A case series of patients with isolated IgG4-related hypophysitis treated with rituximab

Context The acute presentation of Immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis and histology remains the diagnostic gold standard. The high recurrence rate necessitates long term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited. Case description We report three female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with GCs (GC) resulted in good therapeutic response in patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3 necessitating dose reduction. All three patients received RTX and Patients 2 and 3 received further courses when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. RTX treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2 with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted. Conclusion RTX treatment for IgG4-related hypophysitis resulted in sustained remission in two patients treated early in the disease process, but only achieved partial response in a patient with chronic disease suggesting that early therapeutic intervention may be crucial to avoid irreversible changes

A simple and efficient GIS tool for volume calculations of submarine landslides

A numeric tool is presented for calculating volumes of topographic voids such as slump scars of landslides, canyons or craters (negative/concave morphology), or alternatively, bumps and hills (positive/convex morphology) by means of digital elevation models embedded within a geographical information system (GIS). In this study, it has been used to calculate landslide volumes. The basic idea is that a (singular) event (landslide, meteorite impact, volcanic eruption) has disturbed an intact surface such that it is still possible to distinguish between the former (undisturbed) landscape and the disturbance (crater, slide scar, debris avalanche). In such cases, it is possible to reconstruct the paleo-surface and to calculate the volume difference between both surfaces, thereby approximating the volume gain or loss caused by the event. I tested the approach using synthetically generated land surfaces that were created on the basis of Shuttle Radar Topography Mission data. Also, I show the application to two real cases, (1) the calculation of the volume of the Masaya Slide, a submarine landslide on the Pacific continental slope of Nicaragua, and (2) the calculation of the void of a segment of the Fish River Canyon, Namibia. The tool is provided as a script file for the free GIS GRASS. It performs with little effort, and offers a range of interpolation parameters. Testing with different sets of interpolation parameters results in a small range of uncertainty. This tool should prove useful in surface studies not exclusively on earth

Submarine slope failures along the convergent continental margin of the Middle America Trench

We present the first comprehensive study of mass wasting processes in the continental slope of a convergent margin of a subduction zone where tectonic processes are dominated by subduction erosion. We have used multibeam bathymetry along ∼1300 km of the Middle America Trench of the Central America Subduction Zone and deep-towed side-scan sonar data. We found abundant evidence of large-scale slope failures that were mostly previously unmapped. The features are classified into a variety of slope failure types, creating an inventory of 147 slope failure structures. Their type distribution and abundance define a segmentation of the continental slope in six sectors. The segmentation in slope stability processes does not appear to be related to slope preconditioning due to changes in physical properties of sediment, presence/absence of gas hydrates, or apparent changes in the hydrogeological system. The segmentation appears to be better explained by changes in slope preconditioning due to variations in tectonic processes. The region is an optimal setting to study how tectonic processes related to variations in intensity of subduction erosion and changes in relief of the underthrusting plate affect mass wasting processes of the continental slope. The largest slope failures occur offshore Costa Rica. There, subducting ridges and seamounts produce failures with up to hundreds of meters high headwalls, with detachment planes that penetrate deep into the continental margin, in some cases reaching the plate boundary. Offshore northern Costa Rica a smooth oceanic seafloor underthrusts the least disturbed continental slope. Offshore Nicaragua, the ocean plate is ornamented with smaller seamounts and horst and graben topography of variable intensity. Here mass wasting structures are numerous and comparatively smaller, but when combined, they affect a large part of the margin segment. Farther north, offshore El Salvador and Guatemala the downgoing plate has no large seamounts but well-defined horst and graben topography. Off El Salvador slope failure is least developed and mainly occurs in the uppermost continental slope at canyon walls. Off Guatemala mass wasting is abundant and possibly related to normal faulting across the slope. Collapse in the wake of subducting ocean plate topography is a likely failure trigger of slumps. Rapid oversteepening above subducting relief may trigger translational slides in the middle Nicaraguan upper Costa Rican slope. Earthquake shaking may be a trigger, but we interpret that slope failure rate is lower than recurrence time of large earthquakes in the region. Generally, our analysis indicates that the importance of mass wasting processes in the evolution of margins dominated by subduction erosion and its role in sediment dynamics may have been previously underestimated

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy

Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. / Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. / Results: Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (−1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05). / Conclusions: There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted

Multidimensional Model of Racial Identity: A Reconceptualization of African American Racial Identity

Research on African American racial identity has utilized 2 distinct approaches. The mainstream approach has focused on universal properties associated with ethnic and racial identities. In contrast, the underground approach has focused on documenting the qualitative meaning of being African American, with an emphasis on the unique cultural and historical experiences of African Americans. The Multidimensional Model of Racial Identity (MMRI) represents a synthesis of the strengths of these two approaches. The underlying assumptions associated with the model are explored. The model proposes 4 dimensions of African American racial identity: salience, centrality, regard, and ideology. A description of these dimensions is provided along with a discussion of how they interact to influence behavior at the level of the event. We argue that the MMRI has the potential to make contributions to traditional research objectives of both approaches, as well as to provide the impetus to explore new questions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68695/2/10.1207_s15327957pspr0201_2.pd

Large-scale mass wasting in the western Indian Ocean constrains onset of East African rifting

Faulting and earthquakes occur extensively along the flanks of the East African Rift System, including an offshore branch in the western Indian Ocean, resulting in remobilization of sediment in the form of landslides. To date, constraints on the occurrence of submarine landslides at margin scale are lacking, leaving unanswered a link between rifting and slope instability. Here, we show the first overview of landslide deposits in the post-Eocene stratigraphy of the Tanzania margin and we present the discovery of one of the biggest landslides on Earth: the Mafia mega-slide. The emplacement of multiple landslides, including the Mafia mega-slide, during the early-mid Miocene is coeval with cratonic rifting in Tanzania, indicating that plateau uplift and rifting in East Africa triggered large and potentially tsunamigenic landslides likely through earthquake activity and enhanced sediment supply. This study is a first step to evaluate the risk associated with submarine landslides in the region