factors contributing to its occurrence. Herein, we apply machine learning (ML)-based approaches to predict the likelihood of occurrence of edema in patients undergoing tepotinib treatment, and to identify factors influencing its development over time. Data from 612 patients receiving tepotinib in five Phase I/II studies were modeled with two ML algorithms, Random Forest, and Gradient Boosting Trees, to predict edema AE incidence and severity. Probability calibration was applied to give a realistic estimation of the likelihood of edema AE. Best model was tested on follow-up data and on data from clinical studies unused while training. Results showed high performances across all the tested settings, with F1 scores up to 0.961 when retraining the model with the most relevant covariates. The use of ML explainability methods identified serum albumin as the most informative longitudinal covariate, and higher age as associated with higher probabilities of more severe edema. The developed methodological framework enables the use of ML algorithms for analyzing clinical safety data and exploiting longitudinal information through various covariate engineering approaches. Probability calibration ensures the accurate estimation of the likelihood of the AE occurrence, while explainability tools can identify factors contributing to model predictions, hence supporting population and individual patient-level interpretation.

The predictive value of anterior segment optical coherence tomography for postoperative corneal edema in cataract patients.

To evaluate the predictive value of anterior segment optical coherence tomography (AS-OCT) for postoperative corneal edema in cataract patients. A retrospective cohort study of 144 cataract patients from December 2020 to December 2021 was conducted. Patients were divided into edema eyes (84 cases) and observation (60 cases) group based on postoperative corneal edema occurrence. Relevant indicators were compared between groups. Logistic regression identified risk factors for postoperative corneal edema. Receiver operating characteristic curves evaluated the predictive value. The edema eyes group had significantly higher postoperative central corneal thickness (CCT) and lower postoperative endothelial cell density (ECD) than the observation group (P < 0.05). The edema eyes group also had significantly lower preoperative ECD, anterior chamber depth (ACD), anterior chamber angle (ACA), and preoperative lens position (LP) than the observation group (P < 0.05). Logistic regression analysis showed that preoperative ECD, ACD, ACA, and LP were independent risk factors for postoperative corneal edema (P < 0.05), all of which also showed good predictive value for postoperative corneal edema, with areas under the curve (AUCs) of 0.854, 0.812, 0.791, and 0.778, respectively, under the ROC curve analysis. AS-OCT can provide useful information for predicting postoperative corneal edema in cataract patients. Preoperative ECD, preoperative ACD, preoperative ACA, and preoperative LP are important parameters that can be measured by AS-OCT and used as risk factors for postoperative corneal edema.

Different temperature regimes during gastrulation and neurulation influence developmental larval plasticity and survival at mouth opening in longfin yellowtail (Seriola rivoliana)

ABSTRACT We investigated if different temperature regimes during embryogenesis could influence the morphology, the occurrence of oedema, energy reserves, and survival in Seriola rivoliana larvae at mouth opening. Eggs were incubated at six constant (20, 22, 24, 26, 28, 30 °C) and two oscillating (21⇄29 °C) temperatures: decreasing starting (DS) and increasing starting (IS), which resulted in two opposite temperature fluctuating waves: gastrulation and neurulation. Total body length, head length and height were significantly influenced by temperature. Oscillation temperatures reduced major and severe oedema incidence. Mouth gape size was neither influenced by temperature nor by oedema condition. Larvae in DS had the lowest survival (36%) and grew as larvae at 20–24 °C. In contrast, IS showed the highest survival (76%) with larval size similar to 26–28 °C. Constant 28 °C had the lowest survival (48%), which resembled the increase up to 29 °C in DS during neurulation. In contrast, 22–26 °C had higher survivals (55–61%), which resembled the decrease down to 21 °C in IS during neurulation. Larvae at 20 °C and DS had the highest lipids consumption, which suggested detrimental effects on metabolism during gastrulation. Gastrulation and neurulation were likely critical survival and growth-developmental plasticity periods in this species.

Prophylactic management of cerebral vasospasm with clazosentan in real clinical practice: a single-center retrospective cohort study.

