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Background Dopamine is used to treat patients with shock in intensive care units (ICU) throughout the world, despite recent evidence against its use. The aim of this study was to identify the latest practice of dopamine use in Japan and also to explore the consequences of dopamine use in a large Asian population. Methods The Japanese Intensive Care PAtient Database (JIPAD), the largest intensive care database in Japan, was utilized. Inclusion criteria included: 1) age 18 years or older, 2) admitted to the ICU for reasons other than procedures, 3) ICU length of stay of 24 h or more, and 4) treatment with either dopamine or noradrenaline within 24 h of admission. The primary outcome was in-hospital mortality. Multivariable regression analysis was performed, followed by a propensity score-matched analysis. Results Of the 132,354 case records, 14,594 records from 56 facilities were included in this analysis. Dopamine was administered to 4,653 patients and noradrenaline to 11,844. There was no statistically significant difference in facility characteristics between frequent dopamine users ( N  = 28) and infrequent users ( N  = 28). Patients receiving dopamine had more cardiovascular diagnosis codes (70% vs. 42%; p  < 0.01), more post-elective surgery status (60% vs. 31%), and lower APACHE III scores compared to patients given noradrenaline alone (70.7 vs. 83.0; p  < 0.01). Multivariable analysis showed an odds ratio for in-hospital mortality of 0.86 [95% CI: 0.71–1.04] in the dopamine ≤ 5 μg/kg/min group, 1.46 [95% CI: 1.18–1.82] in the 5–15 μg/kg/min group, and 3.30 [95% CI: 1.19–9.19] in the > 15 μg/kg/min group. In a 1:1 propensity score matching for dopamine use as a vasopressor (570 pairs), both in-hospital mortality and ICU mortality were significantly higher in the dopamine group compared to no dopamine group (22.5% vs. 17.4%, p  = 0.038; 13.3% vs. 8.8%, p  = 0.018), as well as ICU length of stay (mean 9.3 days vs. 7.4 days, p  = 0.004). Conclusion Dopamine is still widely used in Japan. The results of this study suggest detrimental effects of dopamine use specifically at a high dose. Trial registration Retrospectively registered upon approval of the Institutional Review Board and the administration office of JIPAD.

Aim Peritoneal metastases (PM) frequently occur in patients with gastric cancer and result in a poor prognosis. Exosomes play pivotal roles in tumor metastasis through the transfer of microRNAs (miRNAs). We examined the exosomal miRNA profile in peritoneal fluids to identify novel biomarkers to reflect tumor burden in the peritoneum. Methods Exosomes were isolated from peritoneal fluids of patients of gastric cancer with macroscopic (P1) or microscopic (P0CY1) peritoneal metastasis (PM) and comprehensive miRNA expression analysis was carried out. Expressions of candidate miRNAs were then validated in all 58 samples using TaqMan Advanced miRNA Assays. Results In initial screening, we carried out comprehensive analysis of exosomal miRNA using peritoneal fluids from 11 and 14 patients with or without PM, respectively, and identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis showed that four miRNAs (miR‐21‐5p, miR‐92a‐3p, miR‐223‐3p, and miR‐342‐3p) were significantly upregulated in 12 PM (+) samples, and their expression levels showed positive correlation with peritoneal cancer index. In contrast, miR‐29 family were all downregulated in patients with PM (+) samples. Moreover, in 24 patients with pT4 tumor, miR‐29 at gastrectomy tended to be lower in six patients with peritoneal recurrence with significant differences in miR‐29b‐3p (P = .012). Conclusion Expression pattern of miRNAs in peritoneal exosomes well reflects the tumor burden in the peritoneal cavity and could be a useful biomarker in the treatment of PM. MicroRNAs contained in exosomes derived from peritoneal fluid were examined in patients with gastric cancer. Four miRNAs (miR‐21‐5p, miR‐92a‐3p, miR‐223‐3p, and miR‐342‐3p) were significantly upregulated, whereas three miR‐29 were downregulated in patients with peritoneal metastasis. Exosomal miRNA profiles in peritoneal fluid reflect the tumor burden in the peritoneal cavity and could be a useful biomarker for peritoneal metastasis

The purpose of this study is to investigate the relationship between medical student readiness for interprofessional learning and interest in community medicine prior to incorporating community-oriented interprofessional education into the curriculum. A questionnaire was administered to students at Nagasaki University School of Medicine in Japan during each of three consecutive years (N=2244). The Readiness for Interprofessional Learning Scale (RIPLS) was administered in addition to a questionnaire to evaluate interest in community medicine. The Kruskal-Wallis and Steel-Dwass tests were used to determine differences between school years. Correlation between the RIPLS score and interest in community medicine was evaluated with Spearman's rank correlation coefficient. Relationships between RIPLS score and demographic parameters, and interest in community medicine were evaluated with multiple linear regression analysis. Eighty-four percent (1891/2244) of students responded. The RIPLS score was highest in school year 1, followed by year 6, year 5, year 3, and years 4 and 2. Interest in community medicine correlated with the RIPLS score (r = 0.332, p < 0.001), but less in year 1 (r = 0.125, p = 0.002) than in other years. RIPLS score was significantly associated with gender, age, school year, interest in community medicine, but not the year that the survey was conducted. Community-oriented interprofessional education has the potential to improve attitudes towards interprofessional learning. When introducing this promising education into the curriculum from year 1, attracting students' interest in community medicine should be considered.

