Grip Work Measurement with the Jamar Dynamometer: Validation of a Simple Equation for Clinical Use.

OBJECTIVES: Previously, we developed and validated an easy test to measure muscle fatigability during sustained maximal handgrip contraction in older persons using a Martin Vigorimeter device. This study aimed at validating the equation to estimate grip work (GW) during sustained maximal handgrip contraction, by monitoring continuously the grip strength (GS) decay using a Jamar Dynamometer-like (JD) device. DESIGN: Cross sectional, explorative study. SETTING: Data collection took place at The National Research Centre for the Working Environment in Copenhagen, Denmark. PARTICIPANTS: 962 subjects, belonging to a subgroup of the Copenhagen Aging and Midlife Biobank, were enrolled. METHODS: GS was recorded continuously during sustained maximal contraction until it dropped to 50% of its maximum and fatigue resistance (FR, time to fatigue) was noted. GW, area under the force-time curve, was compared to its estimate which was calculated as GWestimated=GSmax*0.75*FR. RESULTS: Excellent correlation was found between GWestimated and GWmeasured (R²=0.98 p<0.001). The equation slightly overestimated GW by 6.04 kg*s (95% CI[-0.08, 12.15]) with a coefficient of variation method error of 6%. CONCLUSION: GW estimation is a valid parameter reflecting muscle work output during a sustained maximal grip effort in healthy middle-aged community-dwelling persons when using a JD. GW estimation is a promising outcome parameter in comprehensive geriatric assessment and its validation for commonly used instruments in geriatric practice will increase its clinical implementation.

Evaluation of appendicular lean mass using bio impedance in persons aged 80+: A new equation based on the BUTTERFLY-study.

BACKGROUND: To date, the accuracy of bio-impedance (BIA) to assess body composition & sarcopenia in persons aged 80 and over remains unclear. OBJECTIVE: We aimed to evaluate the agreement between dual energy X-ray absorptiometry (DXA) and BIA equations to determine lean mass, as well as their suitability to identify sarcopenia. DESIGN: 174 community dwelling well-functioning persons (83 women, 91 men) aged 80 and over were included. Appendicular lean mass (ALM) was predicted using BIA-based equations available in literature, and compared to DXA outcomes. Through cross-validation and stepwise multiple linear regression, a new ALM-formula was generated suitable for this population. RESULTS: Literature-based BIA equations systematically overestimated ALM. The new prediction formula that we propose for the 80+ is: ALM = 0,827+(0,19*Impedance Index)+(2,101*Sex)+(0,079*Weight); R2 = 0,888; SEE = 1,450 kg. Sarcopenia classification based on our new BIA equation for ALM showed better agreement with DXA (k ≥ 0,454) compared to literature-based BIA equations (k < 0,368). CONCLUSIONS: Despite the high correlation between both methods, literature-based BIA equations consistently overestimate ALM compared to DXA in persons aged 80 and over. We proposed a new equation for ALM, reaching higher agreement with DXA and thus improving the accuracy of BIA for this specific age group.

Increasing use of cognitive measures in the operational definition of frailty-A systematic review.

Ageing is associated both with frailty and cognitive decline. The quest for a unifying approach has led to a new concept: cognitive frailty. This systematic review explores the contribution of cognitive assessment in frailty operationalization. PubMed, Web of Knowledge and PsycINFO were searched until December 2016 using the keywords aged; frail elderly; aged, 80 and over; frailty; diagnosis; risk assessment and classification, yielding 2863 hits. Seventy-nine articles were included, describing 94 frailty instruments. Two instruments were not sufficiently specified and excluded. 46% of the identified frailty instruments included cognition. Of these, 85% were published after 2010, with a significant difference for publication date (X2 = 8.45, p < .05), indicating increasing awareness of the contribution of cognitive deficits to functional decline. This review identified 7 methods of cognitive assessment: dementia as co-morbidity; objective cognitive-screening instruments; self-reported; specific signs and symptoms; delirium/clouding of consciousness; non-specific cognitive terms and mixed assessments. Although cognitive assessment has been increasingly integrated in recently published frailty instruments, this has been heterogeneously operationalized. Once the domains most strongly linked to functional decline will have been identified and operationalized, this will be the groundwork for the identification of reversible components, and for the development of preventive interventional strategies.

