A case of novel NFKB2 variant with hypertensive emergency and nephrotic syndrome leading to CKD 5D.

Nuclear factor kappa B (NF-κB) family plays a central role in the human immune system. Heterozygous variants in NFKB2 typically cause immunodeficiency with various degrees of central adrenal insufficiency, autoimmunity, and ectodermal dysplasia. No reported case has presented kidney failure as an initial symptom. Moreover, documentation of kidney involvement of this disease is limited. CASE DIAGNOSIS: A 2-year-old female who presented with dyspnea and hypertensive emergency in the setting of new-onset nephrotic syndrome with acute-on chronic kidney injury with resultant chronic kidney disease (CKD) was found to have a novel heterozygous N-terminal variant in NFKB2 (c.880del: p. Tyr294Ilefs*4) with mild hypogammaglobulinemia, but no adrenal insufficiency or ectodermal dysplasia. She became dialysis-dependent during her initial hospitalization and developed CKD stage 5D, requiring continued peritoneal dialysis. She is currently awaiting kidney transplantation. CONCLUSIONS: Whether nephrotic syndrome or kidney injury or failure is the primary symptom of this variant or secondary to some event remains unknown. Further case accumulation is warranted.

Effects of short-term treatment with vibegron for refractory nocturnal enuresis.

BACKGROUND: Long-term nocturnal enuresis treatment leads to stress and lowered self-esteem for children and their parents. This study evaluated the short-term effectiveness and safety of vibegron (50 mg) for children with refractory nocturnal enuresis. METHODS: A retrospective cohort study of children with therapy-resistant enuresis was conducted using data for July to December 2019. Enuresis frequency was recorded during 30 days before and after additional vibegron administration with prior treatment. We assessed the treatment effectiveness based on enuresis frequencies between before and after treatment with vibegron 50 mg. Statistical evaluation was performed using a paired t-test. RESULTS: Among 29 children receiving vibegron, 14 (48.3%) exhibited a partial or complete response to the drug. Enuresis frequencies (mean ± standard deviation [SD]) were, respectively, 15.8 ± 9.2 and 9.5 ± 9.6 before and after treatment with vibegron during the observed 30 days. A statistically significant reduction in enuresis frequency was found (p < 0.001). Moreover, maximum mean±SD morning urine of 200 ± 62.9 mL before treatment with vibegron changed to 232 ± 76.6 mL after treatment. A significant increase in voiding volume in the early morning was found (p < 0.05). No drug-related severe adverse event was found. CONCLUSION: Short-term treatment with vibegron is safe and effective for children with refractory enuresis.

Herpes zoster meningitis in immunocompetent children: Two case reports and a literature review.

We encountered two cases of Herpes zoster (HZ) meningitis, a rarely occurring complication of HZ, in previously healthy children. One patient treated with i.v. acyclovir (ACV, 31 mg/kg/day) did not recover. His symptoms were relieved somewhat by increased ACV dosage, but it caused transient renal dysfunction. Another patient treated with i.v. ACV (30 mg/kg/day) recovered. Treatment for HZ meningitis in immunocompetent children has not been established. In a literature review, 80% of 20 patients were treated with the usual dose of ACV 15-30 mg/kg/day. The present cases suggest that a high dosage of ACV up to 60 mg/kg/day should be considered (while monitoring for side-effects) unless symptoms improve. In the review, one of every three vaccine-strain Varicella zoster virus (VZV) cases was severe, whereas the present cases resulted from wild type. Further investigations must examine different clinical characteristics of HZ meningitis caused by wild-type and vaccine-strain VZV.

Fulminant pseudomembranous colitis caused by Clostridium difficile PCR ribotype 027 in a healthy young woman in Japan.

In the past two decades, Clostridium difficile polymerase chain reaction ribotype 027 strain has rapidly emerged as the leading cause of antibiotic-associated colitis in North America and Europe; however, it has been reported only occasionally in Japan. We report a case of fulminant pseudomembranous colitis caused by this strain in a healthy young woman in Japan without any previous medical history. The strain isolated from our patient was susceptible to both gatifloxacin and moxifloxacin, thus representing a historic strain. The acquisition of fluoroquinolone resistance was reported as the important key genetic event linked to the virulence of this strain. It is noteworthy that the fluoroquinolone-susceptible 027 strain caused fulminant colitis in a healthy young woman in a non-endemic area. Our experience suggests that C. difficile PCR ribotype 027 has the potential virulence factors that are not associated with a fluoroquinolone resistance-conferring mutation.

A Multicenter Study on the Utility of Selective Enrichment Broth for Detection of Group B Streptococcus in Pregnant Women in Japan.

