Surgical and endovascular treatment of pelvic venous disorder: Results of a multicentre retrospective cohort study.

OBJECTIVE: In the present study, we investigated the clinical outcomes after gonadal vein resection (GVR) and gonadal vein embolization (GVE) with coils in patients with pelvic venous disorder (PeVD). We also assessed the rates of procedural complications and disease recurrence. METHODS: Our multicenter retrospective cohort study included 361 female patients with PeVD-related chronic pelvic pain (CPP) and gonadal vein reflux who underwent GVR (n = 184) or GVE with coils (n = 177) from 1999 to 2020. The clinical outcomes (ie, presence and severity of CPP, procedural complications, disease recurrence) were assessed at 1 month and 1, 3, and 5 years after intervention. The pain intensity before and after treatment was assessed using a visual analog scale. All the patients underwent duplex ultrasound after GVR and GVE, and those with persistent CPP and suspected perforation of the gonadal vein by the coils were also evaluated by multiplanar pelvic venography. RESULTS: GVR and GVE was associated with the reduction or elimination of CPP at 1 month after treatment in 100% and 74% of patients and postprocedural complications in 14% and 37% of patients, respectively (Р < 0.01 for both). The most common complication after either GVR or GVE was pelvic vein thrombosis (11% and 22% patients, respectively; P < .01 between groups). GVE was associated with postembolization syndrome in 20%, coil protrusion in 6%, and coil migration in 1% of patients. The long-term recurrence rate after GVR and GVE was 6% and 16%, respectively (P < .01). CONCLUSIONS: Both GVR and GVE were found to be effective in treating patients with PeVD. However, GVR was associated with better efficacy in the relief of CPP and lower rates of procedural complications and disease recurrence.

Clinical Efficacy of Conservative Treatment with Micronized Purified Flavonoid Fraction in Female Patients with Pelvic Congestion Syndrome.

INTRODUCTION: Pelvic congestion syndrome (PCS) may be effectively managed with conservative treatment in certain patients. Treatment with venoactive drugs is common, but supportive data are limited. This study evaluated the clinical efficacy of micronized purified flavonoid fraction (MPFF) in women with PCS. METHODS: In a single-blind, placebo-controlled study, women with duplex ultrasound diagnosis of pelvic varicose veins (PVV) and PCS were randomized to MPFF 1000 mg once daily or placebo for 2 months. Clinical manifestations of PCS were evaluated at baseline and end of treatment (M2) using three assessment tools: disease-specific quality of life (QoL) Pelvic Varicose Vein Questionnaire (PVVQ), Pelvic Venous Clinical Severity Score (PVCSS), and the Visual Analog Scale (VAS) for the main symptoms of the disease. RESULTS: A total of 83 women were included, 42 received MPFF and 41 received placebo. In the MPFF group, the mean global PVVQ QoL index decreased significantly from 45.1 ± 14.7 at baseline to 36.6 ± 10.6 at M2 (mean change: 8.2 ± 10.4); no significant change was observed in the control group (mean change: - 0.3 ± 4.0). The between-group difference was statistically significant (P < 0.001). Compared with control, significant improvements were observed in all four QoL parameters (pain, physical, social, psychological, all P < 0.001). The mean PVCSS summary score decreased significantly by 3.4 ± 3.4 in the MPFF group (P < 0.001) compared with a non-significant change of - 0.2 ± 1.6 in the control group (between-group difference P < 0.001). In the MPFF group, improvements were statistically significant for 6 out of 10 clinical manifestations of PCS measured using the PVCSS, including pain (mean change from baseline: 0.5 ± 0.7) heaviness (0.4 ± 0.7), discomfort (0.6 ± 0.7) and tenderness (0.3 ± 0.5). No significant improvements were observed in the control group. When measured by VAS, between-group differences were statistically significant for the overall summary score (P < 0.001) and for 8 out of 10 PCS symptoms, including: pain (mean MPFF change from baseline: 2.0 ± 2.2), heaviness (1.3 ± 2.1), discomfort (1.5 ± 2.0), tenderness (0.9 ± 1.9), and edema (1.3 ± 2.1). CONCLUSION: In women with PCS, conservative treatment with MPFF was associated with improved QoL and reduced symptom severity. MPFF may be considered an effective and safe treatment option for PCS in routine clinical practice.

