Role of adjunctive surgical therapies during or after Injection PGE-1 infusion therapies (cycles) for relieving the residual symptoms (pain), ulcer healing and limb salvage.

In the past we were doing procedures (operations) which were less often described in the literature as a last resort to save the ischemic limbs in young smokers with occlusion of the superficial femoral and popliteal arteries with no or poor distal runoffs. There were earlier or delayed failures in this group of patients with clinical diagnosis of Buerger’s disease based on the Shionoya criteria.  He have improved the ischemic limb salvage with the improved medical therapies utilizing Intravenous Injection PGE -1 infusions and dual anti platelet drugs given over period of 6 months in monthly cycles.

We are now facing a small but a difficult group of young patients with ischemic limbs (TAO- based on Shionoya criteria) where there is partial relief of the pain symptoms with non-healing or poor healing of toe ulcers. They have atrophy of the calf muscles. The ankle pressures are 30-40 mmHg with portable Doppler probe testing. The ulcers are usually 0.5 cm in diameter with gangrenous margins and dirty pale looking base. Some of them have shown dilated veins in the ischemic leg. They are not active functionally and find it difficult to go for long periods. This group of patients has shown long or short multi segmental arterial occlusive disease at more than 3 places.

Here, in such group of patients we are re-looking at the role of surgical intervention for improvement of the quality of life, healing of ulcers and complete relief of pain. Profundoplasty, sympathectomy, Thrombo-endarterectomy with vein patch or bypass with a vein graft of proximal occlusions are the possibilities. It is well known from the previous studies that intra arterial thrombolytic therapies downsized (limited) the operations and achieved attractive limb salvage rates. We are of the opinion that in similar way, this group of patients with residual symptoms and pain after Injection PGE-1 infusion therapies (6 cycles) may be benefited by the limited surgical therapies based on the angiographic findings.

In the recent past we have performed short segment bypass with vein grafts, limited thrombectomy, lumbar sympathectomy, Profundoplasty as adjunctive procedures to Injection Prostaglandin infusion therapies with relief of symptoms and limb salvage.

Conclusion:  Adjunctive surgical procedures will help a sub group of patients receiving Injection   PGE-1 infusion therapies (6 cycles) with residual ischemia associated symptoms or ulcers. There is a need to characterize such patients and objectively evaluate these selection methods with the help of some kind of clinical score. There is a need to develop a score for selecting the patients for such adjunctive procedures.

Critical limb ischemia (CLI), defined as ischemic rest pain or the presence of a nonhealing arterial ulcer or gangrene, is the most advanced and debilitating form of peripheral artery disease (PAD). An estimated 10% of patients with PAD progress to CLI within 5 years, with the annual incidence of CLI ranging between 500 and 1,000 new cases per 1 million individuals (1). Within 3 months from the time of diagnosis, 9% of CLI patients will die and 12% will require major amputation. One- and 2-year mortality rates of 21% and 31.6% have been reported (1). Collectively, CLI substantially affects patient quality of life and exerts a substantial economic burden to the overall health care system (1,2).

High explosive treatment for ultra Acute Stroke

High explosive treatment for ultra Acute Stroke - is it a hype or hope?

Treatments for acute stroke can be categorized in to four groups. They are 1. Target population based(Ischemic stroke, Intra Cerebral Hemorrhage), 2. Utility ( Proportion of patients who can be treated), 3. magnitude of efficacy and 4.cost.  We can also divide them as High cost therapies and low cost therapies. High cost therapies can be justified of there is high efficacy ( intravenous alteplase, mechanical thrombectomy, hemicraniectomy). Aspirin, the cost therapy typically will have low efficacy. Is it not reasonable to expect and see that medium to high efficacy therapies which are inexpensive are available to our patients.

Intensive blood pressure control has been found to be beneficial in ICH (INTERACT- II trial), but we are not clear if intensive blood pressure is helpful in ischemic stroke patients!

In the recent studies (ENOS trial, RIGHT trial) early GTN therapy has shown benefits in ICH, Ischemic stroke patients. This may change the future of the early stroke management even before the patients are shifted to the hospitals. GTN, the explosive may change the future game plan! Is it a hype or hope? we have to see !! 

