The Impact of Prolonged Operative Time Associated With Minimally Invasive Colorectal Surgery: A Report From the Surgical Care Outcomes Assessment Program.

BACKGROUND: Increased operative time in colorectal surgery is associated with worse surgical outcomes. Laparoscopic and robotic operations have improved outcomes, despite longer operative times. Furthermore, the definition of "prolonged" operative time has not been consistently defined. OBJECTIVE: The first objective was to define prolonged operative time across multiple colorectal operations and surgical approaches. The second was to describe the impact of prolonged operative time on length of stay and short-term outcomes. DESIGN: A retrospective cohort study. SETTING: Forty-two hospitals in the Surgical Care Outcomes Assessment Program from 2011 to 2019. PATIENTS: There were a total of 23,098 adult patients (age 18 years or older) undergoing 6 common, elective colorectal operations: right colectomy, left/sigmoid colectomy, total colectomy, low anterior resection, IPAA, or abdominoperineal resection. MAIN OUTCOME MEASURES: Prolonged operative time defined as the 75th quartile of operative times for each operation and approach. Outcomes were length of stay, discharge home, and complications. Adjusted models were used to account for factors that could impact operative time and outcomes across the strata of open and minimally invasive approaches. RESULTS: Prolonged operative time was associated with longer median length of stay (7 vs 5 days open, 5 vs 4 days laparoscopic, 4 vs 3 days robotic) and more frequent complications (42% vs 28% open, 24% vs 17% laparoscopic, 27% vs 13% robotic) but similar discharge home (86% vs 87% open, 94% vs 94% laparoscopic, 93% vs 96% robotic). After adjustment, each additional hour of operative time above the median for a given operation was associated with 1.08 (1.06-1.09) relative risk of longer length of stay for open operations and 1.07 (1.06-1.09) relative risk for minimally invasive operations. LIMITATIONS: Our study was limited by being retrospective, resulting in selection bias, possible confounders for prolonged operative time, and lack of statistical power for subgroup analyses. CONCLUSIONS: Operative time has consistent overlap across surgical approaches. Prolonged operative time is associated with longer length of stay and higher probability of complications, but this negative effect is diminished with minimally invasive approaches. See Video Abstract . EL IMPACTO DEL TIEMPO OPERATORIO PROLONGADO ASOCIADO CON LA CIRUGA COLORRECTAL MNIMAMENTE INVASIVA UN INFORME DEL PROGRAMA DE EVALUACIN DE RESULTADOS DE ATENCIN QUIRRGICA: ANTECEDENTES:El aumento del tiempo operatorio en la cirugía colorrectal se asocia con peores resultados quirúrgicos. Las operaciones laparoscópicas y robóticas han mejorado los resultados, a pesar de los tiempos operatorios más prolongados. Además, la definición de tiempo operatorio "prolongado" no se ha definido de manera consistente.OBJETIVO:Primero, definir el tiempo operatorio prolongado a través de múltiples operaciones colorrectales y enfoques quirúrgicos. En segundo lugar, describir el impacto del tiempo operatorio prolongado sobre la duración de la estancia y los resultados a corto plazo.DISEÑO:Estudio de cohorte retrospectivo.ESCENARIO:42 hospitales en el Programa de Evaluación de Resultados de Atención Quirúrgica de 2011-2019.PACIENTES:23 098 pacientes adultos (de 18 años de edad y mayores), que se sometieron a seis operaciones colorrectales electivas comunes: colectomía derecha, colectomía izquierda/sigmoidea, colectomía total, resección anterior baja, anastomosis ileoanal con bolsa o resección abdominoperineal.PRINCIPALES MEDIDAS DE RESULTADO:Tiempo operatorio prolongado definido como el cuartil 75 de tiempos operatorios para cada operación y abordaje. Los resultados fueron la duración de la estancia hospitalaria, el alta domiciliaria y las complicaciones. Se usaron modelos ajustados para tener en cuenta los factores que podrían afectar tanto el tiempo operatorio como los resultados en los estratos de abordajes abiertos y mínimamente invasivos.RESULTADOS:El tiempo operatorio prolongado se asoció con una estancia media más prolongada (7 vs. 5 días abiertos, 5 vs. 4 días laparoscópicos, 4 vs. 3 días robóticos), complicaciones más frecuentes (42 % vs. 28 % abiertos, 24 % vs. 17 % laparoscópica, 27% vs. 13% robótica), pero similar alta domiciliaria (86% vs. 87% abierta, 94% vs. 94% laparoscópica, 93% vs. 96% robótica). Después del ajuste, cada hora adicional de tiempo operatorio por encima de la mediana para una operación determinada se asoció con un riesgo relativo de 1,08 (1,06, 1,09) de estancia hospitalaria más larga para operaciones abiertas y un riesgo relativo de 1,07 (1,06, 1,09) para operaciones mínimamente invasivas.LIMITACIONES:Nuestro estudio estuvo limitado por ser retrospectivo, lo que resultó en un sesgo de selección, posibles factores de confusión por un tiempo operatorio prolongado y falta de poder estadístico para los análisis de subgrupos.CONCLUSIONES:El tiempo operatorio tiene una superposición constante entre los enfoques quirúrgicos. El tiempo operatorio prolongado se asocia con una estadía más prolongada y una mayor probabilidad de complicaciones, pero este efecto negativo disminuye con los enfoques mínimamente invasivos. ( Traducción-Dr. Mauricio Santamaria ).

Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury.

BACKGROUND: Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown. OBJECTIVE: Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI. PATIENTS AND METHODS: We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI. RESULTS: Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25). CONCLUSIONS: We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.

Cefepime pharmacokinetics in critically ill children and young adults undergoing continuous kidney replacement therapy.

OBJECTIVES: Cefepime is an antibiotic commonly used to treat sepsis and is cleared by renal excretion. Cefepime dosing requires adjustment in patients with decreased kidney function and in those receiving continuous kidney replacement therapy (CKRT). We aimed to characterize cefepime PK in a diverse cohort of critically ill paediatric patients on CKRT. METHODS: Patients were identified from an ongoing pharmacokinetic/pharmacodynamic (PK/PD) study of beta-lactam antibiotics, and were included if they had received at least two cefepime doses in the ICU and were on CKRT for at least 24 h. PK parameters were estimated using MwPharm++ with Bayesian estimation and a paediatric population PK model. Target attainment was assessed as time of free cefepime concentrations above minimum inhibitory concentration (fT > 1× or 4 × MIC). RESULTS: Seven patients were included in the study (ages 2 to 20 years). CKRT indications included liver failure (n = 1), renal failure (n = 4) and fluid overload (n = 2). Total effluent flow rates ranged from 1833 to 3115 (mean 2603) mL/1.73 m2/h, while clearance was 2.11-3.70 (mean 3.0) L/h/70 kg. Effluent flows were lower, but clearance and fT > MIC were similar to paediatric data published previously. Using Pseudomonas aeruginosa MIC breakpoints, all patients had 100% of dosing interval above MIC, but only one had 100% of dosing interval above 4× MIC. CONCLUSIONS: Since most patients failed to attain stringent targets of 100% fT > 4×  MIC, model-informed precision dosing may benefit such patients.

Ceftriaxone Pharmacokinetics and Pharmacodynamics in 2 Pediatric Patients on Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND: Critically ill patients with cardiac or respiratory failure may require extracorporeal membrane oxygenation (ECMO). Antibiotics are frequently administered when the suspected cause of organ failure is an infection. Ceftriaxone, a ß-lactam antibiotic, is commonly used in patients who are critically ill. Although studies in adults on ECMO have suggested minimal impact on ceftriaxone pharmacokinetics, limited research exists on ceftriaxone pharmacokinetics/pharmacodynamics (PK/PD) in pediatric ECMO patients. We report the PK profiles and target attainment of 2 pediatric patients on ECMO who received ceftriaxone. METHODS: Ceftriaxone concentrations were measured in 2 pediatric patients on ECMO using scavenged opportunistic sampling. PK profiles were generated and individual PK parameters were estimated using measured free ceftriaxone concentrations and a published population PK model in children who are critically ill, using Bayesian estimation. RESULTS: Patient 1, an 11-year-old boy on venovenous ECMO for respiratory failure received 2 doses of 52 mg/kg ceftriaxone 12 hours apart while on ECMO and additional doses every 12 hours off ECMO. On ECMO, ceftriaxone clearance was 13.0 L/h/70 kg compared with 7.6 L/h/70 kg off ECMO, whereas the model-predicted mean clearance in children who are critically ill without ECMO support was 6.54 L/h/70 kg. Patient 2, a 2-year-old boy on venoarterial ECMO due to cardiac arrest received 50 mg/kg ceftriaxone every 12 hours while on ECMO for >7 days. Only clearance while on ECMO could be estimated (9.1 L/h/70 kg). Trough concentrations in both patients were >1 mg/L (the breakpoint for Streptococcus pneumoniae ) while on ECMO. CONCLUSIONS: ECMO increased ceftriaxone clearance above the model-predicted clearances in the 2 pediatric patients studied. Twelve-hour dosing allowed concentrations to remain above the breakpoint for commonly targeted bacteria but not 4 times the breakpoint in one patient, suggesting that precision dosing may be beneficial to ensure target attainment in children on ECMO.

