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Computational Biology and Chemistry Aug 2024Venous leg ulcers (VLUs) pose a growing healthcare challenge due to aging, obesity, and sedentary lifestyles. Despite various treatments available, addressing the...
Venous leg ulcers (VLUs) pose a growing healthcare challenge due to aging, obesity, and sedentary lifestyles. Despite various treatments available, addressing the complex nature of VLUs remains difficult. In this context, this study investigates repurposing boronated drugs to inhibit arginase 1 activity for VLU treatment. The molecular docking study conducted by Schrodinger GLIDE targeted the binuclear manganese cluster of arginase 1 enzyme (2PHO). Further, the ligand-protein complex was subjected to molecular dynamic studies at 500 ns in Gromacs-2019.4. Trajectory analysis was performed using the GROMACS simulation package of protein RMSD, RMSF, RG, SASA, and H-Bond. The docking study revealed intriguing results where the tavaborole showed a better docking score (-3.957 Kcal/mol) compared to the substrate L-arginine (-3.379 Kcal/mol) and standard L-norvaline (-3.141 Kcal/mol). Tavaborole interaction with aspartic acid ultimately suggests that the drug molecule binds to the catalytic site of arginase 1, potentially influencing the enzyme's function. The dynamics study revealed the compounds' stability and compactness of the protein throughout the simulation. The RMSD, RMSF, SASA, RG, inter and intra H-bond, PCA, FEL, and MMBSA studies affirmed the ligand-protein and protein complex flexibility, compactness, binding energy, van der waals energy, and solvation dynamics. These results revealed the stability and the interaction of the ligand with the catalytic site of arginase 1 enzyme, triggering the study towards the VLU treatment.
Topics: Arginase; Humans; Molecular Docking Simulation; Varicose Ulcer; Boron Compounds; Drug Repositioning; Molecular Dynamics Simulation; Enzyme Inhibitors; Bridged Bicyclo Compounds, Heterocyclic; Molecular Structure
PubMed: 38843583
DOI: 10.1016/j.compbiolchem.2024.108112 -
Phlebology Jun 2024This hypothesis introduces pump shoes as a method for the prevention and treatment of varicose veins.
BACKGROUND
This hypothesis introduces pump shoes as a method for the prevention and treatment of varicose veins.
METHOD
An air pump is placed in the shoe, connected to an airbag wrapped around the leg through a hose. With each step, air is pumped into the foot airbag, applying pressure to the leg muscles and superficial veins. This action mimics muscle pumping, helping to push blood back towards the heart. Excess air is released through an outlet hose with an adjustable sphincter, allowing for increased pressure on the leg.
RESULTS & CONCLUSION
These shoes offer a simple mechanism to assist in returning blood from the feet to the heart. They can be beneficial in preventing varicose veins in at-risk individuals or treating those in the early stages of the disease.
PubMed: 38842405
DOI: 10.1177/02683555241260763 -
Drug Design, Development and Therapy 2024Vascular ulcers constitute a serious global public health problem, responsible for causing a significant social and economic impact due to their recurrent, disabling... (Observational Study)
Observational Study
INTRODUCTION
Vascular ulcers constitute a serious global public health problem, responsible for causing a significant social and economic impact due to their recurrent, disabling nature and the need for prolonged therapies to cure them.
OBJECTIVE
To evaluate the use and efficacy of the rhEGF in the epithelialization of patients with a diagnosis of CEAP stage 6 venous insufficiency, in the two regimes of the health system in Colombia, the contributive (equivalent to a health system where citizens with payment capacity contribute a percentage of their salary) and the subsidized (equivalent to a health system where the state covers the vulnerable population and low socioeconomic level) versus the other treatments used.
METHODOLOGY
Observational, descriptive, retrospective, multicenter study, in which 105 medical records with 139 ulcers were reviewed, in 2 centers, one belonging to the subsidized system and the other to the contributive system in Colombia.
RESULTS
The association with the epithelialization variable of the different treatment groups for ulcers according to the application of the mixed effect model test, for both regimes was for the Biologicals (EC 34.401/p = 0.000), Bioactive Agents (Hydrogels) (EC 24.735/p = 0.005) groups; for the rest of the treatment groups, the results were neither associated nor statistically significant.
