Implications of the Use of Artificial Intelligence Predictive Models in Health Care Settings : A Simulation Study.

BACKGROUND: Substantial effort has been directed toward demonstrating uses of predictive models in health care. However, implementation of these models into clinical practice may influence patient outcomes, which in turn are captured in electronic health record data. As a result, deployed models may affect the predictive ability of current and future models. OBJECTIVE: To estimate changes in predictive model performance with use through 3 common scenarios: model retraining, sequentially implementing 1 model after another, and intervening in response to a model when 2 are simultaneously implemented. DESIGN: Simulation of model implementation and use in critical care settings at various levels of intervention effectiveness and clinician adherence. Models were either trained or retrained after simulated implementation. SETTING: Admissions to the intensive care unit (ICU) at Mount Sinai Health System (New York, New York) and Beth Israel Deaconess Medical Center (Boston, Massachusetts). PATIENTS: 130 000 critical care admissions across both health systems. INTERVENTION: Across 3 scenarios, interventions were simulated at varying levels of clinician adherence and effectiveness. MEASUREMENTS: Statistical measures of performance, including threshold-independent (area under the curve) and threshold-dependent measures. RESULTS: At fixed 90% sensitivity, in scenario 1 a mortality prediction model lost 9% to 39% specificity after retraining once and in scenario 2 a mortality prediction model lost 8% to 15% specificity when created after the implementation of an acute kidney injury (AKI) prediction model; in scenario 3, models for AKI and mortality prediction implemented simultaneously, each led to reduced effective accuracy of the other by 1% to 28%. LIMITATIONS: In real-world practice, the effectiveness of and adherence to model-based recommendations are rarely known in advance. Only binary classifiers for tabular ICU admissions data were simulated. CONCLUSION: In simulated ICU settings, a universally effective model-updating approach for maintaining model performance does not seem to exist. Model use may have to be recorded to maintain viability of predictive modeling. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences.

Optimizing the management of castration-resistant prostate cancer patients: A practical guide for clinicians.

BACKGROUND: Advanced prostate cancer (PC) patients, especially those with metastatic prostate cancer (mPC), often require complex management pathways. Despite the publication of clinical practice guidelines by leading urological and oncological organizations that provide a substantial and comprehensive framework, there are numerous clinical scenarios that are not always addressed, especially as new treatments become available, new imaging modalities are developed, and advances in genetic testing continue. METHODS: A 14-member expert review panel comprised of urologists and medical oncologists were chosen to provide guidance on addressing specific topics and issues regarding metastatic castration-resistant prostate cancer (mCRPC) patients. Panel members were chosen based upon their experience and expertise in the management of PC patients. Four academic members (two urologists and two medical oncologists) of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association (LUGPA) practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, each assigned a specific mCRPC topic to review and discuss with the entire panel. RESULTS: This article describes the practical recommendations of an expert panel on the management of mCRPC patients. The target reading audience for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting. CONCLUSION: The panel has provided recommendations for managing mCRPC with regard to specific issues: (a) biomarker monitoring and the role of genetic and molecular testing; (b) rationale, current strategies, and optimal sequencing of the various approved therapies, including hormonal therapy, cytotoxic chemotherapy, radiopharmaceuticals and immunotherapy; (c) adverse event management and monitoring; and (d) imaging advanced PC patients. These recommendations seek to complement national guidelines, not replace them, and a discussion of where the panel agreed or disagreed with national guidelines is included.

Development of a Novel Scoring System Quantifies Opportunities to Reduce Surgery for Benign Renal Neoplasms: A Retrospective Quality Improvement Analysis within the MUSIC-KIDNEY Collaborative.

