Biology:Procalcitonin

From HandWiki
Short description: Precursor of the peptide hormone calcitonin
Figure 1: Immature Calcitonin
Medical diagnostics
A 3D cartoon of procalcitonin's parent compound, calcitonin.png
A 3D cartoon of procalcitonin's daughter compound, calcitonin

Procalcitonin (PCT) is a peptide precursor of the hormone calcitonin, the latter being involved with calcium homeostasis. It arises once preprocalcitonin is cleaved by endopeptidase.[1] It was first identified by Leonard J. Deftos and Bernard A. Roos in the 1970s.[2] It is composed of 116 amino acids and is produced by parafollicular cells (C cells) of the thyroid and by the neuroendocrine cells of the lung and the intestine.

The level of procalcitonin in the blood stream of healthy individuals is below the limit of detection (0.01 µg/L) of clinical assays.[3] The level of procalcitonin rises in a response to a pro-inflammatory stimulus, especially of bacterial origin. It is therefore often classed as an acute phase reactant.[4] The induction period for procalcitonin ranges from 4–12 hours with a half-life spanning anywhere from 22–35 hours.[5] It does not rise significantly with viral or non-infectious inflammations. In the case of viral infections this is due to the fact that one of the cellular responses to a viral infection is to produce interferon gamma, which also inhibits the initial formation of procalcitonin.[6] With the inflammatory cascade and systemic response that a severe infection brings, the blood levels of procalcitonin may rise multiple orders of magnitude with higher values correlating with more severe disease.[7] However, the high procalcitonin levels produced during infections are not followed by a parallel increase in calcitonin or a decrease in serum calcium levels.[8]

Biochemistry

Figure 2: Production pathway of PCT and CT in healthy and infected individuals via the induction of CALC-1 gene

PCT is a member of the calcitonin (CT) superfamily of peptides. It is a peptide of 116 amino acids with an approximate molecular weight of 14.5 kDa, and its structure can be divided into three sections (see Figure 1):[9] amino terminus (represented by the ball and stick model in Figure 1), immature calcitonin (shown in Figure 1 from PDB as the crystal structure of procalcitonin is not yet available), and calcitonin carboxyl-terminus peptide 1.[9] Under normal physiological conditions, active CT is produced and secreted in the C-cells of the thyroid gland after proteolytic cleavage of PCT, meaning, in a healthy individual, that PCT levels in circulation are very low (<.05 ng/mL).[citation needed] The pathway for production of PCT under normal and inflammatory conditions are shown in Figure 2.[10] During inflammation, LPS, microbial toxin, and inflammatory mediators, such as IL-6 or TNF-α, induce the CALC-1 gene in adipocytes, but PCT never gets cleaved to produce CT.[10] In a healthy individual, PCT in endocrine cells is produced by CALC-1 by elevated calcium levels, glucocorticoids, CGRP, glucagon, or gastrin, and is cleaved to form CT, which is released to the blood.[10]

PCT is located on the CALC-1 gene on chromosome 11.[9] Bacterial infections induce a universal increase in the CALC-1 gene expression and a release of PCT (>1 μg/mL).[11] Expression of this hormone occurs in a site specific manner.[9] In healthy and non-infected individuals, transcription of PCT only occurs in neuroendocrine tissue, except for the C cells in the thyroid. The formed PCT then undergoes post-translational modifications, resulting in the production small peptides and mature CT by removal of the C-terminal glycine from the immature CT by peptidylglycine α-amidating monooxygenase (PAM).[12] In a microbial infected individual, non-neuroendocrine tissue also secretes PCT by expression of CALC-1. A microbial infection induces a substantial increase in the expression of CALC-1, leading to the production of PCT in all differentiated cell types.[13] The function of PCT synthesized in nonneuroendocrine tissue due to a microbial infection is currently unknown, but, its detection aids in the differentiation of inflammatory processes.[9]

Diagnostic advantages

Due to PCT’s variance between microbial infections and healthy individuals, it has become a marker to improve identification of bacterial infection and guide antibiotic therapy.[14] The table below is a summary from Schuetz, Albrich, and Mueller,[14] summarizing the current data of selected, relevant studies investigating PCT in different types of infections.

