Diagnosis of pancreatic malignancies using an overnight-stored pancreatic juice cell block specimen.

BACKGROUND AND AIMS: Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease. METHODS: This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB. RESULT: An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30-200) mL, and the median number of cytological examinations was three(2-8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, P = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, P = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry. CONCLUSION: The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment.

Development of method using language processing techniques for extracting information on drug-health food product interactions.

AIMS: Health food products (HFPs) are foods and products related to maintaining and promoting health. HFPs may sometimes cause unforeseen adverse health effects by interacting with drugs. Considering the importance of information on the interactions between HFPs and drugs, this study aimed to establish a workflow to extract information on Drug-HFP Interactions (DHIs) from open resources. METHODS: First, Information on drugs, enzymes, their interactions, and known DHIs was collected from multiple public databases and literature sources. Next, a network consisted of enzymes, HFP, and drugs was constructed, assuming enzymes as candidates for hubs in Drug-HFP interactions (Method 1). Furthermore, we developed methods to analyze the biomedical context of each drug and HFP to predict potential DHIs out of the DHIs obtained in Method 1 by applying BioWordVec, a widely used biomedical terminology quantifier (Method 2-1 and 2-2). RESULTS: 44,965 DHIs (30% known) were identified in Method 1, including 38 metabolic enzymes, 157 HFPs, and 1256 drugs. Method 2-1 selected 7401 DHIs (17% known) from the DHIs of Method 1, while Method 2-2 chose 2819 DHIs (30% known). Based on the different assumptions in these methods where Method 2-1 specifically selects HFPs interacting with specific enzymes and Method 2-2 specifically selects HFPs with similar function with drugs, the propsed methods resulted in extracting a wide variety of DHIs. CONCLUSIONS: By integrating the results of language processing techniques with those of the network analysis, a workflow to efficiently extract unknown and known DHIs was constructed.

Atomic force microscopy observation of surface morphologies and measurements of local contact potential differences of amorphous solid water samples deposited at 15 and 100 K.

We use an ultra-high vacuum cryogenic atomic force microscope to investigate the surface morphology of amorphous solid water (ASW) prepared by oblique deposition of water vapor onto Si(111)7 × 7 substrates at temperatures of 15 and 100 K. Height-height correlation function analysis of topographic images suggests that ASW at 15 K has a columnar structure and that the typical diameter of the column is 5-10 nm. At 100 K, the typical diameter is 10-30 nm, although columnar features are less prominent. The surface roughness (i.e., deviation of the height) is greater at 15 K than at 100 K, indicating that the surface at 100 K exhibits a relatively flat morphology. This result implies that transient diffusion of deposited water molecules affects the surface morphology at 100 K. In addition, measurements of the local contact potential difference between the tip and the ASW surface suggest that the magnitude of the negative surface potential at the microscopic scale, which is attributed to spontaneous polarisation, cannot simply be scaled by the thickness of ASW as predicted in previous experiments with Kelvin probes.

Carbon Atom Condensation on NH3-H2O Ices. An Alternative Pathway to Interstellar Methanimine and Methylamine.

The recent discovery of the nature and behavior of carbon atoms interacting with interstellar ices has prompted a number of investigations on the chemistry initiated by carbon accretion on icy interstellar dust. In this work, we expand the range of processes promoted by carbon accretion to the chemistry initiated by the interaction of this atom with ammonia (NH3) using quantum chemical calculations. We found that carbon addition to the ammonia molecule forms a rather stable radical, CNH3, that is easily hydrogenated. The complete hydrogenation network is later studied. Our calculations reveal that while conversion to simpler molecules like HCN and HNC is indeed a possible outcome promoted by H-abstraction reactions, methylamine is also easily formed (CH3NH2). In fact, the stability of methylamine against hydrogen abstraction makes this molecule the preferred product of the reaction network. Our results serve as a stepping stone toward the accurate modeling of C-addition reactions in realistic astrochemical kinetic models.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. METHODS AND RESULTS: We evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52-69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan-Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326-2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017-5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391-2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997-6.105; p < 0.001]). CONCLUSIONS: The FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. CLINICAL TRIALS: The study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124-12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html.

Efficacy and Safety of Re-administration of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) After EGFR-TKI-Induced Interstitial Lung Disease (CS-Lung-005).

