COVID-19 induced aorto duodenal fistula following evar in the so called "negative" patient.

OBJECTIVES: Since October 2019, SARS-CoV-2 pandemic represents a challenge for the international healthcare system and for the treatment and survival of patients. We normally focus on symptomatic patients, and symptoms can range from the respiratory to the gastrointestinal system. In addition, we consider patients without fever and respiratory symptoms, with both a negative RT nasopharyngeal swab and lung CT, as a "Covid-19 negative patient." In this article, we present a so called Covid-19 "negative" patient, with an unsuspected vascular clinical onset of the viral infection. METHODS: An 80 y.o. man, who previously underwent endovascular aortic repair for an infrarenal abdominal aortic aneurysm, presented to our department with an atypical presentation of an aorto-enteric fistula during the pandemic. While in hospital, weekly nasopharyngeal swab tests were always negative for SARS-CoV-2. However, the absence of aortic endograft complications, the gross anatomy of duodenal ischemic injury, and the recent history of the patient who lived the last months in Bergamo, the Italian city with the highest number of COVID-19 deaths, lead the senior Author to suspect an occult SARS-CoV-2 infection. The patient underwent to resection of the fourth portion of the duodenum and the first jejunal loop, with subsequent duodenum-jejunal latero-lateral anastomosis and the direct suture of the aortic wall. The intestinal specimen was investigated as suspected SARS-CoV-2 bowel infection by the means of immune-histochemistry (IHC). An ileum sample obtained in the pre-COVID-19 era was used as a control tissue. RESULTS: The histological analysis of the bowel revealed sustained wall ischemia and liponecrosis of the duodenal wall, with intramural blood vessels thrombosis. Blood vessel endotheliitis and neo-angiogenesis were also observed. Finally, the IHC was strongly positive for SARS-CoV-2 RNA and for HLA-G presence, with a particular concentration both in blood vessels and in the intestinal villi. The control tissue sample was not positive for both SARS-CoV-2 and HLA-G. CONCLUSIONS: Coronavirus pandemic continues to be an international challenge and more studies and trials must be done to learn its pathogenesis and its complications. As for thromboembolic events caused by SARS-COV-2, vascular surgeons are involved in treatment and prevention of the complications of this syndrome and must be ready with general surgeons to investigate atypical and particular cases such as the one discussed in this article.

Bowel ischemia as onset of COVID-19 in otherwise asymptomatic patients with persistently negative swab.

BACKGROUND: Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab. METHODS: Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed. RESULTS: All tested samples were strongly positive for SARS-CoV-2. CONCLUSIONS: This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.

The Effect of Active Stretching Training in Patients with Chronic Venous Insufficiency Monitored by Raster-Stereography.

(1) Background: Musculoskeletal disorders can be associated with advanced clinical stages of chronic venous insufficiency (CVI). The aim of the study is to investigate the effect of active stretching (AS) training on lower limb venous function and quality of life in patients affected by CVI. (2) Methods: A prospective two-armed pilot randomized controlled was conducted. Twenty (20) CVI patients were randomly assigned to an AS training or to a control group (C) who did not receive any exercise indication. At baseline and after three months all the participants were tested for leg volumetry (LV), air plethysmography (APG), and quality of life (QoL) measured by a disease specific validated questionnaire (VVSymQ), ankle range of motion (ROM), and postural deformities using an optoelectronic body posture machine. (3) Results: At the end of the training in the AS group a significant leg volume reduction was detected (from 2340 ± 239 mL to 2239 ± 237 mL (4.3%); p < 0.0001), whereas in the C group no significant volume changes were found. The ejection fraction rate (EF%) increased significantly from 49.3 ± 9.3 to 61.1 ± 14.5, p < 0.005. A moderate-strong linear correlation with EF% and ankle ROM variation was found (R2 = 0.6790; p < 0.0034). Several postural outcomes such as pelvic tilt, pelvic torsion, and lordotic angle significantly improved in the AS group (p < 0.01, p < 0.04, p < 0.01 respectively). (4) Conclusion: The AS training impacts on the APG parameters related to the musculoskeletal pump efficiency, opening a further possibility in the management of CVI patients by means of an appropriate adapted physical exercise program.

