Faculty Bibliography

IMPORTANCE/UNASSIGNED:Chronic pain is common among individuals with dialysis-dependent kidney failure. OBJECTIVE/UNASSIGNED:To evaluate the effectiveness of pain coping skills training (PCST), a cognitive behavioral intervention, on pain interference. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This multicenter randomized clinical trial of PCST vs usual care was conducted across 16 academic centers and 103 outpatient dialysis facilities in the US. Adults undergoing maintenance hemodialysis and experiencing chronic pain were randomly assigned to PCST or usual care in a 1:1 ratio. Participants were followed in the trial for 36 weeks. Enrollment began on January 4, 2021, and follow-up ended on December 21, 2023. INTERVENTIONS/UNASSIGNED:PCST consisting of 12 weekly coach-led sessions via video or telephone conferencing, followed by 12 weeks of daily interactive voice response sessions. Usual care had no trial-driven pain intervention. MAIN OUTCOMES/UNASSIGNED:The primary outcome was pain interference measured with the Brief Pain Inventory (BPI) Interference subscale (score range of 0-10, with higher scores indicating more pain interference). Secondary outcomes included pain intensity, pain catastrophizing, quality of life, depression, and anxiety. RESULTS/UNASSIGNED:A total of 643 participants (mean [SD] age, 60.3 [12.6] years; 288 [44.8%] female) were randomized, with 319 assigned to PCST and 324 assigned to usual care. At week 12 (primary end point), the PCST group had a larger reduction in the BPI Interference score than the usual care group (between-group difference, -0.49; 95% CI, -0.85 to -0.12; P = .009). The effect persisted at week 24 (between-group difference in BPI Interference score, -0.48; 95% CI, -0.86 to -0.11) but was diminished at week 36 (between-group difference in BPI Interference score, -0.34; 95% CI, -0.72 to 0.04). A decrease in BPI Interference score greater than 1 point (minimal clinically important difference) occurred in 143 of 281 participants (50.9%) in the PCST group vs 108 of 295 participants (36.6%) in the usual care group at 12 weeks (odds ratio, 1.79; 95% CI, 1.28-2.49) and 142 of 258 participants (55.0%) in the PCST group vs 113 of 264 participants (42.8%) in the usual care group at 24 weeks (odds ratio, 1.59; 95% CI, 1.13-2.24). Favorable changes with PCST were also apparent for secondary outcomes of pain intensity, quality of life, depression, and anxiety at weeks 12 and/or 24, as well as for pain catastrophizing at weeks 24 and 36. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this randomized clinical trial of patients undergoing maintenance hemodialysis, PCST had benefits on pain interference and other pain-associated outcomes. While the effect on the overall cohort was of modest magnitude, the intervention resulted in a clinically meaningful improvement in pain interference for a substantial proportion of participants. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04571619.

The United States faces a shortage of primary care physicians. To address this, there have been pioneering efforts to develop accelerated pathways with a primary care focused curriculum for undergraduate medical education. The New York University Grossman Long Island School of Medicine (NYU GLISOM) was conceptualized as the first standalone, accelerated, tuition-free program in the US in over 100 years, with mission-centered curriculum on primary care and health system leadership. The aim of this article is to map the process for the development of a three-year integrated curriculum, describe the pedagogical approach that guided the design of the longitudinal courses, share the student and faculty's perspective about the curriculum, and describe the early outcomes of the first two graduate classes. A major key driver for curricular design is integrating longitudinal courses of Clinical Ambulatory Practice Experience (CAPE), Health Systems Science (HSS), and Learning Community - Social Sciences, Humanities, Ethics and Professionalism (LC-SHEP) over three years and active learning through Problem Based Learning (PBL). We have successfully operationalized an accelerated, standalone, integrated medical school curriculum mission-centered on primary care and health system leadership. Our outcomes reveal a higher percentage (76% N =45) of NYU GLISOM students entering primary care compared to national benchmarks. The integration of the longitudinal courses of HSS, LC-SHEP, and CAPE is a key pillar to reinforce the tenants of primary care and health system leadership. Focused interview of graduates from the pioneer cohort consistently stated that the longitudinal courses prepared them well for residency in primary care and as a health systems' change agent. Despite the challenges of an accelerated program, NYU GLISOM successfully integrated the longitudinal courses with optimal performance and achievement of educational program objectives. Our experience can serve as a model for innovation and design of an accelerated three-year primary care curriculum.

Idiopathic edema (IE) is a disease that occurs predominantly in women. It is characterized by increasing weight gain of >1.4 kg from morning to night, increasing edema, increasing truncal and abdominal girth with bloating when assuming an upright position and nocturia that is unrelated to menses. There is an increase in morbidity but not mortality. Increased capillary membrane leakage appears to be the underlying pathophysiologic abnormality that explains the myriad of clinical presentations. We present 2 cases of life-threatening complications of IE that resulted in seizures related to acute hyponatremia in one and extreme postural dizziness and fainting induced by postural hypotension in the other. The first patient was successfully treated with salt restriction, timely use of furosemide and limitation of water intake; the other was successfully treated by use of support hose. Treatment of these patients required a fundamental understanding of the intricate pathophysiological consequences of a leaky capillary membrane, an understanding of Starling forces and detailing the effectiveness of a low salt diet, use of diuretics and limited water intake in one and why support hose would be beneficial in the other patient. Both patients experienced significant physical and emotional benefits that substantially improved quality of life.

