Label extension, single-arm, phase III study shows efficacy and safety of stempeucel® in patients with critical limb ischemia due to atherosclerotic peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) of lower extremities comprises a clinical spectrum that extends from asymptomatic patients to critical limb ischemia (CLI) patients. 10% to 40% of the patients are at the risk of primary amputation. This study was planned in "no-option" patients of CLI due to atherosclerotic PAD to assess the efficacy and safety of pooled, allogeneic, adult human bone marrow-derived mesenchymal stromal cells which is already approved for marketing in India for CLI due to Buerger's disease. METHODS: This was a single-arm, multi-centric, phase III study where mesenchymal stromal cells was injected as 2 million cells/kg body weight in the calf muscle and around the ulcer. Twenty-four patients of lower extremity CLI due to PAD with Rutherford III-5 or III-6 and ankle-brachial pressure index ≤ 0.6 and having have at least one ulcer with area between 0.5 and 10 cm2 were included in the study. These patients were evaluated over 12 months from drug administration. RESULTS: Over a period of 12 months, statistical significant reduction of rest pain and ulcer size along with improvement in ankle-brachial pressure index and ankle systolic was observed. The quality of life of patients improved together with increase in total walking distance and major amputation-free survival time. CONCLUSION: Mesenchymal stromal cells may be a feasible option to treat "no-option" patients with atherosclerotic PAD. Trial registration This study is registered prospectively in National Institutes of Health and Clinical Trials Registry-India (CTRI) website: CTRI/2018/06/014436. Registered 6th June 2018. http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=24050&EncHid=&userName=stempeutics .

Balloon angioplasty: A promising adjunct to arteriovenous fistula creation compared with hydrostatic dilatation in small-caliber cephalic veins.

BACKGROUND: To maintain the patency and longevity of arteriovenous fistula, the availability of a venous segment with adequate diameter is important. In Indian population, many chronic kidney disease patients have poor caliber veins. The study aimed to evaluate the efficacy of hydrostatic dilatation versus Primary balloon angioplasty of small caliber cephalic veins of (≤2.5 mm) preoperatively in terms of patency rate and maturation time of arteriovenous fistula. METHODS: Patients (n = 80) with an end-stage renal disease requiring arteriovenous access surgery for hemodialysis with small caliber cephalic veins were randomized into two groups, i.e., hydrostatic dilatation and primary balloon angioplasty, each with 40 patients. All patients underwent a thorough clinical examination as well as duplex ultrasound vein mapping of both upper extremities. Patients were followed up for six months and primary patency, maturation time, and complications were noted. RESULTS: Immediate technical success with good palpable thrill was achieved in 97.5% of patients in the primary balloon angioplasty group and 87.5% in the hydrostatic dilatation group. The fistula maturation time in the primary balloon angioplasty group was 34.41 days and 46.18 days in the hydrostatic dilatation group. In the primary balloon angioplasty group, the primary patency of the fistula was 97.5% and 87.5% in the hydrostatic dilatation group, at six months. The arteriovenous fistula functioning rate was 77.5% in the hydrostatic dilatation group as compared to 92.5% in the primary balloon angioplasty group at six months. The incidence of surgical site infection was 5% in the primary balloon angioplasty group as compared to 10% in the hydrostatic dilatation group. CONCLUSION: Primary balloon angioplasty of small caliber cephalic veins (≤2.5 mm) performed prior to arteriovenous fistula creation for hemodialysis is a beneficial procedure.

Phase IV postmarketing surveillance study shows continued efficacy and safety of Stempeucel in patients with critical limb ischemia due to Buerger's disease.

