Endocannabinoid regulation of acute and protracted nicotine withdrawal: effect of FAAH inhibition.

Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.

Transcatheter aortic valve replacement for degenerative bioprosthetic surgical valves: Results from the global valve-in-valve registry.

BACKGROUND Transcatheter aortic valve-in-valve implantation is an emerging therapeutic alternative for patients with a failed surgical bioprosthesis and may obviate the need for reoperation. We evaluated the clinical results of this technique using a large, worldwide registry. METHODS AND RESULTS The Global Valve-in-Valve Registry included 202 patients with degenerated bioprosthetic valves (aged 77.7±10.4 years; 52.5% men) from 38 cardiac centers. Bioprosthesis mode of failure was stenosis (n=85; 42%), regurgitation (n=68; 34%), or combined stenosis and regurgitation (n=49; 24%). Implanted devices included CoreValve (n=124) and Edwards SAPIEN (n=78). Procedural success was achieved in 93.1% of cases. Adverse procedural outcomes included initial device malposition in 15.3% of cases and ostial coronary obstruction in 3.5%. After the procedure, valve maximum/mean gradients were 28.4±14.1/15.9±8.6 mm Hg, and 95% of patients had ≤+1 degree of aortic regurgitation. At 30-day follow-up, all-cause mortality was 8.4%, and 84.1% of patients were at New York Heart Association functional class I/II. One-year follow-up was obtained in 87 patients, with 85.8% survival of treated patients. CONCLUSIONS The valve-in-valve procedure is clinically effective in the vast majority of patients with degenerated bioprosthetic valves. Safety and efficacy concerns include device malposition, ostial coronary obstruction, and high gradients after the procedure.

Role of the paclitaxel-eluting stent and tirofiban in patients with ST-elevation myocardial infarction undergoing postfibrinolysis angioplasty: the GRACIA-3 randomized clinical trial.

BACKGROUND A catheter-based approach after fibrinolysis is recommended if fibrinolysis is likely to be successful in patients with acute ST-elevation myocardial infarction. We designed a 2x2 randomized, open-label, multicenter trial to evaluate the efficacy and safety of the paclitaxel-eluting stent and tirofiban administered after fibrinolysis but before catheterization to optimize the results of this reperfusion strategy. METHODS AND RESULTS We randomly assigned 436 patients with acute ST-elevation myocardial infarction to (1) bare-metal stent without tirofiban, (2) bare-metal stent with tirofiban, (3) paclitaxel-eluting stent without tirofiban, and (4) paclitaxel-eluting stent with tirofiban. All patients were initially treated with tenecteplase and enoxaparin. Tirofiban was started 120 minutes after tenecteplase in those patients randomly assigned to tirofiban. Cardiac catheterization was performed within the first 3 to 12 hours after inclusion, and stenting (randomized paclitaxel or bare stent) was applied to the culprit artery. The primary objectives were the rate of in-segment binary restenosis of paclitaxel-eluting stent compared with that of bare-metal stent and the effect of tirofiban on epicardial and myocardial flow before and after mechanical revascularization. At 12 months, in-segment binary restenosis was similar between paclitaxel-eluting stent and bare-metal stent (10.1% versus 11.3%; relative risk, 1.06; 95% confidence interval, 0.74 to 1.52; P=0.89). However, late lumen loss (0.04+/-0.055 mm versus 0.27+/-0.057 mm, P=0.003) was reduced in the paclitaxel-eluting stent group. No evidence was found of any association between the use of tirofiban and any improvement in the epicardial and myocardial perfusion. Major bleeding was observed in 6.1% of patients receiving tirofiban and in 2.7% of patients not receiving it (relative risk, 2.22; 95% confidence interval, 0.86 to 5.73; P=0.14). CONCLUSIONS This trial does not provide evidence to support the use of tirofiban after fibrinolysis to improve epicardial and myocardial perfusion. Compared with bare-metal stent, paclitaxel-eluting stent significantly reduced late loss but appeared not to reduce in-segment binary restenosis. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00306228.

