The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment.

The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium-sulphur colloid (99m Tc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag® , which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non-inferiority of SentiMag® vs. 99m Tc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between 99m Tc and SentiMag® was 97.9%. The DR per patient was 99.0% for 99m Tc and 97.9% for SentiMag® . SentiMag® appears to be non-inferior to the radiotracer and safe. While 99m Tc remains the standard, SentiMag® DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+® allows effective treatment of breast cancer patients.

Homozygous PKP2 deletion associated with neonatal left ventricle noncompaction.

Left ventricular noncompaction cardiomyopathy (LVNC) is a clinically heterogeneous disorder characterized by a trabecular meshwork and deep intertrabecular myocardial recesses that communicate with the left ventricular cavity. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified. A NGS workflow, based on a panel of 95 genes developed for sequencing most prevalent sudden cardiac death-causing genes, was used to make a rapid and costless molecular diagnosis in two siblings with a severe noncompaction cardiomyopathy starting prenatally and leading to rapid cardiac failure. For the first time, a total homozygous PKP2 deletion was identified. This molecular defect was further confirmed by MLPA and array-comparative genomic hybridization (CGH). Heterozygous PKP2 mutations are usually reported in a significant proportion of Arrhythmogenic Right Ventricular Cardiomyopathy cases. Our results show, for the first time, the involvement of PKP2 in severe cardiomyopathy with ventricular non compaction.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

Organocatalytic route for the synthesis of propionylated starch.

In recent years acetylated, propionylated and butyrylated starches have received special attention due to their capacity to deliver specific short chain fatty acids (SCFAs) to the colon in a sustained and predictable manner, and thus contribute to maintaining the normal physiologic function of the large bowel and preventing specific diseases. In the current contribution a non-conventional organocatalytic solventless route for the eco-friendly propionylation of corn starch is proposed. The catalyst used in the acylation is a naturally occurring α-hydroxy acid (l-tartaric acid). Propionylated starches with degree of substitution (DS) in the 0.05-1.59 interval were obtained and characterized in terms of chemical structure, morphology, crystallinity, thermal stability and hydrophilicity. Results showed that by the proposed methodology propionylated starch with the DS required for clinical use (i.e. 0.2-0.3) could be obtained within 2-3h of reaction. Characterization results evidenced the progressive loss of crystallinity of starch granules as higher substitution levels were conferred.

[Athlete's heart in the young: electrocardiographic and echocardiographic patterns in 107 French athletes]. / Le cœur d'athlète de l'adolescent : aspects électrocardiographiques et échocardiographiques. À propos de 107 sportifs français.

PURPOSE: Since 2009 in France, every people practicing sport in competition must have a cardiovascular exam with electrocardiogram, to prevent sudden cardiac death. Sometimes, an echocardiography will be necessary. Little is known about athlete's heart in the young, particularly in the French people. PATIENTS AND METHODS: One hundred and seven French elite adolescent athletes had an electrocardiogram with echocardiography to establish reference values in this population. RESULTS: QTcorrected (QTc) interval calculated by the Hodges formula, is always in the normal values. Interventricular septal thickness is always ≤ 11 mm and left ventricular end diastolic diameter ≤ 55 mm in about 90 % of the athletes. Females have QTc interval longer than males and interventricular septal thickness finer. Diastolic function (18.9 ± 2.6 cm/s for e', E/e' ratio at 5.3 ± 0.8) is "supernormal" and correlate with age and cardiac frequency. Right ventricular systolic function is always good. CONCLUSION: Adolescent athlete's heart is normal. If QTc interval is not normal, be afraid of a QT long syndrome. Furthermore, when interventricular septal thickness is > 11 mm or left ventricular end diastolic diameter > 55 mm, myocardiopathy will have to be ruled out.

Hyperthermic isolated perfusion with tumor necrosis factor-alpha and doxorubicin for the treatment of limb-threatening soft tissue sarcoma: the experience of the Italian Society of Integrated Locoregional Treatment in Oncology (SITILO).

