Faculty Bibliography

INTRODUCTION/BACKGROUND:Novel long-acting lipoglycopeptide antibiotics allow for the treatment and discharge of selected emergency department (ED) patients with cellulitis who require intravenous antibiotics. Telehealth systems have shown success in remote management of dermatologic conditions; we implemented a telehealth follow-up program for patients diagnosed with cellulitis in the ED, treated with single-dose dalbavancin, and discharged. METHODS:This was a prospective, multi-center observational study. Patients were included based on clinical criteria and ability to complete follow-up using a smartphone and enroll in an online care portal. We examined the rate of successful telehealth follow-up at 24- and 72-hour intervals from discharge. We also examined the ED return rate within 14 days, reviewed any visits to determine cause of return, and for admission. RESULTS:55 patients were enrolled. 54/55 patients completed at least one telehealth follow up encounter (98.2%). 13 patients (23.6%) had a return ED visit within 14 days; no patients required admission for worsening cellulitis. Patient engagement in the telehealth program decreased over time; there was an approximately 11% decrease in engagement between the 24 and 72-hour follow-up call, and a 15% decrease in engagement between the 24 and 72-hour image upload. Patients over 65 had a lower rate of image upload (31%) than younger patients (80.6%). DISCUSSION/CONCLUSIONS:A telehealth follow-up system for discharged emergency department patients with cellulitis demonstrated high rates of engagement. In these patients who -may have otherwise required admission for intravenous antibiotics, telehealth-facilitated outpatient management resulted in a low ED return rate and no inpatient admissions for cellulitis.

BACKGROUND: PCC (Kcentra(R)) is an Food and Drug Administration (FDA)-approved 4-factor PCC used for the treatment of warfarin-related coagulopathy (WRC), but it has also been used off-label to treat non-WRC. Three-factor PCC in the form of coagulation factor IX human (Bebulin(R)) has also been used for WRC and off-label to treat non-WRC. It is unclear whether the use of 3- or 4-factor PCCs is effective for the treatment of non-WRC,. OBJECTIVE: Our aim is to characterize the use of 3- and 4-factor PCCs for patients identified with a non-WRC. METHODS: A retrospective analysis of patients who received PCCs for both WRC and non-WRC between January 2012 and July 2015 was conducted. RESULTS: A total of 187 patients with elevated international normalized ratio (INR) who received PCCs were analyzed; 53.9% of patients in the WRC group and 27.7% in the non-WRC group corrected to an INR of 1.3 or less after 3- or 4-factor PCC administration. In those patients with non-WRC and who had underlying liver disease, 3- and 4-factor PCCs reduced mean INR by 0.98 and 1.43, respectively. CONCLUSION: Three and 4-factor PCCs can reduce INR in patients with WRC and in those with non-WRC secondary to liver disease.

Single nucleotide polymorphisms (SNPs) in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations. Women (n = 75) consumed 480 or 930 mg choline/day (22% as a metabolic tracer, choline-d9) for 10-12 weeks in a controlled feeding study. Genotyping was performed for eight variant SNPs and genetic differences in metabolic flux and partitioning of plasma choline metabolites were evaluated using stable isotope methodology. CHKA rs10791957, CHDH rs9001, CHDH rs12676, PEMT rs4646343, PEMT rs7946, FMO3 rs2266782, SLC44A1 rs7873937, and SLC44A1 rs3199966 altered the use of choline as a methyl donor; CHDH rs9001 and BHMT rs3733890 altered the partitioning of dietary choline between betaine and phosphatidylcholine synthesis via the cytidine diphosphate (CDP)-choline pathway; and CHKA rs10791957, CHDH rs12676, PEMT rs4646343, PEMT rs7946 and SLC44A1 rs7873937 altered the distribution of dietary choline between the CDP-choline and phosphatidylethanolamine N-methyltransferase (PEMT) denovo pathway. Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term.

