Systemic lupus erythematosus is a risk factor for cancer: a nationwide population-based study in Korea.

OBJECTIVE: Specific differences in cancer risk have been observed between systemic lupus erythematosus patients and the general population. Although meta-analyses have estimated cancer incidence in systemic lupus erythematosus patients, results have been inconclusive. Hence, we aimed to assess malignancy risk in systemic lupus erythematosus patients, compared to the risk in the general population. METHODS: Systemic lupus erythematosus patients ( n = 21,016; mean age 41.67 ± 13.14 years; female 90.22%) were selected from the Korean National Health Insurance Service database between 2008 and 2014. Age- and sex-matched controls were randomly sampled in a 5:1 ratio ( n = 105,080). RESULTS: During the 7 years of follow up, malignancy was detected in 763 (3.63%) systemic lupus erythematosus patients and 2667 (2.54%) controls. Systemic lupus erythematosus patients had a higher risk of malignancy than controls (odds ratio 1.44; 95% confidence interval 1.327-1.559), after multivariate adjustment. Systemic lupus erythematosus patients had a higher odds ratio for developing cervical, thyroid, ovarian, and oral cancer, as well as lymphoma, leukemia, and multiple myeloma than controls. Based on subgroup analysis, male systemic lupus erythematosus patients and patients younger than 40 years showed the highest lymphoma risk. CONCLUSIONS: Systemic lupus erythematosus might be an independent risk factor for cancer. Therefore, the importance of cancer screening programs should be emphasized in systemic lupus erythematosus patients. Our study is the first large nationwide cohort study for evaluating the risk of cancer in systemic lupus erythematosus patients.

Systemic lupus erythematosus is a risk factor for cardiovascular disease: a nationwide, population-based study in Korea.

OBJECTIVE: To investigate the incidence and clinical significance of cardiovascular disease in systemic lupus erythematosus patients. METHODS: We included systemic lupus erythematosus patients ( n = 18,575) without previous cardiovascular disease and age- and sex-matched individuals without systemic lupus erythematosus (controls; n = 92,875) from the Korean National Health Insurance Service database (2008-2014). Both cohorts were followed up for incident cardiovascular disease and death until 2015. RESULTS: During follow up, myocardial infarction occurred in 203 systemic lupus erythematosus patients and 325 controls (incidence rate: 1.76 and 0.56 per 1000 person-years, respectively), stroke occurred in 289 patients and 403 controls (incidence rate: 2.51 and 0.70 per 1000 person-years, respectively), heart failure occurred in 358 patients and 354 controls (incidence rate 3.11 and 0.61 per 1000 person-years, respectively), and death occurred in 744 patients and 948 controls (incidence rate 6.54 and 1.64 per 1000 person-years, respectively). Patients with systemic lupus erythematosus had higher risks for myocardial infarction (hazard ratio: 2.74, 95% confidence interval: 2.28-3.37), stroke (hazard ratio: 3.31, 95% confidence interval: 2.84-3.86), heart failure (hazard ratio: 4.60, 95% confidence interval: 3.96-5.35), and cardiac death (hazard ratio: 3.98, 95% confidence interval: 3.61-4.39). CONCLUSIONS: Here, systemic lupus erythematosus was an independent risk factor for cardiovascular disease, thus cardiac assessment and management are critical in systemic lupus erythematosus patients.

Comorbidities Can Predict Mortality of Kidney Transplant Recipients: Comparison With the Charlson Comorbidity Index.

BACKGROUND: Comorbid conditions are important in the survival of kidney transplant recipients. The weights assigned to comorbidities to predict survival may vary based on the type of index disease and advances in the management of comorbidities. We aimed to develop a modified Charlson comorbidity index (CCI) in renal allograft recipients (mCCI-KT), thereby improving risk stratification for mortality. METHODS: A total of 3765 recipients in a multicenter cohort were included to develop a comorbidity score. The weights of the comorbidities, per the CCI, were recalibrated using a Cox proportional hazards model. RESULTS: Peripheral vascular disease, liver disease, myocardial infarction, and diabetes in the CCI were selected from the Cox proportional hazards model. Thus, the mCCI-KT included 4 comorbidities with recalibrated severity weights. Whereas the CCI did not discriminate for survival, the mCCI-KT provided significant discrimination for survival using the Kaplan-Meier method and Cox regression analysis. The mCCI-KT showed modest increases in c-statistics (0.54 vs 0.52, P = .001) and improved net mortality risk reclassification by 16.3% (95% confidence interval, 3.2-29.4; P = .015) relative to the CCI. CONCLUSION: The mCCI-KT stratifies the risk for mortality in renal allograft recipients better than the CCI, suggesting that it may be a preferred index for use in clinical practice.