PURPOSE: This study investigated the safety and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) re-administration after recovery from EGFR-TKI-induced interstitial lung disease (ILD). METHODS: This multicenter retrospective study collected data from consecutive advanced NSCLC patients who underwent EGFR-TKI re-administration after recovery from EGFR-TKI-induced ILD. RESULTS: Fifty-eight patients were registered. The grades of initial TKI-induced ILD were grade 1 to 4. TKIs used for re-administration were erlotinib for 15 patients, osimertinib for 15, gefitinib for 14, afatinib for 13 patients, and dacomitinib for 1 patient. ILD recurred in 13 patients (22.4%), comprising 3 patients with grade 1, 6 patients with grade 2, and 4 patients with grade 3. No significant associations were found between ILD recurrence and age, smoking history, performance status, time from initial ILD to TKI re-administration, or concomitant corticosteroid use. However, the incidence of ILD recurrence was high in cases of repeated use of gefitinib or erlotinib or first time use of osimertinib at TKI re-administration. The ILD recurrence rate was lowest in patients treated with first time use of gefitinib (8%) or erlotinib (8%), followed by patients treated with repeated use of osimertinib (9%). The response rate, median progression-free survival by TKI re-administration, and median overall survival were 55%, 9.6 and 84.8 months, respectively. CONCLUSION: This study showed that EGFR-TKI re-administration is a feasible and effective treatment for patients who recovered from EGFR-TKI-induced ILD. Our results indicate that re-administration of EGFR-TKI is an important option for long-term prognosis after recovery from EGFR-TKI-induced ILD.

Clinical and microbiological characteristics of Ruminococcus gnavus bacteremia and intra-abdominal infection.

OBJECTIVES: Ruminococcus gnavus is a rare human pathogen, and clinical data on R. gnavus infection are insufficient. This retrospective study aimed to investigate the clinical characteristics of R. gnavus infections. METHODS: This study included 13 cases of bacteremia and three cases of non-bacteremia infections caused by R. gnavus. We evaluated the patient data, infection source, clinical outcomes, and antimicrobial susceptibility of R. gnavus isolates for these cases. RESULTS: The median age of patients was 75 years (range 47-95), and eight patients were female. Twelve cases were presumed to have an intra-abdominal infection source, and the remaining four cases had an unknown infection source. The most common underlying conditions were immunosuppression (seven cases), solid tumors (seven cases), and history of gastrointestinal surgery (five cases). Thirteen patients exhibited gastrointestinal problems (dysfunction, bleeding, intra-abdominal infection, or inflammation). Multiple pathogens were observed in six cases, and fatal outcomes were recorded in three cases. Antimicrobial susceptibility data were available for eight isolates, all of which exhibited low minimum inhibitory concentrations to penicillin (≤0.03 µg/mL), ampicillin-sulbactam (≤0.5 µg/mL), piperacillin-tazobactam (≤4 µg/mL), and metronidazole (≤0.5-1 µg/mL). CONCLUSION: Ruminococcus gnavus is frequently associated with an intra-abdominal infection source, and treatment strategies should consider the possibility of multiple pathogens.

Transcriptional downregulation of FAM3C/ILEI in the Alzheimer's brain.

Amyloid-ß (Aß) accumulation in the brain triggers the pathogenic cascade for Alzheimer's disease (AD) development. The secretory protein FAM3C (also named ILEI) is a candidate for an endogenous suppressor of Aß production. In this study, we found that FAM3C expression was transcriptionally downregulated in the AD brain. To determine the transcriptional mechanism of the human FAM3C gene, we delineated the minimal 5'-flanking sequence required for basal promoter activity. From a database search for DNA-binding motifs, expression analysis using cultured cells, and promoter DNA-binding assays, we identified SP1 and EBF1 as candidate basal transcription factors for FAM3C, and found that SMAD1 was a putative inducible transcription factor and KLF6 was a transcription repressor for FAM3C. Genomic deletion of the basal promoter sequence from HEK293 and Neuro-2a cells markedly reduced endogenous expression of FAM3C and abrogated SP1- or EBF1-mediated induction of FAM3C. Nuclear protein extracts from AD brains contained lower levels of SP1 and EBF1 than did those from control brains, although the relative mRNA levels of these factors did not differ significantly between the groups. Additionally, the ability of nuclear SP1 and EBF1 in AD brains to bind with the basal promoter sequence-containing DNA probe was reduced compared with the binding ability of these factors in control brains. Thus, the transcriptional downregulation of FAM3C in the AD brain is attributable to the reduced nuclear levels and genomic DNA binding of SP1 and EBF1. An expressional decline in FAM3C may be a risk factor for Aß accumulation and eventually AD development.

