BACKGROUND:Although deviations in intraoperative blood pressure are assumed to be associated with postoperative mortality, critical blood pressure thresholds remain undefined. Therefore, the authors ...estimated the intraoperative thresholds of systolic blood pressure (SBP), mean blood pressure (MAP), and diastolic blood pressure (DBP) associated with increased risk-adjusted 30-day mortality.
METHODS:This retrospective cohort study combined intraoperative blood pressure data from six Veterans Affairs medical centers with 30-day outcomes to determine the risk-adjusted associations between intraoperative blood pressure and 30-day mortality. Deviations in blood pressure were assessed using three methods(1) population thresholds (individual patient sum of area under threshold AUT or area over threshold 2 SDs from the mean of the population intraoperative blood pressure values), (2). absolute thresholds, and (3) percent change from baseline blood pressure.
RESULTS:Thirty-day mortality was associated with (1) population thresholdsystolic AUT (odds ratio, 3.3; 95% CI, 2.2 to 4.8), mean AUT (2.8; 1.9 to 4.3), and diastolic AUT (2.4; 1.6 to 3.8). Approximate conversions of AUT into its separate components of pressure and time were SBP < 67 mmHg for more than 8.2 min, MAP < 49 mmHg for more than 3.9 min, DBP < 33 mmHg for more than 4.4 min. (2) Absolute thresholdSBP < 70 mmHg for more than or equal to 5 min (odds ratio, 2.9; 95% CI, 1.7 to 4.9), MAP < 49 mmHg for more than or equal to 5 min (2.4; 1.3 to 4.6), and DBP < 30 mmHg for more than or equal to 5 min (3.2; 1.8 to 5.5). (3) Percent changeMAP decreases to more than 50% from baseline for more than or equal to 5 min (2.7; 1.5 to 5.0). Intraoperative hypertension was not associated with 30-day mortality with any of these techniques.
CONCLUSION:Intraoperative hypotension, but not hypertension, is associated with increased 30-day operative mortality.
Positive margins dominate clinical outcomes after surgical resections in most solid cancer types, including head and neck squamous cell carcinoma. Unfortunately, surgeons remove cancer in the same ...manner they have for a century with complete dependence on subjective tissue changes to identify cancer in the operating room. To effect change, we hypothesize that EGFR can be targeted for safe and specific real-time localization of cancer.
A dose escalation study of cetuximab conjugated to IRDye800 was performed in patients (n = 12) undergoing surgical resection of squamous cell carcinoma arising in the head and neck. Safety and pharmacokinetic data were obtained out to 30 days after infusion. Multi-instrument fluorescence imaging was performed in the operating room and in surgical pathology.
There were no grade 2 or higher adverse events attributable to cetuximab-IRDye800. Fluorescence imaging with an intraoperative, wide-field device successfully differentiated tumor from normal tissue during resection with an average tumor-to-background ratio of 5.2 in the highest dose range. Optical imaging identified opportunity for more precise identification of tumor during the surgical procedure and during the pathologic analysis of tissues ex vivo. Fluorescence levels positively correlated with EGFR levels.
We demonstrate for the first time that commercially available antibodies can be fluorescently labeled and safely administered to humans to identify cancer with sub-millimeter resolution, which has the potential to improve outcomes in clinical oncology.
Studies examining changes in skeletal muscle and adipose tissue during treatment for cancer in children, adolescents, and young adults and their effect on the risk of chemotherapy toxicity ...(chemotoxicity) are limited.
Among 78 patients with lymphoma (79.5%) and rhabdomyosarcoma (20.5%), changes were measured in skeletal muscle (skeletal muscle index SMI; skeletal muscle density SMD) and adipose tissue (height-adjusted total adipose tissue hTAT) between baseline and first subsequent computed tomography scans at the third lumbar vertebral level by using commercially available software. Body mass index (BMI; operationalized as a percentile BMI%ile) and body surface area (BSA) were examined at each time point. The association of changes in body composition with chemotoxicities was examined by using linear regression.
