Safety and efficacy of multipolar pulmonary vein ablation catheter vs. irrigated radiofrequency ablation for paroxysmal atrial fibrillation: a randomized multicentre trial.

AIMS: The current challenge in atrial fibrillation (AF) treatment is to develop effective, efficient, and safe ablation strategies. This randomized controlled trial assesses the medium-term efficacy of duty-cycled radiofrequency ablation via the circular pulmonary vein ablation catheter (PVAC) vs. conventional electro-anatomically guided wide-area circumferential ablation (WACA). METHODS AND RESULTS: One hundred and eighty-eight patients (mean age 62 ± 12 years, 116 M : 72 F) with paroxysmal AF were prospectively randomized to PVAC or WACA strategies and sequentially followed for 12 months. The primary endpoint was freedom from symptomatic or documented >30 s AF off medications for 7 days at 12 months post-procedure. One hundred and eighty-three patients completed 12 m follow-up. Ninety-four patients underwent PVAC PV isolation with 372 of 376 pulmonary veins (PVs) successfully isolated and all PVs isolated in 92 WACA patients. Three WACA and no PVAC patients developed tamponade. Fifty-six percent of WACA and 60% of PVAC patients were free of AF at 12 months post-procedure (P = ns) with a significant attrition rate from 77 to 78%, respectively, at 6 months. The mean procedure (140 ± 43 vs. 167 ± 42 min, P<0.0001), fluoroscopy (35 ± 16 vs. 42 ± 20 min, P<0.05) times were significantly shorter for PVAC than for WACA. Two patients developed strokes within 72 h of the procedure in the PVAC group, one possibly related directly to PVAC ablation in a high-risk patient and none in the WACA group (P = ns). Two of the 47 patients in the PVAC group who underwent repeat ablation had sub-clinical mild PV stenoses of 25-50% and 1 WACA patient developed delayed severe PV stenosis requiring venoplasty. CONCLUSION: The pulmonary vein ablation catheter is equivalent in efficacy to WACA with reduced procedural and fluoroscopy times. However, there is a risk of thrombo-embolic and pulmonary stenosis complications which needs to be addressed and prospectively monitored. CLINICALTRIALSGOV IDENTIFIER: NCT00678340.

Relapsed multiple myeloma: who benefits from salvage autografts?

BACKGROUND: Multiple myeloma is incurable despite the advance of autologous stem cell transplant (ASCT) and novel agents (thalidomide, bortezomib, lenalidomide). The role of ASCT as salvage therapy in relapsed myeloma remains unclear. AIM: To identify and refine the predictors of survival following salvage ASCT for relapsed multiple myeloma, so that they can be applied clinically for patient selection. METHODS: Retrospective review of patients treated salvage ASCT for relapsed myeloma at our centre from 1992 to 2011. RESULTS: Following an initial ASCT at diagnosis, 30 patients underwent salvage ASCT for subsequent relapse, with the median time to first relapse/progression being 30.2 months. All patients received reinduction, then melphalan-based conditioning with salvage ASCT. Non-relapse mortality at 100 days following salvage ASCT was 3%. The median overall survival and progression-free survival following salvage ASCT were 45 and 22 months respectively. The progression-free interval (PFI) after initial ASCT predicted survival outcomes in a time-dependent manner. With PFI following initial ASCT of <18, 18-36 and ≥36 months, the median progression-free survival following salvage ASCT was 4.2, 13.8 and 49.1 months respectively (P < 0.0001). The median overall survival was 10.7, 30.9 and 86.1 months respectively (P < 0.0001). CONCLUSIONS: Salvage ASCT is an effective and safe treatment option in selected patients and should be considered in patients relapsing ≥36 months after their initial ASCT. The time-dependent relationship between PFI and salvage ASCT outcome is important when stratifying patient groups who may benefit from this procedure.

High-density substrate mapping in Brugada syndrome: combined role of conduction and repolarization heterogeneities in arrhythmogenesis.