Efficacy and Safety of Treatment of Complex Idiopathic Fistula-in-Ano Using Autologous Centrifuged Adipose Tissue Containing Progenitor Cells: A Randomized Controlled Trial.

BACKGROUND: Mesenchymal stem cells derived from adipose tissue have been successfully used to promote sphincter-saving anal fistula healing. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the use of autologous centrifuged adipose tissue in the healing process of cryptoglandular complex anal fistulas. DESIGN: This is a randomized controlled trial. SETTINGS: This study was conducted at a single center. PATIENTS: Patients with complex perianal fistulas not associated with Crohn's disease were included. Rectovaginal fistulas were not included. INTERVENTIONS: Patients were randomly allocated to receive treatment with centrifuged adipose tissue injection (experimental group) and without injection (control group) in combination with fistula surgery. MAIN OUTCOME MEASURES: The primary outcome was defined as the proportion of patients with complete fistula closure at 4 weeks (short-term outcome) and 6 months after surgery (long-term outcome). Healing was defined as when the external opening was closed with no perianal discharge on clinical assessment. The secondary outcome was safety that was evaluated by the analysis of adverse events up to 3 months after surgery. Pelvic MRI was performed at 3 months to assure safety and the accuracy of the clinical determination of healing. Postoperative pain, return to work/daily activities, persistent closure at 6 months, fecal incontinence, and patient satisfaction were evaluated. RESULTS: Fifty-eight patients who received centrifuged adipose tissue injection and 58 patients who did not receive centrifuged adipose tissue injection were included in the safety and efficacy analysis. After 4 weeks, the healing rate was 63.8% in the experimental group compared with 15.5% in the control group (p < 0.001). No major adverse events were recorded. Postoperative anal pain was significantly lower in the injection group. Time taken to return to work/daily activities was significantly shorter in the experimental group (3 days) than in the control group (17 days). At 6 months, persistent closure was similar in the 2 groups (86.2% vs 81%). Fecal Incontinence Score at 6 months after surgery was identical to the preoperative score. Patient satisfaction was high in both groups. LIMITATIONS: The absence of blinding, the lack of correlation between stem cell content, and the clinical outcome were limitations of the study. CONCLUSIONS: Autologous centrifuged adipose tissue injection may represent a safe, efficacious, and inexpensive option for the treatment of complex fistula-in-ano. See Video Abstract at http://links.lww.com/DCR/B607. CLINICAL TRIALS REGISTRATION: URL: https://www.clinicaltrials.gov. Identifier: NCT04326907. EFICACIA Y SEGURIDAD DEL TRATAMIENTO DE LA FSTULA ANAL COMPLEJA IDIOPTICA UTILIZANDO TEJIDO ADIPOSO CENTRIFUGADO AUTLOGO QUE CONTIENE CLULAS PROGENITORAS UN ENSAYO CONTROLADO ALEATORIO: ANTECEDENTES:Las células madre mesenquimales derivadas del tejido adiposo se han utilizado con éxito para promover la curación de la fístula anal con preservación de esfínter.OBJETIVO:El objetivo de este estudio fue evaluar la eficacia y seguridad del uso de tejido adiposo autólogo centrifugado en el proceso de cicatrización de fístulas anales complejas de origen criptoglandular.DISEÑO:Ensayo controlado aleatorio.ENTORNO CLÍNICO:Estudio unicéntrico.PACIENTES:Se incluyeron pacientes con fístulas perianales complejas no asociadas a Enfermedad de Crohn. No se incluyeron las fístulas rectovaginales.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente para recibir tratamiento con inyección de tejido adiposo centrifugado (grupo experimental) y sin inyección (grupo de control) en combinación con cirugía de fístula.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado primario se definió como la proporción de pacientes con cierre completo de la fístula a las 4 semanas (resultado a corto plazo) y 6 meses después de la cirugía (resultado a largo plazo). La curación se definió cuando orificio externo se cerró sin secreción perianal en la valoración clínica. El resultado secundario fue la seguridad que se evaluó mediante el análisis de los eventos adversos (EA) hasta 3 meses después de la cirugía. La resonancia magnética pélvica se realizó a los 3 meses para garantizar la seguridad y la precisión clínica de la curación. Se evaluó el dolor postoperatorio, el regreso al trabajo / actividades diarias, el cierre persistente a los 6 meses, la incontinencia fecal y la satisfacción del paciente.RESULTADOS:Cincuenta y ocho pacientes que recibieron inyección de tejido adiposo centrifugado y 58 pacientes que no recibieron inyección de tejido adiposo centrifugado se incluyeron en el análisis de seguridad y eficacia. Después de 4 semanas, la tasa de curación fue del 63,8% en el grupo experimental en comparación con el 15,5% en el grupo de control (p <0,001). No se registraron eventos adversos importantes. El dolor anal posoperatorio fue significativamente menor en el grupo de inyección. El tiempo necesario para volver al trabajo / actividades diarias fue significativamente menor en el grupo experimental (3 días) con respecto al grupo de control (17 días). A los 6 meses, el cierre persistente fue similar en los dos grupos (86,2% vs 81%). La puntuación de incontinencia fecal a los 6 meses después de la cirugía fue idéntica a la puntuación preoperatoria. La satisfacción del paciente fue muy alta en ambos grupos.LIMITACIONES:Ausencia de cegamiento, falta de correlación entre el contenido de células madre y el resultado clínico.CONCLUSIONES:La inyección de tejido adiposo centrifugado autólogo puede representar una opción segura, eficaz y económica para el tratamiento de la fístula anal compleja.Registro de ensayos clínicos: www.clinicaltrials.gov, identificador NCT04326907; No patrocinado.Consulte Video Resumen en http://links.lww.com/DCR/B607.

