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Cell Stem Cell Sep 2023Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate...
Life-long reconstitution of a tissue's resident stem cell compartment with engrafted cells has the potential to durably replenish organ function. Here, we demonstrate the engraftment of the airway epithelial stem cell compartment via intra-airway transplantation of mouse or human primary and pluripotent stem cell (PSC)-derived airway basal cells (BCs). Murine primary or PSC-derived BCs transplanted into polidocanol-injured syngeneic recipients give rise for at least two years to progeny that stably display the morphologic, molecular, and functional phenotypes of airway epithelia. The engrafted basal-like cells retain extensive self-renewal potential, evident by the capacity to reconstitute the tracheal epithelium through seven generations of secondary transplantation. Using the same approach, human primary or PSC-derived BCs transplanted into NOD scid gamma (NSG) recipient mice similarly display multilineage airway epithelial differentiation in vivo. Our results may provide a step toward potential future syngeneic cell-based therapy for patients with diseases resulting from airway epithelial cell damage or dysfunction.
Topics: Humans; Animals; Mice; Pluripotent Stem Cells; Cell- and Tissue-Based Therapy; Epithelial Cells; Epithelium; Mice, Inbred NOD; Mice, SCID
PubMed: 37625411
DOI: 10.1016/j.stem.2023.07.014 -
Annals of Vascular Surgery Aug 2024This review article provides an updated review of a relatively common pathology with various manifestations. Superficial venous diseases (SVDs) are a broad spectrum of... (Review)
Review
BACKGROUND
This review article provides an updated review of a relatively common pathology with various manifestations. Superficial venous diseases (SVDs) are a broad spectrum of venous vascular disease that predominantly affects the body's lower extremities. The most serious manifestation of this disease includes varicose veins, chronic venous insufficiency, stasis dermatitis, venous ulcers, superficial venous thrombosis, reticular veins, and spider telangiectasias.
METHODS
The anatomy, pathophysiology, and risk factors of SVD were discussed during this review. The risk factors for developing SVD were related to race, age, sex, lifestyle, and certain genetic conditions as well as comorbid deep vein thrombosis. Various classification systems were listed, focusing on the most common one-the revised Clinical-Etiology-Anatomy-Pathophysiology classification. The clinical features including history and physical examination findings elicited in SVD were outlined.
RESULTS
Imaging modalities utilized in SVD were highlighted. Duplex ultrasound is the first line in evaluating SVD but magnetic resonance imaging and computed tomography venography, plethysmography, and conventional venography are feasible options in the event of an ambiguous venous duplex ultrasound study. Treatment options highlighted in this review ranged from conservative treatment with compression stockings, which could be primary or adjunctive to pharmacologic topical and systemic agents such as azelaic acid, diuretics, plant extracts, medical foods, nonsteroidal anti-inflammatory drugs, anticoagulants and skin substitutes for different stages of SVD. Interventional treatment modalities include thermal ablative techniques like radiofrequency ablationss, endovenous laser ablation, endovenous steam ablation, and endovenous microwave ablation as well as nonthermal strategies such as the Varithena (polidocanol microfoam) sclerotherapy, VenaSeal (cyanoacrylate) ablation, and Endovenous mechanochemical ablation. Surgical treatments are also available and include debridement, vein ligation, stripping, and skin grafting.
CONCLUSIONS
SVDs are prevalent and have varied manifestations predominantly in the lower extremities. Several studies highlight the growing clinical and financial burden of these diseases. This review provides an update on the pathophysiology, classification, clinical features, and imaging findings as well as the conservative, pharmacological, and interventional treatment options indicated for different SVD pathologies. It aims to expedite the timely deployment of therapies geared toward reducing the significant morbidity associated with SVD especially varicose veins, venous ulcers, and venous insufficiency, to improve the quality of life of these patients and prevent complications.
Topics: Humans; Risk Factors; Treatment Outcome; Varicose Veins; Venous Insufficiency; Veins; Predictive Value of Tests
PubMed: 38583765
DOI: 10.1016/j.avsg.2024.01.009 -
Journal of Cosmetic Dermatology Jun 2024The foam's structural longevity, linked to the effectiveness of sclerotherapy, depends on preparation conditions. The factors enhancing the treatment's effectiveness and...