Legend:
✓ = Moderate evidence in favor of PCT
✓✓ = Good evidence in favor of PCT
✓✓✓ = Strong evidence in favor of PCT
~ = Evidence in favor or against the use of PCT, or still undefined

Infection Type/Setting Study Design PCT Cut-Off (ug/L) PCT Benefit Conclusion References
Abdominal Infections observational 0.25 ~ PCT may help exclude ischemia and necrosis in bowel blockage [15][16][17][18]
Arthritis observational 0.1-0.25 ✓ PCT differentiates non-infectious (gout) arthritis from true infection [19][20][21]
Bacteremic infections observational 0.25 ✓✓ Low PCT levels help rule out microbial infections [22][23][24]
Blood stream infection (primary) observational 0.1 ✓✓ PCT differentiates contamination from true infection [25]
Bronchitis RCT 0.1-0. 5 ✓✓✓ PCT reduces antibiotic exposure without adverse outcomes in the ED [26][27]
COPD exacerbation RCT 0.1-0. 5 ✓✓✓ PCT reduces antibiotic exposure without adverse outcomes in the ED and hospital [26][27][28]
Endocarditis observational 2.3 ✓ PCT is an independent predictor with high diagnostic accuracy for acute endocarditis [29][30]
Meningitis before-after 0.5 ✓ PCT reduces antibiotic exposure during outbreak of viral meningitis [31][32][33]
Neutropenia observational 0.1-0.5 ✓ PCT is helpful at identifying neutropenic patients with systemic bacterial infection [34][35][36]
Pancreatitis observational 0.25-0.5 ~ PCT correlates with severity and extent of infected pancreatitis [37][38]
Pneumonia RCT 0.1-0. 5; 80-90% ↓ ✓✓✓ PCT reduces antibiotic without adverse outcomes exposure in the hospital [26][27][39][40][41][42]
Postoperative fever observational 0.1-0.5 ✓ PCT differentiates non-infectious fever from post-operative infections [43]
Postoperative infections RCT 0.5-1.0; 75-85% ↓ ✓✓ PCT reduces antibiotic exposure without adverse outcomes in the surgical ICU [44][45]
Severe sepsis/Shock RCT 0.25-0.5; 80-90% ↓ ✓✓✓ PCT reduces antibiotic exposure without adverse outcomes in the ICU [46][47]
Upper respiratory tract infections RCT 0.1-0.25 ✓✓ PCT reduces antibiotic exposure without adverse outcomes in primary care [48]
Urinary tract infections observational 0.25 ✓ PCT correlates with severity of urinary tract infections [23][49]
Ventilator-associated pneumonia RCT 0.1-0.25 ✓✓ PCT reduces antibiotic exposure without adverse outcomes [47][50]

Medical uses

Sepsis

Measurement of procalcitonin can be used as a marker of severe sepsis caused by bacteria and generally grades well with the degree of sepsis,[51] although levels of procalcitonin in the blood are very low. PCT has the greatest sensitivity (90%) and specificity (91%) for differentiating patients with systemic inflammatory response syndrome (SIRS) from those with sepsis, when compared with IL-2, IL-6, IL-8, CRP and TNF-alpha.[52] Evidence is emerging that procalcitonin levels can reduce unnecessary antibiotic prescribing to people with lower respiratory tract infections.[53] Currently, procalcitonin assays are widely used in the clinical environment.[54]

A meta-analysis reported a sensitivity of 76% and specificity of 70% for bacteremia.[55]

A 2018 systematic review comparing PCT and C-reactive protein (CRP) found PCT to have a sensitivity of 80% and a specificity of 77% in identifying septic patients. In the study, PCT outperformed CRP in diagnostic accuracy of predicting sepsis.[56]

In a 2018 meta-analysis of randomized trials of over 4400 ICU patients with sepsis, researchers concluded that PCT led therapy resulted in lower mortality and lower antibiotic administration.[57]

Organ rejection

Immune responses to both organ rejection and severe bacterial infection can lead to similar symptoms such as swelling and fever that can make initial diagnosis difficult. To differentiate between acute rejection of an organ transplant and bacterial infections, plasma procalcitonin levels have been proposed as a potential diagnostic tool.[58] Typically the levels of procalcitonin in the blood remain below 0.5 ng/mL in cases of acute organ rejection, which has been stated previously to be well below the 1 μg/mL typically seen in bacterial infection.[6]

