Efficacy and Safety of the Surgery-First Approach Compared to the Chemotherapy-First Approach for Treating Low-Risk Gestational Trophoblastic Neoplasia: A Systematic Review and Meta-Analysis.

For gestational trophoblastic neoplasia (GTN) affecting women of reproductive age, the chemotherapy-first approach is often preferred over the surgery-first approach. Low-risk GTN is treated with a chemotherapy-first approach, but the number of courses required can affect fertility. A surgery-first approach may decrease the number of chemotherapy courses, but its efficacy and safety compared to a chemotherapy-first approach are unclear. Thus, we investigated the efficacy and safety of the surgery-first approach compared to the chemotherapy-first approach in treating low-risk GTN. We searched the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases for relevant articles in July 2023. A systematic review and meta-analysis of outcome measures were conducted using a random-effects model. The primary outcomes were remission, the mean number of chemotherapy courses required to cure, and adverse events. The certainty of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study protocol was registered in the Open Science Framework (https://osf.io/kysvn/). Studies for low-risk GTN included a qualitative synthesis (with 2,192 participants and ten studies, eight of which were about second uterine curettage and two about hysterectomy) and a meta-analysis (with 138 participants and two randomized controlled trials (RCTs) that compared first-line treatments of second uterine curettage and chemotherapy). Second uterine curettage may result in little to no difference in remission (risk ratio: 1.00, 95% confidence interval: 0.96-1.05; low certainty) and a slight reduction in adverse events (risk ratio: 0.87, 95% confidence interval: 0.47-1.60; low certainty). The evidence is very uncertain on the mean number of chemotherapy courses (mean difference: 2.84 lower, 95% confidence interval: 7.31 lower to 1.63 higher; very low certainty). Based on clinical outcomes, second uterine curettage can be comparable to the chemotherapy-first approach as a first-line treatment option for low-risk GTN; however, the overall certainty of the evidence was low or very low.

Synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma: A case report.

Mesonephric-like carcinoma histologically resembles mesonephric adenocarcinoma (MA) of the cervix. MA arises from mesonephric duct remnants. However, the origin of mesonephric-like carcinoma is not extensively studied because of its rarity. Here, we present a case of synchronous ovarian and uterine mesonephric-like carcinoma that potentially arose from endometrioid adenofibroma. A 69-year-old woman presented with an abdominal mass with no genital bleeding. She underwent simple total abdominal hysterectomy and bilateral adnexal resection. Histological and immunohistochemical analyses were consistent with mesonephric-like carcinoma involving both ovaries and the uterus. Endometrioid adenofibroma was present in both ovaries, while adenomyosis was observed in the uterus. The glandular duct of the endometrioid adenofibroma in the right ovary had areas suggestive of precursor lesions of mesonephric-like carcinoma. All tumors exhibited the KRAS G12D mutation. These findings suggest that the origin of the mesonephric-like carcinoma was the Müllerian duct, and that the ovarian and uterine tumors were monoclonal.

Mapping and ablation of left atrial roof-dependent tachycardias using an ultra-high resolution mapping system.