Fluoroscopy-assisted epidural catheter placement: an exploratory analysis of 303 pre-operative epidurograms.

BACKGROUND: Epidural catheters that are placed for post-operative analgesia have a significant failure rate in the first 24 hours. Beginning in 2011, we have used fluoroscopic guidance to place all non-obstetrical epidural catheters. In this retrospective analysis, we hypothesized that the characteristics of dye distribution on an epidurogram obtained immediately after catheter placement would predict clinical catheter function after surgery. METHODS: The epidurograms and medical records of 303 consecutive patients who had epidural catheters placed for post-operative analgesia were reviewed. We extracted data on epidural dye distribution on the epidurograms and compared these results to the clinical function of the epidural catheters assessed on post-operative day 1 (POD1). RESULTS: The three-dimensional pattern of epidural dye distribution (cephalad-caudad, right-left, anterior-posterior) had significant correlations with clinical function of an epidural catheter after surgery. Increased cephalad-caudad and anterior dye spread both correlated with decreased epidural solution infusion rates on POD1, whereas right- or left-sided dye distribution correlated with unilateral sensory deficits. A higher catheter placement on the neuraxis correlated with lower pain scores after thoracic surgery. CONCLUSIONS: An epidurogram obtained immediately after epidural catheter placement may have clinical utility for predicting clinical function of the catheter after surgery.

Haploinsufficiency of cathepsin D leads to lysosomal dysfunction and promotes cell-to-cell transmission of α-synuclein aggregates.

Lysosomal dysfunction has been implicated both pathologically and genetically in neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease (PD). Lysosomal gene deficiencies cause lysosomal storage disorders, many of which involve neurodegeneration. Heterozygous mutations of some of these genes, such as GBA1, are associated with PD. CTSD is the gene encoding Cathepsin D (CTSD), a lysosomal protein hydrolase, and homozygous CTSD deficiency results in neuronal ceroid-lipofuscinosis, which is characterized by the early onset, progressive neurodegeneration. CTSD deficiency was also associated with deposition of α-synuclein aggregates, the hallmark of PD. However, whether partial deficiency of CTSD has a role in the late onset progressive neurodegenerative disorders, including PD, remains unknown. Here, we generated cell lines harboring heterozygous nonsense mutations in CTSD with genomic editing using the zinc finger nucleases. Heterozygous mutation in CTSD resulted in partial loss of CTSD activity, leading to reduced lysosomal activity. The CTSD mutation also resulted in increased accumulation of intracellular α-synuclein aggregates and the secretion of the aggregates. When α-synuclein was introduced in the media, internalized α-synuclein aggregates accumulated at higher levels in CTSD+/- cells than in the wild-type cells. Consistent with these results, transcellular transmission of α-synuclein aggregates was increased in CTSD+/- cells. The increased transmission of α-synuclein aggregates sustained during the successive passages of CTSD+/- cells. These results suggest that partial loss of CTSD activity is sufficient to cause a reduction in lysosomal function, which in turn leads to α-synuclein aggregation and propagation of the aggregates.

Clinical Features and Prognosis of Invasive Pulmonary Aspergillosis in Korean Children with Hematologic/Oncologic Diseases.

Invasive pulmonary aspergillosis (IPA) is the most frequent form of invasive fungal diseases in immunocompromised patients. However, there are only a few studies on IPA in immunocompromised children in Korea. This study was designed to characterize IPA in Korean children with hematologic/oncologic diseases. Medical records of children with hematologic/oncologic diseases receiving antifungal therapy were reviewed. The enrolled children were divided into the IPA group (proven and probable IPA) and non-IPA group, and the clinical characteristics and prognosis were compared between the two groups. During the study period, 265 courses of antifungal therapy were administered to 166 children. Among them, two (0.8%) episodes of proven IPA, 35 (13.2%) of probable IPA, and 52 (19.6%) of possible IPA were diagnosed. More children in the IPA group suffered from neutropenia lasting for more than two weeks (51.4% vs. 21.9%, P<0.001) and showed halo signs on the chest computed tomography (78.4% vs. 40.7%, P<0.001) than in the non-IPA group. No other clinical factors showed significant differences between the two groups. Amphotericin B deoxycholate was administered as a first line antifungal agent in 33 (89.2%) IPA group episodes, and eventually voriconazole was administered in 27 (73.0%) episodes. Ten (27.0%) children in the IPA group died within 12 weeks of antifungal therapy. In conclusion, early use of chest computed tomography to identify halo signs in immunocompromised children who are expected to have prolonged neutropenia can be helpful for early diagnosis of IPA and improving prognosis of children with IPA.

Extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae bacteremia in febrile neutropenic children.

This retrospective study was conducted to evaluate clinical outcomes of bacteremia caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their antibiotic susceptibilities in febrile neutropenic children. Clinical characteristics, prognosis, and antibiotic susceptibilities were reviewed and compared between febrile neutropenic children with bacteremia caused by ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae. A total of 61 episodes of E. coli and K. pneumoniae bacteremia, including 21 episodes (34.4%) due to ESBL-producing strains, were diagnosed. There was no significant factor associated with bacteremia by ESBL-producing strains. Empirical antibiotics were appropriate in 85.7% of the ESBL group and 95.0% of the non-ESBL group. In the entire study population, seven deaths (11.5%), including three deaths (4.9%) due to E. coli and K. pneumoniae bacteremia, occurred. The complication and mortality rates were not significantly different between the two groups. Antibiotic susceptibility rates were significantly lower in the ESBL group than in the non-ESBL group in most antibiotics. Although 52.4% and 66.7% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam and cefepime, respectively, 96.7% of all the isolates and 90.5% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam or cefepime in combination with aminoglycoside. In conclusion, the ESBL group did not show a significantly unfavorable outcome, and empirical therapy with piperacillin/tazobactam or cefepime in combination with aminoglycoside might be more useful for febrile neutropenic children, instead of ß-lactam monotherapy in institutions with high prevalence of ESBL-producing E. coli and K. pneumoniae.

Prognostic impact of hyponatraemia in patients with colorectal cancer.

AIM: Hyponatraemia is a common in surgical practice, but its clinical impact in patients with colorectal cancer has not been evaluated. METHOD: We retrospectively assessed 2944 patients who had been admitted to Chonnam National University Hwasun Hospital, Korea with a diagnosis of colorectal cancer. In order to determine the relationship between the serum sodium level and 3-year mortality, we categorized the patients as having normonatraemia (135-147 mEq/l), or mild (130-134 mEq/l), moderate (125-129 mEq/l) or severe hyponatraemia (< 125 mEq/l). RESULTS: Hyponatraemia, defined as a serum sodium level of < 135 mEq/l, was evident in 27.6% of patients during hospitalization. Declining serum sodium levels were associated with increasing age, a higher number of comorbidities, a more advanced TNM stage and worsening biochemical parameters. In a multivariate Cox-proportional regression analysis, the mortality risk was correlated with the severity of hyponatraemia [hazard ratio (HR) 1.65, 95% CI 1.38-1.96; HR 2.24, 95% CI 1.69-2.98; HR 2.20, 95% CI 1.25-3.90, for patients with mild, moderate, and severe hyponatraemia, respectively, compared with patients with normonatraemia]. An independent association between hyponatraemia and long-term mortality was sustained among various subpopulations and patients with persistent hyponatraemia had a worse prognosis than those with hyponatraemia that resolved. CONCLUSION: A substantial proportion of patients developed hyponatraemia during hospitalization, and the long-term mortality risk increased even in mild cases of hyponatraemia. Hyponatraemia should be considered as an important prognostic factor in colorectal cancer.

Bullous cutaneous mastocytosis, a rarely reported disease in Asian children.

Diffuse cutaneous mastocytosis, the most rare form of cutaneous mastocytosis, often manifests as bullous lesions. Although cutaneous mastocytosis should be included in a differential diagnosis for pruritic skin lesions in children, early diagnosis of the disease is not easy due to its rare occurrence. A 17-month-old boy presented with recurrent itchy bullous skin lesions. He had been treated as atopic dermatitis at other hospitals for about one year, however, he was eventually diagnosed with diffuse cutaneous mastocytosis through skin biopsy. Unlike adults, children with cutaneous mastocytosis usually improve with age and do not develop systemic mastocytosis. Therefore, early and accurate diagnosis of cutaneous mastocytosis in children is essential for appropriate care.

Use of intravenous immunoglobulin in a disseminated varicella infection in an immunocompromised child.