Respiratory illnesses

Given procalcitonin is a blood marker for bacterial infections, evidence shows that it is a useful tool in guiding the initiation and duration of antibiotics in patients with bacterial pneumonia and other acute respiratory infections.[59] The use of procalcitonin guided antibiotic therapy leads to lower mortality, less antibiotic usage, decreased side effects due to antibiotics and promotes good antibiotic stewardship.[59] The value in these protocols are evident since a high PCT level correlates with increased mortality in critically ill pneumonia patients especially those with a low CURB-65 pneumonia risk factor score.[60]

In adults with acute respiratory infections, a 2017 systematic review found that PCT-guided therapy reduced mortality, reduced antibiotic use (2.4 fewer days of antibiotics) and led to decreased adverse drug effects across a variety of clinical settings (ED, ICU, primary care clinic).[59]

Procalcitonin-guided treatment limits antibiotic exposure with no increased mortality in patients with acute exacerbation of chronic obstructive pulmonary disease.[61]

Using procalcitonin to guide protocol in acute asthma exacerbation led to reduction in prescriptions of antibiotics in primary care clinics, emergency departments and during hospital admission. This was apparent without an increase in ventilator days or risk of intubation. Be that acute asthma exacerbation is one condition that leads to overuse of antibiotics worldwide, researchers concluded that PCT could help curb over-prescribing.[62]

Cardiovascular disease

PCT serves a marker to help differentiate acute respiratory illness such as infection from an acute cardiovascular concern. It also has value as a prognostic lab value in patients with atherosclerosis or coronary heart disease as its levels correlate with the severity of the illness.[63]

The European Society of Cardiology recently released a PCT-guided algorithm for administering antibiotics in patients with dyspnea and suspected acute heart failure. The guidelines use a cut off point of .2 ng/mL and above as the point at which to give antibiotics.[64] This coincides with a 2017 review of literature which concluded that PCT can help reduce antibiotic overuse in patients presenting with acute heart failure.[65] In regards to mortality, a meta analysis of over 5000 patients with heart failure concluded that elevated PCT was reliable in predicting short term mortality.[66]

Meningitis

Blood procalcitonin levels can help confirm bacterial meningitis and. if negative, can effectively rule out bacterial meningitis. This was shown in a review of over 2000 patients in which PCT had a sensitivity of 86% and a specificity of 80% for cerebrospinal fluid PCT. Blood PCT measurements proved superior to cerebrospinal fluid PCT with a sensitivity of 95% and a specificity of 97% as a marker for bacterial meningitis.[67]

In acute meningitis, serum PCT is useful as a biomarker for sepsis. It can also be of use in determining viral meningitis versus bacterial meningitis. These findings are the result of a 2018 literature review.[68] This followed a 2015 meta analysis that showed that PCT had a sensitivity of 90% and a specificity of 98% in judging viral versus bacterial meningitis. PCT also outperformed other biomarkers such as C-reactive protein.[69]

Gastrointestinal disease

Evidence shows that an elevated PCT above .5 ng/mL could help diagnose infectious complications of inflammatory bowel disease such as abdominal abscesses, bacterial enterocolitis etc. PCT can be effective in early recognition of infections in IBD patients and decisions on whether to prescribe antibiotics.[70]

Kidney disease

Patients with chronic kidney disease and end-stage renal disease are at higher risk for infections, and procalcitonin has been studied in these populations, who often have higher levels. Procalcitonin can be dialyzed, and so levels are dependent upon when patients receive hemodialysis. While there is no formally accepted cutoff value for patients undergoing HD, using a value of greater or equal to 0.5 ng/mL yielded a sensitivity of 97-98% and a specificity of 70-96%.[71]

Hepatitis

PCT, possibly together with CRP, is used to corroborate the MELD score.[72][73]

Septic arthritis

PCT at a cutoff value of .5 ng/mL was effective at ruling in septic arthritis in an analysis of over 8000 patients across 10 prospective studies. PCT had a sensitivity of 54% and specificity of 95%. The study also concluded that PCT outperforms C-reactive protein in differentiating septic arthritis from non-septic arthritis.[74]

