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.

The role of ultrasound and fetal fibronectin in predicting the length of induced labor when the cervix is unfavorable.

OBJECTIVE: To compare cervical clinical data, ultrasound parameters and fetal fibronectin assessment in the prediction of the duration of induced labor when the cervix is unfavorable. METHODS: This was a prospective study of 90 pregnant women with a Bishop score /= 27 mm (P = 0.002 and P = 0.005). CONCLUSION: Cervical dilatation as assessed by digital examination is the best predictor of the duration of the latent phase and of that of the whole of labor. Ultrasound measurement of cervical length is not more accurate at predicting the duration of labor than are clinical data.

Does ultrasound examination when the cervix is unfavorable improve the prediction of failed labor induction?

OBJECTIVE: To compare the Bishop score, ultrasound cervical parameters and fetal fibronectin assessment for predicting failed labor induction when the cervix is unfavorable. METHOD: A prospective observational study was performed in 106 consecutive pregnant women with a Bishop score < or =5 undergoing labor induction. Assessment of fetal fibronectin and ultrasound measurement of cervical length, cervical wedging and cervical lip areas were performed. The relationship between these parameters and failure of labor induction was determined. RESULTS: Failure of labor induction was defined as failure to reach a cervical dilatation of > or =5 cm, and it occurred in 16 patients (15.1%). Induction failure was associated with low Bishop scores before (P = 0.004) and 6 h after the start of induction (P = 0.007), increased clinical cervical length (P = 0.02) and increased ultrasound anterior cervical lip area (P = 0.04). The logistic regression model identified the Bishop score before induction (odds ratio = 2.25; 95% CI, 1.30-3.91; P = 0.003) and the clinical cervical length (odds ratio = 3.95; 95% CI, 1.3-11.7; P = 0.01) as being independent predictors of failed induction. To predict an induction failure, the best Bishop score cut-off value was 4, with a sensitivity of 87.5%, a specificity of 45.6%, a likelihood ratio of 1.58, a positive predictive value of 22.2% and a negative predictive value of 95.4%. CONCLUSION: Compared with the Bishop score, cervical length by ultrasound is not a better predictor for the outcome of labor induction in an unfavorable cervix. Nevertheless, the Bishop score appears to be of poor predictive value for failed induction of labor.

Dynamic endocrine responses to stress: evidence for energetic constraints and status dependence in breeding male green turtles.

During reproduction, male vertebrates may exhibit a continuum of interactions between sex and adrenal steroids during stressful events, the outcome of which may be important in either reducing or promoting male reproductive success. We studied adult male green turtles (Chelonia mydas) to examine if they altered plasma corticosterone (CORT) and androgen levels in response to a standardized capture/restraint stressor as potential mechanisms to maintain reproductive activity during stressful events. At the population level, we found that migrant breeding males had a significantly smaller CORT response to the capture/restraint stressor compared to nonbreeding males and that this decreased response coincided with the generally poorer body condition of migrant breeders. In contrast, plasma androgen levels decreased significantly in response to the capture/restraint stressor in migrant breeding males, but not in nonbreeding and pre-migrant breeding males. For individual migrant breeding males, the magnitude of their CORT and androgen responses to the capture/restraint stressor was highly correlated with their body condition and body length, respectively. Our results demonstrate that male green turtles exhibit complex interactions in their endocrine responses to a capture/restraint stressor and that variation in these interactions is associated with differences in males' reproductive, energetic, and physical state. We hypothesize that interplay between physical status and plasma hormone responses to stressors could have important consequences for male green turtle reproduction.

Lack of progress in cardiogenic shock: lessons from the GUSTO trials.

AIMS: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. METHODS AND RESULTS: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. CONCLUSIONS: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.

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.

Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT)

BACKGROUND: Diltiazem reduces non-fatal reinfarction and refractory ischaemia after non-Q-wave myocardial infarction, an acute coronary syndrome similar to the incomplete infarction that occurs after successful reperfusion. We postulated that this agent would reduce cardiac events in patients after acute myocardial infarction treated initially with thrombolytic agents-a clinical application previously unexplored with heart-rate-lowering calcium antagonists. METHODS: A prospective, randomised, double-blind, sequential trial was done in 874 patients with acute myocardial infarction, but without congestive heart failure, who first received thrombolytic agents. Patients received either 300 mg oral diltiazem once daily, or placebo, initiated within 36-96 h of infarct onset, and given for up to 6 months. The trial primary endpoint was the cumulative first event rate of cardiac death, non-fatal reinfarction, or refractory ischaemia. Additional prespecified endpoints included several composites of non-fatal cardiac events (non-fatal reinfarction combined with refractory ischaemia, all recurrent ischaemia, or the need for myocardial revascularisation). The diagnosis of ischaemia, whether refractory or recurrent, and the need for myocardial revascularisation, was always based on objective electrocardiographical evidence of ischaemia, either at rest or on exertion. RESULTS: For the trial primary endpoint, 131 events occurred in the 444 placebo patients and 97 events in the 430 diltiazem patients (hazard ratio 0.79; 95% CI, 0.61-1.02; p=0.07). For non-fatal cardiac events, diltiazem treatment was associated with a relative decrease (0.76; 0.58-1.00) in the combined event rate of non-fatal reinfarction and refractory ischaemia. There was a similar decrease in the composite non-fatal endpoints of non-fatal reinfarction combined with all recurrent ischaemia (0.80; 0.64-1.00) and non-fatal reinfarction combined with the need for myocardial revascularisation (0.67; 0.46-0.96). The need for myocardial revascularisation alone was significantly reduced by 42% (0.61; 0.39-0.96). No major safety issues were encountered. CONCLUSIONS: Diltiazem did not reduce the cumulative occurrence of cardiac death, non-fatal reinfarction, or refractory ischaemia during a 6-month follow-up, but did reduce all composite endpoints of non-fatal cardiac events, especially the need for myocardial revascularisation.

Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock.

BACKGROUND: The leading cause of death in patients hospitalized for acute myocardial infarction is cardiogenic shock. We conducted a randomized trial to evaluate early revascularization in patients with cardiogenic shock. METHODS: Patients with shock due to left ventricular failure complicating myocardial infarction were randomly assigned to emergency revascularization (152 patients) or initial medical stabilization (150 patients). Revascularization was accomplished by either coronary-artery bypass grafting or angioplasty. Intraaortic balloon counterpulsation was performed in 86 percent of the patients in both groups. The primary end point was mortality from all causes at 30 days. Six-month survival was a secondary end point. RESULTS: The mean age of the patients was 66+/-10 years, 32 percent were women and 55 percent were transferred from other hospitals. The median time to the onset of shock was 5.6 hours after infarction, and most infarcts were anterior in location. Ninety-seven percent of the patients assigned to revascularization underwent early coronary angiography, and 87 percent underwent revascularization; only 2.7 percent of the patients assigned to medical therapy crossed over to early revascularization without clinical indication. Overall mortality at 30 days did not differ significantly between the revascularization and medical-therapy groups (46.7 percent and 56.0 percent, respectively; difference, -9.3 percent; 95 percent confidence interval for the difference, -20.5 to 1.9 percent; P=0.11). Six-month mortality was lower in the revascularization group than in the medical-therapy group (50.3 percent vs. 63.1 percent, P=0.027). CONCLUSIONS: In patients with cardiogenic shock, emergency revascularization did not significantly reduce overall mortality at 30 days. However, after six months there was a significant survival benefit. Early revascularization should be strongly considered for patients with acute myocardial infarction complicated by cardiogenic shock.

SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK: an international randomized trial of emergency PTCA/CABG-trial design. The SHOCK Trial Study Group.

