bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiopoietin-like protein 8: a multifaceted protein instrumental in regulating triglyceride metabolism
Authors: Wen Yi , Chen Yan Q. , Konrad Robert J.
Published: November 2023

Purpose of review

The angiopoietin-like (ANGPTL) proteins ANGPTL3 and ANGPTL4 are critical lipoprotein lipase (LPL) inhibitors. This review discusses the unique ability of the insulin-responsive protein ANGPTL8 to regulate triglyceride (TG) metabolism by forming ANGPTL3/8 and ANGPTL4/8 complexes that control tissue-specific LPL activities.

Recent findings

After feeding, ANGPTL4/8 acts locally in adipose tissue, has decreased LPL-inhibitory activity compared to ANGPTL4, and binds tissue plasminogen activator (tPA) and plasminogen to generate plasmin, which cleaves ANGPTL4/8 and other LPL inhibitors. This enables LPL to be fully active postprandially to promote efficient fatty acid (FA) uptake and minimize ectopic fat deposition. In contrast, liver-derived ANGPTL3/8 acts in an endocrine manner, has markedly increased LPL-inhibitory activity compared to ANGPTL3, and potently inhibits LPL in oxidative tissues to direct TG toward adipose tissue for storage. Circulating ANGPTL3/8 levels are strongly correlated with serum TG, and the ANGPTL3/8 LPL-inhibitory epitope is blocked by the TG-lowering protein apolipoprotein A5 (ApoA5).

ANGPTL8 plays a crucial role in TG metabolism by forming ANGPTL3/8 and ANGPTL4/8 complexes that differentially modulate LPL activities in oxidative and adipose tissues respectively. Selective ANGPTL8 inhibition in the context of the ANGPTL3/8 complex has the potential to be a promising strategy for treating dyslipidemia.
Fluid and electrolyte management in the neonate and what can go wrong
Authors: Segar Jeffrey L. , Jetton Jennifer G.
Published: November 2023

Purpose of review

This review highlights recent advances in understanding fluid and electrolyte homeostasis during the newborn period, including heightened recognition of fluid overload and acute kidney injury contributing to poor clinical outcomes. Particular attention is given towards the care of extremely preterm infants.

Recent findings

Emerging data demonstrate (i) disproportionally large transepidermal water loss in the extremely preterm population, (ii) the relationship between postnatal weight loss (negative fluid balance) and improved outcomes, (iii) the frequency and negative effects of dysnatremias early in life, (iv) the role of sodium homeostasis in optimizing postnatal growth, and (v) the deleterious effects of fluid overload and acute kidney injury.

As clinicians care for an increasing number of preterm infants, understanding progress in approaches to fluid and electrolyte management and avoidance of fluid overload states will improve the care and outcomes of this vulnerable population. Further translational and clinical studies are needed to address remaining knowledge gaps and improve current approaches to fluid and electrolyte management.
Single use flexible ureteroscopes: a review of current technologies and cost effectiveness analysis
Authors: Talyshinskii Ali , Gauhar Vineet , Castellani Daniele , Knoll Thomas , Shah Kaushikkumar , Wan Shaw P. , Somani Bhaskar K.
Published: November 2023

Purpose of review

Flexible ureteroscopy (fURS) has evolved into both diagnostic and therapeutic modalities. Our review discusses the cost-effectiveness of single use flexible ureteroscopes (su-fURS) and the use of these instruments in routine urological practice.

Recent findings

There are studies which support the use of su-fURS with an argument of both cost and clinical utility over reusable flexible ureteroscopes (ru-fURS). However, the cost may vary across countries, hence is difficult to compare the results based on the current literature. Perhaps therefore there is a role for hybrid strategy incorporating ru- and su-fURS, where su-fURS are employed in complex endourological cases with a high risk of scope damage or fracture to preserve ru-fURS, with the ability to maintain clinical activity in such an event.

While there seems to be some cost advantages with su-fURS with reduced sterilization and maintenance costs, the data supporting it is sparse and limited. This choice of scope would depend on the durability of ru-fURS, procedural volumes, limited availability of sterilization units in some centers and potential risk of infectious complications. It is time that cost-benefit analysis is conducted with defined outcomes for a given healthcare set-up to help with the decision making on the type of scope that best serves their needs.
Development and Validation of Subsyndromal Delirium Prediction Model in Patients With Advanced Malignant Tumor
Authors: Wang Pan , Xiao Weisheng
Published: November 2023

Background

Subsyndromal delirium (SSD) is a clinical manifestation between delirium and nondelirium. There is no established guideline for diagnosing SSD, with a few different tools used for diagnosis.

Objectives

To construct and verify the risk prediction model for subdelirium syndrome in patients with advanced malignant tumors and explore its application value in risk prediction.

Methods

A total of 455 patients admitted to the Oncology Department in a tertiary grade A hospital in Hengyang City were recruited from December 2020 to May 2021. They were selected as the modeling group. The model was constructed by logistic regression. A total of 195 patients with advanced malignant tumors from June 2021 to July 2021 were selected to validate the developed model.

