Predictors of Early versus Delayed Neurological Deterioration after Thrombolysis for Ischemic Stroke.

INTRODUCTION: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24-72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs. 0-1 and 3-6 vs. 0-2 and death). RESULTS: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p < 0.001). CONCLUSION: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days.

Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

INTRODUCTION: Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD. METHODS: We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate <60 mL/min/1.73m2 and/or proteinuria) at baseline. Breakfast-skippers were defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the eGFR from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors. RESULTS: During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p=0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI 1.29‒5.26) for the breakfast-skipping group (p=0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR and baseline proteinuria. CONCLUSION: Skipping breakfast was significantly associated with higher risk of CKD progression in the general Japanese population.

Surveillance of the current situation regarding influenza vaccination according to medical oncologists in Japan.

This study aimed to clarify the attitude of oncologists toward influenza vaccination and the current situation and issues regarding influenza vaccination for patients on chemotherapy in Japan. A web-based survey of medical oncologists certified by the Japanese Society of Medical Oncology was conducted between November 1 and December 31, 2019. Of the 1369 medical oncologists who were invited to participate, 415 (30.3%) responded to our survey. The questionnaire comprised 4 sections: "oncologist characteristics," "oncologist attitude toward influenza vaccines and the current status of influenza vaccination for cancer patients undergoing chemotherapy," "incidence of influenza infection and associated treatment complications," and "treatment policy for influenza infection." In total, 153 (36.9%) physicians replied that they did not actively encourage influenza vaccination for patients undergoing chemotherapy. The primary reasons given were lack of evidence (48/153, 31.4%) and uncertainty of appropriate timing (46/153, 30.1%). There was diverse variation in the timing of vaccination and in the levels of encouragement based on the cancer location and medication type. Two hundred eighty-three (68.2%) oncologists reported that their cancer patients had experienced influenza infection while undergoing chemotherapy, and 169 (40.7%) responded that their patients had experienced an administration delay or discontinuation of medication because of influenza infection. Our surveillance revealed some oncologists considered evidence regarding the administration of influenza vaccine to cancer patients undergoing chemotherapy (particularly the optimal timing and level of recommendation by cancer location and medication) to be lacking. It also exposed the adverse impact of influenza infection in cancer patients.

Clioquinol kills astrocyte-derived KT-5 cells by the impairment of the autophagy-lysosome pathway.

Clioquinol has been implicated as a causative agent for subacute myelo-optico-neuropathy (SMON) in humans, although the mechanism remains to be elucidated. In this study, we utilized astrocyte-derived cell line, KT-5 cells to explore its potential cytotoxicity on glial cells. KT-5 cells were exposed in vitro to a maximum of 50 µM clioquinol for up to 24 h. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenylte trazolium bromide (MTT) assay of the cells revealed that clioquinol induced significant cell damage and death. We also found that clioquinol caused accumulation of microtubule-associated protein light chain-3 (LC3)-II and sequestosome-1 (p62) in a dose- and time-dependent manner, suggesting the abnormality of autophagy-lysosome pathway. Consistent with these findings, an exposure of 20 µM clioquinol induced the accumulation of cellular autophagic vacuoles. Moreover, an exposure of 20 µM clioquinol provoked a statistically significant reduction of intracellular lysosomal acid hydrolases activities but no change in lysosomal pH. It also resulted in a significant decline of intracellular ATP levels, enhanced cellular levels of reactive oxygen species, and eventually cell death. This cell death at least did not appear to occur via apoptosis. 10 µM Chloroquine, lysosomal inhibitor, blocked the autophagic degradation and augmented clioquinol-cytotoxicity, whereas rapamycin, an inducer of autophagy, rescued clioquinol-induced cytotoxicity. Thus, our present results strongly suggest clioquinol acts as a potentially cytotoxic agent to glial cells. For future clinical application of clioquinol on the treatment of neurological and cancer disorders, we should take account of this type of cell death mechanism.

Association between serum uric acid and new onset and progression of chronic kidney disease in a Japanese general population: Iki epidemiological study of atherosclerosis and chronic kidney disease.

