Impact of Early Rehabilitation after Endovascular Treatment for Peripheral Arterial Disease.

Objectives: The prevalence of peripheral arterial disease (PAD) is on the rise, with endovascular treatment being a widely accepted surgical intervention. Patients with PAD often experience reduced activities of daily living (ADL). Therefore, we conducted a retrospective cohort study to investigate the impact of early rehabilitation after endovascular treatment in patients with PAD. Methods: Using data from the JMDC hospital database, the study included 529 patients who were hospitalized for PAD and underwent endovascular treatment. Patients were classified into two independent variables: early rehabilitation group (rehabilitation started within 2 days postoperatively) and control group (rehabilitation started within 3-7 days postoperatively). The outcome measures were the occurrence of hospital-associated disability (HAD) and duration of hospitalization. Results: Unadjusted data showed that the early rehabilitation group (n=469) had fewer HAD events (8.5% vs. 23.3%, P <0.001) and a shorter mean hospitalization duration (4.4 vs. 18.9 days, P <0.001) than the control group (n=60). The difference remained significant after adjustment by propensity score analysis. Conclusions: In patients with PAD, early rehabilitation after endovascular treatment may be beneficial in preventing the development of HAD and reducing the duration of hospitalization.

Cholesterol Crystal Embolism: Autopsy-proven Gastrointestinal Lesions, Pancreatitis, and End-stage Kidney Disease Which Developed after Undergoing Selective Abdominal Angiography.

A 78-year-old man with atherosclerosis was diagnosed with hepatocellular carcinoma by transfemoral angiography of the celiac and superior mesenteric arteries (SMA). After surgery, a serum examination revealed progressive renal failure with eosinophilia, leading to end-stage kidney disease, in addition to active gastric ulcers and pancreatitis. Cyanosis in the bilateral toes showed a cholesterol crystal embolism (CCE) in a skin biopsy. Autopsy revealed that CCE involved the arterioles of multiple organs, and its distribution was anatomically consistent with the vascular territories of the celiac artery and SMA. CCE should therefore be considered in patients presenting with multiple types of tissue damage in the vascular territories after angiography.

Effects of acute phase intensive electrical muscle stimulation in COVID-19 patients requiring invasive mechanical ventilation: an observational case-control study.

We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case-control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.

Characterization of the visually impaired patients with diabetes mellitus in Japan.

AIMS/INTRODUCTION: To conduct a multicenter survey of visually impaired patients with diabetes mellitus (DM) and to identify the physical and ocular characteristics that lead to blindness in Japan. MATERIALS AND METHODS: Visually impaired patients with diabetes mellitus in Japan were divided into blind and low-vision groups according to the World Health Organization classification. Data on parameters related to diabetes mellitus and ocular complications in the right and left eyes were collected from 19 highly advanced medical facilities and compared between the two groups. RESULTS: Among 408 visually impaired persons (blind group: 257, low-vision group: 151), 72.1% were under 70 years of age. The rates of neovascular glaucoma (NVG) (right eye, P = 0.041; left eye, P = 0.0031) or proliferative diabetic retinopathy (PDR) (right eye: P = 0.014, left eye: P = 0.0047) and the rate of proliferative membrane beyond half of the retinal area (right eye: P = 0.0263, left eye: P = 0.037) were significantly higher in the blind group. The direct cause of visual impairment was retinal atrophy, common in both groups. Neovascular glaucoma and diabetic macular edema were equally prevalent in the blind and low-vision groups, respectively. CONCLUSIONS: In Japan, blind patients with diabetes mellitus are characterized by severe conditions such as neovascular glaucoma and progressive proliferative diabetic retinopathy upon their initial visit to an advanced care facility. These results highlight the importance of monitoring retinopathy through regular ophthalmological examinations, internal medicine, and appropriate therapeutic intervention.

Design and rationale for an open-label, randomized, controlled pilot trial to evaluate the changes in blood uremic toxins in patients with chronic kidney disease by dietary therapy with sake lees.

