A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma.

The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as "cytotoxic lymphocytes," or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma. We compared the efficacy of U.S. Food and Drug Administration (FDA)-approved PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab) and a newly developed PD-L1 inhibitor (H1A Ab) in eliciting cytotoxic function. CL activity was improved at 3 mo after radical nephrectomy compared with baseline, and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Treatment of PBMCs with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CLs, but a differential response was observed at the individual-patient level. H1A demonstrated superior efficacy in promoting CL activity compared with FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T and NK cells in H1A-treated PBMCs and immunosuppressive regulatory T cells in atezolizumab-treated samples. Our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor and the potential of measuring CTL activity in PBMCs as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma.

End-Stage Kidney Disease After Partial and Radical Nephrectomy Among Patients With Severe Chronic Kidney Disease.

PURPOSE: AUA guidelines prioritize nephron sparing in patients with preexisting chronic kidney disease (CKD). However, few studies analyze long-term renal function in patients with preoperative severe CKD who undergo extirpative renal surgery. Herein, we compare the hazard of progression to end-stage kidney disease (ESKD) following partial nephrectomy (PN) and radical nephrectomy (RN) among patients with preoperative severe CKD. MATERIALS AND METHODS: Patients with stage 4 CKD who underwent PN or RN from 1970 to 2018 were identified. A multivariable Fine-Gray subdistribution hazard model was employed to assess associations with progression to ESKD accounting for the competing risk of death. RESULTS: A total of 186 patients with stage 4 CKD underwent PN (n = 71; 38%) or RN (n = 115; 62%) for renal neoplasms with median follow-up of 6.9 years (interquartile range 3.8-14.1). On multivariable analyses adjusting for competing risk of death, the subdistribution hazard ratio (SHR) for older age at surgery (SHR for 5-year increase 0.81; 95% CI 0.73-0.91; P < .001) and higher preoperative estimated glomerular filtration rate (SHR for 5-unit increase 0.63; 95% CI 0.47-0.84; P = .002) was associated with lower hazard of progression to ESKD. There was no significant difference in hazard of ESKD between PN and RN (SHR 0.82; 95% CI 0.50-1.33; P = .4). CONCLUSIONS: Among patients with preoperative severe CKD, higher preoperative estimated glomerular filtration rate was associated with lower hazard of progression to ESKD after extirpative surgery for renal neoplasms. We did not observe a significant difference in overall hazard for developing ESKD between PN and RN.

Mayo Clinic Validation of the AUA Risk Groups for Localized Renal Cell Carcinoma.

PURPOSE: The AUA guidelines introduced a new risk group stratification system based primarily on tumor stage and grade to guide surveillance for patients treated surgically for localized renal cell carcinoma (RCC). We sought to evaluate the predictive ability of these risk groups using progression-free survival (PFS) and cancer-specific survival (CSS), and to compare their performance to that of our published institutional risk models. MATERIALS AND METHODS: We queried our Nephrectomy Registry to identify adults treated with radical or partial nephrectomy for unilateral, M0, clear cell RCC, or papillary RCC from 1980 to 2012. The AUA stratification does not apply to other RCC subtypes as tumor grading for other RCC, such as chromophobe, is not routinely performed. PFS and CSS were estimated using the Kaplan-Meier method. Predictive abilities were evaluated using C indexes from Cox proportional hazards regression models. RESULTS: A total of 3191 patients with clear cell RCC and 633 patients with papillary RCC were included. For patients with clear cell RCC, C indexes for the AUA risk groups and our model were 0.780 and 0.815, respectively (P < .001) for PFS, and 0.811 and 0.857, respectively (P < .001), for CSS. For patients with papillary RCC, C indexes for the AUA risk groups and our model were 0.775 and 0.751, respectively (P = .002) for PFS, and 0.830 and 0.803, respectively (P = .2) for CSS. CONCLUSIONS: The AUA stratification is a parsimonious system for categorizing RCC that provides C indexes of about 0.80 for PFS and CSS following surgery for localized clear cell and papillary RCC.