BACKGROUND: Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively association with kidney function. The aim of this study was to elucidate the association between SUA and new onset and progression of CKD in a Japanese general population. METHODS: This was a population-based retrospective cohort study using annual health checkup data of residents of Iki Island. A total of 5,507 adults (979 with CKD and 4,528 without) were included. The outcomes were new onset of CKD among participants without CKD at baseline, and progression of CKD among those with CKD. A Cox proportional hazards model was used to evaluate the association between SUA and new onset and progression of CKD. RESULTS: During mean follow-up of 4.6 years, 757 cases of new onset of CKD and 193 with progression of CKD were observed. SUA was significantly associated with new onset of CKD (adjusted hazard ratio 1.13, [95% confidence interval 1.03-1.24] per standard deviation [SD] increase in SUA). In contrast, SUA was not significantly associated with progression of CKD (hazard ratio 1.08, [0.92-1.27] per SD increase). Similar results were obtained when classifying uric acid as categorical. CONCLUSION: SUA was significantly associated with increased risk for new onset of CKD, but not with progression of CKD among a Japanese general population.

Risk of Stroke in Atrial Fibrillation According to Sex in Patients Aged Younger Than 75 Years: A Large-Scale, Observational Study Using Real-World Data.

BACKGROUND: It is unclear whether women have a higher risk of stroke than men. This study aimed to clarify the effects of a sex difference on the risk of ischaemic stroke in patients with atrial fibrillation (AF). METHODS: Health check and insurance claims data were used of people who were aged <75 years from 2005 to 2017 in Japan. Patients with AF who were not on anticoagulation therapy were identified. After excluding patients with artificial valves (n=28), haematological disease (n=1,124), aged ≤20 years (n=207), and taking anticoagulant therapy (n=11,848), 9,733 remained for inclusion into the study. The primary outcome was hospital admission due to ischaemic stroke. RESULTS: Of the 9,733 participants, 7,079 (72.7%) were men. The mean age of women (54.4 years) was significantly higher than that of men (53.2 years). During a mean 2.5-year follow-up period, 143 ischaemic stroke events occurred. Female sex was not associated with ischaemic stroke (adjusted hazard ratio [95% confidence interval]: 1.13 [0.78-1.66]). When stratified using the CHA2DS2-VASc score, the annual incidence of ischaemic stroke was similarly low among women with a CHA2DS2-VASc score of 1 (0.8%) and men with a score of 0 (0.7%). The incidence of ischaemic stroke increased with a CHA2DS2-VASc score of 2 in women and 1 in men. CONCLUSIONS: In this large-scale, real-world study of patients with AF, the risk of ischaemic stroke among those aged <75 years was comparable between women and men. These findings are consistent with the current guidelines, which do not recommend anticoagulant therapy for women with no other risk factors (CHA2DS2-VASc score of 1).

The role of cigarette smoking on new-onset of chronic kidney disease in a Japanese population without prior chronic kidney disease: Iki epidemiological study of atherosclerosis and chronic kidney disease (ISSA-CKD).

BACKGROUND: Studies regarding harmful effects of smoking on the new-onset of chronic kidney disease (CKD) have been limited. Thus, we collected and retrospectively studied 8 years of data from the annual health check-ups of the residents in Iki City (Nagasaki Prefecture, Japan). METHODS: From 2008 to 2016, 4540 adults were enrolled in the study. Information on smoking habits was obtained via a self-reported questionnaire. New-onset CKD was defined as a reduction of the estimated globular filtration rate (eGFR) to less than 60 mL/min/1.73 m2 and/or new-onset proteinuria during the follow-up examinations. RESULTS: During an average follow-up of 4.6 years, proteinuria developed in 218 people (10.4 per 1000 person-years) and eGFR decline to less than 60 mL/min/1.73 m2 was confirmed in 594 people (28.3 per 1000 person-years) including 53 who showed both proteinuria and eGFR reduction (2.8 per 1000 person-years). In terms of proteinuria, current smokers showed a higher incidence than non-smokers (14.1 and 9.17 per 1000 person-years, respectively, p = 0.001), and a significantly high hazard ratio (HR) of 1.39 with a 95% CI of 1.01-1.92 in multivariable Cox's proportional-hazard analyses. The tendency was more drastic among younger participants (p = 0.015 for trend): current smokers who were < 50 years old had a significantly higher HR of 2.55 with a 95% CI of 1.01-6.45 (p = 0.004) than non-smokers. CONCLUSIONS: Smoking significantly increased the risk for new-onset of CKD based on proteinuria development in a Japanese population without CKD, and the association was more predominant in the younger population.

Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity.

Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells. We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity. The data we present here strongly suggest that anti-GM1 caused a significant change in sphingomyelin content of the membrane fraction in PCtrk cells. Both nSMase2 activity and the level of nSMase2 protein were significantly decreased by anti-GM1 treatment of PCtrk cells, while acidic SMase activities remained unchanged. Our results indicate, for the first time, that anti-GM1 may produce profound impacts on lipid metabolism in neuronal cell membranes.

Comparison of regional with general anesthesia on mortality and perioperative length of stay in older patients after hip fracture surgery.

OBJECTIVE: The aim of this study was to examine whether anesthetic technique is associated with 30- or 90-day mortality and perioperative length of stay (LOS). DESIGN: We used a retrospective cohort design using a healthcare insurance claims database. SETTING: The Fukuoka Prefecture's claims database of older patients who underwent hip fracture surgery under general or regional (spinal or epidural) anesthesia from April 2012 to March 2016 was used for analyses. PARTICIPANTS: The database under analyses contained 16 125 participants of hip fracture surgery under general or regional anesthesia. MAIN OUTCOME MEASURE: We measured 30- and 90-day mortalities and perioperative LOS. RESULTS: In a propensity score-matched cohort, we found no significant differences in 30- and 90-day mortalities after adjusting for confounding factors. The reconverted perioperative LOS for the general and regional anesthesia groups was, respectively, 29.7 (29.1-30.4) and 28.0 (27.4-28.6) days in the matched cohort. Therefore, the perioperative LOS in the regional anesthesia group was significantly shorter by 1.7 days than in the general anesthesia group (P < 0.001). CONCLUSIONS: This study demonstrated that the use of regional anesthesia was not associated with 30- or 90-day mortality, but it was associated with slightly shorter perioperative LOS. Since Japan has much longer LOS than other countries, our findings have implications for more efficient healthcare resource utilization and quality assurance in geriatric care.

Association between dipeptidyl peptidase-4 inhibitors and urinary tract infection in elderly patients: A retrospective cohort study.

PURPOSE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. Although they have been reported to increase the risk of infection, the findings are controversial. Given that urinary tract infections (UTIs) are common in the elderly, we conducted a retrospective cohort study by using health care insurance claims data, to elucidate the association between the DPP-4 inhibitors and the incidence of UTI in latter-stage elderly patients. METHODS: We analyzed 25,111 Japanese patients aged 75 years and older between the fiscal years 2011 and 2016. Patients using DPP-4 inhibitors and sulfonylureas (SUs) were matched at a 1:1 ratio using propensity scoring. The Incidence rate ratio (IRR) of UTI was compared between users of SUs and users of DPP-4 inhibitors by Poisson regression. Moreover, subgroup analyses stratified by sex were conducted to evaluate whether the combination of prostatic hyperplasia and DPP-4 inhibitors is associated with the incidence of UTI in male patients. RESULTS: The use of DPP-4 inhibitors was associated with an increased risk of UTI (adjusted IRR 1.23, 95% CI [1.04-1.45]). After propensity score matching, the association remained significant (adjusted IRR 1.28, 95% CI [1.05-1.56]). Moreover, elderly male patients with prostatic hyperplasia who received DPP-4 inhibitors had a higher risk of UTI than SU users without prostatic hyperplasia (Matched: crude IRR 2.90, 95% CI [1.78-4.71]; adjusted IRR 2.32, 95% CI [1.40-3.84]). CONCLUSIONS: The long-term use of DPP-4 inhibitors by elderly patients, particularly male patients with prostatic hyperplasia, may increase the risk of UTI.

Impact of financial incentives for inter-provider care coordination on health-care resource utilization among elderly acute stroke patients.

OBJECTIVE: To examine the impact of inter-provider care coordination on health-care resource utilization among elderly acute stroke patients. DESIGN: A retrospective cohort study using health-care insurance claims data. SETTING: Claims data of the Fukuoka Prefecture Wide-Area Association of Latter-Stage Elderly Healthcare. PARTICIPANTS: About, 6409 patients aged 75 years or older admitted for acute stroke and moved to rehabilitation wards from 1 April 2010 to 30 September 2015. MAIN OUTCOME MEASURE: Lengths of stay (LOS) and total charge (TC) were evaluated according to three groups of care pathways (coordinated care, integrated care and other pathways). RESULTS: Compared with the other care pathway, the coordinated care groups had significantly shorter LOS of 2.0 days in acute ischemic stroke care; they had 2.5 days shorter LOS in hemorrhagic stroke care. However, there were no significant differences in rehabilitation care LOS and TC. CONCLUSIONS: Our findings suggest that a payment system for care coordination is inappropriate since it was not associated with a reduction in overall health-care resource utilization. Further, health-care system reform is necessary to improve care continuity across multiple health-care institutions in Japan.

