Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.

Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.

sFlt-1/PlGF ratio as a predictive and prognostic marker for preeclampsia.

OBJECTIVE: Preeclampsia is clinically unpredictable and associated with adverse outcomes. Pregnant women with suspected preeclampsia require intensive monitoring or hospitalization for elevated sFlt-1 (soluble fms-like tyrosine kinase-1) to PlGF (placental growth factor) ratios before symptoms arise. We aimed to determine the sFlt-1/PlGF ratio's usefulness in predicting adverse pregnancy outcomes in preeclampsia. METHODS: From January 2017 to February 2019, we measured the sFlt-1/PlGF ratio in 73 singleton pregnant women suspected of preeclampsia and classified them into three groups: low-risk (sFlt-1/PlGF ratio < 38, n = 19), intermediate (38 ≤ ratio < 85, n = 9), and high-risk (ratio ≥ 85, n = 32). RESULTS: Although the low- and high-risk groups both experienced weight gain during pregnancy, their body mass index (BMI) differed after pregnancy (p = 0.004). The number of women who had been taking antihypertensive medications for chronic hypertension since early pregnancy was higher in the low-risk group (31.6% vs. 22.2%, 6.7%). The gestational weeks at birth were lower in the high-risk group compared to that of the low-risk group (32.0 weeks vs. 35.79 weeks, p < 0.001). In the high-risk group, the average neonatal weight was significantly lighter (p = 0.021), and the period of stay in the neonatal intensive care unit was longer than that in the low-risk group (p = 0.003). CONCLUSION: The sFlt-1/PlGF ratio is a useful indicator of preeclampsia severity and can be utilized as a prognostic marker.

Detection and genomic analysis of genital group B streptococcus in pregnant Korean women.

AIM: Group B streptococcus (GBS) is a leading cause of life-threatening bacterial infections among newborns, and neonates born to heavily colonized women may be subject to vertical transmission. We sought to determine an appropriate detection method for genital GBS in pregnant women by comparing culture-based methods and real-time polymerase chain reaction (PCR). In addition, we performed molecular serotyping and multilocus sequence typing (MLST) on isolates. METHODS: A total of 150 pregnant women were enrolled and underwent vaginal-rectal swabbing at 16-40 weeks of gestation. GBS was identified by conventional culture and real-time PCR with or without enrichment. Molecular serotyping and MLST were performed on isolates. RESULTS: Overall genital GBS positive rate among the 150 study subjects was 17.3%. Direct culture identified 18 (12.0%) positive specimens, enrichment culture 22 (14.6%), direct PCR 24 (16.0%) and enrichment PCR 25 (16.6%). The sensitivity and specificity by direct and enrichment PCR were as follows: for direct PCR, 90.9% and 96.9%, respectively; and for enrichment PCR, 95.5% and 96.9%, respectively. Resistance rates to clindamycin and erythromycin were 33.3% and 19.1%, respectively. Serotype III-1 was the most common (26.3%), followed by serotype Ib (21.1%), III-3 (15.8%), V (15.8%), II (10.5%), IV (5.3%) and VI (5.3%). Most common sequence types (ST) were ST-1, ST-19 and ST-862 (15.8%), followed by ST-2 and ST-654 (10.5%). CONCLUSION: Direct real-time PCR using vaginal-rectal specimen could be used for detecting GBS in emergent conditions. Molecular serotypes III, Ib and V were most common. MLST analysis frequently presented ST-1, ST-19 and ST-862.

Vascular calcification and left ventricular hypertrophy in hemodialysis patients: interrelationship and clinical impacts.

