Successful procedure with additional omentopexy to suture closure of gallbladder stump in laparoscopic subtotal cholecystectomy.

Laparoscopic subtotal cholecystectomy, a bailout surgery for cholecystitis, can result in postoperative bile leakage, so surgical ingenuity is required. An 88-year-old woman had pain at the right hypochondrium. Abdominal computed tomography showed swelling of the gallbladder and thickness of the gallbladder wall, leading to diagnosis of mild acute cholecystitis. Percutaneous transhepatic gallbladder drainage was performed to alleviate cholecystitis because the patient was taking antiplatelet medicine. Laparoscopic cholecystectomy was then performed within 72 hours from the onset. The gallbladder was operatively found to be strongly fibrotic, so the procedure was switched to laparoscopic subtotal cystectomy, dissecting the gallbladder at the infundibulum-cystic duct level. The gallbladder stump was closed with barbed suture and omentopexy was added due to fragility. There was no significant postoperative bile leakage. Additional omentopexy to stump closure in laparoscopic subtotal cholecystectomy was thought to be useful in prevention of postoperative bile leakage.

Extracellular signal-regulated kinases 2 (Erk2) and Erk5 in the central nervous system differentially contribute to central sensitization in male mice.

Nervous systems are designed to become extra sensitive to afferent nociceptive stimuli under certain circumstances such as inflammation and nerve injury. How pain hypersensitivity comes about is key issue in the field since it ultimately results in chronic pain. Central sensitization represents enhanced pain sensitivity due to increased neural signaling within the central nervous system (CNS). Particularly, much evidence indicates that underlying mechanism of central sensitization is associated with the change of spinal neurons. Extracellular signal-regulated kinases have received attention as key molecules in central sensitization. Previously, we revealed the isoform-specific function of extracellular signal-regulated kinase 2 (Erk2) in spinal neurons for central sensitization using mice with Cre-loxP-mediated deletion of Erk2 in the CNS. Still, how extracellular signal-regulated kinase 5 (Erk5) in spinal neurons contributes to central sensitization has not been directly tested, nor is the functional relevance of Erk5 and Erk2 known. Here, we show that Erk5 and Erk2 in the CNS play redundant and/or distinct roles in central sensitization, depending on the plasticity context (cell types, pain types, time, etc.). We used male mice with Erk5 deletion specifically in the CNS and found that Erk5 plays important roles in central sensitization in a formalin-induced inflammatory pain model. Deletion of both Erk2 and Erk5 leads to greater attenuation of central sensitization in this model, compared to deletion of either isoform alone. Conversely, Erk2 but not Erk5 plays important roles in central sensitization in neuropathic pain, a type of chronic pain caused by nerve damage. Our results suggest the elaborate mechanisms of Erk signaling in central sensitization.

The PRDM14-CtBP1/2-PRC2 complex regulates transcriptional repression during the transition from primed to naïve pluripotency.

The pluripotency-associated transcriptional network is regulated by a core circuitry of transcription factors. The PR domain-containing protein PRDM14 maintains pluripotency by activating and repressing transcription in a target gene-dependent manner. However, the mechanisms underlying dichotomic switching of PRDM14-mediated transcriptional control remain elusive. Here, we identified C-terminal binding protein 1 and 2 (CtBP1 and CtBP2; generically referred to as CtBP1/2) as components of the PRDM14-mediated repressive complex. CtBP1/2 binding to PRDM14 depends on CBFA2T2, a core component of the PRDM14 complex. The loss of Ctbp1/2 impaired the PRDM14-mediated transcriptional repression required for pluripotency maintenance and transition from primed to naïve pluripotency. Furthermore, CtBP1/2 interacted with the PRC2 complexes, and the loss of Ctbp1/2 impaired Polycomb repressive complex 2 (PRC2) and H3K27me3 enrichment at target genes after Prdm14 induction. These results provide evidence that the target gene-dependent transcriptional activity of PRDM14 is regulated by partner switching to ensure the transition from primed to naïve pluripotency.This article has an associated First Person interview with the first author of the paper.

Co-option of the PRDM14-CBFA2T complex from motor neurons to pluripotent cells during vertebrate evolution.

