Influenza vaccination and all-cause mortality in community-dwelling elderly in Ontario, Canada, a cohort study

The objective of this study was to evaluate the effectiveness of influenza vaccines in reducing all-cause mortality among community-dwelling elderly. We included 25,922 Ontario residents over age 65 who responded to population health surveys. After full adjustment, influenza vaccination was associated with a statistically significant reduction in all-cause mortality during influenza seasons (hazard ratio (HR) = 0.61; 95% CI 0.47-0.79). Contrary to expectations, statistically significant associations between influenza vaccination and mortality were also observed during periods preceding (HR = 0.55; 95% CI 0.40-0.75) and following (HR = 0.74; 95% CI 0.59-0.94) influenza seasons, indicating the presence of residual confounding. Adjustment for functional status indicators, excluding individuals with high one-year predicted mortality at baseline, and moving the start date of follow-up failed to eliminate the refractory confounding. Since observational studies are prone to bias, future efforts to estimate vaccine effectiveness in the elderly should strive to minimize bias through improved data quality, novel data sources, and/or new analytical techniques.     

Progressive gray matter damage in patients with relapsing-remitting multiple sclerosis: a longitudinal diffusion tensor magnetic resonance imaging study

BACKGROUND: Diffusion tensor magnetic resonance imaging (DT MRI) has the potential to provide in vivo information about tissue microstructure. In multiple sclerosis (MS), DT MRI has disclosed the presence of occult structural damage in the normal-appearing brain tissues. OBJECTIVE: To investigate whether DT MRI is sensitive to longitudinal changes of brain damage that may occur beyond the resolution of T2-weighted images in patients with relapsing-remitting MS. DESIGN: Twenty-six untreated patients with relapsing-remitting MS were followed up for 18 months. Dual-echo, DT and postcontrast T1-weighted MRIs of the brain were obtained at baseline and then every 3 months. Mean diffusivity (D) histograms of normal-appearing gray (GM) and white matter were produced. Total T2-hyperintense and T1-hypointense lesion volumes; normalized whole brain tissue, GM, and white matter volumes; percentage brain volume change between the study entry and exit images; average lesion D; and fractional anisotropy were also calculated. RESULTS: During the study period, a significant decrease of normalized whole brain tissue, average lesion fractional anisotropy and normal-appearing GM D histogram peak height, and a significant increase of average normal-appearing GM D and T2-hyperintense lesion volumes were observed. Changes of normal-appearing GM diffusivity were independent of the concomitant changes of normalized whole brain tissue and GM volumes. CONCLUSIONS: The DT MRI findings show progressive microstructural changes in the normal-appearing GM of patients with untreated relapsing-remitting MS. Such changes do not reflect a concomitant development of brain atrophy and confirm the importance of GM pathology in MS.     

Successful neridronate therapy in transient osteoporosis of the hip

We report on an uncommon case of bilateral transient osteoporosis of the hip (TOH) occurring in a young woman during pregnancy. The clinical features and the therapeutic action of intramuscular neridronate sodium, a third-generation amino-bisphosphonate, are underlined.     

Ischaemic stroke in young people: a prospective and long-term follow-up study

BACKGROUND: A few studies have comprehensively assessed the epidemiology, aetiology, prognosis, and secondary prevention of ischaemic stroke in young adults. To gain further information on this field, we have prospectively studied a hospital-based series of young adults with a first-ever episode of cerebral ischaemia (CI). METHODS: Sixty consecutive patients aged 17-45 with ischaemic stroke (55 patients) or transient ischaemic attack within 24 h before hospital admission were recruited and investigated by a standardized rigorous protocol. The patients were followed up for >or=1 year after hospital discharge. Arbitrary doses of aspirin 100 mg/d or ticlopidine 250 mg b.i.d. in case of intolerance to aspirin were given for the secondary prevention. Adjusted-dose oral anticoagulation (INR target 2.5) was used in the presence of cardioembolism or hypercoagulable states. Endpoints included the residual disability, rated by modified Rankin Scale (RS) and Barthel Index (BI), and poststroke recurrence. RESULTS: CI was associated with two or more risk factors in 61.6% of patients. Cigarette smoking was more frequently associated with male gender (p < 0.05) and migraine history with female sex (p < 0.05). The atherothrombotic diagnostic subtype and the subtype from 'other cause' predominated significantly among patients >or=35 years old (p < 0.05) and <35 years (p < 0.025), respectively. The 'other cause' subset was more frequent in female gender (p < 0.05). Transoesophageal echocardiography (TEE) detected potential cardiac sources of emboli (PCSE) at an extent 3 times higher (p < 0.0001) than transthoracic echocardiography. Congenital heart defects were nearly threefold more frequent than acquired ones, with a prevalence of patent foramen ovale. At a mean of 6.1 +/- 2.6 years (confidence interval 5.4 to 6.8), follow-up data were available for only 54 patients, since five patients were lost and one died in the acute phase. Poststroke recurrence rate was low (7.4%) and no event was fatal. General handicap was severe to moderately severe (RS>3) in 11% of the patients, slight to moderate (1>or=RSor=95), 38.9% partially dependent (BI 60 to 86), and 11.1% fully dependent (BI <60). Thirty-seven (68.5%) patients returned to work, although adjustments (other job or part-time employment) were necessary for 10 out of them (27%). CONCLUSIONS: The present study, though limited by the relatively small number of subjects, suggests that the overall prognosis of ischaemic stroke in young adults is good. We strongly recommend TEE in all patients with ischaemic stroke as an essential tool to increase the detection of PCSE and make the therapeutic approach more efficient.     