BACKGROUND: Tumor necrosis factor-alpha (TNFalpha)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFalpha dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFalpha. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFalpha dose and doxorubicin (Dx). PATIENTS AND METHODS: HILP with TNFalpha (at a dosage of either 1 mg) and Dx was administered to 75 patients with limb-threatening STS: 37 males and 38 females; median age 50 years; tumor in the lower and upper limbs in 58 and 17 patients, respectively; primary and recurrent tumors in 45 and 30 patients, respectively. Most tumors (77%) were high grade. Tumor resection was carried out 6 to 8 weeks after HILP. RESULTS: The grade of limb toxicity was mild to moderate in the vast majority of patients (76%). Grades IV and V were observed, but only when high muscle temperatures were recorded and high TNFalpha dosages were employed. Systemic toxicity was also mild to moderate and there were no postoperative deaths. Complete and partial tumor responses were 34% and 48%, respectively, with an overall response of 82% . Limb sparing surgery was carried out in 85.3% of patients. At a median follow-up of 28 months, 16 recurrences (21.3%) were recorded, with a 5-year locoregional disease-free survival of 63% . The 5-year disease-free survival and overall survival were 36.7% and 61.6%, respectively. CONCLUSION: HILP with 1 mg of TNFalpha is an effective neoadjuvant therapy resulting in a high rate of limb sparing in limb-threatening STS, with acceptable local reactions and negligible systemic toxicity.

Prognostic factors influencing tumor response, locoregional control and survival, in melanoma patients with multiple limb in-transit metastases treated with TNFalpha-based isolated limb perfusion.

BACKGROUND: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNFalpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNFalpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable dose (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFalpha was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNFalpha-based ILP and identify prognostic factors for response, locoregional control and survival. PATIENTS AND METHODS: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>or=10 nodules3 cm) in 42.5% of the patients and unresectable in 33% . Forty patients were treated with a TNFalpha dosage of >1 mg and 73 with 1 mg. Patients with tumors in the upper and lower limbs were submitted to ILP via axillary and iliac vessels, respectively. TNFalpha was injected in the arterial line of an extracorporeal circuit at the pre-established dose, followed by melphalan (13 and 10 mg/l of limb volume for the upper and lower limbs, respectively) 30 minutes later. RESULTS: Complete responses (CR) and partial responses (PR) were 63% and 24.5%, respectively, with an objective response (OR) of 87.5%. No change (NC) was observed in only 12.5% of the patients. Upon multivariate analysis, only bulky disease maintained its independent value for tumor response with an odds ratio of 4.07 and a p-value of 0.02. The 5-year locoregional disease-free survival was 42.7%. Upon multivariate analysis, the only prognostic factors were stage, age and bulky disease. The 5-year overall survival was 49%. Multivariate analysis showed that only sex, stage and CR maintained their independent values. CONCLUSION: TNFalpha-based ILP was proven to be an effective treatment for melanoma patients with in-transit metastases. The TNFalpha dosage of 1 mg was as effective as 3-4 mg, with lower toxicity and cost. We propose that TNFalpha and melphalan-based ILP should be employed for bulky tumors or after failure of melphalan-based ILP.

[Do convective treatments significantly reduce morbidity and mortality?]. / I trattamenti convettivi riducono significativamente morbilita' e mortalita'?

Standard hemodialysis is a far from ideal treatment for uremia since the morbidity and mortality of patients on hemodialysis are still significantly higher than those of non-hemodialyzed subjects with similar demographic characteristics. Because it has been suggested that the cause could lie in the inadequate removal of ''middle molecules'' by standard hemodialyis, two alternative treatments have been proposed: high-efficiency hemodialyis and high-flux hemodialyis. The 2002 results of the HEMO study showed that both these treatments are associated with a non-significant reduction in the relative risk of death (4% and 8%, respectively). The MPO study, which - unlike the HEMO study - enrolled only incident cases and not did not allow reuse of dialyzers, evaluated the mortality rate with high-flux and low-flux hemodialysis in a sicker population, i.e., patients with hypoalbuminemia, and showed a significant reduction in the relative risk of death especially in patients with diabetes. In an attempt to define the clinical impact of hemodiafiltration, some of the efficacy data from clinical studies are reviewed in light of a number of factors that may be related to the high mortality among hemodialysis patients. The current state of affairs suggests it is reasonable to prefer high-flux hemodialysis in sicker patients, especially diabetics. Moreover, the use of ultrapure dialysis fluid is recommended to reduce chronic inflammation and its consequences.

