Can we treat the Aortic Aneurysms medically?

Abdominal aortic aneurysms (AAA) continue to provide an intractable clinical problem. As a disease that affects nearly 10% of the elderly population and claims over 15,000 lives/yr (USA), it is remarkable that treatment of a ruptured AAA is still associated with high mortality rates (in excess of 80%). Many would argue that physicians remain largely incapable of altering the natural history of this disease, despite our growing understanding of the pathophysiology of the vascular lesion. Several promising therapies, including statins, β-blockers, and antibiotics, have all failed to conclusively improve outcomes in large clinical trials, and no medicine is currently approved to treat AAA formation. In clinical management of Aortic Aneurysms, doctors and patients are often faced with the important decision of whether to perform invasive repair or to manage the condition conservatively. The mortality rate associated with reparative surgery has been reported to be as high as 5.5%.Current guidelines recommend endovascular repair or surgery if the aortic diameter exceeds 5.5 cm and the performance of anatomic imaging every 3 to 6 months for aneurysms above 4 cm. If growth is observed to exceed 1 cm per year in smaller aneurysms, surgical repair is also recommended. However, individual risk is also influenced by gender, age, smoking, and co-morbidities, but its assessment is rarely easy because reliable data regarding how best to evaluate these variables are not readily available. This situation often leaves one with a difficult decision, and many patients are unnecessarily exposed to the risks of reparative surgery when their aneurysm might never have ruptured if left untreated.
Aneurysms are complex entities that differ physiologically from stenotic and atherosclerotic vascular lesions. Although atheromas are dominated by neointimal proliferation and foam cell generation, the AAA is defined by the progressive loss of extracellular matrix and medial degeneration. Macrophages are recruited to the involved vessel in both conditions, but have differing roles in each case. Unlike the subendothelial lipid-laden cells of the fatty streak, macrophages of the abdominal aneurysm accumulate in the medial layer where they present antigens to other leukocytes, secrete collagenases, and elaborate proinflammatory cytokines and chemoattractants. Ultimately, they play a role in progressive aneurysmal dilation and clinical presentation. Novel therapies that can reverse this pathological course are eagerly sought.
A number of studies in patients have suggested that doxycycline can inhibit MMPs in aneurysm tissue. Curci et al66 treated a series of patients with a 3-week course of doxycycline before open aneurysm repair. Tissue levels of MMP-9 were significantly reduced by doxycycline compared with untreated patients. Baxter et al showed in a small series of 36 patients on a 6-month course of doxycycline that plasma MMP-9 levels decreased significantly compared with baseline levels. This work has been followed by a small, prospective, randomized trial of doxycycline in which 32 patients were randomized, with 17 receiving doxycycline (150 mg/d) for 3 months. Patients were followed up for 18 months. C pneumoniae titers were assessed but found not to be affected by doxycycline treatment. The calculated growth rate at the end of the 18-month period of observation was 1.5 mm per year in the doxycycline-treated group versus 3.0 mm per year in the placebo-treated group. This difference did not achieve statistical significance, but the 6- and 12-month time periods did show a significant difference in favor of doxycycline treatment. Level B evidence (from small randomized trials) suggests that roxithromycin or doxycycline will decrease the rate of aneurysm expansion.
A small study by Lindholt et al suggested that serological evidence of a C pneumoniae infection was associated with an increased rate of aneurysm expansion. This led to a randomized clinical trial in which 43 patients received a 1-month course of roxithromycin, whereas 49 patients received placebo.60 Patients in the treatment arm had an expansion rate at the end of the study of 1.56 mm per year compared with a rate of 2.75 mm per year in the placebo-treated group. The inhibition was greater in the first year than the second year. The study did not clarify the mechanism of effect because there was no correlation between Chlamydia titers and roxithromycin ability to inhibit aneurysm expansion.
We need more medical therapies which can alter the natural course of the small aneurysms and prevent the rupture of these Aortic aneurysms which are diagnosed when they are small and note taken up for the interventions.

Risk assessment for recurrent venous thrombosis

(Number of risk factors identified by laboratory screening for thrombophilia in 158 patients without cancer with two episodes of unprovoked venous thrombosis, 3 weeks after the incident event, patients were screened for deficiency of antithrombin, protein C, or protein S; presence of lupus anticoagulant, factor V Leiden, factor II G20210A; and high concentrations of homocysteine, factor VIII, or factor IX.)