PURPOSE: Nonmalignant pathology has been reported in 15% to 20% of surgeries for cT1 renal masses. We seek to identify opportunities for improvement in avoiding surgery for nonmalignant pathology. MATERIALS AND METHODS: MUSIC-KIDNEY started collecting data in 2017. All patients with cT1 renal masses who had partial or radical nephrectomy for nonmalignant pathology were identified. Category for improvement (none-0, minor-1, moderate-2 or major-3) was independently assigned to each case by 5 experienced kidney surgeons. Specific strategies to decrease nonmalignant pathology were identified. RESULTS: Of 1,392 patients with cT1 renal masses 653 underwent surgery and 74 had nonmalignant pathology (11%). Of these, 23 (31%) cases were cT1b. Radical nephrectomy was performed in 17 (22.9%) patients for 5 cT1a and 12 cT1b lesions. Only 6 patients had a biopsy prior to surgery (5 oncocytoma, 1 unclassified renal cell carcinoma). Review identified 25 cases with minor (34%), 26 with moderate (35%) and 10 with major (14%) quality improvement opportunities. Overall 17% of cases had no quality improvement opportunities identified (12 partial nephrectomy, 1 radical nephrectomy). CONCLUSIONS: Review of patients with cT1 renal masses who underwent surgery for nonmalignant pathology revealed a significant number of cases in which this outcome may have been avoided. Approximately half of cases had moderate or major quality improvement opportunities, with radical nephrectomy for nonmalignant pathology being the most common reason. Our data indicate a lowest achievable and acceptable rate of nonmalignant pathology to be 1.9% and 5.4%, respectively. Avoiding interventions for nonmalignant pathology, particularly radical nephrectomy, is an important focus of quality improvement efforts. Strategies to decrease unnecessary interventions for nonmalignant pathology include greater use of repeat imaging, renal mass biopsy and surveillance.

Variation in Guideline Concordant Active Surveillance Followup in Diverse Urology Practices.

PURPOSE: We examined the frequency of followup prostate specific antigen testing and prostate biopsy among men treated with active surveillance in the academic and community urology practices comprising MUSIC (Michigan Urological Surgery Improvement Collaborative). MATERIALS AND METHODS: MUSIC is a consortium of 42 practices that maintains a prospective clinical registry with validated clinical data on all patients diagnosed with prostate cancer at participating sites. We identified all patients in MUSIC practices who entered active surveillance and had at least 2 years of continuous followup. After determining the frequency of repeat prostate specific antigen testing and prostate biopsy, we calculated rates of concordance with NCCN Guidelines® recommendations (ie at least 3 prostate specific antigen tests and 1 surveillance biopsy) collaborative-wide and across individual practices. RESULTS: We identified 513 patients who entered active surveillance from January 2012 through September 2013 and had at least 2 years of followup. Among the 431 men (84%) who remained on active surveillance for 2 years 132 (30.6%) underwent followup surveillance testing at a frequency that was concordant with NCCN® (National Comprehensive Cancer Network®) recommendations. At the practice level, the median rate of guideline concordant followup was 26.5% (range 10% to 67.5%, p <0.001). Among patients with discordant followup, the absence of followup biopsy was common and not significantly different across practices (median rate 82.0%, p = 0.35). CONCLUSIONS: Among diverse community and academic practices in Michigan, there is wide variation in the proportion of men on active surveillance who meet guideline recommendations for followup prostate specific antigen testing and repeat biopsy. These data highlight the need for standardized active surveillance pathways that emphasize the role of repeat surveillance biopsies.

Umbilical Fascial Defects are Common and Predict Trocar Site Hernias After Laparoscopic Appendectomy.

INTRODUCTION: Investigations have demonstrated that trocar site hernia (TSH) is an under-appreciated complication of laparoscopic surgery, occurring in as many as 31%. We determined the incidence of fascial defects prior to laparoscopic appendectomy and its impact relative to other risk factors upon the development of TSH. METHODS: TSH was defined as a fascial separation of ≥ 1 cm in the abdominal wall umbilical region on abdominal computerized tomography scan (CT) following laparoscopic appendectomy. Patients admitted to our medical center who had both a preoperative CT and postoperative CT for any reason (greater than 30 days after surgery) were reviewed for the presence of TSH from May 2010 to December 2018. CT scans were measured for fascial defects, while investigators were blinded to film timing (preoperative or postoperative) and patient identity. Demographic information was collected. RESULTS: 241 patients undergoing laparoscopic appendectomy had both preoperative and late postoperative CT. TSH was identified in 49 (20.3%) patients. Mean preoperative fascial gap was 3.3 ± 4.3 mm in those not developing a postoperative hernia versus 14.8 ± 7.3 mm in those with a postoperative hernia (P < .0001). Preoperative fascial defect on CT was predictive of TSH (P < .001, OR = 1.44), with an Area Under the Curve (AUC) of .921 (95%CI: .88-.92). Other major risk factors for TSH were: age greater than 59 years (P < .031, OR = 2.48); and obesity, BMI > 30 (P < .012, OR = 2.14). CONCLUSIONS: The incidence of trocar site hernia was one in five following laparoscopic appendectomy. The presence of a pre-existing fascial defect, advanced age, and obesity were strong predictors for the development of trocar site hernia.

