Background: Monitoring mortality trends can help design ways to improve survival, but observation of national mortality trends in critically ill children is lacking for the Korean population Methods: We analyzed the incidence and mortality trends of children younger than 18 years admitted to an intensive care unit (ICU) from 2012 to 2018 using the Korean National Health Insurance database. Neonates and neonatal ICU admissions were excluded. Multivariable logistic regression analyses were performed to estimate the odds ratio of in-hospital mortality according to admission year. Trends in incidence and in-hospital mortality of subgroups according to admission department, age, presence of intensivists, admissions to pediatric ICU, mechanical ventilation, and use of vasopressors were evaluated. Results: The overall mortality of critically ill children was 4.4%. There was a significant decrease in mortality from 5.5% in 2012 to 4.1% in 2018 (Pfor trend < 0.001). The incidence of ICU admission in children remained around 8.5/10,000 population years (Pfor trend = 0.069). In-hospital mortality decreased by 9.2% yearly in adjusted analysis (P < 0.001). The presence of dedicated intensivists (Pfor trend < 0.001, mortality decrease from 5.7% to 4.0%) and admission to pediatric ICU (Pfor trend < 0.001, mortality decrease from 5.0% to 3.2%) were associated with significant decreasing trends in mortality. Conclusion Mortality among critically ill children improved during the study period, and the improving trend was prominent in children with high treatment requirements. Varying mortality trends, according to ICU organizations, highlight that advances in medical knowledge should be supported structurally.

Background: and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). Methods: This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. Results: The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. Conclusions IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.

Background: A variety of clinically important pathogens have developed multidrug resistance (MDR), which threatens global public health. This study aimed to determine the incidence, patterns, and trends of MDR of gram-negative bacterial isolates in clinical specimens in the Tamale Teaching Hospital, Ghana. Methods: This retrospective study analyzed gram-negative bacterial isolates and antimicrobial susceptibility test (AST) results of patients who visited the Tamale Teaching Hospital laboratory between 2017 and 2019. Results: A total of 2,779 gram-negative bacterial isolates and their phenotypic AST results were analyzed. From these, 1,297 gram-negative bacteria (46.7%) were isolated from urine samples, while the rest were isolated from sputum (20.9%), wound (14.3%), and swabs (11.7%) samples, etc. Escherichia coli (23.8%) was the most common gram-negative pathogen found predominantly in the urine samples (33.2%). All gram-negative bacteria isolated between 2017 and 2019 showed high MDR. Klebsiella pneumonia gradually increased its MDR from 84.0% in 2017, 89.5% in 2018, to 95.1% in 2019. On the other hand, the MDR rates in Pseudomonas aeruginosa were approximately 65.8%, varying from 59.5% in 2017 to 78.7% in 2019. Among tested antimicrobials, amikacin was the most effective. Resistance to amikacin in Enterobacter spp., E. coli, and K. pneumoniae in vitro were 16.2%, 11.8%, and 17.7%, respectively. Conclusion The study has shown that the high levels of MDR in gram-negative bacteria isolated may be associated with the infections recorded at the Tamale Teaching Hospital.The major gram-negative pathogens isolated have resistance to penicillins, cephalosporins, and fluoroquinolones. Aminoglycosides can offer high antibiotic activity to overcome gramnegative bacterial resistance. Further studies will be needed to decide policy direction on infection prevention and control, and antimicrobial stewardship programs

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes.MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 µg/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes.MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 µg/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.
Anoxia ; Brain Neoplasms ; Cell Death* ; Cell Line ; Dichloroacetic Acid ; Glioblastoma* ; Glucose ; Glycolysis ; Metabolism ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphotransferases ; Pyruvic Acid

