P. Bilbault

Influence of drotrecogin alpha (activated) infusion on the variation of Bax/Bcl-2 and Bax/Bcl-xl ratios in circulating mononuclear cells: a cohort study in septic shock patients.

Objective: Drotrecogin alpha (activated) (DAA), or recombinant human activated protein C, is a new treatment in sepsis‐induced multiple organ failure, leading to significant reduction in the mortality rate, thanks to its anticoagulant properties. It has been suggested that DAA has anti‐inflammatory and antiapoptotic effects in sepsis animal models. This study investigates the potential actions of DAA on circulating mononuclear cells apoptosis in human septic shock. Design: Prospective, cohort study. Setting: Two intensive care wards and two research laboratories in a university hospital. Patients: Twenty‐two septic shock patients with DAA treatment (DAA+), 19 septic shock patients without DAA treatment (DAA−), and 14 healthy controls were successively enrolled, but only 20 DAA+ and 16 DAA− patients fulfilled criteria for statistical analysis. Interventions: Blood samples were collected at inclusion and 24 hrs later. Measurements and Main Results: Circulating mononuclear cell apoptosis levels were assessed by flow cytometry with annexin V, and variations of the apoptotic rheostats (Bax/Bcl‐2 and Bax/Bcl‐xl ratios) were analyzed by real‐time reverse transcription‐polymerase chain reaction. Apoptosis was significantly increased in septic shock patients (DAA+, 12 ± 6.4%; DAA−, 10.4 ± 5%) vs. healthy patients (3.4 ± 2.1%, p < .001). Twenty‐four hours after DAA infusion, apoptosis was significantly lower in the DAA+ group compared with DAA− ones (respectively, 11.7 ± 5.3% and 16.2 ± 7.6%, p < .001). At inclusion, DAA+ and DAA− groups showed comparable Bax/Bcl‐2 ratio (DAA+, 0.92 ± 0.9; DAA−, 1.32 ± 0.87) and Bax/Bcl‐xl ratio (DAA+, 2 ± 1.04; DAA−, 1.31 ± 0.93). In contrast, 24 hrs later we observed a significant decrease in these ratios, indicating an antiapoptotic effect in the DAA+ group (Bax/Bcl‐2, 0.39 ± 0.27; Bax/Bcl‐xl, 0.68 ± 0.35) compared with the DAA− group (Bax/Bcl‐2, 1.81 ± 1.1; Bax/Bcl‐xl, 1.22 ± 0.92, p = .001 and p = .039, respectively). Conclusions: In vivo, in human septic shock, DAA has antiapoptotic effects on circulating mononuclear cells, assessed by a significant decrease of both the Bax/Bcl‐2 and Bax/Bcl‐xl ratios.

Rivaroxaban versus standard anticoagulation for symptomatic venous thromboembolism (REMOTEV observational study): Analysis of 6-month outcomes

BACKGROUND This study aimed to provide safety and efficacy data of rivaroxaban in routine patient care in a non-selected symptomatic venous thromboembolism (VTE) population. METHODS AND RESULTS REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with oral rivaroxaban, VKA or parenteral heparin/fondaparinux alone for at least 3months and who are followed up for 6months. From Nov. 2013 to July 2015, 499 consecutive patients were retained for baseline analysis and 445 for safety analysis. The mean age was 65.1years, 7.6% had previously known active cancer, 18.6% had creatinine clearance 30≤CrCl<60mL/min, and 87.8% had pulmonary embolism with or without deep venous thrombosis. The major and clinically relevant bleeding rate was 5.4% (15/280) in the rivaroxaban group, 9.4%/(9/96) in the VKA group and 7.2% (5/69) in the heparin/fondaparinux group. The recurrent VTE rate was 1.4% (4/280) in the rivaroxaban group, 3.1% (3/96) in the VKA group and 11.6% (8/69) in the heparin/fondaparinux group. In the propensity score-adjusted samples, major and clinically relevant non-major bleeding (HR 0.37 [95% CI, 0.15 to 0.93], p<0.05), all-cause death (HR 0.21 [95% CI, 0.06 to 0.66], p<0.01) and the composite of recurrent VTE, major and clinically relevant non-major bleeding and all-cause mortality (HR 0.35 [95% CI, 0.17 to 0.71], p<0.01), were significantly lower in the rivaroxaban group compared to the VKA group. CONCLUSION In REMOTEV 6-month outcomes are consistent with the findings of the phase 3 randomized trials and post-marketing data, with low rates of major bleeding and symptomatic recurrent VTE.

Confusion after spine injury: cerebral fat embolism after traumatic rupture of a Tarlov cyst: Case report

BackgroundAcute low back pain is a very common symptom and reason for many medical consultations. In some unusual circumstances it could be linked to a rare aetiology.Case presentationWe report a 70-year-old man with an 8-month history of left posterior thigh and leg pain who had sudden confusion after a fall from standing. It was due to cerebral fat embolism suspected by computed tomography scan, later confirmed by brain magnetic resonance imaging (MRI). A spinal MRI scan was then performed and revealed a sacral fracture which drained into an unknown perineurial cyst (Tarlov cyst). Under medical observation the patient fully recovered within three weeks.ConclusionsSacral perineurial cysts are rare, however they remain a potential cause of lumbosacral radiculopathy.