BACKGROUND: Cardiogenic shock (CS) is the leading cause of death in patients hospitalized with acute myocardial infarction (MI). Nonrandomized studies suggest reduced mortality rate with revascularization. TRIAL DESIGN: The SHOCK trial is a multicenter, randomized, and unblinded study with a Registry for trial-eligible and ineligible nonrandomized patients. The trial is testing the hypothesis that a direct invasive strategy of emergency revascularization for patients with cardiogenic shock complicating acute MI will reduce 30-day all-cause mortality rate by 20 absolute percentage points compared with initial medical stabilization. Eligibility criteria include development of CS within 36 hours of an acute transmural MI as evidenced by ST elevation or new left bundle branch block MI; clinical criteria for CS with hemodynamic confirmation; absence of a mechanical, iatrogenic, or other cause of shock; and enrollment within 12 hours of CS diagnosis. Patients randomly assigned to emergency revascularization immediately undergo coronary angiography, with percutaneous transluminal coronary angioplasty or coronary artery bypass grafting depending on the coronary anatomy. Patients assigned to initial medical stabilization may undergo revascularization >/=54 hours after randomization. END POINTS: The primary end point is all-cause 30-day mortality after randomization. Secondary end points include death at trial termination, changes in left ventricular dimensions and function measured by echocardiography at randomization and 2 weeks later, and changes in quality of life and physical functioning from 2 weeks after discharge to 6 months after MI.

Cardiac troponin I as an early marker of myocardial damage after coronary bypass surgery.

STUDY OBJECTIVE: To evaluate the performance of cardiac specific markers, cardiac troponin I (cTnI) and CK-MB by mass assay (CK-MB mass), for the early diagnosis of myocardial ischemia and/or infarction after coronary bypass surgery. METHODS: Prospective clinical, electrocardiograpic and biologic follow-up of 117 patients undergoing isolated coronary surgery with the use of intermittent anterograde normothermic blood cardioplegia. Blood samples for biochemical analysis were drawn before surgery (T0) and at 2 (T1), 6 (T2), 10 (T3) and 20 h (T4) after aortic cross-clamp release. Without knowledge of the biochemical data, patients were classified according to the electrocardiographic evolution into two groups: group 1, uneventful recovery and group 2, evidence of ischemia/infarction based on continuous ST-T segment monitoring and 12-lead ECG. RESULTS: No patients had abnormal markers at T0. At T1, although both markers were elevated, no difference was noted between the two groups. At T2, 6 h after surgery, cTnI and CK-MB mass levels were significantly higher in group 2 than in group 1 (median = 17 microg/l, Interquartile Range (IR): 14.7-27.3 vs. 3.1 microg/l, IR 1.9-5.3 for cTnI and median 42.5 microg/l, IR: 27.1-95.7 vs. 13.6 microg/l, IR: 9.5-18.5 for CK-MB mass). A receiver operating characteristic (ROC) curve analysis shows that a cTnI value of 13.1 microg/ml has 100% specificity and 90% sensitivity to separate both groups, whereas a value of 33.2 microg/ml for CK-MB mass has a specificity of 100% and a sensitivity of 73%. At T3 and T4, the same difference was noted between the groups. cTnI values in all six patients with a Q-wave infarction were > or = 20 ng/ml, whereas only one of five patients with prolonged ischemia had cTnI level > 20 ng/ml. CONCLUSION: As soon as 6 h postoperatively, cTnI and CK-MB by mass assay were able to separate those patients with an uneventful recovery from those with significant ischemia. This is particularly useful in frequent cases when the ECG is difficult to interpret.

Screening of the C677T mutation on the methylenetetrahydrofolate reductase gene in French patients with neural tube defects.

We report the analysis of the distribution of the C677T mutation on the methylenetetrahydrofolate reductase (MTHFR) gene in prenatally diagnosed neural tube defects (NTD) cases and controls. In contrast to previous reports, we found the same distribution in fetuses with NTD and controls, which suggests that the MTHFR C677T mutation cannot be regarded as a genetic risk factor for NTD.

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.

[Current point of view on medical treatment of unstable angina]. / Un point de vue actuel sur le traitement médical de l'angor instable.

The combined death/infarct rate in the weeks following unstable angina ranges from 10 to 40%. Aspirin and GP IIb/IIIa antagonists reduce the mortality and morbidity, which has not been demonstrated with heparin. The short term clinical results of treatment with hirudin are better than those with heparin. A rebound biological effect after heparin or hirudin therapy may have adverse clinical consequences. Nitrate derivatives have a role to play and adjuvant therapy includes the betablockers and some calcium antagonists in special indications.