The subject of hyponatremia is undergoing significant changes after developing a more pathophysiologic approach that is superior to the ineffective volume approach and can more effectively identify the different causes of hyponatremia. This new approach identified cerebral salt wasting (CSW) in 24 (38%) of 62 hyponatremic patients from the medical wards of the hospital with 21 showing no evidence of cerebral disease to support our proposal to change CSW to renal salt wasting (RSW). RSW had to be differentiated from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) because of diametrically opposite therapeutic goals of water-restricting water-logged patients with SIADH or administering salt water to volume-depleted patients with RSW. Both syndromes present with identical clinical parameters that require a difficult protocol to make such a differentiation possible. We describe rat clearance studies demonstrating natriuretic activity in the plasma of patients with neurosurgical and Alzheimer diseases (AD) and eventually identify the protein as haptoglobin-related protein without signal peptide, which can serve as a biomarker to simplify diagnosis of RSW and delivery of the proper management to improve clinical outcomes. We also discuss the introduction of a new syndrome of RSW in AD and its implications. The high prevalence of RSW and identification of the natriuretic factor have created debates over the existence of RSW with none questioning or addressing the pathophysiologic data that identified patients with RSW. We also discuss the potentially large group of patients with RSW who are normonatremic.

The application of pathophysiologic tenets has created significant changes in our approach to hyponatremia and hyponatremia-related conditions. This new approach incorporated the determination of fractional excretion (FE) of urate before and after the correction of hyponatremia and the response to isotonic saline infusion to differentiate the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from renal salt wasting (RSW). FEurate simplified the identification of the different causes of hyponatremia, especially the diagnosis of a reset osmostat and Addison's disease. Differentiating SIADH from RSW has been extremely difficult because both syndromes present with identical clinical parameters, which could be overcome by successfully carrying out the difficult protocol of this new approach. A study of 62 hyponatremic patients from the general medical wards of the hospital identified 17 (27%) to have SIADH, 19 (31%) with reset osmostat, and 24 (38%) with RSW with 21 of these RSW patients presenting without clinical evidence of cerebral disease to warrant changing the nomenclature from cerebral to renal salt wasting. The natriuretic activity found in the plasma of 21 and 18 patients with neurosurgical and Alzheimer's disease, respectively, was later identified as haptoglobin-related protein without signal peptide (HPRWSP). The high prevalence of RSW creates a therapeutic dilemma of deciding whether to water-restrict water-logged patients with SIADH as compared to administering saline to volume-depleted patients with RSW. Future studies will hopefully achieve the following: 1. Abandon the ineffective volume approach; 2. Develop HPRWSP as a biomarker to identify hyponatremic and a projected large number of normonatremic patients at risk of developing RSW, including Alzheimer's disease; 3. Facilitate differentiating SIADH from RSW on the first encounter and improve clinical outcomes.

Our understanding of hyponatremic conditions has undergone major alterations. There is a tendency to treat all patients with hyponatremia because of common subtle symptoms that include unsteady gait that lead to increased falls and bone fractures and can progress to mental confusion, irritability, seizures, coma and even death. We describe a new approach that is superior to the ineffectual volume approach. Determination of fractional excretion (FE) of urate has simplified the diagnosis of a reset osmostat, Addison"™s disease, edematous causes such as congestive heart failure, cirrhosis and nephrosis, volume depletion from extrarenal salt losses with normal renal tubular function and the difficult task of differentiating the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from cerebral/renal salt wasting (C/RSW). SIADH and C/RSW have identical clinical and laboratory parameters but have diametrically opposite therapeutic goals of water-restricting water-loaded patients with SIADH or administering salt water to dehydrated patients with C/RSW. In a study of nonedematous patients with hyponatremia, we utilized FEurate and response to isotonic saline infusions to differentiate SIADH from C/RSW. Twenty-four (38%) of 62 hyponatremic patients had C/RSW with 21 having no clinical evidence of cerebral disease to support our important proposal to change cerebral to renal salt wasting (RSW). Seventeen (27%) had SIADH and 19 (31%) had a reset osmostat. One each from hydrochlorothiazide and Addison"™s disease. We demonstrated natriuretic activity in the plasma of patients with neurosurgical and Alzheimer diseases (AD) in rat clearance studies and have now identified the natriuretic protein to be haptoglobin related protein without signal peptide (HPRWSP). We introduce a new syndrome of RSW in AD that needs further confirmation. Future studies intend to develop HPRWSP as a biomarker to simplify the diagnosis of RSW in hyponatremic and normonatremic patients and explore other clinical applications that can improve clinical outcomes.