External validation of the modified sepsis renal angina index for prediction of severe acute kidney injury in children with septic shock.

BACKGROUND: Acute kidney injury (AKI) occurs commonly in pediatric septic shock and increases morbidity and mortality. Early identification of high-risk patients can facilitate targeted intervention to improve outcomes. We previously modified the renal angina index (RAI), a validated AKI prediction tool, to improve specificity in this population (sRAI). Here, we prospectively assess sRAI performance in a separate cohort. METHODS: A secondary analysis of a prospective, multicenter, observational study of children with septic shock admitted to the pediatric intensive care unit from 1/2019 to 12/2022. The primary outcome was severe AKI (≥ KDIGO Stage 2) on Day 3 (D3 severe AKI), and we compared predictive performance of the sRAI (calculated on Day 1) to the original RAI and serum creatinine elevation above baseline (D1 SCr > Baseline +). Original renal angina fulfillment (RAI +) was defined as RAI ≥ 8; sepsis renal angina fulfillment (sRAI +) was defined as RAI ≥ 20 or RAI 8 to < 20 with platelets < 150 × 103/µL. RESULTS: Among 363 patients, 79 (22%) developed D3 severe AKI. One hundred forty (39%) were sRAI + , 195 (54%) RAI + , and 253 (70%) D1 SCr > Baseline + . Compared to sRAI-, sRAI + had higher risk of D3 severe AKI (RR 8.9, 95%CI 5-16, p < 0.001), kidney replacement therapy (KRT) (RR 18, 95%CI 6.6-49, p < 0.001), and mortality (RR 2.5, 95%CI 1.2-5.5, p = 0.013). sRAI predicted D3 severe AKI with an AUROC of 0.86 (95%CI 0.82-0.90), with greater specificity (74%) than D1 SCr > Baseline (36%) and RAI + (58%). On multivariable regression, sRAI + retained associations with D3 severe AKI (aOR 4.5, 95%CI 2.0-10.2, p < 0.001) and need for KRT (aOR 5.6, 95%CI 1.5-21.5, p = 0.01). CONCLUSIONS: Prediction of severe AKI in pediatric septic shock is important to improve outcomes, allocate resources, and inform enrollment in clinical trials examining potential disease-modifying therapies. The sRAI affords more accurate and specific prediction than context-free SCr elevation or the original RAI in this population.

A Comparison of US Medicare Expenditures for Hemodialysis and Peritoneal Dialysis.

BACKGROUND: Observations that peritoneal dialysis (PD) may be an effective, lower-cost alternative to hemodialysis for the treatment of ESKD have led to policies encouraging PD and subsequent increases in its use in the United States. METHODS: In a retrospective cohort analysis of Medicare beneficiaries who started dialysis between 2008 and 2015, we ascertained average annual expenditures (for up to 3 years after initiation of dialysis) for patients ≥67 years receiving in-center hemodialysis or PD. We also determined whether differences in Medicare expenditures across dialysis modalities persisted as more patients were placed on PD. We used propensity scores to match 8305 patients initiating PD with 8305 similar patients initiating hemodialysis. RESULTS: Overall average expenditures were US$108,656 (2017) for hemodialysis and US$91,716 for PD (proportionate difference, 1.11; 95% confidence interval [CI], 1.09 to 1.13). This difference did not change over time (P for time interaction term=0.14). Hemodialysis had higher estimated intravenous (iv) dialysis drug costs (1.69; 95% CI, 1.64 to 1.73), rehabilitation expenditures (1.35; 95% CI, 1.26 to 1.45), and other nondialysis expenditures (1.34; 95% CI, 1.30 to 1.37). Over time, initial differences in total dialysis expenditures disappeared and differences in iv dialysis drug utilization narrowed as nondialysis expenditures diverged. Estimated iv drug costs declined by US$2900 per patient-year in hemodialysis between 2008 and 2014 versus US$900 per patient-year in PD. CONCLUSIONS: From the perspective of the Medicare program, savings associated with PD in patients ≥67 years have remained unchanged, despite rapid growth in the use of this dialysis modality. Total dialysis expenditures for the two modalities converged over time, whereas nondialysis expenditures diverged.

