A semi-quantitative, rapid, point of care SARS-CoV-2 serologic assay predicts neutralizing antibody levels.

The ongoing COVID-19 pandemic has caused millions of deaths and the continued emergence of new variants suggests continued circulation in the human population. In the current time of vaccine availability and new therapeutic development, including antibody-based therapies, many questions about long-term immunity and protection remain uncertain. Identification of protective antibodies in individuals is often done using highly specialized and challenging assays such as functional neutralizing assays, which are not available in the clinical setting. Therefore, there is a great need for the development of rapid, clinically available assays that correlate with neutralizing antibody assays to identify individuals who may benefit from additional vaccination or specific COVID-19 therapies. In this report, we apply a novel semi-quantitative method to an established lateral flow assay (sqLFA) and analyze its ability to detect the presence functional neutralizing antibodies from the serum of COVID-19 recovered individuals. We found that the sqLFA has a strong positive correlation with neutralizing antibody levels. At lower assay cutoffs, the sqLFA is a highly sensitive assay to identify the presence of a range of neutralizing antibody levels. At higher cutoffs, it can detect higher levels of neutralizing antibody with high specificity. This sqLFA can be used both as a screening tool to identify individuals with any level of neutralizing antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or as a more specific tool to identify those with high neutralizing antibody levels who may not benefit from antibody-based therapies or further vaccination.

Seroepidemiology and risk factors for SARS-CoV-2 infection among household members of food processing and farm workers in North Carolina.

Background: Racial and ethnic minorities have borne a disproportionate burden from coronavirus disease 2019 (COVID-19). Certain essential occupations, including food processing and farm work, employ large numbers of Hispanic migrant workers and have been shown to carry an especially high risk of infection. Methods: This observational cohort study measured the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and assessed the risk factors for seropositivity among food processing and farm workers, and members of their households, in North Carolina, USA. Participants completed questionnaires, blood samples were collected, and an enzyme-linked immunosorbent assay was used to assess SARS-CoV-2 seropositivity. Univariate and multi-variate analyses were undertaken to identify risk factors associated with seropositivity, using generalized estimating equations to account for household clustering. Findings: Among the 218 participants, 94.5% were Hispanic, and SARS-CoV-2 seropositivity was 50.0%. Most seropositive individuals did not report a history of illness compatible with COVID-19. Attending church, having a prior history of COVID-19, having a seropositive household member, and speaking Spanish as one's primary language were associated with SARS-CoV-2 seropositivity, while preventive behaviours were not. Interpretation: These findings underscore the substantial burden of COVID-19 among a population of mostly Hispanic essential workers and their households in rural North Carolina. This study contributes to a large body of evidence showing that Hispanic Americans have suffered a disproportionate burden of COVID-19. This study also highlights the epidemiologic importance of viral transmission within the household.

Outcomes of Convalescent Plasma with Defined High versus Lower Neutralizing Antibody Titers against SARS-CoV-2 among Hospitalized Patients: CoronaVirus Inactivating Plasma (CoVIP) Study.

