In-hospital mortality of older patients with COVID-19 throughout the epidemic waves in the great Paris area: a multicenter cohort study.

BACKGROUND: Mortality is high in older patients hospitalized with COVID-19. Previous studies observed lower mortality during the Omicron wave, yet no data is available on older patients. The objective was to compare in-hospital mortality between the Omicron and previous waves in older patients hospitalized with COVID-19. METHODS: This retrospective observational multicenter cohort study used the Greater Paris University Hospitals Group's data warehouse (38 hospitals). Patients aged ≥ 75 years with a confirmed COVID-19 diagnosis and hospitalized from March 2020 to January 2022 were included. The study period was divided into five waves. The fifth wave (January 1st to 31st 2022) was considered as the Omicron wave as it was the predominant variant (≥ 50%), and was compared with waves 1 (March-July 2020), 2 (August-December 2020), 3 (January-June 2021) and 4 (July-December 2021). Primary outcome was in-hospital mortality. Secondary outcome was occurrence of ICU admission or in-hospital death. Multivariate logistic regression was performed, with a sensitivity analysis according to variant type. RESULTS: Of the 195,084 patients hospitalized with COVID-19, 19,909 patients aged ≥ 75 years were included (median age 85 [IQR 79-90] years, 53% women). Overall in-hospital mortality was 4,337 (22%), reaching 345 (17%) during wave 5. Waves 1 and 3 were significantly associated with increased in-hospital mortality in comparison with wave 5 (adjusted Odds Ratios aOR 1.42 [95%CI 1.21-1.66] and 1.56 [95%CI 1.33-1.83] respectively). Waves 1 to 3 were associated with an increased risk of occurrence of ICU admission or in-hospital death in comparison with wave 5: aOR 1.29 [95% CI 1.12 to 1.49] for wave 1, aOR 1.25 [95% CI 1.08 to 1.45] for wave 2 and aOR 1.56 [95% CI 1.36 to 1.79] for wave 3. Sensitivity analysis found that Omicron variant was associated with decreased mortality, in comparison with previous variants. CONCLUSIONS: Mortality was lower during the 5th Omicron wave in the older population, but remained high, implying that this variant could be considered as "milder" but not "mild". This persistently high mortality during the 5th Omicron wave highlights the importance of including older patients in clinical trials to confirm the benefit/risk balance of COVID-19 treatments in this fragile population.

Comparison of Patients Infected With Delta Versus Omicron COVID-19 Variants Presenting to Paris Emergency Departments : A Retrospective Cohort Study.

BACKGROUND: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave. OBJECTIVE: To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED). DESIGN: Retrospective chart reviews. SETTING: 13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022. PATIENTS: Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification. MEASUREMENTS: Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality. RESULTS: A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [-26.5 to -17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]). LIMITATION: Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded. CONCLUSION: Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival. PRIMARY FUNDING SOURCE: None.

Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.

Importance: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. Objective: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. Interventions: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. Main Outcomes and Measures: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). Results: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). Conclusions and Relevance: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. Trial Registration: ClinicalTrials.gov Identifier: NCT03218722.

Optimal donation of kidney transplants after controlled circulatory death.

Controlled donation after circulatory death (cDCD) is used for "extended criteria" donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12-1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time <18 h, 1.57; 95% CI 1.20-2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31-2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.

Opioid-related genetic polymorphisms do not influence postoperative opioid requirement: A prospective observational study.

