Glucocorticoid Receptors, Brain-Derived Neurotrophic Factor, Serotonin and Dopamine Neurotransmission are Associated with Interferon-Induced Depression.

BACKGROUND: The role of inflammation in mood disorders has received increased attention. There is substantial evidence that cytokine therapies, such as interferon alpha (IFN-alpha), can induce depressive symptoms. Indeed, proinflammatory cytokines change brain function in several ways, such as altering neurotransmitters, the glucocorticoid axis, and apoptotic mechanisms. This study aimed to evaluate the impact on mood of initiating IFN-alpha and ribavirin treatment in a cohort of patients with chronic hepatitis C. We investigated clinical, personality, and functional genetic variants associated with cytokine-induced depression. METHODS: We recruited 344 Caucasian outpatients with chronic hepatitis C, initiating IFN-alpha and ribavirin therapy. All patients were euthymic at baseline according to DSM-IV-R criteria. Patients were assessed at baseline and 4, 12, 24, and 48 weeks after treatment initiation using the Patient Health Questionnaire (PHQ), the Hospital Anxiety and Depression Scale (HADS), and the Temperament and Character Inventory (TCI). We genotyped several functional polymorphisms of interleukin-28 (IL28B), indoleamine 2,3-dioxygenase (IDO-1), serotonin receptor-1A (HTR1A), catechol-O-methyl transferase (COMT), glucocorticoid receptors (GCR1 and GCR2), brain-derived neurotrophic factor (BDNF), and FK506 binding protein 5 (FKBP5) genes. A survival analysis was performed, and the Cox proportional hazards model was used for the multivariate analysis. RESULTS: The cumulative incidence of depression was 0.35 at week 24 and 0.46 at week 48. The genotypic distributions were in Hardy-Weinberg equilibrium. Older age (p = 0.018, hazard ratio [HR] per 5 years = 1.21), presence of depression history (p = 0.0001, HR = 2.38), and subthreshold depressive symptoms at baseline (p = 0.005, HR = 1.13) increased the risk of IFN-induced depression. So too did TCI personality traits, with high scores on fatigability (p = 0.0037, HR = 1.17), impulsiveness (p = 0.0200 HR = 1.14), disorderliness (p = 0.0339, HR = 1.11), and low scores on extravagance (p = 0.0040, HR = 0.85). An interaction between HTR1A and COMT genes was found. Patients carrying the G allele of HTR1A plus the Met substitution of the COMT polymorphism had a greater risk for depression during antiviral treatment (HR = 3.83) than patients with the CC (HTR1A) and Met allele (COMT) genotypes. Patients carrying the HTR1A CC genotype and the COMT Val/Val genotype (HR = 3.25) had a higher risk of depression than patients with the G allele (HTR1A) and the Val/Val genotype. Moreover, functional variants of the GCR1 (GG genotype: p = 0.0436, HR = 1.88) and BDNF genes (Val/Val genotype: p = 0.0453, HR = 0.55) were associated with depression. CONCLUSIONS: The results of the study support the theory that IFN-induced depression is associated with a complex pathophysiological background, including serotonergic and dopaminergic neurotransmission as well as glucocorticoid and neurotrophic factors. These findings may help to improve the management of patients on antiviral treatment and broaden our understanding of the pathogenesis of mood disorders.

Differential gene expression in drought-tolerant sugarcane roots.

Drought is one of the most frequent abiotic stresses limiting the productivity and geographical distribution of sugarcane culture. The use of drought-tolerant genotypes is one approach for overcoming the effects of water stress. We conducted a comparative study to identify gene expression profiles under water stress in tolerant sugarcane roots. Two different cultivars, 1 drought tolerant (RB867515) and 1 drought susceptible (SP86-155), were evaluated at 4 sampling time points (1, 3, 5, and 10 days) using the cDNA-amplified fragment length polymorphism technique. A total of 173 fragments were found to be differentially expressed in response to water stress in the tolerant cultivar. Seventy of these were cloned, sequenced, and categorized. Similarity analysis using BLAST revealed that 64% of the fragments differentially expressed code proteins classified as no hits (23%), hypothetical (21%), or involved in stress response (20%), with others were involved in communication pathways and signal transduction, bioenergetics, secondary metabolism, and growth and development. Four genes were analyzed and validated using real-time quantitative polymerase chain reaction to determine their expression and showed consistency with the cDNA-amplified fragment length polymorphism analyses. Our results contribute insight into the molecular responses to water stress in sugarcane and possibility to the development of cultivars with improved tolerance to drought.