BACKGROUND:Idiopathic edema (IE), a disorder of females, is characterized by edema and weight gains exceeding 1.4 kg while assuming an upright position followed by nocturia and returning to a non-edematous baseline weight in the morning. There is no successful treatment of IE and the importance of nocturia needs to be emphasized. The major underlying abnormality is an increase in vascular membrane permeability (VMP). We present four cases with differing degrees of IE who were successfully managed by manipulating Starling's forces. While we could not alter the increase in VMP, manipulating oncotic and hydrostatic pressures between both compartments were untenable except to decrease intravascular hydrostatic pressure by sodium restriction. All four cases virtually eliminated daily weight gains and nocturia to improve quality of life considerably, two with the assistance of daily hydrochlorothiazide (HCTZ) and all four by furosemide to accelerate recovery from the weight gain to permit occasional dietary indiscretions to improve quality of life. Two cases with milder forms of IE did not quantify sodium intake as meticulously as cases one and four, who appeared to have greater increases in VMP. IE can be treated successfully by sodium restriction with or without use of HCTZ and furosemide to eliminate the distressing edema, weight gain and nocturia with marked improvement in emotional instability after understanding that the weight gains and nocturia were linked to dietary intake of sodium.

Background/UNASSIGNED:Patients on maintenance hemodialysis are particularly vulnerable to infection and hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to immunocompromised patients and the clustering that occurs in outpatient dialysis units, the seroprevalence of COVID-19 antibodies in this population is unknown and has significant implications for public health. Also, little is known about their risk factors for hospitalization. Methods/UNASSIGNED:nasopharyngeal, real-time, reverse-transcriptase PCR (RT-PCR); SARS-CoV-2 IgG seropositivity; hospitalization; and mortality. Results/UNASSIGNED:<0.001) compared with those who tested negative. Higher positivity rates were also observed among those who took taxis and ambulettes to and from dialysis, compared with those who used personal transportation. Antibodies were detected in all of the patients with a positive PCR result who underwent serologic testing. Of those that were seropositive, 32% were asymptomatic. The hospitalization rate on the basis of either antibody or PCR positivity was 35%, with a hospital mortality rate of 33%. Aside from COPD, no other variables were more prevalent in patients who were hospitalized. Conclusions/UNASSIGNED:We observed significant differences in rates of COVID-19 infection within three outpatient dialysis units, with universal seroconversion. Among patients with ESKD, rates of asymptomatic infection appear to be high, as do hospitalization and mortality rates.

PURPOSE OF REVIEW/OBJECTIVE:The topic of hyponatremia is in a state of flux. We review a new approach to diagnosis that is superior to previous methods. It simplifies identifying the causes of hyponatremia, the most important issue being the differentiation of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from cerebral/renal salt wasting (RSW). We also report on the high prevalence of RSW without cerebral disease in the general wards of the hospital. RECENT FINDINGS/RESULTS:We applied our new approach to hyponatremia by utilizing sound pathophysiologic criteria in 62 hyponatremic patients. Seventeen (27%) had SIADH, 19 (31%) had a reset osmostat, 24 (38%) had RSW with 21 having no evidence of cerebral disease, 1 had Addison's disease, and 1 was because of hydrochlorothiazide. Many had urine sodium concentrations (UNa) less than 30 mmol/l. SUMMARY/CONCLUSIONS:RSW is much more common than perceived in the general wards of the hospital. It is important to change the terminology from cerebral to RSW and to differentiate SIADH from RSW. These changes will improve clinical outcomes because of divergent therapeutic goals of water-restricting in SIADH and administering salt and water to a dehydrated patient with RSW. The present review will hopefully spur others to reflect and act on the new findings and different approaches to hyponatremia.

OBJECTIVE:Mycophenolate (MPA) and cyclosporin A (CsA) are two immunosuppressive agents currently used for the treatment of autoimmune diseases. However, reports regarding their effects on inflammation and lipid handling are controversial. Here, we compare the effect of these two drugs on the expression of proteins involved in cholesterol handling and lipid accumulation in a macrophage cell system utilizing M0, M1 and M2 human macrophages and in murine bone marrow-derived macrophages (BMDM). METHODS:. RESULTS:In M0 macrophages, MPA increased expression of ABCA1 and CXCL16 in a concentration-dependent manner. In M1 THP-1 macrophages, MPA caused a significant increase of 27-hydroxylase mRNA and CD36 and SR-A1 receptor mRNAs. Exposure of M2 macrophages to MPA also stimulated expression of 27-hydroxylase, while downregulating all evaluated scavenger receptors. In contrast, CsA had no impact on cholesterol efflux in M0 and M1 macrophages, but significantly augmented expression of ABCA1 and 27-hydroxylase in M2 macrophages. CsA significantly increased expression of the LOX1 receptor in naïve macrophages, downregulated expression of CD36 and SR-A1 in the M1 subpopulation and upregulated expression of all evaluated scavenger receptors. However, CsA enhanced foam cell transformation in M0 and M2 macrophages, while MPA had no effect on foam cell formation unless used at a high concentration in the M2 subtype. CONCLUSIONS:Our results clearly underline the importance of further evaluation of the effects of these drugs when used in atherosclerosis-prone patients with autoimmune or renal disease.