Persistent neurochemical changes in neonatal piglets after hypoxia-ischemia and resuscitation with 100%, 21% or 18% oxygen

BACKGROUND: Neonatal hypoxia-ischemia (HI) is a common complication of pregnancy and delivery. Conventional clinical practice is to resuscitate neonates with 100% O2, and evidence is building to suggest resuscitation with lower O2 concentrations is safer. Significant neurochemical changes are associated with HI injury and persistent changes in amino acids are related to cell death, therefore we used a swine survival model of neonatal HI-reoxygenation (HI/R) to investigate the effects of resuscitation with 100%, 21% or 18% O2 on amino acid neurotransmitters. METHODS: In a blinded randomized fashion, following permanent ligation of the left common carotid artery, newborn pigs (1-4 d, 1.7-2.5 kg) received alveolar normocapnic hypoxia (FiO2=0.15, 2h) and were reoxygenated with 18%, 21% or 100% O2. After a 4-day survival period, brain regions were processed for amino acid levels using high-performance liquid chromatography (HPLC). RESULTS: Results showed that resuscitation with different O2 concentrations caused hemispheric and regional changes in all amino acids investigated including glutamate, alanine, gamma-amino butyric acid, glycine and aspartate, 4 days post-HI. Resuscitation with 100% O2 significantly increased glutamate and glycine in the dorsal cortex contralateral to the ligated common carotid artery, compared to piglets resuscitated with 21% O2. Additionally, piglets resuscitated with 21% O2 had significantly lower alanine levels than those resuscitated with 18% O2. CONCLUSION: Significant resuscitation-dependent changes in amino acid neurotransmitters are still evident 4 days post-HI in the newborn piglet. These data suggest that persistent changes in neurochemistry occur 4 days after HI/R and further studies are warranted to elucidate the consequences of this on neonatal brain development.     

Stair climbing test as a predictor of cardiopulmonary complications after pulmonary lobectomy in the elderly

BACKGROUND: The objective of this study was to assess the role of a symptom-limited stair climbing test in predicting postoperative cardiopulmonary complications in elderly candidates for lung resection. METHODS: A consecutive series of 109 patients more than 70 years of age who underwent pulmonary lobectomy for lung carcinoma from January 2000 through May 2003 formed the prospective database of this study. All patients in the analysis performed a preoperative symptom-limited stair climbing test. Univariate and multivariate analyses were performed to identify predictors of postoperative cardiopulmonary complications. RESULTS: At univariate analysis, the patients with complications had a lower forced expiratory capacity percentage of predicted (p = 0.048), predicted postoperative forced expiratory volume in 1 second percentage of predicted (p = 0.049), climbed a lower height at preoperative stair climbing test (p = 0.0004), and presented a greater proportion of cardiac comorbiditiy with respect to the patients without complications (p = 0.02). After logistic regression analysis, significant predictors of postoperative complications resulted in the presence of a concomitant cardiac disease (p = 0.04) and a low height climbed preoperatively (p = 0.0015). CONCLUSIONS: A symptom-limited stair climbing test was a safe and simple instrument capable of predicting cardiopulmonary complications in the elderly after lung resection.     

Identification and characterization of undifferentiated mast cells in mouse bone marrow

Sequential immunomagnetic isolation with 2 monoclonal antibodies was used to purify and characterize an undifferentiated mast cell in adult mouse bone marrow that had not been previously recognized. This cell represents 0.02% of the cells in the bone marrow, is CD34(+), CD13(+), and c-kit(+), and does not express FcepsilonRI. However, by polymerase chain reaction (PCR) the cell contains message for the alpha and beta subunits of FcepsilonRI, mast cell-specific proteases, and carboxypeptidase A. Morphologically, this cell has a large nucleus, little cytoplasm, few cytoplasmic organelles, and no cytoplasmic granules. In vitro, in the presence of interleukin-3 (IL-3) and stem cell factor (SCF) these cells differentiate only into a granulated mast cell that now expresses CD13, c-kit, mast cell-specific gangliosides, FcepsilonRI, and binds immunoglobulin E (IgE). When injected into lethally irradiated mice, these cells are able to reconstitute the mast cell population in the spleen.     

Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study

Severe acetaminophen hepatotoxicity frequently leads to acute liver failure (ALF). We determined the incidence, risk factors, and outcomes of acetaminophen-induced ALF at 22 tertiary care centers in the United States. Detailed prospective data were gathered on 662 consecutive patients over a 6-year period fulfilling standard criteria for ALF (coagulopathy and encephalopathy), from which 275 (42%) were determined to result from acetaminophen liver injury. The annual percentage of acetaminophen-related ALF rose during the study from 28% in 1998 to 51% in 2003. Median dose ingested was 24 g (equivalent to 48 extra-strength tablets). Unintentional overdoses accounted for 131 (48%) cases, intentional (suicide attempts) 122 (44%), and 22 (8%) were of unknown intent. In the unintentional group, 38% took two or more acetaminophen preparations simultaneously, and 63% used narcotic-containing compounds. Eighty-one percent of unintentional patients reported taking acetaminophen and/or other analgesics for acute or chronic pain syndromes. Overall, 178 subjects (65%) survived, 74 (27%) died without transplantation, and 23 subjects (8%) underwent liver transplantation; 71% were alive at 3 weeks. Transplant-free survival rate and rate of liver transplantation were similar between intentional and unintentional groups. In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States. Susceptible patients have concomitant depression, chronic pain, alcohol or narcotic use, and/or take several preparations simultaneously. Education of patients, physicians, and pharmacies to limit high-risk use settings is recommended.     

Assessment of the knowledge,attitudes, and practices among UNRWA health staff in Jordan concerning mental health programme pre-implementation: a cross-sectional study

Background

Mental health is a major public health priority, particularly among refugees worldwide. The United Nations Relief and Works Agency for Palestine Refugees (UNRWA) started to integrate mental health and psychosocial support (MHPSS) into its primary health-care services in Jordan in late 2017. This baseline study aimed to assess the knowledge, attitudes, practices, and perceived barriers among UNRWA health staff regarding the implementation of the MHPSS programme.

Network meta-analysis of nine large cardiovascular outcome trials of new antidiabetic drugs

The aim of this network meta-analysis (NMA) was to indirectly compare the cardiovascular (CV) safety of new antidiabetic medications in patients with type 2 diabetes mellitus (T2DM).Data synthesisA search of the Embase and MEDLINE databases was conducted systematically to identify cardiovascular outcome trials (CVOTs) of new antidiabetic medications (DPP-4 inhibitors, GLP-1 agonists and SGLT-2 inhibitors) in patients with T2DM. The primary outcomes were the composite endpoint of CV death, nonfatal MI, and nonfatal stroke (MACE), death from CV causes, nonfatal MI, nonfatal stroke and death from any cause. Hospitalization for HF and unstable angina were evaluated as secondary endpoints. A total of 9 trials, including 87,162 patients, met the eligibility criteria and were retained for the analysis.The NMA results showed no significant differences among the DPP-4 inhibitors (sitagliptin, alogliptin, and saxagliptin) in any of the CV endpoints. Similarly, no significant changes were seen in the NMA among the GLP-1 receptor agonists nor the SGLT-2 inhibitors. The pairwise meta-analysis showed that DPP-4 inhibitors have a CV safety profiled comparable to placebo. GLP-1 agonists on the other hand, showed significant reduction in MACE (RR 0.92; 95% CI 0.87–0.97), death from CV causes (RR = 0.88; 95% CI 0.80–0.97), and death from any cause (RR = 0.89; 95% CI 0.82–0.96). SGLT-2 inhibitors showed significant reduction in hospitalization for heart failure events (RR 0.72; 95% CI 0.6–0.86) compared to placebo.ConclusionThis meta-analysis has shown that new antidiabetic medications do not impose any additional CV risk. The indirect comparison among the medications of each class resulted in no significant changes regarding CV endpoints and death from any cause.     

Successful treatment of relapsing autoimmune thrombotic thrombocytopenic purpura with rituximab

Thrombotic thrombocytopenic purpura (TTP) is a rare but life‐threatening condition characterized by thrombotic microangiopathy. The standard treatment for TTP is plasmapheresis. For refractory or relapsing cases, various immunosuppressive agents have been tried, and among them rituximab has shown promising results. TTP is rarer in the pediatric age group and the use of rituximab in children with TTP is limited. Reported herein is the successful treatment of relapsing autoimmune TTP with rituximab in a 12‐year‐old girl.