Intestinal outcome of bone marrow transplantation for monogenic inflammatory bowel disease.

BACKGROUND: Some monogenic inflammatory bowel diseases (IBDs) are known to be refractory to conventional treatments. Although allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has become a curative therapeutic option for certain monogenic IBDs, its effectiveness regarding endoscopic improvements has not been clarified. METHODS: The clinical course and endoscopic findings of patients with monogenic IBDs who were treated with allo-HSCT between December 2017 and November 2018 at the National Center for Child Health and Development, were retrospectively reviewed. The clinical disease activity was assessed using the weighted Pediatric Crohn's Disease Activity Index (wPCDAI) and the endoscopic finding was evaluated using the Simple Endoscopic Score for Crohn's Disease (SES-CD). Clinical remission was defined as a wPCDAI <10 and endoscopic remission was defined as an SES-CD of 2 or less. RESULTS: Four patients with severe monogenic IBDs, including three with X-linked inhibitors of apoptosis protein (XIAP) deficiency and one with interleukin-10 signaling defect, were treated with allo-HSCT with reduced-intensity conditioning. In four patients, the maximum scores of wPCDAI and SES-CD before allo-HSCT ranged from 67.5 to 120 and 20 to 34, respectively. After allo-HSCT, all four patients showed a significant improvement in intestinal inflammation and achieved both clinical and endoscopic remission. Although patients with XIAP deficiency presented with post-transplant hemophagocytic lymphohistiocytosis and a relatively late engraftment, all patients achieved prolonged clinical remission, and IBD medications were successfully discontinued in all patients. CONCLUSION: Allo-HSCT for monogenic IBD resulted in complete clinical resolution with endoscopically confirmed mucosal healing.

Metal atom-guided conformational analysis of single polynuclear coordination molecules.

Microscopic observation of single molecules is a rapidly expanding field in chemistry and differs from conventional characterization techniques that require a large number of molecules. One of such form of single-molecule microscopy is high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), which is especially suitable for coordination compounds because of its atomic number-dependent contrast. However, to date, single-molecule observations using HAADF-STEM has limited to simple planar molecules. In the present study, we demonstrate a direct structural investigation of nonplanar dendronized polynuclear Ir complexes with subnanometer resolution using Ir as an atomic label. Decreasing the electron dose to the dendrimer complexes is critical for the single-molecule observation. A comparison with simulated STEM images of conformational isomers is performed to determine the most plausible conformation. Our results enlarge the potential of electron microscopic observation to realize structural analysis of coordination macromolecules, which has been impossible with conventional methods.

[Small B-cell neoplasm responding to ibrutinib after 17 years of cold agglutinin disease symptom].

In this study, we report a case of a 77-year-old woman who was presented with anemia in the winter of 2002. She was diagnosed with cold agglutinin disease (CAD) and treated with corticosteroids. Further, her hemoglobin levels were maintained between 7.0 g/dl and 8.0 g/dl. In May 2019, mature peripheral blood lymphocytes increased with exacerbation of hemolytic anemia. The lymphocytes were positive for CD19 and CD20, but negative for CD5, CD10, and CD23. Additionally, they were positive for cell surface IgM-κ. The B-cell neoplasm could not be further subclassified due to the lack of BCL2-IgH and BCL1-IgH rearrangement and morphology. The IgM-κ-type M-protein was found in serum, and the direct Coombs test was negative for IgG but positive for C3b/C3d. These findings suggested that small B-cell neoplasm-associated M-protein was involved in the development of CAD through complement activation. Based on the presence of TP53 deletion, the patient was treated with ibrutinib monotherapy. Although hemolysis rapidly improved with a dramatic decrease in lymphocytes, she died from a cerebral hemorrhage. It is assumed that ibrutinib improved CAD through suppression of small B-cell neoplasm-related M-protein. CAD can precede lymphoproliferative disorders; however, the risk of ibrutinib-associated hemorrhage should be noted.

Isomerizations of a Pt4 cluster revealed by spatiotemporal microscopic analysis.

We now report the first direct observation of the fluxional nature in which the four-atomic platinum cluster (Pt4) randomly walks through several isomers. Time-lapse analysis by a Cs-corrected transmission electron microscope allowed us to acquire the atomic coordinates at a sub-angstrom space resolution and 0.2 s time resolution for each cluster isomer. The analysis revealed that the isomerization follows a simple first-order kinetic model.

Exacerbation of autoimmune hemolytic anemia induced by the first dose of programmed death-1 inhibitor pembrolizumab: a case report.