Robotic-assisted aortic surgery with and without minilaparotomy for complicated occlusive disease and aneurysm.

OBJECTIVE: Published reports of robotic-assisted aortic surgery involve a combination of laparoscopy for aortic dissection and a robotic system for vascular reconstruction. The objective of this study is to determine the feasibility and advantage of a total robotic-assisted aortic dissection and vascular reconstruction vs robotic-assisted aortic procedures for aortoiliac occlusive disease (AIOD) and abdominal aortic aneurysm (AAA). METHODS: From February 2006 to August 2010, 21 patients were selected for robotic-assisted aortic procedures: aortobifemoral bypass in 12, AAA repair in 6, iliac aneurysm repair in 1, and ligation of type II endoleak after endovascular aneurysm repair in 2. Inclusion criteria included AAA >5 cm, iliac aneurysm >3 cm, and AIOD TransAtlantic InterSociety Classification (TASC) C or D lesions. The da Vinci S Surgical System (Intuitive Surgical Inc, Sunnyvale, Calif) was used for the abdominal aortic dissection in all cases and for the aortic anastomosis in three cases. RESULTS: The 21 patients (6 women, 15 men) were an average age of 65.7 years (range, 44-86 years), had a body mass index (BMI) of 27.23 kg/m(2), and 90.4% were American Society of Anesthesiologists (ASA) class 3 or 4. Robotic dissection of the abdominal aorta was successful in 20 patients (95.2%). One patient required full conversion to open AAA repair due to trocar injury. Of the remaining 20 patients, the average robotic dissection time of the infrarenal aorta was 113.1 minutes, and the average aortic clamp time was 86 minutes. The procedure in 15 patients was performed with a minilaparotomy using an average abdominal incision of 13 cm to implant the Dacron or polytetrafluoroethylene graft. Five patients underwent a total robotic-assisted procedure with robotic aortic reconstruction or ligation of a type II endoleak. The 30-day survival rate was 100%. Median length of stay was 7.5 days. All grafts were patent at a median follow-up of 32.0 months. CONCLUSIONS: For aortic procedures completed total robotically without an abdominal incision, the estimated blood loss was significantly less than in robotic-assisted procedures with a minilaparotomy. In these selected patients, robotic-assisted technology may be part of the armamentarium for the vascular surgeon as another less invasive method for the treatment of complicated occlusive disease or aneurysm.

Long-term follow-up of patients undergoing percutaneous suprapubic tube drainage after robot-assisted radical prostatectomy (RARP).

UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4 What's known on the subject? and What does the study add? • Initial reports of percutaneous suprapubic tube (PST) drainage following RARP demonstrated feasibility and short-term safety, while decreasing patient discomfort and utilization of anti-cholinergic medication. • This study demonstrates the long-term safety and efficacy of bladder drainage by PST; splinting the urethrovesical anastomosis is simply not essential if mucosal apposition is ensured. OBJECTIVES: • To evaluate the long-term safety and functional outcomes of patients undergoing percutaneous suprapubic tube (PST) drainage after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: • Between January 2008 and October 2009, 339 patients undergoing RARP by one surgeon experienced in RA surgery (M.M.) had postoperative bladder drainage with PST and a minimum of 1-year follow-up for urinary function. • Functional outcomes were obtained via patient-administered questionnaire. • Complications were captured by exhaustive review of multiple datasets, including our prospective prostate cancer database, claims data, as well as electronic medical and institutional morbidity and mortality records. RESULTS: • Urinary function assessed by patient-administered questionnaire was analysed at a mean (sd) follow-up of 11.5 (1.7) months; after RARP with PST placement, 293 patients (86.4%) had total urinary control and only nine (2.7%) required >1 pad/day. • In all, 86 patients (25.4%) never wore a pad; the median time to 0-1 pad/day was 2 weeks (interquartile range [IQR] 0,6); median time to total control was 6 weeks (IQR 1,22). • The mean (sd) follow-up for complications was 23.7 (6.1) months. In all, 15 patients (4.4%) had a procedure-specific complication, of which 13 were minor (Clavien Class I/II 3.8%); one patient had a bladder neck contracture. • In all, 16 patients (4.7%) required Foley placement after RARP for gross haematuria (two patients), urinary retention (three), tube malfunction (four) or need for prolonged Foley catheterization (seven). CONCLUSIONS: • PST placement after RARP is safe and efficacious on long-term follow-up. • Splinting of the urethrovesical anastomosis is not a critical step of RP if a watertight anastomosis and excellent mucosal apposition are achieved.