Cancer

A 2016 literature review showed that PCT has good value in diagnosing infections in oncologic patients. Moreso, it is especially effective in diagnosing major life threatening episodes in cancer patient such as bacteremia and sepsis.[75] Procalcitonin is reliable to monitor recurrence of medullary thyroid carcinoma. In detecting cancer recurrence, PCT had a sensitivity and specificity of 96% and 96% respectively.[76]

Pediatrics

In a meta analysis of 17 studies, PCT had a sensitivity of 85% and a specificity of 54% in diagnosing sepsis in neonates and children. The PCT cut off used was between 2-2.5 ng/mL.[77]

In children presenting with fever without an apparent source, a PCT level of .5 ng/mL had a sensitivity of 82% and specificity of 86%. At a 5 ng/mL value, the sensitivity and specificity were 61% and 94%. PCT can help the clinical decision making while identifying invasive bacterial infection in children with unexplained fever.[78]

PCT levels correlate with the degree of illness in pediatric patients with sepsis or urinary tract infections making it effective as a prognostic lab value in these patients.[79]

Antibiotic stewardship

Procalcitonin guided cessation of antibiotic use reduces duration of antibiotic exposure and lowers mortality in critically ill patients in the Intensive Care Unit.[80]

In adult emergency department patients with respiratory tract illnesses, PCT-guided treatment groups had reduced antibiotic use.[81] PCT references ranges are also used to determine the likelihood a patient has systemic infection (sepsis), thereby reducing incidence of unnecessary antibiotic use in cases where sepsis is unlikely.[82]

Although some literature differs in antibiotic cessation requirements the general consensus is stopping antibiotics when procalcitonin levels fall 80% below peak or below 0.5μg/L at day five or later during antibiotic therapy.[83]

PCT and amphetamines

Excessive overdose on amphetamine or its analogs can induce systemic inflammation; in a case report of amphetamine overdose, without bacterial infection, significant elevations in procalcitonin were observed.[84]

