Macular Microcysts in Mitochondrial Optic Neuropathies: Prevalence and Retinal Layer Thickness Measurements.

PurposeTo investigate the thickness of the retinal layers and to assess the prevalence of macular microcysts (MM) in the inner nuclear layer (INL) of patients with mitochondrial optic neuropathies (MON).MethodsAll patients with molecularly confirmed MON, i.e. Leber's Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA), referred between 2010 and 2012 were enrolled. Eight patients with MM were compared with two control groups: MON patients without MM matched by age, peripapillary retinal nerve fiber layer (RNFL) thickness, and visual acuity, as well as age-matched controls. Retinal segmentation was performed using specific Optical coherence tomography (OCT) software (Carl Zeiss Meditec). Macular segmentation thickness values of the three groups were compared by one-way analysis of variance with Bonferroni post hoc corrections.ResultsMM were identified in 5/90 (5.6%) patients with LHON and 3/58 (5.2%) with DOA. The INL was thicker in patients with MON compared to controls regardless of the presence of MM [133.1±7μm vs 122.3±9μm in MM patients (p<0.01) and 128.5±8μm vs. 122.3±9μm in no-MM patients (p<0.05)], however the outer nuclear layer (ONL) was thicker in patients with MM (101.4±1mμ) compared to patients without MM [77.5±8mμ (p<0.001)] and controls [78.4±7mμ (p<0.001)]. ONL thickness did not significantly differ between patients without MM and controls.ConclusionThe prevalence of MM in MON is low (5-6%), but associated with ONL thickening. We speculate that in MON patients with MM, vitreo-retinal traction contributes to the thickening of ONL as well as to the production of cystic spaces

Il concetto di ordinamento tra 'commandement' e 'arrangement' nella sociologia di Auguste Comte

Sociologia e antiformalismo nell'Ordinamento giuridico di Santi Roman

Longitudinal Study of Optic Disk Perfusion and Retinal Structure in Leber's Hereditary Optic Neuropathy

Purpose: The purpose of this study was to evaluate optic disk perfusion and neural retinal structure in patients with subacute Leber's hereditary optic neuropathy (LHON) and LHON carriers, as compared with healthy controls. Methods: This study included 8 patients with LHON in the subacute stage, 10 asymptomatic carriers of a LHON-associated mitochondrial DNA mutation, and 40 controls. All subjects underwent measurement of the retinal nerve fiber layer (RNFL) thickness, the ganglion cell-inner plexiform layer (GCIPL) thickness using optical coherence tomography and optic disk microvascular perfusion (Mean Tissue [MT]) using laser speckle flowgraphy (LSFG). Patients were re-examined after a median interval of 3 months from the baseline visit. Results: LHON carriers had higher values of RNFL thickness, GCIPL thickness, and disk area than controls (P < 0.05), whereas MT was not different between the two groups (P = 0.936). Median MT and RNFL thickness were 32% and 15% higher in the early subacute stage of the disease than in controls (P < 0.001 and P = 0.001). MT declined below the values of controls during the late subacute stage (P = 0.024), whereas RNFL thickness declined later during the dynamic stage (P < 0.001). GCIPL thickness was lower in patients with LHON than in controls independently of the stage of the disease (P < 0.001). Conclusions: The high blood flow at the optic disk during the early subacute stage may be the consequence of vasodilation due to nitric oxide release as compensation to mitochondrial impairment. Optic disk perfusion as measured by LSFG is a promising biomarker for LHON diagnosis and monitoring as well as an objective outcome measure for assessing response to therapies

Italian real life experience with ibrutinib: Results of a large observational study on 77 relapsed/refractory mantle cell lymphoma

Although sometimes presenting as an indolent lymphoma, mantle cell lymphoma (MCL) is an aggressive disease, hardly curable with standard chemo-immunotherapy. Current approaches have greatly improved patients' outcomes, nevertheless the disease is still characterized by high relapse rates. Before approval by EMA, Italian patients with relapsed/refractory MCL were granted ibrutinib early access through a Named Patient Program (NPP). An observational, retrospective, multicenter study was conducted. Seventyseven heavily pretreated patients were enrolled. At the end of therapy there were 14 complete responses and 14 partial responses, leading to an overall response rate of 36.4%. At 40 months overall survival was 37.8% and progression free survival was 30%; disease free survival was 78.6% at 4 years: 11/14 patients are in continuous complete response with a median of 36 months of follow up. Hematological toxicities were manageable, and main extra-hematological toxicities were diarrhea (9.4%) and lung infections (9.0%). Overall, 4 (5.2%) atrial fibrillations and 3 (3.9%) hemorrhagic syndromes occurred. In conclusions, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; regarding effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL also in a clinical setting mimicking the real world

