How robust are our methods of detecting impaired glomerular filtration rate in the intensive care unit?

Background: Serum creatinine is not a sensitive marker to assess early loss of renal function in acute kidney injury. Timed creatinine clearance and several formula used to predict glomreular filtration rate have not been validated.     

TMEM16A/ANO1 suppression improves response to antibody‐mediated targeted therapy of EGFR and HER2/ERBB2

TMEM16A, a Ca²⁺‐activated Cl^? channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family‐targeting biological therapies. Inhibition of TMEM16A Cl^? channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl^? channel inhibition. Treatment of HNSCC cells with cetuximab, a monoclonal antibody targeting EGFR, and simultaneous TMEM16A suppression led to a pronounced loss of viability. Biochemical analyses of cells subjected to TMEM16A inhibitors or expressing chloride‐deficient forms of TMEM16A provide further evidence that TMEM16A channel function may play a role in regulating EGFR/HER2 signaling. These data demonstrate that TMEM16A regulates EGFR and HER2 in growth and survival pathways. Furthermore, in the absence of TMEM16A cotargeting, tumor cells may acquire resistance to EGFR/HER inhibitors. Finally, targeting TMEM16A improves response to biological therapies targeting EGFR/HER family members.     

The EAACI/GA2LEN/EDF/WAO Guideline for the definition,classification, diagnosis,and management of urticaria: the 2013 revision and update

This guideline is the result of a systematic literature review using the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU‐funded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 national and international societies. Urticaria is a frequent, mast cell‐driven disease, presenting with wheals, angioedema, or both. The life‐time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).     

Effectiveness of combinations of Ayurvedic drugs in alleviating drug toxicity and improving quality of life of cancer patients treated with chemotherapy

Purpose

This study was conducted to assess the effectiveness of combinations of Ayurvedic drugs in alleviating the toxicity of chemotherapy and improving the quality of life of cancer patients. The following was the research question: Can Ayurvedic drugs be used to alleviate the side effects of chemotherapy and improve the quality of life of cancer patients?

Method

Random patients with malignancies of different tissues, grades, and stages were divided into two groups according to their treatment modality. Group 1 consisted of 15 patients treated with six cycles of chemotherapy alone and who did not receive any Ayurvedic drugs (control group). Group 2 consisted of patients (divided into three arms) who received Ayurvedic drugs during chemotherapy and after chemotherapy. Nineteen patients in arm 1 received the Ayurvedic drugs Mauktikyukta Kamdudha (MKD) and Mauktikyukta Praval Panchamruta (MPP) along with a full course of chemotherapy. Fifteen patients in arm 2 received the same Ayurvedic treatment, but the treatment was started after completing the sixth cycle of chemotherapy. Eighteen patients in arm 3 received the Suvarnabhasmadi formulation (SBD) in addition to MKD and MPP after completing the sixth cycle of chemotherapy. Treatment was given for 16 weeks in all three arms. Patients from both groups were observed for a period of 6 months. The assessment criteria depended on Common Toxicity Criteria (CTC designed by NIH and NCI): haemogram; weight; physical examination including Quality of Life Questionnaire (QLQ designed by the European Organization of Research and Treatment of Cancer (EORTC)) for functional, symptom and global scores; and Karnofsky score for assessment of general well-being and activities of daily life. ECOG (Eastern Cooperation Oncology Group) score was also additionally included for assessment of symptoms.

Results

From amongst the symptomatic criteria, there was significant improvement in all the three arms compared with the control group in nausea, loss of appetite, constipation, and fatigue. There was significant improvement in the Karnofsky score and global score of the QLQ, which in fact incorporate symptomatic criteria, general condition, functional ability and disease-related symptoms. These significant differences were observed in group 2 (arms 1, 2, 3) in comparison with group 1 (control), in spite of the fact that in arms 2 and 3, the Ayurvedic treatment was started after completion of chemotherapy. The haemogram did not show a significant difference between the control and the three arms of group 2.

Conclusion

Adjunct treatment with herbo-mineral and metallic Ayurvedic drugs appears to have a significant effect on reducing the toxic side effects of chemotherapy drugs in cancer patients. Our preliminary data suggests that Ayurvedic treatment should be given simultaneously from the beginning of chemotherapy to have the desired effect. However, there is a need to extend this work by conducting a well-planned two-armed study on cancer patients with defined cancer sites with selected Ayurvedic drug combinations, and observing the patients for a longer period of time to confirm the effectiveness of Ayurvedic drugs in reducing the side effects of chemotherapy.