Low-dose vasopressin in the treatment of septic shock in sheep

After induction of cecal perforation, 20 anesthetized sheep were randomized to be treated, when arterial blood pressure fell below 75 mm Hg, with vasopressin (fixed dose of 0.02 U/minute), norepinephrine (0.5-5 microg/kg/minute titrated to maintain mean arterial pressure between 75 and 85 mm Hg), vasopressin + norepinephrine (vasopressin at fixed dose 0.01 U/minute plus norepinephrine titrated as for norepinephrine only group), or no vasopressor (Ringer's lactate [control]). Mean arterial pressure was well maintained in all treatment groups. Superior mesenteric arterial blood flow was significantly lower in the vasopressin + norepinephrine group than in the vasopressin group. Vasopressin alone or combined with norepinephrine limited the increase in blood lactate concentration and ileal PCO2-gap compared with control and norepinephrine groups. Urine output was higher in the vasopressin group than in control and norepinephrine groups. Survival time was longer in the vasopressin (30 +/- 6 hours) and vasopressin + norepinephrine (30 +/- 3 hours) groups than in the norepinephrine group (20 +/- 1 hours, p < 0.05) and in all treatment groups than in the control group (17 +/- 2 hours, p < 0.05). Tissue injury was less severe in the vasopressin and vasopressin + norepinephrine groups than in the others. In this clinically relevant model of septic shock due to peritonitis, vasopressin administration (alone or with norepinephrine) can prolong survival.     

Comparison of sensitivity, specificity, positive predictive value, and negative predictive value of stress testing versus 64-multislice coronary computed tomography angiography in predicting obstructive coronary artery disease diagnosed by coronary angiography

Sixty-four-multislice coronary computed tomographic angiography (CTA) and coronary angiography were performed in 145 patients (mean age 67 +/- 10 years), and stress testing was performed in 47 of these patients to determine the sensitivity, specificity, positive predictive value, and negative predictive value of coronary CTA and of stress testing in diagnosing obstructive coronary artery disease (CAD) in patients with suspected CAD. In 145 patients, coronary CTA had 98% sensitivity, 74% specificity, 90% positive predictive value, and 94% negative predictive value in diagnosing obstructive CAD. In 47 patients, stress testing had 69% sensitivity, 36% specificity, 78% positive predictive value, and 27% negative predictive value for diagnosing obstructive CAD, whereas coronary CTA had 100% sensitivity, 73% specificity, 92% positive predictive value, and 100% negative predictive value for diagnosing obstructive CAD. In conclusion, coronary CTA has better sensitivity, specificity, positive predictive value, and negative predictive value than stress testing in diagnosing obstructive CAD.     

Effect of open-lung vs conventional perioperative ventilation strategies on postoperative pulmonary complications after on-pump cardiac surgery: the PROVECS randomized clinical trial

To evaluate whether a perioperative open-lung ventilation strategy prevents postoperative pulmonary complications after elective on-pump cardiac surgery. In a pragmatic, randomized, multicenter, controlled trial, we assigned patients planned for on-pump cardiac surgery to either a conventional ventilation strategy with no ventilation during cardiopulmonary bypass (CPB) and lower perioperative positive end-expiratory pressure (PEEP) levels (2 cm H2O) or an open-lung ventilation strategy that included maintaining ventilation during CPB along with perioperative recruitment maneuvers and higher PEEP levels (8 cm H2O). All study patients were ventilated with low-tidal volumes before and after CPB (6 to 8 ml/kg of predicted body weight). The primary end point was a composite of pulmonary complications occurring within the first 7 postoperative days. Among 493 randomized patients, 488 completed the study (mean age, 65.7 years; 360 (73.7%) men; 230 (47.1%) underwent isolated valve surgery). Postoperative pulmonary complications occurred in 133 of 243 patients (54.7%) assigned to open-lung ventilation and in 145 of 245 patients (59.2%) assigned to conventional ventilation (p = 0.32). Open-lung ventilation did not significantly reduce the use of high-flow nasal oxygenotherapy (8.6% vs 9.4%; p = 0.77), non-invasive ventilation (13.2% vs 15.5%; p = 0.46) or new invasive mechanical ventilation (0.8% vs 2.4%, p = 0.28). Mean alive ICU-free days at postoperative day 7 was 4.4 ± 1.3 days in the open-lung group vs 4.3 ± 1.3 days in the conventional group (mean difference, 0.1 ± 0.1 day, p = 0.51). Extra-pulmonary complications and adverse events did not significantly differ between groups. A perioperative open-lung ventilation including ventilation during CPB does not reduce the incidence of postoperative pulmonary complications as compared with usual care. This finding does not support the use of such a strategy in patients undergoing on-pump cardiac surgery. Clinicaltrials.gov Identifier: NCT 02866578. https://clinicaltrials.gov/ct2/show/NCT02866578     

