Direct oral anticoagulants increase bleeding risk after endoscopic sphincterotomy: a retrospective study.

BACKGROUND: Bleeding can be a serious adverse event of endoscopic sphincterotomy (EST). However, the risk of EST bleeding between direct oral anticoagulant (DOAC) users and those who received no antithrombotic agents has not been clarified. This study analyzed the risk factors for bleeding after EST in patients on DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES) guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. METHODS: We retrospectively analyzed 524 patients treated with EST who received DOAC or no antithrombotic drug from May 2016 to August 2019. We investigated the risk factors for bleeding. DOAC was typically discontinued for ≤ 1-day based on the JGES guideline. Although DOAC therapy recommenced the next morning after EST in principle, the duration of DOAC cessation and heparin replacement were determined by the attending physician based on each patient's status. RESULTS: The number of patients on DOAC (DOAC group) and those not on antithrombotic drug (no-drug group) was 42 (8.0%) and 482 (92.0%), respectively. DOAC was discontinued for ≤ 1-day in 17 (40.0%) patients and for > 1-day in 25 (60.0%). Of the 524 patients, 21 (4.0%) had EST bleeding. The bleeding rate was higher in the DOAC group (14.0%) (p = 0.004). Multivariate analysis showed that bleeding occurred more frequently in patients on DOAC (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.37-11.4, p = 0.011), patients with low platelet counts (< 100,000/µl) (OR 6.74, 95% CI 2.1-21.6, p = 0.001), and elderly patients (> 80 years old) (OR 3.36, 95%CI 1.17-9.65, p = 0.024). CONCLUSIONS: DOAC treatment, low platelet count, and old age (> 80 years old) are risk factors for EST bleeding. Although the bleeding incidence increased in patients on DOAC who received antithrombotic therapy according to the JGES guidelines, successful hemostasis was achieved with endoscopy in all cases, and no thrombotic events occurred after cessation of DOAC. Thus, the JGES guidelines are acceptable.

Clinical and endoscopic features of aorto-duodenal fistula resulting in its definitive diagnosis: an observational study.

BACKGROUND: Upper gastrointestinal (GI) bleeding is the most important presentation of an aorto-duodenal fistula (ADF). Early diagnosis is difficult, and the disease is associated with high mortality. The present study aimed to examine the clinical and the endoscopic characteristics of ADF in eight patients who presented to our hospital. We also sought to clarify the diagnostic approach towards the disease. METHODS: The present study examined the clinical and the endoscopic/computed tomography (CT) characteristics of ADF in eight patients who were definitively diagnosed with this condition in a 12-year period at our hospital. RESULTS: The patients comprised of five men and three women, with a mean age of 69.8 years. Upper gastrointestinal bleeding was the chief complaint for all the patients. Out of these, two patients presented with shock. The patients' mean haemoglobin at presentation was 7.09 g/dL, and the mean number of blood transfusions was 7.5. All patients had undergone intervention to manage an aortic pathology in the past. As the first investigation, an upper GI endoscopy in 5 and a CT scan in 3 patients were performed. In cases where CT scan was performed first, no definitive diagnosis was obtained, and the diagnosis was confirmed by performing an upper GI endoscopy. In cases where endoscopy was performed first, definitive diagnosis was made in only one case, and the other cases were confirmed by the CT scan. In some cases, tip attachments, converting to long endoscopes, and marking clips were found useful. CONCLUSIONS: In patients who have undergone intervention to manage an aortic pathology and have episodes of upper gastrointestinal bleeding, ADF cannot be definitively diagnosed with only one investigation. In addition, when performing upper GI endoscopy in cases where an ADF is suspected, tip attachment, converting to a long endoscope, and using marking clips can be helpful.

Chemical-induced craniofacial anomalies caused by disruption of neural crest cell development in a zebrafish model.