Background: We examined the relationship and combined effect of vascular calcification (VC) and left ventricular hypertrophy (LVH) on deaths and cardiovascular events (CVEs) in hemodialysis (HD) patients. Methods: Maintenance HD patients (n=341) were included. Echocardiography data and plain chest radiographs were used to assess LVH and aortic arch VC. Results: VC was found in 100 patients (29.3%). LVH was more prevalent in patients with VC compared with those without VC (70% vs. 50.2%, P=0.001). VC was independently associated with a 2.42-fold increased risk of LVH (95% CI, 1.26-4.65). In multivariate analysis, compared with patients with neither VC nor LVH, the coexistence of VC and LVH was independently associated with CVE (HR, 2.01; 95% CI, 1.09-3.72), whereas VC or LVH alone was not. Patients with both VC and LVH had the highest risk for a composite event of deaths or CVE (HR, 1.88; 95% CI, 1.15-3.06). Significant synergistic interaction was observed between VC and LVH (P for interaction=0.039). Conclusions: VC was independently associated with LVH. The coexistence of VC and LVH was associated with higher risk of deaths and CVEs than either factor alone. VC and LVH showed a synergistic interaction for the risk of deaths and CVEs.

Serum 1,25-dihydroxyvitamin D Better Reflects Renal Parameters Than 25-hydoxyvitamin D in Patients with Glomerular Diseases.

Background: Impaired vitamin D metabolism may contribute to the development and progression of chronic kidney disease. The purpose of this study was to determine associations of circulating vitamin D with the degree of proteinuria and estimated glomerular filtration rate (eGFR) in patients with biopsy-proven glomerular diseases. Methods: Clinical and biochemical data including blood samples for 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were collected from patients at the time of kidney biopsy. Results: Serum 25(OH)D levels were not different according to eGFR. However, renal function was significantly decreased with lower serum 1,25(OH)2D levels (P < 0.001). The proportions of nephrotic-range proteinuria and renal dysfunction (eGFR ≤ 60 mL/min/1.73 m2) progressively increased with declining 1,25(OH)2D but not 25(OH)D. Multivariable linear regression analysis showed that 25(OH)D was significantly correlated with serum albumin and total cholesterol (ß = 0.224, P = 0.006; ß = -0.263, P = 0.001) and 1,25(OH)2D was significantly correlated with eGFR, serum albumin and phosphorus (ß = 0.202, P = 0.005; ß = 0.304, P < 0.001; ß = -0.161, P = 0.024). In adjusted multivariable linear regression, eGFR and 24hr proteinuria were independently correlated only with 1,25(OH)2D (ß = 0.154, P = 0.018; ß = -0.171, P = 0.012), but not 25(OH)D. The lower level of 1,25(OH)2D was associated with the frequent use of immunosuppressive agents (P < 0.001). Conclusion: It is noteworthy in these results that circulating 1,25(OH)2D may be superior to 25(OH)D as a marker of severity of glomerular diseases.

Transitional cell carcinoma involving graft kidney in a kidney transplant recipient: a case report.

BACKGROUND: Kidney transplantation (KT) is the treatment option for patients with end stage renal disease (ESRD) to prolong survival and improve quality of life. Although the use of potent immunosuppressive agents increases graft survival in kidney transplantation recipients (KTRs), it may lead to the development of malignancy, including transitional cell carcinoma (TCC). TCC developing in the pelvis of graft kidney is very rare in KTRs. CASE PRESENTATION: A 40-year-old male visited hospital with complaints of nausea, vomiting and gross hematuria. Eleven years ago, he was diagnosed ESRD of unknown origin, and received a living related KT from his father 1 year later. Radiologic findings showed a huge polypoid mass in the pelvis of graft kidney with pelvo-calyceal dilation and a 3.3 cm-sized nodule in aortocaval chain and a 2.5 cm-sized nodule in right iliac chain as TCC stage IV. Sonography-guided percutaneous needle biopsy of pelvis mass in the graft kidney revealed a low grade urothelial cell carcinoma. Radical graft nephroureterectomy was performed and histopathological diagnosis confirmed as a low grade urothelial carcinoma of graft pelvis and ureter lumen, which invaded to perirenal fat and renal parenchyma with lymphovascular presence (T3Nx). The patient started with adjuvant concurrent chemo-radiation therapy and returned to regular hemodialysis. CONCLUSIONS: We report a rare case of TCC in the pelvis of graft kidney with already advanced disease at diagnosis in a young KTR. For the early diagnosis of TCC in KTRs, exposure history to Chinese herb or analgesics should be investigated before KT and high risk population in KTRs should be tightly performed regular postoperative surveillance for TCC and considered of less calcineurin inhibitor-based immunosuppressant protocol.