Characteristics and outcome of Emergency Department intubation in geriatric patients.

INTRODUCTION: The number of elderly patients admitted to the Emergency Department (ED) continues to grow due to the natural aging of the population. Consequently, tracheal intubation will be increasingly used in the oldest old. The objective of this retrospective study is to evaluate the characteristics and outcome of patients of 75 years and older undergoing an endotracheal intubation in the ED. METHODS: In a single center, retrospective study we reviewed digital medical files of patients of 75 years and older in the period from 1/01/2008 to 31/12/2010, who were admitted to the ED of the Universitair Ziekenhuis Brussel in Brussels, Belgium and underwent endotracheal intubation. Survival served as primary outcome and survival without sequelae as secondary endpoint. RESULTS: In the study period, 88 patients of 75 years and older were intubated in the ED. Sixty three (72%) patients died after intubation and 25 (28%) survived until discharge. All 23 patients (26%), who were intubated during cardiopulmonary resuscitation died. A survival rate of 48% was observed in patients, who were intubated for respiratory failure (28%), intracerebral hemorrhage or ischemic stroke (17%), cardiac failure (8%) or other reasons. Non-survivors were significant older, of male sex, had higher APACHE scores and more frequently used cholesterol lowering drugs. CONCLUSION: Senior adults, aged 75 years or older and undergoing endotracheal intubation at the ED, have a high mortality rate. Younger age and female sex at admission were positively correlated with survival. Of those who left the hospital, one-third were able to return home without major sequelae.

Force-time characteristics during sustained maximal handgrip effort according to age and clinical condition.

BACKGROUND: Muscle fatigue, a prominent symptom in older patients, can be assessed by sustained maximal handgrip testing. The force decline during sustained maximal contraction is described for young adults, but data for elderly persons are scarce. The aim of this study was to investigate force-time characteristics during a sustained maximal handgrip effort according to age and clinical condition. METHODS AND MATERIALS: Force-time data were continuously recorded during sustained maximal grip effort in 91 elderly patients (aged 83±5years), 100 elderly controls (aged 74±5years) and 100 young controls (aged 23±3years). The force-time curve was divided in 4 parts per 25% strength drop observed. Time (representing fatigue resistance (FR)) was measured during which grip strength (GS) dropped to 75% (FR75), 50% (FR50), 25% (FR25) of its maximum and to exhaustion (FRexhaustion). Grip work ((GW), the area under the force-time curve) was measured for the 4 parts as well as for the first 20 and 30s of the fatigue protocol test. Strength decay (GWdecay), defined as the difference between the area under the curve (% GW) and a theoretical maximal area under the curve (assuming there's no strength drop), was also studied. In the elderly participants, relationships (controlling for age and sex) of GS, FR and GW with circulating IL-6 and TNF-α were analyzed. RESULTS: FRexhaustion was similar for all groups, whereas the duration of each of the 4 parts was significantly different between the 3 groups. FR75 was shortest in old patients (p=0.004), FR75-50 was almost twice as long in old community-dwelling compared to old patients and young controls (p<0.001). This contrast was inverted for FR50-25 which was significantly shorter in old community-dwelling compared to the other groups (p=0.013). FR25-exhaustionwas significantly longer in young controls compared to the groups of older participants (p=0.017). Old patients showed lower GW for the first 2 parts compared to old community-dwelling and young controls. Also, GWdecay values during the first 20 and 30s were significantly higher in old patients compared to old community-dwelling and young controls (both p<0.001). IL-6 was significantly related to lower GSmax, FR75, FR50, FR25, FRexhaustion, GW75, GW50 and GW75-50. CONCLUSION: This is the first study reporting differences in strength decay during a sustained maximal handgrip effort according to age and clinical condition. Old patients showed a particularly rapid decline in GW during the first part of sustained handgrip. GW was also significantly related to circulating IL-6. Future studies should confirm whether a shorter FR test protocol (i.e. until FR75) but using a continuous registration of the strength decay could be more informative in a clinical setting compared to the classical FR test (measuring only FR50).

