Portal thrombosis after surgical treatment of schistosomatic portal hypertension.

OBJECTIVE: Several studies have investigated the correlation between the effects of different surgical treatments and laboratory exams for schistosomal portal hypertension, especially concerning portal system thrombosis. The etiopathogenic factors of this thrombosis are not fully understood. In this study, the correlation between surgical treatment for schistosomal portal hypertension and the occurrence of postoperative portal system thrombosis was investigated. METHODS: A total of 61 patients who underwent surgical treatment for schistosomal portal hypertension were distributed into four groups: Patients in Group 1 (n=12) underwent portal variceal disconnection associated with splenic artery ligation and spleen preservation. Patients in Group 2 (n=20) underwent portal variceal disconnection and total splenectomy. Patients in Group 3 (n=20) underwent portal variceal disconnection with subtotal splenectomy, preserving the upper splenic pole supplied by the splenogastric vessels. Patients in Group 4 (n=9) underwent portal variceal disconnection with total splenectomy and autogenous splenic implants on the greater omentum. Late postoperative portal vein thrombosis was diagnosed using Doppler ultrasound. RESULTS: Over the 10-year follow-up, portal vein thrombosis occurred in 26 operated patients (42.6%), with no significant difference observed among the four surgical groups (p=0.217). Most of the thrombi only partially occluded the portal system veins. All the patients presented with a thrombus inside the portal vein. There was no difference in hematological and biochemical tests between groups with or without portal vein thrombosis. CONCLUSIONS: Portal vein thrombosis is often observed in the late postoperative period, irrespective of the surgical treatment employed, and is not associated with patient characteristics or any hematological and biochemical tests.

Prevalence of PICC-related thrombosis in patients with hematological malignancies: a systematic review.

PURPOSE: To estimate the prevalence of peripherally inserted central catheter (PICC)-related venous thrombosis in patients with hematological malignancies. METHODS: A systematic review of observational studies that evaluated the occurrence of PICC-related venous thrombosis in children, adults, and older people with hematological malignancies was conducted. Searches were carried out on June 12th, 2023 on PubMed, CINAHL, Embase, Web of Science Core Collection, Scopus, and LILACS, and to gray literature on Google Scholar, and ProQuest Dissertations and Theses Global. Eligibility criteria were applied independently by two reviewers, first on the titles and abstracts on the Rayyan platform and then on the full text of eligible studies. Risk of bias was assessed by the JBI checklist. Data were summarized descriptively, and the meta-analysis was carried out using the MetaXL 5.3 software. The review followed JBI guidelines and PRISMA for reporting. RESULTS: In the 40 studies included, prevalence of PICC-related venous thrombosis was 9% in general, 9% in adults, and 6% in children with hematological malignancies. Most studies only evaluated cases of symptomatic thrombosis (n = 25; 64%). CONCLUSION: Patients with hematological malignancies using PICC have an estimated prevalence of PICC-related venous thrombosis of 9%, and this rate may be underestimated due to the consideration of mostly symptomatic cases.

Circ-USP9X accelerates deep vein thrombosis after fracture by acting as a miR-148b-3p sponge and upregulates SRC kinase signaling inhibitor 1.

OBJECTIVES: This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities. METHODS: An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl2) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments. RESULTS: The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl2-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl2's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified. CONCLUSION: circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.

Catheter-related thrombosis in a neonatal intensive care unit: a case-control study / Trombose relacionada a cateter em unidade de terapia intensiva neonatal: um estudo de caso-controle

INTRODUCTION: Catheter-related thrombosis (CRT) accounts for most thrombotic events in the neonate. OBJECTIVE: Investigate CRT frequency, association with days of catheter use until diagnosis, and number of catheters used, in a single-center Neonatal Intensive Care Unit. METHODS: A case-control study that included 14 cases and 42 controls. Data collection occurred between January 2017 and December 2020 in a public NICU. Crude odds ratios (COR) were calculated. The study complied with ethical standards from national guidelines. RESULTS: Two hundred and ninety-four neonates used central venous catheters, of which 14 (4.7%) were diagnosed with CRT. Catheter in use when diagnosis was made was centrally inserted central catheters in 8 (57.1%). Before diagnosis, the cumulative duration of catheter use was 34.5 days and the median number of catheters used was three. A higher SNAPPE-II (COR 1.03; 95% CI 1.01-1.06; p=0.03), cumulative days of catheter use >30 (COR 19.11; 95% CI 2.28-160.10; p=0.007) and number of catheters used ≥3 (COR 7.66; 95% CI 1.51-38.70; p=0.01) were associated with CRT. CONCLUSION: CRT cases were associated with clinical severity; number of catheters and cumulative days of catheter use. We suggest that screening for thrombosis should be performed in neonates who need a long time of catheter use and more than three catheters. Reducing the duration and number of venous catheters used will help to reduce CRT.

