Prognostic value of geriatric and cardiac parameters for one-year mortality in older heart failure patients. A multicentre, observational, prospective study.

PURPOSE: Heart failure is prevalent among older people and has a poor prognosis. The aim of this study is to identify potential prognostic, geriatric, and cardiac parameters which could help clinicians identify older heart failure patients at high risk for one-year mortality. METHODS: The multicentre, observational cohort study which included 147 heart failure patients aged ≥75 years, hospitalized in the cardiac or geriatric department in two hospitals. One-year survival was the outcome measure. For univariate analysis Chi-square test and independent sample T-test were used; for multivariate analysis Logistic regression and Cox regression for time-dependent analysis. RESULTS: One-year mortality was 28% (41/147). One-year survivors and non-survivors did not differ in the following characteristics: age, gender, sodium level at hospital discharge, ejection fraction, NYHA Class, basic and instrumental activities of daily living, and the presence of a geriatric risk profile. There was a significant lower systolic blood pressure at discharge in non-survivors compared to one-year-survivors (mean 125.26 mmHg vs. 137.59 mmHg). Non-survivors had more severe underlying comorbidities according to the age adjusted Charlson Comorbidity index (CCI) (mean 8.80 vs. 7.40).Both logistic and Cox regression showed a higher risk and rate of mortality with decreasing systolic blood pressure at discharge (OR 0.963, p=0.001 and HR 0.970, p<0.001) and with increasing CCI (OR 1.344, p=0.002 and HR 1.269, p=0.001); the other variables were not significantly related. CONCLUSION: Lower blood pressure and more severe comorbidities, but not functionality nor the presence of a geriatric risk profile, are related to one-year mortality in older, in-hospital heart failure patients.

Methicillin-resistant staphylococcus aureus pneumonia in older people: a diagnostic and therapeutic challenge.

Pneumonia is one of the leading causes of death in older people, with high mortality rates (> 80%). One of the bacterial pathogens causing pneumonia is Staphylococcus aureus. The unique adaptive ability of S. aureus to a broad range of antibiotics has led to the emergence of methicillin-resistant S. aureus (MRSA) strain. MRSA pneumonia remains a relatively uncommon infection in older people, but it is associated with a very high mortality rate. We report two cases of MRSA pneumonia that highlight the severe clinical presentation and virulence of MRSA infections in geriatric population. MRSA pneumonia can present with mostly an uncontrollable clinical evolution and an infaust prognosis. Therefore, clinicians should be aware of MRSA pneumonia in patients with comorbidities, recent hospitalization with antibiotic treatment, previous MRSA infections and also in patients residing in nursing homes/revalidation centers. Low prevalence of MRSA combined with a lack of highly distinctive clinical features makes accurate targeting of empirical treatment with antibiotics very difficult. Currently, monotherapy with linezolid or vancomycin remain the first choice, in adult patients with proven MRSA infection. Despite the higher age related mortality rates, there are no specific treatment guidelines for older patients.

Hand grip strength as a screening tool for frailty in older patients with haematological malignancies.

OBJECTIVES: Frailty is a geriatric syndrome characterized by decreased physiological reserves and an age-related vulnerability to stressors with higher risk of adverse health outcomes. Comprehensive geriatric assessment (CGA) might detect frailty but is time-consuming, implying the need for initial frailty screening. Most frailty screening tools do not include functional measures. Hand grip strength (HGS) is a reliable surrogate for overall muscle strength and predicts functional decline, morbidity and mortality. No studies are available in cancer patients on HGS as screening tool for frailty. We aimed to assess whether HGS can be used as a screening tool to predict an abnormal CGA and therefore frailty. METHODS: Single centre cohort study in 59 patients aged 70 years or more with a haematological malignancy. HGS was measured using a vigorimeter. A patient was considered frail if any of the CGA elements were impaired. RESULTS: Mean HGS before start of therapy in women was 37.0 ± 14.3 kPa and in men 66.1 ± 13.1 kPa. An abnormal CGA was present in 52 subjects (88%). HGS was associated with concurrent abnormal CGA (p = 0.058 in women, p = 0.009 in men). AUC was 0.800 (SE = 0.130) in women and 0.847 (SE = 0.118) in men. Optimal HGS cut-off points for likelihood of abnormal CGA were ≤52 kPa in women and ≤80 kPa in men. DISCUSSION: In older patients with haematological malignancies, impairment in muscle function is present at diagnosis. HGS seems a promising screening tool to identify patients with abnormal CGA.

PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib.