Combination of Genomic and Transcriptomic Approaches Highlights Vascular and Circadian Clock Components in Multiple Sclerosis.

Aiming at exploring vascular components in multiple sclerosis (MS) with brain outflow disturbance, we combined transcriptome analysis in MS internal jugular vein (IJV) wall with WES in MS families with vertical transmission of disease. Main results were the differential expression in IJV wall of 16 MS-GWAS genes and of seven genes (GRIN2A, GRIN2B, IL20RB, IL26, PER3, PITX2, and PPARGC1A) not previously indicated by GWAS but encoding for proteins functionally interacting with MS candidate gene products. Strikingly, 22/23 genes have been previously associated with vascular or neuronal traits/diseases, nine encoded for transcriptional factors/regulators and six (CAMK2G, GRIN2A, GRIN2B, N1RD1, PER3, PPARGC1A) for circadian entrainment/rhythm components. Among the WES low-frequency (MAF ≤ 0.04) SNPs (n = 7) filtered in the 16 genes, the NR1D1 rs17616365 showed significantly different MAF in the Network for Italian Genomes affected cohort than in the 1000 Genome Project Tuscany samples. This pattern was also detected in five nonintronic variants (GRIN2B rs1805482, PER3 rs2640909, PPARGC1A rs2970847, rs8192678, and rs3755863) in genes coding for functional partners. Overall, the study proposes specific markers and low-frequency variants that might help (i) to understand perturbed biological processes in vascular tissues contributing to MS disease, and (ii) to characterize MS susceptibility genes for functional association with disease-pathways.

Effects of Venous Angioplasty on Cerebral Lesions in Multiple Sclerosis: Expanded Analysis of the Brave Dreams Double-Blind, Sham-Controlled Randomized Trial.