References

  1. ↑ Procalcitonin: Reference Range, Interpretation, Collection and Panels. 2017-03-09. https://emedicine.medscape.com/article/2096589-overview. 
  2. ↑ "Calcium and skeletal metabolism". The Western Journal of Medicine 123 (6): 447–58. December 1975. PMID 1105981. 
  3. ↑ "Procalcitonin increase after endotoxin injection in normal subjects". The Journal of Clinical Endocrinology and Metabolism 79 (6): 1605–8. December 1994. doi:10.1210/jcem.79.6.7989463. PMID 7989463. 
  4. ↑ Long, Sarah S., ed (2012). "Bacterial infections in the neonate". Principles and Practice of Pediatric Infectious Diseases (4th ed.). Elsevier. ISBN 978-1437727029. https://books.google.com/books?id=nQ7-o8JAH7kC&pg=PA542. 
  5. ↑ "Procalcitonin as a marker of the systemic inflammatory response to infection". Intensive Care Medicine 26 (9): 1193–200. September 2000. doi:10.1007/s001340000624. PMID 11089742. 
  6. ↑ 6.0 6.1 Sandkovsky, Uriel; Kalil, Andre C.; Florescu, Diana F. (2015-06-22). "The use and value of procalcitonin in solid organ transplantation". Clinical Transplantation 29 (8): 689–696. doi:10.1111/ctr.12568. ISSN 0902-0063. PMID 25996831. http://dx.doi.org/10.1111/ctr.12568. 
  7. ↑ Meisner, Michael (2010). Procalcitonin biochemistry and clinical diagnosis (1st ed.). Bremen: UNI-MED-Verl. ISBN 9783837412413. OCLC 697831954. 
  8. ↑ Assicot, M.; Bohuon, C.; Gendrel, D.; Raymond, J.; Carsin, H.; Guilbaud, J. (1993-02-27). "High serum procalcitonin concentrations in patients with sepsis and infection". Lancet 341 (8844): 515–518. doi:10.1016/0140-6736(93)90277-N. ISSN 0140-6736. PMID 8094770. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 "Procalcitonin: Uses in the Clinical Laboratory for the Diagnosis of Sepsis" (in en). Laboratory Medicine 41 (3): 173–177. 2010-03-01. doi:10.1309/LMQ2GRR4QLFKHCH9. ISSN 0007-5027. 
  10. ↑ 10.0 10.1 10.2 "Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy". Journal of Intensive Care 5: 51. 2017-08-03. doi:10.1186/s40560-017-0246-8. PMID 28794881. 
  11. ↑ "Atomic models for the polypeptide backbones of myohemerythrin and hemerythrin". Biochemical and Biophysical Research Communications 66 (4): 1349–56. October 1975. doi:10.1016/0006-291X(75)90508-2. PMID 5. 
  12. ↑ "Procalcitonin and its component peptides in systemic inflammation: immunochemical characterization". Journal of Investigative Medicine 45 (9): 552–60. December 1997. PMID 9444882. 
  13. ↑ "In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue". Endocrinology 144 (12): 5578–84. December 2003. doi:10.1210/en.2003-0854. PMID 12960010. 
  14. ↑ 14.0 14.1 "Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future". BMC Medicine 9: 107. September 2011. doi:10.1186/1741-7015-9-107. PMID 21936959. 
  15. ↑ "Procalcitonin as a predictor of severe appendicitis in children". European Journal of Clinical Microbiology & Infectious Diseases 24 (7): 484–7. July 2005. doi:10.1007/s10096-005-1360-4. PMID 15995845. 
  16. ↑ "A prospective bicenter study investigating the diagnostic value of procalcitonin in patients with acute appendicitis". European Surgical Research 43 (3): 291–7. 2009. doi:10.1159/000232939. PMID 19672084. 
  17. ↑ "An evaluation of the utility of additional tests in the preoperative diagnostics of acute appendicitis". Langenbeck's Archives of Surgery 395 (8): 1061–8. November 2010. doi:10.1007/s00423-009-0565-x. PMID 19924436. 
  18. ↑ "Predictive value of procalcitonin for bowel ischemia and necrosis in bowel obstruction". Surgery 149 (3): 394–403. March 2011. doi:10.1016/j.surg.2010.08.007. PMID 20869092. 
  19. ↑ "Serum procalcitonin for discrimination between septic and non-septic arthritis". Clinical and Experimental Rheumatology 26 (3): 453–6. May 2008. PMID 18578968. 
  20. ↑ "Procalcitonin as a diagnostic aid in osteomyelitis and septic arthritis". Pediatric Emergency Care 21 (12): 828–32. December 2005. doi:10.1097/01.pec.0000190226.12610.24. PMID 16340758. 
  21. ↑ "Diagnostic value of serum and synovial procalcitonin in acute arthritis: a prospective study of 42 patients". Clinical and Experimental Rheumatology 23 (3): 303–10. May 2005. PMID 15971417. 
  22. ↑ "Lipoid Pneumonia Presenting as Solitary Pulmonary Nodule". Chest 138 (4): 121A. 2010. doi:10.1378/chest.10954. 