CONCLUSION
Intra- and perilesional therapy with rhEGF expands the therapeutic spectrum in patients with venous ulcers, regardless of the type of health system in which it will be applied, shortening the healing time and reaching a possible therapeutic goal, which according to this study there is an association with epithelialization regardless of the regime applied.
Topics: Humans; Colombia; Varicose Ulcer; Retrospective Studies; Male; Female; Middle Aged; Epidermal Growth Factor; Recombinant Proteins; Aged
PubMed: 38831868
DOI: 10.2147/DDDT.S437105 -
Vascular Jun 2024To evaluate the short-term clinical outcomes of radiofrequency ablation (RFA) using a radiofrequency (RF) needle device for varicose ulcers.
OBJECTIVE
To evaluate the short-term clinical outcomes of radiofrequency ablation (RFA) using a radiofrequency (RF) needle device for varicose ulcers.
METHODS
From September 2020 to September 2021, a total of 80 patients with varicose ulcers were included in this study. Based on the different surgical methods, the patients were divided into RF group and control groups, with 40 cases in each group. In the RF group, RFA was performed using an RF needle device and foam sclerotherapy was used for superficial veins. The control group was treated with conventional high-ligation stripping. The surgical data, hospitalization data, clinical efficacy, and postoperative complications of two groups were compared. Meanwhile, the correlation between RBC, HB, HCT, and ulcer healing time was analyzed.
RESULTS
Compared to the control group, RF group had shorter surgery time, duration in the hospital, and less intraoperative bleeding ( < .05). The VCSS and CIVIQ scores in RF group were significantly higher than that in control group ( < .05). The healing time of ulcers was shorter in the RF group ( = 19.766, = .000). The RF group had fewer postoperative complications. There was a positive correlation between RBC, HB, and HCT, and ulcer healing time ( < .05).
CONCLUSION
The use of the RF needle device for RFA to treat patients with varicose ulcers showed acceptable short-term clinical outcomes with less incidence of trauma, faster recovery, and fewer complications.
PubMed: 38828763
DOI: 10.1177/17085381241258192 -
Journal of Vascular Nursing : Official... Jun 2024An evidence-based approach is essential in the treatment of wounds to optimise healing, reduce costs and improve patient outcomes. (Observational Study)
Observational Study
INTRODUCTION
An evidence-based approach is essential in the treatment of wounds to optimise healing, reduce costs and improve patient outcomes.
AIM
This case study aimed to demonstrate our model of care, which assesses and manages patients with venous disease and complex wounds. In this case, venous leg ulcer (VLU) was treated with TLC-NOSF dressing and therapeutic compression. The wound was serially assessed using a smart App that gave the patient a graphic representation of their progress.
DESIGN
Descriptive Observational Case Study.
CLINICAL CARE
An evidence-based approach for managing a chronic, severe VLU. The patient was initially seen at the Outpatient Vascular Wound Clinic twice weekly, then every two weeks for conservative sharp wound debridement, skin care, dressing change, and compression therapy using a compression (Ready) wrap. Wound progress was monitored by the digital application 'Tissue Analytics', a "purposedesigned digital wound management platform that records, tracks, and analyses wounds".
RESULTS
Week 1: On initial review, ulcer length was 3.15cm, width was 3.1 cm, and total surface area was 6.31 cm. The wound base was mildly sloughy (<25%), with areas of good granulation tissue on view. Week 12: Length was 1.32 cm, width 1.50 cm, and total surface area of 1.45 cm, a 77% reduction in wound size. Week 24: The length was 0.48 cm, the width was 0.64 cm, and the total surface area was 0.18 cm. This represented a 97% reduction in wound size. Week 36: Length was 0.01 cm, the width 0.06 cm, with a total surface area of 0.00 cm. This represented a 99.99% reduction in wound size.
