Hemostasis with Metallic Stent for Multiple Metastatic Pancreatic Tumors Complicated with Hemobilia.

Introduction: Hemobilia, which refers to bleeding from the bile duct, is rare and difficult to treat. We report a case of successful hemostasis of a pancreatic tumor complicated by hemobilia. Case Presentation: A 76-year-old man was referred to our hospital with a pancreatic head tumor. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography-FNA were performed, and the patient was diagnosed with pancreatic metastasis of renal cell carcinoma. After discharge, the patient noted worsening jaundice and progressive anemia and was readmitted. ERCP reveals active bleeding from the duodenal papillae. The patient was placed on a fully covered metallic stent and discharged after confirming hemostasis. Conclusion: Renal cell carcinoma is a tumor with abundant blood flow. If hemobilia occurs, bleeding from pancreatic metastatic tumors should be considered. Additionally, hemostasis using a fully covered metallic stent is useful for treating hemobilia in tumors.

Relationship Between Pancreatic Cysts and Cysts in Other Organs in Patients Undergoing Medical Checkup.

OBJECTIVE: We investigated the association between pancreatic cysts and cystic diseases of other organs using abdominal ultrasonography in patients undergoing medical checkup. METHODS: Between April 2021 and March 2022, 4496 patients had a comprehensive medical checkup at our hospital, which included abdominal ultrasonography. RESULTS: Among 4496 patients, 172 (3.8%), 1592 (35.4%), and 1425 (31.7%) had pancreatic, liver, and renal cysts, respectively. Multivariate analysis revealed that the significant factors were female sex and the presence of renal cysts. CONCLUSION: Pancreatic cysts were more common in females. Renal cysts are relatively commonly detected on abdominal ultrasonography. If renal cysts are detected, comorbidities with pancreatic cysts should be considered.

Structural basis of spike RBM-specific human antibodies counteracting broad SARS-CoV-2 variants.

The decrease of antibody efficacy to mutated SARS-CoV-2 spike RBD explains the breakthrough infections and reinfections by Omicron variants. Here, we analyzed broadly neutralizing antibodies isolated from long-term hospitalized convalescent patients of early SARS-CoV-2 strains. One of the antibodies named NCV2SG48 is highly potent to broad SARS-CoV-2 variants including Omicron BA.1, BA.2, and BA.4/5. To reveal the mode of action, we determined the sequence and crystal structure of the Fab fragment of NCV2SG48 in a complex with spike RBD from the original, Delta, and Omicron BA.1. NCV2SG48 is from a minor VH but the multiple somatic hypermutations contribute to a markedly extended binding interface and hydrogen bonds to interact with conserved residues at the core receptor-binding motif of RBD, which efficiently neutralizes a broad spectrum of variants. Thus, eliciting the RBD-specific B cells to the longitudinal germinal center reaction confers potent immunity to broad SARS-CoV-2 variants emerging one after another.

A case of breast cancer with extensive colon metastasis.

Breast cancer is one of the most common malignancies in women worldwide. Although most breast cancers are curable, in cases of metastasis, many are often found in the lungs, bones, liver, and central nervous system; however, metastasis to the gastrointestinal tract is rare. Invasive lobular carcinoma, which represents only 5%-10% of breast cancers, has a higher risk of metastasis to the gastrointestinal tract than invasive ductal carcinoma. Here, we report a rare case of gastrointestinal metastasis of invasive lobular carcinoma that spread extensively to the colonic mucosa. Given the improved survival rates of breast cancer patients with current treatments, many rarer metastatic diseases, including gastrointestinal metastases, are likely to be increased in the future.

Vaccination with the Omicron spike RBD boosts broadly neutralizing antibody levels and confers sustained protection even after acquiring immunity to the original antigen.

