Adaptive Management to Reduce Nest Inundation of a Critically Endangered Freshwater Turtle: Confirming the Win-win.

Inundation of Australian freshwater turtle nests has been identified as a threat to recruitment and long-term viability of species such as the critically endangered white-throated snapping turtle (Elseya albagula). Water level fluctuations within water storage infrastructure can inundate significant proportions of E. albagula nests in any year. Using an ecological risk assessment framework, operating rules for a water storage in the Burnett River (South East Queensland, Australia) were implemented to support nesting of E. albagula. Turtles were encouraged to nest at higher elevations on riverbanks by maintaining higher water levels in the impoundment during the nesting season, followed by lowering of water levels during the incubation period to minimise rates of nest inundation from riverine inflows. To verify the success of the new rules, a three-year confirmation monitoring program of nest heights and water levels was undertaken. Results of confirmation monitoring showed that 3% (2018), 11% (2019) and 0% (2020) of E. albagula nests were inundated under the new operating rules, compared to previously estimated nest inundation rates of >20% in ~24% of years of a 118-year simulation period (1890-2008) under previous storage operating rules. Emergency releases from an upstream storage in 2019 and 2020 for dam safety did not affect the success of the rule, demonstrating its resilience to natural and artificial flow regimes. This study demonstrates the importance of confirmation monitoring in verifying the efficacy of targeted changes to water management, and highlights potential application across other water storage infrastructure with threatened freshwater turtle populations requiring adaptive management.

Exploiting a new strategy to induce immunogenic cell death to improve dendritic cell-based vaccines for lymphoma immunotherapy.

Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion. Consistently, RA/IFNα-treated apoptotic cells and -TCLs were more efficiently phagocytosed by DCs compared to controls. Notably, cytotoxic T cells (CTLs) generated with autologous DCs pulsed with RA/IFNα-TCLs more efficiently recognized and specifically lysed MCL or DLBCL cells or targets loaded with several HLA-A*0201 cyclin D1 or HLA-B*0801 survivin epitopes. These cultures also showed an expansion of Th1 and Th17 cells and an increased Th17/Treg ratio. Moreover, DCs loaded with RA/IFNα-TCLs showed enhanced functional maturation and activation. NOD/SCID mice reconstituted with human peripheral blood lymphocytes and vaccinated with autologous RA/IFNα-TCL loaded-IFN-DCs showed lymphoma-specific T-cell responses and a significant decrease in tumor growth with respect to mice treated with IFN-DC unpulsed or loaded with untreated TCLs. This study demonstrates the feasibility and efficacy of the use of RA/IFNα to generate a highly immunogenic TCL as a suitable tumor antigen formulation for the development of effective anticancer DC-based vaccines.

Cardiac tamponade early after thrombolysis for acute myocardial infarction: a rare but not reported hemorrhagic complication.

Among 392 consecutive patients admitted for acute myocardial infarction and treated with thrombolytic drugs, 4 patients (1%) developed an early hemorrhagic pericardial effusion (without ventricular wall rupture) evolving within 24 h to cardiogenic shock consequent to cardiac tamponade. They all suffered from a large anterior myocardial infarction treated within 4 h after onset of symptoms with intravenous anisoylated plasminogen streptokinase activator complex (one case), recombinant tissue-type plasminogen activator (rt-PA) (two cases) or streptokinase (one case), anticoagulation with heparin (all cases) and aspirin (three cases). As soon as pericardial effusion was established by echocardiography, emergency percutaneous pericardiocentesis was performed at the bedside 20 +/- 6 h after thrombolytic therapy was started. This corrected immediately the clinical and hemodynamic status of each patient and a catheter was left in the pericardial space for 34 +/- 18 h. Thus, in the presence of unexplained clinical and hemodynamic deterioration occurring during the first 24 h after thrombolytic treatment of a large myocardial infarction, cardiac tamponade should be suspected. Immediate percutaneous pericardiocentesis followed by continuous drainage is a simple and definitive treatment for this complication.

Cardiogenic shock with non-ST-segment elevation myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK?

