Self-assessment sheet submission rate predicts technique survival in patients initiating peritoneal dialysis.

AIM: Patients play a crucial role in preventing peritoneal dialysis (PD)-related events, including peritonitis and fluid overload, as PD procedures are mainly carried out at home. We asked patients to submit a PD self-assessment sheet at each outpatient visit in our daily clinical practice and evaluated its usefulness for outcomes in patients initiating PD. METHODS: This retrospective cohort study included patients who underwent PD catheter insertion between January 2008 and October 2018. The submission rate of a PD self-assessment sheet was calculated from medical records until PD cessation or study completion (October 2020). The association between the submission rate and technique survival was analysed. RESULTS: Among the 105 recruited patients (78 men, 60.4 ± 12.2 years), 44 discontinued PD and transferred to haemodialysis during the study period. The follow-up was 52.3 (28.7-79.3) months, and the median submission rate was 78%. The log-rank test showed that technique survival was significantly better in patients with a submission rate ≥ 78% than those with a submission rate <78% (p = .006). The submission rate remained significantly associated with less technique failure (hazard ratio 0.88 per 10%, p = .002) by the Cox regression analysis adjusted for age, sex, Charlson comorbidity index, estimated glomerular filtration rate and geriatric nutritional risk index. CONCLUSION: The submission rate of a PD self-assessment sheet is useful as a predictor of technique survival in patients initiating PD. Instruction that increases submission may improve technique survival in PD patients.

Physical Parameters, Use of Specific Medical Treatments, Nursing Levels, and Activities of Daily Living Are Potential Indicators for Forgoing Maintenance Hemodialysis.

Maintenance hemodialysis (HD) therapy is essential for survival in patients with end-stage renal disease (ESRD); however, HD can also be life-threatening in the final stages of ESRD. Currently, no clear indicators and/or biomarkers exist regarding when HD should be forgone. In the present study, we examined temporal changes in multiple clinical parameters, including biochemical data, physical data, the use of specific medical treatments, nursing care levels, and the activities of daily living (ADL) in 47 ESRD patients who underwent maintenance HD and who died in our hospital. We also investigated the status of informed consents regarding the forgoing of HD in these patients. We found that while biochemical parameters were unaltered, physical parameters such as consciousness levels and blood pressure gradually deteriorated during hospitalization. The use of the following specific medical treatments significantly increased over time: vasopressor use, O2 inhalation, and ventilator use. The need for nursing care increased and the ADL levels decreased toward the time of death. Medical doctors gave information regarding forgoing HD to patients and/or their family/relatives in 55% of cases, obtained agreement to forego HD in 45% of cases, and HD was actually foregone in 38% of cases. Most clinical parameters were not significantly different between the patients whose HD sessions were forgone versus those in whom HD was continued, indicating that HD was foregone in the very last stages of life. The results suggest that physical parameters, the use of specific medical treatments, the levels of nursing care, and ADL are potential indicators for forgoing HD in the final stages of ESRD.

Safety and efficacy of eculizumab in Guillain-Barré syndrome: a multicentre, double-blind, randomised phase 2 trial.

BACKGROUND: Despite the introduction of plasmapheresis and immunoglobulin therapy, many patients with Guillain-Barré syndrome still have an incomplete recovery. Evidence from pathogenesis studies suggests the involvement of complement-mediated peripheral nerve damage. We aimed to investigate the safety and efficacy of eculizumab, a humanised monoclonal antibody against the complement protein C5, in patients with severe Guillain-Barré syndrome. METHODS: This study was a 24 week, multicentre, double-blind, placebo-controlled, randomised phase 2 trial done at 13 hospitals in Japan. Eligible patients with Guillain-Barré syndrome were aged 18 years or older and could not walk independently (Guillain-Barré syndrome functional grade 3-5). Patients were randomly assigned (2:1) to receive 4 weeks of intravenous immunoglobulin plus either eculizumab (900 mg) or placebo; randomisation was done via a computer-generated process and web response system with minimisation for functional grade and age. The study had a parallel non-comparative single-arm outcome measure. The primary outcomes were efficacy (the proportion of patients with restored ability to walk independently [functional grade ≤2] at week 4) in the eculizumab group and safety in the full analysis set. For the efficacy endpoint, we predefined a response rate threshold of the lower 90% CI boundary exceeding 50%. This trial is registered with ClinicalTrials.gov, number, NCT02493725. FINDINGS: Between Aug 10, 2015, and April 21, 2016, 34 patients were assigned to receive either eculizumab (n=23) or placebo (n=11). At week 4, the proportion of the patients able to walk independently (functional grade ≤2) was 61% (90% CI 42-78; n=14) in the eculizumab group, and 45% (20-73; n=5) in the placebo group. Adverse events occurred in all 34 patients. Three patients had serious adverse events: two in the eculizumab group (anaphylaxis in one patient and intracranial haemorrhage and abscess in another patient) and one in the placebo group (depression). The possibility that anaphylaxis and intracranial abscess were related to eculizumab could not be excluded. No deaths or meningococcal infections occurred. INTERPRETATION: The primary outcome measure did not reach the predefined response rate. However, because this is a small study without statistical comparison with the placebo group, the efficacy and safety of eculizumab could be investigated in larger, randomised controlled trials. FUNDING: The Japan Agency for Medical Research and Development, Ministry of Health, Labor and Welfare, and Alexion Pharmaceuticals.

