Impact of Medicare denials on noninvasive vascular diagnostic testing

AbstractPurpose: The purpose of this study was to evaluate the impact of Medicare coverage limitations and claim denials on noninvasive vascular diagnostic testing. Methods: All Medicare claims for noninvasive vascular diagnostic studies from January 1, 1999, to December 31, 1999, were identified from the hospital billing database according to Current Procedural Terminology codes for carotid artery duplex ultrasound scan, venous duplex ultrasound scan, and lower-extremity arterial Doppler scan. Reasons for Medicare denial of payment for these tests were reviewed and a cost analysis was performed. Results: During the 1-year period, there were 1096 noninvasive vascular diagnostic studies performed on Medicare patients. Of these 1096 tests, 176 (16.1%) were denied by Medicare (19.6% of 408 carotid duplex ultrasound scans, 16.8% of 345 venous duplex ultrasound scans, and 11.1% of 343 lower-extremity arterial Doppler scans). Of the noninvasive vascular tests denied by Medicare, an abnormal result was present in 72.5% of carotid duplex ultrasound scans, 32.8% of venous duplex ultrasound scans, and 78.9% of lower-extremity arterial Doppler scans. Overall, 88.1% of all initially denied claims (N = 176) were ultimately reimbursed by Medicare after resubmission, including 77.1% of the 118 claims denied based on compliance rules for “medical necessity.” Conclusion: Because of coverage limitations, Medicare denials of noninvasive vascular diagnostic tests can lead to potential uncompensated physician and hospital technical fees if denied claims are unrecognized. Vascular laboratories performing these tests need to review compliance with Medicare guidelines. Improvements may need to be made at both the provider and Medicare carrier levels in obtaining reimbursement for appropriately ordered noninvasive vascular diagnostic studies. (J Vasc Surg 2001;34:846-53.

Comparison of axillofemoral and aortofemoral bypass for aortoiliac occlusive disease

AbstractPurpose: A comparison of aortofemoral bypass grafting (AOFBG) and axillofemoral bypass grafting (AXFBG) for occlusive disease performed by the same surgeons during a defined interval forms the basis for this report.Methods: Data regarding all patients who underwent AOFBG or AXFBG for lower-extremity ischemia caused by aortoiliac occlusive disease were prospectively entered into a computerized vascular registry. The decision to perform AOFBG rather than AXFBG was based on assessment of surgical risk and the surgeon's preference. This report describes results for surgical morbidity, mortality, patency, limb salvage, and patient survival for procedures performed from January 1988 through December 1993.Results: We performed 108 AXFBGs and 139 AOFBGs. AXFBG patients were older (mean age, 68 years compared with 58 years for AOFBG, p < 0.001), more often had heart disease (84% compared with 38%, p < 0.001), and more often underwent surgery for limb-salvage indications (80% compared with 42%, p < 0.001). No significant differences were found in operative mortality (AXFBG, 3.4%; AOFBG, <1.0%, p = NS), but major postoperative complications occurred more frequently after AOFBG (AXFBG, 9.2%; AOFBG, 19.4%; p < 0.05). Follow-up ranged from 1 to 83 months (mean, 27 months). Five-year life-table primary patency, limb salvage, and survival rates were 74%, 89%, and 45% for AXFBG and 80%, 79%, and 72% for AOFBG, respectively. Although the patient survival rate was statistically lower with AXFBG, primary patency and limb salvage rates did not differ when compared with AOFBG.Conclusion: When reserved for high-risk patients with limited life expectancy, the patency and limb salvage results of AXFBG are equivalent to those of AOFBG. (J VASC SURG 1996;23:263-71.

Descending thoracic aorta to iliofemoral artery bypass grafting: A role for primary revascularization for aortoiliac occlusive disease?

