Angiography-derived functional assessment of left main coronary stenoses.

OBJECTIVES: We aimed to evaluate the diagnostic accuracy of quantitative flow ratio (QFR) in left main (LM) coronary stenoses, using Fractional Flow Reserve (FFR) as reference. BACKGROUND: QFR has demonstrated a high accuracy in determining the functional relevance of coronary stenoses in non-LM. However, there is an important paucity of data regarding its diagnostic value in the specific anatomical subset of LM disease. METHODS: This is a retrospective, observational, multicenter, international, and blinded study including patients with LM stenoses. Cases with significant ostial LM disease were excluded. QFR was calculated from conventional angiograms at blinded fashion with respect to FFR. RESULTS: Sixty-seven patients with LM stenoses were analyzed. Overall, LM had intermediate severity, both from angiographic (diameter stenosis [%DS] 43.8 ± 11.1%) and functional perspective (FFR 0.756 ± 0.105). Mean QFR was 0.733 ± 0.159. Correlation between QFR and FFR was moderate (r = 0.590). Positive and negative predictive value, sensitivity and specificity were 85.4%, 64%, 85.4%, and 69.6% respectively. Classification agreement of QFR and FFR in terms of functional stenosis severity was 78.1%. Area under the receiver operating characteristics of QFR using FFR as reference was 0.82 [95% confidence interval [CI], 0.71-0.93], and significantly better than angiographic evaluation including %DS (area under the receiver-operating characteristic curve [AUC] 0.45 [95% CI, 0.32-0.58], p < 0.001) and minimum lumen diameter (AUC 0.60 [95% CI, 0.47-0.74], p < 0.001). CONCLUSIONS: Compared with FFR, QFR has acceptable diagnostic performance in determining the functional relevance of LM stenosis, being better than conventional angiographic assessment. Nonetheless, caution should be taken when applying functional angiography techniques for the assessment of LM stenosis given its particular anatomical characteristics.

Analysis of risk factors for the development of a post-bronchoscopy respiratory infection in lung cancer patients.

BACKGROUND: The development of pneumonia following bronchoscopy is a very important post-bronchoscopic complication, while lung abscesses after bronchoscopy are rare. However, bronchoscopic techniques have advanced, and recently, we have observed patients with lung abscess after bronchoscopy. Therefore, the risk factors might vary from those in past reports. This study was performed to identify the incidence of and risk factors for post-bronchoscopy respiratory infections. METHODS: We retrospectively studied adult patients diagnosed with lung cancer by bronchoscopy at Fukujuji Hospital from January 2017 to June 2019. The infection and noninfection groups were compared. The incidence of lung abscess was compared between recent periods and 2013, when endobronchial ultrasonography with a guide sheath (EBUS-GS) was not yet used in our hospital. RESULTS: We reviewed 327 patients, including 20 patients (6.1%) with infections. The risk factors for infection were necrosis and/or a cavity in the tumor (p < 0.001), a large tumor diameter (≥30 mm) (p = 0.010), and a low serum albumin level (<4.0 g/dL) (p = 0.010). We developed a predictive score with these risk factors, and the area under the curve was 0.737 (95% Cl: 0.610-0.864). No significant differences in age, current smoking status, or abnormal bronchoscopic findings were observed, although these were previously reported as risk factors. In total, 12 patients had lung abscesses (3.7%), which is a higher incidence than that in 2013 (0.8%). CONCLUSIONS: The risk factors for developing post-bronchoscopy respiratory infection in our study varied from those in past reports, possibly because of the advancements in bronchoscopic techniques, such as EBUS-GS.

FOLFIRINOX as second-line chemotherapy for advanced pancreatic cancer: A subset analysis of data from a nationwide multicenter observational study in Japan.

