Laser spectroscopy of triply charged 229Th isomer for a nuclear clock.

Thorium-229 (229Th) possesses an optical nuclear transition between the ground state (229gTh) and low-lying isomer (229mTh). A nuclear clock based on this nuclear-transition frequency is expected to surpass existing atomic clocks owing to its insusceptibility to surrounding fields1-5. In contrast to other charge states, triply charged 229Th (229Th3+) is the most suitable for highly accurate nuclear clocks because it has closed electronic transitions that enable laser cooling, laser-induced fluorescence detection and state preparation of ions1,6-8. Although laser spectroscopic studies of 229Th3+ in the nuclear ground state have been performed8, properties of 229mTh3+, including its nuclear decay lifetime that is essential to specify the intrinsic linewidth of the nuclear-clock transition, remain unknown. Here we report the trapping of 229mTh3+ continuously supplied by a 233U source and the determination of nuclear decay half-life of the isolated 229mTh3+ to be 1,400 - 300 + 600 s through nuclear-state-selective laser spectroscopy. Furthermore, by determining the hyperfine constants of 229mTh3+, we reduced the uncertainty of the sensitivity of the 229Th nuclear clock to variations in the fine-structure constant by a factor of four. These results offer key parameters for the 229Th3+ nuclear clock and its applications in the search for new physics.

X-ray pumping of the 229Th nuclear clock isomer.

The metastable first excited state of thorium-229, 229mTh, is just a few electronvolts above the nuclear ground state1-4 and is accessible by vacuum ultraviolet lasers. The ability to manipulate the 229Th nuclear states with the precision of atomic laser spectroscopy5 opens up several prospects6, from studies of fundamental interactions in physics7,8 to applications such as a compact and robust nuclear clock5,9,10. However, direct optical excitation of the isomer and its radiative decay to the ground state have not yet been observed, and several key nuclear structure parameters-such as the exact energies and half-lives of the low-lying nuclear levels of 229Th-remain unknown11. Here we present active optical pumping into 229mTh, achieved using narrow-band 29-kiloelectronvolt synchrotron radiation to resonantly excite the second excited state of 229Th, which then decays predominantly into the isomer. We determine the resonance energy with an accuracy of 0.07 electronvolts, measure a half-life of 82.2 picoseconds and an excitation linewidth of 1.70 nanoelectronvolts, and extract the branching ratio of the second excited state into the ground and isomeric state. These measurements allow us to constrain the 229mTh isomer energy by combining them with γ-spectroscopy data collected over the past 40 years.

Effect of mechanical tension on fibroblast transcriptome profile and regulatory mechanisms of myocardial collagen turnover.

Excess deposition of extracellular matrix in the myocardium is a predictor of reduced left ventricular function. Although reducing the hemodynamic load is known to improve myocardial fibrosis, the mechanisms underlying the reversal of the fibrosis have not been elucidated. We focused on the elasticity of myocardial tissue, which is assumed to influence the fibroblast phenotype. Normal and fibrotic myocardium were cultured in 16 kPa and 64 kPa silicone gel-coated dishes supplemented with recombinant TGFß protein, respectively. Matrix-degrading myocardium was cultured in 64 kPa silicone gel-coated dishes with recombinant TGFß protein and then in 16 kPa silicone gel-coated dishes. Cardiac fibroblasts were cultured in this three-part in vitro pathological models and compared. Fibroblasts differentiated into activated or matrix-degrading types in response to the pericellular environment. Comprehensive gene expression analysis of fibroblasts in each in vitro condition showed Selenbp1 to be one of the genes responsible for regulating differentiation of fibroblasts. In vitro knockdown of Selenbp1 enhanced fibroblast activation and inhibited conversion to the matrix-degrading form. In vivo knockdown of Selenbp1 resulted in structural changes in the left ventricle associated with progressive tissue fibrosis and left ventricular diastolic failure. Selenbp1 is involved in regulating fibroblast differentiation and appears to be one of the major molecules regulating collagen turnover in cardiac fibrosis.

