Severe induction of aberrant DNA methylation by nodular gastritis in adults.

BACKGROUND: Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-type gastric cancer in adults. However, it is unknown whether aberrant DNA methylation, which is induced by atrophic gastritis (AG) and is a risk for gastric cancer, is induced by NG. Here, we analyzed methylation induction by NG. METHODS: Gastric mucosal samples were obtained from non-cancerous antral tissues of 16 NG and 20 AG patients with gastric cancer and 5 NG and 6 AG patients without, all age- and gender-matched. Genome-wide methylation analysis and expression analysis were conducted by a BeadChip array and RNA-sequencing, respectively. RESULTS: Clustering analysis of non-cancerous antral tissues of NG and AG patients with gastric cancer was conducted using methylation levels of 585 promoter CpG islands (CGIs) of methylation-resistant genes, and a large fraction of NG samples formed a cluster with strong methylation induction. Promoter CGIs of CDH1 and DAPK1 tumor-suppressor genes were more methylated in NG than in AG. Notably, methylation levels of these genes were also higher in the antrum of NG patients without cancer. Genes related to lymphoid follicle formation, such as CXCL13/CXCR5 and CXCL12/CXCR4, had higher expression in NG, and genes involved in DNA demethylation TET2 and IDH1, had only half the expression in NG. CONCLUSIONS: Severe aberrant methylation, involving multiple tumor-suppressor genes, was induced in the gastric antrum and body of patients with NG, in accordance with their high gastric cancer risk.

Phlegmonous Colitis after Cold Snare Polypectomy in an Immunosuppressed Patient: A Case Report.

Introduction: Cold snare polypectomy (CSP) is a procedure with a low risk of complications. Here, we present our experience of a rare case of submucosal abscess following CSP in an immunosuppressed patient. Case Presentation: Seventy-eight-year-old man underwent CSP, developing a fever, chills, and right lower abdominal pain 8 days later. Ultrasound and computed tomography revealed wall thickening of the ascending colon, presenting as whitening and thickening of the same region, and excretion of pus was observed after biopsy. The diagnosis was made as phlegmonous colitis, for which antibiotic therapy was commenced. The patient was diagnosed with chronic myelomonocytic leukemia (CMML) during admission. We considered the following reasons as possible causes of infectious complications after CSP: (1) the patient had a highly immunosuppressed state with comorbidities such as CMML as well as diabetes mellitus and (2) disruption of the mucosal barrier occurred during endoscopic resection. Conclusion: Although CSP is generally considered safe, our case highlights the potential for serious complications in immunosuppressed patients. Therefore, the decision to perform CSP in such patients should be made with caution to avoid unnecessary interventions. In instances where treatment is essential, thorough bowel preparation and prophylactic antibiotic use may be necessary to mitigate the risks.

Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

Development and validation of a scoring system for in-hospital mortality following band ligation in esophageal variceal bleeding.

OBJECTIVES: We aimed to develop and validate a simple scoring system to predict in-hospital mortality after endoscopic variceal ligation (EVL) for esophageal variceal bleeding. METHODS: Data from a 13-year study involving 46 Japanese institutions were split into development (initial 7 years) and validation (last 6 years) cohorts. The study subjects were patients hospitalized for esophageal variceal bleeding and treated with EVL. Variable selection was performed using least absolute shrinkage and selection operator regression, targeting in-hospital all-cause mortality as the outcome. We developed the Hospital Outcome Prediction following Endoscopic Variceal Ligation (HOPE-EVL) score from ß coefficients of multivariate logistic regression and assessed its discrimination and calibration. RESULTS: The study included 980 patients: 536 in the development cohort and 444 in the validation cohort. In-hospital mortality was 13.6% and 10.1% for the respective cohorts. The scoring system used five variables: systolic blood pressure (<80 mmHg: 2 points), Glasgow Coma Scale (≤12: 1 point), total bilirubin (≥5 mg/dL: 1 point), creatinine (≥1.5 mg/dL: 1 point), and albumin (<2.8 g/dL: 1 point). The risk groups (low: 0-1, middle: 2-3, high: ≥4) in the validation cohort corresponded to observed and predicted mortality probabilities of 2.0% and 2.5%, 19.0% and 22.9%, and 57.6% and 71.9%, respectively. In this cohort, the HOPE-EVL score demonstrated excellent discrimination ability (area under the curve [AUC] 0.890; 95% confidence interval [CI] 0.850-0.930) compared with the Model for End-stage Liver Disease score (AUC 0.853; 95% CI 0.794-0.912) and the Child-Pugh score (AUC 0.798; 95% CI 0.727-0.869). CONCLUSIONS: The HOPE-EVL score practically and effectively predicts in-hospital mortality. This score could facilitate the appropriate allocation of resources and effective communication with patients and their families.