Diagnostic utility of immunochemical fecal occult blood tests to detect lower gastrointestinal lesions in patients with chronic kidney disease.

PURPOSE: The immunochemical fecal occult blood test (iFOBT) is a useful method to screen for lower gastrointestinal (GI) bleeding-related lesions. However, few studies have investigated the diagnostic utility of iFOBT in chronic kidney disease (CKD). METHODS: We included 691 patients with nondialysis-dependent CKD stages 2-5 or those receiving dialysis. Bleeding-related lower GI lesions were identified by colonoscopy, and the diagnostic utility of iFOBT was evaluated. RESULTS: Bleeding-related lower GI lesions were found in 9.2% of 491 patients with CKD stage 2, 17.8% of 107 patients with CKD stage 3/4, and 25.8% of 93 patients with CKD stage 5/dialysis (p < 0.001). Compared with CKD stage 2, CKD stage 5/dialysis was independently associated with a 2.80-fold risk for bleeding-related lesions (p = 0.019). The iFOBT was positive in 92 (13.3%) patients and the area under the receiver operating curve (AUC) for a bleeding-related lesion was 0.64 (p < 0.001). The sensitivity of iFOBT increased as the CKD stage worsened (20.0 vs 52.6 vs 58.3%; p = 0.002). However, the specificity to detect bleeding-related lesions decreased with the severity of CKD stage (94.6 vs. 78.4 vs. 76.8%; p < 0.001). The AUC of iFOBT to detect adenoma or carcinoma was 0.54 (p = 0.046), and a similar pattern of sensitivity and specificity was observed between different CKD stages. CONCLUSIONS: The prevalence of bleeding-related lower GI lesions and the sensitivity of iFOBT to detect these GI lesions increased in advanced CKD. However, iFOBT should be used cautiously in these patients because its specificity decreased.

Clinical significance of chronic kidney disease and atrial fibrillation on morbidity and mortality in patients with acute myocardial infarction.

BACKGROUND/AIMS: Atrial fibrillation (AF) often coexists with acute myocardial infarction (AMI), and chronic kidney disease (CKD) is a major risk for AMI. However, the combined impact of CKD and AF on the mortality and morbidity in AMI population has not been determined. METHODS: Between January 2004 and December 2009, a total of 4,738 AMI patients were enrolled prospectively. Patients were divided into four groups according to the combined status of CKD and AF. The primary endpoint was a combination of 5-year major adverse cardiac and cerebrovascular events (MACCE). RESULTS: The prevalence of AF was significantly higher in CKD patients than in non-CKD patients (6.76 vs. 3.31%, p < 0.001). The highest cumulative event rate of MACCE and death was observed in patients with both CKD and AF (68.5 and 64.0%), respectively. In multivariable analyses, compared with patients with neither AF nor CKD, hazard ratios (HR) for composite of MACCE were 1.66 (95% CI, 1.14-2.41), 1.24 (95% CI, 1.06-1.46), and 2.10 (95% CI, 1.42-3.13) for patients with AF only, those with CKD only, and those with both CKD and AF, respectively (p for interaction = 0.935). Patients with both CKD and AF had a greatest risk for all-cause mortality (HR 2.54; 95% CI, 1.60-4.53), and the significant synergistic interaction was observed between CKD and AF (p for interaction = 0.015). CONCLUSION: The combined effect of AF and CKD on the risk of MACCE after an AMI is stronger than any separate condition, and it confers a synergistic effect on the all-cause mortality risk.

Unresolved subclinical hypothyroidism is independently associated with progression of chronic kidney disease.

