Neonatal AKI: An update.

Neonatal acute kidney injury (AKI) is a common complication, especially in the neonatal intensive care unit, that is associated with long term consequences and poor outcomes. Early detection and treatment is critical. Currently, neonatal AKI is defined with urinary markers and serum creatinine, with limitations on early detection and individual treatment. There have been numerous biomarkers and risk factor scores that have been studied for their ability to predict neonatal AKI. To move towards personalized medicine, neonatal AKI must be categorized into phenotypes and subphenotypes that fully encapsulate the diverse causes and specific treatments. This review aims to advance our understanding of neonatal AKI detection through the use of biomarkers, subphenotypes, and phenotypes to move towards personalized treatment strategies.

Quantifying Brain Iron in Hereditary Hemochromatosis Using R2* and Susceptibility Mapping.

BACKGROUND AND PURPOSE: Brain iron dyshomeostasis is increasingly recognized as an important contributor to neurodegeneration. Hereditary hemochromatosis is the most commonly inherited disorder of systemic iron overload. Although there is an increasing interest in excessive brain iron deposition, there is a paucity of evidence showing changes in brain iron exceeding that in healthy controls. Quantitative susceptibility mapping and R2* mapping are established MR imaging techniques that we used to noninvasively quantify brain iron in subjects with hereditary hemochromatosis. MATERIALS AND METHODS: Fifty-two patients with hereditary hemochromatosis and 47 age- and sex-matched healthy controls were imaged using a multiecho gradient-echo sequence at 3T. Quantitative susceptibility mapping and R2* data were generated, and regions within the deep gray matter were manually segmented. Mean susceptibility and R2* relaxation rates were calculated for each region, and iron content was compared between the groups. RESULTS: We noted elevated iron levels in patients with hereditary hemochromatosis compared with healthy controls using both R2* and QSM methods in the caudate nucleus, putamen, pulvinar thalamus, red nucleus, and dentate nucleus. Additionally, the substantia nigra showed increased susceptibility while the thalamus showed an increased R2* relaxation rate compared with healthy controls, respectively. CONCLUSIONS: Both quantitative susceptibility mapping and R2* showed abnormal levels of brain iron in subjects with hereditary hemochromatosis compared with controls. Quantitative susceptibility mapping and R2* can be acquired in a single MR imaging sequence and are complementary in quantifying deep gray matter iron.

HLA Desensitization Based on Results of the Luminex Technique in Kidney Transplant - A Single-center Experience.

BACKGROUND: There is little experience of human leucocyte antigen (HLA) desensitization in India based on the Luminex single-antigen bead (SAB) testing. We retrospectively analyzed our patients, who underwent HLA desensitization based on Luminex SAB results. METHOD: Between 2014 and 2018, patients with complement-dependent cytotoxicity cross-match (CDC-XM) negativity but flow cytometry crossmatch (FC-XM) positivity were further analyzed with Luminex SAB for donor-specific antibodies (DSAs). A total of 12 patients who had DSA mean fluorescent intensity (MFI) of >1000 and <10,000 were included in the study. Our protocol for desensitization consisted of plasmapheresis (PP) followed by low dose intravenous immunoglobulin (IV IG) 100 mg/kg and induction with antithymocyte globulin (ATG). Patients were taken for transplant when either MFI was <1000 and/or FC-XM was negative. RESULTS: All 12 patients were first transplant and 10 had a history of some sensitizing event; pregnancy in 4, blood transfusions in 4, and both in 2 patients. FC-XM was positive for T-cell in 4, B-cell in 6, and both in 2 patients. On evaluation by Luminex SAB, 6 patients had MFI from 1000 to 2000, and 6 had MFI of >2000. All underwent desensitization successfully. Two patients had an increase in posttransplant DSA titers requiring posttransplant PP. The mean follow-up was 26.6 ± 13.9 months. On follow-up, only one patient developed acute T cell-mediated rejection 1 year after transplant, which responded to pulse steroids. There was no graft or patient loss until the last follow-up. CONCLUSION: This study shows that HLA desensitization is feasible and successful in the Indian setting if patients are properly selected.

Clinical evaluation of serological IgG antibody response on the Abbott Architect for established SARS-CoV-2 infection.