Cost Barriers to More Widespread Use of Peritoneal Dialysis in the United States.

The United States Department of Health and Human Services launched the Advancing American Kidney Health Initiative in 2019, which included a goal of transforming dialysis care from an in-center to a largely home-based dialysis program. A substantial motivator for this transition is the potential to reduce costs of ESKD care with peritoneal dialysis. Studies demonstrating that peritoneal dialysis is less costly than in-center hemodialysis have often focused on the perspective of the payer, whereas less consideration has been given to the costs of those who are more directly involved in treatment decision making, including patients, caregivers, physicians, and dialysis facilities. We review comparisons of peritoneal dialysis and in-center hemodialysis costs, focusing on costs incurred by the people and organizations making decisions about dialysis modality, to highlight the financial barriers toward increased adoption of peritoneal dialysis. We specifically address misaligned economic incentives, underappreciated costs for key stakeholders involved in peritoneal dialysis delivery, differences in provider costs, and transition costs. We conclude by offering policy suggestions that include improving data collection to better understand costs in peritoneal dialysis, and sharing potential savings among all stakeholders, to incentivize a transition to peritoneal dialysis.

Population Pharmacokinetic Modeling of Total and Free Ceftriaxone in Critically Ill Children and Young Adults and Monte Carlo Simulations Support Twice Daily Dosing for Target Attainment.

Critical illness, including sepsis, causes significant pathophysiologic changes that alter the pharmacokinetics (PK) of antibiotics. Ceftriaxone is one of the most prescribed antibiotics in patients admitted to the pediatric intensive care unit (PICU). We sought to develop population PK models of both total ceftriaxone and free ceftriaxone in children admitted to a single-center PICU using a scavenged opportunistic sampling approach. We tested if the presence of sepsis and phase of illness (before or after 48 h of antibiotic treatment) altered ceftriaxone PK parameters. We performed Monte Carlo simulations to evaluate whether dosing regimens commonly used in PICUs in the United States (50 mg/kg of body weight every 12 h versus 24 h) resulted in adequate antimicrobial coverage. We found that a two-compartment model best described both total and free ceftriaxone concentrations. For free concentrations, the population clearance value is 6.54 L/h/70 kg, central volume is 25.4 L/70 kg, and peripheral volume is 19.6 L/70 kg. For both models, we found that allometric weight scaling, postmenstrual age, creatinine clearance, and daily highest temperature had significant effects on clearance. The presence of sepsis or phase of illness did not have a significant effect on clearance or volume of distribution. Monte Carlo simulations demonstrated that to achieve free concentrations above 1 µg/ml for 100% of the dosing intervals, a dosing regimen of 50 mg/kg every 12 h is recommended for most patients. A continuous infusion could be considered if the target is to maintain free concentrations four times above the MICs (4 µg/ml).

Evaluating variation in enhanced recovery for colorectal surgery: a report from the Surgical Care Outcomes Assessment Program.

AIM: Robust data demonstrate that enhanced recovery protocols (ERPs) decrease length of stay, complications and cost. However, little is known about the reasons for variation in compliance with ERPs. The aim of this work was to confirm the efficacy of ERPs in a regional network, and to determine factors that are associated with ERP delivery in diverse hospital settings. METHOD: A prospective cohort of patients was created by recording all elective colorectal operations at hospitals in the Surgical Care Outcomes Assessment Program (SCOAP). The delivery of 12 ERP components was tracked at all sites, and factors associated with ERP component delivery and affecting outcomes were reported. RESULTS: From 2016 to 2019, 9274 elective colorectal operations were performed at 36 hospitals. Indications were 48% cancer, 23% diverticulitis and 8% inflammatory bowel disease. Minimally invasive surgery was used in 71%. The proportion of cases with six or more ERP components received increased from 23% in 2016 to 50% in 2019. An increase in components was associated with a shorter length of stay and fewer combined adverse events and reinterventions. Further, increasing numbers of ERP components provided an incremental benefit to patients even when delivered in a low-volume centre or by a low-volume surgeon, and regardless of patient presentation. CONCLUSION: At SCOAP hospitals, the delivery of increasing numbers of ERP components was associated with improved perioperative outcomes and decreased complications after elective colorectal surgery. The variation in delivery of these evidence-based components in subsets of our cohort indicates an important opportunity for quality improvement initiatives.