Universal screening for Streptococcus agalactiae, Group B Streptococcus (GBS), in pregnant women is important for the prevention of severe infectious diseases in neonates. The subculture method using selective enrichment broth significantly improves GBS detection rates in the United States; however, this method is not widely utilized in Japan mainly because of the lack of large-scale validation. Therefore, we aimed to validate the utility of the subculture method in collaboration with multiple facilities. A total of 1957 vaginal-rectal swab specimens were obtained from pregnant women at 35-37 gestational weeks from March 1, 2020, to August 30, 2020, at Fukushima Medical University Hospital, Aiiku Hospital, Kitano Hospital, and the University of the Ryukyus Hospital. Conventional direct agar plating, subculture using selective enrichment broth, and direct latex agglutination (LA) testing with incubated broth were performed for GBS detection, and discrepant results were confirmed using real-time PCR. The GBS detection rates for direct agar plating, subculture, and direct LA testing were 18.2% (357/1957), 21.6% (423/1957), and 22.3% (437/1957), respectively. The use of selective enrichment broth showed promise for GBS detection with high sensitivity and is therefore recommended for GBS screening to prevent GBS-related infectious diseases in neonates in Japan.

Evaluation of predictors of third-generation cephalosporin non-susceptibility and factors affecting recurrence or death in bacteremia caused by Citrobacter freundii complex, Enterobacter cloacae complex, and Klebsiella aerogenes.

Factors involved in the susceptibility of third-generation cephalosporins (3GCs) to bacteremia caused by Citrobacter freundii complex, Enterobacter cloacae complex, and Klebsiella aerogenes were investigated based on a case-case-control design. Antimicrobial therapy administered 30 days prior to bacteremia and hospitalization within 90 days were common risk factors for the 3GC susceptible and 3GC non-susceptible groups, while hospitalization from an institution or another hospital was a specific risk factor for the 3GC non-susceptible group. We also attempted to examine the factors affecting the clinical outcome of bacteremia. Hospitalization more than 14 days before the onset of bacteremia was an independent factor indicating poor clinical outcome. In contrast, the implementation of source control was an independent predictor of successful treatment. Although a longer hospital stay before the onset of bacteremia was associated with worse clinical outcomes, implementation of source control may have contributed to improved treatment outcomes for bacteremia.

Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy.

BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

The Clinical Evaluation of Third-generation Cephalosporins As Definitive Therapy for Enterobacter spp. and Klebsiella aerogenes Bacteremia.

Objective Third-generation cephalosporins (3GCs) may be susceptible in vitro to Enterobacter spp. and Klebsiella aerogenes. However, treatment with mainly fourth-generation cephalosporins or carbapenems is currently recommended. Diversification of antimicrobial agents in therapy is required to avoid the selection pressure of resistant organisms by broad-spectrum antimicrobial agents. This study investigated the clinical efficacy of 3GC therapy for Enterobacter spp. and Klebsiella aerogenes bacteremia in a multicenter, retrospective, observational study. Methods Patients with Enterobacter spp. or Klebsiella aerogenes detected in blood cultures and treated with a susceptible antimicrobial agent were included in the study. Propensity score matching was performed to align patient background bases, and clinical outcomes between the 3GC and non-3GC groups were compared. Treatment success was defined as having no need for treatment escalation or the addition of other antimicrobial agents, no recurrence, or no death within 30 days. Results The study included 188 cases, of which 57 and 131 were included in the 3GC and non-3GC treatment groups, respectively; 53 patients in each group were matched by propensity score matching. There were no significant differences between groups in rates of switching to a susceptible antimicrobial or adding another agent, relapse within 30 days, or death within 30 days. In the 3GC group, source control was associated with favorable clinical outcomes. Conclusion Definitive 3GC therapy for susceptible Enterobacter spp. and Klebsiella aerogenes bacteremia is as clinically effective and valuable a targeted therapy as non-3GC therapy and can be implemented under conditions in which infection source control measures are in place.

Depressed levels of interferon-gamma and HLA-DR+CD3+ T cells in infants with transient hyperferritinemia.

