Systemic Cyclosporine Therapy for Scleritis: A Proposal of a Novel System to Assess the Activity of Scleritis

In the present study, two female patients with unilateral scleritis without systemic complications were examined. Both patients were suffering from ocular pain and received corticosteroid therapy. The first patient, a 45-year-old woman, was diagnosed with scleritis and iritis in her right eye. Topical corticosteroid treatment could eradicate the iritis but not the scleritis. Oral corticosteroid administration and corticosteroid pulse therapy were applied with little effect. The application of systemic cyclosporine had a satisfactory effect in controlling the scleritis. The other patient, a 60-year-old woman, was suffering from scleritis and lid swelling in her right eye. Not only did topical and systemic corticosteroid therapy prove insufficient, they also resulted in the elevation of her intraocular pressure. After termination of corticosteroid therapy, the systemic cyclosporine was applied orally. Subsequently, the patient''s scleritis improved without any severe side effects. Scleritis is a painful and destructive inflammatory disease of the sclera that causes congestion of the scleral venous plexus. In this study, we have established a new grading system for assessing activity in scleritis that can score the extent of ocular pain and the area of congestion. This system provides a practical method for following the clinical course and monitoring the outcome of therapy. We report two cases of unilateral scleritis that were resistant to corticosteroid therapy but responsive to systemic administration of cyclosporine. Findings from these cases indicate that cyclosporine is an effective drug for controlling severe scleritis.Key Words: Unilateral scleritis, Systemic cyclosporine administration, Scoring system     

Endoscopic Ultrasound-guided Fine Needle Aspiration for the Diagnosis of Duodenal Stenosis Due to Urothelial Carcinoma

Upper tract urothelial carcinoma (UTUC) initially presents with hematuria and hydronephrosis. We report a case of UTUC presenting with initial findings of duodenal stenosis before the appearance of hydronephrosis. A 59-year-old man presented with upper abdominal symptoms on his initial visit. Esophagogastroduodenoscopy (EGD) revealed circumferential stenosis at the descending part of the duodenum. However, the underlying cause of duodenal stenosis was unknown as repeated histopathological examinations of endoscopic biopsy specimens showed no specific findings. We then performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the thickened duodenal wall, and successfully diagnosed duodenal metastasis of UTUC. EUS-FNA is an effective diagnostic method in cases in which the cause of duodenal stenosis is unknown.     

DialBetics: A Novel Smartphone-based Self-management Support System for Type 2 Diabetes Patients

Numerous diabetes-management systems and programs for improving glycemic control to meet guideline targets have been proposed, using IT technology. But all of them allow only limited—or no—real-time interaction between patients and the system in terms of system response to patient input; few studies have effectively assessed the systems’ usability and feasibility to determine how well patients understand and can adopt the technology involved. DialBetics is composed of 4 modules: (1) data transmission module, (2) evaluation module, (3) communication module, and (4) dietary evaluation module. A 3-month randomized study was designed to assess the safety and usability of a remote health-data monitoring system, and especially its impact on modifying patient lifestyles to improve diabetes self-management and, thus, clinical outcomes. Fifty-four type 2 diabetes patients were randomly divided into 2 groups, 27 in the DialBetics group and 27 in the non-DialBetics control group. HbA1c and fasting blood sugar (FBS) values declined significantly in the DialBetics group: HbA1c decreased an average of 0.4% (from 7.1 ± 1.0% to 6.7 ± 0.7%) compared with an average increase of 0.1% in the non-DialBetics group (from 7.0 ± 0.9% to 7.1 ± 1.1%) (P = .015); The DialBetics group FBS decreased an average of 5.5 mg/dl compared with a non-DialBetics group average increase of 16.9 mg/dl (P = .019). BMI improvement—although not statistically significant because of the small sample size—was greater in the DialBetics group. DialBetics was shown to be a feasible and an effective tool for improving HbA1c by providing patients with real-time support based on their measurements and inputs.     

Phase I trial of oral S-1 plus gemcitabine in elderly patients with nonsmall cell lung cancer

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and gemcitabine combination regimen in the treatment of elderly patients (> or = 70 years) with advanced nonsmall cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC were treated with S-1 and gemcitabine. S-1 was administered orally twice daily for 14 days and gemcitabine on days 1 and 15 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 800/60; level 2, 1000/60; level 3, 1000/70; and level 4, 1000/80 [gemcitabine (mg/m2/ day)/S-1 (mg/m2/day)]. The dose-limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle. Sixteen patients were enrolled in this study. The main grade 3 toxicities observed during the first cycle were neutropenia (43.7%), leukopenia (18.7%), and hyperglycemia. One of six patients in level 3 had DLT. Although no patients in level 4 experienced DLT, this level was considered the maximum tolerated dose. Level 4 was selected as the recommended dose. Objective responses were seen in four patients (response rate, 42.9%). The combination of S-1 plus gemcitabine is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC.     

Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with Enteropathogenic Bacteria

Background and Aims

Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it.

Methods

Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration.

Results

Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution.

Conclusions

Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment.

     

Cardiorespiratory Fitness Suppresses Age‐Related Arterial Stiffening in Healthy Adults: A 2‐Year Longitudinal Observational Study

Cardiorespiratory fitness is negatively associated with arterial stiffness, although it is unclear whether it is associated with prospective arterial stiffness changes. The authors examined cardiorespiratory fitness and arterial stiffness progression in a 2‐year follow‐up study of 470 healthy men and women aged 26 to 69 years. Peak oxygen uptake (V˙O2peak) was measured at baseline using a graded cycle exercise test. Arterial stiffness was assessed using brachial‐ankle pulse wave velocity (baPWV) at baseline and after 2 years. Two‐year changes in baPWV were significantly higher in patients in the lowest V˙O2peak tertile (28.8±7.6 cm/s) compared with those in the highest V˙O2peak tertile (−1.4±7.5 cm/s) (P=.024) and were inversely correlated with V˙O2peak (r=−.112, P=.015). Stepwise multiple regression analysis revealed that age, glucose, baPWV, V˙O2peak, and sex were independent correlates of 2‐year changes in baPWV, suggesting that higher cardiorespiratory fitness is associated with age‐related arterial stiffening suppression.

Arterial stiffness increases progressively with advancing age, even in healthy individuals.¹ This arterial stiffening is associated with future hypertension² and cardiovascular (CV) events³ and is recognized as a surrogate marker for CV disease. Therefore, the prevention of arterial stiffening is of great clinical importance.Carotid‐femoral pulse wave velocity (cfPWV) is a standard method for assessing aortic stiffness.⁴ cfPWV is used in clinical practice mainly in Europe, and in the United States to a lesser extent. Recently, brachial‐ankle pulse wave velocity (baPWV) was proposed as an alternative method for assessing arterial stiffness in Asian populations.⁵ A major advantage of baPWV is its measurement method, which simply involves wrapping the four extremities in blood pressure (BP) cuffs.⁶, ⁷ Moreover, the use of either cfPWV or baPWV is accepted by the Japanese guidelines for the management of hypertension as a tool for assessing subclinical target organ damage.⁸ In addition, baPWV has been shown to be associated with an increased risk of total CV events and all‐cause mortality,⁹, ¹⁰ as is cfPWV.¹¹ Cardiorespiratory fitness (CRF) is independently associated with a lower risk of all‐cause mortality and CV events.¹² Thus, previous studies have investigated the relationship between CRF and arterial stiffness as a surrogate marker for CV disease in cross‐sectional research and have suggested that higher CRF was associated with lower arterial stiffness.¹³, ¹⁴, ¹⁵, ¹⁶ To our knowledge, only Ferreira and colleagues¹⁷, ¹⁸ have reported longitudinal research from adolescence to young adulthood. There is no information regarding middle‐aged and elderly populations. In addition, there has been no previous study on whether CRF is associated with the progression of arterial stiffness as assessed by baPWV in longitudinal research.Previous studies have demonstrated that regular aerobic exercise is effective in preventing and reversing arterial stiffening in healthy adults.¹⁹ Regular aerobic exercise results in higher CRF,²⁰ and, consequently, CRF may be associated with a lower CV disease risk. Therefore, we hypothesized that higher CRF would be associated with less progression of age‐related arterial stiffening in healthy adults. To test our hypothesis, we examined the relationship between CRF and the progression of arterial stiffening with a 2‐year follow‐up study.     

Evaluation of an exposed-radiation dose on a dual-source cardiac computed tomography examination with a prospective electrocardiogram-gated fast dual spiral scan

We evaluated exposed-radiation doses on dual-source cardiac computed tomography (CT) examinations with prospective electrocardiogram (ECG)-gated fast dual spiral scans. After placing dosimeters at locations corresponding to each of the thoracic organs, prospective ECG-gated fast dual spirals and retrospective ECG-gated dual spiral scans were performed to measure the absorbed dose of each organ. In the prospective ECG-gated fast dual spiral scans, the average absorbed doses were 5.03 mGy for the breast, 9.96 mGy for the heart, 6.60 mGy for the lung, 6.48 mGy for the bone marrow, 9.73 mGy for the thymus, and 4.58 mGy for the skin. These values were about 5% of the absorbed doses for the retrospective ECG-gated dual spiral scan. However, the absorbed dose differed greatly at each scan, especially in the external organs such as the breast. For effective and safe use of the prospective ECG-gated fast dual spiral scan, it is necessary to understand these characteristics sufficiently.