Alberta stroke program early CT score ( ASPECTS)

What is Alberta stroke program early CT score?

Dr Owen Kang and Dr Haris Sair et al.

The Alberta stroke programe early CT score (ASPECTS) is a 10-point quantitative topographic CT scan score used in patients with middle cerebral artery (MCA) stroke. Segmental assessment of the MCA vascular territory is made and 1 point is deducted from the initial score of 10 for every region involved:

• caudate
• putamen
• internal capsule
• insular cortex
• M1: "anterior MCA cortex," corresponding to frontal operculum
• M2: "MCA cortex lateral to insular ribbon" corresponding to anterior temporal lobe
• M3: "posterior MCA cortex" corresponding to posterior temporal lobe
• M4: "anterior MCA territory immediately superior to M1"
• M5: "lateral MCA territory immediately superior to M2"
• M6: "posterior MCA territory immediately superior to M3"

Important points

1. the initial paper ¹ specifically referred to the internal capsule only involving the posterior limb, however subsequent articles indicate any portion of the internal capsule may be included
2. M1 to M3 are at the level of the basal ganglia
3. M4 to M6 are at the level of the ventricles immediately above the basal ganglia

Clinical use

An ASPECTS score less than or equal to 7 predicts worse functional outcome at 3 months as well as symptomatic haemorrhage.
According to study done by R.I Aviv et al ³ patients with ASPECTS score less than 8 treated with thrombolysis did not have a good clinical outcome.

Treatment of thromboangiitis obliterans (Buerger's disease) with high-potency vasodilators

Treatment of thromboangiitis obliterans (Buerger's disease) with high-potency vasodilators

David -,JiménezGallo et al

Thromboangiitis obliterans (TAO) or Buerger's disease is a vascular inflammatory thrombotic occlusive and segmental disease affecting distal small and medium-sized arteries of the limbs. Tobacco is the main trigger factor and avoiding it is the main treatment. Frequently, it is necessary to use high-potency vasodilators, such as iloprost, bosentan, sildenafil, or alprostadil, to relieve symptoms and reduce the risk of amputation. Iloprost is the only one that has been shown to be effective in randomized clinical trials. We report the third case of TAO treated with sildenafil and a new case treated with bosentan. This condition can be diagnosed and treated by a dermatologist. We would like to highlight the excellent clinical response despite the fact that patients continued to smoke. This finding may have important therapeutic implications because early treatment may prevent amputation and can be effective even during the process of giving up smoking.

We are expecting more medical therapies in the coming years to compete with the existing endovascular and surgical therapies.

Cochrane Database Syst Rev. 2016 Mar 11;3:CD011033. doi: 10.1002/14651858.CD011033.pub3.

Pharmacological treatment for Buerger's disease.

Cacione DG1, Macedo CR, Baptista-Silva JC.

Author information

Abstract

BACKGROUND:

Buerger's disease (thromboangiitis obliterans) is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small and medium sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Pharmacological treatment is an option for patients with severe complications, such as ischaemic ulcers or rest pain.

OBJECTIVES:

To assess the effectiveness of any pharmacological agent (intravenous or oral) compared with placebo or any otherpharmacological agent in patients with Buerger's disease.

SEARCH METHODS:

The Cochrane Vascular Trials Search Co-ordinator searched their Specialised Register (last searched in April 2015) and the Cochrane Register of Studies (Issue 3, 2015). The review authors searched trial registers and the European grey literature; screened reference lists of relevant studies, and contacted study authors and major pharmaceutical companies.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) involving pharmacological agents used in the treatment of Buerger's disease.

DATA COLLECTION AND ANALYSIS:

Two review authors, independently assessed the studies, extracted data and performed data analysis.

