Case Report of 11 Years of Severe Malabsorption, Muscular Atrophy, Seizures, and Immunodeficiency Resolved After Proximal Intercessory Prayer.

We present the case of 11 years of severe malabsorption, muscular atrophy, seizures, and immunodeficiency resolved after proximal intercessory prayer (PIP). A male infant suffered from severe abdominal pain and impaired development with the introduction of solid food at age five months. The patient had previously appeared healthy, having been born to term and breastfed. Neocate and total parenteral nutrition (TPN) were prescribed, and the former was removed due to abdominal pain and diarrhea. Ultimately, the patient became completely dependent on TPN. It was concluded that he suffered from chronic, idiopathic, severe malabsorption. Development of neutropenia, hypogamma-globulinemia, and hypotonia was recorded. Medical records document atrophy and progressive deterioration of muscular symptoms. At five years of age, frontal lobe epilepsy was detected. Over the course of the disease, several genetic tests were performed. Doctors tried unsuccessfully to diagnose an underlying condition, with various mitochondriopathies and Shwachman-Diamond syndrome suggested as possible causes, but no prognosis of recovery was given. Eleven years following the initial presentation of symptoms, proximal intercessory prayer (PIP) was administered in a single session. The patient reported no unusual sensations during prayer. However, oral feedings were immediately tolerated without discomfort from that time onward. Post-PIP medical records indicate discontinuation of TPN, seizures, and seizure medications. Progressive improvement in the hematological disorders, BMI, and muscular symptoms was also observed. The present case report describes a novel association between PIP and the lasting resolution of multiple symptoms likely related to a genetic disorder. The results inform ongoing discussions about faith-based practices in health care and suggest the need for additional studies of PIP on health outcomes.

Knockdown of Esr1 from DRD1-Rich Brain Regions Affects Adipose Tissue Metabolism: Potential Crosstalk between Nucleus Accumbens and Adipose Tissue.

Declining estrogen (E2) leads to physical inactivity and adipose tissue (AT) dysfunction. Mechanisms are not fully understood, but E2's effects on dopamine (DA) activity in the nucleus accumbens (NAc) brain region may mediate changes in mood and voluntary physical activity (PA). Our prior work revealed that loss of E2 robustly affected NAc DA-related gene expression, and the pattern correlated with sedentary behavior and visceral fat. The current study used a new transgenic mouse model (D1ERKO) to determine whether the abolishment of E2 receptor alpha (ERα) signaling within DA-rich brain regions affects PA and AT metabolism. Adult male and female wild-type (WT) and D1ERKO (KD) mice were assessed for body composition, energy intake (EE), spontaneous PA (SPA), and energy expenditure (EE); underwent glucose tolerance testing; and were assessed for blood biochemistry. Perigonadal white AT (PGAT), brown AT (BAT), and NAc brain regions were assessed for genes and proteins associated with DA, E2 signaling, and metabolism; AT sections were also assessed for uncoupling protein (UCP1). KD mice had greater lean mass and EE (genotype effects) and a visible change in BAT phenotype characterized by increased UCP1 staining and lipid depletion, an effect seen only among females. Female KD had higher NAc Oprm1 transcript levels and greater PGAT UCP1. This group tended to have improved glucose tolerance (p = 0.07). NAc suppression of Esr1 does not appear to affect PA, yet it may directly affect metabolism. This work may lead to novel targets to improve metabolic dysfunction following E2 loss, possibly by targeting the NAc.

Identifying trigger cues for hospital blood transfusions based on ensemble of machine learning methods.