PURPOSE: To evaluate if jugular vein flow restoration in various venographic defects indicative of chronic cerebrospinal venous insufficiency (CCSVI) in multiple sclerosis (MS) patients can have positive effects on cerebral lesions identified using magnetic resonance imaging (MRI). MATERIALS AND METHODS: The Brave Dreams trial ( ClinicalTrials.gov identifier NCT01371760) was a multicenter, randomized, parallel group, double-blind, sham-controlled trial to assess the efficacy of jugular venoplasty in MS patients with CCSVI. Between August 2012 and March 2016, 130 patients (mean age 39.9±10.6 years; 81 women) with relapsing/remitting (n=115) or secondary/progressive (n=15) MS were randomized 2:1 to venography plus angioplasty (n=86) or venography (sham; n=44). Patients and study personnel (except the interventionist) were masked to treatment assignment. MRI data acquired at 6 and 12 months after randomization were compared to the preoperative scan for new and/or >30% enlargement of T2 lesions plus new gadolinium enhancement of pre-existing lesions. The relative risks (RR) with 95% confidence interval (CI) were estimated and compared. In a secondary assessment, venograms of patients who underwent venous angioplasty were graded as "favorable" (n=38) or "unfavorable" (n=30) for dilation according to the Giaquinta grading system by 4 investigators blinded to outcomes. These subgroups were also compared. RESULTS: Of the 130 patients enrolled, 125 (96%) completed the 12-month MRI follow-up. Analysis showed that the likelihood of being free of new cerebral lesions at 1 year was significantly higher after venoplasty compared to the sham group (RR 1.42, 95% CI 1.00 to 2.01, p=0.032). Patients with favorable venograms had a significantly higher probability of being free of new cerebral lesions than patients with unfavorable venograms (RR 1.82, 95% CI 1.17 to 2.83, p=0.005) or patients in the sham arm (RR 1.66, 95% CI 1.16 to 2.37, p=0.005). CONCLUSION: Expanded analysis of the Brave Dreams data that included secondary/progressive MS patients in addition to the relapsing/remitting patients analyzed previously showed that venoplasty decreases new cerebral lesions at 1 year. Secondary analysis confirmed the efficacy of the Giaquinta grading system in selecting patients appropriate for venoplasty who were more likely to be free from accumulation of new cerebral lesions at MRI.

A phase II randomized clinical trial for the treatment of recalcitrant chronic leg ulcers using centrifuged adipose tissue containing progenitor cells.

BACKGROUND AIMS: Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs). METHODS: From an initial cohort of 38 patients, 16 patients affected by non-healing VLUs were randomly allocated to the experimental arm (5 men and 3 women) and control arm (5 men and 3 women). In the experimental arm, wounds were treated by debridement, centrifuged adipose tissue (CAT), advanced dressings and compression. No experimental treatment (CAT) was administered to the control arm. We investigated the functional and the immunophenotypical features of the harvested CAT-derived stem cells. The primary outcome measures were healing time and safety of the cell treatment. Secondary outcomes were pain evaluated by numeric rating scale (NRS), complete wound healing at 24 weeks by Margolis Index and wound-healing process expressed in square centimeters per week. The various immunophenotypic and functional characteristics of CAT-derived stem cells were then correlated with the clinical outcomes. RESULTS: No major adverse events were recorded. The healing time was significantly faster by applying CAT, 17.5 ± 7.0 weeks versus 24.5 ± 4.9 weeks recorded in the control arm (P < 0.036). NRS dropped after the first week to 2.7 ± 2.0 in the experimental arm versus 6.6 ± 3.0 in the control group (P < 0.01). The rate of healing at the 24th week was not significantly different between arms. Interestingly, we found a strong reverse correlation between the percent of CD34+/CD45- non-hematopoietic cells, respectively, with the healing time (r = -0.894, P < 0.041) and NRS (r = -0.934, P < 0.020). CONCLUSIONS: CAT is safe and may accelerate healing time in VLUs as well as reduce wound pain. The percentage of CD34+/CD45- cells in stromal vascular fraction (SVF) seems to be a predictive biomarker of successful CAT treatment in these patients.

The eagle jugular syndrome.

BACKGROUND: The elongation of the styloid process is historically associated with two variants of the Eagle syndrome. The classic one, mainly characterized by pain and dysphagia, and the carotid variant characterized by pain and sometimes by cerebral ischemia. We observed a further variant characterized by a styloid elongation coursing adjacent to the transverse process of C1, causing significant compression of the internal jugular vein. METHODS: We reviewed all the cases of Eagle syndrome, including the jugular variant, admitted in our Hospital in the last six years. We compared symptomatology, associated comorbidities and imaging. Data were statistically analyzed. RESULTS: Overall 23 patients were admitted to the Hospital for symptomatic elongation of the styloid process, 11 male and 12 females. The jugular variant of the Eagle syndrome is clinically delineated by significant differences, as compared to the classic variant and carotid variants. Headache was the more prominent symptom (p < .009) as well as a documented peri-mesencephalic hemorrhage was the more significant comorbidity (p < .0003). The group classic-carotid variant was characterized by ipsilateral pain respect to the jugular variant (p < .0003). CT angiography with venous phase extended to the neck veins and imaging reconstruction is highly recommended as imaging technique, complemented by color-Doppler ultrasound. CONCLUSIONS: The elongation of the styloid process may have different paths which creates compression on the surrounding anatomical structures. There may be a possible association of jugular impingement by an elongated styloid process with symptoms. TRIAL REGISTRATION: Protocol n°45-2013.

