Procalcitonin Exerts a Mediator Role in Septic Shock Through the Calcitonin Gene-Related Peptide Receptor.

OBJECTIVES: Clinically, procalcitonin represents the most widely used biomarker of sepsis worldwide with unclear pathophysiologic significance to date. Pharmacologically, procalcitonin was shown to signal through both calcitonin receptor and calcitonin gene-related peptide receptor in vitro, yet the identity of its biologically relevant receptor remains unknown. DESIGN: Prospective randomized animal investigations and in vitro human blood studies. SETTING: Research laboratory of a university hospital. SUBJECTS: C57BL/6J mice and patients with post-traumatic sepsis. INTERVENTIONS: Procalcitonin-deficient mice were used to decipher a potential mediator role in experimental septic shock and identify the relevant receptor for procalcitonin. Cecal ligation and puncture and endotoxemia models were employed to investigate septic shock. Disease progression was evaluated through survival analysis, histology, proteome profiling, gene expression, and flow cytometry. Mechanistic studies were performed with cultured macrophages, dendritic cells, and gamma delta T cells. Main findings were confirmed in serum samples of patients with post-traumatic sepsis. MEASUREMENTS AND MAIN RESULTS: Procalcitonin-deficient mice are protected from septic shock and show decreased pulmonary inflammation. Mechanistically, procalcitonin potentiates proinflammatory cytokine expression in innate immune cells, required for interleukin-17A expression in gamma delta T cells. In patients with post-traumatic sepsis, procalcitonin positively correlates with systemic interleukin-17A levels. In mice with endotoxemia, immunoneutralization of interleukin-17A inhibits the deleterious effect of procalcitonin on disease outcome. Although calcitonin receptor expression is irrelevant for disease progression, the nonpeptide calcitonin gene-related peptide receptor antagonist olcegepant, a prototype of currently introduced antimigraine drugs, inhibits procalcitonin signaling and increases survival time in septic shock. CONCLUSIONS: Our experimental data suggest that procalcitonin exerts a moderate but harmful effect on disease progression in experimental septic shock. In addition, the study points towards the calcitonin gene-related peptide receptor as relevant for procalcitonin signaling and suggests a potential therapeutic application for calcitonin gene-related peptide receptor inhibitors in sepsis, which warrants further clinical investigation.

Pathogenic microbes contaminating mobile phones in hospital environment in Northeast India: incidence and antibiotic resistance.

BACKGROUND: The present study attempts to identify and determine the pattern of drug susceptibility of the microorganisms present in mobile phones of health care workers (HCWs) and non-HCWs in a hospital environment. Mobile phones of 100 participants including both genders were randomly swabbed from nine different wards/units and the bacterial cultures were characterized using VITEK 2 system. RESULTS: Forty-seven mobile phones were culture positive and a total of 57 isolates were obtained which consisted of 28 Gram-positive organisms and 29 Gram-negative organisms. The predominating organisms were Acinetobacter baumannii and Staphylococcus hominis. Among all the isolates from the mobile phones of HCW and non-HCWs, five isolates had ESBL and three isolates had colistin resistance. Incidentally, MRSA was not found on the mobile phones tested. The isolated organisms showed 100% susceptibility to linezolid, daptomycin, vancomycin, imipenem, meropenem, gentamicin, amikacin, ciprofloxacin and tigecycline, while high resistance was shown against benzylpenicillin (75.0%), cefuroxime and cefuroxime axetil (56.5%). Non-HCWs' mobile phones were more contaminated as compared to HCWs (P = 0.001) and irrespective of individuals' gender or toilet habits, both Gram-positive and Gram-negative organisms were present on the mobile phones. CONCLUSION: This study reports for the first time that the mobile phones of non-health care workers harbour more bacterial diversity and are more prone to cause transmission of pathogens. This study can serve to educate the public on personal hand hygiene practices and on maintaining clean mobile phones through antiseptic measures.