BACKGROUND: Patients with chronic kidney disease (CKD) reportedly show dysbiosis, which is the imbalance of gut microbiome. Dysbiosis increases the uremic toxin level in the intestine, and uremic toxins transfer into the blood, causing CKD progression. Sake lees, a traditional Japanese fermented food, may help reduce uremic toxins by altering the gut microbiome. Additionally, D-alanine, which is present in sake lees, may have a renoprotective effect. The present pilot study aims to evaluate the effect of adding sake lees to the standard CKD dietary therapy in reducing blood uremic toxins. METHODS: This pilot study is a single-center, open-label, randomized controlled trial. Twenty-four patients with CKD will be enrolled and allocated 1:1 to the intervention and control groups. The intervention group will receive standard CKD dietary therapy with an additional intake of 50 g of sake lees per day for 8 weeks, whereas the control group will only receive standard CKD dietary therapy. The primary endpoint is the change in serum indoxyl sulfate after 8 weeks. The secondary endpoint is the plasma D-alanine and fecal microbiome changes. CONCLUSION: This pilot study provides insight into the development of a new diet focused on gut microbiome and D-amino acids in patients with CKD. CLINICAL TRIAL REGISTRATION: This protocol was approved by the Clinical Trial Review Board of Kanazawa University Hospital on October 27, 2022 (2022-001 [6139]) and available to the public on the website of the Japan Registry of Clinical Trials on November 22, 2022 (jRCT1040220095).

Trajectory of GFR Decline and Fluctuation in Albuminuria Leading to End-Stage Kidney Disease in Patients With Biopsy-Confirmed Diabetic Kidney Disease.

Introduction: Data on longitudinal trajectory of kidney function decline and fluctuation in albuminuria leading to end-stage kidney disease (ESKD) is sparse in patients with type 2 diabetes. Methods: Using data from an observational study of patients with type 2 diabetes and biopsy-confirmed diabetic kidney disease (DKD), generalized additive mixed models (GAMMs) were performed to quantify patterns of longitudinal trajectory of estimated glomerular filtration rate (eGFR) decline to ESKD associated with repeated measures of urine albumin-to-creatinine ratio (ACR). Results: Over a median follow-up period of 3.3 years, 155 of 319 patients progressed to ESKD. Among these patients, 91.6% exhibited a curvilinear pattern in their eGFR trajectory. The median coefficient of variation for ACR, representing the variability in ACR measurements, was 48.9 (interquartile range: 36.9, 68.2). The median compound annual growth rate (CAGR) for ACR, reflecting the variation in ACR progression over time, was 43.6% (interquartile range: 0.0, 102.5); and 84.5% of patients developed nephrotic-range albuminuria, with a majority remaining nephrotic and subsequently progressing to ESKD. There was a positive association between the instantaneous speed of eGFR decline and ACR. Conclusion: The observed curvilinear pattern in eGFR trajectory, high variability in ACR progression over time, and positive correlation between the speed of eGFR decline and ACR highlight the complex dynamics of disease progression and emphasize close monitoring of ACR fluctuation over time in patients with DKD.

Protective Role of MAVS Signaling for Murine Lipopolysaccharide-Induced Acute Kidney Injury.

Despite treatment advances, acute kidney injury (AKI)-related mortality rates are still high in hospitalized adults, often due to sepsis. Sepsis and AKI could synergistically worsen the outcomes of critically ill patients. TLR4 signaling and mitochondrial antiviral signaling protein (MAVS) signaling are innate immune responses essential in kidney diseases, but their involvement in sepsis-associated AKI (SA-AKI) remains unclear. We studied the role of MAVS in kidney injury related to the TLR4 signaling pathway using a murine LPS-induced AKI model in wild-type and MAVS-knockout mice. We confirmed the importance of M1 macrophage in SA-AKI through in vivo assessment of inflammatory responses. The TLR4 signaling pathway was upregulated in activated bone marrow-derived macrophages, in which MAVS helped maintain the LPS-suppressed TLR4 mRNA level. MAVS regulated redox homeostasis via NADPH oxidase Nox2 and mitochondrial reverse electron transport in macrophages to alleviate the TLR4 signaling response to LPS. Hypoxia-inducible factor 1α (HIF-1α) and AP-1 were key regulators of TLR4 transcription and connected MAVS-dependent reactive oxygen species signaling with the TLR4 pathway. Inhibition of succinate dehydrogenase could partly reduce inflammation in LPS-treated bone marrow-derived macrophages without MAVS. These findings highlight the renoprotective role of MAVS in LPS-induced AKI by regulating reactive oxygen species generation-related genes and maintaining redox balance. Controlling redox homeostasis through MAVS signaling may be a promising therapy for SA-AKI.