Monocarboxylate Transporters 1 and 2 Are Responsible for L-Lactate Uptake in Differentiated Human Neuroblastoma SH-SY5Y Cells.

L-Lactate transport via monocarboxylate transporters (MCTs) in the central nervous system, represented by the astrocyte-neuron lactate shuttle (ANLS), is crucial for the maintenance of brain functions, including memory formation. Previously, we have reported that MCT1 contributes to L-lactate transport in normal human astrocytes. Therefore, in this study, we aimed to identify transporters that contribute to L-lactate transport in human neurons. SH-SY5Y cells, which are used as a model for human neurons, were differentiated using all-trans-retinoic acid. L-Lactate uptake was measured using radiolabeled L-lactate, and the expression of MCT proteins was confirmed Western blotting. L-Lactate transport was pH-dependent and saturated at high concentrations. Kinetic analysis suggested that L-lactate uptake was biphasic. Furthermore, MCT1, 2 selective inhibitors inhibited L-lactate transport. In addition, the expression of MCT1 and 2 proteins, but not MCT4, was confirmed. In this study, we demonstrated that MCT1 and 2 are major contributors to L-lactate transport in differentiated human neuroblastoma SH-SY5Y cells from the viewpoint of kinetic analysis. These results lead to a better understanding of ANLS in humans, and further exploration of the factors that can promote MCT1 and 2 functions is required.

Left ventricular remodeling and long-term outcomes of aortic stenosis patients receiving 19 mm Mosaic.

Mosaic valve shows higher pressure gradient after aortic valve replacement compared to other same size labeled prostheses in postoperative echocardiogram. The purpose of this study was to evaluate the mid-term echocardiogram findings and long-term clinical outcomes of patients receiving a 19 mm Mosaic. Forty-six aortic stenosis patients receiving 19 mm Mosaic and 112 patients receiving either 19 mm Magna or Inspiris, who underwent mid-term follow-up echocardiogram were included in the study. Mid-term hemodynamic measurements evaluated by trans-thoracic echocardiogram and long-term outcomes were compared. Patients receiving Mosaic were significantly older (Mosaic: 76 ± 5.1 years vs. Magna/Inspiris: 74 ± 5.5 years, p = 0.046) and had smaller body surface area (Mosaic: 1.40 ± 0.114m2 vs. Magna/Inspiris: 1.48 ± 0.143m2, p < 0.001). There were no significant differences in comorbidities and medications. Post-operative echocardiogram performed at 1 week after the surgery showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 38 ± 13.5 mmHg vs. Magna/Inspiris: 31 ± 10.7 mmHg, p = 0.002). Furthermore, mid-term echocardiogram follow-up performed at median duration of 53 ± 14.9 months after the surgery continuously showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 45 ± 15.6 mmHg vs. Magna/Inspiris: 32 ± 13.0 mmHg, p < 0.001). However, there were no significant difference in changes in left ventricular mass from baseline in both groups. Kaplan-Meyer curve also showed no difference in long-term mortality and major adverse cardiac and cerebrovascular event between the two groups. Although the pressure gradient across the valve evaluated by echocardiogram was higher in 19 mm Mosaic compared to 19 mm Magna/Inspiris, there were no significant differences in left ventricular remodeling and long-term outcomes between the two groups.

The effect of balloon-expandable stent and self-expanding stent on changes in mitral annular motion after aortic valve replacement in patients with aortic stenosis.