Varicella-zoster virus infection can lead to severe illness in immunocompromised patients. Further the mortality rate of disseminated varicella infection is extremely high particularly in immunocompromised children. We report a case of disseminated varicella infection in a child with acute lymphoblastic leukemia who was receiving chemotherapy, but was initially admitted with only for acute abdominal pain. The patient rapidly developed severe complications, including acute respiratory distress syndrome, acute hepatitis, disseminated intravascular coagulation, and encephalopathy. Acyclovir is a highly potent inhibitor of varicella-zoster virus infection. However, owing to rapid disease progression, it might not be sufficient to control a disseminated varicella infection, especially in immunocompromised patients. Immunoglobulin neutralize virus invasion and suppress viremia, acting synergistically with acyclovir. In this case, early administration of acyclovir and a high-dose of immunoglobulin, combined with mechanical respiratory support, proved adequate for treatment of this severe illness.

Features of Epstein-Barr virus reactivation after allogeneic hematopoietic cell transplantation in Korean children living in an area of high seroprevalence against Epstein-Barr virus.

The present study was conducted to investigate Epstein-Barr virus (EBV) reactivation after hematopoietic cell transplantation (HCT) in Korean children living in an area of a high seroprevalence against EBV and to determine the impact of recipient age on EBV reactivation. Medical records of 248 children and adolescents who had received allogeneic HCT were retrospectively reviewed. The trends of EBV reactivation and post-transplant lymphoproliferative disorders (PTLDs) were evaluated and compared between younger (≤10 years old) and older (11-20 years old) groups. EBV reactivation occurred in 177 cases (71.4 %) and high-level EBV reactivation, defined as a virus DNA titer of 300,000 copies/mL or higher, occurred in 21 cases (8.5 %). PTLD was diagnosed in five cases (2.0 %), and one of these patients died. The EBV reactivation rate was not significantly different between the two age groups; however, high-level reactivation and PTLD were more significantly frequent in the older than in the younger group (P = 0.030 and P = 0.026, respectively). In conclusion, older children and adolescents are more likely to experience high-level EBV reactivation and PTLDs, and higher EBV DNA titers than those previously reported may be a predictor of PTLD in areas with a high seroprevalence against EBV.

Use of IgY antibody to recombinant avian reovirus σC protein in the virus diagnostics.

Avian reovirus (ARV) is an important agent of several diseases causing considerable losses in poultry farming. An outer capsid protein (σC) of ARV, is known as a virus-cell attachment protein essential for virus infectivity. In this study, the σC gene of ARV was cloned and expressed in Escherichia coli. The expressed recombinant protein was used as immunogen for raising a specific IgY antibody in laying hens. At 14 weeks post immunization, the antibody titers in serum and egg yolk reached 302,000 and 355,000, respectively. The IgY antibody was capable to neutralize ARV in BHK-21 cells and it strongly reacted in ELISA with ARV but not with heterologous viruses. The IgY antibody detected ARV in field samples of infected animal tissues in dot blot assay. These results suggest that an efficient, economic and rapid diagnostics of ARV can be performed routinely using the IgY antibody against a recombinant ARV σC protein.

Pulmonary hemorrhage in pediatric lupus anticoagulant hypoprothrombinemia syndrome.

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS), a very rare disease that is caused by the presence of antifactor II antibodies, is usually counterbalanced by the prothrombotic effect of lupus anticoagulant (LAC). Patients with LAHPS are treated using fresh frozen plasma, steroids, immunosuppressive agents, and immunoglobulins for managing the disease and controlling hemorrhages. Notably, steroids are the important treatment for treating hypoprothrombinemia and controlling the bleeding. However, some patients suffer from severe, life-threatening hemorrhages, when factor II levels remain very low in spite of treatment with steroids. Here, we report a case of LAHPS in a 15-year-old girl who experienced pulmonary hemorrhage with rapid progression. She was referred to our hospital owing to easy bruising and prolonged bleeding. She was diagnosed with LAHPS that presented with pancytopenia, positive antinuclear antibody, proloned prothrombin time, activated partial thromboplastin time, positive LAC antibody, and factor II deficiency. Her treatment included massive blood transfusion, high-dose methylprednisolone, vitamin K, and immunoglobulin. However, she died due to uncontrolled pulmonary hemorrhage.

Pertussis seroprevalence in korean adolescents and adults using anti-pertussis toxin immunoglobulin G.