Clazosentan, a selective endothelin receptor subtype A antagonist, reduces vasospasm-related morbidity and all-cause mortality following aneurysmal subarachnoid hemorrhage (SAH) in the Japanese population, as demonstrated by a recent randomized phase 3 trial. However, evidence to suggest clazosentan should be prioritized over the current standard of care to prevent cerebral vasospasm is still lacking. Therefore, we investigated the efficacy and safety of clazosentan in comparison with conventional postoperative management in real-world clinical practice. We conducted a single-center, retrospective, observational cohort study using prospectively collected data from consecutive patients with aneurysmal SAH. After clazosentan was approved for use in Japan, the conventional postoperative management protocol, composed of intravenous fasudil chloride and oral cilostazol (control group, April 2021 to March 2022), was changed to the clazosentan protocol (clazosentan group, April 2022 to March 2023). The primary endpoint was the incidence of vasospasm-related symptomatic infarction. The secondary endpoints were favorable functional outcomes (modified Rankin scale score < 3) at discharge, angiographic vasospasm, and the need for rescue therapy for delayed cerebral ischemia. The analysis included 100 and 81 patients in the control and clazosentan groups, respectively. The incidence of vasospasm-related symptomatic infarction was significantly lower in the clazosentan group than in the control group (6.2% vs. 16%, p = 0.032). Multiple logistic analyses demonstrated that the use of clazosentan was independently associated with fewer incidence of vasospasm-related symptomatic infarct (23.8% vs. 47.5%, odds ratio 0.34 [0.12-0.97], p = 0.032). Clazosentan was significantly associated with favorable outcomes at discharge (79% vs. 66%, p = 0.037). Moreover, both the incidence of angiographic vasospasm (25.9% vs. 44%, p = 0.013) and the need for rescue therapy (16.1% vs. 34%, p = 0.006) was lower in the clazosentan group. The occurrence of pulmonary edema was significantly higher with clazosentan use (19.8% vs. 5%, p = 0.002), which did not result in morbidity. A postoperative management protocol centering on clazosentan was associated with the reduced vasospasm-related symptomatic infarction and improved clinical outcomes compared to the conventional management protocol in Japanese clinical practice. Clazosentan might be a promising treatment option for counteracting cerebral vasospasm after aneurysmal SAH.

Impact of HLA-B51 on Uveitis and Retinal Vasculitis: Data from the AIDA International Network Registries on Ocular Inflammatory Disorders

ABSTRACT Purpose The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet’s disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. Methods Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. Results Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). Conclusions Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.

Spleen derived monocytes regulate pulmonary vascular permeability in Hepatopulmonary syndrome through the OSM-FGF/FGFR1 signaling

Hepatopulmonary syndrome (HPS) is a serious pulmonary complication in the advanced stage of liver disease. The occurrence of pulmonary edema in HPS patients is life-threatening. Increased pulmonary vascular permeability is an important mechanism leading to pulmonary edema, and endothelial glycocalyx (EG) is a barrier that maintains stable vascular permeability. However, in HPS, whether the pulmonary vascular EG changes and its regulatory mechanism are still unclear. Spleen derived monocytes are involved in the pathogenesis of HPS. However, whether they regulate the pulmonary vascular permeability in HPS patients or rats and what is the mechanism is still unclear. Healthy volunteers and HPS patients with splenectomy or not were enrolled in this study. We found that the respiration of HPS patients was significantly improved in response to splenectomy, while the EG degradation and pulmonary edema were aggravated. In addition, HPS patients expressed higher levels of oncostatin M (OSM) and fibroblast growth factor (FGF). Subsequently, the co-culture system of monocytes and human umbilical vein endothelial cells (HUVECs) was constructed. It was found that monocytes secreted OSM and activated the FGF/FGFR1 signaling pathway in HUVECs. Then, an HPS rat model was constructed by common bile duct ligation (CBDL) for in vivo verification. HPS rats were intravenously injected with OSM recombinant protein and/or TNF-α into the rats via tail vein 30 min before CBDL. The results showed that the respiration of HPS rats was improved after splenectomy, while the degradation of EG in pulmonary vessels and vascular permeability were increased, and pulmonary edema was aggravated. Moreover, the expression of OSM and FGF was upregulated in HPS rats, while both were downregulated after splenectomy. Intravenous injection of exogenous OSM eliminated the effect of splenectomy on FGF and improved EG degradation. It can be seen that during HPS, spleen-derived monocytes secrete OSM to promote pulmonary vascular EG remodeling by activating the FGF/FGFR1 pathway, thereby maintaining stable vascular permeability, and diminishing pulmonary edema. This study provides a promising therapeutic target for the treatment of HPS.

