Isolated fetal umbilical vein varix and the association with intrauterine fetal death and fetal growth restriction: A systematic review, meta-analysis, and nested retrospective cohort study.

OBJECTIVES: To assess the risk of intrauterine fetal death (IUFD) and fetal growth restriction (FGR) in fetuses with an isolated fetal intra-abdominal umbilical vein varix (i-FIUVV). METHODS: A retrospective cohort study combined with a systematic review and meta-analysis of the literature was performed. In the retrospective cohort study, all singleton fetuses with an i-FIUVV in the fetal medicine units of the Amsterdam UMC (between 2007 and 2023) were analyzed. The primary outcome measures were IUFD and FGR. The sample proportions of IUFD and FGR were depicted as risk percentages. The IUFD proportion was compared to the regional reference population and the FGR proportion was compared to the reported proportions in Europe. The secondary outcome measures were gestational age at diagnosis, initial and maximal FIUVV diameter, fetal monitoring in pregnancy, turbulent flow in the varix, thrombus formation in the varix, induction of labor, gestational age at birth, and birthweight centile. The proportion of fetuses with a birthweight below the 10th centile was compared with that of the regional reference population. The systematic review included all cases from eligible literature published between 2007 and 2023 supplemented by the data of our retrospective cohort study. In the systematic review and meta-analysis, the pooled proportions of IUFD and FGR were assessed in fetuses with i-FIUVV. RESULTS: The retrospective cohort included 43 singletons with an i-FIUVV. The IUFD risk was 0% [Confidence Interval, CI: 0%-8.2%], which did not differ significantly from 0.3% in the reference population, p = 1.0. The risk of FGR was 16.3% [CI: 6.8%-30.7%] in the studied population, which is higher than the reported incidence of FGR in Europe ranging from 5%-10%. The proportion of fetuses with birthweights below the 10th centile was higher in our cohort compared with the reference population (23.3 vs. 9.9%, p < 0.01). The systematic review included 12 articles, three abstracts, and our current cohort. In total, 513 cases with an i-FIUVV were included. The pooled risk was 0.4% [CI: 0.1%-1.7%] for IUFD and 5.2% [CI: 1.1%-21.3%] for FGR. The mean gestational age at birth did not exceed 39 weeks in neither the cohort (38.7 weeks) nor the pooled literature (37.6 weeks). CONCLUSION: An i-FIUVV in singletons is not associated with an increased IUFD risk up to 39 weeks of gestation but is possibly associated with FGR. The incidence of FGR in our cohort was higher than in the pooled literature (16.3% vs. 5%) but FGR definitions in the included studies varied. The proportion of birthweights below the 10th percentile in our cohort was significantly higher than in the reference group. Thus, based on these findings, we suggest conducting sonographic growth assessments while simultaneously assessing the i-FIUVV. No further monitoring and follow-up are indicated up to 39 weeks of gestation. After 39 weeks of gestation, data on fetuses with i-FIUVV and their outcomes are lacking.

Superficial Venous Disease-An Updated 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.

Differences in risk profile associated with varicose veins and chronic venous insufficiency - results from the Bonn Vein Study 1.