Kidney outcomes associated with haematuria and proteinuria trajectories among patients with IgA nephropathy in real-world clinical practice: The Japan Chronic Kidney Disease Database.

AIM: Among patients with Immunoglobulin A (IgA) nephropathy, we aimed to identify trajectory patterns stratified by the magnitude of haematuria and proteinuria using repeated urine dipstick tests, and assess whether the trajectories were associated with kidney events. METHODS: Using a nationwide multicentre chronic kidney disease (CKD) registry, we analysed data from 889 patients with IgA nephropathy (mean age 49.3 years). The primary outcome was a sustained reduction in eGFR of 50% or more from the index date and thereafter. During follow-up (median 49.0 months), we identified four trajectories (low-stable, moderate-decreasing, moderate-stable, and high-stable) in both urine dipstick haematuria and proteinuria measurements, respectively. RESULTS: In haematuria trajectory analyses, compared to the low-stable group, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) for kidney events were 2.59 (95% CI, 1.48-4.51) for the high-stable, 2.31 (95% CI, 1.19-4.50) for the moderate-stable, and 1.43 (95% CI, (0.72-2.82) for the moderate-decreasing groups, respectively. When each proteinuria trajectory group was subcategorized according to haematuria trajectories, the proteinuria group with high-stable and with modest-stable haematuria trajectories had approximately 2-times higher risk for eGFR reduction ≥50% compared to that with low-stable haematuria trajectory. CONCLUSION: Assessments of both haematuria and proteinuria trajectories using urine dipstick could identify high-risk IgA nephropathy patients.

Predictive Value of the Hemoglobin-Geriatric Nutritional Risk Index in Patients with Heart Failure.

Malnutrition prevails among patients with heart failure (HF), increasing the likelihood of functional decline. We assessed the predictive value of the Hemoglobin-Geriatric Nutritional Risk Index (H-GNRI)-combining hemoglobin and the Geriatric Nutritional Risk Index (GNRI)-on prognosis in older patients with HF. We used the JMDC multicenter database to examine the potential associations between malnutrition risk and other outcome measures. The patients were categorized as low- (H-GNRI score = 0), intermediate- (H-GNRI score = 1), or high-risk (H-GNRI score = 2) based on their H-GNRI scores. The primary outcome measure was the Barthel Index (BI) gain; the secondary outcomes included the BI at discharge, the BI efficiency, length of hospital stay, in-hospital mortality, discharge to home or a nursing home, and hospitalization-associated disability. We analyzed 3532 patients, with 244 being low-risk, 952 being intermediate-risk, and 2336 being high-risk patients. The high-risk group of patients had significantly lower BI values at discharge, lower BI gains, reduced BI efficiency values, and prolonged hospital stays compared to those in the low-risk group. The high-risk patients also had higher in-hospital mortality rates, lower rates of discharge to home or a nursing home, and greater incidences of a hospitalization-associated disability in comparison to the low-risk group. The H-GNRI may serve as a valuable tool for determining prognoses for patients with HF.

Physical function and mental health trajectories in COVID-19 patients following invasive mechanical ventilation: a prospective observational study.