OBJECTIVES: We sought to determine the outcomes of patients with cardiogenic shock (CS) complicating non-ST-segment elevation acute myocardial infarction (MI). BACKGROUND: Such patients represent a high-risk (ST-segment depression) or low-risk (normal or nonspecific electrocardiographic findings) group for whom optimal therapy, particularly in the setting of shock, is unknown. METHODS: We assessed characteristics and outcomes of 881 patients with CS due to predominant left ventricular (LV) dysfunction in the SHOCK Trial Registry. RESULTS: Patients with non-ST-segment elevation MI (n = 152) were significantly older and had significantly more prior MI, heart failure, azotemia, bypass surgery, and peripheral vascular disease than patients with ST-elevation MI (n = 729). On average, the groups had similar in-hospital LV ejection fractions (approximately 30%), but patients with non-ST-elevation MI had a lower highest creatine kinase and were more likely to have triple-vessel disease. Among patients selected for coronary angiography, the left circumflex artery was the culprit vessel in 34.6% of non-ST-elevation versus 13.4% of ST-elevation MI patients (p = 0.001). Despite having more recurrent ischemia (25.7% vs. 17.4%, p = 0.058), non-ST-elevation patients underwent angiography less often (52.6% vs. 64.1%, p = 0.010). The proportion undergoing revascularization was similar (36.8% for non-ST-elevation vs. 41.9% ST-elevation MI, p = 0.277). In-hospital mortality also was similar in the two groups (62.5% for non-ST-elevation vs. 60.4% ST-elevation MI). After adjustment, ST-segment elevation MI did not independently predict in-hospital mortality (odds ratio, 1.30; 95% confidence interval, 0.83 to 2.02; p = 0.252). CONCLUSIONS: Patients with CS and non-ST-segment elevation MI have a higher-risk profile than shock patients with ST-segment elevation, but similar in-hospital mortality. More recurrent ischemia and less angiography represent opportunities for earlier intervention, and early reperfusion therapy for circumflex artery occlusion should be considered when non-ST-elevation MI causes CS.

Cardiogenic shock due to cardiac free-wall rupture or tamponade after acute myocardial infarction: a report from the SHOCK Trial Registry. Should we emergently revascularize occluded coronaries for cardiogenic shock?

OBJECTIVES: We sought to compare the characteristics and outcomes of patients with acute myocardial infarction (MI) and cardiogenic shock (CS) caused by rupture of the ventricular free wall or tamponade versus shock from other causes. BACKGROUND: Free-wall rupture is a recognized cause of mortality in patients with acute MI. Some of these patients present subacutely, which provides an opportunity for intervention. Recognition of factors that distinguish them from the overall shock cohort would be beneficial. METHODS: The international SHOCK Trial Registry enrolled patients concurrently with the randomized SHOCK Trial. Thirty-six centers consecutively enrolled all patients with suspected CS after MI, regardless of trial eligibility. RESULTS: Of the 1,048 patients studied, 28 (2.7%) had free-wall rupture or tamponade. These patients had less pulmonary edema, less diabetes, less prior MI, and less prior congestive heart failure (all p < 0.05). They more often had new Q waves in two or more leads (51.9% vs. 31.5%, p < 0.04), but MI location and time to shock onset after MI did not differ. Of patients with rupture or tamponade, 75% had pericardial effusions. No hemodynamic characteristics identified patients with rupture/tamponade. Most patients with rupture/tamponade had surgery and/or pericardiocentesis (27/28); their in-hospital survival rate was identical to that of the group overall (39.3%). Women and older patients with rupture/tamponade tended to survive intervention less often. CONCLUSIONS: Free-wall rupture and tamponade may present as CS after MI, and survival after intervention is similar to that of the overall shock cohort. All patients with CS after MI should have echocardiography in order to detect subacute rupture or tamponade and initiate appropriate interventions.

Detection of restenosis after successful coronary angioplasty: improved clinical decision making with use of a logistic model combining procedural and follow-up variables.

