Suction drainage fluid culture during septic orthopaedic surgery, a retrospective study.

We evaluated the usefulness of suction drainage fluid culture after septic orthopaedic surgery to predict early surgical reintervention. We conducted a retrospective observational study, at the Groupe Hospitalier Paris Saint-Joseph between 2014 and 2019. All the patients undergoing septic orthopaedic surgery, with perioperative samples and a postoperative suction drainage device, were enrolled. We compared the group with positive or negative postoperative drainage fluid cultures, respectively, on surgical outcome. We included 246 patients. The drainage fluid culture was positive in 42.3% of the cases. Early surgical reintervention concerned 14.6% of the cases (n = 36), including 61.1% of patients with positive drainage fluid culture (n = 22/36). The risk factors associated with positive drainage fluid cultures were the debridement of the infected site (without orthopaedic device removal), an infection located at the spine, perioperative positive cultures to Staphylococcus aureus. The complete change of the orthopaedic device, and coagulase-negative staphylococci on the preoperative samples, was associated with negative drainage fluid cultures. Positive drainage fluid culture was predictive of early surgical reintervention, and coagulase-negative staphylococci in the preoperative samples and knee infection were predictive of surgical success. Postoperative drainage fluid cultures were predictive of early surgical reintervention. Randomized multicentric studies should be further conducted.

Be careful about MICs to amoxicillin for patients with Streptococci-related infective endocarditis.

BACKGROUND: A variety of microorganisms can cause infective endocarditis (IE), with Staphylococci and Streptococci accounting for the majority of cases. Streptococci are a common cause of community-acquired IE but few studies have focused on this subgroup of endocarditis. METHODS: A retrospective multicentre study was conducted between 2012 and 2017 in 12 hospital centres in France. Data were extracted from the local diagnosis-related group database and matched with microbiological results. After identification, the records were retrospectively analysed. RESULTS: A total of 414 patients with streptococcal endocarditis were included. The patients were predominantly male (72.8%) and the median age was 73.2 years (interquartile range [IQR] 61.3-80.9). The majority of patients (70.6%) had native valve endocarditis. Embolic complications were seen in 38.8% of patients. Viridans group Streptococci (VGS) and bovis-equinus group Streptococci (BGS) accounted for 52.4% and 34.5% of isolated strains, respectively. Minimum inhibitory concentrations (MICs) of amoxicillin were <0.125, 0.125-2 and >2 mg/L for 59.6%, 27% and 1% of isolates, respectively. In-hospital mortality for patients with Streptococci-related IE was 17.8%. In multivariate analysis, the only factor associated with in-hospital mortality was MIC for amoxicillin between 0.25 and 2 mg/L (P = 0.04; OR = 2.23 [95% confidence interval (CI) 1.03-4.88]) whereas performance of cardiac surgery for IE was a protective factor (P = 0.001, OR = 0.23 [95% CI 0.1-0.56]). CONCLUSIONS: IE remains a serious and deadly disease despite recent advances in diagnosis and treatment. Adaptation of antibiotic doses to MICs for amoxicillin and surgery may improve patient outcome.

Clinical diagnostic and therapeutic aspects of 221 consecutive anorectal Chlamydia trachomatis and Neisseria gonorrhoeae sexually transmitted infections among men who have sex with men.

OBJECTIVES: Proctitis caused by Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are known as sexually transmitted infections (STI). This study describes their clinical, diagnostic and therapeutic aspects. METHODS: Between 01/2013-03/2015, all MSM consulting for proctitis at proctology Institute-Saint-Joseph's Hospital, Paris, were included. Demographic, past-medical history, STI status and medical treatment were collected. Detection of CT/NG was performed by Transcription-Mediated Amplification (TMA) and antimicrobial susceptibilities for Ng by agar diffusion method. RESULTS: On 441 rectal samples collected, 221 (50.1%) were positive: 109 Ct (49.3%), 70 Ng (31.7%), 42 positive for both etiologies (19%). Among Ng infections, no resistance was detected to azithromycin and ceftriaxone. However, 84 strains (43.2%) were resistant to fluoroquinolones. More than one episode was diagnosed for 10 (5.1%) and 12 (6.2%) patients with CT and NG infections respectively. Anal abscesses were found for 27 (13.9%) patients, and 14 (7.2%) of them underwent surgery for anal fistula. CONCLUSIONS: The prevalence of CT/NG anorectal infections described is high on symptomatic patients, and a significant level of abscess was reported. These results confirm the interest of the association of recommended antibiotics excluding quinolones. Prospective studies would be relevant on complicated forms of anorectal infections.