BACKGROUND AND AIM: Patients with chronic kidney disease (CKD) often have subclinical hypothyroidism. However, few reports have investigated changes in the status of subclinical hypothyroidism in CKD patients and its clinical significance in CKD progression. METHODS: We included 168 patients with nondialysis-dependent CKD stages 2-4. The normalization of subclinical hypothyroidism during follow-up was assessed, and the association between transitions in subclinical hypothyroid status and the rate of decline of the estimated glomerular filtration rate (eGFR) was investigated. RESULTS: At baseline, 127 patients were euthyroid and 41 (24.4%) patients were diagnosed with subclinical hypothyroidism. Of these 41 patients, 21 (51.2%) spontaneously resolved to euthyroid during follow-up. The rate of eGFR decline of patients with resolved subclinical hypothyroidism was similar to that of euthyroid patients. The patients with unresolved subclinical hypothyroidism showed a steeper renal function decline than patients with euthyroidism or resolved subclinical hypothyroidism (all p < 0.05). The progression to end-stage renal disease was more frequent in those with unresolved subclinical hypothyroidism than in those who were euthyroid (p = 0.006). In multivariate linear regression for rate of eGFR decrease, unresolved subclinical hypothyroidism (ß = -5.77, p = 0.001), baseline renal function (ß = -0.12, p < 0.001) and level of proteinuria (ß = -2.36, p = 0.015) were independently associated with the rate of renal function decline. CONCLUSIONS: Half of the CKD patients with subclinical hypothyroidism did not resolve to euthyroidism, and this lack of resolution was independently associated with rapid renal function decline.

Xanthine oxidoreductase inhibition ameliorates high glucose-induced glomerular endothelial injury by activating AMPK through the purine salvage pathway.

Xanthine oxidoreductase (XOR) contributes to reactive oxygen species production. We investigated the cytoprotective mechanisms of XOR inhibition against high glucose (HG)-induced glomerular endothelial injury, which involves activation of the AMP-activated protein kinase (AMPK). Human glomerular endothelial cells (GECs) exposed to HG were subjected to febuxostat treatment for 48 h and the expressions of AMPK and its associated signaling pathways were evaluated. HG-treated GECs were increased xanthine oxidase/xanthine dehydrogenase levels and decreased intracellular AMP/ATP ratio, and these effects were reversed by febuxostat treatment. Febuxostat enhanced the phosphorylation of AMPK, the activation of peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1α and PPAR-α and suppressed the phosphorylation of forkhead box O (FoxO)3a in HG-treated GECs. Febuxostat also decreased nicotinamide adenine dinucleotide phosphate oxidase (Nox)1, Nox2, and Nox4 expressions; enhanced superoxide dismutase activity; and decreased malondialdehyde levels in HG-treated GECs. The knockdown of AMPK inhibited PGC-1α-FoxO3a signaling and negated the antioxidant effects of febuxostat in HG-treated GECs. Despite febuxostat administration, the knockdown of hypoxanthine phosphoribosyl transferase 1 (HPRT1) also inhibited AMPK-PGC-1α-FoxO3a in HG-treated GECs. XOR inhibition alleviates oxidative stress by activating AMPK-PGC-1α-FoxO3a signaling through the HPRT1-dependent purine salvage pathway in GECs exposed to HG conditions.

Ultrasonographic assessment of abnormal fetal growth related to uteroplacental-fetal biometrics and Doppler (U-AID) indices: Protocol for multicenter retrospective cohort study trial.

Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups.

Pretreatment with paricalcitol attenuates inflammation in ischemia-reperfusion injury via the up-regulation of cyclooxygenase-2 and prostaglandin E2.