Results

The predictors incorporated into the model were opioids (odds ratio [OR], 1.818), sleep disorders (OR, 1.783), daily living ability score (OR, 0.969), and pain (OR, 1.810). In the modeling group, the Hosmer-Lemeshow goodness-of-fit test was P = .113, the area under the receiver operating characteristic curve was 0.884, the sensitivity was 0.820, and the specificity was 0.893. In the validation group, the Hosmer-Lemeshow goodness-of-fit test P = .108, the area under the receiver operating characteristic curve was 0.843, the Yuden index was 0.670, the sensitivity was 0.804, and the specificity was 0.866.

Conclusions

This model has excellent precision in the risk prediction of subdelirium in patients with advanced malignant tumors.

Implications for Practice

The model we developed has a guiding significance for specialized tumor nurses to care for patients with advanced malignant tumors and improve their quality of life.
Maximizing Veterans Health Affairs Community Hospice Collaborations
Authors: O'Malley Kelly A. , Baird Lola , Kaiser Anica Pless , Bashian Hannah M. , Etchin Anna G. , Sager Zachary S. , Heintz Hannah , Korsun Lynn , Kemp Katherine , Moye Jennifer
Published: November 2023

Within the United States, approximately 330 000 military veterans die annually, but only 5% of deaths occur in Veterans Health Administration (VHA) facilities. To help provide end-of-life care for veterans, the VHA built community partnerships with community hospice and palliative care (HPC) organizations. Veterans experience unique psychosocial factors making it vital to ensure HPC organizations have access to veteran-specific knowledge and resources to reduce suffering. To better understand the strengths and limitations of these partnerships, community HPC staff (N = 483) responded to quantitative and qualitative survey questions developed using an access to care theory for veterans. Survey responses demonstrated variable perceptions of access to VHA care and resources. Respondents reported excellent experiences (44%) and relationships with their local facility (50%) and had a reliable contact who provided needed assistance (92%). Thematic analysis identified a need for VHA care and barriers to access, which were associated with technical characteristics, and geographical and cultural issues. These findings can help inform future research and policy regarding access to VHA resources for end-of-life care for veterans in the community and guide resource development for community HPC providers.
Syphilis Screening Among Young Black Men Who Have Sex with Women in New Orleans, LA
Authors: Ratnayake Aneeka , Gomes Gérard , Kissinger Patricia J.
Published: November 2023

Background

Current US syphilis screening focuses on men who have sex with men (MSM), due to the increased risk of infection in their sexual networks, and on pregnant people, due to complications associated with congenital syphilis. However, screening for men who have sex with women (MSW) who are at increased risk of syphilis is also recommended. Factors associated with syphilis testing and positivity were assessed among young, Black MSW.

Methods

Data from the Check It study—a seek, test, and treat study for chlamydia in New Orleans, LA among Black MSW aged 15-26—were used. Survey data was used to elicit self-reported syphilis testing, self-reported testing results, and socio-demographic and behavioral factors associated with these two outcomes.

Results

Per CDC, all men in the study were recommended for syphilis screening due to their age, race, and geographic location. Of the 1458 men included, 272 (18.7%) reported ever having been syphilis tested, 267 men reported their results, and 23 (8.6%) reported testing positive. In logistic regression, older age (OR: 1.21 per year older, p < 0.001), prior Ct, GC, and/or HIV testing (OR: 50.32, p < 0.001), and younger age at sexual debut (0.90 per year older, p = 0.005), were significantly associated with prior syphilis testing. Additionally, testing positive for Ct and/or GC during the study was significantly associated with a history of syphilis positivity (OR: 3.08, p = 0.031).

Conclusions

Though syphilis testing was associated with factors that might increase risk of acquisition, only 19% of individuals meeting CDC testing recommendations had ever been screened.
Report of 5146 Cases of Coronavirus Disease 2019-Related Mortality From Cook County, Illinois Causes of Death, Demographics, and Comorbidities
Authors: Lesnikova Iana , Obukhau Aliaksandr , Lashmanova Natalia , Braun Ankica , Venkatraman Sindhuja Murali Kilapandal , Vega Matthew , Wolf Maxim Y. , Arunkumar Ponni
Published: November 2023

A cross-sectional study used 5216 laboratory-confirmed coronavirus disease 2019 (severe acute respiratory syndrome coronavirus 2)–related mortality cases in Cook County of Illinois. The data set included each case's demographic data, manner of death, and comorbidities. The age ranged from 0 to 108 years, with a median of 73.5 years. There were few mortality cases in the age group younger than 30 years, and the incidence of fatal infection increased with age. We demonstrated an increased incidence of mortality in males compared with females (P < 0.01). The urban population had a higher incidence of fatal infection than the suburban population (P < 0.01). We found a significant increase (P < 0.01) in the incidence of fatal coronavirus disease 2019 (severe acute respiratory syndrome coronavirus 2) infection in African American males compared with background frequencies. Latino population demonstrated younger ages at death compared with the non-Latino population. Obesity and hypertension significantly predict fatal outcomes in the younger age group. In comparison, dementia and hypertensive and arteriosclerotic cardiovascular disease are significant predictive factors in the older age group. In a large data set, we demonstrated that the demographical distribution of the population and comorbidities is associated with the risk of fatal complications and death.
Peeling Back the Layers: Sloughing Esophagitis in a Teenager with Chronic Vomiting
Authors: Baran Jessica V. , O’Flanagan Rowan , Trocchia Carolena , Brown Jerry M. , Nguyen Johnny , Karjoo Sara , Wilsey Michael J.
Published: November 2023

