Infant Formula with 50% or More of Palmitic Acid Bound to the sn-2 Position of Triacylglycerols Eliminate the Association between Formula-Feeding and the Increase of Fecal Palmitic Acid Levels in Newborns: An Exploratory Study.

The binding ratio of palmitic acid (PA) at the sn-2 position of triacylglycerols in infant formulas is lower than that in breast milk, resulting in higher levels of fecal PA. Even if the ratio is increased to 40-50%, fecal PA levels in formula-fed infants remain higher than those in breast-fed infants. In Japan, infant formulas with 50% or more of PA bound to sn-2 (high sn-2 PA milk) are commercially available; however, their effects on PA excretion have not been investigated. Therefore, this observational study aimed to preliminarily evaluate whether the feeding volume of high sn-2 PA milk is significantly associated with fecal total/soaped PA levels in newborns. Infant formulas were classified as high (≥50% of PA bound to sn-2) or low sn-2 (<50%) PA milk. Associations between feeding volume of high or low sn-2 PA milk and fecal PA levels were evaluated using multiple regression analysis models. The results showed that the feeding volume of low sn-2 PA milk was positively associated with fecal total/soaped PA levels, while there was no significant association between those of high sn-2 PA milk and fecal total/soaped PA levels. Our preliminary study suggests that high sn-2 PA milk may reduce increased fecal PA levels in formula-fed newborns.

Gender Differences in Patients with Gastric Adenocarcinoma.

Background: Gastric cancer (GC) epidemiology and outcomes vary by gender. Methods: We reviewed 18,436 GC patients from 2008 to 2018 and looked for gender differences in clinical characteristics and survival. Results: The gender proportion was 71% male and 29% female. Males had a significantly (p < 0.001) higher proportion of differentiated GC (66.3%) and a lower proportion of undifferentiated GC (26.3%). Diagnosis through medical check-ups was more common in males (30.0% vs. 26.4%, p < 0.001). Clinical staging revealed 54.6% of males and 52.9% of females had localized disease without lymph node metastasis (LNM), while distant metastasis occurred in 17.4% of males and 16.9% of females (p < 0.001). Kaplan-Meier survival curves indicated females had a significantly higher overall survival (p = 0.0018). The survival advantage for females was evident in the early stages, with a significant difference in localized disease without LNM (p < 0.001) and localized disease with LNM (p = 0.0026, log-rank test) but not in the advanced stages. Multivariate Cox regression analysis showed a significantly reduced mortality risk in females (p < 0.001). Conclusions: Significant gender differences exist with regard to pathological type, presentation, clinical stage, and overall survival. These findings suggest gender-specific strategies for screening, diagnosis, and treatment.

A new grading assessment of eosinophilic esophagitis using red dichromatic imaging: a pilot study.

BACKGROUND AND AIMS: The endoscopic reference score using white-light imaging (WLI) is utilized for objectively evaluating the severity of findings in patients with eosinophilic esophagitis. A novel image-enhanced endoscopy technique, red dichromatic imaging (RDI), can visualize deeper vessels in the GI tract, which may assess edema more precisely than WLI. METHODS: A total of 21 consecutive patients with eosinophilic esophagitis were prospectively evaluated. Patients were categorized according to 3 grades based on the visibility of vessels with RDI. Clinical features, such as peak eosinophil counts and presence of symptoms, were reviewed. RESULTS: There were 10 patients with RDI Grade 0/1 and 11 patients with RDI Grade 2. Peak eosinophil counts and the prevalence of heartburn were significantly higher in patients with RDI Grade 2 than in patients with RDI Grade 0/1. CONCLUSIONS: The severity of eosinophilic infiltration could be predicted more precisely using RDI than by evaluations with WLI.

High accumulation of the Man5GlcNAc2 structure by combining N-acetylglucosaminyltransferase I gene suppression and mannosidase I gene overexpression in Nicotiana tabacum SR1.