Molecular responses to ocean acidification in an Antarctic bivalve and an ascidian.

Southern Ocean organisms are considered particularly vulnerable to Ocean acidification (OA), as they inhabit cold waters where calcite-aragonite saturation states are naturally low. It is also generally assumed that OA would affect calcifying animals more than non-calcifying animals. In this context, we aimed to study the impact of reduced pH on both types of species: the ascidian Cnemidocarpa verrucosa sp. A, and the bivalve Aequiyoldia eightsii, from an Antarctic fjord. We used gene expression profiling and enzyme activity to study the responses of these two Antarctic benthic species to OA. We report the results of an experiment lasting 66 days, comparing the molecular mechanisms underlying responses under two pCO2 treatments (ambient and elevated pCO2). We observed 224 up-regulated and 111 down-regulated genes (FC ≥ 2; p-value ≤ 0.05) in the ascidian. In particular, the decrease in pH caused an upregulation of genes involved in the immune system and antioxidant response. While fewer differentially expressed (DE) genes were observed in the infaunal bivalve, 34 genes were up-regulated, and 69 genes were downregulated (FC ≥ 2; p-value ≤ 0.05) in response to OA. We found downregulated genes involved in the oxidoreductase pathway (such as glucose dehydrogenase and trimethyl lysine dioxygenase), while the heat shock protein 70 was up-regulated. This work addresses the effect of OA in two common, widely distributed Antarctic species, showing striking results. Our major finding highlights the impact of OA on the non-calcifying species, a result that differ from the general trend, which describes a higher impact on calcifying species. This calls for discussion of potential effects on non-calcifying species, such as ascidians, a diverse and abundant group that form extended three-dimensional clusters in shallow waters and shelf areas in the Southern Ocean.

Differential expression of immune response genes associated with subclinical mastitis in dairy buffaloes.

Buffalo milk production has become of significant importance on the world scale, however, there are few studies involving biotechnological tools specifically for buffalo. To verify the effects caused by subclinical mastitis on the components of milk and to study the innate immune system in the udder of dairy buffaloes with subclinical mastitis, we evaluated the levels of expression of the lactoferrin (LTF), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-8 (IL-8), and toll-like receptors 2 (TLR-2) and 4 (TLR-4) genes in buffaloes with and without subclinical mastitis. Milk samples were collected for the determination of milk components: somatic cell score (SCS), fat, protein, lactose, total solids and solids-not-fat (SNF), as well as for RNA extraction of milk cells, complementary DNA synthesis, and expression profile quantification by quantitative real-time PCR. For gene expression, the ΔΔCt was estimated using contrasts of the target genes expression adjusted for the expression of the housekeeping genes between both groups. Linear regression analysis was performed to determine the relationship between the genes studied and the milk components. Subclinical mastitis induced changes in the fat, lactose and SNF in milk of buffaloes, and the messenger RNA abundance was upregulated for TLR-2, TLR-4, TNF-α, IL-1ß and IL-8 genes in milk cells of buffaloes with subclinical mastitis, whereas the LTF gene was not differentially expressed. Results of linear regression analysis showed that TLR-2 gene expression most explains the variation in SCS, and the change in a unit of ΔCt of the TNF-α gene would result in a higher increase in SCS. The study of these immune function genes that are active in the mammary gland is important to characterize the action mechanism of the innate immunity that occurs in subclinical mastitis in dairy buffaloes and may aid the development of strategies to preserve the health of the udder.

[Lung cancer risk in shoe manufacturing]. / Riesgo de presentar cáncer de pulmón en los trabajadores de la manufactura del calzado.

OBJECTIVE: Workers in shoe manufacturing have been reported to be at a greater relative risk for bronchogenic carcinoma. Given the implications for our practice setting, we carried out a study to a) clarify whether working in shoe manufacturing is a risk factor for lung cancer and b) detect histological differences between lung cancers in shoe manufacturers and in other lung cancer patients. PATIENTS AND METHODS: This case-control study compared all lung cancer patients diagnosed in Hospital Elda, Alicante, Spain, between January 1994 and December 1999, with a control group composed of patients admitted to the same hospital for accidental fractures. Information on occupational history and tobacco dependency was collected from all patients by telephone questionnaire. RESULTS: One hundred and ninety-one case patients and 192 control patients were included in the study; 52 of the cases (27.2%) and 48 controls (25%) worked in shoe manufacturing. No statistically significant differences were found between the 2 groups, not even when we limited the cases and controls to only those who had worked more than 30 years in shoe manufacturing or when we analyzed only subjects who had had especially high risk occupations. No differences in tumor histology were found between cancer patients who worked in shoe manufacture and those who did not. CONCLUSIONS: Working in shoe manufacturing has not proven to be a risk factor for bronchogenic carcinoma.

