Assessment of the deformation rate of venous diameter during internal jugular vein puncture using a newly developed thin-tip three-dimensional needle.

BACKGROUND: The internal jugular vein (IJV) is one of the most used sites for central venous access. Some authors revealed the association of a higher deformation rate of the IJV wall with posterior wall penetration, which may cause a hemorrhagic complication. A newly developed thin-tip needle (three-dimensional (3D) needle) reduced the deformation rate in an ex vivo study. Therefore, we conducted a clinical study to investigate its efficacy in reducing vessel deformity during IJV puncture. METHODS: This study retrospectively enrolled 80 adult patients who received central venous port (CVP) implantation via the IJV from April 1, 2022, to November 10, 2023, in our institution. Traditional needle-and-catheter was used for ultrasound (US)-guided IJV puncture (usual group) for the former 40 patients before July 18, 2023. Afterward, the 3D needle was used for the latter 40 patients (3D needle group). US images were stored and analyzed to calculate the deformation rate. RESULTS: The deformation rate was 58.6% (13.2-100) for the usual needle and 41.8% (10.6-100) for the 3D needle (p = 0.0034). Patients who required several punctures included 2 for the usual needle and 12 for the 3D needle, respectively (p = 0.0032). All patients and the usual needle group demonstrated a weak negative correlation between the deformation rate and pre-puncture vessel diameter (r = 0.24 and 0.41, respectively), with no correlation in the 3D needle group. CONCLUSION: The deformation rate of the IJV wall was smaller in the 3D needle group than in the usual needle group. The use of a 3D needle would be safer when puncturing the IJV.

Prospective analysis of patient-reported outcomes and physician-reported outcomes with gynecologic cancer chemotherapy.

OBJECTIVE: Gynecologic cancer chemotherapy impacts the quality of life (QOL) of patients, with lasting adverse events that may require treatment adjustments or discontinuation. Consequently, real-time symptom monitoring before outpatient visits has resulted in improved QOL for patients and extended survival times. This study investigated whether there are differences between electronic patient-reported outcomes (e-PRO-CTCAE) and physician-assessed outcomes (NCI-CTCAE) evaluated in an outpatient setting in gynecologic cancer chemotherapy. METHODS: The study was conducted on 50 patients who received their first chemotherapy treatment at St. Marianna University Hospital Obstetrics and Gynecology from July 1, 2021 to December 31, 2022. PRO-CTCAE and NCI-CTCAE were evaluated at each instance of chemotherapy and 2 weeks after. The PRO-CTCAE was additionally collected weekly using e-PRO. RESULTS: The values for "Joint Pain," "Nausea," "Taste Disturbance," "Constipation," "Insomnia," "Fatigue," "Limb Edema," and "Concentration Impairment" were consistently higher in PRO-CTCAE than in NCI-CTCAE, indicating that physicians underestimated the severity of adverse events. In contrast, there was no significant difference in "Peripheral Neuropathy," demonstrating that physicians had a good understanding of this condition in patients. The weekly responses obtained from e-PRO revealed that symptom exacerbations peaked outside of clinic visits. CONCLUSIONS: This study demonstrated physicians tend to underestimate most adverse events. Moreover, the responses using e-PRO revealed peak symptom deterioration occurred outside of outpatient visits. This suggested that e-PRO and actions taken in response to them can improve patients' QOL.

Higher hemoglobin levels using darbepoetin alfa and kidney outcomes in advanced chronic kidney disease without diabetes: a prespecified secondary analysis of the PREDICT trial.

