Nephrotic Syndrome: Is HIV Associated Nephropathy on Your Differential?

Case Description A 30-year old African American female with no significant past medical history initially presented to our emergency department with three days of sore throat, dysphagia, fever, fatigue, nausea and vomiting. She denied ear pain, rhinorrhea, shortness of breath or any sick contacts. Her social history was negative for tobacco, alcohol and illicit drug use. She works as a security officer, lives with her family and is sexually active only with her husband. On initial examination she was febrile to 101.9° F, with a heart rate of 100 beats per minute, blood pressure of 143/99 mmHg, respiratory rate of 18 breaths per minute and an oxygen saturation of 99% on room air. Her only pertinent physical examination findings were a mildly erythematous oropharynx without exudates, mildly swollen uvula and right tonsil, bilateral tender swollen sub-mandibular lymph nodes and reduced breath sounds on auscultation of the right lower lung base.She was routinely tested for HIV, ruled out for group A strep, and discharged home with the diagnosis of viral pharyngitis on supportive care. Following the identification of a presumptive positive rapid HIV screening test with evidence of HIV-1 p24 antigen and a reactive HIV-1 antibody on the multispot HIV 1 / 2 antibody test she was called to return to the ED for counseling regarding a positive HIV test. She reported continuation of her prior symptoms with worsening dysphagia, as well as new complaints of bilateral lower extremity edema to the knees. Initial laboratory testing revealed an elevated serum creatinine (Cr) of 2.2mg/dL (0.7-1.3 mg/dL) up from \u3c1.0mg/dL one-year prior, with an estimated Creatinine clearance (CrCl) of 43.4 ml/min using the modified Cockcroft-Gault equation. She was admitted for further workup. A trial of IV fluid hydration overnight worsened her symptoms and additional labs demonstrated hypoalbuminemia, 4+ proteinuria with 1+ blood, and a urine protein/creatinine ratio of 17mg/ mg (\u3c0.2 mg/mg), consistent with nephrotic syndrome. Her CD4 count was 115 cells/mm3 (500-1500 cells/ mm3) with an HIV viral load of 117,148 copies/ml. Based off negative labs for syphilis, hepatitis panel, ANA, complement C3/C4, and diabetes, findings were felt to be consistent with HIV Associated Nephropathy (HIVAN). The patient underwent renal biopsy to confirm the diagnosis and was started on abacavir, darunavir, dolutegravir, lamivudine and ritonavir. Pathology results were consistent with HIVAN with tubulointerstitial nephritis and collapsing glomerulonephropathy and electron microscopy showed diffuse epithelial cell injury with effacement of foot processes and segmental collapse of glomerular capillary loops. Her serum Cr peaked at 2.78 on day 7 of her admission. Her serum Cr and urea-nitrogen steadily improved after just one week of HAART therapy leading to a 42% reduction in serum Cr (Figure 1). Additionally, due to her un-resolving dysphagia the patient underwent esophagogastroduodenoscopy, which was unremarkable. However, she subsequently had esophageal manometry, which was consistent with diffuse esophageal spasm for which she was started on diltiazem

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

<div><p>Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.</p></div

Relationship between rainfall, fecal pollution, antimicrobial resistance, and microbial diversity in an urbanized subtropical bay

Urbanized bays are vulnerable to fecal bacterial pollution, and the extent of this pollution, in marine recreational waters, is commonly assessed by quantifying enterococcus concentrations. Recent reports have questioned the utility of enterococci as an indicator of fecal bacterial pollution in subtropical bays impaired by non-point source pollution, and enterococcus data alone cannot identify fecal bacterial sources (i.e., hosts). The purpose of this study was to assess relationships between rainfall, fecal bacterial pollution, antimicrobial resistance, and microbial diversity in an urbanized subtropical bay. Thus, a comprehensive bacterial source tracking (BST) study was conducted using a combination of traditional and modern BST methods. Findings show that rainfall was directly correlated with elevated enterococcus concentrations, including the increased prevalence of Enterococcus faecium, although it was not correlated with an increase in the prevalence of antimicrobial-resistant strains. Rainfall was also correlated with decreased microbial diversity. In contrast, neither rainfall nor enterococcus concentrations were directly correlated with the concentrations of three omnipresent host-associated fecal markers (i.e., human, canine, and gull). Notably, the human fecal marker (HF183) was inversely correlated with enterococcus concentrations, signifying that traditional enterococcus data alone are not an accurate proxy for human fecal waste in urbanized subtropical bays

Predicting Acute Kidney Injury following Transcatheter Aortic Valve Replacement

Purpose: Acute kidney injury occurs in up to a quarter of patients following transcatheter aortic valve replacement (TAVR) and has been associated with increased short and long-term mortality rates. A variety of patient characteristics predictive of post-TAVR acute kidney injury (AKI) have been identified, however discrepancies among studies exist almost uniformly. We investigated the hypothesis that the change in glomerular filtration rate (ΔGFR) in response to contrast administered during pre-TAVR coronary angiography is predictive of ΔGFR post-TAVR. Methods: The study comprised 195 patients who underwent TAVR at a single center between August 2008 and June 2015 and were prospectively included in the CAPITAL TAVR registry. Multiple linear regression analysis was conducted to estimate the effect of independent variables on the change in renal function post-TAVR. Results: There was no relationship identified between the ΔGFR post-angiogram and the ΔGFR post-TAVR (r=0.043, P=0.582). Multiple linear regression analysis revealed that a significant amount of the change in renal function post-TAVR can be explained by the patient’s baseline creatinine (beta coefficient, -0.310,

Contrast-free optical coherence tomography:Systematic evaluation of non-contrast media for intravascular assessment.

BackgroundCoronary revascularization using imaging guidance is rapidly becoming the standard of care. Intravascular optical coherence tomography uses near-infrared light to obtain high resolution intravascular images. Standard optical coherence tomography imaging technique employs iodinated contrast dye to achieve the required blood clearance during acquisition. We sought to systematically evaluate the technical performance of saline as an alternative to iodinated contrast for intravascular optical coherence tomography assessment.Methods and resultsWe performed bench top optical coherence tomography analysis on nylon tubing with sequential contrast/saline dilutions to empirically derive adjustment coefficients. We then applied these coefficients in vivo in an established rabbit abdominal stenting model with both saline and contrast optical coherence tomography imaging. In this model, we assessed the impact of saline on both quantitative and qualitative vessel assessment. Nylon tubing assessment demonstrated a linear relationship between saline and contrast for both area and diameter. We then derived adjustment coefficients, allowing for accurate calculation of area and diameter when converting saline into both contrast and reference dimensions. In vivo studies confirmed reduced area with saline versus contrast [7.43 (5.67-8.36) mm2 versus 8.2 (6.34-9.39) mm2, p = 0.001] and diameter [3.08 mm versus 3.23 mm, p = 0.001]. Following correction, a strong relationship was achieved in vivo between saline and contrast in both area and diameter without compromising image quality, artefact, or strut assessment.ConclusionSaline generates reduced dimensions compared to contrast during intravascular optical coherence tomography imaging. The relationship across physiologic coronary diameters is linear and can be corrected with high fidelity. Saline does not adversely impact image quality, artefact, or strut assessment

Revisiting the Evidence for Dipyridamole in Reducing Restenosis: A Systematic Review and Meta-analysis

Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I-2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I-2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I-2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization