Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging. However, immunotherapy responses are uniquely challenging to ...interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation. We hypothesized that monitoring tumor cell death in real time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy.
We compared longitudinal changes in ctDNA levels with changes in radiographic tumor size and with survival outcomes in 28 patients with metastatic non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitor therapy. CtDNA was quantified by determining the allele fraction of cancer-associated somatic mutations in plasma using a multigene next-generation sequencing assay. We defined a ctDNA response as a >50% decrease in mutant allele fraction from baseline, with a second confirmatory measurement.
Strong agreement was observed between ctDNA response and radiographic response (Cohen's kappa, 0.753). Median time to initial response among patients who achieved responses in both categories was 24.5 days by ctDNA versus 72.5 days by imaging. Time on treatment was significantly longer for ctDNA responders versus nonresponders (median, 205.5 vs. 69 days;
< 0.001). A ctDNA response was associated with superior progression-free survival hazard ratio (HR), 0.29; 95% CI, 0.09-0.89;
= 0.03, and superior overall survival (HR, 0.17; 95% CI, 0.05-0.62;
= 0.007).
A drop in ctDNA level is an early marker of therapeutic efficacy and predicts prolonged survival in patients treated with immune checkpoint inhibitors for NSCLC.
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Within the growing geriatric population, there is an increasing need for emergency operations. Optimizing outcomes can require a structured system of surgical care based on key quality indicators. To ...investigate this, the current study sought to answer 2 questions. First, to what degree does hospital emergency operative volume impact mortality for geriatric patients undergoing emergency general surgery (EGS) operations? Second, at what procedure-specific hospital volume will geriatric patients undergoing an emergency operation achieve at or better than average mortality risk?
Retrospective cohort study of geriatric patients (aged 65 years and older) who underwent 1 of 10 EGS operations identified from the California State Inpatient Database (2010 to 2011). β-Logistic generalized linear regression was used, with the hospital as the unit of analysis, to investigate the relationship between hospital operative volume and in-hospital riskv-adjusted mortality. Hospital operative volume thresholds to optimize probability of survival were defined.
There were 41,860 operations evaluated at 299 hospitals. For each operation, mortality decreased as hospital emergency operative volume increased (p < 0.001 for each operation); for every standardized increase in volume (meaning +1 natural logarithm of volume), the reduction in mortality ranged from 14% for colectomy to 61% for appendectomy. Hospital volume thresholds, which optimize to 95% probability of survival, varied by procedure, with a mean of 14 operations over 2 years. More than 50% of hospitals did not meet the threshold benchmarks, representing 22% of patients.
Survival rates for geriatric patients were improved substantially when emergency operations were performed at hospitals with higher operative volumes. Consistent with all active Quality Programs of the American College of Surgeons, hospital operative volume appears to be an important metric of surgical quality for older patients undergoing emergency operations.
The types of agents used for monitored anesthesia care (MAC) and their possible differential effects on outcomes have received less study despite increased use over general anesthesia (GA) in ...transfemoral aortic valve replacements (TAVRs). In this pilot analysis of patients undergoing TAVR using MAC, the authors described the anesthetic agents used and sought to investigate the possible association of anesthetic agent choice with outcomes and the extent to which total weight and time-adjusted doses of anesthetics declined with increasing 10-year age increments.
Retrospective observational study.
Tertiary teaching hospital.
Ninety-three participants scheduled to undergo TAVR, with a primary plan of conscious sedation between November 2014 and June 2016, were included.
None.
Types of MAC were divided into 4 primary groups, but 2 groups were focused: propofol (n = 39) and dexmedetomidine plus propofol (n = 34). Conversion to GA occurred in 6 participants (6.45%) and was not associated with the type of sedation received. The authors also compared patients who received dexmedetomidine with those who did not in accordance with their a priori analytic plan. There were no associations between the use of dexmedetomidine and postoperative delirium or intensive care unit/hospital length of stay. No significant trends in medication dose adjustments were seen across increasing 10-year age increments.
A wide breadth of MAC medications is in use among TAVR patients and does not support differences in outcomes. Despite recommendations to reduce anesthetic drug dosing in the elderly, no significant trends in dose reduction with increasing age were noted.