This study was conducted to evaluate age-specific seroprevalence of pertussis in Korea and to formulate a strategy to prevent and reduce the incidence of pertussis. Residual serum samples of healthy adolescents and adults 11 yr of age or older were collected between July 2012 and December 2012, and anti-pertussis toxin (PT) IgG titers were measured using a commercial ELISA kit. We compared the mean anti-PT IgG titers and seroprevalence of pertussis of the six age groups: 11-20, 21-30, 31-40, 41-50, 51-60, and ≥ 61 yr. A total of 1,192 subjects were enrolled. The mean anti-PT IgG titer and pertussis seroprevalence were 35.53 ± 62.91 EU/mL and 41.4%, respectively. The mean anti-PT IgG titers and seroprevalence were not significantly different between the age groups. However, the seroprevalence in individuals 51 yr of age or older was significantly higher than in individuals younger than 51 yr (46.5% vs 39.1%, P = 0.017). Based on these results, a new pertussis prevention strategy is necessary for older adults.

Seroepidemiology of tetanus in Korean adults and adolescents in 2012.

This seroepidemiologic study was performed to evaluate the immune status against tetanus in Korean adolescents and adults and to provide evidence to develop strategies for tetanus prevention. Between July 2012 and December 2012, serum samples were collected from adults and adolescents 11 years of age and older, and serum anti-tetanus IgG titers were determined using a commercial ELISA kit. Subjects were divided into six age groups: 11-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years, and ≥61 years. The mean anti-tetanus IgG titers and tetanus seroprevalence of the age groups were compared. A total of 1193 adults and adolescents were enrolled. Mean anti-tetanus IgG titer and tetanus seroprevalence of all subjects were 1.20 ± 3.58 IU/mL and 56.4%, respectively. The mean anti-tetanus IgG titer decreased with an increase in age (p < 0.001). Tetanus seroprevalence increased from 92.0% in the 11-20 year age group to 95.7% in the 21-30 year age group, and then decreased with a further increase in age (p < 0.001). These results reflected an appropriate Td booster vaccine coverage at 11-12 years of age. However, the tetanus seroprevalence of adults older than 41 years was as low as the levels in previous studies: therefore, adults should be more encouraged to acquire decennial Td booster vaccinations recommended by the National Immunization Program.

Tetherins of various species inhibit the release of porcine endogenous retrovirus from human cells.

Pigs are considered as suitable xenotransplantation organ donors. However, the risk of pathogen transmission from pigs to human is a major concern in the transplantation of porcine tissues since it had been shown that porcine endogenous retroviruses (PERVs) can infect human cells. Tetherin has recently been described as a host restriction factor that blocks the release of virus particles from cells infected with some enveloped viruses. We compared tetherins derived from various species in their activity against PERVs by using a pseudotype assay. The results showed that (i) mammalian tetherins inhibit spread of PERVs, (ii) murine and rhesus tetherins are weaker inhibitors than canine and feline ones, (iii) human tetherin is induced by interferon alpha (IFN-α) and (iv) IFN-α treatment of 293T-PERV-PK-CIRCE cells reduced PERV release. We conclude that transgenic overexpression of tetherin combined with its induction by IFN-α may reduce the risk of PERV dissemination in xenotransplantation.

Recurrent lymphadenopathy in children with Kikuchi-Fujimoto disease.

UNLABELLED: Kikuchi-Fujimoto disease (KFD) is characterized by self-limiting regional lymphadenopathy with prolonged fever. Although the reported recurrence rate of KFD is known to be 3-4 %, this rate appears to be higher in our clinical experience, and rates up to 38.5 % have been previously reported. In this retrospective study, we reviewed medical records of children with pathologically confirmed KFD to investigate the factors associated with recurrent KFD. Enrolled children were divided into two groups according to the recurrence of KFD, and clinical and laboratory factors were compared between the two groups. The recurrence of KFD was determined based not on repeated pathologic confirmation but on the presence of clinical febrile lymphadenopathy. A total of 33 children with KFD, 26 boys (78.8 %) and 7 girls (21.2 %), with a median age of 12 years (9 months to 19 years), were enrolled. Thirty-one children (93.9 %) complained of fever, and most of the children (90.9 %) complained of cervical lymphadenopathy. Neutropenia (<1,500/µL) or lymphopenia (<1,500/µL) was observed in 51.5 %. Lactate dehydrogenase level, erythrocyte sedimentation rate, and C-reactive protein level were elevated in 90.9, 96.9, and 54.5 % of children, respectively. Fourteen children (42.4 %) experienced recurrent KFD, including ten children after biopsy and four children before and after biopsy. In a multivariate analysis, a past history of other systemic illnesses (p = 0.013) and a higher absolute lymphocyte count (p = 0.023) were significantly associated with recurrent KFD. These systemic illnesses were chronic idiopathic thrombocytopenic purpura, autoimmune thyroiditis, nephrotic syndrome, perinatal cytomegalovirus infection, and hemophagocytic lymphohistiocytosis. CONCLUSION: Our results suggest that recurrent KFD is more frequent than reported, and recurrent KFD should be considered in children with a history of other systemic illnesses such as immune disorders.

