Survival after out-of-hospital cardiac arrest,Viet Nam: multicentre prospective cohort study

ObjectiveTo investigate factors associated with survival after out-of-hospital cardiac arrest in Viet Nam.MethodsWe did a multicentre prospective observational study of people (> 18 years) presenting with out-of-hospital cardiac arrest (not caused by trauma) to three tertiary hospitals in Viet Nam from February 2014 to December 2018. We collected data on characteristics, management and outcomes of patients with out-of-hospital cardiac arrest and compared these data by type of transportation to hospital and survival to hospital admission. We assessed factors associated with survival to admission to and discharge from hospital using logistic regression analysis.FindingsOf 590 eligible people with out-of-hospital cardiac arrest, 440 (74.6%) were male and the mean age was 56.1 years (standard deviation: 17.2). Only 24.2% (143/590) of these people survived to hospital admission and 14.1% (83/590) survived to hospital discharge. Most cardiac arrests (67.8%; 400/590) occurred at home, 79.4% (444/559) were witnessed by bystanders and 22.3% (124/555) were given cardiopulmonary resuscitation by a bystander. Only 8.6% (51/590) of the people were taken to hospital by the emergency medical services and 32.2% (49/152) received pre-hospital defibrillation. Pre-hospital defibrillation (odds ratio, OR: 3.90; 95% confidence interval, CI: 1.54–9.90) and return of spontaneous circulation in the emergency department (OR: 2.89; 95% CI: 1.03–8.12) were associated with survival to hospital admission. Hypothermia therapy during post-resuscitation care was associated with survival to discharge (OR: 5.44; 95% CI: 2.33–12.74).ConclusionImprovements are needed in the emergency medical services in Viet Nam such as increasing bystander cardiopulmonary resuscitation and public access defibrillation, and improving ambulance and post-resuscitation care.     

Reduction of cerebral infarct volume by apocynin requires pretreatment and is absent in Nox2-deficient mice

Background and purpose:

Reactive oxygen species (ROS) derived from Nox2-containing reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity is reportedly detrimental in cerebrovascular disease. However, ROS generation by other Nox isoforms may have a physiological role. No Nox2-selective inhibitors have yet been identified, and thus it is unclear whether isoform non-selective Nox inhibitors would necessarily improve outcome after stroke. We assessed the effect of apocynin on cerebrovascular ROS production and also on outcome following cerebral ischaemia when administered either before ischaemia or after cerebral reperfusion. The involvement of Nox2-containing NADPH oxidase in the effects of apocynin was assessed using Nox2^−/− mice.

Experimental approach:

Transient cerebral ischaemia was induced by 0.5 h middle cerebral artery occlusion followed by 23.5 h reperfusion. Mice received apocynin (2.5 mg·kg⁻¹, i.p.) either 0.5 h before ischaemia or 1 h after reperfusion. In situ superoxide production after cerebral ischaemia-reperfusion was measured in brain sections of wild-type mice at 24 h using dihydroethidium fluorescence.

Key results:

Treatment with apocynin 0.5 h before ischaemia reduced total infarct volume, neurological impairment and mortality in wild-type but not Nox2^−/− mice. Conversely, treatment with apocynin 1 h after initiation of reperfusion had no protective effect. Cerebral ischaemia and reperfusion increased superoxide production in the brain at 24 h, and pretreatment but not posttreatment with apocynin reduced superoxide levels.

Conclusions and implications:

Apocynin improves outcome following stroke when administered before ischaemia in wild-type but not Nox2^−/− mice.     

Multi-quadrant biopsy technique improves diagnostic ability in large heterogeneous renal masses. Abel EJ,Heckman JE,Hinshaw L,Best S,Lubner M,Jarrard DF,Downs TM,Nakada SY,Lee FT Jr,Huang W,Ziemlewicz T.J Urol. 2015 Oct;194(4):886-91. [Epub 2015 Mar 30]. doi: 10.1016/j.juro.2015.03.106.

Purpose

Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs. a standard biopsy technique.

Choosing the correct metrics for glucose control

Choice of the right renal replacement therapy for severe acute kidney injury in critically ill patients has been investigated many times in the last two decades. Although some questions have been answered, in current practice many different approaches are still used in the ICU. One basic and important issue is the frequency of renal replacement delivery: apart from pathophysiological speculations, in terms of hard outcomes (namely mortality and length of hospital stay) should dialysis be delivered continuously or intermittently? The authors of the CONVINT study provided a (last) response to this debate: in expert hands, the two treatments provide similar outcomes. This study confirms previous studies and is also important for other aspects, such as the possibility that the two modalities are complementary and may be indicated for different purposes.     

Cardioprotective effect of Spathodea campanulata bark on isoproterenol-induced myocardial infarction in rats

ObjectiveTo evaluate the cardioprotective potential of 70% ethanolic extract of bark of Spathodea campanulata P. Beauv (EEBSC).MethodsWister strain rats were pretreated with EEBSC in two different doses (250 and 500 mg/kg) orally for 14 d and then intoxicated with isoproterenol (200 mg/kg, s.c. for 2 consecutive days at an interval of 24 h on 14th and 15th day of treatment protocol) to induce myocardial injury.ResultsCardioprotection was assessed by estimating serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine phosphokinase, triglycerides, total cholesterol, low density lipoproteins and high density lipoproteins. The levels of thiobarbituric acid reactive substances and reduced glutathione were analyzed in heart homogenate. In isoproterenol-treated group, shrinkage of cardiac markers in serum and elevated lipid peroxidation accompanied by decreased content of reduced glutathione in heart. The prior administration of EEBSC significantly (P < 0.05) prevented the isoproterenol-induced alterations and restored the cardiac markers. The observed results were further confirmed by histopathological findings.ConclusionsThese findings indicate that EEBSC exerts cardioprotective effect against isoproterenol induced myocardial infarction due to its free radical scavenging effects, which maintains the tissue defence system against myocardial damage.     