BACKGROUND: In the primary analysis of the PREDICT trial, a higher hemoglobin target (11-13 g/dl) with darbepoetin alfa did not improve renal outcomes compared with a lower hemoglobin target (9-11 g/dl) in advanced chronic kidney disease (CKD) without diabetes. Prespecified secondary analyses were performed to further study the effects of targeting higher hemoglobin levels on renal outcomes. METHODS: Patients with an estimated glomerular filtration rate (eGFR) 8-20 ml/min/1.73 m2 without diabetes were randomly assigned 1:1 to the high- and low-hemoglobin groups. The differences between the groups were evaluated for the following endpoints and cohort sets: eGFR and proteinuria slopes, assessed using a mixed-effects model in the full analysis set and the per-protocol set that excluded patients with off-target hemoglobin levels; the primary endpoint of composite renal outcome, evaluated in the per-protocol set using the Cox model. RESULTS: In the full analysis set (high hemoglobin, n = 239; low hemoglobin, n = 240), eGFR and proteinuria slopes were not significantly different between the groups. In the per-protocol set (high hemoglobin, n = 136; low hemoglobin, n = 171), the high-hemoglobin group was associated with reduced composite renal outcome (adjusted hazard ratio: 0.64; 95% confidence interval: 0.43-0.96) and an improved eGFR slope (coefficient: + 1.00 ml/min/1.73 m2/year; 95% confidence interval: 0.38-1.63), while the proteinuria slope did not differ between the groups. CONCLUSIONS: In the per-protocol set, the high-hemoglobin group demonstrated better kidney outcomes than the low-hemoglobin group, suggesting a potential benefit of maintaining higher hemoglobin levels in patients with advanced CKD without diabetes. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (identifier: NCT01581073).

Hyporesponsiveness to erythropoiesis-stimulating agent in non-dialysis-dependent CKD patients: The BRIGHTEN study.

Among non-dialysis-dependent chronic kidney disease (ND-CKD) patients, a low hematopoietic response to erythropoiesis-stimulating agents (ESAs) is a predictor for poor renal and cardiovascular outcome. To assess the method for evaluating hyporesponsiveness to ESA in patients with ND-CKD, a multicenter, prospective, observational study of 1,980 adult patients with ND-CKD with renal anemia was conducted. Darbepoetin alfa (DA) and iron supplement administrations were provided according to the recommendation of the attached document and the guidelines of JSDT (Japanese Society of Dialysis and Transplantation). The primary outcomes were progression of renal dysfunction and major adverse cardiovascular events. ESA responsiveness was assessed using pre-defined candidate formulae. During the mean follow-up period of 96 weeks, renal and cardiovascular disease (CVD) events occurred in 683 (39.6%) and 174 (10.1%) of 1,724 patients, respectively. Among pre-set candidate formulae, the one expressed by dividing the dose of DA by Hb level at the 12-week DA treatment was statistically significant in predicting renal (hazard ratio [HR], 1.449; 95% confidence interval [CI], 1.231-1.705; P<0.0001) and CVD events (HR, 1.719; 95% CI, 1.239-2.386; P = 0.0010). The optimum cut-off values for both events were close to 5.2. In conclusion, hyporesponsiveness to ESA in ND-CKD cases, which is associated with a risk for renal and CVD events, may be evaluated practicably as the dose of DA divided by the Hb level at the 12-week DA treatment, and the cut-off value of this index is 5.2. A search for the causes of poor response and measures for them should be recommended in such patients. Trial registration: ClinicalTrials. gov Identifier: NCT02136563; UMIN Clinical Trial Registry Identifier: UMIN000013464.

The Utility of Automated ASPECTS in Acute Ischemic Stroke for Intravenous Recombinant Tissue Plasminogen Activator (IV-rtPA) Therapy.

PURPOSE: This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. METHODS: This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0-5) in population #2. RESULTS: The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. CONCLUSIONS: The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy.

Validity of intraoperative voice monitoring undergoing type 2 thyroplasty with titanium bridges for adductor spasmodic dysphonia.

