Patients requiring pediatric palliative care for advanced heart disease in France: A descriptive study.

INTRODUCTION: Pediatric palliative care (PPC) teams address unmet needs and improve the quality of life of patients with life-limiting conditions across pediatric subspecialties. However, little is known about the timing, reasons, and nature of PPC team interventions in advanced heart diseases (AHD). OBJECTIVES: Here we describe how, when, and why PPC teams interact with referred teams of children suffering from AHD. METHODS: We conducted a retrospective nationwide survey among PPC teams in France. All patients referred to participating PPC teams for a cardiologic disease in 2019 were studied. RESULTS: Among six PPC teams, 18 patients with AHD had a PPC consultation in 2019. Six of these patients had cardiomyopathy and 12 had congenital heart disease (CHD). The median age at referral was 0.9 months for CHD and 72 months for cardiomyopathy. An antenatal diagnosis had been made for six families with CHD, and two of them were referred to PPC before birth allowing for a prenatal palliative care plan. The main reason for referral was ethical considerations (50%) followed by organization for home-based palliative care (28%). PPC teams participated in ethical discussions when asked to but also provided family support (12/18), home-based PPC (9/18), coordination of care (5/18), support of the referred team (4/18), and symptoms management (3/18) CONCLUSION: The main reason for referral to PPC was ethical considerations, but PPC interventions followed a holistic model of care. Prospective outcomes measurement and partnerships should be further developed.

Deletion or lack of expression of CDKN2 (CDK4I/MTS1/INK4A) and MTS2 (INK4B) in acute lymphoblastic leukemia cell lines reflects the phenotype of the uncultured primary leukemia cells.

The CDKN2 gene has been recently localized to a chromosomal region found to be deleted in leukemias and solid tumors. CDKN2 encodes a 16 kDa protein product (p16INK4A), which functions as a specific inhibitor or the cyclin-dependent kinases 4 and 6. There have been many reports indicating a higher frequency of deletions of the CDKN2 gene in a variety of tumor cell lines, in comparison to primary tumors. These studies raise the possibility that deletions of CDKN2 may be a rare event in primary tumors, and in fact arise in vitro, during the establishment of permanent cell lines. To address this issue, we determined whether the CDKN2 gene deletions found in acute lymphoblastic leukemia (ALL) cell lines are also detected in the primary leukemia samples. Eleven cell lines were identified which had available frozen primary samples of their original leukemic tissue. Five out of 11 of these cell lines, as well as their primary samples had homozygous CDKN2 deletions. The remaining six cell lines and their primary samples retained at least one copy of the CDKN2 gene. Of the six CDKN2+ cell lines, five expressed CDKN2 mRNA, but only one of these expressed the p16 protein product (as did its primary sample). Our results indicate that CDKN2 deletions present in the studied ALL cell lines arose in the primary leukemic cells, and not during cell line establishment or prolonged in vitro culture.

Erythrocyte spermine levels: a prognostic parameter in childhood common acute lymphoblastic leukemia.

Polyamines have been implicated to play a role in cell proliferation and in cancer development. Ninety percent of the circulating spermidine (Spd) and spermine (Spm) are transported by red blood cells (RBC). RBC Spd and Spm levels were prospectively determined in 63 unselected children with common acute lymphoblastic leukemia. The Spm and Spd levels were not correlated with white blood cell (WBC) count. On the basis of the polyamine levels it was possible to discriminate four groups with P< 10(-3). In C1, C2, C3 and C4 group the Spm level was respectively 90 (39-597), 3.75 (1-7.45), 9.95 (2.9-12.6) and 17(6.3-33.8). The probability of relapse-free survival (RFS) of the 58 children who entered complete remission was 55% +/- 9. For the groups C1 (n = 6), C2 (n = 16), C3 (n = 21) and C4 (n= 15) groups, the RFS was 25% +/- 20, 73% +/- 12, 73% +/- 13 and 32% +/- 13 respectively. For children with Spm levels <13/> or = 13nmol/8 x 10(9) RBC, event-free survival (EFS) was 54% +/- 11/33% +/- 10 and RFS was 64% +/- 12/38% +/- 11 respectively (P < 0.03, P < 0.005). Our clinical study shows clearly that an RBC spermine level could be used as parameter of prognosis at the time of diagnosis, particularly for patients with intermediary WBC count.

Growth inhibition of B-cell precursor acute lymphoblastic leukemia cell lines by monocytes: a role for prostaglandin E2.

Leukemic cell lines have proven invaluable in the molecular analysis of recurring chromosomal translocations but the optimal methods for leukemia cell line establishment are unknown. During in vitro culture, most B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells die within 1 week at least partially mediated by inhibitors elaborated by peripheral blood mononuclear cells (PB MNCs) present within the leukemia sample. In experiments reported here, cyclooxygenase inhibitors (indomethacin and meclofenamic acid) blocked the PB MNC-mediated inhibition of BCP-ALL proliferation. Also, prostaglandin E2 (PGE2) was detected in supernatants from PB MNC cultures. When PGE2 was mixed directly with BCP-ALL cells, proliferation decreased significantly. Under the culture conditions used, PB MNCs secreted PGE2 which appears to be one of the major inhibitors of BCP-ALL growth in vitro.

