Transient pores in hemifusion diaphragms.

Exchange of material across two membranes, as in the case of synaptic neurotransmitter release from a vesicle, involves the formation and poration of a hemifusion diaphragm (HD). The nontrivial geometry of the HD leads to environment-dependent control, regarding the stability and dynamics of the pores required for this kind of exocytosis. This work combines particle simulations, field-based calculations, and phenomenological modeling to explore the factors influencing the stability, dynamics, and possible control mechanisms of pores in HDs. We find that pores preferentially form at the HD rim, and that their stability is sensitive to a number of factors, including the three line tensions, membrane tension, HD size, and the ability of lipids to "flip-flop" across leaflets. Along with a detailed analysis of these factors, we discuss ways that vesicles or cells may use them to open and close pores and thereby quickly and efficiently transport material.

Evaluating the Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) for Clinical Trials of Antibiotics in Pediatric Pneumonia.

Objective outcomes for pediatric community-acquired pneumonia (CAP) are lacking. The desirability of outcome ranking (DOOR) and response adjusted for duration of antibiotic risk (RADAR) outcome encompass clinical benefit and adverse effects, while also accounting for antibiotic exposure. We evaluated DOOR/RADAR through simulations and compared sample size considerations to non-inferiority designs in a hypothetical trial comparing antibiotics to no antibiotics (i.e., placebo) for children with mild CAP. We also evaluated a trial comparing different durations of antibiotics. Three scenarios were considered - one with no difference in DOOR between the two groups, one in which placebo is more efficacious, and another in which amoxicillin is more efficacious than placebo. Power to detect a difference between arms was greater using DOOR/RADAR compared to DOOR. Assuming a sample size of 200, DOOR had 2.5%, 50%, and 65% power to detect a statistical difference between arms for Scenarios 1-3, respectively, significantly less than DOOR/RADAR. Importantly, DOOR/RADAR incorrectly identified placebo as superior in Scenario 3 where amoxicillin was truly efficacious. Sample size requirements for non-inferiority designs were larger to achieve similar levels of power as DOOR and DOOR/RADAR. DOOR/RADAR has the potential to lead to an incorrect conclusion declaring placebo superior when amoxicillin is efficacious.

PACT: a pipeline for analysis of circulating tumor DNA.

MOTIVATION: Detection of genomic alterations in circulating tumor DNA (ctDNA) is currently used for active clinical monitoring of cancer progression and treatment response. While methods for analysis of small mutations are more developed, strategies for detecting structural variants (SVs) in ctDNA are limited. Additionally, reproducibly calling small-scale mutations, copy number alterations, and SVs in ctDNA is challenging due to the lack to unified tools for these different classes of variants. RESULTS: We developed a unified pipeline for the analysis of ctDNA [Pipeline for the Analysis of ctDNA (PACT)] that accurately detects SVs and consistently outperformed similar tools when applied to simulated, cell line, and clinical data. We provide PACT in the form of a Common Workflow Language pipeline which can be run by popular workflow management systems in high-performance computing environments. AVAILABILITY AND IMPLEMENTATION: PACT is freely available at https://github.com/ChrisMaherLab/PACT.

Timing of Kasai Procedure for Biliary Atresia: An Analysis of the Pediatric National Surgical Quality Improvement Program Database.

INTRODUCTION: Biliary atresia is a rare liver disease of unknown etiology affecting approximately 1 in 10,000 children. This disease initially presents as inflammatory obstruction of bile ducts leading to cholestasis and eventually fibrosis of hepatic tissue. Affected patients are ideally treated early with portoenterostomy (Kasai procedure) as age at surgery is an important prognostic factor for native liver survival and need for liver transplant. This study aimed to evaluate the age at which patients in the United States are receiving this procedure. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Pediatric database was used to identify patients between 2012 and 2021 who underwent a primary procedure of portoenterostomy. The age at time of surgery and perioperative analysis was performed. The data underwent simple descriptive statistics. RESULTS: Eight hundred twenty four patients were identified who underwent Kasai procedure. Four hundred seventy four (58.2%) were female with the predominant race being White (49.5%). The median age at surgery was 57 d old (interquartile range 41-71). Readmission and reoperation rates within 30 d were 30% and 15.2%, respectively. There were no deaths within 30 d. CONCLUSIONS: Within the National Surgical Quality Improvement Program database, the median age of pediatric patients undergoing Kasai procedure for biliary atresia in the United States exceeds the goal of 45 d. Further studies are needed to investigate factors that may affect time to diagnosis and time to Kasai procedure.