Although single nucleotide polymorphisms (SNPs) in folate-mediated pathways predict susceptibility to choline deficiency during severe choline deprivation, it is unknown if effects persist at recommended intakes. Thus, we used stable isotope liquid chromatography-mass spectrometry (LC-MS) methodology to examine the impact of candidate SNPs on choline metabolism in a long-term, randomized, controlled feeding trial among pregnant, lactating, and nonpregnant (NP) women consuming 480 or 930 mg/d choline (22% as choline-d9, with d9 indicating a deuterated trimethyl amine group) and meeting folate-intake recommendations. Variants impairing folate metabolism, methylenetetrahydrofolate reductase (MTHFR) rs1801133, methionine synthase (MTR) rs1805087 [wild-type (WT)], MTR reductase (MTRR) rs1801394, and methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (MTHFD1) rs2236225, influenced choline dynamics, frequently through interactions with reproductive state and choline intake, with fewer genotypic alterations observed among pregnant women. Women with these variants partitioned more dietary choline toward phosphatidylcholine (PC) biosynthesis via the cytidine diphosphate (CDP)-choline pathway at the expense of betaine synthesis even when use of betaine as a methyl donor was increased. Choline intakes of 930 mg/d restored partitioning of dietary choline between betaine and CDP-PC among NP (MTHFR rs1801133 and MTR rs1805087 WT) and lactating (MTHFD1 rs2236225) women with risk genotypes. Overall, our findings indicate that loss-of-function variants in folate-metabolizing enzymes strain cellular PC production, possibly via impaired folate-dependent phosphatidylethanolamine-N-methyltransferase (PEMT)-PC synthesis, and suggest that women with these risk genotypes may benefit from choline intakes exceeding current recommendations.-Ganz, A. B., Shields, K., Fomin, V. G., Lopez, Y. S., Mohan, S., Lovesky, J., Chuang, J. C., Ganti, A., Carrier, B., Yan, J., Taeswuan, S., Cohen, V. V., Swersky, C. C., Stover, J. A., Vitiello, G. A., Malysheva, O. V., Mudrak, E., Caudill, M. A. Genetic impairments in folate enzymes increase dependence on dietary choline for phosphatidylcholine production at the expense of betaine synthesis.

BACKGROUND: The objectives of the present study were to report the incidence of pathologic T3a upstaging in a contemporary cohort of patients with clinical stage T1 (cT1) renal tumors treated with partial or radical nephrectomy; investigate the clinical outcomes; and identify the predictors associated with pathologic upstaging. MATERIALS AND METHODS: From a single-institution, institutional review board-approved renal tumor database of 945 patients, we identified 610 patients who had undergone surgery for a cT1 renal mass. Data for 494 patients were available for analysis. Of these, 66 lesions had been pathologically upstaged to T3a after surgery and 428 had not. The oncologic follow-up data and clinical and pathologic features were recorded, and multivariable logistic regression analysis was performed to identify the risk factors for pT3a upstaging, controlling for age, gender, body mass index, and nephrectomy type. RESULTS: The cT1 tumors of 66 patients (13.3%) were upstaged to pT3a after surgery. Of these 66 patients, 44 (66.7%) had undergone partial and 22 (33.3%) radical nephrectomy. The median follow-up period was 50 months. No patient with upstaging developed recurrence, and all were disease free at their last follow-up visit. On multivariable analysis, tumor size > 4 cm (odds ratio [OR], 3.766; 95% confidence interval [CI], 1.417-10.011; P < .008), clear cell histologic features (OR, 4.461; 95% CI, 1.498-13.461; P < .007), and positive surgical margins (hazard ratio, 5.118; 95% CI, 2.088-12.547; P < .0001) were associated with upstaging. CONCLUSION: Of the cT1 lesions in 66 patients, 13% were pathologically upstaged after surgery. The patients with larger tumors, clear cell histologic features, and positive surgical margins were at the greatest risk of upstaging. However, after an intermediate follow-up period, pathologic upstaging did not appear to result in worsened oncologic outcomes.

