[Lower limb venous thrombosis : Management in the acute phase]. / La thrombose veineuse profonde des membres inférieurs : Prise en charge en aigu.

Venous thromboembolism is the third cardiovascular disease in Europe. The cornerstone of the treatment of deep vein thrombosis is anticoagulation. It aims at avoiding harmful complications : thrombosis extension and recurrence, pulmonary embolism and post-thrombotic syndrome. Due to low molecular weight heparins, and recently, to direct oral anticoagulants, most of the patients can get treatment as outpatients. Unfortunately, despite guideline publications, the management of these patients may be complicated in real life and not correspond to evidence-based medicine. This paper aims at helping the practitian when dealing with this potentially dangerous and often misleading disease. The management of the patient after a 3 to 6-month coagulation treatment will be discussed later in a dedicated paper.

La maladie thrombo-embolique veineuse est la troisième maladie cardio-vasculaire en Europe. Le traitement de la thrombose veineuse repose essentiellement sur l'anticoagulation qui vise à prévenir de redoutables complications : extension et récidive de la thrombose, embolie pulmonaire et syndrome post-thrombotique. Grâce aux héparines de bas poids moléculaire et, plus récemment, aux anticoagulants oraux directs, la majorité des patients peut être traitée en ambulatoire. Pourtant, malgré les recommandations qui ont été publiées, force est de constater que celles-ci ne sont pas toujours respectées dans la «vraie vie¼. Le but de cet article est d'aider le praticien dans la prise en charge initiale d'une pathologie potentiellement dangereuse et parfois difficile à cerner. La prise en charge du patient après 3 à 6 mois de traitement sera discutée dans un article ultérieur.

[Management of coronary artery disease at the acute phase]. / Prise en charge d'une mnaladie coronarienne au stade aigu.

In patients with acute coronary syndrome (ACS), early management is of prime importance. However, the median time taken by the patient to call the emergency services is often very long, up to 2 hours. The presence of a physician as first responder ensures good quality resuscitation in case of cardiac arrest, and allows recording of a first ECG, which can be very informative, especially in ACS without ST segment elevation. Treatment at this stage is limited to sublingual nitroglycerin and aspirin. If the first ECG shows ST segment elevation, the patient should be immediately oriented for reperfusion, usually by percutaneous coronary intervention. in the absence of ST segment elevation, the diagnosis of ACS remains unconfirmed. This does not imply that the risk is lesser, but rather that the risk cannot be evaluated accurately in the pre-hospital setting. The use of risk scores can guide the choice of management towards an invasive strategy, including coronary angiography (immediately, or within 24-72 hours). Low-risk patients are candidates for an invasive strategy, provided non-invasive tests demonstrate the presence of ischemia. During the hospital phase, antiplatelet treatment should be initiated and must be adapted to the patient bleeding and thrombotic risk. Clopidogrel is recommended only in patients who are not amenable to prasugrel or ticagrelor. Statin therapy should be initiated from day one, regardless of the initial cholesterol level, preferably with 80 mg atorvastatin. Angiotensin-converting enzyme inhibitors and beta-blockers should also be prescribed to complete the medical prescription both in-hospital and in the long term.

[Treatment of hepatitis E virus infection]. / Traitement de l'infection par le virus de l'hépatite E.

The reduction of immunosuppressive therapy is the first-line therapeutic option in transplant-patients with chronic hepatitis E virus infection. Pegylated-interferon has been used for treating hepatitis E virus infection. Ribavirin alone is the treatment of choice of hepatitis E virus infection. Ribavirin is efficient for treating chronic hepatitis E in transplant patients, HIV patients, and hematology patients receiving or not chemotherapy. Ribavirin should be given to patients presenting hepatitis E virus associated extra-hepatic manifestations. The place of ribavirin therapy at acute phase is yet to be determined.

Fresh frozen plasma for the treatment of hereditary angioedema acute attacks.