BACKGROUND: Traumatic shock is the leading cause of preventable death with most patients dying within the first six hours from arriving to the hospital. This underscores the importance of prehospital interventions, and growing evidence suggests prehospital transfusion improves survival. Optimizing transfusion triggers in the prehospital setting is key to improving outcomes for patients in hemorrhagic shock. Our objective was to identify factors associated with early in-hospital transfusion requirements available to prehospital clinicians in the field to develop a simple algorithm for prehospital transfusion, particularly for patients with occult shock. METHODS: We included trauma patients transported by a single critical care transport service to a level I trauma center between 2012 and 2019. We used logistic regression, Fast and Frugal Trees (FFTs), and Bayesian analysis to identify factors associated with early in-hospital blood transfusion as a potential trigger for prehospital transfusion. RESULTS: We included 2,157 patients transported from the scene or emergency department (ED) of whom 207 (9.60%) required blood transfusion within four hours of admission. The mean age was 47 (IQR = 28 - 62) and 1,480 (68.6%) patients were male. From 13 clinically relevant factors for early hospital transfusions, four were incorporated into the FFT in following order: 1) SBP, 2) prehospital lactate concentration, 3) Shock Index, 4) AIS of chest (sensitivity = 0.81, specificity = 0.71). The chosen thresholds were similar to conventional ones. Using conventional thresholds resulted in lower model sensitivity. Consistently, prehospital lactate was among most decisive factors of hospital transfusions identified by Bayesian analysis (OR = 2.31; 95% CI 1.55 - 3.37). CONCLUSIONS: Using an ensemble of frequentist statistics, Bayesian analysis and machine learning, we developed a simple, clinically relevant prehospital algorithm to help identify patients requiring transfusion within 4 h of hospital arrival.

Critically Assessing the Unanswered Questions of How, Where, and When to Induce Plasticity in the Posttraumatic Stress Disorder Network with Transcranial Magnetic Stimulation.

Extinction of traumatic memory, a primary treatment approach (termed exposure therapy) in post-traumatic stress disorder (PTSD), occurs through relearning and may be subserved at the molecular level by long-term potentiation (LTP) of relevant circuits. In parallel, repetitive transcranial magnetic stimulation (rTMS) is thought to work through LTP-like mechanisms and may provide a novel, safe, and effective treatment for PTSD. Our recent failed randomized controlled trial (1) emphasizes the necessity of correctly identifying cortical targets, directionality of TMS protocol, and role of memory activation. Here we provide a systematic review of TMS for PTSD to further identify how, where, and when TMS treatment should be delivered to alleviate PTSD symptoms. We conducted a systematic review of the literature searching for rTMS clinical trials involving PTSD patients and outcomes. We searched MEDLINE through October 25th, 2023 for "TMS and PTSD" and "transcranial magnetic stimulation and posttraumatic stress disorder." Thirty-one publications met our inclusion criteria (k=17 randomized controlled trials (RCTs), k=14 open label). RCT protocols were varied in TMS protocols, cortical TMS targets, and memory activation protocols. There was no clear superiority across protocols of low-frequency (k=5) vs. high-frequency protocols (k=6), or by stimulation location. Memory provocation or exposure protocols (k=7) appear to enhance response. Overall, TMS appears to be effective in treating PTSD symptoms across a variety of TMS frequencies, hemispheric target differences, and exposure protocols. Disparate protocols may be conceptually harmonized when viewed as potentiating proposed anxiolytic networks or suppressing anxiogenic networks.

Association between low cognitive performance and diabetes-related health indicators across racial and ethnic groups in adults with diabetes.

AIM: To examine the associations between low cognitive performance (LCP) and diabetes-related health indicators (including body mass index [BMI], HbA1c, systolic blood pressure [SBP], low-density lipoprotein [LDL] and self-reported poor physical health) and whether these associations vary across racial/ethnic subgroups. METHODS: We identified adults aged 60 years or older with self-reported diabetes from the 2011-2014 National Health and Nutrition Examination Survey. Individuals with cognitive test scores in the lowest quartile were defined as having LCP. We used regression models to measure the associations of LCP with diabetes-related biometrics (BMI, HbA1c, SBP and LDL); and self-reported poor physical health. Moreover, we explored potential variations in these associations across racial/ethnic subgroups. RESULTS: Of 873 (261 with LCP) adults with diabetes, LCP was associated with higher HbA1c, SBP and LDL (adjusted difference: 0.41%, 5.01 mmHg and 5.08 mg/dL, respectively; P < .05), and greater odds of reporting poor physical health (adjusted odds ratio: 1.59, P < .05). The association between LCP and HbA1c was consistent across racial/ethnic groups, and notably pronounced in Hispanic and Other. BMI worsened with LCP, except for non-Hispanic Black. Excluding the Other group, elevated SBP was observed in people with LCP, with Hispanic showing the most significant association. LDL levels were elevated with LCP for Hispanic and Other. Physical health worsened with LCP for both non-Hispanic Black and Hispanic. CONCLUSIONS: We quantified the association between LCP and diabetes-related health indicators. These associations were more pronounced in Hispanic and Other racial/ethnic groups.