BACKGROUND: Left atrial roof-dependent tachycardias (LARTs) are common macroreentrant atrial tachycardias (ATs). We sought to characterize clinical LARTs using an ultra-high resolution mapping system. METHODS: This study included 22 consecutive LARTs in 21 patients who underwent AT mapping/ablation using Rhythmia systems. RESULTS: Three, 13, 4, and 2 LART patients were cardiac intervention naïve (Group-A), post-roof line ablation (Group-B), post-atrial fibrillation ablation without linear ablation (Group-C), and post-cardiac surgery (Group-D), respectively. The mean AT cycle length was 244 ± 43 ms. Coronary sinus activation was proximal-to-distal or distal-to-proximal in 16 (72.7%) ATs. The activation map revealed 13 (59.1%) clockwise and 9 (40.9%) counter-clockwise LARTs. A 12-lead synchronous isoelectric interval was observed in 10/19 (52.6%) LARTs. The slow conduction area was identified on the LA roof, anterior/septal wall, and posterior wall in 18, 6, and 2 ATs, respectively. Twenty concomitant ATs among 13 procedures were also eliminated, and peri-mitral AT coexisted in 7 of 9 non-group-B patients. In group-B, the conduction gap was predominantly located on the mid-roof. Sustained LARTs were terminated by a single application and linear ablation in 6 (27.3%) and 9 (40.9%), while converting to other ATs in 7 (31.8%) LARTs. Complete linear block was created without any complications in all, however, ablation at the mid-posterior wall was required to achieve block in 4 (18.2%) procedures. During 14.0 (6.5-28.5) months of follow-up, 17 (81.0%) and 19 (90.5%) patients were free from any atrial tachyarrhythmias after single and last procedures. CONCLUSIONS: The LART mechanisms were distinct in individual patients, and elimination of all concomitant ATs was required for the management.

Abdominal Fat Pad Fine-Needle Aspiration for Diagnosis of Cardiac Amyloidosis in Patients with Non-Ischemic Cardiomyopathy.

The diagnosis of cardiac amyloidosis is frequently delayed because histological confirmation is often challenging. Few studies have attempted to clarify the utility and safety of abdominal fat pad fine-needle aspiration (FPFNA) for an initial screening test in patients with suspected cardiac amyloidosis.This study included 77 consecutive patients with suspected non-ischemic cardiomyopathy who had left ventricular dysfunction and/or hypertrophy. All patients underwent abdominal FPFNA and an endomyocardial biopsy. In all patients, the abdominal FPFNA could be performed within less than 5 minutes with no complications; however, in 1 patient (1.3%), the obtained specimen was too small to evaluate. Among the remaining 76 patients, 5 (6.6%) were positive for amyloid (FPFNA[+]) and 7 (9.2%), including the 5 FPFNA[+], were diagnosed with cardiac amyloidosis (AL = 1, ATTR = 6) by endomyocardial biopsy. Positive abdominal FPFNAs indicated cardiac amyloidosis with high accuracy (sensitivity, 71.4%; specificity, 100%).Positive abdominal FPFNAs are directly linked to diagnoses of cardiac amyloidosis. Abdominal FPFNA is simple and useful for the initial screening test for cardiac amyloidosis in patients with non-ischemic cardiomyopathy.

The advantages and disadvantages of the novel fourth-generation cryoballoon as compared to the second-generation cryoballoon in the current short freeze strategy.

BACKGROUND: The novel fourth-generation cryoballoon (4th-CB) is characterized by a shorter-tip that potentially facilitates better time-to-isolation (TTI) monitoring. We sought to clarify the advantages and disadvantages of the 4th-CB compared to the second-generation cryoballoon (2nd-CB) in pulmonary vein isolation (PVI). METHODS: Forty-one and 49 consecutive atrial fibrillation patients underwent 2nd-CB and 4th-CB PVIs using 28-mm balloons and short freeze strategies. When effective freezing was not obtained, the CB was switched to the other CB. RESULTS: The rate of successful PVIs was significantly higher for 2nd-CBs than 4th-CBs (162/162[100%] vs. 178/193[92.2%] PVs, p < 0.0001). The difference was significant for lower PVs, especially right inferior PVs (RIPVs)(p = 0.005). In a total of 15 PVs in 11 patients, 4th-CBs were switched to 2nd-CBs, and 14/15(93.3%) PVs were successfully isolated. The balloon temperature tended to reach -55℃ more frequently with 2nd-CBs than 4th-CBs during RIPV ablations (15/41[36.6%] vs. 12/49[24.5%], p = 0.21). The TTI monitoring capability was significantly higher with 4th-CBs than 2nd-CBs (131/188[69.7%] vs. 83/160[51.9%] PVs, p = 0.0007). The difference was significant for right superior and left inferior PVs, but not for left superior PVs. Even if PVs requiring crossover were excluded, the total freeze duration (715±152 vs. 755±215 seconds, p = 0.31) tended to be shorter for 2nd-CBs than 4th-CBs. The incidence of phrenic nerve injury was similar for 2nd-CB and 4th-CB ablation (0/41 vs. 2/49, p = 0.12) CONCLUSIONS: The 4th-CB's shorter balloon tip enabled a significantly higher capability of TTI monitoring; however, it resulted in significantly lower rates of successful PVIs than the 2nd-CB, especially for the RIPVs.

