Case report: Consecutive hyperbaric oxygen therapy for delayed post-hypoxic leukoencephalopathy resulting from CHANTER syndrome caused by opioid intoxication.

Delayed post-hypoxic leukoencephalopathy (DPHL) is a poorly recognized syndrome characterized by neuropsychiatric symptoms following recovery from an acute hypoxic episode. Although most cases are related to carbon monoxide poisoning, some have been linked to excessive opioid use. Opioid intoxication has recently become known for manifesting the characteristic imaging findings involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome. Herein, we present a patient with severe disturbances in consciousness who was initially diagnosed with CO poisoning but was later found to have taken excessive tramadol. Magnetic resonance imaging (MRI) in the acute phase revealed abnormal intensities in the bilateral globus pallidus and the cerebellum, indicative of CHANTER syndrome. After intensive care, his level of consciousness was restored. However, around the 3rd week after hospitalization, his consciousness gradually deteriorated and he developed severe neurological symptoms. Another MRI on day 25 revealed a new diffuse white matter abnormality; DPHL was suspected. Cerebrospinal fluid collected on day 28 revealed significantly elevated myelin basic protein levels. Although it was challenging to decide on a treatment plan, hyperbaric oxygen (HBO) therapy trials were initiated on day 58; the patient's condition improved after a series of HBO sessions. MRI revealed gradual shrinkage of the white matter abnormality. A total of 63 consecutive HBO sessions were performed, leading to the successful resolution of the serious neurological symptoms. While the effectiveness of HBO therapy for DPHL remains inconclusive, especially in opioid-related cases, this patient made a remarkable recovery, likely due to the therapeutic effect of improved cerebral blood flow and oxygenation.

Comorbid psychiatric disorders and long-term survival after liver transplantation in transplant facilities with a psychiatric consultation-liaison team: a multicenter retrospective study.

OBJECTIVE: Comorbid psychiatric disorders negatively affect the survival rate of patients with some physical disorders. In liver transplant recipients, various psychiatric disorders have been identified as worsening prognosis. However, little is known about how the presence of any comorbid (overall) disorders affect the survival rate of transplant recipients. In this study, we examined the effect of overall comorbid psychiatric disorders on survival rate in liver transplant recipients. METHODS: A total of 1006 recipients who underwent liver transplantation between September 1997 and July 2017 across eight transplant facilities with a psychiatric consultation-liaison team were identified consecutively. Recipients were categorized into those with comorbid psychiatric disorders and those without comorbid psychiatric disorders. In the comorbid psychiatric disorder group, psychiatric disorder diagnosis and time of diagnosis were investigated retrospectively. RESULTS: Of the 1006 recipients, 294 (29.2%) had comorbid psychiatric disorders. Comorbid psychiatric disorders in the 1006 recipients were insomnia (N = 107, 10.6%), delirium (N = 103, 10.2%), major depressive disorder (N = 41, 4.1%), adjustment disorder (N = 19, 1.9%), anxiety disorder (N = 17, 1.7%), intellectual disability (N = 11, 1.1%), autism spectrum disorder (N = 7, 0.7%), somatic symptom disorder (N = 4, 0.4%) schizophrenia (N = 4, 0.4%), substance use disorder (N = 24, 2.4%) and personality disorder (N = 2, 0.2%). The most common time of psychiatric disorder diagnosis was within the first 3 months after liver transplantation (51.6%). The final mortality in patients with comorbid psychiatric disorder diagnosis during the five periods (pretransplant, transplant to 3 months, months to 1 year, 1 to 3 years, and over 3 years posttransplant) was 16.2%, 18.8%, 39.1%, 28.6%, and 16.2% respectively, and there were no significant differences between the five periods (χ2 = 8.05, df = 4, p = 0.09). Overall comorbid psychiatric disorders were significantly associated with shorter survival time (log-rank test: p = 0.01, hazard ratio: 1.59 [95% confidence interval: 1.14-2.21], survival rate at the endpoint [%]: 62.0 vs. 83.3). However, after adjusting for confounding variables using Cox proportional hazards regression, there was no significant effect of overall comorbid psychiatric disorders on prognosis. CONCLUSION: Comorbid psychiatric disorders did not affect the survival rate of liver transplant recipients in this study.