BACKGROUND: Craniofacial anomalies are among the most frequent birth defects worldwide, and are thought to be caused by gene-environment interactions. Genetically manipulated zebrafish simulate human diseases and provide great advantages for investigating the etiology and pathology of craniofacial anomalies. Although substantial advances have been made in understanding genetic factors causing craniofacial disorders, limited information about the etiology by which environmental factors, such as teratogens, induce craniofacial anomalies is available in zebrafish. RESULTS: Zebrafish embryos displayed craniofacial malformations after teratogen treatments. Further observations revealed characteristic disruption of chondrocyte number, shape and stacking. These findings suggested aberrant development of cranial neural crest (CNC) cells, which was confirmed by gene expression analysis of the CNC. Notably, these observations suggested conserved etiological pathways between zebrafish and mammals including human. Furthermore, several of these chemicals caused malformations of the eyes, otic vesicle, and/or heart, representing a phenocopy of neurocristopathy, and these chemicals altered the expression levels of the responsible genes. CONCLUSIONS: Our results demonstrate that chemical-induced craniofacial malformation is caused by aberrant development of neural crest. This study indicates that zebrafish provide a platform for investigating contributions of environmental factors as causative agents of craniofacial anomalies and neurocristopathy.

Limb-Based Patency After Surgical vs Endovascular Revascularization in Patients with Chronic Limb-Threatening Ischemia.

PURPOSE: To determine whether limb-based patency (LBP) after infrainguinal revascularization for chronic limb-threatening ischemia (CLTI) is similar between bypass surgery and endovascular therapy (EVT). MATERIALS AND METHODS: The database for the Surgical Reconstruction vs Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) study was interrogated to identify 130 patients (mean age 73±8 years; 94 men) who underwent bypass surgery and 271 patients (mean age 74±10 years; 178 men) who underwent EVT alone. Skin perfusion pressure (SPP) and the ankle-brachial index (ABI) were measured before the procedure and at 0, 1, and 3 months after revascularization. The outcome measure was hemodynamically evaluated LBP (SPP ≥10 mm Hg or ABI ≥0.1) maintained over the first 3 months after treatment. Any reintervention or major amputation was regarded as loss of LBP. The associations between the revascularization strategy (bypass vs EVT) and between the preoperative characteristics and the study outcome (ie, SPP- or ABI-based LBP), were determined using generalized linear mixed models with a logit link function. Patency rates are presented with the 95% confidence interval (CI). RESULTS: The bypass surgery group had a higher stage of limb severity (WIfI) and anatomic complexity (GLASS) than the EVT group, whereas the EVT group had a higher prevalence of heart failure. Both SPP- and ABI-based LBP rates were higher in the bypass group than in the EVT group. SPP-based LBP rates at 3 months were 73.8% (95% CI 63.4% to 84.2%) in the bypass group and 46.2% (95% CI 38.5% to 53.8%) in the EVT group; the corresponding ABI-based LBP rates were 71.5% (95% CI 61.8% to 81.2%) and 44.0% (95% CI 37.3% to 50.7%). CONCLUSION: LBP is an important concept in the new global vascular guidelines for assessing the anatomic and hemodynamic status of CLTI patients. The present study found that LBP was significantly lower in the EVT group vs the bypass surgery group.

The molecular logic for planarian regeneration along the anterior-posterior axis.

The planarian Dugesia japonica can regenerate a complete individual from a head, trunk or tail fragment via activation of somatic pluripotent stem cells. About a century ago, Thomas Hunt Morgan attempted to explain the extraordinary regenerative ability of planarians by positing two opposing morphogenetic gradients of formative "head stuff" and "tail stuff" along the anterior-posterior axis. However, Morgan's hypothesis remains open to debate. Here we show that extracellular signal-related kinase (ERK) and Wnt/ß-catenin signalling pathways establish a solid framework for planarian regeneration. Our data suggest that ERK signalling forms a spatial gradient in the anterior region during regeneration. The fibroblast growth factor receptor-like gene nou-darake (which serves as an output of ERK signalling in the differentiating head) and posteriorly biased ß-catenin activity negatively regulate ERK signalling along the anterior-posterior axis in distinct manners, and thereby posteriorize regenerating tissues outside the head region to reconstruct a complete head-to-tail axis. On the basis of this knowledge about D. japonica, we proposed that ß-catenin signalling is responsible for the lack of head-regenerative ability of tail fragments in the planarian Phagocata kawakatsui, and our confirmation thereof supports the notion that posterior ß-catenin signalling negatively modulates the ERK signalling involved in anteriorization across planarian species. These findings suggest that ERK signalling has a pivotal role in triggering globally dynamic differentiation of stem cells in a head-to-tail sequence through a default program that promotes head tissue specification in the absence of posteriorizing signals. Thus, we have confirmed the broad outline of Morgan's hypothesis, and refined it on the basis of our proposed default property of planarian stem cells.