INTRODUÇÃO: A trombose relacionada ao cateter (TRC) é responsável pela maioria dos eventos trombóticos no neonato. OBJETIVO: Investigar a frequência da TRC, a associação com os dias de uso do cateter até o diagnóstico e o número de cateteres utilizados em uma Unidade de Terapia Intensiva Neonatal unicêntrico. MÉTODOS: Estudo caso-controle que incluiu 14 casos e 42 controles. A coleta de dados ocorreu entre janeiro de 2017 e dezembro de 2020 em uma UTIN pública. Foram calculadas razões de chances brutas (COR). O estudo respeitou os padrões éticos das diretrizes nacionais. RESULTADOS: Duzentos e noventa e quatro neonatos utilizaram cateter venoso central, dos quais 14 (4,7%) foram diagnosticados com TRC. O cateter em uso no momento do diagnóstico foi o cateter central inserido centralmente em 8 (57,1%). Antes do diagnóstico, o tempo acumulado de uso do cateter foi de 34,5 dias e a mediana do número de cateteres utilizados foi de três. Um maior número de dias de uso do cateter >30 (COR 19,11; IC 95% 2,28-160,10; p=0,007) e número de cateteres utilizados >3 (COR 7,66; IC 95% 1,51-38,70; p=0,01). CONCLUSÃO: Os casos de TRC foram associados à gravidade clínica; número de cateteres e dias cumulativos de uso do cateter. Sugerimos que o rastreamento de trombose seja realizado em neonatos que necessitem de longo tempo de uso do cateter e mais de três cateteres. Reduzir a duração e o número de cateteres venosos usados ajudará a reduzir a TRC.

Disasters that develop in the liver due to hydatid cyst: a case report.

Hilar cavernous transformation is the formation of venous structures rich in collateral around the portal vein. Portal vein thrombosis is a rare entity. Although there are many reasons for its etiology, few cases have been reported secondary to hydatid cysts in the liver. Here, we present a 24-year-old patient with complaints of abdominal pain and swelling. Her CT and MRI scans show cholelithiasis with portal vein thrombosis and hilar cavernous transformation due to giant hydatid cyst compression in the lateral liver sector.

La transformación cavernosa hiliar es la formación de estructuras venosas ricas en colaterales alrededor de la vena porta. La trombosis de la vena porta es una afección poco frecuente. Aunque existen muchas razones en su etiología, se han descrito pocos casos secundarios a quiste hidatídico en el hígado. Aquí se presenta el caso de una paciente de 24 años con quejas de dolor abdominal e hinchazón. La tomografía computarizada y la resonancia magnética mostraron colelitiasis con trombosis de la vena porta y transformación cavernosa hiliar por compresión del quiste hidatídico gigante en el sector lateral del hígado.

Risk of deep venous thrombosis associated with peripherally inserted central catheter: A retrospective cohort study of 11.588 catheters in Brazil.