OBJECTIVES: The purpose of this study was to evaluate the effect of decalcification and existence of stent at the aortic annulus on mitral annular motion after surgery. METHODS: Patients receiving Inspiris (Edwards, CA, USA, n = 117), Intuity (Edwards, n = 36), Perceval (Corcym, London, UK, n = 36), Evolut (Medtronics, MN, USA, n = 81) and Sapien 3 (Edwards, n = 250) were included in the study. Mitral annular motion was evaluated by E', using tissue doppler imaging. RESULTS: After surgery, a significant increase in E' was observed in patients receiving Inspiris (Before: 4.2 ± 1.21 cm/s vs. Discharge: 5.0 ± 1.23 cm/s, p < 0.001). Mid-term echocardiogram performed at 11.8 ± 2.2 months after the surgery, showed a significant increase in E' in patients receiving Inspiris (Before: 4.2 ± 1.21 cm/s vs. Mid-term: 5.2 ± 1.20 cm/s, p < 0.001) and Perceval (Before: 3.9 ± 1.34 cm/s vs. Mid-term: 4.5 ± 1.24 cm/s, p = 0.008). Univariable analysis showed a higher increase in E' in patients with decalcified annulus compared to those without decalcified annulus (Decalcification: 0.15 ± 1.321 cm/s vs. No Decalcification: 0.66 ± 1.420 cm/s, p < 0.001). Multivariable analysis showed that balloon-expandable stent (ß = - 0.6960, p < 0.001) and self-expanding stent (r = - 0.3592, p = 0.042) were independent limiting factors for an increase in E' at discharge. However, balloon-expandable stent (ß = - 0.8382, p < 0.001), and not self-expanding stent (ß = - 0.3682, p = 0.089), was a remaining independent factor associated with E' at mid-term follow-up. CONCLUSIONS: Decalcification was associated with improvement in E' after surgery. Balloon-expandable stent was an independent limiting factor for improvement in E' up to 1 year after the surgery, while self-expanding stent was not a significant factor after 1 year.

Effects of transmembrane serine protease 4 on the survival in patients with pancreatic ductal adenocarcinoma undergoing surgery followed by adjuvant chemotherapy.

PURPOSE: The transmembrane serine protease 4 (TMPRSS4) gene is upregulated in various human cancers. However, its biological functions in pancreatic ductal adenocarcinoma remain unclear. We examined the expression of TMPRSS4 in pancreatic ductal adenocarcinoma tissues and its correlation with clinicopathological parameters in patients with pancreatic ductal adenocarcinoma who underwent surgery. METHODS: The TMPRSS4 expression was immunohistochemically examined in 81 PDAC patients with pancreatic ductal adenocarcinoma. We analyzed the association between the TMPRSS4 expression and clinicopathological factors, the recurrence-free survival (RFS), and the overall survival (OS) and examined the effect of TMPRSS4 expression on cell migration and sensitivity to 5-fluorouracil. RESULTS: The expression rate of TMPRSS4 in the samples was 62.9% (51/81). The TMPRSS4 expression was not correlated with any clinicopathological feature. The five-year overall and recurrence-free survival rates were significantly lower in the TMPRSS4-positive group than in the TMPRSS4-negative group. On a multivariate analysis, TMPRSS4 positivity, poorly differentiated histology, and non-adjuvant chemotherapy predicted a poor OS, while TMPRSS4 positivity and poorly differentiated histology predicted a poor RFS. TMPRSS4-silenced pancreatic ductal adenocarcinoma cells showed higher sensitivity to 5- fluorouracil than did the control siRNA-transfected cells. CONCLUSIONS: TMPRSS4 can be considered a prognostic factor and therapeutic target for pancreatic ductal adenocarcinoma.

Effect of body fat mass loss on prognosis of radical resection for pancreatic ductal adenocarcinoma based on bioelectrical impedance analysis.

BACKGROUND: Few reports have performed a prognostic analysis based on bioelectrical impedance analysis in patients with radical resection of pancreatic ductal adenocarcinoma (PDAC), and its usefulness in prognostic analysis remains unclear. This study aimed to evaluate body composition changes in patients undergoing radical resection for PDAC and analyze its impact on prognosis. METHODS: The medical records of radical resection for patients with PDAC were retrospectively reviewed, and the parameters of body composition, including body weight, skeletal muscle mass, body fat mass (BFM), and extracellular water-total body water ratio, from preoperatively to 12 months postoperatively, for each surgical procedure were measured based on direct segmental multifrequency bioelectrical impedance analysis with an InBody 770 (InBody Inc., Tokyo, Japan) device. The clinicopathological and prognostic factors were analyzed. RESULTS: Among 79 patients who underwent radical resection for PDAC, 36 (46%), 7 (8%), and 36 (46%) underwent pancreatoduodenectomy, total pancreatectomy, and distal pancreatectomy, respectively. The multivariate overall survival analysis demonstrated that BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021), lymph node metastasis (p = 0.014), and non-adjuvant chemotherapy (p <  0.001) were independent poor prognostic factors. Multivariate analysis revealed that preoperative BFM < 12 kg and preoperative albumin < 3.5 g/dL were independently associated with BFM loss percentage at 1 month postoperatively ≧14% (p = 0.021 and p = 0.047, respectively). CONCLUSIONS: Loss of BFM in the early postoperative period may have a poor prognosis in radical resection of PDAC.