BACKGROUND: Two principal mechanisms are thought to be responsible for Brugada syndrome (BS): (1) right ventricular (RV) conduction delay and (2) RV subepicardial action potential shortening. This in vivo high-density mapping study evaluated the conduction and repolarization properties of the RV in BS subjects. METHODS AND RESULTS: A noncontact mapping array was positioned in the RV of 18 BS patients and 20 controls. Using a standard S(1)-S(2) protocol, restitution curves of local activation time and activation recovery interval were constructed to determine local maximal restitution slopes. Significant regional conduction delays in the anterolateral free wall of the RV outflow tract of BS patients were identified. The mean increase in delay was 3-fold greater in this region than in control (P=0<0.001). Local activation gradient was also maximally reduced in this area: 0.33+/-0.1 (mean+/-SD) mm/ms in BS patients versus 0.51+/-0.15 mm/ms in controls (P<0.0005). The uniformity of wavefront propagation as measured by the square of the correlation coefficient, r(2), was greater in BS patients versus controls (0.94+/-0.04 versus 0.89+/-0.09 [mean+/-SD]; P<0.05). The odds ratio of BS hearts having any RV segment with maximal restitution slope >1 was 3.86 versus controls. Five episodes of provoked ventricular tachycardia arose from wave breaks originating from RV outflow tract slow-conduction zones in 5 BS patients. CONCLUSIONS: Marked regional endocardial conduction delay and heterogeneities in repolarization exist in BS. Wave break in areas of maximal conduction delay appears to be critical in the initiation and maintenance of ventricular tachycardia. These data indicate that further studies of mapping BS to identify slow-conduction zones should be considered to determine their role in spontaneous ventricular arrhythmias.

Assessment of a conduction-repolarisation metric to predict Arrhythmogenesis in right ventricular disorders.

BACKGROUND: The re-entry vulnerability index (RVI) is a recently proposed activation-repolarization metric designed to quantify tissue susceptibility to re-entry. This study aimed to test feasibility of an RVI-based algorithm to predict the earliest endocardial activation site of ventricular tachycardia (VT) during electrophysiological studies and occurrence of haemodynamically significant ventricular arrhythmias in follow-up. METHODS: Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n = 11), Brugada Syndrome (BrS) (n = 13) and focal RV outflow tract VT (n = 9) underwent programmed stimulation with unipolar electrograms recorded from a non-contact array in the RV. RESULTS: Lowest values of RVI co-localised with VT earliest activation site in ARVC/BrS but not in focal VT. The distance between region of lowest RVI and site of VT earliest site (Dmin) was lower in ARVC/BrS than in focal VT (6.8 ±â€¯6.7 mm vs 26.9 ±â€¯13.3 mm, p = 0.005). ARVC/BrS patients with inducible VT had lower Global-RVI (RVIG) than those who were non-inducible (-54.9 ±â€¯13.0 ms vs -35.9 ±â€¯8.6 ms, p = 0.005) or those with focal VT (-30.6 ±â€¯11.5 ms, p = 0.001). Patients were followed up for 112 ±â€¯19 months. Those with clinical VT events had lower Global-RVI than both ARVC and BrS patients without VT (-54.5 ±â€¯13.5 ms vs -36.2 ±â€¯8.8 ms, p = 0.007) and focal VT patients (-30.6 ±â€¯11.5 ms, p = 0.002). CONCLUSIONS: RVI reliably identifies the earliest RV endocardial activation site of VT in BrS and ARVC but not focal ventricular arrhythmias and predicts the incidence of haemodynamically significant arrhythmias. Therefore, RVI may be of value in predicting VT exit sites and hence targeting of re-entrant arrhythmias.

Epicardial catheter ablation for ventricular tachycardia on uninterrupted warfarin: A safe approach for those with a strong indication for peri-procedural anticoagulation?