Efficacy and tolerability of 1 L polyethylene glycol plus ascorbic acid with senna versus 2 L polyethylene glycol plus ascorbic acid for colonoscopic bowel preparation: Prospective, randomized, investigator-blinded trial.

OBJECTIVES: Low-volume polyethylene glycol plus ascorbic acid (PEG-Asc) reduces the dosage of colonoscopic bowel preparation (BP) solution, but is still poorly tolerated. Adding laxatives to the BP solution reduces the volume of fluid required, without affecting quality. This study aimed to compare 1 L PEG-Asc plus 24 mg senna (1L-PEG/AS) and conventional 2 L PEG-Asc (2L-PEG/A) regimens on BP quality and patient tolerability. METHODS: A single-center, randomized, investigator-blinded, noninferiority trial was performed between June and August 2022. Outpatients scheduled for colonoscopy were randomized (1:1) to the 1L-PEG/AS or 2L-PEG/A group. The Boston Bowel Preparation Scale (BBPS) was used to evaluate BP quality. Adverse events and tolerability were surveyed using questionnaires. RESULTS: Overall, 344 patients received 1L-PEG/AS or 2L-PEG/A regimens. The baseline characteristics and adverse events of the two groups were comparable. The 1L-PEG/AS group showed noninferior adequate BP rates compared with the 2L-PEG/A group (88% vs. 89%, P = 1.00); overall BBPS was 7.1 ± 1.5 and 7.2 ± 1.5, respectively (P = 0.39). Higher willingness to repeat the BP was observed in the 1L-PEG/AS group (85% vs. 62%, P < 0.01). CONCLUSIONS: The 1L-PEG/AS regimen was comparable to the 2L-PEG/A regimen in terms of BP adequacy, requiring lower BP solution volumes, with better patient tolerance. Thus, it may be a suitable alternative to the conventional BP solution for colonoscopy. The Japan Registry of Clinical Trials (jRCT1051220043).

A case of paradoxical response during anti-tuberculosis treatment in a patient with ulcerative colitis.

Emerging anti-tumor necrosis factor (TNF)-α antibodies therapy changed treatment strategy to inflammatory bowel diseases because of the efficacy. However, TNF-α inhibitor can be associated with an increased risk of infectious complications, especially tuberculosis. A 71-year-old female with steroid-dependent ulcerative colitis (UC) was admitted due to relapse of UC with endoscopically severe active. Golimumab and adjunctive prednisolone started with 30 mg daily resulted in clinical remission. However, she had general fatigue and fever at the time of seventh injection of golimumab without abdominal symptoms. Based on positive interferon-gamma release assay, polymerase chain reaction positive for tuberculosis (TB) in pleural fluid, and chest computed tomography, she was diagnosed as tuberculous pleuritis. Standard anti-TB treatment (isoniazid, rifampicin, ethambutol, and pyrazinamide) was started without cessation of golimumab, because cessation of TNF-α inhibitors during anti-TB treatment could cause the paradoxical response by skewing from regulatory to inflammatory immune responses. However, four weeks after initiation of anti-TB treatment, she got fever-up and pleural effusion increased. We then started prednisolone 30 mg daily as diagnosis of paradoxical response, resulting in improving the symptoms. This is a suggestive case of paradoxical response during anti-TB treatment despite continuous TNF-α inhibitors.

Pyogenic Spondylitis Caused by Staphylococcus schleiferi in a Patient with Crohn's Disease.

Staphylococcus schleiferi has rarely been reported to cause pyogenic spondylitis. A 42-year-old man had been treated for Crohn's disease with immunosuppressive agents and home parenteral nutrition via a central vein (CV) port. The patient was admitted to our hospital, presenting with neck pain and a fever. A neurological examination showed slight weakness in his left-hand muscles, and he was diagnosed with pyogenic spondylitis of C6 and C7 vertebral bodies due to catheter-related blood stream infection caused by S. schleiferi. An early diagnosis by magnetic resonance imaging, CV port removal and antibiotic therapy targeting S. schleiferi improved his symptoms.

Impact of the Lockdown Due to the COVID-19 Pandemic on Patients With Inflammatory Bowel Disease.