DNA metabarcoding focused on difficult-to-culture protists: An effective approach to clarify biological interactions.

DNA metabarcoding on a single organism is a promising approach to clarify the biological interactions (e.g., predator-prey relationships and symbiosis, including parasitism) of difficult-to-culture protists. To evaluate the effectiveness of this method, Radiolaria and Phaeodaria, which are ecologically important protistan groups, were chosen as target taxa. DNA metabarcoding on a single organism focused on the V9 region of the 18S rRNA gene revealed potential symbionts, parasites and food sources of Radiolaria and Phaeodaria. Previously reported hosts and symbionts (parasites) were detected, and newly recognized combinations were also identified. The contained organisms largely differed between Radiolaria and Phaeodaria. In Radiolaria, members of the same order tended to contain similar organisms, and the taxonomic composition of possible symbionts, parasites, and food sources was fixed at the species level. Members of the same phaeodarian family, however, did not contain similar organisms, and body part (i.e., the central capsule or the phaeodium) was the most important factor that divided the taxonomic composition of detected organisms, implying that the selection of appropriate body part is important when trying to ascertain contained organisms, even for unicellular zooplankton. Our results show that DNA metabarcoding on a single organism is effective in revealing the biological interactions of difficult-to-culture protists.

Nrg1/ErbB signaling-mediated regulation of fibrosis after myocardial infarction.

Appropriate fibrotic tissue formation after myocardial infarction (MI) is crucial to the maintenance of the heart's structure. M2-like macrophages play a vital role in post-MI fibrosis by activating cardiac fibroblasts. Because the mechanism by which post-MI cardiac fibrosis is regulated is not fully understood, we investigated, in vitro and in vivo, the cellular and molecular mechanisms of post-MI fibrotic tissue formation, especially those related to the regulation of cellular senescence and apoptosis. CD206+ F4/80+ CD11b+ M2-like macrophages collected from mouse hearts on post-MI day 7 showed increased expression of neuregulin 1 (Nrg1). Nrg1 receptor epidermal growth factor receptors ErbB2 and ErbB4 were expressed on cardiac fibroblasts in the infarct area. M2-like macrophage-derived Nrg1 suppressed both hydrogen peroxide-induced senescence and apoptosis of fibroblasts, whereas blockade of ErbB function significantly accelerated both processes. M2-like macrophage-derived Nrg1/ErbB/PI3K/Akt signaling, shown to be related to anti-senescence, was activated in damaged cardiac fibroblasts. Interestingly, systemic blockade of ErbB function in MI model mice enhanced senescence and apoptosis of cardiac fibroblasts and exacerbated inflammation. Further, increased accumulation of M2-like macrophages resulted in excessive post-MI progression of fibrosis in mice hearts. The molecular mechanism underlying the regulation of fibrotic tissue formation in the infarcted myocardium was shown in part to be attenuation of apoptosis and senescence of cardiac fibroblasts by the activation of Nrg1/ErbB/PI3K/Akt signaling. M2-like macrophage-mediated regulation of Nrg1/ErbB signaling has a substantial effect on fibrotic tissue formation in the infarcted adult mouse heart and is critical for suppressing the progression of senescence and apoptosis of cardiac fibroblasts.