BACKGROUND
The foam's structural longevity, linked to the effectiveness of sclerotherapy, depends on preparation conditions. The factors enhancing the treatment's effectiveness and efficacy are still under discussion.
METHODS
We conducted an in vitro preclinical research, which included 144 independent trials. A total of 8 combinations involving 18 trials were designed according to settings of +4°C and room temperature (20-22°C), liquid-to-air ratios of 1/1 and 1/4, and polidocanol concentrations of 0.5% and 1% using the modified Tessari method. Our study aimed to examine the effect of air ratio, agent temperature, and polidocanol concentration on stability by assessing the foam half-time (FHT) and defining the optimal preparation conditions.
RESULTS
The mean FHT was 117 ± 30.4 s. The longest FHT was in a 1:4 air-to-sclerosant ratio at +4°C, regardless of the sclerosant concentration (for %0.5 mean FHT: 146.2 ± 13.9 s, for % 1 mean FHT: 146.9 ± 18 s). There was a significant interaction among the three variables on FHT (p = 0.001). Temperature emerged as the primary factor (F(1, 136) = 124, p < 0.001, ηp = 0.477), with lower temperatures markedly enhancing the longevity (p < 0.001). Preparation at a temperature of 4°C resulted in an extended FHT of 32.5 s compared to 22°C (95% CI: 24.06-41.04 s).
CONCLUSION
The temperature, agent concentration, and gas ratio significantly influence the stability of the physician-compounded foam. The low temperature at +4°C may offer better FHT for sclerotherapy.
PubMed: 38837644
DOI: 10.1111/jocd.16398 -
Journal of Vascular and Interventional... Dec 2023To assess the effectiveness, safety, and predictors of outcomes and adverse events for percutaneous sclerotherapy using polidocanol for the treatment of venous...
PURPOSE
To assess the effectiveness, safety, and predictors of outcomes and adverse events for percutaneous sclerotherapy using polidocanol for the treatment of venous malformations (VMs).
METHODS
A retrospective single-center analysis was performed, including patients with VMs who were treated with sclerotherapy using polidocanol between January 2011 and November 2021 at a tertiary center. Demographic characteristics, clinical data, and radiologic features were analyzed, and the influence of patient- and VM-related factors on the subjective clinical outcome and adverse events were investigated using a multivariate logistic regression analysis.
RESULTS
In total, 167 patients who received 325 treatment sessions were included in this study. Overall symptom improvement was observed in 67.5%, stable symptoms were observed in 25.0%, and worsening was reported in 7.5% (clinical follow-up, 1.04 ± 1.67 years). The total adverse event rate was 10.2%, with an overall rate of 4.2% for permanent adverse events within the cohort. In multivariate analysis, the clinical outcome was worse in children (P = .01; 57.1% symptom improvement in children [age, <18 years] and 79.7% in adults), and adverse events were more frequently observed after the treatment of VMs located at the extremities (P < .01; 8.4% for VMs of the extremities and 1.2% for VMs in other locations).
CONCLUSIONS
Sclerotherapy using polidocanol can be an effective treatment option for VMs with an acceptable safety profile. However, it can be less effective in children, and adverse events can be more frequently expected for VMs of the extremities.
Topics: Child; Adult; Humans; Adolescent; Polidocanol; Sclerotherapy; Sclerosing Solutions; Retrospective Studies; Vascular Malformations; Treatment Outcome
PubMed: 37640102
DOI: 10.1016/j.jvir.2023.08.032 -
The International Journal of Angiology... Feb 2024The ambulatory selective varicose vein ablation under local anesthesia (ASVAL) method recommends preserving the great saphenous vein (GSV), unless there is a serious...