A prospective study of 111 patients who underwent repeat coronary angiography and exercise thallium-201 scintigraphy 6 +/- 2 months after complete revascularization by percutaneous transluminal coronary angioplasty was performed to assess whether clinical, procedure-related and postangioplasty exercise variables yield independent information for the prediction of angiographic restenosis after angioplasty. Complete revascularization was defined as successful angioplasty of one or more vessels that resulted in no residual coronary lesion with greater than 50% diameter stenosis. Restenosis was defined as a residual stenosis at the time of repeat angiography of greater than 50% of luminal diameter. Restenosis occurred in 40% of the patients. The 111 patients were randomly subdivided into a learning group (n = 84) and a testing group (n = 27). A logistic discriminant analysis was performed in the learning group and the logistic model was used to estimate a logistic probability of restenosis. This probability of restenosis was validated in the testing group. In the learning group of 84 patients univariate analysis of 39 factors revealed 8 factors related to restenosis: recurrence of angina (p less than 0.0001), postangioplasty abnormal finding on exercise thallium-201 scintigram (p less than 0.0001), exercise thallium-201 scintigram score (p less than 0.0001), difference between exercise and rest ST segment depression (p less than 0.001), postangioplasty exercise ST segment depression (p less than 0.001), absolute postangioplasty stenosis diameter (p less than 0.003), postangioplasty exercise work load (p less than 0.03) and postangioplasty exercise heart rate (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Early discharge in the thrombolytic era: an analysis of criteria for uncomplicated infarction from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial.

OBJECTIVES: This study sought to readdress the definition of uncomplicated myocardial infarction and to apply clinical criteria for early discharge of such patients in the thrombolytic era. BACKGROUND: Previous studies proposed early hospital discharge at day 7 to 10 after acute myocardial infarction. The potential for earlier discharge of patients with uncomplicated infarction after thrombolysis remains undemonstrated. METHODS: We defined "uncomplicated infarction" a priori as the absence of death, reinfarction, ischemia, stroke, shock, heart failure (Killip class > 1), bypass surgery, balloon pumping, emergency catheterization or cardioversion or defibrillation in the first 4 hospital days. We applied this definition to 41,021 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial. We examined death at 30 days and 1 year and rates of in-hospital reinfarction, heart failure, recurrent ischemia, shock and stroke in the uncomplicated and complicated groups created by application of our definition. We also assessed lengths of hospital and cardiac care unit stay. RESULTS: Application of our clinical criteria yielded 23,497 (57.3%) patients in the uncomplicated group at day 4 with a very low risk of death and in-hospital complications: 30-day mortality 1%, reinfarction 1.7%, heart failure 2.6%, recurrent ischemia 6.7%, shock 0.4% and stroke 0.2%. One-year mortality was 3.6%. The median hospital stay was 9 days (7, 12 [25th, 75th percentiles, respectively]), and the median cardiac care unit stay 3 days (3, 5). CONCLUSIONS: Simple clinical characteristics can identify a very low risk post-myocardial infarction population by hospital day 4. Use of these criteria for early discharge planning could substantially reduce length of stay for patients with uncomplicated acute myocardial infarction.

Amrinone in the management of low cardiac output after open heart surgery.

Hemodynamic effects of amrinone were studied in 2 groups of patients after open heart surgery. Group I consisted of 10 patients with moderate heart failure. In the absence of inotropic agents, their mean cardiac index (CI) was 2.02 +/- 0.41 liters/min/m2 and mean pulmonary capillary wedge pressure (PCWP) 19 +/- 3 mm Hg. Amrinone was administered 24 hours postoperatively by bolus injection (2 mg/kg) and by 12-hour infusions (20 micrograms/kg/min). Hemodynamic data and plasma concentrations were obtained 10 and 20 minutes after the bolus injection and at 1, 4, 8 and 12 hours during infusion. Significant beneficial changes were noted in CI, PCWP, right atrial pressure, systemic vascular resistance and pulmonary vascular resistance. Group II consisted of 5 patients in severe cardiogenic shock (mean CI 1.97 +/- 0.3 liters/min/m2, mean PCWP 28 +/- 8 mm Hg) despite adrenergic agonists in all patients and intraaortic counterpulsation in 2. After these measures, amrinone was given intravenously for 36 to 72 hours as additional inotropic support. Significant improvement was observed in CI, PCWP, right atrial pressure, systemic vascular resistance and pulmonary vascular resistance. Four patients in this group were discharged; 1 patient died after 5 days in acute renal failure and coma grade IV. No serious adverse effects of amrinone were observed in any group II patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intracoronary thrombolytic therapy on exercise-induced ischemia after acute myocardial infarction.

