A Case of Bilateral Acute Inferior Limb Ischemia in a Patient With Ulcerative Colitis.

A patient was diagnosed with ulcerative colitis (UC) in 2010. In March 2015, she had abdominal pain, diarrhea, bloody stool, and UC has relapsed. In June 2015, pain and sensory disturbance of both lower limbs appeared. Blood flow at the distal femoral artery was not confirmed with magnetic resonance angiography, and it was diagnosed as bilateral acute inferior limb ischemia. Arterial thrombolectomy with Fogarty's balloon catheter was performed and blood flow was improved. The severity of UC was moderate with Mayo score 8. Thrombosis is considered to be a complication with a high incidence in inflammatory bowel disease. Reports of arterial thrombosis are very rare. It is important to evaluate the risk of bleeding and thrombosis in active or severe cases in UC and need to do thrombotic prophylactic treatment simultaneously with UC treatment.

Multiple esophageal ulcers due to tofacitinib 10 mg twice daily for ulcerative colitis.

A 26-year-old man was admitted to our institution for ulcerative colitis treatment. He used mesalamine, steroid, immunomodulators, and anti-TNFα anti-body, but it was difficult to maintain remission. We started induction therapy with tofacitinib (TOF) 10 mg twice daily. He maintained clinical remission but had chest pain 44 days after the start of TOF. Esophagogastroduodenoscopy showed multiple ulcers from middle to lower esophagus. Although rare, TOF induced esophageal ulcers were considered based on his clinical course and endoscopic findings.

Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis.

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.

Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study.

Background and study aims Recently, histological inflammation has been suggested to be an important predictor of sustained remission or relapse of ulcerative colitis (UC). In this study, we retrospectively compared severity of histological inflammation with endoscopic findings in UC patients with mucosal healing (MH) in the remission maintenance phase, and investigated whether histological healing could be a predictor of sustained remission. Patients and methods This study included 166 patients with MH in the remission maintenance phase. Endoscopic evaluation was based on the Mayo endoscopic subscore (MES), and MH was defined as MES 0 or 1. Severity of histological inflammation was graded according to the Matts classification. Patients with Matts 1 and 2 were included in the histological healing (HH) group, and those with Matts 3, 4, and 5, in the non-histological healing (NHH) group. In patients with MH, incidence of relapse was compared and analyzed according to severity of histological inflammation. Results The remission maintenance rate was significantly higher in the MES 0 group than in the MES 1 group ( P  = 0.004). The rate was significantly higher in the HH group than in the NHH group ( P  = 0.003). Within the MES 1 group, the rate was significantly higher in the HH subgroup than in the NHH subgroup ( P  = 0.030). Conclusions This retrospective study suggests that histological healing can be a predictor of sustained remission in UC patients, and examination of histological inflammation provides useful information for long-term management of UC, particularly in patients with MES 1.

A Cross-sectional Survey of the Clinical Manifestations and Underlying Illness of Cough.

AIM: The aim of this study was to identify factors affecting the final diagnosis of cough. MATERIALS AND METHODS: This study recruited 463 consecutive patients who visited five Japanese general hospitals due to cough from October 2006 to September 2007. Of these, 418 patients (90%) who completed a questionnaire designed to acquire data regarding clinical manifestations of cough were included. RESULTS: Most patients with bronchial asthma had cough with seasonal variation and wheezing. Patients with gastro esophageal reflux disease suffered from heartburn and cough without daily or seasonal variation. Cough associated with sinobronchial syndrome was only observed in females and was linked to increased sputum. Patients with whooping cough were bothered by cough interrupting sleep and talking. Patients with cardiogenic cough had exertional dyspnea. CONCLUSION: The specific items on our questionnaire relating to patient characteristics, complications, and triggers of cough, represent useful tools for diagnosing the primary disease producing cough.

Severe acute pancreatitis with inflammation extending to the scrotum.

Extension of inflammation into the scrotum is rare in acute pancreatitis. If inflammation spreads in the scrotum, it may become severe. Clinicians should be aware of this condition as a possible complication. Proactive imaging testing is recommended when complaining of cyst swelling or testicular pain.

Hematemesis due to Drug Allergy to Oral Prednisolone in a Patient with Ulcerative Colitis.

The patient was diagnosed with ulcerative colitis and received remission induction therapy with prednisolone. While they developed muscle pain in the lower extremities after starting prednisolone, they ultimately achieved clinical remission. After discharge, hematemesis and gastric discomfort developed. Esophagogastroduodenoscopy showed mucosal edema, redness, and oozing bleeding in the gastric body. In addition, the patient had bloody stool and was considered to have a relapse of ulcerative colitis. They therefore received remission induction therapy with tacrolimus. The patient achieved clinical remission again; however, gastric discomfort and muscle pain remained. A drug lymphocyte stimulation test revealed positivity for prednisolone; therefore, the patient was diagnosed with an allergy to prednisolone.

Enantioselective Aza-Wacker-Type Cyclization Promoted by Pd-SPRIX Catalyst.

