Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases

Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B cells and widely used in the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. There is a growing amount of literature which suggests that rituximab may be useful for inflammatory ocular diseases and intraocular lymphoma. Few cases have been reported on treatment of refractory scleritis, peripherative ulcerative keratitis, uveitis and ocular surface inflammatory disorders. Rituximab may be effective in the treatment of ocular inflammatory diseases in particular the most aggressive, recalcitrant and sight-threatening forms of inflammation such as uveitis associated to juvenile idiopathic arthritis. We review the literature covering the use of Rituximab in these conditions and report our results on the efficacy of Rituximab in the treatment of 8 children with very severe and long-standing uveitis who failed to respond to one or more TNF blockers. Our patients showed improvement in activity of uveitis, reduction of concomitant corticosteroids and immunosuppressants after a mean follow-up time of 14.87 months on rituximab. No serious adverse events were encountered in our treated patients. Although further studies are needed for assessing the efficacy of rituximab and the exact dosing regimen, rituximab may be considered as a treatment alternative in patients with the most aggressive forms of inflammatory ocular diseases who fail to respond to conventional and anti-TNF immunosuppressive agent

The depositional record of the Odyssea drift (Ross Sea, Antarctica)

The Ross Sea is one of the major areas for Antarctic Bottom Water formation (the Ross Sea Bottom Water, RSBW), representing the densest ocean water mass, filling the deepest ocean basins connected to the southern ocean. Peri- odic refill of the RSBW occurs through formation of dense, cold and saline water masses (brine) forming on the shelf at the Ross Sea permanent polynya by freezing and salt rejection (high-salinity shelf water, HSSW). The HSSW periodically overspills the shelf area and descends along the slope. This mechanism represents the engine of the global ocean circulation regulating the climate. The Hillary Canyon, crossing the Ross Sea continental slope, represents one of the main conducts through which the HSSW descends the slope to reach the deeper ocean. On its western levee, there is a mounded depocen- tre that was mapped and ground-sampled during the Italian ITRS17-ODYSSEA expedition on board the RV OGS-Explora (January-February 2017). Geophysical data allowed interpreting such feature as a sediment drift (ODYSSEA Drift), generated by along-slope, contour currents sediment transport and accumulation through sev- eral hundred-thousands years. It was inferred that contour currents transported and deposited the sediments that descent the Hillary Canyon by means of the HSSW. Therefore, the depositional sequence of the ODYSSEA Drift potentially contains the record of the variability of HSSW formation, the along slope current intensity in associa- tion to climate change, and the interplay between the two bottom currents. A multidisciplinary investigation was applied to six gravity cores collected in the proximal and distal area of the ODYSSEA Drift. The cores were analysed to reconstruct the age model combining AMS radiocarbon dating on foraminifera tests, biostratigraphy, and the sediment palaeomagnetic record; the sediment physical properties (wet bulk density, water content and grain size); and compositional characteristics (XRF core scan and geochemistry). Three main lithofacies were distinguished and associated to depositional processes and climatic conditions: 1) finely laminated and bioturbated sediments characterized by a relatively high Ca content with common presence of biogenic component. Such facies was associated to contour current deposition during relatively warm conditions. 2) Bioturbated sediments with abundant, sparse and/or layered Ice Rafted Debris, and high Ca content. The onset of this facies is characterized by a prominent Mn peak that was associated to bottom ocean oxygenation through ice sheet melting/decay. 3) Laminated, barren sediments associated to steady strong bottom currents under harsh climate conditions. Further preliminary data interpretations are discussed

Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom

PURPOSE: Ocular mucous membrane pemphigoid (OcMMP) is a sight-threatening autoimmune disease in which referral to specialists units for further management is a common practise. This study aims to describe referral patterns, disease phenotype and management strategies in patients who present with either early or established disease to two large tertiary care hospitals in the United Kingdom.\ud \ud PATIENTS AND METHODS: In all, 54 consecutive patients with a documented history of OcMMP were followed for 24 months. Two groups were defined: (i) early-onset disease (EOD:<3 years, n=26, 51 eyes) and (ii) established disease (EstD:>5 years, n=24, 48 eyes). Data were captured at first clinic visit, and at 12 and 24 months follow-up. Information regarding duration, activity and stage of disease, visual acuity (VA), therapeutic strategies and clinical outcome were analysed.\ud \ud RESULTS: Patients with EOD were younger and had more severe conjunctival inflammation (76% of inflamed eyes) than the EstD group, who had poorer VA (26.7%=VA<3/60, P<0.01) and more advanced disease. Although 40% of patients were on existing immunosuppression, 48% required initiation or switch to more potent immunotherapy. In all, 28% (14) were referred back to the originating hospitals for continued care. Although inflammation had resolved in 78% (60/77) at 12 months, persistence of inflammation and progression did not differ between the two phenotypes. Importantly, 42% demonstrated disease progression in the absence of clinically detectable inflammation.\ud \ud CONCLUSIONS: These data highlight that irrespective of OcMMP phenotype, initiation or escalation of potent immunosuppression is required at tertiary hospitals. Moreover, the conjunctival scarring progresses even when the eye remains clinically quiescent. Early referral to tertiary centres is recommended to optimise immunosuppression and limit long-term ocular damage.\ud \u

CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing

PURPOSE: Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations. METHODS: Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B1rms = 2μT, Tsat = 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3-4 ppm, amines: 1.5-2.5 ppm, amide/amine ratio) were calculated with two models: 'asymmetry-based' (AB) and 'fluid-suppressed' (FS). The presence of T2/FLAIR mismatch was noted. RESULTS: IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19qcodel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mutant_1p/19qret (p < 0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p < 0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014). CONCLUSIONS: CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance

Rituximab in refractory Vogt–Koyanagi–Harada disease

IntroductionVogt–Koyanagi–Harada (VKH) prognosis depends on early recognition and treatment; chronic disease may be developed when either delayed or inadequate treatment is performed, whereas other cases despite correct treatment are refractory to different drugs and also become chronic. We report a case of refractory VKH controlled with rituximab treatment.Case reportA 41-year-old female with painful visual loss and headache was examined. (VA 0.4 in RE and hand movements (HM) in LE). Retinal examination demonstrated multiple serous retinal detachments in both eyes. High-dose oral steroids were started, followed by progressive tapering of prednisone. New acute anterior and posterior relapses were achieved, and other immunommodulators were progressively added—new high-dose steroid treatment, adalimumab, cyclosporine, and methotrexate—but patient had new anterior and posterior recurrences associated with tinnitus and headache. Thus, an infusion of 1 g of rituximab was administered after 15 months follow-up; the VA was 0.2 in RE and counting fingers in LE. Three additional doses of 1 g each were administered 1, 6, and 16 months later. We have achieved a final VA after 34 months follow-up of 0.2 in RE and HM in LE, with definitive control of inflammation, without acute relapses since rituximab was administered.ConclusionAfter searching PubMed/Medline, this is the first report of VKH disease treated with rituximab. Additional studies are warranted to confirm the efficacy of this new approach for inflammatory control in refractory cases of VKH disease

Evidence for a large-magnitude Holocene eruption of Mount Rittmann (Antarctica): A volcanological reconstruction using the marine tephra record