Inventory of Youth Adaptation to Loss (IYAL): Psychometric Testing of a New Instrument for Bereaved Youth to Assess Social Support and Coping.

The Inventory of Youth Adaptation to Loss (IYAL) was developed to understand the feelings and social supports experienced by bereaved youth to develop an evidence-base for bereavement interventions. The sample included 400 youth ages 9-17, permitting robust psychometric testing of the IYAL. To evaluate the reliability of the IYAL, the sample framework was national in scope, encompassed a range of different types of youth bereavement programs, and purposively sought diversity in the sample. Exploratory factor analysis identified five factors with distinct sub-scales indicating that the IYAL is a valid and reliable assessment instrument of youth coping with grief and their social support relationships.

Obesity protects against sepsis-induced and norepinephrine-induced white adipose tissue browning.

Sepsis is a dysregulated systemic response to infection and can lead to organ damage and death. Obesity is a significant problem worldwide and affects outcomes from sepsis. Our laboratory demonstrated that white adipose tissue (WAT) undergoes browning during sepsis, a process whereby WAT adopts a brown adipose tissue phenotype. However, this browning process was not observed in obese mice during sepsis. White adipose tissue browning is detrimental in patients with burn injury and cancer. We hypothesize that norepinephrine (NE) induces WAT browning in nonobese mice but not in obese mice similarly to sepsis-induced WAT browning. Six-week-old C57BL/6 male mice were randomized to a high-fat diet or normal diet. After 6-7 wk of feeding, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Norepinephrine was administered intraperitoneally via osmotic minipumps for 18 h or 72 h (no CLP) at which time tissue and plasma were harvested. Controls were mice that underwent CLP (no NE) with 18-h harvest. A separate group of mice underwent pretreatment with NE or vehicle infusion for 72 h, CLP was performed, and at 18 h had tissue and plasma harvested. Sepsis resulted in significant weight loss in both nonobese and obese mice. NE treatment alone caused weight loss in obese mice. Septic nonobese mice had higher uncoupling protein-1 (UCP1) expression compared with control and obese septic mice. NE treatment increased UCP1 expression in nonobese, but not obese mice. NE-treated obese septic mice had lower lung myeloperoxidase (MPO) activity, alanine aminotransferase (ALT), aspartate aminotransferase (AST), TNFα, and IL-6 levels compared with NE-treated nonobese septic mice. Obesity protects mice from septic-induced and NE-induced WAT browning.NEW & NOTEWORTHY White adipose tissue browning is detrimental in patients with burn injury and cancer. WAT browning occurs in nonobese mice and can be induced by ß receptor norepinephrine infusion, but obese mice are resistant to sepsis-induced and norepinephrine-induced WAT browning. We propose that the lack of WAT browning and unchanged inflammatory cytokine response may contribute to the protection of obese mice from sepsis.

Pelvic Floor Nonrelaxation: Approach to Evaluation and Treatment.

Dyssynergic defecation can be a complex, burdensome condition. A multidisciplinary approach to these patients is often indicated based on concomitant pathology or symptomatology across the pelvic organs. Escalating treatment options should be based on shared decision making and include medical and lifestyle optimization, pelvic floor physical therapy with biofeedback, Botox injection, sacral neuromodulation, rectal irrigation, and surgical diversion.

Derivation, Validation, Sustained Performance, and Clinical Impact of an Electronic Medical Record-Based Perioperative Delirium Risk Stratification Tool.

