Aim: Real-world evidence on the management of hemorrhoidal disease (HD) is limited. This international study collected clinical practice data on the effectiveness of conservative treatments for acute HD on symptoms and quality of life (QoL), providing perspectives of treatment modalities from different continents. Patients & methods: The 4-week observational prospective CHORALIS study involved adult outpatients consulting for spontaneous complaints of hemorrhoids (graded using Goligher classification) and prescribed conservative treatments according to usual clinical practice. Assessments were: anal pain/discomfort (visual analog scale [VAS]), other signs/symptoms (patient questionnaire), Patient Global Impression of Change (PGI-C) questionnaire and disease-specific QoL (HEMO-FISS-QoL questionnaire). Results: Of 3592 participants, 3505 were analyzed (58.4% male; age 40.5 ± 13.7 years; history of HD in 48.4%; 72.1% Goligher grade I and II). Pain and discomfort were the most common symptoms. Most treatments were venoactive drugs (VADs; 90.9%), particularly micronized purified flavonoid fraction (MPFF; 73.7%) and diosmin (14.6%). All VAD-based therapies improved signs/symptoms (number/intensity/frequency of pain, discomfort, bleeding, swelling, itching and soiling) and QoL. MPFF was associated with a significantly greater proportion of patients with no symptoms (48.8 vs diosmin 34.4%, p < 0.001), pain disappearance (69.7 vs diosmin 52.8%, p < 0.001), treatment impact at 1 week rated on PGI-C as \'very much better\' (30.5 vs diosmin 17.9%, p < 0.001) and shorter times to improvement (mean ± SD 3.9 ± 1.5 days vs diosmin 4.2 ± 1.7 days). Conclusion: In this prospective real-world study of patients with acute HD, conservative therapies consisting mainly of VADs, including MPFF, improved the clinical signs and symptoms of disease, as well as QoL. This study evidence supports clinical advantages associated with VADs, mostly MPFF, for effectively managing acute HD.

Varicosis is a chronic progressive disease characterized by varicose veins of the lower extremities. Pain, swelling and heaviness of the legs are typical symptoms. These symptoms are caused by a pathological venous reflux, arising from a weakness of the vein wall and progressive venous insufficiency. The indications for invasive surgery are the symptomatic clinical, etiological, anatomical, pathophysiological (CEAP) stages C2s-C6. Compression therapy and venoactive drugs can be recommended for conservative therapy. When it comes to surgical treatment conventional open vein surgery is associated with the best long-term results. Endovenous thermal ablation is associated with few postoperative complications and favors earlier mobilization of the patient. Sclerotherapy has become established with good clinical results for the ablation of reticular and telangiectatic veins, for recurrences and complicated vein anatomy.
UNASSIGNED: Die Varikosis ist eine chronische progressive Krankheit und äußert sich durch Varizen der unteren Extremitäten. Typische Symptome sind Schmerzen, Schwellungen in den Beinen und ein Schweregefühl. Diese Symptome werden durch einen pathologischen venösen Reflux verursacht, der wiederum auf eine Schwäche der Venenwand und progressive venöse Insuffizienz zurückgeht. Indikationen für invasive Varizenchirurgie sind die symptomatischen CEAP(„clinical, etiological, anatomical, pathophysiological“)-Stadien C2s bis C6. Für eine konservative Therapie werden Kompressionstherapie und venoaktive Präparaten empfohlen. Bei der chirurgischen Behandlung erzielt die konventionelle Varizenchirurgie die besten Langzeitergebnisse. Die endovenöse thermische Venenablation geht mit wenigen postoperativen Komplikationen einher und favorisiert eine frühere Mobilisation des Patienten. Die Sklerotherapie hat sich mit guten klinischen Ergebnissen für die Ablation der retikulären und Besenreiservarizen etabliert sowie für Rezidive und komplizierte Venenverläufe.