OBJECTIVE: This study aimed to evaluate the diagnostic performance of the Abbott Architect SARS-CoV-2 IgG assay in COVID-19 patients. METHODS: Residual sera from 177 symptomatic SARS-CoV-2-positive patients and 163 non-COVID-19 patients were tested for antibody with the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, Chicago, USA). Clinical records for COVID-19 patients were reviewed to determine the time from onset of clinical illness to testing. RESULTS: Specificity of the assay was 100.0% (95%CI: 97.1-100.0%). The clinical sensitivity of the assay varied depending on time from onset of symptoms, increasing with longer periods from the onset of clinical illness. The clinical sensitivity at ≤6 days was 8.6% (7/81; 95%CI: 3.8-17.5%), at 7-13 days 43.6% (17/39; 95%CI: 28.2-60.2%), at 14-20 days 84.0% (21/25; 95%CI: 63.1-94.7%), and at ≥21 days 84.4% (27/32; 95%CI: 66.5-94.1%). Clinical sensitivity was higher in the ≥14-day group compared to <14 days. There were no differences between the 14-20-day and ≥21-days groups; the combined clinical sensitivity for these groups (≥14 days) was 84.2% (49/57; 71.6-92.1%). CONCLUSION: The Abbott SARS-CoV-2 IgG test has high specificity. Clinical sensitivity was limited in the early stages of disease but improved from 14 days after the onset of clinical symptoms.

Jugular Anomalies in Multiple Sclerosis Are Associated with Increased Collateral Venous Flow.

BACKGROUND AND PURPOSE: To date, research on extracranial venous collaterals has been focused on structure, with relatively little attention paid to hemodynamics. We addressed this limitation by quantitatively comparing collateral flow in patients with multiple sclerosis and healthy controls by using phase-contrast MR imaging. We hypothesize that patients with MS with structurally anomalous internal jugular veins will have elevated collateral venous flow compared with healthy controls. MATERIALS AND METHODS: The sample consisted of 276 patients with MS and 106 healthy controls. We used MRV to classify internal jugular veins as stenotic and nonstenotic based on an absolute cross-sectional area threshold in 276 patients with MS and 60 healthy controls; 46 healthy controls lacked this imaging. Individual and total vessel flows were quantified by using phase-contrast MR imaging on all patients. Veins were classified by extracranial drainage type: internal jugular veins (I), paraspinal (II), and superficial (III). Differences among healthy controls, patients with MS, nonstenotic patients, and stenotic subgroups in total venous flow by vessel type were evaluated in a general linear model for statistical analysis. RESULTS: In the MS group, 153 patients (55%) evidenced stenosis, whereas 12 (20%) healthy controls were classified as stenotic (P < .001). Compared with healthy controls, the MS group showed lower type I flow and increased type II flow. Stenosis was associated with reduced flow in the type I vessels [F(1272) = 68; P < .001]. The stenotic MS group had increased flow in the type II vessels compared with the nonstenotic MS group [F(1272) = 67; P < .001]. CONCLUSIONS: Compared with healthy controls, patients with MS exhibit reduced venous flow in the main extracerebral drainage vein (internal jugular vein). In contrast, flow in the paraspinal venous collaterals is elevated in patients with MS and exacerbated by venous stenosis. Collateral drainage may be a compensatory response to internal jugular vein flow reduction.

Targeting renin-angiotensin system in malignant hypertension in atypical hemolytic uremic syndrome.

Hypertension is common in hemolytic uremic syndrome (HUS) and often difficult to control. Local renin-angiotensin activation is believed to be an important part of thrombotic microangiopathy, leading to a vicious cycle of progressive renal injury and intractable hypertension. This has been demonstrated in vitro via enhanced tissue factor expression on glomerular endothelial cells which is enhanced by angiotensin II. We report two pediatric cases of atypical HUS with severe refractory malignant hypertension, in which we targeted the renin-angiotensin system by using intravenous (IV) enalaprilat, oral aliskiren, and oral enalapril with quick and dramatic response of blood pressure. Both drugs, aliskiren and IV enalaprilat, were effective in controlling hypertension refractory to multiple antihypertensive medications. These appear to be promising alternatives in the treatment of severe atypical HUS-induced hypertension and hypertensive emergency.

Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers.

Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation. Plasmapheresis (PP) is considered to be the most effective treatment; however, results are variable and relapse is common after stopping plasmapheresis. Here, we report an unusual case of recurrent FSGS, who achieved complete remission with angiotensin receptor blocker therapy.

Eculizumab for atypical hemolytic-uremic syndrome in India: First report from India and the challenges faced.