Pelvic MRI findings in relapsed prostate cancer after radical prostatectomy.

PURPOSE/OBJECTIVE: Little is known about the clinical impact of using multiparametric MRI to plan early salvage radiotherapy after radical prostatectomy. We aimed to evaluate the incidence and location of recurrence based on pelvic multiparametric MRI findings and to identify clinical variables predictive of positive imaging results. MATERIALS AND METHODS: We defined radiological criteria of local and lymph node malignancy and reviewed records and MRI studies of 70 patients with PSA recurrence after radical prostatectomy. We performed univariate and multivariate analysis to identify any association between clinical, pathological and treatment-related variables and imaging results. RESULTS: Multiparametric MRI was positive in 33/70 patients. We found local and lymph node recurrence in 27 patients and 7 patients, respectively, with a median PSA value of 0.38 ng/ml. We found no statistically significant differences between patients with positive and negative multiparametric MRI for any variable. Shorter PSADT was associated with positive lymph nodes (median PSADT: 5.12 vs 12.70 months; p: 0.017). CONCLUSIONS: Nearly half the patients had visible disease in multiparametric MRI despite low PSA. Positive lymph nodes incidence should be considered when planning salvage radiotherapy, particularly in patients with a short PSADT.

Clinical and hemodynamic predictors of survival in patients aged < 65 years with severe congestive heart failure secondary to ischemic or nonischemic dilated cardiomyopathy.

To identify which clinical or hemodynamic parameters predict survival in patients with end-stage heart failure due to dilated cardiomyopathy, 130 consecutive patients aged < 65 years (mean 46 +/- 13) assessed for heart transplantation from May 1986 to April 1991 were studied. Mean follow-up was 15 +/- 11 months. Left ventricular ejection fraction was 22 +/- 7%. Left ventricular end-diastolic pressure was 27 +/- 9 mm Hg, and cardiac index was 2.2 +/- 0.6 liter/min/m2. Symptom class was IV in 91% of patients and III in 9%. Etiology was ischemic in 40% of patients and idiopathic in 60%. After intensive medical therapy, heart transplantation was considered indicated in 53% of patients, contraindicated in 20% and not indicated in 27%. Transplantation was performed in 36% of patients during follow-up, and 35% died and 29% were alive without transplantation. A comparison, excluding patients with transplantation, was performed between those who were alive and had survived > or = 6 months after assessment, and those who died. On multivariate analysis, the following 3 parameters were independent predictors of prognosis: intravenous inotropic requirement (p < 0.001), maximal, tolerated captopril dose (p = 0.013) and systolic blood pressure (p = 0.003). When patients with transplantation were considered as deaths, stabilization on medical therapy also reached statistical significance (p = 0.009). Classic prognostic markers including ventricular arrhythmias, left ventricular end-diastolic pressure, cardiac index, amiodarone therapy and etiology were not associated with prognosis in this homogeneous population of severely ill patients.

Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis.

To assess the incidence of a specific etiology and the role of methods for specific etiologic diagnosis in patients with primary acute pericarditis, we studied 100 patients with primary acute pericarditis consecutively admitted to our hospital between 1991 and 1993. A general diagnostic protocol was performed in all patients, whereas only pericardiocentesis was performed in patients with clinical cardiac tamponade or an unfavorable course with anti-inflammatory drugs. Surgical drainage and pericardial biopsy was performed in patients with tamponade relapse. A specific etiology was discovered in 22 patients (22%) (neoplasms in 7, tuberculosis in 4, other infections in 3, collagen diseases in 3, thyroid disorders in 4, and dissecting aortic aneurysm in 1). The general diagnostic protocol led to a specific diagnosis in 15 patients (68% of all patients with specific acute pericarditis) and pericardiocentesis in the other 7 patients (32%). The role of a diagnostic protocol, therapeutic pericardiocentesis, and diagnostic pericardiocentesis was similar and complementary. Pericardial biopsy results were negative in the 5 patients in whom it was performed. Cardiac tamponade and an unfavorable clinical outcome were significantly (p < 0.001) associated with the finding of a specific etiology; when both features were combined, sensitivity was 86% and specificity 85%, positive predictive value 63% and negative predictive value 96%. We conclude that the specific etiology in patients with primary acute pericarditis is about 20% to 25%, and that about 90% of these specific cases can be discovered by using the described systematic diagnostic protocol only in patients with an unfavorable outcome (cardiac tamponade or poor clinical course).