Superior vena cava isolation using a novel ablation catheter incorporating local impedance monitoring.

BACKGROUND: A novel technology able to measure the local impedance (LI) during radiofrequency ablation has become available for clinical use. We investigated the change in the LI characteristics during superior vena cava isolations (SVCIs) using a novel catheter equipped with mini-electrodes. METHODS: Twenty paroxysmal atrial fibrillation patients (68 ± 9 years; 14 males) underwent an SVCI by targeting breakthroughs. Subsequently, dormant conduction provoked by adenosine triphosphate (ATP) was evaluated. RESULTS: Electrical SVCIs were successfully achieved in all with 7.2 ± 3.0 radiofrequency applications (RFA) without any complications. The procedure and fluoroscopic times were 13.1 ± 8.1 and 2.8 ± 2.3 min. No ablation was required at the anteroseptal SVC in 19 (95.0%) patients. The baseline LI and generator impedance (GI) were 125 ± 23 and 105 ± 14Ω. LI drops during RFA were significantly greater than GI drops (17 ± 12 vs. 4 ± 4Ω, p < 0.001). The correlation between the LI drops and GI drops was relatively high (R = 0.69, p < 0.001). LI drops were highest at the septal SVC and lowest at the lateral followed by antero-lateral SVC. The baseline electrogram amplitude between the mini-electrodes and tip-ring electrodes was 1.2 ± 1.4 and 0.8 ± 0.6 mV. The mini-electrode amplitude is more sharply attenuated with a greater magnitude than the tip-ring amplitude (p < 0.001). ATP-provoked dormant conduction was exposed in 10/17 (58.8%) patients and antero-lateral SVC gap locations in 7. Antero-lateral SVC LI drops were similar between patients with and without dormancy. CONCLUSIONS: The LI drop magnitude during RFA significantly differed among the SVC segments. Antero-lateral SVC ATP-provoked dormant conduction was often exposed, and additional applications are recommended following the isolation for a robust SVCI.

Association between Changes in the Systolic Blood Pressure from Evening to the Next Morning and Night Glucose Variability in Heart Disease Patients.

Objectve To assess the impact of glycemic variability on blood pressure in hospitalized patients with cardiac disease. Methods In 40 patients with cardiovascular disease, the glucose levels were monitored by flash continuous glucose monitoring (FGM; Free-Style Libre™ or Free-Style Libre Pro; Abbott, Witney, UK) and self-monitoring blood glucose (SMBG) for 14 days. Blood pressure measurements were performed twice daily (morning and evening) at the same time as the glucose level measurement using SMBG. Results The detection rate of hypoglycemia using the FGM method was significantly higher than that with the 5-point SMBG method (77.5% vs. 5.0%, p<0.001). Changes in the systolic blood pressure from evening to the next morning [morning - evening (ME) difference] were significantly correlated with night glucose variability (r=0.63, P<0.001). A multiple regression analysis showed that night glucose variability using FGM was more closely correlated with the ME difference [r=0.62 (95% confidence interval, 0.019-0.051); p<0.001] than with the age, body mass index, or smoking history. Night glucose variability was also more closely associated with the ME difference in patients with unstable angina pectoris (UAP) than in those with acute myocardial infarction (AMI) or heart failure (HF) (r=0.83, p=0.058). Conclusion Night glucose variability is associated with the ME blood pressure difference, and FGM is more accurate than the 5-point SMBG approach for detecting such variability.

Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer.

Background Medical castration, gonadotropin-releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration. Methods and Results This study included 149 patients who underwent medical castration using gonadotropin-releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied. The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [P<0.001]; QTc, 416±27 to 439±31 ms [P<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy. In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients. Conclusions Medical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.

Discrepancy between CARTO and Rhythmia maps for defining the left atrial low-voltage areas in atrial fibrillation ablation.

Reported mapping procedures of left atrial (LA) low-voltage areas (LVAs) vary widely. This study aimed to compare the PentaRay®/CARTO®3 (PentaRay map) and Orion™/Rhythmia™ (Orion map) systems for LA voltage mapping. This study included 15 patients who underwent successful pulmonary vein isolation (PVI) for atrial fibrillation. After PVI, PentaRay and Orion maps created for all patients were compared. LVAs were defined as sites with ≥ 3 adjacent low-voltage points < 0.5 mV. LVAs were indicated in 8 (53%) among 15 patients, and the average values of the measured LVAs was comparable between the systems (PentaRay map = 5.4 ± 8.7 cm2; Orion map = 4.3 ± 6.4 cm2, p = 0.69). However, in 2 of 8 patients with LVAs, the Orion map indicated LVAs at the septum and posterolateral sites of the LA, respectively, whereas the PentaRay map indicated no LVAs. In those patients, sharp electrograms of > 0.5 mV were properly recorded at the septum and posterolateral sites during appropriate beats in the PentaRay map. The PentaRay map had a shorter procedure time than the Orion map (12 ± 3 min vs. 23 ± 8 min, respectively; p < 0.01). Our study results showed a discrepancy in the LVA evaluation between the PentaRay and Orion maps. In 2 of 15 patients, the Orion map indicated LVAs at the sites where > 0.5-mV electrograms were properly recorded in the PentaRay map.

Mapping and ablation of clinical spontaneous perimitral atrial tachycardias using an ultra-high-resolution mapping system.

BACKGROUND: Perimitral atrial tachycardias (PMATs) are common atrial tachycardias (ATs), yet their mechanisms vary. OBJECTIVE: The purpose of this study was to characterize clinical spontaneous PMATs using an ultra-high-resolution (UHR) mapping system. METHODS: The study included 32 consecutive PMATs in 31 patients who had undergone AT mapping/ablation using a UHR mapping system. RESULTS: Six, 10, 11, and 5 PMATs occurred in cardiac intervention-naïve (group A), post-lateral/posterior mitral isthmus linear ablation (group B), post-atrial fibrillation ablation without mitral isthmus linear ablation (group C), and post-cardiac surgery (group D) patients, respectively. Group A patients tended to be older, more likely were female, and had sinus node or atrioventricular conduction disturbances more frequently. A 12-lead synchronous isoelectric interval was observed in 15 PMATs (46.9%). Coronary sinus activation was proximal to distal or distal to proximal except in 3 PMATs with straight patterns due to epicardial gaps. Left atrial anterior/septal wall (LAASW) low-voltage areas were smallest in group B. Slow conduction areas (SCAs) were identified in 26 PMATs (81.2%) and were located on the LAASW in all group A and group D patients. Conduction velocity in the SCAs was slowest in group B. In group B, all PMATs were terminated by single applications, and the gaps were located epicardially in 5 of 10 (50%). Anterior (n = 23) or lateral/posterior (n = 9) mitral isthmus linear block was successfully created without any complications in all. Twenty-five concomitant ATs among 18 patients (58.1%) also were eliminated. During a median of 20.0 (11.0-40.0) months of follow-up, 28 patients (90.3%) were free from any atrial tachyarrhythmias. CONCLUSION: An UHR mapping-guided approach with identification of the individual tachycardia mechanism should be the preferred strategy given the distinct and complex arrhythmia mechanisms.