High accumulation of a single high-mannose glycan structure is important to ensure the quality of therapeutic proteins. We developed a glyco-engineering strategy for ensuring high accumulation of the Man5GlcNAc2 structure by combining N-acetylglucosaminyltransferase I (GnT I) gene suppression and mannosidase I (Man I) gene overexpression. Nicotiana tabacum SR1 was used as the glyco-engineered host owing to the lower risk of pathogenic contamination than that in mammalian cells. We generated three glyco-engineered plant strains (gnt, gnt-MANA1, and gnt-MANA2) with suppression of GnT I or the combined suppression of GnT I and overexpression of Man I A1 or A2. The quantitative reverse transcriptase-PCR analysis showed a higher level of upregulation of Man I expression in gnt-MANA1/A2 plants than in the wild-type plants. Man I activity assay showed that the gnt-MANA1 plants had a higher Man I activity than did the wild-type and gnt-MANA2 plants. N-glycan analysis independently performed on two plants of each plant strain showed that gnt-MANA1 plants had a low abundance of the Man6-9GlcNAc2 structure (2.8%, 7.1%) and high abundance of the Man5GlcNAc2 structure (80.0%, 82.8%) compared with those in the wild-type and gnt plants. These results indicated that GnT I knockdown suppressed further modification of the Man5GlcNAc2 structure, and Man I overexpression enhanced the conversion of Man6-9GlcNAc2 structures to the Man5GlcNAc2 structure. The developed glyco-engineered plants have potential for serving as novel expression hosts for therapeutic proteins.

A Marked Eosinophilic Infiltration in Mucosa Could Be a Better Predictive Factor for Intractable Non-Esophageal Eosinophilic Gastrointestinal Disorders.

INTRODUCTION: Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are rare, but their prevalence has recently increased. Although it has been reported that one-half of patients with non-EoE EGIDs have intractable clinical courses, their clinical features are not fully understood. METHODS: This is a multicenter retrospective study in which 10 institutions in Japan participated. Clinical databases from January 1998 to December 2020 were reviewed to identify patients with non-EoE EGIDs. A total of 44 patients were identified; they were divided into two groups based on their clinical course: an intractable group and a non-intractable group. The clinical features were compared between the two groups by a logistic regression analysis. Remarkable eosinophilic infiltration (REI) was defined histologically when the maximal counts of mucosal eosinophils reached a threshold level in the respective area of biopsy. RESULTS: Prevalence of drug allergy and eosinophil counts more than 500/µL (EOS), vomiting symptoms, abnormalities of the stomach, duodenum, and jejunum on computed tomography (upper gastrointestinal abnormality on computed tomography [UACT]), and REI were significantly different between the two groups. Among the factors that were potentially associated with an intractable clinical course, logistic regression revealed that REI, EOS, and UACT were significant factors. Based on an analysis of the area under the receiver operator characteristic curve, a combination of REI and EOS had the lowest Akaike's information criterion, indicating the best model to predict an intractable clinical course. CONCLUSIONS: REI may predict an intractable course in patients with non-EoE EGIDs. In addition, the combination of REI and EOS was a better predictor than REI alone.

The relationship between manometric subtype and symptom details in achalasia.

BACKGROUND: Although dysphagia and chest pain are the two most common symptoms in patients with achalasia, the mechanism of evoking symptoms is still unknown. The aim of this study was to reveal the relationship between symptoms and the subtypes of achalasia defined by the Chicago classification. METHODS: A total of 71consecutive patients with newly diagnosed achalasia were enrolled between March 2009 and December 2017. Esophageal motility was assessed by high-resolution manometry (HRM) with the Chicago classification v 3.0. and esophagograms. Their symptoms were evaluated with structured self-reported questionnaires focused on dysphagia and chest pain. Symptom profiles and radiographic findings according to the manometric subtypes were investigated. RESULTS: Among the total 71 patients, 69 patients (97%) had dysphagia and 39 patients (54%) had chest pain. Regarding dysphagia, type II patients reported dysphagia in the throat the most, while types I and III patients mostly felt it in the epigastrium. Type II patients often felt dysphagia at the time of swallowing (41%), but this was reported in only 8.7% of Type I and 33% of Type III patients (p = 0.02). Concerning chest pain, Type I patients rarely had pain during meals (14%), but more often while sleeping (43%) and in early morning (43%), while type III patients often had pain during meals (67%). Type III patients reported that solid food caused pain more often than other types (I/II/III 0/10/33%, p = 0.09). CONCLUSIONS: Detailed symptoms of achalasia, such as its site and timing, varied by subtypes. The status of the esophageal body might induce those differences in symptoms.