Risk factors for prolonged infection and secondary infection in pediatric severe sepsis.

PURPOSE: Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications. METHODS: We performed a secondary analysis of clinical data from 401 subjects enrolled in the PHENOtyping sepsis-induced Multiple organ failure Study. We examined factors associated with prolonged infection, defined as infection that continued to be identified 7 days or more from initial identification, and secondary infection, defined as new infections identified ≥ 3 days from presentation. Multivariable adjustment was performed to examine laboratory markers of immune depression, with immunocompromised and immunocompetent subjects analyzed separately. RESULTS: Illness severity, immunocompromised status, invasive procedures, and site of infection were associated with secondary infection and/or prolonged infection. Persistent lymphopenia, defined as an absolute lymphocyte count (ALC) < 1000 cells/µL twice in the first five days, and persistent neutropenia, defined as absolute neutrophil count (ANC) < 1000 cells/µL twice in the first five days, were associated with secondary and prolonged infections. When adjusted in multivariable analysis, persistent lymphopenia remained associated with secondary infection in both immunocompromised (aOR = 14.19, 95% CI [2.69, 262.22] and immunocompetent subjects (aOR = 2.09, 95% CI [1.03, 4.17]). Persistent neutropenia was independently associated with secondary infection in immunocompromised subjects (aOR = 5.34, 95% CI [1.92, 15.84]). Secondary and prolonged infections were associated with worse outcomes, including death. CONCLUSIONS: Laboratory markers of immune suppression can be used to predict secondary infection. Lymphopenia is an independent risk factor in immunocompromised and immunocompetent patients for secondary infection.

Fear of cancer recurrence experienced by pediatric survivors of childhood cancer: a scoping review.

PURPOSE: In contrast to the extensive literature on fear of cancer recurrence (FCR) experienced by adults, literature evaluating pediatric FCR has just begun to emerge. Given the rapidly expanding body of work assessing FCR in childhood and adolescence, a scoping review was conducted to synthesize existing findings. We aimed to assess (1) the characteristics and methods of this literature, (2) how pediatric FCR has been measured, and (3) the extant knowledge of FCR experienced by pediatric survivors of cancer. METHODS: Inclusion criteria were: (1) original reports, (2) participants diagnosed with cancer before age 18, (3) current mean age under 18, (4) FCR was explicitly measured (quantitatively) or captured (qualitatively) via survivor self-report, and (6) published in English. Exclusion criteria were: (1) case studies, and (2) grey literature. Three databases (Embase, MEDLINE, PsycINFO) and reference lists from included studies were searched. All studies were screened for inclusion by two authors and all data were extracted by a single author. RESULTS: Of 3906 identified studies, 19 were included. Studies (published 1991 - 2023) encompassed diverse geographical locations, study designs, and measurement methods. Few assessed FCR as a primary aim (n = 6, 32%). FCR was experienced by 43 - 90% of pediatric survivors. FCR was often positively associated with somatic symptoms and negatively associated with quality of life and emotional functioning. CONCLUSION: FCR is a prevalent issue for children and adolescents. Additional evidence is needed to explore and confirm preliminary findings. Future pediatric FCR studies should aim to align with published priority research areas.

Chemerin triggers migration of a CD8 T cell subset with natural killer cell functions.