High Versus Low Load Resistance Training: The Effect of 24 Weeks Detraining on Serum Brain Derived-Neurotrophic Factor (BDNF) in Older Adults.

BACKGROUND: Previously we showed that 12 weeks of mixed-low resistance training (LOW+) significantly increased circulating BDNF in older male individuals. OBJECTIVES: To examine the impact of 24 weeks detraining on circulating BDNF. DESIGN: Randomized intervention study. SETTING: Community-dwelling older adults. PARTICIPANTS AND METHODS: Forty-seven out of 56 participants stopped training (detraining) after 12 weeks of resistance exercise (3x/week) at either HIGH-resistance (5 Males, 5 Females, 2x10-15 repetitions at 80%1RM), LOW-resistance (6 Males, 7 Females, 1x80-100 repetitions at 20%1RM), or mixed-low LOW+-resistance (6 Males, 8 Females, 1x60 repetitions at 20%1RM followed by 1x10-20 repetitions at 40%1RM), of whom 37 (aged 68±5 years) provided sufficient serum samples for BDNF analysis at baseline, 12 week and at 36 weeks (24 weeks detraining). RESULTS: BDNF had initially increased by 31% (from 33.4±10.9 ng/mL to 44.5±13.2 ng/mL, p=0.005) after 12 weeks in the LOW+ exercise group in males and decreased by 26% (from 44.5±13.2 ng/mL to 32.9±10.7 ng/mL) after detraining, though not statistically significant (p=0.082). In females, no significant change in BDNF was found in any of the intervention groups (p>0.05), neither after training, nor detraining. At 36 weeks all of the subgroups showed BDNF levels comparable (all p>0.10) to baseline (before the exercise intervention). CONCLUSIONS: Our results show that a 12-weeks LOW+ resistance exercise increases circulating BDNF in older male subjects but that this reduces back to baseline levels after 24 weeks of detraining. Continuous exercise adherence seems to be needed to sustain the training-induced effects on BDNF in older persons. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed sex difference.

Effects of Physical Exercise on Markers of Cellular Immunosenescence: A Systematic Review.

Aging affects negatively the immune system, defined as immunosenescence, which increases the susceptibility of elderly persons to infection, autoimmune disease, and cancer. There are strong indications that physical exercise in elderly persons may prevent the age-related decline in immune response without significant side effects. Consequently, exercise is being considered as a safe mode of intervention to reduce immunosenescence. The aim of this review was to appraise the existing evidence regarding the impact of exercise on surface markers of cellular immunosenescence in either young and old humans or animals. PubMed and Web of Science were systematically screened, and 28 relevant articles in humans or animals were retrieved. Most of the intervention studies demonstrated that an acute bout of exercise induced increases in senescent, naïve, memory CD4+ and CD8+ T-lymphocytes and significantly elevated apoptotic lymphocytes in peripheral blood. As regards long-term effects, exercise induced increased levels of T-lymphocytes expressing CD28+ in both young and elderly subjects. Few studies found an increase in natural killer cell activity following a period of training. We can conclude that exercise has considerable effects on markers of cellular aspects of the immune system. However, very few studies have been conducted so far to investigate the effects of exercise on markers of cellular immunosenescence in elderly persons. Implications for immunosenescence need further investigation.

Macrophage capping protein CapG is a putative oncogene involved in migration and invasiveness in ovarian carcinoma.

The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38%) of ovarian carcinomas (OC) analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF) of SNP rs6886 (c.1004A/G) was higher and the homozygous (A/A, His335) genotype was significantly more prevalent in patients with fallopian tube carcinomas (50%) as in controls (10%). With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.

