Automated analysis of FDG PET as a tool for single-subject probabilistic prediction and detection of Alzheimer’s disease dementia

Purpose

To introduce, evaluate and validate a voxel-based analysis method of ¹⁸F-FDG PET imaging for determining the probability of Alzheimer’s disease (AD) in a particular individual.

Methods

The subject groups for model derivation comprised 80 healthy subjects (HS), 36 patients with mild cognitive impairment (MCI) who converted to AD dementia within 18 months, 85 non-converter MCI patients who did not convert within 24 months, and 67 AD dementia patients with baseline FDG PET scan were recruited from the AD Neuroimaging Initiative (ADNI) database. Additionally, baseline FDG PET scans from 20 HS, 27 MCI and 21 AD dementia patients from our institutional cohort were included for model validation. The analysis technique was designed on the basis of the AD-related hypometabolic convergence index adapted for our laboratory-specific context (AD-PET index), and combined in a multivariable model with age and gender for AD dementia detection (AD score). A logistic regression analysis of different cortical PET indexes and clinical variables was applied to search for relevant predictive factors to include in the multivariable model for the prediction of MCI conversion to AD dementia (AD-Conv score). The resultant scores were stratified into sixtiles for probabilistic diagnosis.

Results

The area under the receiver operating characteristic curve (AUC) for the AD score detecting AD dementia in the ADNI database was 0.879, and the observed probability of AD dementia in the six defined groups ranged from 8 % to 100 % in a monotonic trend. For predicting MCI conversion to AD dementia, only the posterior cingulate index, Mini-Mental State Examination (MMSE) score and apolipoprotein E4 genotype (ApoE4) exhibited significant independent effects in the univariable and multivariable models. When only the latter two clinical variables were included in the model, the AUC was 0.742 (95 % CI 0.646 – 0.838), but this increased to 0.804 (95 % CI 0.714 – 0.894, bootstrap p?=?0.027) with the addition of the posterior cingulate index (AD-Conv score). Baseline clinical diagnosis of MCI showed 29.7 % of converters after 18 months. The observed probability of conversion in relation to baseline AD-Conv score was 75 % in the high probability group (sixtile 6), 34 % in the medium probability group (merged sixtiles 4 and 5), 20 % in the low probability group (sixtile 3) and 7.5 % in the very low probability group (merged sixtiles 1 and 2). In the validation population, the AD score reached an AUC of 0.948 (95 % CI 0.625 – 0.969) and the AD-Conv score reached 0.968 (95 % CI 0.908 – 1.000), with AD patients and MCI converters included in the highest probability categories.

Conclusion

Posterior cingulate hypometabolism, when combined in a multivariable model with age and gender as well as MMSE score and ApoE4 data, improved the determination of the likelihood of patients with MCI converting to AD dementia compared with clinical variables alone. The probabilistic model described here provides a new tool that may aid in the clinical diagnosis of AD and MCI conversion.     

Biomechanical evaluation of fixation of clavicular fractures

Reproducible fractures of the midshaft of the clavicle were created in 14 fresh frozen human cadaveric clavicles. Under the three-point bending loading by a materials testing machine, the load to failure of fixation of the clavicular fractures treated with steel reconstruction plates (five specimens) and Herbert cannulated bone screw (nine specimens), was compared with a group control formed by five specimens of clavicles without osteosynthesis material. No statistically significant differences were observed between the three groups. In consequence and in terms of biomechanics, in clavicular acute fractures, both plating and intramedullary Herbert cannulated bone screw may be utilized in the treatment of these lesions.     