Influence of heart transplantation on the natural history of patients with severe congestive heart failure.

In an attempt to study the influence of heart transplantation on the natural history of patients with severe congestive heart failure, we have reviewed our experience with 240 consecutive patients who were New York Heart Association class IV or III/IV, who had left ventricular ejection fraction less than 35%, who were younger than 65 years of age, and who were assessed for heart transplantation in our hospital since May 1986. Mean age was 47 +/- 12 years. Left ventricular ejection fraction was 20% +/- 6%. Eighty-seven percent were male. New York Heart Association class was IV in 88% and III/IV in 12%. The cause was ischemic heart disease in 35% of patients, valvular heart disease in 13% of patients, and primary dilated cardiomyopathy in 52% of patients. At initial assessment, heart transplantation was considered to be not indicated in 30% of patients, indicated in 51% of patients, and contraindicated in 19% of patients. During a follow-up of 13 +/- 13 months (2 to 64 months), 110 patients underwent transplantation (46%). Posttransplantation actuarial probability of survival was 70% at 3 years. Three-year probability of survival free from transplantation was significantly lower for patients older than 55 years of age (p < 0.05), for those with left ventricular ejection fraction less than 20% (p < 0.05), ischemic causes (p < 0.05), New York Heart Association class IV (p < 0.001), and indication/contraindication for transplantation (p < 0.001); no difference was noted for gender.(ABSTRACT TRUNCATED AT 250 WORDS)

Repetitive nontreated episodes of grade 1B or 2 acute rejection impair long-term cardiac graft function.

BACKGROUND: Episodes of grade 1B or 2 acute heart rejection are usually not treated, and most of them resolve spontaneously. METHODS: With the aim to assess long-term outcome in patients with repetitive nontreated episodes of low-grade (1B, 2) acute rejection, we have studied 141 heart transplant recipients in whom the evolutive pattern of acute rejection during the first 6 months after transplantation could be determined. RESULTS: Forty-four patients (31%) had only grade 0 or 1A acute rejection episodes (pattern A); 23 patients (16%) had three or more episodes of grade 1B or 2 acute rejection without 3A or more advanced rejection (pattern B); 48 patients (34%) had one or two episodes of grade 3A, 3B, or 4 acute rejection only during the first 6 months after transplantation (pattern C); and 26 patients (19%) had three or more episodes of grade 3A, 3B, or 4 acute rejection (pattern D). Overall mortality was 11%, 26%, 19%, and 46% for patients with patterns A, B, C, and D, respectively. No difference was found among patterns with regard to incidence of graft atherosclerosis. Left ventricular ejection fraction at 1 year after transplantation was significantly lower (p < 0.05) for patients with pattern B (50% +/- 5% versus 59% +/- 7%, 59% +/- 11%, and 56% +/- 6% for patterns A, C, and D, respectively); cardiac index also was lower for patients with pattern B than for those with pattern A (3.6 +/- 0.6 versus 4.1 +/- 0.6 L/min/m2, p < 0.05). CONCLUSIONS: Although mortality was higher for patients with more severe episodes of acute rejection, only repetitive nontreated episodes of grade 1B or 2 rejection significantly impaired long-term graft function.

The typing of botulinal neurotoxins.

The serological identification of Clostridium botulinum neurotoxin (BoNT) subtypes has shown to be elusive when current standard serologic tests are used. Based on (1) the in vivo response expected on quantitative BoNT-antitoxin systems and (2) the actual and the hypothetical antigenic makeup of BoNT subtypes, a comprehensive method for BoNTs typing is proposed.

FIA-fluorimetric determination of thiamine.