This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score < 48 points, and prolonged IMV was significantly associated with lower MRC sum score and handgrip strength. Symptoms were similar between groups at ICU discharge, and the symptoms most commonly reported as moderate-to-severe were impaired well-being (52%), anxiety (43%), tiredness (41%), and depression (35%). Although muscle strength and mobility status were significantly improved after ICU discharge, Edmonton Symptom Assessment System score did not improve significantly in the prolonged IMV group. EuroQol five-dimension five-level summary index was significantly lower in the prolonged than short IMV group at 6 months after ICU discharge. We found substantial negative physical function and mental health consequences in the majority of surviving COVID-19 patients requiring IMV, with prolonged period of IMV showing greater negative effects not only immediately but also at 6 months after discharge from the ICU.

Polar vasculosis is associated with better kidney outcome in type 2 diabetes with biopsy-proven diabetic kidney disease: A multicenter cohort study.

AIMS/INTRODUCTION: This multicenter cohort study retrospectively assessed the association between polar vasculosis and the progression of diabetic kidney disease (DKD) in type 2 diabetes. MATERIALS AND METHODS: We enrolled 811 patients with type 2 diabetes, biopsy-proven DKD, and proteinuria (≥0.15 g/g creatinine [g/day]). The association between polar vasculosis and other kidney lesions was explored. The outcome was DKD progression defined as a composite of renal replacement therapy initiation or 50% decline in estimated glomerular filtration rate (eGFR) from baseline. RESULTS: Of the 811 cases, 677 (83.5%) had polar vasculosis. In multivariate logistic regression analysis, subendothelial widening of the glomerular basement membrane, glomerulomegaly, glomerular class in the Renal Pathology Society classification ≥IIb, vascular lesions, age, eGFR, and hemoglobin A1c were positively associated with polar vasculosis, whereas interstitial fibrosis and tubular atrophy (IFTA) was negatively associated with polar vasculosis. During a median follow-up of 5.2 years, progression of DKD occurred in 322 of 677 (7.4 events/100 person-years) and 79 of 134 (11.4 events/100 person-years) cases with and without polar vasculosis, respectively. Kaplan-Meier analysis showed that polar vasculosis was associated with lower cumulative incidences of DKD progression. Multivariate Cox regression analyses showed that polar vasculosis was associated with a lower risk of DKD progression, regardless of eGFR or proteinuria subgroups. These associations between polar vasculosis and better kidney outcome were unchanged considering all-cause mortality before DKD progression as a competing event. CONCLUSIONS: This study showed that polar vasculosis of DKD was associated with less advanced IFTA and a better kidney outcome in type 2 diabetes with proteinuria.

A comprehensive risk factor analysis using association rules in people with diabetic kidney disease.

Association rule is a transparent machine learning method expected to share information about risks for chronic kidney disease (CKD) among diabetic patients, but its findings in clinical data are limited. We used the association rule to evaluate the risk for kidney disease in General and Worker diabetic cohorts. The absence of risk factors was examined for association with stable kidney function and worsening kidney function. A confidence value was used as an index of association, and a lift of > 1 was considered significant. Analyses were applied for individuals stratified by KDIGO's (Kidney Disease: Improving Global Outcomes) CKD risk categories. A General cohort of 4935 with a mean age of 66.7 years and a Worker cohort of 2153 with a mean age of 47.8 years were included in the analysis. Good glycemic control was significantly related to stable kidney function in low-risk categories among the General cohort, and in very-high risk categories among the Worker cohort; confidences were 0.82 and 0.77, respectively. Similar results were found with poor glycemic control and worsening kidney function; confidences of HbA1c were 0.41 and 0.27, respectively. Similarly, anemia, obesity, and hypertension showed significant relationships in the low-risk General and very-high risk Worker cohorts. Stratified risk assessment using association rules revealed the importance of the presence or absence of risk factors.

Association Between Risperidone Use and Kidney Function Decline in Patients with Schizophrenia: A Retrospective Cohort Study.