CONCLUSION
The patient's treatment for a complex venous leg ulcer included the application of TLC-NOSF dressing in combination with individualised therapeutic compression therapy. We found TLC-NOSF was very effective in combination with the best standard of VLU care (i.e. therapeutic graduated compression therapy). The clinician and patient were impressed with the healing rate at 12 weeks, as the wound dimensions were the lowest since the wound started six years ago. This dramatically improved patient concordance and engagement in care. Despite incomplete healing at 36 weeks, the wound-healing journey over the 36 weeks indicated wound closure was close. In addition, using a wound assessment App, the patient could immediately see the benefits of the new treatment, facilitating patient compliance with the treatment.
Topics: Humans; Wound Healing; Varicose Ulcer; Compression Bandages; Debridement; Male; Female; Skin Care; Aged; Bandages
PubMed: 38823976
DOI: 10.1016/j.jvn.2024.01.002 -
Journal of Vascular Nursing : Official... Jun 2024Approximately 80% of patients presenting with leg ulcers are venous in origin. However, lack of standardisation of care has a human and financial impact for patients and...
Approximately 80% of patients presenting with leg ulcers are venous in origin. However, lack of standardisation of care has a human and financial impact for patients and service providers. Increases in the aging population and number of patients entering older age with co-morbidities results in increases in the demand for venous leg ulcer treatments. A joint initiative between a Registered Advanced Nurse Practitioner (RANP) in tissue viability and wound care, and a vascular consultant, identified deficits in patient care delivery and quality of life. A joint initiative Implementing the principles of the 'Sláintecare' policy was established as the Leg Ulcer Centre Ireland (LUCI) to deliver a pathway for the treatment and management of lower limb venous ulcers. The RANP provides a "one stop shop" for patients, offering a complete care package from diagnosis to surgical intervention - endovenous ablation, follow-up post operative care and discharge. Audit findings include; reduced hospital admissions and waiting times; increased patient satisfaction; and, improved interdisciplinary integrated referral pathways. The RANP offers an effective, efficient diagnosis-to-end treatment service for patients. The results demonstrate improved treatment, cost outcomes and value-based outcomes for patients. The new integrated service facilitates expansion of the service and further enhancement of the nursing skills and role.
Topics: Humans; Ireland; Nurse Practitioners; Varicose Ulcer; Quality of Life; Patient Satisfaction; Practice Patterns, Nurses'; Leg Ulcer
PubMed: 38823970
DOI: 10.1016/j.jvn.2024.02.003 -
Journal of Vascular Surgery. Venous and... May 2024The aim of this study was to assess the utilization of surgical interventions in patients diagnosed with superficial vein thrombosis (SVT) and its potential association...
OBJECTIVE
The aim of this study was to assess the utilization of surgical interventions in patients diagnosed with superficial vein thrombosis (SVT) and its potential association with the occurrence of venous thromboembolism (VTE) and bleeding events.
METHODS
INSIGHTS-SVT, a prospective, non-interventional, multicenter study in Germany, investigated the management and outcomes of patients with acute SVT who received conservative and/or invasive treatments at the discretion of the treating physician.
RESULTS
Among the 872 patients with 12-month data, 657 had medical therapy only, and 215 patients underwent vascular surgery (70 within 3 months of SVT diagnosis, 136 between months 4 and 12, and nine had an intervention in both periods). The most commonly performed procedures included endovenous thermal ablation, ligation of the saphenofemoral or saphenopopliteal junction, and vein stripping. The primary outcome of symptomatic VTE was observed in 5.8% of conservatively treated patients and 6.3% of those who underwent surgical intervention. Additionally, the secondary outcome of recurrent or extended SVT was documented in 4.7% of conservatively treated patients and 5.3% of invasively treated patients. Bleeding events occurred in 1.4% of conservatively treated patients and 2.1% of surgically treated patients. These differences were statistically not significant. Furthermore, our analysis indicated a potential protective effect associated with surgical treatments, such as ligation of the saphenofemoral or saphenopopliteal junction, stripping and endovenous thermal ablation, concerning the endpoint of VTE for patients when applied after 3 months from the index SVT event.
CONCLUSIONS
In line with previous research, our study suggests that surgical interventions are not frequently employed in the management of SVT, although they may be warranted in select cases. Nevertheless, additional research is essential to gain a deeper understanding of the indications, criteria, and benefit of surgical interventions in the treatment of SVT.
PubMed: 38821188
DOI: 10.1016/j.jvsv.2024.101917 -
Frontiers in Genetics 2024Varicose veins (VV) are a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic...