Objectives: The success of type 2 thyroplasty (TP2) for adductor spasmodic dysphonia (AdSD) depends on the selection of optimally sized titanium bridges, which requires accurate assessment of intraoperative vocal changes. While this procedure has traditionally been performed according to the laryngologist's experience, the most appropriate method for voice monitoring and selection of titanium bridge size remains to be determined. This study aimed to investigate evaluation parameters useful for voice monitoring, as these may allow less experienced surgeons to perform TP2 properly. Methods: In this prospective study, voice monitoring was performed in 18 patients with AdSD patients undergoing TP2. Evaluations were performed preoperatively, intraoperatively, 13 weeks postoperatively, and 52 weeks postoperatively using GRBAS (grade, roughness, breathiness, asthenia, and strain), as well as perceptual judgment and acoustic analyses. Results: Preoperative and intraoperative assessments of the G, R, B, and S parameters, perceptual judgment, and harmonic-to-noise ratio (HNR) were in moderate or better agreement. Intraoperative and 13- or 52-week postoperative measurements of the R, B, and G parameters and strangulation, tremor, and HNR were also in high agreement. When two different sizes of titanium bridges were compared (unselected vs. selected), ratings for G, R, S, strangulation, tremor, jitter, shimmer, HNR, standard deviation of F0, and degree of voice breaks were better for the selected width than the unselected width. Conclusion: The candidate items for intraoperative voice monitoring during TP2 for AdSD are G, R, strangulation, tremor, and HNR. The use of these items may help to ensure successful TP2 and contribute to the advancement of laryngeal framework surgery. Level of evidence: Level 4.

The Forward and Lateral Tilt Angle of the Neck and Trunk Measured by Three-Dimensional Gait and Motion Analysis as a Candidate for a Severity Index in Patients with Parkinson's Disease.

(1) Objective: To evaluate the usefulness of a three-dimensional motion-analysis system (AKIRA®) as a quantitative measure of motor symptoms in patients with Parkinson's disease (PD). (2) Method: This study included 48 patients with PD. We measured their motion during 2 m of walking using AKIRA®, we calculated the tilt angles of the neck and trunk, ankle height, and gait speed, then we compared these parameters with the MDS-UPDRS and the Hoehn and Yahr scale. Furthermore, we measured these AKIRA indicators before and after 1 year of observation. (3) Results: The forward tilt angle of the neck showed a strong correlation with the scores on parts II, III, and the total MDS-UPDRS, and the tilt angle of the trunk showed a moderate correlation with those measures. The lateral tilt angle of the trunk showed a moderate correlation with a freezing of the gait and a postural instability. Regarding changes over the course of 1 year (n = 34), the total scores on part III of the MDS-UPDRS and the forward tilt angle of the neck improved, while the lateral tilt angle of the trunk worsened. (4) Conclusion: Taken together, the forward and lateral tilt angles of the neck and trunk as measured by AKIRA® can be a candidate for quantitative severity index in patients with PD.

RAISING is a high-performance method for identifying random transgene integration sites.

Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking clonality via the detection of transgene integration sites. RAISING (Rapid Amplification of Integration Sites without Interference by Genomic DNA contamination) is a sensitive, inexpensive alternative to established methods. Its compatibility with Sanger sequencing combined with our CLOVA (Clonality Value) software is critical for those without access to expensive high throughput sequencing. We analyzed samples from 688 individuals infected with the retrovirus HTLV-1, which causes adult T-cell leukemia/lymphoma (ATL) to model our method. We defined a clonality value identifying ATL patients with 100% sensitivity and 94.8% specificity, and our longitudinal analysis also demonstrates the usefulness of ATL risk assessment. Future studies will confirm the broad applicability of our technology, especially in the emerging gene therapy sector.

Health-Related Quality of Life Evaluation Using the Short Form-36 in Patients With Human T-Lymphotropic Virus Type 1-Associated Myelopathy.