Immune checkpoint inhibitors (ICIs) have demonstrated efficacy against various types of cancers. In addition to immune-related adverse events (irAEs) induced by ICIs, exacerbation of baseline autoimmune disease has been occasionally reported. This is the first report of autoimmune hemolytic anemia (AIHA) exacerbated by pembrolizumab. An 82-year-old Japanese male was diagnosed with lung adenocarcinoma 2 years ago. The patient had chronic anemia with positive direct and indirect Coombs test prior to initiating pembrolizumab therapy at a nearby hospital. However, a definitive diagnosis of AIHA was not made at that time. Seventeen days after the first dose of pembrolizumab, the patient was admitted to the Kobe City Medical Center General Hospital with severe hemolytic anemia (Hb 3.6 g/dL). After thorough examinations including bone marrow biopsy, the patient was diagnosed with pre-existing AIHA exacerbated by pembrolizumab therapy. Two weeks after treatment with prednisone, the levels of hemoglobin became stable with the reduced frequency of blood transfusion and improvements of hemolytic findings on blood tests and the patient was discharged from the hospital. This case report highlighted the importance of determining the patient's pre-existing autoimmune status associated with chronic anemia prior to initiating treatment with ICIs.

Expression of multiple leukemic stem cell markers is associated with poor prognosis in de novo acute myeloid leukemia.

Leukemic stem cells (LSCs) play a crucial role in chemotherapy resistance in acute myeloid leukemia (AML). Although the association between the expression of individual LSC markers and poor prognosis has been reported, few studies have evaluated the prognostic effect of multiple LSC markers in patients with AML. Herein, we examined three LSC markers (CD25, CD96, and CD123) and the combined effect of their expression on clinical outcome. We retrospectively analyzed 80 adult patients with de novo AML who received intensive chemotherapy. Multiple LSC marker expression was significantly associated with shorter three-year overall survival (OS), compared with single or no LSC marker expression (18.2 vs. 65.0%, p < .001). Multivariate analysis showed that the expression of multiple LSC markers remained significant in terms of three-year OS (hazard ratio: 3.80, p = .001). Therefore, the combined evaluation of several LSC markers can predict the clinical outcome in patients with AML.

Fabrication of full-color GaN-based light-emitting diodes on nearly lattice-matched flexible metal foils.

GaN-based light-emitting diodes (LEDs) have been widely accepted as highly efficient solid-state light sources capable of replacing conventional incandescent and fluorescent lamps. However, their applications are limited to small devices because their fabrication process is expensive as it involves epitaxial growth of GaN by metal-organic chemical vapor deposition (MOCVD) on single crystalline sapphire wafers. If a low-cost epitaxial growth process such as sputtering on a metal foil can be used, it will be possible to fabricate large-area and flexible GaN-based light-emitting displays. Here we report preparation of GaN films on nearly lattice-matched flexible Hf foils using pulsed sputtering deposition (PSD) and demonstrate feasibility of fabricating full-color GaN-based LEDs. It was found that introduction of low-temperature (LT) grown layers suppressed the interfacial reaction between GaN and Hf, allowing the growth of high-quality GaN films on Hf foils. We fabricated blue, green, and red LEDs on Hf foils and confirmed their normal operation. The present results indicate that GaN films on Hf foils have potential applications in fabrication of future large-area flexible GaN-based optoelectronics.

[Examination of the effectiveness of heart rate control using intravenous ß-blocker in 64-slice coronary computed tomography angiography].

The purpose of this study is to clarify the effectiveness of the use of ß-blocker in coronary computed tomography angiography (CCTA). In 1783 patients, heart rate was controlled by propranolol injection to patients with heart rates of 61 bpm or more. As a result, the scan heart rate (58.8±6.5 bpm) decreased significantly compared with the initial heart rate (72.7±9.4 bpm). Prospective gating method was used by 61.9% including 64.3% of the intravenous ß-blocker injection group. Moreover, daily use of oral ß-blocker had influence on reduction of the scan heart rate (daily use group: 60.1±6.5 bpm vs. unuse group: 58.5±6.3 bpm p<0.01). When we evaluated the image quality of CCTA by the score, the improvement of the score was obviously admitted by 65 bpm or less of the scan heart rate. The ratio of scan heart rate that was controlled by 65 bpm or less was decreased in the initial heart rate groups that were 81 bpm or more. The incidence of adverse reactions by the propranolol injection was few, and these instances only involved slight symptoms. Therefore, heart rate control with the use of ß-blocker is useful for the image quality improvement of CCTA. This form of treatment can be safely enforced.

Clinical outcome of jejunal pouch double-tract reconstruction after total gastrectomy.

BACKGROUND/AIMS: The importance of the duodenal passage and the need for pouch reconstruction after total gastrectomy are matters of controversy. METHODOLOGY: Twenty consecutive patients with early gastric cancer were studied 20who underwent jejunal pouch double-tract (JPD) reconstruction after total gastrectomy. Nutritional variables were examined for > or =10 years postoperatively. RESULTS: The mean operation time was 204 minutes. There was no anastomotic leakage and no hospital mortality. Anastomotic stenosis between the esophagus and a jejunal pouch developed in 2 patients (10%), and reflux esophagitis was observed in 4 (20%). Symptoms were controlled by conserva tive treatment within 3 years after surgery. Body mass indices in all patients were significantly decreased from 1 month (p<0.05) to 10 years (p<0.005) after the operation. The mean body weight decrease occurring during the first to the tenth postoperative year was 12.7% overall, but 17.8% and 9.1% in patients aged > or =60 years and <60 years, respectively. The body weight decreases from 3 (p<0.05) to 6 (p<0.01), and at 9 years (p<0.01) were significantly lower before 60 years of age than after. CONCLUSIONS: JPD reconstruction facilitates long-term recovery of body weight after total gastrectomy and should be considered before the aged of 60.

