The spectrum of bacterial infections in febrile neutropenic patients: effect on empiric antibiotic therapy

The aim of this retrospective analysis was to look at the spectrum of bacterial isolates and their resistance patterns to the commonly used antIbiotics in the settmg of febrile neutropenia. A total of 127 bacteria were isolated from patients with acute leukemias, lymphoproliferative disorders, aplastic anaemia and various solid tumours. Fifty-four percent organisms were gram negative; while the rest were gram positive. E. coli, pseudomónas aeruginosa, staphylococcus aureus, enterococcus and streptococci were the commonly isolated organisms. Forty-eight percent organisms were isolated from blood, 16% from urine, 13% from wounds and superficial abscesses and 11% from respiratory tract. E. coli exhibited a great degree of resistance to the commonly used antibiotics, such as pipericillin (70%), ofloxacin (50%) and aztreonam (50%). Pseudomonas and kiebsiella also showed varying degree of resistance against the antibiotics. Staphylococcus aureus and staphylococcus epidennidis were almost universally resistant to penicillin and showed a variable degree of resistance to other antibiotices too. Compared to the previous reports, the pattern of bacterial isolates and their resistance to antibiotics has changed over the past years. Aminolgy­cosides and third generation cephalosporins seem to be the choice of antibiotics for the upfront manage­ment of febrile neutropenic patients (JPMA 48:364,1998)

Severe thrombocytopenia in a man with prostatic cancer

A 66 year old gentleman was diagnosed to have metastatic adenocarcinoma of the prostate in 1990, following a CT scan of the abdomen and trans-uretheral resection of prostate (TLJRP). He was started on estrogen therapy (Fos­festerol sodium). Two years later he presented to the emer­gency room with breathlessness and edema of the left ann of a week’s duration. He admitted to persistence of symptoms of pmstatism and was found to have bilateral axillary lymphade­nopathy and pitting edema of the left arm. A doppler scan revealed left subclavian vein thrombosis. The patient was started on i.v. heparin and was maintained on it until the resolution of arm edema and was subsequently switched to oral anticoagulation. The serum Prostate Specific Antigen (PSA) level was found to be 1460 ng/ml. Fosfesterol was discontinued and the patient was started on antiandrogen therapy (Cyproterone acetate). The patient was sent home on anticoagulation, but had to be readmitted shortly thereafter because of the sudden onset of shortness of breath. This time he was found to have bilateral pitting pedal edema and :tenderness in the right calf. Intravenous heparin was reinsti­tuted. An infçrior venacavagram revealed extensive thrombo­sis of the right popliteal vein and the left common iliac vein. A clinical diagnosis of pulmonary embolism was made. Despite continuous i.v. heparin in adequate doses, the patient experi­enced recurrent episodes of shortness of breath. A greenfield filter was placed in the inferior vena cava to prevent further episodes of pulmonary embolism. The patient remained heparinized for more than two weeks, until complete resolu­tionofsyniptoms had occured. Subsequently oral anticoagula­tion was started and the dose of coumarin was adjusted to maintain an international normalized ratio (INR) between 1.8 and2.0

Genetic evidence for the most common risk factors for chronic axonal polyneuropathy in the general population

BACKGROUND AND PURPOSE: Chronic axonal polyneuropathy is a common disease, but the etiology remains only partially understood. Previous etiologic studies have identified clinical risk factors, but genetic evidence supporting causality between these factors and polyneuropathy are largely lacking. In this study, we investigate whether there is a genetic association of clinically established important risk factors (diabetes, body mass index [BMI], vitamin B12 levels, and alcohol intake) with chronic axonal polyneuropathy. METHODS: This study was performed within the population‐based Rotterdam Study and included 1565 participants (median age = 73.6 years, interquartile range = 64.6–78.8, 53.5% female), of whom 215 participants (13.7%) had polyneuropathy. Polygenic scores (PGSs) for diabetes, BMI, vitamin B12 levels, and alcohol intake were calculated at multiple significance thresholds based on published genome‐wide association studies. RESULTS: Higher PGSs of diabetes, BMI, and alcohol intake were associated with higher prevalence of chronic axonal polyneuropathy, whereas higher PGS of vitamin B12 levels was associated with lower prevalence of polyneuropathy. These effects were most pronounced for PGSs with lenient significance thresholds for diabetes and BMI (odds ratio [OR](diabetes, p < 1.0) = 1.21, 95% confidence interval [CI] = 1.05–1.39 and OR(BMI, p < 1.0) = 1.21, 95% CI = 1.04–1.41) and for the strictest significance thresholds for vitamin B12 level and alcohol intake (OR (vitamin B12, p < 5e‐6) = 0.79, 95% CI = 0.68–0.92 and OR(alcohol, p < 5e‐8) = 1.17, 95% CI = 1.02–1.35). We did not find an association between different PGSs and sural sensory nerve action potential amplitude, nor between individual lead variants of PGS (p ) (< 5e‐8) and polyneuropathy. CONCLUSIONS: This study provides evidence for polygenic associations of diabetes, BMI, vitamin B12 level, and alcohol intake with chronic axonal polyneuropathy. This supports the hypothesis of causal associations between well‐known clinical risk factors and polyneuropathy