Effectiveness of antibiotic prophylaxis for acute esophageal variceal bleeding in patients with band ligation: A large observational study.

BACKGROUND: Esophageal variceal bleeding is a severe complication associated with liver cirrhosis and typically necessitates endoscopic hemostasis. The current standard treatment is endoscopic variceal ligation (EVL), and Western guidelines recommend antibiotic prophylaxis following hemostasis. However, given the improvements in prognosis for variceal bleeding due to advancements in the management of bleeding and treatments of liver cirrhosis and the global concerns regarding the emergence of multidrug-resistant bacteria, there is a need to reassess the use of routine antibiotic prophylaxis after hemostasis. AIM: To evaluate the effectiveness of antibiotic prophylaxis in patients treated for EVL. METHODS: We conducted a 13-year observational study using the Tokushukai medical database across 46 hospitals. Patients were divided into the prophylaxis group (received antibiotics on admission or the next day) and the non-prophylaxis group (did not receive antibiotics within one day of admission). The primary outcome was composed of 6-wk mortality, 4-wk rebleeding, and 4-wk spontaneous bacterial peritonitis (SBP). The secondary outcomes were each individual result and in-hospital mortality. A logistic regression with inverse probability of treatment weighting was used. A subgroup analysis was conducted based on the Child-Pugh classification to determine its influence on the primary outcome measures, while sensitivity analyses for antibiotic type and duration were also performed. RESULTS: Among 980 patients, 790 were included (prophylaxis: 232, non-prophylaxis: 558). Most patients were males under the age of 65 years with a median Child-Pugh score of 8. The composite primary outcomes occurred in 11.2% of patients in the prophylaxis group and 9.5% in the non-prophylaxis group. No significant differences in outcomes were observed between the groups (adjusted odds ratio, 1.11; 95% confidence interval, 0.61-1.99; P = 0.74). Individual outcomes such as 6-wk mortality, 4-wk rebleeding, 4-wk onset of SBP, and in-hospital mortality were not significantly different between the groups. The primary outcome did not differ between the Child-Pugh subgroups. Similar results were observed in the sensitivity analyses. CONCLUSION: No significant benefit to antibiotic prophylaxis for esophageal variceal bleeding treated with EVL was detected in this study. Global reassessment of routine antibiotic prophylaxis is imperative.

Renal function and lipid metabolism in Japanese HIV-1-positive individuals 288 weeks after switching from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate: a single-center, retrospective cohort study.

BACKGROUND: Continued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism. METHODS: This single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary ß2 microglobulin (Uß2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uß2MG and factors affecting eGFR decline were examined. RESULTS: Sixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uß2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uß2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uß2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uß2MG had no effect on the eGFR decline. CONCLUSIONS: Switching from TDF to TAF for the long term slows eGFR decline, decreases Uß2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.

Marked intestinal trans-differentiation by autoimmune gastritis along with ectopic pancreatic and pulmonary trans-differentiation.