BACKGROUND: Postoperative delirium is an important problem for surgical inpatients and was the target of a multidisciplinary quality improvement project at our institution. We developed and tested a semiautomated delirium risk stratification instrument, Age, WORLD backwards, Orientation, iLlness severity, Surgery-specific risk (AWOL-S), in 3 independent cohorts from our tertiary care hospital and describe its performance characteristics and impact on clinical care. METHODS: The risk stratification instrument was derived with elective surgical patients who were admitted at least overnight and received at least 1 postoperative delirium screen (Nursing Delirium Screening Scale [NuDESC] or Confusion Assessment Method for the Intensive Care Unit [CAM-ICU]) and preoperative cognitive screening tests (orientation to place and ability to spell WORLD backward). Using data pragmatically collected between December 7, 2016, and June 15, 2017, we derived a logistic regression model predicting probability of delirium in the first 7 postoperative hospital days. A priori predictors included age, cognitive screening, illness severity or American Society of Anesthesiologists physical status, and surgical delirium risk. We applied model odds ratios to 2 subsequent cohorts ("validation" and "sustained performance") and assessed performance using area under the receiver operator characteristic curves (AUC-ROC). A post hoc sensitivity analysis assessed performance in emergency and preadmitted patients. Finally, we retrospectively evaluated the use of benzodiazepines and anticholinergic medications in patients who screened at high risk for delirium. RESULTS: The logistic regression model used to derive odds ratios for the risk prediction tool included 2091 patients. Model AUC-ROC was 0.71 (0.67-0.75), compared with 0.65 (0.58-0.72) in the validation (n = 908) and 0.75 (0.71-0.78) in the sustained performance (n = 3168) cohorts. Sensitivity was approximately 75% in the derivation and sustained performance cohorts; specificity was approximately 59%. The AUC-ROC for emergency and preadmitted patients was 0.71 (0.67-0.75; n = 1301). After AWOL-S was implemented clinically, patients at high risk for delirium (n = 3630) had 21% (3%-36%) lower relative risk of receiving an anticholinergic medication perioperatively after controlling for secular trends. CONCLUSIONS: The AWOL-S delirium risk stratification tool has moderate accuracy for delirium prediction in a cohort of elective surgical patients, and performance is largely unchanged in emergent/preadmitted surgical patients. Using AWOL-S risk stratification as a part of a multidisciplinary delirium reduction intervention was associated with significantly lower rates of perioperative anticholinergic but not benzodiazepine, medications in those at high risk for delirium. AWOL-S offers a feasible starting point for electronic medical record-based postoperative delirium risk stratification and may serve as a useful paradigm for other institutions.

Hepatic STAT3 inhibition amplifies the inflammatory response in obese mice during sepsis.

The purpose of this study was to better understand the role obesity plays in the inflammatory response during sepsis, specifically regarding the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway in the liver. We hypothesized that inhibiting STAT3 would lead to an increase in the inflammatory response and that obesity would amplify this effect. To investigate this, we inhibited STAT3 in two ways: pharmacological systemic inhibition and genetic hepatic-specific inhibition. In pharmacological inhibition studies, male C57BL/6 mice were randomized to a high-fat (60% kcal fat) or normal (16% kcal fat) diet for 6-7 wk and pretreated with Stattic before inducing sepsis by cecal ligation and puncture. In genetic inhibition studies, mice were randomized by genotype before induction of sepsis. To investigate obesity in mice with hepatic-specific STAT3 inhibition, we randomized mice to a high-fat or normal diet as described above for 6 mo before induction of sepsis. Body composition was analyzed using EchoMRI. We found that systemic STAT3 inhibition by Stattic resulted in an increased inflammatory response and that obesity amplified this effect. We also found that genetically inhibiting STAT3 in the liver resulted in higher mortality, increased inflammation, and liver injury. High-fat-fed mice with hepatic STAT3 inhibition gained more weight and had more fat than control mice on the same diet, and obesity increased neutrophil infiltration to the liver of these mice during sepsis. In conclusion, STAT3 plays an important regulatory role in the inflammatory response during sepsis, and obesity contributes to the dysregulated response observed when STAT3 is inhibited.

Automated Breast Density Measurements From Chest Computed Tomography Scans.