An 18-year-old man presented after undergoing multiple investigations for abdominal pain. Retrograde double-balloon enteroscopy showed a protruding red lesion in the ileum with small ulcers, approximately 75 cm proximal to the ileocecal valve, resulting in an intussusception. An inverted Meckel’s diverticulum was strongly suspected. Pressure was applied to the protruding lesion using contrast medium injection after wedging the lumen with a balloon. The intussusception partially reduced, avoiding the need for emergent surgery. Endoscopic tattooing was performed to mark the lesion for subsequent resection. Elective laparoscopy-assisted surgery with minimum laparotomy revealed an inverted Meckel’s diverticulum, which was resected.

Internal hernia is a rare cause of bowel obstruction which often requires emergent surgery. In general, the preoperative diagnosis of internal hernia is difficult. The pelvic cavity has various spaces with the potential to result in a hernia, especially in females. In this report, we describe a patient with an internal hernia secondary to previous gynecologic surgery. A 49-year-old woman presented with acute abdominal pain and a history of previous right oophorectomy for a benign ovarian cyst. Computed tomography scan of the abdomen showed obstruction with strangulation and emergent laparoscopic exploration was performed. Intraoperatively, there was an incarcerated internal hernia in the pelvis, located in the vesicouterine pouch, which was reduced. The orifice of the hernia was a 2 cm defect caused by adhesions between the uterus and bladder. The defect was closed with a continuous suture. The herniated bowel was viable, and the operation was completed without intestinal resection. She was discharged four days after surgery without complications. Laparoscopy is useful to diagnose bowel obstruction in selected patients and may also be used for definitive therapy. It is important to understand pelvic anatomy and consider an internal hernia of the pelvic cavity in females, in the differential diagnosis of bowel obstruction, especially those with a history of gynecological surgery.

Background: A novel potassium-competitive acid blocker, vonoprazan (VPZ), improves first-line Helicobacter pylori eradication success. The aim of this systematic review is to clarify the effectiveness and safety of second-line H. pylori eradication therapy comparing VPZ and proton pump inhibitor (PPI)-based regimens. Methods: Medline (PubMed), EMBASE, Web of Science, Cochrane Library, and the Japan Medical Abstract Society Database were searched. Results: We selected 16 studies for quantitative review. Forest plot analysis showed significant superiority of VPZ over PPI-based regimens in overall second-line H. pylori eradication success (OR 1.51, 95% CI 1.27–1.81, p < 0.001). Forest plots from 2 studies with propensity score matched analysis showed significant superiority of VPZ over PPI-based regimens (OR 3.09, 95% CI 1.71–5.58, p < 0.001). The remaining 14 studies with per-protocol analysis and the full analysis set also showed significant superiority (OR 1.40, 95% CI 1.16–1.69, p < 0.001). Regarding adverse events, Forest plot analysis did not show a significant difference between the 2 regimens (OR 0.88, 95% CI 0.58–1.32, p = 0.53). Conclusions: A VPZ-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. A VPZ-based second-line H. pylori eradication regimen can be the first choice.

BackgroundLinked color imaging (LCI) increases the visibility of early gastric cancers, which may be associated with characteristic findings including background purple mucosae. These lesions are found in areas of chronic gastritis and surrounding mucosa. The aim of this study is to objectively characterize these lesions by color differences and color component values using LCI.MethodsFifty-two patients with early gastric cancer were enrolled. Color differences were calculated prospectively in malignant lesions and adjacent mucosa and compared with histological findings in resected specimens. Color component values of L*, a*, and b* were compared between purple and non-purple mucosae in areas of chronic gastritis. Based on histological findings, the accuracy of identifying gastric intestinal metaplasia was calculated.ResultsCancers and surrounding mucosa in 74% of lesions had similar colors using white light imaging (WLI), whereas purple mucosa surrounded part or all of cancers appearing orange–red, orange or orange–white using LCI. Greater color differences were seen using LCI compared to WLI, including flat-type cancers, leading to higher contrast. The surrounding purple mucosa corresponded histologically to intestinal metaplasia, facilitating the identification of malignant lesions. Forty lesions (83%) with purple mucosa and eight lesions (17%) with non-purple mucosa in areas of chronic gastritis were diagnosed as intestinal metaplasia by biopsy (83% accuracy). Color component values of purple mucosa differ significantly from those of non-purple mucosae.ConclusionsLCI images have higher color contrast between early gastric cancers and surrounding mucosa compared to WLI. A characteristic purple color around gastric cancers using LCI represents intestinal metaplasia.