BACKGROUND: Current guidelines for epicardial catheter ablation for ventricular tachycardia (VT) advocate that epicardial access is avoided in anticoagulated patients and should be performed prior to heparinisation. Recent studies have shown that epicardial access may be safe in heparinised patients. However, no data exist for patients on oral anticoagulants. We investigated the safety of obtaining epicardial access on uninterrupted warfarin. METHODS: A prospective registry of patients undergoing epicardial VT ablation over two years was analysed. Consecutive patients in whom epicardial access was attempted were included. All patients were heparinised prior to epicardial access with a target activated clotting time (ACT) of 300-350s. Patients who had procedures performed on uninterrupted warfarin (in addition to heparin) were compared to those not taking an oral anticoagulant. RESULTS: 46 patients were included of which 13 were taking warfarin. There was no significant difference in clinical and procedural characteristics (except INR and AF) between the two groups. Epicardial access was achieved in all patients. There were no deaths and no patients required surgery. A higher proportion of patients in the warfarin group had a drop in haemoglobin of >2g/dL compared to the no-warfarin group (38.5% versus 27.3%, p=0.74) and delayed pericardial drain removal (7.8% versus 3.03%, p=0.47). There was no difference in overall procedural complication rate. No patients required warfarin reversal or blood transfusion. CONCLUSION: Epicardial access can be achieved safely and effectively in patients' anticoagulated with warfarin and heparinised with therapeutic ACT. This may be an attractive option for patients with a high stroke risk.

Resveratrol inhibits rhabdomyosarcoma cell proliferation.

Rhabdomysarcoma is the most common soft tissue tumour in children under the age of 15. Although the introduction of multimodal treatment programmes, including chemotherapy, radiation therapy and excision have increased the overall survival, the chemotherapeutic agents currently used for the treatment of rhabdomyosarcoma exhibit considerable toxicity. The aim of this study was to investigate the effects and possible mechanism(s) of action of resveratrol on human embryonal rhabdomyosarcoma (RD) cells. Resveratrol is a natural polyphenolic compound produced in a number of edible plants and has received considerable attention as a potential chemopreventive and/or chemotherapeutic agent against various types of cancers. In the present study, resveratrol was shown to inhibit cell proliferation of RD cells in a dose-dependent manner with an IC50 of 48.1 micromol/l and induce an arrest in the S/G2 phase of the cell cycle. As evident from immunocytochemical data, resveratrol treatment increased the size of the RD cells. Furthermore, resveratrol treatment resulted in a significant downregulation of cyclin B expression as demonstrated by western blot analyses. In conclusion, the present study shows that resveratrol exerts a strong inhibition of rhabdomyosarcoma cell proliferation in part by arresting cells in S/G2 phase of the cell cycle. These findings warrant further investigation to establish potential use of resveratrol as a relatively non-toxic chemotherapeutic agent for the treatment of rhabdomyosarcoma.

Adult bacteremic Haemophilus parainfluenzae infections. Seven reports of cases and a review of the literature.

Seven cases of adult Haemophilus parainfluenzae infections diagnosed by positive blood cultures are compared with cases previously reported in the English literature. Three patients had pneumonia, while the others had epiglottitis with meningitis, pharyngitis, arthritis, and endocarditis, respectively. Nonendocarditic manifestations of adult H parainfluenzae infection were reported in four other cases. In addition to the diseases of our patients, H parainfluenzae also has been isolated from cerebral abscesses. Patients did well with antibiotic therapy and there were no deaths. Patients did well with antibiotic therapy and there were no deaths. Report of antibiotic sensitivity testing of 50 strains disclosed 6% of isolates resistant to ampicillin sodium, with all sensitive to chloramphenicol. If the antibiotic sensitivity of the organism is unknown, then chloramphenicol therapy should be instituted until adequate susceptibility studies have been performed. If the organism is sensitive to ampicillin, then this is the drug of choice.

Sternoarticualr pyoarthrosis due to gram-negative bacilli. Report of eight cases.

Of eight patients with Gram-negative bacillary sternoarticular pyoarthrosis, seven were long-term intravenous heroin abusers. Clinical onset was insidious and a long delay (one month or more) in seeking hospitalization was usually noted. Anterior chest discomfort and painful, restricted homolateral shoulder motion were the chief complaints. Fever and monoarticular arthritis were universally present, Open synovial biopsy examination was frequently required for etiologic diagnosis. Pseudomonas aeruginosa was the most common pathogen isolated. Roentgenographic evidence of associated osteomyelitis was usually seen, but tomography was often necessary to delineate this lesion. Intraoperatively, associated osteomyelitis of the clavicular head and/or sternum was present in all eight cases and a perisynovial and/or retrosternal abscess was found in five patients. Early surgical exploration and prolonged antimicrobial therapy yielded excellent results.