Fracturas femorales periprotésicas de rodilla tratadas con clavo intramedular retrógrado y osteosíntesis con placa: comparación de resultados a medio-largo plazo

INTRODUCTION: The femoral periprosthetic fracture of the knee is one of the most feared complications because of its repercussions. Incidence are more and more likely due to the increase of total implanted arthroplasty of the knee, due to the increasing lifespan among the general population. The objective of this study is to analyze some of the perioperative aspects of the treatment of these fractures, comparing the use of osteosynthesis with plates and the retrograde nailing in those patients with femoral periprosthetic knee fractures with a stable implant. MATERIAL AND METODS: The study retrospectively examines 18 cases treated consecutively in our hospital (3 men and 15 women, average age of 72.7 years) between the years of 2000 and 2009. All fractures were located in the distal femur and on a stable implant. Eight were treated through retrograde nailing (Group I) and ten with plates (Group II). The cases are analyzed through the tests of the University of Mann-Withney and the exact Fischer test, with significant values of p≤0.05, the variables of median hospital stay, necessity of transfusion indicated with values of hemoglobin less than 8 mg/ml, preoperative radiological alignment and postoperative alignment of the total knee prosthesis (TKR), measured following the anatomical tibiofemoral axis, time of consolidation and incidence of localized complications in both groups. RESULTS: We did not find any statistically significant differences between the two groups in any of the variables analyzed. Localized complications are more frequent in Group I (62.5 percent of patients) than in Group II (10 percent of patients). The need for transfusion is greater in Group II (40 percent) than in Group I (12.5 percent). CONCLUSIONS: The type of implant used in treatment of femoral periprosthetic knee fracture does not significantly influence perioperative factors. The treatment for this type of fractures should be individually chosen in relation to the type of fracture, characteristics of the patient and stability and prosthesis model of the primary knee.

Prótesis unicompartimental como opción quirúrgica en la gonartrosis medial en el adulto joven

OBJECTIVE: Assess the degree of satisfaction in a series of patients between 50 and 60 years of age who underwent surgery in our unicompartmental prosthesis unit (UPU) for monocompartmental gonarthrosis. Likewise, the definition based on current literature is assessed, as well as our experience in the indications, inconveniences and results of the internal knee unicompartmental arthroplasty discussed with supra-tuberosity tibial osteotomy, which was the common surgical option in these cases.MATERIAL AND METHOD: This study included 19 patients between 50 and 60 years of age (average age 56.7 years) (Interval of 51-60 years) intervened between 7/2007 and 11/2011 by the same surgeon (GDFB). Functional assessment used the Oxford Knee Score (OKS) questionnaire. A bibliographic search was performed in the MEDLINE, COCHRANE and EMBASE databases from 1988 to 2012. RESULTS: With an average follow-up of 29.4 months, 16 of 19 patients stated that they were satisfied with the results obtained and would repeat the intervention. One patient sufered a prosthetic infection and was reviewed for total knee replacement with good results. CONCLUSIONS: the medial, unicompartmental arthroplasty of the knee is a valid surgical option and reproducible in the medium term treatment of monocompartmental gonarthrosis in patients between 50 and 60 years of age.

Thorax, pelvis and hip pattern in the frontal plane during walking in unilateral transtibial amputees: biomechanical analysis.