BACKGROUND: Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics. DESIGN: A single centre prospective study. SETTING: University Hospital, Paris, France, from 2 January 2007 to 15 November 2011. PATIENTS: A total of 438 white adults scheduled for major orthopaedic surgery (spine, hip and knee) under general anaesthesia. The main exclusion criteria were receiving opioids for chronic pain, nonopioid drugs within 2 days prior to surgery, pregnancy, renal insufficiency, sleep apnoea obstruction syndrome, morbid obesity, severe hepatic impairment, cognitive dysfunction. INTERVENTIONS: Assays of plasma concentrations of morphine and metabolites (morphine 3-glucuronide and morphine 6-glucuronide) were performed and common polymorphisms in four candidate genes [OPRM1 A118G rs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A (rs2032582); COMT Val 158 Met (rs4680)] were analysed.Morphine was titrated by staff in the postanaesthesia care unit (PACU) and in the ward patient-controlled intravenous analgesia was used for 24 h. MAIN OUTCOME MEASURES: The dose of morphine required to achieve pain relief and the influence of SNP in genes involved in morphine pharmacodynamics and kinetics on morphine dose requirements. Secondary endpoints were the concentrations of morphine, morphine 6-glucuronide and morphine 3-gluguronide, the proportion of patients requiring a rescue analgesic and the proportion of morphine-related adverse events. RESULTS: A total of 404 patients completed the study to final analysis. The mean ±â€ŠSD morphine dose to achieve pain relief was 15.8 ±â€Š8.8 mg in the PACU and 22.7 ±â€Š18.6 mg during patient-controlled intravenous administration. Morphine-related adverse events were observed in 37%. There was no relationship between any genetic polymorphisms and morphine dose, morphine 3-gluguronide and morphine 6-glucuronide concentration, morphine-related adverse events or pain level. In the PACU only, P-glycoprotein polymorphisms (ex-21; ex-26) were significantly associated with morphine concentration but the prediction of the model was poor (R = 0.04) CONCLUSION: No major relationship has been demonstrated between SNP of OPRM1, ABCB1, COMT and morphine requirement, pain level or adverse effects in the postoperative period. TRIAL REGISTRATION: NCT00822549 (www.clinicaltrials.gov).

Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial.

Importance: The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial. Objective: To prospectively validate the safety of a PERC-based strategy to rule out PE. Design, Setting, and Patients: A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016. Interventions: Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative. Main Outcomes and Measures: The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission. Results: Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]). Conclusions and Relevance: Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department. Trial Registration: clinicaltrials.gov Identifier: NCT02375919.

Comparison of the Prognostic Significance of Initial Blood Lactate and Base Deficit in Trauma Patients.

BACKGROUND: Initial blood lactate and base deficit have been shown to be prognostic biomarkers in trauma, but their respective performances have not been compared. METHODS: Blood lactate levels and base deficit were measured at admission in trauma patients in three level 1 trauma centers. This was a retrospective analysis of prospectively acquired data. The association of initial blood lactate and base deficit with mortality was tested using receiver operating characteristics curve, logistic regression using triage scores (Revised Trauma Score and Mechanism Glasgow scale and Arterial Pressure score), and Trauma Related Injury Severity Score as a reference standard. The authors also used a reclassification method. RESULTS: The authors evaluated 1,075 trauma patients (mean age, 39 ± 18 yr, with 90% blunt and 10% penetrating injuries and a mortality of 13%). At admission, blood lactate was elevated in 425 (39%) patients and base deficit was elevated in 725 (67%) patients. Blood lactate was correlated with base deficit (R = 0.54; P < 0.001). Using logistic regression, blood lactate was a better predictor of death than base deficit when considering its additional predictive value to triage scores and Trauma Related Injury Severity Score. This result was confirmed using a reclassification method but only in the subgroup of normotensive patients (n = 745). CONCLUSIONS: Initial blood lactate should be preferred to base deficit as a biologic variable in scoring systems built to assess the initial severity of trauma patients.

Systematic unenhanced CT for acute abdominal symptoms in the elderly patients improves both emergency department diagnosis and prompt clinical management.

