Preclinical tolerance evaluation of the addition of a cisplatin-based dry powder for inhalation to the conventional carboplatin-paclitaxel doublet for treatment of non-small cell lung cancer.

Despite the advances in targeted therapies and immunotherapy for non-small cell lung cancer (NSCLC) patients, the intravenous administration of carboplatin (CARB) and paclitaxel (PTX) in well-spaced cycles is widely indicated for the treatment of NSCLC from stage II to stage IV. Our strategy was to add a controlled-release cisplatin-based dry-powder for inhalation (CIS-DPI-ET) to the conventional CARB-PTX-IV doublet, administered during the treatment off-cycles to intensify the therapeutic response while avoiding the impairment of pulmonary, renal and haematological tolerance of these combinations. The co-administration of CIS-DPI-ET (0.5 mg/kg) and CARB-PTX-IV (17-10 mg/kg) the same day showed a higher proportion of neutrophils in BALF (35 ± 7% vs 1.3 ± 0.8%), with earlier regenerative anaemia than with CARB-PTX-IV alone. A first strategy of CARB-PTX-IV dose reduction by 25% also induced neutrophil recruitment, but in a lower proportion than with the first combination (20 ± 6% vs 0.3 ± 0.3%) and avoiding regenerative anaemia. A second strategy of delaying CIS-DPI-ET and CARB-PTX-IV administrations by 24 h avoided both the recruitment of neutrophils in BALF and regenerative anaemia. Moreover, all these groups showed higher cytotoxicity (LDH activity, protein content) with no higher renal toxicities. These two strategies seem interesting to be assessed in terms of antitumor efficacy in mice.

Pulmonary and renal tolerance of cisplatin-based regimens combining intravenous and endotracheal routes for lung cancer treatment in mice.

Despite recent advances, platinum-based chemotherapy (partially composed of cisplatin, CIS) remains the backbone of non-small-cell lung cancer treatment. As CIS presents a cumulative and dose-limiting nephrotoxicity, it is currently administered with an interruption phase of 3-4 weeks between treatment cycles. During these periods, the patient recovers from the treatment side effects but so does the tumour. Our strategy is to increase the treatment frequency by delivering a cisplatin controlled-release dry powder for inhalation (CIS-DPI) formulation during these off-cycles to expose the tumour environment for longer to CIS, increasing its effectiveness. This is promising as long as the pulmonary and renal toxicities remain acceptable. The aim of the present investigation was to evaluate the pulmonary and renal tolerance of CIS-DPI (three times per cycle) and CIS using the intravenous (IV) route (CIS-IV) (one time per cycle) as monotherapies and to optimize their combination in terms of dose and schedule. At the maximum tolerated dose (MTD), combining CIS-DPI and CIS-IV impaired the pulmonary and the renal tolerance. Therefore, pulmonary tolerance was improved when the CIS-IV dose was decreased by 25% (to 1.5 mg/kg) while maintaining the MTD for CIS-DPI. In addition to this dose adjustment, a delay of 24 h between CIS-DPI and CIS-IV administrations limited the acute kidney injury.

[Patients assaulted in psychiatric institutions: Literature review and clinical implications]. / Patients agressés en milieu psychiatrique : revue de la littérature et implications cliniques.

BACKGROUND: The psychiatric ward is a place where all forms of violence are treated. Occasionally, this violence involves acts of aggression between patients in emergency psychiatric units or hospital wards. Such events can lead to the development or worsening of posttraumatic stress disorder. METHODS: To establish the context, we first examined the epidemiology data concerning posttraumatic stress disorder in psychiatric patients who were frequently exposed to assaults. Secondly, we examined the issue of sexual and physical assaults between patients receiving treatment in a psychiatric ward. In this context, we studied possible occurrence of posttraumatic stress disorder associated with exposure to assaults of this kind. RESULTS: In certain cases, potentially traumatic exposure to violence was unknown to the medical staff or not taken into consideration. This would induce a risk of later development of posttraumatic stress disorder that would not be treated during the stay in psychiatry. CONCLUSION: To date, few scientific studies have focused on the proportion of patients assaulted by other patients during treatment in a psychiatric ward and the subsequent development of peritraumatic reactions and/or posttraumatic stress disorder associated with these assaults. We know that an insufficient number of public and private health institutions report the existence of such facts to the competent authorities. Also, a minority of clinicians and caregivers are trained in screening and management of trauma victims. Yet, these issues are particularly relevant in the scope of public health and health promotion.