Absolute quantification of bovine lactadherin to screen the anti-rotavirus activity of dairy ingredients.

The anti-rotavirus components in breast milk and infant formulas play an important role in the prevention of rotavirus infection. The present study examined whether the levels of phospholipids and bovine lactadherin, which are the major components and proteins of the milk fat globule membrane complex, are useful indices of the anti-rotavirus activity of dairy ingredients used in infant formulas. We compared the anti-rotavirus activity of 2 types of dairy ingredients enriched in the milk fat globule membrane complex: high-fat whey protein concentrate (high-fat WPC) and butter milk powder (BMP), using 50% inhibition concentration (IC50) and linear inhibition activity to determine levels of solid contents, total proteins, phospholipids, and bovine lactadherin. Here, we developed a quantification method using full-length isotope-labeled proteins to measure bovine lactadherin levels in these dairy ingredients. The evaluation of anti-rotavirus activity showed that the difference in IC50 was the smallest when the 2 dairy ingredients were compared at the bovine lactadherin level, among other indices in this study. Additionally, no significant difference was observed between the inhibition linearity of 2 dairy ingredients when evaluating only bovine lactadherin levels. These results indicated that the level of bovine lactadherin was more strongly associated with anti-rotavirus activity than the level of phospholipids. Our results suggest that bovine lactadherin levels can be used to estimate the anti-rotavirus activity of dairy ingredients and can be a criterion used in selecting ingredients for infant formulas.

Optimizing the Relationship between Regulation and Innovation in Dietary Supplements: A Case Study of Food with Function Claims in Japan.

Regulation has long been a counterpart of innovation in the health care industry, and recent cases have demonstrated that appropriately designed regulations can both coexist with and promote innovation. This study is the first study to explore how the regulatory environment affected the innovation process during the transition of the regulations for functional foods in Japan by examining quantitatively the impact of the foods with function claims (FFC) system on industry, companies, and products. Based on a dataset of Japanese dietary supplement manufacturing companies (n = 169) and their products (n = 731) in 2019, we found that companies that have newly entered the FFC system are smaller in scale than existing companies (p < 0.01, Wilcoxon rank sum test). We also found that companies with FFC products have larger revenue growth (p = 0.01). A multiple regression analysis revealed that FFC product sales increased with in-house clinical testing (coefficient: 26.8, p < 0.0001), diverse active ingredients (coefficient: 7.6, p < 0.001), and the claim of new functions (coefficient: 10.2, p < 0.05). These results suggested that the FFC system facilitated the market entry of small and mid-size enterprises and promoted the creation of high-value products through innovative company efforts.

Validation of red dichromatic imaging score (RDI score) to evaluate the severity of ulcerative colitis.

BACKGROUND: Red dichromatic imaging (RDI) is a new imaging technology that has been closely correlated with the activity index of ulcerative colitis (UC). Although the RDI score has been developed no study has validated a correlation between the RDI score and the activity index of UC. Therefore, this study aims to validate the RDI score prospectively. METHODS: A total of 34 patients with UC in whom colonoscopy was scheduled between May 2019 and October 2021 at our hospital were enrolled prospectively. MES, UCEIS, RDI scores, and Nancy index were evaluated in a blinded fashion. We evaluated the correlation between RDI and WLI scores using still images with histology. RESULTS: We analyzed 191 sites of colorectum. RDI score showed the positive correlation with UCEIS (r = 0.74 P < 0.0001) and MES (r = 0.78 P < 0.0001). RDI score also showed the positive correlation with Nancy index (r = 0.63 P < 0.0001). RDI score was more strongly correlated with Nancy index than UCEIS (r = 0.51) and MES (r = 0.48). CONCLUSIONS: When comparing still images of RDI and WLI scores, we showed RDI had a higher correlation to histology than WLI. CLINICAL TRIAL ID: The University Hospital Medical Information Network (UMIN000041750).