A flow injection-fluorimetric determination of thiamine is reported. The procedure is based on the oxidation of the analyte with potassium hexacyanoferrate(III) immobilized on an anionic exchange resin; the fluorescence is monitored in aqueous basic solution. Concentrations of the vitamin of 0.1-4 ppm have been determined; the relative standard deviation was 1.8%. The injection rate was 28 samples/h. The influence of other substances and the determination of the drug in a pharmaceutical formulation are also reported.

Posterior fossa epidural hematomas: a review and synthesis.

The authors report three patients with posterior fossa epidural hematomas and analyze 80 additional cases in the accessible literature. They occur in the younger age groups with a clear male predominance (3.6 to 1). The loss of consciousness at the time of impact and just before surgical intervention have both proved to be factors indicating a poor prognosis. The clinical symptoms and signs were classified in three general types: increased intracranial pressure, brainstem dysfunction, and cerebellar disturbances. A fracture of the occipital bone was seen in 84.2% of the patients. The source of bleeding often remained undetermined, although a tear of the dural sinuses was a most frequent finding. An associated intracranial lesion was found in 39.7% of the cases, this being another factor indicating a poor prognosis. The overall mortality was 26.5%, while the surgical mortality was only 11.5%. Excellent results were achieved in 65% of the cases.

Prevalence and characterization of Staphylococcus aureus in young goats.

Thirty-six Staphylococcus aureus isolates recovered from 35 of 204 young goats at slaughter were characterized. All isolates were susceptible to cephalothin, clindamycin, chloramphenicol, gentamicin, kanamycin, and amikacin. All but 2 were susceptible to erythromycin and tetracycline, and 19 and 20 were susceptible to penicillin and ampicillin, respectively. Thirteen isolates were classified as biotype A, 9 isolates were classified as biotype B, 8 isolates were classified as biotype C, and 6 isolates were classified as intermediate between B and C or were not biotypable. Six biotype A isolates were enterotoxigenic; 4 produced enterotoxin B, 1 produced enterotoxin C, and 1 produced enterotoxin D. Two biotype B strains produced enterotoxin B, and all 8 biotype C isolates produced enterotoxin C and the toxic shock syndrome toxin-1.

[For whom and when is a heart transplant indicated]. / A quién y cuándo indicar un trasplante cardíaco.

Selection of receptor has a great importance in the field of heart transplantation, due to its influence on short and long-term results after transplantation and to a better profit of available donors and resources. Although several parameters of prognostic value in patients with severe heart failure have been suggested, the indication and timing of heart transplantation are still based on a accurate assessment of contraindications or risk factors in the receptors, as well as on the clinical and functional condition of patients while receiving an adequate medical therapy.

[Infectious endocarditis due to Q fever. A report of 4 new cases]. / Endocarditis infecciosa por fiebre Q. Descripción de 4 nuevos casos.

Q fever (Coxiella burnetii) is an uncommon cause of culture-negative infective endocarditis. Four cases of Q fever endocarditis diagnosed at our hospital in the last 7 years are reported (8% of all infective endocarditis). Infection involved a prosthetic heart valve in 3 cases (15% of all prosthetic valve endocarditis), and one patient with single ventricle and pulmonary stenosis in the remaining case. Important complications developed in all cases, and 3 patients underwent cardiac surgery. Mortality was 50%. Some diagnostic and therapeutical aspects of this disease are discussed.

[Bradyarrhythmias secondary to the use of ophthalmic timolol. A report of 3 cases]. / Bradiarritmias secundarias al uso de timolol oftálmico. Descripción de 3 casos.

Three cases of symptomatic bradycardia due to topical ocular timolol administration are reported. Two patients had syncope related to atrioventricular block, and the other one complained of dizziness due to sinus bradycardia. Heart disease was not present in any case, although a right bundle branch block was observed in one patients. A normal sinus rhythm resumed in all patients after discontinuation of timolol.

[Spontaneous remission in a patient with long-term idiopathic dilated myocardiopathy]. / Remisión espontánea en un paciente con miocardiopatía dilatada idiopática de larga evolución.

The case of a patient with long-term idiopathic dilated cardiomyopathy, functional class IV, very depressed left ventricular ejection fraction (13%) and history of severe dyspnea for more than four years, who experienced an spontaneous clinical and hemodynamic recovery (functional class I, left ventricular ejection fraction 51%) while being on waiting list for heart transplantation is reported. The patient remains in good clinical condition after a follow-up of two years.