To develop an automated method for quantifying percent breast density from chest computed tomography (CT) scans. A naïve Bayesian classifier based on gray-level intensities and spatial relationships was developed on CT scans from 10 patients diagnosed with Hodgkin lymphoma (HL) and imaged as part of routine clinical care. The algorithm was validated on CT scans from 75 additional HL patients. The classifier was developed and validated using a reference dataset with consensus manual segmentation of fibroglandular tissue. Accuracy was evaluated at the pixel-level to examine how well the algorithm identified pixels with fibroglandular tissue using true and false positive fractions (TPF and FPF, respectively). Quantitative estimates of the patient-level CT percent density were contrasted to each other using the concordance correlation coefficient, ρc, and to subjective ACR BI-RADS density assessments using Kendall's τb. The pixel-level TPF for identifying pixels with fibroglandular tissue was 82.7% (interquartile range of patient-specific TPFs 65.5%-89.6%). The pixel-level FPF was 9.2% (interquartile range of patient-specific FPFs 2.5%-45.3%). Patient-level agreement of the algorithm's automated density estimate with that obtained from the reference dataset was high, ρc = 0.93 (95% CI 0.90-0.96) as was agreement with a radiologist's subjective ACR-BI-RADS assessments, τb = 0.77. It is possible to obtain automated measurements of percent density from clinical CT scans.

Positive predictive value of biopsy of palpable masses following mastectomy.

Determine the positive predictive value (PPV) of biopsy of palpable masses following mastectomy (MX). Determine if there are patient characteristics, tumor, or imaging features more predictive of cancer. IRB-approved retrospective review of 16 396 breast ultrasounds June 2008-December 2015 identified patients with MX presenting with palpable masses. Medical records and imaging studies were reviewed. Statistical analysis was performed using Fisher's exact test. 95% confidence intervals (CI) were calculated. In all, 117 patients presented with palpable masses on the MX side. 101/117 patients who had a palpable mass on physical examination had a true sonographic mass to correlate with the clinical findings. 91/101 (90%) underwent biopsy: 19/91 (21%, 95% CI; 13-31) biopsies were malignant. 72/91 (79%) were benign. All 19 cancers were on the original cancer side. Recurrences ranged from 0.4 to 4.5 cm maximum diameter, mean 1.3 cm. Prophylactic vs therapeutic mastectomy was very statistically significant (P = .01). The use of tamoxifen or an AI was also statistically significant (P = .04). Patient age (P = 1.0), radiation therapy (P = 1.05), chemotherapy (P = .2), immediate breast reconstruction (P = .2), or implant vs flap (P = .2) had no statistically significant association with finding cancer on biopsy. Lesion shape (irregular vs oval/round) was highly statistically significant (P = .0003) as was non-parallel orientation on ultrasound (P = .008). Circumscribed vs non-circumscribed margins was also statistically significant (P = .008). The PPV of biopsy of palpable masses on the side of MX was 21% (95% CI; 13-31). All recurrences were on the original cancer side and this was very statistically significant.

Hypothermia, pH, and Postoperative Red Blood Cell Transfusion in Massively Transfused Adult Cardiac Surgery Patients: A Retrospective Cohort Study.

OBJECTIVE: To determine the relationships between hypothermia and pH at surgery end and postoperative red blood cell (RBC) transfusion in massively transfused adult cardiac surgery patients. DESIGN: Retrospective cohort study. SETTING: Single tertiary care, academic medical center. PARTICIPANTS: A total of 395 adult patients having cardiac surgery with cardiopulmonary bypass who were massively transfused during an 8-year period. Patients were excluded if they did not receive an antifibrinolytic drug during surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Body temperature and pH at surgery end were recorded. Postoperative RBC transfusion, a surrogate for postoperative bleeding, was the study's primary outcome. Secondary outcomes were postoperative fresh frozen plasma (FFP) transfusion, postoperative platelet transfusion, reoperation for bleeding, and mortality. Patients with hypothermia did not have more postoperative RBC transfusion (p = 0.56), but patients with acidosis or alkalosis received more RBCs after surgery (p = 0.04). There were no differences in secondary outcomes between groups. In multivariate analysis, both acidosis and alkalosis were independently associated with postoperative RBC transfusion (p = 0.01 and p < 0.0001). CONCLUSION: Hypothermia at surgery end has no association with postoperative RBC transfusion in massively transfused cardiac surgery patients, but pH derangements are associated with increased postoperative transfusion. Thus, normalization of blood pH may be important in reducing postoperative bleeding in massively transfused cardiac surgery patients.

Prenatal Screening for 22q11.2 Deletion Using a Targeted Microarray-Based Cell-Free DNA Test.