Genome-wide somatic mutation analysis via Hawk-Seq™ reveals mutation profiles associated with chemical mutagens.

It is difficult to identify mutagen-induced genome-wide somatic mutations using next generation sequencing; hence, mutagenic features of each mutagen and their roles in cancer development require further elucidation. We described Hawk-Seq™, a highly accurate genome sequencing method and the optimal conditions, for using it to construct libraries that would enable the accurate (c.a. 1 error/107-108 bp) and efficient survey of genome-wide mutations. Genomic mutations in gpt delta mice or Salmonella typhimurium TA100 exposed to methylnitrosourea (MNU), ethylnitrosourea (ENU), diethylnitrosamine (DEN), benzo[a]pyrene (BP), and aristolochic acid (AA) were profiled using Hawk-Seq™ to analyse positions, substitution patterns, or frequencies. The resultant vast mutation data provided high-resolution mutational signatures, including for minor mutational fractions (e.g. G:C>A:T by AA), which enabled the clarification of the mutagenic features of all mutagens. The 96-type mutational signatures of MNU, AA, and BP indicate their partial similarity to signature 11, 22, and 4 or 29, respectively. Meanwhile, signatures attributable to ENU and DEN were highly similar to each other, but not to signature 11, suggesting that the mechanisms of these agents differed from those of typical alkylating agents. Thus, Hawk-Seq™ can clarify genome-wide chemical mutagenicity profiles at extraordinary resolutions, thereby providing insight into mutagen mechanisms and their roles in cancer development.

Germline Defects Caused by Smed-boule RNA-Interference Reveal That Egg Capsule Deposition Occurs Independently of Fertilization, Ovulation, Mating, or the Presence of Gametes in Planarian Flatworms.

Few animals are known to lay eggs in the absence of ovulation or copulation, as it is presumably energetically wasteful and subjected to negative selection. Characterization of Smed-boule, a member of the DAZ family of germline RNA-binding proteins, revealed that egg capsule (or capsule) production and deposition occurs independently of the presence of gametes in the planarian flatworm Schmidtea mediterranea. Reduction of Smed-boule expression by RNA-interference (RNAi) causes ablation of spermatogonial stem cells and the inability of ovarian germline stem cells to undergo oogenesis. Although animals subjected to Smed-boule RNAi lose their gametes and become sterile, they continue to lay egg capsules. Production of sterile capsules is even observed in virgin Smed-boule(RNAi) and control planarians maintained in complete isolation, demonstrating that egg production in S. mediterranea occurs independently of ovulation, fertilization, or mating. Evidence suggests that this is a conserved feature amongst Platyhelminthes, and therefore relevant to the pathology and dissemination of parasitic flatworms. These findings demonstrate that Smed-boule functions at different stages during male and female germline stem cell development, and also demonstrate that egg capsule production by planarian flatworms occurs independently of signals produced by mating or ova.

Genetic dissection of the planarian reproductive system through characterization of Schmidtea mediterranea CPEB homologs.