Background: The aim of this publication is to demonstrate similarities and differences in the association of risk factors with the prevalence of different manifestations of chronic venous disease (CVD), like varicose veins (VV), venous oedema (C3) and severe chronic venous insufficiency (CVI) in the population-based cross-sectional Bonn Vein Study 1 (BVS). Patients and methods: In the BVS 1 between 13.11.2000 and 15.3.2002, 3.072 participants, 1350 men and 1722 women, from a simple random sample of the general population of the city of Bonn and two rural townships aged 18-79 years were included. The overall response proportion was 59%. All participants answered a standardized questionnaire including information about socio-economic data, lifestyle, physical activity, medical history, and quality of life. Venous investigations were performed clinically and by a standardized duplex examination by trained investigators. The CEAP classification in the version of 1996 was used to classify the findings. Logistic regression models were performed for the association of possible risk factors with VV, venous edema (C3) and severe CVI (C4-C6). The predictive risk (PR) describes the association of the diseases and the possible influencing factors. Results: VV, venous oedema (C3) and severe CVI (C4-C6) have common risk factors like higher age, number of pregnancies, family history of VV and overweight or obesity. Female gender is significantly associated with VV and C3 but not with severe CVI (C4-C6). High blood pressure and urban living are only associated with C3 and C4-C6 disease whereas prolonged sitting is associated with C3 and lower social class with C4-C6 exclusively. Discussion: In many epidemiological studies risk factors were associated with chronic venous disorders in general. Our data show that VV, venous edema and severe CVI may have different risk profiles. Venous edema is more often associated with arterial hypertension and sedentary lifestyle whereas lower social class seems to be a risk factor for severe CVI including venous ulcers. Conclusions: The differences in the association of risk factors to VV, venous edema and severe CVI should be considered if prevention and treatment of chronic venous diseases are planned. As examples, compression stockings could be proposed in sitting profession to prevent oedema, VV patients with risk factors like obesity might benefit from early treatment for VV and obesity. More longitudinal evaluation of risk factors is necessary to evaluate the true risk profile of CVD.

Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease.

Venous disease is a term that broadly covers both venous thromboembolic disease and chronic venous disease. The basic pathophysiology of venous thromboembolism and chronic venous disease differ as venous thromboembolism results from an imbalance of hemostasis and thrombosis while chronic venous disease occurs in the setting of tissue damage because of prolonged venous hypertension. Both diseases are common and account for significant mortality and morbidity, respectively, and collectively make up a large health care burden. Despite both diseases having well-characterized environmental components, it has been known for decades that family history is an important risk factor, implicating a genetic element to a patient's risk. Our understanding of the pathogenesis of these diseases has greatly benefited from an expansion of population genetic studies from pioneering familial studies to large genome-wide association studies; we now have multiple risk loci for each venous disease. In this review, we will highlight the current state of knowledge on the epidemiology and genetics of venous thromboembolism and chronic venous disease and directions for future research.

Pelvic vein incompetence and chronic pelvic pain: a case-control study.

OBJECTIVE: To investigate the association between chronic pelvic pain (CPP) and pelvic vein incompetence (PVI) or pelvic varices. DESIGN: Case-control study. SETTING: Gynaecology and vascular surgery services in two teaching hospitals in north-west England. SAMPLE: A total of 328 premenopausal women (aged 18-54 years), comprising 164 women with CPP and 164 matched controls with no history of CPP. METHODS: Symptom and quality-of-life questionnaires and transvaginal duplex ultrasound for PVI and pelvic varices. MAIN OUTCOME MEASURES: Venous reflux of >0.7 s in the ovarian or internal iliac veins (primary outcome) and presence of pelvic varices (secondary outcome). Statistical analysis compared the prevalence of PVI between women with and without CPP using the two-sided chi-square test. Logistic regression was used to compare the odds of having PVI and pelvic varices between women with and without CPP. RESULTS: Pelvic vein incompetence was found on transvaginal duplex ultrasound in 101/162 (62%) women with CPP, compared with 30/164 (19%) asymptomatic controls (OR 6.79, 95% CI 4.11-11.47, p < 0.001). Forty-three of 164 (27%) women with CPP had pelvic varices compared with three of 164 (2%) asymptomatic women (OR 18.9, 95% CI 5.73-62.7, p < 0.001). CONCLUSIONS: There was a significant association between PVI, as detected by transvaginal duplex imaging, and CPP. Pelvic varices were strongly associated with CPP and were infrequently seen in control patients. These results justify further evaluation of PVI and its treatment in well-designed research.

What is the prevalence of chronic venous disease among health care workers? A scoping review.