The ambulatory selective varicose vein ablation under local anesthesia (ASVAL) method recommends preserving the great saphenous vein (GSV), unless there is a serious terminal valve insufficiency, and suggests phlebectomy of superficial varicose reservoir as a primary treatment. To increase patient comfort, foam safety and cosmetic results, we used ASVAL with a mixed phlebectomy/foam technique on local anesthesia. Thirty consecutive patients treated with ASVAL phlebectomy-sclerofoam technique were reviewed retrospectively between December 2022 and April 2023. All patients were evaluated by clinical examination and duplex ultrasound (DUS); the main selection criteria were a minimal GSV insufficiency (main GSV < or = to 1 cm). Muller phlebectomy of tributaries at entry point in the saphenous trunk was performed; after 1 week, patients were checked for foam sclerotherapy of residual trunk. Under visual control, 0.5% polidocanol foam (from 5 to 10 cc. "Tessari Technique") was injected in visible veins and elastic compression with pad was applied for 1 week. Compression with Class I elastic stockings was prescribed, and patients were reviewed after 1 month. Postoperative complications included thigh hematoma in two patients, three thrombosis of injected trunk, and hyperpigmentation in three patients. No GSV thrombosis at DUS was recorded. In 27 patients, a satisfying cosmetic result was achieved, and in 3 patients a new foam session was needed. Phlebectomy/foam ASVAL technique is a safe, low-traumatic technique with no need of US guidance, with less risk of foam migrating in GSV, simple and inexpensive, for patients with less advanced GSV insufficiency.
PubMed: 38352632
DOI: 10.1055/s-0043-1776145 -
International Journal of Nanomedicine 2023Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic...
PURPOSE
Endoscopic ultrasound-guided fine-needle injection (EUS-FNI) offers a promising minimally invasive approach for locally targeted management of advanced pancreatic cancer. However, the efficacy is limited due to the rapid plasma clearance of chemotherapeutic agents. Injectable hydrogels can form drug release depots, which provide a feasible solution for optimizing targeted chemotherapy through EUS-FNI.
METHODS
A drug delivery system was developed, consisting of gemcitabine (GEM) and thermo-sensitive hydrogel (PLGA-PEG-PLGA, PPP). The injectability, gel formation ability, biocompatibility and sustained drug delivery properties of PPP hydrogel were verified in vitro and in vivo. The effects of GEM/PPP hydrogel on cell proliferation, invasion, metastasis, and apoptosis were explored through co-culturing with PANC-1 cells. The therapeutic effects of GEM/PPP hydrogel on xenograft mice were compared with those of GEM, ethanol and polidocanol using the precisely targeted EUS-FNI technology. Tumor sections were examined by H&E, Ki-67, and TUNEL staining.
RESULTS
GEM/PPP hydrogel exhibited excellent injectability, biocompatibility, and the capability of sustained drug delivery for up to 7 days by forming a gel triggered by body temperature. It demonstrated the best therapeutic effects, significantly reducing proliferation, invasion and migration of PANC-1 cells while promoting apoptosis. After precise injection using EUS-FNI technology, GEM/PPP hydrogel resulted in a reduction of tumor weight by up to 75.96% and extending the survival period by 14.4 days with negligible adverse effects. Pathological examination revealed no systemic toxicity and significant apoptosis and minimal proliferation as well.
CONCLUSION
The combination of GEM/PPP hydrogel and EUS-FNI technology provides an optimal approach of precise chemotherapy for pancreatic cancer, builds a bridge for clinical translation of basic research, and brings great hope for innovation of minimally invasive treatment modalities. The first-hand EUS image data obtained in this study also serves as a crucial reference for future clinical trials.
Topics: Humans; Animals; Mice; Hydrogels; Pancreatic Neoplasms; Gemcitabine; Ultrasonography, Interventional
PubMed: 37496690
DOI: 10.2147/IJN.S417445 -
Laryngo- Rhino- Otologie Dec 2023Ultrasound-guided ablation techniques have been increasingly introduced into routine treatment of thyroid lesions as a complement to existing surgical therapies and...
Ultrasound-guided ablation techniques have been increasingly introduced into routine treatment of thyroid lesions as a complement to existing surgical therapies and radioiodine treatment. In cystic or predominantly cystic lesions instillation therapy (ethanol/polidocanol ablation) has yielded good results. Novel thermal ablation techniques, including radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA) and high intensity focused ultrasound (HIFU), induce irreversible cellular effects by locally applying temperatures ≥ 60 °C to the targeted thyroid region. Lesions causing local symptoms or focal hyperfunctionality can thus be selectively treated under continuous sonographic monitoring. While a considerable body of evidence supports the efficacy and safety of various local ablative techniques, future challenges lie in initiating comparative prospective trials and in standardizing clinical practice, training and continuous quality assessment on a regional and superregional level. In the future, it shall be indicated to include local ablative techniques - so far not known to all patients in Germany - into the informed decision-making process as a suitable alternative or supplement to existing therapies.
