Prevention of antibiotic-associated metabolic syndrome in mice by intestinal alkaline phosphatase.

AIMS: To examine whether co-administration of intestinal alkaline phosphatase (IAP) with antibiotics early in life may have a preventive role against metabolic syndrome (MetS) in mice. METHODS: A total of 50 mice were allocated to four treatment groups after weaning. Mice were treated with azithromycin (AZT) ± IAP, or with no AZT ± IAP, for three intermittent 7-day cycles. After the last treatment course, the mice were administered a regular chow diet for 5 weeks and subsequently a high-fat diet for 5 weeks. Body weight, food intake, water intake, serum lipids, glucose levels and liver lipids were compared. 16S rRNA gene pyrosequencing was used to determine the differences in microbiome composition. RESULTS: Exposure to AZT early in life rendered mice susceptible to MetS in adulthood. Co-administration of IAP with AZT completely prevented this susceptibility by decreasing total body weight, serum lipids, glucose levels and liver lipids to the levels of control mice. These effects of IAP probably occur as a result of changes in the composition of specific bacterial taxa at the genus and species levels (e.g. members of Anaeroplasma and Parabacteroides). CONCLUSIONS: Co-administration of IAP with AZT early in life prevents mice from susceptibility to the later development of MetS. This effect is associated with alterations in the composition of the gut microbiota. IAP may represent a novel treatment against MetS in humans.

Carotid endarterectomy versus carotid angioplasty with or without stenting for treatment of carotid artery stenosis: an updated meta-analysis of randomized controlled trials.

Carotid angioplasty with or without stent placement (CAS) has been proposed as an alternative to carotid endarterectomy (CEA) for the treatment of carotid artery stenosis. We performed a systematic review and meta-analysis of randomized controlled trials to compare the safety and efficacy of endovascular techniques with surgery for carotid stenosis. We searched MEDLINE, PubMed and Cochrane databases to identify randomized controlled trials comparing CAS with CEA. Both random and fixed effects models were used to calculate the pooled odds ratios (OR) and their confidence intervals, with values lower than one indicating a benefit from the endovascular approach. Continuity correction was used for studies with zero events in one arm. We identified 11 trials randomizing a total of 3 258 patients; 1 623 to CEA and 1 635 to CAS. By random effects model, there was no significant difference between the treatments for any stroke (OR, 1.28; 95% CI, 0.82-2.02), or death or any stroke at 30-day (OR, 1.30; 95% CI, 0.92-1.84) and death or any stroke at 6 months (OR, 1.34; 95% CI, 0.86-2.09) or 1 year (OR, 1.41; 95% CI, 0.24-8.27). However there was a significantly higher risk of 30-day death or any stroke (OR, 1.33; 95% CI, 1.01-1.75) after CAS by fixed effects model. Endovascular treatment significantly reduced the risk of 30-day cranial nerve injury (OR, 0.13; 95% CI, 0.04-0.44). In conclusion treating carotid artery stenosis with CAS offers lower rates of cranial nerve injury compared with CEA. CAS could not be proved to be as safe as CEA in treating carotid artery stenosis. The results of ongoing randomized trials comparing CAS with CEA are easily awaited because they may provide sufficient evidence for a change in clinical practice.

Transradial access for carotid artery stenting: a single-center experience.

AIM: The aim of this study was to report our initial experience using the radial artery as access for carotid artery stenting (CAS) and review the existing literature. METHODS: From January to June 2008, nine high-risk consecutive patients were treated with carotid stents by using the radial artery as an access point. Major complications (perioperative myocardial infarction, stroke, transient ischemic attack [TIAs] and death) and minor complications (radial artery occlusion or hematomas) were evaluated during this procedure. RESULTS: Seven of these patients had a right (77.8%) and two had a left (22.2%) sided carotid artery stenosis. Patients were symptomatic (TIAs or strokes or both) and had a >60% stenosis of the internal carotid artery. The technical success rate was 100% and all patients mobilized two hours after the procedure and were discharged home on the first postoperative day. No major or minor complications were reported. CONCLUSION: Patients with vessel pathology or unfavorable anatomy in the iliofemoral arteries or/and the aorta, can be candidates for CAS through the radial artery. Refinement of the technique and improvement in endovascular devices may lead to the replacement of the conventional femoral access by the transradial route in the near future.

Case report: reconstruction of the distal tibia with porous tantalum spacer after resection for giant cell tumor.

Treatment options for giant cell tumors of the distal tibia include curettage and cement packing, curettage and bone grafting, or resection and reconstruction for aggressive tumors. Curettage of aggressive tumors often leads to severe bone loss requiring reconstruction. Allograft and autograft may be effective options for reconstruction, but each is associated with drawbacks including the possibility of infection and collapse. We present a case of giant cell tumor of the distal tibia treated with curettage and arthrodesis using a porous tantalum spacer. Complete removal of the tumor and successful arthrodesis of the ankle were accomplished using the spacer. The patient returned to pain-free walking along with eradication of the giant cell tumor. We believe porous tantalum spacers are a reasonable option for reconstructing the distal tibia after curettage of a giant cell tumor with extensive bone loss.