OBJECTIVES: To assess the added-value of systematic unenhanced abdominal computed tomography (CT) on emergency department (ED) diagnosis and management accuracy compared to current practice, in elderly patients with non-traumatic acute abdominal symptoms. METHODS: Institutional review board approval and informed consent were obtained. This prospective study included 401 consecutive patients 75 years of age or older, admitted to the ED with acute abdominal symptoms, and investigated by early systematic unenhanced abdominal CT scan. ED diagnosis and intended management before CT, after unenhanced CT, and after contrast CT if requested, were recorded. Diagnosis and management accuracies were evaluated and compared before CT (clinical strategy) and for two conditional strategies (current practice and systematic unenhanced CT). An expert clinical panel assigned a final diagnosis and management after a 3-month follow-up. RESULTS: Systematic unenhanced CT significantly improved the accurate diagnosis (76.8% to 85%, p=1.1x10-6) and management (88.5% to 95.8%, p=2.6x10-6) rates compared to current practice. It allowed diagnosing 30.3% of acute unsuspected pathologies, 3.4% of which were unexpected surgical procedure requirement. CONCLUSIONS: Systematic unenhanced abdominal CT improves ED diagnosis accuracy and appropriate management in elderly patients presenting with acute abdominal symptoms compared to current practice. KEY POINTS: • Systematic unenhanced CT improves significantly diagnosis accuracy compared to current practice. • Systematic unenhanced CT optimizes appropriate hospitalization by increasing the number of discharged patients. • Systematic unenhanced CT allows detection of about one-third of acute unsuspected abdominal conditions. • It should allow boosting emergency department management decision-making confidence in old patients.

Prognostic value of PCT, copeptin, MR-proADM, MR-proANP and CT-proET-1 for severe acute dyspnea in the emergency department: the BIODINER study.

CONTEXT: Acute dyspnea is a frequent complaint in patients attending the emergency department (ED). OBJECTIVE: To evaluate the accuracy of PCT, MR-proANP, MR-proADM, copeptin and CT-proET1 for the risk-stratification of severe acute dyspnea patients presenting to the ED. METHODS: Multicenter prospective study in adult patients with a chief complaint of acute dyspnea. Pro-hormone type biomarkers concentrations were measured on arrival. Combined primary endpoint was a poor outcome. RESULTS: Three hundred and ninety-four patients were included, 137 (35%) met the primary endpoint. MR-proADM was the only biomarker associated with the primary endpoint (odds ratio 1.43 [95%CI: 1.13-1.82], p = 0.003) as were the presence of paradoxical abdominal breathing (odds ratio 2.48 [95%CI: 1.31-4.68]) or cyanosis (odds ratio 3.18 [1.46-6.89]) Conclusions: In patients with severe acute dyspnea in the ED, pro-hormone type biomarkers measurements have a low added value to clinical signs for the prediction of poor outcome.

Outpatient Appendectomy in an Emergency Outpatient Surgery Unit 24 h a Day: An Intention-to-Treat Analysis of 194 Patients.

OBJECTIVE: To evaluate the feasibility and outcomes of patients operated on for uncomplicated acute appendicitis (UAA) in our 24-h emergency outpatient surgery unit. METHODS: This was a prospective observational study with intention-to-treat (ITT) analysis. From 12/2013 to 03/2015, all consecutive patients admitted for acute appendicitis (AA) were prospectively screened. A computed tomography or abdominal ultrasound confirmed the diagnosis of AA. Eligibility criteria for outpatient appendectomy were: UAA, no comorbidity, no physical or mental condition preventing participation in the study, absence of pregnancy, age older than 15 years, an accompanying adult person available for the hospital discharge and place of residence within 1 h of our hospital. In the case of intraoperative complication (abscess, local or general peritonitis) or complication of general anesthesia, patients were excluded from the outpatient pathway. The primary endpoint was the feasibility of outpatient appendectomy among all consecutive patients admitted for UAA. RESULTS: Of the 194 screened patients, 150 (77%) presented an UAA and 102 (68%) were eligible for an outpatient procedure. Thirteen eligible patients (13%) were excluded from the outpatient circuit (7 intraoperative and 6 postoperative contraindications). Outpatient appendectomy was performed in 89 patients, representing 59% (89/150) of the ITT population and 87% (89/102) of the eligible patients. The median length of hospital stay was 13 h. Postoperative complications were observed in six patients (6%). CONCLUSIONS: This study reports a safe and feasible management of UAA. Our organization allows a short hospitalization for postoperative recovery without using conventional surgery beds and enables discharge throughout the night.