AbstractPurpose: Bypass grafts that originate from the descending thoracic aorta to the iliac or femoral arteries are well described but are not commonly used as primary procedures, and the long-term results remain unknown. A 15-year experience with 50 descending thoracic aorta to iliofemoral artery bypass grafts for aortoiliac occlusive disease is the basis of this report. Methods: From January 1983 to December 1997, patients who underwent bypass grafting procedures from the descending thoracic aorta to the iliac or femoral arteries were identified. Surgical indications, morbidity and mortality rates, primary and secondary patency rates, limb salvage rates, and survival rates were determined. Results: Fifty descending thoracic aorta to iliofemoral artery bypass grafting procedures were performed—24 (48%) for severe claudication, 22 (44%) for rest pain, and 4 (8%) for ischemic ulceration. A primary procedure was performed in 31 patients (62%) for complete occlusion (21 patients) and severe atherosclerotic disease (10 patients) of the infrarenal aorta. The indications for 19 secondary revascularizations (38%) were prior aortic or extra-anatomic graft failure in 17 cases and aortic graft infection in 2 cases. The follow-up periods ranged from 1 to 150 months (mean, 39 months). The cumulative life-table 5-year primary patency, secondary patency, limb salvage, and survival rates were 79%, 84%, 93%, and 67%, respectively. An improved patency trend was observed for patients who underwent operation for severe claudication as compared with limb-threatening ischemia (92% and 69%; P = .07). However, there was no difference between primary and secondary operations in primary patency rates (81% and 79%; P = NS) or survival rates (72% and 62%; P = NS). Conclusion: Descending thoracic aorta to iliofemoral artery bypass grafting has excellent overall long-term results. These results support its more liberal use for primary revascularization, especially for patients with severe atherosclerotic disease or complete occlusion of the infrarenal aorta. (J Vasc Surg 1999;29:249-58.

Descending thoracic aorta to iliofemoral artery bypass grafting: A role for primary revascularization for aortoiliac occlusive disease?

AbstractPurpose: Bypass grafts that originate from the descending thoracic aorta to the iliac or femoral arteries are well described but are not commonly used as primary procedures, and the long-term results remain unknown. A 15-year experience with 50 descending thoracic aorta to iliofemoral artery bypass grafts for aortoiliac occlusive disease is the basis of this report. Methods: From January 1983 to December 1997, patients who underwent bypass grafting procedures from the descending thoracic aorta to the iliac or femoral arteries were identified. Surgical indications, morbidity and mortality rates, primary and secondary patency rates, limb salvage rates, and survival rates were determined. Results: Fifty descending thoracic aorta to iliofemoral artery bypass grafting procedures were performed—24 (48%) for severe claudication, 22 (44%) for rest pain, and 4 (8%) for ischemic ulceration. A primary procedure was performed in 31 patients (62%) for complete occlusion (21 patients) and severe atherosclerotic disease (10 patients) of the infrarenal aorta. The indications for 19 secondary revascularizations (38%) were prior aortic or extra-anatomic graft failure in 17 cases and aortic graft infection in 2 cases. The follow-up periods ranged from 1 to 150 months (mean, 39 months). The cumulative life-table 5-year primary patency, secondary patency, limb salvage, and survival rates were 79%, 84%, 93%, and 67%, respectively. An improved patency trend was observed for patients who underwent operation for severe claudication as compared with limb-threatening ischemia (92% and 69%; P = .07). However, there was no difference between primary and secondary operations in primary patency rates (81% and 79%; P = NS) or survival rates (72% and 62%; P = NS). Conclusion: Descending thoracic aorta to iliofemoral artery bypass grafting has excellent overall long-term results. These results support its more liberal use for primary revascularization, especially for patients with severe atherosclerotic disease or complete occlusion of the infrarenal aorta. (J Vasc Surg 1999;29:249-58.

Prospective screening for postoperative deep venous thrombosis in patients undergoing infrainguinal revascularization

AbstractPurpose: The incidence of deep venous thrombosis (DVT) in patients undergoing infrainguinal bypass graft procedures has not been well documented, and the need for routine prophylaxis remains controversial. The purpose of this study was to prospectively evaluate the risk of postoperative DVT complicating infrainguinal revascularization. Methods: Seventy-four patients undergoing infrainguinal bypass graft procedures during a 12-month period were prospectively screened for DVT. Bilateral lower extremity venous duplex scan imaging was performed preoperatively and within 1 week and 6 weeks, postoperatively. Routine DVT prophylaxis was not used, with anticoagulation reserved for specific indications. Results: Of the 74 patients screened, three patients (4.1%) had DVT identified on preoperative venous duplex scan imaging and were excluded from the study. Of the remaining 71 patients enrolled, only two patients (2.8%) had postoperative DVT. Postoperative DVT was ipsilateral to the bypass graft extremity in both patients, with involvement of the peroneal vein in one patient and the femoral vein in the other. Although routine prophylaxis was not used, 18 of these patients (25%) were anticoagulated for other indications, with DVT occurring in one patient (5.6%). Of the remaining 53 patients who did not receive postoperative anticoagulation, only one patient (1.8%) had DVT. Conclusions: According to this prospective study, the risk of postoperative DVT in patients undergoing infrainguinal revascularization is low. Routine prophylaxis is not recommended, with postoperative anticoagulation reserved for specific indications. (J Vasc Surg 2000;32:669-75.