Dual checkpoint targeting of B7-H3 and PD-1 with enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial.

BACKGROUND: Availability of checkpoint inhibitors has created a paradigm shift in the management of patients with solid tumors. Despite this, most patients do not respond to immunotherapy, and there is considerable interest in developing combination therapies to improve response rates and outcomes. B7-H3 (CD276) is a member of the B7 family of cell surface molecules and provides an alternative immune checkpoint molecule to therapeutically target alone or in combination with programmed cell death-1 (PD-1)-targeted therapies. Enoblituzumab, an investigational anti-B7-H3 humanized monoclonal antibody, incorporates an immunoglobulin G1 fragment crystallizable (Fc) domain that enhances Fcγ receptor-mediated antibody-dependent cellular cytotoxicity. Coordinated engagement of innate and adaptive immunity by targeting distinct members of the B7 family (B7-H3 and PD-1) is hypothesized to provide greater antitumor activity than either agent alone. METHODS: In this phase I/II study, patients received intravenous enoblituzumab (3-15 mg/kg) weekly plus intravenous pembrolizumab (2 mg/kg) every 3 weeks during dose-escalation and cohort expansion. Expansion cohorts included non-small cell lung cancer (NSCLC; checkpoint inhibitor [CPI]-naïve and post-CPI, programmed death-ligand 1 [PD-L1] <1%), head and neck squamous cell carcinoma (HNSCC; CPI-naïve), urothelial cancer (post-CPI), and melanoma (post-CPI). Disease was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 after 6 weeks and every 9 weeks thereafter. Safety and pharmacokinetic data were provided for all enrolled patients; efficacy data focused on HNSCC and NSCLC cohorts. RESULTS: Overall, 133 patients were enrolled and received ≥1 dose of study treatment. The maximum tolerated dose of enoblituzumab with pembrolizumab at 2 mg/kg was not reached. Intravenous enoblituzumab (15 mg/kg) every 3 weeks plus pembrolizumab (2 mg/kg) every 3 weeks was recommended for phase II evaluation. Treatment-related adverse events occurred in 116 patients (87.2%) and were grade ≥3 in 28.6%. One treatment-related death occurred (pneumonitis). Objective responses occurred in 6 of 18 (33.3% [95% CI 13.3 to 59.0]) patients with CPI-naïve HNSCC and in 5 of 14 (35.7% [95% CI 12.8 to 64.9]) patients with CPI-naïve NSCLC. CONCLUSIONS: Checkpoint targeting with enoblituzumab and pembrolizumab demonstrated acceptable safety and antitumor activity in patients with CPI-naïve HNSCC and NSCLC. TRIAL REGISTRATION NUMBER: NCT02475213.

Measurement of intraabdominal pressure in pregnant women at term.

OBJECTIVE: To determine the baseline intraabdominal pressure (IAP) in pregnant women at term. STUDY DESIGN: Pregnant women at term undergoing scheduled cesarean delivery in the absence of labor had IAP measured via an intravesical catheter. Abdominal pressures were obtained in the dorsal supine position with a leftward tilt after the placement of spinal anesthesia. Measurements were taken immediately before and after cesarean delivery. RESULTS: One hundred subjects were included in this Institutional Research Board-approved study. The median preoperative IAP measurement was 22 mm Hg, and the median postoperative IAP measurement was 16 mm Hg. The decrease in the IAP from the preoperative to the postoperative measurement was statistically significant (p < 0.0001). CONCLUSION: The median IAP measurement for pregnant patients at term is 22 mm Hg and is followed by a statistically significant decline after delivery.

A Statewide Quality Improvement Collaborative's Adherence to the 2017 American Urological Association Guidelines Regarding Initial Evaluation of Patients With Clinical T1 Renal Masses.