Cytoplasmic polyadenylation is a mechanism of mRNA regulation prevalent in metazoan germ cells; it is largely dependent on Cytoplasmic Polyadenylation Element Binding proteins (CPEBs). Two CPEB homologs were identified in the planarian Schmidtea mediterranea. Smed-CPEB1 is expressed in ovaries and yolk glands of sexually mature planarians, and required for oocyte and yolk gland development. In contrast, Smed-CPEB2 is expressed in the testes and the central nervous system; its function is required for spermatogenesis as well as non-autonomously for development of ovaries and accessory reproductive organs. Transcriptome analysis of CPEB knockdown animals uncovered a comprehensive collection of molecular markers for reproductive structures in S. mediterranea, including ovaries, testes, yolk glands, and the copulatory apparatus. Analysis by RNA interference revealed contributions for a dozen of these genes during oogenesis, spermatogenesis, or capsule formation. We also present evidence suggesting that Smed-CPEB2 promotes translation of Neuropeptide Y-8, a prohormone required for planarian sexual maturation. These findings provide mechanistic insight into potentially conserved processes of germ cell development, as well as events involved in capsule deposition by flatworms.

Cellular and molecular hypoxic response in common carp (Cyprinus carpio) exposed to linear alkylbenzene sulfonate at sublethal concentrations.

Linear alkylbenzene sulfonate (LAS) is an anionic surfactant commonly used in cleaning agents such as laundry detergents. Trace amounts of LAS are released into environmental waters after processing in wastewater treatment plants after the use of this chemical. Acute toxicity of LAS has been well-studied using various organisms, and its effects are particularly well known in fish. LAS damages fish gill morphology and induces mucous excretion from these organs. LAS also causes hematological changes. These observations suggest that LAS might induce hypoxic conditions in fish. However, the connections between hypoxia and hematological changes at the cellular and molecular levels remain unknown. Common carp were exposed to LAS at concentrations of 625, 1250, and 2500 µg/L for 96 h. A total of 9-10 fish were sampled at the end of the exposure period for each concentration. For hematological analysis, carp blood was sampled from the caudal vein. Gill tissue was used for real-time PCR analysis to evaluate transcriptional changes of hypoxia-induced genes. The number of normal red blood cells and the number of immature red blood cells were significantly decreased and increased, respectively, in fish exposed to 2500 µg/L LAS. The hypoxic marker genes hypoxia inducible factor 1α, myoglobin 1, and erythropoietin 2 were upregulated in these fish. Our results suggest that LAS decreases erythrocyte numbers and induces hypoxic conditions. In addition, LAS-exposed fish increase production of immature erythrocytes and upregulate myoglobin expression in gills to improve oxygen transport and absorption. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 122-130, 2017.

ERK signaling controls blastema cell differentiation during planarian regeneration.

The robust regenerative ability of planarians depends on a population of somatic stem cells called neoblasts, which are the only mitotic cells in adults and are responsible for blastema formation after amputation. The molecular mechanism underlying neoblast differentiation associated with blastema formation remains unknown. Here, using the planarian Dugesia japonica we found that DjmkpA, a planarian mitogen-activated protein kinase (MAPK) phosphatase-related gene, was specifically expressed in blastema cells in response to increased extracellular signal-related kinase (ERK) activity. Pharmacological and genetic [RNA interference (RNAi)] approaches provided evidence that ERK activity was required for blastema cells to exit the proliferative state and undergo differentiation. By contrast, DjmkpA RNAi induced an increased level of ERK activity and rescued the differentiation defect of blastema cells caused by pharmacological reduction of ERK activity. These observations suggest that ERK signaling plays an instructive role in the cell fate decisions of blastema cells regarding whether to differentiate or not, by inducing DjmkpA as a negative regulator of ERK signaling during planarian regeneration.

Malodour from oral malignant fungating wound: sprayed metronidazole - case report.

Metronidazole gel or ointment is recommended for the treatment of malodour from malignant fungating wounds. However, this medication may not settle adequately in oral lesions because its texture causes discomfort and it tends to be washed out by saliva. We report a case of malodour due to an oral lesion that was well controlled with sprayed metronidazole.

Identification of an adverse outcome pathway (AOP) for chemical-induced craniofacial anomalies using the transgenic zebrafish model.