Gene regulatory networks underlying cellular pluripotency are controlled by a core circuitry of transcription factors in mammals, including POU5F1. However, the evolutionary origin and transformation of pluripotency-related transcriptional networks have not been elucidated in deuterostomes. PR domain-containing protein 14 (PRDM14) is specifically expressed in pluripotent cells and germ cells, and is required for establishing embryonic stem cells (ESCs) and primordial germ cells in mice. Here, we compared the functions and expression patterns of PRDM14 orthologues within deuterostomes. Amphioxus PRDM14 and zebrafish PRDM14, but not sea urchin PRDM14, compensated for mouse PRDM14 function in maintaining mouse ESC pluripotency. Interestingly, sea urchin PRDM14 together with sea urchin CBFA2T, an essential partner of PRDM14 in mouse ESCs, complemented the self-renewal defect in mouse Prdm14 KO ESCs. Contrary to the Prdm14 expression pattern in mouse embryos, Prdm14 was expressed in motor neurons of amphioxus embryos, as observed in zebrafish embryos. Thus, Prdm14 expression in motor neurons was conserved in non-tetrapod deuterostomes and the co-option of the PRDM14-CBFA2T complex from motor neurons into pluripotent cells may have maintained the transcriptional network for pluripotency during vertebrate evolution.This article has an associated 'The people behind the papers' interview.

Risk estimation model for nonalcoholic fatty liver disease in the Japanese using multiple genetic markers.

The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for them. For these purposes, 936 histologically proven NAFLD patients were recruited, and genome-wide association (GWA) studies were conducted for 902, including 476 NASH and 58 NASH-HCC patients, against 7,672 general-population controls. Risk estimations for NAFLD and NASH were then performed using the SNPs identified as having significant associations in the GWA studies. We found that rs2896019 in PNPLA3 [p = 2.3x10-31, OR (95%CI) = 1.85 (1.67-2.05)], rs1260326 in GCKR [p = 9.6x10-10, OR (95%CI) = 1.38(1.25-1.53)], and rs4808199 in GATAD2A [p = 2.3x10-8, OR (95%CI) = 1.37 (1.23-1.53)] were significantly associated with NAFLD. Notably, the number of risk alleles in PNPLA3 and GATAD2A was much higher in Matteoni type 4 (NASH) patients than in type 1, type 2, and type 3 NAFLD patients. In addition, we newly identified rs17007417 in DYSF [p = 5.2x10-7, OR (95%CI) = 2.74 (1.84-4.06)] as a SNP associated with NASH-HCC. Rs641738 in TMC4, which showed association with NAFLD in patients of European descent, was not replicated in our study (p = 0.73), although the complicated LD pattern in the region suggests the necessity for further investigation. The genetic variants of PNPLA3, GCKR, and GATAD2A were then used to estimate the risk for NAFLD. The obtained Polygenic Risk Scores showed that the risk for NAFLD increased with the accumulation of risk alleles [AUC (95%CI) = 0.65 (0.63-0.67)]. CONCLUSIONS: We demonstrated that NASH is genetically and clinically different from the other NAFLD subgroups. We also established risk-estimation models for NAFLD and NASH using multiple genetic markers. These models can be used to improve the accuracy of NAFLD diagnosis and to guide treatment decisions for patients.

PRDM14 Drives OCT3/4 Recruitment via Active Demethylation in the Transition from Primed to Naive Pluripotency.

Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here, we exploited the in vitro differentiation of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the molecular and epigenetic functions of PR domain-containing 14 (PRDM14). We found that Prdm14 overexpression in EpiLCs induced their conversion to ESC-like cells even in the absence of leukemia inhibitory factor in adherent culture. This was impaired by the loss of Kruppel-like factor 2 and ten-eleven translocation (TET) proteins. Furthermore, PRDM14 recruited OCT3/4 to the enhancer regions of naive pluripotency genes via TET-base excision repair-mediated demethylation. Our results provide evidence that PRDM14 establishes a transcriptional network for naive pluripotency via active DNA demethylation.

Multicenter study of pegylated interferon α-2a monotherapy for hepatitis C virus-infected patients on hemodialysis: REACH study.