Scrotal ultrasound: pearls, patterns and pitfalls

We present a review of the scrotal ultrasound findings showing normal anatomic variants that may simulate scrotal pathology (rete testis dilatation, normal testicle and epididymis appendages). US patterns of the scrotal pathology may be classified as: calcified (scrotal and albuginea calcifications, microcalcifications, epididymis calcifications, testicular tumors with calcium), cystic appereance (intratesticular and echogenic varicocele, epididymis cysts, albuginea cysts, haematoma, abscess), solid nodular testicular lesions (infarct, neoplasm) and diffuse lesions (orchitis, lymphoid hyperplasia lymphoma, leukemia). Testicular ultrasound may be helpful in detecting extraescrotal pathologies. There is a known relationship between right varicocele and extratesticular neoplasms. We also show some cases of Burn-out testicular tumor and their MR, CT and PET findings. The knowledge of normal US scrotal anatomy, US patterns of the scrotal lesions and scrotal findings that suggest extratesticular pathologies are crucial in the management of testicular pathology and if unnecessary orchiectomies want to be avoided.     

Ultrastrukturelle Veränderungen am Nierenparenchym durch ESWL unter Acetylsalicylsäure (ASS)

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.     

Is congenital cystic adenomatoid malformation a premalignant lesion for pleuropulmonary blastoma?

Background

The relationship between congenital cystic adenomatoid malformation (CCAM) and pleuropulmonary blastoma (PPB), whether causal, correlational, or coincidental, remains controversial. There is a lack of consensus as to the optimal treatment of patients with asymptomatic CCAM.

Method

We reviewed all cases of CCAM and PPB seen at our institution from 1999 to 2008. Institutional Research Ethics Board approval was obtained. The incidence of CCAM and PPB, respectively, was calculated based on birth numbers during the study period.

Results

Seventy-four CCAMs were resected over the study period in 129 children diagnosed with CCAM. Five PPBs were diagnosed during the study period. Three of the 5 PPB cases were initially diagnosed as CCAMs. These PPBs were not clinically or radiologically distinguishable from CCAMs. In our referral area, the incidence of CCAM was 1 in 12,000; and the incidence of PPB was 1 in 250,000 live births. The mortality rate for PPB in this cohort was 20%.

Conclusion

Asymptomatic cystic lung malformations represent a therapeutic dilemma. In this cohort, the incidence of PPB among apparently benign lung lesions was 4%. No clinical or radiological markers differentiated benign CCAMs from PPBs. Our experience provides further justification for resection of all CCAMs. This should be discussed with parents until CCAMs and PPBs can be clearly distinguished preoperatively.     

Posttransplant inflammation associated with onset of chronic kidney disease

Background

Chronic allograft nephropathy (CAN), a major complication in renal transplant patients, is an important cause of graft loss. Inflammation as measured in the pretransplant and posttransplant phases, using various markers, has been associated with worse renal function and a greater risk of cardiovascular disease and of long-term graft loss.

Objective

The objective of our study was to evaluate whether worsening inflammation in the first 3 months postoperatively was a risk factor for developing CAN.

Patients and methods

We performed a cross-sectional study in 207 patients. The following markers of inflammation (MIF) were determined pretransplant and at 3 months after grafting: C-reactive protein (CRP) (mg/L), interleukin (IL)-6 (pg/mL), IL-10 (pg/mL), tumor necrosis factor (TNF)-α (pg/mL), and its soluble receptor (ng/mL), soluble-IL2R (UI/mL), pregnancy-associated plasma protein A (PAPP-A; mUI/L), and IL-4 (pg/mL). We also calculated the ratio at 3 months versus the pre value of MIF.

Results

CAN was diagnosed after the first year in 23 patients (11.3%) always by renal biopsy performed for clinical indications. Patients with CAN showed worse inflammation, eg, MIF ratios over one, with statistically significant differences for the ratios of TNF-α and PAPP-A (P = .032 and P = .051 respectively). Upon multivariate logistic regression analysis, using CAN as the dependent variable and age, sex, donor age, months on dialysis, acute tubular necrosis, acute rejection, and MIF ratios as covariates, we observed that an acute rejection episode (OR = 13.03; CI = 2.8-60.9; P = .001), CRP ratio (OR = 1.36; CI = 1.07-1.73; P = .013), and PAPP-A ratio (OR = 1.80; CI = 0.92-3.53; P = .005) were independent markers of CAN.

Conclusions

Among other factors, inflammation may determine the onset of CAN as diagnosed by renal biopsy.     

POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.