Recurrent Thrombosis is going to increase the morbidity and mortality. If there are two episodes of unprovoked DVT  without cancer, we can expect that there is some kind of hypercoagulable condition with one or more risk factors.

FIELD study - Can we reduce the amputations in Diabetic population with Fenofibrate?

Diabetes mellitus is the leading cause of non-traumatic lower-extremity amputations in the developed world. In the USA in 2001, at least one amputation due to diabetes occurred every 2 h, with an annual cost exceeding US$1·6 billion.Despite rigorous management of reversible factors, probably around one in ten patients with diabetes will eventually need at least one amputation. Neither control of glycaemia or blood pressure nor lowering of cholesterol has prevented the risk of amputation, underscoring the importance of assessing the management of other potential risk factors. Any further therapeutic option to prevent the morbidity and mortality associated with amputation would be highly desirable. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, 9795 patients aged 50—75 years with type 2 diabetes were randomly assigned by computer-generated randomisation sequence to receive fenofibrate 200 mg per day (n=4895) or matching placebo (n=4900) for 5 years' duration. Information about non-traumatic amputation—a prespecified tertiary endpoint of the study—was routinely gathered.The risks of first amputation (45 vs 70 events; hazard ratio [HR] 0·64, 95% CI 0·44—0·94; p=0·02) and minor amputation events without known large-vessel disease (18 vs 34 events; 0·53, 0·30—0·94; p=0·027) were lower for patients assigned to fenofibrate than for patients assigned to placebo, with no difference between groups in risk of major amputations (24 vs 26 events; 0·93, 0·53—1·62; p=0·79)

In POPADAD study, it was found that Aspirin is ineffective in Diabetics with Asymptomatic Peripheral Vascular Disease for primary prophylaxis! (BMJ 2008)

Peripheral arterial disease patients have an increased risk of subsequent myocardial infarction and stroke and are six times more likely to die from cardiovascular disease within10 years than patients without peripheral arterial disease. Patients with peripheral arterial disease have a 15 year accrued survival rate of about 22% compared with a survival rate of 78% in patients without such disease. So, there is always a question about beneficial effect and safety in giving Aspirin in the asymptomatic PAD patients to prevent the CV complications!

After this POPADAD study a question was asked as to whether these diabetic patients were at sufficient risk, in terms of peripheral arterial disease, as the cut-off point of an ankle brachial pressure index of 0.99 or less is higher than that used to define peripheral arterial disease in the population (<0.9). A subgroup analysis did not, however, find evidence of a difference in effect of aspirin between those with an index of 0.91-0.99 and those below this level.
Furthermore, one of the current major interventions in the specialty of diabetes mellitus is statin therapy. Calculations by two of the centres (DM and CK) in over 10 000 people with diabetes showed a mean total cholesterol level of 6.0 mmol/l in 1996 decreasing to 4.3 mmol/l in 2007. As aspirin was the first drug to have an evidence base for secondary prevention of cardiovascular disease it is always given to patients in subsequent trials and it might be asked if aspirin does indeed provide additional benefit when statins are used to good effect. The importance of the neutral effect of aspirin on cardiovascular events is that this drug is not without side effects. Aspirin is the most commonly prescribed drug in Scotland, with about 544 438 person years exposure per year in 2002. The number of prescriptions is increasing. The overwhelming majority of this, in the region of Tayside at least, is prescription based, with only about 7% being from over the counter use. Aspirin is one of the top 10 causes of adverse drug events reported to the Commission on Human Medicines. Gastrointestinal bleeding is associated ith general use of non-steroidal anti-inflammatory drugs in over 80%of reported cases, and 87%of that use is associated with aspirin, either alone or with other non-steroidal anti-inflammatory drugs. The risk of a bleeding event increases with age and also continuous exposure.
Although the calculated risk of major bleeding is relatively small, the number of people taking aspirin is relatively large and therefore in population terms aspirin induced bleeding is a major problem. In a meta-analysis the number needed to treat to cause an adverse event has been calculated as 248, and this is relevant to the large and increasing population with diabetes.
In addition, of concern was the fact that there was a tendency to harm in the antioxidant group. Anecdotally, many people with diabetes supplement with antioxidants after major publicity in the lay press of a deficiency in antioxidants in such people. It was also found there was no evidence for this perceived benefit in the studies.

Conclusion: Both Aspirin and Antioxidants are not useful in Diabetics with asymptomatic peripheral vascular disease in preventing the cardiovascular events!