Many studies have reported poor vital prognosis in hepatitis C virus (HCV)-infected dialysis patients. The rate of HCV-infected dialysis patients in Japan is as high as 9.8%, and antiviral therapy is believed to be important for improving vital prognosis. We conducted a multicenter study to examine the administration method for pegylated interferon α-2a (PEG-IFNα-2a) monotherapy in HCV-infected dialysis. We studied 56 patients: 14 with low viral loads (HCV RNA < 5.0 log IU/mL) were treated with 90 µg PEG-IFNα-2a weekly, 42 with high viral loads (HCV RNA ≥ 5.0 log IU/mL) were treated with 135 µg PEG-IFNα-2a weekly. We examined the sustained virological response (SVR), factors affecting the SVR, and treatment safety. The overall SVR rate was 39% (22/56); that for genotype 1, genotype 2, low viral loads, and high viral loads was 29%, 67%, 93%, and 21%, respectively. From receiver operating characteristic (ROC) analysis, the HCV RNA cutoff values likely to achieve SVR for genotypes 1 and 2 were <5.7 log IU/mL (SVR rate: 64% 9/14) and <6.5 log IU/mL (SVR rate: 88% 7/8), respectively. If there was HCV RNA negativation at 4 weeks (rapid virological response), the SVR rate was 94% (16/17), whereas it was 6% (1/16) if there was HCV RNA positivity at 24 weeks. The rate of treatment discontinuation from adverse events or aggravated complications was 25% (14/56). High SVR rates can potentially be achieved with PEG-IFN monotherapy by identifying the target patients, based on virus type and viral load before initiating treatment and by modifying therapy during treatment according to responsiveness.

Prediction of a null response to pegylated interferon α-2b plus ribavirin in patients with high viral load genotype 1b hepatitis C.

BACKGROUND/AIMS: The present study aimed to clarify whether virological response within 2 weeks after therapy initiation can predict a null response to pegylated interferon α-2b plus ribavirin therapy in patients with high viral load genotype 1b hepatitis C. METHODS: The participants consisted of 72 patients with high viral load genotype 1b. The dynamics of viral load within 2 weeks were measured. RESULTS: Significant differences between null responders and nonnull responders were noted for interleukin (IL)-28B genotype, amino acid 70 substitution, α-fetoprotein, low-density lipoprotein cholesterol, hyaluronic acid, and viral response. The area under the curve (AUC) for the receiver operating characteristic curve of the hepatitis C virus (HCV) RNA level decline at 2 weeks (AUC=0.993) was the highest among the factors predicting the null response. When the cutoff value for the HCV RNA level decline at 2 weeks was set at 0.80 log, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting a null response were 82%, 96%, 82%, 96%, and 94%, respectively. In comparison, values for the non-TT and mutant type of amino acid 70 substitution were similar to those for HCV RNA level decline at 2 weeks. CONCLUSIONS: Virological response at 2 weeks or the combination of IL-28B and amino acid 70 substitution are accurate predictors of a null response.

Molecular hydrogen attenuates neuropathic pain in mice.

Neuropathic pain remains intractable and the development of new therapeutic strategies are urgently required. Accumulating evidence indicates that overproduction of oxidative stress is a key event in the pathogenesis of neuropathic pain. However, repeated intra-peritoneal or intrathecal injections of antioxidants are unsuitable for continuous use in therapy. Here we show a novel therapeutic method against neuropathic pain: drinking water containing molecular hydrogen (H2) as antioxidant. The effect of hydrogen on neuropathic pain was investigated using a partial sciatic nerve ligation model in mice. As indicators of neuropathic pain, temporal aspects of mechanical allodynia and thermal hyperalgesia were analysed for 3 weeks after ligation. Mechanical allodynia and thermal hyperalgesia were measured using the von Frey test and the plantar test, respectively. When mice were allowed to drink water containing hydrogen at a saturated level ad libitum after ligation, both allodynia and hyperalgesia were alleviated. These symptoms were also alleviated when hydrogen was administered only for the induction phase (from day 0 to 4 after ligation). When hydrogen was administered only for the maintenance phase (from day 4 to 21 after ligation), hyperalgesia but not allodynia was alleviated. Immunohistochemical staining for the oxidative stress marker, 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine, showed that hydrogen administration suppressed oxidative stress induced by ligation in the spinal cord and the dorsal root ganglion. In conclusion, oral administration of hydrogen water may be useful for alleviating neuropathic pain in a clinical setting.

Afterload mismatch after MitraClip insertion for functional mitral regurgitation.