Chronic venous disease (CVD) occurs because of structural or functional disturbances to the venous system of the lower limbs. Signs and symptoms include leg pain, swelling, varicose veins, and skin changes, with venous ulceration ultimately occurring in severe disease. To assess the prevalence of CVD among health care workers, a scoping review of existing publications exploring the prevalence of CVD among health care workers was conducted in July 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. A total of 15 papers met the inclusion criteria and these formed the basis of the review. Among health care workers, the mean prevalence of CVD was 58.5% and the mean prevalence for varicose veins was 22.1%. There is an increased prevalence of CVD in health care workers when compared with the general population. Therefore, there is a need for early diagnosis and the use of preventative measures to protect health care workers from CVD and varicose vein development.

Risk Factors for Bleeding Varicose Veins in Patients with Chronic Venous Disease.

Background and Objectives: Chronic venous disease (CVD) is a widespread clinical condition that is very common in western countries in the adult general population with a wide range of clinical manifestations, such as varicose veins (VVs) that in certain circumstances may complicate with rupture and subsequent bleeding that may even be fatal. The aim of this study is to evaluate risk factors for bleeding VVs. Materials and Methods: This is a retrospective study conducted in patients with CVD complicating with bleeding of VVs over a 4-year period (2019-2022). A random sample, for the same 4-year period and with a 3:1 ratio, was selected from other CVD patients without VVs bleeding that served as the control group. Results: From a global population of 1048 patients with CVD over a 4-year period, a total of 33 patients (3.15%) with VVs bleeding were selected. A group of 99 patients without VVs bleeding were randomly selected from the total population of 1048 patients with CVD. Findings of this study showed that advanced clinical stage of CVD (i.e., C4b stage), advanced age, living alone, suffering from cardiovascular co-morbidity (i.e., hypertension and CHF), assuming certain drugs that act on blood coagulation (i.e., aspirin, anticoagulants), assuming psychotropic medication, having particular venous reflux patterns (i.e., below-knee GSV reflux, non-saphenous veins reflux, Cockett's perforators reflux), and not having been assessed and treated previously for CVD (i.e., with VADs, CT, or surgery) may predispose a high risk for bleeding VVs. Conclusions: Bleeding VVs may be a life-threatening complications of CVD patients, and monitoring risk factors found in this study and others that, hopefully, may be discovered in the future through further focused research will help to reduce the impact of this problem in this patient population.

Lower prevalence of stump reflux after endovenous laser flush ablation of the great saphenous vein.

Background: This single center prospective randomized study was performed to compare the effect of endovenous laser flush ablation (EVLAf) of the great saphenous vein (GSV) close to the sapheno-femoral junction (SFJ) with a standard ablation (EVLAs) up to two cm distally of the SFJ on reflux in the GSV stump. Patients and methods: Between April 2013 and January 2016, 146 legs in 146 consecutive patients, meeting the inclusion/exclusion criteria, were treated by EVLA. All patients were randomized into 2 groups. In group 1 EVLAf started from the SFJ level, and in group 2 EVLAs started two cm below the SFJ. The primary endpoint was reflux in the GSV stump after 900 days. Secondary endpoints were reflux in the anterior accessory saphenous vein (AASV), proximal clinically recurrent varicose veins related to reflux in the stump and/or the AASV. Results: At day 900, 27 patients were lost to follow-up. Reflux in the stump was detected in 3.6% in group 1 and in 22.2% in group 2 (p<0.05). Reflux in the AASV was present in 7.1% in group 1 and in 17.46% in group 2 (p=0.09). Proximal clinically recurrent varicose veins were observed in 8.9% in group 1 and in 19.1% in group 2 (p=0.12). The greatest diameter of the stump was significantly larger in group 2 (group 1: 0.41 cm, group 2: 0.6 cm, p<0.001). Conclusions: EVLAf is associated with a significantly lower incidence of reflux in the GSV stump, with a trend to a lower incidence of reflux in the AASV and with a lower incidence of proximal recurrent varicose veins after 900 days follow-up compared to EVLAs. EVLAf may improve the clinical recurrence rate after EVLA of the GSV.

