Effect of canagliflozin on the decline of estimated glomerular filtration rate in chronic kidney disease patients with type 2 diabetes mellitus: A multicenter,randomized, double‐blind,placebo‐controlled,parallel‐group,phase III study in Japan

Aims/IntroductionThe Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial has shown the effects of canagliflozin on preventing clinically important kidney outcomes in patients with type 2 diabetes mellitus and chronic kidney disease; however, not many Japanese patients were included in the trial. The present study evaluated the efficacy and safety of canagliflozin in Japanese chronic kidney disease patients with type 2 diabetes mellitus.Materials and MethodsIn this multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, chronic kidney disease patients with type 2 diabetes mellitus were randomly assigned to receive either 100 mg canagliflozin or a matching placebo once daily for 104 weeks. The primary efficacy end‐point was the incidence of a 30% decline in estimated glomerular filtration rate.ResultsOverall, 308 patients were randomized to the canagliflozin (n = 154) and placebo (n = 154) groups. The incidence of a 30% decline in estimated glomerular filtration rate at week 104 was 18.2% and 29.5%, respectively, and the point estimate of the intergroup difference (placebo − canagliflozin) was 11.3% (95% confidence interval 1.2–21.5, P = 0.029), which was significant. The overall incidence of adverse events was similar in the two groups.ConclusionsThis study suggests that canagliflozin safely reduces the risk of end‐stage renal disease in Japanese chronic kidney disease patients with type 2 diabetes mellitus.     

Epipericardial Fat Necrosis: A Retrospective Analysis in Japan

Objective Epipericardial fat necrosis (EFN) has been considered to be a rare cause of acute chest pain, and especially important for emergency physicians. Chest computed tomography (CT) is often used for the diagnosis of EFN after excluding life-threatening states, such as acute coronary syndrome and pulmonary embolism. While the proportion of EFN patients who underwent chest CT in emergency departments is being clarified, little is still known about other departments in Japan. To investigate the proportion of EFN patients who underwent chest CT for acute chest pain in various departments. Methods Chest CT performed from January 2015 to July 2020 in Asahikawa Medical University Hospital in Japan was retrospectively analyzed in this study. All images were reviewed by two radiologists. Results There were 373 outpatients identified by a search using the word ‘chest pain’ who underwent chest CT. Eight patients satisfying the imaging criteria were diagnosed with EFN. The proportions of patients diagnosed with EFN were 10.7%, 4.8%, 2.8%, 0.9% and 0% in the departments of general medicine, cardiovascular surgery, emergency medicine, cardiovascular internal medicine and respiratory medicine, respectively. Only 12.5% of the patients were correctly diagnosed with EFN, and the other patients were treated for musculoskeletal symptoms, acute pericarditis or hypochondriasis. Conclusion EFN is not rare and is often overlooked in various departments. All physicians as well as emergency physicians should consider the possibility of EFN as the cause of pleuritic chest pain.     

Spinocerebellar Ataxia Type 31 Exacerbated by Anti-amino Terminal of Alpha-enolase Autoantibodies

We herein report a 61-year-old woman who was genetically diagnosed with spinocerebellar ataxia type 31 whose symptoms were modified by anti-amino terminal of alpha-enolase (NAE) antibodies, known as a biomarker of Hashimoto''s encephalopathy (HE), and ultimately responded to immunotherapy. The relative titers of anti-NAE antibodies increased when her cerebellar ataxia showed acute deterioration and decreased after immunotherapy. This is the first report of cerebellar ataxia associated with genetic spinocerebellar ataxia with concomitant cerebellar type HE. Physicians should be mindful of measuring anti-NAE antibodies to prevent overlooking patients with genetic spinocerebellar ataxia with treatable simultaneous ataxic diseases.     

SARC-F scores can predict health status and daily activity in patients with idiopathic pulmonary fibrosis

BackgroundThe strength, assistance in walking, rising from a chair, climbing stairs, and falls questionnaire (SARC-F) is widely used for screening sarcopenia. We aimed to examine the association of SARC-F scores with the measurements of quality of life and activity in patients with idiopathic pulmonary fibrosis (IPF).MethodsThis cross-sectional pilot study prospectively enrolled 54 patients with IPF who completed pulmonary function tests, the 6-min walk test, the chronic obstructive pulmonary disease assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), the Hospital Anxiety and Depression Scale, and a daily step count. The daily step count was measured continuously for 7 consecutive days using a tri-axis accelerometer device.ResultsThe mean age was 73.6±7.9 years and the mean percent predicted forced vital capacity was 80.4%±15.6%. The median [interquartile range] SARC-F score, SGRQ total scores, and CAT scores were 2 [1–3.25], 28.8 [14.4–46.9], and 13 [7–22], respectively. SARC-F scores were correlated with the percent predicted forced vital capacity (r=−0.51, P<0.001), CAT score (r=0.57, P<0.001), SGRQ total score (r=0.77, P<0.001), Hospital Anxiety and Depression Scale anxiety score (r=0.31, P=0.025), and Hospital Anxiety and Depression Scale depression score (r=0.28, P=0.041). Linear regression analyses revealed that the 6-minute walk test (6MWT) (standardized β=0.33, P=0.011) and SARC-F score (standardized β=−0.39, P=0.005), but not the CAT score and SGRQ total score, were significant predictors for daily step count.ConclusionsSARC-F scores were correlated with health status and daily activity in patients with IPF. Further studies are warranted to validate the utility of the SARC-F in patients with IPF.     