OBJECTIVE: To evaluate MUSIC-KIDNEY's adherence to the American Urological Association (AUA) guidelines regarding the initial evaluation of patient's with clinical T1 (cT1) renal masses. METHODS: We reviewed MUSIC-KIDNEY registry data for patients with newly diagnosed cT1 renal masses to assess for adherence with the 2017 AUA guideline statements regarding recommendations to obtain (1) CMP, (2) CBC, (3) UA, (4) abdominal cross-sectional imaging, and (5) chest imaging. An evaluation consisting of all 5 guideline measures was considered "complete compliance." Variation with guideline adherence was assessed by contributing practice, management strategy, and renal mass size. RESULTS: We identified 1808 patients with cT1 renal masses in the MUSIC-KIDNEY registry, of which 30% met the definition of complete compliance. Most patients received care that was compliant with recommendations to obtain laboratory testing with 1448 (80%), 1545 (85%), and 1472 (81%) patients obtaining a CMP, CBC, and UA respectively. Only 862 (48%) patients underwent chest imaging. Significant variation exists in complete guideline compliance for contributing practices, ranging from 0% to 45% as well as for patients which underwent immediate intervention compared with initial observation (37% vs 23%) and patients with cT1b masses compared with cT1a masses (36% vs 28%). CONCLUSION: Complete guideline compliance in the initial evaluation of patients with cT1 renal masses is poor, which is mainly driven by omission of chest imaging. Significant variation in guideline adherence is seen across practices, as well as patients undergoing an intervention vs observation, and cT1a vs cT1b masses. There are ample quality improvement opportunities to increase adherence and decrease variability with guideline recommendations.

Men presenting for radical prostatectomy on preoperative statin therapy have reduced serum prostate specific antigen.

PURPOSE: Studies have suggested that statin (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) medication use may decrease prostate specific antigen in healthy men. We determined the effect of preoperative statin use on total preoperative prostate specific antigen and the risk of biochemical recurrence in patients with prostate cancer presenting for radical prostatectomy. MATERIALS AND METHODS: A retrospective review of 3,828 patients undergoing radical prostatectomy from January 2001 to July 2008 at our institution identified 1,031 on statin medications. We compared these 1,031 patients to the remaining 2,797 not on statins preoperatively. We evaluated differences in prostate specific antigen overall, and when patients were stratified by age specific groups, body mass index and Gleason grades on final pathology. We also investigated differences in biochemical recurrence rates. RESULTS: Overall median serum prostate specific antigen was lower in patients on preoperative statins (5.0 vs 5.2 ng/ml, p = 0.002). Median prostate specific antigen was lower in men on statins with Gleason grades 7 or 8/9 disease (p <0.05). Using a multivariate logistic regression model statin therapy was associated with a 4.7% decrease in prostate specific antigen (p <0.001). Statin therapy was not associated with an overall decreased risk of biochemical recurrence (p = 0.73) at a mean followup of 26 months. CONCLUSIONS: In this cohort of men presenting for radical prostatectomy serum prostate specific antigen is significantly lower in patients with prostate cancer on preoperative statins compared to those not taking these medications. Prospective studies are required to evaluate if this decrease in prostate specific antigen leads to later detection of prostate cancer or variations in oncological outcomes.

Disposition of [1'-(14)C]stavudine after oral administration to humans.

The disposition of stavudine, a potent and orally active nucleoside reverse transcriptase inhibitor, was investigated in six healthy human subjects. Before dosing humans with [1'-(14)C]stavudine, a tissue distribution study was performed in Long-Evans rats. Results from this study showed no accumulation of radioactivity in any of the tissues studied, indicating that the position of the (14)C-label on the molecule was appropriate for the human study. After a single 80-mg (100 microCi) oral dose of [1'-(14)C]stavudine, approximately 95% of the radioactive dose was excreted in urine with an elimination half-life of 2.35 h. Fecal excretion was limited, accounting for only 3% of the dose. Unchanged stavudine was the major drug-related component in plasma (61% of area under the plasma concentration-time curve from time zero extrapolated to infinite time of the total plasma radioactivity) and urine (67% of dose). The remaining radioactivity was associated with minor metabolites, including mono- and bis-oxidized stavudine, glucuronide conjugates of stavudine and its oxidized metabolite, and an N-acetylcysteine (NAC) conjugate of the ribose (M4) after glycosidic cleavage. Formation of metabolite M4 was shown in human liver microsomes incubated with 2',3'-didehydrodideoxyribose, the sugar base of stavudine, in the presence of NAC. In addition, after similar microsomal incubations fortified with GSH, two GSH conjugates, 3'-GS-deoxyribose and 1'-keto-2',3'-dideoxy-3'-GS-ribose, were observed. This suggests that 2',3'-didehydrodideoxyribose underwent cytochrome P450-mediated oxidation leading to an epoxide intermediate, 2',3'-ribose epoxide, followed by GSH addition. In conclusion, absorption and elimination of stavudine were rapid and complete after oral dosing, with urinary excretion of unchanged drug as the predominant route of elimination in humans.

