Faculty Bibliography

Background/UNASSIGNED:Patients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse. Methods/UNASSIGNED:Patients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates. Results/UNASSIGNED:Of 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups. Conclusions/UNASSIGNED:In a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.

AbstractBackground and Objective.Ovarian cancer is usually diagnosed at an advanced stage, with most patients undergoing surgery followed by platinum- and taxane-based chemotherapy. After initial clinical remission, the majority recur, leading to additional treatments, including not only platinums and taxanes but also pegylated liposomal doxorubicin (PLD), gemcitabine, topotecan, and, more recently, bevacizumab, which may extend survival times. PLD, in particular, has been extensively studied by our group, with encouraging therapeutic results. We, however, observed instances of chronic kidney disease (CKD) developing among patients who received long-term treatment for recurrent ovarian cancer. To document the frequency and contributing factors to the emergence of CKD, we initiated a retrospective review at two institutions.Patients and Methods.Fifty-six consecutive patients with recurrent ovarian cancer receiving treatment at New York University Cancer Institute were reviewed for the presence of renal disease in 1997-2010. At Shaare Zedek Medical Center, 73 consecutive patients with ovarian cancer were reviewed in 2002-2010. Patients were diagnosed with CKD if they had an estimated GFR <60 mL/minute per 1.73 m(2) for >3 months and were staged according to the National Kidney Foundation guidelines.Results.Thirteen patients (23%) developed stage >/=3 CKD. Three patients had renal biopsies performed that showed thrombotic microangiopathy.Conclusions.CKD is emerging as a potential long-term consequence of current chemotherapy for recurrent ovarian cancer.

There have been only five reported cases of primary posttransplant T-cell lymphoma. We report the first case associated with the use of sirolimus (Rapamycin, Wyeth-Ayerst, Philadelphia, PA). The patient, receiving prednisone, cyclosporine, and sirolimus treatment, developed ascites, diarrhea, and weight loss 7 months after his second renal transplant. Tissue obtained at laparotomy established the diagnosis of primary T-cell lymphoma. Latent membrane protein-1 for Epstein-Barr virus was negative, but in-site hybridization test for Epstein-Barr-encoded RNA was positive. Despite aggressive chemotherapy, the patient died 8 months posttransplant. This is the sixth reported case of primary intestinal posttransplant T-cell lymphoma, but it is the first case associated with the use of sirolimus. The incidence of posttransplant lymphoproliferative disease in patients receiving sirolimus should be studied.

Increasing intracellular bicarbonate concentration ([HCO3-]i) inhibits calcium-mediated Cl- secretion in rat distal colon and T84 cells. We investigated the effect of [HCO3-]i on Cl- secretion in rat ileum. Segments of intact ileum from Sprague-Dawley rats were studied in Ussing chambers and villus and crypt intracellular pH and [HCO3-]i were determined using BCECF. A range of crypt and villus [HCO3-]i from 0 to 31 mM was obtained by varying Ringer's composition. Basal serosal-to-mucosal Cl- flux (JsmCl) averaged 8.5 +/- 0.2 mu eq.h-1.cm-2 and was unaffected by changing [HCO3-]i or serosal bumetanide. Carbachol increased JsmCl by 3.9 +/- 0.5 mu eq.h-1.cm-2 at [HCO3-]i = 0 mM but only by 1.0 +/- 0.3 mu eq.h-1.cm-2 at high crypt and villus [HCO3-]i. Dibutyryl-cAMP increased JsmCl by 2.5 +/- 0.2 mu eq.h-1.cm-2 at all [HCO3-]i. Carbachol and db-cAMP showed mutual antagonism at low [HCO3-]i and near-additivity at high [HCO3-]i. We conclude that like rat colon and T84 cells, calcium-mediated but not cAMP-mediated Cl- secretion in the ileum is inhibited by increasing [HCO3-]i. Mutual antagonism between carbachol and db-cAMP at low [HCO3-]i was present in ileum and distal colon but not in T84 cells