A Prospective, Multicenter, Randomized Phase II Study to Evaluate the Efficacy and Safety of Eculizumab in Patients with Guillain-Barré Syndrome (GBS): Protocol of Japanese Eculizumab Trial for GBS (JET-GBS).

BACKGROUND: Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy that causes acute flaccid paralysis. Immunoglobulin and plasma exchange are established treatments for GBS; however, a substantial number of patients, particularly those with severe disease, have poor recovery and residual deficits. Recent studies suggest that complement activation plays a pivotal role in GBS-associated axonal degeneration, and eculizumab is a humanized monoclonal antibody that specifically binds to complement component 5 and potently inhibits complement activation. OBJECTIVE: This clinical trial aims to evaluate the efficacy and safety of eculizumab, a humanized monoclonal antibody directed against complement component 5, for treatment of GBS. METHODS: The Japanese Eculizumab Trial for GBS (JET-GBS) is a prospective, multicenter, placebo-controlled, double-blind, randomized phase II study conducted at 13 tertiary neurology centers and is funded by the Japan Agency for Medical Research and Development. A total of 33 GBS patients unable to walk independently within 2 weeks from symptom onset (Hughes functional grade 3-5) were randomized at a 2:1 ratio to receive either intravenous eculizumab (900 mg/day) or placebo once weekly for 4 weeks, followed by 20 weeks of follow-up. The primary endpoint for efficacy is the proportion of patients who regain their ability to walk without aid at 4 weeks after the first dose of the study treatment, while primary safety outcomes are the incidence of adverse events and serious adverse events during the trial. RESULTS: Enrollment for the trial began in August 2015. This trial is still ongoing. All participants have been enrolled, and follow-up will be completed in October 2016. CONCLUSIONS: This study is the first to investigate the efficacy and safety of eculizumab for GBS. In case of a positive result, we will plan a phase III trial to investigate this issue in a larger number of patients. CLINICALTRIAL: UMIN Clinical Trials Registry UMIN 000018171; https:/upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function= brows&action=brows&type=summary&language=J&recptno=R000020978 (Archived by WebCite at http://www.webcitation.org/ 6lTiG8ltG). Clinical Trials.gov NCT02493725; https://clinicaltrials.gov/ct2/show/NCT02493725 (Archived by WebCite at http://www.webcitation.org/6lVJZXKSL).

[Health-related quality of life, depression, and self-esteem in adolescents with leprosy-affected parents: results of a cross-sectional study in Nepal].