Quantification of adverse effects of regular use of triazolam on clinical outcomes for older people with insomnia: a retrospective cohort study.

OBJECTIVE: Older people are more likely to have insomnia. One of the most prescribed hypnotics in Japan is triazolam. Although some studies showed the possibility of adverse effects of triazolam in older people, there have been few studies investigating these effects in a clinical setting. The aim of this study was to determine whether patients who used triazolam regularly had increased risks of pneumonia, trauma, and pressure ulcers. METHODS: The research design was a retrospective cohort study using claim data. The subjects of the study were patients who were insured by Fukuoka Late Stage Elderly Healthcare Insurance. We defined patients who had received triazolam for 180 days or longer during fiscal year 2011 as the triazolam group, and those who had not received any hypnotics during the period as the non-triazolam group. Each patient in the triazolam group was then matched with a unique control from the non-triazolam group according to propensity score. Multivariate conditional logistic regression analyses were used to obtain adjusted odds ratios for pneumonia, trauma, and pressure ulcer in the triazolam group compared with the non-triazolam group. RESULTS: The number of patients in the triazolam and non-triazolam groups in the unmatched cohort was 13,015 and 411,610, respectively. Adjusted odds ratios show that the risks for pneumonia, trauma, and pressure ulcer in the matched cohort increased by approximately 40%, 30%, and slightly less than 30%, respectively (all statistically significant). CONCLUSIONS: Regular use of triazolam is a risk factor for pneumonia, trauma, and pressure ulcer in older people.

Quantification of the effect of chemotherapy and steroids on risk of Pneumocystis jiroveci among hospitalized patients with adult T-cell leukaemia.

This study aimed to quantify the risks of Pneumocystis pneumonia (PCP) among adult T-cell leukaemia (ATL) patients without prophylaxis. We used hospital administrative data collected nationwide in Japan over 4 years. The research design was a retrospective cohort study. Subjects were 4369 patients diagnosed with ATL aged 18 years or older. The subjects were categorized into four treatment groups: no agent, chemotherapy, chemotherapy + steroids and steroids. We described the risks of PCP among ATL patients without prophylaxis. Risks of PCP were 3·2% for the no agent group, 9·7% for the chemotherapy group, 10·0% for the chemotherapy + steroids group and 16·6% for the steroids group. Logistic regression analyses showed that the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risk of PCP than did the no agent group [adjusted odds ratio (AOR) 3·30 (1·55-7·02), P = 0·002 for the chemotherapy group; AOR 3·35 (2·18-5·17), P < 0·001 for the chemotherapy + steroids group; AOR 6·12 (3·99-9·38), P < 0·001 for the steroids group]. In conclusion, the chemotherapy, chemotherapy + steroids and steroids groups had significantly higher risks of PCP. Prophylaxis for PCP among ATL patients being treated with chemotherapy, chemotherapy + steroids and steroids is highly recommended.

Regional differences in performance of bone marrow transplantation, care-resource use and outcome for adult T-cell leukaemia in Japan.

BACKGROUND: Japan has a high prevalence of adult T-cell leukaemia (ATL), especially in the Kyushu/Okinawa region. Regional differences in prevalence might cause regional differences in physicians' experiences and the efficiency of care-resource use. This study investigated regional differences in the performance of bone marrow transplantation (BMT), outcome and care-resource use in patients with ATL in Japan. METHODS: This was a cross-sectional study using a Japanese hospital administrative database in 2010, with a diagnostic-procedure combination/per diem payment system. We examined the association between BMT performance, resource use, outcomes and region. RESULTS: We analysed data for 712 subjects of whom 60.5% were Kyushu/Okinawa residents. Significantly more patients with ATL underwent BMT in Kanto (p = 0.018) and Kansai (p < 0.001) regions compared with the Kyushu/Okinawa regions. The lengths of hospital stay were longer in Kanto (p = 0.002) and Kansai (p = 0.006) regions than in the Kyushu/Okinawa region. Total health-care costs were higher in Kanto (p = 0.001) and Kansai (p = 0.005) regions than the Kyushu/Okinawa region. The risks of in hospital mortality were not significantly different between regions. CONCLUSIONS: There were significant regional differences in BMT performance and resource use within Japan. ATL prevalence was not related to the performance of BMTs, resource use or outcomes. Factors related to regional socioeconomics might affect the performance of BMTs and care resource use within Japan.