The Society for Vascular Surgery, the American Venous Forum, and the American Vein and Lymphatic Society recently published Part I of the 2022 clinical practice guidelines on varicose veins. Recommendations were based on the latest scientific evidence researched following an independent systematic review and meta-analysis of five critical issues affecting the management of patients with lower extremity varicose veins, using the patients, interventions, comparators, and outcome system to answer critical questions. Part I discussed the role of duplex ultrasound scanning in the evaluation of varicose veins and treatment of superficial truncal reflux. Part II focuses on evidence supporting the prevention and management of varicose vein patients with compression, on treatment with drugs and nutritional supplements, on evaluation and treatment of varicose tributaries, on superficial venous aneurysms, and on the management of complications of varicose veins and their treatment. All guidelines were based on systematic reviews, and they were graded according to the level of evidence and the strength of recommendations, using the GRADE method. All ungraded Consensus Statements were supported by an extensive literature review and the unanimous agreement of an expert, multidisciplinary panel. Ungraded Good Practice Statements are recommendations that are supported only by indirect evidence. The topic, however, is usually noncontroversial and agreed upon by most stakeholders. The Implementation Remarks contain technical information that supports the implementation of specific recommendations. This comprehensive document includes a list of all recommendations (Parts I-II), ungraded consensus statements, implementation remarks, and best practice statements to aid practitioners with appropriate, up-to-date management of patients with lower extremity varicose veins.

The use of drug therapies in patients with chronic venous disease (CVD) remains a topic of debate regarding safety, compliance, and effectiveness. Although the beneficial effects of molecules like diosmin have been established in patients with chronic venous insufficiency (CVI) of C3-C6 classes, the evidence for its use in C0-C1 patients is not well documented. This report aims to describe and analyze the positive impact of a new diosmin-based drug therapy on a population of C0-C1 patients in terms of relief of venous symptoms.

The article provides an overview of the development of recommendations for indications of venoactive drugs for treating symptoms and signs associated with chronic venous disease (CVD). Venoactive drugs may be beneficial in patients with subjective problems and/or swelling of the lower limbs, after surgery for varicose veins, in chronic venous insufficiency or in microcirculatory disorders. They are not indicated in asymptomatic patients with CVD, in the prevention of varicose veins or to prevent their progression. Drugs with proven efficacy in clinical trials should be preferred.

Aims: To investigate the effectiveness and tolerability of adjunctive micronized purified flavonoid fraction (MPFF) in patients with chronic venous disease (CVD). Patients & methods: This observational study included adults (≥18 years) with clinical-etiology-anatomy-pathophysiology (CEAP) class C4 CVD for whom MPFF was indicated. Outcomes included changes in subcutaneous adipose thickness, venous clinical severity score, CVD symptoms (using a visual analogue scale) and tolerability. Results: Of 381 patients, 365 completed the study. After 6 months, subcutaneous adipose tissue thickness, venous clinical severity score and visual analogue scale scores significantly improved (all p < 0.001 vs baseline). No adverse drug reactions occurred. Conclusion: Adjunctive MPFF treatment improves skin and subcutaneous tissue conditions in CVD patients. Clinical Trial Registration: NCT04138576 (ClinicalTrials.gov).
Chronic venous disease (CVD) can cause a range of signs and symptoms that reduce patient quality of life. Micronized purified flavonoid fraction (MPFF) is a type of venoactive drug that is recommended in patients with early and advanced CVD. This study investigated the effectiveness and safety of MPFF when added to conservative treatment in patients with advanced CVD with long-term follow-up. After 6 months of MPFF, we observed significant improvements in the skin and subcutaneous tissue, symptoms and patient quality of life; no adverse drug reactions were reported. Therefore, MPFF-based conservative treatment can effectively and safely treat CVD.

Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders (CVD). Among venoactive drugs, diosmin is a naturally occurring flavonoid glycoside that can be isolated from various plant sources; it can also be obtained after conversion of hesperidin extracted from citrus rinds. Micronized purified flavonoid fraction (MPFF) is a preparation that contains mainly diosmin and a small fraction of hesperidin. We performed a state-of-the-art literature review to collect and analyze well-conducted randomized clinical studies comparing diosmin - also called non-micronized or hemisynthetic diosmin - 600 mg a day and MPFF, 1000 mg a day. Three clinical studies met the criteria and were included for this literature review. These clinical studies showed a significant decrease of CVD symptom intensity (up to approximately 50%) and global patient satisfaction after one-to-six-month treatment with diosmin or MPFF, without statistical differences between these two forms of diosmin. Both treatments were well tolerated with few mild adverse drug reactions reported. Overall, based on this literature review, there is no clinical benefit to increase the dose of diosmin beyond 600 mg per day, to use the micronized form, or to add hesperidin, since clinical efficacy on venous symptomatology is achieved with 600 mg per day of pure non-micronized diosmin. This challenges the status of diosmin - 600 mg a day - in guidelines for the management of CVD, which is currently categorized 2C (weak recommendations for use and poor quality of evidence), while the most widely used and assessed preparation MPFF is rated 1B (strong recommendation for use and moderate quality of evidence).

BACKGROUND: In Russia, physicians are virtually unaware of drugs based on needle extract. However, abroad, saponins and, in particular, a combined preparation containing needle extract, hesperidin and vitamin C is one of drugs of choice, if not the leading medication in treatment of venous oedemas and other venous symptoms.
OBJECTIVE: The authors conducted a systematic review of the Russian-and English-language literature using the following search terms: saponins, hesperidin, needle, ruscus, ruscogenin (and their Russian equivalents), each of which was entered in a combination with the word \'venous\' or its Russian equivalent, respectively.
RESULTS: Ruscogenin and neoruscogenin from the root of needle possess anti-inflammatory properties and induce venous wall contraction, thus making it possible to use needle extract in treatment of chronic venous insufficiency. It was experimentally determined that needle extract stimulates vein contractility, decreasing permeability of the venous wall, influencing extracellular matrix proteins, inhibiting leukocyte migration through regulation of both proteins and matrix ribonucleic acid. Analysed herein are the results of original studies of a combination of needle extract, flavonoid hesperidin methyl chalcone and ascorbic acid, also examining in detail the mechanism of action conditioned by synergism of pharmacological effects of these components. This is followed by discussing the place of saponins in the classification of phlebotropic drugs and comparing efficacy of needle root extract with that of other phlebotonics.
CONCLUSIONS: It was experimentally determined that a combination of needle extract, hesperidin and vitamin C possesses multiple additive phlebotropic effects. According to clinical trials, it leads to relief of most symptoms and a decrease in the ankle volume (high level of evidence 1A), being not inferior by clinical efficiency and duration of action to the best-known flavonoids, whereas by the venotonizing effect, decreased permeability of the vascular wall, and inhibition of leukocytic aggression even superior thereto. Further experimental and clinical studies of efficacy of this combination for various forms of chronic venous diseases and venous thromboses are warranted.
В России врачи практически незнакомы с препаратами на основе экстракта иглицы колючей. Хотя за рубежом сапонины и, в частности, комбинированный препарат экстракта иглицы, гесперидина и витамина С является одним из препаратов выбора, если не ведущим в лечении венозных отеков и других венозных симптомов. Авторы выполнили систематический обзор русскоязычной и англоязычной литературы по поисковым запросам: сапонины, гесперидин, иглица колючая, ruscus, ruscogenin, saponin, butcher’s broom, hesperidin, каждый из которых вводился в сочетании со словом \'венозный\' или \'venous\'. Результаты исследования. Рускогенин и неорускогенин из корня иглицы колючей обладают противовоспалительными свойствами и вызывают сокращение стенки вен. Это позволяет использовать экстракт иглицы при лечении хронической венозной недостаточности. Экспериментально установлено, что экстракт иглицы стимулирует сокращение вен, уменьшает проницаемость венозной стенки, влияет на белки экстрацеллюлярного матрикса, подавляет миграцию лейкоцитов посредством регуляции как белков, так и матричной рибонуклеиновой кислоты. Проанализированы результаты оригинальных исследований комбинации экстракта сапонина иглицы колючей, флавоноида гесперидина метилхалькона и аскорбиновой кислоты. Детально изучен механизм действия, обусловленный синергизмом фармакологических эффектов этих компонентов. Обсуждается место сапонинов в классификации флеботропных препаратов и сравнивается эффективность экстракта корня иглицы с другими флеботониками. Заключение. Экспериментально установлено, что комбинация экстракта иглицы, гесперидина и витамина C обладает множественными аддитивными флеботропными эффектами. Согласно клиническим исследованиям это вызывает уменьшение большинства симптомов, а также сокращение объема лодыжек (высокий уровень доказательности 1A), не уступая по клинической результативности и продолжительности действия наиболее известным флавоноидам, а по венотонизирующему эффекту, снижению проницаемости сосудистой стенки и подавлению лейкоцитарной агрессии превосходит последние. Необходимы дальнейшие экспериментальные и клинические исследования по изучению эффективности этой комбинации при различных формах хронических заболеваний вен и венозных тромбозах.