Erythrocyte polyamine levels: an indication of successful engraftment of bone marrow in children.

We studied the evolution of erythrocyte polyamine levels after 17 autologous bone marrow transplants (BMT) in 16 children with malignant diseases. We found that the time to the end of aplasia (0.5 x 10(9) granulocytes per liter) could be divided into 2 distinct periods. The first is characterized by low erythrocyte spermidine (Spd) and spermine (Spm) levels; the second is characterized by normal levels of polyamines. Spd and Spm levels were correlated (r = 0.74) during the second period, but not during the first period or in the control group. Furthermore, the time when Spd concentration was > or = 7 nmol/8 x 10(9) erythrocytes (19 +/- 7) was correlated (r = 0.64) with the advent of end of aplasia (30 +/- 10). We found no correlation between the numbers of CFU-GM and duration of aplasia levels or the duration of period A. The establishment of normal erythrocyte spermidine levels is the earliest index of successful marrow engraftment.

Analysis of the side effects of tianeptine.

The evaluation of clinical and paraclinical safety of tianeptine was performed in (a) clinical pharmacology studies assessing night sleep EEG organization; electrocardiographic stability by continuous 24-h recordings (Holter's method); ocular tonus in patients with stabilized glaucoma; salivary flow; prolactin secretion; photodynamic dermatologic reactions; cerebral electrical activity; hematologic, hepatic, renal and main metabolic parameters; separately, withdrawal phenomena and addictive potential were searched for in drug addicts; (b) double-blind controlled studies versus reference compounds. The results confirm that the therapeutic safety of tianeptine is satisfactory with respect to clinical side effects and paraclinical parameters. Tianeptine does not induce sedation and thus does not disturb the recovery of active life. It does not induce anticholinergic effects (dry mouth, constipation, etc.), even in elderly subjects. It is devoid of heart and blood pressure side effects including postural hypotension tachycardia, ECG abnormalities, and especially atrioventricular or intraventricular conduction disorders. Moreover, tianeptine does not disturb the hematologic, renal, hepatic parameters, even in alcoholic patients in the detoxification period. It does not induce physical or psychological signs of dependence when discontinued, even in alcoholic patients or drug addicts. No abuse of tianeptine and no tolerance were noted in detoxified opiate addicts.

Proximal fractures of the fifth metacarpal: a retrospective analysis of 25 operated cases.

The clinical and radiological outcomes of 25 surgically treated fractures of the proximal third of the fifth metacarpal were retrospectively analysed. Many different methods of osteosynthesis were used. At follow-up after a mean of 3.3 years, 15 of 25 patients had no pain. Most patients regained a nearly full range of motion in the adjacent joints and more than 90% of the contralateral grip strength. X-ray signs of degenerative arthritis in the metacarpohamate joint were observed in 10 of 25 patients. Pain was found to be directly correlated with the presence of degenerative changes.

Effectiveness of nitrous oxide and analgesic cream (lidocaine and prilocaine) for prevention of pain during intramuscular botulinum toxin injections in children.

AIMS: To evaluate the effectiveness of an analgesic protocol with nitrous oxide and anaesthetic cream (lidocaine and prilocaine, EMLA) for children undergoing botulinum toxin injections. PATIENTS AND METHODS: Prospective study including 51 injection sessions, 34 children with a mean age of 5.94 (range 2-15) and 209 injected muscles. Pain was evaluated with the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), the Visual Analogue Scale (VAS) and the Face Pain Scale (FPS) for the children and with a VAS for the parents. RESULTS: CHEOPS score for the 51 sessions was 8.50 (S.D. 3.56). Forty-nine percent of scores were above the therapeutic threshold of 9; 25% of the children evaluated the pain above the therapeutic threshold of 3; 44.74% of the parents' estimations exceeded 3. No correlation was found between age, weight, number of injected muscle and CHEOPS score. CONCLUSION: The association of MEOPA and anaesthetic cream is only effective for 50% of children. This is much lower than treatments for other types of acute induced pain in children. Botulinum toxin injections and cerebral palsy children present certain specificities which require improvements in this analgesic protocol.

Hematopoietic progenitor cell mobilization and harvesting in children with malignancies: do the advantages of pegfilgrastim really translate into clinical benefit?

Our purpose was to assess success rates in children of achieving optimal hematopoietic progenitor cells (HPCs) harvest after mobilization with 300 microg/kg pegfilgrastim. Between January 2005 and January 2007, 26 children with solid malignancies who were referred for HPC collection were consecutively included. Hematopoietic progenitor cell mobilization consisted of one s.c. injection of 300 microg/kg body weight (BW) of pegfilgrastim. The success criterion was defined as at least 5 x 10(6) CD34+ cells/kg during the first standard apheresis (less than 3 blood volumes processed (BVP)). After 26 inclusions, the Bayesian analysis gave a mean estimated success rate of 60.7% (95% credibility interval: 42.0-78.0%). The first apheresis allowed the collection of 8.3 x 10(6) CD34+ cells/kg BW (range 0.6-37.8), with a median of 2.8 BVP (range 1.4-3.0). Overall, the median of CD34+ cells collected was 12.4 x 10(6)/kg (range 2.7-37.8). The cumulative dose of anthracyclin was the only variable associated with the total number of CD34+ collected cells (P<0.05). Mobilization was clinically well tolerated in 20 patients. No drug-related adverse events of grade > or =3 occurred. We conclude that a single injection of 300 microg/kg pegfilgrastim in the hematological steady state is an efficient and well-tolerated method of HPC mobilization in children with solid malignancies.