MAIN RESULTS:

Five randomised controlled trials (total 602 participants) compared prostacyclin analogue with placebo, aspirin, or a prostaglandin analogue, and folic acid with placebo. No studies assessed other pharmacological agents such as cilostazol, clopidogrel and pentoxifylline or compared oral versus intravenous prostanoid.Compared with aspirin, intravenous prostacyclin analogue iloprost improved ulcer healing (risk ratio (RR) 2.65; 95% confidence interval (CI) 1.15 to 6.11; 98 participants; one study; moderate quality evidence), and helped to eradicate rest pain after 28 days (RR 2.28; 95% CI 1.48 to 3.52; 133 participants; one study; moderate quality evidence), although amputation rates were similar six months after treatment (RR 0.32; 95% CI 0.09 to 1.15; 95 participants; one study; moderate quality evidence). When comparing prostacyclin (iloprost and clinprost) with prostaglandin (alprostadil) analogues, ulcer healing was similar (RR 1.13; 95% CI 0.76 to 1.69; 89 participants; two studies; I² = 0%; very low quality evidence), as was the eradication of rest pain after 28 days (RR 1.57; 95% CI 0.72 to 3.44; 38 participants; one study; low quality evidence), while amputation rates were not measured. Compared with placebo, the effects of oral prostacyclin analogue iloprost were similar for: healing ischaemic ulcers (iloprost 200 mcg: RR 1.11; 95% CI 0.54 to 2.29; 133 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 0.90; 95% CI 0.42 to 1.93; 135 participants; one study; moderate quality evidence), eradication of rest pain after eight weeks (iloprost 200 mcg: RR 1.14; 95% CI 0.79 to 1.63; 207 participants; one study; moderate quality evidence, and iloprost 400 mcg: RR 1.11; 95% CI 0.77 to 1.59; 201 participants; one study; moderate quality evidence), and amputation rates after six months (iloprost 200 mcg: RR 0.54; 95% CI 0.19 to 1.56; 209 participants; one study, and iloprost 400 mcg: RR 0.42; 95% CI 0.13 to 1.31; 213 participants; one study). When comparing folic acid with placebo in patients with Buerger's disease and hyperhomocysteinaemia, pain scores were similar, there were no new cases of amputation in either group, and ulcer healing was not assessed (very low quality evidence).Treatment side effects such as headaches, flushing or nausea were not associated with treatment interruptions or more serious consequences. Outcomes such as amputation-free survival, walking distance or pain-free walking distance, and ankle brachial index were not assessed by any study.Overall, the quality of the evidence was very low to moderate, with few studies, small numbers of participants, variation in severity of disease of participants between studies and missing information regarding for example baseline tobacco exposure.

AUTHORS' CONCLUSIONS:

Moderate quality evidence suggests that intravenous iloprost (prostacyclin analogue) is more effective than aspirin for eradicating rest pain and healing ischaemic ulcers in Buerger's disease, but oral iloprost is not more effective than placebo. Verylow and low quality evidence suggests there is no difference between prostacyclin (iloprost and clinprost) and the prostaglandin analogue alprostadil for healing ulcers and relieving pain respectively in severe Buerger's disease. Very-low quality evidence suggests there is no difference in pain scores and amputation rates between folic acid and placebo, in people with Buerger's disease and hyperhomocysteinaemia. High quality trials assessing the effectiveness of pharmacological agents (intravenous or oral) in people with Buerger's disease are needed.

Hepatitis C infections in the hospitalized patients requiring the interventions – Concern, attitude and care of the health care workers providing the services, How can we address them?

It is estimated that nearly 100,000 people die annually in India from HCV infection and co-morbidities. Around 25% of 18 million HCV patients in India are infected by Hepatitis-C genotype 1 virus. This has become a concern in many hospitals, health care workers and more so in dialysis centers, trauma care centers and intensive care units, who frequently deal with blood and blood products during the course of the treatments.

Source of Hepatitis C infection

This is a complex issue observed in the state run hospitals with limited resources and at the same time the risks of operating on such patients with chronic hepatitis C infection can’t be ruled and one needs to organize themselves for these special situations with special provisions and protection measures.

“Who would like to get exposed to the risk of acquiring hepatitis C infection while operating on patients with chronic hepatitis C infections in our elective operation theaters?”  Said an anesthetist, defending his stand of cancelling an operation in a government run tertiary care hospital. The patient and the surgeon were left with no other option. The patient was asked to choose another hospital which can take up such operations. The fear of Hepatitis C infection, is significant due to the lack of availability of appropriate and affordable treatment within reach of the hospitals. Similar situation was there in the past for the patients infected with HIV.

