Self-controlled Case Series Study for Acute Kidney Injury after Starting Proton Pump Inhibitors or Potassium-Competitive Acid Blocker in Patients with Cancer Using a Large Claims Database.

To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.

Changes in intestinal bacteria and imbalances of metabolites induced in the intestines of pancreatic ductal adenocarcinoma patients in a Japanese population: a preliminary result.

BACKGROUND: The relationship between pancreatic ductal adenocarcinoma (PDAC) and the intestinal environment is not fully understood. The purpose of this study was to elucidate the characteristics of the intestinal environment in PDAC. METHODS: We performed a case-control study of 5 Japanese patients with unresectable PDAC located in the body or tail (PDAC-bt). The number of patients analyzed was limited for this preliminary study. We included 68 healthy subjects, herein control, of pre-printed study in the preliminary study. 16S rRNA amplicon sequencing and metabolomic analysis were performed using fecal samples from the subjects. RESULTS: There was no difference in the Shannon index and Principal Coordinate Analysis between PDAC-bt and the control. However, a significant increase in oral-associated bacteria (Actinomyces, Streptococcus, Veillonella, Lactobacillus) was observed. A significant decrease of Anaerostipes was demonstrated in the feces of PDAC-bt compared with the control. The intestinal propionic acid and deoxycholic acid were significantly lower in PDAC-bt compared with the control. CONCLUSIONS: We showed that the intestinal environment of PDAC-bt is characterized by an increase in oral-associated bacteria and an imbalance of metabolites but without changes in alpha and beta diversity of the gut microbiota profiles.Clinical Trial Registration: www.umin.ac.jp, UMIN 000041974, 000023675, 000023970.

Risk Assessment for Heart Failure in Patients with Type 2 Diabetes Mellitus Treated with Dipeptidyl Peptidase 4 Inhibitor Using a Large Claims Dataset.

Heart failure is a prevalent comorbidity in patients with diabetes mellitus (DM). However, it is unclear whether the risk factors for heart failure in DM patients treated with dipeptidyl peptidase-4 (DPP-4) inhibitors are the same as those for the general population. In this study, we evaluated the factors of new-onset heart failure in working-age patients with diabetes who started DPP-4 inhibitor therapy. This study included 7938 working-age patients. The primary endpoint of the study was the proportion of patients developing heart failure within 12 months of starting DPP-4 inhibitor therapy, which was found to be 1.89% (n = 150). In these patients, risk factors of new-onset heart failure were aging, history of atrial fibrillation, and hypertension but not sex, smoking, high body mass index, weight gain of over 10 kg from 20 years of age, levels of low-density lipoprotein or glycated hemoglobin A1c (HbA1c), history of angina pectoris, myocardial infarction, and chronic kidney disease. We confirmed that cardiovascular comorbidities are risk factors for new-onset heart failure in patients with DM, while general risk factors are not. In conclusion, physicians and pharmacists need to carefully monitor working-age patients with cardiovascular history who start DPP-4 inhibitor therapy even if they do not exhibit general risk factors for heart failure.

The risk of weekend biopsy: Impact of specimen source and fixation status on HER2 assessment in the treatment of advanced gastric cancer (The HER_WEEKEND study).

Accurate evaluation of human epidermal growth factor receptor type 2 (HER2) expression is crucial for determining chemotherapy regimens in gastric cancer. However, formalin fixation status has been identified as an important factor affecting HER2 assessment reliability. This retrospective cohort study aimed to investigate the correlation between sample collection day (weekday vs. weekend) and source (biopsy vs. surgical specimens) in assessing HER2 expression in patients with unresectable advanced/recurrent gastric cancer. Data were collected from gastric cancer patients who received chemotherapy at a single public hospital in Japan from 2008 to 2021. The analysis included 177 patients (109 men, 68 women) with a median age of 68.0 (21-88) years, and the primary outcome was the HER2 positivity rate. The overall HER2 positivity rate was 18.1%, with higher rates on weekdays (20.0%) compared to weekends (12.8%). Biopsies had higher positivity rates on weekdays (23.9%) but lower rates on weekends (11.1%) than surgical specimens. Significant differences were observed in formalin fixation times between weekdays and weekends for both biopsies and surgical samples. The study findings suggest that longer formalin fixation times on weekends may lead to underestimating HER2 expression, particularly in biopsies. Therefore, it is crucial to be cautious of excessive formalin fixation when collecting samples, especially during weekend biopsies.