Current practices and opinions on auditory training in adult cochlear implant recipients.

OBJECTIVE: To examine current practices and opinions of cochlear implant (CI) providers with respect to post-implantation auditory training. METHODS: A survey was submitted to the American Cochlear Implant Alliance membership that reviewed current practice and opinions with respect to post-implantation auditory training for adult CI recipients. MAIN OUTCOME MEASURES: Review of respondent practice, center volume, role on CI team, and current usage and opinions surrounding auditory training, including resources used and schedule of use. RESULTS: Most (79 %) of the 79 CI providers surveyed reported working at academic centers, 34 % at high-volume centers (>150 CIs/year), and 38 % were surgeons. Nearly all (99 %) respondents recommend auditory training for new adult CI recipients. Just over half (52 %) provide auditory training resources to the patient in the form of a broad list of patient-directed exercises from which a patient could select. A specific training resource, generally a computer-based auditory training program (e.g., AngelSound™), is recommended to patients by 30 % of the respondents. Regarding timing of rehabilitation, median preferred start time was 0 months (interquartile range [IQR] 0-1) post-activation. Sessions were preferably performed for a median of 3 h per week (IQR 2-4) and continued for a median of 12 months (IQR 6-12). Recommendations for auditory training were fairly consistent between surgeon and non-surgeon providers and by center volume. Non-surgeons more often had specific recommendations on training resources, benefits of music, and training condition (e.g., contralateral ear plugged). CONCLUSIONS: Despite a lack of clinical guidelines for adult post-implantation auditory training, a cross-sectional survey of providers' current practices and opinions demonstrates that these services are widely recommended and regarded as valuable. Training is almost universally patient-directed and believed to be most beneficial if started soon after activation. Interestingly, specific recommendations for which training approaches to use are not common, suggesting a gap in provider knowledge of which resources are most efficacious.

The Impact of Metastasis Histopathology on Oncologic Outcomes for Patients With Surgically Resected Metastatic Renal Cell Carcinoma.

PURPOSE: Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma. However, the relative contribution of histopathological features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. MATERIALS AND METHODS: We studied 266 patients who had undergone nephrectomy between 1970 and 2019, and who had a single site of metastasis completely resected. Two versions of the metastatic clear cell renal cell carcinoma score published by Leibovich et al were calculated, using grade and necrosis from the primary tumor and using grade and necrosis from the metastasis. Predictive abilities of these 2 versions and a third model that included metastatic features only were compared using c-indexes from Cox proportional hazards models. RESULTS: A total of 197 patients died from renal cell carcinoma at a median of 2.3 years (IQR 1.1-4.5); median follow-up among survivors was 13.2 years (IQR 10.0-14.5). The Leibovich score using grade and necrosis from the metastasis (c=0.679) had similar predictive ability compared to the original Leibovich score using grade and necrosis from the primary tumor (c=0.675). A third model (c=0.707) demonstrated that metastasectomy within 2 years after nephrectomy, presence of bone metastasis, high grade, and sarcomatoid differentiation in the metastasis were significantly associated with cancer-specific survival. CONCLUSIONS: Scoring algorithms calculated using histopathological features of the metastasis can be used to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. These findings are of particular importance for instances when primary tumor histopathology is not readily available.

Effect of Dataset Size and Medical Image Modality on Convolutional Neural Network Model Performance for Automated Segmentation: A CT and MR Renal Tumor Imaging Study.

