The role of socio-economic disparities in the relative success and persistence of SARS-CoV-2 variants in New York City in early 2021.

Socio-economic disparities were associated with disproportionate viral incidence between neighborhoods of New York City (NYC) during the first wave of SARS-CoV-2. We investigated how these disparities affected the co-circulation of SARS-CoV-2 variants during the second wave in NYC. We tested for correlation between the prevalence, in late 2020/early 2021, of Alpha, Iota, Iota with E484K mutation (Iota-E484K), and B.1-like genomes and pre-existing immunity (seropositivity) in NYC neighborhoods. In the context of varying seroprevalence we described socio-economic profiles of neighborhoods and performed migration and lineage persistence analyses using a Bayesian phylogeographical framework. Seropositivity was greater in areas with high poverty and a larger proportion of Black and Hispanic or Latino residents. Seropositivity was positively correlated with the proportion of Iota-E484K and Iota genomes, and negatively correlated with the proportion of Alpha and B.1-like genomes. The proportion of persisting Alpha lineages declined over time in locations with high seroprevalence, whereas the proportion of persisting Iota-E484K lineages remained the same in high seroprevalence areas. During the second wave, the geographic variation of standing immunity, due to disproportionate disease burden during the first wave of SARS-CoV-2 in NYC, allowed for the immune evasive Iota-E484K variant, but not the more transmissible Alpha variant, to circulate in locations with high pre-existing immunity.

HIV-1 transmission dynamics among people who inject drugs on the US/Mexico border during the COVID-19 pandemic: a prosepective cohort study.

Background: We examined HIV prevalence and transmission dynamics among people who inject drugs in the U.S./Mexico border region during the COVID-19 pandemic. Methods: People who inject drugs aged ≥18 years from 3 groups were recruited: people who inject drugs who live in San Diego (SD) and engaged in cross-border drug use in Tijuana, Mexico (SD CBDUs), and people who inject drugs in SD and Tijuana (TJ) who did not engage in cross-border drug use (NCBDUs). We computed HIV prevalence at baseline and bivariate incidence-density rates (IR) at 18-month follow-up. Bayesian phylogenetic analysis was used to identify local transmission clusters, estimate their age, and effective reproductive number (Re) over time within the clusters. Findings: At baseline (n = 612), 26% of participants were female, 9% engaged in sex work, and HIV prevalence was 8% (4% SD CBDU, 4% SD NCBDU, 16% TJ NCBDU). Nine HIV seroconversions occurred over 18 months, IR: 1.357 per 100 person-years (95% CI: 0.470, 2.243); 7 in TJ NCBDU and 2 in SD CBDU. Out of 16 identified phylogenetic clusters, 9 (56%) had sequences from both the U.S. and Mexico (mixed-country). The age of three youngest mixed-country dyads (2018-2021) overlapped with the COVID-related US-Mexico border closure in 2020. One large mixed-country cluster (N = 15) continued to grow during the border closure (Re = 4.8, 95% Highest Posterior Density (HPD) 1.5-9.1) with 47% engaging in sex work. Interpretation: Amidst the COVID-19 pandemic and the border closure, cross-border HIV clusters grew. Efforts to end the HIV epidemic in the U.S. should take into account cross-border HIV-1 transmission from Tijuana. Mobile harm reduction services and coordination with municipal HIV programs to initiate anti-retroviral therapy and pre-exposure prophylaxisis are needed to reduce transmission. Funding: This research was supported by the James B. Pendleton Charitable Trust and the San Diego Center for AIDS Research.

Scalable gradients enable Hamiltonian Monte Carlo sampling for phylodynamic inference under episodic birth-death-sampling models.

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number.

The Effect of Immunoglobulin G on the Humoral Immunity in Patients with Tuberculosis/HIV Coinfection.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/µCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

Novel enhancer mediates the RPL36A-HNRNPH2 readthrough loci and GLA gene expressions associated with fabry disease.

