Prevalence and risk factors of trastuzumab induced cardiotoxicity in Tunisian HER2-positive breast cancer patients.

INTRODUCTION: Cardiotoxicity is the most important side effect of Trastuzumab treatment. The purpose of this study is to evaluate the prevalence of Trastuzumab induced cardiotoxicity and to analyze risk factors associated with this side effect. MATERIALS AND METHODS: A retrospective institutional study was carried out from June 2018 to December 2018 at the department of Medical Oncology of Salah Azaiz institute, Tunis, Tunisia. Demographic, clinical characteristics (menopausal status, breast cancer stage, anthracyclines exposure, comorbidities presence…) and left ventricular ejection function (LVEF) measurements, were collected from patient records. RESULTS: Twenty-three women (20%) had Trastuzumab induced cardiotoxicity.65.2% (N = 15) experienced a decrease in LVEF more than 10% with a decrease below normal value and 34.8% (N = 8) experienced a decrease in LVEF more than 20%. Obesity is a risk factor for the occurrence of Trastuzumab induced cardiotoxicity (adjusted odds ratio (OR) = 2.919 (95% confidence interval (CI) [1.0411-8.186]; p = 0.042). CONCLUSION: Our study highlighted that obesity is associated with a high risk of cardiotoxicity in women treated with Trastuzumab. Therefore, close monitoring of cardiac function is recommended especially for obese women during Trastuzumab administering.

Incidence and risk factors associated with development of oxalipatin-induced acute peripheral neuropathy in colorectal cancer patients.

INTRODUCTION: Oxaliplatin utilized in colorectal neoplasms treatment could induce acute peripheral neuropathy (APN) which is a dreadful and frequent adverse event. The objective of this study is to estimate incidence of APN induced by oxaliplatin cumulative incidence in cancer patients colorectal and to describe the distribution of the APN incidence according to demographic and clinical characteristics, as well as according to oxaliplatin cumulative dose. MATERIAL AND METHODS: This is a prospective descriptive study which took place from June to December 2018 at the Salah Azaiz Institute, Tunis. Demographic data, clinical data and data on oxaliplatin administration were collected from patient interview, medical files and pharmaceutical databases. RESULTS: The APN (grade 1, grade 2 and grade 3) cumulative incidence during the period of six months of follow up was 86% (95% CI [0.7815-0.9132]). While 38.3% (95% CI [0.29-0.48]) of the patients had grade 2 or 3 neuropathy. The search for factors associated with the risk of grade 2 and 3 NAP revealed trend significant association with diabetes (adjusted RR = 5.7 (IC95% [0.9- 37.3]; p = 0.07). Moreover, there was significant association with oxaliplatin cumulative dose (≥421 mg/m2) to increase the risk of APN grade 2 and 3 (adjusted RR = 7.8; [2.7-22.7]; p = 0.0001). Furthermore, significant association with obesity to increase the risk of APN grade 2 and 3 (adjusted RR = 5.3 [1.1- 25.4]; p = 0.04) was found. Among the patients included, 31.1% experienced oxaliplatin dose reduction and in the majority of cases this reduction is due to neurotoxicity (90.9%). CONCLUSION: The high incidence of oxaliplatin-induced APN remains an embarrassing and handicapping side effect. Our study has shown that oxaliplatin cumulative dose (≥421 mg/m2), diabetes and obesity are risk factor for the development of grade 2 and 3 APN.

Toxicity, risk factors and management of cisplatin-induced toxicity: A prospective study.