Intracoronary streptokinase (SK) therapy increases vessel patency rate after acute myocardial infarction (AMI) and thus may lead to a greater exercise-induced myocardial ischemia. This hypothesis was tested in 39 patients enrolled in an angiographically randomized trial of intracoronary SK (19 treated with SK and 20 control subjects); all patients underwent thallium-201 scintigraphy at rest before acute angiography, as well as at rest and during stress 5 to 6 weeks after AMI. The patients were classified into 2 groups based on the presence (n = 13) or absence (n = 26) of complete obstruction of the infarct-related coronary artery at the end of the acute angiography. Semiquantitative score of myocardial thallium uptake was expressed as percent of maximal defect score. Thallium defect score at rest between admission and 5 to 6 weeks' study decreased from 10 +/- 16% units in the control group and from 23 +/- 14% units in the SK group (p = 0.01). This decrease was related to opening of the infarct-related artery (opening 23 +/- 16% vs occlusion 5 +/- 10%). The change in exercise-induced defect score was significantly (p = 0.01) larger in patients in the SK group (11 +/- 6% units) than in those in the control group (5 +/- 7% units). The perfusion defect during exercise was larger (p = 0.006) in patients with incomplete obstruction or reperfusion (10 +/- 6% units) than in patients with complete obstruction (3 +/- 7%). This difference was independent of the number of diseased coronary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Overview of randomized trials of intravenous heparin in patients with acute myocardial infarction treated with thrombolytic therapy.

Intravenous heparin is routinely given after thrombolytic therapy for patients with acute myocardial infarction in the United States and in some, but by no means all, other countries. Several trials have documented improved infarct-artery patency in patients treated with heparin; however, none was large enough individually to assess the effect of heparin on clinical outcomes. We performed a systematic overview of the 6 randomized controlled trials (1,735 patients) to summarize the available data concerning the risks and benefits of intravenous heparin versus no heparin after thrombolytic therapy. Mortality before hospital discharge was 5.1% for patients allocated to intravenous heparin compared with 5.6% for controls (relative risk reduction of 9%, odds ratio 0.91, 95% confidence interval 0.59 to 1.39). Similar rates of recurrent ischemia and reinfarction were observed among those allocated to heparin therapy or control. The rates of total stroke, intracranial hemorrhage, and severe bleeding were similar in patients allocated to heparin; however, the risk of any severity of bleeding was significantly higher (22.7% vs 16.2%; odds ratio 1.55, 95% confidence interval 1.21 to 1.98). There was no significant difference in the observed effects of heparin between patients receiving tissue-type plasminogen activator and those receiving streptokinase or anisoylated plasminogen streptokinase activator complex, or between patients who did and did not receive aspirin. The findings of this overview demonstrate that insufficient clinical outcome data are available to support or to refute the routine use of intravenous heparin therapy after thrombolysis. It is not known if these findings are due to lack of statistical power, inappropriate levels of anticoagulation, or lack of benefit of intravenous heparin. Large randomized studies of heparin (and of new antithrombotic regimens) are needed to establish the role of such therapy.

Pharmacokinetics, thrombolytic efficacy and hemorrhagic risk of different streptokinase regimens in heparin-treated acute myocardial infarction.