Helicobacter pylori  in smokers with peripheral vascular disease - Shoud we consider quadruple therapy for eradication routinely?

Infection with Helicobacter pylori is a substantial public health problem that affects 20 to 50% of people in industrialised nations and up to 80% in less-developed countries. H pylori is associated with many gastroduodenal disorders, including peptic ulcer disease, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. In regions with high incidence of gastric carcinoma, eradication of H pylori is advocated to prevent the development of this disease. Further, patients benefit from eradication after endoscopic resection of early gastric carcinoma because it reduces the risk for metachronous gastric neoplasia.
A previous international study, which assessed the efficacy and safety of 10 days of omeprazole with a single (three-in-one) capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) for H pylori eradication in patients with peptic ulcer disease or non-ulcer dyspepsia, reported overall eradication rates greater than 90%.

Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy.

Long term follow up (8 yrs) after Endorepair of Thoracic Aortic dissection.

This gentleman was admitted with acute ischemia in both the lower limbs in middle of the night and in emergency the resident on duty attempted thrombectomy but failed to retreive the thrombus. The next morning further investigations revealed dissection of aorta from the left subclavian origin to abdominal aortic bifurcation. After discussions it was decided to do the endorepair. Endorepair was successfully done and remained intact for the past 8 years. He has developed diabetes in the followup. His blood pressure was controlled with medications and he is advised to monitor blood pressure regularly at home.

Obesity and Venous disease (Varicose veins): Weight management in venous disease (varicose veins) patients is very difficult. It is becoming a common problem in the vascular surgery out patient clinics. Some may still feel that obesity is not a major problem in Indian hospitals. In the venous subset of population attending the vascular clinics this is a significant problem. A recent study by the University of Maryland and the National Council of Applied Economic Research found 22 per cent of Indians living in cities were overweight and 7 per cent were obese. The following is the typical presentation in our clinic. Here is a man weighing 107 Kgs with history of bleeding from the leg veins. He was advised to loose 5 kgs by adjusting diet and life styles along with class II stockings. He came back to the clinic after 4 weeks with a weight of 110Kgs. But he is regular with his stockings and there were no episodes of bleeding from the leg. This is a common problem to see weight gain when you advise them to loose weight. Weight management needs special attention to the details and it would not be sufficient if we simply advice the patients to loose weight. Very few patients (from low socioeconomic group) succeed in loosing the weight with a simple advice in the outpatient clinics. India has 70 million people who have been re-classified as overweight or obese, after a lowering of obesity thresholds. In India the BMI limits have been lowered to 23 for being overweight and 25 for being obese, to reflect the risks to the population. Indians also have lower thresholds for waist circumference measurements.

Changing Health care  in west (UK, USA), we need better understanding of medical health insurance and future needs ?

We did not  dream that this would be happening to health care industry in United Kingdom three decades back. It seems, Since its establishment in July, 1948, the aim of the NHS has been to offer a comprehensive service to improve health and prevent illness, available to all in England and Wales (and then extended throughout the UK), which is largely free of charge. Health care for all, for free, has been the common ethos and philosophy throughout the NHS. But in 60 years things changed, it has been forced to look for better ways to provide health care even in the countries like United kingdom and few others.The money barrier, of course is crucial in making decisions.Now, GPs will return to the market place and will decide what care they can afford to provide for their patients, and who will be the provider and insuring agent. There is fear that the emphasis will move from clinical need (GPs' forte) back to cost (not what GPs were trained to evaluate). The ethos will become that of the individual providers and insurers, and will differ accordingly throughout England, replacing the philosophy of a genuinely national health service. We in Andhrapradesh India, introduced a system to reach people known as "Aarogyasree" public(Govt) funded health insurance scheme, managed through the web (internet) approval of patient selection and procedures and release of money. I forsee that there is going to be a need for similar systems (with modifications) in the other countries also to reach the needy people. That means the robust medical insurance has come to the lime light in many parts of the world by force. We need to understand more about the Medical insurance and It should be a subject for study during undergraduate studies for Medical graduates.

Can we make the vascular access for hemodialysis through the neck lines (central lines) more safer and long lasting?

