Influence of surgical bleeding on the relationship between admission coagulopathy and risk of massive transfusion: lesson from 704 severe trauma patients.

BACKGROUND: This study hypothesized that the relationship between early coagulopathy and massive transfusion (MT) in trauma was highly dependent on the presence of surgical bleeding. METHODS: Consecutive severe trauma patients admitted to our institution over a 4-year period were included in this retrospective study. Surgical bleeding was defined as an injury requiring an invasive endovascular or surgical haemostatic procedure. The ability of prothrombin time ratio (PTr) and activated partial thromboplastin time ratio (aPTTr) to predict MT (≥10 units of packed red blood cells during the first 24 h) was determined by ROC curves. The strength of association and interaction between PTr, surgical bleeding and MT was assessed using a logistic regression analysis. RESULTS: Among the 704 patients included (ISS 21·0 ± 16·2), MT rate was higher in patients with surgical bleeding than in those with no surgical bleeding (47% vs. 5%; P < 0·001). The global performance of PTr and aPTTr to predict MT was only fair in our study population (AUCs 0·83 and 0·81). MT rate was widely higher in the surgical bleeding group whatever the severity of coagulopathy (P < 0·001). PTr was found to be significantly associated with TM [PTr ≥ 1·5, OR 23·6 (95% CI 13·4-41·7); PTr 1·2-1·5, OR 3·0 (95% CI 1·7-5·3)]. Corresponding ORs were reduced after adjusting for the surgical bleeding: 12·1 (95% CI 6·5-22·5) and 2·1 (95% CI 1·2-4·0), respectively. However, no significant interaction was found regression models. CONCLUSION: The strength of association between MT and coagulation status on admission was found strongly influenced by surgical bleeding. The admission coagulopathy monitoring in trauma patients without considering the surgical bleeding does not allow a reliable determination of MT probability.

Early macrophage response to obesity encompasses Interferon Regulatory Factor 5 regulated mitochondrial architecture remodelling.

Adipose tissue macrophages (ATM) adapt to changes in their energetic microenvironment. Caloric excess, in a range from transient to diet-induced obesity, could result in the transition of ATMs from highly oxidative and protective to highly inflammatory and metabolically deleterious. Here, we demonstrate that Interferon Regulatory Factor 5 (IRF5) is a key regulator of macrophage oxidative capacity in response to caloric excess. ATMs from mice with genetic-deficiency of Irf5 are characterised by increased oxidative respiration and mitochondrial membrane potential. Transient inhibition of IRF5 activity leads to a similar respiratory phenotype as genomic deletion, and is reversible by reconstitution of IRF5 expression. We find that the highly oxidative nature of Irf5-deficient macrophages results from transcriptional de-repression of the mitochondrial matrix component Growth Hormone Inducible Transmembrane Protein (GHITM) gene. The Irf5-deficiency-associated high oxygen consumption could be alleviated by experimental suppression of Ghitm expression. ATMs and monocytes from patients with obesity or with type-2 diabetes retain the reciprocal regulatory relationship between Irf5 and Ghitm. Thus, our study provides insights into the mechanism of how the inflammatory transcription factor IRF5 controls physiological adaptation to diet-induced obesity via regulating mitochondrial architecture in macrophages.

[Digoxin-Josamycin: a dangerous drug interaction in children]. / Digoxine-Josamycine: une interaction dangereuse chez l'enfant.

Digitalis intoxication is usually accidental in children. We report the case of a young infant with congenital heart disease in whom the coadministration of digoxin and josamycin led to a 50% increase in the digoxin concentration, generating sinoatrial block and cardiac failure. Clinical and electrocardiographic symptoms very quickly resolved following immunotherapy with antidigitalis Fab fragments. Digoxin concentrations must be carefully monitored in patients concomitantly receiving macrolides to ensure that the digoxin dose can be readjusted if necessary.

A haemoperitoneum does not indicate active bleeding in the peritoneum in 50% of hypotensive blunt trauma patients: a study of 110 severe trauma patients.

