Long-term outcome after nonsurgical management of Paget-Schroetter syndrome.

OBJECTIVE: Paget-Schroetter syndrome (PSS) is an uncommon disease with potentially debilitating long-term effects. The optimal therapy for PSS is unclear, and the role of surgical decompression of the thoracic outlet is still being questioned. In this study, we present long-term results of patients treated with catheter-directed thrombolysis (CDT) and anticoagulation without surgical management. METHODS: This is a retrospective case series of all patients who previously underwent treatment of PSS in our institution between the years 2007 and 2019. Patients were evaluated for clinical signs of post-thrombotic syndrome (PTS) using a modified Villalta scoring scale, including measurements of the circumference of the treated and untreated arms. Duplex ultrasound examination of the treated vein was performed, and quality of life was evaluated using the shortened Disabilities of the Arm, Shoulder, and Hand questionnaire. RESULTS: Eighteen consecutive patients previously treated for PSS with CDT and anticoagulation compose the cohort of this study. None underwent surgical thoracic outlet decompression. All were contacted and invited for clinical and ultrasound evaluation. Follow-up was available for all patients. Mean age at diagnosis was 29 years (range, 16-46 years), and 15 (79%) were male. Mean time from the index event to the follow-up clinic visit was 109 months (range, 37-176 months). Patients were treated with anticoagulation for a mean period of 26 months (range, 6-120 months). Seventeen patients (94%) had a Villalta score of 0 to 3, consistent with nonexistence of PTS. Fourteen patients (78%) were completely asymptomatic. Seven patients (39%) had no difference in arm circumference. A difference in arm circumference between the treated arm and the healthy arm of 1 cm and 2 cm was seen in nine (50%) and two (11%) patients, respectively. Based on the shortened Disabilities of the Arm, Shoulder, and Hand score, none of the patients suffered from impaired quality of life. Duplex ultrasound scanning of the affected veins was performed on 16 of the 18 patients (89%). The vein appeared patent in all examined patients. In three patients, the wall of the examined vein was thickened and irregular. CONCLUSIONS: This study suggests that PSS patients can be treated with anticoagulation and CDT alone, without the need for surgical thoracic outlet decompression. This is based on long-term follow-up of these patients objectively evaluated by means of valid scoring systems. These findings suggest that symptoms or signs of PTS rarely develop, the patients do not suffer from impaired quality of life, and patency of the diseased vein is commonly maintained.

Angiotensin 1-7, but not the thrombin-cleaved osteopontin C-terminal fragment, attenuates osteopontin-mediated macrophage-induced endothelial-cell inflammation.

OBJECTIVE AND DESIGN: Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1-7. MATERIAL AND SUBJECTS: Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages. TREATMENT: Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1-7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1-7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation. METHODS: Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay. RESULTS: Conditioned media of macrophages treated with OPN-C induced hcECs' NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1-7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines. CONCLUSIONS: OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1-7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.

Low Osteopontin N-Terminal Fragment and Carotid Plaque Stability Associated with Statin or Antiplatelet Therapy.

INTRODUCTION: Full-length osteopontin (OPN-FL), whose levels are elevated in association with atherosclerosis, is cleaved by thrombin, resulting in the formation of a putatively biologically-active N-terminal cleavage product (OPNN). This study addresses the hypothesis that statin and antiplatelet therapy in hypertensive patients specifically reduces OPN-N, rather than OPN-FL, in carotid plaques. METHODS: Seventy-four carotid plaques were collected from patients who underwent carotid endarterectomy (CEA). Plaque tissue was used to measure OPN proteins and for histological and immunohistochemical characterization. RESULTS: There were 22 statin-negative and 52 statin-treated patients. In the carotid plaque, immunohistochemical staining for macrophages was higher in statin-negative vs. statin-treated patients (high CD68 immunostaining was in 61.9 vs. 28.6%, p=.03, respectively). OPN-FL staining had a similar trend, but without statistical significance (78.7 vs. 47.8%, p=.08, respectively). Western blot analysis of plaque OPN-FL showed that statin treatment was not associated with significant alteration of its abundance, but with a significantly lower plaque content of OPN-N [median 0.08 (IQR 0.05-1.01) vs. 0.81 (IQR 0.27-2.86), respectively, p=.015]. Comparable pattern of association between OPN proteins and antiplatelet therapy was found: the abundance of OPN-FL was not different in plaques from untreated or treated patients, while the abundance of OPN-N was significantly reduced in antiplatelet treated vs. non-treated patients [0.08, (IQR 0.05-0.66) vs. 0.89, (IQR 0.13-1.94), p=0.004]. CONCLUSION: The effect of anti-atherosclerotic treatment on carotid plaques of hypertensive patients more readily associates with OPN-N than with OPN-FL expression, suggesting that anti-atherosclerotic treatment including statins and antiplatelet drugs modulates the "OPN system".