[False aneurysm complicating ligation of patent ductus arteriosus operated on successfully]. / Faux anévrisme après ligature d'un canal artériel opéré avec succès.

Postoperative aneurysm of ductus arteriosus is a rare complication but may be lethal without treatment. It is less frequent than spontaneous aneurysm of ductus arteriosus. We report the case of 5 years-old girl who underwent a ligation of patent ductus arteriosus complicated, 6 months later, with a false aneurysm of ductus arteriosus and endocarditis of the ductus and the aortic valve. The diagnosis of the aneurysm was suspected on the anteroposterior chest X-ray which showed a left superior mediastinal opacity and confirmed by echocardiography. Through bilateral thoracotomy, an anevrismorraphy and aortic repair was carried out without problem. The postoperative course was unremarkable.

[Obstructive left triatrial heart in the adult. Echocardiographic appearances]. / Coeur triatrial obstructif gauche chez l'adulte. Aspects échocardiographiques.

The authors report the case of a 23-year old man who presented with signs of pulmonary hypertension due to an obstructive left triatrial heart in adulthood. Transthoracic and transoesophageal echocardiography showed a partially calcified intra-left atrial membrane perforated in its centre. Doppler analysis of flow through the membrane showed continuous systolo-diastolic flow at high velocity indicating haemodynamic obstruction. The systolic pulmonary artery pressure was estimated at 80 mmHg. The patient was treated by surgical excision of the intra-left atrial membrane.

[Hypocalcemic dilated cardiomyopathy: rare cause of heart failure]. / Une cause rare d'insuffisance cardiaque: la cardiomyopathie dilatée hypocalcémique.

Hypocalcemic dilated cardiomyopathy is a rare cause of heart failure in adults. We report a case in a 19-year-old woman who developed congestive heart failure induced by severe chronic hypocalcemia disclosing primary hypoparathyroidism. Complete regression of the clinical signs was achieved with vitamin-calcium treatment, but left ventricular systolic dysfunction persisted eight months after treatment.

[Follow-up of patients treated by conduits between the right ventricle and the pulmonary artery]. / Suivi des patients traités par conduits entre le ventricule droit et l'artère pulmonaire.

Between 1981 and 1998, 77 right ventricle-pulmonary artery conduits were implanted in 67 patients (37 boys, 30 girls, average age 6.3 years; range: 3 months to 17 years). The diagnoses were transposition of the great arteries with ventricular septal defect and obstruction of the pulmonary outflow tract (N = 22), tetralogy of Fallot (N = 16), truncus arteriosus (N = 9), double outlet right ventricle with pulmonary stenosis or atresia (N = 8) and agenesis of the pulmonary valve with pulmonary stenosis (N = 2). The implanted conduits were homografts in 50 cases (43 aortic and 7 pulmonary), 11 valved Dacron grafts, 4 valved polystans grafts and 2 non-valved conduits. The average follow-up period was 3.6 years (range: 1 month to 17 years). Early death was observed in 8 patients (12%) and late death in 6 patients (9%). The 5, 10 and 15 year survival rates were 78.4%, 65.3%, and 65.3%, respectively. The conduits had to be replaced in 10 patients (15%). The non-replacement rate of all conduits at 5, 10 and 15 years was 81.4%; 40.7% and 40.7%, respectively. The causes of replacement were pure stenosis (54.5%), pure regurgitation (9%) and mixed stenosis and regurgitation (27.2%). These results are comparable to other published series showing a 15 year survival rate of 65% and a 59% reoperation rate at 15 years. Homografts have a slightly longer life compared with valved Dacron conduits but the difference is not statistically significant.

Aorticoright atrial tunnel.

Two unusual cases of aorticoright atrial tunnel are described. Both patients were referred to our institution for evaluation of a continuous heart murmur best heard along the right upper sternal border. Ascending aortography showed the tunnel taking its origin from the aortic root and entering the right atrium through a tortuous link. Both patients underwent surgical closure. In addition, a review of similar cases in the literature is presented.