Feasibility and first long-term results after laparoscopic rectal segment resection and vaginal specimen retrieval for deep infiltrating endometriosis.

INTRODUCTION: Radical resection of deep infiltrating endometriosis (DIE), including bladder and bowel resection, provides relief from pain in symptomatic patients. The laparoscopic approach to treatment is well established for bowel resection but normally requires additional abdominal incisions for specimen retrieval. Here we describe our technique of laparoscopically assisted rectal resection and transvaginal specimen retrieval (LARRT) and provide follow-up information on pain scores and complications. MATERIALS AND METHODS: Retrospective observational monocentric study on all DIE patients with rectal infiltration treated between 2008 and 2010 with LATRR at our department. Follow-up was obtained for at least 3 years, including baseline 1-year and 3-year pain scores. RESULTS: We identified four patients undergoing LARRT available for follow-up. DIE was confirmed by histology in all cases. There were no intraoperative complications. Two patients had transient postoperative urinary retention, one patient developed recto-vaginal fistula and required transient colostomy. One patient suffered from persistent vaginal dryness. All patients, however, reported persistent pain relief, including at the end of follow-up period. CONCLUSION: LARRT is a feasible variation of laparoscopic bowel resection for DIE with rectal infiltration. In our study it has promising results with respect to pain control. Larger studies will, however, be required to determine the safety of this procedure.

Recovery of muscular performance after surgical stress in elderly patients.

INTRODUCTION: Inflammation is related to muscle wasting in elderly persons. Since surgery is accompanied by an important inflammatory response, the degree of muscle wasting and related symptoms such as weakness and tiredness might exacerbate very rapidly in elderly surgery patients. METHODS: PubMed and Web of Science were systematically screened for articles reporting the influence of surgery-induced inflammation on muscle performance and/or fatigue in elderly patients. Studies reporting surgery-induced inflammation and changes in muscle performance and/or fatigue, but without analyzing their association were excluded. Although 5 relevant articles were identified including older patients (highest ages reported were 71-92 years), none focused exclusively on elderly patients. Only 2 studies assessed muscle performance, and in none muscle mass was evaluated. Overall, we found evidence that in elderly patients higher surgery-induced inflammation was significantly related to worse muscle performance and fatigue in the first postoperative days as well as after more than one month (especially for fatigue) following the intervention. Pre-operative anti-inflammatory treatment using steroids or glucocorticoids can reduce the surgery-induced inflammatory response and improve the recovery of muscle performance and postoperative fatigue in elderly elective abdominal surgery or arthroplasty patients. CONCLUSION: We can conclude that to date, only few studies have investigated the association between surgery-induced inflammation and changes in postoperative muscle performance and fatigue in elderly patients. More research is warranted focusing on both the short -and long-term effects of surgical stress on muscle performance in elderly patients as well as the on risks and benefits of peri-operative anti-inflammatory treatment.

Prevalence of orthostatic hypotension and relationship with drug use amongst older patients.

INTRODUCTION: Orthostatic hypotension (OH) is said to be highly prevalent in older people. Drugs are often involved as causative factor. Nevertheless, few data are available about the prevalence of OH and its relationship with drugs in olders. OBJECTIVES: To review data about (i) the prevalence and characteristics of OH in older patients; and (ii) the relationship between OH and drugs. METHODS: Review of publications from Ovid (PubMed) from 1980 to May 2011 using the following key words: "orthostatic hypotension" combined with "elderly" or equivalent for the analysis of prevalence (first search) and "orthostatic hypotension" combined with "drugs" or equivalent to assess the relationship between OH and drugs (second search). RESULTS: Fifty-one publications (of which 14 with original data) were retrieved from the prevalence search, 31 for the second search (8 with original data: 7 retrospective studies and 1 prospective cohort study) and 12 reviews or experts opinions. Prevalence of OH varies according to the characteristics of the subjects, the settings of the studies, and the procedures of blood pressure measurement. In acute geriatrics units, two studies reported a prevalence of over 30% and one study mentioned that 68% of the patients presented with at least one episode during the day. OH was associated with several geriatric problems: gait disorders, balance disorders, falls, cerebral hypoperfusion, transient ischemic attacks, cognitive impairment, acute myocardial infarct and systolic hypertension. OH can also be asymptomatic or with atypical presentation: falls, gait disorders and confusion. Psychotropic agents (antipsychotics, sedatives, antidepressants), and cardiovascular drugs (antihypertensive agents, vasodilators, diuretics) were associated with OH. DISCUSSION: If the hypothesis of causality between drug treatment and OH is confirmed, the identification of the involved drugs could be of value for the prevention of OH and its complications. In this context, the Working Group Pharmacology Pharmacotherapy and Pharmaceutical Care of the Belgian Society of Gerontology and Geriatrics proposes to conduct a multicentre study to assess the prevalence of OH in Belgian acute geriatrics units and its relationship with drugs.