BACKGROUND: Autoimmune gastritis (AIG) is a prevalent chronic inflammatory disease with oncogenic potential that causes destruction of parietal cells and severe mucosal atrophy. We aimed to explore the distinctive gene expression profiles, activated signaling pathways, and their underlying mechanisms. METHODS: A comprehensive gene expression analysis was conducted using biopsy specimens from AIG, Helicobacter pylori-associated gastritis (HPG), and non-inflammatory normal stomachs. Gastric cancer cell lines were cultured under acidic (pH 6.5) conditions to evaluate changes in gene expression. RESULTS: Gastric mucosa with AIG had a unique gene expression profile compared with that with HPG and normal mucosa, such as extensively low expression of ATP4A and high expression of GAST and PAPPA2, which are involved in neuroendocrine tumorigenesis. Additionally, the mucosa with AIG and HPG showed the downregulation of stomach-specific genes and upregulation of small intestine-specific genes; however, intestinal trans-differentiation was much more prominent in AIG samples, likely in a CDX-dependent manner. Furthermore, AIG induced ectopic expression of pancreatic digestion-related genes, PNLIP, CEL, CTRB1, and CTRC; and a master regulator gene of the lung, NKX2-1/TTF1 with alveolar fluid secretion-related genes, SFTPB and SFTPC. Mechanistically, acidic conditions led to the downregulation of master regulator and stemness control genes of small intestine, suggesting that increased environmental pH may cause abnormal intestinal differentiation in the stomach. CONCLUSIONS: AIG induces diverse trans-differentiation in the gastric mucosa, characterized by the transactivation of genes specific to the small intestine, pancreas, and lung. Increased environmental pH owing to AIG may cause abnormal differentiation of the gastric mucosa.

Systemic AL amyloidosis with multiple submucosal hematomas of the colon: a case report and literature review.

Amyloid light-chain (AL) amyloidosis rarely causes colorectal submucosal hematoma. A 76-year-old man presented with a complaint of bloody stool. An initial colonoscopy revealed ulcerative lesions in the descending colon, leading to a diagnosis of ischemic colitis. One month later, he presented with cardiac failure, suspected cardiac amyloidosis, and underwent a second colonoscopy. Although it revealed multiple ulcerative lesions from the ascending to transverse colon, biopsy samples did not confirm amyloid deposition. He underwent a third colonoscopy 3 weeks later due to recurrent bloody stool. It showed multiple submucosal hematomas from the ascending to descending colon concomitant with ulcerative lesions in the descending colon and multiple elevated lesions in the sigmoid colon. Biopsy samples confirmed amyloid deposition. Using a systemic search, multiple myeloma with AL amyloidosis was diagnosed. Colorectal submucosal or intramural hematomas are conditions usually encountered in trauma, antithrombotic use, or coagulation disorders. Based on our review of the literatures, we identified several differences between colorectal intramural hematoma caused by amyloidosis and those caused by other etiologies. We believe that amyloidosis should be considered when relatively small and multiple colorectal hematomas, not restricted to the sigmoid colon, and with concomitant findings of erosions and ulcers, are observed.

Precancerous nature of intestinal metaplasia with increased chance of conversion and accelerated DNA methylation.

OBJECTIVE: The presence of intestinal metaplasia (IM) is a risk factor for gastric cancer. However, it is still controversial whether IM itself is precancerous or paracancerous. Here, we aimed to explore the precancerous nature of IM by analysing epigenetic alterations. DESIGN: Genome-wide DNA methylation analysis was conducted by EPIC BeadArray using IM crypts isolated by Alcian blue staining. Chromatin immunoprecipitation sequencing for H3K27ac and single-cell assay for transposase-accessible chromatin by sequencing were conducted using IM mucosa. NOS2 was induced using Tet-on gene expression system in normal cells. RESULTS: IM crypts had a methylation profile unique from non-IM crypts, showing extensive DNA hypermethylation in promoter CpG islands, including those of tumour-suppressor genes. Also, the IM-specific methylation profile, namely epigenetic footprint, was present in a fraction of gastric cancers with a higher frequency than expected, and suggested to be associated with good overall survival. IM organoids had remarkably high NOS2 expression, and NOS2 induction in normal cells led to accelerated induction of aberrant DNA methylation, namely epigenetic instability, by increasing DNA methyltransferase activity. IM mucosa showed dynamic enhancer reprogramming, including the regions involved in higher NOS2 expression. NOS2 had open chromatin in IM cells but not in gastric cells, and IM cells had frequent closed chromatin of tumour-suppressor genes, indicating their methylation-silencing. NOS2 expression in IM-derived organoids was upregulated by interleukin-17A, a cytokine secreted by extracellular bacterial infection. CONCLUSIONS: IM cells were considered to have a precancerous nature potentially with an increased chance of converting into cancer cells, and an accelerated DNA methylation induction due to abnormal NOS2 expression.

Exploration of predictors associated with bleeding in computed tomography-guided core needle splenic biopsy: A retrospective study.

