Triple-combination antiviral drug for pandemic H1N1 influenza virus infection in critically ill patients on mechanical ventilation.

A recent in vitro study showed that the three compounds of antiviral drugs with different mechanisms of action (amantadine, ribavirin, and oseltamivir) could result in synergistic antiviral activity against influenza virus. However, no clinical studies have evaluated the efficacy and safety of combination antiviral therapy in patients with severe influenza illness. A total of 245 adult patients who were critically ill with confirmed pandemic influenza A/H1N1 2009 (pH1N1) virus infection and were admitted to one of the intensive care units of 28 hospitals in Korea were reviewed. Patients who required ventilator support and received either triple-combination antiviral drug (TCAD) therapy or oseltamivir monotherapy were analyzed. A total of 127 patients were included in our analysis. Among them, 24 patients received TCAD therapy, and 103 patients received oseltamivir monotherapy. The 14-day mortality was 17% in the TCAD group and 35% in the oseltamivir group (P = 0.08), and the 90-day mortality was 46% in the TCAD group and 59% in the oseltamivir group (P = 0.23). None of the toxicities attributable to antiviral drugs occurred in either group of our study, including hemolytic anemia and hepatic toxicities related to the use of ribavirin. Logistic regression analysis indicated that the odds ratio for the association of TCAD with 90-day mortality was 0.58 (95% confidence interval, 0.24 to 1.42; P = 0.24). Although this study was retrospective and did not provide virologic outcomes, our results suggest that the treatment outcome of the triple combination of amantadine, ribavirin, and oseltamivir was comparable to that of oseltamivir monotherapy.

Effects of CAY10404 on the PKB/Akt and MAPK pathway and apoptosis in non-small cell lung cancer cells.

BACKGROUND AND OBJECTIVE: Lung cancer is the most common cause of cancer death in men and women worldwide. The mechanism of cell death induced by CAY10404, a highly selective cyclooxygenase-2 inhibitor, was evaluated in three non-small cell lung cancer (NSCLC) cell lines (H460, H358, H1703). METHODS: To measure the effects of CAY10404 on proliferation of NSCLC cells, 3 x 10(3) cells/well were plated in 96-well plates and allowed to adhere overnight at 37 degrees C. After treatment with CAY10404 for 3 days, cell proliferation was measured by the 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In the H460 NSCLC cells, evidence of apoptosis was sought using the terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay and western blot analysis. RESULTS: Treatment with CAY10404 in the range of 10-100 microM caused dose-dependent growth inhibition, with an average 50% inhibitory concentration (IC(50)) of 60-100 micromol/L, depending on the cell line. Western blot analysis of CAY10404-treated cells showed cleavage of poly (ADP-ribose) polymerase (PARP) and procaspase-3, signifying caspase activity and apoptotic cell death. CAY10404 treatment inhibited the phosphorylation of Akt, glycogen synthase kinase-3beta and extracellular signal-regulated kinases 1/2 in H460 and H358 cells. CONCLUSIONS: These results suggest that CAY10404 is a potent inducer of apoptosis in NSCLC cells, and that it may act by suppressing multiple protein kinase B/Akt and mitogen-activated protein kinase pathways.

Who experiences endoscopic retrograde cholangiopancreatography after laparoscopic cholecystectomy for symptomatic gallstone disease?

PURPOSE: Laparoscopic cholecystectomy (LC) has become a standard treatment of symptomatic gallstone disease. But, some patients suffer from retained common bile duct stones after LC. The aim of this study is to analyze the predicting factors associated with subsequent postoperative endoscopic retrograde cholangiopancreatography (ERCP) after LC. METHODS: We retrospectively reviewed a database of every LC performed between July 2006 and September 2012. We classify 28 patients who underwent ERCP within 6 months after LC for symptomatic gallstone disease as the ERCP group and 56 patients who underwent LC for symptomatic gallstone disease during same period paired by sex, age, underlying disease, operation history, and body mass index as the control group. To identify risk factor performing postoperative ERCP after LC, we compared admission route, preoperative biochemical liver function test, number of gall stones, gallstone size, adhesion around GB, wall thickening of GB, and existence of acute cholecystitis between the 2 groups. RESULTS: Admission route, preoperative AST, ALT, and ALP, stone size, longer operation time, and acute cholecystitis were identified as risk factors of postoperative ERCP in univariate analyses. But, longer operation time (P = 0.004) and acute cholecystitis (P = 0.048) were identified as independent risk factors of postoperative ERCP in multivariate analyses. CONCLUSION: The patient who underwent ERCP after LC for symptomatic gallstone disease are more likely experienced longer operation time and acute cholecystitis than the patient who did not undergo ERCP after LC.

Risk Factors for Mechanical Ventilation in Patients with Scrub Typhus Admitted to Intensive Care Unit at a University Hospital.