Trauma-Induced Coagulopathy: Prevalence and Association with Mortality Persist Twenty Years Later.

INTRODUCTION: A 2003 landmark study identified the prevalence of eTIC at 28% with a strong association with mortality of 8.9%. Over the last 20 years there have been significant advances in both the fundamental understanding of eTIC and therapeutic interventions. METHODS: A retrospective cohort study was performed from 2018-2022 on patients ≥18 using prospectively collected data from two level 1 trauma centers and compared to data from 2003. Demographics, laboratory data and clinical outcomes were obtained. RESULTS: There were 20,107 patients meeting criteria: 65% male, 85% blunt, mean age 54 ± 21 years, median injury severity score (ISS) 10 [10, 18]), 8% of patients were hypotensive on arrival, with an all-cause mortality 6.0%. The prevalence of eTIC remained high at 32% in patients with an abnormal PT and 10% with an abnormal PTT, for an overall combined prevalence of 33.4%. Coagulopathy had a major impact on mortality over all injury severity ranges, with the greatest impact with lower ISS. In a hybrid logistic regression/Classification and Regression Trees analysis, coagulopathy was independently associated with a 2.1-fold increased risk of mortality (95% CI 1.5-2.9); the predictive quality of the model was excellent (AUROC 0.932). CONCLUSION: The presence of eTIC conferred a higher risk of death across all disease severities and was independently associated with a greater risk of death. Biomarkers of coagulopathy associated with eTIC remain strongly predictive of poor outcome despite advances in trauma care.

Characterization of adverse events in injured patients at risk of hemorrhagic shock: a secondary analysis of three harmonized prehospital randomized clinical trials.

Background: The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness. Methods: We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes. Results: We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ2=81.27, p<0.001) compared with those without an AE documented. Patients with a single AE had a significant higher mortality than those with multiple AEs, potentially due to survival bias (log-rank χ2=11.80, p=0.006). When relatedness of each individual AE was characterized, over 97% of AEs were classified as 'definitely not related' or 'probably not related' to the intervention. Conclusions: AEs in hemorrhagic shock trials are common, occur early and are associated with mortality and survival bias. The potential for inaccurate reporting exists, and education and training remain essential for appropriate treatment arm comparison. The current results have important relevance to injury-related clinical trials. Trial registration numbers: NCT01818427, NCT02086500 and NCT03477006. Level of evidence: II.

A new angle on transcranial magnetic stimulation coil orientation: A targeted narrative review.

Transcranial magnetic stimulation (TMS) is used to treat several neuropsychiatric disorders including depression, where it is effective in approximately half of patients for whom pharmacological approaches have failed. Treatment response is related to stimulation parameters such as the stimulation frequency, pattern, intensity, location, total number of pulses and sessions applied, as well as target brain network engagement. One critical but underexplored component of the stimulation procedure is the orientation or yaw angle of the commonly used figure-of-eight TMS coil, which is known to impact neuronal response to TMS. However, coil orientation has remained largely unchanged since TMS was first used to treat depression and continues to be based on motor cortex anatomy which may not be optimal for the dorsolateral prefrontal cortex treatment site. This targeted narrative review evaluates experimental, clinical, and computational evidence indicating that optimizing coil orientation may potentially improve TMS treatment outcomes. The properties of the electric field induced by TMS, the changes to this field caused by the differing conductivities of head tissues, and the interaction between coil orientation and the underlying cortical anatomy are summarized. We describe evidence that the magnitude and site of cortical activation, surrogate markers of TMS dosing and brain network targeting considered central in clinical response to TMS, are influenced by coil orientation. We suggest that coil orientation should be considered when applying therapeutic TMS and propose several approaches to optimizing this potentially important treatment parameter.