Craniofacial anomalies are one of the most frequent birth defects worldwide and are often caused by genetic and environmental factors such as pharmaceuticals and chemical agents. Although identifying adverse outcome pathways (AOPs) is a central issue for evaluating the teratogenicity, the AOP causing craniofacial anomalies has not been identified. Recently, zebrafish has gained interest as an emerging model for predicting teratogenicity because of high throughput, cost-effectiveness and availability of various tools for examining teratogenic mechanisms. Here, we established zebrafish sox10-EGFP reporter lines to visualize cranial neural crest cells (CNCCs) and have identified the AOPs for craniofacial anomalies. When we exposed the transgenic embryos to teratogens that were reported to cause craniofacial anomalies in mammals, CNCC migration and subsequent morphogenesis of the first pharyngeal arch were impaired at 24 hours post-fertilization. We also found that cell proliferation and apoptosis of the migratory CNCCs were disturbed, which would be key events of the AOP. From these results, we propose that our sox10-EGFP reporter lines serve as a valuable model for detecting craniofacial skeletal abnormalities, from early to late developmental stages. Given that the developmental process of CNCCs around this stage is highly conserved between zebrafish and mammals, our findings can be extrapolated to mammalian craniofacial development and thus help in predicting craniofacial anomalies in human.

Systemic Opioids for Dyspnea in Cancer Patients: A Real-world Observational Study.

CONTEXT: Although Systemic opioids are recommended as a pharmacological treatment for cancer-related dyspnea, their effectiveness and safety needs to be investigated in a real-world context OBJECTIVES: To evaluate the effectiveness and safety of systemic regular opioids for dyspnea in cancer patients, in the real-world palliative care practice. METHODS: This was a multicenter prospective observational study. We consecutively enrolled adult cancer patients starting regular opioids (morphine, oxycodone, hydromorphone, or fentanyl) for dyspnea from 12 palliative care services across Japan. We evaluated dyspnea intensity using the Numerical Rating Scale (NRS) and Integrated Palliative Outcome Scale (IPOS) every 24 hours until 72 hours after starting opioids (T1-T3). We also evaluated common opioid-related adverse events (AEs) and other severe AEs. RESULTS: We enrolled 402 cancer patients. The proportion of responders was 68.8% (95%confidence intervals (CI): 0.63-0.74) at T1, 75.7% (95%CI: 0.70-0.81) at T2, and 82.1% (95%CI: 0.76-0.87) at T3. The mean differences in dyspnea NRS from baseline were 1.73 (95%CI: 1.46-1.99) at T1, 1.99 (95%CI: 1.71-2.28) at T2, and 2.47 (95%CI:2.13-2.82) at T3. The most common treatment-emergent AE was somnolence with an incidence of the severe form of approximately 10% throughout the study period. In the multivariate analysis, baseline dyspnea NRS ≥6 had a positive correlation with dyspnea relief by systemic regular opioids, while liver metastasis, clinician-predicted survival days, and opioid tolerance had a negative correlation. CONCLUSION: Regular systemic opioids were effective for dyspnea in real-world cancer patients.

Multidrug resistance-associated protein 2 (MRP2) is an efflux transporter of EGCG and its metabolites in the human small intestine.

Green tea polyphenols have various beneficial effects on human health, such as antiobesity and anti-carcinogenesis. (-)-Epigallocatechin-gallate (EGCG) is one of the major potent green tea catechins; however, detailed mechanisms of EGCG transport and metabolism in the human small intestine remain unknown due to lack of a suitable model. We investigated metabolite profiles of EGCG in the fresh human duodenal biopsy, cryopreserved human duodenal mucosal enterocytes and Caco-2 cells, and found that EGCG was readily metabolized into methylated and sulphate conjugates, which are major metabolites in these models. Next, we examined possible efflux transporters of EGCG and its metabolites using specific inhibitors of MRP2, P-gp and BCRP in Caco-2 cell monolayers. MRP2 was thereby identified as an efflux transporter, and further analysis using MRP2-knockout Caco-2 cells and vesicular transport assays confirmed that MRP2 is a selective efflux transporter of EGCG and its metabolites. Assuming that functional inhibition of MRP2 would result in efficient uptake of EGCG, we screened for MRP2 functional blockade and identified quercetin, which led to increased intracellular accumulation and basal transport of EGCG in Caco-2 cells. This result suggested that co-administration of quercetin and EGCG would enable efficient transport of EGCG in the human intestine. Therefore, we performed co-oral administration of quercetin and EGCG in human subjects to examine whether this occurred in humans. These studies demonstrated that MRP2 is a selective transporter of EGCG and conjugates and Caco-2 is a model to examine transport mechanisms and metabolites of polyphenols in the human small intestine.