A case of sepsis-induced cardiomyopathy successfully treated with venoarterial extracorporeal membrane oxygenation.

Introduction: Sepsis with concomitant acute pyelonephritis, secondary to urolithiasis, is common. We report a case of sepsis-induced cardiomyopathy with acute pyelonephritis, successfully managed with venoarterial extracorporeal membrane oxygenation. Case presentation: A 64-year-old woman presented with fever and disturbed consciousness. Abdominal computed tomography revealed right hydronephrosis with ipsilateral ureteral stone. Despite ureteral stent placement and antibiotic treatment, her hemodynamics worsened. She was diagnosed with sepsis-induced cardiomyopathy and underwent venoarterial extracorporeal membrane oxygenation. Her hemodynamics improved rapidly; venoarterial extracorporeal membrane oxygenation was withdrawn on postoperative day-3. She was discharged from our hospital after sufficient antibiotic treatment. Conclusion: Venoarterial extracorporeal membrane oxygenation may be initiated in patients with sepsis-induced cardiomyopathy. Evaluation of left ventricular ejection fraction via echocardiography is important to determine the indication for venoarterial extracorporeal membrane oxygenation.

Efficacy of using red dichromatic imaging throughout endoscopic submucosal dissection procedure.

BACKGROUND: Management of bleeding during endoscopic submucosal dissection (ESD) is critical. Red Dichromatic Imaging (RDI), a novel image-enhanced endoscopy technology, has been reported to improve the visibility of deep vessels and bleeding source compared to white light imaging (WLI). We hypothesized that using RDI during the entire cutting process (full time RDI ESD: FTR-ESD), higher R0 resection rate, shorter procedure time and fewer complications could be achieved. Therefore, the aims of the present study were to investigate the efficacy and safety of FTR-ESD. METHODS: This retrospective observational study included a total of 82 consecutive patients who underwent ESD by a single expert endoscopist for 40 esophageal, 17 gastric and 25 colorectal cancers at our institution from January 2018 to March 2021. The clinicopathological data were collected from patients' medical records and the treatment outcomes were analyzed according to the treatment phase (early; 57 WLI-ESD and late; 25 FTR-ESD). RESULTS: The median of the greatest diameter of resected specimen was 40.0 mm. The median procedure time was relatively shorter in the FTR-ESD group (35 min) than in the WLI-ESD group (40 min), but the difference was not statistically significant (p = 0.34). The median dissection speed in the FTR-ESD group (27.23 mm2/min) was significantly faster than that in the WLI-ESD group (20.94 mm2/min) (p = 0.025). The dissection speed was not different among different organs. A multivariate analysis revealed that tumor size (more than 30 mm) and FTR-ESD were significant independent factors contributing to faster dissection speed (p < 0.05). There were no significant differences in the rates of en bloc resection, HM0, VM0 or occurrence of adverse events between WLI-ESD and FTR-ESD. CONCLUSIONS: FTR-ESD significantly increases the dissection speed compared to WLI-ESD. FTR-ESD can be performed safely and therapeutic outcomes in FTR-ESD are comparable with WLI-ESD. A further multicenter prospective study is warranted to confirm our results.