Risk Factors for Superficial Thrombophlebitis: A Retrospective Case Control Study.

BACKGROUND: Data regarding risk factors for superficial thrombophlebitis (STP) cases presenting to a hospital is limited. OBJECTIVES: To investigate and stratify clinical and laboratory risk factors for STP. METHODS: We conducted a retrospective case control study comparing patients presenting to the emergency department with STP and age- and gender-matched controls. We collected data on multiple risk factors and five blood indices. RESULTS: The study comprised 151 patients and matched controls. Patients with STP were more likely to have varicose veins (43.7% vs. 5.3%, P < 0.001), recent immobilization (14.6% vs. 1.3%, P < 0.001), obesity (36.4% vs. 18.5%, P = 0.001), a history of venous thromboembolism (VTE) or STP (27.2% vs. 0.7%, P < 0.001), and inherited thrombophilia (9.3% vs. 1.3%, P = 0.002). Following multivariate analysis, all five risk factors remained significant, with a history of VTE or STP associated with the largest risk (odds ratio [OR] 35.7), followed by immobilization (OR 22.3), varicose veins (OR 12.1), inherited thrombophilia (OR 6.1), and obesity (OR 2.7). Mean platelet volume was higher (8.5 vs 7.9 fl, P = 0.003) in STP cases. CONCLUSIONS: A history of VTE or STP, immobilization, varicose veins, inherited thrombophilia, and obesity serve as independent clinical risk factors for STP presenting to hospital.

Persistence and stability of sublingual varices over time and their connection to underlying factors: an 8 year follow up study.

OBJECTIVE: To investigate whether sublingual varices are constant or inconstant over time and whether this is connected to background variables, cardiovascular risk factors or disease. DESIGN: This longitudinal observational study was performed between 2010 and 2020 at the Public Dental Services Västra Vall, Varberg, Sweden. The study was based on 431 patients included in a previous study in which the relationship between sublingual varices and hypertension was examined. In connection to the annual dental examination, 281 patients were included in the follow-up study. They completed a questionnaire about background and health factors and diseases. Length and weight were measured. Two intraoral photos were taken with a digital camera. Two dentists independent of each other graded all photographs as none/few visible sublingual varices (nSV) or medium/severe sublingual varices (SV). RESULTS: The prevalence of SV was 25.6% at baseline and 30.6% at follow-up. At the follow up, a total of 76.5% had maintained their sublingual vascular status. Of those with nSV at baseline (n209), 80.9% still had nSV, and 19.1% had developed SV during the 8-year follow-up period. Of those 72 participants who had SV at baseline, 46 (63.9%) were unchanged at follow-up, and 26 (36.1%) were classified as nSV. Those who had developed SV at follow-up had a higher mean age (p = 0.003) and a higher prevalence of cardiovascular disease (CVD), 13.2% versus 3.0% (p = 0.021). This association with CVD did not persist after an adjustment for sex and age (OR 3.2, 95% CI 0.81-12.46). They exhibited more hypertension (35.0% vs. 22.5%) and diabetes type 2 (7.5% vs. 3.0%), but with no significant difference. CONCLUSIONS: This study revealed that 76.5% of the participants had an unchanged status regarding sublingual varices during an 8-year period and that the development from nSV to SV was associated with advanced age.

Incidence, risk factors, and outcomes of jejunal varix of the afferent loop after pancreatoduodenectomy.

