Checklist for a complete chronic urticaria medical history : an easy tool

ABSTARCT: Existing guidelines do not offer a quick, efficient alternative to the patient's recollection of relevant clinical features during anamnesis and physical examination for chronic urticaria (CU). This study aimed to identify specific items reflecting the main characteristics of CU that should be included in a comprehensive medical history for patients with CU. We also aimed to clarify possible eliciting factors for CU to support accurate diagnosis of the disease. METHODS: A panel of postgraduate dermatologists conducted a literature search for relevant studies on CU using Medline, the Cochrane database, and PubMed. RESULTS: We identified82 articles from which we drew a collection of items to inform development of an easy-to-use checklist and collection of items that should be included in a correct medical history. The final version of the checklist included42 items across two areas: essential clues for anamnesis and diagnosis of CU; and typical symptoms/parameters or characteristics according to subtype, etiology, and laboratory findings. Items included time of disease onset; duration, shape, size, color, and distribution of wheals; associated angioedema; atopy; and triggering factors. CONCLUSIONS: Our guide provides an easy-to-use tool to support clinicians to focus, orient themselves, and save time in medical consultations for CU, allowing better diagnosis and management of this disease

Best practice approach for assessment of microchip-associated tumors in preclinical safety studies: Position of the Registry of Industrial Toxicology Animal-data (RITA)

Microchip (passive radio-frequency identification device) implantation is a common and widely employed means of animal identification in laboratory animal facilities. However, these devices have been associated with tumors of the skin and subcutis in rodents. While microchip-associated tumors are rare, they pose a challenge for accurate diagnosis and documentation in preclinical toxicity studies. Documentation of these tumors should differentiate microchip-associated lesions with spontaneously occurring or test article–induced tumors. Standardizing criteria for microchip-associated lesions will aid the diagnostic process and allow for preclinical regulatory standardization. To this end, the Registry of Industrial Toxicology Animal-data have developed clear recommendations for diagnosis and documentation of microchip-associated lesions

A Global Cndp1-Knock-Out Selectively Increases Renal Carnosine and Anserine Concentrations in an Age- and Gender-Specific Manner in Mice

Carnosinase 1 (CN1) is encoded by the Cndp1 gene and degrades carnosine and anserine, two natural histidine-containing dipeptides. In vitro and in vivo studies suggest carnosine- and anserine-mediated protection against long-term sequelae of reactive metabolites accumulating, e.g., in diabetes mellitus. We have characterized the metabolic impact of CN1 in 11- and 55-week-old Cndp1-knockout (Cndp1-KO) mice and litter-matched wildtypes (WT). In Cndp1-KO mice, renal carnosine and anserine concentrations were gender-specifically increased 2- to 9-fold, respectively in the kidney and both most abundant in the renal cortex, but remained unchanged in all other organs and in serum. Renal oxidized/reduced glutathione concentrations, renal morphology and function were unaltered. In Cndp1-KO mice at week 11, renal asparagine, serine and glutamine levels and at week 55, renal arginine concentration were reduced. Renal heat-shock-protein 70 (Hspa1a/b) mRNA declined with age in WT but not in Cndp1-KO mice, transcription factor heat-shock-factor 1 was higher in 55-week-old KO mice. Fasting blood glucose concentrations decreased with age in WT mice, but were unchanged in Cndp1-KO mice. Blood glucose response to intraperitoneal insulin was gender- but not genotype-dependent, the response to intraperitoneal glucose injection was similar in all groups. A global Cndp1-KO selectively, age- and gender-specifically, increases renal carnosine and anserine concentrations, alters renal amino acid- and HSP70 profile and modifies systemic glucose homeostasis. Increase of the natural occurring carnosine and anserine levels in the kidney by modulation of CN1 represents a promising therapeutic approach to mitigate or prevent chronic kidney diseases such as diabetic nephropathy

Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine

Abstract GDF15 has recently emerged as a key driver of the development of various disease conditions including cancer cachexia. Not only the tumor itself but also adverse effects of chemotherapy have been reported to contribute to increased GDF15. Although regulation of GDF15 transcription by BET domain has recently been reported, the molecular mechanisms of GDF15 gene regulation by drugs are still unknown, leaving uncertainty about the safe and effective therapeutic strategies targeting GDF15. We screened various cardiotoxic drugs and BET inhibitors for their effects on GDF15 regulation in human cardiomyocytes and cancer cell lines and analyzed in-house and public gene signature databases. We found that DNA damaging drugs induce GDF15 in cardiomyocytes more strongly than drugs with other modes of action. In cancer cells, GDF15 induction varied depending on drug- and cell type-specific gene signatures including mutations in PI3KCA, TP53, BRAF and MUC16. GDF15 suppression by BET inhibition is particularly effective in cancer cells with low activity of the PI3K/Akt axis and high extracellular concentrations of pantothenate. Our findings provide insights that the risk for GDF15 overexpression and concomitant cachexia can be reduced by a personalized selection of anticancer drugs and patients for precision medicine

Is it possible for chronic urticaria diagnostic approach to be simplified? A clinical data checklist

Background: Existing clinical guidelines do not offer an efficient alternative for the collection of data on relevant clinical traits during history and physical of the patient with chronic urticaria. Objective: Our aim was to provide a clinical data checklist together with its guide to allow for thorough information to be obtained and for a physical exam that identifies the main features and triggering factors of the disease to be carried out. Methods: A search was conducted for relevant literature on chronic urticaria in Medline, the Cochrane library and PubMed. Results: We developed an easy-to-use clinical data checklist with its corresponding clinical guide, comprised by 42 items based on two components: essential clues for history taking and chronic urticaria diagnosis (typical symptoms according to subgroups, etiology and laboratory results). Some components are the time of disease onset, wheals’ duration, shape, size, color and distribution, associated angioedema, atopy, triggering factors and others. Conclusions: The clinical data checklist and its guide constitute a tool to focus, guide and save time in medical consultation, with the main purpose to aid physicians in providing better diagnosis and management of the disease