Life-threatening cervical necrotizing fasciitis after a common dental extraction.

We report a case of cervical necrotizing fasciitis (NF) with severe sepsis occurring 8 hours after a banal dental extraction in a healthy adult. A 44-year-old man was admitted for cervical NF and severe sepsis in the emergency department. An early diagnosis was based on clinical examination (violent pain, swelling of face, and crepitation), confirmed by computed tomography scan, which showed subcutaneous gas and a fracture of the maxillary sinus in regard of the extracted tooth. Broad spectrum antibiotherapy was started quickly followed by surgical debridement. Operative and sinus pus cultures were positive for polymicrobial strains (aerobes and anaerobe). Ventilatory and hemodynamic supports (large fluid infusion and catecholamine) were mandatory during a week. Successful outcome occurred within 2 weeks. Cervical NF is a rare but life-threatening disease with fulminant course. The mortality rate is high if the diagnosis and treatment are not begun promptly and vigorously. Therefore, the emergency medicine community must be aware of its initial symptoms.

Emergency step-by-step specific immunotherapy in severe digoxin poisoning: an observational cohort study.

Objective To evaluate the efficacy and safety of a step-by-step fixed dose of specific immunotherapy protocol in case of severe digoxin poisoning in an open uncontrolled prospective study. Methods Twenty consecutive patients were admitted because of severe digoxin poisoning. The inclusion criteria were: digoxin overdose and either life-threatening arrhythmia; high-degree atrioventricular block, ventricular arrhythmia, or bradycardia less than 50 bpm and hyperkalaemia (>5.5 mmol/l). A two-step protocol of antidigoxin antibodies treatment was carried out. At admission, every patient received two vials of specific Fab-fragments. If after 1 h following infusion ECG signs regressed, no more treatment was given. If ECG signs did not regress, patients were given two more vials. At inclusion and 6 h after immunotherapy, clinical (cardiac rhythm, ECG records) and biological (serum digoxin concentration, potassium) findings were recorded. Results Patients had a median (interquartile range) age of 83 (75–90) years. Four patients had acute poisoning and 16 chronic overdoses. Eleven patients showed ventricular arrhythmia, and five had high-degree atrioventricular block. Seventy percent of the patients needed only the first step. Significant decreases were observed in the number of cardiac dysrhythmia (16 vs. three patients), in the median (interquartile range) of serum digoxin concentration [5 μg/l (3.8–6.2) vs. 0.4 μg/l (0.3–2.2)] and in serum potassium [4.6 mmol/l (4.1–5.5) vs. 3.85 mmol/l (3.7–4.55)] before and after immunotherapy. The digoxin-related mortality was 5%. Conclusion This protocol of step-by-step digoxin-specific immunotherapy seems to be as effective as the equimolar treatment, and there was significant cost reduction in case of acute poisoning.

Increased risk and severity of unprovoked venous thromboembolism with clustering cardiovascular risk factors for atherosclerosis: Results of the REMOTEV registry

BACKGROUND The role of cardiovascular risk factors (CVRF) for atherosclerosis in venous thromboembolic disease (VTE) is controversial. The aim of this study was to evaluate the impact of CVRF and their cumulative effects on the occurrence of unprovoked VTE, severity, recurrence and survival. METHODS AND RESULTS This is a prospective cohort from the REMOTEV registry including all consecutively hospitalized patients for acute symptomatic VTE. From November 2013 to December 2016, 515 patients with 6months follow-up (FU) were selected for the analysis. Events were classified as unprovoked or provoked VTE. In univariate analysis, hypertension (OR 1.44, [95% CI 1.01-2.06]), diabetes (OR 2.07, [95% CI: 1.25-3.55]) and age (OR 1.94, [95% CI: 1.31-2.88]) were significantly associated with the risk of unprovoked VTE. After adjustment, diabetes (OR 1.82, [95% CI: 1.07-3.18]) and age (OR 1.79, [95% CI: 1.15-2.8]) remained associated with the risk of unprovoked VTE. The proportion of unprovoked VTE increased significantly with the number of CVRF adjusted for thrombophilia (1 CVRF: OR 3 [95% CI: 1.44-6.52]) 2 CVRF: OR 4.33 [95% CI: 2.07-9.49] and ≥3 CVRF: OR 4.58 [95% CI: 2.27-9.7]). The severity of pulmonary embolism was significantly associated with CVRF clustering. There were more VTE recurrences and deaths during the 6months of FU with cumulative CVRF. CONCLUSION The risks of unprovoked VTE and PE severity are associated with clustering CVRF. The role of cumulative CVRF predominates rather than the specific burden of each of the CVRF in the risk of VTE occurrence.