Esophagitis dissecans superficialis (EsoDS) is a rare condition characterized by the shedding of superficial esophageal epithelium. Limited data exists on EsoDS in the pediatric population. We present a case of a 17-year-old female with chronic nausea and vomiting diagnosed with EsoDS. Endoscopy revealed esophageal mucosal sloughing, and histology confirmed esophagitis with mucosal necrosis. EsoDS is underrecognized, and its association with psychoactive medications remains unclear. Fortunately, EsoDS cases tend to resolve spontaneously without complications. Awareness of EsoDS is essential, and further research is needed to understand its prevalence and outcomes in pediatric patients.
Esophagogastric Fistula: The Consequence of High-Powered Magnets Ingestion
Authors: Quezada Hugo , Levine Anne E. , Dellinger Matthew , Rice-Townsend Samuel , Zheng Hengqi Betty
Published: November 2023

A 17-month-old female had an unwitnessed ingestion of 26 high-powered magnets, resulting in the creation of an esophagogastric fistula via the left crus of the diaphragm. This case highlights a rare injury to the stomach and esophagus caused by high-powered magnets requiring surgical intervention. Furthermore, this case report illustrates the risks that high-powered magnets pose to young children. Additionally, this case highlights the importance of maintaining a high level of suspicion for ingestion in young patients along with a multidisciplinary team to manage sequelae of injury.
Gastric Foveolar Hyperplastic Polyps in 2 Children With Short Bowel Syndrome on Long-Term Teduglutide
Authors: Salazar Jonathan A. , Goldsmith Jeffrey D. , Jimenez Lissette , Fox Victor L. , Duggan Christopher P. , Carey Alexandra N.
Published: November 2023

The natural history of short bowel syndrome involves intestinal adaptation wherein the remnant small intestine undergoes histologic and anatomic changes aimed at increasing absorption. Teduglutide—a glucagon-like peptide 2 analog approved for pediatric use in 2019—stimulates this process by causing proliferation of intestinal epithelial cells resulting in increased villous height and crypt depth. Food and Drug Administration approval for pediatric patients followed safety and efficacy studies in children that were limited to 24-week duration. Pediatric-specific postmarketing studies evaluating long-term safety and efficacy are underway. Formation of colorectal polyps has been repeatedly observed in studies of adult patients on long-term teduglutide, including in individuals without endoscopic evidence of polyps before treatment initiation. Recent studies, however, suggest increased risk of small bowel hyperplastic and dysplastic polyp formation with long-term glucagon-like peptide 2 analog use. We report 2 cases of small bowel foveolar hyperplastic polyps found during surveillance endoscopies after 1 year of treatment with teduglutide.
Diversity in Cancer Care
Authors: Akimoto Kai , Taparra Kekoa , Brown Thelma , Patel Manali I.
Published: November 2023

Access to and participation in cancer clinical trials determine whether such data are applicable, feasible, and generalizable among populations. The lack of inclusion of low-income and marginalized populations limits generalizability of the critical data guiding novel therapeutics and interventions used globally. Such lack of cancer clinical trial equity is troubling, considering that the populations frequently excluded from these trials are those with disproportionately higher cancer morbidity and mortality rates. There is an urgency to increase representation of marginalized populations to ensure that effective treatments are developed and equitably applied. Efforts to ameliorate these clinical trial inclusion disparities are met with a slew of multifactorial and multilevel challenges. We aim to review these challenges at the patient, clinician, system, and policy levels. We also highlight and propose solutions to inform future efforts to achieve cancer health equity.
Social Drivers of Cancer Risk and Outcomes Among African American Men
Authors: Halbert Chanita Hughes
Published: November 2023

Social risk factors play an important role in minority health and cancer health disparities. Exposure to stress and stress responses are important social factors that are now included in conceptual models of cancer health disparities. This report summarizes results from studies that examined stress exposure and responses among African Americans. Data from studies that were conducted as part of a transdisciplinary and translational research center are also presented to provide additional insight about the nature of racial differences in specific stressors among African American and White prostate cancer patients.
Primary Prevention of Cancer
Authors: Gorin Sherri Sheinfeld , Hirko Kelly
Published: November 2023