Vascular access for hemodialysis is known to frequently thrombose and force us to go for revision or create a new vascular access. Central lines are flushed with heparin to prevent the thrombosis but even then some catheters get blocked due to thrombosis and others develop the infection. Such catheters are treated with rtPA (1mg) to lyse the clots in the catheter. Loss of access can be expensive and one has to go for another one. In a recent study published in NEJM it was observed routine use of rtPA (1mg) once in a week in addition to twice a week Heparin irrigation of the catheter can prevent the thrombosis and bacteremia. Brenda RH ( preCLOT study group) did this study and it is very interesting to findout that elective use of rtPA can increase the patency and prevent the bacteremia in those patients undergoing dialysis through the central neck lines. Soon the 1mg rtPA prefilled syringes may be available in many countries to irrigate the the central lines for better patency. We can congratulate Brenda R H et al for conducting this study which can help the hemodialysis patients.

Economics and venous disease in the developing nations
In the coming years venous disease is going to be diagnosed more often and therapies will be suggested by doctors to the patients. It is due to the availability of the Ultrasound scans (doppler) in every medical centre. This can tremendously increase the demand for the treatments which are day care and minimally invasive. Endovenous ablative therapies are going to be popularised by the hospital based doctors. In India, the cost of varicose veins -ablative therapies will be around Rs 40,000/= in the coming years.

Chronic venous ulcers

Patients develop venous ulcers after sufferring from chronic venous hypertension over a period of time ( 8 to 10 years). The venous ulcers fail to heal and they also recur after healing. Patients also become indifferent to the treatments as they have seen failures more often than success with treatments. This patient had ulcer for more than 10 years. The skin around the ulcer is indurated and there are pale grannualtion tissues in the base of the ulcer.

Pulsatile swelling in the Hypothenar eminence

Traumatic(repeated) injury to the ulnar artery can result in aneurysm formation. The radial artery is patent and the palmar arch is also supplied by the radial artery. This patient is advised repair of the ulnar artery aneurysm under tourniquet.

Femoral artery Pseudo aneurysm (post traumatic) in middle aged man.

This gentleman sustained injury to the thigh (Bamboo stick) while working near the cattle at home 1 month back. He developed profuse bleeding and later swelling of the thigh. He waited for 1 month with local therapies. Then he came to our clinic under the Aarogyasri scheme. We operated on him in emergency after getting the approval from Aarogyasri insurance scheme. A short segment of saphenous vein graft was interposed to repair the damaged artery segment. The sartorius muscle (flap) was used to cover the graft. Usually patients from low socioeconomic status are able to reach the tertiary care hospital after a minimum of 2 to 4 weeks and Aarogysri is helping them to get the vascular surgical therapies in emergency situations.

Intra operative photograph showing the vein graft after excision of aneurysm

Post thrombotic syndrome and its prevention by early clearance of thrombus load from the DVT patients is going to attract the attention of doctors as it is promising to clear the vein load of thrombus. Catheter directed thrombolysis in combination with the percutaneous mechanical thrombectomy seem to be future mode of management  of the ilio-femoral deep vein thrombosis. However the cost of such treatment may not make it best choice of treatment for majority of the people who are living in India who can not afford such expensive therapies. The appropriate cost for such therapies will not be less than Rs 1,50,000/= . We donot know if the 3rd party insurance companies will be approving such expensive therapies for the ilio-femoral DVT!



Intraarterial Administration of Bone Marrow Mononuclear Cells in Patients With Critical Limb Ischemia

Critical limb ischemia due to peripheral arterial occlusive disease is associated with a severely increased morbidity and mortality. There is no effective pharmacological therapy available. Injection of autologous bone marrow-derived mononuclear cells (BM-MNC) is a promising therapeutic option in patients with critical limb ischemia, but double-blind, randomized trials are lacking. A Randomized-Start, Placebo-Controlled Pilot Trial (PROVASA) was published in Circulation - cardiovascular interventions.In this study Limb salvage and amputation-free survival rates did not differ between the control and study groups. However, cell therapy was associated with significantly improved ulcer healing (ulcer area, 3.2±4.7 cm² to 1.89±3.5 cm²P=0.014] versus placebo, 2.92±3.5 cm²² [P=0.5]) and reduced rest pain (5.2±1.8 to 2.2±1.3 [P=0.009] versus placebo, 4.5±2.4 to 3.9±2.6 [P=0.3]) within 3 months. 

We in India, need to be careful in jumping to conclusions without adequate  supportive evidence in favor of the cell therapies to treat the critical limb ischaemia for the present. If the strong evidence becomes available certainly and eagerly we are waiting to bring that in to our clinical practice.

What is optimum anticoagulation with Heparin in peripheral vascular treatments?