INTRODUCTION: Deep Venous Thrombosis (DVT) due to Peripherally Inserted Central Catheter (PICC) is one of the most threatening complications after device insertion. OBJECTIVE: To assess the rate of PICC-associated DVT and analyze the risk factors associated with this event in cancer and critically ill patients. METHODS: We conducted a descriptive, retrospective cohort study with 11,588 PICCs from December 2014 to December 2019. Patients ≥ 18 years receiving a PICC were included. Pre-and post-puncture variables were collected and a logistic regression was used to identify the independent factors associated with the risk of DVT. RESULTS: The DVT prevalence was 1.8% (n = 213). The median length of PICC use was 15.3 days. The median age was 75 years (18; 107) and 52% were men, 53.5% were critically ill and 29.1% oncological patients. The most common indications for PICC's were intravenous antibiotics (79.1%). Notably, 91.5% of PICC showed a catheter-to-vein ratio of no more than 33%. The tip location method with intracavitary electrocardiogram was used in 43%. Most catheters (67.9%) were electively removed at the end of intravenous therapy. After adjusting for cancer profile ou chemotherapy, regression anaysis revealed that age (OR 1.011; 95% CI 1.002-1.020), previous DVT (OR 1.96; 95% CI 1.12-3.44) and obstruction of the device (OR 1.60; 95% CI 1.05-2.42) were independent factors associated with PICC-associated DVT, whereas the use of an anticoagulant regimen was a protective variable (OR 0.73; 95% CI 0.54-0.99). CONCLUSION: PICC is a safe and suitable intravenous device for medium and long-term therapy, with low rates of DVT even in a cohort of critically ill and cancer patients.

Evaluation of common femoral vein thickness as a diagnostic tool for Behçet's disease in a non-endemic area.

OBJECTIVES: To evaluate common femoral vein thickness (CFVT) as a diagnostic tool in Brazilian patients with Behçet's disease (BD) and to analyse associations between increased CFVT and disease features. METHODS: A cross-sectional study was performed including 100 BD patients and 100 controls. The CFVT and the diameters of great saphenous vein (GSV), and small saphenous vein (SSV) were measured by Doppler ultrasound. RESULTS: BD patients had higher right CFVT [0.600mm (0.500-0.700) vs. 0.525mm (0.450-0.637); p=0.012] and left CFVT [0.550mm (0.450-0.650) vs. 0.500mm (0.450-0.550); p=0.004] compared to controls. Vascular involvement of BD and previous deep venous thrombosis were associated with increased CFVT (p<0.05). The number of vascular events correlated with right and left CFVT (Rho = 0.475 p=0.030 and Rho = 0.429 p=0.052, respectively). The 0.575mm cut-off point of right and left CFVT had area under the curve (AUC) of 0.602; 95% confidence interval (95% CI): 0.524-0.680 and AUC: 0.615; 95% CI: 0.537-0.693, respectively. The right and left CFVT had a sensitivity for BD diagnosis of 52% and 43%, and a specificity of 64% and 77%, respectively. No significant differences were found between BD patients and controls regarding the GSV and SSV diameters in both legs (p>0.05). CONCLUSIONS: In this study, CFVT measurement was not shown to be a reliable diagnostic test for BD. CFVT was increased in BD patients presenting vascular involvement and correlated with the number of previous events.

Cardiovascular benefits of GLP-1 receptor agonists in patients who are obese or overweight: a meta-analysis of randomized controlled

Backgroun|D: GLP-1 receptor agonists (GLP-1 RAs) have emerged as an effective therapeutic class for weight loss. However, the efficacy of these agents in cardiovascular endpoints among patients who are obese or overweight requires additional investigation. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1 RAs vs. placebo in patients who are obese or overweight. PubMed, Cochrane, and Embase were searched. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). RESULTS: A total of 12 RCTs were included, with 12,908 patients. Compared with placebo, GLP-1 RAs were associated with significant reductions in systolic blood pressure (MD -4.45 mmHg; 95% CI -5.31, -3.60; p<0.01) and diastolic blood pressure (MD -1.43 mmHg; 95% CI -2.63, -0.22; p=0.02). There were no significant differences between groups for unstable angina (UA) (RR 0.90; 95% CI 0.29-2.84; p=0.86), stroke (RR 0.65; 95% CI 0.28-1.49; p=0.30), atrial fibrillation (AF) (RR 0.87; 95% CI 0.33-2.30; p=0.78), myocardial infarction (MI) (RR 0.57; 95% CI 0.17-1.90; p=0.36), or deep vein thrombosis (RR 0.45; 95% CI 0.08-2.65; p=0.38). CONCLUSION: In patients who are overweight or obese, GLP-1 receptor agonists reduce systolic and diastolic blood pressure, with a neutral effect on the incidence of UA, stroke, AF, MI, and deep vein thrombosis.