Cancer continues to be the second most common cause of death in the United States. Racially and ethnically minoritized populations continue to experience disparities in cancer prevention compared with majority populations. Multilevel interventions—from policy, communities, health care institutions, clinical teams, families, and individuals—may be uniquely suited to reducing health disparities through behavioral risk factor modification in these populations. The aim of this article is to provide a brief overview of the evidence for primary prevention among racially and ethnically minoritized subpopulations in the United States. We focus on the epidemiology of tobacco use, obesity, diet and physical activity, alcohol use, sun exposure, and smoking, as well as increasing uptake of the Human Papillomavirus Vaccine (HPV), as mutable behavioral risk factors. We describe interventions at the policy level, including raising excise taxes on tobacco products; within communities and with community partners, for safe greenways and parks, and local healthful food; health care institutions, with reminder systems for HPV vaccinations; among clinicians, by screening for alcohol use and providing tailored weight reduction approaches; families, with HPV education; and among individuals, routinely using sun protection. A multilevel approach to primary prevention of cancer can modify many of the risk factors in racially and ethnically minoritized populations for whom cancer is already a burden.
Prostate Cancer, Race, and Health Disparity
Authors: Roach Mack , Coleman Pamela W. , Kittles Rick
Published: November 2023

Prostate cancer (PCa) in African American men is one of the most common cancers with a great disparity in outcomes. The higher incidence and tendency to present with more advanced disease have prompted investigators to postulate that this is a problem of innate biology. However, unequal access to health care and poorer quality of care raise questions about the relative importance of genetics versus social/health injustice. Although race is inconsistent with global human genetic diversity, we need to understand the sociocultural reality that race and racism impact biology. Genetic studies reveal enrichment of PCa risk alleles in populations of West African descent and population-level differences in tumor immunology. Structural racism may explain some of the differences previously reported in PCa clinical outcomes; fortunately, there is high-level evidence that when care is comparable, outcomes are comparable.
Satisfaction survey toward an innovative orthosis for children with cerebral palsy with pes planovalgus
Authors: Viallard Lisa , Cordillet Sébastien , Dohin Julie , Gaultier Odile , Maignan Laurane , Rauscent Hélène , Bonan Isabelle
Published: November 2023

Background:

Pes planovalgus (PPV) is common in children with cerebral palsy and can cause pain and gait alterations over time. Initial treatment of flexible PPV includes orthotics, despite a lack of consensus on the type of orthosis. We developed an innovative ankle-foot orthosis (RAFO). RAFO is a one-piece orthosis designed to correct both the valgus and the flat of the foot. Its conception situated above the malleolar enables a moderate anti equinus effect. Its precise description and fabrication’s process is detailed.

Objective(s):

We wanted to assess user's satisfaction after several months of use and looked for clinical criteria of satisfaction.

Study Design:

Retrospective.

Methods:

We conducted a satisfaction study through a telephonic QUEST (Quebec User Evaluation of Satisfaction with Assistive Technology) survey analysing the device and the process in children and parents. 24 parents were contacted, whose child was wearing RAFO on a daily basis for at least 4 months. 20 parents answered the questionnaire. The results were then related to clinical data to research satisfaction’ criteria.

Results:

Mean QUEST satisfaction was 4.25/5 (4.18/5 for device and 4.38/5 for process). Advantages reported concerned weight and dimensions (95%), although 20% reported the necessity to change to a shoe size above, ease of use (90%) and level of comfort (80%). Parent’s satisfaction regarding perceived effectiveness was 80%. Children with equinus due to triceps surae spasticity were more susceptible to develop pain with our orthosis.

Conclusions:

Parents were overall very satisfied with the orthosis. Its technical characteristics allowing both to be a corrector of flat foot and valgus and at the same time to be comfortable and discreet makes it innovative. The presence of spastic equinus is a limit for its utilization.
A Review of Radiation-Induced Vascular Injury and Clinical Impact
Authors: Kameni Lionel E. , Januszyk Michael , Berry Charlotte E. , Downer Mauricio A. , Parker Jennifer B. , Morgan Annah G. , Valencia Caleb , Griffin Michelle , Li Dayan J. , Liang Norah E. , Momeni Arash , Longaker Michael T. , Wan Derrick C.
Published: November 2023

The number of cancer survivors continues to increase because of advances in therapeutic modalities. Along with surgery and chemotherapy, radiotherapy is a commonly used treatment modality in roughly half of all cancer patients. It is particularly helpful in the oncologic treatment of patients with breast, head and neck, and prostate malignancies. Unfortunately, among patients receiving radiation therapy, long-term sequalae are often unavoidable, and there is accumulating clinical evidence suggesting significant radiation-related damage to the vascular endothelium. Ionizing radiation has been known to cause obliterative fibrosis and increased wall thickness in irradiated blood vessels. Clinically, these vascular changes induced by ionizing radiation can pose unique surgical challenges when operating in radiated fields. Here, we review the relevant literature on radiation-induced vascular damage focusing on mechanisms and signaling pathways involved and highlight microsurgical anastomotic outcomes after radiotherapy. In addition, we briefly comment on potential therapeutic strategies, which may have the ability to mitigate radiation injury to the vascular endothelium.
Ultrasound-Guided Transversus Abdominis Plane Blocks Versus Local Infiltration Anesthesia on Postanesthesia Care Unit Pain Control in Patients Undergoing Abdominoplasty
Authors: Heffern Jadyn N. , Puyana Salomon , Hajebian Hooman H. , Kresofsky Kevin , Chaffin Abigail E. , Lindsey John T.
Published: November 2023

Goals/Purpose

The goal of this study was to compare ultrasound-guided transversus abdominis plane (TAP) blocks to local infiltration anesthesia with or without blind rectus sheath blocks in patients who underwent abdominoplasty at an outpatient surgery center.