OBJECTIVE: To determine the safety and efficacy of fresh frozen plasma (FFP) infusion for the treatment of hereditary angioedema (HAE). METHODS: The medical records of patients with HAE admitted to Peking Union Medical College Hospital who had received FFP infusion during 2004 and 2010 were reviewed and PubMed database from 1966 to the present were searched using the following hereditary angioedema and fresh frozen plasma. The patient's age, sex, body location of HAE attacks, the dose of FFP infusion, time of beginning to improvement, time to complete remission, complication, C1 inhibitor activity, and outcome were analyzed. RESULTS: A total of 13 enrolled patients (7 male and 6 female) received 16 times of FFP infusion, including 2 patients undergoing FFP infusion in Peking Union Medical College Hospital and 11 patients reported in the literature. The mean dosage of FFP infusion was 586∓337 mL. Two cases suffered from worsening abdominal pain and one case experienced skin rash. Only 1 patient had no improvement in symptom owing to transfusion related reaction. There was a definite improvement in symptom 49∓19 minutes after beginning FFP infusion. The remission time decreased from 61.7∓27.0 hours to 3.3 (2.0, 12.0) hours after FFP infusion. FFP infusion was effective for both type I and type II HAE. CONCLUSION: FFP seems to be safe and effective for acute attacks of HAE.

Downgrading MELD improves the outcomes after liver transplantation in patients with acute-on-chronic hepatitis B liver failure.

BACKGROUND: High score of model for end-stage liver diseases (MELD) before liver transplantation (LT) indicates poor prognosis. Artificial liver support system (ALSS) has been proved to effectively improve liver and kidney functions, and thus reduce the MELD score. We aim to evaluate whether downgrading MELD score could improve patient survival after LT. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and twenty-six LT candidates with acute-on-chronic hepatitis B liver failure and MELD score ≥30 were included in this prospective study. Of the 126 patients, 42 received emergency LT within 72 h (ELT group) and the other 84 were given ALSS as salvage treatment. Of the 84 patients, 33 were found to have reduced MELD score (<30) on the day of LT (DGM group), 51 underwent LT with persistent high MELD score (N-DGM group). The median waiting time for a donor was 10 for DGM group and 9.5 days for N-DGM group. In N-DGM group there is a significantly higher overall mortality (43.1%) than that in ELT group (16.7%) and DGM group (15.2%). N-DGM (vs. ECT and DGM) was the only independent risk factor of overall mortality (P = 0.003). Age >40 years and the interval from last ALSS to LT >48 h were independent negative influence factors of downgrading MELD. CONCLUSIONS/SIGNIFICANCE: Downgrading MELD for liver transplant candidates with MELD score ≥30 was effective in improving patient prognosis. An appropriate ALSS treatment within 48 h prior to LT is potentially beneficial.

Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy.

BACKGROUND: Although cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI. METHODS: Rats underwent a controlled cortical impact (CCI) injury or sham injury, were killed at 6, 12, 24, 48, and 72 hours, and intracerebral fluid (IF) was isolated from the direct injury, penumbral, ipsilateral frontal, and contralateral regions. Cortical and hippocampal areas were also isolated. Regional cytokine levels were measured. Polymorphonuclear cell (PMN) oxidative burst and marker expression were assessed after incubation with the IF. Immunohistochemistry was used to identify intracerebral CD68(+) cells (microglia/macrophages). RESULTS: The proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor-alpha were significantly elevated after CCI in the injury and penumbral regions. Increases in the same cytokines were localized to the cortex and the hippocampus. Increased PMN expression of CD11b and L-selectin was identified after incubation with injury or penumbral area IF, without change in PMN oxidative burst. CD68(+) cells were noted in the direct injury and penumbral areas. CONCLUSION: The local cerebral milieu in the first 48 hours after TBI is highly proinflammatory. This response is most pronounced in areas at or proximal to the direct injury. The local, acute proinflammatory response after TBI may serve as a therapeutic target of early cell therapy or, conversely, may create an unfavorable local milieu, limiting the efficacy of early cellular therapy.