De novo malignancy after solid organ transplantation in children.

The aim of this study was to assess the prevalence of de novo malignancy after solid organ transplantation in childhood. A retrospective questionnaire-based survey was sent to 9 referral centers for pediatric organ transplantation in France. Among 1326 children who underwent solid organ transplantation since 1996, 80 (6%) presented with de novo malignancy posttransplantation during childhood: posttransplant lymphoproliferative disease was the most common (5% of pediatric recipients) comprising 80% of all tumors, with a disproportionately high prevalence among combined liver and small bowel recipients (18%). Various solid tumors were observed mainly among kidney recipients. No skin cancer was reported.

[Clinical usefulness of new-generation pulse oximetry in the paediatric cardiac surgery setting]. / Utilisation clinique d'un oxymètre de pouls de nouvelle génération dans le cadre de la chirurgie cardiaque pédiatrique.

OBJECTIVES: Arterial oxygen saturation (SaO(2)) monitoring using pulse oximeter (SpO(2)) is mandatory in the intensive care unit. The aim was to assess bias and precision of new (SpO(2)ng) and old (SpO(2)og) pulse oximeter technologies in the postoperative period following pediatric cardiac surgery in cyanotic children. STUDY DESIGN: Prospective, monocentric. PATIENTS AND METHODS: Ten patients (7 days to 53 months old) were studied in the postoperative period following palliative cardiac surgery. SaO(2), SpO(2)og, and SpO(2)ng were obtained every 4 hours. SaO(2) of arterial blood sample was obtained from an intra-arterial catheter located in the radial artery, on the same side as the oximeters. Bias and precision were assessed using Bland-Altman analysis. RESULTS: We obtained 136 SaO(2) determinations. Mean SaO(2) was 76+/-15%. SpO(2)og was significantly different from SaO(2), while SpO(2)ng was not different from SaO(2). In 21 (15%) cases, SpO(2)og was not available whereas SpO(2)ng was available in 136 (100%) cases. In the remaining 115 cases, SpO(2)ng's precision was significantly better than SpO(2)og's precision. DISCUSSION: SpO(2)ng is more accurate and more reliable than SpO(2)og for SaO(2) monitoring in the postoperative period following pediatric cardiac surgery in cyanotic children.

[Intravenous thrombolysis in pediatric arterial ischemic stroke: a case report and a review of the literature]. / L'utilisation de la thrombolyse intraveineuse dans l'infarctus cérébral artériel aigu de l'enfant, en dehors de la période néonatale : à propos d'un cas et revue de la littérature.

Pediatric arterial ischemic stroke (AIS) is little known by pediatricians, as it is rare and difficult to diagnose. Current therapeutic approaches include platelet aggregation inhibitors, anticoagulation using heparin or thrombolysis with rt-PA, and therapeutic abstention in the absence of consensus, in contrast with stroke in adults. We report the case of a 3-year-old child who benefited from intravenous thrombolysis with rt-PA 2h after a major AIS of the anterior and middle left arteries due to embolism from the heart. Neurological progression was marked by a persistent, severe functional deficiency, in spite of the early use of thrombolysis. No hemorrhagic complication occurred. This observation raises the problem of therapeutic indications in childhood AIS and more particularly the question of the use of intravenous thrombolysis. Currently, few studies exist on this subject and only a few case report of children and teenagers having received effective intravenous or intra-arterial thrombolysis further to an AIS are available in the literature. A single study describes 46 cases of children with AIS having received thrombolysis but reports numerous complications. However, the absence of symptomatic hemorrhagic complications is noteworthy. There is currently insufficient evidence to recommend thrombolysis in pediatric AIS; nevertheless it can be proposed in certain rare cases, similar to the observation reported herein.