Acute exposure to tris(2,4-di-tert-butylphenyl)phosphate elicits cardiotoxicity in zebrafish (Danio rerio) larvae via inducing ferroptosis

Tris(2,4-di-tert-butylphenyl)phosphate (AO168 =O), a novel organophosphate ester, is prevalent and abundant in the environment, posing great exposure risks to ecological and public health. Nevertheless, the toxicological effects of AO168 =O remain entirely unknown to date. The results in this study indicated that acute exposure to AO168 =O at 10 and 100 μg/L for 5 days obviously impaired cardiac morphology and function of zebrafish larvae, as proofed by decreased heartbeat, stroke volume, and cardiac output and the occurrence of pericardial edema and ventricular hypertrophy. Transcriptomics, polymerase chain reaction, and molecular docking revealed that the strong interaction of AO168 =O and transferrin receptor 1 activated the transportation of ferric iron into intracellular environment. The release of free ferrous ion to cytoplasmic iron pool also contributed to the iron overload in heart region, thus inducing ferroptosis in larvae via generation of excessive reactive oxygen species, glutathione peroxidase 4 inhibition, glutathione depletion and lipid peroxidation. Ferroptosis inhibitor (Fer-1) co-exposure effectively relieved the cardiac dysfunctions of zebrafish, verifying the dominant role of ferroptosis in the cardiotoxicity caused by AO168 =O. This research firstly reported the adverse impact and associated mechanisms of AO168 =O in cardiomyogenesis of vertebrates, underlining the urgency of concerning the health risks of AO168 =O.

Cilnidipine, a Dual L/N-type Ca2+ Channel Blocker in Hypertension Management: A Review.

Calcium channel blockers (CCBs) are widely used antihypertensive agents due to their effectiveness in reducing blood pressure (BP), along with their good tolerability and evidence of reducing hypertension (HTN)-related cardiovascular and renal diseases. Cilnidipine, a unique dihydropyridine calcium antagonist, exhibits potent inhibitory action on both N-type and L-type voltage-dependent calcium channels. With excellent oral absorption and a prolonged duration of action, it demonstrates a significant antihypertensive effect. It effectively reduces BP both systolic and diastolic while providing renal, neurological, and cardiovascular protection. Unlike L-type CCBs, cilnidipine does not increase pulse rates (PRs) and is associated with reduced occurrence of pedal edema. Cilnidipine is an effective treatment choice for individuals with mild to moderate essential HTN, whether it is administered alone or in conjunction with other treatment modalities.

Incidence and Risk Factors of Macular Edema After Phacoemulsification in Southern Pakistan

Objective: To determine the incidence and risk factors of macular edema (ME) after phacoemulsification at Institute of Ophthalmology, Liaquat University of Medical and Health Sciences (LUMHS)/ Jamshoro Sindh. Methodology: This descriptive cross-sectional study was conducted in Institute of Ophthalmology LUMHS, Jamshoro, during six months from December 2020 to June 2021. Patients who underwent phacoemulsification surgery for cataract removal, aged 18 years or older, both male and female patients with adequate follow-up post-surgery were included. All patients underwent Phacoemulsification, receive standard post-operative topical medication i.e, Moxifloxacin 0.5% and Prednisolone 1% (1 hourly for 1 week, and 4 times per day after 1 week). The patients were undergone routine follow up and were subjected to visual acuity measurement. The measurement of postoperative CME by SS-OCT was done 1 week postoperatively followed by 3th week and 6th week. All the information was entered ana analyzed into SPSS 26 version. Results: A total of 96 patients, those who underwent phacoemulsification were studied; their mean age was 54.11 +8.97 years. Males were 58.3% and females were 41.7%. Out of all, 24.0% cases were diabetes, 8.3% were hypertensive. After surgery on 3rd post-operative week macular edema was found in 9.4% of the cases and on 6th post-operative week it was found in 19.8% of the cases. Post operative macular edema was found statistically significant according to diabetes mellitus and hypertension, (p = &lt; 0.05), while it was statistically insignificant according to age, gender, ME in fellow eye and high myopia on 3rd postoperative week p-values were quite insignificant (p= &gt;0.05), while macular edema (6th week) was found statistically significant according to age (p-0.038) while statistically insignificant according to gender, diabetes mellitus, hypertension, ME in fellow eye and high myopia on 3rd postoperative week p-values were quite insignificant (p= &gt;0.05). Conclusion: As per study conclusion the occurrence of macular edema was observed to be the less frequent after phacoemulsification. Male gender, age more than 45 years and diabetes mellitus were observed to be the most common risk factors.

Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury

PurposeCerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. MethodsThis case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q1, Q3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. ResultsAccording to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 − 25.42, p = 0.002), 2.85 (95% CI: 1.11 − 7.31, p = 0.030), 2.62 (95% CI: 1.12 − 6.13, p = 0.027), 2.44 (95% CI: 1.25 − 4.76, p = 0.009), and 1.5 (95% CI: 1.10 − 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. ConclusionOur study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Hypochlorous acid-the future of wound care?

Dear Editor, Wounds, especially chronic wounds and associated infections, impose a substantial burden on individuals and healthcare systems, leading to escalated morbidity rates and a significant ris in healthcare costs. Chronic wounds create ideal conditions for infection and the formation of biofilms, making it essential to implement comprehensive wound care techniques to promote wound healing1. Antiseptics are substances that impede or eradicate pathogens found within wounds or on the skin. Iodine-based agents such as povidone-iodine (PVP-I) have been used to treat wounds for decades. PVP-I is widely used and accepted due to its broad activity spectrum against gram-positive and negative bacteria, no development of cross-resistance upon use and its ability to penetrate biofilms. While being widely utilized worldwide, certain concerns have been raised regarding hypersensitivity, inadequate penetration, and potential cytotoxicity on host cells associated with its use. Reports have emerged documenting instances of both immediate and delayed allergic reactions to PVP-I. There have also been reports of iodine toxicity in patients when PVP-I was used as a constant wound irrigant2. Hypochlorous acid (HOCl) is a potent antimicrobial compound naturally synthesized by the immune system. It exhibits remarkable efficacy against a wide range of bacterial, viral, and fungal pathogens, effectively neutralizing their presence. A study conducted by Sakarya et al. concluded that stabilized HOCl solution is minimally allergenic as it’s produced naturally in the body and is also an ideal wound care solution3. A few comparative studies have been conducted between HOCl and PVP-I. In very recent research, it was concluded that in neonatal circumcision, the group of patients that used PVP-I had a greater occurrence of edema and delayed wound healing as compared to patients that used HOCl4. Moreover, PVP-I has been demonstrated to be cytotoxic to cellular components of wound healing while HOCl controls bacterial spread without disrupting the wound healing process as it is non-cytotoxic to cells at concentrations that achieve antimicrobial action. The amount of exudate also decreases when Hypochlorous acid is used instead of Povidone iodine5. To sum it up, Physicians and nurses face a formidable hurdle in identifying a topical antiseptic agent that is both safe and efficacious. PVP-I is being widely used as an antiseptic agent for wound healing but patients do experience some side effects. Research suggests that hypochlorous acid is also an effective option to treat lesions with less adverse effects, although more research should be conducted to reach absolute conclusive results.

Decreased brain volume may be associated with the occurrence of peri-lead edema in Parkinson's disease patients with deep brain stimulation