Afterload mismatch, defined as acute impairment of left ventricular function after mitral surgery, is a major issue in patients with low ejection fraction and functional mitral regurgitation (FMR). Safety and efficacy of MitraClip therapy have been assessed in randomized trials, but limited data on its acute hemodynamic effects are available. This study aimed to investigate the incidence and prognostic role of afterload mismatch in patients affected by FMR treated with MitraClip therapy. We retrospectively analyzed patients affected by FMR and submitted to MitraClip therapy from October 2008 to December 2012. Patients were assigned to 2 groups according to the occurrence of the afterload mismatch: patients with afterload mismatch (AM+) and without afterload mismatch (AM-). Of 73 patients, 19 (26%) experienced afterload mismatch in the early postoperative period. Among preoperative variables, end-diastolic diameter (71 ± 8 vs 67 ± 7 mm, p = 0.02) and end-systolic diameter (57 ± 9 vs 53 ± 7 mm, p = 0.04) were both significantly larger in AM+ group. An increased incidence of right ventricular dysfunction (68% vs 31%, p = 0.049) and pulmonary hypertension (49 ± 10 vs 40 ± 10 mm Hg, p = 0.0009) was found in AM+ group. Before hospital discharge, left ventricular ejection fraction (LVEF) became similar in both groups (31 ± 9% vs 33 ± 11%, p = 0.65). Long-term survival was comparable between the 2 groups (p = 0.44). A low LVEF in the early postoperative period (LVEF <17%) was significantly associated with higher mortality rate in long-term follow-up (p = 0.048). In conclusion, reduction of mitral regurgitation with MitraClip can cause afterload mismatch; however, this phenomenon is transient, without long-term prognostic implications.

The role of intravascular ultrasound and quantitative angiography in the functional assessment of intermediate coronary lesions: correlation with fractional flow reserve.

BACKGROUND: The correlation between fractional flow reserve (FFR) and intravascular ultrasound (IVUS) metrics including minimal lumen area (MLA), plaque burden and morphology remain a matter of debate. METHODS: Between June 2008 and May 2013, 132 intermediate stenoses in 109 patients were assessed by FFR, IVUS and quantitative angiography. Receiver-operating characteristic (ROC) curve analyses were used to identify MLA/lesion length/plaque burden cut-off values predictive of FFR <0.80. RESULTS: FFR <0.80 was observed in 39 lesions. In the entire cohort, MLA value <2.70mm(2) had 79.5% sensitivity, 76.3% specificity, 0.822 area under curve (AUC), 58.5% positive predictive value, 89.9% negative predictive value and 77.3% accuracy in predicting a positive FFR. In lesions with reference diameter vessel (RVD) ≥3.0mm, the MLA cut-off value was 2.84mm(2) (sensitivity 72.2%, specificity 83.0%, AUC 0.842) whereas in lesions with RVD <3.0mm, 2.59mm(2) (sensitivity 90.5%, specificity 69.6%, AUC 0.823). A moderate correlation was observed between MLA and FFR (r=0.429, p<0.001). The cut-off lesion length predictive of FFR <0.80 was 11.0mm with a weak correlation between the two (r=-0.348, p<0.001). Plaque morphology did not significantly affect FFR (p=0.485). On multivariable analysis, MLA (OR: 0.15; 95% CI: 0.05-0.40; p<0.001) and plaque burden (OR: 1.11; 95% CI: 1.04-1.20; p<0.003) were independent predictors of FFR <0.80. CONCLUSION: A modest, yet significant correlation was observed between MLA and FFR. The high negative predictive value of large MLAs (using afore-mentioned cut-off values) may provide some degree of confidence that the lesion in question is not functionally significant.

Low-dose pegylated interferon-α2a plus ribavirin therapy for elderly and/or cirrhotic patients with HCV genotype-1b and high viral load.