The immune evasion of SARS-CoV-2 Omicron variants caused by multiple amino acid replacements in the receptor-binding domain (RBD) of the spike protein wanes the effectiveness of antibodies elicited by current SARS-CoV-2 booster vaccination. The vaccines that target Omicron strains have been recently developed, however, there has been a concern yet to be addressed regarding the negative aspect of the immune response known as original antigenic sin. Here, we demonstrate that the breadth of neutralizing antibodies against SARS-CoV-2 variants is barely elicited by immunizing monovalent viral antigens via vaccination or natural infection in mice and human subjects. However, vaccination of Omicron BA.1 RBD to pre-immunized mice with the original RBD conferred sustained neutralizing activity to BA.1 and BA.2 not only original pseudoviruses. The acquisition of neutralizing antibody breadth was further confirmed in vaccinated-then-Omicron convalescent human sera in which neutralizing activity against BA.1 and BA.2 pseudoviruses was highly induced. Thus, our data suggest that Omicron-specific vaccines or the infection with Omicron viruses can boost potent neutralizing antibodies to the Omicron variants even in the host pre-vaccinated with the original antigen.

Impact of organizational justice and manager's mental health on staff nurses' affective commitment: A multilevel analysis of the work environment of hospital nurses in Japan-Part II (WENS-J-II).

Background: Nursing shortage is a global and priority issue. Affective commitment has been identified as a key to retention in the workplace. Exploring the way to promote the nurse's affective commitment is necessary to maintain the nursing workforce and care quality. The staff nurse's organizational justice (procedural and interactional justice) and the manager's condition of mental health have the potential to be related to the staff nurse's affective commitment. Objective: To explore the impact on the nurse's affective commitment from procedural and interactional justices at individual and unit levels and the manager's mental health. Design: A multi-site longitudinal design. Settings: Nine Japanese hospitals with more than 200 beds and located in an area with more than 150,000 people. Participants: 385 staff nurses and their 42 nurse managers who completed both surveys in 2016 and 2017. Methods: We analyzed the data from a two-year national survey of the Work Environment for hospital Nurses in Japan part II. Nurse staff and their managers completed the surveys. This multilevel analysis performed four random intercept models on affective commitment and entered the variables of procedural and interactional justices and manager mental health into the models. Results: The staff nurse's affective commitment was positively associated with procedural justice climate (unit level), interactional justice climate (unit-level), and the perception of interactional justice (individual justice). The manager's mental health (psychological distress) had a negative relationship with affective commitment. Conclusions: The climates of procedural and interactional justice, the individual perception of interactional justice, and the manager's mental health impacted the nurses' affective commitment as a predictor of retention. Moreover, the perception of interactional justice and the organizational contexts (organizational justice climates and managers' psychological distress) were mediated by affective commitment. Thus, support to maintain the manager's mental health is required to promote staff's affective commitment related to retention. Registration: None. Tweetable abstract: Nurse staff's affective commitment was stimulated by interactional justice, two types of organizational justice climate, and the manager's mental health.

Percutaneous Transhepatic Obliteration for Treating Stomal Variceal Bleeding Using a Microballoon Catheter with Systemic Drainage Vein Compression.

We report a case of successful treatment of stomal variceal bleeding with percutaneous transhepatic obliteration using a microballoon catheter concomitantly with drainage vein compression. A 72-year-old man with alcoholic cirrhosis was admitted to our hospital due to repeated hemorrhage of stomal varices. Percutaneous transhepatic obliteration was then selected for treatment because computed tomography revealed the stomal varices being fed by only two branches of the superior and inferior mesenteric veins. During microballoon inflation, 5% ethanolamine oleate with iopamidol was injected into each branch, and the systemic drainage veins were compressed by the gauze from the body surface near the stoma. No rebleeding from the stomal varices has been observed 14 months after the procedure.

Efficacy and Safety of Endoscopic Removal for Asymptomatic Common Bile Duct Stones in Comparison with Symptomatic Stones.