Clinical features and images of malignant lymphoma localized in the pancreatic head to differentiate from pancreatic ductal adenocarcinoma: a case series study.

BACKGROUND: Pathological examination by endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been reported to be useful in diagnosing pancreatic malignant lymphoma (ML), but some ML cases are difficult to be differentiated from pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective study included 8 patients diagnosed with ML that had a pancreatic-head lesion at initial diagnosis and 46 patients with resected PDAC in the pancreatic head between April 2006 and October 2021 at our institute. ML and PDAC were compared in terms of patients' clinical features and imaging examinations. RESULTS: The median tumor size was larger in ML than in PDAC (45.8 [24-64] vs. 23.9 [8-44] mm), but the median diameter of the caudal main pancreatic duct (MPD) was larger in PDAC (2.5 [1.0-3.5] vs. 7.1 [2.5-11.8] mm), both showing significant differences between these malignancies (both, P < 0.001). In the analysis of covariance, MLs showed a smaller caudal MPD per tumor size than PDACs, with a statistical difference (P = 0.042). Sensitivity and specificity using sIL-2R ≥ 658 U/mL plus CA19-9 < 37 U/mL for the differentiation of ML from PDAC were 80.0% and 95.6%, respectively. CONCLUSIONS: Diagnosing pancreatic ML using cytohistological examination through EUS-FNA can be difficult in some cases. Thus, ML should be suspected if a patient with a pancreatic tumor has a small MPD diameter per tumor size, high serum sIL-2R level, normal CA19-9 level. If the abovementioned features are present and still cannot be confirmed as PDAC, re-examination should be considered.

Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study.

BACKGROUND: Type 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation. METHODS: We analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18-36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors. RESULTS: After discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001). CONCLUSIONS: A high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Palonosetron for prevention of delayed chemotherapy-induced nausea and vomiting in pediatric patients: a meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) are common adverse events in patients undergoing emetogenic chemotherapy. Palonosetron, a second-generation 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), has demonstrated non-inferiority to first-generation 5-HT3 RAs for CINV in pediatric patients. Although palonosetron has a long half-life and prolonged antiemetic action, its efficacy against delayed CINV in pediatric patients is not well understood. Therefore, this meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of palonosetron for delayed CINV in pediatric patients. METHODS: A literature search of MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science databases was performed. A meta-analysis was performed using forest plots, and risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. A funnel plot was constructed to explore publication bias. RESULTS: The literature search retrieved 842 records, of which 23 full-text articles were assessed, including six RCTs. Meta-analysis of four RCTs that reported on the complete response (CR: defined as no emesis and no rescue medication) rate for delayed CINV revealed that palonosetron was statistically superior to first-generation 5-HT3 RAs (RR = 1.21 [95% CI 1.09-1.35]; p < 0.01). Although the number of studies included was small, no publication bias was observed in the funnel plots. In addition, the CR rate for overall and acute CINV was also significantly higher for palonosetron (RR = 1.25 [95% CI 1.01-1.54]; p = 0.04 and RR = 1.06 [95% CI 1.01-1.12]; p = 0.03, respectively). CONCLUSION: Palonosetron is effective in the prophylaxis of delayed CINV in pediatric patients.

Acid suppressants reduce the therapeutic effect of immune checkpoint inhibitors and increase the risk of acute kidney injury: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy; however, they can lead to immune-related adverse events (irAEs) through immune function of patients. Therefore, this meta-analysis aimed to assess the concomitant effect of acid suppressants (ASs) on ICIs, including several subgroup analyses. METHODS: We identified related studies and generated the forest plot. The primary endpoint was defined as the change in progression free survival (PFS) and overall survival (OS) with or without ASs administration. We also evaluated the effect of ASs on the incidence of irAEs. RESULTS: The total hazard ratio (HR) of ASs on PFS with ICI treatment was 1.39 and the 95% confidence interval (95% CI) was 1.21-1.59 (Z: p < 0.00001). Moreover, the total HR of ASs on OS was 1.40 and the 95% CI was 1.21-1.61 (Z: p < 0.00001), suggesting that ASs reduced ICI's therapeutic effect. The total odds ratio (OR) for evaluating the effect of ASs on irAEs was 1.23 with a 95% CI of 0.81-1.88 (Z: p = 0.34). However, ASs significantly worsened acute kidney injury (AKI) (total OR 2.10; 95% CI 1.74-2.53 (Z, p < 0.00001)). Furthermore, although proton pump inhibitors (PPIs) reduced ICI's therapeutic effect, histamine H2-receptor antagonists (H2RAs) did not affect OS. CONCLUSIONS: It was shown that ASs, especially PPIs, reduced ICI's therapeutic effect, while H2RAs had no effect, and ASs did not affect irAEs; however, it is a risk factor for ICIs-induced AKI.