The recruitment of cells with effector functions into the tumor microenvironment holds potential for delaying cancer progression. We show that subsets of human CD28-effector CD8 T cells, CCR7- CD45RO+ effector memory, and CCR7- CD45RO- effector memory RA phenotypes, express the chemerin receptor CMKLR1 and bind chemerin via the receptor. CMKLR1-expressing human CD8 effector memory T cells present gene, protein, and cytotoxic features of NK cells. Active chemerin promotes chemotaxis of CMKLR1-expressing CD8 effector memory cells and triggers activation of the α4ß1 integrin. In an experimental prostate tumor mouse model, chemerin expression is downregulated in the tumor microenvironment, which is associated with few tumor-infiltrating CD8+ T cells, while forced overexpression of chemerin by mouse prostate cancer cells leads to an accumulation of intra-tumor CD8+ T cells. Furthermore, α4 integrin blockade abrogated the chemerin-dependent recruitment of CD8+ T effector memory cells into implanted prostate tumors in vivo. The results identify a role for chemerin:CMKLR1 in defining a specialized NK-like CD8 T cell, and suggest the use of chemerin-dependent modalities to target effector CMKLR1-expressing T cells to the tumor microenvironment for immunotherapeutic purposes.

Association of an In-Hospital Desirability of Outcomes Ranking Scale With Postdischarge Health-Related Quality of Life: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation.

OBJECTIVES: To develop a desirability of outcome ranking (DOOR) scale for use in children with septic shock and determine its correlation with a decrease in 3-month postadmission health-related quality of life (HRQL) or death. DESIGN: Secondary analysis of the Life After Pediatric Sepsis Evaluation prospective study. SETTING: Twelve U.S. PICUs, 2013-2017. PATIENTS: Children (1 mo-18 yr) with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied a 7-point pediatric critical care (PCC) DOOR scale: 7: death; 6: extracorporeal life support; 5: supported by life-sustaining therapies (continuous renal replacement therapy, vasoactive, or invasive ventilation); 4: hospitalized with or 3: without organ dysfunction; 2: discharged with or 1: without new morbidity to patients by assigning the highest applicable score on specific days post-PICU admission. We analyzed Spearman rank-order correlations (95% CIs) between proximal outcomes (PCC-DOOR scale on days 7, 14, and 21, ventilator-free days, cumulative 28-day Pediatric Logistic Organ Dysfunction-2 (PELOD-2) scores, and PICU-free days) and 3-month decrease in HRQL or death. HRQL was measured by Pediatric Quality of Life Inventory 4.0 or Functional Status II-R for patients with developmental delay. Patients who died were assigned the worst possible HRQL score. PCC-DOOR scores were applied to 385 patients, median age 6 years (interquartile range 2, 13) and 177 (46%) with a complex chronic condition(s). Three-month outcomes were available for 245 patients (64%) and 42 patients (17%) died. PCC-DOOR scale on days 7, 14, and 21 demonstrated fair correlation with the primary outcome (-0.42 [-0.52, -0.31], -0.47 [-0.56, -0.36], and -0.52 [-0.61, -0.42]), similar to the correlations for cumulative 28-day PELOD-2 scores (-0.51 [-0.59, -0.41]), ventilator-free days (0.43 [0.32, 0.53]), and PICU-free days (0.46 [0.35, 0.55]). CONCLUSIONS: The PCC-DOOR scale is a feasible, practical outcome for pediatric sepsis trials and demonstrates fair correlation with decrease in HRQL or death at 3 months.

Social Determinants of Health and Health-Related Quality of Life Following Pediatric Septic Shock: Secondary Analysis of the Life After Pediatric Sepsis Evaluation Dataset, 2014-2017.

