The Genomic Grade Index predicts postoperative clinical outcome in patients with soft-tissue sarcoma.

Background: Soft-tissue sarcomas (STSs) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. We hypothesized that the Genomic Grade Index (GGI), a 108-gene signature previously developed in early-stage breast cancer, might improve the prognostic assessment of patients with early-stage STS. Patients and methods: We collected gene expression and clinicopathological data of 678 operated STS, and searched for correlations between the GGI-based classification and clinicopathological variables, including the metastasis-free survival (MFS). Results: Based on GGI, 275 samples (41%) were classified as 'GGI-low' and 403 (59%) as 'GGI-high'. The 'GGI-high' class was more associated with poor-prognosis features than the 'GGI-low' class: pathological grade 3 (P = 9.50E-11), undifferentiated sarcomas and leiomyosarcomas (P < 1.00E-06), location in extremities (P < 1.00E-06), and complex genetic profile (P = 2.1E-20). The 5-year MFS was 53% (95%CI 47-59) in the 'GGI-high' class versus 78% (95%CI 72-85) in the 'GGI-low' class (P = 3.02E-11), with a corresponding hazard ratio for metastatic relapse equal to 2.92 (95%CI 2.10-4.07; P = 2.23E-10). In multivariate analysis, the GGI-based classification remained significant, whereas the pathological grade did not. In fact, the GGI-based classification stratified the patients with pathological grades 1 and 2 and those with pathological grade 3 in two classes with different 5-year MFS. Comparison of the GGI and CINSARC multigene signatures revealed similar correlations with clinicopathological variables, which were, however, stronger with GGI than with CINSARC, a strong concordance (71%) in terms of low-risk or high-risk classifications, and independent prognostic value for MFS in multivariate analysis, suggesting complementary prognostic information. Conclusion: GGI refines the prediction of MFS in operated STS and might improve the tailoring of adjuvant chemotherapy. Further clinical validation is warranted in larger retrospective, then prospective series, as well as the functional validation of relevant genes that could provide new therapeutic targets.

Correlation between overall survival and growth modulation index in pre-treated sarcoma patients: a study from the French Sarcoma Group.

BACKGROUND: Growth modulation index (GMI), the ratio of two times to progression measured in patients receiving two successive treatments (GMI = TTP2/TTP1), has been proposed as a criterion of phase II clinical trials. Nevertheless, its use has been limited until now. PATIENTS AND METHODS: We carried out a retrospective multicentre study in soft tissue sarcoma patients receiving a second-line treatment after doxorubicin-based regimens to evaluate the link between overall survival and GMI. Second-line treatments were classified as 'active' according to the EORTC-STBSG criteria (3-month progression-free rate >40% or 6-month PFR >14%). Comparisons used chi-squared and log-rank tests. RESULTS: The population consisted in 106 men and 121 women, 110 patients (48%) received 'active drugs'. Median OS from the second-line start was 317 days. Sixty-nine patients experienced GMI >1.33 (30.4%). Treatments with 'active drug' were not associated with OS improvement: 490 versus 407 days (P = 0.524). Median OS was highly correlated with GMI: 324, 302 and 710 days with GMI <1, GMI = [1.00-1.33], and GMI >1.33, respectively (P < 0.0001). In logistic regression analysis, the sole predictive factor was the number of doxorubicin-based chemotherapy cycles. CONCLUSION: GMI seems to be an interesting end point that provides additional information compared with classical criteria. GMI >1.33 is associated with significant OS improvement.

[Sinus node dysfunction associated with cardiac sarcoidosis: A case report]. / Dysfonction sinusale au cours de la sarcoïdose cardiaque: à propos d'un cas.

INTRODUCTION: Sarcoidosis is a multisystemic granulomatous disease of unknown cause occurring in young adults. Cardiac sarcoidosis patients are at increased risk for atrioventricular blocks and ventricular arrhythmias. Sinus node dysfunction is scarcely reported. OBSERVATION: We report a case of cardiac sarcoidosis revealed by a sinus node dysfunction and focus on cardiac and thoracic imaging to guide diagnosis. CONCLUSION: Sinus node dysfunction may be the first manifestation of cardiac sarcoidosis. In unexplained sinus node dysfunction in young patients, advanced cardiac imaging is a key to cardiac sarcoidosis diagnostic. Early recognition of cardiac sarcoidosis enables to start immunosuppressive treatment and discuss implantable cardioverter defibrillator implantation.

Quality assessment of pelvic ultrasound for uterine myoma according to the CNGOF guidelines.