Intracranial vertebral artery dissection with subarachnoid hemorrhage: clinical characteristics and outcomes in conservatively treated patients.

OBJECT: Intracranial vertebral artery (VA) dissection with subarachnoid hemorrhage is notorious for frequent rebleeding and a poor prognosis. Nevertheless, some patients survive with a good final outcome. The factors associated with the prognosis of this disease are not fully understood and appropriate treatment strategies continue to be debated. The authors retrospectively evaluated the clinical features of conservatively treated patients to elucidate the relationship between the clinical and angiographic characteristics of the disease and final outcomes. METHODS: This study includes 24 patients who were treated by conservative methods between 1990 and 2000. Conservative treatment was chosen because of delayed diagnosis, poor clinical condition, or anatomical features such as bilateral lesions and contralateral VA hypoplasia. Of nine patients with an admission Hunt and Kosnik Grade I or II, eight had good outcomes (mean follow-up period 8 years and 4 months). All 15 patients with Grade III, IV, or V died and in 10 of these the cause of death was rebleeding. Among the 24 patients, 14 suffered a total of 35 rebleeding episodes; in 10 (71.4%) of these 14 patients rebleeding occurred within 6 hours and in 13 (93%) within 24 hours. Compared with the survivors, there was a female preponderance (0.022) among patients who died. These patients also had significantly shorter intervals between onset and hospital admission (p = 0.0067), a higher admission Hunt and Kosnik grade (p = 0.0001), a higher incidence of prehospitalization (p = 0.0296) and postadmission (p = 0.0029) rebleeding episodes, and a higher incidence of angiographically confirmed pearl-and-string structure of the lesion (p = 0.0049). CONCLUSIONS: In our series of preselected patients, poor admission neurological grade, rebleeding episode(s), and lesions with a pearl-and-string structure were predictive of poor outcomes. Our findings indicate that patients with these characteristics may be candidates for aggressive attempts to prevent rebleeding during the acute stage. Patients without these characteristics may be good candidates for conservative treatment, especially those who survive the acute phase without rebleeding.

[Acute-phase reaction]. / Le syndrome inflammatoire.

The systemic changes induced by inflammation have been referred as the acute-phase response. The changes in the concentrations of acute-phase proteins are due largely to changes in their production by hepatocytes induced by pro-inflammatory cytokines. Because of its specificity, sensibility and short half-life, C-reactive protein is the most useful indicator among all the acute-phase proteins. The clinical strategy to deal with an acute-phase response is to search the aetiology: infections, neoplasms, auto-immune and allergic diseases. The treatment of an acute-phase response is the treatment of its aetiology.

High frequency percussive ventilation and conventional ventilation after smoke inhalation: a randomised study.

Inhalation injury and bacterial pneumonia represent some of the most important causes of mortality in burn patients. Thirty-five severely burned patients were randomised on admission for conventional ventilation (CV; control group) versus high frequency percussive ventilation (HFPV; study group). HFPV is a ventilatory mode, introduced 10 years ago which combines the advantages of CV with some of those of high frequency ventilation. Arterial blood gases, ventilatory and hemodynamic variables were recorded for 5 days at 2h intervals. Incident complications were classically managed. A statistical analysis (Student's t-test and Wilcoxon signed rank test) demonstrated a significant higher PaO(2)/FiO(2) from days 0 to 3 in the HFPV group. No significant differences were observed for the other parameters. Our findings suggest that HFPV can improve blood oxygenation during the acute phase following inhalation injury allowing reduction of FiO(2). No significant differences were observed between groups for mortality nor incidence of infectious complications in this study.