The aim of this study is to investigate the use of an exponential-plateau model to determine the required training dataset size that yields the maximum medical image segmentation performance. CT and MR images of patients with renal tumors acquired between 1997 and 2017 were retrospectively collected from our nephrectomy registry. Modality-based datasets of 50, 100, 150, 200, 250, and 300 images were assembled to train models with an 80-20 training-validation split evaluated against 50 randomly held out test set images. A third experiment using the KiTS21 dataset was also used to explore the effects of different model architectures. Exponential-plateau models were used to establish the relationship of dataset size to model generalizability performance. For segmenting non-neoplastic kidney regions on CT and MR imaging, our model yielded test Dice score plateaus of [Formula: see text] and [Formula: see text] with the number of training-validation images needed to reach the plateaus of 54 and 122, respectively. For segmenting CT and MR tumor regions, we modeled a test Dice score plateau of [Formula: see text] and [Formula: see text], with 125 and 389 training-validation images needed to reach the plateaus. For the KiTS21 dataset, the best Dice score plateaus for nn-UNet 2D and 3D architectures were [Formula: see text] and [Formula: see text] with number to reach performance plateau of 177 and 440. Our research validates that differing imaging modalities, target structures, and model architectures all affect the amount of training images required to reach a performance plateau. The modeling approach we developed will help future researchers determine for their experiments when additional training-validation images will likely not further improve model performance.

Electrical stimulation of the cochlea for treatment of chronic disabling tinnitus: an open-label trial towards the development of an implantable device.

BACKGROUND: Chronic tinnitus affects millions of people globally and constitutes the most commonly compensated disability among military service members in the United States. Existing treatment options largely surround helping patients cope with their disease as opposed to directly suppressing tinnitus perception. The current study investigated the efficacy of electrical stimulation of the cochlea on chronic disabling tinnitus. METHODS: In this single-arm, open-label clinical trial, 22 adult subjects with severe-range asymmetric or unilateral non-pulsatile tinnitus underwent electrical stimulation of the cochlea through use of an extra-cochlear electrode positioned on the cochlear promontory. Each subject underwent 3 stimulation treatments over 3 weeks at 7-day intervals. Tinnitus severity was determined by Tinnitus Handicap Inventory (THI), Tinnitus Functional Index (TFI), and Tinnitus Visual Analog Scale (VAS). Inclusion criteria required subjects have no worse than moderate sensorineural hearing loss determined by pre-enrollment audiometric testing. The primary outcome was nadir post-treatment THI scores, obtained at seven timepoints following electrical stimulation, with clinically significant improvement defined as a decrease of ≥ 7. RESULTS: All 22 (100%) subjects experienced clinically significant improvement in the THI during the study period with a mean decrease in scores of - 31 (95% CI - 38 to - 25) from a baseline of 48. Twenty (91%) experienced clinically significant improvement detectable on at least two of the three tinnitus survey instruments and 17 (77%) experienced clinically significant improvement detectable on all three survey instruments (i.e., THI, TFI, and VAS). Eight (36%) subjects reported either complete (THI of 0; n = 3) or near-complete (THI 1-4; n = 5) suppression of their tinnitus following a stimulation session. Thirteen (59%) subjects reported a nadir following stimulation at or below the threshold for "no or slight handicap" on the THI (≤ 16). No adverse events were observed. CONCLUSIONS: These findings establish the foundation for the development of an extra-cochlear implantable device that delivers electrical stimulation to the cochlea for the treatment of disabling tinnitus. For patients considering device implantation, trans-tympanic cochlear promontory stimulation can facilitate patient selection. Trial Registration ClinicalTrials.gov Identifier: NCT03759834. URL: https://clinicaltrials.gov/ct2/show/NCT03759834.

Unplanned Conversion From Partial to Radical Nephrectomy: An Analysis of Incidence, Etiology, and Risk Factors.