Elevated blood alcohol impacts hospital mortality following motorcycle injury: A National Trauma Data Bank analysis.

BACKGROUND: Motorcyclists who drink and drive are at a higher risk of death and disability than other types of drivers. The purpose of this study was to query a national trauma database to evaluate the impact of elevated blood alcohol concentration (BAC) on outcomes in patients who sustained injury following a motorcycle crash. METHODS: The National Trauma Data Bank (NTDB) data was accessed from 2012 to 2014. Patients ≥ 18 years of age who sustained a traumatic injury following a motorcycle accident with a confirmed blood alcohol test at the time of arrival to the hospital were included. Other variables examined were: sex, race, injury severity score (ISS), and initial Glasgow Coma Scale motor score (GCSMOT), systolic blood pressure (SBP, mm Hg), SBP <90, and comorbidities. Patients with a blood alcohol concentration (BAC) at or beyond the legal limit (0.08 g/dL) comprised the "alcohol positive" group, while those with a BAC confirmed negative comprised the "alcohol negative" group. The patients who tested BAC < 0.08 g/dl were excluded from the analysis. The primary outcome of the study was in-hospital mortality. Univariate followed by propensity matched analysis was performed. All p-values were 2 sided and p-values < 0.05 were considered statistically significant. RESULTS: Of 113,843 patients involved in motorcycle crash, 67,183 patients underwent BAC testing. The majority (68.52%) tested negative, 21.14% tested positive above the legal limit and remaining 10.34% tested with a BAC <0.08 g/dl . A total of 29,922 patients, satisfied the inclusion criteria for final analysis. After propensity score matching, there was 100% improvement on standardized mean difference on matching variables (age, sex, race).However, differences continued between the groups on, SBP < 90, ISS and GCSMOT. The hospital mortality rates were 3.1% vs 3.9% (P < 0.001) between alcohol negative and the alcohol positive groups, respectively. The odds ratio of mortality in alcohol positive group was 1.27 (95% CI: 1.07, 1.53) and the absolute risk difference in hospital mortality was 0.008 (CI: 0.002, 0.014). CONCLUSION: Patients who tested with a BAC above the legal limit sustained a higher injury severity score and higher in-hospital mortality compared to patients who tested negative.

Successful Full-Thickness Skin Regeneration Using Epidermal Stem Cells in Traumatic and Complex Wounds: Initial Experience.

Skin grafts generated from cultured autologous epidermal stem cells may have potential advantages when compared to traditional skin grafting. In this report, we will share our initial experience with a new technique for the treatment of difficult cutaneous wounds. Eight patients with traumatic or complex wounds underwent full-thickness skin harvesting and processing of epidermal stem cells, followed by the application of our novel management protocol. The patients were at high risk for non-healing and/or severe scar formation due to large traumatic de-gloving crush injuries, wounds from necrotizing fasciitis, or chronic wounds from osteomyelitis. We examined the percent graft success, recipient to donor size ratios, the median time to epithelialization, and two-point sensory discrimination. An international scale (The Patient and Observer Scar Assessment Scale - POSAS) was used to evaluate wound cosmesis and included parameters such as pain, pruritus, vascularity, pigmentation, and thickness of the healing wound. In total, 10 out of 11 wounds had 100% survival of the graft, and one patient had an 80% graft take. The largest wound was 1600 cm2, and all wounds were harvested from small-donor sites, which were closed primarily. The mean wound to donor ratio was >25:1. Most wounds were fully epithelialized within 30 days. Neurologically, four out of six patients studied exhibited two-point discrimination similar to the adjacent native uninjured skin. The majority of patients reported their wounds to have limited pain or pruritus, and similar pigmentation to adjacent skin.