COVID-19 convalescent plasma (CCP) was an early and widely adopted putative therapy for severe COVID-19. Results from randomized control trials and observational studies have failed to demonstrate a clear therapeutic role for CCP for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Underlying these inconclusive findings is a broad heterogeneity in the concentrations of neutralizing antibodies (nAbs) between different CCP donors. We conducted this study to evaluate the effectiveness and safety of nAb titer-defined CCP in adults admitted to an academic referral hospital. Patients positive by a SARS-CoV-2 nucleic acid amplification test and with symptoms for <10 days were eligible. Participants received either CCP with nAb titers of >1:640 (high-titer group) or ≥1:160 to 1:640 (standard-titer group) in addition to standard of care treatments. The primary clinical outcome was time to hospital discharge, with mortality and respiratory support evaluated as secondary outcomes. Adverse events were contrasted by CCP titer. Between 28 August and 4 December 2020, 316 participants were screened, and 55 received CCP, with 14 and 41 receiving high- versus standard-titer CCP, respectively. Time to hospital discharge was shorter among participants receiving high- versus standard-titer CCP, accounting for death as a competing event (hazard ratio, 1.94; 95% confidence interval [CI], 1.05 to 3.58; Gray's P = 0.02). Severe adverse events (SAEs) (≥grade 3) occurred in 4 (29%) and 23 (56%) of participants receiving the high versus standard titer, respectively, by day 28 (risk ratio, 0.51; 95% CI, 0.21 to 1.22; Fisher's P = 0.12). There were no observed treatment-related AEs. (This study has been registered at ClinicalTrials.gov under registration no. NCT04524507). IMPORTANCE In this study, in a high-risk population of patients admitted for COVID-19, we found an earlier time to hospital discharge among participants receiving CCP with nAb titers of >1:640 compared with participants receiving CCP with a lower nAb titer and no CCP-related AEs. The significance of our research is in identifying a dose response of CCP and clinical outcomes based on nAb titer. Although limited by a small study size, these findings support further study of high-nAb-titer CCP defined as >1:640 in the treatment of COVID-19.

Ethnoracial Disparities in SARS-CoV-2 Seroprevalence in a Large Cohort of Individuals in Central North Carolina from April to December 2020.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths around the world within the past 2 years. Transmission within the United States has been heterogeneously distributed by geography and social factors with little data from North Carolina. Here, we describe results from a weekly cross-sectional study of 12,471 unique hospital remnant samples from 19 April to 26 December 2020 collected by four clinical sites within the University of North Carolina Health system, with a majority of samples from urban, outpatient populations in central North Carolina. We employed a Bayesian inference model to calculate SARS-CoV-2 spike protein immunoglobulin prevalence estimates and conditional odds ratios for seropositivity. Furthermore, we analyzed a subset of these seropositive samples for neutralizing antibodies. We observed an increase in seroprevalence from 2.9 (95% confidence interval [CI], 1.8 to 4.5) to 12.8 (95% CI, 10.6 to 15.2) over the course of the study. Latinx individuals had the highest odds ratio of SARS-CoV-2 exposure at 6.56 (95% CI, 4.66 to 9.44). Our findings aid in quantifying the degree of asymmetric SARS-CoV-2 exposure by ethnoracial grouping. We also find that 49% of a subset of seropositive individuals had detectable neutralizing antibodies, which was skewed toward those with recent respiratory infection symptoms. IMPORTANCE PCR-confirmed SARS-CoV-2 cases underestimate true prevalence. Few robust community-level SARS-CoV-2 ethnoracial and overall prevalence estimates have been published for North Carolina in 2020. Mortality has been concentrated among ethnoracial minorities and may result from a high likelihood of SARS-CoV-2 exposure, which we observe was particularly high among Latinx individuals in North Carolina. Additionally, neutralizing antibody titers are a known correlate of protection. Our observation that development of SARS-CoV-2 neutralizing antibodies may be inconsistent and dependent on severity of symptoms makes vaccination a high priority despite prior exposure.

SARS-CoV-2 seroprevalence and risk factors among meat packing, produce processing, and farm workers.

Meat packing, produce processing, and farm workers are known to have an elevated risk of COVID-19, but occupational risk factors in this population are unclear. We performed an observational cohort study of meat packing, produce processing, and farm workers in North Carolina in fall 2020. Blood, saliva, and nasal turbinate samples were collected to assess for SARS-CoV-2 seropositivity. Risk factors for SARS-CoV-2 seropositivity were investigated using chi-square tests, two-sample t-tests, and adjusted risk ratio analyses. Among 118 enrolled workers, the baseline SARS-CoV-2 seroprevalence was 50.0%. Meat packing plant workers had the highest SARS-CoV-2 seroprevalence (64.6%), followed by farm workers (45.0%) and produce processing workers (10.0%), despite similar sociodemographic characteristics. Compared to SARS-CoV-2 seronegative workers, seropositive workers were more likely to work in loud environments that necessitated yelling to communicate (RR: 1.83, 95% CI: 1.25-2.69), work in cold environments (RR: 1.58, 95% CI: 1.12-2.24), or continue working despite developing symptoms at work (RR: 1.63, 95% CI: 1.14-2.32). After adjusting for age and working despite symptoms, high occupational noise levels were associated with a 1.72 times higher risk of SARS-CoV-2 seropositivity (95% CI: 1.16-2.55). Half of food processing workers showed evidence of past SARS-CoV-2 infection, a prevalence five times higher than most of the United States population at the time of the study. Work environments with loud ambient noise may pose elevated risks for SARS-CoV-2 transmission. Our findings also highlight the disproportionate burden of COVID-19 among underserved and economically disadvantaged Latinx communities in the United States.