Leprosy is a chronic infectious disease that has an impact on the Health-Related Quality of Life (HRQOL) of sufferers as well as their children. To date, no study has investigated the effects of parental leprosy on the well-being of adolescent children. A cross-sectional study was conducted in the Lalitpur and Kathmandu districts of Nepal. Adolescents with leprosy-affected parents (n=102; aged 11-17 years) and those with parents unaffected by leprosy (n=115; 11-17 years) were investigated. Self-reported data from adolescents were collected using the Kinder Lebensqualität Fragebogen (KINDLR) questionnaire to assess HRQOL, the Center for Epidemiological Studies-Depression Scale (CES-D), and the Rosenberg Self-esteem Scale (RSES). Analysis of covariance (ANCOVA) was used to compare scores between the two groups. Multiple regression analysis was conducted to explore the determinants of HRQOL for adolescents with leprosy-affected parents. ANCOVA revealed that the KINDLR and RSES scores were significantly lower among adolescents with leprosy-affected parents compared with unaffected parents. The CES-D score was significantly higher among adolescents with leprosy-affected parents than for adolescents with unaffected parents. The KINDLR scores for adolescents with both parents affected were significantly lower than the scores for those with one parent affected. Multiple regression analysis revealed that adolescents with leprosy-affected parents who had higher levels of depressive symptoms were more likely to have lower KINDLR scores. A similar result was seen for adolescents where both parents had leprosy. Adolescents with leprosy-affected parents had higher levels of depressive symptoms, lower levels of self-esteem, and lower HRQOL compared with adolescents whose parents were unaffected by leprosy.

Health-related quality of life, depression, and self-esteem in adolescents with leprosy-affected parents: results of a cross-sectional study in Nepal.

BACKGROUND: Leprosy is a chronic infectious disease that has an impact on the Health-Related Quality of Life (HRQOL) of sufferers as well as their children. To date, no study has investigated the effects of parental leprosy on the well-being of adolescent children. METHODS: A cross-sectional study was conducted in the Lalitpur and Kathmandu districts of Nepal. Adolescents with leprosy-affected parents (n = 102; aged 11-17 years) and those with parents unaffected by leprosy (n = 115; 11-17 years) were investigated. Self-reported data from adolescents were collected using the Kinder Lebensqualität Fragebogen (KINDLR) questionnaire to assess HRQOL, the Center for Epidemiological Studies-Depression Scale (CES-D), and the Rosenberg Self-esteem Scale (RSES). Analysis of covariance (ANCOVA) was used to compare scores between the two groups. Multiple regression analysis was conducted to explore the determinants of HRQOL for adolescents with leprosy-affected parents. RESULTS: ANCOVA revealed that the KINDLR and RSES scores were significantly lower among adolescents with leprosy-affected parents compared with unaffected parents. However, the scores of "Friends" and "School" subscales of KINDLR were similar between the two groups. The CES-D score was significantly higher among adolescents with leprosy-affected parents than for adolescents with unaffected parents. The KINDLR scores for adolescents with both parents affected (n = 41) were significantly lower than the scores for those with one parent affected (n = 61). Multiple regression analysis revealed that adolescents with leprosy-affected parents who had higher levels of depressive symptoms were more likely to have lower KINDLR scores. A similar result was seen for adolescents where both parents had leprosy. CONCLUSIONS: Adolescents with leprosy-affected parents had higher levels of depressive symptoms, lower levels of self-esteem, and lower HRQOL compared with adolescents whose parents were unaffected by leprosy. Thus, mental health support programs might be necessary for adolescents with leprosy-affected parents, particularly for adolescents where both parents are leprosy-affected. Further studies with larger sample sizes are necessary to draw decisive conclusions.

Reliability and validity of a Nepalese version of the Kiddo-KINDL in adolescents.

The objective of this study was to assess the reliability and validity of a Nepalese version of the Kiddo-KINDL to measure Health-Related Quality of Life (HRQOL) in adolescents. We collected data from 204 students between 13 to 16 years old from four secondary schools in Lalitpur district, Nepal. The students answered a Nepalese version of the Kiddo-KINDL and the Center for Epidemiological Studies-Depression Scale (CES-D) with a self-administrated questionnaire. We conducted a test-retest study on the instrument at an interval of 10 days and then compared the Kiddo-KINDL scores between the low CES-D score group and the high CES-D score group students. The instrument showed good reliability and a small response variation. The internal consistency (Cronbach's alpha) of the total score was 0.93. Corrected item-total correlations showed that all items ranged from 0.47 to 0.79. The reproducibility was satisfactory with an Intraclass Correlation Coefficient (ICC) of 0.88-0.95. The Kiddo-KINDL scores in the low CES-D score group were significantly lower than those in the high CES-D score group students. The optimal cut-off score of the Kiddo-KINDL was estimated at 54.7, with an Area Under the Curve (AUC) score of 0.83 and both sensitivity (73.5%) and specificity (71.8%) were acceptably high. We recommended a mean change in Kiddo-KINDL total scores of 4.0 to be used to define a minimal important difference according to two-point CES-D score changes. Our results showed that a Nepalese version of the Kiddo-KINDL has internal consistency, reproducibility, responsiveness, interpretability, and discriminant validity.