INTRODUCTION: French guidelines regarding the minimum criteria for gynaecological ultrasound were given in a recent report in 2016, by the French National College of Obstetricians and Gynaecologists (CNGOF). An accurate report is essential for the optimal care of women, especially those presenting myomas. The goal of this study was to evaluate the quality of gynaecological ultrasound reports for women with type 0 to 2 uterine myomas, referring to the items contained in the French guidelines. MATERIALS AND METHODS: A retrospective descriptive study was conducted from reports of ultrasounds performed in private offices and in the gynaecologic department of a hospital, between June 2014 and June 2016 (before the report of CNGOF). These reports involved women who underwent hysteroscopic resection of myoma(s). A search of validated items was conducted for all of the reports, and the missing items were analysed. The different types of practitioners and between hospital and private medical offices were also compared with Chi-square tests. RESULTS: A total of 138 reports were analysed; 71 were performed in private offices and 67 were performed in the gynaecologic unit of the hospital. Many items were missing in the reports, with disparities between the type of institution (private offices or hospital) and the speciality of practitioners (radiologists or gynaecologists). Specific items regarding myomas, such as the International Federation of Gynaecologists and Obstetricians (FIGO) classification or measurement of the posterior wall, were more often missing in reports from radiologists (89.7% and 79.5%, respectively) than in reports from gynaecologists (21.2% and 34.3%, respectively) (P<0.05). A significant difference was also observed for these data between private offices' reports and hospitals' reports. Items relative to ultrasound structures, such as the appearance of myomas or associated abdominal effusion, were more frequently missing in gynaecologists' reports (88.9% and 49.5%, respectively) compared to radiologists' reports (56.4% and 12.8%, respectively) (P<0.05). CONCLUSIONS: Certain items are present in all the reports, while others are insufficiently mentioned. These inequalities can be explained in part by the type of practice; however, methods to overcome these difficulties must be developed. Information campaigns to educate professionals on the minimum reporting and training conducted jointly by radiologists and gynaecologist surgeons might improve reports and improve the care of women.

Short- and long-term prognosis, functional outcome following ICU for elderly.

Among 1532 ICU patients we analysed 295 elderly patients (19%) aged more than 70-years-old. We determined prospectively the immediate and subsequent one-year outcome with a study of the predictive value of their ICU admission parameters. Then we followed the ICU survivors over the year after discharge (1, 6, 12 months) by quality of life questionnaires. ICU mortality was 26.7%; SAPS was the only predictor of short term mortality. On ICU discharge, 216 elderly were followed at 1, 6, 12 months; the one-year cumulative mortality was 49% from ICU discharge, majority of deaths occurring over the first month. Age, previous health status and SAPS had a predictor value of one-year mortality for ICU survivors. 103 patients were alive at one year: 88% returned to home, 72% had a relatively good functional status allowing an independent life, and 82% had the same or improved functional status.

[Early somatosensory (SEP) and auditory (AEP) evoked potentials in anoxic coma: prognostic value]. / Les potentiels évoqués somesthésiques (PESp) et auditifs (PEAp) précoces dans les comas anoxiques: valeur pronostique.

Early somatosensory (SEP) and auditory (BAEP) evoked potentials, when recorded within the first seven days of the course of anoxic coma, appear to be reliable to evaluate anoxic ischemic cortical or under-cortical lesions. Prognosis depends especially on cortical SEP (N20-P25): the lack of SEP is a good outcome predictor of death (abnormal BAEP) or of vegetative status (normal BAEP); the presence of normal and bilateral cortical SEP (with normal BAEP) allows to predict awakening, without prejudging of neurologic sequelae, even if they are severe.

[Acute ajmaline poisoning. Study of 7 cases]. / Intoxication aiguë par l'ajmaline. Etude de 7 observations.

Seven cases of acute ajmaline overdose admitted over a 3 year period to a polyvalent intensive care unit are reported. The severity of this condition is related to the membrane stabilising and depolarising effects of ajmaline on the myocardium. The dose ingested varied from 10 to 40 mg/kg. The delay between ingestion and hospital admission ranged from 3 to 6 1/2 hours. The first cardiac disturbances can appear one hour after ingestion. Three cardiac arrests and one hypovolemic shock occurred. Three atrioventricular blocks, six intraventricular blocks, three ventricular tachycardias, and six prolongations of the QT interval were observed. Serum ajmaline levels varied from 0,8 to 6 mg/l. Symptomatic therapy was mainly based on sodium, temporary cardiac pacing, external DC shock, sympathomimetics and external cardiac massage with assisted ventilation. Cardiac bypass should be a part of the therapeutic arsenal. Elimination of the drug is assisted by a complete digestive evacuation. Renal or extrarenal dialysis is not indicated. One of the seven patients died. Prophylaxis is based on the non-prescription of ajmaline for benign cardiac disturbances.