Chromatin structure of two genomic sites for targeted transgene integration in induced pluripotent stem cells and hematopoietic stem cells.

Achieving transgene integration into preselected genomic sites is currently one of the central tasks in stem cell gene therapy. A strategy to mediate such targeted integration involves site-specific endonucleases. Two genomic sites within the MBS85 and chemokine (C-C motif) receptor 5 (CCR5) genes (AAVS1 and CCR5 zinc-finger nuclease (CCR5-ZFN) sites, respectively) have recently been suggested as potential target regions for integration as their disruption has no functional consequence. We hypothesized that efficient transgene integration maybe affected by DNA accessibility of endonucleases and therefore studied the transcriptional and chromatin status of the AAVS1 and CCR5 sites in eight human induced pluripotent stem (iPS) cell lines and pooled CD34+ hematopoietic stem cells (HSCs). Matrix chromatin immunoprecipitation (ChIP) assays demonstrated that the CCR5 site and surrounding regions possessed a predominantly closed chromatin configuration consistent with its transcriptional inactivity in these cell types. In contrast, the AAVS1 site was located within a transcriptionally active region and exhibited an open chromatin configuration in both iPS cells and HSCs. To show that the AAVS1 site is readily amendable to genome modification, we expressed Rep78, an AAV2-derived protein with AAVS1-specific endonuclease activity, in iPS cells after adenoviral gene transfer. We showed that Rep78 efficiently associated with the AAVS1 site and triggered genome modifications within this site. On the other hand, binding to and modification of the CCR5-ZFN site by a ZFN was relatively inefficient. Our data suggest a critical influence of chromatin structure on efficacy of site-specific endonucleases used for genome editing.

Inflammation-related muscle weakness and fatigue in geriatric patients.

Inflammation in older persons is associated with muscle wasting, leading to frailty and functional decline. Most studies have focused on IL-6 and TNF-α. In order to further elucidate the underlying mechanisms of muscle wasting and reduced muscle mass and strength we investigated a large panel of cytokines and chemokines, as well as cytoprotective heat shock proteins (Hsp), and measured lean body mass (LBM) and grip strength (GS), fatigue resistance (FR), and grip work (GW) in 33 geriatric patients (median age 84 years) admitted with acute infection-induced inflammation. Higher expression of Hsp27 without heat challenge (WHC) in circulating monocytes and lymphocytes correlated with better FR (r=0.363, p<0.05 and r=0.602, p<0.001 respectively) suggesting a protective effect, as Hsp27 is abundant in muscle. On the other hand, higher serum levels of the inflammatory chemokines CCL11/Eotaxin and CCL2/MCP-1 were related to lower GS and lower LBM (r=-0.393, p<0.05; r=-0.431, p<0.05) respectively. Our results point to a complex pattern of pro-and anti-inflammatory substances that interact with skeletal muscle performance during acute inflammation.

Adenovirus-mediated intratumoral expression of immunostimulatory proteins in combination with systemic Treg inactivation induces tumor-destructive immune responses in mouse models.