A systematic mechanistic survey on the reactions between OH radical and CH3OH on ice.

A systematic mechanistic survey was performed for the CH3OH + OH reaction on ice. ONIOM(ωB97X-D/Def2-TZVP:AMOEBA09) calculations suggested a range of binding energies for the CH2OH radical (0.29-0.69 eV) and CH3OH (0.15-0.72 eV) molecule on hexagonal water ice (Ih) and amorphous solid water (ASW). Computed average binding energies of CH2OH radical (0.49 eV) and CH3OH (0.41 eV) are relatively stronger compared to the CH3O radical binding energies (0.32 eV, Sameera et al., J. Phy. Chem. A, 2021, 125, 387-393). Thus, the CH3OH molecule, CH2OH and CH3O radicals can adsorb on ice, where the binding energies follow the order CH2OH > CH3OH > CH3O. The multi-component artificial force-induced reaction (MC-AFIR) method systematically determined the reaction mechanisms for the CH3OH + OH reaction on ice, where two reaction paths, giving rise to CH2OH and CH3O radicals, were confirmed. A range of reaction barriers, employing the ωB97X-D/Def2-TZVP level of theory, was found for each reaction (0.03-0.11 eV for CH2OH radical formation, and 0.03-0.44 eV for CH3O radical formation). Based on the lowest energy reaction paths, we suspect that both reactions operate on ice. The computed data in this study evidence that the nature of the binding site or the reaction site has a significant effect on the computed binding energies or reaction barriers. Thus, the outcomes of the present study will be very useful for the computational astrochemistry community to determine reliable binding energies and reaction barriers on ice.

Radical reactions on interstellar icy dust grains: Experimental investigations of elementary processes.

Molecular clouds (MCs) in space are the birthplace of various molecular species. Chemical reactions occurring on the cryogenic surfaces of cosmic icy dust grains have been considered to play important roles in the formation of these species. Radical reactions are crucial because they often have low barriers and thus proceed even at low temperatures such as ∼10 K. Since the 2000s, laboratory experiments conducted under low-temperature, high-vacuum conditions that mimic MC environments have revealed the elementary physicochemical processes on icy dust grains. In this review, experiments conducted by our group in this context are explored, with a focus on radical reactions on the surface of icy dust analogues, leading to the formation of astronomically abundant molecules such as H2, H2O, H2CO, and CH3OH and deuterium fractionation processes. The development of highly sensitive, non-destructive methods for detecting adsorbates and their utilization for clarifying the behavior of free radicals on ice, which contribute to the formation of complex organic molecules, are also described.

Behavior of Hydroxyl Radicals on Water Ice at Low Temperatures.

ConspectusBecause chemical reactions on/in cosmic ice dust grains covered by amorphous solid water (ASW) play important roles in generating a variety of molecules, many experimental and theoretical studies have focused on the chemical processes occurring on the ASW surface. In laboratory experiments, conventional spectroscopic and mass-spectrometric detection of stable products is generally employed to deduce reaction channels and mechanisms. However, despite their importance, the details of chemical reactions involving reactive species (i.e., free radicals) have not been clarified because of the absence of experimental methods for in situ detection of radicals. Because OH radicals can be easily produced in interstellar conditions by not only the photolysis and/or ion bombardments of H2O but also the reaction of H and O atoms, they are thought to be one of the most abundant radicals on ice dust. In this context, the development of a close monitoring method of OH radicals on the ASW surface may help to elucidate the chemical reactions occurring on the ASW surface.Recently, to detect OH radicals adsorbed on the ASW surface, we applied our developed method to sensitively and selectively detect surface adsorbates with a combination of photostimulated desorption and resonance-enhanced multiphoton ionization techniques. Using this method, we showed that an OH radical on the ASW surface can be desorbed upon one-photon absorption at 532 nm, at which wavelength both the OH radical and H2O molecule are transparent. Theoretical calculations addressing an OH radical adsorbed on water clusters indicated that the valence A-X transition of an OH radical significantly red-shifts by ∼2 eV when the OH radical is strongly adsorbed to ice through three hydrogen bonds. With this method, the number density of surface OH can be monitored as a snapshot so that the behaviors of OH radicals, such as surface diffusion, can be studied. Moreover, the development of a system for studying the wavelength dependence of photodesorption may establish a foundation for future research investigating the absorption spectra of surface adsorbed species.Owing to the large electron affinity of OH radicals on ice, they are expected to easily become OH- by electron attachment on the ASW surface. We characterized the behavior of OH- on ASW at low temperatures, which may be relevant not only to physicochemical processes on cosmic ice dust and planetary atmosphere but also to understanding the electrochemical properties of ice. A negative constant current was found when ASW at temperatures below 50 K was exposed to both UV photons and electrons. It was demonstrated that the negative current is initiated by the formation of OH- ions on the ASW surface, and they are transported to the bulk via the proton-hole transfer mechanism, which was predicted 100 years ago as a mirror image of proton transfer known as the Grotthuss mechanism. These results indicate that OH- ions are readily transported to the bulk ice and further induce reactions, even at low temperatures where thermal diffusion is negligible. Therefore, in-mantle chemical processes that have been considered inactive at low temperatures are worth reevaluating.