Buerger's disease or thromboangiitis obliterans is a type of obstructive vascular diseases categorized as vasculitis and usually present in 95% of young smoker men. The main pathogenetic mechanism is interplay between immune system and inflammation. Earlier our phase II study has shown that Stempeucel is safe when injected at 2 million cells/kg body weight by virtue of its anti-inflammatory, immunomodulatory, and angiogenetic properties. The present study was conducted to further assess the safety and efficacy of Stempeucel in critical limb ischemia due to Buerger's disease after obtaining approval from Indian FDA based on the data generated in the phase II study. This is an open label, multicenteric phase IV PMS study conducted across India with experienced vascular surgeons. Fifty patients of critical limb ischemia due to Buerger's disease with Rutherford III-5 or III-6 were included in the study and each individual received a dose of 2 million cells/kg body weight of Stempeucel in the calf muscles and around the ulcer. These patients were evaluated over 12 months from drug administration. The present study showed the continued long term efficacy over a period of 12 months follow up in these patients corroborating the result obtained in the previous phase II studies. There was significant improvement in rest pain, ankle systolic pressure, and ankle brachial pressure index with accelerated ulcer healing. In conclusion, the present study shows that the intramuscular administration of Stempeucel continues to be safe, tolerable, and effective alternative treatment in patients with Buerger's disease.

Single-stage basilic vein transposition-An effective and viable autogenous access for dialysis.

INTRODUCTION: The National Kidney Foundation's/Kidney Disease Outcomes Quality Initiative recommends autogenous arteriovenous fistulas as the preferred method for long-term hemodialysis access. Basilic vein transposition is not only an alternative in patients with failed arteriovenous access but also can be the first option for arteriovenous access in patients with inadequate cephalic vein. Several studies have shown better patency rates, cost-effectiveness, and fewer complications of autogenous access over prosthetic arteriovenous grafts. AIMS AND OBJECTIVES: To analyze patency, complication rates, and outcomes of single-stage basilic vein transposition. MATERIALS AND METHODS: A single-center retrospective non-randomized study conducted at Ramaiah Medical College and Hospitals, Bangalore from July 2015 to June 2018. A total of 94 consented patients who underwent single-stage basilic vein transposition were included in the study. All the surgeries were done in a single stage under regional anesthesia. All the complications and patency rates were calculated at the end of one year. Statistical analysis was performed using the Chi-square test, and patency rates were assessed using the Kaplan-Meir survival curve. RESULTS: A total of 94 single-stage basilic vein transposition was performed. Fifty-four patients had a previous failed autogenous access and 40 had either absent or thrombosed cephalic vein. The mean age was 56.6 years with 59.57% males. The mean basilic vein and brachial artery diameter was 3.6 and 3.8 mm, respectively. The primary patency rate at one year was 84%. Edema and thrombosis were the most common complication in our study. CONCLUSION: Single-stage basilic vein transposition is a feasible surgical option in end-stage renal disease patients and provides durable autogenous access with very reasonable outcomes in terms of complication rates and patency rates.

Giant abdominal aortic aneurysm of uncommon etiology due to Behçet disease.

Behçet disease is a multisystem disorder presenting with recurrent oral and genital ulcerations as well as with ocular involvement. Vascular involvement can occur in up to 50% of affected patients. Arterial aneurysms are often multiple and are characterized by a saccular configuration with increased risk of unexpected rupture, thrombosis, and aneurysm recurrence. Here we report a case of giant infrarenal abdominal aortic aneurysm in a 34-year-old man with Behçet disease who underwent aneurysmorrhaphy and aortobifemoral bypass.

Role of Brachial Artery Ligation in Management of Prosthetic Arteriovenous Graft Infections.