Fabry disease (FD) is a rare genetic condition caused by mutations in the GLA gene, located on the X chromosome in the RPL36-HNRNPH2 readthrough genomic region. This gene produces an enzyme called alpha-galactosidase A (α-Gal A). When the enzyme does not function properly due to the mutations, it causes harmful substances called globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) to build up in the body's lysosomes. This accumulation can damage the kidneys, heart, eyes, and nervous system. Recent studies have shown that the RPL36A-HNRNPH2 readthrough loci, which include RPL36A and HNRNPH2 genes, as well as the regulatory sequence known as the GLA-HNRNPH2 bidirectional promoter, may also play a role in FD. However, the involvement of enhancer RNAs (eRNAs) in FD is still poorly understood despite their known role in various diseases. To investigate this further, we studied an RPL36A enhancer called GH0XJ101390 and showed its genomic setting in the RPL36-HNRNPH2 readthrough region; the eRNA is rich in Homotypic Clusters of TFBSs (HCTs) type and hosts a CpG Island (CGI). To test the functional correlation further with GLA, RPL36A, and HNRNPH2, we used siRNAs to knock down GH0XJ101390 in human kidney embryonic cells 293T. The results showed a significant decrease in RPL36A and GLA expression and a non-significant decrease in HNRNPH2 expression. These findings could have important implications for understanding the regulatory mechanisms of GH0XJ101390 and its potential role in FD. A better understanding of these mechanisms may improve diagnostic and therapeutic methods for FD, which could ultimately benefit patients with this rare condition.

Scalable gradients enable Hamiltonian Monte Carlo sampling for phylodynamic inference under episodic birth-death-sampling models.

Birth-death models play a key role in phylodynamic analysis for their interpretation in terms of key epidemiological parameters. In particular, models with piecewise-constant rates varying at different epochs in time, to which we refer as episodic birth-death-sampling (EBDS) models, are valuable for their reflection of changing transmission dynamics over time. A challenge, however, that persists with current time-varying model inference procedures is their lack of computational efficiency. This limitation hinders the full utilization of these models in large-scale phylodynamic analyses, especially when dealing with high-dimensional parameter vectors that exhibit strong correlations. We present here a linear-time algorithm to compute the gradient of the birth-death model sampling density with respect to all time-varying parameters, and we implement this algorithm within a gradient-based Hamiltonian Monte Carlo (HMC) sampler to alleviate the computational burden of conducting inference under a wide variety of structures of, as well as priors for, EBDS processes. We assess this approach using three different real world data examples, including the HIV epidemic in Odesa, Ukraine, seasonal influenza A/H3N2 virus dynamics in New York state, America, and Ebola outbreak in West Africa. HMC sampling exhibits a substantial efficiency boost, delivering a 10- to 200-fold increase in minimum effective sample size per unit-time, in comparison to a Metropolis-Hastings-based approach. Additionally, we show the robustness of our implementation in both allowing for flexible prior choices and in modeling the transmission dynamics of various pathogens by accurately capturing the changing trend of viral effective reproductive number.

Change in Urinary Inflammatory Biomarkers and Psychological Health with Gut Microbiome Modulation after Six Months of a Lifestyle Modification Program in Children.

Background: Obesity is a metabolic disorder that negatively impacts the quality of life. Long-term methods such as exercise and low-fat diets can help regulate this health issue, but 93.3 million Americans continue to struggle. Our research investigates if lifestyle changes can affect urinary inflammation markers and psychological aspects through the modification of gut microbiome composition. Methods: Our study included 16 healthy controls with normal BMI as a comparison group and 22 overweight/obese (OW/OB) adolescents. We collected demographic, clinical, psychological, stool, and urine sample data at enrollment and six months after implementing lifestyle modifications. Bacterial genomic data and inflammatory markers in these samples were analyzed. Results: The lifestyle interventions were associated with decreased inflammation and enhanced mental health among overweight teens. We observed differences in bacterial community compositions between healthy participants and those who underwent treatment, including exercise and dietary habit adjustments, although there was no significant change in bacterial species richness. Mental health correlated with gut microbiota compositions without any demographic influences. The research also uncovered connections between inflammatory markers, psychological factors, and gut microbiota phyla through carbohydrate metabolism alterations. Conclusion: Our findings demonstrate that lifestyle modifications are associated with improved mental health and a reduction in inflammation in overweight adolescents by adjusting the gut microbiota composition.

Will the Russian war in Ukraine unleash larger epidemics of HIV, TB and associated conditions and diseases in Ukraine?