Background: Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) is a neuroinflammatory disease, causing various neurological symptoms, including motor, sensory, and bladder and bowel dysfunctions. This study was designed to reveal the impact of HAM and related symptoms on health-related quality of life (HRQoL). Methods: We analyzed the Short Form-36 (SF-36) and clinical data of 538 patients with HAM registered in the HAM-net, a nationwide patient registry for HAM in Japan. HRQoL was evaluated using the SF-6D (a health state utility value calculated from the SF-36) and eight SF-36 subscales. A general liner model was used to estimate the impact of major HAM-related symptoms, including gait dysfunction, sensory disturbance in the legs (pain and numbness), urinary dysfunction, and constipation, on the SF-6D and SF-36 subscale scores. Results: The mean age and disease duration were 62.0 and 16.5 years, respectively. Of the patients, 73.2% needed walking aid; 42.7 and 67.1% had leg pain and numbness, respectively; 92.1% had urinary dysfunction; and 77.9% had constipation. The mean SF-6D score was 0.565, which was significantly lower than the national average (0.674 in the 60-69 years age group; p < 0.001), exceeding the minimal important difference (0.05-0.1). All the major symptoms were significantly associated with a decrease in the SF-6D score. The SF-36 subscale scores were significantly lower than the national standard of 50 (p ≤ 0.001), except for mental health (MH). Gait dysfunction was associated with lower scores in physical functioning (PF), limitations on role functioning because of physical health, bodily pain, general health perception (GH), vitality (VT), and social functioning; however, no association was observed between gait dysfunction and limitations on role functioning because of emotional problems and MH. Meanwhile, sensory disturbance in the legs was associated with a decrease in scores in all subscales. Urinary dysfunction was associated with worse PF, GH, VT, and MH. Constipation was associated only with PF. Conclusion: HRQoL of patients with HAM was worse than that of the general population and was associated with all major symptoms. Thus, patients should be comprehensively managed to achieve better HRQoL.

Efficacy of Corticosteroid Therapy for HTLV-1-Associated Myelopathy: A Randomized Controlled Trial (HAMLET-P).

Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were assigned (1:1) to receive or not receive a 3-day course of intravenous methylprednisolone in addition to oral prednisolone therapy. Meanwhile, slow progressors were assigned (1:1) to receive oral prednisolone or placebo. The primary outcomes were a composite of ≥1-grade improvement in the Osame Motor Disability Score or ≥30% improvement in the 10 m walking time (10 mWT) at week 2 for rapid progressors and changes from baseline in 10 mWT at week 24 for slow progressors. In the rapid progressor trial, all four patients with but only one of four without intravenous methylprednisolone achieved the primary outcome (p = 0.14). In the slow progressor trial, the median changes in 10 mWT were -13.8% (95% CI: -20.1--7.1; p < 0.001) and -6.0% (95% CI: -12.8-1.3; p = 0.10) with prednisolone and placebo, respectively (p for between-group difference = 0.12). Whereas statistical significance was not reached for the primary endpoints, the overall data indicated the benefit of corticosteroid therapy. (Registration number: UMIN000023798, UMIN000024085).

Integrated Analysis of Two Probucol Trials for the Secondary Prevention of Atherosclerotic Cardiovascular Events: PROSPECTIVE and IMPACT.

AIMS: In this study, we integrated two randomized control trials, PROSPECTIVE and IMPACT, to address the effect of probucol on cerebrocardiovascular events and carotid intima-media thickness (IMT) in Japanese, Korean, and Chinese patients with coronary artery disease (CAD). METHODS: A total of 1,025 patients from the PROSPECTIVE and IMPACT studies were enrolled. The time to the first major adverse cerebrocardiovascular event, in addition to carotid IMT and lipid levels, was compared between the control and probucol groups. RESULTS: In the integrated analysis, the adjusted hazard ratio (HR) and 95% confidence interval (CI) were 0.67 and 0.44-1.03, respectively, indicating a tendency to show the effect of probucol on cerebrocardiovascular events in secondary prevention. We also found no significant differences between the control and probucol groups in the mean IMT of the carotid arteries and its changes. However, we found a significant decrease in cerebrocardiovascular events in patients with reduced levels of HDL cholesterol (HDL-C) (≥ 6.25 mg/dL) compared with those with levels ＜6.25 mg/dL (p=0.024), without any increase in adverse events such as severe ventricular arrhythmias. CONCLUSION: We demonstrated a marginal effect of probucol on cerebrocardiovascular events in Asian patients with CAD, with reasonable safety profiles. A larger study may be needed to support the effect of probucol for cardiovascular prevention.