Rhabdomyolysis associated with initiation of febuxostat therapy for hyperuricaemia in a patient with chronic kidney disease.

WHAT IS KNOWN AND OBJECTIVE: Febuxostat is now recommended as the first-line pharmacological urate-lowering therapy for gout in the American College of Rheumatology guidelines. There is no case of rhabdomyolysis associated with febuxostat among reported side effects of the drug. Our objective is to report on a case of rhabdomyolysis associated with initiation of febuxostat in a patient with chronic kidney disease (CKD). CASE SUMMARY: A 73-year-old male patient visited our emergency room due to progressive weakness in both lower extremities starting 3 days earlier. Ten days before presentation, his primary physician had changed his prescription from allopurinol to febuxostat (80 mg) because of poor control of uric acid levels. There was tenderness in both thighs. Initial creatinine kinase (CK) was 7652 U/L (0-170 U/L), and a bone scan using (99m) Tc-HDP revealed strong uptake in soft tissues in both thighs and buttocks. Electromyography (EMG) and nerve conduction velocity (NCV) showed abnormal spontaneous activities (ASA), suggesting myopathy, not nerve damage. On day 7 of admission, after conservative management and febuxostat withdrawal, he could walk on the ward. He is being followed in our clinic as an outpatient with no sequelae. WHAT IS NEW AND CONCLUSION: This report is first case of rhabdomyolysis associated with initiation of febuxostat. Febuxostat should be withdrawn when rhabdomyolysis is confirmed.

Phospholipase D1 regulates autophagic flux and clearance of α-synuclein aggregates.

Many neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by abnormal accumulations of aggregated proteins. Brains in these diseases also show accumulation of autophagic vesicles in the neuronal cytoplasm, suggesting impairment of the autophagic process. As autophagy involves de novo membrane production and vesicle fusion, extensive changes in lipid molecules are necessary. However, the involvement of signaling lipid-modifying enzymes in autophagy and their roles in neurodegenerative diseases are not clear. Using specific inhibitor, we show that loss of phospholipase D1 (PLD1) activity resulted in an accumulation of microtubule-associated protein light chain 3 (LC3), p62, and polyubiquitinated proteins, signs representing malfunction in autophagic flux. Fluorescence and electron microscopic analyses demonstrated impaired fusion of autophagosomes with lysosomes, resulting in accumulation of autophagosomes. Within the cells with impaired autophagic flux, α-synuclein aggregates accumulated in autophagosomes. Knockdown of PLD1 expression using small interfering RNA also resulted in impaired autophagic flux and accumulation of α-synuclein aggregates in autophagosomes. Neuronal toxicity caused by α-synuclein accumulation was rescued by overexpression of PLD1; however, expression of activity-deficient mutant, PLD1-KRM, showed reduced rescue effects. Finally, we demonstrated that both PLD activity and expression levels were reduced in brain tissues of dementia with Lewy bodies (DLB) patients, whereas the amounts of α-synuclein and p62 were increased in the same tissue samples. Collectively, these results suggest that insufficient PLD activity, and therefore, the changes in phospholipid compositions within membranes, might be an important contributor to impaired autophagic process and protein accumulation in Lewy body diseases.

A case of myocarditis following neonatal meningitis caused by coxsackievirus B1 in spite of intravenous immunoglobulin treatment.

Enteroviral infection is one of the most common neonatal infections, and most patients recover without complications. This report describes a neonate who experienced meningitis followed by myocarditis. A 4-day-old boy was admitted with fever, diagnosed with enteroviral meningitis and treated with intravenous immunoglobulin (IVIG). However, myocarditis was subsequently diagnosed in spite of IVIG treatment, and coxsackievirus B1 (CXB1) was revealed as a cause. A left ventricular aneurysm persisted even though the patient recovered with repeated high-dose IVIG treatment and cardiac supportive care. This report describes a rare case where myocarditis developed several days after a diagnosis of CXB1 meningitis in spite of IVIG treatment. It is important to pay attention to the patient's clinical condition until the end of the second viremia of enterovirus and to consider high-dose IVIG treatment when treating enteroviral infections for neonates.