Human cytomegalovirus (HCMV) is a member of the herpesvirus family. HCMV infection persists throughout the host lifespan in a latent state following primary infection. The ability of HCMV to escape control by the host immune system and its resulting reactivation suggests the importance of ongoing immune surveillance in the prevention of HCMV reactivation. HCMV is a common cause of opportunistic infection that causes severe and fatal disease in immune-compromised individuals. In inflammatory bowel disease patients, particularly those with ulcerative colitis (UC), HCMV is often reactivated because these patients are frequently treated with immunosuppressive agents. This reactivation exacerbates colitis. Additionally, HCMV infection can induce severe colitis, even in patients with UC who have never been treated with immunosuppressive agents. However, the role of HCMV in colonic inflammation in patients with UC remains unclear. Here, we present previous and current clinical data on the diagnosis and treatment of HCMV infection in UC. Additionally, our experimental data from a newly established mouse model mimicking UC with concomitant CMV infection clearly demonstrate that inflammation could result in the exacerbation of UC disease activity with induction of HCMV reactivation. In summary, optimal control of colonic inflammation should be achieved in UC patients who are refractory to conventional immunosuppressive therapies and are positive for HCMV.
Animals ; Colitis ; Colitis, Ulcerative* ; Colon ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Diagnosis* ; Humans ; Immune System ; Immunosuppressive Agents ; Inflammation* ; Inflammatory Bowel Diseases ; Mice ; Opportunistic Infections ; Tumor Necrosis Factor-alpha ; Ulcer* ; United Nations

BACKGROUND/AIMS: Our physicians work to expand the possibilities to treat female patients with inflammatory bowel disease (IBD) who wish to become pregnant. Although many drugs, including 5-aminosalicylate (5-ASA), corticosteroids, immunomodulators, and biologics, are used safely during pregnancy, few reports have described the therapeutic regimen throughout pregnancy and the management of patients who relapse during pregnancy precisely. The aim of this study was to assess the management of patients with IBD during pregnancy. METHODS: We identified 19 patients (five with Crohn's disease and 14 with ulcerative colitis [UC]) who became pregnant with a total of 23 pregnancies between May 2005 and May 2015 by reviewing the medical records of Kyoto University Hospital. The following data were collected: the maternal variables, the IBD treatment type, the disease activity, the pregnancy outcome, and the mode of delivery. RESULTS: Among the 19 patients, 18 had become pregnant after being diagnosed with IBD, while one had developed UC newly after pregnancy. Throughout the gestation, all patients were treated with probiotics, 5-ASA, prednisolone, cytapheresis, or infliximab. The relapse rate during pregnancy was 21.7% (5/23 cases). The five patients who experienced a relapse were able to pursue their pregnancy after intensification of their treatments. There were no adverse fetal or neonatal problems, except in one case that required an emergency Caesarean section because of placental dysfunction and in which a very low-birth-weight infant was born preterm. CONCLUSIONS: Our present data confirmed that even if the disease flares up during pregnancy, good pregnancy outcomes can be achieved with an optimal intensification of the patient's treatment.
Adrenal Cortex Hormones ; Asian Continental Ancestry Group* ; Biological Products ; Cesarean Section ; Colitis, Ulcerative ; Crohn Disease ; Cytapheresis ; Emergencies ; Female ; Humans ; Immunologic Factors ; Infant, Low Birth Weight ; Infant, Newborn ; Inflammatory Bowel Diseases* ; Infliximab ; Medical Records ; Mesalamine ; Prednisolone ; Pregnancy ; Pregnancy Outcome ; Probiotics ; Recurrence

BACKGROUND/AIMS: Early use of biologics in patients with Crohn's disease (CD) improves quality of life. However, the effects of the early use of immunomodulators on long-term outcomes remain unclear. This study aimed to evaluate the effects of immunomodulators in patients with CD. METHODS: Between January 2004 and December 2011, 47 biologic-naive CD patients treated with thiopurines alone for remission maintenance were analyzed. The patients were classified into 2 groups depending on the presence or absence of digestive complications. We evaluated the efficacy of and predictive factors for thiopurine use for remission maintenance. RESULTS: The cumulative relapse rates at 24 and 60 months were 13.7% and 35.4%, respectively. Regarding patient characteristics, there was a significant difference in patient history of surgery between the non-relapse and relapse groups (P=0.021). The cumulative relapse rate was lower in patients without a history of surgery than in those with such a history (27.2% and 52.9% at 60.0 months, respectively). Multivariate analysis suggested that the prevalence of stricturing and penetrating complications is an independent factor for relapse. The cumulative relapse rate in patients without a history of surgery was significantly lower in the non-stricturing and non-penetrating group than in the stricturing and penetrating group (11.8% at 85.0 months vs. 58.5% at 69.0 months; P=0.036). CONCLUSIONS: Thiopurine use might be beneficial for the long-term maintenance of remission in biologic-naive Crohn's disease patients without digestive complications and a history of surgery.
Asian Continental Ancestry Group* ; Biological Products ; Crohn Disease* ; Humans ; Immunologic Factors ; Multivariate Analysis ; Prevalence ; Quality of Life ; Recurrence