Methods/Technique

A retrospective review was conducted of patients who underwent outpatient abdominoplasty performed by the senior surgeon (J.T.L.). Group 1 received local infiltration anesthesia with or without blind rectus sheath blocks between April 2009 and December 2013. Group 2 received surgeon-led, intraoperative, ultrasound-guided, 4-quadrant TAP blocks between January 2014 and December 2021. Outcomes measured were opioid utilization (morphine milligram equivalents), pain level at discharge, and time spent in postanesthesia care unit (PACU).

Results

Sixty patients in each of the 2 study groups met the study criteria for a total of 120 patients. The study groups were similar except for a lower average age in group 1. Patients who received TAP blocks (group 2) had significantly lower morphine milligram equivalent requirements in the PACU (3.07 vs 8.93, P = 0.0001) and required a shorter stay in PACU (95.4 vs 117.18 minutes, P = 0.0001). There were no significant differences in pain level at discharge.

Conclusions

Surgeon-led, intraoperative, ultrasound-guided, 4-quadrant TAP blocks statistically significantly reduced opioid utilization in PACU by 65.6% and average patient time in the PACU by 18.5% (21.8 minutes).
Prostacyclin in trauma patients with hemorrhagic shock: A randomized clinical trial
Authors: Johansson Pär I. , Fenger Eriksen Christian , Bovbjerg Pernille E. , Gaarder Christine , Pall Marlene , Henriksen Hanne Hee , Pedersen Kristine H. , Vigstedt Martin , Lange Theis , Næss Pål Aksel , Strømgaard Andersen Mikkel , Kirkegaard Hans , Stensballe Jakob
Published: November 2023

BACKGROUND

A main cause of trauma morbidity and mortality is multiple-organ failure, and endotheliopathy has been implicated. Pilot studies indicate that low-dose prostacyclin improves endothelial functionality in critically ill patients, suggesting that this intervention may improve trauma patient outcome.

METHODS

We conducted a multicenter, randomized, blinded, clinical investigator-initiated trial in 229 trauma patients with hemorrhagic shock who were randomized 1:1 to 72 hours infusion of the prostacyclin analog iloprost (1 ng/kg/min) or placebo. The primary outcome was the number of intensive care unit (ICU)–free days alive within 28 days of admission. Secondary outcomes included 28-day all-cause mortality and hospital length of stay.

RESULTS

The mean number of ICU-free days alive within 28 days was 15.64 days in the iloprost group versus 13.99 days in the placebo group (adjusted mean difference, −1.63 days [95% confidence interval (CI), −4.64 to 1.38 days]; p = 0.28). The 28-day mortality was 18.8% in the iloprost group versus 19.6% in the placebo group (odds ratio, 1.01 [95% CI, 0.51–2.0]; p = 0.97). The mean hospital length of stay was 19.96 days in the iloprost group versus 27.32 days in the placebo group (adjusted mean difference, 7.84 days [95% CI, 1.66–14.02 days], p = 0.01).

CONCLUSION

Iloprost did not result in a statistically significant increase in the number of ICU-free days alive within 28 days of admission, whereas it was safe and a statistically significant reduction in hospital length of stay was observed. Further research on prostacyclin in shocked trauma patients is warranted.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
TiME OUT: Time-specific machine-learning evaluation to optimize ultramassive transfusion
Authors: Meyer Courtney H. , Nguyen Jonathan , ElHabr Andrew , Venkatayogi Nethra , Steed Tyler , Gichoya Judy , Sciarretta Jason D. , Sikora James , Dente Christopher , Lyons John , Coopersmith Craig M. , Nguyen Crystal , Smith Randi N.
Published: November 2023

BACKGROUND

Ultramassive transfusion (UMT) is a resource-demanding intervention for trauma patients in hemorrhagic shock, and associated mortality rates remains high. Current research has been unable to identify a transfusion ceiling or point where UMT transitions from lifesaving to futility. Furthermore, little consideration has been given to how time-specific patient data points impact decisions with ongoing high-volume resuscitation. Therefore, this study sought to use time-specific machine learning modeling to predict mortality and identify parameters associated with survivability in trauma patients undergoing UMT.

METHODS

A retrospective review was conducted at a Level I trauma (2018–2021) and included trauma patients meeting criteria for UMT, defined as ≥20 red blood cell products within 24 hours of admission. Cross-sectional data were obtained from the blood bank and trauma registries, and time-specific data were obtained from the electronic medical record. Time-specific decision-tree models predicating mortality were generated and evaluated using area under the curve.

RESULTS

In the 180 patients included, mortality rate was 40.5% at 48 hours and 52.2% overall. The deceased received significantly more blood products with a median of 71.5 total units compared with 55.5 in the survivors (p < 0.001) and significantly greater rates of packed red blood cells and fresh frozen plasma at each time interval. Time-specific decision-tree models predicted mortality with an accuracy as high as 81%. In the early time intervals, hemodynamic stability, undergoing an emergency department thoracotomy, and injury severity were most predictive of survival, while, in the later intervals, markers of adequate resuscitation such as arterial pH and lactate level became more prominent.