OBJECTIVES: Social determinants of health (SDOH) are associated with disparities in disease severity and in-hospital outcomes among critically ill children. It is unknown whether SDOH are associated with later outcomes. We evaluated associations between SDOH measures and mortality, new functional morbidity, and health-related quality of life (HRQL) decline among children surviving septic shock. DESIGN: Secondary analysis of the Life After Pediatric Sepsis Evaluation (LAPSE) prospective cohort study was conducted between 2014 and 2017. SETTING: Twelve academic U.S. PICUs were involved in the study. PATIENTS: Children younger than 18 years with community-acquired septic shock were involved in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed associations between race, ethnicity, income, education, marital status, insurance, language, and home U.S. postal code with day 28 mortality, new functional morbidity at discharge per day 28, and HRQL decline using logistic regression. Of 389 patients, 32% ( n = 98) of families had household income less than $50,000 per year. Median Pediatric Risk of Mortality (PRISM) score was 11 (interquartile range 6, 17). We found that English language and Area Deprivation Index less than 50th percentile were associated with higher PRISM scores. Mortality was 6.7% ( n = 26), new functional morbidity occurred in 21.8% ( n = 78) of patients, and HRQL decline by greater than 10% occurred in 31.0% of patients ( n = 63). We failed to identify any association between SDOH measures and mortality, new functional morbidity, or HRQL decline. We are unable to exclude the possibility that annual household income greater than or equal to $50,000 was associated with up to 81% lesser odds of mortality and, in survivors, more than three-fold greater odds of HRQL decline by greater than 10%. CONCLUSIONS: In this secondary analysis of the 2014-2017 LAPSE dataset, we failed to identify any association between SDOH measures and in-hospital or postdischarge outcomes following pediatric septic shock. This finding may be reflective of the high illness severity and single disease (sepsis) of the cohort, with contribution of clinical factors to functional and HRQL outcomes predominating over prehospital and posthospital SDOH factors.

Early Cardiac Arrest Hemodynamics, End-Tidal C o2 , and Outcome in Pediatric Extracorporeal Cardiopulmonary Resuscitation: Secondary Analysis of the ICU-RESUScitation Project Dataset (2016-2021).

OBJECTIVES: Cannulation for extracorporeal membrane oxygenation during active extracorporeal cardiopulmonary resuscitation (ECPR) is a method to rescue patients refractory to standard resuscitation. We hypothesized that early arrest hemodynamics and end-tidal C o2 (ET co2 ) are associated with survival to hospital discharge with favorable neurologic outcome in pediatric ECPR patients. DESIGN: Preplanned, secondary analysis of pediatric Utstein, hemodynamic, and ventilatory data in ECPR patients collected during the 2016-2021 Improving Outcomes from Pediatric Cardiac Arrest study; the ICU-RESUScitation Project (ICU-RESUS; NCT02837497). SETTING: Eighteen ICUs participated in ICU-RESUS. PATIENTS: There were 97 ECPR patients with hemodynamic waveforms during cardiopulmonary resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall, 71 of 97 patients (73%) were younger than 1 year old, 82 of 97 (85%) had congenital heart disease, and 62 of 97 (64%) were postoperative cardiac surgical patients. Forty of 97 patients (41%) survived with favorable neurologic outcome. We failed to find differences in diastolic or systolic blood pressure, proportion achieving age-based target diastolic or systolic blood pressure, or chest compression rate during the initial 10 minutes of CPR between patients who survived with favorable neurologic outcome and those who did not. Thirty-five patients had ET co2 data; of 17 survivors with favorable neurologic outcome, four of 17 (24%) had an average ET co2 less than 10 mm Hg and two (12%) had a maximum ET co2 less than 10 mm Hg during the initial 10 minutes of resuscitation. CONCLUSIONS: We did not identify an association between early hemodynamics achieved by high-quality CPR and survival to hospital discharge with favorable neurologic outcome after pediatric ECPR. Candidates for ECPR with ET co2 less than 10 mm Hg may survive with favorable neurologic outcome.

mTBI evaluation, management, and referral to allied healthcare: practices of first-line healthcare professionals.

PRIMARY OBJECTIVE: To gain an understanding of current evaluation practices, post-injury recommendations, and referrals to allied healthcare professions (AHP) by first-line healthcare professionals (FHPs) providing care for people with mild traumatic brain injury (mTBI). RESEARCH DESIGN: Survey study. METHODS AND PROCEDURES: Physicians, physician assistants, nurse practitioners, nurses, and athletic trainers (n = 126) completed an online survey, including Likert scale and free response question relating to mTBI evaluation, management, and referral practices. MAIN OUTCOMES AND RESULTS: FHPs surveyed reported being confident in their ability to evaluate patients with suspected mTBI, relying most heavily on patient-reported symptoms and physical signs as methods of evaluation. Most FHPs reported making recommendations to compensate for the symptoms experienced following mTBI diagnosis. In contrast, FHPs expressed challenges in the evaluation and management of symptoms associated with mTBI along with limited knowledge of and referrals to AHPs. CONCLUSIONS: Overall, FHPs feel confident in the diagnosis of mTBI but experience assessment and management challenges. AHPs are underutilized on mTBI management teams calling for a need for multidisciplinary collaboration on research, education, and rehabilitation efforts to optimally care for people experiencing mTBI symptoms.