Sentinel node biopsy in cutaneous melanoma: correlations between melanoma prognostic factors and sentinel node status.

This study aims to correlate the most important prognostic factors of primary melanoma with sentinel node (SN) positive for metastases. We have enrolled 84 patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's thickness > or = 0.75 mm by using an intra-operative gamma probe after lymphoscintigraphy, without blue dye support. SN metastases were reported in 27% of cases (14% by histology and 13% by immunohistochemistry). By chi-square test Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02), ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically significant (p < 0.05) with reference to SN positive for metastases, unlike the site of cutaneous melanoma, vertical growth phase, tumour infiltrating lymphocytes, regression and vascular invasion. Breslow's thickness remains the first prognostic factor to be considered for sentinel node biopsy in cutaneous melanoma, but other markers must be carefully estimated.

Current patterns of infective endocarditis in congenital heart disease.

OBJECTIVE: To assess the changing profile of infective endocarditis in patients with congenital heart disease. METHODS: All cases diagnosed from 1966 to 2001 (revised Duke criteria) were retrospectively reviewed and categorised in periods I (< 1990) and II (>or= 1990). RESULTS: 153 episodes occurred, 81 in period I and 72 in period II. Mean age of affected patients was higher in period II. Non-operated ventricular septal defect, Rastelli correction and palliated cyanotic heart disease increased. Infective endocarditis in corrective surgery changed to patients with prosthetic material. Post-surgical cases decreased. Dental problems were the leading cause (period I 20% v II 33% of cases) with a large variety of pathological organisms (multiple species of Streptococcus). Cutaneous causative infections increased (5% to 17%) with different species of Staphylococcus. Negative blood cultures lessened (20% to 7%, p = 0.03). Streptococci were the most common causative organisms in both periods. Severe heart failure and cardiac complications lessened (20% to 4% and 31% to 18% during periods I and II, respectively). Early surgery was more frequent in period II (32% v 18.5%, p = 0.02). One- and 10-year survival was 91% v 97% in period I and 89% v 97% in period II, respectively (NS). CONCLUSION: Current targets include complex cyanotic disease, congenital heart disease corrected with prosthetic material and small ventricular septal defect. Postoperative cases lessened; dental and cutaneous causes increased. Survival was unchanged. Prophylactic measures targeted at dental and cutaneous sources should be emphasised.

Reduction in urea distribution volume over time in clinically stable dialysis patients.

We have previously shown that, assuming urea distribution volume (V) remains constant for 1 month, ionic dialysance (ID) allows the dialysis dose to be calculated without the need for blood sampling. The aim of this multicenter study was to verify whether the assumption of a constant V can be extended to 1 year. In clinically stable patients receiving thrice-weekly hemodialysis at 13 dialysis centers, V and Kt/V were assessed during three dialysis sessions at baseline and 1 year later using ID as dialyzer urea clearance and the single-pool urea kinetic model. Baseline albumin, hemoglobin, and C reactive protein were prespecified covariates for predicting the change in V over time. Of the 52 enrolled patients, 40 (25 males; age 63.0+/-13.5 years) completed the study. Baseline end-dialysis body weight (62.4+/-13.7 kg) showed a non-significant 1% reduction during follow-up (-0.6+/-2.8 kg; P=0.175), whereas V significantly decreased from 29.0+/-6.8 to 27.4+/-6.0 l (-1.6+/-3.0 l or 4.5%; P=0.002). The reduction in V was greater when baseline albumin was lower (P=0.001) and baseline V was higher (P=0.005). The single-pool K(t)/V calculated using baseline V underestimated the actual value by 0.07+/-0.16 (P=0.008). The slight underestimate of Kt/V during follow-up suggests that annual V evaluations may be sufficient for dialysis dose quantification as the only risk is underestimating the actually delivered dialysis dose. However, the relationship between baseline albumin and the reduction in V over time may have nutritional value, and suggests more frequent V evaluations.