[Patients with an acute myocardial infarct treated in a coronary unit or in a general cardiology ward A comparative study]. / Pacientes con infarto agudo de miocardio tratados en unidad coronaria o en sala general de cardiología. Un estudio comparativo.

INTRODUCTION AND OBJECTIVES: Coronary care units have been accepted as the standard location for treatment for patients with acute myocardial infarction. Nevertheless, controversy over their clinical impact, current role and cost-effectiveness still remains. Due to the increased incidence of coronary artery disease in Spain, coronary care units are often full, and patients with acute myocardial infarction must be cared for in a general cardiology ward. METHODS: We have studied the features and results of 420 patients with acute myocardial infarction consecutively admitted to our hospital and compared patients cared for in the coronary care unit (329 [78%]) with those cared for in the cardiology ward (91 [22%]). Admission to cardiology ward or coronary care unit was based on the clinical judgment of emergency room physicians and the bed availability. No differences in age, sex, risks factors, prior history of coronary heart disease, blood pressure on admission, extension and complications of myocardial infarction were found between both groups. RESULTS: The percentage of patients with evolved and non-Q wave acute myocardial infarction, and admission electrocardiogram not suggestive of infarction was significantly higher in ward group (23 versus 2.4%, p < 0.001; 19 versus 11%, p < 0.01; and 43 versus 15%, p < 0.01; respectively). Although patients admitted to the coronary care unit underwent intravenous thrombolysis and coronary artery revascularization procedures in a higher proportion, mortality was similar in both groups (14% for ward patients and 17% for coronary care unit patients). When patients with evolved or non-Q wave infarctions and those with admission electrocardiograms not suggestive of infarction were excluded from the analysis, mortality rates remained similar. Subgroups mortality was in general similar for patients cared for in cardiology ward or in coronary care unit, although patients without shock, with Killip class I or II, and older than 70 years, had a slightly lesser mortality when treated in the Cardiology ward (5 versus 11%, 6 versus 11%, and 14 versus 28%, respectively). By contrast, patients with shock, Killip class III or IV, and electrocardiogram at admission not suggestive of infarction, had a lesser mortality when cared for in coronary care unit. CONCLUSIONS: We conclude that some subgroups of patients with acute myocardial infarction can be, if needed, effective and safely cared for in cardiology ward.

[Acute myocarditis with severe cardiac dysfunction in the pediatric population. The evolution and differential characteristics with respect to adult myocarditis]. / Miocarditis aguda con disfunción cardíaca severa en la problación pediátrica. Evolución y características diferenciales con respecto a la miocarditis del adulto.

AIMS: The aim of our study was to assess the spontaneous outcome of acute myocarditis associated with severe cardiac dysfunction in children, as well as to compare these features with those occurring in adult patients. METHODS: Fifty patients consecutively diagnosed of acute myocarditis during the last 7 years in our hospital were studied; 15 patients were children younger than 14 years, and 35 were adults. Immunosuppressive therapy was not used in any patient. RESULTS: Mean age was 2 +/- 3 years in children, ranging from 2 months to 12 years. One patient required temporary pacing for a third-degree atrioventricular block, while the remaining 14 children had severe congestive heart failure, with a left ventricular ejection fraction of 30 +/- 12% (16 to 44%). After a mean follow-up of 21 +/- 26 months, only 3 children died, at 1, 4 and 10 months after the initial diagnosis. Death was sudden in all 3 patients. Left ventricular ejection fraction rose to 45 +/- 14% at 1 month after diagnosis, and to 58 +/- 15% at the end of follow-up. Unfavorable evolution (death or evolution to chronic dilated cardiomyopathy, with a left ventricular ejection fraction < 45%) occurred in 6 children (40%) at 1 month after diagnosis and in only 4 (25%) at the end of follow-up. The 9 children with 1-month favorable outcome were alive and had an ejection fraction > 45% at long-term, while only 2 of the 6 children with 1-month unfavorable outcome were alive and had an ejection fraction > 45% at long-term. Only the 3 children who died had an ejection fraction < 30% at 1-month. Favorable outcome was more frequent in children that in adult patients with acute myocarditis (75% versus 46%). CONCLUSIONS: The outcome of acute myocarditis with severe cardiac dysfunction was favorable in a majority of pediatric patients; this favorable evolution was less frequent in adults. Patients in whom left ventricular ejection fraction did not increase at short-term had a higher risk of death, and they should probably be considered for heart transplantation.