Does clinical practice supported by artificial intelligence improve hypertension care management? A pilot systematic review.

Although artificial intelligence (AI) is considered to be a promising tool, evidence for the effectiveness of AI-supported clinical practice for lowering blood pressure (BP) in the real world is scarce. We conducted a systematic review to elucidate whether AI-supported clinical care improves BP control. We identified two randomized control trials (RCTs) in a literature search. The results revealed no significant difference between AI-supported care and usual care in a random-effects model meta-analysis of RCTs (AI vs. usual care: systolic/diastolic BP difference: -2.13 [95% confidence interval: -4.72 to 0.46] / -1.03 [-2.52 to 0.46]). In this review, we were unable to clarify whether AI-supported clinical practice improved BP control compared with usual care. Further studies will be needed to provide robust evidence for the effectiveness of AI-supported care in clinical settings.

Influence of Socioeconomic Status on Functional Outcomes After Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: This review aimed to quantify the impact of socioeconomic status on functional outcomes from stroke and identify the socioeconomic status indicators that exhibit the highest magnitude of association. METHODS AND RESULTS: We performed a systematic literature search across Medline and Embase from inception to May 2022, to identify observational studies (n≥100, and in English). Risk of bias was assessed using the modified Newcastle Ottawa Scale. Random effects meta-analysis was used to pool data. We included 19 studies (157 715 patients, 47.7% women) reporting functional outcomes measured with modified Rankin Scale or Barthel index, with 10 assessed as low risk of bias. Measures of socioeconomic status reported were education (11 studies), income (8), occupation (4), health insurance status (3), and neighborhood socioeconomic deprivation (3). Pooled data suggested that low socioeconomic status was significantly associated with poor functional outcomes, including incomplete education or below high school level versus high school attainment and above (odds ratio [OR], 1.66 [95% CI, 1.40-1.95]), lowest income versus highest income (OR, 1.36 [95% CI, 1.02-1.83]), a manual job/being unemployed versus a nonmanual job/working (OR, 1.62 [95% CI, 1.29-2.02]), and living in the most disadvantaged socioeconomic neighborhood versus the least disadvantaged (OR, 1.55 [95% CI, 1.25-1.92]). Low health insurance status was also associated with an increased risk of poor functional outcomes (OR, 1.32 [95% CI, 0.95-1.84]), although this was association was not statistically significant. CONCLUSIONS: Despite great strides in stroke treatment in the past decades, social disadvantage remains a risk factor for poor functional outcome after an acute stroke. Further research is needed to better understand causal mechanisms and disparities.

Risk of recurrent stroke and dementia following acute stroke by changes in kidney function: results from the Perindopril Protection Against Recurrent Stroke Study.