Therapeutic regimens for anorectal gonococcal infection in males.

Anorectal gonococcal infection is particularly prevalent in women and homosexual men. Although the currently recommended Public Health Service therapeutic regimens for uncomplicated gonorrhea appear to be effective also for anorectal gonorrhea in women, their efficacy for anorectal infection in men has not been adequately evaluated. We report a case of gonococcal proctitis in a homosexual man that did not respond to therapy with ampicillin plus probenecid and tetracycline, but subsequently responded to spectinomycin therapy. Currently available therapeutic regimens for anorectal gonococcal infection in males are reviewed.

Role of anaerobic bacteria in subdural empyema. Report of four cases and review of 327 cases from the English literature.

Anaerobic bacteria were isolated from the subdural space in all four cases of subdural empyema encountered over a 2 and a half year period. Only one aerobe was isolated in these cases. The bacteriology of subdural empyema was further analyzed from a review of 327 cases reported in the English literature. Anaerobes accounted for 12 per cent of 234 cases; In addition, 27 per cent of cases were reportedly "sterile." These data support our finding that anaerobic bacteria may play a far more important role in subdural empyema than was previously appreciated.

Role of anaerobic bacteria in spontaneous peritonitis of cirrhosis: report of two cases and review of the literature.

The role of anaerobic or microaerophillic bacteria in spontaneous peritonitis of cirrhosis has not been clearly defined. Among 126 cases recorded in the literature, in only eight (6 per cent), including the two reported here, was bacterascites associated with anaerobic or microaerophilic bacteria. Clinical features in these cases were indistinguishable from those associated with aerobic bacteria. However, polymicrobial bacterascites occurred in four of eight cases associated with anaerobes, as contrasted with only 10 of 118 cases (8 per cent) associated with aerobes alone. On the other hand, concurrent bacteremia occurred in only one of eight cases associated with anaerobes as contrasted with 52 of 118 cases (44 per cent) of aerobic spontaneous peritonitis. Experimental evidence is cited in an attempt to explain this relatively low incidence of spontaneous peritonitis associated with anaerobic or microaerophilic bacteria, despite the high density of these organisms in the normal bowel flora.

Lactobacillemia--report of nine cases. Important clinical and therapeutic considerations.

Serious infections due to lactobacilli have been rarely cited. We report our findings in nine recent patients with lactobacillemia. In the combined literature and current experience, endocarditis and sepsis from localized suppuration were the most common clinical syndromes, most frequently arising from prior oropharyngeal infections. Lactobacillus endocarditis showed a predilection for left-sided cardiac involvement (100 per cent) and systemic arterial embolization (55 per cent). The nine clinical isolates were tested for minimal inhibitory and bactericidal concentrations (MICs and MBCs) against five drugs with broad gram-positive spectrums; of note, these organisms demonstrated a high incidence of both unachievable MBCs (64 per cent) and widely disparate (greater than 100 fold) MIC:MBC ratios (38 per cent). This is in accord with observations in Lactobacillus endocarditis of poor in vivo clinical response despite "appropriate" regimens and achievable MICs of the organisms. Bactericidal synergistic studies on two endocarditis isolates indicated that the penicillins plus aminoglycosides may be potentially useful in the treatment of deep-seated Lactobacillus infections when single antimicrobials fail to achieve a cure.

Necrotizing pneumonia and empyema due to Clostridium perfringens. Report of a case and review of the literature.

Clostridia are rare causes of pleuropulmonary infections in the absence of penetrating chest injuries; only 10 previous cases have been reported from civilian practice. An additional case of a rapidly progressive, necrotizing pneumonia and empyema is reported. Clostridial pneumonia is more likely to occur in patients with underlying pleuropulmonary disease. Unlike clostridial myonecrosis, it is rarely associated with toxemia; its mortality rate is comparable to that of nonclostridial pleuropulmonary infections. Appropriate antimicrobial therapy with surgical drainage of the empyema is the treatment of choice. Among the cases reviewed, an iatrogenic cause of infection involving an invasive procedure into the pleural cavity could be identified in seven of 11 cases. Aspiration of oropharyngeal contents was the likely route of infection in three other cases. In the remaining case, bacteremic seeding of the pleural cavity was the most probable mode of infection.