Prognostic value of (99m)Tc-sestamibi washout in predicting response of locally advanced breast cancer to neoadjuvant chemotherapy.

This study evaluated the role of (99m)Tc-sestamibi washout in the prediction of pathologic tumor response to neoadjuvant chemotherapy in 30 patients with locally advanced breast cancer. METHODS: Two (99m)Tc-sestamibi studies were performed before and after chemotherapy for each patient. Early (10 min) and delayed (240 min) planar breast views were acquired after a 740-MBq (99m)Tc-sestamibi intravenous injection, and the washout rate (WOR) was computed. All patients underwent radical mastectomy with pathologic evaluation of the residual tumor size. RESULTS: The pretherapy (99m)Tc-sestamibi WOR ranged from 14% to 92% (mean +/- SD, 50% +/- 18%). At pathologic examination, 15 patients showed no tumor response to chemotherapy and 15 patients showed an objective response to chemotherapy. The pretherapy (99m)Tc-sestamibi study predicted chemoresistance (WOR > 45%) in 18 of 30 patients and no chemoresistance (WOR < or = 45%) in 12 of 30 patients. When the WOR cutoff was set at >45%, the prognostic performance of the test was indicated by a sensitivity of 100%; a specificity of 80%; positive and negative predictive values of 83% and 100%, respectively; and a likelihood ratio of 5. The repeatability of the test was good, with 80%-93% interreader agreement (kappa = 0.57-0.85). Posttherapy (99m)Tc-sestamibi studies confirmed the pretherapy study prediction in 29 of 30 patients. CONCLUSION: (99m)Tc-Sestamibi WOR is a reliable test for predicting tumor response to neoadjuvant chemotherapy. In fact, negative findings (WOR < or = 45%) rule out chemoresistance and positive findings (WOR > 45%) indicate a high risk of chemoresistance.     

Macrophage migration inhibitory factor protein and mRNA expression in cutaneous melanocytic tumours

Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in various biological processes. Although MIF's functions in cancer have not been completely elucidated, its expression has usually been correlated with tumour progression and aggressiveness, and it is currently discussed as a new promising target for novel therapies. Recent studies seem to confirm its active role in melanoma pathobiology; however, its expression has not yet been extensively studied in melanocytic tumours. We evaluated MIF protein expression in 126 skin lesions, including benign and atypical nevi, melanoma and melanoma metastases. In 55 cases, we also assessed MIF mRNA expression by real-time RT-PCR. Benign nevi were subdivided into nevocytic and Spitz/blue types; and melanomas into the radial, and vertical growth phase. A strong cytoplasmic MIF positivity was found in most samples, although it was more heterogeneous in malignant tumours; MIF nuclear expression characterized Spitz/blue nevi, atypical nevi, melanomas and metastases. All samples expressed MIF mRNA but it was significantly lower in benign nevi vs atypical nevi, melanomas and metastases (p=0.001; p<0.0001; p=0.002, respectively). Our study shows a widespread distribution of MIF among melanocytic tumours. Whereas we observed a trend towards higher expression levels of mRNA in atypical and malignant tumours, MIF protein was highly expressed in all lesions, although limited to the cytoplasm in most benign nevi. These observations suggest differences in MIF protein storage, subcellular location and properties in most benign nevi vs atypical and malignant tumours that should be confirmed by further investigation and correlation with clinical outcome.     

Point Mutations and Deletion Responsible for the Bombay H null and the Reunion H weak Blood Groups

Objective: Definition of the molecular basis of the Reunion and the Bombay red cell and salivary H-deficient phenotypes. Methods: Sequence and expression of FUT1 and FUT2 genes from H-deficient individuals. Family segregation analysis of the mutations responsible for the fucosyltransferase defects of H, secretor and Lewis systems. Results: The Indian red cell H null Bombay phenotype depends on a new mutation of the FUT1 gene. T725→G changing Leu242→Arg. Their salivary nonsecretor phenotype is secondary to a complete deletion of the FUT2 gene. The red cell H weak Reunion phenotype depends on another new mutation of FUT1, C349→T which induces a change of His117→Tyr. Their salivary nonsecretor phenotype is due to the known Caucasian inactivating mutation G428→A. Conclusion: Single prevalent FUT1 and FUT2 point mutations and a deletion are responsible for the Indian Bombay H null and the Reunion H weak phenotypes found on Reunion island. This is in contrast with other H-deficient phenotypes where sporadic nonprevalent inactivating mutations are the rule.