Effect of Nicotinamide Mononucleotide Concentration in Human Milk on Neurodevelopmental Outcome: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

(1) Background: Breast milk is the only source of nutrition for breastfed infants, but few studies have examined the relationship between breast milk micronutrients and infant neurodevelopmental outcome in exclusively breastfed infants. The aim of this study was to characterize the association between nicotinamide adenine dinucleotide (NAD)-related compounds in the breast milk of Japanese subjects and infant neurodevelopmental outcome. (2) Methods: A total of 150 mother-child pairs were randomly selected from the three-generation cohort of the Tohoku Medical Megabank in Japan. Infants were exclusively breastfed for up to 6 months. Breast milk was collected at 1 month postpartum, and the quantity of NAD-related substances in the breast milk was quantified. The mothers also completed developmental questionnaires at 6, 12, and 24 months. The relationship between the concentration of NAD-related substances in breast milk and developmental indicators was evaluated via ordinal logistic regression analysis. (3) Results: Nicotinamide mononucleotide (NMN) was quantified as the major NAD precursor in breast milk. The median amount of NMN in the breast milk was 9.2 µM. The NMN concentration in breast milk was the only NAD-related substance in breast milk that showed a significant positive correlation with neurodevelopmental outcome in infants at 24 months. (4) Conclusions: The results suggest that NMN in human milk may be an important nutrient for early childhood development.

[Ulcerative colitis complicated by pyoderma gangrenosum and multiple aseptic abscesses].

A woman in her 30s was diagnosed with ulcerative colitis (UC) 4 years ago and treated with tacrolimus, azathioprine, and prednisolone 5mg (PSL). Skin ulcers appeared on the right lower leg during the course of treatment, diagnosed as pyoderma gangrenosum (PG). The patient initially improved with an increased PSL and infliximab dose, but then developed multiple skin ulcers and folliculitis throughout her body. She was transferred to our hospital for PG exacerbation treatment. She developed fever after transfer and contrast-enhanced computed tomography showed multiple abscesses in the lungs and kidneys. PSL was decreased and infliximab was discontinued. Antibiotic therapy and granulocyte/monocyte apheresis (GMA) were started. Fever persisted even after antibiotic treatment, and her general condition did not improve. A right renal abscess puncture was performed. Pus was sterile. A sterile abscess associated with PG was suspected. The PSL dose was increased to 1mg/kg and infliximab restarted. Thereafter, the patient's general condition improved, and both lung and renal abscesses contracted. Skin ulcer epithelialization was also observed. Abdominal symptoms were mild during the course of the disease, and colonoscopy showed only a localized ulcerative lesion in the rectum. The patient was later transferred to the department of dermatology at our hospital for PG treatment. Aseptic abscesses are caused by neutrophil infiltration without infection and have been reported to be associated with neutrophilic dermatosis and inflammatory bowel disease. UC-associated aseptic abscess is rare. This is only the sixth case in Japan. Aseptic abscesses can occur in various sites, including subcutaneous and deep organs, but this is the first kidney abscess case. In previous reports, PSL, infliximab, colchicine, and infliximab+GMA were used for aseptic abscesses associated with UC. They all showed abscess reduction. Aseptic abscesses associated with PG should be considered if abscess lesions occur during the course of UC, and a treatment strategy including enhanced immunosuppression should be considered.

The role of endoscopy in the management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disease that may cause a huge economic burden. Endoscopy is performed not only to rule out other organic diseases but also to diagnose reflux esophagitis or Barrett's esophagus. Non-erosive GERD (non-erosive reflux disease [NERD]) is called endoscopy-negative GERD; however, GERD-related findings could be obtained through histological assessment, image-enhanced endoscopy, and new endoscopic modalities in patients with NERD. Moreover, endoscopy is useful to stratify the risk for the development of GERD. In addition, endoscopic treatments have been developed. These techniques could significantly improve patients' quality of life as well as symptoms.

Endoscopic tissue shielding with polyglycolic acid sheet, fibrin glue, and endoclip for perforation during balloon dilation for esophageal stricture after endoscopic submucosal dissection.