BackgroundPeri-lead edema (PLE) is a poorly understood complication of deep brain stimulation (DBS), which has been described in patients presenting occasionally with profound and often delayed symptoms with an incidence ranging from 0.4% up to even 100%. Therefore, our study aims to investigate the association of brain and brain compartment volumes on magnetic resonance imaging (MRI) with the occurrence of PLE in Parkinson's disease (PD) patients after DBS implantation in subthalamic nuclei (STN). MethodsThis retrospective study included 125 consecutive PD patients who underwent STN DBS at the Department of Neurosurgery, Dubrava University Hospital from 2010 to 2022. Qualitative analysis was done on postoperative MRI T2-weighted sequence by two independent observers, marking PLE on midbrain, thalamus, and subcortical levels as mild, moderate, or severe. Quantitative volumetric analysis of brain and brain compartment volumes was conducted using an automated CIVET processing pipeline on preoperative MRI T1 MPRAGE sequences. In addition, observed PLE on individual hemispheres was delineated manually and measured using Analyze 14.0 software. ResultsIn our cohort, PLE was observed in 32.17%, mostly bilaterally. Mild PLE was observed in the majority of patients, regardless of the level observed. Age, sex, diabetes, hypertension, vascular disease, and the use of anticoagulant/antiplatelet therapy showed no significant association with the occurrence of PLE. Total grey matter volume showed a significant association with the PLE occurrence (r = −0.22, p = 0.04), as well as cortex volume (r = −0.32, p = 0.0005). Cortical volumes of hemispheres, overall hemisphere volumes, as well as hemisphere/total intracranial volume ratio showed significant association with the PLE occurrence. Furthermore, the volume of the cortex and total grey volume represent moderate indicators, while hemisphere volumes, cortical volumes of hemispheres, and hemisphere/total intracranial volume ratio represent mild to moderate indicators of possible PLE occurrence. ConclusionThe results of our study suggest that the morphometric MRI measurements, as a useful tool, can provide relevant information about the structural status of the brain in patients with PD and represent moderate indicators of possible PLE occurrence. Identifying patients with greater brain atrophy, especially regarding grey matter before DBS implantation, will allow us to estimate the possible postoperative symptoms and intervene in a timely manner. Further studies are needed to confirm our findings and to investigate other potential predictors and risk factors of PLE occurrence.

The effect of alfalfa supplementation during the peripartum period on udder oedema and fertility in dairy sheep

AbstractIn recent years, there has been a trend towards hyperoestrogenic feeding methods in field conditions, particularly in dairy small ruminants. This study aimed to investigate the effect of alfalfa supplemented ration in the prepartum period on the occurrence of udder oedema in dairy ewes and its impact on fertility problems (dystocia, vaginal prolapse, uterine prolapse, retained placenta) and diseases (mastitis, udder dermatitis) occurring in the postpartum period. In addition, it aimed to follow up the data on maternal rejection behaviours and litter viability, which are believed to affect the future productivity and fertility of the herd. The ewes were divided into two groups: the oedema group (n = 20) and the control group (n = 23). For trial purposes in the oedema group, primiparous animals were provided with alfalfa supplementation. The control group consisted of ewes fed the same ration but without alfalfa supplementation. Ingredient analysis of the rations was performed in the groups. In biochemical analyses, the oedema group demonstrated significantly higher levels of serum urea (p &lt; .05), Ca (p &lt; .000) and Ca/P ratio (p &lt; .01) compared to the control group. Clinical mastitis (0–7 days, p = .051) and (8–30 days, p = .149) were reported at a higher rate in the oedema group compared to the control group. Udder dermatitis cases were more common in the oedema group (p = .005). The mother's rejection of the lamb was higher in the oedema group. Dystocia was determined to be 30% in the oedema group (p = .023). In conclusion, applying hyperoestrogenic feeding strategies during the periparturient period firstly exacerbates physiological udder oedema in ewes, thus predisposing them to various herd fertility problems. This feeding strategy, frequently encountered in field conditions, seriously harms the physiological fertility process.

Developmental Toxicity of C10 Massoia Lactone, the Main Constituent of Cryptocarya massoia, on Zebrafish (Danio rerio) Embryos

C10 massoia lactone (C10) is the main component of massoia essential oil derived from Cryptocarya massoia plant bark, which is used as natural flavoring agent of “generally recognized as safe” status. In this study, the developmental toxicity of C10 was evaluated on zebrafish (Danio rerio) embryos at an exposure level of 0–2000 µg·L−1, and acute toxicity was determined with respect to lethal effects, hatching rates, and morphological changes. Additionally, morphological changes were determined for the endpoints as the occurrence of yolk edema, pericardial edema, spine curvature, and shortened body length after treatment until 96 h post-fertilization (hpf). The complete lethality of C10 was achieved with embryos treated at 2000 µg·L−1, and most embryos treated at 1000 µg·L−1 developed pericardial edemas with some spine curvature. Some embryos exhibited delayed development with shortened body length when compared with the control. Hatchability was completely accomplished at the tested dose of 1000 µg·L−1, and cardiac malformation was observed using a transgenic zebrafish line Tg(cmlc:EGFP), with a lower heartbeat rate in embryos treated with C10 for 72 hpf. After 96 hpf, heartbeat rates were normalized when compared with the control group, and two cardiac development-related genes such as nppa and canca1 were differently expressed in C10-treated embryos by 2.3-fold and 0.4-fold, respectively. Therefore, C10 must be studied further in other higher organisms for its risk.