Clinically Manifesting Air Embolisms in Cryoballoon Ablation: Can Novel Water Buckets Reduce the Risk?

Air embolisms can lead to lethal results; however, few reports have systemically investigated this issue. Of 348 consecutive patients with atrial fibrillation who underwent cryoballoon ablation, procedures were performed conventionally in 251 patients. In the remaining 97 patients, a water bucket was used while inserting the cryoballoon into the sheath. A total of 10 coronary air embolisms with ST-segment elevation in the inferior leads were observed among 9 (2.6%) patients. Multiple air bubbles were identified in 2 patients on emergent coronary angiography. All recovered under conservative treatment without any sequela. The incidence decreased when using the water bucket (1 of 97 [1.03%] vs. 8 of 251 [3.2%], p = 0.454).

Cryothermal atrial linear ablation in patients with atrial fibrillation: An insight from the comparison with radiofrequency atrial linear ablation.

BACKGROUND: Atrial linear lesions are generally created with radiofrequency energy. We sought to evaluate the feasibility of cryothermal atrial linear ablation. METHODS AND RESULTS: Twenty-one atrial fibrillation (AF) patients underwent linear ablation on the left atrial (LA) roof, mitral isthmus (MI), and cavotricuspid isthmus (CTI) with 8-mm-tip cryocatheters following pulmonary vein isolation. The data were compared with those of 31 patients undergoing linear ablation with irrigated-tip radiofrequency catheters. Conduction block was successfully created in 18 of 20 (90%), 9 of 21 (43%), and 20 of 20 (100%) on the LA roof, MI, and CTI by endocardial cryoablation alone with 19.0 (12.0-24.0), 30.0 (23.0-34.0), and 14.0 (14.0-16.0) minute cryo applications, respectively. The presence of either an interposed circumflex artery or pouch at the MI was significantly associated with failed MI block (P = .04). Conduction block was created in 25 of 31 (83.9%), 27 of 31 (87.1%), and 30 of 31 (96.8%) on the roof, MI, and CTI, respectively, by radiofrequency ablation. During the 17.5 (13.0-31.7) months of follow-up, freedom from AF/atrial tachycardia (AT) was significantly higher in the cryo group (P = .05); especially, recurrent AT was more frequent in the RF group (8/31 vs 1/21; P = .03). Conduction block across the roof, MI, and CTI was durable in 6 of 12 (50.0%), 4 of 12 (33.3%), and 9 of 12 (75.0%) patients during second procedures. All nine patients (except one) with recurrent ATs had at least one roof or MI conduction resumption. CONCLUSIONS: Cryoablation is effective for creating a roof and CTI linear block, however, creating MI block by endocardial ablation alone was often challenging. Conduction resumption of LA linear block is common and recurrent arrhythmias, especially iatrogenic ATs, are more frequently observed after radiofrequency linear ablation.

Pressure-guided second-generation cryoballoon pulmonary vein isolation: Prospective comparison of the procedural and clinical outcomes with the conventional strategy.