BACKGROUND AND PROPOSE: Cisplatin is a cytotoxic drug that triggers several toxicities. However, nephrotoxicity and ototoxicity remain major clinical limitations. The aim of our study was to evaluate the incidence of chemotherapy toxicity induced by cisplatin and to analyze the influence of risk factors in the Tunisian population. METHODS: We performed a prospective descriptive study in a period of four months. Patients were eligible if they had pathologically confirmed malignancies and treated with cisplatin-regimen chemotherapy. Nephrotoxicity and digestive toxicity were graded according to the World Health Organization toxicity scale and ototoxicity was scored clinically according to the Common Terminology Criteria for Adverse Events (CTCAE). Multivariate logistic regression analysis was performed to evaluate the influence of clinical variables on cisplatin-induced toxicity. RESULTS: A total of 150 patients were included. Forty-four percent of patients developed cisplatin-regimen toxicity: 15% developed cisplatin-induced nephrotoxicity, 9% cisplatin-induced ototoxicity and 27% digestive toxicity. In the multivariate analysis, age >65 years (OR= 6.129, p = 0.010), metastatic cancer (OR = 0.171, p = 0.007) and cumulative dose (OR= 1.004 mg/m2; p = 0.042) were strong predisposing factors for CDDP-induced nephrotoxicity. The cumulative dose was an independent prognostic indicator for digestive toxicity (OR = 0.997, p = 0.002). CONCLUSION: In our study, age >65 years and metastatic cancer were risk factors for cisplatin-induced nephrotoxicities. We also found the correlation between cumulative dose and nephrotoxicity or digestive toxicity.

A Survey of Aedes (Diptera: Culicidae) Mosquitoes in Tunisia and the Potential Role of Aedes detritus and Aedes caspius in the Transmission of Zika Virus.

The present study aimed to update the list of Aedes mosquito species occurring in Tunisia and to test the vector competence of Aedes (Ochlerotatus) caspius (Pallas) and Ae. (Ochlerotatus) detritus (Haliday), the locally most abundant and widespread species, to transmit Zika virus (ZIKV). In 2017-2018, mosquito larvae were collected from 39 different larval habitats in seven bioclimatic zones of Tunisia. The salinity and pH of each breeding site were measured. The survey revealed the presence of 10 Aedes species in Tunisia: Ae. (Stegomyia) albopictus (Skuse), Ae. (Ochlerotatus) berlandi (Séguy), Ae. caspius, Ae. detritus, Ae. (Finlaya) echinus (Edwards), Ae. (Finlaya) geniculatus (Olivier), Ae. (Acartomyia) mariae (Sergent and Sergent), Ae. (Ochlerotatus) pulcritarsis (Rondani), Ae. (Aedimorphus) vexans (Meigen), and Ae. (Fredwardsius) vittatus (Bigot). Of these 10 species, Ae. caspius and Ae. detritus were the most abundant in Tunisia. Aedes detritus and Ae. caspius larvae were reared until the imago stage under insectary conditions to test autogeny. The study showed that Ae. detritus is autogenous and stenogamous and Ae. caspius, anautogenous and eurygamous. Finally, the collected strains of these two species were experimentally infected with the Asian genotype of ZIKV, originally isolated from a patient in April 2014 in New Caledonia, to test their vector competence. Neither of these species was able to transmit ZIKV at 7 and 14 d postexposure. Further investigations are needed to test the competence of other Tunisian mosquito species that may be associated with ZIKV transmission.

Potential of Aedes albopictus to cause the emergence of arboviruses in Morocco.

In 2015, the mosquito Aedes albopictus was detected in Rabat, Morocco. This invasive species can be involved in the transmission of more than 25 arboviruses. It is known that each combination of mosquito population and virus genotype leads to a specific interaction that can shape the outcome of infection. Testing the vector competence of local mosquitoes is therefore a prerequisite to assess the risks of emergence. A field-collected strain of Ae. albopictus from Morocco was experimentally infected with dengue (DENV), chikungunya (CHIKV), zika (ZIKV) and yellow fever (YFV) viruses. We found that this species can highly transmit CHIKV and to a lesser extent, DENV, ZIKV and YFV. Viruses can be detected in mosquito saliva at day 3 (CHIKV), day 14 (DENV and YFV), and day 21 (ZIKV) post-infection. These results suggest that the local transmission of these four arboviruses by Ae. albopictus newly introduced in Morocco is a likely scenario. Trial registration: ClinicalTrials.gov APAFIS#6573-201606l412077987v2.