Accumulating evidence suggests that metformin reduces the incidence and mortality of colorectal cancer (CRC). However, underlying mechanisms have not been fully clarified. The aim of this study was to examine the pathological characteristics of resected CRC from patients treated with metformin for type 2 diabetes mellitus (DM). In total, 267 patients with DM underwent curative colectomy for Stage I‐III CRC and 53 (19.9%) patients had been treated medically including metformin. Pathological N‐stage was significantly lower in metformin‐treated patients (P < .05) with prolonged disease‐free survival (DFS) (P < .05). Immunohistochemistry showed that the densities of CD3(+) and CD8(+) tumor‐infiltrating lymphocytes (TILs) in the invasive front area were significantly higher in 40 patients treated with metformin compared with propensity score matched cases without metformin (P < .05). The density of tertiary lymphoid structures (TLS) in tumor stroma was markedly increased in metformin‐treated patients (P < .001). In those tumors, there were more CD68(+) tumor‐associated macrophages (TAM) infiltrated (P < .05), while the ratio of CD163(+) M2‐phenotype was markedly reduced (P < .001). Stromal fibrosis tended to be suppressed by metformin intake (P = .051). These findings suggested that metformin drastically changes the characteristics of infiltrating immune cells in CRC and reprograms the tumor microenvironment from immunosuppressive to immunocompetent status, which may lead to suppression of microscopic tumor spread and improve the outcomes of patients with CRC and type 2 DM. Metformin treatment is associated with fewer lymphatic metastases with prolonged disease‐free survival in patients with stage I‐III colorectal cancer and diabetes mellitus. Densities of tumor‐infiltrating CD3(+) and CD8(+) T cells and tertiary lymphoid structures are significantly increased, while the ratio of CD163(+) M2 type tumor‐associated macrophages is decreased in metformin‐treated colorectal tumor. Metformin may suppress tumor spread by changing the immunosuppressive tumor microenvironment to an immunocompetent status.

There are few reports describing the association of naldemedine with defecation in critically ill patients with opioid-induced constipation. The purpose of this study was to determine whether naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation. In this retrospective cohort study, patients admitted to the Intensive Care Unit (ICU) without defecation for 48 hours while receiving opioids were eligible for enrollment. The primary endpoint was the time of the first defecation within 96 hours after inclusion. Secondary endpoints included presence of diarrhea, duration of mechanical ventilation, ICU length of stay, ICU mortality, and in-hospital mortality. The Cox proportional hazard regression analysis with time-dependent covariates was used to evaluate the association naldemedine with earlier defecation. A total of 875 patients were enrolled and were divided into 63 patients treated with naldemedine and 812 patients not treated. Defecation was observed in 58.7% of the naldemedine group and 48.8% of the no-naldemedine group during the study (p = 0.150). The naldemedine group had statistically significantly prolonged duration of mechanical ventilation (8.7 days vs 5.5 days, p < 0.001) and ICU length of stay (11.8 days vs 9.2 days, p = 0.001) compared to the no-naldemedine group. However, the administration of naldemedine was significantly associated with earlier defecation [hazard ratio:2.53; 95% confidence interval: 1.71-3.75, p < 0.001]. The present study shows that naldemedine is associated with earlier defecation in critically ill patients with opioid-induced constipation.

BackgroundWe introduce a novel operative technique to dissect lymph nodes adjacent to the recurrent laryngeal nerve, referred to as the “native tissue preservation” technique. Using this technique, there was no damage to the recurrent laryngeal nerve, which is maintained in its anatomical position.MethodsFrom September 2016 to December 2018, minimally invasive esophagectomy was performed in the left lateral decubitus position in 87 patients with esophageal cancer. The native tissue preservation technique for lymphadenectomy around the recurrent laryngeal nerve was used, and all patients were evaluated for recurrent laryngeal nerve paralysis.ResultsMinimally invasive esophagectomy was completed in all patients without conversion to thoracotomy. Although an extended lymphadenectomy was performed in all patients, there were no grade II or higher complications (Clavien–Dindo classification) and no incidence of recurrent laryngeal nerve paralysis.ConclusionThe native tissue preservation technique may reduce the incidence of recurrent laryngeal nerve paralysis after minimally invasive esophagectomy with radical lymph node dissection.