JEDI (jugular entrapment, dilated ventricles, intracranial hypertension) syndrome: a new clinical entity? A case report.

Patients with idiopathic intracranial hypertension are frequently obese women with normal/slit ventricles. Patients with high-pressure hydrocephalus, instead, present enlarged ventricles. We describe a 63-year-old woman with signs and symptoms of intracranial hypertension. Brain MRI revealed hydrocephalus. Venous Doppler ultrasound showed external compression of the omohyoid muscles on the internal jugular veins. During jugular vein decompression, intracranial pressure dropped from 18 to 6 mmHg. Patient is asymptomatic at 2-year follow-up, with decreased brain ventricles. These findings could represent a novel form of high-pressure hydrocephalus that can be successfully treated without a CSF shunt. We called this syndrome JEDI (jugular entrapment dilated ventricles intracranial hypertension).

A near-infrared spectroscopy-assisted test discriminates patients with peripheral arterial disease and venous insufficiency with changes of foot oxygenation following light elastic compression therapy.

Background: Elastic compression therapy (CT) in patients with peripheral artery disease (PAD) and chronic venous insufficiency (CVI) may compromise arterial perfusion. We evaluated the feasibility of a toe-flexion test, which quantifies dynamic foot perfusion by near-infrared spectroscopy (NIRS), for the assessment of hemodynamic sustainability of CT in PAD patients with CVI. Patients and methods: In this prospective observational study, PAD patients aged 50-85 with combined CVI at CEAP stages II-IV were studied. The ankle-brachial index (ABI) was measured, and foot perfusion was determined after 10 consecutive toe-flexion movements with NIRS sensors placed on the dorsum of each foot. Knee-high open-toe compression stockings were applied, and the degree of compression was measured. Toflex-area was determined by calculating the area under the curve of the oxygenated hemoglobin track recorded by NIRS. A toflex-area reduction > 20 % following CT was arbitrarily defined to identify limbs of patients with improved foot perfusion. These subjects received CT to be worn and a diary to report adherence and symptoms. Results: Forty-seven PAD patients (74 ± 9 years; ABI 0.67 ± 0.24) with CVI were enrolled. For all legs, superimposable toflex-areas were observed for the first two attempts (ICC 0.92). Following application of CT (17 ± 2 mmHg), the toflex-area improved (from -162 ± 110 a.u. to -112 ± 104 a.u.; p < .001). Sixty-two limbs (n = 32 patients) exhibited improved foot perfusion after CT, with a mean variation of 80 ± 47 a.u., while 32 limbs (n = 23 patients) showed stable or worsened values. In a regression model, favorable variations in toflex-area after CT were linked to a worse baseline toflex-area (R2 = 0.18; p < 0.001; rpartial = -0.42) while the percentage improvement directly correlated with CEAP class (p = 0.033). Conclusions: The NIRS-assisted test, which is feasible in a laboratory context, objectively discriminates the hemodynamic tolerability of the treatment and identifies subjects with combined PAD and CVI with improved perfusion after CT, in spite of the presence of PAD.