The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum

The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE 1) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C2; GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration ≥500 ms, vein diameter ≥3.5 mm) located underneath healed or active ulcers (CEAP class C5-C6; GRADE 2B). We suggest treatment of pelvic congestion syndrome and pelvic varices with coil embolization, plugs, or transcatheter sclerotherapy, used alone or together (GRADE 2B)

Hepatocytes undergo punctuated expansion dynamics from a periportal stem cell niche in normal human liver

Background & Aims: While normal human liver is thought to be generally quiescent, clonal hepatocyte expansions have been observed, though neither their cellular source nor their expansion dynamics have been determined. Knowing the hepatocyte cell of origin, and their subsequent dynamics and trajectory within the human liver will provide an important basis to understand disease-associated dysregulation. Methods: Herein, we use in vivo lineage tracing and methylation sequence analysis to demonstrate normal human hepatocyte ancestry. We exploit next-generation mitochondrial sequencing to determine hepatocyte clonal expansion dynamics across spatially distinct areas of laser-captured, microdissected, clones, in tandem with computational modelling in morphologically normal human liver. Results: Hepatocyte clones and rare SOX9+ hepatocyte progenitors commonly associate with portal tracts and we present evidence that clones can lineage-trace with cholangiocytes, indicating the presence of a bipotential common ancestor at this niche. Within clones, we demonstrate methylation CpG sequence diversity patterns indicative of periportal not pericentral ancestral origins, indicating a portal to central vein expansion trajectory. Using spatial analysis of mitochondrial DNA variants by next-generation sequencing coupled with mathematical modelling and Bayesian inference across the portal-central axis, we demonstrate that patterns of mitochondrial DNA variants reveal large numbers of spatially restricted mutations in conjunction with limited numbers of clonal mutations. Conclusions: These datasets support the existence of a periportal progenitor niche and indicate that clonal patches exhibit punctuated but slow growth, then quiesce, likely due to acute environmental stimuli. These findings crucially contribute to our understanding of hepatocyte dynamics in the normal human liver. Impact and implications: The liver is mainly composed of hepatocytes, but we know little regarding the source of these cells or how they multiply over time within the disease-free human liver. In this study, we determine a source of new hepatocytes by combining many different lab-based methods and computational predictions to show that hepatocytes share a common cell of origin with bile ducts. Both our experimental and computational data also demonstrate hepatocyte clones are likely to expand in slow waves across the liver in a specific trajectory, but often lie dormant for many years. These data show for the first time the expansion dynamics of hepatocytes in normal liver and their cell of origin enabling the accurate measurment of changes to their dynamics that may lead to liver disease. These findings are important for researchers determining cancer risk in human liver

The Efficacy of Generating Three Independent Anti-HIV-1 siRNAs from a Single U6 RNA Pol III-Expressed Long Hairpin RNA

RNA Interference (RNAi) effectors have been used to inhibit rogue RNAs in mammalian cells. However, rapidly evolving sequences such as the human immunodeficiency virus type 1 (HIV-1) require multiple targeting approaches to prevent the emergence of escape variants. Expressed long hairpin RNAs (lhRNAs) have recently been used as a strategy to produce multiple short interfering RNAs (siRNAs) targeted to highly variant sequences. We aimed to characterize the ability of expressed lhRNAs to generate independent siRNAs that silence three non-contiguous HIV-1 sites by designing lhRNAs comprising different combinations of siRNA-encoding sequences. All lhRNAs were capable of silencing individual target sequences. However, silencing efficiency together with concentrations of individual lhRNA-derived siRNAs diminished from the stem base (first position) towards the loop side of the hairpin. Silencing efficacy against HIV-1 was primarily mediated by siRNA sequences located at the base of the stem. Improvements could be made to first and second position siRNAs by adjusting spacing arrangements at their junction, but silencing of third position siRNAs remained largely ineffective. Although lhRNAs offer advantages for combinatorial RNAi, we show that good silencing efficacy across the span of the lhRNA duplex is difficult to achieve with sequences that encode more than two adjacent independent siRNAs