BACKGROUND/AIMS: The long-term clinical outcomes of patients with bio-naive ulcerative colitis (UC) who maintain remission with thiopurine are unclear. The aim of this study was to assess the long-term efficacy and safety of maintenance treatment with thiopurine in UC patients. METHODS: This was a retrospective observational cohort analysis conducted at a single center. Between December 1998 and August 2013, 59 of 87 patients with bio-naive UC who achieved remission after induction with treatments other than biologics were enrolled. Remission maintenance with thiopurine was defined as no concomitant treatment needed other than 5-aminosalicylate without relapse. We assessed the remission-maintenance rate, mucosal healing rate, colectomy-free rate, and treatment safety in UC patients who received thiopurine as maintenance treatment. RESULTS: The 84-month cumulative remission-maintenance and colectomy-free survival rates in the UC patients who were receiving maintenance treatment with thiopurine and 5-aminosalicylate were 43.9% and 88.0%, respectively. Of the 38 patients who underwent colonoscopy during thiopurine maintenance treatment, 23 (60.5%) achieved mucosal healing. Of the 59 patients who achieved clinical remission with thiopurine, 6 patients (10.2%) discontinued the thiopurine therapy because of adverse events. CONCLUSIONS: Our study demonstrates the long-term efficacy and safety of thiopurine treatment in patients with bio-naive UC.
Asian Continental Ancestry Group* ; Biological Products ; Cohort Studies ; Colitis, Ulcerative* ; Colonoscopy ; Humans ; Mesalamine ; Recurrence ; Retrospective Studies ; Survival Rate

A 75-year-old man was admitted to our hospital with sudden onset of vomiting and abdominal distension. The patient was taking medication for arrhythmia. Computed tomography showed stenosis of the ileum and a small bowel dilatation on the oral side from the region of stenosis. A transnasal ileus tube was placed. Enteroclysis using contrast medium revealed an approximately 6-cm afferent tubular stenosis 10 cm from the terminal ileum and thumbprinting in the proximal bowel. Transanal double-balloon enteroscopy showed a circumferential shallow ulcer with a smooth margin and edema of the surrounding mucosa. The stenosis was so extensive that we could not perform endoscopic balloon dilation therapy. During hospitalization, the patient's nutritional status deteriorated. In response, we surgically resected the region of stenosis. Histologic examination revealed disappearance of the mucosal layer and transmural ulceration with marked fibrosis, especially in the submucosal layer. Hemosiderin staining revealed sideroferous cells in the submucosal layers. Based on the pathologic findings, the patient was diagnosed with ischemic enteritis. The patient's postoperative course was uneventful.
Aged ; Arrhythmias, Cardiac ; Constriction, Pathologic* ; Dilatation ; Double-Balloon Enteroscopy ; Edema ; Enteritis* ; Fibrosis ; Hemosiderin ; Hospitalization ; Humans ; Ileum ; Ileus ; Intestines ; Ischemia ; Mucous Membrane ; Nutritional Status ; Ulcer ; Vomiting

Objective：Home visits conducted in the early rehabilitation phase through an online connection between the patient's home and the hospital are termed online home visits. They enable real-time sharing of home information and patient and family wishes between the family and the therapists participating from home with healthcare professionals at the hospital. This study aimed to evaluate the usefulness of online home visits.Methods：We enrolled 75 patients with musculoskeletal or cerebrovascular disease discharged from a convalescent rehabilitation ward and classified them as those who received online home visits (online group, n＝25) and in-person home visits (non-online group, n＝50) within 7 days of hospitalization. Functional independence measure (FIM) efficiency was compared between the groups. Rehabilitation treatment changes made by therapists after virtual home visits were surveyed.Results：In patients with musculoskeletal diseases, FIM efficiency was significantly higher, and the length of hospital stay was significantly shorter in the online group (n＝14, 1.0 ± 0.5 points/day) than in the non-online group (n＝26, 0.7 ± 0.5 points/day) (p＜0.05). Many therapists who participated in virtual home visits modified their rehabilitation therapy afterwards by recreating the home environment in the rehabilitation room and implementing rehabilitation therapy for home activities.Conclusion：Virtual home visits can facilitate rehabilitation therapy more appropriate to the home environment because they provide visual information about the home. The present findings indicate the contribution of online home visits to FIM efficiency improvement and home discharge preparation.