OBJECTIVE: Endoscopic removal is recommended for common bile duct stones (CBDs). However, in patients with asymptomatic CBDs, follow-up without treatment may be recommended because of the increased complication risks associated with asymptomatic CBDs removal. The objective of our study was to investigate the efficacy and safety of CBDs removal in asymptomatic patients. METHODS: Consecutive patients with naive papilla who underwent endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of CBDs from April 2016 to August 2020 were retrospectively analyzed. We compared the efficacy and safety of CBDs removal in asymptomatic and symptomatic patients. RESULTS: We enrolled 300 patients, 53 asymptomatic and 247 symptomatic patients. Endoscopic CBDs removal was successful in all patients, except one symptomatic patient. However, the complete stone removal rate in a single session was significantly higher in the asymptomatic group than that in the symptomatic group. ERCP-related complications did not differ between the asymptomatic and symptomatic patients. The incidence of post-ERCP pancreatitis was similar and liver cirrhosis was the only significant risk factor for pancreatitis. CONCLUSION: Complication risks associated with endoscopic CBDs removal was not significantly different between asymptomatic and symptomatic patients. Liver cirrhosis was a significant risk factor of ERCP-related pancreatitis.

Analysis of Comorbidity for Patients with Pancreatic Cysts in Medical Checkup Screening.

OBJECTIVES: We investigated whether there is a difference in the frequency of comorbidity between patients with pancreatic cysts and those without pancreatic cysts by abdominal ultrasonography in patients undergoing medical checkup screening. METHODS: The subjects were 6,627 patients who underwent abdominal ultrasonography at Tokai University Hachioji Hospital's Health Screening Center between April 2019 and March 2020. RESULTS: Of the total 6,627 patients, 158 (2.4%) were pointed out to have pancreatic cysts. Multivariate analysis revealed that the related factors were female sex, age 60 years or older, diabetes, lung cancer, and uterine/ovarian cancer. CONCLUSION: Unlike pancreatic cancer, pancreatic cysts are more common in women. In addition, it is known that pancreatic cysts have a high complication rate of cancers of other organs; lung cancer and uterine/ovarian cancer were identified as high-risk factors in this study.

A concept analysis of psychological safety: Further understanding for application to health care.

AIM: To clarify the concept of psychological safety in a healthcare context and to provide the first theoretical framework for improving interpersonal relationships in the workplace to better patient care. DESIGN: A Rodgers' concept analysis. METHODS: The concept analysis was conducted using a systematic search strategy on PubMed, CINAHL, PsycINFO and Ichushi-Web. RESULTS: An analysis of 88 articles studying psychological safety in health care identified five attributes: perceptions of the consequences of taking interpersonal risks, strong interpersonal relationships, group-level phenomenon, safe work environment for taking interpersonal risks and non-punitive culture. The antecedents included structure/system factors, interpersonal factors and individual factors. The four consequences included performance outcomes, organizational culture outcomes, and psychological and behavioural outcomes.

Highly Stable and Active Solid-Solution-Alloy Three-Way Catalyst by Utilizing Configurational-Entropy Effect.

Since 1970, people have been making every endeavor to reduce toxic emissions from automobiles. After the development of a three-way catalyst (TWC) that concurrently converts three harmful gases, carbon monoxide (CO), hydrocarbons (HCs), and nitrogen oxides (NOx ), Rh became an essential element in automobile technology because only Rh works efficiently for catalytic NOx reduction. However, due to the sharp price spike in 2007, numerous efforts have been made to replace Rh in TWCs. Nevertheless, Rh remains irreplaceable, and now, the price of Rh is increasing significantly again. Here, it is demonstrated that PdRuM ternary solid-solution alloy nanoparticles (NPs) exhibit highly durable and active TWC performance, which will result in a significant reduction in catalyst cost compared to Rh. This work provides insights into the design of highly durable and efficient functional alloy NPs, guiding how to best take advantage of the configurational entropy in addition to the mixing enthalpy.