BACKGROUND: Data on FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer are limited. In the JASPAC06 study-a nationwide, multicenter, observational study-FOLFIRINOX for patients with unresectable or recurrent pancreatic cancer as any line of treatment showed favorable efficacy and safety in Japanese clinical practice. METHODS: We performed exploratory analyses of patients with unresectable or recurrent pancreatic cancer who received FOLFIRINOX as the second-line chemotherapy in Japanese clinical settings. RESULTS: Of the 399 evaluable patients, 44 were eligible for inclusion in the analysis. The patients' characteristics were as follows: median age, 62 years; men, 26 (59%); Eastern Cooperative Oncology Group-Performance status 0/1, 30 (68%)/14 (32%); disease status, recurrent/local/metastatic: 4 (9%)/8 (18%)/32 (73%). The initial dose was reduced in 28 (64%) patients. The median time to treatment failure and number of cycles were 4.5 (range, 0.2-19.1) months and 6 cycles (range, 1-13 or more), respectively. The major grade 3/4 adverse events were neutropenia in 29 (66%), leucopenia in 17 (39%), anorexia in 7 (16%), febrile neutropenia in 5 (11%), and anemia in 5 (11%) patients. The median overall survival, progression-free survival, and 1-year survival rates were 10.3 (95% confidence interval [CI], 7.2-13.3), 4.1 (95% CI, 2.6-5.5) months, and 30%, respectively. CONCLUSION: Our findings suggest that FOLFIRINOX as a second-line chemotherapy for advanced pancreatic cancer was effective in patients with a good performance status. It displayed toxicity similar to that observed with its use as a first-line treatment.

Effect of QTU prolongation on hyperemic instantaneous wave-free ratio value: a prospective single-center study.

We hypothesized that in patients with QT prolongation, resistance might not decrease in the wave-free period, because QTU prolongation cannot be detected by instantaneous wave-free ratio (iFR) analysis software. We investigated whether corrected QTU (QTUc) prolongation affects the hyperemic iFR value. Forty-two consecutive patients with intermediate stenosis (≥ 50%) in the left anterior descending coronary artery (LAD) were analyzed. Fractional flow reserve (FFR) and hyperemic iFR were simultaneously and continuously recorded with intravenous adenosine triphosphate (ATP) and papaverine infusions. In 17 patients with stenosis in the proximal LAD, coronary flow was measured. Patients were divided into two groups according to the median absolute deviation of the QTUc by ATP administration/QTUc by papaverine administration. FFR, hyperemic iFR, and flow data were compared between each stimulus and group. Moreover, influences of pressure and electrocardiogram parameters on differences in iFR values under ATP and papaverine administration were compared between the following two groups (group 1: the absolute difference of hyperemic iFR values between ATP and papaverine administration is ≤ 0.05; group 2: that is > 0.05). The paired t test and t test were used in analysis. Hyperemic iFR values of patients under the use of papaverine were lower than those of patients under the use of ATP when QTUc was more prolonged by papaverine administration than by ATP administration (ATP 0.74 ± 0.14, papaverine 0.71 ± 0.15, P = 0.025). No significant differences were observed in the FFR value and flow data between the groups. Regarding QTU, QTUc, and QTUc by ATP/QTUc by papaverine, significant differences were observed between group 1 and group 2. Pressure parameters did not induce significant differences. QTUc prolongation induced by papaverine was associated with lower hyperemic iFR values. An iFR-based assessment might lead to inappropriate treatment of patients with QTUc prolongation.

Low body mass index and lymphocytopenia associate with Mycobacterium avium complex pulmonary disease in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) are at an increased risk of Mycobacterium avium complex pulmonary disease (MAC-PD). We aimed to identify factors associated with MAC-PD in RA patients, and investigate their clinical significance for diagnosis of this disease. METHODS: We examined 396 patients with RA for the presence of MAC-PD, using the criteria of the American Thoracic Society and conducted three years of follow-up on these patients. Multivariate logistic analyses were employed for selecting factors associated with MAC-PD. We developed a point system based on these factors which we call MAC-PD score to improve diagnosis of MAC-PD. RESULTS: During this study, 14 out of 396 patients were newly diagnosed with MAC-PD. Multivariate analyses revealed body mass index (BMI) <18.0 kg/m2 and lymphocyte count <1500/µl were associated with MAC-PD in RA patients. Points were assigned to them and totalled to provide the MAC-PD score. Among 20 patients with high-resolution computer tomography images consistent with MAC-PD, the scores were significantly higher in 14 patients with MAC-PD than those in six patients without MAC-PD. CONCLUSION: Using these data, in the forms of the MAC-PD score, could help to identify patients who should be considered for bronchoscopy more selectively.

[A case of resected synchronous hepatocellular and cholangiolocellular carcinoma in the background of resolved hepatitis B virus infection].