[Safety and Efficacy of Robot-Assisted Surgery for Early Uterine Cancer in Our Institution over Five Years Since Its Introduction].

Lacking experience of laparoscopic surgery against gynecologic malignancies, we started performing robot-assisted surgery for uterine cancer in September 2017. Here we compared the safety and efficacy of robot-assisted surgery with those of open surgery in early-stage uterine cancer patients. The surgical time was significantly longer and the blood loss and hospital stay were significantly shorter for robot-assisted versus open surgery. No recurrence was observed after robot-assisted surgery. Robot-assisted surgery can be safely performed even in general hospitals and is an effective treatment option for early-stage uterine cancer patients.

Identification of the Components of Proton Pump Inhibitors and Potassium-Competitive Acid Blocker That Lead to Cardiovascular Events in Working-Age Individuals: A 12-Month Retrospective Cohort Study Using a Large Claims Database.

This study aimed to identify the components of proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) that lead to cardiovascular events in individuals of working age. We analyzed large claims data of individuals who were administered PPIs or PCAB. We enrolled working-age individuals administered PPI or PCAB without cardiovascular history with a 12-month screening and 12-month observation period and determined the proportion of cardiovascular events and the predictive factors of cardiovascular events in this population. Among the eligible individuals, 0.5% (456/91098) had cardiovascular events during the 12-month observation period. Predictive factors for cardiovascular events were age for +1 year (p < 0.0001), male sex (p < 0.0001), hypertension (p = 0.0056), and diabetes mellitus (p < 0.0001). The cardiovascular disease risk was higher in working-age individuals administered lansoprazole than in those administered other drugs (vs. rabeprazole; p = 0.0002, vs. omeprazole; p = 0.0046, vs. vonoprazan; p < 0.0001, and vs. esomeprazole; p < 0.0001). We identified the risk for cardiovascular events in individuals being treated with lansoprazole. Lansoprazole is known for its higher CYP2C19 inhibition activity compared with other PPIs or PCAB. A possible mechanism by which lansoprazole may lead to cardiovascular events is inhibiting the generation of epoxyeicosatrienoic acids from arachidonic acids, an intrinsic cardioprotective activator via CYP2C19 inhibition. Thus, we recommend avoiding administering lansoprazole to working-age individuals require PPIs or PCAB.

[Traumatic Neuroma Mimicking Lymph Node Metastasis of Pancreatic Neuroendocrine Neoplasms Developed after Pancreatoduodenectomy-A Case Report].

A traumatic neuroma is a benign tumor consisting of a non-neoplastic growth of injured nerves as a result of trauma or surgery. It is rarely found in an abdominal cavity, but some reports showed that it occurred around the bile duct. We report a case of a 72-year-old man who underwent subtotal stomach-preserving pancreatoduodenectomy for pancreatic neuroendocrine neoplasms 4 years ago. An abdominal contrast-enhanced CT follow-up examination revealed a growing nodule on the dorsal surface of the portal vein. The lesion showed a mild increase in fluorodeoxyglucose uptake in FDG-PET⊘CT. A lymph node metastasis of pancreatic neuroendocrine neoplasms was suspected. Nodule resection was performed for purpose of diagnosis and treatment. The final pathological diagnosis was traumatic neuroma with no evidence of recurrence. Traumatic neuromas developed after pancreatoduodenectomy have not been reported. Postoperative masses around the bile ducts should also be considered traumatic neuromas.

Controlled Tetradeuteration of Straight-Chain Fatty Acids: Synthesis, Application, and Insight into the Metabolism of Oxidized Linoleic Acid.

We describe a concise and reliable protocol for the precisely controlled tetradeuteration of straight-chain fatty acids (FAs) at the α- and ß-positions that is generally applicable to a variety of FAs, including trans-FAs, polyunsaturated FAs (PUFAs), and their oxidized derivatives. The precisely controlled introduction of four deuterium atoms into the FAs enables their persistent and quantitative tracking by LC-MS/MS analysis based on their molecular structures. In addition, the phosphatidylcholine (PC) species prepared from the tetradeuterated FAs thus obtained give a diagnostic peak, namely, a phosphocholine fragment that contains deuterium, in the LC-MS/MS analysis. With these features, the metabolism of a representative oxidized linoleic acid, that is, hydroxyoctadecadienoic acid (HODE), was investigated, leading to the identification of acyltransferases that transfer the acyl moiety derived from HODE to lysophosphatidylcholine.

Barthel Index Score Predicts Mortality in Elderly Heart Failure　- A Goal of Comprehensive Cardiac Rehabilitation.

