Clinical outcomes after zotarolimus and everolimus drug eluting stent implantation in coronary artery bifurcation lesions: insights from the RESOLUTE All Comers Trial

OBJECTIVE We investigated clinical outcomes after treatment of coronary bifurcation lesions with second generation drug eluting stents (DES). DESIGN Post hoc analysis of a randomised, multicentre, non-inferiority trial. SETTING Multicentre study. PATIENTS All comers study with minimal exclusion criteria. INTERVENTIONS Patients were treated with either zotarolimus or everolimus eluting stents. The patient population was divided according to treatment of bifurcation or non-bifurcation lesions and clinical outcomes were compared between groups. MAIN OUTCOMES MEASURES Clinical outcomes within 2-year follow-up. RESULTS A total of 2265 patients were included in the present analysis. Two-year follow-up data were available in 2223 patients: 1838 patients in the non-bifurcation group and 385 patients in the bifurcation group. At 2-year follow-up the bifurcation and the non-bifurcation lesion groups showed no significant differences in terms of cardiac death (2.3 vs 2.1, p=0.273), target lesion failure (9.7% vs 13.8%, p=0.255), major adverse cardiac events (11.5% vs 15.1%, p=0.305), target lesion revascularisation (4.7% vs 6.0%, p=0.569), and definite or probable stent thrombosis (1.6% vs 1.8%, p=0.419). CONCLUSIONS The use of second generation DES for the treatment of coronary bifurcation lesions was associated with similar long term mortality and clinical outcomes compared with non-bifurcation lesions.

Sexual function after vaginal and abdominal fistula repair

OBJECTIVE The purpose of this study was to compare clinical outcomes and sexual function between transvaginal and transabdominal repairs of vesicovaginal fistulae (VVF). STUDY DESIGN Participants (99 women with VVF at a tertiary referral center) were treated with urinary catheterization for 12 weeks and, if the procedure was unsuccessful, underwent repair either the transvaginal (Latzko) or transabdominal technique. Objective clinical parameters were analyzed; subjective outcomes were recorded prospectively at the 6-month follow-up examination with the use of the female sexual function index to evaluate sexual function and the visual analogue scale to measure general disturbance by the fistula. RESULTS After bladder drainage for 12 weeks, 8 patients had spontaneous fistula closure. Demographic variables were similar in the transvaginal (n = 60) and transabdominal (n = 31) repair groups. The transvaginal procedure showed significantly shorter operation times, less blood loss, and shorter hospital stay. Continence rates 6 months after surgery were 82% (transvaginal) and 90% (transabdominal). Sexual function in the 64 sexually active patients was significantly improved, and overall disturbance by the fistula was reduced with both operative techniques. Neither surgical intervention was superior to the other regarding any domain of sexual function or visual analog scale. CONCLUSION Fistula repair improves sexual function and quality of life with no difference attributable to surgical route. Given this and that operating time, blood loss and length of stay are less with the transvaginal approach, the transvaginal approach is preferred in VVF repair if fistula and patient characteristics are suitable.

Risk factors associated with the longevity of multi-rooted teeth. Long-term outcomes after active and supportive periodontal therapy

AIM To investigate risk factors for the loss of multi-rooted teeth (MRT) in subjects treated for periodontitis and enrolled in supportive periodontal therapy (SPT). MATERIAL AND METHODS A total of 172 subjects were examined before (T0) and after active periodontal therapy (APT)(T1) and following a mean of 11.5 ± 5.2 (SD) years of SPT (T2). The association of risk factors with loss of MRT was analysed with multilevel logistic regression. The tooth was the unit of analysis. RESULTS Furcation involvement (FI) = 1 before APT was not a risk factor for tooth loss compared with FI = 0 (p = 0.37). Between T0 and T2, MRT with FI = 2 (OR: 2.92, 95% CI: 1.68, 5.06, p = 0.0001) and FI = 3 (OR: 6.85, 95% CI: 3.40, 13.83, p < 0.0001) were at a significantly higher risk to be lost compared with those with FI = 0. During SPT, smokers lost significantly more MRT compared with non-smokers (OR: 2.37, 95% CI: 1.05, 5.35, p = 0.04). Non-smoking and compliant subjects with FI = 0/1 at T1 lost significantly less MRT during SPT compared with non-compliant smokers with FI = 2 (OR: 10.11, 95% CI: 2.91, 35.11, p < 0.0001) and FI = 3 (OR: 17.18, 95% CI: 4.98, 59.28, p < 0.0001) respectively. CONCLUSIONS FI = 1 was not a risk factor for tooth loss compared with FI = 0. FI = 2/3, smoking and lack of compliance with regular SPT represented risk factors for the loss of MRT in subjects treated for periodontitis.

Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT.

