Frequency of Oral Mucositis and Local Virus Reactivation in Herpes Simplex Virus Seropositive Children with Myelosuppressive Therapy.

BACKGROUND: Oral mucositis (OM) is a common chemo- and radiotherapy adverse effect in oncological pediatric patients. Herpes simplex virus (HSV) infection can cause a severe clinical course. We hypothesize, that HSV seropositivity is a risk factor for local HSV-1 reactivation and increased frequency of OM in patients with myelosuppressive therapies. PATIENTS AND METHOD: We evaluated the prevalence of seropositivity of HSV-1 between June 2011 and April 2014 in patients with potential oncological disease and correlated it to the frequency of OM and local viral reactivation in OM under myelosuppressive therapy. RESULTS: The overall rate of HSV-seropositivity in our cohort was 22%. 48 patients underwent myelosuppressive therapy. Of these, 7 were HSV-1 IgG positive and 41 negative. All patients with OM under myelosuppressive therapy and positive local swab for viral HSV (l-PCR) were HSV-1 IgG positive before the start of therapy (100%). The absolute risk for OM in HSV-1 IgG positive patients was increased by 58.5% (95%CI: 20.0 - 72.2%) corresponding to a relative risk (RR) of 2.4 (95%CI: 1.7-3.5, P=0.009). The multivariable adjusted OR to suffer 2 or more OM episodes in HSV-1 IgG positivity was 8.8 (95%CI: 1.5-95.8, P=0.014). DISCUSSION AND CONCLUSION: In HSV-1 IgG positive patients half of the OM episode showed HSV reactivation, and the risk for multiple OM episodes was increased. These patients should be investigated for HSV-infection in every OM episode. Prophylactic and preemptive therapeutic measures should be discussed early, but prospective data on HSV prophylaxis and preemptive treatment is required.

[Hybrid procedures in congenital heart disease]. / Interventions hybrides et malformations cardiaques congénitales.

Increasing complexity in management of congenital heart disease imposes more frequent surgeries and interventions. Each technique has its own limitations, which could impair the anticipated result. Hybrid procedures join the advantages of cardiac surgery and interventions, creating a synergy in the management of these patients with cardiac anomalies. In our experience, hybrid procedures shorten cardiopulmonary bypass, reduce morbidity of surgery and reduce duration of stay in the intensive care unit. For some complex congenital heart diseases for which there are no ideal surgical or interventional options, hybrid procedures are becoming increasingly important in their management. Finally hybrid procedures allow surgeons and cardiologist to achieve complex procedures that could not be possible in another way.

[Stents valves for percutaneous valve replacement]. / Remplacement valvulaire percutané au moyen de stent-valves--une nouvelle approche thérapeutique.

Stents have a long history in traditional valve surgery as both, porcine biological valves as well as pericardial valves are mounted on stents prior to implantation. Recently stent-mounted biological devices have been compressed up to the point, where they can be passed through a catheter. Various routes can be distinguished for implantation: open access, the trans-vascular route in antegrade or retrograde fashion, as well as direct trans-apical or trans-atrial access. Direct access has the potentialforvideo-endoscopic valve replacement. In theory, as well as in the experimental setting, valved stents have been implanted in tricuspid and caval position respectively, as well as in pulmonary, mitral and aortic locations. The largest clinical experience has been achieved in pulmonary position whereas current efforts target the aortic position.

[Cell therapies in cardiology: results from the first randomized clinical trials]. / Thérapie cellulaire en cardiologie: bilan des premiers essais cliniques randomisés.

Following acute myocardial infarction, necrotic cardiac tissue is replaced by scar leading to ventricular remodeling and pump failure. Transplantation of autologous bone marrow-derived cells into the heart, early post-infarct, aims to prevent ventricular remodeling. This strategy has been evaluated in four controlled, randomized clinical trials, which provided mixed results. A transient improvement in ventricular function was observed in one trial, and a modest improvement (the duration of which remains to be determined) in an additional trial, whereas two trials showed negative results. A modest benefit of bone marrow cell transplantation was also observed in patients with chronic ischemic heart disease. Despite mixed results reported so far, cell therapy of heart disease still is in its infancy and has considerable room for improvement.

[Transposition of the great arteries: long-term follow-up]. / Transposition des gros vaisseaux: suivi a long-terme.

