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103


Understanding the Relationship Between Antiviral Prescription Data and COVID-19 Incidence in New York City: A Retrospective Cohort Study

Kaul, Christina M; Cohen, Gabriel M; Silverstein, Matthew; Wallach, Andrew B; Diago-Navarro, Elizabeth; Holzman, Robert S; Foote, Mary K
The coronavirus disease 2019 (COVID-19) pandemic has caused more than 675 million confirmed cases and nearly 7 million deaths worldwide [1]. While testing for COVID-19 was initially centered in health care facilities, with required reporting to health departments, it is increasingly being performed in the home with rapid antigen testing [2]. Most at-home tests are self-interpreted and not reported to a provider or health department, which could lead to delayed reporting or underreporting of cases [3]. As such, there is a strong possibility that reported cases may become a less reliable indicator of transmission over time.
PMCID:10270561
PMID: 37333721
ISSN: 2328-8957
CID: 5518382

Effect of Vancomycin on the Gut Microbiome and Plasma Concentrations of Gut-Derived Uremic Solutes

Nazzal, Lama; Soiefer, Leland; Chang, Michelle; Tamizuddin, Farah; Schatoff, Daria; Cofer, Lucas; Aguero-Rosenfeld, Maria E; Matalon, Albert; Meijers, Bjorn; Holzman, Robert; Lowenstein, Jerome
Introduction/UNASSIGNED:Declining renal function results in the accumulation of solutes normally excreted by healthy kidneys. Data suggest that some of the protein-bound solutes mediate accelerated cardiovascular disease. Many of the poorly dialyzable protein-bound uremic retention solutes are products of gut bacterial metabolism. Methods/UNASSIGNED:We performed a blinded-randomized controlled trial comparing the changes in plasma concentrations of a panel of protein-bound solutes and microbiome structure in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 12 weeks in a cohort of stable patients with end-stage kidney disease. We also examined the pattern of recovery of the solutes and gut microbiome over 12 weeks of placebo administration following vancomycin. Results/UNASSIGNED:. We demonstrated microbiome recovery after stopping vancomycin. However, recovery in the solutes was highly variable between subjects. Conclusions/UNASSIGNED:We demonstrated that microbiome suppression using vancomycin resulted in changes in multiple gut-derived uremic solutes. Future studies are needed to address whether reduction in those uremic solutes results in improvement of cardiovascular outcomes in ESKD patients.
PMCID:8343810
PMID: 34386661
ISSN: 2468-0249
CID: 4966092

Prevalence of Strongyloidiasis Among Cardiothoracic Organ Transplant Candidates in a Non-Endemic Region; A Single Center Experience with Universal Screening

Kottkamp, Angelica C; Filardo, Thomas D; Holzman, Robert S; Aguero-Rosenfield, Maria; Neumann, Henry J; Mehta, Sapna A
Disseminated strongyloidiasis and hyperinfection syndrome can cause significant morbidity and mortality after transplantation. Screening and treatment prior to transplantation can reduce or prevent this disease. Targeted screening of transplant candidates, based on assessed risk, fails to identify all who would benefit. We implemented universal serology-based screening for Strongyloides at our transplant center, located in a non-endemic area. Of 200 transplant candidates who were evaluated for cardiothoracic transplant from January 2018 to June 2019, 169 were screened serologically and 21 (12.4%) were seropositive. Among seropositive patients, 57% reported travel to an endemic region, 38% were born outside the USA, 38% had eosinophilia, 5% had history of gram-negative bacteremia. We estimate that universal screening for strongyloidiasis could identify an average of 17 additional candidates for preventive treatment for every 200 transplant candidates.
PMID: 33844416
ISSN: 1399-3062
CID: 4841002

Trends in Mortality From Human Immunodeficiency Virus Infection, 1984-2016: An Autopsy-Based Study

Nizami, Sobia; Morales, Cameron; Hu, Kelly; Holzman, Robert; Rapkiewicz, Amy
CONTEXT.—/UNASSIGNED:With increasing use and efficacy of antiretroviral therapy for human immunodeficiency virus (HIV) infection, deaths from acquired immunodeficiency syndrome (AIDS)-defining conditions have decreased. OBJECTIVE.—/UNASSIGNED:To examine trends in the cause of death of HIV-infected patients who underwent autopsy at a major New York City hospital from 1984 to 2016, a period including the major epochs of the AIDS epidemic. DESIGN.—/UNASSIGNED:Retrospective review of autopsy records and charts with modeling of trends by logistic regression using polynomial models. RESULTS.—/UNASSIGNED:< .001). CONCLUSIONS.—/UNASSIGNED:Despite limitations of autopsy studies, many trends in the evolution of the HIV/AIDS epidemic are readily discernable.
PMID: 31460770
ISSN: 1543-2165
CID: 4054442