BACKGROUND: We hypothesised that in blunt trauma patients with haemodynamic instability and haemoperitoneum on hospital admission, the haemorrhagic source may not be confined to the peritoneum. The purpose of this study was to describe the incidence and location of bleeding source in this population. METHODS: The charts of trauma patients admitted consecutively between January 2005 and January 2010 to our level I Regional Trauma Centre were reviewed retrospectively. All hypotensive patients presenting a haemoperitoneum on admission were included. Hypotension was defined by a systolic blood pressure ≤ 90 mmHg. The haemoperitoneum was quantified on CT images or from operative reports as moderate (Federle score<3 or between 200 and 500 ml) or large (Federle score ≥ 3 or >500 ml). Active bleeding (AB) was defined as injury requiring a surgical or radiologic haemostatic procedure, regardless of origin (peritoneal (PAB) or extraperitoneal (EPAB)). RESULTS: Of 1079 patients admitted for severe trauma, 110 patients met the inclusion criteria. Seventy-eight (71%) were male, mean age 35.3 (SD 19) years and mean ISS 36.5 (SD 20.5). Among the 91 patients who had AB, 37 patients (41%) had PAB, 34 (37%) had EPAB and 20 had both (22%). Forty-eight (53%) of them had moderate haemoperitoneum and 43 (47%) had large haemoperitoneum. A large haemoperitoneum had positive predictive value for PAB of 88% (95% CI 75-95%) and negative predictive value of 65% (95% CI 49-79%). The corresponding values in the subgroup of patients with EPAB were 65% (95% CI 38-86%) and 76% (95% CI 59-88%). CONCLUSION: Haemoperitoneum was associated with PAB in only 52% of hypotensive blunt trauma patients and 63% of bleeding patients. In contrast, 59% of bleeding patients had at least one EPAB. The screening of a haemoperitoneum as a marker of active haemorrhagic source may be confusing and lead to misdiagnosis and inappropriate strategy. Clinician should exclude carefully the presence of any EPAB explaining haemorrhagic shock, before to decide haemostatic treatment.

Effect of renal angioembolization on post-traumatic acute kidney injury after high-grade renal trauma: a comparative study of 52 consecutive cases.

BACKGROUND: Acute kidney injury (AKI) is associated with unfavourable outcomes and higher mortality after trauma. Renal angioembolization (RAE) has proved efficiency in the management of high-grade renal trauma (HGRT), but inevitably expose to unavoidable ischaemic areas or contrast medium nephrotoxicity which may impair renal function in the following hours. The aim of this study was to assess the potential acute impact of RAE on renal function in a consecutive series of HGRTs treated nonoperatively. MATERIALS AND METHODS: Of 101 cases of renal trauma admitted to our Regional Trauma Center between January 2005 and January 2010, 52 cases of HGRT were treated nonoperatively; they were retrospectively classified into 2 groups according to whether RAE was used. Incidence and progression of AKI (RIFLE classification), maximum increase in serum creatinine (SCr), level since admission and recovery of renal function at discharge were compared between the groups. Multivariable analysis was performed to determine the role of RAE as an independent risk factor of AKI. RESULTS: RAE was performed in 10 patients within the first 48h. The RAE and no RAE groups were comparable in terms of severity score, renal injury grade, and level of SCr on admission. AKI incidence (RIFLE score Risk or worse) after 48 and 96h was 33% and 10%, respectively and did not differ significantly between groups at 48h (p=1.00) or 96h (p=1.00). The median maximum increase in SCr was significantly higher in no RAE than RAE group (30.4% vs. 6.9%, p=0.04). RAE was not found to be a significant variable in a multiple linear regression analysis predicting maximum SCr rise (p=0.34). SCr at discharge was >120% of baseline in only 5 patients, with no difference according to RAE (p=0.24). CONCLUSION: In a population of nonoperatively treated HGRT, the incidence of AKI decreased from almost 30% to 10% at 48h and 96h. RAE proceeding did not seem to affect significantly the occurrence and course of AKI or renal recovery. The decision to use RAE should probably not be restricted by fear of worsening renal function.