Sex Disparities and Neutralizing-Antibody Durability to SARS-CoV-2 Infection in Convalescent Individuals.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2 months after infection or the reason for the discrepancy in COVID-19 disease and sex. Using convalescent-phase sera collected from 101 COVID-19-recovered individuals 21 to 212 days after symptom onset with 48 additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations of individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to 6 months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex and in individuals with cardiometabolic comorbidities. IMPORTANCE In this study, we found that neutralizing antibody responses in COVID-19-convalescent individuals vary in magnitude but are durable and correlate well with receptor binding domain (RBD) Ig binding antibody levels compared to other SARS-CoV-2 antigen responses. In our cohort, higher neutralizing antibody titers are independently and significantly associated with male sex compared to female sex. We also show for the first time that higher convalescent antibody titers in male donors are associated with increased age and symptom grade. Furthermore, cardiometabolic comorbidities are associated with higher antibody titers independently of sex. Here, we present an in-depth evaluation of serologic, demographic, and clinical correlates of functional antibody responses and durability to SARS-CoV-2 which supports the growing literature on sex discrepancies regarding COVID-19 disease morbidity and mortality, as well as functional neutralizing antibody responses to SARS-CoV-2.

Sex disparities and neutralizing antibody durability to SARS-CoV-2 infection in convalescent individuals.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now caused over 2 million deaths worldwide and continues to expand. Currently, much is unknown about functionally neutralizing human antibody responses and durability to SARS-CoV-2. Using convalescent sera collected from 101 COVID-19 recovered individuals 21-212 days after symptom onset with forty-eight additional longitudinal samples, we measured functionality and durability of serum antibodies. We also evaluated associations between individual demographic and clinical parameters with functional neutralizing antibody responses to COVID-19. We found robust antibody durability out to six months, as well as significant positive associations with the magnitude of the neutralizing antibody response and male sex. We also show that SARS-CoV-2 convalescent neutralizing antibodies are higher in individuals with cardio-metabolic comorbidities.

Renal Transplantation Significantly Improves Autonomic Function with Normalization of Baroreflex Sensitivity as Early as Three-Month Post-transplantation.

The most common cause of mortality in chronic kidney disease patients is cardiovascular events. Cardiovascular autonomic dysfunction is likely to contribute high incidence of cardiovascular mortality, and in addition to adrenergic overdrive in these patients, there is the presence of impaired reflex control of both sympathetic and parasympathetic outflow to the heart and vasculature. Very few studies are available which show that renal transplantation (RT) improves the baroreflex function along with improvement in cardiovascular variability parameters. This prospective study was designed for the assessment of the autonomic function, i.e., heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) in end-stage renal disease (ESRD) patients before RT and three and six months after RT and to study the effects of RT on cardiac and vascular autonomic tone and on BRS. We studied 81 ESRD patients prospectively slated for RT but only 64 patients (mean age: 33 years) completed both three and six months visits after RT for autonomic function study. Patients were evaluated in detail clinically as well as routine biochemical parameters were done on every three visits. Baroreflex function was quantified by the sequence method. Assessment of short-term HRV and BPV were done using power spectrum analysis of RR intervals and systolic BP by frequency domain analysis. The parameters of HRV after RT showed significant changes in high-frequency domain measures six months post-RT but not in low frequency. HRV in total power was also statistically significant as early as three months postrenal transplant and remained at six months. The favorable effect of RT on decreasing BPV and improving BRS is seen by as early as three months.