The renal transport of hippurate and protein-bound solutes

Kumar, Rohit; Adiga, Avinash; Novack, Joshua; Etinger, Alex; Chinitz, Lawrence; Slater, James; de Loor, Henriette; Meijers, Bjorn; Holzman, Robert S; Lowenstein, Jerome
Measurement of the concentration of hippurate in the inferior vena cava and renal blood samples performed in 13 subjects with normal or near-normal serum creatinine concentrations confirmed the prediction that endogenous hippurate was cleared on a single pass through the kidney with the same avidity as that reported for infused para-amino hippurate. This suggests that a timed urine collection without infusion would provide a measure of effective renal plasma flow. Comparison of the arteriovenous concentration differences for a panel of protein-bound solutes identified solutes that were secreted by the renal tubule and solutes that were subjected to tubular reabsorption.
PMCID:7041931
PMID: 32097533
ISSN: 2051-817x
CID: 4324292

Potential use of sexually transmitted infection (STI) testing for expanding HIV pre-exposure prophylaxis (PREP) at an Urban Hospital Center [Meeting Abstract]

Pitts, R; Holzman, R; Greene, R; Lam, E; Carmody, E; Braithwaite, S
Background. Despite the high efficacy of PrEP, it continues to be underutilized. We examined the extent to which patients with a documented positive test for STIs were provided PrEP at an urban municipal medical center. Methods. We reviewed data of all patients seen between January 1, 2014 and July 30, 2017 who were > 18 years old and had an initial HIV negative test and >=1 positive test for Chlamydia, Gonorrhea, or Syphilis. We examined PrEP prescription data by gender, race/ethnicity, and clinic location. Differences between groups were compared using Chi-squared analysis and logistic regression. Results. Of 1,142 initially HIV- patients who were identified as having a positive STI result, 52% were female, 89% either Black or Hispanic, with a median age of 40 years (quartiles 30, 47). 58% had Medicare/Medicaid and 34% were self-pay or uninsured (Table 1). Only 25 (2.1%) of 1,142 patients who had >=1 STI test positive were prescribed PrEP. No women received PrEP. Whites (aOR: 21.7 [95% CI:4.4, 107, P < 0.001] and Hispanics (aOR:6.64 [95% CI:1.35, 32.8, P = 0.02] were both more likely to receive PrEP than Blacks, after adjusting for age, sex, marital status, and insurance. All PrEP prescriptions originated from the Medicine, Emergency, or HIV specialty clinics although most STI testing was obtained in Emergency and Obstetrical/Gynecological clinics (Table 2). Conclusion. There were significant missed opportunities for HIV prevention among patients with STIs within the medical center, particularly among Hispanic and Black patients. Enrichment programs to educate providers and increase PrEP prescriptions may have a major impact on expanding HIV prevention, especially for women. (Figure Presented)
EMBASE:629443563
ISSN: 2328-8957
CID: 4119272

The effect of isohydric hemodialysis on the binding and removal of uremic retention solutes

Etinger, Aleksey; Kumar, Sumit; Ackley, William; Soiefer, Leland; Chun, Jonathan; Singh, Prabjhot; Grossman, Eric; Matalon, Albert; Holzman, Robert S; Meijers, Bjorn; Lowenstein, Jerome
BACKGROUND:There is growing evidence that the accumulation of protein- bound uremic retention solutes, such as indoxyl sulfate, p-cresyl sulfate and kynurenic acid, play a role in the accelerated cardiovascular disease seen in patients undergoing chronic hemodialysis. Protein-binding, presumably to albumin, renders these solutes poor-dialyzable. We previously observed that the free fraction of indoxyl sulfate was markedly reduced at the end of hemodialysis. We hypothesized that solute binding might be pH-dependent and attributed the changes in free solute concentration to the higher serum pH observed at the end of standard hemodialysis with dialysis buffer bicarbonate concentration greater than 35 mmol/L. We observed that acidification of uremic plasma to pH 6 in vitro greatly increased the proportion of freeIS. METHODS:We tested our hypothesis by reducing the dialysate bicarbonate buffer concentration to 25 mmol/L for the initial half of the hemodialysis treatment ("isohydric dialysis"). Eight stable hemodialysis patients underwent "isohydric dialysis" for 90 minutes and then were switched to standard buffer (bicarbonate = 37mmol/L). A second dialysis, 2 days later, employed standard buffer throughout. RESULTS:We found a clearcut separation of blood pH and bicarbonate concentrations after 90 minutes of "isohydric dialysis" (pH = 7.37, bicarbonate = 22.4 mmol/L) and standard dialysis (pH = 7.49, bicarbonate = 29.0 mmol/L). Binding affinity varied widely among the 10 uremic retention solutes analyzed. Kynurenic acid (0.05 free), p-cresyl sulfate (0.12 free) and indoxyl sulfate (0.13 free) demonstrated the greatest degree of binding. Three solutes (indoxyl glucuronide, p-cresyl glucuronide, and phenyl glucuronide) were virtually unbound. Analysis of free and bound concentrations of uremic retention solutes confirmed our prediction that binding of solute is affected by pH. However, in a mixed models analysis, we found that the reduction in total uremic solute concentration during dialysis accounted for a greater proportion of the variation in free concentration, presumably an effect of saturation binding to albumin, than did the relatively small change in pH produced by isohydric dialysis. The effect of pH on binding appeared to be restricted to those solutes most highly protein-bound. The solutes most tightly bound exhibited the lowest dialyzer clearances. An increase in dialyzer clearance during isohydric and standard dialyses was statistically significant only for kynurenic acid. CONCLUSION/CONCLUSIONS:These findings provide evidence that the binding of uremic retention solutes is influenced by pH. The effect of reducing buffer bicarbonate concentration ("isohydric dialysis:"), though significant, was small but may be taken to suggest that further modification of dialysis technique that would expose blood to a greater decrease in pH would lead to a greater increase the free fraction of solute and enhance the efficacy of hemodialysis in the removal of highly protein-bound uremic retention solutes.
PMCID:5823377
PMID: 29470534
ISSN: 1932-6203
CID: 2964022