PURPOSE: Conversions from partial to radical nephrectomy are uncommon and reports on this topic are rare. In this study we present a detailed analysis of conversions from partial to radical nephrectomy in a single-institutional contemporary experience and provide an analysis of preoperative risk factors. MATERIALS AND METHODS: Patients who underwent converted (cases) and completed (controls) partial nephrectomy from 2000 to 2015 were matched 1:1 for analysis. Perioperative imaging was reviewed and RENAL (for radius, exophytic/endophytic properties, anterior/posterior descriptor, and location relative to the polar line) nephrometry scores were calculated. Reasons for conversions were abstracted from operative reports. Multivariable conditional logistic regression analyses were used to assess preoperative risk factors for conversion. RESULTS: A total of 168 cases (6.1% of all partial nephrectomies) were identified and matched on tumor size, year of surgery, and surgical approach to 168 controls. Conversion rates decreased from 13% in 2000-2003 to 4% in 2012-2015. Oncologic considerations, such as concern for upstaging and positive margins, were the most cited (56%) reasons for conversion. On multivariable analyses, male sex (odds ratio 2.34; P = .03), Charlson score (odds ratio per 1-unit increase: 1.28; P = .03), posterior and middle (on anteroposterior axis) location (reference: anterior, odds ratio 2.83, P = .02 and odds ratio 6.38, P < .001, respectively) and hilar location (reference: peripheral/central, odds ratio 5.61; P < .001) were associated with increased odds of conversion. CONCLUSIONS: Rates of conversion from partial to radical nephrectomy in our experience were low and decreased over time. Preoperative characteristics such as hilar, posterior, and middle locations were significantly associated with conversions after controlling for tumor size, and offer guidance for operative planning and patient counseling.

Harnessing the power of spaced repetition learning and active recall for trainee education in otolaryngology.

Medical education is rapidly evolving. The historical reliance on textbook reading is being increasingly replaced by trainees in favor of using non-traditional platforms such as podcasts, videos, and app-based learning. Neuroscience research on human learning has demonstrated superior long-term retention when the synergistic principles of spaced repetition and active recall are employed. Spaced repetition entails the repeated exposure to learned material over successive iterations, whereas active recall involves the intentional reconstructive process of retrieving previously learned material, often through prompting (e.g., answering open-ended questions without multiple choice answers), rather than passively reviewing previously learned information (e.g., re-reading a textbook chapter). These concepts have revolutionized medical student education, with use of open-source spaced repetition platforms, such as Anki, and question banks becoming ubiquitous. Paralleling educational platforms within otolaryngology are emerging. Headmirror's OtoRecall app provides a free, peer-reviewed, open-access option for otolaryngology trainees to harness the power of these learning principles.

Assessment of ED triage of anaphylaxis patients based on the Emergency Severity Index.

OBJECTIVES: To describe the emergency department (ED) triage of anaphylaxis patients based on the Emergency Severity Index (ESI), assess the association between ESI triage level and ED epinephrine administration, and determine characteristics associated with lower acuity triage ESI assignment (levels 3 and 4). METHODS: We conducted a cohort study of adult and pediatric anaphylaxis patients between September 2010 and September 2018 at an academic ED. Patient characteristics and management were compared between Emergency Severity Index (ESI) triage level 1 or 2 versus levels 3 or 4 using logistic regression analysis. We adhered to STROBE reporting guidelines. RESULTS: A total of 1090 patient visits were included. There were 26 (2%), 515 (47%), 489 (45%), and 60 (6%) visits that were assigned an ESI triage level of 1, 2, 3, and 4, respectively. Epinephrine was administered in the ED to 53% of patients triaged ESI level 1 or 2 and to 40% of patients triaged ESI level 3 or 4. Patients who were assigned a lower acuity ESI level of 3 or 4 had a longer median time from ED arrival to epinephrine administration compared to those with a higher acuity ESI level of 1 or 2 (28 min compared to 13 min, p < .001). A lower acuity ESI level was more likely to be assigned to visits with a chief concern of hives, rash, or pruritus (OR 2.33 [95% CI, 1.20-4.53]) and less likely to be assigned to visits among adults (OR, 0.43 [0.31-0.60]), patients who received epinephrine from emergency medical services (OR 0.56 [0.38-0.82]), presented with posterior pharyngeal or uvular angioedema (OR, 0.56 [0.38-0.82]), hypoxemia (OR, 0.34 [0.18-0.64]), or increased heart (OR 0.83 [0.73-0.95]) or respiratory (OR 0.70 [0.60-0.82]) rates. CONCLUSION: Patients triaged to lower acuity ESI levels experienced delays in ED epinephrine administration. Adult and pediatric patients with skin-related chief concerns were more likely to be to be assigned lower acuity ESI levels. Further studies are needed to identify interventions that will improve ED anaphylaxis triage.