Synthesis of Polyfluorinated Thia- and Oxathiacalixarenes Based on Perfluoro-m-xylene.

Perfluorinated tetrathiacalix[4]arene was obtained by heating perfluoro-m-xylene with thiourea or 2,5-difluoro-4,6-bis(trifluoromethyl)benzene-1,3-dithiol at 90 °C. Interaction of perfluoro-m-xylene with resorcinol or orcinol under mild conditions and subsequent heating of the mixture with 2,5-difluoro-4,6-bis(trifluoromethyl)benzene-1,3-dithiol leads to polyfluorinated dioxadithiacalix[4]arenes. Triphenyl and pentaphenyl ethers formed by the interaction of perfluoro-m-xylene with resorcinol under heating with thiourea gives polyfluorinated oxathiacalixarenes containing six and five aromatic nuclei, respectively.

The First Berberine-Based Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), an Important DNA Repair Enzyme.

A series of berberine and tetrahydroberberine sulfonate derivatives were prepared and tested against the tyrosyl-DNA phosphodiesterase 1 (Tdp1) DNA-repair enzyme. The berberine derivatives inhibit the Tdp1 enzyme in the low micromolar range; this is the first reported berberine based Tdp1 inhibitor. A structure-activity relationship analysis revealed the importance of bromine substitution in the 12-position on the tetrahydroberberine scaffold. Furthermore, it was shown that the addition of a sulfonate group containing a polyfluoroaromatic moiety at position 9 leads to increased potency, while most of the derivatives containing an alkyl fragment at the same position were not active. According to the molecular modeling, the bromine atom in position 12 forms a hydrogen bond to histidine 493, a key catalytic residue. The cytotoxic effect of topotecan, a clinically important topoisomerase 1 inhibitor, was doubled in the cervical cancer HeLa cell line by derivatives 11g and 12g; both displayed low toxicity without topotecan. Derivatives 11g and 12g can therefore be used for further development to sensitize the action of clinically relevant Topo1 inhibitors.

Reduced Contraction of Blood Clots in Venous Thromboembolism Is a Potential Thrombogenic and Embologenic Mechanism.

Contraction (retraction) of the blood clot is a part of the clotting process driven by activated platelets attached to fibrin that can potentially modulate the obstructiveness and integrity of thrombi. The aim of this work was to reveal the pathogenic importance of contraction of clots and thrombi in venous thromboembolism (VTE). We investigated the kinetics of clot contraction in the blood of 55 patients with VTE. In addition, we studied the ultrastructure of ex vivo venous thrombi as well as the morphology and functionality of isolated platelets. Thrombi from VTE patients contained compressed polyhedral erythrocytes, a marker for clot contraction in vivo. The extent and rate of contraction were reduced by twofold in clots from the blood of VTE patients compared with healthy controls. The contraction of clots from the blood of patients with pulmonary embolism was significantly impaired compared with that of those with isolated venous thrombosis, suggesting that less compacted thrombi are prone to embolization. The reduced ability of clots to contract correlated with continuous platelet activation followed by their partial refractoriness. Morphologically, 75% of platelets from VTE patients were spontaneously activated (with filopodia) compared with only 21% from healthy controls. At the same time, platelets from VTE patients showed a 1.4-fold reduction in activation markers expressed in response to chemical activation when compared with healthy individuals. The results obtained suggest that the impaired contraction of thrombi is an underappreciated pathogenic mechanism in VTE that may regulate the obstructiveness and embologenicity of venous thrombi.