Interleukin-10 gene down-expression in circulating mononuclear cells during infusion of drotrecogin-α activated: a pilot study.

IntroductionThe purpose of this study was to investigate the gene expression of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) in circulating mononuclear cells harvested from septic shock patients on drotrecogin-α activated (DAA) in order to determine whether this treatment has any effect on the inflammation phase.MethodsWe conducted a prospective cohort study in two intensive care departments. Blood samples were collected at inclusion (T1) and 36 hours later (T2) to measure plasma cytokines and the changes in intracellular TNF-α, IL-10 and IFN-γ mRNA expressions using the real-time quantitative polymerase chain reaction (RT-qPCR). Thirty-two septic shock patients were included: 16 with DAA at 24 μg/kg/h for 96 hours (DAA+) and 16 control (DAA-) eligible but contraindicated for DAA because of low platelet count.ResultsThe basal characteristics were similar in both groups: mortality (50%), plasma cytokine concentrations, and baseline IFN-γ, TNF-α and IL-10 mRNA expressions (DAA+ vs. DAA-). At T2, there was a significant IFN-γ gene down-regulation in DAA+ but not in DAA- patients (-0.34 (-0.62; +1.54) vs. +1.41 (+0.35; +5.87), P = 0.008). In survivors, DAA administration was associated with a down-expression of both IFN-γ (-0.65 (-0.93; 0.48) vs. +0.7 (-0.04; +1.26), P = 0.01) and IL-10 (-0.78 (-0.92; -0.6) vs. -0.18 (-0.68; +0.46), P = 0.038). In the non-survivors, DAA infusion was associated with IL-10 over-expression when compared with survivors (+0.54 (-0.35; +11.52) vs. -0.78 (-0.92; -0.6), P < 0.001).ConclusionsIn this study, lack of IL-10 gene down-expression despite a 36-hour infusion of DAA is an ominous sign in septic shock patients suggesting that DAA is not able to reverse the outcome. Our results suggest that DAA can decrease the expression of anti-inflammatory cytokines in septic shock patients. IL-10 or IFN-γ gene down-expression could represent markers of DAA response.

Abrupt alcohol withdrawal: another cause of ketoacidosis often forgotten.

A 54-year-old woman was admitted to our emergency department for acute confusion. She had only a history of chronic alcohol abuse with an abrupt withdrawal. The initial diagnosis was delirium tremens. Biological findings, however, showed a severe degree of metabolic acidosis (plasma pH 7.07, bicarbonate 9.6 mmol/l) with an increased anion gap (39.6 mmol/l). Serum glucose was normal and ketonuria was present. Ketoacidosis was also suspected and treated by fluid infusion and delivery of glucose with a favorable outcome. Differential ketoacidosis is discussed in the emergency room.

Chest pain in young people: Is cannabis a risk factor?

Notwithstanding this, GISTs are the least common of small intestinal malignant neoplasms and, because of their insidious presentation, they are often not suspected prior to surgery. Consequently, their diagnosis is often delayed or even overlooked, and usually it is made after laparotomy and formal pathologic examination.[2] Small bowel tumors are uncommon and can have a long delay prior to diagnosis because they are usually asymptomatic, especially in their early stages, and they often go unrecognized until severe symptoms ensue, which can create surgical emergencies.[2,3] GISTs tend to grow in an extraluminal fashion; however, they can also erode into the lumen of the gastrointestinal tract, inducing significant hemorrhage or anemia from occult bleeding.[4] They can also rupture into the peritoneal cavity causing significant hemorrhage. [5] In addition to symptoms from mass effect or bleeding, GISTs can cause intussusception or, rarely, intestinal obstruction. [1,5] In this case, the patient was asymptomatic until intestinal obstruction developed. Radiological studies such as computed tomographic scans, barium studies, abdominal US, plain film and radionuclide studies may be useful in its pre-operative diagnosis. [1,3] Intussusception is correctly diagnosed pre-operatively in only one-third of the cases. Enteric intussusception is characterized in longitudinal section by an oval “tumor,” which, in cross-section, has a “target” appearance with infolding of bright luminal interfaces giving multiple concentric rings, which was present in this case. Their biological behavior is difficult to predict, ranging from benign to malignant, thus rendering their size and mitotic index the most reliable prognostic factors.

Une cause inattendue de gonalgie

Un homme, âgé de 81 ans, consultait aux urgences pour une ouleur du genou gauche survenue la veille en se relevant de la osition assise. L’examen clinique retrouvait une impotence foncionnelle totale du membre inférieur avec une douleur localisée à la ace latérale du genou. Il n’existait pas autre anomalie clinique, en articulier pas d’épanchement articulaire ni d’anomalie vasculaire u neurologique. Des radiographies du genou étaient pratiquées uis complétées par un scanner (Fig. 1).