Changes in expression profiles of internal jugular vein wall and plasma protein levels in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disorder of the central nervous system (CNS). Several observations support interactions between vascular and neurodegenerative mechanisms in multiple sclerosis (MS). To investigate the contribution of the extracranial venous compartment, we analysed expression profiles of internal jugular vein (IJV), which drains blood from CNS, and related plasma protein levels. METHODS: We studied a group of MS patients (n = 19), screened by echo-color Doppler and magnetic resonance venography, who underwent surgical reconstruction of IJV for chronic cerebrospinal venous insufficiency (CCSVI). Microarray-based transcriptome analysis was conducted on specimens of IJV wall from MS patients and from subjects undergoing carotid endarterectomy, as controls. Protein levels were determined by multiplex assay in: i) jugular and peripheral plasma from 17 MS/CCSVI patients; ii) peripheral plasma from 60 progressive MS patients, after repeated sampling and iii) healthy individuals. RESULTS: Of the differentially expressed genes (≥ 2 fold-change, multiple testing correction, P < 0.05), the immune-related CD86 (8.5 fold-change, P = 0.002) emerged among the up regulated genes (N = 409). Several genes encoding HOX transcription factors and histones potentially regulated by blood flow, were overexpressed. Smooth muscle contraction and cell adhesion processes emerged among down regulated genes (N = 515), including the neuronal cell adhesion L1CAM as top scorer (5 fold-change, P = 5 × 10- 4). Repeated measurements in jugular/peripheral plasma and overtime in peripheral plasma showed conserved individual plasma patterns for immune-inflammatory (CCL13, CCL18) and adhesion (NCAM1, VAP1, SELL) proteins, despite significant variations overtime (SELL P < 0.0001). Both age and MS disease phenotypes were determinants of VAP1 plasma levels. Data supported cerebral related-mechanisms regulating ANGPT1 levels, which were remarkably lower in jugular plasma and correlated in repeated assays but not between jugular/peripheral compartments. CONCLUSIONS: This study provides for the first time expression patterns of the IJV wall, suggesting signatures of altered vascular mRNA profiles in MS disease also independently from CCSVI. The combined transcriptome-protein analysis provides intriguing links between IJV wall transcript alteration and plasma protein expression, thus highlighting proteins of interest for MS pathophysiology.

Comparison Between Duplex Ultrasound and Multigate Quality Doppler Profile Software in the Assessment of Lower Limb Perforating Vein Direction.

OBJECTIVES: The aim was to assess more accurately the net flow of the lower limb perforating veins (PVs). MATERIAL AND METHODS: This was an observational prospective study. Two hundred and twenty one limbs with chronic venous disease (C1-6EpAs,pPr) of 193 patients underwent a duplex ultrasound (DUS). All identified PVs were scanned also by means of quality Doppler profile (QDP) multigate analysis in order to determine their net inward and outward flow direction. A comparison between the traditional pulsed wave Doppler analysis and QDP was performed to detect potential discrepancy between the traditional definition of PV incompetence and a net outward flow. RESULTS: The DUS investigation identified 774 PVs. Only 7.7% of the PVs showed an outward flow lasting more than 500 ms. Among the PVs showing a longer than 500 ms outward flow, QDP assessment revealed net outward flow in only 84% of the PVs along the thigh and in 28.6% along the lower leg. Among the PVs showing a shorter than 500 ms outward flow, QDP assessment reported a net outward flow in 2.4% of the PVs along the thigh and in 47.3% of those along the lower leg. The sensitivity of an outward flow lasting more than 500 ms in detecting an actual net outward flow was 13.9% (9-20.1%). The specificity of an outward flow lasting less than 500 ms in detecting a net inward flow was 96.4% (93.2-98.3%). CONCLUSIONS: A lack of overlap exists between the finding of a PV outward flow lasting more than 500 ms and the net outward flow of the same vessel. The traditional definition of PV incompetence is challenged by the reported data and further investigations are required to identify a gold standard assessment.

Oscillatory flow suppression improves inflammation in chronic venous disease.

BACKGROUND: To assess if suppression of the oscillatory component of reflux may improve the inflammatory phenotype in chronic venous disease (CVD). MATERIALS AND METHODS: From 193 CVD patients, we selected 54 (13 males, 41 females, CEAP C2-4EpAsPr) for a blinded, case-control prospective investigation. All of them underwent echo-color-Doppler assessment of reflux parameters. In the same patients a blood systemic assessment of 19 inflammatory cytokines was obtained. Follow-up lasted 6 months. The control group (C) was constituted by 21 homogenous CVD patients, unselected and not operated. RESULTS: Thirty-one of 54 patients were excluded from post-operative evaluation in consequence of reported new other inflammatory episodes. Twenty-three (23) completed the follow up, showing the suppression of the oscillatory component of venous reflux; 4 of the 19 cytokines decreased significantly after the procedure: Tumor Necrosis Factor-α (TNFα), Granulocyte Colony Stimulating Factor (G-CSF), Interferon gamma-induced Protein 10 (IP-10), Interleukin-15 (IL-15). Particularly, TNFα and IP-10 even returned inside a physiological range: 5.3 ± 2.7 to 4.2 ± 2.2 pg/mL (P < 0.003) and from 303.7 ± 168.4 to 254.0 ± 151.6 pg/mL (P < 0.024), respectively. Both cytokines showed a weak but significant correlation with parameters of oscillatory flow correction. Finally, three cytokines implicated in repair and remodeling of tissue, Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 and Platelet Derived Growth Factor-BB (PDGF-BB), significantly increased. Our findings are further reinforced by the significant changes of the same cytokines when compared to C group. CONCLUSIONS: The surgical suppression of the oscillatory component of reflux modulates the inflammatory phenotype, suggesting a pivotal role of flow among factors concurring to inflammation in CVD.

