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Background As there are no large-scale reports of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with nephrotic syndrome using immunosuppressive agents, we conducted the prospective study. Methods SARS-CoV-2 mRNA vaccines were administered to patients with nephrotic syndrome receiving immunosuppressive agents. The titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. We evaluated factors associated with antibody titers after vaccination and analyzed adverse events. Results We enrolled 40 patients and evaluated vaccine immunogenicity in 35 of them. Seroconversion (> 0.8 U/mL) was achieved in all patients, and the median antibody titer was 598 U/mL (interquartile range, 89-1380 U/mL). Patients using mycophenolate mofetil (MMF) showed lower antibody titers than those who were not (median: 272 U/mL vs. 2660 U/mL, p = 0.0002), and serum immunoglobulin G (IgG) levels showed a weak linear relationship with antibody titers (R.sup.2 = 0.16). No breakthrough infections were noted. Three patients (7.5%) suffered from a relapse of nephrotic syndrome (2 and 3 days, respectively, after the first dose and 8 days after the second dose), two of whom had a history of relapse within 6 months before the vaccination. Conclusions The SARS-CoV-2 mRNA vaccine was immunogenic in patients with nephrotic syndrome using immunosuppressive agents, although the use of MMF and low levels of serum IgG were associated with lower antibody titers after vaccination. Patients with high disease activity may experience a relapse of nephrotic syndrome after vaccination. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information, Author(s): Koichi Kamei [sup.1] , Masao Ogura [sup.1] , Mai Sato [sup.1] , Kentaro Nishi [sup.1] , Kensuke Shoji [sup.2] , Takanori Funaki [sup.2] , Chikara Ogimi [sup.2] , Shuichi [...]

Pharmacokinetics of drugs can be affected by physiologic changes during pregnancy. Our aim was to assess the influence of covariates on tenofovir (TFV) pharmacokinetics in pregnant and postpartum women receiving tenofovir disoproxil fumarate (TDF). Population pharmacokinetic parameter estimates and the influence of covariates were assessed using nonlinear mixed-effects modeling (NONMEM 7.4). Forty-six women had intensive pharmacokinetic evaluations during the second and third trimesters of pregnancy, with another evaluation postpartum. A two-compartment pharmacokinetic model with allometric scaling for body weight and first-order absorption best described the tenofovir plasma concentration data. Apparent oral clearance (CL/F) and volume of distribution at steady state (Vss/F) were increased during pregnancy. Weight, serum creatinine (SCr), pregnancy, albumin, and age were associated with TFV CL/F during univariate assessment, but in the multivariate analysis, changes in CL/F and Vss/F were only associated with increased body weight and enhanced renal function. Due to greater weight and lower SCr during pregnancy, CL/F was 28% higher during pregnancy than postpartum. In the final model, CL/F (liters per hour) was described as 2.07 × (SCr/0.6)0.65 × weight0.75, with a low between-subject variability (BSV) of 24%. The probability of target attainment (proportion exceeding area under the concentration-time curve of >1.99 μg·h/ml, the 10th percentile of average TFV exposure for nonpregnant historical controls) was 68%, 80%, 87%, and 93% above the target with 300 mg, 350 mg, 400 mg, and 450 mg of TDF, respectively, during pregnancy and 88%, 92%, 96%, and 98% above the target with same doses in postpartum women. Dose adjustment of TDF during pregnancy is not generally warranted, but any modification should be based on weight and renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT00042289.).

BackgroundPostoperative bloodstream infection (BSI) is the most important determinant of recipient morbidity and mortality after liver transplantation (LT). Children who underwent LT are at the highest risk of developing BSI because of the significant surgical intervention, use of multiple devices, and administration of immunosuppressive agents. However, information regarding the risk factors for BSI in children after LT is limited.MethodsWe retrospectively reviewed 210 children who underwent living-donor LT at the largest pediatric LT center in Japan. Patients' characteristics, blood culture results and clinical outcomes were extracted from electronic medical records. Univariate and multivariate analyses were performed to identify the risk factors for BSI.ResultsAmong the 210 LT recipients, 53 (25%) recipients experienced 86 episodes of BSI during the observational period. The source of the BSI was identified only in 38%: catheter-related BSI (27%) peritonitis (7%), urinary tract infection (2%), pneumonia (1%) and infectious endocarditis (1%). A multivariate analysis demonstrated that body weight (P = 0.03), volume of blood loss during LT (P < 0.001) and cytomegalovirus (CMV) antigenemia positivity (P = 0.04) were independently associated with the development of BSI. The risk factors for BSI differed when we analyzed the subjects according to age (≤24 months and >24 months), blood loss and pediatric end-stage liver disease/model for end-stage liver disease versus positive CMV antigenemia.ConclusionsThe volume of blood loss, postoperative CMV antigenemia positivity and body weight were associated with the development of BSI after LT in pediatric living-donor recipients. To identify the age-specific predictors of BSI in children who underwent LT, age-specific analyses are crucial.

The article focuses on the importance of mentorship in medical education, particularly for underrepresented groups in healthcare. Topics include the benefits of mentorship for career development and job satisfaction, qualities of effective pediatric mentors, and the cultural context of mentorship in Japan.

Background: Information on the etiology and prognosis for leukemoid reaction (LR) in children is still limited and little is known about the factors that distinguish LR from hematological malignancy (HM). Methods: This was a single‐center, case–control study. Pediatric patients (<18 years) with a white blood cell (WBC) count of 50,000/μL or more were included in the study. Clinical information and laboratory test results were extracted from the electronic medical records. Patients were divided into the LR and HM groups. Logistic regression analysis was performed to investigate the factors that discriminated LR from HM. Results: We found 214 cases (115 cases in the LR group and 99 cases in the HM group) eligible for analysis. Approximately half of the LR cases were due to infectious diseases (n = 58, 50%); bacteremia and respiratory infections were the most common infections. Age younger than 2 years (odds ratio [95% confidence interval]) (2.154 [0.690–6.727]), presence of known underlying diseases (10.006 [3.119–32.102]), WBC count <60,555/μL (20.676 [6.357–67.251]), platelet count 118,000/μL or higher (15.059 [3.876–58.504]), lactate dehydrogenase (LDH) below 781 U/L (4.219 [1.378–12.915]), and C‐reactive protein (CRP) ≥0.91 mg/dL (10.568 [2.736–40.825]) were identified as the predictive factors for LR by logistic regression analysis. Thirty‐day mortality was higher in the LR group than in the HM group but the difference was not statistically significant (13% vs. 6%, p = 0.087). Conclusions: Approximately half of the etiology of LR was infectious diseases and prognosis was poorer for LR than for HM. Age, presence of known underlying conditions, and laboratory tests, including WBC count, platelet count, LDH, and CRP, may be useful in distinguishing LR from HM. [ABSTRACT FROM AUTHOR]