Case of hepatitis B virus reactivation after ibrutinib therapy in which the patient remained negative for hepatitis B surface antigens throughout the clinical course.

A 71-year-old man was diagnosed with B-cell chronic lymphocytic leukemia. He was negative for hepatitis B surface antigen (HBsAg), positive for antibodies against the hepatitis B surface and core, and negative for hepatitis B virus (HBV)-DNA before starting chemotherapy. A total of 13 months after the initiation of ibrutinib (a Bruton's tyrosine kinase inhibitor), the patient's alanine aminotransferase levels suddenly increased to 427 U/L. As the level of serum HBV-DNA increased to 5.2 logIU/mL, a diagnosis of HBV reactivation was made, whereas the patient remained negative for HBsAg. The patient's serum alanine aminotransferase levels normalized after the initiation of entecavir at a dose of 1 mg/day. However, it took >1 year to achieve an undetectable level of HBV-DNA, even with an add-on therapy of tenofovir disoproxil fumarate. Interestingly, the patient remained negative for HBsAg throughout the clinical course owing to triple HBsAg escape mutations: Q101K, M133L, and G145A.

Increase in the Lipopolysaccharide Activity and Accumulation of Gram-Negative Bacteria in the Stomach With Low Acidity.

INTRODUCTION: Lipopolysaccharides (LPSs) of Gram-negative bacteria (GNB) are highly toxic and induce inflammation. Therefore, we investigated both the LPS activity and composition of GNB in the gastric fluid (GF) to assess the potential toxicity of them accumulated in the stomach. METHODS: GF and saliva samples were obtained from 158 outpatients who were undergoing upper gastrointestinal endoscopy and 36 volunteers using a nasogastric tube. The LPS activity was measured by assay kits including recombinant Factor C or Limulus amebocyte lysate. To assess the bacterial composition in the samples, a 16S ribosomal DNA-based operational taxonomic unit analysis was performed. We focused on the genera representing >0.1% of the whole microbiota. RESULTS: We found a high LPS activity in the GF samples with weak acidity (approximately > pH 4), whereas little/no activity in those with strong acidity (approximately < pH 2). Spearman test also demonstrated a close correlation between pH and LPS in those samples (r = 0.872). The relative abundance of GNB in the saliva showed no significant difference between the subject groups with weak- and strong-acidity GF. In addition, in the subjects whose GF acidity was weak, the GNB abundance in the GF was almost the same as that in the saliva. By contrast, in the subjects whose GF acidity was strong, the GNB abundance in the GF was significantly lower than that in the saliva. DISCUSSION: GNB that have recently moved from the oral cavity might account for the prominent LPS activity in a stomach with weak acidity.

A Case of Rare Cutaneous Metastasis from Advanced Pancreatic Cancer.

A 71-year-old woman presented to a nearby hospital with an occipital scalp ulcer with exudate. Thoracoabdominal enhanced computed tomography (CT) was performed due to suspected cancer. The imaging results showed tumors in the pancreatic tail and at multiple sites in the lung, whereupon she was referred to our hospital for further investigation. Histological analysis of the occipital scalp ulcer and the pancreatic tumor led to the diagnosis of pancreatic adenocarcinoma with cutaneous metastasis and multiple lung metastases. Combination chemotherapy (gemcitabine and nab-paclitaxel) was started, and about 4 months later the patient experienced right lower back pain. Abdominal CT showed partial sclerosis of the right iliac bone and multiple spinal lesions, which were diagnosed as multiple bone metastases. Narcotic analgesia was started for the right lower back pain. Since then, FOLFIRINOX has been introduced as second-line chemotherapy against tumor growth, and treatment has been ongoing for 10 months since the initial chemotherapy. Pancreatic cancer is a rapidly growing cancer and can show early metastasis to other organs, lymph node metastasis, and peritoneal dissemination; therefore, the prognosis of pancreatic cancer is very poor. Cutaneous metastasis from pancreatic cancer is rare, and only a few cases have been reported. Here, we report an unusual case of pancreatic adenocarcinoma with cutaneous metastasis and multiple lung and bone metastases.