The median age at cancer diagnosis of this cohort (62.8% male; 55.1% non-Hispanic White) was 12.7 years (2.5-21.1 years). The median time between scans was 48 days (range, 8-207 days). By adjusting for demographics and disease characteristics, this study found that patients undergo a significant decline in SMD (β ± standard error SE = -4.1 ± 1.4; p < .01). No significant changes in SMI (β ± SE = -0.5 ± 1.0; p = .7), hTAT (β ± SE = 5.5 ± 3.9; p = .2), BMI% (β ± SE = 4.1 ± 4.8; p = .3), or BSA (β ± SE = -0.02 ± 0.01; p = .3) were observed. Decline in SMD (per Hounsfield unit) was associated with a greater proportion of chemotherapy cycles with grade ≥3 nonhematologic toxicity (β ± SE = 1.09 ± 0.51; p = .04).
This study shows that children, adolescents, and young adults with lymphoma and rhabdomyosarcoma undergo a decline in SMD early during treatment, which is associated with a risk of chemotoxicities. Future studies should focus on interventions designed at preventing the loss of muscle during treatment.
We show that among children, adolescents, and young adults with lymphoma and rhabdomyosarcoma receiving chemotherapy, skeletal muscle density declines early during treatment. Additionally, a decline in skeletal muscle density is associated with a greater risk of nonhematologic chemotoxicities.
IMPORTANCE: It is unclear how effective intermittent fasting is for losing weight and body fat, and the effects may depend on the timing of the eating window. This randomized trial compared ...time-restricted eating (TRE) with eating over a period of 12 or more hours while matching weight-loss counseling across groups. OBJECTIVE: To determine whether practicing TRE by eating early in the day (eTRE) is more effective for weight loss, fat loss, and cardiometabolic health than eating over a period of 12 or more hours. DESIGN, SETTING, AND PARTICIPANTS: The study was a 14-week, parallel-arm, randomized clinical trial conducted between August 2018 and April 2020. Participants were adults aged 25 to 75 years with obesity and who received weight-loss treatment through the Weight Loss Medicine Clinic at the University of Alabama at Birmingham Hospital. INTERVENTIONS: All participants received weight-loss treatment (energy restriction ER) and were randomized to eTRE plus ER (8-hour eating window from 7:00 to 15:00) or control eating (CON) plus ER (≥12-hour window). MAIN OUTCOMES AND MEASURES: The co–primary outcomes were weight loss and fat loss. Secondary outcomes included blood pressure, heart rate, glucose levels, insulin levels, and plasma lipid levels. RESULTS: Ninety participants were enrolled (mean SD body mass index, 39.6 6.7; age, 43 11 years; 72 80% female). The eTRE+ER group adhered 6.0 (0.8) days per week. The eTRE+ER intervention was more effective for losing weight (−2.3 kg; 95% CI, −3.7 to −0.9 kg; P = .002) but did not affect body fat (−1.4 kg; 95% CI, −2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (−4.2%; 95% CI, −14.9 to 6.5%; P = .43). The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d. The eTRE+ER intervention also improved diastolic blood pressure (−4 mm Hg; 95% CI, −8 to 0 mm Hg; P = .04) and mood disturbances, including fatigue-inertia, vigor-activity, and depression-dejection. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups. In a secondary analysis of 59 completers, eTRE+ER was also more effective for losing body fat and trunk fat than CON+ER. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, eTRE was more effective for losing weight and improving diastolic blood pressure and mood than eating over a window of 12 or more hours at 14 weeks. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03459703
There is limited research on outcomes of patients with posttraumatic stress disorder (PTSD) who also develop stroke, particularly regarding racial disparities. Our goal was to determine whether PTSD ...is associated with the risk of hospital readmission after stroke and whether racial disparities existed.
The analytical sample consisted of all veterans receiving care in the Veterans Health Administration who were identified as having a new stroke requiring inpatient admission based on the
codes. PTSD and comorbidities were identified using the
codes and given the date of first occurrence. The retrospective cohort data were obtained from the Veterans Affairs Corporate Data Warehouse. The main outcome was any readmission to Veterans Health Administration with a stroke diagnosis. The hypothesis that PTSD is associated with readmission after stroke was tested using Cox regression adjusted for patient characteristics including age, sex, race, PTSD, smoking status, alcohol use, and comorbidities treated as time-varying covariates.
Our final cohort consisted of 93 651 patients with inpatient stroke diagnosis and no prior Veterans Health Administration codes for stroke starting from 1999 with follow-up through August 6, 2022. Of these patients, 12 916 (13.8%) had comorbid PTSD. Of the final cohort, 16 896 patients (18.0%) with stroke were readmitted. Our fully adjusted model for readmission found an interaction between African American veterans and PTSD with a hazard ratio of 1.09 (95% CI, 1.00-1.20
=0.047). In stratified models, PTSD has a significant hazard ratio of 1.10 (95% CI, 1.02-1.18
=0.01) for African American but not White veterans (1.05 95% CI, 0.99-1.11;
=0.10).