Splenic diseases may be caused by infections and can be either malignant, such as lymphoma and lung cancer, or benign, such as hemangioma. In some cases, diagnostic uncertainty of imaging persists, and image-guided splenic needle biopsy is a useful diagnostic tool to avoid the disadvantages of incorrect diagnosis, including performing unnecessary splenectomy or not giving the necessary treatment. Splenic biopsies can be divided into ultrasound-guided, computed tomography (CT)-guided fine-needle aspiration, or core needle biopsy (CNB). However, few studies have focused exclusively on complications associated with CT-guided CNB of the spleen. Therefore, we assessed bleeding, the most common complication of CT-guided CNB of the spleen, and evaluated factors associated with the bleeding. Using the biopsy database maintained at the institution, all patients who underwent CT-guided CNB of the spleen between May 2012 and September 2022 were identified retrospectively. The 18 identified patients were divided into post-biopsy bleeding and non-bleeding groups for analysis. In total, 17 patients (94.4%) could be diagnosed accurately with CT-guided CNB. Bleeding complications occurred in 7 cases of CT-guided CNB; of these, 2 patients with Common Terminology Criteria for Adverse Events grade 4 disease required transcatheter arterial embolization. The bleeding group was characterized by diffuse spleen tumors in all cases, with significantly more diffuse spleen tumors than the non-bleeding group. CT-guided CNB is a useful option for neoplastic lesions of the spleen that are difficult to diagnose using imaging alone. However, consideration should be given to post-biopsy bleeding in patients with diffuse splenic tumors.

Endoscopic Papillary Balloon Dilation Can Be Safely Performed in Patients on Dual Antiplatelet Therapy: A Pilot Study.

BACKGROUND AND AIMS: Endoscopic papillary balloon dilation (EPBD), a low-risk procedure for bleeding, has been suggested as an alternative to endoscopic sphincterotomy for papillary dilatation in patients undergoing endoscopic stone removal who are at a higher risk of bleeding. Several guidelines recommend that combination of two antiplatelet agents should be reduced to single antiplatelet therapy when endoscopic sphincterotomy is performed. However, there is no evidence that EPBD affects the risk of bleeding in patients receiving a combination of two antiplatelet agents; thus, we aimed to explore this problem. METHODS: We included 31 patients who underwent EPBD for common bile duct stones at our hospital from May 2014 to August 2022 and received either a combination of two antiplatelet agents or single antiplatelet therapy prior to the procedure. The group receiving a combination of two antiplatelet agents included patients who underwent EPBT without antiplatelet therapy withdrawal or with a shorter withdrawal period than those recommended by the guidelines. RESULTS: In the group that received a combination of two antiplatelet agents, one of the two antiplatelet agents used was thienopyridine. No bleeding was observed after EPBD in this study. We did not find any significant between-group differences in hemoglobin levels and rate of post-endoscopic retrograde cholangiopancreatography pancreatitis. CONCLUSIONS: In patients treated with a combination of two antiplatelet agents, EPBD could be safely performed without bleeding. Therefore, future prospective studies are warranted.

Efficacy for diagnoses of scirrhous gastric cancer and safety of endoscopic ultrasound-guided fine-needle aspiration: A systematic review and meta-analysis.

Scirrhous gastric cancer (SGC) is diagnosed using endoscopy and/or biopsy; however, SGC diagnosis remains challenging owing to its special growth form and morphologic features. Hence, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is minimally invasive and has a high proportion of diagnostic tissue, may be an alternative investigative modality for patients with suspected SGC. This systematic review and meta-analysis aimed to identify and evaluate the evidence for the efficacy and safety of EUS-FNA in patients with suspected SGC. We conducted a systematic review using the PubMed (MEDLINE) and Ichushi-Web (NPO Japan Medical Abstracts Society) databases and included all entries in which SGC was evaluated using EUS-FNA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the databases' inception to October 10, 2022. The primary outcome was the proportion of SGC diagnosed using EUS-FNA. In addition, we analyzed the proportion of adverse events associated with EUS-FNA. The electronic search identified 1890 studies; overall, four studies met the selection criteria and reported data on EUS-FNA performed on 114 patients with suspected SGC. The overall diagnostic yield of EUS-FNA for SGC was 82.6% (95% confidence interval, 74.6-90.6%) and the statistical heterogeneity was 0% (I 2 = 0%), indicating a low heterogeneity. Furthermore, the EUS-FNA diagnostic proportion for SGC lymph node metastasis was 75-100%, indicating a high diagnostic performance. The adverse event rate of EUS-FNA was 0%. EUS-FNA may be an alternative investigation mode for SGC patients with negative esophagogastroduodenoscopy-biopsy results.