PURPOSE: Several D-amino acids have been shown to be protective against kidney injury in mice. Risperidone, a currently used atypical antipsychotic agent for schizophrenia, is also known to inhibit the activity of D-amino acid oxidase, which degrades certain D-amino acids. Based on the hypothesis that risperidone would prevent kidney disease progression, this study investigated the association between risperidone use and kidney function decline in patients with schizophrenia. METHODS: This retrospective cohort study included patients who were diagnosed with schizophrenia and had data available from two or more serum creatinine measurements between April 1, 2010, and March 31, 2020. Patients who used risperidone for at least 30 days were included in the risperidone group, whereas those who had no record of risperidone use were included in the control group. Cox regression models were used to evaluate the risk for 40% decline in estimated glomerular filtration rate (eGFR) in patients treated with risperidone compared to that in the control group. FINDINGS: Overall, 212 patients used risperidone and 1468 patients had no record of risperidone use. The mean age was 55 years, 759 (45%) of the patients were male, and the mean eGFR at baseline was 88 mL/min/1.73 m2. The mean age in the risperidone group was less than that in the control group (52 vs 56 years); other baseline characteristics were comparable between the two groups. During a mean follow-up of 1.6 years, 267 patients (16%) had a 40% eGFR decline. The incidence rate of 40% eGFR decline was lower in the risperidone group than in the control group (60 vs 104 per 1000 person-years). After adjustment for baseline age, sex, and eGFR, risperidone use was associated with a decreased risk for 40% eGFR decline (hazard ratio = 0.54; 95% CI, 0.33-0.87; P = 0.01). IMPLICATIONS: Risperidone use may be associated with decreased risk for kidney function decline in patients with schizophrenia. Further studies are warranted to validate these findings.

Myocardin-related transcription factor contributes to renal fibrosis through the regulation of extracellular microenvironment surrounding fibroblasts.

Fibroblast accumulation and extracellular matrix (ECM) deposition are common critical steps for the progression of organ fibrosis, but the precise molecular mechanisms remain to be fully investigated. We have previously demonstrated that lysophosphatidic acid contributes to organ fibrosis through the production of connective tissue growth factor (CTGF) via actin cytoskeleton-dependent signaling, myocardin-related transcription factor family (MRTF) consisting of MRTF-A and MRTF-B-serum response factor (SRF) pathway. In this study, we investigated the role of the MRTF-SRF pathway in the development of renal fibrosis, focusing on the regulation of ECM-focal adhesions (FA) in renal fibroblasts. Here we showed that both MRTF-A and -B were required for the expressions of ECM-related molecules such as lysyl oxidase family members, type I procollagen and fibronectin in response to transforming growth factor (TGF)-ß1 . TGF-ß1 -MRTF-SRF pathway induced the expressions of various components of FA such as integrin α subunits (αv , α2 , α11 ) and ß subunits (ß1 , ß3 , ß5 ) as well as integrin-linked kinase (ILK). On the other hand, the blockade of ILK suppressed TGF-ß1 -induced MRTF-SRF transcriptional activity, indicating a mutual relationship between MRTF-SRF and FA. Myofibroblast differentiation along with CTGF expression was also dependent on MRTF-SRF and FA components. Finally, global MRTF-A deficient and inducible fibroblast-specific MRTF-B deficient mice (MRTF-AKO BiFBKO mice) are protected from renal fibrosis with adenine administration. Renal expressions of ECM-FA components and CTGF as well as myofibroblast accumulation were suppressed in MRTF-AKO BiFBKO mice. These results suggest that the MRTF-SRF pathway might be a therapeutic target for renal fibrosis through the regulation of components forming ECM-FA in fibroblasts.

Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease.