Prognostic Accuracy of Sepsis-3 Criteria for In-Hospital Mortality Among Patients With Suspected Infection Presenting to the Emergency Department.

Importance: An international task force recently redefined the concept of sepsis. This task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of systemic inflammatory response syndrome (SIRS) criteria to identify patients at high risk of mortality. However, these new criteria have not been prospectively validated in some settings, and their added value in the emergency department remains unknown. Objective: To prospectively validate qSOFA as a mortality predictor and compare the performances of the new sepsis criteria to the previous ones. Design, Settings, and Participants: International prospective cohort study, conducted in France, Spain, Belgium, and Switzerland between May and June 2016. In the 30 participating emergency departments, for a 4-week period, consecutive patients who visited the emergency departments with suspected infection were included. All variables from previous and new definitions of sepsis were collected. Patients were followed up until hospital discharge or death. Exposures: Measurement of qSOFA, SOFA, and SIRS. Main Outcomes and Measures: In-hospital mortality. Results: Of 1088 patients screened, 879 were included in the analysis. Median age was 67 years (interquartile range, 47-81 years), 414 (47%) were women, and 379 (43%) had respiratory tract infection. Overall in-hospital mortality was 8%: 3% for patients with a qSOFA score lower than 2 vs 24% for those with qSOFA score of 2 or higher (absolute difference, 21%; 95% CI, 15%-26%). The qSOFA performed better than both SIRS and severe sepsis in predicting in-hospital mortality, with an area under the receiver operating curve (AUROC) of 0.80 (95% CI, 0.74-0.85) vs 0.65 (95% CI, 0.59-0.70) for both SIRS and severe sepsis (P < .001; incremental AUROC, 0.15; 95% CI, 0.09-0.22). The hazard ratio of qSOFA score for death was 6.2 (95% CI, 3.8-10.3) vs 3.5 (95% CI, 2.2-5.5) for severe sepsis. Conclusions and Relevance: Among patients presenting to the emergency department with suspected infection, the use of qSOFA resulted in greater prognostic accuracy for in-hospital mortality than did either SIRS or severe sepsis. These findings provide support for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in the emergency department setting. Trial Registration: clinicaltrials.gov Identifier: NCT02738164.

[The hospital care of victims of terrorist attacks]. / La prise en charge hospitalière des victimes des attentats.

The treatment of victims of terrorist attacks in a trauma centre requires the putting in place of plans, training and simulation exercises. Previous experiences have highlighted the areas which require improvement. As exceptional health situations are unpredictable, it is essential to always be vigilant and prepared for an unforeseen event.

Preoperative Score to Predict Postoperative Mortality (POSPOM): Derivation and Validation.

BACKGROUND: An accurate risk score able to predict in-hospital mortality in patients undergoing surgery may improve both risk communication and clinical decision making. The aim of the study was to develop and validate a surgical risk score based solely on preoperative information, for predicting in-hospital mortality. METHODS: From January 1, 2010, to December 31, 2010, data related to all surgeries requiring anesthesia were collected from all centers (single hospital or hospitals group) in France performing more than 500 operations in the year on patients aged 18 yr or older (n = 5,507,834). International Statistical Classification of Diseases, 10th revision codes were used to summarize the medical history of patients. From these data, the authors developed a risk score by examining 29 preoperative factors (age, comorbidities, and surgery type) in 2,717,902 patients, and then validated the risk score in a separate cohort of 2,789,932 patients. RESULTS: In the derivation cohort, there were 12,786 in-hospital deaths (0.47%; 95% CI, 0.46 to 0.48%), whereas in the validation cohort there were 14,933 in-hospital deaths (0.54%; 95% CI, 0.53 to 0.55%). Seventeen predictors were identified and included in the PreOperative Score to predict PostOperative Mortality (POSPOM). POSPOM showed good calibration and excellent discrimination for in-hospital mortality, with a c-statistic of 0.944 (95% CI, 0.943 to 0.945) in the development cohort and 0.929 (95% CI, 0.928 to 0.931) in the validation cohort. CONCLUSION: The authors have developed and validated POSPOM, a simple risk score for the prediction of in-hospital mortality in surgical patients.

