Protective effect of previous infection and vaccination against reinfection with BA.5 Omicron subvariant: a nationwide population-based study in Japan.

Background: The Omicron variant of SARS-CoV-2 was reported to evade immunity derived from vaccination and previous infection. A better understanding of hybrid immunity informs effective infection control strategies. Since the reinfection risk was not well-assessed in East Asia, this study aims to evaluate the risk of infection with Omicron subvariant BA.5 among previously infected individuals in Japan. Methods: All notified cases were extracted from the Japanese national COVID-19 surveillance database including 20,297,335 records up to 25 September 2022. Reinfection with BA.5 was defined as the infection notified during the BA.5 dominated period with any prior SARS-CoV-2 infection. The protective effect of prior infections against reinfections with BA.5 was estimated by applying a case-population design and the protective effect of vaccination was estimated by a multivariable Cox regression adjusting for age, sex, variants of prior infection, and the time since the last vaccination. Findings: Among 19,830,548 SARS-CoV-2 first infections, 233,424 (1.2%) were reinfected with BA.5. The protective effect against BA.5 reinfection of prior infection with Wuhan strain was 46%, Alpha variant was 35%, Delta variant was 41%, and BA.1/BA.2 subvariant was 74%. The reduced risk of BA.5 reinfection by 7%, 33%, and 66% was associated with two, three, and four doses of vaccination, respectively, compared with one-dose vaccination. Interpretation: The prior infections with Omicron subvariant BA.1/BA.2 protected BA.5 reinfection more than pre-Omicron variants. Increased frequency of vaccination led to more protection from reinfection with BA.5. Up-to-date vaccination may be encouraged to prevent future reinfection among the previously infected population. Funding: None.

Perioperative Venous Thromboembolism in Ulcerative Colitis: A Multicenter Prospective Study in Japan.

Background: Recently, the prevalence of venous thromboembolism (VTE) in Asian patients with inflammatory bowel disease (IBD) is gradually increasing. IBD surgery is a well-recognized risk factor for VTE. However, there are no prospective studies about VTE after surgery for ulcerative colitis (UC) in Asia. This multicenter prospective study aimed to clarify the prevalence and risk factors for perioperative VTE in UC surgery in Japan. Methods: A total of 134 patients with UC were included from January 1, 2013 to December 31, 2014. Preoperative screening was performed in all patients. In the perioperative period, standard VTE prophylaxis based on risk assessment was administered. The prevalence of pre- and postoperative VTE, its risk factors, and mortality rates were investigated. Results: Perioperative deep vein thrombosis and pulmonary embolism were diagnosed in 15 (11.1%) and 1 patient (0.7%), respectively. All patients were asymptomatic. No surgery-related deaths were found (mortality rate 0%). Seven patients (5.2%) were diagnosed, and 8 (6.4%) during postoperative follow-up by ultrasonography or computed tomography. Forty-seven percent of VTE cases was developed preoperatively. A preoperative hospital length stay of over 5 days was a significant risk factor [P = 0.04; odds ratio: 8.26 (1.06-64.60)] for preoperative VTE. Postoperative deep vein thrombosis occurred in 8 of the 127 patients (6.4%). Six out of these 8 (75.0%) occurred after postoperative day 14. Perioperative blood transfusion was a significant risk factor [P = 0.04; odds ratio: 8.26 (1.06-64.60)] for postoperative VTE. Conclusion: A VTE-conscious perioperative management is as necessary in Asia as in Western countries.

Scale effect of slip boundary condition at solid-liquid interface.

Rapid advances in microelectromechanical systems have stimulated the development of compact devices, which require effective cooling technologies (e.g., microchannel cooling). However, the inconsistencies between experimental and classical theoretical predictions for the liquid flow in microchannel remain unclarified. Given the larger surface/volume ratio of microchannel, the surface effects increase as channel scale decreases. Here we show the scale effect of the boundary condition at the solid-liquid interface on single-phase convective heat transfer characteristics in microchannels. We demonstrate that the deviation from classical theory with a reduction in hydraulic diameters is due to the breakdown of the continuum solid-liquid boundary condition. The forced convective heat transfer characteristics of single-phase laminar flow in a parallel-plate microchannel are investigated. Using the theoretical Poiseuille and Nusselt numbers derived under the slip boundary condition at the solid-liquid interface, we estimate the slip length and thermal slip length at the interface.

Isolation of 6-deoxytetrodotoxin from the pufferfish, Takifugu pardalis, and a comparison of the effects of the C-6 and C-11 hydroxy groups of tetrodotoxin on its activity.