Scheimpflug Tomography as a Predictor of Corneal Edema After Phacoemulsification in Fuchs Endothelial Corneal Dystrophy.

To determine if Scheimpflug tomography pachymetry map and posterior elevation map patterns can predict the occurrence of corneal edema following uneventful phacoemulsification surgery in Fuchs endothelial corneal dystrophy (FECD). Observational prospective case-control study. Fifty FECD eyes (50 patients) with visually significant cataract: 25 with subclinical corneal edema (SCE) versus 25 without SCE. Preoperatively, FECD was clinically assessed, and only patients devoid of clinical corneal edema were enrolled. Utilizing the Mayo Clinic classification for subclinical corneal edema (SCE), eligible FECD eyes were stratified based on Scheimpflug imaging pachymetry map and posterior elevation map characteristics, including loss of regular isopachs, displacement of the cornea's thinnest point, and the presence of posterior surface depression, into two groups: Group A representing FECD with SCE, and Group B: FECD without SCE. One week postoperatively, clinical and tomographic evaluation was performed. Regression analysis was conducted to evaluate predictors of corneal edema after uneventful phacoemulsification surgery in both groups. All patients were successfully imaged before and 1 week after surgery. Visual acuity was significantly improved in both groups (P < 0.001). No postoperative clinical edema was observed in Group B, while 23 (92%) had mild edema and 2 (8%) had moderate edema in Group A. Both groups showed a significant increase in postoperative central corneal thickness (CCT) and thinnest corneal thickness (TCT) (both P < 0.001). Compared to Group B, Group A showed a significant central flattening of the anterior corneal surface (P = 0.007 and P = 0.04 for K1 and K2 respectively), and a significant increase in the postoperative posterior surface depression. Multivariate analysis showed that 94% of postoperative corneal edema could be predicted by the presence of preoperative posterior surface depression (P = 0.04, ARR = 5.8 (1.89-35.7)). Scheimpflug tomography pachymetry map and posterior elevation map patterns can predict corneal edema after uneventful phacoemulsification surgery in FECD with subclinical corneal edema.

The Promise of Cilnidipine in Hypertension with Comorbidities: National Consensus Statement: National Consensus Group Comprises Cardiologists, Nephrologists, and Diabetologists from India in a National Meet at New Delhi held on 22nd May 2022.

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.

Evaluation of abnormal Chest X-rays for hemodialysis patients

Background: A chest x-ray is the most practical way to evaluate lung disease. There are different degrees of pulmonary abnormalities in hemodialysis patients. The diagnosis of pulmonary disease in hemodialysis patients can be challenging due to the complex findings and multiple manifestations. Objective: This study aimed to identify and evaluate the accuracy and consistency of chest radiographs in the diagnosis of pulmonary abnormalities in hemodialysis patients, Also highlight the limitations of CXR for diagnoses. Materials and methods: We collected and reviewed chest radiographs of 60 hemodialysis patients with various pulmonary manifestations. Two experienced radiologists independently interpreted CXR uptake to diagnose pulmonary disease. The degree of incompatibility among radiologists was assessed using SPSS statistical analysis (chi-square test).Results: The two radiologists showed slight agreement in pneumonia (29.6%), pleural effusion (28.6%), pulmonary edema (25.0%) and cardiomegaly (20.0%). Where the level of disagreement between radiologists 1 and 2 was in cardiomegaly (80.0%), pulmonary edema (75.0%) ), pneumonia (70.4%) and pleural effusion (71.4 %). The total level of agreement was 31.7% and 63.3% disagreement. This result indicates that there is a significant difference in terms of diagnosis (X2 = 8.067, p-value &lt;0.05).Conclusion: The chest X-ray upon admission is limited in accurately diagnosing pulmonary abnormalities in hemodialysis patients, primarily due to the presence of multiple diseases in the same patient and the increased occurrence of pulmonary edema in these patients. This poses a challenge to diagnosis without clinical data or the utilization of other imaging techniques.