The Russian war in Ukraine poses many risks for the spread of HIV, TB and associated conditions, including possible increases in the numbers of people who inject drugs or engage in sex work in the years ahead. Ukrainian civil society and volunteer efforts have been able to maintain and at times expand services for HIV Key Populations. The extent of mutual-aid and volunteer efforts as well as the continued strength and vitality of harm reduction organizations such as the Alliance for Public Health and the rest of civil society will be crucial resources for postwar efforts to assist Key Populations and prevent the spread of HIV, TB and other diseases. The postwar period will pose great economic and political difficulties for Ukrainians, including large populations of people physically and/or psychically damaged and in pain who might become people who inject drugs. Local and international support for public health and for harm reduction will be needed to prevent potentially large-scale increases in infectious disease and related mortality.

The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2.

The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 has led to increased sampling of related sarbecoviruses circulating primarily in horseshoe bats. These viruses undergo frequent recombination and exhibit spatial structuring across Asia. Employing recombination-aware phylogenetic inference on bat sarbecoviruses, we find that the closest-inferred bat virus ancestors of SARS-CoV and SARS-CoV-2 existed just ~1-3 years prior to their emergence in humans. Phylogeographic analyses examining the movement of related sarbecoviruses demonstrate that they traveled at similar rates to their horseshoe bat hosts and have been circulating for thousands of years in Asia. The closest-inferred bat virus ancestor of SARS-CoV likely circulated in western China, and that of SARS-CoV-2 likely circulated in a region comprising southwest China and northern Laos, both a substantial distance from where they emerged. This distance and recency indicate that the direct ancestors of SARS-CoV and SARS-CoV-2 could not have reached their respective sites of emergence via the bat reservoir alone. Our recombination-aware dating and phylogeographic analyses reveal a more accurate inference of evolutionary history than performing only whole-genome or single gene analyses. These results can guide future sampling efforts and demonstrate that viral genomic fragments extremely closely related to SARS-CoV and SARS-CoV-2 were circulating in horseshoe bats, confirming their importance as the reservoir species for SARS viruses.

Hepatitis C Virus in people with experience of injection drug use following their displacement to Southern Ukraine before 2020.

BACKGROUND: Due to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine. METHODS: In this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships. RESULTS: Between June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement. CONCLUSIONS: Locally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.

Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum IgA levels. High polygenic score for IgAN was associated with earlier onset of kidney failure. In a comprehensive functional annotation analysis of candidate causal genes, we observed convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets.

Restorative yoga therapy for third-year medical students in pediatrics rotation: Working to improve medical student well-being.

BACKGROUND: Stress experienced by medical students is a well-documented and widespread phenomenon that may have physical and psychological effects on their well-being. One solution is to provide students with the tools to recognize and cope with stress. The aim of this study was to incorporate restorative yoga training-a well-recognized tool for stress reduction-in the third-year medical student pediatrics clerkship and assess the intervention's impact on students' well-being. MATERIALS AND METHOD: Restorative yoga, as a prospective intervention, was offered to third-year medical students at Texas Tech University Health Sciences Center during their pediatrics rotation. The study was between March and August 2020. Each yoga session lasted 45-minutes, once a week for six weeks. Participants completed anonymous questionnaires before and after the intervention via the Warwick-Edinburgh Mental Well-being Scale (WEMWBS). RESULT: Over the six-month study period, 25 (71%) of 35 medical students, having been given the option, chose to participate. The WEMWBS contains 14 statements on well-being, and all but one from the list showed a positive increase in average rating from pre intervention to post intervention. The statements "I've been feeling more relaxed" and "I've been thinking clearly" showed the greatest average increase. Following Chi-squared testing, two statements were found to be significantly different (P < 0.05) before intervention and after intervention: "I've been feeling more relaxed" and "I've been feeling good about myself." CONCLUSION: Students' well-being is paramount to medical schools. Restorative yoga offers hopeful outcomes for effective mitigation of the stresses of medical education and may be recommended for wider use.

Pregnancy History and Kidney Disease Progression Among Women Enrolled in Cure Glomerulonephropathy.