Hemorrhoidal disease (HD) is a common and recurrent problem for many adults worldwide. Venoactive drugs, such as micronized purified flavonoid fraction (MPFF; Daflon®), have been used to treat HD and their clinical benefits have been demonstrated in previous meta-analyses of clinical trials. The aim of this study was to evaluate the efficacy of MPFF across the broader spectrum of signs and symptoms following treatment of patients with HD.
We performed a systematic review of the literature to identify randomized clinical trials in which MPFF treatment was compared to placebo or no treatment for acute HD or for relief of symptoms after patients had undergone medical management or a surgical procedure to remove hemorrhoids. The main endpoints investigated were bleeding, pain, pruritus, discharge or leakage, and overall improvement. There was no limit on treatment duration.
From 351 unique records retrieved, 11 studies reported in 13 articles were included. On the basis of findings from qualitative analysis, MPFF was reported in most studies to be beneficial in treating bleeding, pain, pruritus, anal discharge/leakage, and tenesmus, and in overall improvement. Quantitative meta-analysis of four studies indicated that MPFF treatment provided significant benefits for bleeding (odds ratio [OR] 0.082, 95% confidence interval [CI] 0.027-0.250; P < 0.001), discharge/leakage (OR 0.12, 95% CI 0.04-0.42; P < 0.001), and overall improvement according to patients (OR 5.25, 95% CI 2.58-10.68; P < 0.001) and investigators (OR 5.51, 95% CI 2.76-11.0; P < 0.001). MPFF also tended to decrease pain (OR 0.11, 95% CI 0.01-1.11; P = 0.06).
Taken together, these results suggest that MPFF treatment can improve the most important signs and symptoms of HD.

Chronic venous disease (CVD) is one of the most prevalent diseases worldwide. The health condition of most patients with early stage CVD will worsen over time, and this progression increases the burden as well as the costs of treatment and reduces patient quality of life (QoL). This highlights the importance and the likely cost-effectiveness of treatment of patients with early stage CVD. Options for managing the early stages of CVD include lifestyle changes together with venoactive drugs (VAD); VADs may be used alone or in conjunction with interventional treatment of varices such as sclerotherapy, surgery, or endovenous treatments. Micronized purified flavonoid fraction (MPFF; Daflon®) is a well-studied VAD which has anti-inflammatory activities, reduces endothelial activation and leukocyte adhesion, and increases capillary resistance and integrity, to eventually improve venous tone, CVD symptoms and QoL. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by the author.