Improvement in Pulse Wave Velocity and Baroreflex Sensitivity Three-and Six-Month Postrenal Transplantation.

Cardiovascular diseases are an important cause of mortality in end-stage renal disease (ESRD) and increased arterial stiffness and autonomic dysfunction have been proposed to explain part of this excess cardiovascular risk. This prospective study was designed with the aim of noninvasive assessment of the vascular function, i.e., arterial stiffness in the form of pulse wave velocity (PWV) and autonomic function in the form of baroreflex sensitivity (BRS) in ESRD patients before renal transplantation (RT) and three and six months after RT. The study was conducted in 64 patients of ESRD slated for RT in the Department of Nephrology and was being followed up during all three visits (pretransplant, three-, and six-month posttransplant). The period of patient recruitment and data collection lasted for approximately 1½ years. Although PWV did not show a significant change, the change in PWV was negatively correlated with baseline PWV, and it was statistically significant. The BRS after RT had a significant improvement as early as three months. The correlation between change in PWV and change in BRS postrenal transplant was not seen. RT improves BRS, but it is still unknown that it is through amelioration of arterial properties or neural components or/and a relative contribution of both. We suggest that the improvement in BRS postrenal transplant is probably because of the improvement in autonomic neural functions rather than the improvement in compliance of barosensitive regions of large arteries.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.

Reduced Baroreflex Sensitivity, Decreased Heart Rate Variability with Increased Arterial Stiffness in Predialysis.

High cardiovascular morbidity and mortality is observed in predialytic chronic kidney disease (CKD) patients. The underlying mechanism of cardiovascular dysfunction often remains unclear. The present study was designed to perform multiparametric assessment of baroreflex sensitivity (BRS), arterial stiffness indices, and cardiovascular variabilities (heart rate variability [HRV] and blood pressure variability [BPV]) together in predialytic CKD patients; compare it with normal healthy controls; and determine their relationships in predialytic nondiabetic CKD patients. Thirty CKD Stage 4 and 5 predialytic non-diabetic patients and 30 healthy controls were enrolled in the study. BRS was determined by spontaneous sequence method. Short-term HRV and BPV were assessed using 5 min beat-to-beat data of RR intervals and blood pressure by time domain and frequency domain analysis. Arterial stiffness indices - carotid-femoral pulse wave velocity (PWV) and augmentation index - were measured using SphygmoCor Vx device (AtCor Medical, Australia). Predialytic CKD patients had significantly low BRS, high PWV, and low HRV as compared to healthy controls. Independent predictors of reduced systolic BRS in predialytic CKD patient group on multiple regression analysis emerged to be increase in calcium-phosphate product, increase in BPV, and decrease in HRV. Predialytic nondiabetic CKD Stage 4 and 5 patients have poor hemodynamic profile (higher PWV, lower HRV, and reduced BRS) than healthy controls. Reduced HRV and altered calcium-phosphate homeostasis emerged to be significant independent predictors of reduced BRS.

Sequential, Autologous Hematopoietic Stem Cell Transplant Followed by Renal Transplant in Multiple Myeloma.

A 30-year-old female was symptomatic with headache, fatigue, and weakness since October 2011 and was told to have anemia. In January 2012, she was admitted outside with pulmonary edema. Investigations revealed advanced azotemia, anemia, and hypercalcemia. Urine showed 2 + proteins and 30-35 red blood cells. There was no history of oral ulcers, rash, Raynaud's phenomenon, or hemoptysis. She was evaluated for causes of rapidly progressive "renal failure." Hemolytic work-up; antinuclear antibody, double-stranded DNA, and anti-neutrophil cytoplasmic antibody were negative. Kidney biopsy was done and interpreted as acute interstitial nephritis with hyaline casts. She was started on hemodialysis and treated with steroids and cyclophosphamide. She came to our institute in January 2012. Investigations showed evidence of paraproteinemia with kappa restriction. Bone marrow showed 15% plasma cells. Kidney biopsy was reviewed and was diagnostic of cast nephropathy. She was treated with 6 monthly cycles of dexamethasone and bortezomib. She achieved complete remission in July 2012. Maintenance doses of bortezomib were continued until May 2014. Autologous bone marrow transplantation was performed on June 06, 2014. Monthly, bortezomib was continued till April 2015. Subsequently, workup for renal transplantation was started with her father as her donor. Test for sensitization was negative. Renal transplantation was done on January 1, 2016, with prednisolone, mycophenolate, and tacrolimus. She achieved a serum creatinine of 0.6 mg% on the 4th postoperative day. Thereafter, she continues to remain stable.