Recently, germline and somatic heterozygous mutations in the platelet-derived growth factor receptor ß (PDGFRB) have been associated with familial infantile myofibromatosis (IM), which is characterized by soft tissue tumors, and overgrowth syndrome, a disease that predisposes to cancer. These mutations have not been functionally characterized. In the present study, the activity of three PDGFRB mutants associated with familial IM (R561C, P660T and N666K) and one PDGFRB mutant found in patients with overgrowth syndrome (P584R) was tested in various models. The P660T mutant showed no difference with the wild-type receptor, suggesting that it might represent a polymorphic variant unrelated to the disease. By contrast, the three other mutants were constitutively active and able to transform NIH3T3 and Ba/F3 cells to different extents. In particular, the germline mutant identified in overgrowth syndrome, P584R, was a stronger oncogene than the germline R561C mutant associated with myofibromatosis. The distinct phenotypes associated with these two mutations could be related to this difference of potency. Importantly, all activated mutants were sensitive to tyrosine kinase inhibitors such as imatinib, nilotinib and ponatinib. In conclusion, the PDGFRB mutations previously identified in familial IM and overgrowth syndrome activate the receptor in the absence of ligand, supporting the hypothesis that these mutations cause the diseases. Moreover, imatinib seems to be a promising treatment for patients carrying these mutations. To our knowledge, these are the first confirmed gain-of-function point mutations of PDGFRB in human cancer.

PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations.

Activating mutations in the platelet-derived growth factor (PDGF) receptor alpha (PDGFRA) have been described in patients with gastrointestinal stromal tumors or myeloid malignancies associated with hypereosinophilia. These patients respond well to imatinib mesylate, raising the question as to whether patients with a PDGF receptor mutation in other tumor types should receive a tyrosine kinase inhibitor treatment. We characterized 10 novel somatic point mutations in PDGFRA that have been reported in isolated cases of glioblastoma, melanoma, acute myeloid leukemia, peripheral nerve sheath tumors and neuroendocrine carcinoma. The PDGFRA transmembrane domain mutation V536E stimulated Ba/F3 cell growth and signaling via ERK and STAT5 in the absence of ligand. This mutant, identified in glioblastoma, was strongly inhibited by imatinib. Modeling suggested that the mutation modulates the packing of the transmembrane domain helices in the receptor dimer. By contrast, two mutations in highly conserved residues affected the receptor traffic to the cell surface or kinase activity, thereby preventing the response to PDGF. The other mutations had no significant impact on the receptor activity. This functional analysis matched the predictions of SIFT and PolyPhen for only five mutations and these algorithms do not discriminate gain from loss of function. Finally, an E996K variant that had been identified in a melanoma cell line was not expressed in these cells. Altogether, several newly identified PDGFRA mutations do not activate the receptor and may therefore represent passenger mutations. Our results also underline the importance of characterizing novel kinase alterations in cancer patients.

The Belgian geriatric day hospitals as part of a care program for the geriatric patient: first results of the implementation at the national level.

PURPOSE: In order to deliver individual, specialized and multidisciplinary care for older people, the Belgian national health authorities developed the care program for the geriatric patient. In that context, 48 geriatric day hospitals (GDHs) have been financed by the government since January 1st 2006. The main objective of this study is to describe the patient characteristics, facility features and activities related to the Belgian GDHs. METHODS: A prospective, multicenter study was performed from October 1st till December 31st 2006 in all 48 GDHs. For each GDH a transversal data collection was carried out. In the same period all patients scheduled for the GDHs were registered and followed for 3 months. Therefore two questionnaires were developed using Filemaker software: one for each GDH and one for each patient. There were no exclusion criteria. RESULTS: Six GDHs did not complete one or both questionnaires. Consequently, the results of 42 GDHs were included. GDHs with more years of activity had significantly more new patient contacts per day. Activities in the Belgian GDHs were mainly diagnostic with emphasis on geriatric syndromes and specific medical problems. The reason for admission to the GDH was often multifactorial. The syndromes that motivated patients 75 or older to visit the GDH were clearly geriatric (mainly cognitive disorders) and represent the principle public health problems in this age category. Despite the legal provision preserving GDHs for patients 75 years or older a quarter of all patients was younger than 75, presenting with a geriatric syndrome. The contribution of the general practitioners was limited. CONCLUSIONS: Activities in the Belgian GDHs are mainly diagnostic with emphasis on geriatric syndromes (particularly cognitive disorders) and specific medical problems. More information is needed on the knowledge and expectations of general practitioners in order to establish a closer collaboration.

[Fresh posterior luxation of the shoulder: irreducibility due to interposition of the long biceps. Apropos of 2 cases]. / Luxation postérieure récente de l'épaule: irréductibilité par interposition du long biceps. A propos de deux cas.

Two cases of irreducibility of recent posterior dislocation of the shoulder due to interposition of the long biceps are reported. The diagnostic procedures, the lesions noted during surgery and the therapeutic approach are described in the light of data found in the relevant literature.