[Surgical Outcomes of Prosthetic Valve Endocarditis].

Prosthetic valve endocarditis is a fatal complication after valve replacement surgery. Early surgical intervention is recommended for patients who suffer from complications such as heart failure, valve dysfunction, and abscesses. In the present study, we evaluated the clinical characteristics of 18 patients who underwent surgery for prosthetic valve endocarditis at our institution between December 1990 and August 2022, and examined the appropriateness of the timing and method of surgery, and whether there was improvement in cardiac function. Guidelines-based surgical intervention resulted in improved survival and improved cardiac function in the early and late postoperative period.

[Non-A Non-B Aortic Dissection Complicated with Right Aortic Arch Treated by Extended Thoracic Aortic Repair].

A 44-year old man with a history of Stanford type B acute aortic dissection was admitted for the treatment of acute aortic dissection. Computed tomography( CT) scan showed a descending entry-type non-A non-B aortic dissection with a maximum diameter of 65 mm occurring in a patient with Edwards typeⅢ right aortic arch whose left subclavian artery was obliterated. The patient was initially treated conservatively and underwent one-stage extended aortic repair from the ascending aorta to the descending thoracic aorta via median sternotomy 22 days after the symptom onset. Although the patient suffered from right empyema postoperatively, he was discharged from the hospital on postoperative day 64 after 4 weeks antibiotics therapy. The patient was also complicated by right recurrent nerve palsy, hoarseness improved over the 8 months after surgery.

Long-standing diabetes mellitus increases concomitant pancreatic cancer risk in patients with intraductal papillary mucinous neoplasms.

BACKGROUND: When monitoring patients with an intraductal papillary mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed the risk factors for concomitant PDAC in IPMN. METHODS: In total, 547 patients with pancreatic cysts, including IPMNs inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance by imaging examination once or twice a year. RESULTS: Five IPMNs with high-grade dysplasia and one IPMN associated with invasive carcinoma were encountered. In comparison, 14 concomitant PDACs were encountered. The prognosis was very poor for concomitant PDACs. All 14 PDAC patients had IPMNs. In patients with IPMNs, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analyses (P < 0.001 and P < 0.01, respectively). Furthermore, patients with IPMNs and diabetes mellitus had a high frequency of concomitant PDACs (9.5%, 9/95) in a median 48-month surveillance period. CONCLUSIONS: When monitoring IPMNs, the development of not only IPMN-derived carcinomas but also concomitant PDACs should be considered. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

A three-dimensional biomodel of type A aortic dissection for endovascular interventions.

Thoracic endovascular aortic repair is widely used for type B aortic dissection. However, there is no favorable stent-graft for type A aortic dissection. A significant limitation for device development is the lack of an experimental model for type A aortic dissection. We developed a novel three-dimensional biomodel of type A aortic dissection for endovascular interventions. Based on Digital Imaging and Communication in Medicine data from the computed tomography image of a patient with a type A aortic dissection, a three-dimensional biomodel with a true lumen, a false lumen, and an entry tear located at the ascending aorta was created using laser stereolithography and subsequent vacuum casting. The biomodel was connected to a pulsatile mock circuit. We conducted four tests: an endurance test for clinical hemodynamics, wire insertion into the biomodel, rapid pacing, and simulation of stent-graft placement. The biomodel successfully simulated clinical hemodynamics; the target blood pressure and cardiac output were achieved. The guidewire crossed both true and false lumens via the entry tear. The pressure and flow dropped upon rapid pacing and recovered after it was stopped. This simulation biomodel detected decreased false luminal flow by stent-graft placement and detected residual leak. The three-dimensional biomodel of type A aortic dissection with a pulsatile mock circuit achieved target clinical hemodynamics, demonstrated feasibility for future use during the simulated endovascular procedure, and evaluated changes in the hemodynamics.