  23. ↑ 23.0 23.1 "Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study". Critical Care 14 (6): R206. 2010-11-17. doi:10.1186/cc9328. PMID 21083886. 
  24. ↑ "Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department". American Journal of Clinical Pathology 135 (2): 182–9. February 2011. doi:10.1309/ajcp1mfyinqlecv2. PMID 21228358. 
  25. ↑ "Serum procalcitonin for discrimination of blood contamination from bloodstream infection due to coagulase-negative staphylococci". Infection 35 (5): 352–5. October 2007. doi:10.1007/s15010-007-7065-0. PMID 17882355. http://doc.rero.ch/record/319561/files/15010_2007_Article_7065.pdf. 
  26. ↑ 26.0 26.1 26.2 "Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial". Lancet 363 (9409): 600–7. February 2004. doi:10.1016/s0140-6736(04)15591-8. PMID 14987884. 
  27. ↑ 27.0 27.1 27.2 "Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial". JAMA 302 (10): 1059–66. September 2009. doi:10.1001/jama.2009.1297. PMID 19738090. 
  28. ↑ "Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy". Chest 131 (1): 9–19. January 2007. doi:10.1378/chest.06-1500. PMID 17218551. 
  29. ↑ "Procalcitonin in 759 patients clinically suspected of infective endocarditis". The American Journal of Medicine 123 (12): 1121–7. December 2010. doi:10.1016/j.amjmed.2010.07.018. PMID 20870199. 
  30. ↑ "Procalcitonin and the early diagnosis of infective endocarditis". Circulation 109 (14): 1707–10. April 2004. doi:10.1161/01.cir.0000126281.52345.52. PMID 15066945. 
  31. ↑ "Measurement of procalcitonin levels in children with bacterial or viral meningitis". Clinical Infectious Diseases 24 (6): 1240–2. June 1997. doi:10.1086/513633. PMID 9195090. 
  32. ↑ "Procalcitonine et méningites virales : réduction des traitements antibiotiques inutiles par le dosage en routine au cours d'une épidémie". Archives de Pédiatrie 9 (4): 358–364. 2002. doi:10.1016/s0929-693x(01)00793-x. PMID 11998420. 
  33. ↑ "[Acute meningitidis, acute phase proteins and procalcitonin]" (in fr). Annales de Biologie Clinique 61 (2): 127–37. 2003. PMID 12702467. 
  34. ↑ "Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children". Pediatric Critical Care Medicine 6 (2): 129–35. March 2005. doi:10.1097/01.pcc.0000149317.15274.48. PMID 15730597. 
  35. ↑ "The role of procalcitonin in febrile neutropenic patients: review of the literature". Infection 36 (5): 396–407. October 2008. doi:10.1007/s15010-008-7374-y. PMID 18759057. 
  36. ↑ "Elevated procalcitonin predicts Gram-negative sepsis in haematological patients with febrile neutropenia". Scandinavian Journal of Infectious Diseases 43 (6–7): 471–8. July 2011. doi:10.3109/00365548.2011.554855. PMID 21299364. 
  37. ↑ "Assessment of the prognostic value of certain acute-phase proteins and procalcitonin in the prognosis of acute pancreatitis". Pancreas 37 (4): 449–53. November 2008. doi:10.1097/mpa.0b013e3181706d67. PMID 18953261. 
  38. ↑ "The value of procalcitonin at predicting the severity of acute pancreatitis and development of infected pancreatic necrosis: systematic review". Surgery 146 (1): 72–81. July 2009. doi:10.1016/j.surg.2009.02.013. PMID 19541012. 
  39. ↑ "Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial". American Journal of Respiratory and Critical Care Medicine 174 (1): 84–93. July 2006. doi:10.1164/rccm.200512-1922oc. PMID 16603606. 
  40. ↑ "Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission--a randomized trial". Clinical Microbiology and Infection 15 (5): 481–7. May 2009. doi:10.1111/j.1469-0691.2009.02709.x. PMID 19416298. 
  41. ↑ "[The value of serum procalcitonin in treatment of community acquired pneumonia in outpatient]". Zhonghua Nei Ke Za Zhi 48 (3): 216–9. March 2009. PMID 19576090. 
  42. ↑ "Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia". Respirology 16 (5): 819–24. July 2011. doi:10.1111/j.1440-1843.2011.01978.x. PMID 21507143. 
  43. ↑ "The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery". The Journal of Bone and Joint Surgery. American Volume 92 (1): 138–48. January 2010. doi:10.2106/jbjs.h.01600. PMID 20048106. 
  44. ↑ "Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial". Critical Care 13 (3): R83. 2009-06-03. doi:10.1186/cc7903. PMID 19493352. 