BACKGROUND: Limited data exist on the relationship between declining kidney function and cardiovascular events, dementia, and mortality in patients with a history of stroke.Thus the aims of the study were to investigate functional relationships between dynamic kidney function change and cardiovascular outcomes, and clarify whether adding kidney parameters to conventional cardiovascular risk factors improves model discrimination. METHODS: Post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) clinical trial of blood pressure lowering for the secondary prevention of stroke. We examined the association between dynamic kidney function defined as percentage change (declines of >30%, and >0 to ≤30%, and increases of ≥0 to <30%, and ≥30%) in estimated glomerular filtration rate (eGFR) over 2 years and recurrent stroke, major cardiovascular events, dementia and all-cause death over the next 2 years using Cox proportional hazard models controlling for eGFR at registration and potential confounders. Restricted cubic splines were used to assess the functional relationships. C-statistics and Net Reclassification Improvement (NRI) at 2 years were used to assess model discrimination. RESULTS: In 4591 patients followed for a mean of approximately 2 years, 254 (5.5%) developed recurrent stroke, 391 (8.5%) had a major cardiovascular event, 221 (4.8%) developed dementia, and 271 (5.9%) died. Reverse J-like or U-like relationships were observed for percent declines in eGFR and outcomes. Using declines in eGFR of >0 to ≤30% as a reference, increased risks were evident for a greater decline (>30%) in relation to recurrent stroke [adjusted hazard ratio 1.85, 95% confidence interval (CI) 1.20-2.85], major cardiovascular event (2.24, 1.62-3.10) and all-cause death (2.09, 1.39-3.15). A larger increase (≥30%) in eGFR was also associated with a greater risk of all-cause death (1.96, 1.14-3.37). Improvements in the C-statistic were found by adding baseline eGFR and percent change compared with a model with conventional cardiovascular risk factors alone, for major cardiovascular events, dementia, and all-cause mortality. CONCLUSION: Declining kidney function following an incident cerebrovascular event is associated with additional risk of a major cardiovascular events, dementia, and 2-year mortality. However, a large increase in kidney function was also found to be associated with a higher risk of mortality.

Relationship between abdominal circumference and the incidence of hyperuricemia in the general Japanese population.

In this study, we aimed to separately evaluate the relationship between waist circumference and the incidence of hyperuricemia in men and women in the general Japanese population. We performed a population-based longitudinal study using data from the annual health examination of residents of Iki City, Japan. A total of 5567 participants without hyperuricemia at baseline were included in the analysis. The men and women were placed into groups according to the tertile of waist circumference. The outcome was incident hyperuricemia (uric acid > 416 µmol/L [7.0 mg/dL]). The relationship between waist circumference and the incidence of hyperuricemia was investigated using Cox proportional hazards models. During the follow-up period, hyperuricemia developed in 697 people (551 men and 146 women). The incidence (per 1000 person-years) of hyperuricemia increased with increasing waist circumference in the men (34.9 for tertile 1, 49.9 for tertile 2 and 63.3 for tertile 3; Ptrend < 0.001) and women (5.5 for tertile 1, 6.3 for tertile 2 and 11.9 for tertile 3; Ptrend < 0.001). Significant associations were identified after adjustment for potential confounders (men: Ptrend < 0.001; women: Ptrend = 0.014). In conclusion, both men and women with larger waist circumferences were at higher risks of subsequent hyperuricemia.

A case of immunoglobulin G4-related retroperitoneal fibrosis and hypophysitis with antecedent respiratory disease followed by spontaneous remission and recurrence.

A 65-year-old man presented with apparent bronchopneumonia. After treatment with antibiotics, he showed eosinophilia. Computed tomography (CT) imaging revealed bilateral consolidation, ground-glass opacities with nodular consolidations, and pleural effusion. Lung biopsy showed organising pneumonia with lymphoplasmacytic infiltration in the alveolar septa and in the thickened pleura and interlobular septa. All pulmonary abnormalities spontaneously went into remission within 12 months. At 73 years old, a follow-up CT scan revealed small nodules in both lungs and the review of the head CT scan showed thickening of the pituitary stalk in studying prolonged headache. Two years later, he visited the hospital complaining of severe oedema on the lower extremities with high serum immunoglobulin (Ig)G4 186 mg/dl. A whole-body CT scan showed retroperitoneal mass surrounding aortic bifurcation and compressing inferior vena cava, pituitary stalk thickening and gland swelling, and enlarged pulmonary nodules. Anterior pituitary stimulation tests showed central hypothyroidism, central hypogonadism, and adult growth hormone deficiency with partial primary hypoadrenocorticism. Retroperitoneal mass biopsy showed storiform fibrosis and obliterative phlebitis with marked lymphoplasmacytic infiltration with moderate IgG4-positivity. Immunostaining of the former lung specimen revealed dense interstitial infiltration of IgG4-positive cells. These findings indicated metachronous development of IgG4-related disease in lung, hypophysis, and retroperitoneum, according to the recent comprehensive diagnostic criteria of IgG4-related disease. Glucocorticoid therapy ameliorated oedema, on the other hand, unmasked partial diabetes insipidus at the initial dose of the treatment. Hypothyroidism and retroperitoneal mass regressed at 6 months of the treatment. This case warns us that long-term follow-up from prodromal to remission is necessary for the treatment of IgG4-related disease.