An 85-year-old male patient was referred to our hospital for further examination of a liver tumor. Imaging examination revealed a 90-mm tumor in segment 4/8 and 30-mm tumor in segment 6 of the liver. Histopathological examination revealed that the tumor in segment 4/8 was cholangiolocellular carcinoma (CLC) and the tumor in segment 6 was hepatocellular carcinoma (HCC). This case shows that although the frequency of CLC is very low, recent studies have indicated the novel knowledge of CLC. Herein, we report a surgical case of CLC and HCC in the background of resolved hepatitis B virus infection.

Stimulated Excitation of an Optical Cavity by a Multibunch Electron Beam via Coherent-Diffraction-Radiation Process.

With a low emittance and short-bunch electron beam at a high repetition rate realized by a superconducting linac, stimulated excitation of an optical cavity at the terahertz spectrum range is shown. The electron beam passes through small holes in the cavity mirrors without being destroyed. A sharp resonance structure which indicates wideband stimulated emission via coherent diffraction radiation is observed while scanning the round-trip length of the cavity.

Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial.

BACKGROUND: The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence. METHODS: This trial was a multicentre, double-blind, placebo-controlled, randomised phase 3 trial. Non-diabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were enrolled into the study from five hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive oral metformin (250 mg daily) or identical placebo tablets by a stratified computer-based randomisation method, with stratification by institute, age, sex, and body-mass index. All patients, endoscopists, doctors, and investigators were masked to drug allocation until the end of the trial. After 1 year of administration of metformin or placebo, colonoscopies were done to assess the co-primary endpoints: the number and prevalence of adenomas or polyps. Our analysis included all participants who underwent random allocation, according to the intention-to-treat principle. This trial is registered with University Hospital Medical Information Network (UMIN), number UMIN000006254. FINDINGS: Between Sept 1, 2011, and Dec 30, 2014, 498 patients who had had single or multiple colorectal adenomas resected by endoscopy were enrolled into the study. After exclusions for ineligibility, 151 patients underwent randomisation: 79 were assigned to the metformin group and 72 to the placebo group. 71 patients in the metformin group and 62 in the placebo group underwent 1-year follow-up colonoscopy. The prevalence of total polyps (hyperplastic polyps plus adenomas) and of adenomas in the metformin group was significantly lower than that in the placebo group (total polyps: metformin group 27 [38·0%; 95% CI 26·7-49·3] of 71 patients, placebo group 35 [56·5%; 95% CI 44·1-68·8] of 62; p=0·034, risk ratio [RR] 0·67 [95% CI 0·47-0·97]; adenomas: metformin group 22 [30·6%; 95% CI 19·9-41·2] of 71 patients, placebo group 32 [51·6%; 95% CI 39·2-64·1] of 62; p=0·016, RR 0·60 [95% CI 0·39-0·92]). The median number of polyps was zero (IQR 0-1) in the metformin group and one (0-1) in the placebo group (p=0·041). The median number of adenomas was zero (0-1) in the metformin group and zero (0-1) in the placebo group (p=0·037). 15 (11%) of patients had adverse events, all of which were grade 1. We recorded no serious adverse events during the 1-year trial. INTERPRETATION: The administration of low-dose metformin for 1 year to patients without diabetes was safe. Low-dose metformin reduced the prevalence and number of metachronous adenomas or polyps after polypectomy. Metformin has a potential role in the chemoprevention of colorectal cancer. However, further large, long-term trials are needed to provide definitive conclusions. FUNDING: Ministry of Health, Labour and Welfare, Japan.

Left atrial appendage flow velocity after successful ablation of persistent atrial fibrillation: clinical perspective from transesophageal echocardiographic assessment during sinus rhythm.