BACKGROUND: The purpose of this study was to describe the clinicopathologic characteristics and oncologic outcomes of patients who underwent nephrectomy for cystic renal masses. PATIENTS AND METHODS: Using an institutional review board-approved database, we retrospectively reviewed the clinical, pathologic, radiologic, and oncologic outcome data of patients who received nephrectomy for a complex cystic renal mass. RESULTS: Sixty-one patients were identified who received nephrectomy for a complex cystic lesion. Average age was 64 years. Thirty-nine (64%) patients were male. At the time of resection, 1 (1.6%), 3 (4.8%), 53 (86.8%), and 4 (6.5%) had a Bosniak category II, IIF, III, and IV cystic lesion, respectively. Nineteen (31.1%) patients were initially managed expectantly but underwent surgery because of progression of complexity on follow-up. Mean pathologic tumor size was 3.3 cm (range, 0.7-12 cm). Forty-eight (78.6%) of the lesions were found to be malignant. Thirty-seven (77.1%), 5 (10.4%), 4 (8.3%), and 2 (4.1%) were stage T1a, T1b, T2a, and T3a, respectively. Clear cell was the most common histologic subtype (44%), followed by papillary (21.3%), and unclassified RCC (4.9%). With a mean and median follow-up of 48.4 and 43.0 months, respectively, no patients developed a local or metastatic recurrence. All patients were alive at last follow-up. CONCLUSION: In our series with moderate follow-up, cystic RCCs do not appear to recur or progress regardless of size, histologic subtype, or grade. These findings suggest the malignant potential of cRCCs is significantly less than solid RCCs. Further investigation is required to determine if cRCCs should be classified and managed independently from solid RCCs.

OBJECTIVES: * To report the potency and oncological outcomes of patients undergoing robot-assisted radical prostatectomy (RARP) using a risk-stratified approach based on layers of periprostatic fascial dissection. * We also describe the surgical technique of complete hammock preservation or nerve sparing grade 1. PATIENTS AND METHODS: * This is a retrospective study of 2317 patients who had robotic prostatectomy by a single surgeon at a single institution between January 2005 and June 2010. * Included patients were those with >/= 1 year of follow-up and who were potent preoperatively, defined as having a sexual health inventory for men (SHIM) questionnaire score of >21; thus, the final number of patients in the study cohort was 1263. * Patients were categorized pre-operatively by a risk-stratified approach into risk grades 1-4, where risk grade 1 patients received nerve-sparing grade 1 or complete hammock preservation and so on for risk grades 2-4, as long as intraoperative findings permitted the planned nerve sparing. * We considered return to sexual function post-operatively by two criteria: i) ability to have successful intercourse (score of >/= 4 on question 2 of the SHIM) and ii) SHIM >21 or return to baseline sexual function. RESULTS: * There was a significant difference across different NS grades in terms of the percentages of patients who had intercourse and returned to baseline sexual function (P < 0.001), with those that underwent NS grade 1 having the highest rates (90.9% and 81.7%) as compared to NS grades 2 (81.4% and 74.3%), 3 (73.5% and 66.1%), and 4 (62% and 54.5%). * The overall positive surgical margin (PSM) rates for patients with NS grades 1, 2, 3, and 4 were 9.9%, 8.1%, 7.2%, and 8.7%, respectively (P = 0.636). * The extraprostatic extension rates were 11.6%, 14.3%, 29.3%, and 36.2%, respectively (P < 0.001). * Similarly, in patients younger than 60, intercourse and return to baseline sexual function rates were 94.9% and 84.3% for NS grade 1 as compared to 85.5% and 77.2% for NS grades 2, 76.9% and 69% for NS grades 3, and 64.8% and 57.7% for NS Grade 4 (P < 0.001). CONCLUSIONS: * The risk-stratified approach and anatomical technique of neural-hammock sparing described in the present manuscript was effective in improving potency outcomes of patients without compromising cancer control. * Patients with greater degrees of NS had higher rates of intercourse and return to baseline sexual function without an increase in PSM rates.