Introduction: The number of patients with chronic kidney disease (CKD) is increasing worldwide. Cognitive impairment is one of the comorbidities of CKD. With the increased number of aged population, novel biomarkers of impaired cognitive function are required. Intra-body profile of amino acid (AA) is reportedly altered in patients with CKD. Although some AAs act as neurotransmitters in the brain, it is not clear whether altered AA profile are associated with cognitive function in patients with CKD. Therefore, intra-brain and plasma levels of AAs are evaluated with respect to cognitive function in patients with CKD. Methods: Plasma levels of AAs were compared between 14 patients with CKD, including 8 patients with diabetic kidney disease, and 12 healthy controls to identify the alteration of specific AAs in CKD. Then, these AAs were evaluated in the brains of 42 patients with brain tumor using non-tumor lesion of the resected brain. Cognitive function is analyzed with respect to intra-brain levels of AAs and kidney function. Moreover, plasma AAs were analyzed in 32 hemodialyzed patients with/without dementia. Results: In patients with CKD, plasma levels of asparagine (Asn), serine (Ser), alanine (Ala), and proline (Pro) were increased as compared to patients without CKD. Among these AAs, L-Ser, L-Ala, and D-Ser show higher levels than the other AAs in the brain. Intra-brain levels of L-Ser was correlated with cognitive function and kidney function. The number of D-amino acid oxidase or serine racemase-positive cells was not correlated with kidney function. Moreover, the plasma levels of L-Ser are also decreased in patients with declined cognitive function who are treated with chronic hemodialysis. Conclusion: The decreased levels of L-Ser are associated with impaired cognitive function in CKD patients. Especially, plasma L-Ser levels may have a potential for novel biomarker of impaired cognitive function in patients with hemodialysis.

Cardiac Rehabilitation in Severe Heart Failure Patients with Impella 5.0 Support via the Subclavian Artery Approach Prior to Left Ventricular Assist Device Implantation.

Impella 5.0 circulatory support via subclavian artery (SA) access may be a safe approach for patients undergoing cardiac rehabilitation (CR). In this case series, we retrospectively analyzed the demographic characteristics, physical function, and CR data of six patients who underwent Impella 5.0 implantation via the SA prior to left ventricular assist device (LVAD) implantation between October 2013 and June 2021. The median age was 48 years, and one patient was female. Grip strength was maintained or increased in all patients before LVAD implantation (pre-LVAD) compared to after Impella 5.0 implantation. The pre-LVAD knee extension isometric strength (KEIS) was less than 0.46 kgf/kg in two patients and more than 0.46 kgf/kg in three patients (unavailable KEIS data, n = 1). With Impella 5.0 implantation, two patients could ambulate, one could stand, two could sit on the edge of the bed, and one remained in bed. One patient lost consciousness during CR due to decreased Impella flow. There were no other serious adverse events. Impella 5.0 implantation via the SA allows mobilization, including ambulation, prior to LVAD implantation, and CR can be performed relatively safely.

Association between the amount of rehabilitation and the outcomes in patients with aspiration pneumonia.

The appropriate amount of rehabilitation for aspiration pneumonia remains unknown. We conducted a historical cohort study to investigate the association between the amount of rehabilitation provided and the outcome of patients with aspiration pneumonia. A total of 4148 patients with aspiration pneumonia recruited from a database created by JMDC were categorized into three groups based on daily rehabilitation units: none or <1 unit (low-volume group), 1-2 units (medium-volume group), and more than 2 units (high-volume group). The main outcome measures were death in the hospital, discharge home, and length of hospital stay. The results showed that the middle-volume and high-volume groups had significantly fewer in-hospital deaths [middle-volume group, odds ratio (OR) 0.62; 95% confidence interval (CI), 0.46-0.83; high-volume group, OR 0.66; 95% CI, 0.45-0.97], more patients were discharged home (middle-volume group, OR 1.29; 95% CI, 1.03-1.62; high-volume group, OR 2.00; 95% CI, 1.48-2.71), and shorter hospital stay (middle-volume group, coefficient -3.30; 95% CI, -6.42 to -0.19; high-volume group, coefficient -4.54; 95% CI, -8.69 to -0.40) compared with the low-volume group. In conclusion, higher rehabilitation units per day provided to patients with aspiration pneumonia were associated with fewer deaths, more home discharges, and shorter hospital stays.

Sex differences in risk factors for end-stage kidney disease and death in type 2 diabetes: A retrospective cohort study.