Partial versus radical nephrectomy in clinical T2 renal masses.

OBJECTIVE: To report perioperative, renal functional and oncologic outcomes for patients undergoing partial or radical nephrectomy for cT2 renal masses. METHODS: Retrospective review of patients who underwent partial (n = 72) or radical nephrectomy (n = 379) for cT2 renal masses from 2000 to 2016. After propensity adjustment using inverse probability weighting, the following were compared by surgery (partial or radical nephrectomy): complications, renal function measured by estimated glomerular filtration rate as continuous and as <60 mL/min/1.73 m2 at 1 and 3 years postoperatively and overall, metastases-free survival and cancer-specific survival in patients with renal cell carcinoma. RESULTS: After propensity adjustment, clinical and radiographic features were well-balanced between groups. Overall and severe complications were more common for partial compared with radical nephrectomy, although not statistically significant (19 vs 13%, P = 0.14 and 4 vs 2%, P = 0.3, respectively). Estimated glomerular filtration rate change at 1 and 3 years was more pronounced in radical compared with partial nephrectomy (median -16 vs -5 and -14 vs -2, respectively, P < 0.001). A greater proportion of radical nephrectomy patients had an estimated glomerular filtration rate <60 at 1 and 3 years (55 vs 17% and 48 vs 17%, respectively, P < 0.01). In renal cell carcinoma patients, overall, metastases-free and cancer-specific survival were not significantly different between groups (median survivor follow up 7.1 years, interquartile range 3.6-11.4). CONCLUSIONS: Partial nephrectomy appears to be a relatively safe and a potentially effective treatment for cT2 renal masses, conferring better renal functional preservation compared with radical nephrectomy. These data support continued use of partial nephrectomy for renal masses >7 cm in appropriately selected patients.

Increased body mass index is associated with decreased imaging quality of point-of-care abdominal aortic ultrasonography.

BACKGROUND: Given that abdominal aorta is a retroperitoneal structure, increased body mass index (BMI) may have an adverse effect upon the quality of aortic ultrasonographic imaging. PURPOSE: To assess the hypothesis that increased BMI is associated with worsening point-of-care abdominal aortic ultrasonographic image quality. METHODS: This is a retrospective single-center study of point-of-care abdominal aortic ultrasound examinations performed in an academic emergency department (ED) with fellowship-trained emergency ultrasonography faculty performing quality assurance review. RESULTS: Mean ± SD BMI was 27.4 ± 6.2, among the 221 included records. The overall quality rating decreased as BMI increased (correlation coefficient - 0.24; P < .001) and this persisted after adjustment for age and sex (P < .001). Although BMI was higher on average in the records that were of insufficient quality for clinical decisions when compared with those of sufficient quality (mean BMI 28.7 vs 27.0), this did not reach statistical significance in a univariable setting (P = .11) or after adjusting for age and sex (P = .14). CONCLUSION: This study data shows a decrease in point-of-care abdominal aorta ultrasound imaging quality as BMI increases, though this difference did not result in a statistically significant impairment in achieving the minimum quality for clinical decisions. This finding may help ameliorate some clinician concerns about ultrasonography for patients with high BMI.

Complete Surgical Metastasectomy of Renal Cell Carcinoma in the Post-Cytokine Era.

PURPOSE: Data supporting complete metastasectomy of metastatic renal cell carcinoma were derived primarily from the era of cytokine therapy. Whether complete metastasectomy remains beneficial in patients who receive more recently approved systemic therapies has not been well studied. The objective of this study was to examine survival outcomes among patients treated with complete metastasectomy in the era of targeted therapy and checkpoint blockade availability. MATERIALS AND METHODS: We queried our institutional nephrectomy registry and identified 586 patients who underwent partial or radical nephrectomy of unilateral, sporadic renal cell carcinoma with a first occurrence of metastasis between 2006 and 2017. Of these patients 158 were treated with complete metastasectomy. Associations of complete metastasectomy with cancer specific and overall survival were assessed using Cox proportional hazards models. RESULTS: Median followup after the diagnosis of metastasis was 3.9 years, during which 403 patients died, including 345 of renal cell carcinoma. Of the patients treated with complete metastasectomy 147 (93%) did not receive any systemic treatment of the index metastatic lesion(s). Two-year cancer specific survival was significantly greater in patients with vs without complete metastasectomy (84% vs 54%, p <0.001). After adjusting for age, gender, and the timing, number and location of metastases complete metastasectomy was associated with a significantly reduced likelihood of death from renal cell carcinoma (HR 0.47, 95% CI 0.34-0.65, p <0.001). CONCLUSIONS: Complete surgical resection of metastases of renal cell carcinoma was associated with improved cancer specific survival in the post-cytokine era. It may be considered in appropriate patients after a process of shared decision making.

