Ansel Mucormycosis Staging and Outcome Evaluation Score: Our Experience in Soaring Stage of Mucormycosis.

To propose Mucormycosis staging and Outcome evaluation score. (i) To provide method of conveying clinical experience to others without ambiguity. (ii) To facilitate an estimation of prognosis. (iii) To provide useful information for treatment decision. Retrospective observational study. Tertiary care center, Rajkot. 556 confirmed operated case of mucormycosis. It was a single center observational study of 556 confirmed cases of mucormycosis. In suspected cases of fungal infection, clinical symptoms were noted along with covid history and comorbid condition. Clinical findings were noted after nasal endoscopy. Rest neurological examination was done to rule out CNS involvement. Representative sample from nasal mucosa sent for microbiological examination. MRI PNS with Brain and Orbit was advised. After surgery, specimen was sent for histopathological confirmation. We reported most common age group was 51-60 years. 52% cases presented early with only nasal involvement and 1.8% cases with late cerebral involvement presentation. From recorded all above findings we have described this diseases progression in 4 components limited to nasal, orbital, palate and/or skull base, cerebral involvement. It is bases on anatomical progression on clinical and radiological findings. Considering all four components, staging system is designed that includes stage I to stage Vb. Outcome evaluation score designed to consider factors like patient's age, comorbidity, stage of disease while presentation, IV antifungal coverage and patient's psychological condition. Our clinical and radiological diagnostic staging and outcome evaluation score may helpful for others for early and better management of mucormycosis.

Gene regulatory biomarker identification for skin toxicities induced by EGFR inhibitor treatment.

1 Federal Institute for Drugs and Medical Devices (BfArM), Research Division, Bonn, 2 Institute of Pharmacology of Natural Products and Clinical Pharmacology, 3 Department of Internal Medicine II, University of Ulm, Ulm, 4 Pneumology, Thoracic Oncology, Sleep- and Respiratory Critical Care Medicine, Clinics Kempten-Oberallgäu, Kempten, and 5 Department of Internal Medicine I, University of Ulm, Ulm, and 4 Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, Germany.

HLA polymorphisms influence the development of skin rash arising from treatment with EGF receptor inhibitors.

AIM: Development of a skin rash under treatment with EGF receptor (EGFR) inhibitors (EGFRIs) has been linked to a favorable prognosis in some studies, suggesting a possible immunological role for EGFRIs in addition to direct antagonistic downstream effects. The present study aimed to investigate whether particular HLA polymorphisms found in cancer patients treated with EGFRIs are associated with the development of skin rash and overall survival rates. PATIENTS & METHODS: HLA typing was performed on 105 cancer patients and the development of skin rash was rated during the first 4 weeks of therapy with EGFRIs. RESULTS: A significantly lower incidence of skin rash was found in patients carrying the HLA-A*02:01 or HLA-A*03:01 alleles (hazard ratio: 0.277; 95% CI: 0.121-0.634; p = 0.002 and hazard ratio: 0.292; 95% CI: 0.113-0.752; p = 0.011, respectively); however, no association with worse survival was seen. CONCLUSION: The chances of developing a skin rash in patients treated with EGFRIs may be lower in patients that carry the HLA-A*02:01 or HLA-A*03:01 alleles, while the antitumor efficacy of EGFRIs does not seem to be significantly impaired in these patients.

Impact of UGT2B7 His268Tyr polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer.