BACKGROUND: This study investigated the sex differences in the risk of end-stage kidney disease (ESKD) and mortality, as well as the effect modification of sex on associated factors in patients with type 2 diabetes. METHODS: This multicenter observational cohort study included 4328 patients with type 2 diabetes. Hazard ratios (HRs) with 95% confidence intervals (CIs) of sex for ESKD and death were estimated using Cox proportional regression with adjustment for baseline covariates. For assessing risk modification, HRs and incidence rates for ESKD and death were compared between sexes across patient characteristics using Cox proportional and Poisson regression models. RESULTS: During a median follow-up of 7 years, 276 patients (70% men) developed ESKD, and 241 patients (68% men) died. Men had higher risks of ESKD (HR 1.34; 95% CI 1.02-1.75; p = .034) and death (HR 1.64; 95% CI 1.24-2.16; p = .001) versus women after adjusting for multiple covariates. Among patients with microalbuminuria, men had a substantially higher risk of ESKD versus women, compared to those with normo- and macroalbuminuria (p for interaction .04). Incidence rates were also increased in men versus women with albuminuria of around 300 mg/g. No differences were detected in the association of sex and death across baseline patient subgroups. CONCLUSIONS: In type 2 diabetes, men had an increased risk of ESKD and death versus women. Moderately increased albuminuria was strongly associated with sex difference in developing ESKD.

[Interaction of Phenytoin with Enteral Formulas, Proteins, and Dietary Fiber in Vitro and in Vivo].

Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined the binding of phenytoin with enteral formulas and its components by quantifying the free phenytoin concentration. Furthermore, we investigated the effect of enteral formulas on gastrointestinal absorption of phenytoin in rats. The free phenytoin rate was reduced in vitro when phenytoin and enteral formula or pectin, a dietary fiber in enteral formulas, were co-administered. In vivo, when phenytoin and the enteral formula Mei Balance R® were co-administered, the time to maximum plasma concentration (Tmax) after oral administration was significantly increased. Moreover, the area under the phenytoin concentration-time curve from time zero to 6 h (AUC0-6 h) was significantly increased by co-administration of phenytoin with the enteral formula PG Soft EJ®. These results showed the gastrointestinal absorption of phenytoin differs according to the type of enteral formula. In addition, we found the first time that plasma phenytoin levels increase when combined with enteral formula. Among the components of enteral formulas, in particular, milk protein delayed the absorption of phenytoin. Moreover, milk protein, casein and carrageenan tended to increase AUC0-6 h. These results suggest the change in phenytoin concentration is due not only to the binding of enteral formula but also to the disintegration of components such as protein. Therefore, when co-administrated of phenytoin and enteral formula, phenytoin must be monitored frequently according to the enteral formula interaction.

The effect of preoperative rehabilitation on the prevention of postoperative ileus in colorectal cancer patients.

PURPOSE: Previous research suggests that the preoperative rehabilitation of colorectal cancer patients can reduce postoperative ileus. However, the evidence is insufficient and further research is warranted. This study aimed to investigate whether short-term preoperative rehabilitation, both on an outpatient and inpatient basis, can reduce the incidence of postoperative ileus after colorectal cancer surgery. METHODS: This was a retrospective cohort study that drew on data from multicenter electronic medical records. Patients with stage 1-3 colorectal cancer who underwent surgery and postoperative rehabilitation were included. The incidence of postoperative ileus was compared between patients who received short-term preoperative rehabilitation and those who did not. Propensity score adjustment using inverse probability weighting and subgroup analysis by type of surgery was performed. RESULTS: Four thousand seventy-six eligible patients (43.4% female; mean age 75.1 ± 10.9 years) were included; 1914 (47.0%) received short-term preoperative rehabilitation. The preoperative rehabilitation group had a significantly lower incidence of postoperative ileus than the no preoperative rehabilitation group (pre-adjustment: 5.5% vs. 9.9%, p < 0.001; post-adjustment: 5.2% vs. 9.0%, p < 0.001). Therefore, preoperative rehabilitation was significantly associated with a lower incidence of postoperative ileus (OR: 0.554, 95% CI: 0.415-0.739, p < 0.001). In an adjusted analysis of surgery type subgroups, the incidence of postoperative ileus was significantly lower in the preoperative rehabilitation group for all types of surgery. CONCLUSION: Our study showed that short-term preoperative rehabilitation for patients with stage 1-3 colorectal cancer, both with inpatients and outpatients, significantly reduces the incidence of postoperative ileus.