ResearchConnect.info: An Interactive Web-Based Platform for Building Academic Collaborations.

RATIONALE AND OBJECTIVES: Radiology is a rapidly evolving field that benefits from continuous innovation and research participation among trainees. Traditional methods for involving residents in research are often inefficient and limited, usually due to the absence of a standardized approach to identifying available research projects. A centralized online platform can enhance networking and offer equal opportunities for all residents. MATERIALS AND METHODS: Research Connect is an online platform built with PHP, SQL, and JavaScript. Features include project and collaboration listing as well as advertisement of project openings to medical/undergraduate students, residents, and fellows. The automated system maintains project data and sends notifications for new research opportunities when they meet user preference criteria. Both pre- and post-launch surveys were used to assess the platform's efficacy. RESULTS: Before the introduction of Research Connect, 69% of respondents used informal conversations as their primary method of discovering research opportunities. One year after its launch, Research Connect had 141 active users, comprising 63 residents and 41 faculty members, along with 85 projects encompassing various radiology subspecialties. The platform received a median satisfaction rating of 4 on a 1-5 scale, with 54% of users successfully locating projects of interest through the platform. CONCLUSION: Research Connect addresses the need for a standardized method and centralized platform with active research projects and is designed for scalability. Feedback suggests it has increased the visibility and accessibility of radiology research, promoting greater trainee involvement and academic collaboration.

Whole Blood and Blood Component Resuscitation in Trauma: Interaction and Association with Mortality.

OBJECTIVE: Evaluate the interaction between whole blood (WB) and blood component resuscitation in relation to mortality following trauma. SUMMARY BACKGROUND DATA: WB is increasingly available in civilian trauma resuscitation, and it is typically transfused concomitantly with blood components. The interaction between WB and blood component transfusions is unclear. METHODS: Adult trauma patients with a shock index >1 who received ≥4 combined units of red blood cells (RBC) or WB within 4 hours across 501 United States trauma centers were included using the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) database. The associations between 1)WB resuscitation and mortality, 2)WB to total transfusion volume ratio (WB:TTV) and mortality, 3)balanced blood component transfusion in the setting of combined WB and component resuscitation and mortality were evaluated with multivariable analysis. RESULTS: A total of 12,275 patients were included (WB: 2,884 vs. component-only: 9,391). WB resuscitation was associated with lower odds of 4-hour (adjusted odds ratio [aOR]: 0.81 [0.68-0.97]), 24-hour, and 30-day mortality compared to component-only. Higher WB:TTV ratios were significantly associated with lower 4-hour, 24-hour, and 30-day mortality, with a 13% decrease in odds of 4-hour mortality for each 10% increase in the WB:TTV ratio (0.87 [95%CI:0.80 - 0.94]). Balanced blood component transfusion was associated with significantly lower odds of 4-hour (aOR: 0.45 [95%CI: 0.29 - 0.68]), 24-hour, and 30-day mortality in the setting of combined WB and blood component resuscitation. CONCLUSIONS: WB resuscitation, higher WB:TTV ratios, and balanced blood component transfusion in conjunction with WB were associated with lower mortality in trauma patients presenting in shock requiring 4 units of RBC and/or WB transfusion within 4 hours of arrival.

Longitudinal Monitoring of Clinician-Patient Video Visits During the Peak of the COVID-19 Pandemic: Adoption and Sustained Challenges in an Integrated Health Care Delivery System.