Liver cyst with biliary communication treated with endoscopic ultrasound-guided drainage: A case report.

RATIONALE: Simple liver cysts are common, and usually benign and asymptomatic, requiring little to no treatment. Liver cysts with biliary communication, however, are rare and require effective treatment to avoid recurrence. PATIENT CONCERNS: A 70-year-old woman with breast cancer visited our hospital for treatment. Physical examination revealed abdominal distension and bilateral lower leg edema. DIAGNOSIS: Abdominal contrast-enhanced computed tomography revealed a giant liver cyst, inducing inferior vena cava compression that was causing her edema. INTERVENTIONS: Percutaneous transhepatic cyst drainage was performed. Since the bilirubin level in the drained fluid was high, the patient was diagnosed with a liver cyst with biliary communication. After the procedure, her symptoms improved and the cyst decreased in size. However, the drainage volume did not decrease after approximately 2 weeks. Sclerotherapy with minocycline was ineffective. Thus, endoscopic retrograde cholangiopancreatography was performed, and an endoscopic nasobiliary drainage tube was inserted. The percutaneous drainage tube was clamped, and the cyst showed increase in size. Therefore, endoscopic ultrasound-guided cyst drainage, which is less invasive than surgery, was performed. OUTCOMES: The cyst tended to decrease in size even after the percutaneous drainage tube had been removed. At 3years follow-up, the cyst has almost disappeared. LESSONS: Endoscopic ultrasound-guided drainage can treat liver cyst with biliary communication.

Clinical features and progress of ischemic gastritis with high fatalities: Seven case reports.

BACKGROUND: Ischemic gastritis is a clinically rare and highly fatal disease that occurs when the hemodynamics of a patient with vascular risk is disrupted. Early diagnosis and treatment are possible only with upper endoscopy after symptom appearance. We report seven cases of ischemic gastritis and its clinical features, prognosis, and indicators that may help in early detection. CASE SUMMARY: Of the seven patients, six had vascular risk and five died within 2 wk of diagnosis. Their symptoms included hematemesis and hypotension. Although surgery is a choice for radical treatment, not all patients were tolerant. For such patients, conservative treatment was selected, but all of them died. In contrast, patients who underwent repeat endoscopy showed improved mucosal findings, suggesting that this improvement may not affect prognosis. Some ischemic changes such as wall thickening, mural emphysema, and fluid retention in the stomach were observed before diagnosis through endoscopy and computed tomography (CT). The CT scan can be effective for early detection, and improvement in circulatory failure and aggressive treatment may save the lives of patients with this disease. CONCLUSION: The characteristic CT findings enable early detection of ischemic gastritis. Early diagnosis increases the chance of survival if early therapeutic intervention and improvement of circulatory dynamics can be achieved in this highly fatal disease.

Regeneration in an evolutionarily primitive brain--the planarian Dugesia japonica model.

A unique aspect of planarians is that they can regenerate a brain from somatic pluripotent stem cells called neoblasts, which have the ability to produce themselves (self-renew) and to give rise to all missing cell types during regeneration. Recent molecular studies have revealed that the planarian brain is composed of many distinct neuronal populations, which are evolutionarily and functionally conserved ones, and acts as an information-processing center to elicit distinct behavioral traits depending on a variety of signals arising from the external environment. How can planarians regenerate such a brain? On the basis of our recent findings, here we review the cellular and molecular mechanisms that regulate the stem cell dynamics involved in the brain regeneration of the planarian Dugesia japonica. Our findings suggest the possible value of in vivo planarian studies for guiding regenerative medicine to treat neurodegenerative diseases via interlinking stem cell biology and regeneration biology.

Role of c-Jun N-terminal kinase activation in blastema formation during planarian regeneration.