Pt-Co Alloy Nanoparticles on a γ-Al2 O3 Support: The Synergistic Effect between Isolated Electron-Rich Pt and Co for Automotive Exhaust Purification.

Invited for this month's cover is the group of Dr. Katsutoshi Sato and Prof. Dr. Katsutoshi Nagaoka (Kyoto University) and collaborators at Oita and Kyushu Universities. The cover picture shows the proposed mechanism for automotive exhaust purification over a Pt-Co alloy nanoparticle catalyst with an extremely low Pt/Co molar ratio. In the catalyst, the isolated electron-rich Pt atoms are present on the surface of the nanoparticles and play an important role in NOx capture and activation, which are important elementary steps in exhaust purification. Read the full text of the article at 10.1002/cplu.201800542.

Pt-Co Alloy Nanoparticles on a γ-Al2 O3 Support: Synergistic Effect between Isolated Electron-Rich Pt and Co for Automotive Exhaust Purification.

There is interest in minimizing or eliminating the use of Pt in catalysts by replacing it with more widely abundant and cost-effective elements. The alloying of Pt with non-noble metals is a potential strategy for reducing Pt use because interactions between Pt and non-noble metals can modify the catalyst structure and electronic properties. Here, a γ-Al2 O3 -supported bimetallic catalyst [Pt(0.1)Co(1)/Al2 O3 ] was prepared which contained 0.1 wt % Pt and 1 wt % Co and thus featured an extremely low Pt : Co ratio (<1 : 30 mol/mol). The Pt and Co in this catalyst formed alloy nanoparticles in which isolated electron-rich Pt atoms were present on the nanoparticle surface. The activity of this Pt(0.1)Co(1)/Al2 O3 catalyst for the purification of automotive exhaust was comparable to the activities of 0.3 and 0.5 wt % Pt/γ-Al2 O3 catalysts. Electron-rich Pt and metallic Co promoted activation of NOx and oxidization of CO and hydrocarbons, respectively. This strategy of tuning the surrounding structure and electronic state of a noble metal by alloying it with an excess of a non-noble metal will enable reduced noble metal use in catalysts for exhaust purification and other environmentally important reactions.

Sex Differences in the Blood Concentration of Tacrolimus in Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients with CYP3A5*3/*3.

The purpose of this study was to describe the impact of sex and cytochrome P450 3A5 (CYP3A5) variant on the blood concentration of tacrolimus in patients with systemic lupus erythematosus or rheumatoid arthritis. The blood concentration of tacrolimus (ng/mL) divided by the daily dose of tacrolimus (mg/day) and the patient's weight (kg) (C/D) was obtained from 55 patients. The C/D value was analysed according to genetic variation in CYP3A5 or ATP binding cassette subfamily B member 1 (ABCB1), sex, and age. The C/D value in the CYP3A5*3/*3 group was significantly higher than in the CYP3A5*1/*1 and *1/*3 groups (p < 0.05, effect size: d = 1.40). In the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in men than in women (p < 0.05, effect size: d = 1.78). Furthermore, in the CYP3A5*3/*3 group, the concentration of tacrolimus was significantly higher in women aged over 50 years than in women aged under 50 years (p < 0.05, effect size: d = 1.18). In contrast, ABCB1 genetic variations did not show any significant effect on the C/D value. Since the blood concentration of tacrolimus in patients with CYP3A5*3/*3 varies depending on sex and age, these factors should be considered when studying the difference of sex in CYP3A.

TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis.