BACKGROUND: Numerous prior opinion papers, administrative electronic health record data studies, and cross-sectional surveys of telehealth during the pandemic have been published, but none have combined assessments of video visit success monitoring with longitudinal assessments of perceived challenges to the rapid adoption of video visits during the pandemic. OBJECTIVE: This study aims to quantify (1) the use of video visits (compared with in-person and telephone visits) over time during the pandemic, (2) video visit successful connection rates, and (3) changes in perceived video visit challenges. METHODS: A web-based survey was developed for the dual purpose of monitoring and improving video visit implementation in our health care system during the COVID-19 pandemic. The survey included questions regarding rates of in-person, telephone, and video visits for clinician-patient encounters; the rate of successful connection for video visits; and perceived challenges to video visits (eg, software, hardware, bandwidth, and technology literacy). The survey was distributed via email to physicians, advanced practice professionals, and clinicians in May 2020. The survey was repeated in March 2021. Differences between the 2020 and 2021 responses were adjusted for within-respondent correlation across surveys and tested using generalized estimating equations. RESULTS: A total of 1126 surveys were completed (511 surveys in 2020 and 615 surveys in 2021). In 2020, only 21.7% (73/336) of clinicians reported no difficulty connecting with patients during video visits and 28.6% (93/325) of clinicians reported no difficulty in 2021. The distribution of the percentage of successfully connected video visits ("Over the past two weeks of scheduled visits, what percentage did you successfully connect with patients by video?") was not significantly different between 2020 and 2021 (P=.74). Challenges in conducting video visits persisted over time. Poor connectivity was the most common challenge reported by clinicians. This response increased over time, with 30.5% (156/511) selecting it as a challenge in 2020 and 37.1% (228/615) in 2021 (P=.01). Patients not having access to their electronic health record portals was also a commonly reported challenge (109/511, 21.3% in 2020 and 137/615, 22.3% in 2021, P=.73). CONCLUSIONS: During the pandemic, our health care delivery system rapidly adopted synchronous patient-clinician communication using video visits. As experience with video visits increased, the reported failure rate did not significantly decline, and clinicians continued to report challenges related to general network connectivity and patient access to technology.

Determining evolutionary origin and phylogenetic relationships of mallard-like ducks of Oceania, greater Indonesia, and the Philippines with ddRAD-seq data.

AIM: We aim to determine the evolutionary origins and population genetics of mallard-like ducks of Oceania, greater Indonesia, and the Philippines. LOCATION: Oceania, greater Indonesia, and the Philippines. TAXON: Mallard (Anas platyrhynchos), Pacific black duck (A. superciliosa spp.), and Philippine duck (A. luzonica) METHODS: Thousands of nuclear ddRAD-seq loci and the mitochondrial DNA control region were assayed across individuals representative of each species' range. We assessed population structure and phylogenetic relationships, as well as estimated demographic histories to reconstruct the biogeographical history of each species. RESULTS: Philippine and Pacific black ducks represent unique genetic lineages that diverged from the mallard 1-2 million years ago. We find no support for the Philippine duck representing a hybrid species as once posited; however, their low levels of genetic diversity requires further attention. We find a lack of substructure among Philippine ducks. However, we found pronounced differentiation between subspecies of Pacific black ducks, especially between A. s. superciliosa from New Zealand and A. s. rogersi from Australia, Papua New Guinea, and Timor-Leste, Indonesia. Anas superciliosa pelewensis gave mixed results; individuals from the Solomon Islands were differentiated from the other subspecies, but those from the island of Aunu'u, American Samoa, were genetically more similar to A. s. rogersi than A. s. pelewensis samples from the Solomon Islands. Finally, we find limited evidence of interspecific gene flow at evolutionary scales, and mallard introgression among contemporary samples. MAIN CONCLUSIONS: Mallard-like ducks radiated across Oceania, greater Indonesia, and the Philippines within the last 2 million years. Only the Pacific black duck showed unique sub-structuring that largely followed known sub-species ranges, except for A. s. pelewensis. We posit that the high interrelatedness among Solomon Island samples suggests that their genetic distinctiveness may simply be the result of high levels of genetic drift. In contrast, we conclude that mainland Australian Pacific black ducks were the most likely source for the recent colonization of American Samoa. As a result, our findings suggest that either the A. s. pelewensis subspecies designations and/or its geographical range may require re-evaluation. Continued re-evaluation of evolutionary and taxonomic relationships is necessary when attempting to reconstruct and understand biogeographical histories, with important implications towards any attempts to implement conservation strategies.