Identification of new tetrodotoxin (TTX, 1) analogues would be significant in the elucidation of its biosynthetic pathway and a study of its structure-activity relationships. In this study, a new TTX analogue, 6-deoxyTTX (2), was isolated from the ovary of the pufferfish, Takifugu pardalis, and the structure was determined using spectroscopic methods. Compound 2 was also identified in other marine animals, Nassarius snail and blue-ringed octopuses, using LC-MS. Furthermore, we investigated the voltage-gated sodium channel blocking activity of 2 by examination of the inhibitory activities to cytotoxicity induced by ouabain and veratridine in mouse neuroblastoma cells (Neuro-2a). The activities were then compared with those of 1, 11-deoxyTTX (3), and 6,11-dideoxyTTX (4). The EC50 value for 2 was estimated to be 6.5±2.2 nM, approximately 3-fold larger than that of 1 (2.1±0.6 nM) and approximately 20-fold smaller than that of 3. These results suggested that contribution of the C-6 hydroxy group to the activity is less than that of the C-11 hydroxy group.

Time trend and risk factors for reoperation in Crohn's disease in Japan.

BACKGROUND/AIMS: We aimed to evaluate time changes in reoperation rate after initial surgery in Crohn's disease (CD) over the last five decades in Japan and to assess the risk factors for reoperation, given that a decrease in the reoperation rate for CD remains controversial. METHODOLOGY: CD patients (n-476) who underwent initial intestinal surgery were examined. Case records were collected from 13 institutions and scrutinized retrospectively. The primary outcome measure was the reoperation rate needing intestinal surgery. To evaluate the time changes, we compared medical treatment and reoperation rate in patients from two different periods of time; before and after 2002 when infliximab became available in Japan (1963-2002 and 2003-2008 groups). Univariate and multivariate analyses were performed to examine the influence of independent variables on the cumulative reoperation rate. RESULTS: A total of 201 patients underwent reoperation. Overall 5-year and 10-year cumulative reoperation rates were 31.4% and 61.2%, respectively. In multivariate analysis, an onset of the disease between 1963-2002 (p=0.0199) and postoperative administration of infliximab (p=0.0003) and immunosuppressants (p<0.0001) were significant risk factors for reoperation. The cumulative 5-year reoperation rate decreased significantly in the 2003-2008 group compared to the 1963-2002 group (6.3% vs. 32.9%, p<0.05). CONCLUSIONS: The reoperation rate for CD has decreased significantly in recent years in Japan. However, to further confirm this time trend, we need to evaluate CD patients with a longer follow-up period.

Interval of less than 5 years between the first and second operation is a risk factor for a third operation for Crohn's disease.

BACKGROUND: Previous studies have shown various risk factors for the initial and/or the second operation for Crohn's disease (CD). However, limited data are available with regard to the risk factors for a third operation. We aimed to clarify the risk factors for a third operation for CD. METHODS: A total of 200 CD patients who underwent a second intestinal surgery at 13 institutions were examined. We performed univariate and multivariate analyses to examine the influence of independent variables on the cumulative rate of needing a third operation. RESULTS: A total of 95 patients underwent a third operation. The overall 5-year and 10-year cumulative rates for the third operation were 42.2% and 71.0%, respectively. In univariate analysis, the interval between the initial and the second operation (P = 0.0069), postoperative administration of infliximab (P = 0.0030), and the anatomical site of the disease (P = 0.0132) were significant risk factors for the third operation. In multivariate analysis, the interval between the initial and the second operation (P = 0.0287) and postoperative administration of infliximab (P = 0.0297) remained significant risk factors for the third operation. The cumulative 5-year third operation rate was significantly higher in patients with an interval of less than 5 years between the first and second operations than for those with an interval of 5 years or more (47.8% versus 35.2%, P = 0.0232). CONCLUSIONS: An interval of less than 5 years between the first and the second operations is a significant risk factor for a third operation in patients with CD.

[A case of anal cancer with rapidly rising CEA in longstanding perianal Crohn disease after infliximab administration].

Infliximab is effective in the treatment of steroid-resistant Crohn disease. However, there is clinical concern about a possible correlation between an increased risk of anorectal cancer and infliximab treatment. We report a case of anorectal cancer in long-standing perianal Crohn disease. A 34-year-old patient with a long-standing perianal lesion of Crohn disease underwent 3 sessions of infliximab therapy. After therapy, the concentration of plasma CEA was 36.5ng/ml and rose to 91.4ng/ml. We suspected anorectal cancer, so abdominoperineal resection was performed. The histological findings indicated mucinous adenocarcinoma. Monitoring of patients with long-standing perianal Crohn disease is considered essential for early diagnosis of anal cancer after obtaining biopsy samples from perianal lesions. Additionally, when infliximab is started for perianal Crohn disease, thorough examination for perianal lesion should be performed.