BACKGROUND: A strategy to predict mortality in elderly heart failure (HF) patients has not been established.Methods and Results:We retrospectively enrolled 413 HF patients aged ≥65 years (mean age 78 years) who had received comprehensive cardiac rehabilitation (CR) during hospitalization. Basic activities of daily life were assessed before discharge using the Barthel index (BI). Of 413 HF patients, 116 (28%) died during a median follow-up period of 1.90 years (interquartile range 1.20-3.23 years). An adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increased in an almost linear manner as the BI score decreased, and that a BI score of 85 corresponded to an HR of 1.0. Kaplan-Meier survival curves showed that the survival rate was lower for patients with a low BI (<85) than for those with a high BI (≥85; 65% vs. 74%, respectively; P=0.007). In multivariate Cox regression analyses, low BI was independently associated with higher mortality after adjusting for predictors, including B-type natriuretic peptide. Inclusion of the BI into the adjusted model improved the accuracy of the prediction of mortality. CONCLUSIONS: A BI score <85 at the time of discharge is associated with increased mortality independent of known prognostic markers, and achieving functional status with a BI score ≥85 by comprehensive CR during hospitalization may contribute to favorable outcomes in elderly HF patients.

High percent body fat mass predicts lower risk of cardiac events in patients with heart failure: an explanation of the obesity paradox.

BACKGROUND: Although high body mass index (BMI) is a risk factor of heart failure (HF), HF patients with a higher BMI had a lower mortality rate than that in HF patients with normal or lower BMI, a phenomenon that has been termed the "obesity paradox". However, the relationship between body composition, i.e., fat or muscle mass, and clinical outcome in HF remains unclear. METHODS: We retrospectively analyzed data for 198 consecutive HF patients (76 years of age; males, 49%). Patients who were admitted to our institute for diagnosis and management of HF and received a dual-energy X-ray absorptiometry scan were included regardless of left ventricular ejection fraction (LVEF) categories. Muscle wasting was defined as appendicular skeletal muscle mass index < 7.0 kg/m2 in males and < 5.4 kg/m2 in females. Increased percent body fat mass (increased FM) was defined as percent body fat > 25% in males and > 30% in females. RESULTS: The median age of the patients was 76 years (interquartile range [IQR], 67-82 years) and 49% of them were male. The median LVEF was 47% (IQR, 33-63%) and 33% of the patients had heart failure with reduced ejection fraction. Increased FM and muscle wasting were observed in 58 and 67% of the enrolled patients, respectively. During a 180-day follow-up period, 32 patients (16%) had cardiac events defined as cardiac death or readmission by worsening HF or arrhythmia. Kaplan-Meier survival curves showed that patients with increased FM had a lower cardiac event rate than did patients without increased FM (11.4% vs. 22.6%, p = 0.03). Kaplan-Meier curves of cardiac event rates did not differ between patients with and those without muscle wasting (16.5% vs. 15.4%, p = 0.93). In multivariate Cox regression analyses, increased FM was independently associated with lower cardiac event rates (hazard ratio: 0.45, 95% confidence interval: 0.22-0.93) after adjustment for age, sex, diabetes, muscle wasting, and renal function. CONCLUSIONS: High percent body fat mass is associated with lower risk of short-term cardiac events in HF patients.

Laparoscopic Synchronous Resection for Descending Colon Cancer and Tailgut Cyst.

A 67-year-old woman underwent polypectomy for a tumor at the descending colon. Pathologically, the tumor was diagnosed as adenocarcinoma with an invasion of 2000 µm. Computed tomography showed a swollen paracolic lymph node and a mass lesion in the presacral space. Magnetic resonance imaging revealed a multio-cular cystic lesion. On diagnosis of descending colon cancer and tailgut cyst, she underwent synchronous lapa-roscopic resection. Histopathologically, the colon cancer was diagnosed as pT1bN1M0, pStage IIIa. The pre-sacral cystic lesion was diagnosed as a nonmalignant tailgut cyst with negative surgical margin. The patient is currently doing well without recurrence at 28 months.

[Successful Resection Using a Posterior Approach of a Tailgut Cyst in the Retrorectal Space].

We present the case of a Tailgut cyst occurring in the retrorectal space that was curatively resected using a posterior approach. A 40-year-old man presented to the Kochi Health Sciences Center with the chief complaint of perineal incongruity. Pelvic magnetic resonance imaging revealed a multilocular cystic lesion in the retrorectal space, with high signal intensity on T2-weighted imaging. After diagnosing a Tailgut cyst, we performed resection of the tumor using a posterior approach. The lesion was removed en bloc with the coccyx. Histopathologically, the lesion was diagnosed as a non-malignant Tailgut cyst, and the surgical margin was negative. The patient is currently doing well without recurrence at 20 months.