P-glycoprotein expression in human plasma cell myeloma: correlation with prior chemotherapy

Multidrug-resistant (MDR) myeloma patients failing chemotherapy may express P-glycoprotein (PGP), which serves as an efflux pump protecting the neoplastic cells. Unknown is whether PGP expression might relate to prior cytotoxic drug exposure. To address this question, we studied 106 consecutive bone marrow samples from 104 myeloma patients with samples studied either before or after therapy and at the time of relapse. We performed an established immunocytochemical assay of PGP using an MDR-1- specific monoclonal antibody and correlated PGP status with prior chemotherapy dosage. Myeloma patients with no prior therapy had a low incidence of PGP expression (6%, 3/47), whereas those receiving chemotherapy had a significantly higher incidence (43%, 21/49) (P < .0001). A substantially higher incidence of PGP expression (50%, 83%, respectively) occurred when the total vincristine dose exceeded 20 mg and when doxorubicin exceeded 340 mg. In the 11 patients who received both high vincristine and doxorubicin dosages (> 20 mg, > 340 mg total dose) there was 100% incidence of PGP expression in the tumor cells. These data provided the basis for a predictive mathematical model from which dose-related PGP expression normograms were generated. Time with myeloma for PGP-negative patients (mean 33 months) had overlapping confidence limits with PGP-positive patients (mean 42 months), suggesting that disease duration was not a significant variable. PGP expression did not correlate with other clinical factors or immunophenotypic factors. Our findings indicate a strong correlation between PGP expression in myeloma and past chemotherapy in myeloma, in particular, related to prior exposure to the natural product agents vincristine and doxorubicin. Additionally, the proportion of PGP- positive plasma cells was significantly higher in the doxorubicin- treated patients than the nondoxorubicin-treated patients (87.7% v 65.17%; P = .013). Combined high vincristine and doxorubicin total dosage appear highly predictive of PGP expression.     

Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin's lymphomas: a prospective Southwest Oncology Group trial

The growth fraction of tumors from patients with non-Hodgkin's lymphomas (NHL) has been shown to correlate with survival in retrospective studies. The growth fraction can be evaluated using immunohistochemical techniques employing the Ki-67 monoclonal antibody (MoAb) that marks a nuclear protein present in cycling cells. The purpose of this study was to evaluate the clinical utility of the Ki-67 MoAb for predicting survival. Using a prospective trial design in a multi-institutional cooperative trials group, the proliferative index, clinical outcome, and statistical correlations were independently assessed for previously untreated patients with advanced stages of intermediate- and high-grade histologies of NHL treated on Southwest Oncology Group study (SWOG 8516, Intergroup 0067). The proportion of Ki- 67-positive cells was determined on snap-frozen thin tissue sections. A proliferative index of 80% or greater, as determined from prior retrospective studies, identified a group of patients (18%) who had a poor outcome. Overall survival was significantly reduced in these patients with a high Ki-67-associated proliferative index compared with those with a low proliferative index (P = .001). One-year survival estimates were 82% (low proliferative index) versus 18% (high proliferative index). A multivariate regression analysis incorporating commonly used clinical prognostic features confirmed the independent effect of proliferation on survival (relative risk estimate 5.9; 95% confidence interval, 2.2, 16.1). The Ki-67 MoAb identifies a group of patients with rapidly fatal NHL for whom currently available chemotherapy is inadequate.     

Direct comparison by limiting dilution analysis of long-term culture- initiating cells in human bone marrow, umbilical cord blood, and blood stem cells

Limiting-dilution analysis of long-term culture-initiating cells (LTCIC) is a quantitative method of estimating hematopoietic stem cell activity in clinical samples. We compared the numbers of LTCIC in bone marrow (BM), umbilical cord blood, and blood progenitor cells (obtained from patients with solid tumors at leukapheresis after mobilization with induction chemotherapy and filgrastim administration), using a two- stage long-term culture system and a limiting-dilution technique, scoring cobblestone areas of greater than 15 hematopoietic cells weekly for up to 8 weeks. Samples were obtained from 30 normal BMs, 20 human umbilical cords, and 32 leukapheresis products. Direct comparison of LTCIC in the three sources showed that the median proportions of cells generating hematopoietic foci from unfractionated mononuclear cells at 5 and 8 weeks, respectively, were 1:13,314 and 1:33,949 for BM, 1:12,506 and 1:34,546 for umbilical cord blood, and 1:10,302 and 1:12,891 for leukapheresis product. The estimated proportions of LTCIC from unfractionated mononuclear cells and CD34+ cells were similar in experiments with leukapheresis product. Leukapheresis product was superior to umbilical cord blood and cord blood to BM at 5 and 8 weeks of culture (P = .01). In two-stage long-term cultures, more colonies per flask and CD34+ cells were found in assays of leukapheresis product than in BM or umbilical cord blood cultures (P = .0005). Results obtained by this simplified limiting-dilution analysis correlated well with standard long-term cultures and can be used as a measure of the stem cell population. These data suggest that the incidence of putative stem cells in leukapheresis product and umbilical cord blood are at least comparable with that of BM.