Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.

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High incidences of myocarditis and acute kidney injury were observed, which indicates that the children were treated at a late stage of the disease. Clinicians should be cognizant that myocarditis and acute kidney injury are serious manifestations of pediatric scrub typhus.

Abstract.Receiver

While studies show that prolonged initial prednisone therapy reduces the frequency of relapses in nephrotic syndrome, they lack power and have risk of bias. In order to examine the effect of prolonged therapy on frequency of relapses, we conducted a blinded, 1:1 randomized, placebo-controlled trial in 5 academic hospitals in India on 181 patients, 1-12 years old, with a first episode of steroid-sensitive nephrotic syndrome. Following 12 weeks of standard therapy, in random order, 92 patients received tapering prednisolone while 89 received matching-placebo on alternate days for the next 12 weeks. On intention-to-treat analyses, primary outcome of number of relapses at 1 year was 1.26 in the 6-month group and 1.54 in the 3-month group (difference -0.28; 95% confidence interval (CI) -0.75, 0.19). Relative relapse rate for 6- vs. 3-month therapy, adjusted for gender, age, and time to initial remission, was 0.70 (95% CI 0.47-1.10). Similar proportions of patients had sustained remission, frequent relapses, and adverse effects due to steroids. Adjusted hazard ratios for first relapse and frequent relapses with prolonged therapy were 0.57 (95% CI, 0.36-1.07) and 1.01 (95% CI, 0.61-1.67), respectively. Thus, extending initial prednisolone treatment from 3 to 6 months does not influence the course of illness in children with nephrotic syndrome. These findings have implications for guiding the duration of therapy of nephrotic syndrome.

[1] The lithospheric structure of the Indian plate has been investigated using converted wave techniques (P and S receiver functions) and a novel stacking analysis technique (without using deconvolution) applied to a large seismological data set from permanent and temporary broadband seismic stations. We observe coherent energy from at least two seismic discontinuities, i.e., the crust-mantle (Moho) and lithosphere-asthenosphere boundary (LAB) in the uppermost mantle. Here we provide a novel seismic image of the Indian lithosphere showing definitive evidence of its flexure, which is interpreted to be primarily caused by the hard collision at~55 Myr resulting in the world's highest mountain chain-the Himalayas and the Tibetan plateau. Results from geoidal and gravity studies do suggest postcollisional flexuring of the Indian plate; however, the flexure lacks observational constraints. The observed wavelength of the flex is~1000 km with the thickness of the Indian shield lithosphere varying from~70 km to 140 km; such a low value for a continent implies that the Indian plate has been reworked in the past. The plate deepens in the Himalayan region to a depth of~170 km. Further, the converted phases are interpreted to be resulting from the bottom of the lithosphere. We clearly demonstrate that these are distinct and different from the midlithospheric discontinuity. For a large number of stations, the midlithospheric discontinuity and LAB are clearly separated in depth. Our observations suggest that the Archaean lithosphere is no longer intact and is prone to deformation.

S U M M A R YThe Archean Dharwar craton in south India is known for long time to be different from most other cratons. Specifically, at station Hyderabad (HYB) the Ps converted phases from the 410-and 660-km mantle discontinuities arrive up to 2 s later than in other cratons of comparable age, which implies lower upper mantle velocities. To resolve the unique lithosphere-asthenosphere system of the Dharwar craton, we inverted jointly P and S receiver functions and teleseismic P and S traveltime residuals at 10 seismograph stations. This method operates in the same depth range as long-period surface waves but differs by much higher lateral and radial resolution. We observe striking differences in crustal structures between the eastern and western Dharwar craton (EDC and WDC, respectively): crustal thickness is of around 31 km, with predominantly felsic velocities, in the EDC and of around 55 km, with predominantly mafic velocities, in the WDC. In the mantle we observe significant variations in the P velocity with depth, practically without accompanying variations in the S velocity. In the mantle S velocity there are azimuthdependent indications of the Hales discontinuity at a depth of ∼100 km. The most conspicuous feature of our models is the lack of the high velocity mantle keel with the S velocity of ∼4.7 km s −1 , typical of other Archean cratons. The S velocity in our models is close to 4.5 km s −1 from the Moho to a depth of ∼250 km. There are indications of a similar upper mantle structure in the northeast of the Indian craton and of a partial recovery of the normal shield structure in the northwest. A division between the high S-velocity western Tibet and low S-velocity eastern Tibet may be related to a similar division between the northeastern and northwestern Indian craton.

1] This study presents the first results of the seismic character of the underthrusting Indian crust in the Sikkim Himalaya deduced through an analysis of ∼3600 receiver functions (RFs) abstracted from waveforms registered at 11 broadband stations spanning a 110 km long N-S profile from the foothills to the higher Himalaya. Common conversion point stacks of receiver functions prominently trace the northward dipping geometry of the Indian Moho beneath the Himalaya. Monte Carlo inversion of the azimuthal variations of the RFs at individual stations adopting the nearest neighborhood algorithm approach reveals that the crustal thickness varies from ∼40 km to 61 km from south to north, with a dip varying between 4°and 10°among stations. A Moho doublet prominently seen at a depth of ∼40 km in the higher Himalaya to the north of Main Boundary Thrust has been interpreted in terms of possible (partial) eclogitization of a granulitic Indian lower crust, akin to the finding just north of the study region beneath southern Tibet. A strong layer of anisotropy (∼17%) localized within a low-velocity layer between 20 and 30 km has a NW-SE oriented fast polarization direction counterintuitive to the convergence-parallel and range-perpendicular alignment expected in a convergent setting due to shear processes. Midcrustal transcurrent deformation in Sikkim and Bhutan, evidenced by a conjugate system of strike-slip faulting with NW to NE trending P axis orientations is the most feasible mechanism for causing a near strike parallel oriented fast axis of anisotropy in this segment of Himalaya.