Bosutinib-induced late-onset severe liver injury preceded by eosinophilia.

Tyrosine kinase inhibitors (TKIs) have dramatically changed the way chronic myeloid leukemia (CML) is treated. Although TKI therapy improves the overall survival of patients with CML, the management of various adverse events (AEs) from the therapy has become a major barrier to its adherence. Bosutinib is a second-generation TKI and an effective first-line treatment for CML. The most frequent AE is diarrhea; however, liver toxicity is also a major complication. In general, drug-induced hepatic enzyme elevation occurs within 1-2 weeks after treatment initiation. However, we noticed that, in a certain number of patients, liver injury appeared late (4-7 weeks) and was accompanied by eosinophilia. Herein, we retrospectively analyzed patients with CML treated with bosutinib at the Juntendo University School of Medicine and observed five patients with CML who developed late-onset liver injury with an elevation of the eosinophil count. In all cases, the liver enzyme level was within the normal range or grade 1 during the first 3 weeks of the bosutinib treatment and then elevated steeply thereafter. The pattern of hepatic toxicity was hepatocellular injury. In addition, all cases of eosinophilia tended to precede or coincide with an elevated liver enzyme level. Thus, the elevation of the eosinophil count may be a predictor for bosutinib-induced liver injury. Careful attention should be paid to delayed-onset hepatic injury, especially at 4-6 weeks after bosutinib initiation.

Impact of Preoperative Nutritional Status on the Outcome of Catheter Ablation for Atrial Fibrillation.

BACKGROUND: The relationship between nutritional status and the incidence or prognosis of atrial fibrillation (AF) has been reported, but no studies have described the relationship between the outcomes of AF catheter ablation (CA) and nutritional status as assessed by various scoring tools. We aimed to verify the hypothesis that preoperative nutritional status is associated with arrhythmia recurrence after CA for AF.Methods and Results:We evaluated 913 patients (age, 67±10 years; men, 72%; paroxysmal AF, 56%) who underwent CA for AF between November 2011 and November 2017. Patients were systematically followed with an endpoint of atrial tachyarrhythmia recurrence, the predictive value of which was compared among 3 scoring tools (Controlling Nutritional Status [CONUT] score / Geriatric Nutritional Risk Index [GNRI] / Prognostic Nutritional Index [PNI]). Patients were divided into normal nutrition (CONUT <2 [n=637] / GNRI >98 [n=836] / PNI >38 [n=910]) and undernutrition (CONUT ≥2 [n=276] / GNRI ≤98 [n=77] / PNI ≤3 [n=3]) groups. AF recurred in 274 patients (mean follow-up, 2.3±0.8 years). The AF recurrence rate was higher in patients with undernutrition than in those with normal nutrition (CONUT/GNRI) status. Multivariate Cox regression analysis identified undernutrition status (GNRI ≤98) as an independent predictor of atrial tachyarrhythmia recurrence. CONCLUSIONS: The AF recurrence rate after CA was higher in patients with undernutrition than in those with normal nutrition as stratified by the nutrition scoring tools.

A Survey of Near-Miss Dispensing Errors in Hospital Pharmacies in Japan: DEPP-J Study-Multi-Center Prospective Observational Study-

The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

Assessment of appropriate body mass index cut-off points for long-term mortality among ST-elevation myocardial infarction survivors in Asian population using machine learning algorithm.