Biomarkers Profile in Provoked Versus Unprovoked Deep Venous Thrombosis.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Serial values of hematologic variables and deep venous thrombosis: Red cell distribution width is associated with deep venous thrombosis

Abstract Introduction As 30 to 50% of deep venous thrombosis (DVT) cases remain idiopathic, an increased focus on hematologic variables may therefore reveal novel correlates of DVT. Very few studies have investigated the association of hematological parameters with DVT and the causal relationship between them is still to be elucidated. Therefore, we aimed to investigate the association between serial values of hematologic variables and DVT. Methods Complete blood count parameters were serially measured at baseline and then at approximately 3-month intervals for 12 months in 152 adults with the first episode of DVT and 152 age- and sex-matched controls. The odds ratio (OR) with the 95% confidence interval (95%CI) was calculated as a measure of association between hematological parameters and DVT. Results The red cell distribution width (RDW) was the only hematologic variable which showed an independent and consistent association with DVT at all time points (multivariable-adjusted OR [95%CI] 3.38 [1.28 - 8.91] at baseline, 2.24 [0.85 - 5.92] at 3 months and 2.12 [0.81 - 5.55] at 12 months for RDW > 14.0%). This association was higher for provoked DVT than unprovoked DVT and for DVT plus pulmonary embolism than DVT alone. No significant correlation was found between the high RDW and classical thrombotic risk factors, except malignancy. Conclusions We demonstrated an independent and consistent association of the high RDW with the first episode of DVT in adult patients. The study was probably underpowered to evaluate the association between the high RDW and recurrent DVT. Further large studies with long follow-up are needed to confirm this association.

Paralabral Cyst of the Hip Causing Deep Vein Thrombosis Treated with Arthroscopic Decompression and Labral Repair.

In the setting of femoroacetabular impingement of the hip joint, paralabral cysts are well-documented sequelae. These cysts are typically associated with labral tears caused by CAM and/or pincer-type bony lesions. Synovial fluid extravasation through a tear in the labrum, similar to a popliteus cyst, leads to formation of a capsular-based cyst that is usually self-limiting. Few documented cases of these cysts causing compression of nearby neurovascular structures exist. There are several studies documenting arthroscopic decompression of these cysts, but none reporting compression of the femoral vein by a paralabral cyst resulting in deep vein thrombosis. We present the case of a large anterior paralabral cyst causing compression of the right femoral vein in a patient presenting with deep vein thrombosis and hip pain. Treatment consisted of arthroscopic decompression, followed by definitive aspiration by interventional radiology after labral repair and bipolar hip osteoplasty. The purpose of this case report was to document this rare presentation and offer learning points from our experience.

Diagnosis of chronic iliac venous obstruction

Stenting has become the first line of treatment for symptomatic chronic iliofemoral venous obstruction in patients with quality-of-life impairing clinical manifestations who have failed conservative therapy. Patient selection for such intervention is however dependant on clear identification of relevant clinical manifestations and subsequent testing to confirm the diagnosis. In this regard the physician engaged in management of such patients need to be well aware of symptoms and signs of chronic iliofemoral venous obstruction (CIVO), instruments used to grade chronic venous insufficiency (CVI) and determine quality of life in addition to diagnostic tests available and their individual roles. This review serves to provide an overview of the diagnosis of CIVO and patient selection for stenting.

Recanalization of portal vein thrombosis after pediatric liver transplantation: Efficacy and safety of the transsplenic access.

BACKGROUND: Endovascular management of portal vein thrombosis (PVT) is challenging. Transsplenic access (TSA) is growing as an access option to the portal system but with higher rates of bleeding complications. The aim of this article is to evaluate the efficacy and safety of transsplenic portal vein recanalization (PVR) using a metallic stent after pediatric liver transplantation. MATERIALS AND METHODS: This is a retrospective review of 15 patients with chronic PVT who underwent PVR via TSA between February 2016 and December 2020. Two children who had undergone catheterization of a mesenteric vein tributary by minilaparotomy were excluded from the patency analysis but included in the splenic access analysis. The technical and clinical success of PVR and complications related to the procedure via TSA were evaluated. RESULTS: Thirteen children with PVT were treated primarily using the TSA. The mean age was 4.1 years (range, 1.5-13.7 years), and the most common clinical presentation was hypersplenism (60%). Technically successful PVR was performed in 11/13 (84.6%) children, and clinical success was achieved in 9/11 (81.8%) children. No major complications were observed, and one child presented moderate pain in the TSA (from a total of 17 TSA). The median follow-up was 48.2 months. The median primary patency was 9.9 months. Primary patency in the first 4 years was 75%, and primary assisted patency was 100% in the follow-up period. CONCLUSIONS: Transsplenic PVR is a safe and effective method for the treatment of PVT after pediatric liver transplantation.