Introduction: Preeclampsia increases the risk for future chronic kidney disease (CKD). Among those diagnosed with CKD, it is unclear whether a prior history of preeclampsia, or other complications in pregnancy, negatively impact kidney disease progression. In this longitudinal analysis, we assessed kidney disease progression among women with glomerular disease with and without a history of a complicated pregnancy. Methods: Adult women enrolled in the Cure Glomerulonephropathy study (CureGN) were classified based on a history of a complicated pregnancy (defined by presence of worsening kidney function, proteinuria, or blood pressure; or a diagnosis of preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome), pregnancy without these complications, or no pregnancy history at CureGN enrollment. Linear mixed models were used to assess estimated glomerular filtration rate (eGFR) trajectories and urine protein-to-creatinine ratios (UPCRs) from enrollment. Results: Over a median follow-up period of 36 months, the adjusted decline in eGFR was greater in women with a history of a complicated pregnancy compared to those with uncomplicated or no pregnancies (-1.96 [-2.67, -1.26] vs. -0.80 [-1.19, -0.42] and -0.64 [-1.17, -0.11] ml/min per 1.73 m2 per year, P = 0.007). Proteinuria did not differ significantly over time. Among those with a complicated pregnancy history, eGFR slope did not differ by timing of first complicated pregnancy relative to glomerular disease diagnosis. Conclusions: A history of complicated pregnancy was associated with greater eGFR decline in the years following glomerulonephropathy (GN) diagnosis. A detailed obstetric history may inform counseling regarding disease progression in women with glomerular disease. Continued research is necessary to better understand pathophysiologic mechanisms by which complicated pregnancies contribute to glomerular disease progression.

Phylodynamics and migration data help describe HIV transmission dynamics in internally displaced people who inject drugs in Ukraine.

Internally displaced persons are often excluded from HIV molecular epidemiology surveillance due to structural, behavioral, and social barriers in access to treatment. We test a field-based molecular epidemiology framework to study HIV transmission dynamics in a hard-to-reach and highly stigmatized group, internally displaced people who inject drugs (IDPWIDs). We inform the framework by Nanopore generated HIV pol sequences and IDPWID migration history. In June-September 2020, we recruited 164 IDPWID in Odesa, Ukraine, and obtained 34 HIV sequences from HIV-infected participants. We aligned them to publicly available sequences (N = 359) from Odesa and IDPWID regions of origin and identified 7 phylogenetic clusters with at least 1 IDPWID. Using times to the most recent common ancestors of the identified clusters and times of IDPWID relocation to Odesa, we infer potential post-displacement transmission window when infections likely to happen to be between 10 and 21 months, not exceeding 4 years. Phylogeographic analysis of the sequence data shows that local people in Odesa disproportionally transmit HIV to the IDPWID community. Rapid transmissions post-displacement in the IDPWID community might be associated with slow progression along the HIV continuum of care: only 63% of IDPWID were aware of their status, 40% of those were in antiviral treatment, and 43% of those were virally suppressed. Such HIV molecular epidemiology investigations are feasible in transient and hard-to-reach communities and can help indicate best times for HIV preventive interventions. Our findings highlight the need to rapidly integrate Ukrainian IDPWID into prevention and treatment services following the dramatic escalation of the war in 2022.

Network-level HIV risk norms are associated with individual-level HIV risk and harm reduction behaviors among people who inject drugs: a latent profile analysis.

The COVID-19 related U.S.-Mexico border-crossing restrictions disrupted social networks and HIV harm reduction services among people who inject drugs (PWID) in San Diego and Tijuana. We assessed associations of descriptive network norms on PWID's HIV vulnerability during this period. Between 10/2020 and 10/2021, 399 PWID completed a behavioral and egocentric questionnaire. We used Latent Profile Analysis to categorize PWID into network norm risk profiles based on proportions of their network (n = 924 drug use alters) who injected drugs and engaged in cross-border drug use (CBDU), among other vulnerabilities. We used logistic and linear regressions to assess network profile associations with individual-level index of HIV vulnerability and harm reduction behaviors. Fit indices specified a 4-latent profile solution of descriptive network risk norms: lower (n = 178), moderate with (n = 34) and without (n = 94) CBDU and obtainment, and higher (n = 93). Participants in higher risk profiles reported more HIV vulnerability behaviors and fewer harm reduction behaviors. PWID's gradient of HIV risk was associated with network norms, warranting intervention on high-vulnerability networks when services are limited.