Pressure-sensitive multivesicular liposomes as a smart drug-delivery system for high-altitude pulmonary edema

Changes in bodily fluid pressures, such as pulmonary artery pressure, play key roles in high-altitude pulmonary edema (HAPE) and other disorders. Smart delivery systems releasing a drug in response to these pressures might facilitate early medical interventions. However, pressure-responsive delivery systems are unavailable. We here constructed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) based on the incomplete filling of the internal vesicle space with neutral lipids. These liposomes were loaded with amlodipine besylate (AB), a next-generation calcium channel inhibitor, to treat HAPE on time. AB-loaded PSMVLs (AB-PSMVLs) were destroyed, and AB was released through treatment under hydrostatic pressure of at least 25 mmHg. At 25 mmHg, which is the minimum pulmonary artery pressure value in HAPE, 38.8% of AB was released within 1 h. In a mouse HAPE model, AB-PSMVLs concentrated in the lung and released AB to diffuse into the vascular wall. Intravenously injected AB-PSMVLs before HAPE modeling resulted in a stronger protection of lung tissues and respiratory function and lower occurrence of pulmonary edema than treatment with free drug or non-pressure-sensitive AB-loaded liposomes. This study offers a new strategy for developing smart drug delivery systems that respond to changes in bodily fluid pressures.

PREVALENCE OF LOWER LIMB EDEMA IN NATAL AND POST-NATAL PERIOD

Introduction: Pregnancy is a very special period for women, they experience emotional, physical, and physiological deviations. The majority of females encounter peripheral edema during their gestation time. The objective of this study was to determine the occurrence of edema in the natal and post-natal period, risk factors, and their association with edema.&#x0D; Methods: An observational study was conducted at Cantonment Hospital and Benazir Bhutto Hospital, Rawalpindi, Pakistan from August 2018 to January 2019. Out of 405 females, 18-35 years of age and 3rd trimester of gestation or post-natal period and women with previous venous diseases or high-risk gestations were included. Whereas women with edema in other body parts and those after puerperium were excluded. The data was collected by self-structured questionnaire, edema grading scale, and limb measurement. Data were analyzed by SPSS 23.&#x0D; Results: The frequency of leg edema was 65.9% and higher in the third trimester, especially during the eighth and nine months of pregnancy. It could lead to several other symptoms like pain and cramps that could be intensified by long-standing and comforted through rest whereas a few other factors that affect edema contain less water intake and lack of exercise. There is a significant association between edema and its related risk factors including months of pregnancy, exercises during pregnancy, and activity level (p &lt; 0.001).&#x0D; Conclusion(s): Lower limb edema is prevalent in late pregnancy, especially during the 8th - 9th month. There is a significant association between edema and its related risk factors including months of pregnancy, exercises during pregnancy, and activity level.&#x0D; Keywords: Edema, lower limb, pregnancy, prevalence.

Exercise-Induced Fluid Retention, Cardiac Volume Overload, and Peripheral Edema in Ultra-Distance Cyclists

IntroductionUltracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and investigate the potential occurrence of peripheral edema. MethodsSerial laboratory analyses of blood and urine, bioelectrical impedance analyses and echocardiography were performed at four time points during a six-day bicycle ride in 13 ultracyclists (5 female, 8 male). Throughout the ride, participants continuously tracked fluid intake, measured extremity circumferences daily, and self-tested urinary electrolytes using a point-of-care testing device. Portrait photos were judged by 20 physicians for occurrence of facial and eyelid edema. ResultsParticipants covered a mean distance of 1,205 km and 19,417 vertical meters. From baseline to day 6, body weight remained stable (p = 0.479), but body composition changed with increasing total body water (+1.98 L ± 1.37, p = 0.003) and plasma volume (+18.86 % ± 10.7, p < 0.001). A significant increase in NT-proBNP (+297.99 ng/L ± 190.42, p < 0.001) until day 6 indicates concomitant cardiac volume overload. Swelling of face and eyelids peaked on day 5 (both p ≤ 0.033). On recovery, changes partly resolved. While urinary sodium concentration showed a nadir on day 4 (-32.18 mmol/L ± 23.88, p = 0.022), plasma osmolality (+5.69 mmosmol/kg ± 5.88, p = 0.004) and copeptin (+38.28 pg/mL ± 18.90, p < 0.001) increased steadily until day 6. ConclusionUltracycling over multiple days induces extracellular volume expansion, peripheral edema and cardiac volume overload. Renal sodium and water retention is likely contributing to this condition.