Infective anoproctitis in men having sex with men: Don't forget Mycoplasma genitalium.

OBJECTIVES: The aim was to describe the clinical characteristics of symptomatic anoproctitis and the occurrence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG) infections in a prospective cohort of MSM patients. METHODS: From February 2018 to January 2020, all consecutive patients presenting at the Leopold Bellan Proctology Institute of Saint-Joseph Hospital, Paris, France with symptoms of anoproctitis were tested on rectal samples for C. trachomatis (CT), N. gonorrhoeae (NG), M. genitalium (MG). Clinical, microbiological, biological data, STI risk factors, medical history and treatments were collected. RESULTS: Three hundred and sixty-five patients were included for suspected infective anoproctitis. CT was detected in 84/365 (23%) patients, NG in 45/365 (12%) and MG in 46/315 patients (15%), associated with macrolide resistance in 28/46 MG strains (61%). The most frequent symptoms were rectal pains, rectal bleeding, purulent discharge in 253 (79%), 191 (60%), and 164 (51%) of cases respectively. In comparison with MG infections, ulcerations, erythematous proctitis, rectorragia and false needs were more frequently described in CT infections, while purulent proctitis, functional pain and purulent discharge were more often observed in NG and CT anoproctitis. CONCLUSION: We found a high prevalence rate of STIs due to CT, NG, while MG detection was associated with a high rate of macrolide resistance in a cohort of MSM patients. Our results confirm that in cases of symptomatic anoproctitis, MG should be tested in association with other STI pathogens.

Long-term use of pharmacological treatment in Alzheimer's disease: a retrospective cohort study in real-world clinical practice.

PURPOSE: To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression. METHODS: We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10. RESULTS: At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09-0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14-0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70-0.96) were associated with a significantly lower risk of AD progression. CONCLUSION: Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage.

SARS-CoV-2 was already spreading in France in late December 2019.

The COVID-19 epidemic is believed to have started in late January 2020 in France. Here we report a case of a patient hospitalised in December 2019 in an intensive care unit in a hospital in the north of Paris for haemoptysis with no aetiological diagnosis. RT-PCR was performed retrospectively on the stored respiratory sample and confirmed the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Based on this result, it appears that the COVID-19 epidemic started much earlier in France.

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

Nutrient patterns and brain biomarkers of Alzheimer's disease in cognitively normal individuals.

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable lifestyle factors, and risk of Alzheimer's disease (AD) is rapidly increasing. However, there is little or no evidence for a direct association between dietary nutrients and brain biomarkers of AD. This study identifies nutrient patterns associated with major brain AD biomarkers in a cohort of clinically and cognitively normal (NL) individuals at risk for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women, Clinical Dementia Rating=0, MMSE>27, neuropsychological test performance within norms by age and education) with complete dietary information and cross-sectional, 3D T1-weighted Magnetic Resonance Imaging (MRI; gray matter volumes, GMV, a marker of brain atrophy), 11C-Pittsburgh compound-B (PiB; a marker of fibrillar amyloid-ß, Aß) and 18F-fluorodeoxyglucose (FDG; a marker of glucose metabolism, METglc) Positron Emission Tomography (PET) scans were examined. MEASUREMENTS: Dietary intake of 35 nutrients associated with cognitive function and AD was assessed using the Harvard/Willet Food Frequency Questionnaire. Principal component analysis was used to generate nutrient patterns (NP) from the full nutrient panel. Statistical parametric mapping and voxel based morphometry were used to assess the associations of the identified NPs with AD biomarkers. RESULTS: None of the participants were diabetics, smokers, or met criteria for obesity. Five NPs were identified: NP1 was characterized by most B-vitamins and several minerals [VitB and Minerals]; NP2 by monounsaturated and polyunsaturated fats, including ω-3 and ω-6 PUFA, and vitamin E [VitE and PUFA]; NP3 by vitamin A, vitamin C, carotenoids and dietary fibers [Anti-oxidants and Fibers]; NP4 by vitamin B12, vitamin D and zinc [VitB12 and D]; NP5 by saturated, trans-saturated fats, cholesterol and sodium [Fats]. Voxel-based analysis showed that NP4 scores [VitB12 and D] were positively associated with METglc and GMV, and negatively associated with PiB retention in AD-vulnerable regions (p<0.001). In addition, both METglc and GMV were positively associated with NP2 scores [VitE and PUFA], and negatively associated with NP5 scores [Fats] (p<0.001), and METglc was positively associated with higher NP3 scores [Anti-oxidants and Fibers] (p<0.001). Adjusting for age, gender, ethnicity, education, caloric intake, BMI, alcohol consumption, family history and Apolipoprotein E (APOE) status did not attenuate these relationships. The identified 'AD-protective' nutrient combination was associated with higher intake of fresh fruit and vegetables, whole grains, fish and low-fat dairies, and lower intake of sweets, fried potatoes, high-fat dairies, processed meat and butter. CONCLUSION: Specific dietary NPs are associated with brain biomarkers of AD in NL individuals, suggesting that dietary interventions may play a role in the prevention of AD by modulating AD-risk through its effects on Aß and associated neuronal impairment.