Comparison of outcomes between surgically placed and percutaneously placed peritoneal dialysis catheters: A retrospective study.

There is lack of adequate data on comparison of outcomes between percutaneously placed peritoneal dialysis (PD) catheters inserted by nephrologists and PD catheters placed by surgeons. The aim of this study is to retrospectively analyze the outcomes of PD catheters inserted by surgeons (by open surgical or laparoscopic technique) and compare them with those inserted by nephrologists among ESRD patients who underwent elective PD catheter insertions between January 2009 and December 2012. The primary outcome measure was the proportion of catheters removed because of primary nonfunction. The secondary outcome measures were catheter survival, patient survival, and incidence of complications of catheter insertion. A total of 143 PD catheter insertions (88 by surgeons and 55 by nephrologists) performed in 132 patients were considered for the analysis. The primary nonfunction rate of PD catheter insertions in both groups was comparable (18.2% and 7.3%, P = 0.08). Break-in period was shorter in Group N (p = <0.001). No differences were noted in patient or catheter survival. Percutaneously placed PD catheters performed by nephrologists have comparable outcomes with surgically placed PD catheters among selected cases and have the advantage of lower costs, avoidance of operation theater scheduling issues, smaller incision length, and shorter break-in period. Therefore, more nephrologists should acquire the expertise on percutaneous PD catheter placement as it leads to lesser waiting times and better utilization of PD.

Pegylated interferon monotherapy for hepatitis C virus infection in patients on hemodialysis: A single center study.

There is no published study from India on hepatitis C virus (HCV) treatment in dialysis patients. Patients on dialysis with HCV infection treated with pegylated interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV-polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month therapy while those with genotypes 2 and 3 were given 6 months therapy. Response was classified as per standard criteria of rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR), and sustained virological response (SVR). A total of 85 patients were treated. Mean age was 35.2 ± 10.5 (range 15-67) years, and 77.6% were males. HCV genotypes were 1 in 40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was 10(6) copies/mL. Mean liver biopsy grade was 4 ± 1.7 and stage 0.8 ± 0.8. Mean time from diagnosis of HCV infection and the treatment start was 10.7 ± 14.3 months. One patient died of unrelated illness, one was lost to follow-up, and three could not sustain treatment due to cost. Forty-three of the 80 (54%) patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like symptoms were seen in all patients. Sixty-four (80%) patients required increase in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment-limiting). Five patients developed tuberculosis, five bacterial pneumonia, and one bacterial knee monoarthritis. None of the patients developed depression. Our study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis patients with HCV infection. Therapy was well-tolerated with minimal side effects. There was no effect of viral genotype on response to therapy.

Idiopathic collapsing glomerulopathy: A clinicopathologic analysis of 30 cases.

