Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Inducible Caspase9-mediated suicide gene for MSC-based cancer gene therapy

Cellular therapies based on mesenchymal stromal/stem cells (MSC) are promising strategies in regenerative medicine and oncology. Despite encouraging results, there is still some level of concerns on inoculating MSC in cancer patients. To face this issue, one possibility resides in engineering MSC by incorporating a suicide gene in order to control their fate once infused. Strategies based on Herpes Simplex Virus Thymidine Kinase (HSV-TK) and the Cytosine Deaminase genes have been developed and more recently a novel suicide gene, namely, iCasp9, has been proposed. This approach is based on a variant of human Caspase9 that binds with high affinity to a synthetic, bioinert small molecule (AP20187) leading to cell death. Based on this technology so far marginally applied to MSC, we tested the suitability of iCasp9 suicide strategy in MSC to further increase their safety. MSC have been transfected by a lentiviral vector carrying iCasp9 gene and then tested for viability after AP20187 treatment in comparison with mock-transfected cells. Moreover, accounting our anti-tumor approaches based on MSC expressing potent anti-cancer ligand TNF-Related Apoptosis-Inducing Ligand (TRAIL), we generated adipose MSC co-expressing iCasp9 and TRAIL successfully targeting an aggressive sarcoma type. These data show that anti-cancer and suicide mechanisms can coexist without affecting cells performance and hampering the tumoricidal activity mediated by TRAIL. In conclusion, this study originally indicates the suitability of combining a MSC-based anti-cancer gene approach with iCasp9 demonstrating efficiency and specificity

Clinical and epidemiological aspects of a hepatitis E outbreak in Bangui, Central African Republic

<p>Abstract</p> <p>Background</p> <p>Outbreaks of hepatitis E frequently occur in tropical developing countries during the rainy season due to overflowing drains, short-circuiting of networks of clean water and use of contaminated water from wells. Hepatitis E virus (HEV) infections are usually accompanied by general symptoms of acute liver disease. This study was conducted to define the clinical and epidemiological aspects of the HEV outbreak that occurred in May 2004 in Bangui.</p> <p>Methods</p> <p>Blood samples were collected from 411 patients aged 1-87 years, most of whom presented with jaundice, asthenia or signs of uncomplicated malaria, for a transversal study from June 2004 to September 2005. Patients were recruited at 11 health care centres, including two referral hospitals, after they had given informed consent. The diagnosis of HEV was made with a commercial ELISA test to detect IgM and/or IgG antibodies. HEV RNA was amplified by RT-PCR to confirm the presence of the viral genome.</p> <p>Results</p> <p>The most frequent clinical signs found were jaundice (93.4%), vomiting (50.7%), hepatalgia (47.4%), hepatomegaly (30.9%) and asthenia (26.8%), which are the general clinical signs of hepatic disease. Acute hepatitis E was found in 213 patients (51.8%) who were positive for HEV IgM antibodies. The IgG anti-HEV seroprevalence during this outbreak was high (79.5%). The age group 18-34 years was more frequently infected (91.2%) than those aged 1-17 (78.0%) or over 34 (64.9%) (p < 10^-6). RT-PCR performed on 127 sera from the 213 IgM-HEV-positive patients was amplified, and the presence of the viral genome was found in 65 samples.</p> <p>Conclusion</p> <p>Although no specific clinical signs exist for hepatitis E infection, people presenting with jaundice, vomiting, hepatalgia, asthenia, hepatomegaly or distended abdomen with no signs of uncomplicated malaria in tropical developing countries should be sent to a laboratory for testing for hepatitis E.</p

Dipstick Test for Rapid Diagnosis of Shigella dysenteriae 1 in Bacterial Cultures and Its Potential Use on Stool Samples

International audienceBACKGROUND: We describe a test for rapid detection of S. dysenteriae 1 in bacterial cultures and in stools, at the bedside of patients. METHODOLOGY/PRINCIPAL FINDINGS: The test is based on the detection of S. dysenteriae 1 lipopolysaccharide (LPS) using serotype 1-specific monoclonal antibodies coupled to gold particles and displayed on a one-step immunochromatographic dipstick. A concentration as low as 15 ng/ml of LPS was detected in distilled water and in reconstituted stools in 10 minutes. In distilled water and in reconstituted stools, an unequivocal positive reaction was obtained with 1.6×10⁶ CFU/ml and 4.9×10⁶ CFU/ml of S. dysenteriae 1, respectively. Optimal conditions to read the test have been determined to limit the risk of ambiguous results due to appearance of a faint yellow test band in some negative samples. The specificity was 100% when tested with a battery of Shigella and unrelated strains in culture. When tested on 328 clinical samples in India, Vietnam, Senegal and France by laboratory technicians and in Democratic Republic of Congo by a field technician, the specificity (312/316) was 98.7% (95% CI:96.6-99.6%) and the sensitivity (11/12) was 91.7% (95% CI:59.8-99.6%). Stool cultures and the immunochromatographic test showed concordant results in 98.4 % of cases (323/328) in comparative studies. Positive and negative predictive values were 73.3% (95% CI:44.8-91.1%) and 99.7% (95% CI:98-100%). CONCLUSION: The initial findings presented here for a simple dipstick-based test to diagnose S. dysenteriae 1 demonstrates its promising potential to become a powerful tool for case management and epidemiological surveys