Recommendations for multimodal noninvasive and invasive screening for detection of extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency: a position statement of the International Society for Neurovascular Disease.

Under the auspices of the International Society for Neurovascular Disease (ISNVD), four expert panel committees were created from the ISNVD membership between 2011 and 2012 to determine and standardize noninvasive and invasive imaging protocols for detection of extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency (CCSVI). The committees created working groups on color Doppler ultrasound (US), magnetic resonance (MR) imaging, catheter venography (CV), and intravascular US. Each group organized a workshop focused on its assigned imaging modality. Non-ISNVD members from other societies were invited to contribute to the various workshops. More than 60 neurology, radiology, vascular surgery, and interventional radiology experts participated in these workshops and contributed to the development of standardized noninvasive and invasive imaging protocols for the detection of extracranial venous abnormalities indicative of CCSVI. This ISNVD position statement presents the MR imaging and intravascular US protocols for the first time and describes refined color Doppler US and CV protocols. It also emphasizes the need for the use of for noninvasive and invasive multimodal imaging to diagnose adequately and monitor extracranial venous abnormalities indicative of CCSVI for open-label or double-blinded, randomized, controlled studies.

Acute oxygenation changes on ischemic foot of a novel intermittent pneumatic compression device and of an existing sequential device in severe peripheral arterial disease.

BACKGROUND: Intermittent pneumatic compression (IPC) improves haemodynamics in peripheral arterial disease (PAD), but its effects on foot perfusion were scarcely studied. In severe PAD patients we measured the foot oxygenation changes evoked by a novel intermittent IPC device (GP), haemodynamics and compliance to the treatment. Reference values were obtained by a sequential foot-calf device (SFC). METHODS: Twenty ischemic limbs (Ankle-Brachial Index = 0.5 ± 0.2) of 12 PAD patients (7 male, age: 74.5 ± 10.8 y) with an interval of 48 ± 2 hours received a 35 minute treatment in supine position with two IPC devices: i) a Gradient Pump (GP), which slowly inflates a single thigh special sleeve and ii) an SFC (ArtAssist®, ACI Medical, San Marcos, CA, USA), which rapidly inflates two foot-calf sleeves. MAIN OUTCOME MEASURE: changes of oxygenated haemoglobin at foot (HbO2foot) by continuous near-infrared spectroscopy recording and quantified as area-under-curve (AUC) for periods of 5 minutes. Other measures: haemodynamics by echo-colour Doppler (time average velocity (TAV) and blood flow (BF) in the popliteal artery and in the femoral vein), patient compliance by a properly developed form. RESULTS: All patients completed the treatment with GP, 9 with SFC. HbO2foot during the working phase, considered as average value of the 5 minutes periods, increased with GP (AUC 458 ± 600 to 1216 ± 280) and decreased with SFC (AUC 231 ± 946 to -1088 ± 346), significantly for most periods (P < 0.05). The GP treatment was associated to significant haemodynamic changes from baseline to end of the treatment (TAV = 10.2 ± 3.3 to 13.5 ± 5.5 cm/sec, P = 0.004; BF = 452.0 ± 187.2 to 607.9 ± 237.8 ml/sec, P = 0.0001), not observed with SFC (TAV = 11.2 ± 3.4 to 11.8 ± 4.3 cm/sec; BF = 513.8 ± 203.7 to 505.9 ± 166.5 ml/min, P = n.s.). GP obtained a higher score of patient compliance (P < 0.0001). CONCLUSIONS: A novel IPC thigh device, unlike a traditional SFC device, increased foot oxygenation in severe PAD, together with favourable haemodynamic response and high compliance to the treatment under the present experimental conditions.