BACKGROUND
Varicose veins (VV) are a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic burden on the healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, to identify potential pathogenic genes and drug targets for VV treatment.
METHODS
This study conducted Summary-data-based Mendelian Randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies and cis-expression quantitative trait loci databases. Only genes with PP.H4 > 0.7 in colocalization were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization (MR) analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies and The Drug-Gene Interaction Database data to identify and screen the remaining genes and identified four drug targets for the treatment of VV.
RESULTS
We identified four genes significantly associated with VV, namely, [Odds ratio (OR) = 1.08, 95% Confidence interval (CI): 1.05-1.11, = 1.42e-10] and (OR = 1.13, 95% CI: 1.06-1.20, = 6.90e-5), (OR = 1.05, 95% CI: 1.01-1.11, = 1.42e-2) and (OR = 0.87, 95% CI: 0.81-0.95, = 3.67e-3). Increased expression of three genes, namely, , , and , was associated with increased risk of the disease, and increased expression of was associated with decreased risk of the disease. These four genes could be targeted for VV therapy.
CONCLUSION
We identified four potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that , , , and might be potential drug targets for varicose veins.
PubMed: 38818040
DOI: 10.3389/fgene.2024.1385293 -
World Journal of Clinical Cases May 2024Acute upper gastrointestinal bleeding is a common medical emergency that has a 10% hospital mortality rate. According to the etiology, this disease can be divided into...
BACKGROUND
Acute upper gastrointestinal bleeding is a common medical emergency that has a 10% hospital mortality rate. According to the etiology, this disease can be divided into acute varicose veins and nonvaricose veins. Bleeding from esophageal varices is a life-threatening complication of portal hypertension. Portal hypertension is a clinical syndrome defined as a portal venous pressure that exceeds 10 mmHg. Cirrhosis is the most common cause of portal hypertension, and thrombosis of the portal system not associated with liver cirrhosis is the second most common cause of portal hypertension in the Western world. Primary myeloproliferative disorders are the main cause of portal venous thrombosis, and somatic mutations in the gene () can be found in approximately 90% of polycythemia vera, 50% of essential thrombocyrosis and 50% of primary myelofibrosis.
CASE SUMMARY
We present a rare case of primary myelofibrosis with gastrointestinal bleeding as the primary manifestation that presented as portal-superior-splenic mesenteric vein thrombosis. Peripheral blood tests revealed the presence of the mutation. Bone marrow biopsy ultimately confirmed the diagnosis of myelofibrosis (MF-2 grade).
CONCLUSION
In patients with acute esophageal variceal bleeding due to portal hypertension and vein thrombosis without cirrhosis, the possibility of myeloproliferative neoplasms should be considered, and the mutation test should be performed.
PubMed: 38817215
DOI: 10.12998/wjcc.v12.i15.2621 -
Phlebology May 2024The SYNCHRONOUS-study investigates simultaneous ASV-ablation with great saphenous vein (GSV) treatment in endovenous laser ablation (EVLA) for preventing varicose vein...
Safety of synchronous prophylactic ablation of the anterior saphenous vein in patients undergoing great saphenous vein thermal ablation- 6 months follow-up data of the SYNCHRONOUS study.
BACKGROUND
The SYNCHRONOUS-study investigates simultaneous ASV-ablation with great saphenous vein (GSV) treatment in endovenous laser ablation (EVLA) for preventing varicose vein recurrence. This sub-study examines complication rates associated with prophylactic ASV-ablation.
METHODS
Among 1173 patients with refluxing GSV, 604 underwent GSV-ablation only, and 569 received additional ASV-ablation. Complication rates were compared over 6 months.
RESULTS
Approximately 80% of patients were complication-free with minor bruising and dysesthesia being most common complications. After 6 months, additional prophylactic ASV-ablation did not increase the rate of complications compared to GSV-only treatment.
CONCLUSION
The 6-months follow-up data suggests that prophylactic ASV-closure, alongside GSV-treatment, is safe, with similar complication rates to GSV-only EVLA.
PubMed: 38815590
DOI: 10.1177/02683555241257840