BACKGROUND Lower limb amputees exhibit postural control deficits during standing which can affect their walking ability. OBJECTIVES The primary purpose of the present study was to analyze the thorax, pelvis, and hip kinematics and the hip internal moment in the frontal plane during gait in subjects with Unilateral Transtibial Amputation (UTA). METHOD The participants included 25 people with UTA and 25 non-amputees as control subjects. Gait analysis was performed using the Vicon(r) Motion System. We analyzed the motion of the thorax, pelvis, and hip (kinematics) as well as the hip internal moment in the frontal plane. RESULTS The second peak of the hip abductor moment was significantly lower on the prosthetic side than on the sound side (p=.01) and the control side (right: p=.01; left: p=.01). During middle stance, the opposite side of the pelvis was higher on the prosthetic side compared to the control side (right: p=.01: left: p=.01). CONCLUSIONS The joint internal moment at the hip in the frontal plane was lower on the prosthetic side than on the sound side or the control side. Thorax and pelvis kinematics were altered during the stance phase on the prosthetic side, presumably because there are mechanisms which affect postural control during walking.

Prótesis unicompartimental lateral de rodilla. Indicaciones, técnica y resultados a mediocorto plazo

Objectives: In patients with lateral osteoarthritis of the knee, use of external unicompartmental knee arthroplasty it is a well known surgical alternative, used by the minor trauma involved, short hospital stay and rapid recovery. The purpose of this study is to show the clinical outcomes to short-medium term of patients undergoing this procedure. Methods: we describe the technique used and the peculiarities of the prosthesis (A Mobile-bearing lateral unicompartmental knee replacement, Oxford Domed ®). This is an observational retrospective longitudinal study, of 15 arthroplasties performed in 13 women and 2 men, between 2010 and 2013, with a mean age of 60’7 years, with a diagnosis of lateral osteoarthritis of the knee, without involvement of the medial or patellofemoral compartment and cruciate ligaments functionally intact, with a mean follow up of 25 months. All patients complete the Oxford Knee Score and Visual Analog Scale (VAS) during the study. Results: The results are favorable, with an improvement of 6.60 points on the EVA, 3.73 for 1 in the postoperatory funcionality, the OKS very satisfactory with an average of 38 points over 50 and without any postoperative function surgical revision. Anserine tendinitis was observed in 20% of cases. Conclusions: The benefits of this surgery against their alternatives are assessed, and their potential drawbacks. External unicompartmental knee arthroplasty is an effective alternative in cases of knee osteoarthritis of the lateral compartment with no other associated injuries.

Prevention of the renarrowing of coronary arteries using drug-eluting stents in the perioperative period: an update.

The management of patients scheduled for surgery with a coronary stent, and receiving 1 or more antiplatelet drugs, has many controversies. The premature discontinuation of antiplatelet drugs substantially increases the risk of stent thrombosis (ST), myocardial infarction, and cardiac death, and surgery under an altered platelet function could also lead to an increased risk of bleeding in the perioperative period. Because of the conflict in the recommendations, this article reviews the current antiplatelet protocols after positioning a coronary stent, the evidence of increased risk of ST associated with the withdrawal of antiplatelet drugs and increased bleeding risk associated with its maintenance, the different perioperative antiplatelet protocols when patients are scheduled for surgery or need an urgent operation, and the therapeutic options if excessive bleeding occurs.

Resuscitated sudden cardiac death caused by left main coronary artery compression by an aneurysm of the sinus of Valsalva.

A 49-year-old woman, without known cardiovascular risk factors. Hoarseness of voice caused by a paralysis of left vocal cord. She was admitted to hospital because of acute coronary syndrome, associated to resuscitated cardiac arrest (asystolia documented) without later neurology sequels. Physical examination was anodyne. Echocardiographic study demonstrated a compatible image with a large left sinus of Valsalva aneurysm (SVA) (Panel A) and mild aortic regurgitation. Cardiac catheterization confirmed the presence of left SVA (Panel B) that produced extrinsic compression of the left main coronary artery (Panels C and D). Repair surgery was made by means of closing the aneurysmal orifice with a patch of dacron. Intra-operatory echocardiographic control study found severe aortic regurgitation, so valvular replacement with 19 mm mechanical prosthesis and extension of the valve annulus with patch of dacron was performed, associated with bypass with safena vein graft to left coronary artery. SVA is a very infrequent cardiac anomaly, generally with silent clinical course until it ruptures. Myocardial ischaemia caused by coronary artery compression is unusual. We described the case of a patient diagnosed of left SVA, whose initial clinical manifestation was the appearance of resuscitated sudden cardiac death in the context of an acute coronary syndrome.

Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation.

BACKGROUND It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). CONCLUSIONS PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.

Variability of indication criteria in knee and hip replacement: an observational study

BACKGROUND. Total knee (TKR) and hip (THR) replacement (arthroplasty) are effective surgical procedures that relieve pain, improve patients' quality of life and increase functional capacity. Studies on variations in medical practice usually place the indications for performing these procedures to be highly variable, because surgeons appear to follow different criteria when recommending surgery in patients with different severity levels. We therefore proposed a study to evaluate inter-hospital variability in arthroplasty indication. METHODS. The pre-surgical condition of 1603 patients included was compared by their personal characteristics, clinical situation and self-perceived health status. Patients were asked to complete two health-related quality of life questionnaires: the generic SF-12 (Short Form) and the specific WOMAC (Western Ontario and Mcmaster Universities) scale. The type of patient undergoing primary arthroplasty was similar in the 15 different hospitals evaluated.The variability in baseline WOMAC score between hospitals in THR and TKR indication was described by range, mean and standard deviation (SD), mean and standard deviation weighted by the number of procedures at each hospital, high/low ratio or extremal quotient (EQ5-95), variation coefficient (CV5-95) and weighted variation coefficient (WCV5-95) for 5-95 percentile range. The variability in subjective and objective signs was evaluated using median, range and WCV5-95. The appropriateness of the procedures performed was calculated using a specific threshold proposed by Quintana et al for assessing pain and functional capacity. RESULTS. The variability expressed as WCV5-95 was very low, between 0.05 and 0.11 for all three dimensions on WOMAC scale for both types of procedure in all participating hospitals. The variability in the physical and mental SF-12 components was very low for both types of procedure (0.08 and 0.07 for hip and 0.03 and 0.07 for knee surgery patients). However, a moderate-high variability was detected in subjective-objective signs. Among all the surgeries performed, approximately a quarter of them could be considered to be inappropriate. CONCLUSIONS. A greater inter-hospital variability was observed for objective than for subjective signs for both procedures, suggesting that the differences in clinical criteria followed by surgeons when indicating arthroplasty are the main responsible factors for the variation in surgery rates.

Free flaps in surgical dermatology. Comparison between fasciocutaneous and myocutaneous free flaps in facial reconstructions.

BACKGROUND Dermatologic surgeons routinely harvest pedicled flaps at distance with an axial or random pattern to repair facial defects. These types of skin flaps are time-consuming and have high economic, social and personal costs. These drawbacks could be avoided with the introduction of a single-step transfer of free flaps to the recipient site, with microvascular anastomosis. OBJECTIVE To demonstrate that better results are obtained with myocutaneous or fasciocutaneous free flaps and which one is more suitable in surgical dermatology. MATERIAL AND METHODS We selected two patients of opposite sexes and similar ages who had undergone Mohs surgery to remove recurrent malignant tumors that were located in the upper cheek bordering the zygomatic zone. The woman was treated with a fasciocutaneous radial free flap and the man with a rectus abdominis free flap. RESULTS Both patients had excellent immediate postoperative outcomes. Complications observed in the male patient were related to a previous pulmonary alteration. The fasciocutaneous radial free flap reconstruction was easier to perform than the rectus abdominis free flap; nevertheless, the radial free flap is very thin and, although the palmaris longus tendon is used, it does not yield enough volume, requiring later use of implants. In contrast, the rectus abdominis free flap transfers a wide flap with enough fat tissue to expand in the future. As for the cosmetic results regarding the donor site, the rectus abdominis free flap produces better-looking scars, since secondary defects of the palmar surface cannot be directly closed and usually require grafting - a situation that some patients do not accept. CONCLUSIONS In surgical dermatology, each case, once the tumor has been extirpated, requires its own reconstructive technique. The radial free flap is suitable for thin patients who are willing to cover their arm with a shirt. The rectus abdominis free flap is best suited for obese patients with deep and voluminous defects, although it is necessary to dislocate the navel from its original position.