CONCLUSION

This study supports that the decision of “when to stop” in UMT resuscitation is not based exclusively on the number of units transfused but rather the complex integration of patient and time-specific data. Machine learning is an effective tool to investigate this concept, and further research is needed to refine and validate these time-specific decision-tree models.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
The interaction between geriatric and neighborhood vulnerability: Delineating prehospital risk among older adult emergency general surgery patients
Authors: Zogg Cheryl K. , Falvey Jason R. , Kodadek Lisa M. , Staudenmayer Kristan L. , Davis Kimberly A.
Published: November 2023

BACKGROUND

When presenting for emergency general surgery (EGS) care, older adults frequently experience increased risk of adverse outcomes owing to factors related to age (“geriatric vulnerability”) and the social determinants of health unique to the places in which they live (“neighborhood vulnerability”). Little is known about how such factors collectively influence adverse outcomes. We sought to explore how the interaction between geriatric and neighborhood vulnerability influences EGS outcomes among older adults.

METHODS

Older adults, 65 years or older, hospitalized with an AAST-defined EGS condition were identified in the 2016 to 2019, 2021 Florida State Inpatient Database. Latent variable models combined the influence of patient age, multimorbidity, and Hospital Frailty Risk Score into a single metric of “geriatric vulnerability.” Variations in geriatric vulnerability were then compared across differences in “neighborhood vulnerability” as measured by variations in Area Deprivation Index, Social Vulnerability Index, and their corresponding subthemes (e.g., access to transportation).

RESULTS

A total of 448,968 older adults were included. For patients living in the least vulnerable neighborhoods, increasing geriatric vulnerability resulted in up to six times greater risk of death (30-day risk-adjusted hazards ratio [HR], 6.32; 95% confidence interval [CI], 4.49–8.89). The effect was more than doubled among patients living in the most vulnerable neighborhoods, where increasing geriatric vulnerability resulted in up to 15 times greater risk of death (30-day risk-adjusted HR, 15.12; 95% CI, 12.57–18.19). When restricted to racial/ethnic minority patients, the multiplicative effect was four-times as high, resulting in corresponding 30-day HRs for mortality of 11.53 (95% CI, 4.51–29.44) versus 40.67 (95% CI, 22.73–72.78). Similar patterns were seen for death within 365 days.

CONCLUSION

Both geriatric and neighborhood vulnerability have been shown to affect prehospital risk among older patients. The results of this study build on that work, presenting the first in-depth look at the powerful multiplicative interaction between these two factors. The results show that where a patient resides can fundamentally alter expected outcomes for EGS care such that otherwise less vulnerable patients become functionally equivalent to those who are, at baseline, more aged, more frail, and more sick.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
INCREASED PLATELET MITOCHONDRIAL FUNCTION CORRELATES WITH CLOT STRENGTH IN A RODENT FRACTURE MODEL
Authors: Littlejohn James Blake , Grenn Emily Evans , Carter Kristen T. , Palei Ana C. , Spradley Frank T. , Hosler Jonathan P. , Hoang Ngoc H. , Edwards Kristin S. , Kutcher Matthew E.
Published: November 2023

Background

Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging due to a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function, but has not yet been correlated with functional coagulation studies.

Methods

Wistar rats underwent anesthesia and either immediate sacrifice for baseline values [n = 6] or (1) bilateral hindlimb orthopedic injury [n = 12], versus (2) sham anesthesia [n = 12] with terminal phlebotomy/hepatectomy after 24 hours. High resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex-I and Complex-II driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate.

Results

Citrated native TEG maximal amplitude (MA) was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared to sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol/s*108 cells, p = 0.045), with similar trends in mitochondrial leak rate (p = 0.19) when compared to sham animals. Overall, platelet basal respiration significantly correlated with TEG-MA (r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex-I driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e-/min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen.

Conclusions

Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.
SIRT1 downregulation in pneumonia is associated with an immature neutrophil response and increased disease severity
Authors: Labiner Hanna E. , Sas Kelli M. , Hoying Joseph , Sepeda Jesse A. , Wolf Nick , Perez Emma C. , Sas Andrew R. , Sims Carrie A.
Published: November 2023

BACKGROUND

Pneumonia remains a common complication in trauma patients. Sirtuin 1 (SIRT1) is an anti-inflammatory NAD+-dependent deacetylase that has been shown to reduce the severity of ARDS in polymicrobial sepsis. The impact of SIRT1 in acute pneumonia, however, remains unknown. We hypothesized that SIRT1 deletion in pneumonia would worsen the inflammatory response and clinical severity, and that increased SIRT1 expression would be protective.

METHODS

Ten- to 14-week-old male and female SIRT1 knockout (S1KO) mice, SIRT1 overexpressor (S1OE) mice, and their wildtype (WT) littermates underwent intra-tracheal inoculation with Pseudomonas aeruginosa. Rectal temperature was recorded, SIRT1 lung protein was quantified by western blotting, Sirt1 mRNA was measured by qPCR, and lung leukocyte subpopulations were analyzed by flow cytometry. Data were analyzed by one-way ANOVA using Prism software.