Collapsing glomerulopathy (CG) is a distinct clinicopathologic entity associated with various infections, medications and acute ischemia. There have been few scattered reports of CG from India. This study aimed at evaluating the clinicopathologic features of idiopathic CG in Indian patients with comparison between adult-onset and childhood CG. This study included all cases of idiopathic CG diagnosed over a period of 4 years (2006-2009). Appropriate clinical details and laboratory findings were retrieved. Renal biopsies were reviewed and detailed pathologic features assessed. Statistical analysis was performed to compare various features between adult-onset and childhood CG. Over these 4 years, 30 cases of idiopathic CG were diagnosed. Of these, 11 were children. Childhood CG cases had longer duration of symptoms and lower serum urea and creatinine levels compared with adult patients. In renal histology, tubular atrophy and interstitial fibrosis was frequent in our cases. Pediatric cases of CG showed a higher proportion of segmental glomerulosclerosis. On clinical follow-up, nine of the 30 patients progressed to end-stage renal disease and these included two pediatric patients. Idiopathic CG is a significant cause of renal dysfunction in both pediatric and adult patients. Childhood and adult-onset CG differ in few clinicopathologic features. Early and accurate diagnosis of CG is imperative for appropriate management of these patients.

Multiple intracranial space-occupying lesions in a renal transplant recipient from an area endemic for tuberculosis (TB): TB vs. toxoplasmosis.

Renal transplant recipients may present with intracranial space-occupying lesions (SOLs) due to infections as well as a post-transplant lymphoproliferative disorder (PTLD). Here, we discuss a renal transplant recipient who presented with neurologic symptoms and magnetic resonance imaging (MRI) of the brain showed multiple focal SOLs. Tuberculosis (TB), toxoplasmosis, nocardiosis, fungal infections, and PTLD were considered in the differential diagnosis. MRI spectroscopy was suggestive of an infectious cause, such as toxoplasmosis or TB. Serologic tests using Toxoplasma were negative. A brain biopsy followed by immunohistochemical staining using Toxoplasma antibody demonstrated multiple intravascular cysts of toxoplasma. This case highlights the diagnostic dilemma in an immunocompromised patient with multiple focal brain lesions, especially in areas where TB is endemic.

Oxidative stress, endothelial function, carotid artery intimal thickness and their correlates among chronic peritoneal dialysis patients.

We evaluated important nontraditional cardiovascular risk factors, endothelial function and oxidative stress (OS) among stable peritoneal dialysis (PD) patients. Their association with carotid intimal medial thickness (CIMT) was also assessed. Thirty-eight adult patients (13 diabetics, 20 males) on PD for >6 months and 15 age and sex-matched controls were studied. Duration of dialysis (DOD), residual urine output (UO), weekly Kt/V urea, detailed biochemical and lipid profile were noted. OS was measured by serum concentration of antioxidants; vitamin C and ferric reducing ability of plasma (FRAP) and pro-oxidant; thiobarbituric acid-reactive substances (TBARS). High-resolution ultrasonography was used to determine CIMT and flow-mediated dilatation of brachial artery [endothelium-dependent dilatation (EDD)] and dilatation subsequent to nitrate spray [endothelium-independent dilatation (EID)]. Mean age, DOD, UO and Kt/V of study population were 49.3 ± 11.6 years, 19.4 ± 11.8 months, 508.2 ± 422.9 ml/day and 1.73 ± 0.24, respectively. As compared to controls PD patients had higher CIMT (0.46 ± 0.05 vs 0.50 ± 0.07 mm, P = 0.003) and TBARS (1.5 ± 0.4 vs 5.1 ± 2.3 nM/ml, P < 0.001) but lower Vitamin C (1.7 ± 0.3 vs 0.6 ± 0.2 mg%, P < 0.001), FRAP (990.8 ± 78.1 vs 328.7 ± 183.5 µM/L, P < 0.001) and EDD (26.2 ± 5.4 vs 9.8 ± 4.6 %, P < 0.001). TBARS correlated positively with DOD and negatively with hemoglobin. Vitamin C and FRAP correlated positively with serum albumin. EDD correlated positively with UO, Kt/V and hemoglobin. CIMT correlated negatively with Kt/V and hemoglobin. Among themselves CIMT correlated negatively with EDD and vitamin C. EDD correlated positively with vitamin C, while FRAP correlated positively with vitamin C and negatively with TBARS. PD patients have higher OS, poorer endothelial function and higher structural atherosclerosis. These parameters are closely linked to each other, hemoglobin, DOD, residual UO, serum albumin and small solute clearances.