The management of transposition of the great arteries has changed importantly over the last decades. New techniques are employed for the diagnosis and surgical intervention has improved. This has lead to an increasing number of long-term survivors, who require specialised and focussed follow-up, depending on their type of surgical repair Mustard/Senning of arterial Switch. The long-term problems vary for each type of repair and require a specific approach, pharmacotherapy, catheter intervention or surgery. These complex sequellae implicate that transposition patients are never completely cured and probably will have a limited life span.

[Surgical options for terminal heart failure]. / Options chirurgicates pour l'insuffisance cardiaque terminale.

Terminal heart failure can be the cause or the result of major dysfunctions of the organisms. Although, the outcome of the natural history is the same in both situations, it is of prime importance to differentiate the two, as only heart failure as the primary cause allows for successful mechanical circulatory support as bridge to transplantation or towards recovery. Various objective parameters allow for the establishment of the diagnosis of terminal heart failure despite optimal medical treatment. A cardiac index <2.0 l/min, and a mixed venous oxygen saturation <60%, in combination with progressive renal failure, should trigger a diagnostic work-up in order to identify cardiac defects that can be corrected or to list the patient for transplantation with/without mechanical circulatory support.

[Pediatrics. Advantages of prenatal diagnosis in congenital cardiopathies]. / Pédiatrie. Avantages du diagnostic prénatal dans les cardiopathies congénitales.

The diagnosis of a congenital heart disease can be made by fetal ultrasound as soon as the 12th week of pregnancy. The main indications for fetal echocardiography are maternal and fetal. Sequential approach is necessary to precise the anatomy and to elaborate a therapeutic strategy for that patient. For severe heart lesions delivery and postnatal care can be programmed, avoiding thus severe hypoxia and acidosis after birth. The prognosis of these children are thus much improved.

[The heart transplant in Lausanne from 1987 to 2003]. / La greffe cardiaque à Lausanne de 1987 à 2003.

Since the availability of ciclosporine, the survival after heart transplantation has dramatically improved. We present our results since the beginning of our experience in 1987. We treated in the Lausanne University hospital, 150 patients for end-stage cardiac disease. Hundred and fifty-two transplantations were performed. The survival rate is comparable to the literature with 81% at one year, 70% at five year and 63 at ten year included the hospital mortality. We review the incidence of complications during the follow-up and report the modification in the management of these patients especially concerning the immunosuppression.

[Open heart radio frequency left atrial compartmentation during mitral valve surgery: an alternative to the labyrinth procedure?]. / Compartimentation auriculaire gauche par radiofréquence à ciel ouvert lors de chirurgie mitrale: une alternative possible à l'opération du labyrinthe?

The authors report their experience of radiofrequency left atrial compartimentation during open heart mitral valve surgery on 37 patients with a 42 +/- 12 months history of atrial fibrillation. The preoperative left ventricular ejection fraction was 62 +/- 8%; the left atrial diameter was 59 +/- 11 mm. The mean operative time was 245 +/- 60 minutes, which included 19 +/- 5 minutes for the ablation procedure. There were 2 early postoperative deaths and 2 deaths from non-cardiac causes at 3 and 6 months. The left ventricular ejection fraction and left atrial dimension were significantly decreased at the time of hospital discharge (54 +/- 12% and 51 +/- 7 mm respectively) (p < 0.01). After an average follow-up of 1 year, 81% of patients were free of atrial fibrillation: 6 patients had undergone DC cardioversion and 1 had a dual-chamber pacemaker. Patients in sinus rhythm after the ablation were associated with shorter periods of atrial fibrillation and smaller left atrial dimensions postoperatively than those who remained in fibrillation. The authors conclude that radiofrequency compartimentation of the left atrium associated with antiarrhythmic therapy can interrupt atrial fibrillation in 81% of patients at 1 year: the ablation procedure takes only 8% of the operation time. Predictive factors of success of ablation should be defined to determine which patients benefit most from this technique.

Left atrial radiofrequency compartmentalization for chronic atrial fibrillation during heart surgery.