Comprehensive review on small common bile duct stones.

Common bile duct stones are among the most common conditions encountered by endoscopists. Therefore, it is well researched; however, some items, such as indications for endoscopic papillary balloon dilatation (EPBD), safety of EPBD and endoscopic sphincterotomy in patients receiving dual antiplatelet therapy or direct oral anticoagulant, selection strategy for retrieval balloons and baskets, lack adequate evidence. Therefore, the guidelines have been updated with new research, while others remain unchanged due to weak evidence. In this review, we comprehensively summarize the standard methods in guidelines and new findings from recent studies on papillary dilation, stone retrieval devices, difficult-to-treat cases, troubleshooting during the procedure, and complicated cases of cholangitis, cholecystolithiasis, or distal biliary stricture.

A case of unsuccessful obliteration of percutaneous transhepatic gastric varices using the IMPEDE embolization plug.

Key Clinical Message: Embolization with IMPEDE embolization plug cannot be confirmed on site. Therefore, we propose that the diameter of the device selected be up to 50% larger than the vein diameter to prevent embolization failure and recanalization. Abstract: Balloon-occluded retrograde transvenous obliteration and percutaneous transhepatic obliteration (PTO) are performed for treating sporadic gastric varices. IMPEDE embolization plug has been recently developed for these procedures; however, no studies have reported its use. This is the first report on its use in PTO of gastric varices.

Comprehensive review on endoscopic ultrasound-guided tissue acquisition techniques for solid pancreatic tumor.

Pancreatic ductal adenocarcinoma is speculated to become the second leading cause of cancer-related mortality by 2030, a high mortality rate considering the number of cases. Surgery and chemotherapy are the main treatment options, but they are burdensome for patients. A clear histological diagnosis is needed to determine a treatment plan, and endoscopic ultrasound (EUS)-guided tissue acquisition (TA) is a suitable technique that does not worsen the cancer-specific prognosis even for lesions at risk of needle tract seeding. With the development of personalized medicine and precision treatment, there has been an increasing demand to increase cell counts and collect specimens while preserving tissue structure, leading to the development of the fine-needle biopsy (FNB) needle. EUS-FNB is rapidly replacing EUS-guided fine-needle aspiration (FNA) as the procedure of choice for EUS-TA of pancreatic cancer. However, EUS-FNA is sometimes necessary where the FNB needle cannot penetrate small hard lesions, so it is important clinicians are familiar with both. Given these recent dev-elopments, we present an up-to-date review of the role of EUS-TA in pancreatic cancer. Particularly, technical aspects, such as needle caliber, negative pressure, and puncture methods, for obtaining an adequate specimen in EUS-TA are discussed.

Clinical features of acute esophageal mucosal lesions and reflux esophagitis Los Angeles classification grade D: A retrospective study.

BACKGROUND: Acute esophageal mucosal lesions (AEMLs) are an underrecognized and largely unexplored disease. Endoscopic findings are similar, and a higher percentage of AEML could be misdiagnosed as reflux esophagitis Los Angeles classification grade D (RE-D). These diseases could have different pathologies and require different treatments. AIM: To compare AEML and RE-D to confirm that the two diseases are different from each other and to clarify the clinical features of AEML. METHODS: We selected emergency endoscopic cases of upper gastrointestinal bleeding with circumferential esophageal mucosal injury and classified them into AEML and RE-D groups according to the mucosal injury's shape on the oral side. We examined patient background, blood sampling data, comorbidities at onset, endoscopic characteristics, and outcomes in each group. RESULTS: Among the emergency cases, the AEML and RE-D groups had 105 (3.1%) and 48 (1.4%) cases, respectively. Multiple variables exhibited significantly different results, indicating that these two diseases are distinct. The clinical features of AEML consisted of more comorbidities [risk ratio (RR): 3.10; 95% confidence interval (CI): 1.68-5.71; P < 0.001] and less endoscopic hemostasis compared with RE-D (RR: 0.25; 95%CI: 0.10-0.63; P < 0.001). Mortality during hospitalization was higher in the AEML group (RR: 3.43; 95%CI: 0.82-14.40; P = 0.094), and stenosis developed only in the AEML group. CONCLUSION: AEML and RE-D were clearly distinct diseases with different clinical features. AEML may be more common than assumed, and the potential for its presence should be taken into account in cases of upper gastrointestinal bleeding with comorbidities.