Reacao tipo I em paciente virchoviano dez anos apos cura clinica / Type I reaction in lepromatous patients ten years after cura

É apresentado o caso de um paciente virchoviano tratado com rifampicina e dapsona durante seis meses e depois somente com dapsona durante 14 anos. Depois de permanecer sem lesões e com baciloscopia negativa por 10 anos, voltou a apresentar lesões, desta vez do tipo dimorfo e com aparecimento de bacilos. Os autores sugerem que paciente sempre tenha sido um dimorfo e que havia piorado a ponto de apresentar aspectos virchovianos. Quando os bacilos voltaram a aparecer, a imunidade celular que o paciente sempre teve começou a destruí-los e daí o aparecimento de lesões dimorfas como deve ter sido no início de sua doença. Eles discutem também as causas possíveis que levaram os bacilos, possivlmente persistentes, a voltarem a se multiplicar.

Evaluation of TNF-alpha and IL-1 blockade in collagen-induced arthritis and comparison with combined anti-TNF-alpha/anti-CD4 therapy.

We have evaluated the effects of anti-TNF-alpha, anti-IL-1, and combined anti-TNF-alpha/anti-CD4 therapy in collagen-induced arthritis. Blockade of TNF-alpha or IL-1 before disease onset delayed, but did not prevent, the induction of arthritis. When treatment was initiated after onset of arthritis, anti-TNF-alpha, anti-IL-1beta, and anti-IL-1R (which blocks IL-1alpha and IL-1beta) were all found to be effective in reducing the severity of arthritis, with anti-IL-1R and anti-IL-1beta showing greater efficacy than anti-TNF-alpha. Anti-IL-1beta was equally as effective as anti-IL-1R, indicating that IL-1beta plays a more prominent role than IL-1alpha in collagen-induced arthritis. An additive effect was observed between anti-TNF-alpha and anti-IL-1R in the prevention of joint erosion and in normalization of the levels of serum amyloid P. Combined anti-TNF-alpha/anti-CD4 therapy also caused normalization of serum amyloid P levels. The therapeutic effect of anti-TNF-alpha plus anti-CD4 was comparable to that of anti-TNF-alpha plus anti-IL-1R, suggesting that combined anti-TNF-alpha/anti-CD4 therapy prevents both TNF-alpha- and IL-1-mediated pathology. Anti-TNF-alpha treatment reduced IL-1beta expression in the joint and, conversely, anti-IL-1beta treatment reduced TNF-alpha expression. Combined anti-TNF-alpha/anti-CD4 treatment almost completely blocked the expression of IL-1beta, thereby confirming the ability of this form of combination therapy to prevent IL-1ss-mediated pathology.

Respuesta inflamatoria sistémica: definiciones, marcadores inflamatorios y posibilidades terapéuticas / Systemic inflammatory response: definitions, inflammatory markers and therapeutic possibilities

Introducción. Se analizan las definiciones y las teorías fisiopatológicas que se han elaborado para explicar la evolución del síndrome inflamatorio hacia la disfunción multisistémica, analizando el valor predictivo de los diferentes mediadores y de los cambios metabólicos. Tras revisar las características del síndrome inflamatorio se recogen los diferentes intentos terapéuticos para modular el SIRS. Material. Se ha revisado la bibliografía recogida en Medline, fundamentalmente estudios clínicos realizados en pacientes críticos. Resumen. Se describen tres síndromes (SIRS, CARS y MARS) que pueden configurar la respuesta inflamatoria. La evolución hacia la disfunción multisistémica es explicada por diversas teorías, pero queda por estudiar los mecanismos que permiten la modulación y supresión de la respuesta inflamatoria. A pesar de su importancia fisiopatológica, las citocinas de inicio no son buenos marcadores pronósticos. Los marcadores de fase aguda, así como los cambios en el metabolismo lipídico y del hierro, muestran una mejor correlación con la evolución. Tras comentar que la respuesta inflamatoria no es proporcional, estructural ni universal, se revisan los diversos intentos terapéuticos que pretenden antagonizar dicha respuesta. Se comentan las tres líneas que deben regir para las investigaciones futuras (AU)

Attenuation of the acute-phase response in thermally injured rats by cholesterol-containing cationic liposomes used as a delivery system for gene therapy.