This is a complex issue observed in the state run hospitals with limited resources and at the same time the risks of operating on such patients with chronic hepatitis C infection can’t be ruled and one needs to organize themselves for these special situations with special provisions and protection measures.

 

In the recent past the hope of curing hepatitis C infection is on the cards in many countries with introduction of the new drug treatments. Harvoni, the fixed-dose combination of ledipasvir-sofosbuvir of 90mg and 400mg, respectively, is an improved version of Gilead’s Hepatitis-C drug Sovaldi or sofosbuvir, seems to be playing a major role in the coming years. Biocon will be selling the generic Harvoni under brand name CIMIVIR-L. The potential market size for these drugs could be Rs.500 crore or even Rs. 1,000 crores in the foreseeable future. This type of treatment would cost Rs.63 lakhs in USA today for one individual. But the Indian company is determined to supply this medicine at an affordable price (< Rs. 70,000). In the absence of vaccination for the Hepatitis C infection, there should be provision for the supply of these medicines with the help of insurance to the health care workers. Hospital management should take a lead and assure the health care workers that there is support for them in any exposed gets hepatitis C infection during their service.

Pinjala R K

 

Should we worry about the renal function loss in patients undergoing endovascular therapies?

This paper published in Jl of Vascular Surgery, needs attention from all those who would like to do Endovascular procedures for all the vascular lesions in the patients! 

http://www.jvascsurg.org/article/S0741-5214(16)00822-3/abstract

Loss of kidney function in patients with critical limb ischemia treated endovascularly or surgically

Tim A. Sigterman, MD et al

Background  Acute kidney injury after the administration of contrast material during endovascular procedures for peripheral arterial disease generally recovers with supportive treatment. However, long-term effects of endovascular procedures for critical limb ischemia on renal function remain to be investigated.Methods : This retrospective observational cohort study included all patients who newly presented to the vascular surgery outpatient clinic with Rutherford class 4 to class 6 peripheral arterial disease and who were treated with either endovascular or surgical interventions. Changes in estimated glomerular filtration rate (eGFR) after 1 year were compared between the two types of intervention. Multivariate linear regression analysis was done to correct for potential confounders.Results: One year after treatment, eGFR was reduced by 15.0 mL/min (95% confidence interval [CI], 13.1-17.0; P < .001) after endovascular interventions (n = 209) and by 7.6 mL/min (95% CI, 5.1-10.0; P < .001) after surgical therapy (n = 81). Although eGFR rates decreased in both groups, loss of renal function was significantly greater in patients after endovascular interventions (P < .001). Furthermore, 77% of patients receiving endovascular interventions experienced fast renal decline (defined as >4 mL/min loss of eGFR within 1 year) compared with 54% of patients treated surgically (P < .001). After correction for potential confounders, endovascular intervention was associated with 7.4 mL/min (95% CI, 5.4-9.3; P < .001) greater loss of renal function compared with patients treated surgically.Conclusions:  Endovascular procedures for critical limb ischemia are associated with clinically relevant permanent long-term loss of kidney function. This loss of renal function is greater than in comparable patients who were treated with open surgery.

Supervised exercise program for the claudicants

Claudication is the common symptom in peripheral arterial disease. It can be progressive or stable. In those patients with stable claudication medical managements and supervised exercise programs may be helpful. But in our hospitals there are very few such programs encouraging the patients to follow these practices. Doctors tell their patients about the benefits of regular walking, but rarely they are able supervise such measures. Even in the physiotherapy departments there is no such provision in many hospitals. Very few trials are conducted in India in this direction. The Angioplasty and Stenting of superficial femoral artery, popliteal artery is advocated in some places to save the limbs. Open surgery is performed to bypass the occluded FP segments in some centers.