Objective：Home visits conducted in the early rehabilitation phase through an online connection between the patient's home and the hospital are termed online home visits. They enable real-time sharing of home information and patient and family wishes between the family and the therapists participating from home with healthcare professionals at the hospital. This study aimed to evaluate the usefulness of online home visits.Methods：We enrolled 75 patients with musculoskeletal or cerebrovascular disease discharged from a convalescent rehabilitation ward and classified them as those who received online home visits (online group, n＝25) and in-person home visits (non-online group, n＝50) within 7 days of hospitalization. Functional independence measure (FIM) efficiency was compared between the groups. Rehabilitation treatment changes made by therapists after virtual home visits were surveyed.Results：In patients with musculoskeletal diseases, FIM efficiency was significantly higher, and the length of hospital stay was significantly shorter in the online group (n＝14, 1.0 ± 0.5 points/day) than in the non-online group (n＝26, 0.7 ± 0.5 points/day) (p＜0.05). Many therapists who participated in virtual home visits modified their rehabilitation therapy afterwards by recreating the home environment in the rehabilitation room and implementing rehabilitation therapy for home activities.Conclusion：Virtual home visits can facilitate rehabilitation therapy more appropriate to the home environment because they provide visual information about the home. The present findings indicate the contribution of online home visits to FIM efficiency improvement and home discharge preparation.

Background: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%–6.4%, 6.5%–7.4%, and ≥7.5%. Results: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%–6.4%, 6.5%–7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%– 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. Conclusion Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%–7.4%, contributing to NAFLD progression.

Objective: Our knowledge of human neural crest stem cells (NCSCs) is expanding, owing to recent advances in technologies utilizing human-induced pluripotent stem cells (hiPSCs) that generate NCSCs. However, the clinical application of these technologies requires the reduction of xeno-materials. To overcome this significant impediment, this study aimed to devise a novel method to induce NCSCs from hiPSCs without using a feeder cell layer.Materials and Methods: hiPSCs were cultured in feeder-free maintenance media containing the Rho-associated coiled-coil forming kinase inhibitor Y-27632. When the cells reached 50–70% confluence, differentiation was initiated by replacing the medium with knockout serum replacement (KSR) medium containing Noggin and SB431542. The KSR medium was then gradually replaced with increasing concentrations of Neurobasal medium from day 5 to 11.Results: Immunocytochemistry and flow cytometry were performed 12 days after induction of differentiation and revealed that the cells generated from hiPSCs expressed the NCSC markers p75 and HNK-1, but not the hiPSC marker SOX2.Conclusion: These findings demonstrate that hiPSCs were induced to differentiate into NCSCs in the absence of feeder cells.

[Objective] This study aimed to investigate the awareness and perceptions of cosmetic acupuncture among ordinary women.[Method] A questionnaire method was adopted, with a target population of 1,000 ordinary women living in Shizuoka prefecture, which is considered a suitable location for test marketing in Japan.Questionnaires were distributed through the Chambers of Commerce in the prefecture by age group, according to the population ratio, and responses were obtained. The items included (1) basic information; (2) presence and type of facial cosmetic concerns; (3) experience of acupuncture, awareness of cosmetic acupuncture, the medium through which they learned of it, perception of effects, and experience of cosmetic acupuncture; (4) effects and types of cosmetic acupuncture, presence or absence of adverse effects, current treatment status, desired treatment outcomes and reasons for seeking treatment, wishes from treatment clinics, and wishes from practitioners; and (5) 1 month's investment in beauty.[Result] The response rate was 56.2%, and 91.8% of the participants perceived that they had facial cosmetic concerns; 28.8% had experience with acupuncture, whereas 42.0% had knowledge regarding cosmetic acupuncture. Television (45.3%) was the primary source of information regarding this. The most prevalent perception of the effects of cosmetic acupuncture was lifting (44.8%), and 43.2% of the 521 participants inexperienced with cosmetic acupuncture consented to treatment. Participants mostly reported being somewhat interested in the procedure as their reason for wanting to receive treatment (45.3%). The most common reason for opting out of treatment was due to pain (52.6%). Of those who experienced cosmetic acupuncture, 60.0% said they experienced positive effects, and lifting (62.5%) is the most frequently perceived outcome, which matched the commonly held perception. However, among the participants, 45.0% reported negative effects, while 47.5% received the treatment two or more times in the past but did not continue. Participants mainly wanted clean treatment centers and skilled practitioners. The most common monthly investment in beauty was between 3,000 yen and 5,000 yen (28.5%).[Discussion/Conclusion] The results suggest that many women have cosmetic concerns regarding their faces and expect lifting from cosmetic acupuncture. The low treatment rate among women and their reasons for not seeking re-treatment were elucidated in this study, despite their degree of awareness. Further, the problems associated with the development of cosmetic acupuncture were clarified.