Inflammation

How exactly do urinary tract infections (UTIs) cause delirium in my elderly patients?

FA Manian MD, MPH, , , , , , , , Leave a comment

 UTIs are often considered in the differential diagnosis of causes of delirium in the elderly. Though largely speculative, 2 possible pathophysiologic basis for this association are suggested:1-3

  •  Direct brain insult (eg, in the setting of sepsis/hypotension)
  • Indirect aberrant stress response, involving cytokines/inflammatory pathways,  hypothalamic-pituitary-adrenal [HPA] axis and sympathetic nervous system (SNS). One or both pathways can interact with the neurotransmitter and intracellular signal transduction systems underlying delirium in the brain, which may already be impaired in the elderly due to age-related or other pathologic changes.

The indirect aberrant stress pathway suggests that not only pain and discomfort (eg from dysuria) can contribute to delirium but UTI-associated circulating cytokines may also cause delirium.  Indeed, a large study of older adults undergoing elective surgery found a significant association between delirium postoperatively (postop day 2) and serum proinflammatory cytokine levels such as IL-6. 4  

The corollary is that bacteriuria is unlikely to be associated with delirium in the absence of significant systemic inflammatory response, pain or discomfort. We just need to do proper studies to prove it!

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References

1.Trzepacz P, van der Mast R. The neuropathophysiology of delirium. In Lindesay J,  Rockwood K, Macdonald A (Eds.). Delirium in old age, pp. 51–90. Oxford University Press, Oxford , 2002.

2.Flacker JM, Lipsitz LA. Neural mechanisms of delirium: current hypotheses and evolving concepts. J Gerontol A Biol Sci Med Sci. 1999; 54: B239–B246 https://www.ncbi.nlm.nih.gov/pubmed/10411009

3. Maclullich AM, Ferguson KJ, Miller T, de Rooij SE, Cunningham C. Unravelling the pathophysiology of delirium: a focus on the role of aberrant stress responses. J Psychosom Res. 2008;65:229–38. https://www.ncbi.nlm.nih.gov/pubmed/18707945

4. Vasunilashom SM, Ngo L, Inouye SK, et al. Cytokines and postoperative delirium in older patients undergoing major elective surgery. J Gerontol A Biol Sci Med Sci 2015;70:1289-95. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817082/pdf/glv083.pdf

Contributed by Henrietta Afari MD, Mass General Hospital, Boston, MA

How exactly do urinary tract infections (UTIs) cause delirium in my elderly patients?

Why has my hospitalized patient with head and neck cancer developed thrombocytosis few days following surgery?

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

Thrombocytosis or elevated platelet count is not uncommon among hospitalized patients and may be related to several factors, including “tissue damage” from a surgical procedure, infection, acute blood loss, iron deficiency, and less well known, enoxaparin.1-4 

Postoperative thrombocytosis is thought to be related to increased platelet production as well as redistribution of platelets from the splenic platelet pool to the general circulation.1  Increased levels of megakaryocytic growth factors such as thrombopoietin, and pro-or anti-inflammatory cytokines such as interleukin (IL)-1, 3, 6, or 11 may also stimulate megakaryopoeisis in the setting of inflammation.2 The mechanism of iron deficiency causing thrombocytosis is unknown.4

Enoxaparin-related thrombocytosis usually develops within the first 2 weeks of therapy and resolves 2 weeks following its discontinuation.3

In our patient, although malignancy is also associated with secondary thrombocytosis, given its acute nature in our patient, it is less likely to be playing a role.

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References

  1. Griesshammer M, Bangerter M, Sauer T, et al. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med 1999;245:295-300. https://www.ncbi.nlm.nih.gov/pubmed/10205592
  2. Kulnigg-Dabsch S, Schmid W, Howaldt S, et al. Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial. Inflamm Bowel Dis 2013;published online, DOI10.1097/MIB.0b013e318281f4db. https://www.ncbi.nlm.nih.gov/pubmed/23644823
  3. Hummel MC, Morse BC, Hayes LE. Reactive thrombocytosis associated with enoxaparin. Pharmacotherapy 2006;26:1667-1670. https://www.ncbi.nlm.nih.gov/pubmed/17064215
  4. Dan K. Thrombocytosis in iron deficiency anemia. Intern Med 2005;44: 1025-6. https://www.jstage.jst.go.jp/article/internalmedicine/44/10/44_10_1025/_pdf

 

Why has my hospitalized patient with head and neck cancer developed thrombocytosis few days following surgery?

Is there a seasonal variation in the incidence of cardiovascular (CV) events or venous thromboembolism (VTE)?

FA Manian MD, MPH, , , , , , , , , , 1 Comment

Seasonal variation, primarily characterized by a winter peak, has been reported for acute CV events, such as acute myocardial infarction (AMI) and sudden death, aortic rupture or dissection, and ischemic or hemorrhagic stroke, and VTE (1). A meta-analysis involving patients with VTE, primarily with a diagnosis of pulmonary embolism, revealed a 20% absolute increase in the incidence of VTE during January (1).  

Potential physiological mechanisms for these observations include increased sympathetic activity, decreased loss of fluids and sodium, increase in LDL cholesterol, increase in serum fibrinogen levels and other coagulation markers and C-reactive protein, and lower vitamin D levels due to shorter daylight hours during winter months (1,2).  At least in the case of AMI in the U.S., the higher incidence in winter is not affected by climate (2).  

Respiratory virus infections as a cause of acute inflammation leading to  CV or VTE events is another intriguing explanation (3). Indeed, influenza vaccination has been associated with reduction in hospitalization for cardiac disease and stroke among the elderly (4) and, in patients with cardiovascular disease, a reduction in death due to combined cardiovascular disease events such as heart attacks and strokes (5).

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References

  1. Dentali F, Ageno W, Rancan E, et al. Seasonal and monthly variability in the incidence of venous thromboembolism. A systematic review and a meta-analysis of the literature. Thromb Haemost 2011;106:439-447. https://www.ncbi.nlm.nih.gov/pubmed/21725580
  2. Spencer FA, Goldberg RJ, Becker RC, et al. Seasonal distribution of acute myocardial infarction in the Second National Registry of Myocardial Infarction. J Am Coll Cardiol 1998;31:1226-33.h ttps://www.ncbi.nlm.nih.gov/pubmed/9581712
  3. Woodhouse PR, Khaw KT, Plummer M, et al. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994;343:435-39.  https://www.ncbi.nlm.nih.gov/pubmed/7508540
  4. Nichol KL, Nordin J, Mulloly J, et al. Influenza vaccination and reduction in hospitalization for cardiac disease and stroke among the elderly. N Engl J Med 2003; 348:1322-1332. http://www.nejm.org/doi/full/10.1056/NEJMoa025028
  5. Clar C, Oseni Z, Flowers N, et al. Cochrane Database of Systematic Reviews 2015. DOI: 10.1002/14651858.CD005050.pub3h ttp://www.cochrane.org/CD005050/VASC_flu-vaccines-for-preventing-cardiovascular-disease  

 

 

 

 

Is there a seasonal variation in the incidence of cardiovascular (CV) events or venous thromboembolism (VTE)?