INTRODUCTION: Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7(His268Tyr) polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment. METHODS: This is a pharmacogenetic study based on samples collected from 745 breast cancer patients of the Austrian Tumor of breast tissue: Incidence, Genetics, and Environmental Risk factors (TIGER) cohort who did not present metastases at baseline. This cohort included 205 women with epirubicin-based combination chemotherapy, 113 patients having received chemotherapy without epirubicin and 427 patients having received no chemotherapy at all. Of the epirubicin-treated subgroup, 120 were subsequently treated with tamoxifen. For all women UGT2B7(His268Tyr) was genotyped. Invasive disease-free survival was assessed using Kaplan-Meier and Cox's proportional hazard regression analysis. RESULTS: Among the 205 epirubicin-treated patients, carriers of two UGT2B7(268Tyr) alleles had a mean invasive disease-free survival of 8.6 (95% confidence interval (CI) 7.9 to 9.3) years as compared to 7.5 (95% CI 6.9 to 8.0) years in carriers of at least one UGT2B7(268His) allele (adjusted hazard ratio (HR) = 2.64 (95% CI 1.22 to 5.71); P = 0.014). In addition, the impact of the UGT2B7(His268Tyr) polymorphism became even more pronounced in patients subsequently treated with tamoxifen (adjusted HR = 5.22 (95% CI 1.67 to 26.04); P = 0.015) whereas no such difference in invasive disease-free survival was observed in patients not receiving epirubicin. CONCLUSIONS: Breast cancer patients carrying the UGT2B7(268Tyr/Tyr) genotype may benefit most from adjuvant epirubicin-based chemotherapy. These results warrant confirmation in further studies.

Variability in transport and biotransformation of cytarabine is associated with its toxicity in peripheral blood mononuclear cells.

AIM: To adopt an individualized approach to assess cytarabine (ara-C) hematotoxicity, we studied the relationship between pharmacogenetic variability in the cytidine deaminase gene (CDA) and ara-C toxicity in native peripheral blood mononuclear cells from 100 healthy volunteers. MATERIALS & METHODS: Peripheral blood mononuclear cells were incubated for 48 h with 3 µM ara-C, and cell viability was analyzed by flow cytometry with and without the addition of an equilibrative nucleoside transporter transport inhibitor. CDA promoter and exonic variants were genotyped to derive haplotypes for the CDA gene. RESULTS: Significant between-subject variability was observed in ara-C toxicity (21-fold with 40.1% coefficient of variation compared with 1.2-fold within-subject variability [9.6% coefficient of variation]). Inhibition of hENT1 reversed ara-C cytotoxicity. The linked CDA promoter variants -451C>T, -92A>G, -31Del and the exonic 79A>C variant were associated with ara-C toxicity (p < 0.05). CDA*2A haplotype was associated with ara-C toxicity (p = 0.03). CONCLUSION: Genetic polymorphisms within CDA may be risk factors for ara-C-induced hematotoxicity. Original submitted 6 October 2010; Revision submitted 29 November 2010.

Impact of CYP2D6*4 genotype on progression free survival in tamoxifen breast cancer treatment.

OBJECTIVE: The cytochrome P450 2D6 (CYP2D6) polymorphism was reported to have a significant impact on outcome of tamoxifen treatment in estrogen receptor positive breast cancer patients. The objective of this study was to explore the effect of the CYP2D6*4 polymorphism on tamoxifen treatment outcome in a cohort of patients from a single clinical trial which included women with a history of previous chemotherapy. RESEARCH DESIGN AND METHODS: A total of 493 patients of the Austrian TIGER study receiving adjuvant tamoxifen therapy were studied for this pharmacogenetic interaction. All women with estrogen receptor positive tumors and tamoxifen therapy longer than 6 months were genotyped for CYP2D6*4 using TaqMan technology. Time to tumor progression, defined as local, regional, distant recurrence or contralateral breast cancer and progression free survival, was analyzed. RESULTS: No significant difference in time to tumor progression or progression free survival between the CYP2D6*4 genotype groups in the overall study cohort was found. In a subgroup of patients treated with chemotherapy the CYP2D6*4 poor metabolizers had a tendency towards a shorter mean time to progression. In this group the mean time to tumor progression and the progression free survival were 1.0 years in the CYP2D6*4/*4 group, 6.3 years in the *1/*4 group and 4.97 years in the *1/*1 group (Wilcoxon p = 0.104). CONCLUSION: While earlier data on CYP2D6 and tamoxifen excluded women with prior chemotherapy, the present analysis suggests that CYP2D6*4 genotype might be particularly crucial in this group of high-risk patients. Key limitations are restriction to the CYP2D6*4 allele and missing data of comedication.