BACKGROUND: Left atrial appendage flow velocity (LAAFV) is a predictor of thromboembolism in atrial fibrillation (AF) patients, as well as CHA2DS2-VASc score. However, little is known about LAAFV in sinus rhythm (SR) after catheter ablation. The aim of this study was to determine clinical predictors of low LAAFV in patients in whom stable SR had been maintained after catheter ablation for persistent AF. METHODS: The study comprised 104 patients with persistent AF (median AF duration 24 months) in whom SR had been achieved and maintained for at least 6 months after the final ablation procedure. Transesophageal echocardiography was performed to assess LAAFV during SR after ablation. Lower LAAFV was defined as ≤40 cm/s. RESULTS: Mean LAAFV before ablation was 29 ± 11 cm/s (range 10-67 cm/s). In 23 (22%) patients, LAAFV remained low even after being in SR for at least 6 months. Multiple logistic regression analysis showed that CHA2DS2-VASc scores of ≥2 (odds ratio 2.18, 95% CI 1.19-3.99, P = .012) was an independent predictor of lower LAAFV after successful ablation. Seventeen (74%) of the 23 patients with low LAAFV during SR presented CHA2DS2-VASc scores of ≥2 complicated by spontaneous echo contrast during AF. CONCLUSIONS: Long-term maintenance of SR after catheter ablation for persistent AF does not guarantee LAAFV recovery. The CHA2DS2-VASc score appears to predict poor recovery of LAAFV. Further studies are necessary to confirm the usefulness of LAAFV during SR as a surrogate marker predicting thromboembolism in patients after AF ablation.

Papaverine-induced polymorphic ventricular tachycardia during coronary flow reserve study of patients with moderate coronary artery disease.

BACKGROUND: Papaverine is useful for evaluating the functional status of a coronary artery, but it may provoke malignant ventricular arrhythmia (VA). The aim of this study was to investigate the incidence, and clinical and ECG characteristics of patients with papaverine-induced VAs. METHODS AND RESULTS: The 182 consecutive patients underwent fractional flow reserve (FFR) measurement of 277 lesions. FFR was determined after intracoronary papaverine administration by standard procedures. The clinical and ECG characteristics were compared between patients with and without ventricular tachycardia (VT: ≥3 successive premature ventricular beats (PVBs), or ventricular fibrillation (VF)). After papaverine administration, the QTc interval, QTUc interval, and T-peak to U-end interval were prolonged significantly. Single PVBs on the T-wave or U-wave type developed in 29 patients (15.9%). Polymorphic VT (torsade de pointes) occurred in 5 patients (2.8%), and of those, VF developed in 3 patients (1.7%). No clinical and baseline ECG parameters were predictors for VT or VF except for sex and administration of papaverine into the left coronary artery. Excessive prolongation of QT (or QTU), T-peak to U-end intervals and giant T-U waves were found immediately prior to the ventricular tachyarrhythmias (VTAs), which were unpredictable from the baseline data. CONCLUSIONS: Intracoronary administration of papaverine induced fatal VTAs, although the incidence is rare. Excessive prolongation of the QT (and QTU) interval appeared prior to VTAs; however, they were unpredictable.

Conditional knockout of the leptin receptor in the colonic epithelium revealed the local effects of leptin receptor signaling in the progression of colonic tumors in mice.

Leptin, secreted by the adipose tissue and known to be related to obesity, is considered to be involved in the onset and progression of colorectal cancer. However, the exact role of leptin in colorectal carcinogenesis is still unclear, as several controversial reports have been published on the various systemic effects of leptin. The aim of this study was to clarify the local and precise roles of leptin receptor (LEPR)-mediated signaling in colonic carcinogenesis using intestinal epithelium-specific LEPRb conditional knockout (cKO) mice. We produced and used colonic epithelium-specific LEPRb cKO mice to investigate the carcinogen-induced formation of aberrant crypt foci (ACF) and tumors in the colon, using their littermates as control. There were no differences in the body weight or systemic condition between the control and cKO mice. The tumor sizes and number of large-sized tumors were significantly lower in the cKO mice as compared with those in the control mice. On the other hand, there was no significant difference in the proliferative activity of the normal colonic epithelial cells or ACF formation between the control and cKO mice. In the control mice, marked increase of the LEPRb expression level was observed in the colonic tumors as compared with that in the normal epithelium; furthermore, signal transducer and activator of transcription (STAT3) was activated in the tumor cells. These findings suggest that STAT3 is one of the important molecules downstream of LEPRb, and LEPRb/STAT3 signaling controls tumor cell proliferation. We demonstrated the importance of local/regional LEPR-mediated signaling in colorectal carcinogenesis.

Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study.

Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ATL patients who received allogeneic HCT and survived at least 30 days posttransplant with sustained engraftment. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that the development of grade 1-2 acute GVHD was significantly associated with higher overall survival (hazard ratio [HR] for death, 0.65; P = .018) compared with the absence of acute GVHD. Occurrence of either grade 1-2 or grade 3-4 acute GVHD was associated with lower disease-associated mortality compared with the absence of acute GVHD, whereas grade 3-4 acute GVHD was associated with a higher risk for treatment-related mortality (HR, 3.50; P < .001). The development of extensive chronic GVHD was associated with higher treatment-related mortality (HR, 2.75; P = .006) compared with the absence of chronic GVHD. Collectively, these results indicate that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of allografted patients with ATL.

Metabolic factors accelerate colorectal adenoma recurrence.

BACKGROUND: Metabolic factors have been reported to increase the prevalence of colorectal adenomas, however, whether metabolic factors might also accelerate the recurrence after removal of adenomas has not yet been discussed. In this retrospective multicenter study, we clarified the risk factors for adenoma recurrence focusing on metabolic factors. METHODS: We analyzed the medical records of 43,195 patients who had undergone colonoscopy between January 2005 and December 2011 at 5 hospitals in Japan. Of these, the data of 1111 patients who had undergone removal of adenomas at the first screening colonoscopy, and then been followed up by colonoscopy 1 year and 2 years later were analyzed. RESULTS: The following 8 factors were demonstrated with a multivariate analysis as being associated with colorectal adenomas recurrence: for adenoma-related factors, 5 factors (villous features, grade of dysplasia, location and size of the largest removed adenoma, and number of the removed adenomas) were identified; for metabolic factors and other factors, 3 factors (age, body mass index (BMI), and fasting blood glucose (FBG)) were identified. A risk score (0-10 points) was developed based on these 8 factors. The risk of adenoma recurrence increased as the risk score increased. When the risk score was ≥3 (3-10) points, the odds ratio relative to <3 (0-2) points was 7.07 (95% CIs 5.30-9.43). CONCLUSIONS: In addition to adenoma-related factors (villous features, grade of dysplasia, location, size and number), 3 factors (age, BMI and FBG) were demonstrated to influence the recurrence rate of colorectal adenoma. When the risk score was ≥3, the risk of recurrence was significantly elevated.

Impact of atrial fibrillation termination site and termination mode in catheter ablation on arrhythmia recurrence.

BACKGROUND: Although atrial fibrillation (AF) termination has been reported as a predictor of clinical outcome after persistent AF (PsAF) ablation, the relationship between AF termination site and mode and clinical outcome has not been fully evaluated. METHODS AND RESULTS: A total of 135 patients (62±9 years) underwent their first ablation procedure for PsAF (76 longstanding PsAF). With an endpoint of AF termination, the ablation procedure was performed sequentially in the following order: pulmonary vein (PV) antrum isolation, and left atrial and right atrial substrate modification. AF termination was achieved in 69 patients (51%; 24 at the PV antrum, and 45 in the atrium; direct conversion to sinus rhythm in 21, and atrial tachycardia [AT] in 48). With a mean of 1.7±0.7 procedures/patient, 100 patients (74%) were free from atrial tachyarrhythmia (ATa) during a median of 15.0 months of follow-up. During the initial procedure, the AF termination site (atrium vs. PV antrum, hazard ratio [HR], 1.38; 95% confidence interval [CI]: 0.72-3.77; no termination vs. PV antrum, HR, 2.32; 95% CI: 1.26-6.30; P=0.023) and mode (AT vs. sinus rhythm, HR, 1.47; 95% CI: 0.77-4.01; no termination vs. sinus rhythm, HR, 2.38; 95% CI: 1.26-6.46; P=0.017) were independent predictors of ATa recurrence after the last ablation procedure. CONCLUSIONS: The site and mode of AF termination during the index ablation procedure predict ATa recurrence following multiple catheter ablation procedures for PsAF.

Bortezomib suppresses function and survival of plasmacytoid dendritic cells by targeting intracellular trafficking of Toll-like receptors and endoplasmic reticulum homeostasis.