4-factor prothrombin complex concentrate is not inferior to andexanet alfa for the reversal or oral factor Xa inhibitors: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Andexanet Alfa (AA) is the only FDA approved reversal agent for apixaban and rivaroxaban (DOAC). There are no studies comparing its efficacy with 4-Factor Prothrombin Complex Concentrate (PCC). This study aimed to compare PCC to AA for DOAC reversal, hypothesizing non-inferiority of PCC. METHODS: We performed a retrospective, non-inferiority multicenter study of adult patients admitted from July 1, 2018 to December 31, 2019 who had taken a DOAC within 12 hours of injury, were transfused red blood cells (RBCs) or had traumatic brain injury, and received AA or PCC. Primary outcome was PRBC unit transfusion. Secondary outcome with ICU length of stay. MICE imputation was used to account for missing data and zero-inflated poisson regression was used to account for an excess of zero units of RBC transfused. 2 Units difference in RBC transfusion was selected as non-inferior. RESULTS: Results: From 263 patients at 10 centers, 77 (29%) received PCC and 186 (71%) AA. Patients had similar transfusion rates across reversal treatment groups (23.7% AA vs 19.5% PCC) with median transfusion in both groups of 0 RBC. According to the Poisson component, PCC increases the amount of RBC transfusion by 1.02 times (95% CI: 0.79-1.33) compared to AA after adjusting for other covariates. The averaged amount of RBC transfusion (non-zero group) is 6.13. Multiplying this number by the estimated rate ratio, PCC is estimated to have an increase RBC transfusion by 0.123 (95% CI: 0.53-2.02) units compared to AA. CONCLUSION: PCC appears non-inferior to AA for reversal of DOACs for RBC transfusion in traumatically injured patients. Additional prospective, randomized trials are necessary to compare PCC and AA for the treatment of hemorrhage in injured patients on DOACs. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III.

Updated core competencies in pharmacoepidemiology to inform contemporary curricula and training for academia, government, and industry.

PURPOSE: The first paper to specify the core content of pharmacoepidemiology as a profession was published by an ISPE (International Society for Pharmacoepidemiology) workgroup in 2012 (Jones JK et al. PDS 2012; 21[7]:677-689). Due to the broader and evolving scope of pharmacoepidemiology, ISPE considers it important to proactively identify, update and expand the list of core competencies to inform curricula of education programs; thus, better positioning pharmacoepidemiologists across academic, government (including regulatory), and industry positions. The aim of this project was to update the list of core competencies in pharmacoepidemiology. METHODS: To ensure applicability of findings to multiple areas, a working group was established consisting of ISPE members with positions in academia, industry, government, and other settings. All competencies outlined by Jones et al. were extracted from the initial manuscript and presented to the working group for review. Expert-based judgments were collated and used to identify consensus. It was noted that some competencies could contribute to multiple groups and could be directly or indirectly related to a group. RESULTS: Five core domains were proposed: (1) Epidemiology, (2) Clinical Pharmacology, (3) Regulatory Science, (4) Statistics and data science, and (5) Communication and other professional skills. In total, 55 individual competencies were proposed, of which 25 were new competencies. No competencies from the original work were dropped but aggregation or amendments were made where considered necessary. CONCLUSIONS: While many core competencies in pharmacoepidemiology have remained the same over the past 10 years, there have also been several updates to reflect new and emerging concepts in the field.

Long-term survival is not affected by severity of complications following esophagectomy.