Low body mass index (BMI) is a predictor of adverse events in patients with ST-elevated myocardial infarction (STEMI) in Western countries. Because the average BMI of Asians is significantly lower than that of the Western population, the appropriate cut-off BMI value and its role in long-term mortality are unclear in Asian patients. Between January 2006 and December 2017, 1215 patients who underwent percutaneous coronary intervention (PCI) for acute STEMI and were alive at discharge (mean age, 67.7 years; male, 75.4%) were evaluated. The cut-off BMI value, which could predict all-cause mortality within 10 years, was detected using a survival classification and regression tree (CART) model. The causes of death according to the BMI value were evaluated in each group. Based on the CART model, the patients were divided into three groups (BMI < 18 kg/m2: 54 patients, 18 kg/m2 ≤ BMI ≤ 20 kg/m2: 109 patients, and BMI > 20 kg/m2: 1052 patients). The BMI decreased with age; with an increased BMI, patients with dyslipidemia, diabetes mellitus, and smoking habit increased. During the study period (median, 4.9 years), 194 patients (26.8%) died (cardiac death, 59 patients; non-cardiac death, 135 patients). All-cause mortality was more frequent as the BMI decreased (BMI < 18 kg/m2; 72.8%, 18 kg/m2 ≤ BMI ≤ 20 kg/m2; 40.5%, and BMI > 20 kg/m2; 22.8%; log-rank p < 0.001). Non-cardiac deaths were more frequent than cardiac deaths in all groups, and the dominance of non-cardiac death was highest in the lowest BMI group. Cut-off BMI values of 18 kg/m2 and 20 kg/m2 can predict long-term mortality after PCI in Asian STEMI survivors, whose cut-off value is lower than that in the Western populations. The main causes of death in this cohort differed according to the BMI values.

Improving patient outcomes by promoting antimicrobial stewardship for patients with positive blood cultures: Investigation of patients with gram negative bacterium.

WHAT IS KNOWN AND OBJECTIVE: In this study, changes in patient outcomes were analysed to evaluate the effects of prospective audit and feedback (PAF), which was promoted under a new system of antimicrobial stewardship (AS), in patients with gram-negative rod (GNR)-positive blood cultures. METHODS: This study included patients with positive blood cultures treated at Kagawa University Hospital between 2019 and 2020. The effects of PAF, as promoted in 2020 and performed within a few days of treatment initiation, were examined in terms of patient prognosis and estimated cost of extra hospital stay associated with GNR infection. RESULTS AND DISCUSSION: As AS activities under the new system, proposals were made for targeted therapy based on susceptibility results and for the duration of antimicrobial therapy, escalation and dose increases, and imaging evaluation. Between 2019 and 2020, there was no difference in the rate of de-escalation in the form of switching to a narrower-spectrum intravenous antimicrobial, the rate of image inspection, but the rate of switching to oral therapy after receiving culture results increased from 19.7% to 31.3%, the rate of sensitivity-based treatment increased from 76.4% to 92.2%. Regarding patient outcomes, the 90-day mortality rate and the duration of hospital stay were similar between the groups. The rate of recurrent bloodstream infections decreased from 8.7% to 0.9%. WHAT IS NEW AND CONCLUSION: Most of the changes in the indicators related to patient outcomes analysed in this study suggest that the increased use of PAF in AS activities improved patient outcomes.

High Internal Atrial Defibrillation Threshold Is Related to a High Risk of Recurrence After Catheter Ablation for Long-Standing Persistent Atrial Fibrillation But Not for Persistent Atrial Fibrillation.

BACKGROUND: The atrial defibrillation threshold (ADFT) for internal cardioversion is theoretically related to the critical mass for sustaining atrial fibrillation (AF). OBJECTIVE: This study aimed to investigate the association of ADFT for internal cardioversion with the outcome of catheter ablation for non-paroxysmal AF (non-PAF). METHODS: We included 368 consecutive patients who underwent first-time catheter ablation for non-PAF. Based on the degree of ADFT recorded by the internal cardioversion before pulmonary vein isolation, we divided the patients into low ADFT (<20 J) and high ADFT (≥20 J) groups and analysed the association between ADFT and atrial tachyarrhythmia recurrence. RESULTS: There were 234 and 134 patients in the low and high ADFT groups, respectively. Of these, 39 patients (16.7%) and 41 (30.6%) patients, respectively, had atrial tachyarrhythmia recurrence during the 2.6±1.0 year follow-up. The high ADFT group showed a significantly higher atrial tachyarrhythmia recurrence than the low ADFT group (p=0.002). This finding was also noted in patients with long-standing persistent AF (p=0.032) but not in patients with persistent AF (p=0.159). The significant predictors of arrhythmia recurrence on multivariate analysis were high ADFT (p=0.004) and long-standing persistent AF (p=0.011). In multivariate analysis within the long-standing persistent AF group, only ADFT remained a significant risk factor for AF recurrence (p=0.035). CONCLUSIONS: The high ADFT of internal cardioversion was found to be a risk factor for post-catheter ablation recurrence in patients with long-standing persistent AF but not in those with persistent AF.