The robust regenerative abilities of planarians absolutely depend on a unique population of pluripotent stem cells called neoblasts, which are the only mitotic somatic cells in adult planarians and are responsible for blastema formation after amputation. Little is known about the molecular mechanisms that drive blastema formation during planarian regeneration. Here we found that treatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125 blocked the entry of neoblasts into the M-phase of the cell cycle, while allowing neoblasts to successfully enter S-phase in the planarian Dugesia japonica. The rapid and efficient blockage of neoblast mitosis by treatment with the JNK inhibitor provided a method to assess whether temporally regulated cell cycle activation drives blastema formation during planarian regeneration. In the early phase of blastema formation, activated JNK was detected prominently in a mitotic region (the "postblastema") proximal to the blastema region. Furthermore, we demonstrated that undifferentiated mitotic neoblasts in the postblastema showed highly activated JNK at the single cell level. JNK inhibition by treatment with SP600125 during this period caused a severe defect of blastema formation, which accorded with a drastic decrease of mitotic neoblasts in regenerating animals. By contrast, these animals still retained many undifferentiated neoblasts near the amputation stump. These findings suggest that JNK signaling plays a crucial role in feeding into the blastema neoblasts for differentiation by regulating the G2/M transition in the cell cycle during planarian regeneration.

Salvage endovascular embolization of the left pulmonary artery for recurrent pseudoaneurysm.

BACKGROUND: Pulmonary pseudoaneurysm (PPA) is a potentially lethal complication of lung resection with a high risk of recurrence after endovascular coiling. CASE PRESENTATION: We report a case in which recurrent hemoptysis due to PPA after left lower lobe sleeve resection was treated by endovascular embolization of the left main pulmonary artery as a salvage treatment. The first hemoptysis was managed by endovascular coil embolization with extracorporeal membrane oxygenation, but refractory hemorrhage occurred 3 months later due to penetration of the endovascular coil into the bronchial anastomosis site. Because left completion pneumonectomy was considered too high risk, the left main pulmonary artery was palliatively embolized using an Amplatzer vascular plug (St. Jude Medical, MN, USA) to totally disrupt the left pulmonary arterial flow. CONCLUSIONS: Total embolization of the left main pulmonary artery for repeated PPA rupture may be useful as a palliative treatment in patients unable to tolerate pneumonectomy.

Effect of Antibiotic Resistance of Pathogens on Initial Antibiotic Therapy for Patients With Cholangitis.

Objectives Considering that pathogens resistant to initial antibiotic therapies for cholangitis can affect mortality rates, appropriate initial empiric antibiotic therapy is important. However, evidence regarding the influence of pathogens resistant to initial antibiotics in patients with cholangitis who have undergone early endoscopic retrograde cholangiopancreatography (ERCP) is limited, and the conditions in several cases can improve with early ERCP even when pathogens resistant to initial antibiotics are detected on time. Therefore, this study aimed to assess the influence of pathogens resistant to initial antibiotics on the course of cholangitis in patients undergoing early ERCP. Materials and methods Patients (n=266) with positive blood or bile culture results treated with early ERCP were divided into those with cultures that were resistant to the initial antibiotics (antibiotic-resistant group; n=66; 24.8%) and those with cultures that were sensitive to the initial antibiotics (antibiotic-sensitive group; n=200; 75.2%). The duration of hospitalization, in-hospital mortality rates due to cholangitis, rates of increased disease severity, and complications during hospitalization were studied. Results Enterococcus, Enterobacter, Citrobacter, and Pseudomonas species showed high resistance to several antibiotics. No significant between-group differences were found in the duration of hospitalization, in-hospital mortality rates due to cholangitis, and rates of increased disease severity. However, the rate of post-ERCP cholecystitis was significantly higher in the antibiotic-resistant group than in the antibiotic-sensitive group (p=0.0245). Conclusions Even if the initial antibiotics were ineffective, the rate of fatal outcomes did not increase among patients with cholangitis who had undergone early ERCP. However, when initial antibiotics were ineffective, the frequency of post-ERCP cholecystitis increased even after early bile duct decompression.