An enantioselective aza-Wacker-type reaction was developed. When alkenyl sulfonamide substrates were treated with the Pd-SPRIX catalyst in the presence of oxone as an oxidant, the olefin was attacked intramolecularly by the nitrogen nucleophile to construct several heterocycles such as morpholines, piperazines, piperidines, and their benzo-fused derivatives in up to 88% yield with up to 80% ee.

Jejunal Metastasis from Hepatocellular Carcinoma.

A 76-year-old man with hepatocellular carcinoma associated with alcoholic cirrhosis was hospitalized for lightheadedness and melena. He had undergone multiple surgeries and had been treated with transcatheter arterial chemoembolization and sorafenib. Neither upper nor lower gastrointestinal endoscopy detected the source of bleeding. Oral double-balloon enteroscopy revealed a mass lesion in the upper jejunum, 20 cm from the Treitz ligament on the anal side, which was identified as the source of bleeding. Subsequently, a biopsy was performed. A histopathological examination detected a hepatocellular carcinoma, and a final diagnosis of jejunal metastasis from hepatocellular carcinoma was established.

An Open-Label, Multi-Institutional, Randomized Study to Evaluate the Additive Effect of a Leukotriene Receptor Antagonist on Cough Score in Patients with Cough-Variant Asthma Being Treated with Inhaled Corticosteroids.

Cough-variant asthma is one of the most common reasons for chronic cough. It is important to treat appropriately cough-variant asthma because 30% to 40% of cough-variant asthma becomes a typical asthma. However, little is known about the treatment of cough-variant asthma except for inhaled corticosteroid (ICS). The aim of this study was to validate the additive efficacy of a leukotriene receptor antagonist (LTRA) on cough score and respiratory function in patients with cough-variant asthma being treated with ICS. A total 28 patients were randomly assigned to either an ICS + LTRA group or an ICS group. There were statistically significant improvements in cough scores in the ICS + LTRA group from 0 weeks (6.7 ± 4.4) to 2 weeks (2.9 ± 3.2) (P < 0.05), 4 weeks (0.7 ± 1.1) (P < 0.001), and 8 weeks (0.8 ± 1.2) (P < 0.001). However similar improvements were not evident in the ICS group from 0 weeks (6.7 ± 4.4) to 2 weeks (5.6 ± 10.0) (P = 0.59), 4 weeks (4.6 ± 7.6) (P = 0.32), and 8 weeks (2.9 ± 5.2) (P = 0.08). On the other hand, no significant changes were evident in the forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC). In conclusion, the LTRA was useful in improving cough in patients with cough-variant asthma, even though it appeared to be ineffective in improving respiratory function.

Endoscopic balloon dilation for stenotic lesions in Crohn's disease.

BACKGROUND/AIMS: Endoscopic balloon dilation (EBD) can serve as an alternative to surgery for intestinal stenosis associated with Crohn's disease (CD). However, there has been controversy regarding the efficacy and safety of EBD. Here we sought to determine the therapeutic efficacy and safety of EBD for intestinal stenosis in CD. MATERIALS AND METHODS: Of 43 patients with CD accompanied by intestinal stenosis, 30 underwent EBD. These 30 patients were examined retrospectively in terms of the scope passage rate, surgery-free rate, and whether or not the observation of the distal intestinal tract influenced the therapeutic strategy. RESULTS: The overall scope passage and surgery-free rates were 90.0% and 76.7%, respectively. There were no statistically significant differences in the site of the dilated intestinal tract among groups. Patients who had inflammation in the distal intestinal tract alone after EBD accounted for 56.7%. The rate of re-dilation was 46.7%, and time until re-dilation was 6.6±3.6 months. CONCLUSION: EBD was associated with favorable short-term and long-term outcomes and good safety. Observation of the distal intestinal tract influenced the decision-making process for therapeutic strategies. The results of this study suggest that EBD may allow the postponement or even avoidance of surgery, enabling not only intestinal dilation but also the evaluation of mucosal healing to be performed. Thus, EBD is considered to be an effective alternative treatment for intestinal stenotic lesions in patients with CD.

Ulcerative Colitis-associated Cancer/Dysplasia Detected Using Surveillance Colonoscopy Performed in the Clinical Remission Phase: A Report of Five Cases.

We herein report five cases of ulcerative colitis-associated cancer/dysplasia. Although clinical remission had been achieved in all patients, mucosal inflammation had been resolved in only one patient. Thus, in order to prevent cancer from developing, appropriate medical therapy aiming not only to relieve the clinical symptoms, but also to suppress chronic inflammation appears to be necessary. Moreover, cancer occurred as early as 4 years after the diagnosis in one patient. In patients without complete resolution of mucosal inflammation, careful surveillance colonoscopy should be initiated in the early phase.

Timing for dose-down of 5-ASA depends on mucosal status with ulcerative colitis.