INTRODUCTION: Outcomes following esophagectomy for esophageal cancer have continued to improve over the last 30 years. Post-operative complications impact upon peri-operative and short-term survival but the effect on long-term survival remains debated. This study aims to investigate the effect of post-operative complications on long-term survival following esophagectomy. MATERIALS AND METHODS: All patients who underwent an esophagectomy between January 2010 and January 2019 were included from a single high-volume center. Data was collected contemporaneously. Patients were separated into three groups; those who experienced no, or very minor complications (Clavien-Dindo 0 or 1), minor complications (Clavien-Dindo 2), and major complications (Clavien-Dindo 3-4), at 30 days. To correct for short-term mortality effects, those who died during the index hospital admission were excluded. Overall survival was analyzed using Kaplan-Meier and log rank testing. RESULTS: The study cohort comprised 721 patients. There were 42.4% (306/721), 29.5% (213/721) and 25.7% (185/721) in the Clavien-Dindo 0-1, Clavien-Dindo 2, and Clavien-Dindo 3-4 group respectively. Seventeen patients (2.4%) died during their index hospital admission and were therefore excluded. There was no significant difference between median survival across the 3 groups (50, 57 and 52 months). Across all 3 groups, overall long-term survival rates were equivalent at 1 (87.5%, 84.9%, 83.2%), 3 (59.7%, 59.6%, 54.2%), and 5 years (43.9%, 48.9%, 45.7%) (p = 0.806). The only factors independently associated with survival in this cohort, were male gender, Charlson comorbidity index, and overall pathological stage of disease. CONCLUSION: Long-term survival is not affected by peri-operative complications, irrespective of severity, following esophagectomy. Further study into the long-term quality of life is required.

Increased platelet to red blood cell transfusion ratio associated with acute kidney injury in children with life-threatening bleeding.

INTRODUCTION: Transfusion may increase the risk of organ failure through immunomodulatory effects. The primary objective of this study was to assess for patient or transfusion-related factors that are independently associated with the risk of acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in a cohort of children with life-threatening bleeding from all etiologies. METHODS: In a secondary analysis of the prospective observational massive transfusion in children (MATIC) study, multivariable logistic regression was performed in an adjusted analysis to determine if blood product ratios or deficits were independently associated with AKI or ARDS in children with life-threatening bleeding. RESULTS: There were 449 children included with a median (interquartile range, IQR) age of 7.3 years (1.7-14.7). Within 5 days of the life-threatening bleeding event, AKI occurred in 18.5% and ARDS occurred in 20.3% of the subjects. Every 10% increase in the platelet to red blood cell transfusion ratio is independently associated with a 12.7% increase in the odds of AKI (adjusted odds ratio 1.127; 95% confidence interval 1.025-1.239; p-value .013). Subjects with operative or medical etiologies were independently associated with an increased risk of AKI compared to those with traumatic injury. No transfusion-related variables were independently associated with the risk of developing ARDS. CONCLUSION: The use of increased platelet to red blood cell transfusion ratios in children with life-threatening bleeding of any etiology may increase the risk of AKI but not ARDS. Prospective trials are needed to determine if increased platelet use in this cohort increases the risk of AKI to examine possible mechanisms.

Patient sex and outcomes in children with life-threatening hemorrhage.

BACKGROUND: Recent data suggest female sex imparts a survival benefit after trauma in adults. The independent associations between patient sex and age with outcomes have not been examined in children with life-threatening hemorrhage (LTH) from all etiologies. STUDY DESIGN AND METHODS: In a secondary analysis of a multicenter prospective observational study of children with LTH, Massive Transfusion in Children (MATIC), we analyzed if patient sex and age were associated with differences in severity of illness, therapies, and outcomes. Primary outcomes were 24 hour mortality and weight-adjusted transfusion volume during LTH. Kruskal-Wallis, chi-square testing, and multivariable linear regression were used for adjusted analyses. RESULTS: Of 449 children, 45% were females and 55% were males. Females were more commonly younger, white, and with less trauma as the etiology of LTH compared to males. Markers of clinical severity were similar between groups, except injury severity score (ISS) was higher in females in the trauma subgroup. In terms of resuscitative practices, females received greater weight-adjusted total transfusion volumes compared to males (76 (40-150) mL/kg vs. 53 (24-100) mL/kg), as well as increased red blood cells (RBCs), plasma, and platelets compared to males. After adjustment for confounders, female sex and age 0-11 years were independently associated with increased transfusion volume during LTH. There were no differences in mortality or adverse outcomes according to patient sex. CONCLUSION: Patient sex and age may impact factors associated with LTH and therapies received. Studies in developmental hemostasis are needed to determine the optimal transfusion strategy for LTH according to patient sex and age.

Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: results of two harmonized randomized clinical trials.

INTRODUCTION: Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements and any dose response relationships require further elucidation. METHODS: A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events and 24-hour red cell transfusion requirements were compared between TXA and placebo groups. Regression analyses were utilized to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics and shock severity across a broad spectrum of injured patients. Dose response relationships were similarly characterized based upon grams of prehospital TXA administered. RESULTS: A total of 1744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR: 5-26). TXA was independently associated with a lower risk of 28-day mortality (HR: 0.72, 95% CI 0.54, 0.96, p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR: 0.78, 95% CI 0.63, 0.96, p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (ß: -0.31, 95% CI -0.61, -0.01, p = 0.04) with a dose-response relationship (ß: -0.24, 95% CI -0.45, -0.02, p = 0.03). There was no independent association of prehospital TXA administration on VTE, seizure, or stroke. CONCLUSIONS: In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit, lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Identifying Trigger Cues for Hospital Blood Transfusions Based on Ensemble Learning Methods.

Background: Traumatic shock is the leading cause of preventable death with most patients dying within the first 6 hours. This underscores the importance of prehospital interventions, and growing evidence suggests prehospital transfusion improves survival. Optimizing transfusion triggers in the prehospital setting is key to improving outcomes for patients in hemorrhagic shock. Our objective was to identify factors associated with early in-hospital transfusion requirements available to prehospital clinicians in the field to develop a simple algorithm for prehospital transfusion, particularly for patients with occult shock. Methods: We included trauma patients transported by a single critical care transport service to a level I trauma center between 2012 and 2019. We used logistic regression, Fast and Frugal Trees (FFTs), and Bayesian analysis to identify factors associated with early in-hospital blood transfusion as a potential trigger for prehospital transfusion. Results: We included 2,157 patients transported from the scene or emergency department (ED) of whom 207 (9.60%) required blood transfusion within 4 hours of admission. The mean age was 47 (IQR = 28-62) and 1,480 (68.6%) patients were male. From 13 clinically relevant factors for early hospital transfusions, four were incorporated into the FFT in following order: 1) SBP, 2) prehospital lactate concentration, 3) Shock Index, 4) AIS of chest (sensitivity = 0.81, specificity = 0.71). The chosen thresholds were similar to conventional ones. Using conventional thresholds resulted in lower model sensitivity. Consistently, prehospital lactate was among most decisive factors of hospital transfusions identified by Bayesian analysis (OR = 2.31; 95% CI 1.55-3.37). Conclusions: Using an ensemble of frequentist statistics, Bayesian analysis and machine learning, we developed a simple, clinically relevant, prehospital algorithm to help identify patients requiring transfusion within 4 hours of hospital arrival.

Monkey Prefrontal Cortex Learns to Minimize Sequence Prediction Error.

In this study, we develop a novel recurrent neural network (RNN) model of pre-frontal cortex that predicts sensory inputs, actions, and outcomes at the next time step. Synaptic weights in the model are adjusted to minimize sequence prediction error, adapting a deep learning rule similar to those of large language models. The model, called Sequence Prediction Error Learning (SPEL), is a simple RNN that predicts world state at the next time step, but that differs from standard RNNs by using its own prediction errors from the previous state predictions as inputs to the hidden units of the network. We show that the time course of sequence prediction errors generated by the model closely matched the activity time courses of populations of neurons in macaque prefrontal cortex. Hidden units in the model responded to combinations of task variables and exhibited sensitivity to changing stimulus probability in ways that closely resembled monkey prefrontal neurons. Moreover, the model generated prolonged response times to infrequent, unexpected events as did monkeys. The results suggest that prefrontal cortex may generate internal models of the temporal structure of the world even during tasks that do not explicitly depend on temporal expectation, using a sequence prediction error minimization learning rule to do so. As such, the SPEL model provides a unified, general-purpose theoretical framework for modeling the lateral prefrontal cortex.