  45. ↑ "Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study". Langenbeck's Archives of Surgery 394 (2): 221–6. March 2009. doi:10.1007/s00423-008-0432-1. PMID 19034493. 
  46. ↑ "Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial". American Journal of Respiratory and Critical Care Medicine 177 (5): 498–505. March 2008. doi:10.1164/rccm.200708-1238OC. PMID 18096708. 
  47. ↑ 47.0 47.1 "Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial". Lancet 375 (9713): 463–74. February 2010. doi:10.1016/s0140-6736(09)61879-1. PMID 20097417. 
  48. ↑ "Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection". The European Respiratory Journal 36 (3): 601–7. September 2010. doi:10.1183/09031936.00163309. PMID 20185423. 
  49. ↑ "Procalcitonin: a marker of severity of acute pyelonephritis among children". Pediatrics 114 (2): e249–54. August 2004. doi:10.1542/peds.114.2.e249. PMID 15286264. 
  50. ↑ "Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study". The European Respiratory Journal 34 (6): 1364–75. December 2009. doi:10.1183/09031936.00053209. PMID 19797133. 
  51. ↑ "Comparison of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS". Critical Care 3 (1): 45–50. 1999. doi:10.1186/cc306. PMID 11056723. 
  52. ↑ "Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit". Critical Care 7 (1): 85–90. February 2003. doi:10.1186/cc1843. PMID 12617745. 
  53. ↑ "Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial". JAMA 302 (10): 1059–66. September 2009. doi:10.1001/jama.2009.1297. PMID 19738090. 
  54. ↑ "Measurement of serum procalcitonin: a step closer to tailored care for respiratory infections?". JAMA 302 (10): 1115–6. September 2009. doi:10.1001/jama.2009.1318. PMID 19738100. 
  55. ↑ "Procalcitonin test in the diagnosis of bacteremia: a meta-analysis". Annals of Emergency Medicine 50 (1): 34–41. July 2007. doi:10.1016/j.annemergmed.2006.10.020. PMID 17161501. 
  56. ↑ "The diagnostic accuracy of procalcitonin and C-reactive protein for sepsis: A systematic review and meta-analysis". Journal of Cellular Biochemistry 120 (4): 5852–5859. November 2018. doi:10.1002/jcb.27870. PMID 30417415. 
  57. ↑ "Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials". Critical Care 22 (1): 191. August 2018. doi:10.1186/s13054-018-2125-7. PMID 30111341. 
  58. ↑ Yu, X. -Y.; Wang, Y.; Zhong, H.; Dou, Q. -L.; Song, Y. -L.; Wen, H. (2014-01-01). "Diagnostic Value of Serum Procalcitonin in Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis" (in en). Transplantation Proceedings 46 (1): 26–32. doi:10.1016/j.transproceed.2013.07.074. ISSN 0041-1345. PMID 24507021. http://www.sciencedirect.com/science/article/pii/S004113451301110X. 
  59. ↑ 59.0 59.1 59.2 "Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections". The Cochrane Database of Systematic Reviews 10 (5): CD007498. October 2017. doi:10.1002/14651858.CD007498.pub3. PMID 29025194. PMC 6485408. https://pure.rug.nl/ws/files/71631497/Schuetz_et_al_2017_Cochrane_Database_of_Systematic_Reviews.pdf. 
  60. ↑ "Prognostic value of procalcitonin in pneumonia: A systematic review and meta-analysis". Respirology 21 (2): 280–8. February 2016. doi:10.1111/resp.12704. PMID 26662169. 
  61. ↑ "Meta-analysis and systematic review of procalcitonin-guided treatment in acute exacerbation of chronic obstructive pulmonary disease". The Clinical Respiratory Journal 12 (1): 10–15. January 2018. doi:10.1111/crj.12519. PMID 27328801. 
  62. ↑ "Effects of procalcitonin-guided treatment on antibiotic use and need for mechanical ventilation in patients with acute asthma exacerbation: Meta-analysis of randomized controlled trials". International Journal of Infectious Diseases 65: 75–80. December 2017. doi:10.1016/j.ijid.2017.10.005. PMID 29038045. 
  63. ↑ "Procalcitonin: A new biomarker for the cardiologist". International Journal of Cardiology 223: 390–397. November 2016. doi:10.1016/j.ijcard.2016.08.204. PMID 27543716. 
  64. ↑ "2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC". European Heart Journal 37 (27): 2129–2200. July 2016. doi:10.1093/eurheartj/ehw128. PMID 27206819. 
  65. ↑ "The role of procalcitonin in acute heart failure patients". ESC Heart Failure 4 (3): 203–208. August 2017. doi:10.1002/ehf2.12189. PMID 28772049. 