Much progress has been made in understanding the pathophysiology and treatment of atypical hemolytic uremic syndrome (aHUS). Plasma therapy is the mainstay of treatment for aHUS. The availability of the first effective anti-complement therapeutic agent, eculizumab, has dramatically changed the outlook of this disease. However, its use in clinical practice raises important questions, such as who should receive the drug, when to start such therapy, and is it safe to stop treatment once the disease is controlled. We describe here for the 1st time in India, use of eculizumab in a 12-year-old boy with aHUS. We also describe in this report challenges faced in procuring the drug, and an ideal, evidence-based method of treating aHUS in children.

Validation of a Hemodynamic Model for the Study of the Cerebral Venous Outflow System Using MR Imaging and Echo-Color Doppler Data.

BACKGROUND AND PURPOSE: A comprehensive parameter model was developed to investigate correlations between cerebral hemodynamics and alterations in the extracranial venous circulation due to posture changes and/or extracranial venous obstruction (stenosis). The purpose of this work was to validate the simulation results by using MR imaging and echo-color Doppler experimental blood flow data in humans. MATERIALS AND METHODS: To validate the model outcomes, we used supine average arterial and venous extracerebral blood flow, obtained by using phase-contrast MR imaging from 49 individuals with stenosis in the acquisition plane at the level of the disc between the second and third vertebrae of the left internal jugular vein, 20 with stenosis in the acquisition plane at the level of the disc between the fifth and sixth vertebrae of the right internal jugular vein, and 38 healthy controls without stenosis. Average data from a second group of 10 healthy volunteers screened with an echo-color Doppler technique were used to evaluate flow variations due to posture change. RESULTS: There was excellent agreement between experimental and simulated supine flows. Every simulated CBF fell inside the standard error from the corresponding average experimental value, as well as most of the simulated extracerebral arterial flow (extracranial blood flow from the head and face, measured at the level of the disc between second and third vertebrae) and venous flows. Simulations of average jugular and vertebral blood flow variations due to a change of posture from supine to upright also matched the experimental data. CONCLUSIONS: The good agreement between simulated and experimental results means that the model can correctly reproduce the main factors affecting the extracranial circulation and could be used to study other types of stenotic conditions not represented by the experimental data.

ABO-incompatible renal transplantation in developing world - crossing the immunological (and mental) barrier.

ABO incompatibility has been considered as an important immunological barrier for renal transplantation. With the advent of effective preconditioning protocols, it is now possible to do renal transplants across ABO barrier. We hereby present a single center retrospective analysis of all consecutive ABOi renal transplants performed from November 2011 to August 2014. Preconditioning protocol consisted of rituximab, plasmapheresis and intravenous immunoglobulin (IVIG) and maintenance immunosuppression consisted of tacrolimus, mycophenolate sodium, and prednisolone. The outcome of these ABOi transplants was compared with all other consecutive ABO-compatible (ABOc) renal transplants performed during same time. Twenty ABOi renal transplants were performed during the study period. Anti-blood group antibody titer varied from 1:2 to 1:512. Patient and graft survival was comparable between ABOi and ABOc groups. Biopsy proven acute rejection rate was 15% in ABOi group, which was similar to ABOc group (16.29%). There were no antibody-mediated rejections in ABOi group. The infection rate was also comparable. We conclude that the short-term outcome of ABOi and ABOc transplants is comparable. ABOi transplants should be promoted in developing countries to expand the donor pool.

A simulation model to study the role of the extracranial venous drainage pathways in intracranial hemodynamics.

Alterations in the extracranial venous circulation due to posture changes, and/or extracranial venous obstructions in patients with vascular diseases, can have important implications on cerebral hemodynamics. A hemodynamic model for the study of cerebral venous outflow was developed to investigate the correlations between extracranial blood redistributions and changes in the intracranial environment. Flow data obtained with both magnetic resonance (MR) and Echo-Color Doppler (ECD) technique are used to validate the model. The very good agreement between simulated supine and upright flows and experimental results means that the model can correctly reproduce the main factors affecting the extracranial venous circulation.

Effect of fly ash application on soil microbial response and heavy metal accumulation in soil and rice plant.