Familial hemophagocytic lymphohistiocytosis (FHL), which typically has its onset during infancy, is uniformly fatal if not treated. It therefore requires prompt therapeutic intervention. Although hyperferritinemia has been emphasized as a useful marker for FHL, some nonfatal cases in infants with spontaneous remission also manifest with hyperferritinemia. However, distinguishing them is difficult because initial clinical features of these infants are similar. The authors encountered 14 infants with hyperferritinemia (serum ferritin >674 ng/mL), which normalized within 3 weeks following a benign clinical course. The authors compared the levels of HLA-DR+CD3+ T-cell subsets and interferon-gamma (IFN-γ) in the peripheral blood between these infants and FHL cases: one of the authors' own patients and others from the literature. Serum IFN-γ was not detected in infants with hyperferritinemia. Moreover, levels of HLA-DR+CD3+ T cells were extremely depressed. In contrast, serum IFN-γ was elevated and HLA-DR+CD3+ T cells were not depressed in FHL. Measurement of activated T cells and serum IFN-γ might help differentiate FHL in febrile infants with transient hyperferritinemia.

Comparison of varicella-zoster virus-specific immunity of patients with diabetes mellitus and healthy individuals.

Cell-mediated immunity (CMI) has been shown to be critical for the prevention and control of varicella-zoster virus (VZV)-related diseases. Because a large population-based study has revealed that diabetes mellitus is a risk factor for herpes zoster, we studied VZV-specific immune responses of patients with diabetes mellitus and compared them with those of healthy individuals. In this study, we found that patients with diabetes mellitus had significantly lower CMI to VZV than did healthy individuals. These results suggest that the increased risk for herpes zoster among patients with diabetes mellitus may be related to decreased VZV-specific CMI.

Early therapy with corticosteroid and surfactant for acute idiopathic pulmonary hemorrhage in infants: Two case reports.

RATIONALE: Acute idiopathic pulmonary hemorrhage (AIPH) in infants is a rare condition, and a clear treatment protocol has not yet been established. PATIENT CONCERNS: We report 2 infant cases of AIPH in a 3-month-old male and a 1-month-old female, who presented at an emergency room with epistaxis and respiratory distress. Both were immediately intubated, which revealed a bloody intratracheal aspirate. DIAGNOSIS: Pulmonary hemorrhage was confirmed by X-ray and computed tomography imaging in both cases. The extensive evaluation revealed no specific etiology for the acute pulmonary hemorrhage, and AIPH was therefore diagnosed in both cases. INTERVENTIONS: Intravenous methylprednisolone resulted in a rapid improvement in oxygenation and a reduction in high airway pressure during mechanical ventilation. Methylprednisolone was subsequently tapered off within 13 and 3 days in cases 1 and 2, respectively. In case 1, intratracheal administration of a surfactant also resulted in an immediate improvement in respiratory condition and the patient was extubated after 2 days; no effect was seen in case 2, and the patient was extubated after 10 days. OUTCOME: Both infants recovered well without sequelae or further relapse after 23 and 71 months of follow-up, respectively. LESSONS: Early administration of corticosteroid therapy and intratracheal administration of diluted surfactant should be considered for severe acute pulmonary hemorrhage in infants.

Hereditary spherocytosis in 3 children coexisting with UDP-glucuronyl transferase 1A1 deficiency.

Simultaneous presence of hemolytic anemia and bilirubin UDP-glucuronosyltransferase deficiency is a possible cause of misdiagnosis. Seven-year-old and 17-year-old brothers and a 15-year-old sister consecutively suffered from aplastic crises. Although few spherocytes were present, the siblings and their mother had diagnoses of hereditary spherocytosis with flow cytometric analysis of eosin-5'-maleimide-labeled red blood cells in addition to osmotic fragility test. However, inappropriately high values of bilirubin compared with mild hemolysis persisted. Further analysis of UDP-glucuronyltransferase 1A1 revealed all 3 siblings were heterozygous for A(TA)7TAA-P229Q. We report here the importance of careful evaluation of mild hereditary spherocytosis masking UDP-glucuronyltransferase 1A1 deficiency.

Altered immunogenicity of 23-valent pneumococcal polysaccharide vaccine in elderly patients with diabetes who revealed lower responses to concomitant administration of BIKEN varicella zoster vaccine: Results of post hoc analysis of a randomized double-blind trial.

AIMS: This double-blind randomized controlled study of 52 elderly patients with diabetes assessed cell-mediated immunity and safety of BIKEN varicella-zoster vaccine (BVZV). Cellular and humoral responses to VZV at 3 months after BVZV and 23-valent polysaccharide pneumococcal vaccine (PPSV23) vaccination elicited poor results. Post-hoc analyses assessed the effects of immunogenicity of PPSV23. METHODS: Using standardized enzyme-linked immunosorbent assay, pneumococcal 6B and 23F serotype-specific immunoglobulin G (IgG)-binding antibody concentrations were measured in stored samples retrospectively before administration and 3 months after. Responders increased more than twofold in at least one serotype-specific IgG. RESULTS: The geometric mean concentration ratio (GMCR) of serum anti-pneumococcal 6B IgG was 1.76 (95%C.I.: 0.58, 5.34) in patients receiving concurrent PPSV23 and BVZV, compared to 2.39 (95%C.I.: 0.53, 10.76) in patients receiving PPSV23 and placebo (P = .055). The GMCR of serum anti-pneumococcal 23F IgG was 2.54 (95%C.I.: 0.57, 11.43) in PPSV23/BVZV vaccinees compared to 3.34 (95%C.I.: 0.84, 12.92) in PPSV23/placebo vaccinees (P = .424). Responder rates, those who developed antibodies to either/both serotypes, were 68% in the BVZV group and 85% in the placebo group (P = .007). CONCLUSIONS: Results suggest that concurrent administration of BVZV influenced humoral responses to PPSV23 in elderly subjects with diabetes.