  66. ↑ "Prognostic and diagnostic value of elevated serum concentration of procalcitonin in patients with suspected heart failure. A review and meta-analysis". Biomarkers 23 (5): 407–413. July 2018. doi:10.1080/1354750X.2018.1443511. PMID 29465002. 
  67. ↑ "Diagnostic Accuracy of Procalcitonin in Bacterial Meningitis Versus Nonbacterial Meningitis: A Systematic Review and Meta-Analysis". Medicine 95 (11): e3079. March 2016. doi:10.1097/MD.0000000000003079. PMID 26986140. 
  68. ↑ "The Role of Procalcitonin in the Diagnosis of Meningitis: A Literature Review". Journal of Clinical Medicine 7 (6): 148. June 2018. doi:10.3390/jcm7060148. PMID 29891780. 
  69. ↑ "The role of serum procalcitonin in the diagnosis of bacterial meningitis in adults: a systematic review and meta-analysis". International Journal of Infectious Diseases 38: 68–76. September 2015. doi:10.1016/j.ijid.2015.07.011. PMID 26188130. 
  70. ↑ "Procalcitonin in inflammatory bowel disease: Drawbacks and opportunities". World Journal of Gastroenterology 23 (47): 8283–8290. December 2017. doi:10.3748/wjg.v23.i47.8283. PMID 29307988. 
  71. ↑ "Use of procalcitonin in patients with various degrees of chronic kidney disease including renal replacement therapy". Clinical Infectious Diseases 59 (12): 1761–7. December 2014. doi:10.1093/cid/ciu732. PMID 25228701. 
  72. ↑ "[Prognostic value of procalcitonin, endotoxin and common inflammatory markers combining MELD score in patients with chronic severe hepatitis]". Zhong Nan da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences 38 (4): 388–94. April 2013. doi:10.3969/j.issn.1672-7347.2013.04.009. PMID 23645239. 
  73. ↑ "Adding C-reactive protein and procalcitonin to the model of end-stage liver disease score improves mortality prediction in patients with complications of cirrhosis". Journal of Gastroenterology and Hepatology 33 (3): 726–732. March 2018. doi:10.1111/jgh.13928. PMID 28840619. 
  74. ↑ "Serum procalcitonin levels as a diagnostic marker for septic arthritis: A meta-analysis". The American Journal of Emergency Medicine 35 (8): 1166–1171. August 2017. doi:10.1016/j.ajem.2017.06.014. PMID 28623003. 
  75. ↑ "Use of procalcitonin in clinical oncology: a literature review". The New Microbiologica 39 (3): 174–180. July 2016. PMID 27284982. 
  76. ↑ "Procalcitonin as Marker of Recurrent Medullary Thyroid Carcinoma: A Systematic Review and Meta-Analysis". Endocrinology and Metabolism 33 (2): 204–210. June 2018. doi:10.3803/EnM.2018.33.2.204. PMID 29947178. 
  77. ↑ "Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis". BMC Infectious Diseases 17 (1): 302. April 2017. doi:10.1186/s12879-017-2396-7. PMID 28438138. 
  78. ↑ "Procalcitonin performance in detecting serious and invasive bacterial infections in children with fever without apparent source: a systematic review and meta-analysis". Expert Review of Anti-Infective Therapy 15 (11): 1041–1057. November 2017. doi:10.1080/14787210.2017.1400907. PMID 29103336. 
  79. ↑ "Procalcitonin: The marker of pediatric bacterial infection". Biomedicine & Pharmacotherapy 96: 936–943. December 2017. doi:10.1016/j.biopha.2017.11.149. PMID 29203386. 
  80. ↑ "Systematic Review and Meta-Analysis of Procalcitonin-Guidance Versus Usual Care for Antimicrobial Management in Critically Ill Patients: Focus on Subgroups Based on Antibiotic Initiation, Cessation, or Mixed Strategies". Critical Care Medicine 46 (5): 684–690. May 2018. doi:10.1097/CCM.0000000000002953. PMID 29293146. 
  81. ↑ "Procalcitonin-guided therapy for the initiation of antibiotics in the ED: a systematic review". The American Journal of Emergency Medicine 34 (7): 1286–93. July 2016. doi:10.1016/j.ajem.2016.03.065. PMID 27130585. 
  82. ↑ "Core Elements | Antibiotic Stewardship Program" (in en-US). https://www.thermofisher.com/procalcitonin/us/en/antibiotic-stewardship/core-elements-and-programs.html. 
  83. ↑ "PCT testing in sepsis protocols". Frontiers in Analytical Science 3. July 2023. doi:10.3389/frans.2023.1229003. 
  84. ↑ "Extreme Procalcitonin Elevation without Proven Bacterial Infection Related to Amphetamine Abuse". Case Reports in Critical Care 2014: 1–3. 2014. doi:10.1155/2014/179313. PMID 24826347. 

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Procalcitonin&oldid=3722652"