Marie de Saint-Hubert

Clinical profiles of patients colonized or infected with extended-spectrum beta-lactamase producing Enterobacteriaceae isolates: a 20 month retrospective study at a Belgian University Hospital.

BackgroundDescription of the clinical pictures of patients colonized or infected by ESBL-producing Enterobacteriaceae isolates and admitted to hospital are rather scarce in Europe. However, a better delineation of the clinical patterns associated with the carriage of ESBL-producing isolates may allow healthcare providers to identify more rapidly at risk patients. This matter is of particular concern because of the growing proportion of ESBL-producing Enterobacteriaceae species isolates worldwide.MethodsWe undertook a descriptive analysis of 114 consecutive patients in whom ESBL-producing Enterobacteriaceae isolates were collected from clinical specimens over a 20-month period. Clinical data were obtained through retrospective analysis of medical record charts. Microbiological cultures were carried out by standard laboratory methods.ResultsThe proportion of ESBL-producing Enterobacteriaceae strains after exclusion of duplicate isolates was 4.5% and the incidence rate was 4.3 cases/1000 patients admitted. Healthcare-associated acquisition was important (n = 104) while community-acquisition was less frequently found (n = 10). Among the former group, two-thirds of the patients were aged over 65 years and 24% of these were living in nursing homes. Sixty-eight (65%) of the patients with healthcare-associated ESBL, were considered clinically infected. In this group, the number and severity of co-morbidities was high, particularly including diabetes mellitus and chronic renal insufficiency. Other known risk factors for ESBL colonization or infection such as prior antibiotic exposure, urinary catheter or previous hospitalisation were also often found. The four main diagnostic categories were: urinary tract infections, lower respiratory tract infections, septicaemia and intra-abdominal infections. For hospitalized patients, the median hospital length of stay was 23 days and the average mortality rate during hospitalization was 13% (Confidence Interval 95%: 7-19). Escherichia coli, by far, accounted as the most common ESBL-producing Enterobacteriaceae species (77/114; [68%]) while CTX-M-1 group was by far the most prevalent ESBL enzyme (n = 56).ConclusionIn this retrospective study, the clinical profiles of patients carrying healthcare-associated ESBL-producing Enterobacteriacae is characterized by a high prevalence rate of several major co-morbidities and potential known risk factors. Both, the length of hospital stay and overall hospital mortality rates were particularly high. A prospective case-control matched study should be designed and performed in order to control for possible inclusion bias.

COMPARISON OF THREE TOOLS PREDICTING FUNCTIONAL DECLINE AFTER HOSPITALIZATION OF OLDER PATIENTS

patotoxicity in older adults than reported in previous studies of younger adults, which found that clinical hepatitis developed in 1.1% (14/1,264) of patients receiving a rifampicin-containing regimen and hyperbilirubinemia in 0.6% of patients. The difference may be attributable to the effects of aging on hepatic function. In addition, the findings of the current study indicate the importance of close monitoring of liver function while using rifampicin for MRSA bacteremia in older adults. In conclusion, treatment with a rifampicin-containing regimen for MRSA bacteremia is likely to rapidly induce rifampicin resistance, especially in very old patients. The higher mortality rate of patients with emergence of rifampicin-resistant MRSA during rifampicin-containing treatment and the higher frequency of hepatotoxicity in patients with current rifampicin usage in MRSA bacteremia warrant clinical attention and further study.

Transcriptomic biomarkers of human ageing in peripheral blood mononuclear cell total RNA

Age-related changes of gene expression contribute to the physiological alteration observed with human ageing. Herein, the abundance of a selection of 148 transcripts involved in immunosenescence and stress response was compared in total RNA of PBMC of healthy young to middle-age probands (35.0 +/- 6.5 year old) and healthy old probands (82.5 +/- 6.8 year old). This study provides a list of 16 differentially abundant transcripts species in the healthy old probands. Thus, these changes of abundance can be considered as easily accessible biomarkers of ageing. Some of these differential abundances like CD28, CD69, LCK (decreased abundance in old subjects), CD86, Cathepsin D, H and S (increased abundance in old subjects) might explain biochemical and cytochemical changes observed at the protein level in the immune system and thus might correspond to regulatory processes affecting the ageing process. Indeed these changes reflect the low-grade pro-inflammatory status observed in old persons and suggest a hypo-responsiveness of T-cells together with an increase in antigen presentation potential. In addition, among the differentially abundant transcripts were transcripts involved in the oxidative stress response HMOX1 and HSPA6 mRNAs were found as more abundant in PBMC from elderly subjects.