BACKGROUND: The effect of paricalcitol on renal ischemia-reperfusion injury (IRI) has not been investigated. We examined whether paricalcitol is effective in preventing inflammation in a mouse model of IRI, and evaluated the cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) pathways as a protective mechanism of paricalcitol. METHODS: Paricalcitol (0.3 µg/kg) was administered to male C57BL/6 mice 24 h before IRI. Bilateral kidneys were subjected to 23 min of ischemia, and mice were killed 72 h after IRI. The effects of paricalcitol on renal IRI were evaluated in terms of renal function, tubular necrosis, apoptotic cell death, inflammatory cell infiltration and inflammatory cytokines. The effects of paricalcitol on COX-2, PGE2 and its receptors were investigated. RESULTS: Paricalcitol pretreatment improved renal function (decreased blood urea nitrogen and serum creatinine levels), tubular necrosis and apoptotic cell death in IRI-mice kidneys. The infiltration of inflammatory cells (T cells and macrophages), and the production of proinflammatory cytokines (RANTES, tumor necrosis factor-α, interleukin-1ß and interferon-γ) were reduced in paricalcitol-treated mice with IRI. Paricalcitol up-regulated COX-2 expression, PGE2 synthesis and mRNA expression of receptor subtype EP4 in post-ischemic renal tissue. The cotreatment of a selective COX-2 inhibitor with paricalcitol restored functional injury and tubular necrosis in paricalcitol-treated mice with IRI. CONCLUSIONS: Our study demonstrates that paricalcitol pretreatment prevents renal IRI via the inhibition of renal inflammation, and the up-regulation of COX-2 and PGE2 is one of the protective mechanisms of paricalcitol in renal IRI.

Rifampin-associated tubulointersititial nephritis and Fanconi syndrome presenting as hypokalemic paralysis.

BACKGROUND: Rifampin is one of the most important drugs in first-line therapies for tuberculosis. The renal toxicity of rifampin has been reported sporadically and acute tubulointerstitial nephritis (ATIN) is a frequent histological finding. We describe for the first time a case of ATIN and Fanconi syndrome presenting as hypokalemic paralysis, associated with the use of rifampin. CASE PRESENTATION: A 42-year-old man was admitted with sudden-onset lower extremity paralysis and mild renal insufficiency. He had been treated for pulmonary tuberculosis with isoniazid, rifampin, and ethambutol for 2 months. Laboratory tests revealed proteinuria, profound hypokalemia, hyperchloremic metabolic acidosis with a normal anion gap, positive urine anion gap, hypophosphatemia with hyperphosphaturia, hypouricemia with hyperuricosuria, glycosuria with normal serum glucose level, generalized aminoaciduria, and ß2-microglobulinuria. A kidney biopsy revealed findings typical of ATIN and focal granular deposits of immunoglubulin A and complement 3 in the glomeruli and tubules. Electron microscopy showed epithelial foot process effacement and electron-dense deposits in the subendothelial and mesangial spaces. Cessation of rifampin resolved the patient's clinical presentation of Fanconi syndrome, and improved his renal function and proteinuria. CONCLUSION: This case demonstrates that rifampin therapy can be associated with Fanconi syndrome presenting as hypokalemic paralysis, which is a manifestation of ATIN. Kidney function and the markers of proximal tubular injury should be carefully monitored in patients receiving rifampin.

Inhibition of erythropoiesis by Smad6 in human cord blood hematopoietic stem cells.

Bone morphogenetic proteins (BMPs) that belong to the transforming growth factor-ß (TGF-ß) superfamily cytokines, play crucial roles in hematopoiesis. However, roles of Smad6 in hematopoiesis remained unknown in contrast to the other inhibitory Smad (I-Smad), Smad7. Here we show that Smad6 inhibits erythropoiesis in human CD34(+) cord blood hematopoietic stem cells (HSCs). Smad6 was specifically expressed in CD34(+) cord blood HSCs, which was correlated with the expression of BMP2/4/6/7 and BMP type I receptor (BMPRI). BMP-specific receptor-regulated Smads (R-Smads), Smad1 and Smad5 in cooperation with Smad4 induced transcription of the Smad6 gene. Instead of affecting cell cycle, apoptosis, self-renewal, and stemness of CD34(+) cells, Smad6 knockdown enhanced, whereas Smad6 overexpression suppressed erythropoiesis in stem cell culture and colony formation assay. Consistently, Smad6 suppressed the expression of the genes essential for erythropoiesis, such as Kruppel-like factor 1 (erythroid) (KLF1/EKLF) and GATA binding protein 2 (GATA-2). Promoter analyses showed that Smad6 repressed Smad5/4-induced transcription of the Klf1 gene. Thus, our data suggest that Smad6 indirectly maintains stemness by preventing spontaneous erythropoiesis in HSCs.