On the applicability of cosine-modulated pulses for high-resolution solid-state NMR of quadrupolar nuclei with spin > 3/2.

In MQMAS-based high-resolution solid-state NMR experiments of half-integer spin quadrupolar nuclei, the high radiofrequency (RF) field requirement for the MQ excitation and conversion steps with two hard-pulses is often a sensitivity limiting factor in many practical applications. Recently, the use of two cosine-modulated (cos) low-power (lp) pulses, lasting one-rotor period each, was successfully introduced for efficient MQ excitation and conversion of spin-3/2 nuclei with a reduced RF amplitude. In this study, we extend our previous investigations of spin-3/2 nuclei to systems with higher spin values and discuss the applicability of coslp-MQ excitation and conversion in MQMAS and MQ-HETCOR experiments under slow and fast spinning conditions. For the numerical simulations and experiments we used a moderate magnetic field of 14.1 T. Two spin-5/2 nuclei (85Rb and 27Al) are mainly employed with a large variety of CQ values, but we show that the practical set up is also available for higher spin values, such as spin-9/2 with 93Nb in Cs4Nb11O30. We demonstrate for nuclei with spin value larger than 3/2 a preferential use of coslp-MQ acquisition for low-gamma nuclei and/or large CQ values with a much reduced RF-field with respect to that of hard-pulses used with conventional methods.

A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level.

COVID-19 afflicts patients with acute symptoms and longer term sequelae. One of the sequelae is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is often difficult to diagnose, having no established tests. In this article, we synthesize information from literature reviews on patients with ME/CSF that developed after recovery from COVID-19.

The effect of hand therapy on alleviating chemotherapy-induced peripheral neuropathy in a model mouse.

The use of neurotoxic chemotherapeutic agents induces numbness in the limbs through chemotherapy-induced peripheral neuropathy (CIPN). Recently, we found that hand therapy involving finger massage improved mild to moderate numbness in CIPN patients. In this study, we behaviorally, physiologically, pathologically, and histologically investigated the mechanisms underlying hand therapy-induced numbness improvement in a CIPN model mouse. Hand therapy was performed for 21 days after the disease induction. Its effects were evaluated using mechanical and thermal thresholds and blood flow in the bilateral hind paw. Moreover, 14 days after the hand therapy was administered, we assessed the blood flow and conduction velocity in the sciatic nerve, the level of serum galectin-3, and the histological myelin and epidermis-related changes in the hindfoot tissue. Hand therapy significantly improved allodynia, hyperalgesia, blood flow, conduction velocity, serum galectin-3, and epidermal thickness in the CIPN model mouse. Furthermore, we observed the images of repairs of the myelin degeneration. Thus, we found that hand therapy could improve numbness in the CIPN model mouse and that it could help to repair peripheral nerves by promoting blood circulation in the limbs.

Gastric adenocarcinoma of fundic gland type with autoimmune gastritis.

An 87-year-old man with dysphagia presented to our hospital. He was diagnosed with autoimmune gastritis (AIG) with severe atrophy and hypergastrinemia. The patient was positive for parietal cell antibody (PCA) and anti-intrinsic factor antibody (IFA), without evidence of H. pylori infection. A flat elevated tumor was detected in the middle corpus, and therapeutic endoscopic submucosal dissection was performed. Histopathological examination revealed atypical cells mimicking the fundic glands, which were positive for pepsinogen-I and partially positive for MUC6 and H + /K + -ATPase, proliferating to the deep layer. The final diagnosis was gastric adenocarcinoma of the fundic gland type (GAFG). AIG is expected to be difficult to develop GAFG because the basal gastric glands are highly atrophic due to the production of PCA. However, some chief cells may remain and could have the potential to develop into malignancy during AIG progression. Therefore, careful observation is required in patients with AIG when considering the occurrence of GAFG.