Usefulness of White Blood Cell Count (WBCC) During Infection in Geriatric Patient
Usefulness of White Blood Cell Count (WBCC) During Infection in Geriatric Patient
In the general population, increased WBCC and neutrophil count are widely used as markers for
 infection during inflammatory states 1. However, 32% of geriatric patients with an infection
 do not develop an increase in WBCC 2. The hypothesis is that with inflammation, geriatric
 patients have a misadapted response of the immune system (IS) 3.

 Our recent retrospective study 4 has shown that total and differential WBCC were not
 correlated with infection in a geriatric hospitalized population. Therefore, WBCC does not
 seem to be a reliable marker for infection in geriatric hospitalized patients. The
 neutrophil/lymphocyte ratio, and CRP, seem to be better markers.

 the aim of the study to investigate this hypothesis prospectively and assess the role of
 aging and chronic diseases (such as cardiovascular diseases (CVD) and risk factors (CVRF) 5,
 cytomegalovirus (CMV) infection 6, periodontitis 7, onychomycosis 8 ) in this process and
 assess the role of a geriatric assessment.

 To assess the usefulness of WBCC in the diagnosis of infection in geriatric patients and to
 address the contribution of ongoing chronic co-morbidities and age to WBCC-kinetics during an
 acute inflammatory syndrome, young and geriatric hospitalized patients with an inflammatory
 syndrome with and without infection will be compared
Study design Observational prospective study

 The subjects Number of subjects 200 subjects: Average value CRP: group 1: 55; group 2: 84
 Average standard deviation: 70.52 Power 80%: 158 deelnemers Power 90%: 202 deelnemers alpha =
 0.05 2-sample T-test.

 Inclusion criteria

 Acute inflammation is defined as a CRP ≥ 10 mg/l. We will include 2 groups of participants:

 -  A) A group with an inflammatory syndrome and infection; infection being defined as:

 1. Viral infection confirmed by nasopharynx swab for: influenza, RSV, parainfluenza,
 rhinovirusses, coronavirusses.

 2. Bacterial infection confirmed with positive blood culture, positive articular
 punction, positive expectorations, pneumonia on chest radiograph, or infection
 documented by abdominal imagery (CT or echo), a positive urine culture with a
 confirmed pyelonephritis with a renal echography or a DMSA scintigraphy or specific
 clinical symptoms for pyelonephritis and positive hemoculture. A positive urine
 culture alone is not considered as urine infection because of the high prevalence
 of asymptomatic bacteriuria in geriatric patients.

 -  B) A group with inflammatory syndrome and inflammatory diseases without infection:
 defined as:

 1. Confirmed pulmonary embolism (PE) by CT or ventilation-perfusion scintigraphy

 2. Microcrystalline arthritis diagnosed by articular punction

 3. Crush syndrome or rhabdomyolyses defined by history of a fall and raised creatine
 kinase in blood sample.

 Exclusion criteria Immunosuppressive therapy (NSAIDs, corticosteroids, chemotherapy,
 immunotherapy), active cancer, antibiotics before admission, hematological diseases

 Replacement of subjects None.

 Restrictions and prohibitions for the subjects None.

 Procedures

 A) Questionnaires:

 taken at UZ Brussels

 -  Social: age, home, sex, marital status.

 -  Clinical: smoking and alcohol habits, streptococcus pneumoniae and influenza vaccination
 status, allergies, BMI, medical history, current treatment, reason for current
 hospitalization.

 -  Comprehensive geriatric assessment:

 -  CIRS-G (Cumulative Illness Rating Score): to quantify disease burden. It rates each
 organ system on a scale of 0 to 4, and differentiates older adults with the highest risk
 of and severity of infection, from those with lower infection risk. 20

 -  Katz scale (ADL: assessment of activities of daily living): It rates 6 tasks of daily
 living (bathing, dressing, toilet, transfer, continence and eating) on a scale from 1 to
 4. A low score means absence of dependence, and a high score the maximum of dependence
 for the task. 21

 -  MMSE (Mini Mental Status Examination): a 0-30 score of cognitive functions, <24/30
 meaning cognitive function impairment. 22 Patients with dementia:the investigators will
 request approval to be included in the study to the family of the patients.