Successful Conservative Treatment of Mycotic Pulmonary Artery Aneurysms Caused by MRSA Bacteremia.

Mycotic pulmonary artery aneurysms (MPAAs) are rare and life-threatening with currently no recommended treatment strategies. In this report, we describe a successfully treated case of ventricular septal defect in an 11-month-old girl who developed bacteremia, infective endocarditis, and MPAA caused by methicillin-resistant Staphylococcus aureus (MRSA). We first started vancomycin, gentamycin, and panipenem-betamipron for infective endocarditis but switched to teicoplanin and arbekacin on day 3 after initiating treatment because bacteremia persisted, and vancomycin minimum inhibitory concentration was relatively high at 2 mg/L. Although we added clindamycin on day 5 and fosfomycin on day 7, MRSA bacteremia persisted, and we finally added daptomycin at 10 mg/kg per day on day 8, whereupon the bacteremia subsided within a day. Although the bacteremia subsided, the patient developed septic pulmonary embolisms and septic arthritis on her left knee. We continued daptomycin but switched the concomitant drug to linezolid, trimethoprim-sulfamethoxazole, and rifampicin on day 11. After several repeats of puncture and lavage of her knee joint, she became afebrile on day 16. Computed tomography scans taken on day 32 revealed right pulmonary artery MPAAs. She was treated with long-term multidrug therapy, and MPAAs were absent on subsequent computed tomography scans on day 184. Multidrug therapy mainly based on daptomycin could be a possible salvage therapy for refractory MRSA bacteremia with high vancomycin minimum inhibitory concentration. Conservative treatment should be selectively considered as a treatment option for clinically stable MPAA instead of surgical and endovascular treatment.

Presepsin and procalcitonin as biomarkers of systemic bacterial infection in patients with rheumatoid arthritis.

AIM: To assess the diagnostic values of presepsin and procalcitonin in patients with rheumatoid arthritis (RA) by identifying those with bacterial infection METHOD: During June 2014-September 2015, 126 patients with RA and 25 healthy controls were enrolled. RA patients were divided into an infection group and a non-infection group. Infection was diagnosed by clinical symptoms, microbiological or radiographic methods, and good response to antibiotics. Concentrations of plasma presepsin, serum procalcitonin, C-reactive protein (CRP), and white blood cell counts (WBC) were measured and compared in each group. The correlations with the Sequential Organ Failure Assessment (SOFA) Score and these markers were calculated. RESULTS: RA patients included 26 patients in the infection group, 45 patients in the CRP-positive non-infection group (CRP > 0.3 mg/dL), and 55 patients in the CRP-negative non-infection group (CRP < 0.3 mg/dL). Levels of presepsin and procalcitonin in the infection group were highest and significantly higher than those in the CRP-positive non-infection group (presepsin 682.8 ± 158.1 pg/mL vs. 192.0 ± 12.0 pg/mL [P < 0.0001]; procalcitonin 4.052 ± 1.637 ng/mL vs. 0.120 ± 0.032 ng/mL [(P < 0.0001]). According to receiver operating characteristic curve (ROC) analysis, presepsin and procalcitonin levels appeared to have a higher diagnostic accuracy for infection than CRP or WBC. For the infection group, the SOFA Score positively correlated with the concentration of presepsin but not with that of procalcitonin. CONCLUSION: Presepsin and procalcitonin may be useful to identify infection in RA patients. Presepsin may better reflect infection severity than procalcitonin.

Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants.

