Always Contact a Vascular Interventional Specialist Before Amputating a Patient with Critical Limb Ischemia

Patients with severe critical limb ischemia (CLI) due to long tibial artery occlusions are often poor candidates for surgical revascularization and frequently end up with a lower limb amputation. Subintimal angioplasty (SA) offers a minimally invasive alternative for limb salvage in this severely compromised patient population. The objective of this study was to evaluate the results of SA in patients with CLI caused by long tibial occlusions who have no surgical options for revascularization and are facing amputation. We retrospectively reviewed all consecutive patients with CLI due to long tibial occlusions who were scheduled for amputation because they had no surgical options for revascularization and who were treated by SA. A total of 26 procedures in 25 patients (14 males; mean age, 70 ± 15 [SD] years) were evaluated. Technical success rate was 88% (23/26). There were four complications, which were treated conservatively. Finally, in 10 of 26 limbs, no amputation was needed. A major amputation was needed in 10 limbs (7 below-knee amputations and 3 above-knee amputations). Half of the major amputations took place within 3 months after the procedure. Cumulative freedom of major amputation after 12 months was 59% (SE = 11%). In six limbs, amputation was limited to a minor amputation. Seven patients (28%) died during follow-up. In conclusion, SA of the tibial arteries seem to be a valuable treatment option to prevent major amputation in patients with CLI who are facing amputation due to lack of surgical options

Recent improvements in the development of A2B adenosine receptor agonists

Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary artery disorders and atherosclerosis

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Subintimal angioplasty of tibial vessel occlusions in the treatment of critical limb ischaemia: mid-term results.

OBJECTIVES: to evaluate the feasibility and preliminary results at 1 year of subintimal angioplasty of tibial occlusions in critical limb ischaemia (CLI). MATERIAL: from December 1997 to December 1999, we intended to treat 36 patients and 40 limbs by subintimal angioplasty of occlusions of tibial vessels. Thirty-one had gangrene or ulceration and nine had rest pain. Twenty-seven occlusions were more than 10 cm, 10 were 5 to 10 cm and three were less than 5 cm in length. Three patients had an occluded previous ipsilateral bypass graft. All patients were followed 3 monthly for a median of 10 months by means of clinical and duplex examination. RESULTS: the technical success rate was 78% (31/40). Nine technical failures were treated by conventional surgery or angioplasty of another diseased tibial vessel. The clinical success rate was 68% (27/40). Four below-the-knee amputations were performed despite a patent recanalisation. Primary and secondary patency rates at 12 months were 56% (72% without technical failures). The 12-month limb salvage rate was 81% and survival rate was 78%. Three of five complications were treated by endovascular procedures. The length of occlusion (>10 cm) but not the location of distal re-entry, the type of vessel re-entry and the presence of diabetes are predictors of technical success and patency. CONCLUSIONS: subintimal angioplasty can be used to treat tibial occlusions in patients with CLI. Technical failure does not preclude conventional surgery and complications may often be treated by endovascular procedures. However, the durability of angioplasty is as yet uncertain

Primary Squamous-cell Carcinoma of the Colon - a Case-report

We report a new case of S.C.C. of the large bowel with multiple liver metastases. A resection of the primary tumour and liver biopsies were performed with administration of a postoperative chemotherapy (5-Fluorouracil). After a stabilization of 3 months, the metastases were rapidly progressive and the patient died a year after the diagnosis. About 70 cases of S.C.C. of the colon and rectum have been described in the literature. It is most common in the fifth decade and occurs equally in male and female. The most frequent locations are the rectum and the sigmoid. Clinical and physical features and common diagnostic methods do not differentiate the S.C.C. from adenocarcinoma. Treatment is the same but the prognosis of S.C.C. appears to be worse than that of adenocarcinoma

ABO-incompatible orthotopic liver allografting in urgent indications.

The influence of ABO-compatibility was reviewed in 70 emergency orthotopic hepatic transplantations (OHT) performed at our institution in 60 highly urgent recipients between February 1984 and March 1989. Thirty-eight were ABO-identical (Id); 16, compatible (Comp), and 16, incompatible (Inc) transplants, respectively. The three groups did not differ statistically with respect to the indications, the adult/child ratio and the proportions of first OHT and retransplantations. Graft survival rates of ABO-Id, ABO-Comp and ABO-Inc OHT at one year were 47, 38 and 19 per cent, respectively (p less than 0.02). Incidences of perioperative mortality, arterial thrombosis and irreversible rejection were slightly (although not significantly) higher in the ABO-Inc group. Retransplantation rates were 19, 7 and 36 per cent in the ABO-Id, Comp and Inc groups, respectively. Patient survival rates at one year were 59 per cent for the ABO-Id group versus 43 per cent for both ABO-Comp and Inc combinations (NS). The results of this series of highly urgent OHT confirm that graft survival is lower with ABO-Inc livers; their use should be strictly considered as a short term life-saving procedure. Improvement of patient survival after a first urgent ABO-Inc OHT may require an aggressive policy of retransplantation

Monoclonal antibodies in prophylactic immunosuppression after liver transplantation. A randomized controlled trial comparing OKT3 and anti-IL-2 receptor monoclonal antibody LO-Tact-1.

A prospective trial was conducted to assess the efficacy of induction immunosuppression with antilymphocyte monoclonal antibodies in 129 primary liver transplant patients who were randomly divided into three groups according to immunosuppression during the first 10 days post-OLT: triple drug therapy only (TDIS: cyclosporine, steroids, azathioprine) (group I: n = 42); TDIS with a 10-day course of OKT3 (group II: n = 44); and LO-Tact-1 (anti-IL-2 receptor mAb) (group III: n = 43). Biopsy-proved acute rejection (AR) was treated using the same biopsy-guided protocol in the 3 groups. One-year patient survival rates were 67%, 84%, and 93% in groups I, II, and III, respectively (I vs. II, NS; I vs. III, P = 0.001; II vs. III, P = 0.044). Incidences of AR were studied in the subgroup of 100 patients who were exposed to the risk of developing rejection, with an overall rate of 89% during the first 3 months post-OLT, similar in the 3 groups. However, incidences of steroid-resistant rejection diagnosed during the 10 first days post-OLT were 54%, 24%, and 34% in groups I, II, and III and 46%, 26%, and 11%, respectively, during the 10-90 days interval. Sixteen patients with CMV had received OKT3, whereas the 5 remaining CMV cases had not (P = 0.019). In summary: (1) mAbs did not modify crude incidence of AR; (2) in the early period (< 10 days), TDIS immunoprophylaxis combined with OKT3 was more efficient than TDIS alone; (3) when compared with groups I and II, LO-Tact-1 apparently better prevented steroid-resistant rejection during the 10-90 days post-OLT; (4) OKT3 significantly increased incidence of CMV infection. In conclusion, TDIS with LO-Tact-1 seemed to achieve the better risk-benefit ratio in induction immunosuppression after OLT