Clinical course of neurogenic bladder dysfunction in human T-cell leukemia virus type-1-associated myelopathy/tropical spastic paraparesis: a nationwide registry study in Japan.

BACKGROUND: Most patients with human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develop neurogenic bladder dysfunction. However, longitudinal changes and treatment effects remain poorly understood. This study aimed to characterize the clinical course of urinary dysfunction in this population. METHODS: This prospective observational study included 547 patients enrolled in HAM-net, a nationwide registry for HAM/TSP in Japan. Urinary dysfunction severity was evaluated using the HAM/TSP-bladder dysfunction symptom score (HAM-BDSS) and the HAM/TSP-bladder dysfunction severity grade (HAM-BDSG). These specific measures were recently developed for assessing urinary dysfunction in HAM/TSP. We analyzed longitudinal changes over a 6-year follow-up period, associations between urinary and gait dysfunction, and treatment efficacy of urinary catheterization and mirabegron (a ß3-adrenergic agonist for overactive bladder symptoms). RESULTS: The mean (standard deviation [SD]) age and disease duration at enrollment were 61.9 (10.7) years and 16.6 (11.6) years, respectively, and 74.6% of patients were women. Only 8.0% were free from urinary symptoms (HAM-BDSG 0), 65.4% had urinary symptoms or were on medication (HAM-BDSG I), and 23.2% and 3.3% used intermittent and indwelling catheters (HAM-BDSG II and III), respectively. HAM-BDSG and BDSS were worse in patients with greater gait dysfunction (p < 0.001 for both). During the 6-year follow-up, 66.7% of patients with HAM-BDSG 0 developed new urinary symptoms. Of those with HAM-BDSG I at enrollment, 10.8% started using urinary catheters. Importantly, HAM-BDSS significantly improved after initiating catheterization (mean [SD] change, - 8.93 [10.78], p < 0.001). The number of patients receiving mirabegron increased in the fourth year. Multivariable linear regression analysis significantly associated mirabegron with improvement in HAM-BDSS (- 5.82, 95% confidence interval - 9.13 to - 2.51, p = 0.001). CONCLUSIONS: Urinary dysfunction affected 92% of patients and progressed over the 6-year follow-up. Urinary symptoms were more severe in patients with poorer gait function. Urinary catheterization and mirabegron were effective in relieving symptoms. Effective utilization of real-world data is key to establishing evidence for rare diseases, such as HAM/TSP.

Probucol Trial for Secondary Prevention of Atherosclerotic Events in Patients with Coronary Heart Disease (PROSPECTIVE).

AIMS: Although intensive statin therapy reduced cardiovascular risks, cardiovascular events have not been completely prevented. Probucol is a potent antioxidant and reduces tendon xanthomas in familial hypercholesterolemia patients despite reduction of high-density lipoprotein (HDL)-cholesterol (HDL-C). We investigated whether probucol can reduce cardiovascular events on top of conventional lipid-lowering therapy in patients with coronary heart disease (CHD). METHODS: PROSPECTIVE is a multicenter, randomized, prospective study that recruited 876 Japanese patients with CHD and dyslipidemia with a low-density lipoprotein (LDL)-cholesterol (LDL-C) level of ≥ 140 mg/dL without medication or those treated with lipid-lowering drugs. Lipid-lowering agents were administered during the study period in the control group (n=438), and probucol 500 mg/day was added to lipid-lowering therapy in the probucol group (n=438). Patients were randomly assigned to two treatment groups by adjusting the LDL-C level and presence of diabetes and hypertension and followed up for more than 3 years. The primary end point was a composite of cerebrovascular and cardiovascular events (cardiovascular disease death including sudden death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, hospitalization for heart failure, or coronary revascularization). The secondary end point was carotid intima-media thickness in a subset of patients. RESULTS: The incidence of the primary end point showed a trend to be lower in the probucol group compared with that in the control group despite reduced HDL-C without serious adverse events. Anti-atherogenic effects of probucol may be attributed to its potent antioxidative function and enhancement of reverse cholesterol transport. CONCLUSION: Since there was no statistical significance between the probucol and control groups despite a marked reduction of HDL-C, further studies on the clinical outcomes of probucol on top of conventional therapy may be necessary in the future (UMIN000003307).