Background: The government of Japan declared a state of emergency on April 16, 2020, owing to the coronavirus disease 2019 (COVID-19) pandemic. The subsequent lockdown altered lifestyles and worsened mental illnesses. Inflammatory bowel disease (IBD) is an intestinal disorder that is affected by environmental factors. Therefore, we aimed to assess the effects of COVID-19 and the state of emergency on the lifestyle and disease activity of patients with IBD. Methods: We conducted a questionnaire survey on patients with IBD from June 16 to August 21, 2020 during their regular follow-up at our hospital, 2 months after the state of emergency was declared. Results: Overall, 241 patients with ulcerative colitis (UC) and 210 with Crohn's disease (CD) completed the survey, of which 82 (34%) and 97 (46%) patients, respectively, reported disease exacerbation within 2 months after the lockdown. Multivariate logistic regression analysis identified age at enrollment (odds ratio, OR 0.98, 95% CI 0.96-0.99; P < 0.05), sleep hours (OR, 0.74; 95% CI, 0.57-0.97; P < 0.05), and increased stress due to the COVID-19 pandemic (OR, 6.06; 95% CI, 1.79-20.50; P < 0.01) as independent factors associated with UC exacerbation. Patients with exacerbated CD were younger at CD onset and had higher patient-reported outcome 2 scores before the state of emergency than patients with non-exacerbated CD. On multivariate analysis, age (OR, 0.97; 95% CI, 0.95-0.99; P < 0.01) and active disease before the state of emergency (OR, 2.20; 95% CI, 1.23-3.95; P < 0.01) were independently associated with CD exacerbation. Conclusions: Improving sleep quality and preventing psychological stress may be crucial in IBD management during a pandemic, especially in young patients.

Lithium intoxication-induced dysgeusia accompanied by glossalgia in a patient receiving lithium carbonate: a case report.

BACKGROUND: Lithium carbonate is widely used as a first-line therapeutic agent for the depressive and manic phases of bipolar disorder. Although limb tremors and hypothyroidism are well-known side effects of lithium carbonate, other rare adverse reactions can also occur. CASE PRESENTATION: A 53-year-old Japanese woman diagnosed with lithium intoxication developed dysgeusia and glossalgia during treatment with lithium carbonate. She also showed symptoms of a swaying gait, finger tremors, and dysarthria. All of these symptoms subsided when her blood lithium concentration was reduced to a level below that which induces intoxication. CONCLUSIONS: We present a rare case of lithium carbonate-induced dysgeusia accompanied by glossalgia. Early detection of these symptoms is important in clinical settings because they can be overlooked until patients lose their appetite, which severely impairs their quality of life.

Slco2a1 deficiency exacerbates experimental colitis via inflammasome activation in macrophages: a possible mechanism of chronic enteropathy associated with SLCO2A1 gene.

Loss-of-function mutations in the solute carrier organic anion transporter family, member 2a1 gene (SLCO2A1), which encodes a prostaglandin (PG) transporter, have been identified as causes of chronic nonspecific multiple ulcers in the small intestine; however, the underlying mechanisms have not been revealed. We, therefore, evaluated the effects of systemic knockout of Slco2a1 (Slco2a1-/-) and conditional knockout in intestinal epithelial cells (Slco2a1ΔIEC) and macrophages (Slco2a1ΔMP) in mice with dextran sodium sulphate (DSS)-induced acute colitis. Slco2a-/- mice were more susceptible to DSS-induced colitis than wild-type (WT) mice, but did not spontaneously develop enteritis or colitis. The nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 (NLRP3) inflammasome was more strongly upregulated in colon tissues of Slco2a-/- mice administered DSS and in macrophages isolated from Slco2a1-/- mice than in the WT counterparts. Slco2a1ΔMP, but not Slco2a1ΔIEC mice, were more susceptible to DSS-induced colitis than WT mice, partly phenocopying Slco2a-/- mice. Concentrations of PGE2 in colon tissues and macrophages from Slco2a1-/- mice were significantly higher than those of WT mice. Blockade of inflammasome activation suppressed the exacerbation of colitis. These results indicated that Slco2a1-deficiency increases the PGE2 concentration, resulting in NLRP3 inflammasome activation in macrophages, thus exacerbating intestinal inflammation.