Dendritic cells (DCs) play a pivotal role in the pathogenesis of inflammatory disorders, so suppressing the activity of DCs is instrumental in treating such diseases. In the present study, we show that a proteasome inhibitor, bortezomib, suppresses the survival and immunostimulatory function of human plasmacytoid DCs (pDCs) by targeting 2 critical points, intracellular trafficking of nucleic acid-sensingToll-like receptors (TLRs) and endoplasmic reticulum (ER) homeostasis. Among the immune cells in blood, pDCs were the most susceptible to the killing effect of bortezomib. This correlates with a decrease in the spliced form of a transcription factor XBP1, which rescues cells from apoptosis by maintaining ER homeostasis. Bortezomib suppressed the production of interferon-α and interleukin-6 by pDCs activated with a TLR9-stimulating CpG DNA and a TLR7-stimulating influenza virus, which appears to be partially independent of apoptosis. Bortezomib inhibited translocation of TLR9 from the ER to endolysosomes but not of an ER membrane protein, Unc93B1, that delivers TLR9 to endolysosomes. Thus, bortezomib suppresses the activity of pDCs by inhibiting intracellular trafficking of TLRs through disrupting the coordinated translocation of TLRs and Unc93B1 and by disturbing ER homeostasis. This study suggests that proteasome inhibitors may alleviate inflammatory disorders such as lupus and psoriasis that involve pDCs.

Conduction recovery after electrical isolation of superior vena cava--prevalence and electrophysiological properties.

BACKGROUND: Superior vena cava (SVC) is an infrequent yet an important source of atrial fibrillation (AF). The data on SVC reconnection are limited. METHODS AND RESULTS: Following pulmonary vein (PV) antrum isolation for AF, SVC isolation was systemically performed under angiographic and mapping guidance using 4-mm non-irrigated tip catheter. SVC reconnection could be evaluated in 76 consecutive patients (65 ± 9 years, 59 male) who underwent repeat AF ablation after 16 ± 16 months. SVC was isolated at the 1(st), 2(nd), 3(rd) and 4(th) AF ablation procedure in 63, 7, 5 and 1 patient by 7.3 ± 3.1 radiofrequency applications. SVC reconnection was observed in 56 patients (74%). In the majority, the conduction gap was located at the anterolateral SVC-right atrium (RA) junction. After re-isolation of SVC, 2/7 patients (29%) had reconnection at the following procedure. Among 63 patients who underwent PV and SVC isolation at the initial procedure, the prevalence of reconnection for PV and that for SVC were similar (53/63, 84% vs. 46/63, 73%; P=0.129). Dissociated activity, however, was more frequently observed in the PVs than in the SVC (47/63, 73% vs. 10/63, 16%; P<0.0001). During the procedure, AF initiation from a thoracic vein was identified in 19/63 patients (30%). CONCLUSIONS: SVC reconnection is common after 1 or more previous isolation procedures undertaken for AF ablation. Its prevalence is similar to that of PV reconnection. The location of the conduction gap varies widely but is most frequently found at the anterolateral SVC-RA junction.

Six-year follow-up of catheter ablation in paroxysmal atrial fibrillation.

BACKGROUND: Although pulmonary vein (PV) antrum isolation is an established therapy for drug-resistant paroxysmal atrial fibrillation (PAF), long-term (>5 years) follow-up data are limited. This study investigated long-term clinical outcome of catheter ablation. METHODS AND RESULTS: From September 2003 to August 2006, 161 patients (mean age, 60±9 years; 119 male) with symptomatic drug-refractory PAF who underwent extensive encircling PV isolation (EEPVI) with a double Lasso technique were included. Right-sided and left-sided circular lesions encircling the ipsilateral PVs were created. The procedure endpoint was electrical isolation of the PV antrum. Patients with recurrent atrial tachyarrhythmia (ATa) had their previous lesions assessed and consolidated. Trigger ablation was added if necessary. EEPVI was successfully performed at the initial procedure. During a median follow-up of 6.4 years (25th-75th percentile, 5.8-7.1 years), 86 patients (53.4%) had recurrent ATa. Among 78, 15 and 4 patients undergoing 2nd, 3rd and 4th procedures, PV reconnections were observed in 68, 10 and 2, respectively. During a median follow-up of 6.0 years (25th-75th percentile, 5.2-6.9 years) after a mean of 1.6±0.7 procedures per patient, 144 patients (89.4%) were free from ATa. No progression toward persistent AF was observed in any patients. CONCLUSIONS: The vast majority of drug-resistant PAF could be controlled by EEPVI without an additional atrial substrate modification. No progression toward persistent AF was observed during a median follow-up of 6 years.

Impact of low-dose dipyridamole injection on adenosine test after pulmonary vein isolation.