Effectiveness and safety of droperidol in a United States emergency department.

BACKGROUND: Droperidol is a dopamine receptor antagonist that functions as an analgesic, sedative, and antiemetic. In 2001, the U.S. Food and Drug Administration required a black box warning in response to case reports of QT prolongation and potential fatal arrhythmias. The aim of this study was to evaluate the effectiveness and safety of droperidol in patients presenting to a United States Emergency Department (ED). METHODS: Observational cohort study of all droperidol administrations from 1/1/2012 through 4/19/2018 at an academic ED. The primary endpoint was mortality within 24 h of droperidol administration. Secondary endpoint included use of rescue analgesics. RESULTS: A total of 6,881 visits by 5,784 patients received droperidol of whom 6,353 visits authorized use of their records for research, including 5.4% administrations in children and 8.2% in older adults (≥65). Droperidol was used as an analgesic for pain (N = 1,387, 21.8%) and headache (N = 3,622, 57.0%), as a sedative (N = 550, 8.7%), and as an antiemetic (N = 794, 12.5%). No deaths secondary to droperidol administration were recorded within 24 h. Need for rescue analgesia occurred in 5.2% of patients with headache (N = 188) and 7.4% of patients with pain (N = 102); 1.1% of patients with headache received rescue opioids (N = 38) after droperidol, as did 5.4% of patients with pain other than headache (N = 75). No patients had fatal arrhythmias. Akathisia occurred in 2.9%. CONCLUSION: No fatalities were seen among this large cohort of patients who received droperidol in the ED. Our findings suggest droperidol's effectiveness and safety when used as an analgesic, antiemetic and/or sedative.

Impact of scribes on throughput metrics and billing during an electronic medical record transition.

OBJECTIVE: Evaluate an established scribe program on throughput and revenue capture in an Emergency Department (ED) undergoing an EMR transition. METHODS: A prospective cohort design comparing patients managed with and without scribes in an academic ED. Throughput metrics (medians, min) and relative value units (RVUs, means) were collected. Data was evaluated in its entirety (three months), as well as in two subsets: go live (immediate two weeks) and adoption (two weeks post implementation to end). RESULTS: All patients: There was no significant difference in throughput or RVUs during the three month period. During go-live, scribes showed improvement in total RVUs per patient (4.63 vs 4.40, p = 0.048). During adoption, scribed patients had decreased length of stay (LOS, 221 vs 231, p = 0.023). Adults: Door to provider (28 vs 37, p = 0.014) and total RVUs (5.20 vs 4.92, p = 0.042) were improved with scribes in the go-live period. Scribes improved go-live morning and overnight shifts, while lengthening provider to disposition during afternoon shifts. No significant differences were seen in the adoption period, except for increased provider to disposition time overnight with scribes (154 vs 146, p = 0.030). Pediatrics: When all pediatric patients were compared, scribe patients had a decreased professional RVU charge (2.78 vs 2.90, p = 0.037). During go live and adoption, no significant differences were found in any other parameter or subgrouping. CONCLUSIONS: A scribe's ability to mitigate operational inefficiencies introduced by an EMR transition seems limited in an academic hospital. Previous research highlighting the impact of scribes on revenue was not replicated during this study.

Validation of the Elderly Risk Assessment Index in the Emergency Department.