Studies on pancreatic stones. II. Citrate secretion in the canine pancreatic juice.

In a previous study, we found that pancreatic stones could be dissolved in vitro by a citrate solution. We then decided to look for the possible secretion of citrate into the pancreatic juice, and to find a means of increasing it. Pancreatic juice secretion was collected in Thomas fistula dogs submitted to four protocols: basal conditions, secretin stimulation (0.5 and 2.0 U . kg-1 . h-1), caerulein boluses (25 and 100 ng . kg-1) superimposed on 0.5 U . kg-1 . h-1 secretion and intraduodenal citrate infusion (1.05 mmol . kg-1 . h-1). Under basal conditions mean citrate output per 15 min was 0.11 +/- 0.02 mumol. During secretin and caerulein stimulation, citrate output paralleled that of protein, and a linear regression was calculated: Ycitrate = -0.013 + 0.019 Xprotein (mumol/mg). Intraduodenal citrate infusion induced a sharp increase in citrate output which reached 11.5 mumol/15 min, but only 0.12% of the infused citrate amount was secreted into pancreatic juice during 1 h.

[Thiamine deficiency in chronic alcoholics. Value of pre- and postoperative treatment]. / Carence en thiamine chez les éthyliques chroniques. Intérêt du traitement pré et post opératoire.

Thiamine deficiency in the chronic alcoholic would appear to have a triple origin: inadequate intake, absorption and utilisation. Its consequences are well known: peripheral neuropathy, WERNICKE and KORSAKOFF type encephalopathies and cardiac problems (with asystole at the extreme). The active principle of thiamine, TPP or cocarboxylase, is involved as a coenzyme of pyruvate decarboxylase and of alphaketoglutarate decarboxylase in the ocidative decarboxylation reactions of the Krebs cycle. TPP is involved as a coenzyme of transketolase in the transketolisation reactions of the pentose pathway. The stimation of transketolase demonstrates a deficiency in thiamine. Fourteen patients suffering from surgical ENT malignancies were involved in the present study. Seven patients received vitamin B therapy before and after the operation. The results showed a significant decrease in thiamine deficiency. Seven were used as controls and did not receive vitamin B therapy. Transketolase estimations showed and increase in the deficiency. Thiamine deficiency exists in the chronic alcoholic and may be corrected by the administration of B vitamins.

Controlled trial of 3-day quinine-clindamycin treatment versus 7-day quinine treatment for adult travelers with uncomplicated falciparum malaria imported from the tropics.

We conducted a randomized, double-blind, placebo-controlled trial to compare a 3-day quinine-clindamycin regimen (group QC) with a 7-day quinine regimen (group Q) for the treatment of uncomplicated Plasmodium falciparum malaria in travelers returning from the tropics. A total of 55 and 53 patients in groups Q and QC were analyzed, respectively. Adverse effects were similar in both groups, although two patients in group Q had severe adverse reactions, leading to the cessation of treatment. The 28-day cure rate for the evaluated patients (per-protocol analysis) was 100% for group QC, whereas it was 96.3% for group Q (P = 0.5). The 28-day cure rate in the intention-to-treat analysis was 96.2% for group QC, whereas it was 94.6% for group Q (P = 1). There were no significant differences between the two regimens with regard to parasite and fever clearance times. Our study shows that the 3-day quinine-clindamycin regimen is well tolerated and compares favorably with a 7-day quinine treatment. This short-term regimen had previously been evaluated only in areas of endemicity. According to our results, the 3-day quinine-clindamycin regimen may be an alternative for the treatment of imported uncomplicated P. falciparum malaria in travelers returning from the tropics.

1,4-Dimethoxy-9(10H)-acridinone derivatives. Synthesis, DNA binding studies and trypanocidal activity.

New acridinonic derivatives, which are hydroxy- and methoxy-substituted in positions 1, 4, and 1,4 were prepared with a view to obtain antiparasitic drugs. These compounds were tested against Trypanosoma cruzi strains and their capability of interacalation into DNA was determined. Nucleus substitutions, DNA binding, and trypanocidal activities have been correlated.