Infective endocarditis: Clinical presentation, etiology, and early predictors of in-hospital case fatality.

OBJECTIVE: We aimed to assess the clinical presentation, microbial etiology and outcome of patients presenting with infective endocarditis (IE). PATIENTS AND METHODS: We conducted a four-year retrospective study including all patients presenting with IE. RESULTS: We included 121 patients in the study. The median age was 74.8years. Most patients had native valve IE (57%). Staphylococcus aureus accounted for 24.8% of all IE. Surgery was indicated for 70 patients (57.9%) but actually performed in only 55 (44.7%). Factors associated with surgery were younger age (P=0.002) and prosthetic valve IE (P=0.001). Risk factors associated with in-hospital mortality were diabetes mellitus (OR=3.17), chronic renal insufficiency (OR=6.62), and surgical indication (OR=3.49). Mortality of patients who underwent surgery was one sixth of that of patients with surgical indication who did not have the surgery (P<0.001).

Spondylodiscitis due to anaerobic bacteria about a case of Parvimonas micra infection.

Parvimonas micra is a rare isolate in clinical specimens. We report a case of spondylodiscitis caused by P. micra, a rarely reported Gram positive cocci. The case was an elderly patient with joint surgery and ischaemic heart disease history. Infection resolved after adequate antibiotic therapy.

Generic vancomycin products: Analysis of serum concentrations in patients with acute myeloid leukemia.

UNLABELLED: Concerns have recently emerged about the quality of generic vancomycin products. Our aim is to analyze serum vancomycin concentrations measured 48 hours after the start of an empirical treatment regimen in patients with acute myeloid leukemia (AML) who received one of the two generic vancomycin products available in France. PATIENTS AND METHODS: Seventy-nine AML patients treated with vancomycin during two study periods were included in the study. Our vancomycin dosing regimen was based on the patients' total body weight adjusted for renal clearance. RESULTS: A total of 93 serum vancomycin concentrations were collected: 31 in period 1 and 62 in period 2. In bivariate analysis, the mean serum vancomycin concentrations were not significantly different (19.9 ± 11.2 mg/L in period 1 vs 18.9 ± 6.0 mg/L in period 2, P=0.64). In the final generalized estimating equations model, serum vancomycin concentrations correlated statistically with a positive coefficient for age (P<0.001) and with negative coefficients for male sex (P=0.001) and hemoglobin level (P=0.021). CONCLUSION: Serum vancomycin concentrations measured 48 hours after the start of an empirical treatment were not influenced by the nature of the generic product but correlated with age, sex and hemoglobin level in AML patients.

Evaluation properties of the French version of the OUT-PATSAT35 satisfaction with care questionnaire according to classical and item response theory analyses.

PURPOSE: The present study investigates the properties of the French version of the OUT-PATSAT35 questionnaire, which evaluates the outpatients' satisfaction with care in oncology using classical analysis (CTT) and item response theory (IRT). METHODS: This cross-sectional multicenter study includes 692 patients who completed the questionnaire at the end of their ambulatory treatment. CTT analyses tested the main psychometric properties (convergent and divergent validity, and internal consistency). IRT analyses were conducted separately for each OUT-PATSAT35 domain (the doctors, the nurses or the radiation therapists and the services/organization) by models from the Rasch family. We examined the fit of the data to the model expectations and tested whether the model assumptions of unidimensionality, monotonicity and local independence were respected. RESULTS: A total of 605 (87.4%) respondents were analyzed with a mean age of 64 years (range 29-88). Internal consistency for all scales separately and for the three main domains was good (Cronbach's α 0.74-0.98). IRT analyses were performed with the partial credit model. No disordered thresholds of polytomous items were found. Each domain showed high reliability but fitted poorly to the Rasch models. Three items in particular, the item about "promptness" in the doctors' domain and the items about "accessibility" and "environment" in the services/organization domain, presented the highest default of fit. A correct fit of the Rasch model can be obtained by dropping these items. Most of the local dependence concerned items about "information provided" in each domain. A major deviation of unidimensionality was found in the nurses' domain. CONCLUSIONS: CTT showed good psychometric properties of the OUT-PATSAT35. However, the Rasch analysis revealed some misfitting and redundant items. Taking the above problems into consideration, it could be interesting to refine the questionnaire in a future study.

