NFL strongly correlates with TNF-R1 in the plasma of AD patients, but not with cognitive decline.

Peripheral inflammation mechanisms involved in Alzheimer's disease (AD) have yet to be accurately characterized and the identification of blood biomarker profiles could help predict cognitive decline and optimize patient care. Blood biomarkers described to date have failed to provide a consensus signature, which is mainly due to the heterogeneity of the methods used or the cohort. The present work aims to describe the potential informativity of peripheral inflammation in AD, focusing in particular on the potential association between the level of plasma neurofilament light (NFL), peripheral inflammation (by quantifying IL-1ß, IL-6, TNFα, CCL5, TNF-R1, sIL-6R, TIMP-1, IL-8 in blood) and cognitive decline (assessed by the MMSE and ADAScog scales) through a 2-year follow-up of 40 AD patients from the Cytocogma cohort (CHU Poitiers, Pr M. Paccalin). Our results show for the first time a strong correlation between plasma NFL and TNF-R1 at each time of follow-up (baseline, 12 and 24 months), thus opening an interesting perspective for the prognosis of AD patients.

Determinants of doctors' antibiotic prescriptions for patients over 75 years old in the terminal stage of palliative care.

INTRODUCTION: Notwithstanding high prevalence of presumably bacterial infections in elderly persons (EP) in palliative care (PC), there exists no recommendation on the role of antibiotic therapy (ABP) in this type of situation. OBJECTIVE: To describe the determinants of antibiotic prescription by general practitioners (GP) and by doctors practicing in institutions (DPI) for patients>75 years, in end-of-life situations in PC. METHOD: Descriptive investigation by anonymous self-administered questionnaire disseminated in France by e-mail. RESULTS: A total of 301 questionnaires analyzed: 113 GP, 188 DPIs. The latter were mainly geriatricians (69, 36.6%) and infectologists/internists (41, 21.8%). Sixty-three (55,75%) GPs and 144 (78.7%) DPIs stated that they had prescribed antibiotics. Practice in "EHPAD" retirement homes or intensive care was often associated with non-prescription of antibiotics. Age, PC training and number of patients monitored bore no influence. Family involvement in decision-making was more frequent for GPs than for DPIs. The main purpose of antibiotic therapy was to relieve different symptoms (fever, respiratory congestion, functional urinary signs). Most of the doctors (81%) had previously encountered complications (allergy, adverse effect), which represented the main causes of treatment discontinuation. CONCLUSION: Antibiotic use in end-of-life EPs in PC seems frequent. In accordance with the principle of beneficence, its goal of often symptom-related; that said, in the absence of scientific data, antibiotic prescription in end-of-life situations should be individualized in view of observing the other ethical caregiving principles (beneficence, non-maleficence, justice, patient autonomy) and re-evaluated daily.

Comprehensive geriatric assessment in older patients suffering from infective endocarditis. A prospective multicentric cohort study.

OBJECTIVES: The aim was to describe the impact of infective endocarditis (IE) on functional, cognitive and nutritional statuses, and to estimate the influence of these parameters on surgical management and mortality. METHOD: This was a prospective study over 13 months in 14 French hospitals, including patients ≥75 years of age with definite or possible IE. A comprehensive geriatric assessment (CGA) was performed during the first week of hospitalization, including a retrospective estimation of functional status 2 months before hospitalization, and 3 months after. RESULTS: A total of 120 patients were included (mean age 83.1 ± 5.0 (75-101) years). IE was associated with a dramatic impairment of functional status between 2 months prior hospitalization and the first geriatric evaluation (90.8% able to walk vs. 35.5% (p < 0.0001), ADL (Activities in Daily Living) 5.0 ± 1.7 vs. 3.1 ± 2.1 (p < 0.0001)). The 19 operated patients (15.8%) had less comorbidities (cumulative illness rating scale geriatric 10.8 ± 8.2 vs. 15.3 ± 7.1 (p 0.0176)), better functional (ADL 5.9 ± 0.4 vs. 4.9 ± 1.8 (p 0.0171) and nutritional (mini nutritional assessment 20.4 ± 5.0 vs. 17.3 ± 6.2 (p 0.0501)) statuses than non-operated patients. Among all infectious, cardiac and geriatric parameters, body mass index (HR 0.9, range 0.8-1, p 0.05) and ADL at the time of the first evaluation (HR 0.7, range 0.6-0.9, p 0.002) were the sole independent predictors of the 3-month (32.5%) and 1-year mortality (42.5%). Three months later, the 57 assessed patients only partially recovered their ADL (3.7 ± 1.9 vs. 5.3 ± 1.4 2 months prior hospitalization and 4.6 ± 1.9 at the first CGA; p < 0.0001). CONCLUSION: Functional and nutritional abilities are crucial components that can be accurately explored through a CGA when managing IE in oldest patients.

Diagnostic criteria for urinary tract infection in hospitalized elderly patients over 75 years of age: a multicenter cross-sectional study.