Decisive indicator for gastrointestinal workup in anemic patients with nondialysis chronic kidney disease.

BACKGROUND: Anemia and iron deficiency are universal problems in patients with chronic kidney disease (CKD). However, decisive indicator to guide the further gastrointestinal (GI) workup has not been determined. METHODS: We included 104 anemic patients with nondialysis-dependent CKD stages 3-5 (38 patients at stage 3, 26 patients at stage 4, and 40 patients at stage 5). Hemoglobin, serum ferritin, transferrin saturation (TSAT), mean corpuscular volume (MCV), and corrected reticulocyte count data were assessed to evaluate diagnostic utility for bleeding-related GI lesions, which were identified by esophagogastroduodenoscopy and colonoscopy. RESULTS: Bleeding-related GI lesions were found in 55 (52.9%) patients, and patients with stage 5 CKD had a higher prevalence of gastric lesions than patients with CKD stage 3 or 4 (all p < 0.05). The areas under the receiver operating characteristic curves used to predict bleeding-related lesions were 0.69 for TSAT (p = 0.002) and 0.61 for serum ferritin (p = 0.085). The sensitivity and specificity of a cutoff value for TSAT < 20% were 0.59 and 0.74, respectively. Hemoglobin, MCV, and corrected reticulocyte levels had no significant diagnostic utility. On multivariable logistic regression, the chance of GI lesions increased by 6% for each 1% reduction in TSAT and increased 4.1-fold for patients with CKD stage 5 (all p < 0.05). CONCLUSIONS: TSAT is a useful indicator for determining the GI workup in anemic patients with nondialysis-dependent CKD stages 3-5. Stage 5 CKD is independently associated with bleeding-related lesions and TSAT should be used cautiously in these patients.

Clinical Characteristics and Pregnancy-Related Outcomes of Pregnant Women Hospitalized with COVID-19 During the Delta Wave: A Single-Center Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) during pregnancy is associated with increased disease severity and an increased risk of perinatal complications. However, few studies of pregnant women with COVID-19 have been conducted in Korea. The purpose of this study was to describe the clinical course and pregnancy outcomes of pregnant women admitted to our hospital with COVID-19 according to the severity. MATERIALS AND METHODS: This retrospective cohort study included women aged 18 years of age or older who were hospitalized in the Gachon University Gil Medical Center with COVID-19 during pregnancy between July 1, 2021 and January 31, 2022. COVID-19 severity was classified according to the "Criteria for severity classification by symptoms of COVID-19" presented by the Korea Disease Control and Prevention Agency. Severe cases were defined as those who required oxygen treatment administered via a high-flow nasal cannula or invasive mechanical ventilation or should be applied extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy. RESULTS: A total of 103 pregnant women were hospitalized with COVID-19 during the study period. Their mean age was 33 (± 4.14) years, and 4 (3.9%) had been vaccinated against COVID-19. At the time of diagnosis of COVID-19, 3 (2.9%), 33 (32.0%), and 67 (65.1%) patients were in the first, second, and third trimester, respectively. The most common symptoms were cough (99 patients, 96.1%) and fever (85 patients, 82.5%). There was 1 (1.0%) asymptomatic patient. Forty patients (38.8%) required supplemental oxygen and 19 patients (18.4%) had severe disease. Of the 19 severe cases, 7 were in the 2nd trimester and 12 were in the 3rd trimester. Forty-one (39.8%) patients delivered, including two twin deliveries. Of the 41 cases of delivery, 14 were premature, 4 out of 21 (19.0%) in mild, 4 out of 12 (25.0%) in moderate, and 6 out of 8 (75.0%) in severe. Severe disease was associated with an increased rate of preterm birth (P = 0.012). Four of the 43 neonates (9.1%) received oxygen treatment. CONCLUSION: Pregnant women with COVID-19 had a high rate of severe disease and a high preterm delivery rate, especially among those with severe disease.