Initial responsiveness to darbepoetin alfa and its contributing factors in non-dialysis chronic kidney disease patients in Japan.

BACKGROUND: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with cardiovascular events and poor renal outcome in patients with chronic kidney disease (CKD). This study aimed to investigate the initial responsiveness to darbepoetin alfa (DA) and its contributing factors using the data from the BRIGHTEN. METHODS: Of 1980 patients enrolled at 168 facilities, 1695 were included in this analysis [285 patients were excluded mainly due to lack of hemoglobin (Hb) values]. The initial ESA response index (iEResI) was defined as a ratio of Hb changes over 12 weeks after DA administration per weight-adjusted total DA dose and contributing factors to iEResI were analyzed. RESULTS: The mean age was 70 ± 12 years (male 58.8%; diabetic nephropathy 27.6%). The median creatinine and mean Hb levels at DA initiation were 2.62 mg/dL and 9.8 g/dL, respectively. The most frequent number of DA administration during 12 weeks was 3 times (41.1%), followed by 4 (15.6%) times with a wide distribution of the total DA dose (15-900 µg). Remarkably, 225 patients (13.3%) did not respond to DA. Multivariate analysis showed that male gender, hypoglycemic agent use, iron supplementation, high eGFR, low Hb, low CRP, low NT-proBNP, and low urinary protein-creatinine ratio were independently associated with better initial response to DA (P = < 0.0001, 0.0108, < 0.0001, 0.0476, < 0.0001, 0.0004, 0.0435, and 0.0009, respectively). CONCLUSIONS: Non-responder to DA accounted for 13.3% of patients with non-dialysis CKD. Iron supplementation, low CRP, low NT-proBNP, and less proteinuria were predictive and modifiable factors associated with better initial response to DA.

Protective Factors Modulate the Risk of Beta Amyloid in Alzheimer's Disease.

AIM: To identify the factors protecting Abeta-positive subjects with normal cognition (NC) or mild cognitive impairment (MCI) from conversion to Alzheimer's disease (AD). METHODS: Subjects with MCI in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with baseline data for neuropsychological tests, brain beta amyloid (Abeta), magnetic resonance imaging (MRI), APOE genotyping, and 18F-FDG-PET (FDG), were included for analysis. RESULTS: Elevated brain amyloid was associated with a higher risk of conversion from MCI to AD (41.5%) relative to Abeta levels of <1.231 (5.5%) but was not associated with conversion from NC to AD (0.0 vs. 1.4%). In the multivariate Cox regression analyses, elevated Abeta increased the risk of AD, while higher whole-brain cerebral glucose metabolism (CGM) assessed by FDG decreased the risk of AD in subjects with the same amount of Abeta. Even in the patients with heavily elevated brain amyloid, those with FDG > 5.946 had a lower risk of AD. ApoE4 carrier status did not influence the protective effect. CONCLUSION: Higher average CGM based on FDG modified the progression to AD, indicating a protective function. The results suggest that the inclusion of this CGM measured by FDG would enrich clinical trial design and that increasing CGM along with the use of anti-Abeta agents might be a potential prevention strategy for AD.