[Acute amiodarone poisoning. Clinical and pharmacokinetic study]. / Intoxication aiguë à l'amiodarone. Etude clinique et pharmacocinétique.

A 73 years old patient, treated with Amiodarone for ventricular tachycardia, ingested 6 000 mg of Amiodarone. This did not induce hemodynamic troubles or aggravation of ventricular arrhythmia. Treatment included a gastric lavage and purging at the third hour. Plasma assay revealed a concentration of 3.69 mg/l at the fourth hour. Their evolution can be described as the sum of two exponentials. The half-life of the first exponential is 4.9 hours ; the half-life of the second one is 544 hours. Amiodarone is an antiarrhythmic agent of high safety.

[Methanol poisoning]. / Intoxication au méthanol.

The neurological signs, the cerebral CAT scan aspects and the ocular problems seen in five cases of acute methanol poisoning are reported; these were, respectively, coma requiring assisted ventilation, convulsions, hypotonicity, hypodensity of the putamen, and amaurosis and papillary oedema. The simplified acute physiologic score varied from 11 to 26; the value of 26 was observed in the only death of the series. Pathogenesis of the metabolic acidosis, as well as the different parts played by formic acid, lactic acid and ketone bodies are discussed. A normal or lowered serum potassium in a case of unexplained metabolic acidosis associated with an osmotic gap should make one think of the diagnosis. Macrocytosis, an indirect sign of folic acid deficiency, was in favour of a poor prognosis. The treatment included early gastric lavage, alkalinization, blocking of the metabolism of methanol by ethanol and haemodialysis with a bicarbonate dialysate enriched in ethanol; this corrected the acidosis and permitted the elimination of the toxic metabolites (clearance of methanol: 159 ml X min-1; half-life of methanol during purification: 3.46 +/- 1.32 h; quantity extracted: 246 g). The possible advantages of 4-methyl-pyrazol and alkyldiol derivatives need further confirmation.

[Posttraumatic fat embolism]. / Embolies graisseuses post-traumatiques.

Between 1977 and 1982, fifty cases of post-traumatic fat embolism were treated in a general intensive care unit. Average age of patients was 25.5 +/- 13 years; there was no male majority. Mean free interval was 39 +/- 27 h. 12 cases (24%) had single fractures and 38 (76%) multiple fractures. Forty-four patients had a fractured femur. Thirty-two patients presented the complete clinical syndrome with general, respiratory, neurological and cutaneous signs. Thrombocytopaenia and hypocholesterolaemia were the biological signs most often seen. In forty-four patients, orthopaedic treatment consisted of immediate immobilization, usually with traction. Twenty-six patients were reoperated on: intramedullary nail for twenty patients, plate for the other six. Fat embolism appeared in spite of surgery in six cases; it worsened after surgery in six others. Seven patients had per- or postanaesthetic problems. Fourteen per cent of patients died. The decrease in mortality was mainly due to an improvement in mechanical ventilation techniques. Early surgical fixation remained the rule if there was no serious respiratory distress or haemodynamic instability, although it did not seem to change the mortality rate in this group of patients.

[Bilateral diaphragmatic paralysis, the cause of acute insufficiency in chronic obstructive bronchopathy. The value of nasal mechanical ventilation]. / Paralysie diaphragmatique bilatérale, cause de décompensation aiguë d'une bronchopathie chronique obstructive. Intérêt de la ventilation mécanique par voie nasale.

A 57 year old man with chronic bronchitis sought a consultation for dyspnoea at rest associated with an absolute inability to lie flat. Examination revealed paradoxical respiration and respiratory function testing revealed a mixed ventilation disturbance, which was predominantly obstructive and was aggravated in the dorsal decubitus position. Radiology revealed bilateral diaphragmatic paralysis, which was confirmed on measurement of transdiaphragmatic pressure. The patient benefited from assisted ventilation by the nasal route with an excellent result in both the short and the medium term. Investigation into the cause was negative, in particular there was no evidence of any neuromuscular abnormality. This case recalls the role of the diaphragm in acute respiratory failure and shows the value of mechanical ventilation by the nasal route in the treatment of certain types of diaphragmatic paralysis.

