Idiopathic severe hypermagnesemia in an extremely low birth weight infant on the first day of life

A preterm female infant born at 27 weeks of gestation with a birth weight of 990 g developed acute hypotonia, apnea, hypotension and bradycardia mimicking septic shock syndrome at 14h after birth. Laboratory tests indicated a severe hypermagnesemia of 45 mg/dL. The renal function, complete blood count and maternal blood concentrations of magnesium were normal, and the blood cultures were negative. The patient recovered with treatment including exchange transfusion. However, the etiology of the severe hypermagnesemia remains unknown

A Case of Non-Hodgkin's Lymphoma in Patient with Coombs' Negative Hemolytic Anemia and Idiopathic Thrombocytopenic Purpura

Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma

Intraosseous Nerve Sheath Tumors in the Jaws

Although the head and neck region is recognized as the most common location for peripheral nerve sheath tumors, central involvement, particularly in the jaw bones, is quite unusual. Neurofibroma is one of the most common nerve sheath tumors occurring in the soft tissue and generally appears in neurofibromatosis 1 (NF1 or von Recklinghausen's disease). Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that almost always arise in the soft tissue. Here, we report four cases of intraosseous peripheral nerve sheath tumors occurring in the jaw bones and compare the clinical, radiologic, and pathologic findings in order to make a differential diagnosis

Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas

Background The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. Methods We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. Results PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low tumor-infiltrating lymphocytes (TILs), and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines. Conclusions The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of tumoral PD-L1/immune cell PD-L1/CD8+ TILs may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.This work was supported by the Basic Science Research Program of the National Research Foundation of Korea, which is funded by the Ministry of Education (2016R1D1A1B01010316)

The Mildly Elevated Serum Bilirubin Level is Negatively Associated with the Incidence of End Stage Renal Disease in Patients with IgA Nephropathy

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte

Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.Support was provided by: the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (NRF-2017R1A2A1A17069780) http://www.nrf.re.kr/

Trends in Overall Mortality, and Timing and Cause of Death among Extremely Preterm Infants near the Limit of Viability.

To investigate the trends in mortality, as well as in the timing and cause of death, among extremely preterm infants at the limit of viability, and thus to identify the clinical factors that contribute to decreased mortality.We retrospectively reviewed the medical records of 382 infants born at 23-26 weeks' gestation; 124 of the infants were born between 2001 and 2005 (period I) and 258 were born between 2006 and 2011 (period II). We stratified the infants into two subgroups-"23-24 weeks" and "25-26 weeks"-and retrospectively analyzed the clinical characteristics and mortality in each group, as well as the timing and cause of death. Univariate and multivariate logistic regression analyses were done to identify the clinical factors associated with mortality.The overall mortality rate in period II was 16.7% (43/258), which was significantly lower than that in period I (30.6%; 38/124). For overall cause of death, there were significantly fewer deaths due to sepsis (2.4% [6/258] vs. 8.1% [10/124], respectively) and air-leak syndrome (0.8% [2/258] vs. 4.8% (6/124), respectively) during period II than during period I. Among the clinical factors of time period, 1-and 5-min Apgar score, antenatal steroid identified significant by univariate analyses. 5-min Apgar score and antenatal steroid use were significantly associated with mortality in multivariate analyses.Improved mortality rate attributable to fewer deaths due to sepsis and air leak syndrome in the infants with 23-26 weeks' gestation was associated with higher 5-minute Apgar score and more antenatal steroid use

Predicting mortality in extremely low birth weight infants: Comparison between gestational age, birth weight, Apgar score, CRIB II score, initial and lowest serum albumin levels.

We explored GA, BW, Apgar score, CRIB II score, and serum albumin levels as univariate predictors of mortality in extremely low birth weight infants. Medical records of 564 extremely low birth weight infants were reviewed retrospectively. The infants were grouped as survivors (group I), expired ≤ 7th postnatal day (group II), and expired > 7th postnatal day (group III). The predictive value for mortality of gestational age, birth weight, Apgar scores at 1 and 5 min, clinical risk index for babies II score, and first and lowest serum albumin levels was assessed by calculating the associated area under the curve (AUC) in receiver operating characteristic (ROC) curves. The overall survival and mortality rates of groups I, II, and III were 81.0% (457/564), 7.6% (43/564), and 11.4% (64/564), respectively. Birth weight, Apgar scores at 1 and 5 min, and first serum albumin levels were significantly higher, while the clinical risk index for babies II score was significantly lower in group I when compared to groups II and III. Gestational age and lowest serum albumin level in group I were significantly higher than group III, but not group II. However, gestational age, birth weight, and clinical risk index for babies II score showed gestational age dependent variations regardless of survival or mortality. Apgar score at 5 min (0.756) and lowest serum albumin level (0.771) demonstrated the highest AUC of the ROC curve in predicting mortality in group II and III, respectively. In conclusion, Apgar score at 5 min and lowest serum albumin level were the most effective predictors for mortality in extremely low birth weight infants during ≤ 7th and > 7th postnatal days, respectively

Ionospheric F2-Layer Semi-Annual Variation in Middle Latitude by Solar Activity

We examine the ionospheric F2-layer electron density variation by solar activity in middle latitude by using foF2 observed\ud at the Kokubunji ionosonde station in Japan for the period from 1997 to 2008. The semi-annual variation of foF2\ud shows obviously in high solar activity (2000-2002) than low solar activity (2006-2008). It seems that variation of geomagnetic\ud activity by solar activity influences on the semi-annual variation of the ionospheric F2-layer electron density.\ud According to the Lomb-Scargle periodogram analysis of foF2 and Ap index, interplanetary magnetic field (IMF) Bs (IMF\ud Bz <0) component, solar wind speed, solar wind number density and flow pressure which influence the geomagnetic\ud activity, we examine how the geomagnetic activity affects the ionospheric F2-layer electron density variation. We find\ud that the semi-annual variation of daily foF2, Ap index and IMF Bs appear clearly during the high solar activity. It suggests\ud that the semi-annual variation of geomagnetic activity, caused by Russell-McPherron effect, contributes greatly to the\ud ionospheric F2-layer semi-annual electron density variation, except dynamical effects in the thermosphere