Serious infections in adults due to group B streptococci. Clinical and serotypic characterization.

Serious infections in adults due to group B streptococci have been infrequently reported. We describe 24 such patients. Bacteremic pyelonephritis, pneumonitis and endometritis were the most common clinical syndromes observed. Group B streptococci infections tended to occur in patients with underlying illnesses, particularly genitourinary disorders and diabetes mellitus. Mortality was surprisingly low (8 per cent). Type III was the serotype most commonly isolated, and there was no significant correlation of different serotypes with specific organ-system involvement. Group B streptococcal isolates from these patients were uniformly sensitive to penicillin, ampicillin, cephalothin, chloramphenicol, erythromycin and clindamycin; all were highly resistant to kanamycin. Eighty-seven per cent were resistant to tetracycline. Although consistently sensitive to penicillin, the minimal inhibitory concentrations were significantly higher for group B than group A streptococci (p less than 0.0005).

Sepsis associated with decubitus ulcers.

Among 21 patients with sepsis attributed solely to decubitus ulcers, bacteremia was documented in 16 (76 per cent)9 Bacteremia involved obligate anaerobes in eight patients (50 per cent) and was polymicrobial in eight patients (50 per cent). Twelve of 17 patients who received antibiotics had persistent bacteremia; in five patients, bacteremia was terminated only after surgical debridement. Ten of these 21 patients died, eight despite appropirate antibiotics. Among 14 patients who underwent surgical debridement, only four patients died. Surgical debridement and antibiotics effective against aerobic as well as anaerobic bacteria are both important in the treatment of this serious complication.

Ocular penetration of N-formimidoyl thienamycin (MK-787) and potentiation by dipeptidase inhibitor (MK-791).

N-formimidoyl thienamycin (MK-787) is a new beta-lactam with potent activity against both aerobic and anaerobic gram-positive and gram-negative bacteria. Its spectrum and activity suggest it may be useful in treatment of complicated intraocular infections. Its ocular penetration was studied in New Zealand white rabbits immediately before and after the third dose of 40 mg/kg administered intravenously at q6h intervals. Plasma, aqueous humor, and vitreous humor were obtained by direct aspiration, and antibiotic levels were assayed using an agar well diffusion method. MK-787 penetrated uninflamed intraocular fluids, including vitreous humor, although vitreous concentrations achieved (0.1-0.2 micrograms/ml) were significantly lower than the mean peak plasma (15 micrograms/ml) and aqueous concentrations (7 micrograms/ml). Nevertheless, the intraocular levels attained approached or exceeded the MIC90 for most sensitive organisms including some gram-negative bacilli important in bacterial endophthalmitis. When administered in combination with the renal enzyme inhibitor MK-791, plasma and aqueous concentrations of MK-787 were markedly potentiated, although vitreous concentrations were minimally affected. The potential usefulness of MK-787 in conjunction with MK-791 in the infected eye should be examined further in an animal model of bacterial endophthalmitis.

Primary meningococcal pericarditis presenting with tamponade.

An unusual case of a patient with primary meningococcal pericarditis presenting with tamponade is reported. tdespite repeated aspiration and appropriate antibiotic therapy with eradication of group C Neisseria meningitidis, pericardial effusion continued to reaccumulate. Institution of high-dosage corticosteroid therapy resulted in rapid resolution of the effusion. Only six other cases of primary meningococcal pericarditis have been reported in the English literature. Early manifestations of this disease are due to bacterial invasion of the pericardium. The later phase of intensive reaccumulation of sterile pericardial fluid may conceivably be related to meningococcal endotoxin and appears to be responsive to corticosteroid or salicylate therapy. Recognition of this phenomenon may obviate the necessity for a pericardiectomy.

Campylobacter fetus associated with pulmonary abscess and empyema.