Azathioprine Is Useful for Maintaining Long-term Remission Induced by Tacrolimus for the Treatment of Ulcerative Colitis: An Inverse Probability of a Treatment Weighing Analysis.

Objective The need for and efficacy of immunomodulators for maintaining remission after tacrolimus therapy have not been sufficiently defined. This study evaluated the efficacy of immunomodulators for maintaining remission in patients with ulcerative colitis after tacrolimus therapy. Methods Patients with active ulcerative colitis who started oral tacrolimus between January 2009 and September 2017 and were responsive were retrospectively evaluated. Long-term outcomes were compared using Cox proportional hazard regression with inverse probability of treatment weighting. Results Among the 63 patients in the study, 45 received immunomodulators. During the follow-up, 30 patients (47.6%) experienced a relapse. The relapse-free survival rate was significantly worse in the group that did not receive immunomodulators than in those that did (p=0.01, log-rank test); the 2-year relapse-free rates were 22.5% and 63.6% in the non-immunomodulator and immunomodulator groups, respectively. A multivariate analysis showed immunomodulator treatment to be an independent protective factor for clinical relapse (adjusted hazard ratio: 0.35, 95% confidence interval: 0.16-0.78, p=0.01). A Cox regression analysis using inverse probability of treatment weighting also showed that immunomodulator maintenance therapy was correlated with a longer relapse-free survival (hazard ratio: 0.31, 95% confidence interval: 0.15-0.64, p<0.01), A similar response was also observed in non-steroid-dependent patients (hazard ratio: 0.36, 95% confidence interval: 0.14-0.99, p=0.047). No serious adverse events occurred due to tacrolimus or immunomodulator, and immunomodulator use did not increase the incidence of adverse events caused by tacrolimus. Conclusion Our data suggest that the use of immunomodulators to maintain remission after tacrolimus therapy is beneficial for patients with ulcerative colitis.

Pretreatment neutrophil-to-lymphocyte ratio predicts clinical relapse of ulcerative colitis after tacrolimus induction.

OBJECTIVES: Although tacrolimus is useful as an induction therapy in patients with ulcerative colitis (UC), information regarding the long-term outcome after tacrolimus therapy is insufficient. The aim of this study was to evaluate the clinical significance of the pretreatment neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor in patients with UC receiving tacrolimus, to aid treatment selection. MATERIALS AND METHODS: Patients with moderate-to-severe active UC who received oral tacrolimus induction therapy and subsequent immunomodulatory maintenance therapy at our hospital between 2009 and 2017 and who showed clinical response at week 12, were retrospectively enrolled. Cox regression analysis was conducted to study the prognostic role of the pretreatment NLR. The combined impact of the NLR and other known prognostic factors was investigated with multivariate regression. RESULTS: Among 45 patients included in this study, 21 patients experienced relapse during a median follow-up period of 16.6 months. Multivariate Cox regression analysis identified the pretreatment NLR (hazard ratio [HR]: 0.82, 95% confidence interval [CI]: 0.72-0.94, P < 0.01) and the use of immunomodulators at the start of tacrolimus treatment (HR: 0.18, 95% CI: 0.05-0.66, P = 0.01) as independent predictors of clinical relapse. CONCLUSIONS: The pretreatment NLR is an independent prognostic factor in patients with UC treated with tacrolimus.

Recurrent Massive Uterine Bleeding from a Cesarean Scar Treated Successfully by Laparoscopic Surgery.

A cesarean scar can cause abnormal uterine bleeding including prolonged menstruation or postmenstrual spotting. Our patient showed massive uterine bleeding from a cesarean scar and needed blood transfusion for hemorrhagic shock. A cesarean section had only been performed once for delivery stop 9 years ago. Recurrent hemorrhage could not be controlled by conservative treatment, and we performed laparoscopic scar resection and repair. The abnormal uterine bleeding was successfully stopped, and the menstrual cycle was normalized after surgical treatment. We should be aware that even an uneventful cesarean section may have a risk of massive hemorrhage postoperatively as in the present case.

Multiple part umbilical cord entanglement and neonatal outcomes.