OBJECTIVES: The Elderly Risk Assessment (ERA) score is a validated index for primary care patients that predict hospitalizations, mortality, and Emergency Department (ED) visits. The score incorporates age, prior hospital days, marital status, and comorbidities. Our aim was to validate the ERA score in ED patients. METHODS: Observational cohort study of patients age ≥ 60 presenting to an academic ED over a 1-year period. Regression analyses were performed for associations with outcomes (hospitalization, return visits and death). Medians, interquartile range (IQR), odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: The cohort included 27,397 visits among 18,607 patients. Median age 74 years (66-82), 48% were female and 59% were married. Patients from 54% of visits were admitted to the hospital, 16% returned to the ED within 30 days, and 18% died within one year. Higher ERA scores were associated with: hospital admission (score 10 [4-16] vs 5 [1-11], p < 0.0001), return visits (11 [5-17] vs 7 [2-13], p < 0.0001); and death within one year (14 [7-20] vs 6 [2-13], p < 0.0001). Patients with ERA score ≥ 16 were more likely to be admitted to the hospital, OR 2.14 (2.02-2.28, p < 0.0001), return within 30 days OR 1.99 (1.85-2.14), and to die within a year, OR 2.69 (2.54-2.85). CONCLUSION: The ERA score can be automatically calculated within the electronic health record and helps identify patients at increased risk of death, hospitalization and return ED visits. The ERA score can be applied to ED patients, and may help prognosticate the need for advanced care planning.

Timing and distribution of early renal cell carcinoma recurrences stratified by pathological nodal status in M0 patients at the time of nephrectomy.

OBJECTIVES: To evaluate the timing and distribution of first renal cell carcinoma metastasis after nephrectomy stratified by nodal status. METHODS: We evaluated patients treated with nephrectomy for sporadic, unilateral renal cell carcinoma between 1970 and 2011 who subsequently developed distant metastasis to three or fewer sites. Site-specific metastases-free 2-year survival rates were estimated using the Kaplan-Meier method. Associations of nodal status with time to metastasis were evaluated using multivariable Cox regression models. RESULTS: A total of 1049 patients met the inclusion criteria (135 pN1, 914 pN0/x patients). The median time to identification of first distant metastasis for pN1 patients was 0.4 years (interquartile range 0.2-1.1 years) versus 2.2 years (interquartile range 0.6-6.0 years) in pN0/x patients. The most common site of metastasis was to the lung, but this occurred earlier in pN1 patients (median 0.3 years vs 2.0 years). pN1 was associated with significantly lower site-specific 2-year metastases-free survival when compared with pN0/x for lung (37% vs 70%, P < 0.001), bone (63% vs 87%, P < 0.001), non-regional lymph nodes (60% vs 96%, P < 0.001) and liver metastases (79% vs 91%, P < 0.001). On multivariable analysis, pN1 status remained significantly associated with lung, bone, and non-regional lymph node (all P < 0.001) metastases, but it was no longer associated with liver metastases (P = 0.3). CONCLUSIONS: pN1 nodal status in M0 patients treated with nephrectomy for renal cell carcinoma is associated with more frequent early metastasis to sites conferring poor prognosis when compared with pN0/x. Our findings highlight the importance of rigorous, early surveillance though the multimodal use of a comprehensive history, physical, laboratory and radiological studies, as outlined in societal guidelines.

Increased body mass index does not impact the imaging quality of focused assessment with sonography in trauma.

BACKGROUND: Many clinicians believe that a patient's body mass index (BMI) affects the likelihood of obtaining high quality ultrasound images. OBJECTIVES: To assess the hypothesis that increased BMI is associated with worsening focused assessment with sonography in trauma (FAST) image quality. METHODS: We conducted a retrospective single-center study of FAST examinations performed in a large academic emergency department (ED) with fellowship-trained emergency ultrasonography faculty performing quality assurance review. RESULTS: Mean (SD) BMI was 28.0 (6.6) among the 302 included studies. The overall quality rating tended to decrease as BMI increased but did not achieve statistical significance in a univariable setting (P = .06) or after adjustment for age and sex (P = .06). Operators perception of image adequacy was largely unaffected by BMI, with the exception of the pericardial view. CONCLUSION: This study did not identify a statistically significant difference in FAST quality with increased BMI. This result may help assuage clinician concerns about ultrasonography for patients in the ED.