Radiographic and Histomorphometric Evaluation of Sinus Floor Augmentation Using Biomimetic Octacalcium Phosphate Alloplasts: A Prospective Pilot Study.

This prospective single-arm clinical study aimed to radiographically and histomorphometrically evaluate the efficacy of the lateral approach for sinus floor elevation (LSFE) using biomimetic octacalcium phosphate (OCP) synthetic bone graft (Bontree®). LSFE using Bontree® was performed on 10 patients (15 implant placement sites) willing to undergo implant surgery, followed by implant placements after 6 months of the healing period. The vertical bone height (VBH) and Hounsfield unit (HU) values at each implant placement site were evaluated radiographically using cone-beam computed tomography at baseline immediately after surgery (T1) and 6 months after surgery (T2). A histomorphometric evaluation of the bone core biopsy specimen was also performed. The mean VBH and HU changes at all sites included a decrease by 0.91 mm and a statistically significant increase by 431.86, respectively, from T1 to T2. The mean ratio of the newly formed bone (23.34% ± 10.63%) was greater than that of the residual bone graft (19.09% ± 8.74%), indicating that Bontree® is effective for new bone formation. This pilot study suggests that Bontree® is a promising bone substitute for LSFE.

Effect of smartphone app-based health care intervention for health management of high-risk mothers: a study protocol for a randomized controlled trial.

BACKGROUND: The 4th Industrial Revolution with the advent of the smart era, in which artificial intelligence, such as big data analysis and machine learning, is expected, and the provision of healthcare services using smartphones has become a reality. In particular, high-risk mothers who experience gestational diabetes, gestational hypertension, and prenatal and postpartum depression are highly likely to have adverse effects on the mother and newborn due to the disease. Therefore, continuous observation and intervention in health management are needed to prevent diseases and promote healthy behavior for a healthy life. METHODS: This randomized controlled trial will provide mothers 18 years of age or older with health care information collected based on evidence-based literature data using a smartphone app for 6 weeks. About 500 mothers will be selected in consideration of the dropout rate due to the characteristics of mothers. The study group and control group will be computer-generated in a 1:1 ratio through random assignment. The research group will receive health management items through the app, and health management information suitable for the pregnancy cycle is pushed to an alarm. The control group will receive the health management information of the paper. We also followed the procedure for developing mobile apps using the IDEAS framework. DISCUSSION: These results show the effectiveness of smart medical healthcare services and promote changes in health behaviors throughout pregnancy in high-risk mothers. TRIAL REGISTRATION: Clinical trial registration information for this study has been registered with WHO ICTRP and CRIS (Korea Clinical Research Information Service, CRIS). Clinical trial registration information is as follows: Study of development of integrated smart health management service for the whole life cycle of high-risk mothers and newborns based on community, KCT0007193 . Registered on April 14, 2022, prospectively registered. This protocol version is Version 1.0. April 14, 2022.

Analysis of the inorganic component of autogenous tooth bone graft material.

This study was performed to identify the calcium phosphate minerals, chemical element and Ca/P ratio and to examine the surface structure of autogenous tooth bone grafting material (AutoBT) which recently developed and applied clinically as a bone graft materials. The analytical results showed that AutoBT is composed of low-crystalline hydroxyapatite (HA) and possibly other calcium phosphate minerals, which is similar to the minerals of human bone tissues. And the dental crown portion was composed of high-crystalline calcium phosphate minerals (mainly HA) with higher Ca/P ratio while the root portion was mainly composed of low-crystalline calcium phosphates with relatively low Ca/P ratio.