Cu(I)/sucrose-catalyzed hydroxylation of arenes in water: the dual role of sucrose.

A protocol for the hydroxylation of aryl halides catalyzed by copper(i) and sucrose in neat water has been developed. The dual role of sucrose, the reaction pathway, and the high selectivity for hydroxylation were investigated using a combination of experimental and theoretical techniques.

Clinical Risk Factors and Prognostic Impact of Osteoporosis in Patients With Chronic Heart Failure.

BACKGROUND: The clinical significance of osteoporosis in chronic heart failure (CHF) remains unclear.Methods and Results:A total of 303 CHF patients (75 years, [interquartile range (IQR) 66-82 years]; 41% female) were retrospectively examined. Bone mineral densities (BMDs) at the lumbar spine, femoral neck, and total femur were measured by using dual-energy X-ray absorptiometry (DEXA), and osteoporosis was diagnosed when the BMD at any of the 3 sites was <70% of the Young Adult Mean percentage (%YAM). The prevalence of osteoporosis in CHF patients was 40%. Patients with osteoporosis were older (79 [IQR, 74-86] vs. 72 [IQR, 62-80] years), included a large percentage of females, had slower gait speed and had a lower body mass index. Multivariate logistic regression analysis indicated that sex, BMI, gait speed, loop diuretics use and no use of direct oral anticoagulants (DOACs) were independently associated with osteoporosis. Kaplan-Meier survival curves showed that the rate of death and heart failure hospitalization was higher in patients with osteoporotic BMD at 2 or 3 sites than in patients without osteoporosis (hazard ratio 3.45, P<0.01). In multivariate Cox regression analyses, osteoporotic BMD at 2 or 3 sites was an independent predictor of adverse events after adjustment for prognostic markers. CONCLUSIONS: Loop diuretics use and no DOACs use are independently associated with osteoporosis in CHF patients. Osteoporosis is a novel predictor of worse outcome in patients with CHF.

Two-Step Vapochromic Luminescence of Proton-Conductive Coordination Polymers Composed of Ru(II)-Metalloligands and Lanthanide Cations.

Two proton-conductive and phosphorescent porous coordination polymers, La3-[H5.5RuP]2 and Pr3-[H5.5RuP]2 (H12RuP = [Ru(H4dpbpy)3]2+, H4dpbpy = 2,2'-bipyridine-4,4'-bis(phosphonic acid), composed of Ru(bpy)3-type metalloligands (bpy = 2,2'-bipyridine) functionalized with six phosphonate groups and lanthanide cations (Ln3+ = La3+ or Pr3+) were successfully synthesized. X-ray diffraction studies revealed that six to seven protons of the H12RuP metalloligand were removed in the coordination polymerization reaction to form the porous coordination framework (Ln3-[H5.5RuP]2) with Ln3+ cations (Ln3+ = La3+ or Pr3+). Although their porous structures collapsed on the removal of water molecules from the porous channels, the original porous structures were reconstructed by water adsorption. Interestingly, the triplet metal-to-ligand charge-transfer (3MLCT) emission of Ln3-[H5.5RuP]2 was blue-shifted on increasing the relative humidity (RH) in the low RH region, whereas the inverse red shift was observed in the high RH region, resulting in the highest-energy 3MLCT emission at medium RH. The origin of this two-step vapochromic luminescence (that is, the blue and red shifts of the 3MLCT emission) is ascribable to the water-adsorption-triggered reconstruction of the porous structure and the proton release from the H5.5RuP metalloligand to the water filled channels, respectively. The proton conductivity of Ln3-[H5.5RuP]2 is about 1000-times higher at 20% RH and 10-times higher at 95% RH than that of the carboxylate analog, La7-[RuC]4 (H6RuC = [Ru(H2dcbpy)3]2+; H2dcbpy = 2,2'-bipyridine-4,4'-bis(carboxylic acid)), probably because of the highly acidic phosphonic acid groups.

Copper-catalyzed arene amination in pure aqueous ammonia.

A simple protocol for copper-catalyzed arene amination using aqueous ammonia without any additional ligands and organic coordinating solvents has been developed. The reaction pathway via a Cu(i)/Cu(iii) mechanism is proposed based on the results of control experiments as well as DFT calculations.