OBJECTIVE: Although aminosalicylic acid (ASA) preparations have been used as first-line drugs for the treatment of ulcerative colitis (UC), no consistent view has been established regarding the ASA dose during the remission-maintenance phase of the disease. In this study, we examined whether the ASA dose should be reduced during the remission-maintenance phase. MATERIALS AND METHODS: This study included 203 patients in the remission-maintenance phase of UC. The Mayo endoscopic subscore (MES) was used to evaluate mucosa. Comparison and analysis were performed between patients whose ASA dose had been unchanged and whose dose had been reduced, between patients with endoscopic healing (EH) group and those without endoscopic healing (WEH) group, and between patients with an MES of 0 and 1. RESULTS: Comparison between the unchanged-ASA and reduced-ASA groups revealed that the remission-maintenance rate was higher in the unchanged-ASA group (p < 0.001). Next, the remission-maintenance rate was higher in the EH/unchanged-ASA group than in the EH/reduced-ASA group (p = 0.042). Comparison between the MES 0 and 1 groups revealed that the remission-maintenance rate was higher in the MES 0 group (p = 0.007). In addition, no significant difference in remission-maintenance rates was observed between the MES 0/unchanged-ASA group and the MES 0/reduced-ASA group (p = 0.108). CONCLUSION: When the same ASA dose is maintained regardless of the presence or absence of EH, remission is more likely to be maintained. If the ASA dose must be reduced, dose reduction is more advantageous after an MES of 0 is achieved.

Palladium-Catalyzed Direct C-H Arylation of Isoxazoles at the 5-Position.

A palladium-catalyzed direct arylation of isoxazoles with aryl iodides has been achieved. The C-H bond at the 5-position is activated selectively to give coupling products in moderate to good yields. This direct arylation was applied to the synthesis of a spiro-type chiral ligand, which proved to be most effective to the palladium-catalyzed tandem cyclization of a dialkenyl alcohol.

Structural Features and Asymmetric Environment of i-Pr-SPRIX Ligand.

Novel chiral diisopropyl spiro bis(isoxazoline) ligands, anti-i-Pr-SPRIX and syn-i-Pr-SPRIX, were designed and synthesized. Their catalytic utility, X-ray crystallographic analyses, and complexation studies demonstrated the structural features of tetraisopropyl spiro bis(isoxazoline) ligand, i-Pr-SPRIX, which is a prominent ligand in various enantioselective Pd catalytic processes: All i-Pr groups work in collaboration to create an effective asymmetric environment.

Pd-catalyzed enantioselective intramolecular α-arylation of α-substituted cyclic ketones: facile synthesis of functionalized chiral spirobicycles.

Catalytic synthesis of chiral spirocyclic ketones was accomplished via the Pd-catalyzed intramolecular α-arylation of α-substituted cyclic ketones. The obtained spirocyclic ketone could be converted into a bifunctional organocatalyst.

Palladium enolate umpolung: cyclative diacetoxylation of alkynyl cyclohexadienones promoted by a Pd/SPRIX catalyst.

A novel palladium-catalyzed reaction involving an unusual nucleophilic attack on a palladium enolate was developed using a spiro-bis(isoxazoline) (SPRIX) ligand. Treatment of alkynyl cyclohexadienone substrates with a Pd/SPRIX catalyst in acetic acid under an oxygen atmosphere furnished diacetoxylated benzofuranone derivatives in good yields. This cyclative diacetoxylation proceeded enantioselectively in the presence of an optically pure SPRIX ligand.

Enantioselective Pd(II)-Pd(IV) catalysis utilizing a SPRIX ligand: efficient construction of chiral 3-oxy-tetrahydrofurans.

Novel enantioselective catalysis involving a Pd(II)-Pd(IV) cycle was developed by utilizing a SPRIX ligand. Treatment of alkenyl alcohols with a catalytic amount of Pd-SPRIX and TfOH in the presence of PhI(OAc)2 gave optically active 3-oxy-tetrahydrofuran derivatives in good yields.

DFT study of a 5-endo-trig-type cyclization of 3-alkenoic acids by using Pd-spiro-bis(isoxazoline) as catalyst: importance of the rigid spiro framework for both selectivity and reactivity.

The reaction pathway of an enantioselective 5-endo-trig-type cyclization of 3-alkenoic acids catalyzed by a chiral palladium-spiro-bis(isoxazoline) complex, Pd-SPRIX, has been studied by density functional theory calculations. The most plausible pathway involves intramolecular nucleophilic attack of the carboxylate moiety on the C=C double bond activated by Pd-SPRIX and ß-H elimination from the resulting organopalladium intermediate. The enantioselectivity was determined in the cyclization step through the formation of a π-olefin complex, in which one of the two enantiofaces of the olefin moiety was selected. The ß-H elimination occurs via a seven-membered cyclic structure in which the acetate ligand plays a key role in lowering the activation barrier of the transition state. In the elimination step, the SPRIX ligand was found to behave as a monodentate ligand due to the hemilability of one of the isoxazoline units thereby facilitating the elimination. Natural population analysis of this pathway showed that the more weakly electron-donating SPRIX ligand, compared with the bis(oxazoline) ligand, BOX, facilitated the formation of the π-olefin complex intermediate, leading to a smaller overall activation energy and a higher reactivity of the Pd-SPRIX catalyst.