BACKGROUND: The excellent results of the Maze III operation have demonstrated that a surgical cure of atrial fibrillation (AF) is possible. A simplified Maze procedure with radiofrequency (RF)ablation of the atrial tissue added to open heart surgery may help to cure chronic AF with low risk. METHODS: From May 1998 to March 2001, an RF left atrial compartmentalization concomitant to a cardiac surgical intervention was performed on 40 of 1,258 patients (3.2 %). Thirty-seven patients had mitral valve disease, two had aortic valve disease and one had coronary artery disease. All patients presented with chronic refractory AF for a mean time of 40.4 months ranging from 4 months to 18 years. RESULTS: Mitral valve replacement (MVR) was performed in 19 patients, mitral valve repair in 12, combined aortic and mitral valve procedures were performed in 6, aortic valve replacement(AVR) in 2 and CABG in 1 patient. Cardiopulmonary bypass time for the complete procedure was 138 +/- 32 minutes with an ablation time of 19 +/- 5 minutes. No complication related to RF application was noted. Sinus rhythm was present in 68% after 12.5 +/- 8.5 months. CONCLUSIONS: RF left atrial compartmentalization combined with cardiac surgical interventions proved to be easy and safe to perform. The long-term results still have to be confirmed with further regular patient follow-up examinations.

Surgery for aortic coarctation: a 30 years experience.

OBJECTIVE: A retrospective study to review the experience of a single center with surgery for aortic coarctation over a period of 30 years (1970-1999). METHODS: Criteria for inclusion: (a) aortic coarctation, isolated or associated with congenital heart defect; (b) surgery between 1970 and 1999. Data recorded: (1) date of surgery; (2) age at surgery; (3) associated lesions; (4) surgical technique; (5) simultaneous surgical procedures; (6) early and late surgical results in term of: (a) deaths; (b) need for reoperation because of re-coarctation or other cardiac lesion; (c) residual/recurrent pressure gradient, evaluated at cuff/Doppler at rest; (d) systemic hypertension, requiring medical treatment. RESULTS: One hundred and forty-one patients underwent surgery for aortic coarctation: 30 neonates, 29 infants, 45 children and 37 adults. Associated lesions were found in 8/37 (=21.6%) adults and in 73/104 (=70.1%) pediatric patients. There were no hospital deaths. During the follow-up there were one late death in the adults group (1/37=2.7%) and three late deaths in the pediatric group (3/104=2.9%), all unrelated with aortic coarctation. Re-operation because of re-coarctation occurred only in ten late survivors of the pediatric group (10/101=9.9%), 9/10 operated on before 1980 (P<0.00001). End-to-end anastomosis, enlarged to the aortic arch in neonates, was associated with the lowest incidence of re-coarctation (P<0.005). A significant (>20 mmHg at rest) pressure gradient was found in none of the adults, and in seven of the 91 pediatric patients (7/91=7.7%) late survivors. Three adults (3/36=8.3%) late survivors are on medical treatment to control systemic hypertension. CONCLUSIONS: The long-term results of our retrospective study confirm that surgery has to be considered the gold standard for the treatment of aortic coarctation. The interventional angioplasty techniques have to provide long-term outcome at least similar to the results obtained with surgery.

T cell involvement in cutaneous drug eruptions.

BACKGROUND: The most frequent side-effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear. OBJECTIVE: In this prospective study we investigated the T cell activation and drug specificity in different forms of drug-induced exanthemas from 22 patients. METHODS: During acute drug allergy, liver parameters and T cell subset activation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch-patch tests. RESULTS: Seventeen of 22 (17/22) patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4(+) and/or CD8(+) T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4(+) T cells dominated; a higher percentage of circulating CD8(+) T cells was found in patients with bullous skin reactions or hepatic involvement. CONCLUSION: Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8(+) T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4(+) cells elicits mainly maculo-papular reactions.

Tricuspid valve involvement in combined mitral and aortic valve surgery.

BACKGROUND: Combined mitral and aortic valve disease requiring surgery may involve the tricuspid valve as well. Our treatment policy is conservative especially for tricuspid regurgitation which is operated on when severe only. METHODS: A retrospective study was performed at a tertiary and secondary referral center for cardiovascular disease. Over a 15-year period, 65 consecutive patients underwent aortic and mitral surgery with concomitant tricuspid regurgitation and/or stenosis. Fifty-five/65 (85%) patients were in NYHA class III-IV. Fifty-eight/65 (89%) patients had tricuspid regurgitation secondary to right chamber dilatation and 7/65 (11%) had tricuspid stenosis and/or regurgitation because of previous endocarditis. Twenty-two/65 (34%) tricuspid valves were operated on: 18/22 (82%) de Vega annuloplasty, 2/22 (9%) commissurotomies and 2/22 (9%) prosthetic valves. Mortality and complications were recorded during a mean follow-up of 5.3 yrs (range, 6 months-15.3 yrs). Event-free survivals were determined using the Kaplan-Meier method. RESULTS: Hospital mortality was 6.2% (4/65) and the complication rate was 18.5% (12/65). The freedom from late valve related mortality and morbidity at 5, 10 and 15 years was 86+/-5.5%, 81.9+/-6.8%, and 81.9+/-6.8% respectively. One valve related complication was due to the tricuspid valve. At last follow-up, 87% (47/54) of the survivors were in NYHA class I-II. CONCLUSIONS: With a conservative policy of tricuspid valve intervention, functional results of this patient population are good and long-term valve related morbidity and mortality are mainly related to the mitral and aortic valve procedures.