BACKGROUND: Jejunal varix is a concerning late complication after pancreatoduodenectomy (PD) due to the risk of recurrent and intractable bleeding. Our aim was to investigate the incidence, risk factors, and outcomes of jejunal varix after PD. METHODS: A total of 709 patients who underwent PD between 2007 and 2017 were included. Preoperative and postoperative CT images were reviewed to evaluate the development of portal vein (PV) stenosis (≥50%) and jejunal varices. RESULTS: Jejunal varix developed in 83 (11.7%) patients at a median of 12 months after PD. Eighteen (21.7%) patients experienced variceal bleeding. PV stenosis (P < 0.001; odds ratio [OR] 33.2, 95% confidence interval [CI] 15.6-66.7) and PV/superior mesenteric vein resection (P = 0.028; OR 2.3, 95% CI 1.1-4.7) were independent risk factors for jejunal varix. Of the nine patients who underwent stent placement for PV stenosis before the formation of jejunal varices, none experienced variceal bleeding. By contrast, 18 (27.3%) of the 135 patients without PV stent placement experienced at least one episode of variceal bleeding. CONCLUSIONS: The incidence of jejunal varix was substantial after PD. PV stenosis was a strong risk factor for jejunal varix. Early PV stent placement and maintaining stent patency could reduce the risk of variceal bleeding in patients with PV stenosis.

[Prevalence and detection rate of senile cataract in individuals with cardiovascular diseases]. / Rasprostranennost' i vyyavlyaemost' vozrastnoi katarakty pri zabolevaniyakh serdechno-sosudistoi sistemy.

OBJECTIVE: To determine the prevalence of senile cataracts and its detection rate among the population at the age of 40 and older with diseases of the cardiovascular system. MATERIAL AND METHODS: This observational cross-sectional study was based on the information extracted from electronic health records (EHR) of patients aged 40-99 years assigned for medical services to a city polyclinic. RESULTS: Among the population with essential hypertension (EH) senile cataract occurs with the frequency of 10.4±0.3% (95% CI 9.8-10.9%) of cases, in patients with cerebrovascular diseases (CVD) - 17.1±0.2% (95% CI 16.6-17.5%) of cases, with varicose veins of the lower extremities - 19.9±0.2% (95% CI 19.4-20.3%) of cases, with ischemic heart disease (IHD) - 15.8±0.2% (95% CI 15.4-16.2%) of cases. At the same time, senile cataract is associated with an increase in the likelihood of its detection in patients with hypertension by 6.8 times (OR 6.57; 95% CI 5.89-7.74), with CVD by 5 times (OR 5.02; 95% CI 4.64-5.44), with varicose veins by 3.7 times (OR 3.70; 95% CI 3.34-4.10), with IHD by 3.5 times (OR 3.53; 95% CI 3.20-3.90). Female gender is associated with an increased likelihood of developing senile cataracts in the presence of EH by 1.4 times (OR 1.420; 95% CI 1.299-1.553), in the presence of CVD by 1.2 times (OR 1.199; 95% CI 1.066-1.348), in the presence of varicose veins by 1.4 times (OR 1.355; 95% CI 1.064-1.725), in the presence of IHD by 1.5 times (OR 1.476; 95% CI 1.298-1.679). The detection rate of senile cataract is highest at the ages of 70-79 years, amounting to 18.1% of cases with hypertension, 24.0% of cases with CVD, 29.2% of cases with varicose veins, and 33.7% of cases with ischemic heart disease. CONCLUSION: Target population groups have been identified for more effective screening studies in order to detect senile cataracts among them.

Lower limb venous and arterial peripheral diseases and work conditions: systematic review.

OBJECTIVES: The individual peripheral vascular disease risk factors are well documented, but the role of work conditions remains equivocal. This systematic review aims to assess relationships between lower limb peripheral venous diseases (lower limb varicose veins (LLVV), venous thromboembolism (VTE) comprising deep vein thrombosis and pulmonary embolism), peripheral arterial disease (intermittent claudication, aortic dissection, aortic aneurysm) and occupational constraints among working adults. METHODS: Several databases were systematically searched until February 2019 for observational studies and clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was used for article selection. Quality assessment and risk of bias were evaluated using Strengthening the Reporting of Observational Studies in Epidemiology and Newcastle-Ottawa scales. RESULTS: Among the 720 screened articles, 37 remained after full-text evaluation. Among the 21 studies on LLVV, prolonged standing was significantly associated to a higher risk of varicose veins with a threshold probably around >3 to 4 hours/day but exposure duration in years was not sufficiently considered. Seated immobility was often observed in workers, with no sufficient evidence to prove that prolonged sitting at work is related to VTE. Carrying heavy loads, stress at work and exposure to high temperatures have emerged more recently notably in relation to varicose veins but need to be better explored. Only three studies discussed the potential role of work on peripheral arterial disease development. CONCLUSIONS: Although some observational studies showed that prolonged standing can be related to varicose veins and that seated immobility at work could be linked to VTE, very little is known about peripheral arterial disease and occupational constraints. Clinical trials to determine preventive strategies at work are needed. PROSPERO REGISTRATION NUMBER: CRD42019127652.