BACKGROUND: The reactivation of varicella-zoster virus from latency causes zoster and is common among recipients of hematopoietic-cell transplants. METHODS: We randomly assigned patients who were scheduled to undergo autologous hematopoietic-cell transplantation for non-Hodgkin's or Hodgkin's lymphoma to receive varicella vaccine or no vaccine. Heat-inactivated, live attenuated varicella vaccine was given within 30 days before transplantation and 30, 60, and 90 days after transplantation. The patients were monitored for zoster and for immunity against varicella-zoster virus for 12 months. RESULTS: Of the 119 patients enrolled, 111 received a transplant. Zoster developed in 7 of 53 vaccinated patients (13 percent) and in 19 of 58 unvaccinated patients (33 percent) (P=0.01). After two patients in whom zoster developed before transplantation were excluded, the respective rates were 13 percent and 30 percent (P=0.02). In vitro CD4 T-cell proliferation in response to varicella-zoster virus (expressed as the mean stimulation index) was greater in patients who received the vaccine than in those who did not at 90 days, after three doses (P=0.04); at 120 days, after all four doses (P<0.001); at 6 months (P=0.004); and at 12 months (P=0.02). The risk of zoster was reduced for each unit increase in the stimulation index above 1.6; a stimulation index above 5.0 correlated with greater than 93 percent protection. Induration, erythema, or local pain at the injection site was observed in association with 10 percent of the doses. CONCLUSIONS: Inactivated varicella vaccine given before hematopoietic-cell transplantation and during the first 90 days thereafter reduces the risk of zoster. The protection correlates with reconstitution of CD4 T-cell immunity against varicella-zoster virus.

Safety and efficacy of anti-influenza drugs, intravenous peramivir against influenza virus infection in elderly patients with underlying disease.

We retrospectively analyzed data of 38 elderly patients, each with an underlying disease, to evaluate peramivir safety and efficacy. Six patients (15.8%) experienced adverse events, all tolerated. Median time from administration until the return to normal temperatures was 31.5 h (95% CI: 22.4-40.6). Results confirm intravenous peramivir's usefulness.

Recurrence of Escherichia coli meningitis in a preterm infant and co-infection of echovirus 18.

Introduction: Bacterial meningitis may relapse after adequate antibiotic treatment. In most cases, however, the pathophysiology cannot be identified. Presentation of case: We describe a preterm infant with recurrent episodes of meningitis due to infection with an identical Escherichia coli strain both at birth and at 10 days after cessation of a 3 week course of appropriate antibiotic treatment. At the time of recurrence, the patient presented with fulminant severe cardiac failure due to acute myocarditis, coupled with a concurrent echovirus 18 infection (confirmed by stool culture and serological analysis). Conclusion: Co-infection by echovirus may underlie recurrence of Escherichia coli meningitis in this case.

Vaccine-strain herpes zoster found in the trigeminal nerve area in a healthy child: A case report.

A previously healthy 2-year-old girl, vaccinated for varicella at 17 months, was admitted because of left-sided facial herpes zoster caused by vaccine-strain varicella-zoster virus (VZV). She recovered fully with no complication after intravenous treatment using acyclovir. Earlier reports have described that herpes zoster (HZ) rashes caused by vaccine-strain VZV tend to occur on the dermis corresponding to the skin area where the varicella vaccine was received. However, rashes appeared on this girl only in the trigeminal nerve area, which is unrelated to the vaccinated site. Results underscore the importance of distinguishing vaccine-strain VZV from wild-type VZV whenever encountering HZ cases after vaccination, even in immunocompetent children, irrespective of the skin lesion site. Monitoring vaccine-strain HZ incidence rates is expected to elucidate many aspects of varicella vaccine safety.

Concentrations of thioredoxin, a redox-regulating protein, in umbilical cord blood and breast milk.

Growing evidence indicates that oxidative stress occurs during the fetal-to-neonatal transition. Such stress plays an important role in the pathogenesis of many neonatal diseases. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced in various cells against oxidative stress and is secreted extracellularly. This study was undertaken to examine the clinical and biological importance of TRX in the perinatal setting. We measured concentrations of TRX in umbilical cord blood and breast milk using a sandwich ELISA. Our study demonstrated that concentrations of TRX in umbilical cord blood were six to seven times higher than those in blood of healthy adults. This study also showed that umbilical concentrations of TRX were correlated significantly with the extent of prematurity of the newborn, and that they were elevated significantly in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. In contrast, concentrations of coenzyme Q(10) and vitamin E in umbilical blood were lower than adult blood levels. Breast milk concentrations of TRX during the early postpartum period were seven to eight times higher than those in blood of lactating women. Those of the coenzyme Q(10) were lower than adult blood levels, while those of vitamin E were comparable to adult blood levels. Our findings suggest that the systemic release of TRX is enhanced at birth, and that early breast milk is a rich source of this protein. Consequent high levels of TRX in newborns may provide a unique protective mechanism that allows the maintenance of redox balance during the fetal-to-neonatal transition.