BACKGROUND: The utility of pressure waveform analyses to assess pulmonary vein (PV) occlusions has been reported in cryoballoon PV isolation (CB-PVI) using first-generation CBs. This prospective randomized study compared the procedural and clinical outcomes of pressure-guided and conventional CB-PVI. METHODS AND RESULTS: Sixty patients with paroxysmal atrial fibrillation underwent CB-PVI with 28-mm second-generation CBs. PV occlusions were assessed either by real-time pressure waveforms without contrast utilization (pressure-guided group) or contrast injections (conventional group) and randomly assigned. Before the randomization, 24 patients underwent pressure-guided CB-PVIs. In the derivation study, a vein occlusion was obtained in 88/96 (91.7%) PVs among which 86 (97.7%) were successfully isolated by the application. In the validation study, the nadir balloon temperature and total freezing time did not significantly differ per PV between the two groups. The positive predictive value of the vein occlusion for predicting successful acute isolations was similar (93 of 103 [90.2%] and 89 of 98 [90.8%] PVs; P = 1.000), but the negative predictive value was significantly higher in pressure-guided than angiographical occlusions (14 of 17 [82.3%] vs 7 of 22 [31.8%]; P = .003). Both the procedure (57.7 ± 14.2 vs 62.6 ± 15.8 minutes; P = .526) and fluoroscopic times (16.3 ± 6.4 vs 20.1 ± 6.1; P = .732) were similar between the two groups, however, the fluoroscopy dose (130.6 ± 97.7 vs 353.2 ± 231.4 mGy; P < .001) and contrast volume used (0 vs 17.5 ± 7.7 mL; P < .001) were significantly smaller in the pressure-guided than conventional group. During 27.8 (5-39) months of follow-up, the single procedure arrhythmia freedom was similar between the two groups (P = .438). CONCLUSIONS: Pressure-guided second-generation CB-PVIs were similarly effective and as safe as conventional CB-PVIs. This technique required no contrast utilization and significantly reduced radiation exposure more than conventional CB-PVIs.

Effects of Sitagliptin on the Coronary Flow Reserve, Circulating Endothelial Progenitor Cells and Stromal Cell-derived Factor-1alpha.

Objective Circulating endothelial progenitor cells (EPCs) are regulated by stromal cell-derived factor-1alpha (SDF-1α) and are reduced in type 2 diabetes mellitus (DM). SDF-1α is a substrate of dipeptidyl-peptidase-4 (DPP-4), so we investigated whether or not DPP-4-inhibitors modulate EPC levels in type 2 DM patients with coronary artery disease (CAD). Methods Thirty patients with CAD and type 2 DM treated using an ordinary regimen were enrolled. EPC and SDF-1α levels were compared between those receiving additional 24-week treatment with a DPP-4-inhibitor (n=11) and no additional treatment (n=19). We determined the HbA1c, 1.5-Anhydro-D-glucitol (1,5-AG), coronary flow reserve (CFR), brain natriuretic peptide (BNP), E/e', and circulating EPC proportion and SDF-1α levels at baseline and the end of follow-up. The CFR was assessed using a dual-sensor-equipped guidewire. The primary endpoints were changes in the EPC count, SDF-1α levels, and CFR from baseline to the end of follow-up. The secondary endpoints were changes in the HbA1c and 1,5-AG, which are useful clinical markers of postprandial hyperglycemia, as well as the BNP and E/e'. Results After the 6-month follow-up, compared with ordinary regimen subjects, the patients receiving a DPP-4-inhibitor showed no significant increase in the EPC proportion (-0.01±0.50 vs. 0.02±0.77%, p=0.87), SDF-1α level (-600.4±653.6 vs. -283.2±543.1 pg/mL, p=0.18), or CFR (0.0±0.2 vs. 0.1±0.6, p=0.20), whereas both the 1.5-AG level (2.4±4.6 vs. -0.7±2.5 µg/dL, p=0.07) and HbA1c (-0.8±1.8 vs. 0.0±0.7%, p=0.02) were improved. There were no significant differences between the two groups in changes in the BNP and E/e'. Conclusion DPP-4 inhibition with sitagliptin did not increase or decrease the EPC proportion, SDF-1α level, or CFR, although the glycemic control was improved.

Involvement of selective epithelial cell death in the formation of feather buds on a bioengineered skin.