Early diagnosis and early corticosteroid administration improves healing of peristomal pyoderma gangrenosum in inflammatory bowel disease.

PURPOSE: To evaluate the efficacy of early diagnosis and early administration of corticosteroid for peristomal pyoderma gangrenosum, a prospective study was carried out. METHODS: In April 1998, we began studying a new treatment regimen of peristomal pyoderma gangrenosum in which prednisone at a dose of 20 to 40 mg was administered systemically immediately after diagnosis. Early-stage peristomal pyoderma gangrenosum was treated concurrently with topical cadexomer iodine, and at the granulation stage, treatment with clobetasol ointment was started. Healing of peristomal pyoderma gangrenosum was determined by complete epithelialization of ulcer without pain or exudates. Patients were assigned to group A (n = 7) before April 1998 and group B (n = 10) after April 1998, and historical comparison was done between the 2 groups. RESULTS: In group A, all patients had ulcerative colitis, and in group B, 7 patients had ulcerative colitis, 2 had Crohn's disease, and one had indeterminate colitis. In group B, significantly earlier diagnosis (P = 0.0093), earlier start of treatment (P = 0.0057), higher initial dose of corticosteroid (P = 0.0052), and earlier healing of peristomal pyoderma gangrenosum (P = 0.0023) were observed. CONCLUSIONS: Early diagnosis and early corticosteroid administration appeared to be effective for promoting healing of peristomal pyoderma gangrenosum.

[Carcinoma arising from ileorectal fistula in a patient with Crohn's disease].

A 72-year-old man was given a diagnosis of Crohn's disease in 1976 at age 44, and partial resection of is ileum was performed. In November 1982, barium enema examination revealed on ileorectal fistula. As he had no complaint, conservative therapy was chosen. In August 2003, he had high fever and CT scan revealed presacral abscess. Ileocecal resection, partial resection of is small intestine and loop sigmoid colostomy were performed. In December 2004, the serum level of CEA was gradually elevated and he complained of anal mucus discharge. Endoscopic examination showed a fistula orifice in the rectum and biopsy of the fistula revealed mucinous adenocarcinoma. We performed abdominoperineal resection of the rectum with partial resection of the sacrum. We thought that careful observation helped the detection of such a rare case of carcinoma arising from a fistula tract.

Infiltration of CD19+ plasma cells with frequent labeling of Ki-67 in corticosteroid-resistant active ulcerative colitis.

Abnormalities in humoral immunity are implicated in the pathogenesis of ulcerative colitis. However, the detailed mechanisms of B-cell activation in the locale remain unaccounted for. We analyzed ulcerative colitis from the standpoint of lymphocytic expansion in the loco. Intestinal specimens obtained at surgery from 30 patients with ulcerative colitis treated with corticosteroids and 15 with Crohn's disease were analyzed by immunohistochemistry and flow cytometry. Ulcerative colitis was characterized by a diffuse distribution of Ki-67(+) small round cells particularly in the ulcer base (that were CD19(+) and CD20(-)), with a significant number of them also CD138(+). Immunoelectron microscopy for CD19 revealed an abundance of rough endoplasmic reticulum in the cytoplasm. These indicated that they are of immature plasma lineage cells. By contrast, plasma cells in Crohn's disease were negative for CD19, and the labeling for Ki-67 was infrequent, showing mature phenotype. Flow cytometry revealed an occurrence of CD19(+) and CD20(-) cells in ulcerative colitis but not in Crohn's disease. The labeling index of Ki-67 among CD19(+) plasma cells was positively correlated with the clinical activity of ulcerative colitis. High labeling of Ki-67 in CD19(+) plasma cells is specific for active ulcerative colitis that was resistant to medical treatment by corticosteroids.

Measurement of phosphatidylcholine hydroperoxide in mild ischemia-reperfusion injury in rat intestine.

In the pathogenesis of intestinal ischemia-reperfusion injury, the measurement of lipid peroxides needs to be established. Sprague-Dawley rat intestines were assessed after 30 minutes of occlusion of the superior mesenteric artery followed by reperfusion at 30, 60, 120, 180, 360 minutes. Grade of the mucosal injury, accumulation of the activated neutrophils and ICAM-1 expression were transiently increased after reperfusion. Two measuring methods of mucosal lipid peroxides using thiobarbituric acid reacting substance (TBARS) and phosphatidylcholine hydroperoxide (PCOOH) were compared. PCOOH level was significantly increased after reperfusion, while the mucosal TBARS level showed no significant change. In conclusion, lipid peroxidation could be detected with high specificity and sensitivity by measuring the mucosal phosphatidylcholine hydroperoxide level.