Among African American veterans who experienced stroke, preexisting PTSD was associated with increased risk of readmission, which was not significant among White veterans. This study highlights the need to focus on high-risk groups to reduce readmissions after stroke.
IMPORTANCE Timing of prophylactic antibiotic administration for surgical procedures is a nationally mandated and publicly reported quality metric sponsored by the Centers for Medicare and Medicaid ...Services Surgical Care Improvement Project. Numerous studies have failed to demonstrate that adherence to the Surgical Care Improvement Project prophylactic antibiotic timely administration measure is associated with decreased surgical site infection (SSI). OBJECTIVE To determine whether prophylactic antibiotic timing is associated with SSI occurrence. DESIGN Retrospective cohort study using national Veterans Affairs patient-level data on prophylactic antibiotic timing for orthopedic, colorectal, vascular, and gynecologic procedures from 2005 through 2009. SETTING National Veterans Affairs Surgical Care Improvement Project data from 112 Veterans Affairs hospitals and matched Veterans Affairs Surgical Quality Improvement Program data. PATIENTS Patients undergoing hip or knee arthroplasty, colorectal surgical procedures, arterial vascular surgical procedures, and hysterectomy. INTERVENTION Timing of prophylactic antibiotic administration with respect to surgical incision time. MAIN OUTCOMES AND MEASURES Data for prophylactic antibiotic agent, prophylactic antibiotic timing with respect to surgical incision, and patient and procedure risk variables were assessed for their relationship with the occurrence of a composite superficial or deep incisional SSI within 30 days after the procedure. Nonlinear generalized additive models were used to examine the association between antibiotic timing and SSI. RESULTS Of the 32 459 operations, prophylactic antibiotics were administered at a median of 28 minutes (interquartile range, 17-39 minutes) prior to surgical incision, and 1497 cases (4.6%) developed an SSI. Compared with procedures with antibiotic administration within 60 minutes prior to incision, higher SSI rates were observed for timing more than 60 minutes prior to incision (unadjusted odds ratio OR = 1.34; 95% CI, 1.08-1.66) but not after incision (unadjusted OR = 1.26; 95% CI, 0.92-1.72). In unadjusted generalized additive models, we observed a significant nonlinear relationship between prophylactic antibiotic timing and SSI when considering timing as a continuous variable (P = .01). In generalized additive models adjusted for patient, procedure, and antibiotic variables, no significant association between prophylactic antibiotic timing and SSI was observed. Vancomycin hydrochloride was associated with higher SSI occurrence for orthopedic procedures (adjusted OR = 1.75; 95% CI, 1.16-2.65). Cefazolin sodium and quinolone in combination with an anaerobic agent were associated with fewer SSI events (cefazolin: adjusted OR = 0.49; 95% CI, 0.34-0.71; quinolone: adjusted OR = 0.55; 95% CI, 0.35-0.87) for colorectal procedures. CONCLUSIONS AND RELEVANCE The SSI risk varies by patient and procedure factors as well as antibiotic properties but is not significantly associated with prophylactic antibiotic timing. While adherence to the timely prophylactic antibiotic measure is not bad care, there is little evidence to suggest that it is better care.
1 Cardiovascular Division, Department of
Internal Medicine, and Department of Molecular Physiology and
Biological Physics, and Cardiovascular Research Center, University of
Virginia Health Sciences ...Center, Charlottesville, Virginia 22908; and
2 Medical Automation Systems, Charlottesville,
Virginia 22903
Entropy, as it relates to
dynamical systems, is the rate of information production. Methods for
estimation of the entropy of a system represented by a time series are
not, however, well suited to analysis of the short and noisy data sets
encountered in cardiovascular and other biological studies. Pincus
introduced approximate entropy (ApEn), a set of measures of system
complexity closely related to entropy, which is easily applied to
clinical cardiovascular and other time series. ApEn statistics,
however, lead to inconsistent results. We have developed a new and
related complexity measure, sample entropy (SampEn), and have compared ApEn and SampEn by using them to analyze sets of random numbers with
known probabilistic character. We have also evaluated cross-ApEn and
cross-SampEn, which use cardiovascular data sets to measure the
similarity of two distinct time series. SampEn agreed with theory much
more closely than ApEn over a broad range of conditions. The improved
accuracy of SampEn statistics should make them useful in the study of
experimental clinical cardiovascular and other biological time series.
probability; nonlinear dynamics
Social determinants of health (SDH) are individually associated with incident coronary heart disease (CHD) events. Indices reflecting social deprivation have been developed for population management, ...but are difficult to operationalize during clinical care. We examined whether a simple count of SDH is associated with fatal incident CHD and nonfatal myocardial infarction (MI).