Selective cell death by apoptosis plays important roles in organogenesis. Apoptotic cells are observed in the developmental and homeostatic processes of several ectodermal organs, such as hairs, feathers, and mammary glands. In chick feather development, apoptotic events have been observed during feather morphogenesis, but have not been investigated during early feather bud formation. Previously, we have reported a method for generating feather buds on a bioengineered skin from dissociated skin epithelial and mesenchymal cells in three-dimensional culture. During the development of the bioengineered skin, epithelial cavity formation by apoptosis was observed in the epithelial tissue. In this study, we examined the selective epithelial cell death during the bioengineered skin development. Histological analyses suggest that the selective epithelial cell death in the bioengineered skin was induced by caspase-3-related apoptosis. The formation of feather buds of the bioengineered skin was disturbed by the treatment with a pan-caspase inhibitor. The pan-caspase inhibitor treatment suppressed the rearrangement of the epithelial layer and the formation of dermal condensation, which are thought to be essential step to form feather buds. The suppression of the formation of feather buds on the pan-caspase inhibitor-treated skin was partially compensated by the addition of a GSK-3ß inhibitor, which activates Wnt/ß-catenin signaling. These results suggest that the epithelial cell death is involved in the formation of feather buds of the bioengineered skin. These observations also suggest that caspase activities and Wnt/ß-catenin signaling may contribute to the formation of epithelial and mesenchymal components in the bioengineered skin.

Endothelial damage and thromboembolic risk after pulmonary vein isolation using the latest ablation technologies: a comparison of the second-generation cryoballoon vs. contact force-sensing radiofrequency ablation.

Experimental data suggest that cryoenergy is associated with less endothelial damage and thrombus formation than radiofrequency energy. This study aimed to compare the impact of pulmonary vein isolation (PVI) on the endothelial damage, myocardial damage, inflammatory response, and prothrombotic state between the two latest technologies, second-generation cryoballoon (CB2) and contact force-sensing radiofrequency catheter (CFRF) ablation. Eighty-six paroxysmal atrial fibrillation (AF) patients (55 men; 65 ± 12 years) underwent PVI with either the CB2 (n = 64) or CFRF (n = 22). Markers of the endothelial damage (L-arginine/asymmetric dimethylarginine [ADMA]), myocardial injury (creatine kinase-MB [CK-MB], troponin-T, and troponin-I), inflammatory response (high-sensitive C-reactive protein), and prothrombotic state (D-dimer, soluble fibrin monomer complex, and thrombin-antithrombin complex) were determined before and up to 24-h post-procedure. The total application time was shorter (1,460 ± 287 vs. 2,395 ± 571 [sec], p < 0.01) and total procedure time tended to be shorter (199 ± 37 vs. 218 ± 38 [min], p = 0.06) with CB2 than CFRF ablation. The amount of myocardial injury was greater (CK-MB: 45 ± 17 vs. 11 ± 3 [IU/l], p < 0.01) with CB2 than CFRF ablation. The L-arginine/ADMA ratio was lower (160 ± 51 vs. 194 ± 38, p = 0.028) after CB2 than CFRF ablation. Inflammatory and all prothrombotic markers were significantly elevated post-ablation; however, the magnitude was similar between the two groups. During a mean follow-up of 20 ± 6 months, the single-procedure AF freedom was similar between the CB2 and CFRF groups (60/64 vs. 20/22, p = 0.82). CB2-PVI produces significantly lesser endothelial damage with greater myocardial injury than CFRF-PVI; however, similar anticoagulant regimens are required during the peri-procedural periods in both technologies.

Mid-axillary pacemaker re-implantation after contralateral pocket infection in an emaciated elderly case.

The number of implantations of cardiac implantable electrophysiological devices (CIEDs) has increased over the past several years. However, the aging population and expansion of indications for CIEDs have led to an increase in associated infections. We experienced a case of a 99-year-old man presenting with skin erosion at the pocket site, where a 6-month-old implantable pacemaker was replaced. He was referred for pacemaker pocket infection and presented with fever accompanied by pain and swelling around pacemaker generator. We could not explant 7-year-old pacemaker leads and the patient refused to undergo either laser lead extraction or surgical removal. We planned to re-implant in the contralateral chest. However, the patient was emaciated with low body-mass-index (15.2 kg/m2), thus concerns arose about the possibility of tissue disruption and re-infection owing to thin skin and absence of sufficient subcutaneous tissue in contralateral subclavian region. Axillary placement of CIEDs has been adopted in patients with limited venous access. We applied a mid-axillary pacemaker implant procedure to this elderly and emaciated patient. Postoperative clinical course was uneventful. After discharge, no history of unexplained fever or illness was recorded. Mid-axillary pacemaker pocket could be an alternative approach for re-implantation in patients with emaciated, cachexic, or limited pocket preparation. .