The systemic activator activity of 4 streptokinase (SK) regimens (250,000 IU intracoronary, group A; 500,000 IU, group B; 1.5 X 10(6) IU, group C; and 30 U anisoylated plasminogen streptokinase activator complex (APSAC) intravenously, group D) was tested with the fibrin plate technique. One hour after initiation of treatment, the activator activity was highest after APSAC (3.6 +/- 0.9 U), slightly but not significantly less after SK 1.5 X 10(6) IU (3.0 +/- 0.7), and significantly less after SK 500,000 IU (1.6 +/- 0.5) and 250,000 IU (0.6 +/- 0.5), p less than 0.001. After SK, activator activity half-lives were 184 minutes (group B) and 169 minutes (group C), and after APSAC 188 minutes (group D). These were all in agreement with greater than 12 hour duration of changes in other markers of systemic fibrinolysis (euglobulin lysis time) and substrates depletion (fibrinogen, plasminogen, alpha 2 antiplasmin). In extended pilot clinical groups given identical thrombolytic regimens during full anticoagulation with heparin, angiographic coronary patency was found in 83% (35 of 42) after intracoronary SK (group 1), in 73 and 75%, respectively, after 500,000 IU (31 of 43) and 1.5 X 10(6) IU (30 of 40) (group 2 and 3, difference not significant) and 80% (8 of 10) after the 30-U bolus of APSAC (group 4). The overall hemorrhagic risk was 24%, equally distributed among the 4 regimens and mostly (91%) related to catheters. The incidence of bleeding unrelated to vessel puncture was 4%; no deaths occurred. It is concluded that APSAC is the most fibrinolytic regimen but its potential thrombolytic superiority over SK remains to be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery reperfusion in acute myocardial infarction: assessment by pre- and postintervention thallium-201 myocardial perfusion imaging.

In a randomized trial of intracoronary streptokinase (STK) therapy in acute myocardial infarction, 44 patients (21 control subjects and 23 patients treated with STK) underwent sequential thallium-201 planar imaging before angiography and after 4 hours (redistribution), 4 days and 6 weeks. Patients were classified according to the presence or absence of angiographic reperfusion of the infarct-related artery. The semiquantitative score of myocardial thallium uptake was expressed as percent of maximal defect score. Both in control and in STK-treated groups, thallium defect scores decreased over time, but this decrease was smaller in the control group (before angiography, 33 +/- 4%; redistribution, 29 +/- 4%; 4 days, 25 +/- 4%; and 6 weeks, 22 +/- 4%) than in the STK group (44 +/- 4%, 38 +/- 4%, 26 +/- 4% and 21 +/- 3%, respectively). In patients in whom reperfusion was achieved (20 STK-treated, 6 control subjects), a marked decrease in thallium score was observed (before angiography, 40 +/- 4%; redistribution, 32 +/- 4%; 4 days, 20 +/- 5%; and 6 weeks, 14 +/- 22%) compared with patients in whom reperfusion was not achieved (37 +/- 4%, 36 +/- 5%, 33 +/- 5% and 33 +/- 4%, respectively). These results indicate that serial thallium imaging is an accurate method of assessing changes in myocardial perfusion after acute myocardial infarction. Restoration of thallium uptake was observed after reperfusion of the infarct-related artery whether this recanalization was seen spontaneously or after successful thrombolysis.

Analysis of coagulation and fibrinolysis after intravenous anisoylated plasminogen streptokinase activator complex or heparin in patients with acute myocardial infarction. A Belgian multicentre study.

A multicentre randomised trial including 87 patients admitted for acute myocardial infarction compared the effects of a single intravenous bolus of an anisoylated plasminogen streptokinase activator complex (APSAC) 30 units with those of heparin treatment on haemostasis during the first 4 days after treatment. In the APSAC group, a rapid and significant reduction in fibrinogen, plasminogen and alpha 2-antiplasmin was observed, associated with an increase of fibrin(ogen) degradation products, reflecting a strong systemic lytic activity. None of these parameters were significantly modified by heparin, but the anticoagulant effect was apparent as assessed by the activated partial thromboplastin time. The systemic fibrinolysis induced after different regimens of streptokinase infusion demonstrated that an intravenous bolus of APSAC 30U was as potent as streptokinase 500,000 or 1,500,000IU administered intravenously over 45 minutes and definitely more fibrinolytic than intracoronary infusion of streptokinase 250,000IU. Despite the demonstrated fibrin specificity of the drug at a low dose, a high dose of APSAC (30U intravenously) induced an important systemic lytic state for at least 12 hours.