Tumor-associated antigens (TAAs) include overexpressed self-antigens (for example, Her2/neu) and tumor virus antigens (for example, HPV-16 E6/E7). Although in cancer patients, TAA-specific CD4+ and CD8+ cells are often present, they are not able to control tumor growth. In recent studies, it became apparent that tumor site-located immune evasion mechanisms contribute to this phenomenon and that regulatory T cells have a major role. We tested in Her2/neu+ breast cancer and HPV-16 E6/E7+ cervical cancer mouse models, whether intratumoral expression of immunostimulatory proteins (ISPs), for example, recombinant antibodies (αCTLA-4, αCD137, αCD3), cyto/chemokines (IL-15, LIGHT, mda-7) and costimulatory ligands (CD80), through adenovirus(Ad)-mediated gene transfer would overcome resistance. In both the breast and cervical cancer model, none of the Ad.ISP vectors displayed a significant therapeutic effect when compared with an Ad vector that lacked a transgene (Ad.zero). However, the combination of Ad.ISP vectors with systemic T regulatory (Treg) depletion, using anti-CD25 mAb (breast cancer model) or low-dose cyclophosphamide (cervical cancer model) resulted in a significant delay of tumor growth in mice treated with Ad.αCTLA4. In the cervical cancer model, we also demonstrated the induction of a systemic antitumor immune response that was able to delay the growth of distant tumors. Ad.αCTLA4-mediated tumor-destructive immune responses involved NKT and CD8+ T cells. In both models no autoimmune reactions were observed. This study shows that Ad.αCTLA4 in combination with systemic Treg depletion has potentials in the immunotherapy of cancer.

Anemia and transfusions in geriatric patients: a time for evaluation.

Anemia is common in the elderly, especially in very old patients who are often frail and may be institutionalized. Senescence, the ageing process, puts the elderly at risk of developing anemia for multiple reasons, but anemia may not be attributed to senescence unless a thorough diagnostic workup has excluded other etiologies. Nutritional deficiencies are common and need to be identified and treated appropriately. Inflammatory diseases and renal failure are also frequent etiological factors and tend to be chronic. Myelodysplastic syndromes increase in frequency with age and may be difficult to diagnose and only a minority of cases respond to appropriate treatment. Anemia is associated with poor outcome and symptomatic treatment with transfusions frequently has to be considered. Red blood cell transfusion has a high therapeutic index and is likely to be effective only if anemia is symptomatic or particularly severe, as a consequence, its use has been restricted to this group. Much of the evidence on usage is limited to younger adults and specific clinical situations. Geriatricians have to deal with a large number of patients with significant anemia but with an absence of well constructed guidelines for the frail and the very old. The object of the present article is to raise awareness that anemia in the geriatric group is multi-factorial and that the patients are more than merely older than those included in most studies, that the results of ongoing trials should be appropriately interpreted and will be important in guiding future practice.

Anaemia in the elderly.

Anaemia is highly prevalent in elderly populations, particularly in long term care facilities and geriatric wards. Even mild anaemia is associated with adverse health outcomes. Although senescence is considered to be a contributing factor, underlying pathology always has to be thoroughly explored. The most frequent etiologies of anaemia in the elderly are anaemia of chronic disease/inflammation; iron, folate and cobalamin deficiency; and myelodysplastic syndrome. Multiple concomitant etiologies are frequently present. The diagnostic workup is straightforward, not very invasive and should be done systematically. Nutrient deficiencies require complete workup and cure. Anaemia of chronic disease/inflammation ideally is taken care of by treating the underlying disease. If this is not possible and if glomerular filtration rate is significantly decreased, treatment with erythropoietin should be considered. Most cases of myelodysplastic syndrome will benefit from supportive care, but a specific subgroup responds particularly well to oral thalidomide analogues. Transfusions should be avoided.

[Aerococcus urinae endocarditis: first case report in Belgium and review of the literature]. / Endocardite a Aerococcus urinae: premier cas en Belgique et revue de la littérature.