INTRODUCTION: Urinary tract infection (UTI) is one of the most frequent infections in geriatric patients. Nevertheless, the diagnosis remains difficult because of the high prevalence of asymptomatic bacteriuria (AB). We studied the diagnosis criteria used by physicians in geriatric patients 75 years of age or more. METHOD: A multicenter study was carried out in October 2009 in acute care wards (geriatrics, infectious diseases, internal medicine). During 1 week, the local investigator collected all positive urine microscopy and culture in geriatric patients 75 years of age or more and filled out a questionnaire on the final diagnosis (AB, cystitis, pyelonephritis, prostatitis), symptoms, clinical signs, and other infectious diagnosis. RESULTS: Two hundred and forty-one questionnaires were filled out in 48 wards. Physicians diagnosed AB in 91 patients (37.8%), cystitis in 72 (29.9%), pyelonephritis in 48 (19.9%), prostatitis in 20 (8.3%). 28.2% of patients were asymptomatic; 35% presented with clinical signs. General signs were significantly associated with invasive infection and the absence of functional signs with AB. Among the patients presenting with an invasive UTI, 27.9% also presented with another infection. This other infection was not statistically associated with AB, cystitis, or invasive UTI. CONCLUSION: Too many urine microscopy and culture procedures are not justified, and too many patients are diagnosed with several infections. Usual functional and clinical signs are important for the diagnosis but are infrequent. It seems necessary to review the range of clinical presentations and diagnostic criteria for UTI in geriatric patients.

Prevention of the ß-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures.

BACKGROUND: Inflammation may be involved in the pathogenesis of Alzheimer's disease (AD). There has been little success with anti-inflammatory drugs in AD, while the promise of anti-inflammatory treatment is more evident in experimental models. A new anti-inflammatory strategy requires a better understanding of molecular mechanisms. Among the plethora of signaling pathways activated by ß-amyloid (Aß) peptides, the nuclear factor-kappa B (NF-κB) pathway could be an interesting target. In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR) controls the NF-κB signaling pathway. It is well-known that PKR is activated in AD. This led us to study the effect of a specific inhibitor of PKR on the Aß42-induced inflammatory response in primary mixed murine co-cultures, allowing interactions between neurons, astrocytes and microglia. METHODS: Primary mixed murine co-cultures were prepared in three steps: a primary culture of astrocytes and microglia for 14 days, then a primary culture of neurons and astrocytes which were cultured with microglia purified from the first culture. Before exposure to Aß neurotoxicity (72 h), co-cultures were treated with compound C16, a specific inhibitor of PKR. Levels of tumor necrosis factor-α (TNFα), interleukin (IL)-1ß, and IL-6 were assessed by ELISA. Levels of PT451-PKR and activation of IκB, NF-κB and caspase-3 were assessed by western blotting. Apoptosis was also followed using annexin V-FITC immunostaining kit. Subcellular distribution of PT451-PKR was assessed by confocal immunofluorescence and morphological structure of cells by scanning electron microscopy. Data were analysed using one-way ANOVA followed by a Newman-Keuls' post hoc test RESULTS: In these co-cultures, PKR inhibition prevented Aß42-induced activation of IκB and NF-κB, strongly decreased production and release of tumor necrosis factor (TNFα) and interleukin (IL)-1ß, and limited apoptosis. CONCLUSION: In spite of the complexity of the innate immune response, PKR inhibition could be an interesting anti-inflammatory strategy in AD.

[Late diagnosis of Dandy-Walker syndrome revealed by gait disorders in an elderly]. / Diagnostic tardif d'un syndrome de Dandy-Walker révélé par des troubles de la marche chez le sujet âgé.

The Dandy-Walker syndrome is a rare malformation usually diagnosed during pregnancy or early in the course of life. We report a case in an elderly hospitalised for gait disorders and recurrent falls. Cerebral MRI revealed hydrocephalus and posterior fossa cyst. The patient improved after ventriculocisternostomia.

[Primary localized amyloidosis of the urinary tract. A case series of five patients]. / Amylose primitive localisée à l'appareil urinaire. A propos de cinq cas.

PURPOSE: To describe the clinical and radiographic features of patients with primary localized amyloidosis of the urinary tract. METHODS: We report a case of localized amyloidosis of the ureters and bladder. The medical records of four other cases from the French Register of localized amyloidosis were reviewed. RESULTS: The mean age of three men and two women was 53 years. All patients presented with gross hematuria, four patients presented with renal colic, only one patient had irritative lower urinary tract symptoms. Ureter and bladder were involved in three patients, both ureters in two patients and the bladder only, in one patient. Clinical and radiographic presentations mimicked a neoplasia excluded by histologic analysis. Immunohistochemical study was performed in only two cases and revealed lambda light chain amyloidosis. The median follow-up was eight years. Various treatments were performed, and recurrences occurred in two cases. None of the five patients developed monoclonal gammapathy or systemic amyloidosis. CONCLUSION: Primary localized amyloidosis of the urinary tract is a rare disorder and can easily be confused with a neoplasm. The physiopathology is unknown, the prognosis is usually good. There is no specific treatment, and repeated work-up for systemic amyloidosis is unnecessary as local recurrences appear to be the main complication.

[Association of systemic diseases and myelodysplastic syndromes. A retrospective study of 14 cases]. / Association maladies systémiques et syndromes myélodysplasiques. Etude rétrospective portant sur 14 observations.