Does percutaneous transluminal renal artery angioplasty improve blood pressure control and renal function in patients with atherosclerotic renal artery stenosis?

BACKGROUND: Percutaneous angioplasty (PTA) and stenting is an established procedure for the treatment of hypertension caused by atherosclerotic renal artery stenosis. However recently, the decision whether or notto perform this procedure has raised considerable debate. OBJECTIVES: To examine the association between the basic clinical and radiological characteristics of candidates for renal artery PTA and the clinical outcome of the procedure in terms of improvement of blood pressure control and renal function. METHODS: We conducted a retrospective cohort study of all patients who underwent percutaneous transluminal renal artery angioplasty (PTRA) and stent implantation in a tertiary medical center during the period 2000-2007. The clinical and radiological data were extracted from the medical file of each patient. Blood pressure measurements and creatinine level were recorded before the procedure and 1 month, 6 months, 12 months and 18 months after PTRA. RESULTS: Thirty-two patients were included in the final statistical analysis. The mean age of the study population was 66.6 +/- 8.8 years old and 75% were men. There was a significant reduction in both systolic and diastolic blood pressure 1 month after the procedure: 160.5 +/- 24.7 vs. 141.8 +/- 23.6 mmHg and 83.8 +/- 12.9 vs. 68.8 +/- 11.8 mmHg respectively (P < 0.001). The reduction in blood pressure was constant throughout the follow-up period and was evident 18 months after the procedure: 160.5 +/- 24.7 vs. 135.0 +/- 35.1 mmHg and 83.8 +/- 12.9 vs. 71.3 +/- 16.5 mmHg respectively (P < 0.001). However, no improvement in renal function was observed at any time during the follow-up period. We could not demonstrate an association between clinical or radiological features and the clinical outcome after PTRA. CONCLUSIONS: Our findings show that PTRA can be considered an effective procedure for improving blood pressure control in patients with atherosclerotic renal artery stenosis (ARAS) and resistant hypertension. This research, together with previous studies, strengthens the knowledge that the decline in glomerular filtration rate seen in many patients with ARAS is non-reversible and is not improved by PTRA.

Blood-brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome.

Cerebral hyperperfusion syndrome (CHS) may occur as a severe complication following surgical treatment of carotid stenosis. However, the mechanism inducing neurological symptoms in CHS remains unknown. We describe a patient with CHS presenting with seizures 24 h following carotid endarterectomy. Imaging demonstrated early ipsilateral blood-brain barrier (BBB) breakdown with electroencephalographic evidence of cortical dysfunction preceding brain edema. Using in vitro experiments on rat cortical tissue, we show that direct exposure of isolated brain slices to a serum-like medium induces spontaneous epileptiform activity, and that neuronal dysfunction is triggered by albumin. We propose BBB breakdown and subsequent albumin extravasation as a novel pathogenic mechanism underlying CHS and a potential target for therapy.

An examination of the Medicaid undercount in the current population survey: preliminary results from record linking.

OBJECTIVE: To assess reasons why survey estimates of Medicaid enrollment are 43 percent lower than raw Medicaid program enrollment counts (i.e., "Medicaid undercount"). DATA SOURCES: Linked 2000-2002 Medicaid Statistical Information System (MSIS) and the 2001-2002 Current Population Survey (CPS). DATA COLLECTION METHODS: Centers for Medicare and Medicaid Services provided the Census Bureau with its MSIS file. The Census Bureau linked the MSIS to the CPS data within its secure data analysis facilities. STUDY DESIGN: We analyzed how often Medicaid enrollees incorrectly answer the CPS health insurance item and imperfect concept alignment (e.g., inclusion in the MSIS of people who are not included in the CPS sample frame and people who were enrolled in Medicaid in more than one state during the year). PRINCIPAL FINDINGS: The extent to which the Medicaid enrollee data were adjusted for imperfect concept alignment reduces the raw Medicaid undercount considerably (by 12 percentage points). However, survey response errors play an even larger role with 43 percent of Medicaid enrollees answering the CPS as though they were not enrolled and 17 percent reported being uninsured. CONCLUSIONS: The CPS is widely used for health policy analysis but is a poor measure of Medicaid enrollment at any time during the year because many people who are enrolled in Medicaid fail to report it and may be incorrectly coded as being uninsured. This discrepancy should be considered when using the CPS for policy research.