Serum Il-6 and IGF-1 improve clinical prediction of functional decline after hospitalization in older patients

Background and aims: Although inflammatory and hormonal markers have been associated with further functional adverse outcomes in community-dwelling seniors, these markers have not been studied from this perspective in acutely ill older patients. This prospective study was designed to determine whether biological markers can improve the predictive value of a clinical screening tool to assess the risk of functional decline in hospitalized older patients. Methods: Patients aged 75 years and over admitted for hip fracture, acute heart failure or infection (n=118) were recruited. The clinical screening tool SHERPA was filled in on admission, with concomitant measurement of interleukin-6 (IL-6), insulin-like growth factor 1 (IGF-1), C-reactive protein (CRP), white blood cells, urea, albumin, pre-albumin and total cholesterol. Functional decline was defined as a decrease of one point in the activities of daily living scale between pre-admission and 3-month post-discharge status. We compared the discrimination calibration of SHERPA vs SHERPA+, a logistic regression model including SHERPA and selected biomarkers. Results: Three months after discharge, functional decline had occurred in 46 patients. Interleukin-6 (IL-6) and insulinlike growth factor 1 (IGF-1) were selected, since their levels were significantly different between decliners and non-decliners, and were included in the new logistic regression model SHERPA+. Areas under the ROC curve [95% CI] for functional decline prediction were 0.73 [0.63–0.81] for SHERPA vs 0.79 [0.69–0.86] for SHERPA+ (p=0.14). However, SHERPA+ was better calibrated, as the average predicted risk of functional decline within subgroups matched the proportion which actually underwent functional decline (Brier score=0.185). Since functional decline was higher in patients with hip fracture, the SHERPA+ model was challenged by including the diagnosis. Only SHERPA, IGF-1 and diagnosis were significantly associated with functional decline. Conclusions: Selected biological markers may marginally improve the clinical prediction of post-discharge functional decline in hospitalized patients, and to stratify them appropriately. The predictive value of these biomarkers is not fully independent of disease status. Further studies are needed to confirm these results in a cohort representative of older patients admitted through the emergency department.

Transcriptomic biomarkers of the response of hospitalized geriatric patients admitted with heart failure. Comparison to hospitalized geriatric patients with infectious diseases or hip fracture.

The abundance of a preselection of transcripts involved in inflammation, immunosenescence and stress response was compared between PBMC of healthy aged donors and aged patients in acute phase of heart failure and at recovery. This study identified 22 transcripts differentially abundant in acute phase of heart failure versus healthy aged subjects. Transcripts involved in inflammation and oxidative stress were more abundant. Those associated with T-cell functions were less abundant. The results were compared to two other major acute geriatric issues: infectious diseases and hip fracture. In acute phase, compared to healthy aged subjects, the abundance of 15/22 transcripts was also altered in both geriatric infectious diseases and hip fracture. Many variations had not vanished at the recovery phase. The abundance of CD28, CD69, LCK, HMOX1, TNFRSF1A transcripts, known to be altered in healthy aged versus healthy young subjects, was further affected in acute phase of the three geriatric diseases considered. The transcript levels of BCL2, CASP8, CCL5, DDIT3, EGR3, IL10RB, IL1R2, SERPINB2 and TIMP1 were affected in all three pathological conditions compared to healthy aged, but not versus healthy young subjects. In conclusion, this work provides critical targets for therapeutic research on geriatric heart failure, infectious diseases and hip fracture.

Transcriptomic biomarkers of the response of hospitalized geriatric patients with infectious diseases.

BackgroundInfectious diseases are significant causes of morbidity and mortality among elderly populations. However, the relationship between oxidative stress, immune function and inflammatory response in acute phase of the infectious disease is poorly understood.ResultsHerein the abundance of a selection of 148 transcripts involved in immunosenescence and stress response was compared in total RNA of PBMC of 28 healthy aged probands and 39 aged patients in acute phase of infectious disease (day 2-4 after hospitalization) or in convalescence phase (day 7-10). This study provides a list of 24 differentially abundant transcript species in the acute phase versus healthy aged. For instance, transcripts associated with inflammatory and anti-inflammatory reactions (TNFRSF1A, IL1R1, IL1R2, IL10RB) and with oxidative stress (HMOX1, GPX1, SOD2, PRDX6) were more abundant while those associated with T-cell functions (CD28, CD69, LCK) were less abundant in acute phase. The abundance of seven of these transcripts (CD28, CD69, LCK, CTSD, HMOX1, TNFRSF1A and PRDX6) was already known to be altered in healthy aged probands compared to healthy young ones and was further affected in aged patients in acute phase, compromising an efficient response.ConclusionThis work provides insights of the state of acute phase response to infections in elderly patients and could explain further the lack of appropriate response in the elderly compared to younger persons.