BACKGROUND: Pegylated interferon (PEG-IFN) plus ribavirin therapy is still recommended for elderly and/or cirrhotic patients. This study examined whether sustained virological response (SVR) to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/or cirrhotic patients could be predicted based on viral reduction within 2 weeks after therapy initiation or interleukin IL-(28B) polymorphism and viral mutations. METHODS: Participants comprised 115 elderly (≥65 years) and/or cirrhotic patients with genotype-1b and high viral load. Reduced doses of PEG-IFN-α2a (90 µg/kg/week) and ribavirin (400-800 mg/day) were administered for 48-72 weeks based on virological response of each patient. RESULTS: SVR was achieved in 34% (39/115), and treatment was discontinued in 15% (17/115). Univariate analysis identified age, α-fetoprotein, fibrosis marker, interferon sensitivity-determining region (ISDR), IL-28B polymorphism and level of viral reduction within 2 weeks as factors contributing significantly to SVR. However, no significant differences were noted in core amino acid substitutions. Multivariate analysis identified age, hyaluronic acid, ISDR and viral reduction as factors independently associated with SVR. Positive predictive value (PPV) and negative predictive value (NPV) of SVR based on the level of viral reduction at 2 weeks (cutoff level, 1.7 log IU/ml) were 83% and 84%, respectively. The PPV of SVR based on IL-28B major and ISDR mutant was 70%, and the NPV of SVR based on IL-28B minor and wild-type ISDR was 89%. CONCLUSIONS: Evaluations of viral reduction at 2 weeks or both IL-28B and ISDR are useful to predict SVR to low-dose PEG-IFN-α2a plus ribavirin therapy for elderly and/or cirrhotic patients.

Comparison of abluminal biodegradable polymer biolimus-eluting stents and durable polymer everolimus-eluting stents in the treatment of coronary bifurcations.

OBJECTIVES: To compare biodegradable polymer biolimus-eluting (BES) with abluminal drug elution and durable polymer everolimus-eluting (EES) stents in the treatment of bifurcation lesions. BACKGROUND: The persistence of a polymer in drug-eluting stents (DES) following drug elution has been viewed as a possible culprit for restenosis. DES with biodegradable polymer may thus be associated with improved clinical outcomes, especially in high-risk lesions such as those at bifurcation sites. METHODS: We performed a retrospective study of consecutive de novo bifurcation lesions treated with EES between October 2006 and October 2011 and BES between February 2008 and March 2012. Study endpoints included major adverse cardiac events (MACE) defined as all-cause death, myocardial infarction (MI), including peri-procedural MI, and target vessel revascularization (TVR) as well as target lesion revascularization (TLR) separately. RESULTS: We analyzed 236 bifurcation lesions treated with either BES (79 lesions in 69 patients) or EES (157 lesions in 154 patients). Patient and procedural characteristics were broadly similar between the two groups. Estimated MACE and TVR rates at 2-year follow-up were similar between the BES and EES groups (MACE = 13.6 ± 4.6% vs. 14.6 ± 3.2% (P = 0.871); TVR = 6.9 ± 3.5% vs. 8.0 ± 2.7% (P = 0.889). No significant differences were noted between the two groups following propensity-score matched analysis. There was no probable or definite stent thrombosis. CONCLUSION: BES use in the treatment of bifurcation lesions appears to be associated with good clinical outcomes, comparable to those seen with EES, at long-term follow-up. These results are hypothesis-generating and need to be validated with larger studies.

The role of drug-eluting balloons alone or in combination with drug-eluting stents in the treatment of de novo diffuse coronary disease.

OBJECTIVES: This study sought to investigate the role of drug-eluting balloons (DEB) alone or in combination with drug-eluting stents (DES) in the treatment of diffuse de novo coronary artery disease (CAD) (>25 mm). BACKGROUND: The use of DEB in diffuse CAD, either alone or in combination with DES, offers an alternative to stenting alone. Data regarding DEB in this context are limited. METHODS: We retrospectively evaluated all patients treated with DEB for diffuse CAD between June 2009 and October 2012. Endpoints analyzed were major adverse cardiac events, defined as all-cause death, myocardial infarction, and target vessel revascularization (TVR), as well as TVR and target lesion revascularization separately. Results were compared with those obtained from a cohort of patients with similar characteristics treated with DES alone. RESULTS: A total of 69 patients (93 lesions) were treated with DEB ± DES, and 93 patients with DES alone (93 lesions). A high proportion of patients were diabetic (46.4% vs. 44.1%, p = 0.77). Of the DEB-treated lesions, 56.0% were treated with DEB alone, 7.4% with DEB and DES as bail out, and 36.6% with DES and DEB as part of a hybrid approach for very long disease. Outcome rates with DEB ± DES were comparable to those with DES alone at 2-year follow-up (major adverse cardiac events = 20.8% vs. 22.7%, p = 0.74; TVR = 14.8% vs. 11.5%, p = 0.44; target lesion revascularization = 9.6% vs. 9.3%, p = 0.84). CONCLUSIONS: DEB may have a role in the treatment of diffuse de novo CAD, either alone in smaller vessels or in combination with DES in very long disease.