BACKGROUND: Previous studies have suggested that a B-type natriuretic peptide(BNP) test can provide important information on diagnosis, as well as predicting the severity and prognosis of heart failure. Myocardial dysfunction is often observed in critically ill noncardiac patients admitted to the Intensive Care Unit, and the prognosis of the myocardial dysfunction needs to be determined. This study evaluated the predictability of BNP on the prognosis of critically ill noncardiac patients. METHODS: 32 ICU patients, who were hospitalized from June to October 2002 and in whom the BNP test was evaluated, were enrolled in this study. The exclusion criteria included the conditions that could increase the BNP levels irrespective of the severity, such as congestive heart failure, atrial fibrillation, ischemic heart disease, and renal insufficiencies. A triage B-Type Natriuretic Peptide test with a RIA-kit was used for the fluorescence immunoassay of BNP test. In addition, the acute physiology and the chronic health evaluation (APACHE)IIscore and mortality were recorded. RESULTS: There were 16 males and 16 females enrolled in this study. The mean age was 59 years old. The mean BNP levels between the ICU patients and control were significantly different (186.7+/-274.1pg/mL vs. 19.9+/-21.3 pg/mL, p=0.033). Among the ICU patients, there were 14(44%) patients with BNPlevels above 100 pg/mL. The APACHEIIscore was 16.5+/-7.6. In addition, there were 11 mortalities reported. The correlation between the BNP and APACHEIIscore, between the BNP and mortality were significant (r=0.443, p=0.011 & r=0.530, p=0.002). The mean BNP levels between the dead and alive groups were significantly different (384.1+/-401.7 pg/mL vs. 83.2+/-55.8 pg/mL p=0.033). However, the PaO2/FiO2 did not significantly correlate with the BNP level. CONCLUSION: This study evaluated the BNP level was elevated in critically ill, noncardiac patients. The BNP level could be a useful, noninvasive tool for predicting the prognosis of the critically ill, noncardiac patients.
Atrial Fibrillation ; Critical Illness* ; Diagnosis ; Female ; Fluorescence ; Heart Failure ; Humans ; Immunoassay ; Intensive Care Units ; Male ; Middle Aged ; Mortality ; Myocardial Ischemia ; Natriuretic Peptide, Brain* ; Physiology ; Prognosis ; Renal Insufficiency ; Triage

Diabetic gastroparesis is a pathologic condition of delayed gastric emptying with gastrointestinal symptoms such as nausea, early satiety and vomiting in the absence of mechanical obstruction in patients with diabetes mellitus. We report a case of diabetic gastroparesis who had diabetes mellitus for 13 years and suffered from nausea and vomiting with marked gastric dilatation of acute onset. Blood glucose level of the patient was very high and any mechanical obstruction was not found by gastroduodenal endoscopy, hypotonic duodenography, celiac angiography, electrogastrography and CT scan. Acute gastric dilatation was resolved with conservative treatment of gastric drainage, glucose control and hydration. Gastrointestinal symptoms of nausea and vomiting improved and diet was well tolerated thereafter.
Angiography ; Blood Glucose ; Diabetes Mellitus ; Diet ; Drainage ; Endoscopy ; Gastric Dilatation* ; Gastric Emptying ; Gastroparesis* ; Glucose ; Humans ; Nausea ; Tomography, X-Ray Computed ; Vomiting

The Korean hemorrhagic fever is an acute febrile disease, which characteristically accompanies high fever, abdominal pain, headache, vomiting, bleeding tendency and renal failure. The Korean hemorrhagic fever displays various clinical manifestations and courses. Complication includes hypertension, intra-organ bleeding, respiratory problems including pulmonary edema, pituitary insufficiency, infection and anemia. In rare cases, cardiac complications, such as acute myocarditis and atrioventricular conduction block were reported. In addition, an acute pancreatitis, which accompanied serum amylase and lipase elevation, was rarely reported as one of the cause of abdominal pain in the patients with the Korean hemorrhagic fever. We report a patient, who were diagnosed with Korean hemorrhagic fever and displayed persistent abdominal pain, elevation of serum amylase and lipase, and detection of diffuse edema of the pancreas and fluid collection in the retroperitoneal space, especially around the pancreas and kidney, in the ultrasound and CT scan.
Abdominal Pain ; Amylases ; Anemia ; Atrioventricular Block ; Edema ; Fever ; Headache ; Hemorrhage ; Hemorrhagic Fever with Renal Syndrome* ; Humans ; Hypertension ; Hypopituitarism ; Kidney ; Lipase ; Myocarditis ; Pancreas ; Pancreatitis* ; Pulmonary Edema ; Renal Insufficiency ; Retroperitoneal Space ; Tomography, X-Ray Computed ; Ultrasonography ; Vomiting