Somatotrope GHRH/GH/IGF‐1 axis at the crossroads between immunosenescence and frailty

Immunosenescence, characterized by complex modifications of immunity with age, could be related to frailty syndrome in elderly individuals, leading to an inadequate response to minimal aggression. Functional decline (i.e., the loss of ability to perform activities of daily living) is related to frailty and decreased physiological reserves and is a frequent outcome of hospitalization in older patients. Links between immunosenescence and frailty have been explored and 20 immunological parameters, including insulin‐like growth factor‐1 (IGF‐1), thymopoeisis, and telomere length, were shown to be affected in elderly patients with functional decline. A strong relationship between IGF‐1 and thymic ouput was evidenced. IGF‐1, a mediator of growth hormone (GH), was subsequently shown to induce interleukin‐7 secretion in cultured primary human thymic epithelial cells. We are exploring the stress hypothesis in which an acute stressor is used as the discriminator of frailty susceptibility. GH can counteract the deleterious immunosuppressive effects of stress‐induced steroids. Under nonstress conditions, the immunosenescent system preserves physiological responses, while under stress conditions, the combination of immunosenescence and a defect in the somatotrope axis might lead to functional decline.

Differentially abundant transcripts in PBMC of hospitalized geriatric patients with hip fracture compared to healthy aged controls

The abundance of a selection of transcript species involved in inflammation, immunosenescence and stress response was compared between PBMC of 35 geriatric patients with hip fracture in acute phase (days 2-4 after hospitalization) or convalescence phase (days 7-10) and 28 healthy aged controls. Twenty-nine differentially abundant transcripts were identified in acute phase versus healthy ageing. Twelve of these transcripts remained differentially abundant in convalescence phase, and 22 were similarly differentially abundant in acute phase of geriatric infectious diseases. Seven of these 22 transcripts were previously identified as differentially abundant in PBMC of healthy aged versus healthy young controls, with further alteration for CD28, CD69, LCK, CTSD, HMOX1, and TNFRSF1A in acute phase after geriatric hip fracture and infectious diseases. The next question is whether these alterations are common to other geriatric diseases and/or preexist before the clinical onset of the diseases.

A high sense of coherence protects from the burden of caregiving in older spousal caregivers

OBJECTIVES Caregiving is often associated with burden and chronic stress. Sense of coherence (SOC) may help the caregivers in coping with their stress and was identified as a positive factor for health outcomes and quality of life. We aimed to study the links between SOC, burden, depression and positive affects among caregivers of frail older patients. METHODS Seventy-nine spousal caregivers were recruited via the geriatric outpatient clinic. DATA COLLECTED Zarit Burden Inventory, SOC-13, Geriatric Depression Scale, Caregiver Reaction Assessment (CRA), sleep, time of supervision, Katz Index, Global Deterioration Scale and Neuropsychiatric Inventory. ANALYSES Caregivers characteristics were analyzed by burden severity and SOC level. Multivariable logistic regressions were used in order to identify the variable that best predict caregiver burden and high SOC. RESULTS The mean age was 79.4±5.3; 53% were women. Among care-recipient, 82% had cognitive impairment and the median Katz Index was 3. Caregivers with a high SOC and an older age reported a lower burden (Odds Ratio (OR) 0.18, 95% confidence interval (CI) 0.04-0.65 and OR 0.87, 95% CI 0.76-0.98, respectively). A higher burden was associated with patient functional limitations (OR 8.69, 95% CI 2.28-40.46). DISCUSSION Having a high sense of coherence seems to be a protective factor against the burden. To support caregivers, health providers should recognize the expertise of the caregivers and the meaningfulness of this care situation.

Impact of caregiving for older people and pro-inflammatory biomarkers among caregivers: a systematic review

IntroductionEvidence suggests that providing care for an older loved one may present a risk to the health of the caregiver. To understand the link between the psychosocial stress of caregiving and damage to the health of caregivers, numerous studies have assessed the presence of inflammatory biomarkers among caregivers. These biomarkers are measured to understand the relationships between the social stress of caregiving and the health of caregivers.ObjectiveTo provide a complete summary of the current literature regarding the most clinically relevant pro-inflammatory biomarkers associated with caregiving.MethodsWe searched articles in MEDLINE and EMBASE from January 1980 to 30 April 2016 for all studies that assessed biomarkers (cortisol, interleukin-6 and c-reactive protein) among caregivers of community-dwelling older persons. The quality of the selected studies was assessed by two reviewers using the STROBE or CONSORT checklist.ResultsTwenty-four studies were included. Most of the studies were cross-sectional and focused on dementia caregiving. Increases in biomarkers were associated with problems such as disturbed sleep, burden or pain and caregiving characteristics, including daily stressors and the duration of caregiving. Cognitive-behavioural therapy and participation in leisure activities were associated with significantly lower levels of cortisol and IL-6, respectively.DiscussionWe found little evidence concerning the association between caregiving status and biomarkers of stress and inflammation. We discuss potential sources of bias and suggest some directions for further research. This stress model can be expanded by taking into account the positive aspects of caregiving and the potential resources of caregivers.