OBJECTIVE Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. METHODS We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. RESULTS Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. CONCLUSIONS This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement.

Hepatic steatosis is associated with surgical-site infection after hepatic and colorectal surgery.

BACKGROUND Obesity and increased visceral fat deposits are important risk factors for surgical-site infection (SSI). Interestingly, a potential role of hepatic steatosis on complications after extrahepatic surgery remains unknown. The aim of the present study was to investigate the impact of hepatic steatosis on SSI in patients that underwent open abdominal surgery. METHODS A total of 231 patients that underwent either liver (n = 116) or colorectal (n = 115) resection and received preoperative contrast-enhanced computed tomography scans were retrospectively investigated. Signal attenuation of the liver parenchyma was measured on computed tomography scans to assess hepatic steatosis. RESULTS More SSIs (including types 1, 2, and 3) were found in the group with hepatic steatosis (56/118 [47.5%]) compared with the control group (30/113 [26.6%]; P = .001). Patients with hepatic steatosis showed greater median body mass index than patients without hepatic steatosis (26.6 kg/m(2) [range 16.8-47.0 kg/m(2)] vs 23.2 kg/m(2) [15.9-32.7 kg/m(2)]; P < .001). Patients with hepatic steatosis experienced longer median operation times (297 minutes [52-708 minutes] vs 240 minutes [80-600 minutes]; P = .003). In a multivariate analysis, hepatic steatosis was identified as an independent risk factor for SSI in patients undergoing hepatic (odds ratio 10.33 [95% confidence interval 1.19-89.76]; P = .03) or colorectal (odds ratio 6.67 [95% confidence interval 1.12-39.33]; P = .04) operation. CONCLUSION Hepatic steatosis is associated with SSI after hepatic and colorectal operation.

After-effects and after-effects and after-effects of after-effects: The multiple side effects of prospective memory

In a prospective memory task responding to a prospective memory target involves switching between ongoing and prospective memory task which can result in a slowing of subsequent ongoing task performance (i.e., an after-effect). Moreover, a slowing can also occur when prospective memory targets occur after the prospective memory task is deactivated (i.e., another after-effect). In this study, we investigated both after-effects within the same study. Moreover, we also tested whether the latter after-effects even occur on subsequent ongoing task trials. The results show, in fact, after-effects of all kinds. Thus, (1) correctly responding to prospective memory targets results in after-effects, a so far neglected cost on ongoing task performance, (2) responding to deactivated prospective memory targets also slows down performance, probably due to the involuntary retrieval of the intention, and (3) this slowing is present even on subsequent ongoing task trials, suggesting that even deactivated intentions are sufficient to induce a conflict that requires subsequent adaptation. Overall, these results indicate that performance slowing in a prospective memory experiment includes various kinds of sources, not only monitoring cost, and these sources may be understood best in terms of conflict adaptation.

Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures

Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-d-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern of labeling in the hippocampal formation identical to that evoked by kindling. A large proportion of cells displaying TUNEL-positive nuclei was double-labeled by the neuron-specific antigen NeuN, demonstrating the neuronal identity of apoptotic cells. Either 1 or 40 kindling stimulations also gave rise to a marked increase of the number of cells double-labeled with the mitotic marker bromodeoxyuridine and NeuN in the subgranular zone and on the hilar border of the dentate granule cell layer. The present data show that single and intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons. We hypothesize that these processes, occurring early during epileptogenesis, are primary events in the development of hippocampal pathology in animals and possibly also in patients suffering from temporal lobe epilepsy.

Murine hematopoietic reconstitution after tagging and selection of retrovirally transduced bone marrow cells

A major problem facing the effective treatment of patients with cancer is how to get the specific antitumor agent into every tumor cell. In this report we describe the use of a strategy that, by using retroviral vectors encoding a truncated human CD5 cDNA, allows the selection of only the infected cells, and we show the ability to obtain, before bone marrow transplantation, a population of 5-fluouraci-treated murine bone marrow cells that are 100% marked. This marked population of bone marrow cells is able to reconstitute the hematopoietic system in lethally irradiated mice, indicating that the surface marker lacks deleterious effects on the functionality of bone marrow cells. No gross abnormalities in hematopoiesis were detected in mice repopulated with CD5-expressing cells. Nevertheless, a significant proportion of the hematopoietic cells no longer expresses the surface marker CD5 in the 9-month-old recipient mice. This transcriptional inactivity of the proviral long terminal repeat (LTR) was accompanied by de novo methylation of the proviral sequences. Our results show that the use of the CD5 as a retrovirally encoded marker enables the rapid, efficient, and nontoxic selection in vitro of infected primary cells, which can entirely reconstitute the hematopoietic system in mice. These results should now greatly enhance the power of studies aimed at addressing questions such as generation of cancer-negative hematopoiesis.