Clinical safety and efficacy of tianeptine in 1,858 depressed patients treated in general practice.

1,927 outpatients were included by 392 general practitioners in an open study in order to evaluate the safety of tianeptine in the ambulatory treatment of depression. The results of 1,858 depressed patients without melancholia and psychotic features, fulfilling DSM III criteria of Major Depressive Episode or Dysthymic Disorder, could be analysed. 1,458 patients completed the 3-month treatment period. The group treated with 37.5 mg/day of tianeptine showed improvement on the Montgomery-Asberg Depression Rating Scale. With regard to the clinical tolerance of tianeptine, somatic complaints were rarely reported and adverse events necessitating premature termination of treatment (4.8% of included patients) were without clinical severity. Cardiovascular, haematologic, hepatic and biochemical safety were verified. No signs of dependence and no specific withdrawal symptoms were found after discontinuation of treatment.

Use of intravenous ketamine-midazolam association for pain procedures in children with cancer. A prospective study.

We evaluated the safety and efficacy of midazolam-ketamine association to control pain induced by diagnostic procedures in paediatric oncology patients. 226 procedures were carried out in 92 patients aged three days to 18 years. Drugs were given i.v. by an anaesthesiologist. Midazolam dose was 25 microg.kg-1 and ketamine 0. 5 to 2 mg.kg-1, depending on number and invasiveness of procedures. The mean dose of ketamine was 1 mg.kg-1. Mean duration of sedation was ten min. No complication was observed and analgesia was considered satisfactory in 89 out of 92 patients. These results indicate that midazolam-ketamine is a safe and effective association in pain management for paediatric oncology patients and efficiently induces brief unconscious sedation with analgesia.

[Orbital and muscular relapse of Burkitt's lymphoma]. / Rechute orbitaire et musculaire d'un lymphome de Burkitt.

We report the case of a child presenting with abdominal Burkitt's lymphoma in whom a relapse presented as orbital and muscle involvement. This clinical feature is extremely rare. Two muscle and one orbital biopsies were necessary to obtain proper diagnosis. A new extension check-up showed bone marrow invasion and normal cerebrospinal fluid. This relapse was successfully treated by conventional chemotherapy and consolidated with high-dose chemotherapy, total body irradiation and autologous bone marrow transplantation. Eighteen months after transplantation, the child may be considered as definitively cured.

Myelodysplastic syndrome with t(5;12)(q31;p12-p13) and eosinophilia: a pediatric case with review of literature.

PURPOSE: Myelodysplastic syndrome with chromosomal translocation t(5;12)(q31-33;p12-13) and eosinophilia is a new entity recently described. Nine cases have been described in adults. We report the first pediatric case with a long follow-up (7 years). PATIENTS AND METHODS: An 8-year-old girl presented with hyperleukocytosis, eosinophilia, and no clinical symptoms. Bone marrow investigations revealed myeloid hyperplasia and clonal chromosomal translocation t(5;12)(q31;p12-13). No treatment was prescribed, but 4 years later the white blood cell count reached 144 X 10(9)/L with immature myeloid cells and splenic enlargement. Hydroxyurea chemotherapy led to a hematopoietic remission. The patient is now 16 years old and well, >7 years after the initial diagnosis. RESULTS: The association: myelodysplastic syndrome, eosinophilia and translocation t(5;12)(q31-33;p12-13), seems to be a specific hematologic disorder. Study of cases previously reported in the literature shows the most important characteristics of this disease. However, there are still a number of questions about the disease itself (especially its treatment) and the significance of the chromosomal abnormalities. CONCLUSION: This case seems to be the first report of the disease in a child and has had the longest follow-up. Other data should be collected to improve our knowledge of this hematopoietic disorder.

Cerebral non-Hodgkin's lymphoma discovered when treating Hodgkin's disease.

Case report of the appearance of a highly malignant cerebral non-Hodgkin's lymphoma of a diffuse large cell type, type B, occurring at the immediate onset of chemotherapy for a stage IV (mediastino-pulmonary) Hodgkin's disease (nodular sclerosis) diagnosed in a 16-year-old boy. The treatment of this cerebral lymphoma associated primary chemotherapy with high dose methotrexate, high dose aracytine, etoposide, and ifosfamide. The chemotherapy proved to be highly efficient, producing complete remission. Thoracic and abdominal irradiation for Hodgkin's disease was performed concomitantly with chemotherapy for the non-Hodgkin's lymphoma. This treatment was followed by 36 Gy of cerebral irradiation. Thirty-six months after the discovery of the cerebral non-Hodgkin's lymphoma the patient was still disease-free and doing well.