BACKGROUND: Arteriovenous graft (AVG) infections can present as major life-threatening hemorrhage or sepsis in a chronic kidney disease patient. Frequently, all these patients present in critical condition which need prompt and expeditious management. Various procedures are described for management of infected grafts and its bleeding complications. However, these procedures are associated with postop-operative bleeding and persistent infection. The aim was to study brachial artery ligation (BAL) near the elbow joint in the management of an infected AVG. METHODS: It was a retrospective study where data collection was done for 51 patients who underwent BAL in infected AVGs from January 2007 to December 2016. RESULTS: During the study period, AVG infections were treated in 62 patients. Fifty-one BALs were done in 62 limbs treated. All were arm grafts (brachial artery to axillary vein) using expanded polytetrafluoroethylene grafts. In 49 patients, BAL was done as a primary procedure. In 2 patients, BAL was done after they presented with uncontrolled infection after initial subtotal excision with oversewing of graft stump at arterial anastomosis. There were 36 men and 15 women, with a mean age of 49 years (range, 23-82). The primary etiologies for renal failure were hypertension (56.2%), diabetes (34.3%), and others (9.5%). Follow-up was 100% at 1 month and 82.3% (42 patients) at 3 months, and none showed any signs of ischemia or sepsis. All had biphasic signals in radial and ulnar arteries with normal peripheral capillary oxygen saturation readings in fingers. None of the patients underwent additional interventions. CONCLUSIONS: BAL in AVG infections is a safe alternative considering the critical general condition of chronic kidney disease patient. It reduces the operative time significantly and avoids complex revascularization and anastomotic dehiscence without any ischemic or bleeding complications. BAL near the elbow joint in patients with good back-bleeding can be used as a primary approach in an infected AVG. However, close monitoring of patient in postoperative period is essential.

Transplant renal artery stenosis: The impact of endovascular management and their outcomes.

INTRODUCTION: Transplant renal artery stenosis (TRAS) is a well-known vascular complication of renal transplantation. The aim of this analysis was to assess the short and midterm outcomes of endovascular therapy to salvage transplant kidney. METHODS: We retrospectively analyzed our transplant database from 2000 to 2015. Percutaneous transluminal angioplasty/stenting was done in 24 patients (22 men and two women) with significant TRAS. The mean age was 59 ± 12 years. The parameters analyzed were: Technical success, pre- and post-treatment serum creatinine and number of antihypertensive drugs before and after treatment and vessel patency on Doppler ultrasonography at 3 and 6 months. RESULTS: Overall incidence of TRAS in this study was 5.06%. Incidence of TRAS following live donor transplantation was 4.68% while that in deceased donors was 11.5%. Technical success was 100%. There were no periprocedural deaths. Renal function was improved from 2.32 ± 0.5 mg/dL to 1.72 ± 0.3 mg/dL (P < 0.001) and number of antihypertensive medications after the procedure was reduced from 2.9 ± 0.7 to 2 ± 0.6 (P < 0.001) at 6 months follow-up. One patient developed restenosis within 5 months (4.2%). Clinical success at 6 months follow-up was 79.2%. CONCLUSIONS: Endovascular treatment of TRAS has high technical success with minimal complications. It also provides satisfactory clinical success with improvement in overall transplant renal function and renovascular hypertension in early follow-up.

Arrive: A retrospective registry of Indian patients with venous thromboembolism.

BACKGROUND AND AIM: There is lack of substantial Indian data on venous thromboembolism (VTE). The aim of this study was to provide real-world information on patient characteristics, management strategies, clinical outcomes, and temporal trends in VTE. SUBJECTS AND METHODS: Multicentre retrospective registry involving 549 medical records of patients with confirmed diagnosis of VTE (deep vein thrombosis [DVT] confirmed by Doppler ultrasonography; pulmonary embolism [PE] by computed tomography, pulmonary angiography and/or V/Q scan) from 2006 to 2010 at three Indian tertiary care hospitals. RESULTS: Acute DVT without PE, acute DVT with PE, and PE alone were reported in 64% (352/549), 23% (124/549), and 13% (73/549) patients, respectively. Mean age was 47 (±16) years, and 70% were males. H/o DVT (34%), surgery including orthopedic surgery (28%), trauma (16%), and immobilization >3 days (14%) were the most common risk factors for VTE. Hypertension (25%), diabetes (19%), and neurological disease (other than stroke) (8%) were the most common co-morbidities. Most (94%) were treated with heparin alone (82%) or fondaparinux (2%) for initial anticoagulation; low molecular weight heparin alone (5%) or warfarin/acenocoumarol (76%) for long-term anticoagulation. Anticoagulant treatment was stopped because of bleeding in 2% (9/515) patients. Mortality was 7% among patients diagnosed with VTE during hospital stay versus 1% in those hospitalized with diagnosed VTE. The annual incidence of DVT (±PE) increased from 2006 to 2010. CONCLUSION: Acute DVT alone was responsible for the substantial burden of VTE in Indian patients. Bleeding was not the limiting factor for anticoagulant treatment in most patients.