The clinical impact of splenic artery ligation on the occurrence of digestive varices after pancreaticoduodenectomy with combined portal vein resection: a retrospective study in two institutes.

PURPOSE: Pancreaticoduodenectomy (PD) concomitant with portal vein resection (PVR) often develops into digestive varices with an occurrence rate of 30-50%, and the variceal bleeding is sometimes untreatable and results in fatality. Against this issue, splenic artery (SpA) ligation during PD-PVR is emerging as an easy and effective prophylactic surgical option. The aim of this study was to investigate the significance of SpA ligation in the development of digestive varices in patients undergoing PD-PVR. METHOD: We retrospectively investigated 97 patients with PDAC who received PD-PVR in two hospitals. Vascular reconstruction of the splenic vein (SpV) was not performed in either hospital. We assessed the occurrence rate of digestive varices in these patients in association with the performance of SpA ligation. RESULTS: The occurrence rate of digestive varices was 23%. SpA ligation was the only significant decreasing factor for the development of digestive varices (odds ratio 0.3, p = 0.035). Although SpV resection was not a significant risk factor for the development of digestive varices in all patients, SpV resection was a significant risk factor for the development of digestive varices in patients without SpA ligation, as demonstrated in previous reports. SpA ligation did not increase surgical complications or impair pancreatic function. CONCLUSION: PD-PVR surgery was accompanied by a 23% incidence of digestive varices, and SpA ligation significantly decreased the development of digestive varices without causing clinically significant complications. TRIAL REGISTRATION: No. 18196 (Osaka International Cancer Institute) and no. 19006 (National Hospital Organization Osaka National Hospital).

Metformin reduces risk of varicose veins in patients with type 2 diabetes.

AIM: This population-based retrospective cohort study compared the incidence of varicose veins in an unmatched cohort and a cohort of 1:1 propensity score (PS)-matched pairs of ever and never users of metformin in type 2 diabetes patients. METHODS: Patients with new-onset type 2 diabetes during 1999 to 2005 were enrolled from Taiwan's National Health Insurance and followed until December 31, 2011. Analyses were conducted in an unmatched cohort of 123 710 ever users and 15 095 never users and in 15 088 PS-matched pairs of ever users and never users. Hazard ratios were estimated by Cox proportional hazards model incorporated with the inverse probability of treatment weighting using the PS. RESULTS: New-onset varicose veins were diagnosed in 126 never users and 633 ever users in the unmatched cohort and in 126 never users and 80 ever users in the matched cohort. The respective incidences were 191.36 and 110.04 per 100 000 person-years in the unmatched cohort and 191.41 and 115.81 per 100 000 person-years in the matched cohort. The hazard ratio for ever versus never users in the unmatched cohort was 0.57 (95% confidence interval, 0.47-0.69) and was 0.60 (0.45-0.80) for the matched cohort. In the unmatched cohort, the hazard ratios for the first, second, and third tertiles of cumulative duration were 1.03 (0.83-1.28), 0.55 (0.44-0.69), and 0.29 (0.23-0.37), respectively. The respective hazard ratios in the matched cohort were 0.97 (0.65-1.43), 0.79 (0.55-1.15), and 0.24 (0.13-0.42). CONCLUSION: Metformin use is associated with a lower risk of varicose veins in patients with type 2 diabetes.