This study aimed to answer 2 questions: first, to what degree does hospital operative volume affect mortality for adult patients undergoing 1 of 10 common emergency general surgery (EGS) operations? ...Second, at what hospital operative volume threshold will nearly all patients undergoing an emergency operation realize the average mortality risk?
Nontrauma surgical emergencies are an underappreciated public health crisis in the United States; redefining where such emergencies are managed may improve outcomes. The field of trauma surgery established regionalized systems of care in part because studies demonstrated a clear relationship between hospital volume and survival for traumatic emergencies. Such a relationship has not been well-studied for nontrauma surgical emergencies.
Retrospective cohort study of all acute care hospitals in California performing nontrauma surgical emergencies. We employed a novel use of an ecological analysis with beta regression to investigate the relationship between hospital operative volume and mortality.
A total of 425 acute care hospitals in California performed 165,123 EGS operations. Risk-adjusted mortality significantly decreased as volume increased for all 10 EGS operations (P < 0.001 for each); the relative magnitude of this inverse relationship differed substantially by procedure. Hospital operative volume thresholds were defined and varied by operation: from 75 cases over 2 years for cholecystectomy to 7 cases for umbilical hernia repair.
Survival rates for nontrauma surgical emergencies were improved when operations were performed at higher-volume hospitals. The use of ecological analysis is widely applicable to the field of surgical outcomes research.
Red blood cell (RBC) transfusion has been linked to increased morbidity and mortality. However, strict RBC transfusion recommendations recently have been questioned. The aim of this study was to ...investigate the short- and long-term mortality outcomes after RBC transfusion in patients undergoing coronary artery bypass graft surgery (CABG).
This was a retrospective medical record review.
Tertiary care academic medical center.
The study included patients who underwent CABG from June 2006 to May 2013.
Adult (>18 years) cardiac surgery patients who were admitted to the cardiothoracic intensive care unit in a tertiary care academic medical center from June 2006 to May 2013 were collected. In all, 2,180 patients who underwent CABG surgery were included into propensity-score matching analyses, which were matched 1:1. Patients who did not receive transfusion of packed red blood cells (PRBC) (n = 937) were compared with those who received 1 to 5 U (n = 1,113). The study outcomes included mortality rates at 1, 3, and 6 months (short-term) and 1, 2, 3, and 4 years (long-term).
No statistical significant differences were found for the 1-month (2% v 1.1%, p = 0.292), 3-month (2.9% v 2%, p = 0.396), or 6-month mortality rate (4.3% v 3.4%, p = 0.602) in 446 patients with 1 to 5 U versus 446 matched patients with no PRBC transfusion. Patients in the transfused group compared with those in the no-transfusion group had statistically significant higher 3-year mortality rate (11% v 6.7%; hazard ratio, 1.64; 95% confidence interval, 1.03-2.63; p = 0.038).
In the present study, patients undergoing CABG surgery and receiving <6 U of PRBC did not have statistically increased risk for in-hospital mortality and up to 2 years postoperatively. A modestly statistically significant difference was noted at 3 years. However, cumulatively, there was no statistical difference between the transfused and nontransfused groups at 4 years. Further studies are needed to confirm the findings and define the population that will benefit the most from blood transfusion.
The objective of the study was to compare the performance of intravenous (IV) lorazepam (IVL) and intranasal midazolam (INM) for seizure termination and prevention of seizure clusters in adults ...admitted to the epilepsy monitoring unit (EMU) in whom seizures were captured on continuous video-electroencephalogram.
Retrospective cohort of consecutive adults (≥18 years) with epilepsy admitted to the EMU at a single tertiary academic center, who experienced epileptic seizures (confirmed electroencephalographically) and required rescue therapy. The study spanned from January 2015 until December 2016, which included one year before and one year after transitioning from IVL to INM as the standard rescue therapy at our institution.