Permanent pacemaker implantation after transcatheter aortic valve implantation: impact on late clinical outcomes and left ventricular function.

BACKGROUND Very few data exist on the clinical impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation. The objective of this study was to assess the impact of PPI after transcatheter aortic valve implantation on late outcomes in a large cohort of patients. METHODS AND RESULTS A total of 1556 consecutive patients without prior PPI undergoing transcatheter aortic valve implantation were included. Of them, 239 patients (15.4%) required a PPI within the first 30 days after transcatheter aortic valve implantation. At a mean follow-up of 22±17 months, no association was observed between the need for 30-day PPI and all-cause mortality (hazard ratio, 0.98; 95% confidence interval, 0.74-1.30; P=0.871), cardiovascular mortality (hazard ratio, 0.81; 95% confidence interval, 0.56-1.17; P=0.270), and all-cause mortality or rehospitalization for heart failure (hazard ratio, 1.00; 95% confidence interval, 0.77-1.30; P=0.980). A lower rate of unexpected (sudden or unknown) death was observed in patients with PPI (hazard ratio, 0.31; 95% confidence interval, 0.11-0.85; P=0.023). Patients with new PPI showed a poorer evolution of left ventricular ejection fraction over time (P=0.017), and new PPI was an independent predictor of left ventricular ejection fraction decrease at the 6- to 12-month follow-up (estimated coefficient, -2.26; 95% confidence interval, -4.07 to -0.44; P=0.013; R(2)=0.121). CONCLUSIONS The need for PPI was a frequent complication of transcatheter aortic valve implantation, but it was not associated with any increase in overall or cardiovascular death or rehospitalization for heart failure after a mean follow-up of ≈2 years. Indeed, 30-day PPI was a protective factor for the occurrence of unexpected (sudden or unknown) death. However, new PPI did have a negative effect on left ventricular function over time.

Acute haematogenous prosthetic joint infection: prospective evaluation of medical and surgical management

The optimum treatment for prosthetic joint infections has not been clearly defined. We report our experience of the management of acute haematogenous prosthetic joint infection (AHPJI) in patients during a 3-year prospective study in nine Spanish hospitals. Fifty patients, of whom 30 (60%) were female, with a median age of 76 years, were diagnosed with AHPJI. The median infection-free period following joint replacement was 4.9 years. Symptoms were acute in all cases. A distant previous infection and/or bacteraemia were identified in 48%. The aetiology was as follows: Staphylococcus aureus, 19; Streptococcus spp., 14; Gram-negative bacilli, 12; anaerobes, two; and mixed infections, three. Thirty-four (68%) patients were treated with a conservative surgical approach (CSA) with implant retention, and 16 had prosthesis removal. At 2-year follow-up, 24 (48%) were cured, seven (14%) had relapsed, seven (14%) had died, five (10%) had persistent infection, five had re-infection, and two had an unknown evolution. Overall, the treatment failure rates were 57.8% in staphylococcal infections and 14.3% in streptococcal infections. There were no failures in patients with Gram-negative bacillary. By multivariate analysis, CSA was the only factor independently associated with treatment failure (OR 11.6; 95% CI 1.29-104.8). We were unable to identify any factors predicting treatment failure in CSA patients, although a Gram-negative bacillary aetiology was a protective factor. These data suggest that although conservative surgery was the only factor independently associated with treatment failure, it could be the first therapeutic choice for the management of Gram-negative bacillary and streptococcal AHPJI, and for some cases with acute S. aureus infections.