Alternative normalization methods demonstrate widespread cortical hypometabolism in untreated de novo Parkinson's disease.

AIM: Previous positron emission tomography (PET) [18F]fluorodeoxyglucose ([18F]FDG) studies in Parkinson's disease (PD) demonstrated that moderate to late stage patients display widespread cortical hypometabolism, whereas early stage PD patients exhibit little or no cortical changes. However, recent studies suggested that conventional data normalization procedures may not always be valid, and demonstrated that alternative normalization strategies better allow detection of low magnitude changes. We hypothesized that these alternative normalization procedures would disclose more widespread metabolic alterations in de novo PD. METHODS: [18F]FDG PET scans of 26 untreated de novo PD patients (Hoehn & Yahr stage I-II) and 21 age-matched controls were compared using voxel-based analysis. Normalization was performed using gray matter (GM), white matter (WM) reference regions and Yakushev normalization. RESULTS: Compared to GM normalization, WM and Yakushev normalization procedures disclosed much larger cortical regions of relative hypometabolism in the PD group with extensive involvement of frontal and parieto-temporal-occipital cortices, and several subcortical structures. Furthermore, in the WM and Yakushev normalized analyses, stage II patients displayed more prominent cortical hypometabolism than did stage I patients. CONCLUSION: The use of alternative normalization procedures, other than GM, suggests that much more extensive cortical hypometabolism is present in untreated de novo PD patients than hitherto reported. The finding may have implications for our understanding of the basic pathophysiology of early-stage PD.

Alzheimer's disease: genetic basis and amyloid imaging as endophenotype.

To date, all known Alzheimer's disease genes influence amyloid ß (Aß). Imaging of Aß deposition in the human brain using positron emission tomography (PET) tracers as [11C]Pittsburgh Compound B ([(11)C]PiB) or [18F]FDDNP offers the possibility of using cortical tracer binding as a quantitative endophenotype for genetic studies of late-onset Alzheimer's disease (AD). In this review we investigate the association between cerebral Aß burden, as measured by amyloid PET imaging, and different genetic risk factors involved in AD. Through a look at the major genetic risk factors for both early-onset familial and late-onset sporadic forms of AD, we discuss the possible role of amyloid PET imaging as an endophenotype in AD. Several PET studies confirmed the high heritability of amyloid load estimated by PET imaging and its association with the major genetic risk factors for early and late onset AD, suggesting that cerebral binding of these amyloid tracers could represent an useful trait for large-scale genetic studies of AD.

Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC-1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI.

Imaging of macrophages with superparamagnetic iron oxide particles (SPIO) has been performed to improve detection of atherosclerotic plaque inflammation in human and mouse studies by molecular magnetic resonance imaging (MRI). Since affinity of the monocyte/macrophage integrin MAC-1 (CD11b/CD18) is upregulated in inflammation, we generated a contrast agent targeting CD11b (CD11b-SPIOs) for improved macrophage detection in plaques. CD11b-SPIOs and non-targeted SPIOs (control-SPIOs) were incubated in vitro with human monocytes/macrophages. As quantified by SPIO-induced MRI signal extinction, intracellular iron-content was significantly higher in monoytes/macrophages incubated with CD11b-SPIO than with control-SPIO in vitro (p < 0.05), suggesting an improved uptake of CD11b-SPIOs into monocytes. Therefore, the aortic arch (AA) and vessel branches of ApoE(-/-)-knockout mice on a Western-type diet were imaged before and 48 h after contrast agent injection of either CD11b-SPIOs or control-SPIOs, using a 9.4 T animal MRI system. The SPIO-induced change in the MRI signal was quantified, as well as the macrophage-content by anti-CD68 immunhistochemistry and the iron-content by Prussian-blue staining. However, SPIO-induced signal extinction in in vivo-MRI was similar in CD11b-SPIO and control-SPIO-injected animals, with a non-significant trend towards an improved uptake of CD11b-SPIOs in the subclavian artery and subsections of the AA. These data correlated well with the results obtained by histology. Although in vitro MRI-data indicated an increased uptake of targeted CD11b-SPIOs in monocytes/macrophages, in vivo mouse data do not allow improved atherosclerotic plaque detection compared WITH non-targeted SPIOs. Therefore, CD11b-targeted MRI contrast labelling of monocytes/macrophages does not seem to be a successful strategy in stable atherosclerotic plaques such as found in the ApoE(-/-)-knockout-model. However, the impressive correlation between MRI and histology data encourages further development of inflammation- and plaque-specific contrast agents for vulnerable plaque imaging.