 -  MUST (Malnutrition Universal Screening Tool): to assess nutritional status. It divides
 patients into 3 groups: A low risk of malnutrition (score 0). A medium risk of
 malnutrition (score 1): then it is recommended to observe the patient for dietary
 intake. A high risk of malnutrition (score ≥2): treat the malnutrition. 23

 -  Questionnaire for periodontal health. The newly developed questionnaire produces a
 reliable assessment of the individual risk of periodontitis (total score) and the need
 for periodontal treatment as well as the differentiation between gingivits and
 peridontitis. 24

 -  Grip strength: Inflammatory states in the elderly are also associated with a decrease in
 muscle strength and fatigue resistance, as seen at UZ Brussels by Bautmans et al. The
 reduced strength and fatigue resistance in geriatric patients with inflammation are
 significantly related with the concentration of circulating CRP levels. 25 In the study,
 the investigators will use the martin vigorimeter which is at our disposal at the
 geriatrics ward of UZ Brussels, to measure the patients' grip strength and muscle
 fatiguability and determine which factors seem to contribute to a decrease in muscle
 strength (CRP, CVD, CVR, infection, periodontitis, CMV status, onychomycosis, age). the
 investigators will use the Martin vigorimeter (Elmed, Addison, IL) to assess grip
 strength and fatiguibility. The investigators will ask the patients to squeeze the
 rubber bulb of the vigorimeter as hard as possible in 3 consecutive attempts, to assess
 their grip strength. The highest score for each hand is recorded. Fatigue resistance
 will be assessed by asking the patient to squeeze the bulb of the vigorimeter as hard as
 possible and to maintain this pressure as long as possible; the time (seconds) until the
 pressure diminished to half of the maximal grip strength is recorded for each hand.25 26
 B) Collection of data from physical examination C) Clinical evaluation of onychomycosis
 of the toenails: the investigators will perform a clinical examination of the toenails.
 Following parameters are found to be significantly related to positive mycology results
 in onychomycosis patients 8: scaling on one or both soles, white crumbly patches on the
 nail surface, and an abnormal colour of the nail.

 D) Follow up of bacterial and viral culture analyses

 Observational data from bacterial and viral samples during hospitatalization :

 1. Viral infection confirmed by nasopharynx swab for: influenza, RSV, parainfluenza,
 rhinovirusses, coronaviruses

 2. Bacterial infection confirmed with positive blood culture, positive articular punction,
 positive expectorations, pneumonia on chest radiograph, or infection documented by
 abdominal imagery (CT or echo), a positive urine culture with a confirmed pyelonephritis
 with a renal echography or a DMSA scintigraphy or specific clinical symptoms for
 pyelonephritis and positive hemoculture. A positive urine culture alone is not
 considered as urine infection because of the high prevalence of asymptomatic bacteriuria
 in geriatric patients.

 E) Follow up of blood analyses:

 Observational data from blood samples during hospitalization:

 -  Day 0 (at the emergency department): CRP, total and differential WBCC, renal function

 -  Day 1: at hospitalization, within 24h of admission

 -  Geriatric patients: CRP, total and differential WBCC, renal function, hepatic function
 (transaminases), albumin, prealbumin, protein profile and monoclonal protein, vitamin
 B12, folic acid, hemoglobin, hematocrit, TSH, CMV-serology.

 -  Young patients: CRP, total and differential WBCC, renal function, albumin, vitamin B12,
 folic acid, TSH, CMV-serology.

 -  Day 3: CRP, total and differential WBCC.

 -  Day 5: CRP, total and differential WBCC.

 Flowchart Questionnaires, blood samples: conducted by Hanne Maes. Supervising MD: Dr.
 Nathalie Compté, UZ Brussels.

 Randomisation/blinding Observational study, not applicable.

 Prior and concomitant therapy All medication can be continued during this study.

 Study analysis Statistical analysis the investigators will perform student t-tests or
 Mann-Whitney rank sum tests to compare geriatric/young patients with and without infection.
 To assess the contribution of age, comorbidities and geriatric syndrome in the kinetics of
 WBCC, the investigators will perform univariate and multivariate analyses.
Inclusion Criteria:

 Acute inflammation is defined as a CRP ≥ 10 mg/l. We will include 2 groups of participants:

 -  A) A group with an inflammatory syndrome and infection; infection being defined as:

 1. Viral infection confirmed by nasopharynx swab for: influenza, RSV, parainfluenza,
 rhinovirusses, coronavirusses.

 2. Bacterial infection confirmed with positive blood culture, positive articular
 punction, positive expectorations, pneumonia on chest radiograph, or infection
 documented by abdominal imagery (CT or echo), a positive urine culture with a
 confirmed pyelonephritis with a renal echography or a DMSA scintigraphy or
 specific clinical symptoms for pyelonephritis and positive hemoculture. A
 positive urine culture alone is not considered as urine infection because of the
 high prevalence of asymptomatic bacteriuria in geriatric patients.

 -  B) A group with inflammatory syndrome and inflammatory diseases without infection:
 defined as:

 1. Confirmed pulmonary embolism (PE) by CT or ventilation-perfusion scintigraphy

 2. Microcrystalline arthritis diagnosed by articular punction

 3. Crush syndrome or rhabdomyolyses defined by history of a fall and raised creatine
 kinase in blood sample.

 Exclusion Criteria:

 Immunosuppressive therapy (NSAIDs, corticosteroids, chemotherapy, immunotherapy), active
 cancer, antibiotics before admission, hematological diseases