OBJECTIVE: To determine the performance of a targeted microarray-based cell-free DNA (cfDNA) test (Harmony Prenatal Test®) for the identification of pregnancies at increased risk for 22q11.2 deletion. METHODS: Test performance was determined in 2 steps including a total of 1,953 plasma samples. Analytical validation was performed in 1,736 plasma samples. Clinical verification of performance was performed in an additional 217 prospectively ascertained samples from pregnancies with fetal deletion status determined by diagnostic testing. RESULTS: Analytical sensitivity was 75.4% (95% CI: 67.1-82.2%) based on 122 samples with deletions ranging from 1.96 to 3.25 Mb. In 1,614 presumed unaffected samples, specificity was determined to be at least 99.5% (95% CI: 99.0-99.7%). In the clinical cohort, 5 of 7 samples from pregnancies affected with 22q11.2 deletion were determined to have a high probability of deletion. There were no false positive results in the 210 unaffected samples in this cohort. These clinical data are consistent with the performance demonstrated in the analytical validation. CONCLUSIONS: cfDNA testing using a targeted microarray-based technology is able to identify pregnancies at increased risk for 22q11.2 deletions of 3.0 Mb and smaller while maintaining a low false positive rate.

High fat diet-induced obesity increases myocardial injury and alters cardiac STAT3 signaling in mice after polymicrobial sepsis.

Little is known about how obesity affects the heart during sepsis and we sought to investigate the obesity-induced cardiac effects that occur during polymicrobial sepsis. Six-week old C57BL/6 mice were randomized to a high fat (HFD) (60% kcal fat) or normal diet (ND) (16% kcal fat). After 6weeks of feeding, mice were anesthetized with isoflurane and polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Plasma and cardiac tissue were obtained for analysis. Echocardiography was performed on a separate cohort of mice at 0 and 18h after CLP. Following 6-weeks of dietary intervention, plasma cardiac troponin I was elevated in obese mice at baseline compared to non-obese mice but troponin increased only in non-obese septic mice. IL-17a expression was 27-fold higher in obese septic mice versus non-obese septic mice. Cardiac phosphorylation of STAT3 at Ser727 was increased at baseline in obese mice and increased further only in obese septic mice. Phosphorylation of STAT3 at Tyr705 was similar in both groups at baseline and increased after sepsis. SOCS3, a downstream protein and negative regulator of STAT3, was elevated in obese mice at baseline compared to non-obese mice. After sepsis non-obese mice had an increase in SOCS3 expression that was not observed in obese mice. Taken together, we show that obesity affects cardiac function and leads to cardiac injury. Furthermore, myocardial injury in obese mice during sepsis may occur through alteration of the STAT3 pathway.

Comparison of Background Parenchymal Enhancement at Contrast-enhanced Spectral Mammography and Breast MR Imaging.

Purpose To assess the extent of background parenchymal enhancement (BPE) at contrast material-enhanced (CE) spectral mammography and breast magnetic resonance (MR) imaging, to evaluate interreader agreement in BPE assessment, and to examine the relationships between clinical factors and BPE. Materials and Methods This was a retrospective, institutional review board-approved, HIPAA-compliant study. Two hundred seventy-eight women from 25 to 76 years of age with increased breast cancer risk who underwent CE spectral mammography and MR imaging for screening or staging from 2010 through 2014 were included. Three readers independently rated BPE on CE spectral mammographic and MR images with the ordinal scale: minimal, mild, moderate, or marked. To assess pairwise agreement between BPE levels on CE spectral mammographic and MR images and among readers, weighted κ coefficients with quadratic weights were calculated. For overall agreement, mean κ values and bootstrapped 95% confidence intervals were calculated. The univariate and multivariate associations between BPE and clinical factors were examined by using generalized estimating equations separately for CE spectral mammography and MR imaging. Results Most women had minimal or mild BPE at both CE spectral mammography (68%-76%) and MR imaging (69%-76%). Between CE spectral mammography and MR imaging, the intrareader agreement ranged from moderate to substantial (κ = 0.55-0.67). Overall agreement on BPE levels between CE spectral mammography and MR imaging and among readers was substantial (κ = 0.66; 95% confidence interval: 0.61, 0.70). With both modalities, BPE demonstrated significant association with menopausal status, prior breast radiation therapy, hormonal treatment, breast density on CE spectral mammographic images, and amount of fibroglandular tissue on MR images (P < .001 for all). Conclusion There was substantial agreement between readers for BPE detected on CE spectral mammographic and MR images. © RSNA, 2016.