             Beyond the heparin dose ( initially up to 60 U/kg) and the ACT level (250 seconds) , in the multivariate analysis it was found that female sex, creatinine clearance <60 mL/min per 1.73m² age >70 years, preprocedural anemia, history of heart failure, hybrid vascular surgery, rest pain, and below-knee interventions were independent predictors of higher postprocedural bleeding risk. These findings are consistent with those from 2 large retrospective databases of patients undergoing PCI and a registry of 24 045 patients with acute coronary syndromes from the Global Registry of Acute Coronary Events (GRACE).Less aggressive anticoagulation, or use of an alternative anticoagulant strategy such as a direct thrombin inhibitor, may decrease the incidence of bleeding complications in these subgroups of high-risk patients.
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References

1. Moscucci M, Fox KA, Cannon CP et al. Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J. 2003; 24: 1815– 1823
2. Shammas NW,Allie D,Hall P: Predictors of in-hospital and 30-day complications of peripheral vascular interventions using bivalirudin as the primary anticoagulant: results from the APPROVE Registry. J Invasive Cardiol. 2005; 17: 356– 359

Surgical site infections in the Hospital patients - Guidelines can prevent them?
American Journal of Surgery - Volume 201, Issue 1 (January 2011)

Surgical site infections (SSIs) occur in more than 500,000 patients annually and result in increased length of hospital stay, readmissions, costs, and mortality in USA. [1] , [2] Up to 60% of SSIs have been estimated to be preventable, [3] , [4] , [5] largely by using recommended evidence-based guidelines such as timely and appropriate administration of antibiotics for prophylaxis and maintenance of perioperative normothermia. [3] , [6] , [7] , [8] A number of hospitals have reported decreased infection rates by improving utilization of these guidelines. [9] , [10] Furthermore, lack of compliance with these guidelines is associated with a significant increase in mortality.[11] Despite the evidence that these measures improve outcome, compliance with these guidelines is suboptimal in many hospitals, as demonstrated by data from large administrative databases and cohort studies. [9] , [12] , [13] , [14] Bratzler et al evaluated a random sample of 34,133 Medicare patients and found that only 56% of patients received antimicrobial therapy within 1 hour before incision and that only 40% had appropriate discontinuation of prophylactic antibiotics after 24 hours.[13] Based on poor compliance with these guidelines and the high morbidity and mortality of postoperative complications, the Surgical Care Improvement Project (SCIP) was developed as a collaborative effort to prevent infectious, thromboembolic, cardiac, and respiratory complications.[15]



1 Kirkland K.B., Briggs J.P., Trivette S.L., et al: The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol 20. 725-730.1999; Abstract


2 Weinstein R.A.: Nosocomial infection update. Emerg Infect Dis 4. 416-420.1998; Abstract

3 Mangram A.J., Horan T.C., Pearson M.L., et al: Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory CommitteeAm J Infect Control 27. 97-132.1999; Full Text

4 Page C.P., Bohnen J.M., Fletcher J.R., et al: Antimicrobial prophylaxis for surgical wounds. Guidelines for clinical careArch Surg 128. 79-88.1993; Abstract

5 Platt R., Munoz A., Stella J., et al: Antibiotic prophylaxis for cardiovascular surgery. Efficacy with coronary artery bypassAnn Intern Med 101. 770-774.1984; Abstract

6 Chodak G.W., Plaut M.E.: Use of systemic antibiotics for prophylaxis in surgery: a critical review. Arch Surg 112. 326-334.1977; Abstract

7 Horan T.C., Gaynes R.P., Martone W.J., et al: CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Infect Control Hosp Epidemiol 13. 606-608.1992; Citation

8 Kurz A., Sessler D.I., Lenhardt R.: Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature GroupN Engl J Med 334. 1209-1215.1996; Abstract

9 Dellinger E.P., Hausmann S.M., Bratzler D.W., et al: Hospitals collaborate to decrease surgical site infections. Am J Surg 190. 9-15.2005; Full Text

10 Hedrick T.L., Heckman J.A., Smith R.L., et al: Efficacy of protocol implementation on incidence of wound infection in colorectal operations. J Am Coll Surg 205. 432-438.2007; Full Text

11 Mahid S.S., Polk , Jr , JrH.C., Lewis J.N., et al: Opportunities for improved performance in surgical specialty practice. Ann Surg 247. 380-388.2008; Abstract