CT-Detected MTA Score Related to Disability and Behavior in Older People with Cognitive Impairment

Our study aims to investigate the relationship between medial temporal lobe atrophy (MTA) score, assessed by computed tomography (CT) scans, and functional impairment, cognitive deficit, and psycho-behavioral disorder severity. Overall, 239 (M = 92, F = 147; mean age of 79.3 ± 6.8 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. MTA was evaluated from 0 (no atrophy) to 4 (severe atrophy). The homocysteine serum was set to two levels: between 0 and 10 µmol/L, and >10 µmol/L. The cholesterol and glycemia blood concentrations were measured. Hypertension and atrial fibrillation presence/absence were collected. A total of 14 patients were MTA 0, 44 patients were MTA 1, 63 patients were MTA 2, 79 patients were MTA 3, and 39 patients were MTA 4. Cognitive (p p p p p p = 0.001) increased according to MTA severity. This study encourages and supports the potential role of MTA score and CT scan in the field of neurodegenerative disorder research and diagnosis

Neurocognitive Disorders and Dehydration in Older Patients: Clinical Experience Supports the Hydromolecular Hypothesis of Dementia

Abnormalities of water homeostasis can be early expressions of neuronal dysfunction, brain atrophy, chronic cerebrovasculopathy and neurodegenerative disease. The aim of this study was to analyze the serum osmolality of subjects with cognitive impairment. One thousand and ninety-one consecutive patients attending the Alzheimer’s Evaluation Unit were evaluated with the Mini-Mental State Examination (MMSE), 21-Item Hamilton Depression Rating Scale (HDRS-21), Activities of Daily Living (ADL), Instrumental-ADL (IADL), Mini Nutritional Assessment (MNA), Exton-Smith Scale (ESS), and Cumulative Illness Rating Scale (CIRS). For each patient, the equation for serum osmolality developed by Khajuria and Krahn was applied. Five hundred and seventy-one patients had cognitive decline and/or depression mood (CD-DM) and 520 did not have CD-DM (control group). Patients with CD-DM were less likely to be male (p < 0.001), and were more likely to be older (p < 0.001), have a significant clear cognitive impairment (MMSE: p < 0.001), show the presence of a depressive mood (HDRS-21: p < 0.001) and have major impairments in ADL (p < 0.001), IADL (p < 0.001), MNA (p < 0.001), and ESS (p < 0.001), compared to the control group. CD-DM patients had a higher electrolyte concentration (Na+: p < 0.001; K+: p < 0.001; Cl−: p < 0.001), risk of dehydration (osmolality p < 0.001), and kidney damage (eGFR: p = 0.021), than the control group. Alzheimer’s disease (AD) patients showed a major risk for current dehydration (p ≤ 0.001), and dehydration was associated with the risk of developing a type of dementia, like AD or vascular dementia (VaD) (OR = 2.016, p < 0.001). In the multivariate analysis, the presence of dehydration state was associated with ADL (p < 0.001) and IADL (p < 0.001), but independently associated with age (r2 = 0.0046, p = 0.77), ESS (r2 = 0.0052, p = 0.54) and MNA (r2 = 0.0004, p = 0.48). Moreover, younger patients with dementia were significantly more dehydrated than patients without dementia (65–75 years, p = 0.001; 76–85 years, p = 0.001; ≥86 years, p = 0.293). The hydromolecular hypothesis intends to explain the relationship between dehydration and cognitive impairment in older patients as the result of protein misfolding and aggregation, in the presence of a low interstitial fluid volume, which is a defect of the microcirculation. Defective proteins were shown to impair the amount of information in brain biomolecular mechanisms, with consequent neuronal and synaptic damage