Pericardial tamponade as the first manifestation of dermatopolymyositis.

Pericardial involvement in polymyositis and dermatomyositis (PM/DM) is rare, usually asymptomatic and exceptionally part of the initial presentation. We describe a 37-year-old patient hospitalized for overt acute pericarditis, revealing dermatomyositis, which to our knowledge has not been previously reported. Pericardial puncture relieved the patient. The pericardial fluid was citrine yellow, exsudative, and mainly contained lymphocytes. Search for LE cells and anti-DNA antibodies was negative, whereas the antinuclear antibodies and the rheumatoid factor were present in the pericardial fluid. A biopsy of the pericardium showed a non-specific chronic inflammatory state and the search for an etiology was negative. There was no sign of tuberculosis, systemic lupus, nor neoplasia. Moreover bacteriological cultures and HIV serology were negative. After pericardiostomy associated with corticosteroid therapy at the dose of 1 mg/kg/day, outcome was good with a resolution of the pericarditis confirmed at one-year follow-up. Since pericardial tamponade, even though rare, may be fatal in a patient with dermatomyositis, we emphasize that a two dimensional echocardiographic study should be performed in all patient presenting with dermatopolymyositis.

[Deep venous thromboses and occult cancers]. / Thromboses veineuses profondes et cancers occultes.

The association between venous thrombosis and cancer has been known for a long time. Thrombophlebitis often occurs during the course of a known cancer, but sometimes constitutes the presenting sign. Based on a series of 10 cases of deep venous thrombosis (DVT) revealing an underlying cancer, the authors analyse the various aspects of this association and the elements which help to guide the diagnosis towards a cancer. A simple assessment comprising clinical examination, full blood count and differential white cell count, erythrocyte sedimentation rate, protein electrophoresis, chest x-ray and abdomino-pelvic ultrasonography was performed on admission in 75 cases of presumably idiopathic DVT and revealed a cancer in 10 cases: 6 women and 4 men with a mean age of 53 years. Cancers were located in the urogenital tract in 5 cases, in the bronchi in 2 cases, in the stomach in one case, and there was one case of acute myeloblastic leukaemia (AML) and another case of liposarcoma of the left iliac fossa. The histological type most frequently encountered was adenocarcinoma in 6 cases. In 9 out of 10 cases, the cancer was discovered at the stage of metastases. However, a localized cancer was detected in one case, in which surgical treatment allowed cure of the patient. Comparison of the various characteristics of DVT between the group of DVT revealing a cancer and the group of DVT which remained idiopathic did not reveal any statistically significant difference. A simple, inexpensive assessment looking for a cancer must be systematically performed in all cases of idiopathic DVT in patients between the ages of 50 and 85 years. Other more elaborate examinations may be requested on the basis of the results of the preliminary assessment.

[Imaging in cardiac hydatid cyst. Apropos of a case]. / Apport de l'imagerie dans l'hydatidose cardiaque. A propos d'un cas.

Cardiac hydatid disease is rare. Its dificult diagnosis is based on a series of arguments in which hydatid serology and imaging play a predominant role. A young patient with multiple cardiac hydatid cysts was investigated by 2D echocardiography, transoesophageal echocardiography and magnetic resonance imaging. This case illustrates the value of the various noninvasive imaging techniques in the diagnosis of cardiac hydatid disease and emphasizes the importance of surgical treatment before the development of complications.

[Mediastinal malignant schwannoma disclosed by pericardial tamponade in von Recklinghausen disease]. / Schwannome malin médiastinal révélé par une tamponnade péricardique au cours de la maladie de von Recklinghausen.

The authors report a case of a 47-years-old patient with Von Recklinghausen's disease. He was admitted with pericardial tamponade. 2D echocardiography showed, in addition to the compressive pericardial effusion, an enormous intrapericardial tumor compressing the left cardiac cavities. The patient died soon after pericardial drainage. The post-mortem examination revealed the diagnosis of malignant schwannoma of the left costo-vertebral gutter with an anterior intrapericardial development. A review of the literature showed that malignant schwannomas are seldom localized in the mediastinum, are associated with Von Recklinghausen's disease in 2 to 13% of cases, and have a poor prognosis. Pericardial tamponade is an exceptional presenting sign of mediastinal malignant schwannoma.