In Antarctica, the near-source exposures of volcanic eruption deposits are often limited as they are not well preserved in the dynamic glacial environment, thus making volcanological reconstructions of explosive eruptions extremely challenging. Fortunately, pyroclastic deposits from explosive eruptions are preserved in Southern Ocean sediments surrounding Antarctica, and the tephrostratigraphy of these sequences offers crucial volcanological information including the timing and tempo of past eruptions, their magnitude, and eruption dynamics. Here we report the results of a tephrostratigraphy and tephrochronology study focused on four sediment cores recovered from the Wood Bay area in the western Ross Sea, Antarctica. In all these sedimentary sequences, we found a well-stratified primary tephra of considerable thickness, up to 80 cm, hereafter named the Aviator Tephra (AVT). According to the characteristics of the tephra deposit and its distribution, the AVT was associated with an eruption of considerable intensity, potentially representing one of the largest Holocene eruptions recorded in Antarctica. Based on the major and trace element geochemistry and the mineral assemblage of the tephra, Mount Rittmann was identified as the source of the AVT. A Holocene age of ∼11 ka was determined by radiocarbon dating organic material within the sediments and 40Ar-39Ar dating of alkali-feldspar crystals included in the tephra. Eruption dynamics were initially dominated by hydromagmatic magma fragmentation conditions producing a sustained, relatively wet and ash-rich eruptive cloud. The eruption then evolved into a highly energetic, relatively dry magmatic Plinian eruption. The last phase was characterized by renewed efficient magma-water interaction and/or collapse of the eruptive column producing pyroclastic density currents and associated co-ignimbritic plumes. The distal tephra deposits might be linked to the widespread lag breccia layer previously identified on the rim of the Mount Rittmann caldera which share the same geochemical composition. Diatoms found in the sediments surrounding the AVT and the primary characteristics of the tephra indicate that the Wood Bay area was open sea at the time of the eruption, which is much earlier than previously thought. AVT is also an excellent tephrostratigraphic marker for the Wood Bay area, in the Ross Sea, and a useful marker for future synchronization of continental ice and marine archives in the region

Normative brain mapping of interictal intracranial EEG to localize epileptogenic tissue

The identification of abnormal electrographic activity is important in a wide range of neurological disorders, including epilepsy for localising epileptogenic tissue. However, this identification may be challenging during non-seizure (interictal) periods, especially if abnormalities are subtle compared to the repertoire of possible healthy brain dynamics. Here, we investigate if such interictal abnormalities become more salient by quantitatively accounting for the range of healthy brain dynamics in a location-specific manner. To this end, we constructed a normative map of brain dynamics, in terms of relative band power, from interictal intracranial recordings from 234 subjects (21,598 electrode contacts). We then compared interictal recordings from 62 patients with epilepsy to the normative map to identify abnormal regions. We hypothesised that if the most abnormal regions were spared by surgery, then patients would be more likely to experience continued seizures post-operatively. We first confirmed that the spatial variations of band power in the normative map across brain regions were consistent with healthy variations reported in the literature. Second, when accounting for the normative variations, regions which were spared by surgery were more abnormal than those resected only in patients with persistent post-operative seizures (t=-3.6, p = 0.0003), confirming our hypothesis. Third, we found that this effect discriminated patient outcomes (AUC = 0.75 p = 0.0003). Normative mapping is a well-established practice in neuroscientific research. Our study suggests that this approach is feasible to detect interictal abnormalities in intracranial EEG, and of potential clinical value to identify pathological tissue in epilepsy. Finally, we make our normative intracranial map publicly available to facilitate future investigations in epilepsy and beyon

Hypopyon uveitis associated with systemic lupus erythematosus and antiphospholipid antibody syndrome

To report a case of hypopyon uveitis associated with systemic lupus erythematosus and antiphospholipid antibody syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47393/1/417_2004_Article_1022.pd

DNA copy number loss and allelic imbalance at 2p16 in lung cancer associated with asbestos exposure

Five to seven percent of lung tumours are estimated to occur because of occupational asbestos exposure. Using cDNA microarrays, we have earlier detected asbestos exposure-related genomic regions in lung cancer. The region at 2p was one of those that differed most between asbestos-exposed and non-exposed patients. Now, we evaluated genomic alterations at 2p22.1-p16.1 as a possible marker for asbestos exposure. Lung tumours from 205 patients with pulmonary asbestos fibre counts from 0 to 570 million fibres per gram of dry lung, were studied by fluorescence in situ hybridisation (FISH) for DNA copy number alterations (CNA). The prevalence of loss at 2p16, shown by three different FISH probes, was significantly increased in lung tumours of asbestos-exposed patients compared with non-exposed (P=0.05). In addition, a low copy number loss at 2p16 associated significantly with high-level asbestos exposure (P=0.02). Furthermore, 27 of the tumours were studied for allelic imbalances (AI) at 2p22.1–p16.1 using 14 microsatellite markers and also AI at 2p16 was related to asbestos exposure (P=0.003). Our results suggest that alterations at 2p16 combined with other markers could be useful in diagnosing asbestos-related lung cancer