120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

[Use of dialysate conductivity to obtain neutral sodium balance in chronic hemodialysis patients]. / L'utilizzo della conduttività del dialisato per il conseguimento del bilancio fisiologico del sodio nei pazienti in trattamento emodialitico periodico.

In order to assure a zero sodium balance in hemodialysis patients, attaining 'constant' values of total body water and plasma water sodium concentration at the end of each dialysis session is a basic pre-requisite. This is achieved by matching the ultrafiltration to the inter-dialytic weight gain and by individualizing dialysate sodium concentration at each dialysis session by making use of a kinetic model. Clinical results suggest that the single pool variable volume sodium kinetic model allows the targeted end-dialysis plasma water sodium concentration to be obtained. Nevertheless, this model is not suitable for routine clinical application, because of difficulties in the real-time determination of initial plasma water sodium concentration and 'effective' sodium dialysance. Measuring dialysate conductivity at the inlet and outlet ports of the dialyzer allows the estimation of sodium transfer during dialysis, if the function of concentration versus conductivity is known. If sodium transfer is measured at two different inlet dialysate conductivities, it is possible to determine ionic dialysance and systemic plasma water conductivity, which can be used routinely to apply the single pool sodium kinetic model. Given that ionic dialysance and plasma water conductivity can be measured easily repeatedly and inexpensively at each dialysis session without the need for blood sampling or laboratory determinations, it can be expected that conductivity kinetic models will soon become a part of everyday clinical practice.

[Evolution of the Fontan operation and results in patients with single ventricles or mixed congenital malformations]. / Evolution et résultats des opérations de Fontan dans les cardiopathies congénitales univentriculaires ou assimilées.

STUDY OBJECTIVES: To examine the results of right heart derivations and clinical outcomes according to preoperative characteristics and operative strategy implemented. METHODS: Fontan operations were performed in 65 patients (mean age = 10.3 years, 41 males). The majority of cardiopathies were single ventricles (SV) with (49% of patients) or without (26%) tricuspid atresia. A palliative bidirectional cavo-pulmonary (BCP) anastomosis was performed prior to Fontan in 15 patients. Intra-atrial Fontan tunnelling was performed in 43 patients, Kreutzer-type operations in 10, and extracardiac tubes were used in 8 patients. The mean duration of follow-up was 6.1 +/- 0.3 years. RESULT: The 30-day mortality was 13.8%. Early mortality was higher among patients with SV with than without tricuspid atresia (P < 0.01), and among patients < 4 years old. Early reoperations were required in 5 patients, including dismounting in 1, BCP anastomosis after Kreutzer procedure in 1, and tube thrombosis in 1 patient. A single death occurred past 30 days, and late adverse events included protein-losing enteropathy in 1 patient, complete atrioventricular block in 1, and tube thrombosis treated with heparin in 2 patients. At the end of follow-up, 75% were in New York Heart Association functional class I. CONCLUSION: Our intermediate-term results of Fontan-type operations were satisfactory, and steadily improving. The prognosis was better in patients operated at age 4 or older. A prior BCP anastomosis improved the results. A higher morbidity was observed with intra- than with extra-atrial Fontan procedures. The merit of fenestration procedures with respect to morbidity remains the be evaluated.

[Doxorubicin in antiblastic hyperthermic perfusion in the treatment of advanced soft-tissue sarcoma of the limbs]. / La doxorubicina nella perfusione ipertermico antiblastica nel trattamento dei sarcomi avanzati dei tessuti molli degli arti.