12 Bratzler D.W., Houck P.M.: Antimicrobial prophylaxis for surgery: an advisory statement from the national surgical infection prevention project. Clin Infect Dis 38. 1706-1715.2004; Abstract

13 Bratzler D.W., Houck P.M., Richards C., et al: Use of antimicrobial prophylaxis for major surgery: baseline results from the national surgical infection prevention project. Arch Surg 140. 174-182.2005; Abstract

14 Silver A., Eichorn A., Kral J., et al: Timeliness and use of antibiotic prophylaxis in selected inpatient surgical procedures. The Antibiotic Prophylaxis Study GroupAm J Surg 171. 548-552.1996; Abstract

15 Bratzler D.W., Hunt D.R.: The surgical infection prevention and surgical care improvement projects: national initiatives to improve outcomes for patients having surgery. Clin Infect Dis 43. 322-330.2006; Abstract

Healing of Venous ulcers and cost of therapy


The treatment of venous leg ulcers (VLU) represents 23% of new patient visits and 36% of all patient visits in vascular surgery practice. Depending on the age of the patient cohort, VLU affects between 0.2% and 1% of the population.1 In first world countries, the treatment of VLU may represent a maximum of 3% of health care expenditures.2 Presently, the standard of care for VLU remains compression therapy, in many cases Unna’s boot, but ideally multilayer wraps.3 With this current treatment, healing rates in patients with normal arterial perfusion is reported to be between 63% at 10 weeks retrospectively and 33% at 12 weeks prospectively.[4] and [5] Overall, annual direct costs for the treatment of VLU are in the range of $30,000 per patient per annum, with only 60-80% of them healing at 6 months. Dr O’Donnell has accurately pointed out that “any treatment modality improving VLU healing time or proportion healed would reduce the burden of VLU care.”6


Others have noted that a maximum of 15% of the limbs affected by VLU observed in large volume vascular practices have an ankle–brachial index (ABI) of <0.8.4 Patients with an ABI of <0.8 were noted to take 19 weeks to heal 50% of their ulcers as compared with 9 weeks taken by the normally perfused group. In another study, which evaluated the closure rate of mixed arterial venous ulcers, the closure rate for the standard of care arm at 16 weeks was 46.2% as compared with the 82.6% in the cohort treated with porcine-derived intestinal submucosa (SIS) (Cook Medical Inc., Bloomington IN).7 A 2004 study conducted in the United Kingdom reported that 13.6% of patients presenting with VLU had an ABI of 0.5-0.85 and 2.2% had an ABI of <0.5.8 M.L. Humphreys, A.H. Stewart and M.S. Gohel et al., Management of mixed arterial and venous leg ulcer, Br J Surg 94 (2007), pp. 1104–1107. View Record in Scopus Cited By in Scopus (9)8 Therefore, to assess the effect of intervening percutaneously on the arterial circulation of patients with mixed arterial venous disease who were dependent on compression therapy. This therefore excluded the few patients who had mixed arterial venous disease with easily correctable, superficial-only venous reflux. The hypothesis was that improving or “normalizing” the lower extremity perfusion, as assessed by ABI and pulse volume recordings (PVRs), would normalize the healing trajectory of this hard-to-close patient subset. Few others have applied this protocol selectively but with a large proportion of patients who underwent arguably more morbid open procedures.8

Second - hand smoking and mortality

Worldwide, 40% of children, 33% of male non-smokers, and 35% of female non-smokers were exposed to second-hand smoke in 2004. This exposure was estimated to have caused 379 000 deaths from ischaemic heart disease, 165 000 from lower respiratory infections, 36 900 from asthma, and 21 400 from lung cancer. 603 000 deaths were attributable to second-hand smoke in 2004, which was about 1·0% of worldwide mortality. 47% of deaths from second-hand smoke occurred in women, 28% in children, and 26% in men. DALYs lost because of exposure to second-hand smoke amounted to 10·9 million, which was about 0·7% of total worldwide burden of diseases in DALYs in 2004. 61% of DALYs were in children. The largest disease burdens were from lower respiratory infections in children younger than 5 years (5 939 000), ischaemic heart disease in adults (2 836 000), and asthma in adults (1 246 000) and children (651 000).

The Lancet, Volume 377, Issue 9760, Pages 139 - 146, 8 January 2011

Post thrombotic syndrome after thrombolytic therapy- Do we have enough support for considering thrombolytic therapy?