RESULTS

Pneumonia created a functional SIRT1 knockdown in the lungs of WT mice by 4 hours, resulting in comparable SIRT1 levels and temperatures to the S1KO mice by 12 hours. Pneumonia also partially reduced SIRT1expression in S1OE mice, but S1OE mice still had improved thermoregulation 12 hours after pneumonia. In all groups, Sirt1 mRNA expression was not affected by infection. Sirtuin 1 deletion was associated with decreased neutrophil infiltration in the lung, as well as a shift toward a more immature neutrophil phenotype. SIRT1 deletion was also associated with decreased myeloperoxidase-positive neutrophils in the lungs following pneumonia, indicating decreased neutrophil activity. S1OE mice had no change in lung leukocyte subpopulations when compared to WT.

CONCLUSION

Pneumonia creates a functional SIRT1 knockdown in mice. SIRT1 deletion altered the early inflammatory cell response to pneumonia, resulting in a neutrophil response that would be less favorable for bacterial clearance. Despite overexpression of SIRT1, S1OE mice also developed low SIRT1 levels and exhibited only minimal improvement. This suggests increasing SIRT1 transcription is not sufficient to overcome pneumonia-induced downregulation and has implications for future treatment options. Targeting SIRT1 through increasing protein stability may promote a more efficient inflammatory cell response to pneumonia, thereby preventing subsequent lung injury.
Intraoperative Monitoring of the External Urethral Sphincter Reflex: A Novel Adjunct to Bulbocavernosus Reflex Neuromonitoring for Protecting the Sacral Neural Pathways Responsible for Urination, Defecation and Sexual Function
Authors: Silverstein Justin W. , Block Jon , Olmsted Zachary T. , Green Ross , Pieters Thomas , Babarevech Kristiana , Ballas-Williamson Alicia , Skinner Stanley A. , Sciubba Daniel M. , Larry Lo Sheng-Fu
Published: November 2023

Purpose:

Intraoperative bulbocavernosus reflex neuromonitoring has been utilized to protect bowel, bladder, and sexual function, providing a continuous functional assessment of the somatic sacral nervous system during surgeries where it is at risk. Bulbocavernosus reflex data may also provide additional functional insight, including an evaluation for spinal shock, distinguishing upper versus lower motor neuron injury (conus vs. cauda syndromes) and prognosis for postoperative bowel and bladder function. Continuous intraoperative bulbocavernosus reflex monitoring has been utilized to provide the surgeon with an ongoing functional assessment of the anatomical elements involved in the S2–S4 mediated reflex arc including the conus, cauda equina and pudendal nerves. Intraoperative bulbocavernosus reflex monitoring typically includes the electrical activation of the dorsal nerves of the genitals to initiate the afferent component of the reflex, followed by recording the resulting muscle response using needle electromyography recordings from the external anal sphincter.

Methods:

Herein we describe a complementary and novel technique that includes recording electromyography responses from the external urethral sphincter to monitor the external urethral sphincter reflex. Specialized foley catheters embedded with recording electrodes have recently become commercially available that provide the ability to perform intraoperative external urethral sphincter muscle recordings.

Results:

We describe technical details and the potential utility of incorporating external urethral sphincter reflex recordings into existing sacral neuromonitoring paradigms to provide redundant yet complementary data streams.

Conclusions:

We present two illustrative neurosurgical oncology cases to demonstrate the utility of the external urethral sphincter reflex technique in the setting of the necessary surgical sacrifice of sacral nerve roots.
General anaesthesia reduces the uniqueness of brain connectivity across individuals and across species
Authors: Luppi Andrea I. , Golkowski Daniel , Ranft Andreas , Ilg Rudiger , Jordan Denis , Bzdok Danilo , Owen Adrian M. , Naci Lorina , Stamatakis Emmanuel A. , Amico Enrico , Misic Bratislav
Published: November 2023

The human brain is characterised by idiosyncratic patterns of spontaneous thought, rendering each brain uniquely identifiable from its neural activity. However, deep general anaesthesia suppresses subjective experience. Does it also suppress what makes each brain unique? Here we used functional MRI under the effects of the general anaesthetics sevoflurane and propofol to determine whether anaesthetic-induced unconsciousness diminishes the uniqueness of the human brain: both with respect to the brains of other individuals, and the brains of another species. We report that under anaesthesia individual brains become less self-similar and less distinguishable from each other. Loss of distinctiveness is highly organised: it co-localises with the archetypal sensory-association axis, correlating with genetic and morphometric markers of phylogenetic differences between humans and other primates. This effect is more evident at greater anaesthetic depths, reproducible across sevoflurane and propofol, and reversed upon recovery. Providing convergent evidence, we show that under anaesthesia the functional connectivity of the human brain becomes more similar to the macaque brain. Finally, anaesthesia diminishes the match between spontaneous brain activity and meta-analytic brain patterns aggregated from the NeuroSynth engine. Collectively, the present results reveal that anaesthetised human brains are not only less distinguishable from each other, but also less distinguishable from the brains of other primates, with specifically human-expanded regions being the most affected by anaesthesia.
The Cardiac Calcium Handling Machinery is Remodeled in Friedreich’s Ataxia
Authors: Czornobil Roman , Abou-Assali Obada , Remily-Wood Elizabeth , Lynch David R , Noujaim Sami F. , Chidipi Bojjibabu
Published: November 2023