OBJECTIVE: Umbilical cord entanglement is known to be a major cause of fetal hypoxia and to be correlated with several neonatal complications, but almost all of the previous reports were restricted to nuchal cord. In this study, we retrospectively examined the correlation between multiple part cord entanglement and pregnancy outcomes. MATERIALS AND METHODS: A total of 2156 cases were recruited from term deliveries in our hospital from 2008 to 2012. We counted umbilical cord loop numbers not only for nuchal cord but also for trunk and limb cord entanglement. We classified the cases into three groups: no loop, single loop and multiple loops group. We statistically analyzed pregnancy outcomes statistically in the three groups. RESULTS: One thousand, four hundred and fifty-eight cases had no cord entanglement, 594 cases had single loop entanglement and 104 cases had multiple loops entanglement. Values of umbilical artery blood, pH (p = 0.002) and base excess (p < 0.001) showed significantly unfavorable status in entanglement cases, especially in the multiple loops group. A significantly larger percentage of neonates in the multiple loops group needed for oxygen (p < 0.001). CONCLUSION: Multiple umbilical cord entanglement is highly correlated with early neonatal unfavorable status and need for resuscitation.

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease.

BACKGROUND AND AIM: Secondary loss of response to adalimumab (ADA-LOR) commonly occurs in patients with Crohn's disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA-LOR in adult CD patients. METHODS: Patients were divided into either an ED (≥900 kcal/day) or a non-ED group (<900 kcal/day). Cumulative non-ADA-LOR rates were compared between groups. The effects of ED intake to reduce ADA-LOR were also assessed in antitumor necrosis factor-alpha (TNF-α)-naïve and infliximab (IFX)-intolerant or refractory CD patients. Serum ADA and TNF-α levels were measured. RESULTS: We enrolled 117 CD patients into the ED (n = 25) or non-ED (n = 92) groups. Although the cumulative non-ADA-LOR rate was higher in the ED group than in the non-ED group, ED intake was not an independent reducing factor for ADA-LOR (adjusted hazard ratio = 0.725; 95% confidence interval: 0.448-1.180; P = 0.196) in all patients. ED intake was significantly more effective in reducing ADA-LOR in IFX-intolerant or refractory patients than in anti-TNF-α-naïve patients in a dose-related manner (P for interaction <0.20). Serum ADA levels did not differ between the groups. Serum TNF-α levels were significantly lower in the ED group than in the non-ED group at week 28 (P = 0.044) and week 52 (P = 0.043). CONCLUSIONS: Concomitant ED therapy reduced ADA-LOR in IFX-intolerant or refractory patients in a dose-related manner. Reductions in the TNF-α levels by concomitant ED intake may contribute to reduce ADA-LOR in CD patients.

Bidirectional effects of dexmedetomidine on human platelet functions in vitro.

Platelets express the imidazoline (I)-receptor, I1 and I2, as well as the α2-adrenoceptor. Although dexmedetomidine, a selective α2-adrenoceptor agonist with some affinity for the I-receptor is expected to affect platelet function, the effects of dexmedetomidine on platelet functions remain unclear. In the present study, we investigated the effects of dexmedetomidine on human platelet functions in vitro. The effects of dexmedetomidine on platelet aggregation were examined using aggregometers. The formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in platelets was measured by an enzyme immunoassay. In addition, P-selectin expression in platelets was estimated by flow cytometry. We showed that dexmedetomidine enhances platelet aggregation. But in the presence of yohimbine, an α2-antagonist, dexmedetomidine suppressed platelet aggregation. Efaroxan, an I1-antagonist, and methylene blue, a soluble guanylate cyclase inhibitor, abolished the suppressive effect of dexmedetomidine, whereas idazoxan, an I2-antagonist, showed no effect. Dexmedetomidine suppressed cAMP formation and enhanced P-selectin expression in platelets, and these effects were inhibited by yohimbine. Dexmedetomidine increased cGMP formation in platelets in the presence of yohimbine, and this increase was suppressed by efaroxan. These results demonstrated that dexmedetomidine has both enhancing and suppressive effects on human platelet functions through its action on the α2-adrenoceptor and on the I1-imidazoline receptor, respectively.