Correction: The effect of isohydric hemodialysis on the binding and removal of uremic retention solutes [Correction]

Etinger, Aleksey; Kumar, Sumit R; Ackley, William; Soiefer, Leland; Chun, Jonathan; Singh, Prabjhot; Grossman, Eric; Matalon, Albert; Holzman, Robert S; Meijers, Bjorn; Lowenstein, Jerome
[This corrects the article DOI: 10.1371/journal.pone.0192770.].
PMCID:6047821
PMID: 30011331
ISSN: 1932-6203
CID: 3217952

Effect of vancomycin on plasma concentration of uremic solutes [Meeting Abstract]

Soiefer, L R; Chang, M; Tamizuddin, F; Schatoff, D; Cofer, L; Matalon, A; Nazzal, L; Meijers, B; Holzman, R; Lowenstein, J
Background: Many uremic retention solutes are products of gut bacterial metabolism. Protein-binding renders these solutes poorly dialyzable. In a prior study we observed that a single dose of 250 mg of vancomycin, given by mouth, resulted in a significant (40%) decrease in the plasma concentration of indoxyl sulfate and p-cresyl sulfate over a period of one week. In this study we compared the changes in plasma concentration of a panel of protein-bound uremic retention solutes in response to the once-weekly oral administration of 250 mg of vancomycin or placebo over a period of 8 weeks.
Method(s): Eight subjects with chronic, stable ESRD on thrice-weekly hemodialysis via AV fistula in the River Renal Dialysis Unit in Bellevue Hospital, were randomized to two groups, utilizing a single-blinded procedure. Baseline plasma samples were collected prior to the initial dose of vancomycin or placebo and at weeks one, two, three, four, and eight. Uremic retention solutes were measured by MS-HPLC.
Result(s): Six of the eight uremic retention solutes (Table 1) demonstrated a significant decline in concentration over the eight week period of once-weekly vancomycin administration. The magnitude of the decline makes it more likely that gut production was reduced rather than renal excretion increased. Solute concentrations remained unchanged over the same period of placebo administration.
Conclusion(s): The significant decline in the plasma concentrations of multiple uremic retention solutes provides evidence of the importance of the gut microbiome in the generation of these solutes. The reduction in concentrations of indoxyl sulfate, p-cresyl sulfate, and kynurenic acid, recognized as likely uremic toxins, suggests that altering the gut microbiome might provide a valuable therapeutic strategy in the management of ESRD
EMBASE:633734138
ISSN: 1533-3450
CID: 4755842

Renal and dialytic clearances of uremic solutes [Meeting Abstract]

Lowenstein, J; Etinger, A; Slater, J; Meijers, B; Holzman, R
Background: Many uremic solutes are protein bound and removed by proximal tubular organic anion transporters (OATs) rather than filtration.
Method(s): In 4 subjects undergoing right heart catheterization, samples were obtained from the right renal vein and the inferior vena cava below the renal veins.Total and ultrafiltrate concentrations of uremic solutes were measured utilizing MS-HPLC.
Result(s): Renal extraction ratio (removal across the renal vascular bed) and renal excretion fraction (renal clearance of solute relative to creatinine) varied greatly. HA and PAG exhibited the highest renal extraction ratios and excretion fractions approximating values reported for para-amino-hippurate (PAH). The dialytic clearance of these solutes exhibited the same pattern but never exceeded estimated creatinine clearance. Highly bound solutes (IS, PCS) exhibited low renal extraction and low renal excretion fractions. KA was an anomaly. Though highly bound, renal extraction and excretion were higher than expected, possibly related to pKa or other unique properties of this solute.
Conclusion(s): The findings suggest that endogenous hippurate clearance might provide a measure of effective renal plasma flow. The finding that uremic retention solutes such as IS, PCS, and KA, known to bind to OAT receptors on vascular endothelium where they act as transcription factors, are also tightly bound to albumin suggests that protein binding serves to deliver solutes to receptors in a manner analogous to the delivery of hormones, bound to carrier proteins, from an endocrine source to distant receptors
EMBASE:633733782
ISSN: 1533-3450
CID: 4755862