The sex prevalence of lower limb varicose vein networks.

OBJECTIVE: To determine the sex prevalence of lower limb varicose networks fed by reflux of the great saphenous vein (GSV), anterior accessory saphenous vein (AASV), and small saphenous vein singularly or in combination. METHODS: We scanned by the means of the same color Doppler ultrasound protocol 3000 lower limbs in 1500 consecutive patients, affected by symptomatic chronic venous insufficiency from 2013 to 2023. Limbs with normal venous function, incomplete scans, or that were affected by post-thrombotic syndrome, pelvic reflux, isolated perforator reflux, venous malformation, phlebolymphedema and Clinical, Etiological, Anatomical, Pathophysiological clinical class C5 and C6 were excluded from the final analysis. RESULTS: Overall, 1072 patients-252 (23.5%) males and 820 (76.5%) females (P < .0001) matched for age (P = .692)-were included in the study for a total of 1956 limbs affected by primary chronic venous insufficiency, clinical class C2 to C4. The main finding was the significant prevalence of varicose networks fed by reflux of the AASV alone (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.26-3.06; P = .001) or combined with GSV (OR, 1.84; 95% CI, 1.34-2.52; P = .0002) in females. In contrast, GSV insufficiency alone was significantly prevalent in males (OR, 0.54; 95% CI, 0.43-0.68; P < .0001). No significant sex differences regarding SSV reflux were detected. Moreover, we considered the presence of competent terminal valve (TV+) at the level of the saphenofemoral junction, which resulted more significantly present in female (OR, 1.57; 95% CI, 1.12-2.19; P = .0083); to the contrary incompetent terminal valve (TV-) was more common in males (OR, 0.64; 95% CI, 0.46-0.89; P = .0083). Finally, considering reflux in the AASV territory in the presence of a TV+, a strong prevalence in females was detected (OR, 2.28; 95% CI, 1.48-3.52; P = .0002), whereas males developed reflux along the GSV when a concomitant TV- was present (OR, 0.62; 95% CI, 0.41-0.94; P = .0244). CONCLUSIONS: The analysis of the lower limb varicose networks highlights that reflux along the AASV alone, in presence of a TV+ at the junction or coupled with GSV insufficiency, is more prevalent in females. In contrast, GSV resulted the main trunk feeding varicose veins in males, in particular when a TV- was detected. Our findings suggest that females could be more prone to developing varicose veins with an ascending mechanism, whereas in males the descending one seems to be more common.

Endothelial PDGF-BB produced ex vivo correlates with relevant hemodynamic parameters in patients affected by chronic venous disease.

Surgical specimens of vein were obtained from the tertiary venous network and/or saphenous vein from patients (n=20) affected by chronic venous disease (CVD). Into the venous segments, which subsequently were surgically ablated, the following hemodynamic parameters were assessed by echo-color-doppler (ECD): peak systolic velocity, end diastolic velocity, whose combination allowed the calculation of the resistance index (RI) and the reflux time (RT). Highly purified venous endothelial cell (VEC) cultures derived from venous segments of these CVD patients were then characterized for the profile of cytokines and chemokines released in the culture supernatants. Among the 27 cytokines and chemokines examined, we found a positive and significant correlation (R=0.5; p=0.03) only between the spontaneous release of PDGF-BB by VEC cultures and the RT values of the patients from which the VEC were isolates. In addition, the release of PDGF-BB in the VEC culture supernatants was significantly (p<0.01) increased upon in vitro treatment with recombinant TNF-α. By using pharmacological inhibitors, specific for the main pathways, NF-kB, ERK1/2 and p38 MAPK, activated by exposure of endothelial cells to TNF-α, we found that only NF-kB appeared to be significantly involved in mediating the PDGF-BB induction by TNF-α. Of interest, the release of PDGF-BB in response to the in vitro inflammatory stimulation, maintained a positive and significant correlation with RT (R=0.6; p=0.01), while showing a negative correlation with RI (R=-0.5; p=0.03). The potential implications of our findings for the pathophysiology of CVD are discussed.