We used data from the prospective longitudinal REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke), a national population-based sample of community-dwelling Black and White adults age ≥45 years recruited from 2003 to 2007. Seven SDH from the 5 Healthy People 2020 domains included social context (Black race, social isolation); education (educational attainment); economic stability (annual household income); neighborhood (living in a zip code with high poverty); and health care (lacking health insurance, living in 1 of the 9 US states with the least public health infrastructure). Outcomes were expert adjudicated fatal incident CHD and nonfatal MI.
Of 22 152 participants free of CHD at baseline, 58.8% were women and 42.0% were Black; 20.6% had no SDH, 30.6% had 1, 23.0% had 2, and 25.8% had ≥3. There were 463 fatal incident CHD events and 932 nonfatal MIs over a median of 10.7 years (interquartile range, 6.6 to 12.7). Fewer SDHs were associated with nonfatal MI than with fatal incident CHD. The age-adjusted incidence per 1000 person-years increased with the number of SDH for both fatal incident CHD (0 SDH, 1.30; 1 SDH, 1.44; 2 SDH, 2.05; ≥3 SDH, 2.86) and nonfatal MI (0 SDH, 3.91; 1 SDH, 4.33; ≥2 SDH, 5.44). Compared with those without SDH, crude and fully adjusted hazard ratios for fatal incident CHD among those with ≥3 SDH were 3.00 (95% CI, 2.17 to 4.15) and 1.67 (95% CI, 1.18 to 2.37), respectively; hazard ratios for nonfatal MI among those with ≥2 SDH were 1.57 (95% CI, 1.30 to 1.90) and 1.14 (95% CI, 0.93 to 1.41), respectively.
A greater burden of SDH was associated with a graded increase in risk of incident CHD, with greater magnitude and independent associations for fatal incident CHD. Counting the number of SDHs may be a promising approach that could be incorporated into clinical care to identify individuals at high risk of CHD.
OBJECTIVE:To investigate the effects of enhanced recovery after surgery (ERAS) on racial disparities in postoperative length of stay (pLOS) after colorectal surgery.
BACKGROUND:Racial disparities in ...surgical outcomes exist. We hypothesized that ERAS would reduce disparities in pLOS between black and white patients.
METHODS:Patients undergoing ERAS in 2015 were 1:1 matched by race/ethnicity, age, sex, and procedure to a pre-ERAS group from 2010 to 2014. After stratification by race/ethnicity, expected pLOS was calculated using the American College of Surgeons National Surgical Quality Improvement Project Risk Calculator. Primary outcome was the observed pLOS and observed-to-expected difference in pLOS. Secondary outcomes were National Surgical Quality Improvement Project postoperative complications including 30-day readmissions and mortality. Adjusted sensitivity analyses on pLOS were also performed.
RESULTS:Of 420 patients (210 ERAS and 210 pre-ERAS) examined, 28.3% were black. Black and white patients were similar in age, body mass index, sex, American Anesthesia Association class, and minimally invasive approaches. Within the pre-ERAS group, black patients stayed a mean of 2.7 days longer than expected compared with white patients (P < 0.05). Overall, ERAS patients had a significantly shorter pLOS (5.7 vs 8 days) and observed-to-expected difference (−0.7 vs 1.4 days) compared with pre-ERAS patients (P < 0.01). In the ERAS group, disparities in pLOS were reduced with no differences in readmissions or mortality between black and white patients. On sensitivity analyses, race/ethnicity remained a significant predictor of pLOS among pre-ERAS patients, but not for ERAS patients.
CONCLUSIONS:ERAS eliminated racial differences in pLOS between black and white patients undergoing colorectal surgery. Reduced pLOS occurred without increases in mortality, readmissions, and most postoperative complications. ERAS may provide a practical approach to reducing disparities in surgical outcomes.
Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation
. ...Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid
. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation
. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft
. Although past missions have utilized impactors to investigate the properties of small bodies
, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos
demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.
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