Guided remote endarterectomy for superficial femoral artery occlusions: a technical note.

The aim of this paper was to describe a new modification of the remote endarterectomy for the treatment of long superficial femoral artery (SFA) occlusions and to present our preliminary results. Through a subinguinal incision and arteriotomy over the SFA origin, a hydrophilic guidewire was introduced into the subintimal plane of the SFA and advanced distally until reentry into the distal patent popliteal artery. The hydrophilic guidewire is exchanged for an Ablatz wire to provide support for the advancement of the single endarterectomy ring. The MollRing Cutter was introduced in the SFA after the removal of the single endarterectomy ring and it was advanced until the re-entry point. The atherosclerotic core was removed and a nitinol self-expanding stent was placed at the peripheral end of the endarterectomy. Arteriotomy was closed with a patch. Guided subintimally-assisted remote endarterectomy seems to be a successful and safe modification of the traditional technique in the treatment of SFA occlusion, in patients with critical limb ischemia.

Meta-analysis of rare events: an update and sensitivity analysis of cardiovascular events in randomized trials of rosiglitazone.

BACKGROUND: A meta-analysis of randomized controlled trials suggested that rosiglitazone, a drug used for the treatment of diabetes, may be associated with an increased risk of cardiovascular adverse events. Three large randomized trials, designed specifically to address cardiovascular outcomes of rosiglitazone treatment, have published new or updated results. PURPOSE: To provide a cumulative summary of the clinical trial evidence on rosiglitazone along with a sensitivity analysis of different methods to estimate the combined effect. METHODS: A previous meta-analysis (N Engl J Med 2007; 356: 2457-2471) was updated to include event rates of myocardial infarction and death due to cardiovascular causes from the recent reports of the RECORD, DREAM and ADOPT trials. Odds ratios (OR) with their confidence intervals were calculated for all outcomes using the Mantel-Haenszel method with Robins-Breslow-Greenland variance estimation and a fixed effects model. Sensitivity analysis was performed, using different methods for estimating the combined effect and using different continuity corrections for studies with zero events in one or both arms. RESULTS: Rosiglitazone was associated with an increased risk of myocardial infarction (OR, 1.29; CI: 1.01-1.66; p = 0.05) but not death due to cardiovascular causes (OR, 1.12; CI: 0.80-1.55; p = 0.58). Pooled analysis of the ADOPT, RECORD, and DREAM trials did not reach statistical significance for either myocardial infarction (OR, 1.29; CI: 0.95-1.74; p = 0.12) or death due to cardiovascular causes (OR, 0.90; CI: 0.61-1.33; p = 0.67). Based on these three trials, rosiglitazone was associated with a clear increase in the risk of heart failure (OR, 2.17; CI: 1.49-3.17; p < 0.0001). Despite minor discrepancies, different calculation methods demonstrated an increased risk of myocardial infarction for rosiglitazone treated patients. There was no evidence of an association between rosiglitazone and death due to cardiovascular causes regardless of the calculation method used. The increased risk of heart failure conferred by rosiglitazone treatment was consistently demonstrated across different calculation methods. LIMITATIONS: Trials with short-term follow-up and trials not specifically designed to evaluate cardiovascular outcomes were included in this meta-analysis and patient-level data where not available. CONCLUSIONS: Rosiglitazone appears to be associated with an increased risk of myocardial infarction and heart failure, but not death due to cardiovascular causes. When a meta-analysis of rare events is contemplated, a thorough sensitivity analysis using different methods to combine studies and an evaluation of different continuity corrections should be undertaken. When possible, an individual patient data meta-analysis should be performed, allowing time-to-event analysis and the identification of patient subgroups at an increased risk of adverse outcomes.

Comparison of carotid endarterectomy using primary closure, patch closure, and eversion techniques.

BACKGROUND: This study was undertaken to evaluate the role of eversion endarterectomy in the management of extracranial carotid occlusive disease. METHODS: A retrospective review was performed of all patients undergoing carotid endarterectomy between July 1994 and July 1998. After reviewing the records, patients were assigned to one of three groups: eversion (ECEA); open with primary closure (CEA); or open with patch closure (CEAP). Statistical comparisons were made. RESULTS: The 190 index cases comprised 33 ECEA (17%), 15 CEA (8%), and 142 CEAP (75%). Both ECEA and CEA were more likely to be done on males versus females compared with CEAP (P = 0.01). For the entire 190 cases, stroke occurred in 1 patient (0.5%); and myocardial infarction in 2 patients (1%), resulting in death in both. Two patients (1.4%) in the CEAP group have undergone redo surgery at 8 and 24 months. CONCLUSIONS: This study demonstrates that eversion endarterectomy achieves early results similar to open endarterectomy with and without patch closure.