A total of 50 subjects received rescue therapy and were included in the analysis. In the first year, out of 216 patients with epilepsy admitted to the EMU, 27 (13%) received IVL; in the second year, 23/217 (11%) received INM. There were no differences in baseline characteristics and markers of epilepsy severity, the median duration of index seizure (1.7 min interquartile range (IQR): 1.1–2.7 in IVL vs. 2.0 min IQR: 1.5–2.6 in INM group, p = 0.20), or in the number of subjects requiring repeat benzodiazepine administrations (IVL 8/27 29.6% vs. INM 7/23 30.4%, p = 0.95). There were no differences in the median number of recurrent seizures in 24 h (1 IQR: 1–3 in IVL vs. 2 IQR: 1–4 in INM, p = 0.27), occurrence of status epilepticus (IVL 4/27 14.8% subjects vs. INM 1/23 4.3% subjects, p = 0.36), incidence of seizure clusters (IVL 8/27 29.6% subjects vs. INM 7/23 30.4% subjects, p = 0.95), need for transfer to an intensive care unit (ICU), or other adverse events.
In our retrospective study, INM was comparable with IVL for seizure termination and prevention of seizure clusters in the adult EMU. Intranasal midazolam circumvents the need for IV access to be maintained throughout hospitalization and is an attractive alternative to IVL as a rescue therapy in this setting. Ideally, future large, prospective, randomized, and double blind studies are needed to confirm these findings.
•Rapid penetration into the central nervous system is a critical feature for the efficacy of anti-seizure.•INM is an attractive option due to its rapid absorption and subsequent CNS delivery without the need for IV access.•Our results suggest that INM is comparable to IVL for the treatment of prolonged seizures in this setting.
OBJECTIVE:This study aimed to answer 2 questionsfirst, to what degree does hospital operative volume affect mortality for adult patients undergoing 1 of 10 common emergency general surgery (EGS) ...operations? Second, at what hospital operative volume threshold will nearly all patients undergoing an emergency operation realize the average mortality risk?
BACKGROUND:Nontrauma surgical emergencies are an underappreciated public health crisis in the United States; redefining where such emergencies are managed may improve outcomes. The field of trauma surgery established regionalized systems of care in part because studies demonstrated a clear relationship between hospital volume and survival for traumatic emergencies. Such a relationship has not been well-studied for nontrauma surgical emergencies.
METHODS:Retrospective cohort study of all acute care hospitals in California performing nontrauma surgical emergencies. We employed a novel use of an ecological analysis with beta regression to investigate the relationship between hospital operative volume and mortality.
RESULTS:A total of 425 acute care hospitals in California performed 165,123 EGS operations. Risk-adjusted mortality significantly decreased as volume increased for all 10 EGS operations (P < 0.001 for each); the relative magnitude of this inverse relationship differed substantially by procedure. Hospital operative volume thresholds were defined and varied by operationfrom 75 cases over 2 years for cholecystectomy to 7 cases for umbilical hernia repair.
CONCLUSIONS:Survival rates for nontrauma surgical emergencies were improved when operations were performed at higher-volume hospitals. The use of ecological analysis is widely applicable to the field of surgical outcomes research.
It has been theorized that a tiered, regionalized system of care for emergency general surgery (EGS) patients-akin to regional trauma systems-would translate into significant survival benefits. Yet ...data to support this supposition are lacking. The aim of this study was to determine the potential number of lives that could be saved by regionalizing EGS care to higher-volume, lower-mortality EGS institutions.
Adult patients who underwent one of 10 common EGS operations were identified in the California Inpatient Database (2010-2011). An algorithm was constructed that "closed" lower-volume, higher-mortality hospitals and referred those patients to higher-volume, lower-mortality institutions ("closure" based on hospital EGS volume-threshold that optimized to 95% probability of survival). Primary outcome was the number of lives saved. Fifty thousand regionalization simulations were completed (5,000 for each operation) employing a bootstrap resampling method to proportionally redistribute patients. Estimates of expected deaths at the higher-volume hospitals were recalculated for every bootstrapped sample.