BACKGROUND: The purpose of this study was to evaluate the risk factors for mechanical ventilation in the patients with scrub typhus admitted to intensive care unit (ICU) at a university hospital. METHODS: We retrospectively selected and analyzed clinical data from the medical records of 70 patients (32 men, 38 women) admitted to the ICU with scrub typhus between 2004 and 2014. The patients had a mean±standard deviation age of 71.2±11.1 years and were evaluated in two groups: those who had been treated with mechanical ventilation (the MV group, n=19) and those who had not (the non-MV group, n=51). Mean ages of the MV group and the non-MV group were 71.2±8.3 years and 71.2±11.1 years, respectively. RESULTS: Significant differences between the two groups were observed with respect to acute respiratory failure (p=0.008), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p=0.015), Sequential Organ Failure Assessment (SOFA) score (p=0.013), death (p=0.014), and ICU duration (p<0.01). Multivariate analysis indicated that the following factors were significantly associated with mechanical ventilation: acute respiratory failure (p=0.011), SOFA score (p=0.005), APACHE II score (p=0.011), platelet count (p=0.009), and lactate dehydrogenase (LDH) (p=0.011). CONCLUSION: Thus, five factors-acute respiratory failure, SOFA score, APACHE II score, platelet count, and LDH-can be the meaningful indicators for mechanical ventilation for the patients with scrub typhus admitted to ICU.

Transfusion Related Acute Lung Injury after Cesarean Section in a Patient with HELLP Syndrome.

Transfusion-related acute lung injury (TRALI) is a serious adverse reaction of transfusion, and presents as hypoxemia and non-cardiogenic pulmonary edema within 6 hours of transfusion. A 14-year-old primigravida woman at 34 weeks of gestation presented with upper abdominal pain without dyspnea. Because she showed the syndrome of HELLP (hemolysis, elevated liver enzymes, and low platelet count), an emergency cesarean section delivery was performed, and blood was transfused. In the case of such patients, clinicians should closely observe the patient's condition at least during the 6 hours while the patient receives blood transfusion, and should suspect TRALI if the patient complains of respiratory symptoms such as dyspnea. Furthermore, echocardiography should be performed to distinguish between the different types of transfusion-related adverse reactions.

Agranulocytosis induced by ethambutol in a patient with pulmonary tuberculosis.

We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of 70/µL. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months.

Parenteral 17beta-estradiol decreases fasting blood glucose levels in non-obese mice with short-term ovariectomy.

AIMS: long-term ovariectomy-induced metabolic changes such as insulin resistance and glucose intolerance might be caused directly by estrogen deficiency and may occur partly as secondary effects of obesity arising due to the orexigenic effects of estrogen deficiency. Long-term estrogen treatment prevented those by exerting anorexigenic and metabolic actions in ovariectomized mice. However, the effect of short-term estrogen treatment on glucose metabolism in mice with short-term ovariectomy, during which ovariectomy-induced obesity does not develop, is not yet clear. The aim of this study was to evaluate the effect of short-term parenteral 17beta-estradiol treatment on glucose metabolism and blood glucose levels in mice at 2 weeks after ovariectomy, a time period during which ovariectomy-induced obesity does not develop. MAIN METHODS: we examined the effect of three 17beta-estradiol injections on fasting blood glucose levels, insulin resistance, components of the insulin signaling pathway, AMPK activation, and the expression of genes related to glucose metabolism in liver, skeletal muscle, and white adipose tissues of non-obese C57BL/6N mice with short-term ovariectomy. KEY FINDINGS: three 17beta-estradiol injections decreased the fasting blood glucose levels, activated AMPK, and decreased the expression of gluconeogenic genes, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase and peroxisome proliferator-activated receptor-γ coactivator-1α in the liver. But three 17beta-estradiol injections did not affect insulin sensitivity and the components of the insulin signaling pathway in the liver and skeletal muscle. SIGNIFICANCE: short-term parenteral 17beta-estradiol treatment decreases the fasting blood glucose levels not via insulin sensitivity of the skeletal muscle in non-obese mice with short-term ovariectomy.

A case of scar sarcoidosis.

Infiltration of sarcoid granuloma in old cutaneous scars is one of the uncommon cutaneous manifestations of sarcoidosis. Here, we report the case of a 47-year-old female who presented with swelling and irritation in 5 old scars. She had acquired these scars 9 years ago in a traffic accident. An incisional scar biopsy revealed noncaseating granulomas consistent with sarcoidosis. High-resolution CT (HRCT) revealed right paratracheal, both hilar, paraaortic, and subcarinal lymphadenopathy without any nodular densities in both lung fields. Successful regression of cutaneous inflammation was achieved using a short course of oral steroids.

Characteristics of mechanical ventilation employed in intensive care units: a multicenter survey of hospitals.

A 1D point-prevalence study was performed to describe the characteristics of conventional mechanical ventilation in intensive care units (ICUs). In addition, a survey was conducted to determine the characteristics of ICUs. A prospective, multicenter study was performed in ICUs at 24 university hospitals. The study population consisted of 223 patients who were receiving mechanical ventilation or had been weaned off mechanical ventilation within the past 24 hr. Common indications for the initiation of mechanical ventilation included acute respiratory failure (66%), acute exacerbation of chronic respiratory failure (15%) (including tuberculosis-destroyed lung [5%]), coma (13%), and neuromuscular disorders (6%). Mechanical ventilation was delivered via an endotracheal tube in 68% of the patients, tracheostomy in 28% and facial mask with noninvasive ventilation (NIV) in 4%. NIV was used in 2 centers. In patients who had undergone tracheostomy, the procedure had been performed 16.9+/-8.1 days after intubation. Intensivists treated 29% of the patients. A need for additional educational programs regarding clinical practice in the ICU was expressed by 62% of the staff and 42% of the nurses. Tuberculosis-destroyed lung is a common indication for mechanical ventilation in acute exacerbation of chronic respiratory failure, and noninvasive ventilation was used in a limited number of ICUs.