BACKGROUND: Dipyridamole increases the levels of extracellular adenosine. The study investigates the impact of low-dose intravenous dipyridamole on adenosine test after pulmonary vein (PV) isolation (PVI). METHODS AND RESULTS: This prospective study included 12 paroxysmal atrial fibrillation (AF) patients (61 ± 12 years; nine men) who underwent PVI at the first procedure. Transient PV reconnection was provoked by adenosine test in 4/48 PVs. In 44 PVs without reconnection, intravenous infusion of low-dose (10 mg) dipyridamole preceded the adenosine test. Additional six patients (PVs) with transient dormant conduction were included. Among the total 10 PVs with transient reconnection, it was eliminated by radiofrequency (RF) application(s) until no dormant conduction was exposed by adenosine test(s) in five PVs. Then, dipyridamole potentiated adenosine test was undertaken to provoke dormant conduction (group 1). In the remaining five PVs, dipyridamole potentiated adenosine test was followed by RF elimination of conduction gap and repeat adenosine test to confirm complete elimination (group 2). Low-dose dipyridamole prolonged the duration of adenosine-induced atrioventricular block without vasodilatatory hypotension. There was no evidence of reconnection in 44 PVs without dormant conduction and in group 1 wherein transient reconnection was eliminated by 4.8 ± 3.2 RF applications in 8.8 ± 3.0 minutes and adenosine injected 3.1 ± 1.8 times. In group 2, dipyridamole plus adenosine test revealed the same dormant conduction that persisted longer than during adenosine alone. It was eliminated by single RF application in 3.4 ± 0.9 minutes, and adenosine was injected once. CONCLUSIONS: Low-dose dipyridamole safely prolongs the electrophysiological effects of adenosine test without provoking additional PV reconnection. This allows sustained visualization and facilitates complete RF elimination of the electrical conduction gap.

HIV-1 viral infectivity factor interacts with TP53 to induce G2 cell cycle arrest and positively regulate viral replication.

Viral infectivity factor, an accessory protein encoded in the HIV-1 genome, induces G2 cell cycle arrest; however, the biological significance and mechanism(s) remain totally unclear. Here we demonstrate that the TP53 pathway is involved in Vif-mediated G2 cell cycle arrest. Vif enhances the stability and transcriptional activity of TP53 by blocking the MDM2-mediated ubiquitination and nuclear export of TP53. Furthermore, Vif causes G2 cell cycle arrest in a TP53-dependent manner. HXB2 Vif lacks these activities toward TP53 and cannot induce G2 cell cycle arrest. Using mutagenesis, we demonstrate that the critical residues for this function are located in the N-terminal region of Vif. Finally, we construct a mutant NL4-3 virus with an NL4-3/HXB2 chimeric Vif defective for the ability to induce cell cycle arrest and show that the mutant virus replicates less effectively than the wild-type NL4-3 virus in T cells expressing TP53. These data imply that Vif induces G2 cell cycle arrest through functional interaction with the TP53/MDM2 axis and that the G2 cell cycle arrest induced by Vif has a positive effect on HIV-1 replication. This report demonstrates the molecular mechanisms and the biological significance of Vif-mediated G2 cell cycle arrest for HIV-1 infection.

[A case of HER2-positive gastric cancer successfully treated with trastuzumab plus capecitabine plus cisplatin chemotherapy as third-line treatment].

A 67-year-old woman was diagnosed as having advanced gastric cancer(poorly differentiated adenocarcinoma)with multiple liver metastases. She had received combined S-1 plus cisplatin chemotherapy as first-line treatment and weekly paclitaxel chemotherapy as second-line treatment, however, both had eventually proved ineffective. Because the gastric cancer was HER2-positive, she was treated with trastuzumab plus capecitabine plus cisplatin(XP)chemotherapy as third-line treatment. The primary lesion and liver metastatic lesions were confirmed to show remarkable regression. The ToGA trial revealed increased efficacy of trastuzumab in first-line treatment of cancers showing high expression levels of the HER2- protein. This case suggested the increased efficacy of trastuzumab in third-line treatment. Neutropenia and hand foot syndrome of grade 2 were all reported adverse events. She could receive trastuzumab plus XP chemotherapy safely by dose reduction or dormancy temporarily of capecitabine.