Emergency Care for Homeless Patients: A French Multicenter Cohort Study.

OBJECTIVES: To determine whether homeless patients experience suboptimal care in the emergency department (ED) by the provision of fewer health care resources. METHODS: We conducted a prospective multicenter cohort study in 30 EDs in France. During 72 hours in March 2015, all homeless patients that visited the participating EDs were included in the study. The primary health care service measure was the order by the physician of a diagnostic investigation or provision of a treatment in the ED. Secondary measures of health care services included ED waiting time, number and type of investigations per patient, treatment in the ED, and discharge disposition. RESULTS: A total of 254 homeless patients and 254 nonhomeless patients were included. After excluding homeless patients that attended the ED for the sole purpose of housing, we analyzed 214 homeless and 214 nonhomeless. We found no significant difference between the 2 groups in terms of health care resource consumption, and for our secondary endpoints. CONCLUSIONS: We did not find significant differences in the level of medical care delivered in French EDs to homeless patients compared with matched nonhomeless patients.

French Ministry of Health's response to Paris attacks of 13 November 2015.

On Friday November 13th at 9:20 pm, three kamikaze bombs went off around the Stade de France a stadium in Saint-Denis just outside Paris, 4 different shootings took place and bombings in Paris and hundreds of people were held hostage in a theater.This multi-site terrorist attack was the first of this magnitude in France. Drawing the lessons of these attacks and those which occurred in other countries from a health perspective is essential to continuously adapt and improve the French response to possible future attacks. Several issues would need to be further explored: Management of uncertainties: When to trigger the plans: after the 1st attack, the 2nd? When do attacks end and when to release mobilized resources? Management of victims: How to ensure that all victims are secured or taken care of? How to provide assistance when attacks are ongoing? Management of teams: Proper follow-up of persons involved in the response: health professionals, police and firemen, emergency call centers but also civil servants within administration that contributed to the response. Communication: Reactivity of all is a key element to secure appropriate resource is mobilized for the response. All actors have to be able to communicate quickly in a secured way.

Lack of Analgesic Effect Induced by Ropivacaine Wound Infiltration in Thyroid Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Surgical site infiltration with local anesthetic reduces analgesic requests in various types of surgeries. Because thyroid surgery may induce severe postoperative pain, we tested the hypothesis that ropivacaine surgical site infiltration would significantly decrease postoperative administration of morphine in patients undergoing thyroid surgery. METHODS: We performed a double-blind, placebo-controlled superiority trial to assess the efficacy of surgical site analgesia with ropivacaine (10 mL, 75 mg) performed at the end of thyroid surgery in adult patients. The primary end point was the proportion of patients not requiring IV morphine in the postanesthesia care unit. RESULTS: One hundred sixty-three patients completed the study, 85 in the placebo group and 88 in the ropivacaine group. The proportion of patients requiring morphine administration in the postanesthesia care unit (55% vs 53%, P = 0.80), the dose of IV morphine administered (5.6 ± 6.1 vs 5.5 ± 6.0 mg, P = 0.90), the total dose of opioids administered (expressed as oral morphine equivalent dose: 64 ± 27 vs 69 ± 29 mg, P = 0.20), and the visual analog pain scale over the first 24 hours were not significantly different between groups. The incidence of adverse events (36% vs 39%, P = 0.88), morphine-related adverse events (19% vs 17%, P = 0.84), serious adverse events (0% vs 2%, P = 0.50), and the patient satisfaction scores (9 ± 1 vs 9 ± 1, P = 0.70) was not significantly different between the 2 groups. CONCLUSIONS: Surgical site analgesia with ropivacaine at the end of thyroid surgery is not associated with any significant analgesic benefit.

Modification of the ß-Adrenoceptor Stimulation Pathway in Zucker Obese and Obese Diabetic Rat Myocardium.