Iron excess limits HHIPL-2 gene expression and decreases osteoblastic activity in human MG-63 cells.

UNLABELLED: In order to understand mechanisms involved in osteoporosis observed during iron overload diseases, we analyzed the impact of iron on a human osteoblast-like cell line. Iron exposure decreases osteoblast phenotype. HHIPL-2 is an iron-modulated gene which could contribute to these alterations. Our results suggest osteoblast impairment in iron-related osteoporosis. INTRODUCTION: Iron overload may cause osteoporosis. An iron-related decrease in osteoblast activity has been suggested. METHODS: We investigated the effect of iron exposure on human osteoblast cells (MG-63) by analyzing the impact of ferric ammonium citrate (FAC) and iron citrate (FeCi) on the expression of genes involved in iron metabolism or associated with osteoblast phenotype. A transcriptomic analysis was performed to identify iron-modulated genes. RESULTS: FAC and FeCi exposure modulated cellular iron status with a decrease in TFRC mRNA level and an increase in intracellular ferritin level. FAC increased ROS level and caspase 3 activity. Ferroportin, HFE and TFR2 mRNAs were expressed in MG-63 cells under basal conditions. The level of ferroportin mRNA was increased by iron, whereas HFE mRNA level was decreased. The level of mRNA alpha 1 collagen type I chain, osteocalcin and the transcriptional factor RUNX2 were decreased by iron. Transcriptomic analysis revealed that the mRNA level of HedgeHog Interacting Protein Like-2 (HHIPL-2) gene, encoding an inhibitor of the hedgehog signaling pathway, was decreased in the presence of FAC. Specific inhibition of HHIPL-2 expression decreased osteoblast marker mRNA levels. Purmorphamine, hedgehog pathway activator, increased the mRNA level of GLI1, a target gene for the hedgehog pathway, and decreased osteoblast marker levels. GLI1 mRNA level was increased under iron exposure. CONCLUSION: We showed that in human MG-63 cells, iron exposure impacts iron metabolism and osteoblast gene expression. HHIPL-2 gene expression modulation may contribute to these alterations. Our results support a role of osteoblast impairment in iron-related osteoporosis.

Prevalence of low-virulence Listeria monocytogenes strains from different foods and environments.

Various studies have demonstrated variations in the levels of virulence of different L. monocytogenes strains. In our laboratory, a plaque-forming assay followed by subcutaneous footpad inoculation of mice enabled us to estimate the prevalence of the low-virulence strains. This value fell from 16.3% to 1.7% with bacteria collected before 1994 and after 1997 respectively. This could be related to the modification in 1997 of the reference method EN ISO 11 290-1 of Listeria detection which recommended the use of polymyxin-acriflavine-LiCl-ceftazidime-aesculin-mannitol (PALCAM) medium. The aim of this study was to determine whether the percentage of low-virulence strains detected has changed due to the modification of the detection method recommending the use of the ALOA medium. After analyzing 380 L. monocytogenes strains, no increase in the percentage of low-virulence strains could be detected. The prevalence reached only 2.6% (ten of the 380 strains tested). The low virulence of L. monocytogenes strains was not related to rare serotypes and was also observed in serotypes usually involved in human disease. Low-virulence strains were found in dairy, meat, ready-to-eat products and also in the environment, highlighting the absence of one specific source. These results are discussed in terms of detection methods and the definition of low virulence.

[Ductal carcinoma in situ: role of the boost]. / Radiothérapie des carcinomes canalaires in situ: impact du complément d'irradiation du lit tumoral.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Comparison of the in vitro efficacies of moxifloxacin and amoxicillin against Listeria monocytogenes.