Nephrectomy and IVC thrombectomy in renal cancer: a narrative review.

Renal cell carcinoma accounts for two to three percent of adult malignancies and can lead to inferior vena cava (IVC) thrombosis. This condition can decrease the rate of 5-year survival for patients to 60%. The treatment of choice in such cases is radical nephrectomy and inferior vena cava thrombectomy. This surgery is one of the most challenging due to many perioperative complications. There are many controversial methods reported in the literature. Achieving the free of tumor IVC wall and the possibility of thrombectomy in cases of level III and level IV IVC thrombosis are two essential matters previously advocated open approaches. Nevertheless, open approaches are being replaced by minimally invasive techniques despite the difficulty of the surgical management of IVC thrombectomy. This paper aims to review recent evidence about new surgical methods and a comparison of open, laparoscopic, and robotic approaches. In this review, we present the latest surgical strategies for IVC thrombectomy and compare open and minimally invasive approaches to achieve the optimal surgical technique. Due to the different anatomy of the left and right kidneys and variable extension of venous thrombosis, we investigate surgical methods for left and right kidney cancer and each level of IVC venous thrombosis separately.

Biomarkers profile in provoked versus unprovoked deep venous thrombosis

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Reconstrucción de ligamento cruzado anterior: incidencia de infecciones y trombosis venosa profunda en una serie de 714 casos consecutivos / ACL reconstruction. Incidence of Infection and deep venous thrombosis. 714 case series

Introducción: La reconstrucción artroscópica del ligamento cruzado anterior (LCA) tiene un bajo índice de complicaciones postoperatorias. Cuando se presenta una infección en el postoperatorio inmediato, tanto el cirujano como el paciente se enfrentan a un escenario complejo y de difícil aceptación, que en algunos casos tiene consecuencias graves. En este contexto es importante conocer la incidencia reportada en la literatura para compararla con lo que ocurre en nuestras instituciones. El objetivo del presente trabajo es evaluar la incidencia de infección en una serie de casos consecutivos de reconstrucciones de LCA. Materiales y métodos: se realizó un estudio retrospectivo del período comprendido entre enero de 2015 y diciembre de 2017, donde se evaluó la incidencia de infección en una serie consecutiva de reconstrucciones de LCA. Fueron evaluados un total de setecientos catorce pacientes: seiscientos veintinueve masculinos y ochenta y cinco femeninos con un promedio de edad de veintiocho años (15-50).Resultados: de los setecientos catorce casos analizados, se encontraron seis infecciones postquirúrgicas (dos profundas y cuatro superficiales). Conclusiones: la incidencia de infección aguda postoperatoria luego de reconstrucción artroscópica del LCA fue del 0.84%, similar a lo reportado en la literatura. Se observó un franco predominio de infecciones en las reconstrucciones de LCA con injerto de isquiotibiales con respecto al resto de los injertos. Nivel de Evidencia: IV

Introduction: Complication rate of arthroscopic anterior cruciate ligament (ACL) reconstruction is low. Post-operative infection place both, the surgeon and patient in a difficult situation with an unknown outcome and possible serious sequalae. It is important to investigate the incidence of these complications in our institutions to compare them with existing literature. The aim of this study is to report the incidence of infection in a consecutive case series of ACL reconstruction. Materials and methods: retrospective study of consecutive ACL reconstructions performed between January 2015 to December 2017. The incidence of infection was evaluated in 714 cases, 629 males and 85 females, with average age of 28 years (15-50).Results: six post-operative infections were found (four superficial and two deep infections). Conclusions: the incidence of infection was 0.84% in this case series. Most of the infections were in patients with autologous gracilis-semitendinous grafts. Level of Evidence: IV