Early, Persistent Lymphopenia Is Associated With Prolonged Multiple Organ Failure and Mortality in Septic Children.

OBJECTIVES: Sepsis-associated immune suppression correlates with poor outcomes. Adult trials are evaluating immune support therapies. Limited data exist to support consideration of immunomodulation in pediatric sepsis. We tested the hypothesis that early, persistent lymphopenia predicts worse outcomes in pediatric severe sepsis. DESIGN: Observational cohort comparing children with severe sepsis and early, persistent lymphopenia (absolute lymphocyte count < 1,000 cells/µL on 2 d between study days 0-5) to children without. The composite outcome was prolonged multiple organ dysfunction syndrome (MODS, organ dysfunction beyond day 7) or PICU mortality. SETTING: Nine PICUs in the National Institutes of Health Collaborative Pediatric Critical Care Research Network between 2015 and 2017. PATIENTS: Children with severe sepsis and indwelling arterial and/or central venous catheters. INTERVENTIONS: Blood sampling and clinical data analysis. MEASUREMENTS AND MAIN RESULTS: Among 401 pediatric patients with severe sepsis, 152 (38%) had persistent lymphopenia. These patients were older, had higher illness severity, and were more likely to have underlying comorbidities including solid organ transplant or malignancy. Persistent lymphopenia was associated with the composite outcome prolonged MODS or PICU mortality (66/152, 43% vs 45/249, 18%; p < 0.01) and its components prolonged MODS (59/152 [39%] vs 43/249 [17%]), and PICU mortality (32/152, 21% vs 12/249, 5%; p < 0.01) versus children without. After adjusting for baseline factors at enrollment, the presence of persistent lymphopenia was associated with an odds ratio of 2.98 (95% CI [1.85-4.02]; p < 0.01) for the composite outcome. Lymphocyte count trajectories showed that patients with persistent lymphopenia generally did not recover lymphocyte counts during the study, had lower nadir whole blood tumor necrosis factor-α response to lipopolysaccharide stimulation, and higher maximal inflammatory markers (C-reactive protein and ferritin) during days 0-3 ( p < 0.01). CONCLUSIONS: Children with severe sepsis and persistent lymphopenia are at risk of prolonged MODS or PICU mortality. This evidence supports testing therapies for pediatric severe sepsis patients risk-stratified by early, persistent lymphopenia.

The North American Monsoon buffers forests against the ongoing megadrought in the Southwestern United States.

The US Southwest has been entrenched in a two-decade-long megadrought (MD), the most severe since 800 CE, which threatens the long-term vitality and persistence of regional montane forests. Here, we report that in the face of record low winter precipitation and increasing atmospheric aridity, seasonal activity of the North American Monsoon (NAM) climate system brings sufficient precipitation during the height of the summer to alleviate extreme tree water stress. We studied seasonally resolved, tree-ring stable carbon isotope ratios across a 57-year time series (1960-2017) in 17 Ponderosa pine forests distributed across the NAM geographic domain. Our study focused on the isotope dynamics of latewood (LW), which is produced in association with NAM rains. During the MD, populations growing within the core region of the NAM operated at lower intrinsic and higher evaporative water-use efficiencies (WUEi and WUEE , respectively), compared to populations growing in the periphery of the NAM domain, indicating less physiological water stress in those populations with access to NAM moisture. The disparities in water-use efficiencies in periphery populations are due to a higher atmospheric vapor pressure deficit (VPD) and reduced access to summer soil moisture. The buffering advantage of the NAM, however, is weakening. We observed that since the MD, the relationship between WUEi and WUEE in forests within the core NAM domain is shifting toward a drought response similar to forests on the periphery of the NAM. After correcting for past increases in the atmospheric CO2 concentration, we were able to isolate the LW time-series responses to climate alone. This showed that the shift in the relation between WUEi and WUEE was driven by the extreme increases in MD-associated VPD, with little advantageous influence on stomatal conductance from increases in atmospheric CO2 concentration.