Acute cardiogenic pulmonary edema and pregnancy: a ten-year experience.

We reviewed the cardiac emergencies that occurred during or soon after pregnancy and required admission in an intensive care unit. The study sample consisted of 22248 pregnant women representing the whole obstetrical population collected from 3 hospitals over a ten-year period. Among the 88 patients admitted to our ICU during this decade, only 5 suffered from a specific cardiac disorder. Acute pulmonary edema was the common clinical presentation in the 4 cases reported. Despite the severity of cardiac involvement on admission none had previous evidence of heart disease that could have heralded acute left ventricular failure. From these observations it can be concluded that preexisting cardiovascular disease and circulatory changes related to pregnancy should no longer be regarded as the unique contributors to the development of severe heart failure during pregnancy.

Early diagnosis of peritoneal infection by simultaneous measurement of lactate concentration in peritoneal fluid and blood.

The level of lactate in peritoneal fluid has been suggested to be of great value in the early diagnosis of peritoneal infection [5]. However, this value is affected by multiple systemic factors producing lactic acidosis; these contributed to the high rate of false positive results, obtained in that study. In our study, a better correlation has been found between the peritoneal fluid to blood lactate gradient levels and the presence or absence of peritoneal infection. A threshold gradient level of 2.2 mmol/l in a total of 37 infected and 48 non-infected samples gave the best prediction with a sensitivity of 95% and a specificity of 96%.

Glycosyltransferase activities in normal and leukaemic monocytic cells.

Glycosyltransferase activities were measured in normal monocytes and in leukaemic monoblasts. Biosynthesis of glycosylated derivatives of dolichyl-monophosphate, which act as intermediates in glycosylation, was measured. Transfer of mannose from GDP-mannose was greatly increased in leukaemic monoblasts. Galactosyltransferase activities, using endogenous protein acceptors, were increased in leukaemic cells of the monocytic lineage compared to normal cells. No significant difference was observed on specific exogenous glycoprotein acceptors. These selective increases of some glycosyltransferase activities in normal and leukaemic monocytic cells can be correlated either with different expression of specific carbohydrate structures or with changes in glycosylation regulation.

Antenatal exposure to atenolol and retroperitoneal fibromatosis.

We present a case of retroperitoneal fibromatosis in a fetus whose mother took atenolol during pregnancy. A 25-year-old obese woman was treated for hypertension with 100 mg atenolol daily from the second month until the end of pregnancy. At 29 weeks, echography disclosed a retroperitoneal mass and at 37 weeks, a boy was delivered. A biopsy of the tumor showed a fibromatosis with medullary compression, treated by antimitotics until 3 months of age. At the age of 4, the mass had disappeared but severe scoliosis was present. This in utero exposure to atenolol drew our attention because the retroperitoneal localization of the tumor is similar to that of fibroses reported in adults after exposure to atenolol and for other reasons: transplacental carcinogenesis has been demonstrated in humans, at least for diethylstilboestrol, atenolol crosses the placental barrier, the drug was taken during nearly the whole pregnancy, and retroperitoneal fibromatosis is exceptional as a neonatal tumour.

Isolation of the left coronary artery ostium by an aortic cusp attachment: a rare cause of myocardial ischemia.

A 34-year-old woman experienced a 3-month history of recurrent chest pain on exertion. Extensive investigation, including coronary angiography, revealed severe aortic incompetence with suspicion of single-vessel coronary disease. At operation the aortic valve was tricuspid but the left coronary cusp was adherent to the aortic wall, resulting in isolation of the left coronary artery with only a tiny communication with the aortic lumen. The three cusps were excised. An aortic valve replacement was performed with an aortic homograft. The postoperative course was uneventful and myocardial ischemia was totally relieved.