OBJECTIVES: Although metabolic syndrome is associated with increased sympathetic activity that chronically stimulates ß-adrenoceptors, the ß-adrenoceptor signaling pathway has been poorly studied in this situation. We studied the ß-adrenoceptor signaling pathway in Zucker lean, obese, and obese diabetic rats. DESIGN: Experimental, prospective study. SETTING: University medical research laboratory. SUBJECTS: Adult male Zucker lean (control), obese, and obese diabetic rats. INTERVENTIONS: The effects of ß-adrenoceptor stimulation were investigated in vitro in isolated left ventricular papillary muscles in control, obese, and obese diabetic rats. ß1-, ß2-, and ß3-adrenoceptors and multidrug resistance-associated protein 4 were quantified by Western Blotting. Triglyceride, cholesterol, leptin, adiponectin, and C-peptide plasma concentrations were measured. Data are mean ± SD. MEASUREMENTS AND MAIN RESULTS: Hyperlipidemia, high leptin, and C-peptide concentrations were observed in obese and obese diabetic strains, whereas hyperglycemia occurred only in the diabetic strain. The positive inotropic effect of isoproterenol was slightly reduced in obese rats (183% ± 11% of baseline; p = 0.003; n = 7) and markedly reduced in obese diabetic rats (137% ± 18% of baseline; p < 0.001; n = 10) when compared with control rats (210% ± 17% of baseline; n = 9). ß1-adrenoceptors were down-regulated in obese (-41%; p = 0.02) and diabetic (-54%; p = 0.003) when compared with control rats, whereas ß3-adrenoceptors and multidrug resistance-associated protein expression remained unchanged. Direct stimulation of adenylate cyclase with forskolin or administration of 3',5'-cyclic adenosine monophosphate suggests that subtle impairments also occurred beside the down-regulation of ß1-adrenoceptor. CONCLUSIONS: The positive inotropic effect of ß-adrenoceptor stimulation is slightly decreased in Zucker obese rats and was more markedly decreased in Zucker diabetic rats. These decreases are mainly related to ß1-adrenoceptor down-regulation.

First experience of liver transplantation with type 2 donation after cardiac death in France.

Organ donation after unexpected cardiac death [type 2 donation after cardiac death (DCD)] is currently authorized in France and has been since 2006. Following the Spanish experience, a national protocol was established to perform liver transplantation (LT) with type 2 DCD donors. After the declaration of death, abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate the abdominal organs until harvesting and cold storage. Such grafts were proposed to consenting patients < 65 years old with liver cancer and without any hepatic insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers. Six patients had a rapid and uneventful postoperative recovery. However, primary nonfunction occurred in 3 patients, with each requiring urgent retransplantation, and 4 early allograft dysfunctions were observed. One patient developed a nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a control group of patients receiving grafts from brain-dead donors (n = 41), donor age and cold ischemia time were significantly lower in the type 2 DCD group. Time spent on the national organ wait list tended to be shorter in the type 2 DCD group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar (85% in the type 2 DCD group versus 93% in the control group), but the 1-year graft survival rate was significantly lower in the type 2 DCD group (69% versus 93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT with type 2 DCD donors is possible as long as strict donor selection is observed.

Effects of acute respiratory and metabolic acidosis on diaphragm muscle obtained from rats.

BACKGROUND: Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. METHODS: Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. RESULTS: Respiratory acidosis induced a significant decrease in maximum shortening velocity (-33%, P < 0.001), active isometric force (-36%, P < 0.001), and peak power output (-59%, P < 0.001), slowed relaxation, and decreased the number of cross-bridges (-35%, P < 0.001) but not the force per cross-bridge, and impaired recovery from fatigue. Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction-relaxation coupling under isotonic (-26%, P < 0.001) or isometric (-44%, P < 0.001) conditions. In contrast, no significant differences in diaphragmatic contraction, relaxation, or contraction-relaxation coupling were observed in the metabolic acidosis group. CONCLUSIONS: In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.