[Myocardial infarction during postoperative peridural analgesia with opiates]. / Infarctus myocardique au cours d'une analgésie péridurale postopératoire aux opiacés.

A case of postoperative myocardial infarction is reported. It occurred seven days after intra-abdominal surgery (left hemicolectomy), in a patient with coronary heart disease. Diagnosis was delayed because of lack of pain; it was suggested by cardiogenic shock occurring 48 h after the initial phase. The patient had been receiving postoperative epidural analgesia with an opioid (pethidine); this may explain the pain was missing, so delaying the diagnosis.

[Early somatosensory and auditory evoked potentials in anoxic coma. Role in evaluating and prognostic value]. / Les potentiels évoqués somesthésiques et auditifs précoces dans les comas anoxiques. Intérêt dans le bilan lésionnel et valeur pronostique.

Early somatosensory (ESEP) and auditory (EAEP) evoked potentials were recorded in 27 patients with severe coma (Glasgow score less than 5) following cardiorespiratory arrest, within the first 7 days of its course. Somatosensory responses were elicited by stimulation of the median nerve. ESEP were abolished in 17 patients due to a parietal thalamo-cortical lesion. Among these, 6 patients died within one month and 11 presented with a persistent vegetative state. In all patients EAEP were obtained, showing functional brainstem activity. Low-voltage EAEP, especially for peak V (inferior colliculus or upper part of the brainstem), was sometimes observed. One patient, in whom ESEP and EAEP were initially abolished, died rapidly. In 9 other patients scalp-recorded ESEP and EAEP were normal; all emerged from coma including 5 with good neurological recovery and 4 with neurological sequelae. Clinical, electroencephalographic and computerized tomographic data appeared to be devoid of predictive value at the same initial period. In view of their sensitivity to anoxia and to cerebral oedema, even with neurosedative drugs, ESEP seemed to be reliable in predicting outcomes and in evaluating central nervous system lesions at cortical and subcortical levels (basal ganglia and brainstem) after cardiorespiratory arrest.

[Thrombolytic therapy with rt-PA of recurrent thrombosis in tricuspid valve prosthesis during pregnancy]. / Traitement thrombolytique par rt-PA d'une thrombose récidivante de prothèse valvulaire tricuspidienne durant la grossesse.

The authors report a case of a woman who had two episodes of a tricuspid Saint-Jude prosthesis thrombosis treated with fibrinolysis using rt-PA, during the fourth month of pregnancy. A first course of thrombolytic therapy was successful with normal valve function despite threatening abortion and uterine bleeding. An early rethrombosis of the prosthetic valve and a failure of a second course of thrombolysis required the interruption of pregnancy with a replacement of the tricuspid valve prosthesis.

[Acute water intoxication induced by oxytocin]. / Intoxication aiguë par l'eau induite par l'oxytocine.

A new case of oxytocin-induced water intoxication is reported in a 30 year old gravid woman. The severe symptoms of this uncommon complication are principally neurological; biological signs are a hyponatraemia with low plasma osmolality. Usually, biological and clinical signs are rapidly cleared up by treatment, but maternal death or neonatal water intoxication may occur. Such accidents must be prevented by clinical monitoring, watching out for alarm signals (oliguria is always found, resulting from the effect of oxytocin on the kidney), minimum fluid and proportional salt intakes, careful monitoring of oxytocin infusion rates, facilitated by the use of a constant flow-rate pump.

["Spontaneous" resolution of two severe methotrexate-induced pneumonias]. / Résolution spontanée de deux pneumopathies sévères au méthotrexate.

The beneficial role of corticosteroid therapy for the treatment of methotrexate-induced pneumonia remains controversial. We report two cases of acute severe interstitial pneumonia induced by methotrexate in patients with non-Hodgkin lymphoma given a polychemotherapy protocol (M'BACOD). The first signs appeared on the eleventh day of the first cycle in patient one and on the tenth day of the third cycle in patient two. The causal implication of methotrexate was based on the history, the clinical and radiological presentation, and the negative tests in both patients: lymphocyte alveolitis with granulomatous lesions on the transbronchial biopsy in patient one and positive leukocyte migration test in the presence of methotrexate in patient two. Early acute respiratory failure required high flow rate oxygen therapy with positive expiratory pressure ventilatory assistance. The course was rapidly favorable both for blood gases and radiographic presentation without corticosteroids. These two cases illustrate that pulmonary disease can be cured without corticosteroids despite severe respiratory failure at onset. This provides a further argument on reservations about using corticosteroids for suspected methotrexate-induced pneumonia.