Topics: Humans; Thyroid Gland; Iodine Radioisotopes; Prospective Studies; Ablation Techniques; Ultrasonography, Interventional; Catheter Ablation; Treatment Outcome
PubMed: 37734389
DOI: 10.1055/a-2144-4132 -
European Journal of Vascular and... Oct 2023To assess the safety and efficacy of available interventions in the treatment of lower limb reticular veins and telangiectasias. (Review)
Review
OBJECTIVE
To assess the safety and efficacy of available interventions in the treatment of lower limb reticular veins and telangiectasias.
DATA SOURCES
An electronic search was performed on Scopus, Embase, and Google scholar.
REVIEW METHODS
A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Following data extraction and processing, a Bayesian network meta-analysis and meta-regression was undertaken. The primary endpoint was telangiectasia and reticular vein clearance.
RESULTS
Nineteen studies, 16 randomised controlled trials and three prospective case series, including 1 356 patients and 2 051 procedures, were finally incorporated. All interventions, apart from 0.5% sodium tetradecyl sulphate (STS) and 0.25% STS displayed statistically significantly superior telangiectasia and reticular vein clearance compared with normal saline (N/S), Meta-regression analysis employing the type of the venule treated (telangiectasia or reticular vein) as a covariable, revealed a positive correlation between Nd:YAG 1064 nm laser and telangiectasia clearance (β = 1.38, 95% CI 0.56 - 2.14). Further exploration unveiled the superiority of Nd:YAG 1064 nm in the treatment of telangiectasias compared with all included interventions except 72% chromated glycerin (CG). STS 0.25% increased the risk of hyperpigmentation compared with all interventions except 0.5% STS, and 1% polidocanol. CG 72% decreased the risk of matting compared with polidocanol foam (risk ratio [RR] 0.14, 95% CI 0.02 - 0.80) and STS (RR 0.31, 95% CI 0.07 - 0.92). Non-statistically significant differences were identified between interventions regarding pain outcomes.
CONCLUSION
This network meta-analysis has demonstrated a proportional relationship between sclerosant potency and side effect occurrence in the treatment of telangiectasias and reticular veins and the superiority of laser therapy compared with injection sclerotherapy in treating telangiectasias. The transition of telangiectasia and reticular vein treatment from highly potent detergent solutions to equally effective but milder sclerosants could potentially reduce undesirable adverse events.
PubMed: 37209995
DOI: 10.1016/j.ejvs.2023.05.029 -
Techniques in Coloproctology Jan 2024This systematic review and meta-analysis aimed to evaluate the safety and efficacy of sclerotherapy methods for hemorrhoidal disease (HD) over the past 40 years. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the safety and efficacy of sclerotherapy methods for hemorrhoidal disease (HD) over the past 40 years.
METHODS
The review followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive literature search was conducted, including studies reporting the use of sclerotherapy in patients with HD. Study eligibility criteria were defined, and data were extracted independently by the authors. Random-effects meta-analyses were performed to assess outcomes of interest.
RESULTS
Out of 1965 records identified, 44 studies met the inclusion criteria, involving 9729 patients. The majority of studies were conducted in Japan, followed by the UK, Italy, and Portugal. The median age of participants was 52 years, and the majority were male. The Goligher grade distribution indicated varying degrees of HD severity. Sclerotherapy was predominantly administered through anoscopy, with polidocanol being the most commonly used agent. The procedure was generally performed without pre-injection analgesia. The meta-analysis of 14 randomized controlled trials (RCTs) revealed that sclerotherapy was not inferior to control interventions in terms of success rate (risk ratio [RR] 1.00, 95% CI 0.71-1.41) and recurrence rate (RR 1.11, 95% CI 0.69-1.77), while resulting in fewer complications (RR 0.46, 95% CI 0.23-0.92).
CONCLUSIONS
This systematic review highlights the safety and efficacy of sclerotherapy for HD, which yields similar success rates and fewer complications compared to other conservative or surgical approaches. Further research is warranted to optimize sclerotherapy techniques and evaluate long-term outcomes.
REGISTRATION
PROSPERO 2023 CRD42023396910.
Topics: Male; Humans; Female; Middle Aged; Sclerotherapy; Hemorrhoids; Italy; Odds Ratio; Polidocanol
PubMed: 38261136
DOI: 10.1007/s10151-023-02908-w