Esophageal endoscopic submucosal dissection can cause esophageal strictures. Endoscopic balloon dilation is the standard treatment for esophageal strictures, but has complications, including perforation, and sometimes requires surgery. We report a case of perforation during endoscopic balloon dilation for esophageal stricture secondary to esophageal submucosal dissection that was successfully treated conservatively. A 66-year-old man with superficial carcinoma in the upper thoracic esophagus underwent circumferential endoscopic submucosal dissection with local steroid injections. Endoscopic balloon dilation was performed weekly for esophageal stricture. However, during the sixth procedure, an attempt to increase the size of the balloon to 13.5 mm resulted in perforation. The patient was treated conservatively using polyglycolic acid sheet with fibrin glue at the perforation site, which was fixed using an endoclip. However, the esophageal stricture persisted after the perforation was closed and Endoscopic balloon dilation was carefully repeated twice weekly up to a maximum of 17 mm, and the endoscope was able to pass through, and associated symptoms improved. This report indicates that endoscopic tissue shielding using polyglycolic acid sheet with fibrin glue and endoclip to correct perforation, followed by additional endoscopic balloon dilation, is an alternative to surgery.

Regional Antimicrobial Stewardship Program in a Provincial Medical Zone in Japan: a Multifaceted Approach.

Antimicrobial resistance (AMR) is a threat to patient health. However, data to optimize antimicrobial use are limited. Furthermore, reducing antibiotic use raises concerns regarding patient safety. The effectiveness of antibiotics in reducing the prevalence of AMR is controversial. Researchers at the Japanese Red Cross Ishinomaki Hospital (JRCIH), the only tertiary care hospital in the medical zone, along with local medical and pharmacy associations and public health centers have been leading the AMR control program since 2018. The program involves lectures aimed at optimizing antimicrobial use, regular publication of surveillance data of drug-resistant strains at the JRCIH, and presentation of first-line treatments for community-acquired infections. The delivery of oral antimicrobial agents across the region in 2020 was 28.7% lower than that in 2013, with delivery of cephalosporins, quinolones, and macrolides decreasing by 34.8%, 46.8%, and 56.0%, respectively. Despite these reductions, there has been no associated increase in the number of patients with severe infectious diseases admitted to the JRCIH. The rates of representative drug-resistant bacterial strains, such as extended-spectrum beta-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus, decreased by half. Herein, we demonstrated the potential of collaborative efforts to optimize antimicrobial agent use and reduce the AMR prevalence without compromising patient safety.

Prescription drug survey of elderly patients with degenerative musculoskeletal disorders.

AIMS: Elderly patients with musculoskeletal disorders are generally expected to receive many prescription drugs for non-musculoskeletal comorbidities and for alleviating chronic musculoskeletal pains. The aims of this study were to review the use of prescription drugs in elderly patients with elective surgeries for musculoskeletal disorders and to identify the factors associated with polypharmacy in elderly patients with musculoskeletal disorders. METHODS: We retrospectively collected the clinical data of patients aged ≥65 years who underwent knee arthroplasty, total hip arthroplasty, or spinal surgery for lumbar or cervical degenerative disorders at our institution. The following data were evaluated: age, body mass index, sex, surgical site, prescription drugs used, American Society of Anesthesiologists physical status grade, and medical history, including hypertension, hyperlipidemia, diabetes, stroke, malignancy, and smoking. Polypharmacy was defined as the use of six or more drugs. RESULTS: In the present study, 767 consecutive patients were evaluated retrospectively. The prevalence of polypharmacy was >50% in the elderly patients with musculoskeletal disorders. The mean numbers of total drugs and pain relief medications were significantly higher in the lumbar surgery group than in the other surgery groups. Multivariable analysis revealed that the factors associated with polypharmacy were lumbar surgery, hypertension, hyperlipidemia, diabetes, and malignancy. CONCLUSIONS: This is the first study to cross-sectionally review the drugs prescribed to patients with degenerative musculoskeletal disorders. It clearly identified the factors associated with polypharmacy in elderly patients with degenerative musculoskeletal disorders. Particular attention should be paid to polypharmacy in elderly patients with lumbar degenerative disorders. Geriatr Gerontol Int 2022; 22: 121-126.