Faculty Bibliography

OBJECTIVE:Patients on ticagrelor undergoing cardiac surgery before completing guideline-recommended washout are at high risk for severe bleeding. This study evaluated whether a novel drug removal device reduces bleeding in patients operated within 2 days from ticagrelor discontinuation. METHODS:Eligible patients were randomized 1:1 to intraoperative DrugSorb-ATR or sham control. Primary safety endpoint was adverse events at 30 days. Efficacy was assessed by composite endpoints comprising bleeding events using Universal Definition of Perioperative Bleeding (UDPB) and 24-hour chest tube drainage (CTD) in the overall and isolated coronary artery bypass grafting (CABG) populations with a hierarchical win ratio (WR) method. RESULTS:140 patients were randomized, 132 had surgery and received a study device; 92% were isolated CABG. Mean age was 65±5 years, 15% females. The primary safety endpoint was met, with similar adverse events between groups. The primary efficacy endpoint was not met in the overall or CABG populations (WR 1.07, 95% CI 0.72-1.58, p=0.748; WR 1.33, 95% CI 0.86-2.04, p=0.202 respectively). The supplementary efficacy endpoint was met in the CABG population (WR 1.59, 95% CI 1.02-2.46, p=0.041) with significant reductions also shown in large CTD bleeding events (p=0.016) and the composite of severe bleeding events or CTD≥1L (p=0.041). The number needed to treat to prevent a severe bleed was 6. CONCLUSIONS:Intraoperative use of DrugSorb-ATR is safe in patients operated within 2 days of ticagrelor discontinuation. Although the primary endpoint was not met in the overall population there were significant reductions in severe bleeding events in the prespecified CABG population.

The digitization of health records and growing availability of tumour DNA sequencing provide an opportunity to study the determinants of cancer outcomes with unprecedented richness. Patient data are often stored in unstructured text and siloed datasets. Here we combine natural language processing annotations^1,2 with structured medication, patient-reported demographic, tumour registry and tumour genomic data from 24,950 patients at Memorial Sloan Kettering Cancer Center to generate a clinicogenomic, harmonized oncologic real-world dataset (MSK-CHORD). MSK-CHORD includes data for non-small-cell lung (n = 7,809), breast (n = 5,368), colorectal (n = 5,543), prostate (n = 3,211) and pancreatic (n = 3,109) cancers and enables discovery of clinicogenomic relationships not apparent in smaller datasets. Leveraging MSK-CHORD to train machine learning models to predict overall survival, we find that models including features derived from natural language processing, such as sites of disease, outperform those based on genomic data or stage alone as tested by cross-validation and an external, multi-institution dataset. By annotating 705,241 radiology reports, MSK-CHORD also uncovers predictors of metastasis to specific organ sites, including a relationship between SETD2 mutation and lower metastatic potential in immunotherapy-treated lung adenocarcinoma corroborated in independent datasets. We demonstrate the feasibility of automated annotation from unstructured notes and its utility in predicting patient outcomes. The resulting data are provided as a public resource for real-world oncologic research.

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.

OBJECTIVE: To study the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in lupus nephritis (LN) as a potential marker of injury and/or prognostic indicator for response to therapy. METHODS: mEPCR expression was analysed by immunohistochemistry in normal kidney and in 59 biopsies from 49 patients with LN. Clinical parameters were assessed at baseline, 6 months and 1 year. RESULTS: mEPCR was expressed in the medulla, arterial endothelium and cortical peritubular capillaries (PTCs) in all biopsies with LN but not in the cortical PTCs of normal kidney. Positive mEPCR staining in >25% of the PTCs was observed in 16/59 biopsies and associated with poor response to therapy. Eleven (84.6%) of 13 patients with positive staining for mEPCR in >25% of the PTCs and follow-up at 6 months did not respond to therapy, compared with 8/28 (28.6%) with mEPCR staining in < or =25% PTCs, P = 0.0018. At 1 year, 10 (83.3%) of 12 patients with positive mEPCR staining in >25% of the PTCs did not respond to therapy (with two progressing to end-stage renal disease) compared with 8/24 (33.3%) with positive staining in < or =25% of the PTCs, P = 0.0116. Although tubulo-interstitial damage (TID) was always accompanied by mEPCR, this endothelial marker was extensively expressed in the absence of TID suggesting that poor response could not be attributed solely to increased TID. mEPCR expression was independent of International Society of Nephrology/Renal Pathology Society class, activity and chronicity indices. CONCLUSION: Increased mEPCR expression in PTCs may represent a novel marker of poor response to therapy for LN

Acute renal failure is rarely the presenting manifestation of non-Hodgkin's lymphoma. Of the reported cases of renal insufficiency secondary to diffuse renal infiltration with lymphoma, few have presented with acute renal failure. We present a patient with acute renal failure secondary to diffuse bilateral renal infiltration by a B-cell non-Hodgkin's lymphoma. The findings of an elevated serum lactate dehydrogenase (LDH), lymphopenia, and homogenous bilateral renal enlargement on computed tomographic (CT) imaging were important in suggesting the diagnosis of primary renal lymphoma. Renal biopsy with immunohistochemical and ultrastructural analysis was instrumental in confirming this diagnosis

Pulmonary embolism is diagnosed by a mismatched perfusion-ventilation lung scan. The probability is increased further when there is an associated 'hot spot' in the perfusion study caused by focal pulmonary edema

We have examined the effects of antihypertensive therapy on glomerular dynamics and on the clinical and morphologic features of a model of nephrotoxic serum nephritis (NSN) in which hypertension occurs. NSN was induced in uninephrectomized male Sprague Dawley rats, which drank 0.9% sodium chloride ad libitum. One-half were assigned randomly to a treated group whose blood pressure was normalized on a regimen of reserpine, hydralazine, and hydrochlorothiazide. Hypertension continued throughout the 6 weeks of study in untreated rats (blood pressure 148 +/- 5 vs. 103 +/- 3 mm Hg in treated rats, P less than 0.01). Urinary protein excretion was greater (437 +/- 110 vs. 254 +/- 81 mg/24 hr, P less than 0.005), and serum albumin lower (1.6 +/- 0.4 vs. 2.9 +/- 0.3 g/dl, P less than 0.01) in hypertensive animals. Diffuse glomerular endo- and extracapillary proliferation and arteriolar medial hypertrophy were observed frequently in nephritic rats with untreated hypertension. By contrast, structural abnormalities were limited primarily to focal segmental proliferation involving fewer than one-third of glomeruli in the absence of vascular changes in treated normotensive rats. Micropuncture studies performed 8 to 16 days after induction of nephritis showed a reduction in glomerular capillary pressure (46 +/- 1 vs. 55 +/- 1 mm Hg, P less than 0.001), glomerular plasma flow rate (115 +/- 20 vs. 160 +/- 20 nl/min, P less than 0.01), and single nephron filtration rate (42 +/- 4 vs. 56 +/- 5 nl/min, P less than 0.001) with antihypertensive treatment, suggesting that a hemodynamic mechanism may have been responsible for enhanced glomerular injury in the hypertensive nephritic animals