Deep venous thrombosis (DVT) of the lower limbs can lead to post-thrombotic syndrome. There is a strong correlation between post-thrombotic syndrome and the extent of the thrombotic process. The progress of distal DVTs is benign with a high rate of recanalization and low rate of venous reflux. Persistence of chronic occlusion and venous reflux is common in extensive DVTs. The proximal DVT (upto 96%) may progress with reflux and/or venous obstruction. Venous segments with evidence of reflux after DVT recanalization were those presenting a spontaneous fibrinolysis up to 7 times longer than the observed in competent segments, suggesting that thrombus removal time is also an important factor in vein valve preservation. The use of locally infused fibrinolytic agents presents the possibility of direct intervention for immediate thrombus removal.Theoretically, this specific feature of thrombolysis should lead to immediate improvement of clinical results in extensive cases of DVT, as well as to preservation of valvular competence and venous wall morphology as has been described by experimental studies. So, we can think in favor of Thrombolytic therapy in extensive proximal DVT cases.

References:

1. Masuda EM, Kessler DM, Kistner RL, Eklof B, Sato DT. The natural history of calf vein thrombosis: lysis of thrombi and development of reflux. J Vasc Surg. 1998;28:67-74. [ Links ]
2. McLafferty RB, Moneta GL, Passman MA, Brant BM, Taylor LM Jr, Porter JM. Late clinical and hemodynamic sequelae of isolated calf vein thrombosis. J Vasc Surg. 1998;27:50-7. [ Links ]
3. O'Shaughnessy AM, FitzGerald DE. The patterns and distribution of residual abnormalities between the individual proximal venous segments after an acute deep vein thrombosis. J Vasc Surg. 2001;33:379-84. [ Links ]
4. Lindner DJ, Edwards JM, Phinney ES, Taylor LM Jr, Porter JM. Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis. J Vasc Surg. 1986;5:436-42. [ Links ]
5. Haenen JH, Janssen MC, van Langen H, van Asten WN, Wollersheim H, Heystraten FM, et al. Duplex ultrasound in the hemodynamic evaluation of the late sequelae of deep venous thrombosis. J Vasc Surg. 1998;3:472-8. [ Links ]
6. Meissner MH, Manzo RA, Bergelin RO, Markel A, Strandness DE Jr. Deep venous insufficiency: The relationship between lysis and subsequent reflux. J Vasc Surg. 1993;18:596-608. [ Links ]
7. Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology. 1999;211:39-49. [ Links ]
8. Emanuelli G, Segramora V, Frigerio C. Selected strategies in venous thromboembolism: local thrombolytic treatment and caval filters. Haematologica. 1995;80 (2 Suppl):84-6. [ Links ]
9. Molina JE, Hunter DW, Yedlicka JW. Thrombolytic therapy for iliofemoral venous thrombosis. Vasc Surg. 1992;26:630-7. [ Links ]
10. Verhaeghe R, Stockx L, Lacroix H, Vermylen J, Baert AL. Catheter directed lysis of iliofemoral vein thrombosis with use of rt-PA. Eur Radiol. 1997;7:996-1001. [ Links ]
11. Palombo D, Porta C, Brustia P, Peinetti F, Udini M, Antico A, et al. La thrombolyse loco-régionale dans la thrombose veineuse profonde. Phlebologie. 1993;46:293-302. [ Links ]
12. Burkart DJ, Borsa JJ, Anthony JP, Thurlo SR. Thrombolysis of occluded peripheral arteries and veins with tenecteplase: a pilot study. J Vasc Interv Radiol. 2002;13:1099-102. [ Links ]
13. Sugimoto K, Hofmann LV, Razavi MK, Kee ST, Sze DY, Dake MD, et al. The safety, efficacy, and pharmacoeconomics of low-dose alteplase compared with urokinase for catheter-directed thrombolysis of arterial and venous occlusions. J Vasc Surg. 2003;37:512-7. [ Links ]
14. Shortell CK, Queiroz R, Johansson M, Waldman D, Illig KA, Ouriel K, et al. Safety and efficacy of limited-dose tissue plasminogen activator in acute vascular occlusion. J Vasc Surg. 2001;34:854-9. [ Links ]
15. Rhodes JM, Cho S-J, Gloviczki P, Mozes G, Rolle R, Miller VM. Thrombolysis for experimental deep venous thrombosis maintains valvular competence and vasoreactivity. J Vasc Surg. 2000;31:1193-205.