Circulating immunocompetent cell profiles during oral cyclosporin therapy for immunoglobulin-resistant Kawasaki disease

Although the standard treatment for Kawasaki disease (KD)is intravenous immunoglobulin (IVIG) combined with oral aspirin,18％ of 1st IVIG is refractory [1].Recen...     

Determination of paroxetine in human saliva by reversed-phase high-performance liquid chromatography with UV detection.

A rapid and sensitive high-performance liquid chromatographic method was validated and described for determination of paroxetine in human saliva. Following liquid-liquid extraction of the drug and an internal standard (dibucaine), chromatographic separation was accomplished using a C18 analytical column with a mobile phase consisting of 0.05 mol/L sodium phosphate buffer, pH 5.0, and acetonitrile (A 30:70, v/v; B 60:40, v/v). Paroxetine and the internal standard were detected by ultraviolet absorbance at 205 nm. The average recoveries of the drug and internal standard were 92.5% and 89%, respectively. The lower limits of detection and quantification were 1 and 4 ng/ml, respectively, and the calibration curve was linear over a concentration range of 4 ng/ml. The saliva level of paroxetine in patients with depression taking 10 to 40 mg/day of the drug was significantly correlated with the plasma level of paroxetine in each patient (r = 0.617, P < 0.004, n = 19). These data indicate that the saliva level of paroxetine could be a useful marker to predict the plasma level of the drug.     

Massive cystic lymphangiomas of a fetus

We present a fetus with progressive massive subcutaneous lymphangiomas leading to intrauterine death. A 28-year-old woman was referred to our hospital because of a precordial cystic mass of the fetus. An ultrasound revealed lymphangiomas extending from bilateral axillae to the anterior chest wall. At 18 weeks' gestation, amniocentesis was performed and the karyotype of the fetus was found to be normal 46, XY. Thereafter the lesions increased in size gradually and spread over the body. Amniotic fluid decreased, pericardial, and pleural effusion appeared, and cardiomegaly became evident. The fetus died in utero at 25 weeks' gestation. Postmortem examination revealed a male fetus surrounded with multicystic soft masses spreading over the body, and syndactyly (left third and fourth fingers) was present. Histologically, a number of irregularly dilated lymphatics extended through subcutaneous tissues to the skeletal muscles. No communications between the cysts and the thoracic or abdominal cavity existed, and no lymphatic dilations in the viscera were confirmed. As far as we know, such conditions have rarely been reported. Considering that in previous literature, a favorable prognosis of a fetus with an atypically located (lateral cervical or non-cervical) lymphangioma with a normal karyotype has been reported, our case may be included in a distinct pathological entity. When we find a lymphangioma in a fetus, careful follow-up by ultrasound is mandatory.     

Effect Estimate of Time-varying Social Support and Trust on the Physical and Mental Health of Mothers at 2.5 Years Postpartum: The Japan Environment and Children’s Study (JECS)

BackgroundMany epidemiological studies have reported the association between various social factors and health status in mothers during and after pregnancy. However, little is known about their joint and longitudinal impact. We examined the association of lack of social support and trust during pregnancy and at 2.5 years postpartum with health status in mothers.MethodsTo adequately address time-varying exposure, marginal structural models were fitted to a pseudopopulation constructed using inverse probability weighting. The model included records of 90,071 mothers participating in the Japan Environment and Children’s Study. Social support and trust were measured using a 9-item questionnaire (Q1–9). Mental and physical health were measured using Mental and Physical Component Summary scores from the 8-item Short-Form Health Survey.ResultsFor the Mental Component Summary, the magnitude of the effect estimate was largest when participants lacked close friends/neighbors (Q4) at only 2.5 years postpartum (effect estimate, −6.23), followed by a lack in emotional support (Q2) at the same time point (effect estimate, −4.94). For the Physical Component Summary, effect estimates were negligible. The magnitude of the effect estimates of lack of social support and trust tended to be larger when there was a lack at only 2.5 years postpartum than at both time points.ConclusionThese findings suggest that, after childbirth, a loss in social support, particularly in an emotional aspect, carries high risk, especially for mental health. Our results highlight the importance of supporting mothers for more than a few years after pregnancy.Key words: SF-8, emotional support, inverse probability of treatment weighting, causal association, pregnant women