Darbepoetin Alfa in Patients with Advanced CKD without Diabetes: Randomized, Controlled Trial.

BACKGROUND AND OBJECTIVES: Large, randomized, controlled trials targeting higher hemoglobin level with erythropoiesis-stimulating agents for Western patients with CKD showed harm. However, the effect of anemia correction using erythropoiesis-stimulating agents may differ between CKD subpopulations. The Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease study, a multicenter, randomized, open-label, parallel-group study, aimed to examine the effect of targeting hemoglobin levels of 11-13 g/dl using darbepoetin alfa with reference to a low-hemoglobin target of 9-11 g/dl on kidney outcome in patients with advanced CKD without diabetes in Japan. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We enrolled 491 patients with CKD without diabetes, and an eGFR of 8-20 ml/min per 1.73 m2. Of these 491 patients, 239 and 240 were ultimately assigned to the high- and low-hemoglobin groups, respectively (12 patients were excluded). The primary outcome was a kidney composite end point (starting maintenance dialysis, kidney transplantation, eGFR≤6 ml/min per 1.73 m2, and 50% reduction in eGFR). RESULTS: Mean hemoglobin levels were 11.2±1.1 and 10.0±0.9 g/dl in the high- and low-hemoglobin groups, respectively, during the mean study period of 73.5±29.7 weeks. The kidney composite end point occurred in 105 (44%) and 116 (48%) patients in the high- and low-hemoglobin groups, respectively (log-rank test; P=0.32). The adjusted Cox proportional hazards model showed that the hazard ratio for the high- versus low-hemoglobin group was 0.78 (95% confidence interval, 0.60 to 1.03; P=0.08). Cardiovascular events occurred in 19 (8%) and 16 (7%) patients in each group, respectively, with no significant between-group difference (log-rank test; P=0.66). CONCLUSIONS: Targeting a higher hemoglobin level (11-13 g/dl) with darbepoetin alfa did not improve kidney outcome compared with targeting a lower hemoglobin level (9-11 g/dl) in patients with advanced CKD without diabetes. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Prevention of ESKD by Darbepoetin Alfa in CKD Patients with Non-diabetic Kidney Disease (PREDICT), NCT01581073.

Prospective Registry of Embolization of Intracranial Aneurysms Using HydroSoft Coils: Results of the Japanese HydroSoft Registry.

BACKGROUND: The effect of HydroSoft coils on the prevention of recanalization and thrombosis after embolization is unclear. We herein report the results of the single-armed prospective Japanese HydroSoft Registry. METHODS: Aneurysms with a diameter of <10 mm that were treated with a ≥50% length of HydroSoft coils were registered. We evaluated the safety and recanalization rate and analyzed the factors related to their recanalization and thrombosis 1 year later. RESULTS: In total, 122 aneurysms were registered. Their mean maximum diameter and neck length were 6.4 and 3.9 mm, respectively. The mean length of the HydroSoft coils was 84.3%. No intracranial hemorrhage occurred, but 2 patients developed minor ischemic strokes. Angiographic examination immediately after the procedure showed complete obliteration, neck remnant (NR), and body filling (BF) in 20 (16.4%), 32 (26.2%), and 67 (54.9%) cases, respectively. One-year follow-up angiography showed complete obliteration, NR, and BF in 68 (55.7%), 15 (12.3%), and 15 (12.3%) cases, respectively, and 5 aneurysms (4.1%) were recanalized (4 and 1 with BF and NR as their initial angiographic result, respectively). Another 11 aneurysms still showed BF, although their thrombosis was promoted. No significant factors related to recanalization were identified. A high volume embolization ratio and small neck were significantly associated with thrombosis 1 year after embolization with HydroSoft coils. CONCLUSIONS: The safety and prevention of recanalization 1 year after the treatment appeared acceptable. The high volume embolization ratio associated with HydroSoft coils could induce progression of thrombosis for aneurysms characterized by NR and BF during the follow-up period.