Fly ash (FA), a byproduct of coal combustion in thermal power plants, has been considered as a problematic solid waste and its safe disposal is a cause of concern. Several studies proposed that FA can be used as a soil additive; however its effect on microbial response, soil enzymatic activities and heavy metal accumulation in soil and grain of rice (cv. Naveen) to fly ash (FA) application was studied in a pot experiment during dry season 2011 in an Inceptisol. Fly ash was applied at a rate of zero per cent (FS), five per cent (FA5), ten per cent (FA10), twenty per cent (FA20), 40 per cent (FA40) and 100 per cent (FA100) on soil volume basis with nitrogen (N), phosphorus (P) and potassium (K) (40:20:20mg N:P:Kkg(-1) soil) with six replications. Heavy metals contents in soil and plant parts were analysed after harvest of crop. On the other hand, microbial population and soil enzymatic activities were analysed at panicle initiation stage (PI, 65 days after transplanting) of rice. There was no significant change in the concentration of zinc (Zn), iron (Fe), copper (Cu), manganese (Mn), cadmium (Cd) and chromium (Cr) with application of fly ash up to FA10. However, at FA100 there was significant increase of all metals concentration in soil than other treatments. Microorganisms differed in their response to the rate of FA application. Population of both fungi and actinomycetes decreased with the application of fly ash, while aerobic heterotrophic bacterial population did not change significantly up to FA40. On the other hand, total microbial activity measured in terms of Fluorescein diacetate (FDA) assay, and denitrifiers showed an increased trend up to FA40. However, activities of both alkaline and acid phosphatase were decreased with the application of FA. Application of FA at lower levels (ten to twenty per cent on soil volume basis) in soil enhanced micronutrients content, microbial activities and crop yield.

Methemoglobinemia due to quinine causing severe acute kidney injury in a child.

Congenital methemoglobinemia is a rare condition resulting from a deficiency of nicotinamide adenine dinucleotide-cytochrome b5 reductase. Acquired methemoglobinemia may result due to certain drugs, chemicals and food items. Information on epidemiological determinants from India is sparse. This report describes methemoglobinemia in a 4-year-old child after parenteral administration of quinine causing acute kidney injury. This case emphasizes the need of awareness of potential adverse events of antimalarial drugs. Prompt management of methemoglobinemia is essential to avoid potential life-threatening complications.

Renal transplantation across ABO barrier.

In India, patients without a compatible blood group donor are usually excluded from renal transplantation. For young patients, it is a difficult therapeutic choice to stay on long-term dialysis. We describe the case of a 19-year-old male patient who had blood group O +ve and had no compatible donor in the family. His mother was B +ve and was willing to donate. The patient had an initial anti-B antibody titer of 1:512 and underwent antibody depletion with plasmapheresis (11 sessions) and intravenous immunoglobulin (IVIG) 100 mg/kg after every plasmapheresis. He also received rituximab 500 mg for 3 days prior to transplant and was induced with basiliximab. At the time of transplant, his anti-B titers were <1:8. Post-operatively, he required four sessions of plasmapheresis and IVIG as his titers rebounded to 1:64. The titers then spontaneously subsided to <1:16 and have stayed at the same level for 6 months post-transplant. The patient continues to have normal renal function with a creatinine of 1.4 mg/dl% and has had no episodes of rejection.

Giant cell transformation of podocytes: A unique histological feature associated with cystinosis.

Fanconi's syndrome is an unusual cause of renal insufficiency in pediatric patients. Infantile cystinosis is one of the identifiable and treatable etiologies of Fanconi's syndrome. Early diagnosis of cystinosis permits institution of specific therapy with cysteamine. A 3-year-old girl presented with failure to thrive, polyuria, and polydipsia. She was found to have renal tubular defect with renal dysfunction and bilateral small contracted kidneys. A renal biopsy revealed extensive giant cell transformation of podocytes in the glomeruli with focal tubular atrophy and dilatation. However, no crystals were identified. Subsequent ophthalmoscopic examination revealed fine cystine crystals in the cornea and a diagnosis of cystinosis causing Fanconi's syndrome was made. Polykaryocytic transformation of visceral epithelial cells is an important diagnostic clue of nephropathic cystinosis and should be carefully looked for in renal biopsy from a child with Fanconi's syndrome and renal insufficiency.

Ministry of health clinical practice guidelines: screening of cardiovascular disease and risk factors.

The Ministry of Health (MOH) publishes clinical practice guidelines on Screening of Cardiovascular Disease and Risk Factors to provide doctors and patients in Singapore with evidence-based guidance on the screening of cardiovascular disease and risk factors. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Screening of Cardiovascular Disease and Risk Factors, for the information of readers of the Singapore Medical Journal. Page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=25776). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Elderly woman with cerebrovascular accident and refractory arrhythmias.

Fatal bilateral cerebro-vascular accident with variable atrio-ventricular blocks, atrial fibrillation and refractory tachy-arrhythmias in a previously healthy 75-years-old hypertensive female is presented.