Patient Length of Stay Under the Two-Midnight Rule: Assessing the Accuracy of Providers' Predictions.

EXECUTIVE SUMMARY: We sought to determine emergency medicine physicians' accuracy in designating patients' disposition status as "inpatient" or "observation" at the time of hospital admission in the context of Medicare's Two-Midnight rule and to identify characteristics that may improve the providers' predictions. We conducted a 90-day observational study of emergency department (ED) admissions involving adults aged 65 years and older and assessed the accuracy of physicians' disposition decisions. Logistic regression models were fit to explore associations and predictors of disposition. A total of 2,257 patients 65 and older were admitted through the ED. The overall error rate in physician designation of observation or inpatient was 36%. Diagnoses most strongly associated with stays lasting less than two midnights included diverticulitis, syncope, and nonspecific chest pain. Diagnoses most strongly associated with stays lasting two or more midnights included orthopedic fractures, biliary tract disease, and back pain. ED physicians inaccurately predicted patient length of stay in more than one third of all patients. Under the Two-Midnight rule, these inaccurate predictions place hospitals at risk of underpayment and patients at risk of significant financial liability. Further work is needed to increase providers' awareness of the financial repercussions of their admission designations and to identify interventions that can improve prediction accuracy.

JAK2/PD-L1/PD-L2 (9p24.1) amplifications in renal cell carcinomas with sarcomatoid transformation: implications for clinical management.

Amplifications of JAK2, PD-L1, and PD-L2 at 9p24.1 lead to constitutive expression of PD-L1. This, coupled with JAK2-activation dependent upregulation of PD-L1 and adaptive/induced expression leads to higher tumor PD-L1 expression and immune evasion. Renal tumors were therefore evaluated for 9p24.1 amplifications. A combination of next generation sequencing-based copy number analysis, fluorescence in situ hybridization for JAK2/INSL6 and PD-L1/PD-L2 and immunohistochemistry for phospho-STAT3 (downstream target of JAK2), PD-L1, PD-L2, and PD-1 was performed. In this study we interrogated a "Discovery" cohort of 593 renal tumors, a "Validation" cohort of 398 high-grade renal tumors, The Cancer Genome Atlas (879 cases) and other public datasets (846 cases). 9p24.1 amplifications were significantly enriched in renal tumors with sarcomatoid transformation (5.95%, 15/252) when compared to all histologic subtypes in the combined "Discovery", "Validation" and public datasets (16/2636, 0.6%, p < 0.00001). Specifically, 9p24.1 amplifications amongst sarcomatoid tumors in public datasets, the "Discovery" and "Validation" cohorts were 7.7% (6/92), 15.1% (5/33), and 3.1% (4/127), respectively. Herein, we describe 13 cases and amplification status for these was characterized using next generation sequencing (n = 9) and/or fluorescence in situ hybridization (n = 10). Correlation with PD-L1 immunohistochemistry (n = 10) revealed constitutive expression (mean H-score: 222/300, n = 10). Analysis of outcomes based on PD-L1 expression in tumor cells performed on 282 cases ("Validation" cohort) did not reveal a significant prognostic effect and was likely reflective of advanced disease. A high incidence of constitutive PD-L1 expression in tumor cells in the "Validation" cohort (H-Score ≥250/300) was noted amongst 83 rhabdoid (6%) and 127 sarcomatoid renal tumors (7.1%). This suggests additional mechanisms of constitutive expression other than amplification events. Importantly, two patients with 9p24.1-amplified sarcomatoid renal tumors showed significant response to immunotherapy. In summary, a subset of renal tumors with sarcomatoid transformation exhibits constitutive PD-L1 overexpression and these patients should be evaluated for enhanced response to immunotherapy.