Early Detection of Deep Venous Thrombosis in Trauma Patients.

Background This study was performed to determine whether trauma patients are at an increased risk of developing deep venous thrombosis (DVT) within the first 48 hours of hospitalization. Materials and methods A retrospective review was performed using a prospectively maintained database of patients admitted to a trauma center during a five-year time period. Patients hospitalized for greater than 48 hours who received a screening venous duplex for DVT were included in the study. Results There were 1067 venous duplex scans obtained, 689 (64.5%) within the first 48 hours of admission (early DVT group), 378 (35.4%) after the first 48 hours (late DVT group). Only 142 (13.2%) patients had a positive duplex scan for DVT, 55 (early group), 87 (late group). Comorbid conditions of congestive heart failure (P = 0.02), pelvic fractures (P = 0.04), and a lower initial systolic blood pressure on presentation (p = 0.04) were associated with early DVT. Head trauma (P < 0.01), mechanical ventilation (P < 0.001), and transfusion of blood products (P < 0.001), were predictors of DVT in the late group. Conclusions Trauma patients are at an increased risk of developing venous thrombosis early in the hospital course due to comorbidities associated with trauma. Whereas, venous thrombosis in trauma patients diagnosed after the first 48 hours of hospitalization appears to be associated with prolonged patient immobility.

Controversies in Tracheostomy for Patients With COVID-19: The When, Where, and How.

COVID-19 has impacted how we deliver care to patients, and much remains unknown regarding optimal management of respiratory failure in this patient population. There are significant controversies regarding tracheostomy in patients with COVID-19 related to timing, location of procedure, and technique. In this narrative review, we explore the recent literature, publicly available guidelines, protocols from different institutions, and clinical reports to provide critical insights on how to deliver the most benefit to our patients while safeguarding the health care force. Consensus can be reached that patients with COVID-19 should be managed in a negative-pressure environment with proper personal protective equipment, and that performing tracheostomy is a complex decision that should be made through multidisciplinary discussions considering patient prognosis, institutional resources, staff experience, and risks to essential health care workers. A broad range of practices exist because there is no conclusive guidance regarding the optimal timing or technique for tracheostomy.

Putting a halt to unnecessary transfers: Do patients with isolated subarachnoid hemorrhage and Glasgow Coma Scale of 13 to 15 need a trauma center?

OBJECTIVES: Trauma patients with isolated subarachnoid hemorrhage (iSAH) presenting to nontrauma centers are typically transferred to an institution with neurosurgical availability. However, recent studies suggest that iSAH is a benign clinical entity with an excellent prognosis. This investigation aims to evaluate the neurosurgical outcomes of traumatic iSAH with Glasgow Coma Scale (GCS) of 13 to 15 who were transferred to a higher level of care. METHODS: The American College of Surgeon Trauma Quality Improvement Program was retrospectively analyzed from 2010 to 2015 for transferred patients 16 years and older with blunt trauma, iSAH, and GCS of 13 or greater. Those with any other body region Abbreviated Injury Scale of 3 or greater, positive or unknown alcohol/drug status, and requiring mechanical ventilation were excluded. The primary outcome was need for neurosurgical intervention (i.e., intracranial monitor or craniotomy/craniectomy). RESULTS: A total of 11,380 patients with blunt trauma, iSAH, and GCS of 13 to 15 were transferred to an American College of Surgeon level I/II from 2010 to 2015. These patients were 65 years and older (median, 72 [interquartile range (IQR), 59-81]) and white (83%) and had one or more comorbidities (72%). Eighteen percent reported a bleeding diathesis/chronic anticoagulation on admission. Most patients had fallen (80%), had a GCS of 15 (84%), and were mildly injured (median Injury Severity Score, 9 [IQR, 5-14]). Only 1.7% required neurosurgical intervention with 55% of patients being admitted to the intensive care unit for a median of 2 days (IQR, 1-3 days). Furthermore, 2.2% of the patients died. The median hospital length of stay was only 3 days (IQR, 2-5 days), and the most common discharge location was home with self-care (62%). Patient factors favoring neurosurgical intervention included high Injury Severity Score, low GCS, and chronic anticoagulation. CONCLUSION: Trauma patients transferred for iSAH with GCS of 13 to 15 are at very low risk for requiring neurosurgical intervention. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

Development and Preliminary Clinical Activity of PD-1-Guided CTLA-4 Blocking Bispecific DART Molecule.