Impact of prosthesis-patient mismatch on late outcomes after bioprosthetic mitral valve replacement for mitral regurgitation.

Negative impact of prosthesis-patient mismatch on long-term survival after valve replacement has been reported. However, the effect of prosthesis-patient mismatch after bioprosthetic mitral valve replacement has not yet been well examined. The purpose of this study was to investigate the effect of prosthesis-patient mismatch on late outcomes after bioprosthetic mitral valve replacement for mitral regurgitation. A total of 181 patients underwent bioprosthetic mitral valve replacement between April 2008 and December 2016. After excluding patients with mitral stenosis and those with incomplete data, 128 patients were included in the study. Postoperative transthoracic echocardiography was performed before discharge for all patients and the effective orifice area of bioprosthetic mitral valve was calculated using the formula: 220/pressure half-time, and the effective orifice area index was calculated by the formula: effective orifice area/body surface area. Prosthesis-patient mismatch was defined as a postoperative effective orifice area index ≤ 1.2 cm2/m2. The characteristics and outcomes were compared between the groups. There were 34 patients (26.6%) with prosthesis-patient mismatch and 94 patients (73.4%) without prosthesis-patient mismatch. There were no significant differences in the in-hospital mortality and morbidities. Multivariable analysis showed that prosthesis-patient mismatch was an independent predictor of late mortality (hazard ratio 3.38; 95% confidence interval 1.69-6.75; p = 0.001) and death from heart failure (hazard ratio 31.03, 95% confidence interval 4.49-214.40, p < 0.001). Prosthesis-patient mismatch at discharge after mitral valve replacement for mitral regurgitation was associated with long-term mortality and death from heart failure.

Evaluation of oversizing in association with conduction disorder after implantation of a rapid deployment valve.

Rapid deployment valve has expanded surgical indication for high-risk patients with aortic stenosis despite its accommodated risk for conduction disorder (CD). The purpose of this study was to evaluate the degree of oversizing in association with postoperative CD. During June 2019 to September 2021, 25 patients underwent aortic valve replacement with Edwards INTUITY. Device size selection was evaluated intraoperatively using provided sizers. Oversizing was evaluated retrospectively by measuring the difference of the dimension of the annulus and left ventricular outflow tract (LVOT) compared to the dimensions of the device used by preoperative-computed tomography. Although there was no incidence of pacemaker implantation, seven patients (28.0%) experienced CD after surgery. There was no difference in device area and annulus area (CD: - 37 ± 22.7 mm2 vs. no CD: - 56 ± 63.6 mm2, p = 0.47), and device circumference and annulus circumference (CD: - 4.4 ± 2.77 mm vs. no CD: - 6.9 ± 5.60 mm, p = 0.26) in patients with and without CD. However, there was a significant difference in area of the device skirt and sub-annular area at the LVOT (CD: 114 ± 28.4 mm2 vs. no CD: - 8 ± 80.0 mm2, p < 0.001), and circumference of device skirt and the LVOT (CD: 3.9 ± 2.08 mm vs. no CD: - 4.6 ± 5.24 mm, p < 0.001) between the two groups. Receiver operating characteristic curve analysis showed that an area difference of 77.7 mm2 and circumference difference of 0.91 mm at LVOT were associated with postoperative CD with specificities of 0.83, 0.78 and sensitivity of 1.0, 1.0, respectively. Preoperative measurement of the LVOT may be useful in evaluating the risk of postoperative CD in patients receiving rapid deployment valve.