Long-term association of pregnancy and maternal brain structure:the Rotterdam Study

The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women’s lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β = 0.14, 95% CI = 0.09–0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-021-00818-5

Bone mineral density and the risk of incident dementia:A meta-analysis

Background: It is not known whether bone mineral density (BMD) measured at baseline or as the rate of decline prior to baseline (prior bone loss) is a stronger predictor of incident dementia or Alzheimer's disease (AD). Methods:We performed a meta-analysis of three longitudinal studies, the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Rush Memory and Aging Project (MAP), modeling the time to diagnosis of dementia as a function of BMD measures accounting for covariates. We included individuals with one or two BMD assessments, aged ≥60 years, and free of dementia at baseline with follow-up available. BMD was measured at the hip femoral neck using dual-energy X-ray absorptiometry (DXA), or at the heel calcaneus using quantitative ultrasound to calculate estimated BMD (eBMD). BMD at study baseline (“baseline BMD”) and annualized percentage change in BMD prior to baseline (“prior bone loss”) were included as continuous measures. The primary outcome was incident dementia diagnosis within 10 years of baseline, and incident AD was a secondary outcome. Baseline covariates included age, sex, body mass index, ApoE4 genotype, and education. Results: The combined sample size across all three studies was 4431 with 606 incident dementia diagnoses, 498 of which were AD. A meta-analysis of baseline BMD across three studies showed higher BMD to have a significant protective association with incident dementia with a hazard ratio of 0.47 (95% CI: 0.23–0.96; p = 0.038) per increase in g/cm2, or 0.91 (95% CI: 0.84–0.995) per standard deviation increase. We observed a significant association between prior bone loss and incident dementia with a hazard ratio of 1.30 (95% CI: 1.12–1.51; p &lt; 0.001) per percent increase in prior bone loss only in the FHS cohort. Conclusions: Baseline BMD but not prior bone loss was associated with incident dementia in a meta-analysis across three studies.</p

Maximising the Potential of Longitudinal Cohorts for Research in Neurodegenerative Diseases: A Community Perspective

Despite a wealth of activity across the globe in the area of longitudinal population cohorts, surprisingly little information is available on the natural biomedical history of a number of age-related neurodegenerative diseases (ND), and the scope for intervention studies based on these cohorts is only just beginning to be explored. The Joint Programming Initiative on Neurodegenerative Disease Research (JPND) recently developed a novel funding mechanism to rapidly mobilise scientists to address these issues from a broad, international community perspective. Ten expert Working Groups, bringing together a diverse range of community members and covering a wide ND landscape (Alzheimer’s, Parkinson’s, frontotemporal degeneration, amyotrophic lateral sclerosis, Lewy-body and vascular dementia) were formed to discuss and propose potential approaches to better exploiting and coordinating cohort studies. The purpose of this work is to highlight the novel funding process along with a broad overview of the guidelines and recommendations generated by the ten groups, which include investigations into multiple methodologies such as cognition/functional assessment, biomarkers and biobanking, imaging, health and social outcomes, and pre-symptomatic ND. All of these were published in reports that are now publicly available online.The EU Joint Programming Initiative on Neurodegenerative Disease Research (JPND) supported the ten Working Groups described in this manuscript with funding from the following: The Canadian Institutes of Health Research (CIHR), French National Research Agency (ANR), German Federal Ministry of Education and Research (BMBF), Innovation Fund Denmark, Italian Ministry of Health (IT-MOH), Luxembourg National Research Fund (FNR), Netherlands Organisation for Health Research and Development (ZonMw), Research Council of Norway, Swedish Research Council for Health, Working Life and Welfare, and UK Medical Research Council (MRC)

Modeling the brain morphology distribution in the general aging population

<p>Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.</p