Early detection of Alzheimer's disease with PET imaging.

Preclinical diagnosis of Alzheimer's disease (AD) is one of the major challenges for the prevention of AD. AD biomarkers are needed not only to reveal preclinical pathologic changes, but also to monitor progression and therapeutics. PET neuroimaging can reliably assess aspects of the molecular biology and neuropathology of AD. The aim of this article is to review the use of FDG-PET and amyloid PET imaging in the early detection of AD.

Evaluation of Early Dementia (Mild Cognitive Impairment).

Early diagnosis of Alzheimer disease (AD) is one of the major challenges for the prevention of this dementia. The pathologic lesions associated with AD develop many years before the clinical manifestations of the disease become evident, during a likely transitional period between normal aging and the appearance of first cognitive symptoms. AD biomarkers are needed not only to reveal these early pathologic changes but also to monitor progression in cognitive and behavioral decline and brain lesions. PET neuroimaging can reliably assess indirect and direct aspects of the molecular biology and neuropathology of AD. This article reviews the use of [18F] 2-fluoro-2-deoxy-D-glucose-PET and amyloid PET imaging in the early detection of AD.

[Inadequate treatment and control of arterial hypertension in patients with type 2 diabetes mellitus]. / L'ipertensione arteriosa non e' adeguatamente trattata e controllata nei pazienti con diabete mellito di tipo 2.

BACKGROUND: Aim of this study is to evaluate the treatment and control of arterial hypertension in patients with type 2 diabetes. METHODS: We identified 5815 diabetic patients in our health-care district (191,568 inhabitants) through prescriptions for insulin and/or hypoglycaemic drugs in the first 6 months of 2000; 3810 of them (65%) also had prescriptions for antihypertensive drugs. We evaluated a randomly selected sample of 171 patients with type 2 diabetes, 100 of whom were receiving antihypertensive drugs (94 males and 77 females, mean age 66.6 +/- 8 years, mean diabetes duration 12+/-9 years). RESULTS: Fifty-seven out of 71 patients not treated with antihypertensive drugs (80.3%) had a BP = 130/85 mmHg; 24.4% of them had a diastolic BP = 85 mmHg and 79% had a systolic BP = 130 mmHg. Thirteen out of 100 treated patients (13%) had a BP < 130/85 mmHg. Among the patients treated with antihypertensive drugs 36% received one drug, 36% two drugs and 28%=3 drugs; mean 1.98 +/- 0.9 drugs/patients. Among the patients treated with monotherapy 36.1% received ACE-inhibitors, 36.1% dihydropyridinic calcium-antagonists, 11.1% alpha-blockers, 11%, diuretics, 2.8% non-dihydropyridinic calcium-antagonists, and 2.8% angiotensin II antagonists. Patients treated with two antihypertensive drugs received more frequently an ACE-inhibitor plus a diuretic (31%) or an ACE-inhibitor plus an alpha-blocker (23%) or an ACE-inhibitor plus a dihydropyridinic calcium-antagonists (20%). A diuretic was used in 40% of the patients with two antihypertensive drugs and in 78% of those with >= 3 drugs. CONCLUSIONS: Many hypertensive type 2 diabetic patients are left untreated and only a minority of those treated reach optimal blood pressure control. The importance of an elevated systolic pressure is underestimated, and the number of antihypertensive drugs prescribed is suboptimal.