An unusual case of community-acquired necrotizing aspiration pneumonia with pulmonary abscess and empyema associated with Campylobacter fetus (formerly Vibrio fetus) in mixed culture is reported. This microaerophilic gram-negative curved bacillus has been increasingly associated with human disease. Unlike most pathogens associated with community-acquired aspiration pneumonia, this organism is usually resistant to penicillin. Infection associated with this organism is characteristically relapsing in nature and requires protracted antimicrobial therapy.

Prosthetic valve endocarditis. Experience with porcine bioprostheses.

Prosthetic valve endocarditis remains an infrequent but serious complication of cardiac valvular replacement. Prosthetic valve endocarditis was diagnosed in 56 (1.8%) of 3200 patients in whom one or more porcine bioprostheses were implanted between 1975 and 1988. Of the 56 patients with prosthetic valve endocarditis, there were 40 men and 16 women, with a mean age at initial implantation of 57 years (27 to 81 years). Of the 56 patients, 6 were initially treated for native valve endocarditis. There were 8 cases of early prosthetic valve endocarditis (defined as occurring less than 60 days after initial surgical intervention) and 48 cases of late prosthetic valve endocarditis (occurring after 60 days). The overall mortality rate of the 56 patients was 32% (18 patients). Of the 8 patients with early prosthetic valve endocarditis, 6 (75%) died. Of the 48 patients with late prosthetic valve endocarditis, 12 (25%) died. The predominant organisms were Staphylococcus epidermidis (12 cases), Streptococcus viridans (8 cases) and Staphylococcus aureus (7 cases). The presence of hemodynamic compromise, including congestive heart failure, septic embolism, persistent sepsis, and echocardiographic evidence of vegetations, dictated the mode and timing of the addition of surgical intervention to medical therapy. The survival rate for medically and surgically treated patients with late prosthetic valve endocarditis was 91% (20 patients); none of the patients with early prosthetic valve endocarditis survived (all had severe hemodynamic compromise). We analyzed 18 factors for the prediction of early and late death. The predictors of death by univariate analysis for both early and late prosthetic valve endocarditis were age, diagnosis time, renal status, sepsis, management mode, fever, dental procedures, and dental prophylaxis. The predictors by multivariate analysis were age, diagnosis time, renal status, and management mode for early prosthetic valve endocarditis, and only diagnosis time for late prosthetic valve endocarditis. Annular abscess formation occurred in 27% of the patients. There were no complex aortic or mitral reconstructions. There was one reoperation for recurrent and residual endocarditis. There was one late death as a result of recurrent prosthetic valve endocarditis. We advocate early diagnosis and aggressive combined medical and surgical treatment before the development of hemodynamic compromise and other characteristic signs when the culprit organisms are Staphylococcus aureus, gram-negative organisms, and Candida albicans.

Adoption of guidelines for Universal Precautions and Body Substance Isolation in Canadian acute-care hospitals.

The impact of recently recommended hospital infection control guidelines on Canadian acute-care hospitals is unknown. A confidential cross-sectional mailed survey of all acute-care Canadian hospitals was conducted to determine rates of receipt and adoption of published guidelines for Universal Precautions (UP) or Body Substance Isolation (BSI), rationale for adoption and knowledge of costs and benefits. Five hundred and seventy-nine of 943 sites (61%) responded (exceeding 80% in urban centers); 94% among hospitals with at least 300 beds and 57% among those under 300 beds. Seventy-four percent of responders claimed adoption of UP (65%) or BSI (9%), staff protection being their primary motivation. Adoption of either UP or BSI was associated with size (p less than .001), increasing progressively from 45% in the smallest group (less than 25 beds) to 84% in the largest (greater than or equal to 500 beds). Many hospitals introduced modifications and some substituted names other than UP or BSI in adopting a new strategy. In practice, UP and BSI now mean different things in different hospitals, and the distinction between them has become blurred. Furthermore, only 5% claiming adoption of a new strategy adopted all of the fundamental policies expected under UP or BSI. Receipt of guidelines was also correlated with size: one-third of hospitals under 200 beds had not received key publications defining UP and BSI. Only 19% claiming adoption of a new strategy indicated knowledge of cost implications. These results suggest a need for closer collaboration among hospitals and government agencies in developing uniform infection control policies, and for systematic evaluation of the cost and effectiveness of new strategies.