Combination immunotherapy with antibodies directed against PD-1 and CTLA-4 shows improved clinical benefit across cancer indications compared to single agents, albeit with increased toxicity. Leveraging the observation that PD-1 and CTLA-4 are co-expressed by tumor-infiltrating lymphocytes, an investigational PD-1 x CTLA-4 bispecific DART molecule, MGD019, is engineered to maximize checkpoint blockade in the tumor microenvironment via enhanced CTLA-4 blockade in a PD-1-binding-dependent manner. In vitro, MGD019 mediates the combinatorial blockade of PD-1 and CTLA-4, confirming dual inhibition via a single molecule. MGD019 is well tolerated in non-human primates, with evidence of both PD-1 and CTLA-4 blockade, including increases in Ki67+CD8 and ICOS+CD4 T cells, respectively. In the ongoing MGD019 first-in-human study enrolling patients with advanced solid tumors (NCT03761017), an analysis undertaken following the dose escalation phase revealed acceptable safety, pharmacodynamic evidence of combinatorial blockade, and objective responses in multiple tumor types typically unresponsive to checkpoint inhibitor therapy.

Model-based approach to characterize efavirenz autoinduction and concurrent enzyme induction with carbamazepine.

Characterization of the time course and magnitude of enzyme induction due to multiple inducers is important for interpretation of clinical data from drug-drug interaction studies. A population interaction model was developed to quantify efavirenz autoinduction and further induction with concurrent carbamazepine coadministration. Efavirenz concentration data in the absence and presence of carbamazepine following single- and multiple-dose oral administrations in healthy subjects were used for model development. The proposed model was able to describe the time-dependent efavirenz autoinduction and the further induction with carbamazepine when the agents were combined. The estimated population averages of efavirenz oral clearance were 5.5, 9.4, 14.4, and 16.7 liters/h on days 1, 14, and 35 and at steady state for the interaction, respectively, for efavirenz monotherapy for 2 weeks followed by the coadministration of carbamazepine for 3 weeks. The estimated times to 50% of the steady state for efavirenz autoinduction and for the induction resulting from the concurrent administration of efavirenz and carbamazepine were similar (around 10 to 12 days). With this model-based analysis, efavirenz exposures can be projected prior to and at the steady state of induction, allowing a better understanding of the time course and magnitude of enzyme induction.

Salvage robotic-assisted radical prostatectomy: initial results and early report of outcomes.

OBJECTIVE: To evaluate the initial results of salvage robotic-assisted radical prostatectomy (SRARP) after recurrence following primary radiotherapy (RT) for localized prostate cancer. PATIENTS AND METHODS: Between December 2002 and January 2008, 11 patients had SRARP with pelvic lymph node dissection by one surgeon from one institution. Six patients had brachytherapy, three had external beam RT (EBRT), one intensity-modulated RT, and one received brachytherapy with an EBRT boost. All patients had prostate cancer on biopsy after RT, with negative computed tomography and bone scan. The mean (range) follow-up was 20.5 (1-77) months. RESULTS: The mean interval from RT to SRARP was 53.2 months; the mean preoperative prostate-specific antigen (PSA) level was 5.2 ng/mL, the operative duration 183 min and the estimated blood loss 113 mL. One patient had prolonged lymphatic drainage, one had an anastomotic leak, and one had an anastomotic stricture requiring direct vision internal urethrotomy at 3 months. The mean duration of catheterization was 10.4 days and the hospital stay 1.4 days. Three patients had a biochemical recurrence, at 1, 2 and 43 months. In one of two patients with node-positive carcinoma of the prostate the PSA level failed to reach a nadir of zero after surgery. In patients with a minimum follow-up of 2 months, eight of 10 are continent (defined as zero to one pad per day) and two have erections adequate for intercourse with the use of phosphodiesterase-5 inhibitors. CONCLUSION: SRARP after RT-resistant disease recurrence is feasible with minimal perioperative morbidity. Early functional outcomes appear to be at least equivalent with historical salvage RP series. Robotic extended pelvic lymph node dissection is safe and can improve the accuracy of surgical staging. A longer follow-up is necessary to better assess the functional and oncological outcomes.