Characterization of granulocyte-macrophage colony-stimulating factor receptor on the blast cells of acute myeloblastic leukemia

Iodinated granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to document the specific binding of GM-CSF to all acute myeloblastic leukemia (AML) samples examined in the present study. There was some heterogeneity in the number of GM-CSF binding sites per cell. To determine whether the low level of binding to some patient samples may be attributed to receptor occupancy by an endogenous source of GM-CSF, we devised an acid wash procedure that could remove surface-bound GM-CSF without affecting receptor properties. We thus document that GM-CSF specific binding to AML blasts before or after acid wash was the same, indicating that the observed heterogeneity in binding is not the result of receptor occupancy by an endogeneous source of GM-CSF. Saturation analyses are in favor of the presence of two classes of binding sites on AML blasts: a high-affinity receptor that binds GM-CSF with a dissociation constant (kd) of 3 to 73 pmol/L and a second class of low-affinity receptor that binds GM-CSF with a kd of 1 to 10 nmol/L. Binding studies with two established cell lines KG-1, and IRCM-8 also showed the presence of two classes of binding sites with high and low affinities. Analysis of GM-CSF titration curves in culture indicate that the median effective concentration required for stimulation of blast colony formation (EC50 = 5-36 pmol/L) were in the range of the kd of the high-affinity binding site, suggesting that this high-affinity binding site mediates the proliferative response.     

Practical difficulties in the management of hepatitis B in the Asia-Pacific region

The Asia-Pacific Expert Committee on Hepatitis B Management recently reviewed the impact of hepatitis B in the region and assessed the differences and similarities observed in the practical management of the disease in individual Asia-Pacific countries. Hepatitis B is a major health concern in the Asia-Pacific region, and of all chronically infected carriers worldwide, approximately 75% are found in Asia. The disease poses a considerable burden on healthcare systems, and is likely to remain a cause of substantial morbidity and mortality for several decades. Disease prevention activities, including screening and vaccination programs, have been implemented successfully in some Asia-Pacific countries and similar measures are being established in other parts of the region. The management of hepatitis B in the Asia-Pacific varies throughout the region, with each country confronting different issues related to treatment options, disease monitoring and duration of therapy. The influence of cost, availability of diagnostic equipment, and patient awareness and compliance are of additional concern. Although guidelines such as those developed by the Asian Pacific Association for the Study of the Liver have been created to address problems encountered in the management of hepatitis B, many physicians in the region still find it difficult to make satisfactory management decisions because of the treatment choices available. This article examines the different approaches to hepatitis B management in a number of Asia-Pacific countries, and highlights the difficulties that can arise when adhering to treatment guidelines and disease prevention solutions that have proved to be successful in the region.     

Water magnetic relaxation dispersion in biological systems: the contribution of proton exchange and implications for the noninvasive detection of cartilage degradation

Magnetic relaxation has been used extensively to study and characterize biological tissues. In particular, spin-lattice relaxation in the rotating frame (T(1rho)) of water in protein solutions has been demonstrated to be sensitive to macromolecular weight and composition. However, the nature of the contribution from low frequency processes to water relaxation remains unclear. We have examined this problem by studying the water T(1rho) dispersion in peptide solutions ((14)N- and (15)N-labeled), glycosaminoglycan solutions, and samples of bovine articular cartilage before and after proteoglycan degradation. We find in model systems and tissue that hydrogen exchange from NH and OH groups to water dominates the low frequency water T(1rho) dispersion, in the context of the model used to interpret the relaxation data. Further, low frequency dispersion changes are correlated with loss of proteoglycan from the extra-cellular matrix of articular cartilage. This finding has significance for the noninvasive detection of matrix degradation.