Of the 165,123 patients who underwent EGS operations over the 2-year period, 17,655 (10.7%) were regionalized to a higher-volume hospital. On average, 128 (48.8%) of lower-volume hospitals were "closed," ranging from 68 (22.0%) hospital closures for appendectomy to 205 (73.2%) for small bowel resection. The simulations demonstrated that EGS regionalization would prevent 9.7% of risk-adjusted EGS deaths, significantly saving lives for every EGS operation: from 30.8 (6.5%) deaths prevented for appendectomy to 122.8 (7.9%) for colectomy. Regionalization prevented 4.6 deaths per 100 EGS patient-transfers, ranging from 1.3 for appendectomy to 8.0 for umbilical hernia repair.
This simulation study provides important new insight into the concept of EGS regionalization, suggesting that 1 in 10 risk-adjusted deaths could be prevented by a structured system of EGS care. Future work should expand upon these findings using more complex discrete-event simulation models.
Therapeutic/Care Management, level IV.
•The interpretation of urine buprenorphine testing can be complex.•Urine samples from patients with opioid use disorder are analyzed.•Patterns of urine buprenorphine and norbuprenorphine levels are ...described.•Metabolite levels to detect potentially adulterated urine specimens are suggested.
Quantitative urine buprenorphine testing is used to monitor patients receiving buprenorphine for the treatment of opioid use disorder (OUD), however the interpretation of urine buprenorphine testing is complex. Currently, interpretation of quantitative buprenorphine testing is guided by data from drug assay development studies and forensic labs rather than clinical treatment cohorts.
In this retrospective study, we describe the patterns of urine buprenorphine and norbuprenorphine levels in patients prescribed sublingual buprenorphine for OUD in an office-based addiction treatment clinic. Urine buprenorphine and norbuprenorphine levels were analyzed in patients who reported having adulterated their urine, patients clinically suspected of adulterating their urine, and patients without concern for urine adulteration. Finally, we tested the accuracy of urine buprenorphine, norbuprenorphine, and norbuprenorphine: buprenorphine ratio (Norbup:Bup) to identify adulterated urine samples.
Patients without suspicion for urine adulteration rarely provided specimens with buprenorphine >=1000ng/ml (4.4%), while the proportion provided by those who endorsed or were suspected of urine adulteration was higher (42.9%, 40.6%, respectively). Compared to patients without reported urine adulteration, specimens from patients who reported or were suspected of urine adulteration had significantly higher buprenorphine (p=0.0001) and lower norbuprenorphine (<0.0001) levels, and significantly lower Norbup:Bup ratios (p=0.04). Buprenorphine >=700ng/ml offered the best accuracy for discriminating between adulterated and non-adulterated specimens.
This study describes the patterns of urine buprenorphine and norbuprenorphine levels from patients with OUD receiving buprenorphine treatment in an office-based addiction treatment clinic. Parameters for identifying urine adulterated by submerging buprenorphine medication in the urine specimen are discussed.
As the geriatric population grows, the need for hospitals performing high quality emergency general surgery (EGS) on older patients will increase. Identifying clusters of high-performing geriatric ...emergency general surgery hospitals would substantiate the need for in-depth analyses of hospital-specific structures and practices that benefit older EGS patients. The objectives of this study were therefore to identify clusters of hospitals based on mortality performance for geriatric patients undergoing common EGS operations and to determine if hospital performance was similar for all operation types.
Hospitals in the California State Inpatient Database were included if they performed a range of eight common EGS operations in patients 65 years or older, with a minimum requirement of three of each operation performed over 2 years. Multivariable beta regression models were created to define hospital-level risk-adjusted mortality. Centroid cluster analysis was used to identify groups of hospitals based on mortality and to determine if mortality-performance differed by operation.
One hundred seven hospitals were included, performing a total of 24,279 operations in older patients. Hospitals separated into three distinct clusters: high, average, and low performers. The high-performing hospitals had survival rates 1 to 2 standard deviations better than the low-performers (p < 0.001). For each cluster, high performance in any one EGS operation consistently translated into high performance across all EGS operations.
Hospitals conducting EGS operations in the geriatric patient population cluster into three distinct groups based on their survival performance. High-performing hospitals significantly outperform the average and low performers across every operation. The high-performers achieve reliable, high-quality results regardless of operation type. Further qualitative research is needed to investigate the perioperative drivers of hospital performance in the geriatric EGS population.
Study Type Prognostic, level III.
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