First- versus second-generation drug-eluting stents for the treatment of coronary bifurcations.

BACKGROUND: Randomized controlled trials have demonstrated that second-generation drug-eluting stents (DESs) for the treatment of obstructive coronary artery disease are associated with comparable, if not improved, clinical outcomes as compared to those of their first-generation counterparts. The aim of this study was to compare the long-term clinical outcomes associated with first- versus second-generation DESs for the treatment of coronary bifurcation lesions. METHODS AND MATERIALS: This was a retrospective study of consecutive de novo bifurcation lesions, excluding those at the left main, treated with either second-generation DES (everolimus-eluting or resolute zotarolimus-eluting stents) between October 2006 and October 2011 (199 bifurcation lesions in 192 patients) or first-generation DES (sirolimus-eluting or paclitaxel-eluting stents) between April 2002 and December 2005 (289 bifurcation lesions in 273 patients). RESULTS: Second-generation DES use in this setting was associated with less major adverse cardiac events (MACE) (23.1% vs. 14.4%, p=0.02) as well as lower target vessel revascularization (TVR) rates (15.5% vs. 8.3%, p=0.01) at 2-year follow-up. Target lesion revascularization, both per patient (12.6% vs. 7.4%, p=0.02) and per bifurcation (11.8% vs. 7.0%, p=0.03), was also improved with second-generation DES over the same follow-up period. Propensity-score adjusted analysis suggested that second-generation DES was associated with a lower incidence of MACE (HR, 0.53; 95% CI, 0.33-0.85; p=0.01) and TVR (HR, 0.44; 95% CI, 0.24-0.83; p=0.01). CONCLUSIONS: Our results suggest that the use of second-generation DES for the treatment of bifurcation lesions is associated with better clinical outcomes as compared to first-generation DES, largely due to a lower need for repeat revascularization.

The role of everolimus-eluting and resolute zotarolimus-eluting stents in the treatment of coronary bifurcations.

OBJECTIVES: To compare the long-term clinical outcomes of everolimus-eluting (EES) and Resolute zotarolimus-eluting (R-ZES) stents in the treatment of coronary bifurcation lesions. BACKGROUND: Recent studies have suggested that the R-ZES is comparable to the EES in the treatment of de novo coronary artery disease. Available data on how these compare in the treatment of bifurcation lesions are limited. METHODS: We retrospectively analyzed consecutive de novo bifurcation lesions, including left main stem lesions, treated with either EES or R-ZES between October 2006 and October 2011. Study endpoints examined included major adverse cardiac events (MACEs), defined as the composite of all-cause death, myocardial infarction (MI), including periprocedural MI, and target vessel revascularization (TVR). Target lesion revascularization (TLR) per patient and per bifurcation as well as stent thrombosis (ST) were also analyzed. RESULTS: We identified 235 bifurcation lesions treated with either EES (157 lesions in 154 patients) or R-ZES (78 lesions in 73 patients). Baseline clinical and procedural characteristics were broadly similar between the two groups. No significant differences in MACE (14.6% vs 11.5%; P=.99) or TVR (8.0% vs 7.3%; P=.45) rates were noted between the two groups at 2-year follow-up. The incidence of ST was low and similar in both groups (0% vs 1.4%). CONCLUSIONS: EES and R-ZES are associated with acceptable and comparable long-term clinical outcomes when used in the treatment of bifurcation lesions. Further evaluation into the role of currently available drug-eluting stents in bifurcation percutaneous coronary intervention is required.

A Case-Control Study of Esomeprazole Plus Rebamipide vs. Omeprazole Plus Rebamipide on Post-ESD Gastric Ulcers.