Background

Friedreich’s ataxia (FA) is an inherited neurodegenerative disorder that causes progressive nervous system damage resulting in impaired muscle coordination. FA is the most common autosomal recessive form of ataxia and is caused by an expansion of the DNA triplet guanine–adenine–adenine (GAA) in the first intron of the Frataxin gene (FXN), located on chromosome 9q13. In the unaffected population, the number of GAA repeats ranges from 6 to 27 repetitions. In FA patients, GAA repeat expansions range from 44 to 1,700 repeats which decreases frataxin protein expression. Frataxin is a mitochondrial protein essential for various cellular functions, including iron metabolism. Reduced frataxin expression is thought to negatively affect mitochondrial iron metabolism, leading to increased oxidative damage. Although FA is considered a neurodegenerative disorder, FA patients display heart disease that includes hypertrophy, heart failure, arrhythmias, conduction abnormalities, and cardiac fibrosis.

Objective

In this work, we investigated whether abnormal Ca2+handling machinery is the molecular mechanism that perpetuates cardiac dysfunction in FA.

Methods

We used the frataxin knock-out (FXN-KO) mouse model of FA as well as human heart samples from donors with FA and from unaffected donors. ECG and echocardiography were used to assess cardiac function in the mice. Expression of calcium handling machinery proteins was assessed with proteomics and western blot. In left ventricular myocytes from FXN-KO and FXN-WT mice, the IonOptix system was used for calcium imaging, the seahorse assay was utilized to measure oxygen consumption rate (OCR), and confocal imaging was used to quantify the mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS).

Results

We found that major contractile proteins, including SERCA2a and Ryr2, were downregulated in human left ventricular samples from deceased donors with FA compared to unaffected donors, similar to the downregulation of these proteins in the left ventricular tissue from FXN-KO compared to FXN-WT. On the ECG, the RR, PR, QRS, and QTc were significantly longer in the FXN-KO mice compared to FXN-WT. The ejection fraction and fractional shortening were significantly decreased and left ventricular wall thickness and diameter were significantly increased in the FXN-KO mice versus FXN-WT. The mitochondrial membrane potential Δψm was depolarized, ROS levels were elevated, and OCR was decreased in ventricular myocytes from FXN-KO versus FXN-WT.

Conclusion

The development of left ventricular contractile dysfunction in FA is associated with reduced expression of calcium handling proteins and mitochondrial dysfunction.
Intrinsic epigenetic state of primary osteosarcoma drives metastasis
Authors: Singh Irtisha , Rainusso Nino , Kurenbekova Lyazat , Nirala Bikesh K. , Dou Juan , Muruganandham Abhinaya , Yustein Jason T.
Published: November 2023

Osteosarcoma (OS) is the most common primary malignant bone tumor affecting the pediatric population with high potential to metastasize to distal sites, most commonly the lung. Insights into defining molecular features contributing to metastatic potential are lacking. We have mapped the active chromatin landscapes of OS tumors by integrating histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary OS tumors from patients with metastasis (primary met) have a distinct active chromatin landscape compared to primary tumors from patients without metastatic disease (localized). The difference in chromatin activity shapes the transcriptional profile of OS. We identified novel candidate genes involved in OS pathogenesis and metastasis, includingPPP1R1B,PREX1andIGF2BP1, which exhibit increased chromatin activity in primary met along with higher transcript levels. Overall, differential chromatin activity in primary met occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and extracellular matrix suggestive of their role in facilitating OS metastasis. Furthermore, chromatin profiling of tumors from metastatic lung lesions noted increases in chromatin activity in genes involved in cell migration and key intracellular signaling cascades, including the Wnt pathway. Thus, this data demonstrates that metastatic potential is intrinsically present in primary metastatic tumors and the cellular chromatin profiles further adapt to allow for successful dissemination, migration, and colonization at the distal metastatic site.
Connecting Syncmers to FracMinHash: similarities and advantages
Authors: Liu Shaopeng , Koslicki David
Published: November 2023

Motivation

Sketching methods provide scalable solutions for analyzing rapidly growing genomic data. A recent innovation in sketching methods, syncmers, has proven effective and has been employed for read alignment. Syncmers share fundamental features with the FracMinHash technique, a recent modification of the popular MinHash algorithm for set similarity estimation between sets of different sizes. Although previous researchers have demonstrated the effectiveness of syncmers in read alignment, their potential for broader usages in metagenomic analysis (the primary purpose for which FracMinHash was designed) and sequence comparisons remains underexplored.

Results

We demonstrated that a open syncmer sketch is equivalent to a FracMinHash sketch when appled tok-mer-based similarities, yet it exhibits superior distance distribution and genomic conservation. Moreover, we expanded the concept ofk-mer truncation to open syncmers, creating multi-resolution open syncmers for metagenomic applications as well as flexible-sized seeding for sequence comparisons.

Reproducibility

All analysis scripts can be found onGitHub.