Predicting functional and quality-of-life outcomes following pediatric sepsis: performance of PRISM-III and PELOD-2.

BACKGROUND: Illness severity scores predict mortality following pediatric critical illness. Given declining PICU mortality, we assessed the ability of the Pediatric Risk of Mortality-III (PRISM) and Pediatric Logistic Organ Dysfunction-2 (PELOD) scores to predict morbidity outcomes. METHODS: Among 359 survivors <18 years in the Life After Pediatric Sepsis Evaluation multicenter prospective cohort study, we assessed functional morbidity at hospital discharge (Functional Status Scale increase ≥3 points from baseline) and health-related quality of life (HRQL; Pediatric Quality of Life Inventory or Functional Status II-R) deterioration >25% from baseline at 1, 3, 6, and 12 months post-admission. We determined discrimination of admission PRISM and admission, maximum, and cumulative 28-day PELOD with functional and HRQL morbidity at each timepoint. RESULTS: Cumulative PELOD provided the best discrimination of discharge functional morbidity (area under the receive operating characteristics curve [AUROC] 0.81, 95% CI 0.76-0.87) and 3-month HRQL deterioration (AUROC 0.71, 95% CI 0.61-0.81). Prediction was inferior for admission PRISM and PELOD and for 6- and 12-month HRQL assessments. CONCLUSIONS: Illness severity scores have a good prediction of early functional morbidity but a more limited ability to predict longer-term HRQL. Identification of factors beyond illness severity that contribute to HRQL outcomes may offer opportunities for intervention to improve outcomes. IMPACT: Illness severity scores are commonly used for mortality prediction and risk stratification in pediatric critical care research, quality improvement, and resource allocation algorithms. Prediction of morbidity rather than mortality may be beneficial given declining pediatric intensive care unit mortality. The PRISM and PELOD scores have moderate to good ability to predict new functional morbidity at hospital discharge following pediatric septic shock but limited ability to predict health-related quality of life outcomes in the year following PICU admission. Further research is needed to identify additional factors beyond illness severity that may impact post-discharge health-related quality of life.

Robotic Surgery for Pediatric Choledochal Cysts: An American Case Series and Literature Review.

INTRODUCTION: Choledochal cysts are rare congenital biliary cystic dilations. The US incidence rate varies between 5 and 15 cases per 1,000,000 people. In contrast, Asians, which are a large subset of the population of Hawaii, have an incidence of approximately one in every 1000 births. We report our experience with robot-assisted laparoscopic surgical management with biliary reconstruction of choledochal cysts which to date is the largest American case series to be reported. MATERIALS AND METHODS: From 2006 to 2021, patients diagnosed with a choledochal cyst(s) at a tertiary children's hospital were retrospectively reviewed. Perioperative analysis was performed. Complications were defined as immediate, early, or late. The data underwent simple descriptive statistics. RESULTS: Nineteen patients underwent choledochal cystectomy and hepaticoduodenostomy. Thirteen underwent a robotic approach while the rest were planned laparoscopic. Eighteen of 19 were female with 15/19 of Asian descent. The ages ranged from 5 mo to 21 y. Presenting diagnoses included jaundice, primary abdominal pain, pancreatitis, and cholangitis. Sixty eight percent had type 1 fusiform cysts while the rest were type 4a. Operative time and length of stay for robotic versus laparoscopic were 321 versus 267 min and 8.2 versus 17.3 d, respectively. For the robotic group, there was one immediate complication due to peritonitis. One-year follow-up revealed two patients requiring endoscopic retrograde cholangiopancreatography with dilation/stenting for an anastomotic stricture. There were no anastomotic leaks. CONCLUSIONS: Robot-assisted laparoscopic choledochal cystectomy with hepaticoduodenostomy is associated with overall good outcomes with the most common long-term complication being anastomotic stenosis.

Disparities and Risk Factors for Surgical Complication in American Indians and Native Hawaiians.