Aerococcus urinae is a rarely reported pathogen, possibly due to difficulties in the identification of the organism. Only sixteen cases of A. urinae endocarditis have yet been described. Generally, patients were males with predisposing conditions and the outcomes were bad. We describe the first Belgian case of endocarditis due to A. urinae. Which occurred to a 79-year-old female patient. The diagnostic of A. urinae endocarditis was based on the cardiac ultrasonography and the isolation of the bacteria in 6/7 pairs of blood culture. The patient has been successfully treated by a long course of intravenous antibiotics (38 days) and surgery (aortic valve replacement by bioprothesis). We review the 14 cases published in the English literature and discuss the best clinical management of this type of endocarditis.

Management of an outbreak of Clostridium difficile-associated disease among geriatric patients.

OBJECTIVE: To describe a nosocomial outbreak of Clostridium difficile-associated disease (CDAD). DESIGN: A traditional outbreak investigation. SETTING: Geriatric department of a tertiary care teaching hospital from March through April 2003. METHODS: The outbreak was detected by the C. difficile surveillance program of the infection control unit. CDAD was diagnosed by stool culture and fecal toxin A detection with a qualitative rapid immunoassay. Isolates of C. difficile were serotyped and genotyped using pulsed-field gel electrophoresis. RESULTS: The incidence of CDAD increased from 27 cases per 100,000 patient-days in the 6-month period before the outbreak to 99 cases per 100,000 patient-days during the outbreak. This outbreak involved 21 of 92 patients in 4 geriatric wards, which were located at 2 geographically distinct sites and staffed by the same medical team. The mean age of patients was 83 years (range, 71-100 years). Five (24%) of the 21 patients had community-acquired diarrhea, and secondary hospital transmission resulted in 3 clusters involving 16 patients. Serotyping and genotyping were performed on isolates in stool specimens from 19 different patients; 16 of these isolates were serotype A1, whereas 3 displayed profiles different from the outbreak strain. Management of this outbreak consisted in reinforcement of contact isolation precautions for patients with diarrhea, cohorting of infected patients in the same ward, and promotion of hand hygiene. Relapses occurred in 6 (29%) of 21 patients. CONCLUSION: Control of this rapidly developing outbreak of CDAD was obtained with early implementation of cohorting and ward closure and reinforcement of environmental disinfection, hand hygiene, and enteric isolation precautions.

Interleukin-18 expression in BAL cells of sarcoidosis patients is decreased in vivo but protein secretion is not impaired in vitro.

Recently, increased expression of interleukin-18 (IL-18) has been shown in sarcoid airway epithelium. However, IL-18 expression has not been investigated extensively in bronchoalveolar lavage (BAL) cells in sarcoidosis yet. Expression of IL-18 and tumour necrosis factor-alpha (TNFalpha) mRNA in cells of the BAL of 23 patients with sarcoidosis and nine healthy volunteers was determined using semiquantitative RT-PCR. IL-18 protein in BAL cells was investigated by immunocytochemistry (ICC). IL-18 protein levels in BAL cell culture supernatants from patients and controls with and without LPS stimulation were measured by enzyme-linked immuno-sorbent assay. BAL cells from patients were stimulated with either IL-10 or IL-13 and IL-18 protein levels were determined. IL-18 mRNA expression was significantly decreased in BAL cells of patients compared to control subjects (1.62 +/- 0.27 vs. 4.29 +/- 0.77, P < 0.05). TNFalpha mRNA expression was significantly increased in BAL cells of patients in comparison to control subjects (0.63 +/- 0.09 vs. 0.11 +/- 0.08, P < 0.05). ICC showed less positive alveolar macrophages in sarcoidosis patients than in control subjects (26 vs. 53%). IL-18 protein levels did not differ significantly between both groups. Stimulation with IL-10 significantly reduced IL-18 protein concentration in sarcoidosis patients. Our results suggest that BAL cells may not be the main source of IL-18 production in sarcoidosis in vivo. Since IL-18 production of BAL cells was not impaired in culture antiinflammatory cytokines might contribute to decreased IL-18 expression in vivo.