HYPOTHESIS: Cholesterol-containing cationic liposomes alone modulate the acute-phase response and cytokine expression in thermally injured rats and are an effective delivery system for gene therapy in trauma. SETTING: Laboratory. INTERVENTION: Fifty-six adult male Sprague-Dawley rats with a full-thickness scald burn covering 60% of total body surface area were randomly divided into 2 groups to receive either intravenous injections of cholesterol-containing cationic liposomes or saline (control). MAIN OUTCOME MEASURES: Body weights, muscle and liver dry-wet weights, serum levels of constitutive hepatic proteins, acute-phase protein levels, and cytokine levels were determined at 1, 2, 5, and 7 days after thermal injury. RESULTS: Rats receiving cholesterol-containing cationic liposomes had less body weight loss, increased serum transferrin levels, and decreased serum alpha1-acid glycoprotein levels when compared with controls (P<.05). Serum interleukin 1beta and tumor necrosis factor alpha levels were decreased in rats receiving liposomes at 1 and 2 days after burn compared with controls (P<.05). CONCLUSIONS: These results suggest that cholesterol-containing cationic liposomes alone may have a beneficial effect in modulating the hypermetabolic response after burn injury by decreasing type 1 acute-phase proteins and the expression of the proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha. Therefore, cholesterol-containing cationic liposomes appear to be suitable as a delivery system for gene therapy in trauma.

Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis.

BACKGROUND: In patients with major trauma and burns, total enteral nutrition (TEN) significantly decreases the acute phase response and incidence of septic complications when compared with total parenteral nutrition (TPN). Poor outcome in acute pancreatitis is associated with a high incidence of systemic inflammatory response syndrome (SIRS) and sepsis. AIMS: To determine whether TEN can attenuate the acute phase response and improve clinical disease severity in patients with acute pancreatitis. METHODS: Glasgow score, Apache II, computed tomography (CT) scan score, C reactive protein (CRP), serum IgM antiendotoxin antibodies (EndoCAb), and total antioxidant capacity (TAC) were determined on admission in 34 patients with acute pancreatitis. Patients were stratified according to disease severity and randomised to receive either TPN or TEN for seven days and then re-evaluated. RESULTS: SIRS, sepsis, organ failure, and ITU stay, were globally improved in the enterally fed patients. The acute phase response and disease severity scores were significantly improved following enteral nutrition (CRP: 156 (117-222) to 84 (50-141), p < 0.005; APACHE II scores 8 (6-10) to 6 (4-8), p < 0.0001) without change in the CT scan scores. In parenterally fed patients these parameters did not change but there was an increase in EndoCAb antibody levels and a fall in TAC. Enterally fed patients showed no change in the level of EndoCAb antibodies and an increase in TAC. CONCLUSION: TEN moderates the acute phase response, and improves disease severity and clinical outcome despite unchanged pancreatic injury on CT scan. Reduced systemic exposure to endotoxin and reduced oxidant stress also occurred in the TEN group. Enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial.

[Mechanisms of action of intravenous immunoglobulins]. / Wirkmechanismen intravenöser Immunglobuline.

Intravenous immunoglobulins (IVIG) are now used to treat various diseases, including autoimmune diseases, systemic inflammatory diseases, allografts and for replacement therapy in the case of IgG deficiency. Only in some of the indications has the efficacy of this treatment been confirmed in large-scale studies. Also, in many cases the modes of action remain unclear. Principally, the following therapeutic strategies can be differentiated: Replacement treatment, blocking of the effector molecules, influencing of the cellular and humoral limbs of the immune defence system and interaction with cytokines. In certain CNS diseases, displacement of pathological immunoglobulins may be involved. It would be desirable to acquire more detailed knowledge about modes of action with the aim of using IVIG with greater specificity in the future.