A Case of Primary Colonic Signet Ring Cell Carcinoma in a Young Man which Preoperatively Mimicked Phlebosclerotic Colitis.

A 35-year-old man was referred to our hospital for chronic abdominal pain and diarrhea. Computed tomography showed wall thickening, poor contrast enhancement and calcification of the ascending colon, which were consistent with phlebosclerotic colitis. Malignant character was not detected from a biopsy specimen. Operatively, we observed a scirrhous mass of the ascending colon invading surrounding tissue, which was diagnosed as signet ring cell carcinoma based on analysis of an intraoperative frozen section. Right hemicolectomy with regional lymph node dissection was performed. This case was extremely similar to phlebosclerotic colitis in clinical findings; surgical resection was required for correct diagnosis.

A Simple and Easy Method of Monitoring Doxorubicin Release from a Liposomal Drug Formulation in the Serum Using Fluorescence Spectroscopy.

Formulation of a drug as liposomes facilitates its delivery to the disease target. Rightly, liposomes are gaining popularity in the medical field. In order for the drug to show efficacy, release of the encapsulated drug from the liposome at the target site is required. However, the release is affected by the permeability of the lipid bilayer of the liposome, and it is important to examine the effect of the surrounding environment on the permeability. In this study, we showed the usefulness of fluorescence analysis, especially fluorescence fingerprint, for a rapid and simple monitoring of release of an encapsulated anticancer drug (doxorubicin) from its liposomal formulation (DOXIL). Our result indicated that the release is accelerated by the existence of membrane permeable ions, such as tris(hydroxymethyl)aminomethane, and blood proteins like albumin. Hence, monitoring of doxorubicin release by fluorescence analysis is useful for the efficacy evaluation of DOXIL in a biomimetic environment.

Appendicular muscle mass and exercise/sports participation history in young Japanese women.

Background: It remains unclear how past exercise habits can affect the skeletal muscle mass in adulthood in Japanese populations. Aim: The purpose of the present investigation was to examine the association of appendicular muscle mass (AMM) and skeletal muscle mass index (SMI) with the history of exercise and/or physical activity participation in Japanese women. Subjects and methods: One hundred and twenty females, aged between 18 and 28 years old, participated in the present investigation. Using a dual-energy X-ray absorptiometry scanner, the appendicular lean soft tissue, which is considered as a measure of AMM, was evaluated. Skeletal muscle mass index (SMI) was also assessed. Furthermore, all subjects answered a physical activity questionnaire. Results: Exercise habits at 7 years of age or older positively affected the AMM and SMI. The results of the multiple regression analysis showed that exercise history at 16-18 years of age as well as the current status of exercise and/or physical activity participation was a significant predictor of SMI and AMM. Conclusions: These results indicate that not only the past history of participation in physical and/or sports activities but also the current status of daily physical activity and sports activity play an important role in maintaining appropriate SMI and AMM in young women.

Phylogenetic Characterization of Salmonella enterica Serovar Typhimurium and Its Monophasic Variant Isolated from Food Animals in Japan Revealed Replacement of Major Epidemic Clones in the Last 4 Decades.

Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) and its monophasic variant (Salmonella 4,[5],12:i:-) are the major causes of gastroenteritis in both humans and animals. Pulsed-field gel electrophoresis and multilocus variable-number tandem-repeat analysis have been used widely as subtyping methods for these pathogens in molecular epidemiological analyses, but the results do not precisely reflect phylogenetic information. In this study, we performed a phylogenetic analysis of these serovars using whole-genome sequencing data and identified nine distinct genotypic clades. Then, we established an allele-specific PCR-based genotyping method detecting a clade-specific single nucleotide polymorphism to rapidly identify the clade of each isolate. Among a total of 815 isolates obtained from cattle in Japan between 1977 and 2017, clades 1, 7, and 9 contained 77% of isolates. Obvious replacement of the dominant clone was observed five times in this period, and clade 9, which mostly contains Salmonella 4,[5],12:i:-, is currently dominant. Among 140 isolates obtained from swine in Japan between 1976 and 2017, clades 3 and 9 contained 64% of isolates. Clade 9 is the latest clone as is the case in cattle isolates. Clade 9 is similar to an epidemic clone from Europe, which is characterized by sequence type 34 (ST34), chromosomal Salmonella genomic island 3, and a composite transposon containing antimicrobial resistance genes. The increased prevalence of clade 9 among food animals in Japan might be a part of the pandemic of the European Salmonella 4,[5],12:i:- clone.