Impaired myocardial microcirculation in the flow-glucose metabolism mismatch regions in revascularized acute myocardial infarction.

BACKGROUND: In successfully revascularized acute myocardial infarction (AMI), microvascular function in a myocardial flow-glucose metabolism mismatch pattern has not been reported. We aimed to elucidate myocardial flow reserve (MFR) and myocardial viability in mismatch segments. METHODS: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and adenosine stress 13N-ammonia PET were performed in eighteen AMI patients to evaluate myocardial glucose metabolism, myocardial blood flow (MBF), and MFR. Infarct segments were classified into 3 groups: normal (preserved resting MBF), mismatch (preserved FDG uptake but reduced resting MBF), and match (reduced FDG uptake and resting MBF). Regional wall motion score (WMS) was assessed immediately after reperfusion and recovery periods. RESULTS: MFR in the mismatch group was significantly lower than that in non-infarct-related segments (1.655 ± 0.516 vs 2.282 ± 0.629, P < .01) and similar to that in the match group (1.635 ± 0.528, P = .999). WMS in the mismatch group was significantly improved (3.07 ± 0.48 vs 2.07 ± 1.14, P = .003); however, in recovery periods, WMS in the mismatch group was significantly higher than that in the normal group (1.05 ± 1.04, P < .01). CONCLUSIONS: In successfully revascularized AMI, microvascular function is impaired despite preserved myocardial glucose metabolism in mismatch segments.

Association of CD34/CD133/VEGFR2-Positive Cell Numbers with Eicosapentaenoic Acid and Postprandial Hyperglycemia in Patients with Coronary Artery Disease.

OBJECTIVES: Circulating endothelial progenitor cells (EPCs), which have the ability to differentiate into mature endothelial cells, can elicit angiogenesis, vasculogenesis and vessel repair in cardiac ischemia and vascular injuries caused by endothelial damage. Serum 1,5-anhydro-d-glucitol (1,5-AG), which is a useful clinical marker of postprandial hyperglycemia, eicosapentaenoic acid (EPA), and arachidonic acid (AA) are newly identified risk factors for coronary artery disease (CAD). However, no previous study has reported the associations between EPCs and 1,5-AG, EPA, and AA levels in CAD patients with type 2 diabetes mellitus (DM). METHODS: Peripheral EPCs, assessed as CD34+ cells co-expressing CD133 and vascular endothelial growth factor receptor-2, were studied in 76 CAD patients (mean age, 69.2±11.3years) with DM. Serum 1,5-AG, EPA, and AA levels were measured. RESULTS: EPC numbers showed a significant association with 1,5-AG and HbA1c (r=0.290; p=0.037 and r=-0.328; p=0.011, respectively). In addition, there were significant associations between EPC numbers and EPA and body mass index (BMI) (r=0.354; p=0.027 and r=-0.402; p=0.002, respectively). In multiple linear regression analysis, HbA1c, BMI, and EPA values had significant associations with EPC numbers (ß=-0.316, 95% confidence interval (CI) -0.256 to -0.008, p=0.037; ß=-0.413, 95% CI -0.099 to -0.017, p=0.007; and ß=0.400, 95% CI 0.004 to 0.002, p=0.010, respectively). CONCLUSIONS: EPC number is associated with HbA1c, 1,5-AG, EPA, and BMI values, suggesting that postprandial hyperglycemia and n-3 polyunsaturated fatty acids contribute to EPC recruitment in CAD patients with type 2 DM.