[Paratesticular Low-Grade Fibromyxoid Sarcoma: A Case Report].

A 36-year-old man presented with painless swelling in the right side scrotum. Ultrasonography showed a hypoechoic tumor with mosaic pattern. Plain computed tomograghy (CT) revealed a 67 mm scrotal cystic lesion with low density area. We suspected an intrascrotal tumor and performed right side radical orchiectomy. The removed sample was yellow clear and elastic hard. A 7 cm multilocular cystic tumor was present on the head side of the normal testis. The cut-surface and the contents of the mass revealed a jelly-like viscous liquid. On the microscopic examination, the tumor was composed of mucinous stroma and spindle-shaped atypical cells with hyperchromatic oval nuclei and eosinophilic cytoplasm. There was a characteristic network of blood vessesls with hyperhyalinization in the myxoid zones. Immunohistochemically, CDK4, MDM2, AE1/AE3, S-100, Alpha-SMA and desmin were negative, but MUC4 showed focal cytoplasmic positivity in the neoplastic cells. In the reverse transcription polymerase chain reaction assay, no FUS-CREB3L2/FUS-CREB3L1 fusion transcripts were identified although the detectable messages of the housekeeping genes were noted. The tumour was finally diagnosed as a paratesticular low-grade fibromyxoid sarcoma. Postoperative course was uneventful and no recurrence or metastasis was seen four months after the operation.

mDia1/3 generate cortical F-actin meshwork in Sertoli cells that is continuous with contractile F-actin bundles and indispensable for spermatogenesis and male fertility.

Formin is one of the two major classes of actin binding proteins (ABPs) with nucleation and polymerization activity. However, despite advances in our understanding of its biochemical activity, whether and how formins generate specific architecture of the actin cytoskeleton and function in a physiological context in vivo remain largely obscure. It is also unknown how actin filaments generated by formins interact with other ABPs in the cell. Here, we combine genetic manipulation of formins mammalian diaphanous homolog1 (mDia1) and 3 (mDia3) with superresolution microscopy and single-molecule imaging, and show that the formins mDia1 and mDia3 are dominantly expressed in Sertoli cells of mouse seminiferous tubule and together generate a highly dynamic cortical filamentous actin (F-actin) meshwork that is continuous with the contractile actomyosin bundles. Loss of mDia1/3 impaired these F-actin architectures, induced ectopic noncontractile espin1-containing F-actin bundles, and disrupted Sertoli cell-germ cell interaction, resulting in impaired spermatogenesis. These results together demonstrate the previously unsuspected mDia-dependent regulatory mechanism of cortical F-actin that is indispensable for mammalian sperm development and male fertility.

Myocardial salvage after ST-segment-elevation myocardial infarction: comparison between prasugrel and clopidogrel in the presence or absence of high-residual platelet reactivity.

BACKGROUND: The effect of prasugrel over clopidogrel on myocardial salvage in ST-segment-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (p-PCI) is not fully elucidated. METHODS: Among 854 consecutive STEMI patients who underwent p-PCI, 446 patients were evaluated by two-phase (7 days and 3 months) single-photo emission computed tomography (SPECT). Patients were divided into two groups based on the loading P2Y12 inhibitor. The clopidogrel group was further divided based on the result of platelet function testing. Thus, the prasugrel group included 227 patients; the clopidogrel without high-residual platelet reactivity (HRPR) group, 109 patients; and the clopidogrel with HRPR group, 107 patients. The primary endpoint was the Myocardial Salvage Index (MSI), determined by SPECT. RESULTS: The incidence of final TIMI 0/1 and TIMI myocardial perfusion grade 0/1 was higher in the clopidogrel with HRPR group (0.9%, 1.8%, and 7.5%, P =  .002; 19.8%, 29.4%, and 41.1%, P = .0002, in the prasugrel, clopidogrel without HRPR, and clopidogrel with HRPR groups, respectively). The MSI was significantly lower in the clopidogrel with HRPR group (48% [27-66], 44% [30-72], and 36% [15-55], P =  .006, respectively). CONCLUSIONS: Prasugrel in STEMI patients was associated with an increased MSI compared with clopidogrel in the presence of HRPR.