Clinical outcome of proximal gastrectomy in patients with early gastric cancer in the upper third of the stomach.

OBJECTIVE: To determine whether clinical outcomes after proximal gastrectomy are better than those after total gastrectomy with Roux-en Y reconstruction. METHODS: We studied 10 consecutive patients with early gastric cancer who underwent esophagogastrostomy after proximal gastrectomy (PG group). Nutritional variables in these patients were compared with those in 10 consecutive patients who underwent Roux-en Y reconstruction after total gastrectomy (TG group). Patients were followed up for 5 years after operation. RESULTS: There was no anastomotic leakage. The total cholesterol level 1 year after operation was higher in the PG group than in the TG group (p< 0.05). Body mass index was significantly lower than the preoperative value between 1 month and 2 years postoperation in the PG group, whereas the TG group showed decreases between 3 months to 5 years postoperation. The percent decreases in body weight at 3 and 4 years in the PG group were lower than those in the TG group (both p< 0.05). Postoperative weight loss was thus milder in the PG group than in the TG group. CONCLUSION: Esophagogastrostomy after PG may produce better clinical outcomes than Roux-en Y reconstruction after TG in patients with early gastric cancer arising in the upper third of the stomach.

Esophagogastrostomy before proximal gastrectomy in patients with early gastric cancers in the upper third of the stomach.

OBJECTIVE: This study was designed to assess the outcome of esophagogastrostomy before proximal gastrectomy in patients with early gastric cancers in the upper third of the stomach. METHODS: From 1997 through 2004, we studied 10 consecutive patients. A stapler was introduced into the stomach, and an esophagogastrostomy was performed before proximal gastrectomy. Hill's posterior gastropexy and Dor's anterior fundic wrap were performed to prevent reflux esophagitis. RESULTS: The operation time was 171 ± 44 minutes, and the intraoperative bleeding volume was 294 ± 228 mL. There was no anastomotic leakage. Anastomotic stenosis, occurring in 40% of the patients, required endoscopic balloon dilatation. Symptoms of reflux esophagitis, occurring in 40% of the patients, resolved within 2 years after operation. As compared with the preoperative value, body mass index was significantly decreased 1 and 2 years after operation, but was similar at 3 to 5 years. The percent decrease in body weight after operation fluctuated between 6% and 8% between 2 and 5 years. Postoperative weight loss was thus mild. CONCLUSIONS: Esophagogastrostomy before proximal gastrectomy may be less invasive, simpler, and produce better outcomes than conventional procedures for the surgical treatment of early gastric cancer in the upper third of the stomach.

Focus on the conditions of resection and reconstruction in gastric cancer. What extent of resection and what kind of reconstruction provide the best outcomes for gastric cancer patients?

To assess the roles of the extent of gastric resection and duodenal food passage reconstruction in gastric cancer, we examined a consecutive series of 1,061 patients who underwent total or partial (proximal and distal) gastrectomies with or without duodenal food passage reconstruction between August of 1974 and January of 2002, and received gastrectomies with D2-3 lymph node dissection. Patients who underwent distal or proximal gastrectomy were found to have significantly better survival rates than those who underwent total gastrectomy in stages 1A (10-year survival: 86.6 and 78.9 vs. 61.6%), 2 (56.5 and 65.6 vs. 34.4%), 3A (45.9 and 33.3 vs. 15.2%), and 4 (5-year survival rates: 23.7 and 50.0 vs. 7.1%). Additionally, patients with duodenal food passage reconstruction or double tract reconstruction also showed significantly better survival rates than those without duodenal food reconstruction in stages 1A (10-year survival: 86.4 and 82.5 vs. 61.7%), 1B (69.9 and 90.6 vs. 54.1%), 2 (60.5 and 63.3 vs. 16.5%), and 3A (39.9 and 47.4 vs. 23.1%). In multivariate analysis, the independent prognostic factors were age at operation, depth of tumor, duodenal food passage reconstruction, and lymph node metastasis. Our results indicate that both the extent of gastric resection and duodenal food passage reconstruction were important factors in the outcome of gastric cancer patients, and that surgeons should perform minimal gastric resection with preservation of the duodenal food passage when the gastric stump is tumor-free.

[A case of advanced gastric cancer with multiple liver metastases responding to TS-1 and CDDP].

A 44-year-old male presented to our hospital with abdominal pain. The upper endoscopy revealed advanced gastric cancer. On the abdominal CT, there was evidence of multiple, massive liver metastases. After total gastrectomy, the patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks' rest and 6 weekly infusions of 10 mg CDDP in an intra-hepatic artery as 1 cycle. On the follow-up CT, the liver metastases had decreased significantly both in size and number after 2 cycles. The current case suggests that TS-1 and CDDP may have a potent therapeutic efficacy in cases of advanced gastric cancer with multiple liver metastases.