Listeria monocytogenes is a facultative intracellular bacterium that causes severe infections associated with a high mortality rate. Moxifloxacin presents extended activity against gram-positive bacteria and has recently been suggested to be a potential alternative in the treatment of listeriosis. We evaluated the in vitro efficacy of moxifloxacin against L. monocytogenes using a combination of epidemiological and experimental approaches. The median MIC of moxifloxacin for a large collection of L. monocytogenes strains of various origins (human, food, and environment) was 0.5 microg/ml (MIC range, 0.064 to 1 microg/ml). No differences were observed, irrespective of the origin of the strains. Moreover, no cross-resistance with fluoroquinolones was detected in strains that have been reported to be resistant to ciprofloxacin. The in vitro activities of moxifloxacin and amoxicillin were compared by time-kill curve and inhibition of intracellular growth experiments by using a model of bone marrow-derived mouse macrophages infected by L. monocytogenes EGDe. Both moxifloxacin and amoxicillin were bactericidal in broth against extracellular forms of L. monocytogenes. However, moxifloxacin acted much more rapidly, beginning to exert its effects in the first 3 h and achieving complete broth sterilization within 24 h of incubation. Moxifloxacin has a rapid bactericidal effect against intracellular reservoirs of bacteria, whereas amoxicillin is only bacteriostatic and appears to prevent cellular lysis and the subsequent bacterial spreading to adjacent cells. No resistant bacteria were selected during the in vitro experiments. Taken together, our results suggest that moxifloxacin is an interesting alternative to the reference treatment, combining rapid and bactericidal activity, even against intracellular bacteria.

Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel.

Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.

Clinical management of adverse events in adjuvant therapy for hormone-responsive early breast cancer.

Systemic adjuvant therapy has proven highly effective at reducing recurrences and deaths in patients who have received primary therapy for early breast cancer. However, as with all treatments, adjuvant therapy can cause unwanted side effects, and effective management of these events is essential to ensure that patients comply with, and continue, treatment. Adjuvant endocrine therapy is not associated with the more severe, acute toxicities of chemotherapy, and can therefore be taken for many years. At present, the standard duration of postoperative adjuvant endocrine therapy is 5 years. Prevention and treatment of adverse events associated with long-term endocrine therapy is particularly important in the adjuvant setting, where patients are clinically cancer free. In this situation, the efficacy benefits are not, therefore, obvious to the patient, but side effects may have a negative impact on daily life. Tamoxifen has been the gold standard endocrine therapy for hormone-receptor-positive early breast cancer for many years, and the long-term side effects of this agent are well documented. In recent years, the aromatase inhibitors (AIs) have begun to displace tamoxifen as the adjuvant therapy of choice, owing to greater efficacy and good tolerability. Predictably, the AIs and tamoxifen have partially overlapping side-effect profiles. Both therapies are associated with typical symptoms of estrogen deprivation; however, tamoxifen also has estrogenic activity in some tissues, which can cause either detrimental (genital tract) or beneficial (bone, cardiovascular system, lipids) effects that are not associated with AI use. To reduce treatment discontinuations, it is important that patients are made aware of the possible side effects of adjuvant therapy and the management strategies available to them, prior to starting therapy. The role of physical, alternative and pharmaceutical therapies in the management of adverse events associated with endocrine therapy has been investigated, and strategies are now available to alleviate symptoms and enable patients to benefit from adjuvant endocrine therapy without a significant adverse impact on quality of life.

Epirubicin-vinorelbine vs FEC100 for node-positive, early breast cancer: French Adjuvant Study Group 09 trial.

The aim of the study was to compare our reference adjuvant chemotherapy, FEC100 (fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2) and cyclophosphamide 500 mg m(-2), six cycles every 21 days), to an epirubicin-vinorelbine (Epi-Vnr) combination for early, poor-prognosis breast cancer patients. Patients (482) were randomised to receive FEC100, or Epi-Vnr (epirubicin 50 mg m(-2) day 1 and vinorelbine 25 mg m(-2), days 1 and 8, six cycles every 21 days). The 7-year disease-free survival rates were 59.4 and 58.8%, respectively (P=0.47). The relative dose intensity of planned epirubicin doses was 89.1% with FEC100 and 88.9% with Epi-Vnr. There were significantly more grades 3-4 neutropenia (P=0.009) with Epi-Vnr, and significantly more nausea-vomiting (P<0.0001), stomatitis (P=0.0007) and alopecia (P<0.0001) with FEC100. No cases of congestive heart failure were reported, whereas four decreases in left ventricular ejection fraction occurred after FEC100 and five after Epi-Vnr. One case of acute myeloblastic leukaemia was registered in the FEC100 arm. After 7 years of follow-up, there was no difference between treatment arms. Epi-Vnr regimen provided a good efficacy in such poor-prognosis breast cancer patients, and could be an alternative to FEC100, taking into account respective safety profiles of both regimens.

Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.

BACKGROUND: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. PATIENTS AND METHODS: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. RESULTS: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. CONCLUSION: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors.

Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial.

BACKGROUND: The purpose of this study was to determine optimal adjuvant therapy between complete hormonal blockade in premenopausal patients with hormone receptor positive breast cancer and one to three positive nodes. PATIENTS AND METHODS: We randomised 333 patients to receive either LHRH agonist (triptorelin 3.75 mg i.m., monthly) plus tamoxifen 30 mg/day for 3 years (TAM-LHRHa, n=164), or fluorouracil 500 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for six cycles, without any hormonal treatment (FEC50, n=169). RESULTS: The 7-year disease-free survival (DFS) was 76% with TAM-LHRHa, and 72% with FEC50 (P=0.13). The 7-year overall survival (OS) was 91% and 88%, respectively (P=0.20). The multivariate analysis confirmed that both treatments were not different for DFS and OS (P=0.83 and P=0.41, respectively). Amenorrhoea occurred in 64% of patients treated with FEC50; it was temporary in 58% of cases after hormonotherapy and in 31% after chemotherapy. CONCLUSION: In intermediate-risk breast cancer, complete hormonal blockade and chemotherapy provided similar outcomes. Hormonal treatment is an alternative to chemotherapy in hormone-sensitive patients, considering the preference of patients in terms of quality of life.

The evolving role of letrozole in the adjuvant setting: first results from the large, phase III, randomized trial BIG 1-98.

Tamoxifen has been a standard adjuvant therapy, despite its limited 5-year efficacy window and risk of thromboembolism and endometrial malignancy. The potent aromatase inhibitor letrozole (Femara) has emerged as a viable alternative to tamoxifen for the treatment of advanced, metastatic breast cancer, as well as in the neoadjuvant and extended adjuvant settings. Here we describe the first efficacy and safety analysis of BIG 1-98, a large, randomized, independently conducted clinical trial designed specifically to assess and compare the efficacy of sequential or up-front use of letrozole and/or tamoxifen as adjuvant therapy for patients with early breast cancer. The analysis reported here combined the monotherapy arms of letrozole and tamoxifen with the truncated sequential arms. Patients randomized to letrozole had a 19% reduction in the risk of a disease-free survival event (hazard ratio 0.81; P=0.003), especially reducing distant metastases (hazard ratio 0.73; P=0.0012). These results establish letrozole as part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer.

Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy.

BACKGROUND: Anthracycline-induced cardiotoxicity has led to the adoption of empirical dose limits that may restrict continued use of anthracyclines among patients who might benefit. Dexrazoxane, a cardioprotective agent, has been shown to reduce the risk of anthracycline-associated cardiotoxicity when given from first dose of anthracycline. This study sought to confirm the benefit of dexrazoxane in patients at high risk of cardiotoxicity due to prior anthracycline use. PATIENTS AND METHODS: A total of 164 female breast cancer patients, previously treated with anthracyclines, received anthracycline-based chemotherapy either with (n = 85) or without (n = 79) dexrazoxane for a maximum of six cycles. RESULTS: Compared with those receiving anthracycline alone, patients treated with dexrazoxane experienced significantly fewer cardiac events (39% versus 13%, P < 0.001) and a lower and less severe incidence of congestive heart failure (11% versus 1%, P < 0.05). Tumor response rate was unaffected by dexrazoxane therapy. The frequency of adverse events was similar between groups and there were no significant between-group differences in the number of dose modifications/interruptions. CONCLUSION: Dexrazoxane significantly reduced the occurrence and severity of anthracycline-induced cardiotoxicity in patients at increased risk of cardiac dysfunction due to previous anthracycline treatment without compromising the antitumor efficacy of the chemotherapeutic regimen.