Common site of Claudication in Femoral-Popliteal disease

A systematic review of the uptake and adherence rates to supervised exercise programmes in patients with intermittent claudication was conducted by A.E. Harwood et al from Hull Royal infirmary and published in Annals of vascular surgery.  
They said that reporting of SEP trials was poor with regard to the numbers of subjects screened and reasons for exclusions. Only approximately 1 in 3 screened IC patients was suitable for and willing to undertake SEP. Levels of adherence to SEPs and definitions of satisfactory adherence were also lacking in the majority of the current literature. Current clinical guidelines based upon this evidence base may not be applicable to the majority of IC patients and changes to SEPs may be needed to encourage/retain participants.
This type of papers should encourage us to do more detailed study on supervised exercise programs in Indian hospitals. This may help our patients and reduce burden of angioplasty or bypass surgery in Peripheral arterial disease patients. 

Reference
http://www.annalsofvascularsurgery.com/article/S0890-5096(16)30174-1/abstract 

Osteosarcoma

It originates more frequently in the metaphyseal region of tubular long bones, with 42% occurring in the femur, 19% in the tibia, and 10% in the humerus. About 8% of all cases occur in the skull and jaw, and another 8% in the pelvis.

CT Angiogram in Sarcoma patient

The impact of chronic renal insufficiency on vascular surgery patient outcomes

Renal insufficiency is associated with an increased incidence of poor outcomes, including cardiovascular events and death, in the general population. Renal dysfunction appears to have a particularly negative impact in patients undergoing vascular surgery and endovascular therapy. Although the exact mechanism is unknown, increased levels of inflammatory and biochemical modulators associated with adverse cardiovascular outcomes, as well as endothelial dysfunction, appear to play a role in the association between renal insufficiency and adverse outcomes. Outcomes after the surgical and endovascular treatment of abdominal aortic aneurysms, carotid disease, and peripheral arterial disease are all negatively affected by renal insufficiency. Patients with renal dysfunction may warrant intervention for the treatment of critical limb ischemia and symptomatic carotid stenosis, given the comparatively worse outcomes associated with medical management. Open repair of aortic aneurysms and carotid intervention for asymptomatic disease in patients with severe renal dysfunction should be performed with significant caution, as the risks of repair may outweigh the benefits in this population. Further study is needed to better delineate the risks of medical management for these conditions in patients with coexisting severe renal dysfunction.

Lastly, current guidelines for the management of vascular diseases, including objective performance goals for critical limb ischemia, are likely not applicable in patients with severe renal insufficiency.

Stages of chronic kidney disease.

CKD stage	Description	GFR (mL/min/1.73 m2)
I	Normal or mildly decreased GFR	≥90
II	Normal or mildly decreased GFR	60−89
III	Moderately decreased GFR	30−59
IV	Severely decreased GFR	15−29
V	Severely decreased GFR	<15 td="">

----------------------------------------------

Abbreviations: CKD, chronic kidney disease; GFR, glomerular filtration rate.

http://www.semvascsurg.com/article/S0895-7967%2815%2900007-1/fulltext 

Abdominal Aortic Aneurysm Repair by Principle of Exclusion and Aortic Bypass: Single Centre Experience

Abdominal Aortic Aneurysm Repair by Principle of Exclusion and Aortic Bypass: Single Centre Experience

Sandeep M* and Ramakrishna P

Department of Vascular Surgery, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, India

http://www.esciencecentral.org/journals/abdominal-aortic-aneurysm-repair-by-principle-of-exclusion-and-aorticbypass-single-centre-experience-2329-6925-1000253.pdf

Abstract
Purpose: Non-respective treatment of the abdominal aortic aneurysm by proximal and distal ligation of the aneurysm sac (exclusion) combined with aortic bypass known as Debakey Procedure has been previously reported. A 2 year experience with 10 patients undergoing this procedure was reviewed.
Methods: From 2010 to 2012, 10 patients of abdominal aortic aneurysm underwent repair with the retroperitoneal exclusion technique. Preoperative morbidity and mortality, blood loss and transfusion requirements, naturally of the excluded aneurysm sac were all assessed.
Results: The operative mortality rate for patients undergoing exclusion and bypass was 10% (one out of 10 patients). The incidence of nonfatal preoperative complications was 5%. Blood loss requiring transfusion in the preoperative period measured 600 mL to 900 mL on an average. On follow-up, only one out of 10 patients was found to have patent aneurysm sacs as detected by duplex examination which required surgical Intervention. No cases of graft infection or Aorto-enteric fistula have been noted.
Conclusion: Retroperitoneal exclusion and bypass is a viable alternative to traditional open endoaneurysmorraphy in surgery for abdominal aortic aneurysm. Most excluded aneurysm sacs have thrombosis without any long or short-term complications; however, in a small number of patients delayed rupture of patent aneurysm occurs, thus emphasizing the need for diligent follow-up and appropriate intervention.