Racial and Ethnic Disparities in Acute Care Utilization Among Patients With Glomerular Disease.

RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. EXPOSURE: Race and ethnicity as a participant-reported social factor. OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits. ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. RESULTS: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. LIMITATIONS: We used proxies for SES and lacked direct information on income, household unemployment, or disability. CONCLUSIONS: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.

Left behind on the path to 90-90-90: understanding and responding to HIV among displaced people.

INTRODUCTION: In 2021, the number of people affected by displacement worldwide reached the highest on record, with an estimated 30.5 million refugees and 4.6 million asylum seekers seeking safety across international borders and further 53.2 million people displaced within their countries of origin. Most forcibly displaced persons come from or relocate to lower- and middle-income countries (LMICs) and many of those countries have large HIV epidemics. In this commentary, we describe some of the challenges at the intersection of HIV and displacement vulnerabilities that cannot be easily addressed in resource-limited environments. DISCUSSION: HIV transmission and prevention and treatment efforts in the context of displacement are affected by myriad behavioural, social and structural factors across different stages of the displacement journey. For example, structural barriers faced by people experiencing displacement in relation to HIV prevention and care include funding constraints and legal framework deficiencies. Such barriers prevent all forced migrants, and particularly those whose sexual identities or practices are stigmatized against, access to prevention and care equal to local residents. Xenophobia, racism and other social factors, as well as individual risky behaviours facilitated by experiences of forced migration, also affect the progress towards 90-90-90 targets in displaced populations. Current evidence suggests increased HIV vulnerability in the period before displacement due to the effect of displacement drivers on medical supplies and infrastructure. During and after displacement, substantial barriers to HIV testing exist, though following resettlement in stable displacement context, HIV incidence and viral suppression are reported to be similar to those of local populations. CONCLUSIONS: Experiences of often-marginalized displaced populations are diverse and depend on the context of displacement, countries of origin and resettlement, and the nature of the crises that forced these populations to move. To address current gaps in responses to HIV in displacement contexts, research in LMIC, particularly in less stable resettlement settings, needs to be scaled up. Furthermore, displaced populations need to be specifically addressed in national AIDS strategies and HIV surveillance systems. Finally, innovative technologies, such as point-of-care viral load and CD4 testing, need to be developed and introduced in settings facing displacement.

Clinical presentation and management of nephrotic syndrome in the first year of life: A report from the Pediatric Nephrology Research Consortium.

Background and objectives: Nephrotic syndrome (NS) in the first year of life is called congenital (CNS) if diagnosed between 0-3 months, or infantile (INS) if diagnosed between 3-12 months of age. The aim of this study was to determine if there were clinically meaningful differences between CNS and INS patients, regarding clinical presentation, management and outcomes. Design setting participants and measurements: Eleven Pediatric Nephrology Research Consortium sites participated in the study, using IRB-approved retrospective chart reviews of CNS and INS patients born between 1998 and 2019. Data were collected on patient characteristics, pertinent laboratory tests, provided therapy, timing of unilateral/bilateral nephrectomy and initiation of renal replacement therapy (RRT). Results: The study included 69 patients, 49 with CNS and 20 with INS, with a median age at diagnosis of 1 and 6 months, respectively. Management for the two groups was similar regarding nutrition, thyroxin supplementation, immunoglobulin administration, and thrombosis prophylaxis. Within the first 2 months after diagnosis, daily albumin infusions were used more often in CNS vs. INS patients (79 vs. 30%; p = 0.006), while weekly infusions were more common in INS patients (INS vs. CNS: 50 vs. 3%; p = 0.001). During the 6 months preceding RRT, albumin infusions were more frequently prescribed in CNS vs. INS (51 vs. 15%; p = 0.007). Nephrectomy was performed more often in CNS (78%) than in INS (50%; p = 0.02). End-stage kidney disease tended to be more common in children with CNS (80%) vs. INS (60%; p = 0.09). Conclusion: Compared to INS, patients with CNS had a more severe disease course, requiring more frequent albumin infusions, and earlier nephrectomy and RRT. Despite center-specific variations in patient care, 20-40% of these patients did not require nephrectomy or RRT.