CONTEXT: The association of a systemic disease (SD) and a myelodysplastic syndrome (MDS) may not be a coincidence. We report 14 cases. METHODS: A retrospective study was conducted in patients presenting with an MDS, hospitalised between 1989 and 1999, in the search for a concomitant systemic disease. RESULTS: Ninety-seven patients, 61 men and 36 women, with a mean age of 74 +/- 11 years suffered from an MDS and 14 of them a concomitant SD: one nodular periateritis, 2 systemic vascularitis, 2 cutaneous vascularitis, 2 atrophic polychondritis, 4 Gougerot-Sjogrën syndrome, 2 systemic lupus and one cutaneous lupus. The systemic disease did not appear to influence survival. CONCLUSION: It is possible that the association is not a coincidence and therefore an MDS should be searched for when confronted with an SD, so that treatment may be adapted appropriately.

[Treatment of high-grade, disseminated non-Hodgkin's lymphoma in elderly patients]. / Traitement du lymphome malin non hodgkinien de haut grade et de stade disséminé du sujet âgé.

PURPOSE: Treatment of non-Hodgkin's lymphoma (NHL) in the elderly is difficult because of an increased risk of toxicity and frequent chronic or debilitating diseases. The aim of this paper is to describe the main studies in this field. CURRENT KNOWLEDGE AND KEY POINTS: Most recent clinical trials deal with anthracyclin or assimilated drugs regimens. Potential interest of chemotherapy and associated immunotherapy is on study. Without any influence on survival duration, haematopoietic growth factors seem to improve the tolerance of the treatment. FUTURE PROSPECTS AND PROJECTS: For elderly patients with good performance status and without severe co morbidity, curative strategy with anthracyclin-containing regimen like CHOP is still the standard chemotherapy. Association with rituximab improves the prognosis. For patients with poor performance status and/or associated disease, optimal strategy remains to be defined with quality of life evaluation.

[Primary thyroid lymphoma: report of 8 cases]. / Lymphome malin primitif de la thyroïde: à propos de huit cas.

PURPOSE: Primary thyroid lymphoma (PTL) is a rare disease. Few patients are reported in the literature. We report eight new cases of PTL with long-term follow-up. RESULTS: The clinical presentation was usually an enlarging neck mass squeezing surrounding structures. The diagnosis was established after thyroidectomy with histopathologic and immunohistochemical studies. Histology showed infiltrates of chronic lymphocytic thyroiditis in all cases. Three patients had thyroid lymphoma arising from mucosa-associated lymphoid tissue. One patient died postoperatively. The other seven were treated with combined chemotherapy and radiotherapy. They were still in remission after a 6-year follow-up. CONCLUSION: Diagnosis of PTL should be suspected when there is a recent thyroid enlargement. Surgery associated with chemotherapy and radiation gave good results in our study with long-term follow-up, though surgery was not always recommended in previous reports.

Central venous catheter-related infection due to Comamonas testosteroni in a woman with breast cancer.

A 75-y-old woman with breast cancer presented with bacteremia due to Comamonas testosteroni. Evolution was favorable following adapted antimicrobial therapy and removal of a central venous catheter. This germ seems to be a rare pathogen; as reported in the literature, it is mostly encountered in patients with predisposing factors.

[Effect of age on the prognosis of infectious endocarditis]. / Influence de l'âge sur le pronostic de l'endocardite infectieuse.

The aim of this study was to evaluate the influence of age on the prognosis of infectious endocarditis. A retrospective study from 1987 to 1997 of 136 patients with infectious endocarditis on native, prosthetic valves or cardiac pacing catheter was performed. The outcome was analysed with the help of general practitioners. Two groups of patients were compared: 87 patients of 65 years of age or more (Group 1) and 49 patients under 65 years of age (Group 2). With a follow-up period of 5 years, the global mortality was 35%, but greater in Group 1 (p = 0.06). Cardiac failure was the main cause of death. The mortality was significantly higher in patients who were not operated (p < 0.002). The authors conclude that age of over 65 does not significantly worsen the prognosis of infectious endocarditis. The absence of surgery seems to be an indirect factor of a poor prognosis. Long-term follow-up of patients is necessary to diagnose and treat cardiac failure at an early stage and to consider referral for surgery.

Cat-scratch disease simulating a malignant process of the chest wall.

UNLABELLED: Cat-scratch disease is a well-known cause of regional adenopathy in immunocompetent children. Rarely, patients may present with symptoms simulating a neoplastic disease. The case of a 12-year-old boy with fever, swelling of the chest wall and hepatosplenic nodules is reported. Histological analysis of biopsy specimen obtained from the chest wall lesion and the liver revealed granulomatous reaction without malignant cells. Serological investigations were positive for Bartonella species. The symptoms and the lesions disappeared after oral antibiotic therapy (ciprofloxacin) was started. The patient remained symptom-free 12 months later. CONCLUSION: The present case emphasizes the wide spectrum of clinical manifestations associated with cat-scratch disease which should be investigated as differential diagnosis of manifestations suggesting a neoplastic disease in children.