Signal-peptide peptidase (SPP) is an intramembrane protease that participates in the production of the mature core protein of hepatitis C virus (HCV). Here we show that SPP inhibition reduces the production of infectious HCV particles and pathogenesis. The immature core protein produced in SPP-knockout cells or by treatment with an SPP inhibitor is quickly degraded by the ubiquitin-proteasome pathway. Oral administration of the SPP inhibitor to transgenic mice expressing HCV core protein (CoreTg) reduces the expression of core protein and ameliorates insulin resistance and liver steatosis. Moreover, the haploinsufficiency of SPP in CoreTg has similar effects. TRC8, an E3 ubiquitin ligase, is required for the degradation of the immature core protein. The expression of the HCV core protein alters endoplasmic reticulum (ER) distribution and induces ER stress in SPP/TRC8 double-knockout cells. These data suggest that HCV utilizes SPP cleavage to circumvent the induction of ER stress in host cells.

Hepatocyte Factor JMJD5 Regulates Hepatitis B Virus Replication through Interaction with HBx.

UNLABELLED: Hepatitis B virus (HBV) is a causative agent for chronic liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HBx protein encoded by the HBV genome plays crucial roles not only in pathogenesis but also in replication of HBV. Although HBx has been shown to bind to a number of host proteins, the molecular mechanisms by which HBx regulates HBV replication are largely unknown. In this study, we identified jumonji C-domain-containing 5 (JMJD5) as a novel binding partner of HBx interacting in the cytoplasm. DNA microarray analysis revealed that JMJD5-knockout (JMJD5KO) Huh7 cells exhibited a significant reduction in the expression of transcriptional factors involved in hepatocyte differentiation, such as HNF4A, CEBPA, and FOXA3. We found that hydroxylase activity of JMJD5 participates in the regulation of these transcriptional factors. Moreover, JMJD5KO Huh7 cells exhibited a severe reduction in HBV replication, and complementation of HBx expression failed to rescue replication of a mutant HBV deficient in HBx, suggesting that JMJD5 participates in HBV replication through an interaction with HBx. We also found that replacing Gly(135) with Glu in JMJD5 abrogates binding with HBx and replication of HBV. Moreover, the hydroxylase activity of JMJD5 was crucial for HBV replication. Collectively, these results suggest that direct interaction of JMJD5 with HBx facilitates HBV replication through the hydroxylase activity of JMJD5. IMPORTANCE: HBx protein encoded by hepatitis B virus (HBV) plays important roles in pathogenesis and replication of HBV. We identified jumonji C-domain-containing 5 (JMJD5) as a novel binding partner to HBx. JMJD5 was shown to regulate several transcriptional factors to maintain hepatocyte function. Although HBx had been shown to support HBV replication, deficiency of JMJD5 abolished contribution of HBx in HBV replication, suggesting that HBx-mediated HBV replication is largely dependent on JMJD5. We showed that hydroxylase activity of JMJD5 in the C terminus region is crucial for expression of HNF4A and replication of HBV. Furthermore, a mutant JMJD5 with Gly(135) replaced by Glu failed to interact with HBx and to rescue the replication of HBV in JMJD5-knockout cells. Taken together, our data suggest that interaction of JMJD5 with HBx facilitates HBV replication through the hydroxylase activity of JMJD5.

Morganella morganii Peritonitis Associated with Continuous Ambulatory Peritoneal Dialysis (CAPD) after Colonoscopy.

A 79-year-old man on continuous ambulatory peritoneal dialysis (CAPD) developed abdominal pain and cloudy peritoneal fluid two days after colonoscopy that revealed multiple diverticula. The white blood cell count was 9,000 cells/µL, C-reactive protein level was 6.86 mg/dL, and the white blood cell count of the peritoneal fluid was 7,800 cells/µL, suggesting acute peritonitis. Empiric therapy consisting of cefazolin and ceftazidime slowly improved the patient's symptoms. The initial microbiological examination of the peritoneal fluid demonstrated Morganella morganii. He was changed from CAPD to hemodialysis. It is important to consider M. morganii peritonitis in patients with colonic diverticula.