Postnatal neovascularization by endothelial progenitor cells immortalized with the simian virus 40T antigen gene.

Endothelial progenitor cells (EPCs) contribute to blood vessel formation in ischemic and tumorous tissues, but comprise only a small population in circulation. We attempted to immortalize putative EPCs from human cord blood. Human CD34+ cord blood cells were cultured in the presence of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and transfected with a retroviral vector encoding the simian virus 40 large T (SV40T) antigen. This resulted in the immortalization of cord blood cells, leading to the establishment of several cell lines. One of these lines, HYCEC-1, exhibited a phenotype characteristic of the endothelial lineage, including expression of von Willebrand factor and VEGF receptor-2 (VEGFR-2/KDR/Flk-1) and uptake of acetylated-low density lipoprotein. Flow cytometric analysis revealed that HYCEC-1 cells were strongly positive for CD31 and CD146, moderately positive for CD144, weakly positive for CD133 and CD34, and negative for CD14 and CD45. HYCEC-1 cells formed capillary-like structures on basement matrix gel in vitro. Upon transplantation into the ischemic hind limb of nude rats, HYCEC-1 cells efficiently participated in neovascularization and augmented blood flow. The immortalized HYCEC-1 cells are suggested to be a class of EPCs that can efficiently participate in postnatal neovasculogenesis in the ischemic hind limb, and may also be a useful tool for studying tumor vessel formation.

Interferon-gamma production by human cord blood monocyte-derived dendritic cells.

Interferon (IFN)-gamma is produced by T cells and natural killer cells and activates monocytes and dendritic cells (DCs). Recently, IFN-gamma has been shown to be produced by mouse DCs following stimulation with interleukin (IL)-12, which is markedly augmented by the addition of IL-18. We here analyzed whether human DCs secrete IFN-gamma in response to IL-12 and/or IL-18. Human immature DCs, generated from cord blood CD14(+) monocytes by treating with granulocyte-macrophage colony-stimulating factor and IL-4, were incubated with IL-12 and/or IL-18 and assayed for IFN-gamma production. IL-12, but not IL-18, weakly induced IFN-gamma production, while IL-12 together with IL-18 induced high levels of IFN-gamma production. Similar results were obtained with mature DCs, although levels of IFN-gamma production were less than those in immature DCs. Also with mature and immature DCs, IL-12 upregulated the expression of IL-18 receptor alpha (Ralpha), and costimulation with IL-12 and IL-18 upregulated CD40 expression. Anti-IL-18Ralpha antibody abrogated both the IFN-gamma induction and the CD40 upregulation by IL-12 plus IL-18. These findings suggest that IL-12 upregulates IL-18Ralpha expression on human DCs and acts synergistically with IL-18 to induce high levels of IFN-gamma, which subsequently enhances CD40 expression on DCs in an autocrine manner.

Idiopathic interstitial pneumonia following stem cell transplantation.

Idiopathic interstitial pneumonia (IIP) can occur after stem cell transplantation, but the aetiology is unknown. Based on the association between angiitis syndrome and Helicobacter pylori infection, we identified possible risk factors common to these two conditions. Among 83 patients who underwent stem cell transplantation, four developed IIP. We elucidated various parameters and clinical features in four patients with IIP and 79 patients without, after allogeneic stem cell transplantation. In all four patients, (1) the conditioning regimen induced total body irradiation, (2) serological reactivation of cytomegalovirus and/or human herpesvirus-6 preceded the onset of IIP, (3) their human leucocyte antigen types were among those suspected to increase susceptibility to angiitis syndrome, (4) serum anti-H. pylori antibody was positive before conditioning and remained positive throughout the post-transplantation course, (5) inflammatory cytokines (interleukin-6, 8 and 12) were increased during the period of leucocyte recovery after transplantation and (6) the levels of intercellular adhesion molecule-1, thrombomodulin and plasminogen activator inhibitor-1 were increased at the onset of IIP. These findings suggest the possibility that angiitis syndrome and H. pylori infection are involved in the pathogenesis of post-transplantation IIP.