INTRODUCTION: American Indian and Alaskan Natives (AIAN) and Native Hawaiian and Pacific Islanders (NHPI) research is limited, particularly in postoperative surgical outcomes. This study analyzes disparities in AIAN and NHPI surgical complications across all surgical types and identifies factors that contribute to postoperative complications. METHODS: This retrospective cohort study examined all surgeries from 2011 to 2020 in the National Surgical Quality Improvement Program, queried by race. Multivariable models analyzed the association of race and ethnicity and 30-day postoperative complication. Next, multivariable models were used to identify preoperative variables associated with postoperative complications, specifically in AIAN and NHPI patients. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated. RESULTS: AIAN patients were associated with higher odds of postoperative complication (AOR: 1.008 [CI: 1.005-1.011], P < 0.001) compared to non-Hispanic white patients. The comorbidities that were of higher incidence in AIAN patients, which also adversely contributed to postoperative complication, included dependent functional status, diabetes, congestive heart failure (CHF), open wounds, preoperative weight loss, bleeding disorders, preoperative transfusion, sepsis, hypoalbuminemia, along with an active smoking status and ASA ≥3. In NHPI patients, dependent functional status, CHF, renal failure, preoperative transfusion, open wounds, and sepsis were of higher incidence and significantly contributed to postoperative complication. CONCLUSIONS: Surgical outcome disparities exist particularly in AIAN patients. Identification of modifiable patient risk factors may benefit perioperative care for AIAN and NHPI patients, which are historically understudied racial groups.

Racial Disparities in General Surgery Outcomes.

INTRODUCTION: While disparities in Black and Hispanic and Latino patients undergoing general surgeries are well described, most analyses leave out Asian, American Indian or Alaskan Native (AIAN), and native Hawaiian or Pacific Islander patients. This study identified general surgery outcomes for each racial group in the National Surgical Quality Improvement Program. METHODS: National Surgical Quality Improvement Program was queried to identify all procedures conducted by a general surgeon from 2017 to 2020 (n = 2,664,197). Multivariable regression models were used to investigate the impact of race and ethnicity on 30-day mortality, readmission, reoperation, major and minor medical complications, and non-home discharge destinations. Adjusted odds ratios (AOR) and 95% confidence intervals were calculated. RESULTS: Compared to non-Hispanic White patients, Black patients had higher odds of readmission and reoperation, and Hispanic and Latino patients had higher odds of major and minor complications. AIAN patients had higher odds of mortality (AOR: 1.003 (1.002-1.005), P < 0.001), major complication (AOR: 1.013 (1.006-1.020), P < 0.001), reoperation (AOR: 1.009, (1.005-1.013), P < 0.001), and non-home discharge destination (AOR: 1.006 (1.001-1.012), P = 0.025), while native Hawaiian or Pacific Islander patients had lower odds of readmission (AOR: 0.991 (0.983-0.999), P = 0.035) and non-home discharge destination (AOR: 0.983 (0.975-0.990), P < 0.001) compared to non-Hispanic White patients. Asian patients had lower odds of each adverse outcome. CONCLUSIONS: Black, Hispanic and Latino, and AIAN patients are at higher odds for poor postoperative results than non-Hispanic White patients. AIANs had some of the highest odds of mortality, major complications, reoperation, and non-home discharge. Social health determinants and policy adjustments must be targeted to ensure optimal operative results for all patients.

The carbon balance of plants: economics, optimization, and trait spectra in a historical perspective.

Over fifty years have passed since the publication of Harold Mooney's formative paper, "The Carbon Balance of Plants" on pages 315-346 of Volume 3 (1972) of Annual Review of Ecology and Systematics. Arguably, the conceptual framework presented in that paper, and the work by Mooney and his students leading up to the paper, provided the foundational principles from which core disciplines emerged in plant economic theory, functional trait theory and, more generally, plant physiological ecology. Here, we revisit the primary impacts of those early discoveries to understand how researchers constructed major concepts in our understanding of plant adaptations, and where those concepts are likely to take us in the near future. The discipline of functional trait ecology, which is rooted in the principles of evolutionary and economic optimization, has captured the imagination of the plant physiological ecology research community, though its emphasis has shifted toward predicting species distributions and ecological roles across resource gradients. In the face of 'big-data' research pursuits that are revealing trait expression patterns at the cellular level and mass and energy exchange patterns at the planetary scale, an opportunity exists to reconnect the principles of plant carbon balance and evolutionary optimization with trait origins at the genetic and cellular scales and trait impacts at the global scale.

