Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing. Results: Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016). Conclusion High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.

In order to avoid the risk of COVID-19 among our clinic staffs, remote medical care using tablet-type devices was conducted in our fever outpatient clinic. In about 5 months, there were 87 patients with COVID-19 diagnosed by PCR test. Among them, 24 patients (15 men and 9 women, average age 36.2 years) were treated with Kampo medicine. Four of 24 patients required hospitalization. All patients, including those hospitalized cases, improved their symptoms during the observation period. We believe that Kampo medicine is effective in the early treatment of COVID-19. In addition, we consider that remote medical care using tablet-type devices is one of the useful methods in the treatment of highly contagious infectious diseases.

BACKGROUND: Excess winter mortality caused by cardiovascular disease is particularly profound in cold houses. Consistent with this, accumulating evidence indicates that low indoor temperatures at home increase blood pressure. However, it remains unclear whether low indoor temperatures affect other cardiovascular biomarkers. In its latest list of priority medical devices for management of cardiovascular diseases, the World Health Organization (WHO) included electrocardiography systems as capital medical devices. We therefore examined the association between indoor temperature and electrocardiogram findings. METHODS: We collected electrocardiogram data from 1480 participants during health checkups. We also measured the indoor temperature in the living room and bedroom for 2 weeks in winter, and divided participants into those living in warm houses (average exposure temperature ≥ 18 °C), slightly cold houses (12-18 °C), and cold houses (< 12 °C) in accordance with guidelines issued by the WHO and United Kingdom. The association between indoor temperature (warm vs. slightly cold vs. cold houses) and electrocardiogram findings was analyzed using multivariate logistic regression models, with adjustment for confounders such as demographics (e.g., age, sex, body mass index, household income), lifestyle (e.g., eating habit, exercise, smoking, alcohol drinking), and region. RESULTS: The average temperature at home was 14.7 °C, and 238, 924, and 318 participants lived in warm, slightly cold, and cold houses, respectively. Electrocardiogram abnormalities were observed in 17.6%, 25.4%, and 30.2% of participants living in warm, slightly cold, and cold houses, respectively (p = 0.003, chi-squared test). Compared to participants living in warm houses, the odds ratio of having electrocardiogram abnormalities was 1.79 (95% confidence interval: 1.14-2.81, p = 0.011) for those living in slightly cold houses and 2.18 (95% confidence interval: 1.27-3.75, p = 0.005) for those living in cold houses. CONCLUSIONS: In addition to blood pressure, living in cold houses may have adverse effects on electrocardiogram. Conversely, keeping the indoor thermal environment within an appropriate range through a combination of living in highly thermal insulated houses and appropriate use of heating devices may contribute to good cardiovascular health. TRIAL REGISTRATION The trial was retrospectively registered on 27 Dec 2017 to the University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, https://www.umin.ac.jp/ctr/ , registration identifier number UMIN000030601 ).
Aged ; Cardiovascular Diseases/prevention & control* ; Cold Temperature/adverse effects* ; Cross-Sectional Studies ; Electrocardiography ; Female ; Housing ; Humans ; Japan/epidemiology* ; Male ; Middle Aged ; Temperature

We report two cases of irritable bowel syndrome (IBS) with predominant constipation successfully treated with daijokito and then diagnosed as Alzheimer's dementia. [Case 1] An 82-year-old man. He had been treated for IBS with probiotic and purgative. However, the symptom of IBS did not get cured and he had suffered from digestive symptom with iracund mental condition. [Case 2] A 74-year-old man. He suffered from abdominal pain and constipation so he needed enema and stool extraction frequently. He sometimes angered if he could not get treatment without delay. In both cases, their bowel and mental condition improved after treatment with daijokito. After their conditions improved, we checked their cognitive function, and found the levels of their cognitive function were low. We diagnosed them as Alzheimer's dementia. The patients probably had felt the difficulty and gotten mental stress on usual days because of dementia, so the mental stress could complicate the symptoms of IBS. Daijokito probably improved the digestive symptom due to IBS and the mental stress from dementia of these patients, and after the treatment we could diagnose the dementia. Elderly patients with constipation and iracund mental condition might have dementia.

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

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

Behcet's disease (BD) is a systemic vasculitis, while myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic disorders characterized by ineffective hematopoiesis. Some studies suggest a relationship between MDS and BD, especially intestinal BD, and trisomy 8 seems to play an important role in both diseases. There are several reports on patients with BD comorbid with MDS involving trisomy 8 that frequently have intestinal lesions refractory to conventional medical therapies. Tumor necrosis factor (TNF)-alpha is strongly involved in the pathophysiology of several autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and BD. In addition, TNF-alpha plays an important role in the pathophysiology of MDS by inhibiting normal hematopoiesis and inducing the programmed cell death of normal total bone marrow cells and normal CD34+ cells. Recent clinical reports demonstrate the favorable effect of TNF-alpha antagonists in patients with refractory intestinal BD and in those with MDS. We present the case of a patient with intestinal BD and MDS involving trisomy 8 who was successfully treated with adalimumab.
Adalimumab ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Behcet Syndrome ; Bone Marrow Cells ; Cell Death ; Hematopoiesis ; Humans ; Inflammatory Bowel Diseases ; Myelodysplastic Syndromes* ; Systemic Vasculitis ; Trisomy* ; Tumor Necrosis Factor-alpha

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

A population-based cohort study on pediatric infectious diseases was established at Khanh Hoa Province, central Vietnam in 2006, to determine the etiology and risk factors for severe pediatric infectious diseases (SPID) such as acute respiratory infection (ARI), diarrhea and dengue which are the major causes of under 5 mortality. A population census survey was conducted in Nha-Trang and Ninh-Hoa to collect demographic, social-behavioral data and disease burden on SPID. The study site covered a population of 353,525 residing in 75,826 households with 24,781 children less than 5 years. Hospital databases from two hospitals covering the region were obtained. Linking the census and hospital databases, we were able to investigate on a variety of SPID such as environmental tobacco smoking exposure and increased risked of pediatric pneumonia hospitalization, population density, water supply and risk of dengue fever and animal livestock and risk of hospitalized diarrhea. To determine incidence, viral etiology and risk factors for pediatric ARI/pneumonia, we setup a population based prospective hospitalized Pediatric ARI surveillance at Khanh Hoa General Hospital, Nha-Trang in February 2007. The study has revealed RSV, rhinovirus and influenza A as major viral pathogens, role of multiple viral infection and its interaction with bacteria in the development of pneumonia. In addition, we are also conducting a birth cohort study to investigate the incidence of congenital infection and its impact on physical-neurological development, and role of host genetic polymorphism on SPID hospitalization in Vietnam. Population mobility, high cost of regular census update and low mortality are the challenges.