OBJECTIVES: Endoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. There is no report about the efficacy of post-ESD gastric ulcers by esomeprazole. We examined retrospectively the efficacy of a combination therapy of esomeprazole plus rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing comparing with omeprazole plus rebamipide. METHODS: We reviewed the medical records of patients who underwent ESD for gastric neoplasia. We conducted a case-control study to compare the healing rates within 4 weeks effected by esomeprazole plus rebamipide (group E) and omeprazole plus rebamipide (group O). The sizes of the artificial ulcers were divided into normal-sized or large-sized. RESULTS: The baseline characteristics did not differ significantly between the two groups except age and sex. Stage S1 disease was observed in 27.6% and 38.7% of patients after 4 weeks of treatment in the group E and O, respectively. In large-sized artificial ulcers, the healing rate of stage S1 in group E is significantly higher than that in group O in 4 weeks.(25% VS 0%:P = 0.02). CONCLUSIONS: The safety and efficacy profiles of esomeprazole plus rebamipide and omeprazole and rebamipide are similar for the treatment of ESD-induced ulcers. In large-sized ulcers, esomeprazole plus rebamipide promotes ulcer healing.

Comparison of first- and second-generation drug-eluting stents in saphenous vein grafts used as aorto-coronary conduits.

Saphenous vein grafts (SVGs) are prone to an aggressive atherosclerotic process, and the efficacy of drug-eluting stents (DES) in treating this is still debated. In recent years, second-generation DES have been increasingly used in SVG intervention. The main objective of this study was to compare midterm clinical outcomes between first- and second-generation DES in SVGs because data regarding the use of second-generation DES in SVG are lacking. Patients treated with first-generation DES (127 patients with 143 lesions) and those treated with second-generation DES (84 patients with 100 lesions) were included in the study. Major adverse cardiac events, defined as the composite of all-cause death, myocardial infarction, and target vessel revascularization, as well as target vessel revascularization and target lesion revascularization separately, were evaluated at 30-day, 12-month, and 18-month follow-up. Baseline characteristics were similar between the 2 groups. Older grafts were treated with second-generation DES (11.6 ± 5.3 vs 14.3 ± 6.0 years, p = 0.001). Stent length was longer in the first-generation group (34.1 ± 25.1 vs 30.5 ± 19.4 mm, p = 0.006), and maximum balloon diameter was smaller in the second-generation group (3.42 ± 0.42 vs 3.30 ± 0.41 mm, p = 0.003). Embolic protection device use was higher in the second-generation DES group (55.2% vs 72.0%, p = 0.012). At 18-month follow-up, rates of major adverse cardiac events, target vessel revascularization, and target lesion revascularization for the first- and second-generation groups were 24.4% versus 20.2% (p = 0.479), 18.1% versus 14.2% (p = 0.465), and 15.0% versus 10.7% (p = 0.373), respectively. In conclusion, second-generation DES are at least comparable with first-generation DES with regard to clinical outcomes at midterm follow-up.

The long-term clinical outcome of T-stenting and small protrusion technique for coronary bifurcation lesions.

OBJECTIVES: This study sought to report long-term clinical outcomes in patients treated with the provisional T-stenting and small protrusion (TAP) technique. BACKGROUND: Several strategies have been proposed for treating bifurcation lesions, each with its own merits and technical challenges. The TAP technique is a relatively new strategy that is technically less challenging, ensures complete coverage of the side-branch ostium, and minimizes stent overlap. Although there is reasonable amount of data for other bifurcation strategies, the long-term clinical outcomes for TAP technique are limited. METHODS: We retrospectively evaluated all patients who underwent TAP technique with drug-eluting stents between July 2005 and January 2012. The measured endpoints at follow-up were major adverse cardiac events defined as composite of cardiac death, myocardial infarction, and target vessel revascularization. RESULTS: A total of 95 patients (81.1% men) with a mean age of 64.8 years underwent TAP stenting. Procedural success was achieved in 100% of cases. True bifurcation was observed in 75 (78.9%) patients. First-generation drug-eluting stents were used in 55.8% of patients. The outcome rates at 3-year follow-up of major adverse cardiac events, cardiac death/follow-up myocardial infarction, target vessel revascularization, and target lesion revascularization were 12.9%, 3.1%, 9.7%, and 5.1%, respectively. There were no cases of follow-up myocardial infarction or stent thrombosis (definite and probable). CONCLUSIONS: These results demonstrate that TAP technique is associated with acceptable clinical outcomes with no episodes of definite and probable stent thrombosis. Further studies should compare TAP technique with other 2-stent strategies.