Treatment of congenital aortic valve stenosis: impact of the Ross operation.

GOAL: To evaluate the impact of the Ross operation, recently (1997) introduced in our unit, for the treatment of patients with congenital aortic valve stenosis. METHODS: The period from January 1997 to December 2000 was compared with the previous 5 years (1992-96). Thirty-seven children (< 16 yrs) and 49 young adults (16-50 yrs) with congenital aortic valve stenosis underwent one of these treatments: percutaneous balloon dilatation (PBD), aortic valve commissurotomy, aortic valve replacement and the Ross operation. The Ross operation was performed in 16 patients, mean age 24.5 yrs (range 9-46 yrs) with a bicuspid stenotic aortic valve, 7/10 adults with calcifications, 2/10 adults with previous aortic valve commissurotomy, 4/6 children with aortic regurgitation following PBD, and 1/6 children who had had a previous aortic valve replacement with a prosthetic valve and aortic root enlargement. RESULTS: PBD was followed by death in two neonates (fibroelastosis); all other children survived PBD. Although there were no deaths, PBD in adults was recently abandoned, owing to unfavourable results. Aortic valve commissurotomy showed good results in children (no deaths). Aortic valve replacement, although associated with good results (no deaths), has been recently abandoned in children in favour of the Ross operation. Over a mean follow-up of 16 months (2-40 months) all patients are asymptomatic following Ross operation, with no echocardiographic evidence of aortic valve regurgitation in 10/16 patients and with trivial regurgitation in 6/16 patients. CONCLUSIONS: The approach now for children and young adults with congenital aortic valve stenosis should be as follows: (1) PBD is the first choice in neonates and infants; (2) Aortic valve commissurotomy is the first choice for children, neonates and infants after failed PBD; (3) The Ross operation is increasingly used in children after failed PBD and in young adults, even with a calcified aortic valve.

A prospective randomized trial comparing stenting to internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis: the SIMA trial. Stenting vs Internal Mammary Artery.

OBJECTIVE: To compare coronary artery bypass grafting (CABG) with percutaneous transluminal coronary angioplasty (PTCA) in patients with proximal, isolated de novo left anterior descending coronary artery disease and left ventricular ejection fraction of 45%. PATIENTS AND METHODS: In the multicenter Stenting vs Internal Mammary Artery (SIMA) study, patients were randomly assigned to PTCA and stent implantation or to CABG (using the internal mammary artery). The primary clinical composite end point was event-free survival, including death, myocardial infarction, and the need for additional revascularization. Secondary end points were functional class, antianginal treatment, and quality of life. Analyses were by intention to treat. RESULTS: Of 123 patients who accepted randomization, 59 underwent CABG, and 62 were treated with stent implantation (2 patients were excluded because of protocol violation). At a mean +/- SD follow-up of 2.4+/-0.9 years, a primary end point had occurred in 19 patients (31%) in the stent group and in 4 (7%) in the CABG group (P<.001). This significant difference in clinical outcome is due to a higher incidence of additional revascularization in the stent group, the incidence of death and myocardial infarction being similar (7% vs 7%, respectively; P=.90). The functional class, need for antianginal drug, and quality-of-life assessment showed no significant differences. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective treatments to relieve symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Both are associated with a low and comparable incidence of death and myocardial infarction. However, similar to PTCA alone, a percutaneous approach using elective stent placement remains hampered by a higher need for repeated intervention because of restenosis.

Intestinal absorption in patients after cardiac surgery.