The effect of a connexin43-based Peptide on the healing of chronic venous leg ulcers: a multicenter, randomized trial.

The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury and during wound healing, and is abnormally upregulated at the epidermal wound margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, and wound reepithelialization. In a prospective, multicenter clinical trial conducted in India, adults with chronic VLUs were randomized to treatment with an ACT1 gel formulation plus conventional standard-of-care (SOC) protocols, involving maintaining wound moisture and four-layer compression bandage therapy, or SOC protocols alone. The primary end point was mean percent ulcer reepithelialization from baseline to 12 weeks. A significantly greater reduction in mean percent ulcer area from baseline to 12 weeks was associated with the incorporation of ACT1 therapy (79% (SD 50.4)) as compared with compression bandage therapy alone (36% (SD 179.8); P=0.02). Evaluation of secondary efficacy end points indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Incorporation of ACT1 in SOC protocols may represent a well-tolerated, highly effective therapeutic strategy that expedites chronic venous ulcer healing by treating the underlying ulcer pathophysiology through Cx43-mediated pathways.

Value of preoperative sonographic vascular evaluation of haemodialysis access in upperlimb.

OBJECTIVE: To know the value of preoperative Dopplerultrasonography vascular mapping of upper limb for hemodialysis access placement. MATERIALS AND METHODS: Prospective ultrasonographic assess- ment of upper extremity vessels was performed in 60 patients prior to hemodialysis access placement and potential access sites were selected (based on the standard criteria). The findings were correlated with the operative findings. Discrepancies found between ultrasonographic and operative findings were analysed. RESULTS: All the 60 patients who underwent vascular mapping had vascular access placed. 80% of them had native arteriovenous fistulae (AVF) placed. In 95% of patients, at the selected sites, the vascular parameters as determined by ultrasonography matched with the operative findings. In 5% of patients there were discrepancies between the ultrasonography findings and operative findings. There was no negative surgical exploration. There was strong correlation between the diameters measured by ultrasonography and surgery. CONCLUSION: Preoperative ultrasonography vascular mapping prior to hemodialysis access placement has facilitated definite selection of potential sites in difficult patient population in whom evaluation by physical examination was inconclusive. It also helped in maximizing the native AVFs and decreasing the negative surgical exploration rates.

Remote endarterectomy: an alternative to surgical bypass.

We present our preliminary results of remote endarterectomy performed during June 2003 to June 2010. 8 cases of unilateral ileofemoral disease, 3 cases of bilateral ileofemoral disease and 4 cases of femoro-popliteal disease constituting 18 limbs were successfully operated. All patients had comorbid conditions like Diabetes mellitus, hypertension, cardiac disease and smoking. Patency at 3 months with loss of one patient for follow up was 100 %. At one year follow up, the overall success rate was 90.90 %. One patient with Iliofemoral Endarterectomy had progression of the disease and hence had to undergo Aorto-Femoral bypass. All patients who had tissue loss, showed complete recovery by 3 months and one patient was lost to follow up. A 5 year follow up had a patency rate of 74 %. Remote endarterectomy is a viable and durable alternative to standard bypass procedures. Remote endarterectomy combines the advantages of minimally invasive surgery with endovascular techniques.

A rare intramuscular hemangioma - case report.

Intramuscular hemangiomas are rare, slow growing, angiomatous tumors, generally asymptomatic, and rarely presenting with complications. We report a rare case of a Hemangioma of the Flexor Digitorum Superficialis in a 13-year-old boy, present since birth and with extensive involvement, necessitating excision of the muscle. The patient is presently doing well, barring minimal weakness in finger flexion.