Association of Sex and Age with Mortality and Health-Related Quality of Life in Children with Septic Shock: A Secondary Analysis of the Life After Pediatric Sepsis Evaluation.

Introduction: Sepsis is more common in males than females, but whether outcomes differ by sex in various pediatric age groups is unclear. The Life After Pediatric Sepsis Evaluation (LAPSE) was a multicenter prospective cohort study that evaluated health-related quality of life (HRQL) in children after community-acquired septic shock. In this secondary analysis, we evaluated whether male children are at increased risk of mortality or long-term decline in HRQL than female children by age group. Methods: Children (1 month-18 years) with community-acquired septic shock were recruited from 12 pediatric intensive care units in the U.S. Data included sex, age group (<1 year, 1-<13 years, 13-18 years), acute illness severity (acute organ dysfunction and inflammation), and longitudinal assessments of HRQL and mortality. Persistent decline in HRQL was defined as a 10% decrease in HRQL comparing baseline to 3 months following admission. Male and female children were stratified by age group and compared to evaluate the difference in the composite outcome of death or persistent decline in HRQL using the Cochran-Mantel-Haenszel test. Results: Of 389 children, 54.2% (n = 211) were male. Overall, 10% (21/211) of males and 12% (22/178) of females died by 3 months (p = 0.454). Among children with follow-up data, 41% (57/138) of males and 44% (48/108) of females died or had persistent decline in HRQL at 3 months (p = 0.636), with no observed difference by sex when stratified by age group. There was no significant difference in acute illness severity between males and females overall or stratified by age group. Conclusions: In this secondary analysis of the LAPSE cohort, HRQL, and mortality were not different between male and female children when stratified by age group. There were no significant differences by sex across multiple measures of illness severity or treatment intensity.

Change in Functional Status During Hospital Admission and Long-Term Health-Related Quality of Life Among Pediatric Septic Shock Survivors.

OBJECTIVES: To investigate whether change in functional status from pre-hospitalization baseline to hospital discharge is associated with long-term health-related quality of life (HRQL) among children surviving septic shock. DESIGN: Secondary analysis of Life After Pediatric Sepsis Evaluation (LAPSE), a prospective cohort study of children with community-acquired septic shock, enrolled from January 2014 to June 2017. SETTING: Twelve U.S. academic PICUs. PATIENTS: Children, 1 month to 18 years, who survived to hospital discharge and had follow-up data for HRQL at 3 and/or 12 months. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Functional Status Scale (FSS) was assessed around enrollment to ascertain baseline status (pre-hospitalization) and at 28 days or hospital discharge. Two measures of HRQL were utilized: children with significant development delay were measured with the Functional Status II-R (FSII-R); typically, developing children were measured with the Pediatric Quality of Life Inventory (PedsQL). Each group was analyzed separately with multivariable regression modeling to determine the association between change in FSS from baseline to day 28 and HRQL at 3 and 12 months from PICU admission. Of the original 389 LAPSE participants, 224 (58%) are included. Among children with developmental delay ( n = 88), worsened FSS was associated with lower FSII-R at 3 months from PICU admission (-2.02; 95% CI, -3.34 to -0.0.71; p = 0.003), but not 12 months. Among developmentally typical children ( n = 136), worsened FSS was associated with lower PedsQL at both 3 and 12 months. Developmentally typical children with a neurologic insult during the PICU stay had the largest decrement in PedsQL at 12 months (-14.04 mo; 95% CI, -22.15 to -5.94 mo; p < 0.001). However, worsened FSS remained associated with poor HRQL-PedsQL at 3 and 12 months, after controlling for neurologic events (both p < 0.001). CONCLUSIONS: Change in FSS during hospitalization for septic shock is associated with long-term reductions in HRQL and could serve as a useful tool for identifying children at risk for this sequela.