OBJECTIVES: We designed this study to assess intestinal absorption in patients with adequate or altered hemodynamic status after cardiac surgery and to test clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive study. SETTING: Surgical intensive unit in a university teaching hospital. PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided into two groups according to hemodynamic status: group I, 16 patients with adequate hemodynamic status; group II, 23 patients with hemodynamic failure. These groups were compared with healthy controls (group III, n = 6). INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric or postpyloric paracetamol administration. Early postpyloric or conventional gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations were measured on days 1 and 3, and area under the curve (AUC) was calculated. Absorption was strongly reduced on day 1 in all patients after gastric administration (lower peak paracetamol and AUC), but normal after postpyloric delivery. Duration of anesthesia and of circulatory bypass did not affect paracetamol absorption. On day 3, AUC was close to normal in case of hemodynamic failure. Peak absorption on day 1 was negatively correlated with opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output, despite lower peak paracetamol, shows absorption was not suppressed, only delayed, because of decreased pyloric motility. The decrease on day 1 can be attributed to opiates, known to alter pyloric function and to slow down the intestinal transit.

Distinct serum cytokine levels in drug- and measles-induced exanthema.

BACKGROUND: Macular or maculopapular skin reactions are frequent events in drug allergy as well as in viral infections. Clinically, the differentiation may be difficult in the absence of a clear relationship to drug intake or failure to detect virus-specific antibodies of the IgM class. Studies on drug-specific T cell lines and T cell clones isolated from drug-allergic patients have suggested that these cells may represent a significant source of IL-5. On the other hand, viral infections are frequently associated with elevated IFN-gamma levels. OBJECTIVE: Determination of serum-cytokine levels to differentiate between drug- and virally induced skin eruptions. PATIENTS: 18 patients suffering from acute drug allergy and 19 patients with acute measles, rubella or parvovirus infection. MEASUREMENTS: Cytokine-ELISA (IL-5, IL-4 and IFN-gamma) of sera collected during acute drug allergy or during acute measles, rubella or parvovirus infection. RESULTS: In 12/18 patients with drug allergy, IL-5 and/or IL-4 were elevated. A significant correlation (r(Spearman) = 0.84) between IL-5 serum levels and eosinophil counts in the blood was found. No correlation was detected between IL-4 and blood eosinophilia or between IL-4 and IL-5 levels. After remission, IL-5 and IL-4 decreased to undetectable levels. IFN-gamma on the other hand was not measurable in patients with drug allergy while elevated IFN-gamma serum levels were detected in 17/19 patients with measles, rubella or parvovirus infection; 2 patients with acute virus infection had elevated IL-5, and/or IL-4 and IFN-gamma levels. CONCLUSION: These data underline the distinct pathogenesis of these morphologically similar exanthemas and suggest that the combined analysis of eosinophilia in the blood, IL-4 and IFN-gamma might help in differentiating skin eruptions.

Extramediastinal surgical problems in heart transplant recipients.

BACKGROUND: As heart transplantation has gained wide acceptance, a growing number of recipients are at risk of experiencing extramediastinal surgical problems. STUDY DESIGN: We retrospectively reviewed our experience in the diagnosis and management of surgical problems occurring in 94 consecutive patients having heart transplantation. During the period of the study, we progressively adopted a policy of low-level immunosuppression, aiming toward monotherapy with cyclosporine. RESULTS: Seventy-four extramediastinal surgical problems developed in 44 of 94 patients (47%). The type of problems were gastrointestinal in 17 of 74 (23%), vascular in 13 of 74 (17.5%), urogenital in 8 of 74 (11%), and neurologic in 4 of 74 (5.5%). There were also 9 of 74 cases of trauma (12%), 9 of 74 skin tumors (12%), and 14 of 74 miscellaneous diseases (19%). Sixty-two surgical diseases occurring in 40 patients required 75 surgical interventions, 11 of them (15%) on an emergency basis. Operations were performed for 12 of 74 neoplasms (16%) and 12 of 74 infectious or potentially infectious diseases (16%). Surgical diseases occurred most commonly within the first 6 months after transplantation (20 of 74; 27%). Complications occurred in 8 of 75 surgical interventions (9%). A high proportion of surgical disease was potentially related to immunosuppressive therapy (37 of 74; 50%) or to transplantation itself (7 of 74; 9%). CONCLUSIONS: Extramediastinal diseases after heart transplantation involve most surgical specialties. Most of them are potentially linked with either the immunosuppressive therapy or the transplantation procedure, supporting our low-level immunosuppression policy. Expectant management is not justified in this population, who withstands operations well both early and late after transplantation.