Different antineoplastic drugs have been associated to hyperthermia in the treatment of advanced soft tissue limb sarcoma with a good results in terms of conservative surgery (77%-97%), locoregional control (77%-87%) and overall survival (72%). Two different studies were performed: the first was carried out to analyze the doxorubicin-TNFalpha-hyperthermia association (three different trials) in terms of toxicity and efficacy of the treatment (tumor response, locoregional control, disease free and overall survival). The results showed that the trimodality association (doxorubicin TNFalpha and hyperthermia) is the best regimen able to obtain a 77% of objective response and 77% of limb sparing in patients candidate to amputation but may result in high local toxicity if high temperatures (>41.5 degrees C) were maintained during perfusion. The second study describes the employment of liposomal doxorubicin in hyperthermic antiblastic perfusion (HAP) in terms of tumor response, conservative surgery and toxicity; the maximum tolerable dose (MTD) of doxorubicin was 16 mg/l of perfused limb volume at the temperature of 41.5 degrees C; the conservative surgery was possible in 91% of the cases and mild (grade I and II) toxicity was observed in the perfused limb with high temperature (>41.5 degrees C).

[Characteristics of infectious endocarditis in ventricular septal defects in children and adults]. / Caractéristiques de l'endocardite infectieuse sur communication interventriculaire chez l'enfant et l'adulte.

The aim of this retrospective study was to analyse cases of infectious endocarditis (IE) of native or repaired ventricular septal defects (VSD) to determine its incidence, the circumstances of its occurrences, the outcome and prognosis of this complication. From 1966 to 2002, 36 IE occurred in 19 boys and 17 girls: the age at diagnosis was 13.4 +/- 11.8 years; 26 had an isolated VSD and 10 had VSD associated with a minor lesion. Eleven of the 36 cases (30.5%) had been previously operated: repair of an isolated VSD with a patch in 5 cases, associated with a Crafoord procedure for coarctation of the aorta in 2 cases, three times with conservative treatment of associated aortic regurgitation (AR) and with ligature of patent ductus arteriosus (PDA) in 1 case. Twenty-five of the 36 cases (69.5%) had not been operated before: 21 isolated type 1 VSD; 2 VSD + AR, 1 VSD with PDA (undiagnosed), 1 VSD with valvular pulmonary stenosis (PS). The portal of entry was post-surgical in 7 out of 36 cases (19.4%): 4 VSD patches, 2 VSD patches + Crafoord and 1 VSD patch with ligature of PDA. The source of infection was dental in 14 out of the 36 cases (38.9%): one isolated VSD repair with residual shunt, 11 native VSDs, and 2 cases of unoperated VSD + AR. The other infectious causes (15 = 41.7%) were ENT (2 cases), skin (2 cases), gastrointestinal (2 cases), pulmonary (1 case) or unknown (8 cases), on operated lesions (3 VSD patches + AR) or native lesions (12 cases: 10 isolated VSDs, 1 VSD with PSD and 1 VSD with PS). Twelve episodes occurred (33.3%) despite antibiotic prophylaxis, 7 out of 7 post-surgical and 5 out of 14 dental cases. The commonest localisation was the tricuspid valve (10 cases, always in isolated VSD). Embolism was observed in 60% of right heart endocarditis (always multiple) and in 55% of IE of the left heart (single embolism). Early surgery was required in 6 patients (16.7%). The risk of early surgery was higher in patients with VSDs associated with other lesions (4 out of 10 = 40%) than in isolated VSD (2 out of 26, 7.7%, p = 0.027). Thirteen patients underwent secondary surgery after an average interval of 2.96 years, median 0.86 years (from 4 months to 22.8 years) for VSD repair (10 cases), aortic valve replacement (2 cases) and aorto-aortic conduit (1 case). The global follow-up period was 7.4 +/- 8.3 years, from 28 days to 27.9 years (median 3.3 years). Five deaths were observed on average 3.7 +/- 6.2 years after the episode of IE (median 6 months): 2 were early, occurring less than 6 months after IE and directly related to the infective episode. The survival was 97.1% at 1 month, 94.3% at 6 months, 91.4% at 1 year and 86.6% at 5 and 10 years after IE. VSD is a benign cardiac lesion, the prognosis of which can be severely compromised by infectious endocarditis: surgical repair reduces the risk but does not totally exclude it because of minor associated abnormalities. Prophylactic antibiotic therapy and the diagnosis of latent infectious problems, particularly dental, remains essential before and after cardiac surgery.