Retrospective evaluation of risk factors of postoperative varices after pancreaticoduodenectomy with combined portal vein resection.

BACKGROUND: Combined portal vein (PV) resection is performed for pancreatic head cancer to achieve clear resection margins. This can be complicated by the formation of varices due to sinistral portal hypertension after pancreaticoduodenectomy (PD) with combined PV resection. However, clinical strategies to prevent varices formation due to sinistral portal hypertension remain controversial. Moreover, the critical vein among splenic vein (SPV), inferior mesenteric vein, left gastric vein, or middle colonic vein requiring preservation to prevent the development of varices remains unclear. METHODS: We retrospectively analyzed patients with pancreatic cancer who underwent PD with combined PV resection over 18 years at our institution. Varices were evaluated using enhanced computed tomography (CT) and endoscopy. Preoperative types of porto-mesenterico-splenic confluence, venous drainage, and venous resection types were determined by operative records and CT findings. RESULTS: Of the 108 subjects, the incidence of postoperative varices was observed in 24.1% of cases over 5.6 months. These varices were classified into five types based on location, as pancreaticojejunostomy anastomotic (11.5%), gastrojejunostomy anastomotic (11.5%), esophageal (11.5%), splenic hilar-gastric (23.1%), and right colonic (65.4%) varices. No case of variceal bleeding occurred. Multivariate analysis showed SPV ligation as the greatest risk factor of varices (P < 0.001), with a higher incidence of left-sided varices in patients with all the SPV venous drainage sacrificed (60%) than in the others (16.7%). Therefore, sacrificing all the SPV venous drainage was the only independent risk factor of varices (P = 0.049). CONCLUSIONS: Preservation of SPV venous drainage should be considered during SPV ligation to prevent post-PD varices.

Incidence of deep vein thrombosis from screening by venous ultrasonography in Japanese patients.

The aim of the present study was to investigate the incidence of deep vein thrombosis (DVT) patients in a Japanese population by screening them with venous ultrasonography. This retrospective, single-center analysis examined 963 patients who underwent venous ultrasonography in 2015. The primary outcome was the incidence of DVT, and secondary outcomes were predictive factors of DVT in patient characteristics, treatment strategy for DVT patients, and proportion of post thrombotic syndrome (PTS). The overall incidence rate of DVT was 10.3% (100/963). The location of thrombus was the iliac vein in 3.6% (n = 35), the femoral vein in 4.4% (n = 43), and the calf vein in 8.2% (n = 79) of the patients. The main complaint or purpose of examination was perioperative screening in 37% of the patients, leg edema and/or limb swelling in 27% of the patients, and skin disease in 8% of the patients. In a multivariate analysis, the incidence of DVT was significantly higher in the hospitalization group and the "having symptoms" group. Fifty percent of DVTs received treatment, and almost all therapies were medical treatment with oral anticoagulants (OAC). Within a three-year follow-up period, the proportion of PTS was 27% with no significant difference between anticoagulation or non-anticoagulation patients; the risk of PTS was in concomitant varicose veins. In conclusion, of the patients, 10.3% were diagnosed with DVT, and only half received treatment with only anticoagulation.

The clinical spectrum of Fontan-associated liver disease: results from a prospective multimodality screening cohort.