Incremental Health Care Burden of Bleeding Among Patients with Venous Thromboembolism in the United States.

J Manag Care Spec Pharm. 2015 Oct;21(10):965-72. Amin A¹, Bruno A, Trocio J, Lin J, Lingohr-Smith M.¹University of California, Irvine, UCIMC, 101 The City Drive South, Bldg. 58, Rm 110, ZC-4076H, Mail Code: 4076, Irvine, CA 92868. anamin@uci.edu.

The health care and economic burden of venous thromboembolism (VTE) has been evaluated in regard to acute VTE, VTE recurrence, and some VTE complications, such as postthrombotic syndrome, but the cost burden attributed to bleedings is not well understood.

OBJECTIVE: To evaluate health care resource utilization and costs associated with major bleeding (MB) and clinically relevant nonmajor bleeding (CRNMB) among a large U.S. commercially and Medicare-insured population with VTE.

METHODS: Patients (≥ 18 years of age, continuously insured) with a diagnosis of VTE between January 1, 2008, and December 31, 2011, were identified from the Truven Health Analytics Commercial and Medicare MarketScan databases. Patients who did not have any bleedings during the study period were grouped into a no-bleedings cohort and a random date after VTE diagnosis was selected as the index date. VTE patients who experienced MB within 1 year of the initial VTE diagnosis were grouped into a MB cohort, and patients without MB but with CRNMB were grouped into a CRNMB cohort. Baseline patient demographics and clinical characteristics were determined for study cohorts. All-cause and bleeding-related health care resource utilization and costs (inflation adjusted to 2013 level) during a 12-month follow-up period after the index date of the initial bleeding event were measured and compared. Descriptive statistics were used to evaluate differences in demographics, clinical characteristics, and unadjusted health care resource utilization and costs of patient cohorts. Multivariable generalized linear models were used to evaluate incremental health care costs of bleedings after adjusting for key patient characteristics.  

RESULTS: Among the 112,885 patients identified with a VTE diagnosis, 14% (n = 15,897) had MB and 14% (n = 15,842) had CRNMB; 72% (n = 81,146) had neither of these events occur during the study period. The mean ages of the MB and CRNMB cohorts were both 63.6 years, while the mean age of the no-bleedings cohort was significantly lower at 59.6 years (P  less than  0.001). Mean Charlson Comorbidity Index scores were highest for the MB cohort (3.2), followed by those of the CRNMB cohort (2.5) and the no-bleedings cohort (1.6). The MB cohort had the greatest proportion of patients with an initial VTE event of pulmonary embolism only (23.5%), followed by that of the CRNMB cohort (20.2%), and the no-bleedings cohort (16.7%). For MB and CRNMB cohorts, the total mean bleeding-related inpatient and outpatient costs during the follow-up period were $49,779 (SE = $820) and $2,187 ($89), respectively. After adjustment for key patient characteristics, the estimated mean differences in total bleeding-related medical costs were $45,367 ($1,853) for patients with MB and $2,140 ($88) for patients with CRNMB versus patients with no bleedings.

CONCLUSIONS: Among patients with VTE diagnosis in the United States, approximately 28% have a bleeding event within 1 year of VTE diagnosis, and about half of these patients experience MB. Patients with MB have greatly elevated health care costs.

Is there any impact of regular physical activity on weekly warfarin dose requirement? Yes there is !!

http://link.springer.com/article/10.1007/s11239-015-1248-9 

Warfarin is an oral anticoagulant agent with a narrow therapeutic index. There is a marked inter- and intra-patient variability in warfarin dose requirement. All factors influencing warfarin response are not known and this study aims to evaluate if regular physical activity (RPA) is a determining factor. RPA level was collected with the Stanford Brief Activity Survey in 1064 incident warfarin users, as part of the Quebec Warfarin Cohort (QWC), and with the Global Physical Activity Questionnaire in 618 patients from the Montreal Heart Institute (MHI) Biobank. Linear regression was performed to model relationship of warfarin dose after 3 months of therapy in the QWC with RPA, while controlling for height, weight, age, CYP2C9 (*2 and *3 alleles) and VKORC1 (*2 allele) genotype. Warfarin dose of prevalent users was modeled in the MHI Biobank for replication. A higher level of physical activity was associated with higher doses of warfarin in both cohorts. In the QWC, physical activity could explain 5.4 % (P < 0.001) and 0.9 % (P = 3.23 × 10−5) of variance in dose, in univariate and multivariable models, respectively. Similarly, RPA was found to be associated with 1.7 % (P = 0.0012) and 0.5 % (P = 0.0391) of inter-individual variability in warfarin dose requirement before and after adjustment for other covariables, respectively. 
RPA is associated with higher warfarin dose requirement. The relevance of clinical recommendations on RPA to maintain a steady response to warfarin should be assessed in further studies.

Conventional surgery, Endovenous laser ablation and Ultrasound-guided foam sclerotherapy in patients with great saphenous varicose veins, which is better?

Br J Surg. 2015 Sep;102(10):1184-94. doi: 10.1002/bjs.9867. Epub 2015 Jul 1.

Five-year results of a randomized clinical trial of conventional surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy in patients with great saphenous varicose veins.

van der Velden SK¹, Biemans AA², De Maeseneer MG^1,3, Kockaert MA¹, Cuypers PW⁴, Hollestein LM¹, Neumann HA¹, Nijsten T¹, van den Bos RR¹.

BACKGROUND:A variety of techniques exist for the treatment of patients with great saphenous vein (GSV) varicosities. Few data exist on the long-term outcomes of these interventions.

METHODS:Patients undergoing conventional surgery, endovenous laser ablation (EVLA) and ultrasound-guided foam sclerotherapy (UGFS) for GSV varicose veins were followed up for 5 years. Primary outcome was obliteration or absence of the treated GSV segment; secondary outcomes were absence of GSV reflux, and change in Chronic Venous Insufficiency quality-of-life Questionnaire (CIVIQ) and EuroQol - 5D (EQ-5D™) scores.

RESULTS: A total of 224 legs were included (69 conventional surgery, 78 EVLA, 77 UGFS), 193 (86.2 per cent) of which were evaluated at final follow-up. At 5 years, Kaplan-Meier estimates of obliteration or absence of the GSV were 85 (95 per cent c.i. 75 to 92), 77 (66 to 86) and 23 (14 to 33) per cent in the conventional surgery, EVLA and UGFS groups respectively. Absence of above-knee GSV reflux was found in 85 (73 to 92), 82 (72 to 90) and 41 (30 to 53) per cent respectively. CIVIQ scores deteriorated over time in patients in the UGFS group (0.98 increase per year, 95 per cent c.i. 0.16 to 1.79), and were significantly worse than those in the EVLA group (-0.44 decrease per year, 95 per cent c.i. -1.22 to 0.35) (P = 0.013). CIVIQ scores for the conventional surgery group did not differ from those in the EVLA and UGFS groups (0.44 increase per year, 95 per cent c.i. -0.41 to 1.29). EQ-5D™ scores improved equally in all groups.

CONCLUSION: EVLA and conventional surgery were more effective than UGFS in obliterating the GSV 5 years after intervention. UGFS was associated with substantial rates of GSV reflux and inferior CIVIQ scores compared with EVLA and conventional surgery.

REGISTRATION NUMBER: NCT00529672 (http://www.clinicaltrials.gov).

Combined assessment of thrombotic and haemorrhagic risk in acute medical patients

It is important to assess thrombosis risk and hemorrhage risk in our patients !