AIMS: Liver fibrosis and cirrhosis are a consequence of a Fontan physiology, and determine prognosis. It is unclear whether non-invasive assessment of liver pathology is helpful to provide clinically relevant information. The aims of this study were to assess the spectrum of Fontan-associated liver disease (FALD) and usefulness of non-invasive methods to assess biopsy confirmed liver fibrosis. METHODS AND RESULTS: Hepatic screening of consecutive patients consisted of a blood panel, ultrasonography, elastography, contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) scan, and liver biopsy (scored with Fontan specific fibrosis scores and collagen proportionate area; CPA). Fibrosis parameters, varices, ascites, and splenomegaly were measured on imaging. Thirty-eight of 49 referred patients (27 ± 6.6 years, 73.7% male) underwent the complete screening protocol. Liver fibrosis on biopsy was present in all patients, and classified as severe (Stages 3-4) in 68%. Median CPA was 22.5% (16.9-29.5) and correlated with individual fibrosis scores. ELF® and liver stiffness were elevated, but MELD-XI scores were low in all patients. Fibrosis severity neither correlated to ELF® and liver stiffness, nor to (semi-) quantitative fibrosis parameters on MRI/CT. Varices were present in 50% and hyperenhancing nodules in 25% of patients, both independent of fibrosis stage, but varices were associated with higher CPA values. CONCLUSION: The FALD spectrum includes both hepatic congestion and severe fibrosis, with signs of portal hypertension and hyperenhancing nodules as significant manifestations. Routine imaging, transient elastography, and serum biomarkers are unable to accurately assess severity of liver fibrosis in this cohort. Future research should focus on validating new diagnostic tools with biopsy as the reference standard.

Clinical and Genetic Determinants of Varicose Veins.

BACKGROUND: Varicose veins are a common problem with no approved medical therapies. Although it is believed that varicose vein pathogenesis is multifactorial, there is limited understanding of the genetic and environmental factors that contribute to their formation. Large-scale studies of risk factors for varicose veins may highlight important aspects of pathophysiology and identify groups at increased risk for disease. METHODS: We applied machine learning to agnostically search for risk factors of varicose veins in 493 519 individuals in the UK Biobank. Predictors were further studied with univariable and multivariable Cox regression analyses (2441 incident events). A genome-wide association study of varicose veins was also performed among 337 536 unrelated individuals (9577 cases) of white British descent, followed by expression quantitative loci and pathway analyses. Because height emerged as a new candidate risk factor, we performed mendelian randomization analyses to assess a potential causal role for height in varicose vein development. RESULTS: Machine learning confirmed several known (age, sex, obesity, pregnancy, history of deep vein thrombosis) and identified several new risk factors for varicose vein disease, including height. After adjustment for traditional risk factors in Cox regression, greater height remained independently associated with varicose veins (hazard ratio for upper versus lower quartile, 1.74; 95% CI, 1.51-2.01; P<0.0001). A genome-wide association study identified 30 new genome-wide significant loci, identifying pathways involved in vascular development and skeletal/limb biology. Mendelian randomization analysis provided evidence that increased height is causally related to varicose veins (inverse-variance weighted: odds ratio, 1.26; P=2.07×10-16). CONCLUSIONS: Using data from nearly a half-million individuals, we present a comprehensive genetic and epidemiological study of varicose veins. We identified novel clinical and genetic risk factors that provide pathophysiological insights and could help future improvements of treatment of varicose vein disease.

Major risk factors for chronic venous disease development in women: is childbirth among them?

Many studies have reported that Chronic venous disease (CVD) occurs more in females than males, due to pregnancy. The study was conducted over the period 2014-2015 at the Dermatovenereological clinic, Novi Sad, Serbia. We performed a cross-sectional study of 554 women. According to Clinical-Etiology-Anatomy-Pathophysiology (CEAP) staging, the sample was divided into three groups: Mild CVD (classes 1-3 by CEAP) - n = 72; Severe CVD (classes 4-6 by CEAP) - n = 122 and a Control (no CVD) - n = 360 patients. The age range of participants was 18 to 93 years (average 54.92 years). Most important CVD risk factors were examined in detail. Out of 554 examinees, 22.03% had severe CVD, and 12.99% had mild CVD. Bivariate analyses showed a significantly higher proportion of women who had deliveries in the severe CVD and mild CVD groups, compared with the control group. Other significantly related factors were older age, family history of varicose veins, standing job position and hypertension. After performing multiple logistic regression analysis, older age, standing job position and family history of varicose veins remained significant, while childbirth lost its significance. Our results suggest that childbirths are not associated with the occurrence of CVD.