Online Supplementary Material

M. La Regina (1), F. Orlandini (1), F. Marchini (1), A. Marinaro (1), R. Bonacci (1), P. Bonanni (1), F. Corsini (1), A. M. Ceraudo (1), E. Pacetti (1), L. Scuotri (1), D. Costabile (2), F. Dentali

(1) Department of Internal Medicine, Ligurian East Hospital, La Spezia, Italy; (2) Elco S. r. l., Cairo Montenotte (Savona), Italy

venous thromboembolism, internal medicine, anticoagulants, prophylaxis, haemorrhage

Acute medical patients have a high risk of venous thromboembolic events (VTE). Unfortunately, the fear of bleeding complications limits the use of antithrombotic prophylaxis in this setting. To stratify the VTE and haemorrhagic risk, two clinical scores (PADUA, IMPROVE) have recently been developed. However, it is not clear how many patients have a concomitant high VTE and haemorrhagic risk and what is the use of prophylaxis in this situation. To clarify these issues we performed a prospective cohort study enrolling consecutive patients admitted to internal medicine. Patients admitted to internal medicine (January to December 2013) were included. VTE and haemorrhagic risk were evaluated in all the included patients. Use and type of anti-thrombotic prophylaxis was recorded. A total of 1761 patients (mean age 77.6 years) were enrolled; 76.8 % (95 % CI 74.7–78.7) were at high VTE risk and 11.9 % (95 % CI 10.4–13.5) were at high haemorrhagic risk. Anti-thrombotic prophylaxis was used in 80.5 % of patients at high VTE risk and in 6.5 % at low VTE risk (p< 0.001), and in 16.6 % at high haemorrhagic risk and in 72.5 % at low haemorrhagic risk (p< 0.001). Prophylaxis was used in 20.4 % at both high VTE and haemorrhagic risk and in 88.9 % at high VTE risk but low haemorrhagic risk. At multivariate-analysis, use of prophylaxis appeared highly influenced by the VTE risk (OR 68.2, 95 % CI 43.1 - 108.0). In conclusion, many patients admitted to internal medicine were at high risk of VTE. Since almost 90 % of them were at low haemorrhagic risk, pharmacological prophylaxis may be safely prescribed in most of these patients.

Intra-arterial Therapy in the Early Treatment of Acute Ischaemic Stroke

http://www.ejves.com/article/S1078-5884(15)00575-4/abstract

Intra-arterial Therapy in the Early Treatment of Acute Ischaemic Stroke

In 1995, intravenously administered recombinant tissue-type plasminogen activator (rtPA) was demonstrated to be effective as a treatment for acute ischaemic stroke provided it was commenced within 3 hours of stroke onset.1 In 2008, the ECASS-2 trial demonstrated that the time window for intravenous thrombolysis could be increased to 4.5 hours.2 More recently, intra-arterial thrombectomy (IAT), in addition to intravenous rtPA, has been shown to be highly beneficial when administered within 6 hours after acute stroke onset in six randomized clinical trials.

The introduction of IAT may also increase the need for expedited carotid interventions such as endarterectomy or stenting. It may be challenging for interventionists to stent a severe stenosis of the extracranial carotid artery at the same time as they treat an occluded intracranial artery. From a pragmatic point of view, this may seem a good approach, but it is unknown if the patient will benefit from a simultaneous procedure, or if it would be better to perform deferred carotid surgery after a few days. In the Mr Clean study, additional carotid interventions were performed in one out of eight patients (13%) who were treated with thrombolysis. It is well known that carotid endarterectomy should be performed within a few days after onset of a TIA or minor disabling stroke, but we know little about the safety of this procedure in patients with a severe carotid artery stenosis who only very recently suffered from a major stroke that was successfully treated with IAT. Expedited carotid surgery within 24 hours of lysis completion has shown promising results, but more data on stenting versus surgery and especially the optimal timing are still required.

In summary, 2015 will be remembered as the year in which IAT was established as a highly beneficial therapy for patients with acute ischaemic stroke affecting the anterior circulation. Stroke teams should now move to implement IAT in their treatment strategies and adapt their organization accordingly. More knowledge about the best indications for IAT and the need for additional carotid interventions will be forthcoming in the future.