bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 370: Oral-Mucosal PCO
2
During Hemorrhagic Shock Closely Monitors Its Time Course, Severity, and Reversal Outperforming Blood Lactate Measurement
Authors: Razi Armin , Ayoub Iyad , Baetiong Alvin , Aiello Salvatore , Gazmuri Raul J
Published: December 2023

Objective:
Oral-Mucosal PCO
2
(P
OM
CO
2
) has been shown to closely correlate with the splanchnic mucosal PCO
2
and provide information on its microcirculation. We used a swine model of controlled hemorrhagic shock to assess the potential clinical relevance of monitoring P
OM
CO
2
to assess its clinical course, severity, and treatment effect.

Methods:
The study was performed on six male domestic pigs (37.9±1.4 kg). P
OM
CO
2
was measured using a non-invasive disposable sensor clipped to the cheek, developed by ExoStat Medical. Blood was removed over 120 minutes from the right atrium using a LabVIEW-controlled pump according to a mono-exponential decay curve modeling spontaneous bleeding and reinfused in 20 minutes observing the animal for a total of 180 minutes.

Results:
A total of 1,491±193 ml corresponding to 65.5% of the estimated blood volume were removed inducing the characteristic hemodynamic features of hemorrhagic shock including tachycardia, hypotension, reduced cardiac output, and reduced systemic oxygen delivery with increased systemic oxygen extraction. P
OM
CO
2
closely paralleled the time course of blood removal showing an early and steady increase from 85±5 mmHg at baseline to 144±32 mmHg after 120 minutes. Blood reinfusion rapidly reduced the P
OM
CO
2
to 130±17 mmHg after 20 minutes and 96±14 mmHg at the end of 180 minutes, coincident with reversal of hemorrhagic shock. P
OM
CO
2
also closely tracked changes in systemic oxygen extraction. Concurrent measurements of blood lactate demonstrated a slower increase during the hemorrhagic shock period (from 1.1±0.3 to 3.0±0.3 mmol/l) with further increase (not decrease) to 5.4±2.0 mmol/l after blood reinfusion, remaining at 4.3±0.8 mmol/l by the end of the 180-minute observation period.

Conclusions:
The study demonstrated capability of P
OM
CO
2
to closely and non-invasively track hemodynamic and metabolic changes occurring during hemorrhagic shock. P
OM
CO
2
outperformed blood lactate which exhibited a slower and delayed response. Thus, P
OM
CO
2
may provide a clinically practical and non-invasive means to monitor hemorrhagic shock assessing its severity, clinical course, and treatment effect.
Abstract 371: Physiological Predictors of Cerebral Oxygenation During Hemorrhage in Swine
Authors: Gould Jeffrey R , Clark Lyra R , Badin Jill , Harvey Joshua , Lampe Joshua W
Published: December 2023

Introduction:
Measurements of cerebral oxygenation (rSO
2
) using near-infrared spectroscopy (NIRS) have been used to predict survival in retrospective clinical studies. However, the physiology underlying changes in rSO
2
during critical states such as hemorrhage is not completely understood. This analysis examined the effect of blood pressures, intracranial pressure, and heart rate on rSO
2
.

Methods:
Eight swine were instrumented with invasive pressure catheters in the aorta, right atrium, and cerebrum and underwent a pressure-targeted arterial hemorrhage protocol. Animals were bled at a rate of 20mL/min to a target diastolic pressure of 35 mmHg. Brief periods of increased baseline airway pressure (15 cm H
2
O) were introduced to cause transient drops in arterial blood pressure. The aortic pressure waveform was used to identify individual heartbeats. The first 100 heartbeats represent baseline data, while heart beats 4900-5000 (time from start of bleed; 40±7 min) capture data late into the bleed for all animals. Data from 53,315 heart beats were entered into a regression model: rSO
2
= mean diastolic aortic pressure + mean diastolic right atrial pressure + intracranial pressure + heart rate + animal.

Results:
The hemorrhage reduced diastolic aortic pressure from 61.7±9.6 (heart beats 1-100) to 35.0±9.2 mmHg (heart beats 4900-5000), increased right atrial pressure from 4.1±3.6 to 4.9±6.9 mmHg, reduced intracranial pressure from 33.6±23.2 mmHg to 16.3±2.5 mmHg, and increased heart rate from 101±14 to 144±40 beats/min. Output from the regression model (Table 1) shows that mean diastolic aortic pressure, but not right atrial pressure, intracranial pressure or heart rate, is a significant predictor of rSO
2
.

Conclusions:
rSO
2
values are largely driven by arterial blood pressure and may serve as a useful non-invasive tool as a surrogate for arterial blood pressure during hemorrhage. Further work should investigate the use of this technology to provide real-time feedback.
Abstract 373: Traumatic Bleeding Severity Score: An External Validation Study for the Predictive Accuracy of the Need for Massive Transfusion
Authors: Kimoto Kei , Ogura Takayuki , Fujita Kensuke , Kimura Takuya , Misumi Kayo , Hagiwara Yoshihiro ,   JAST: J-OCTET2 study group
Published: December 2023

Background:
The Traumatic Bleeding Severity Score (TBSS) was developed to predict the need for massive transfusion (MT). The aim of this study was to conduct the first external validation study about the TBSS in Japan, and to compare its prediction value to other pre-existing MT prediction scores.

Methods:
A multicenter retrospective observational study was conducted in Japan (Japanese observational study for coagulation and Thrombolysis in Early Trauma 2 : J-OCTET 2). Twenty-five tertiary critical care centers in Japan participated in this study, and severe trauma patients (Injury Severity Score : ISS ≥ 16) admitted from 2018 to 2019 were enrolled. At the analysis of the TBSS external validation, patients with isolated head injuries were excluded from the analysis. In this study, MT was defined as 10 units or more of red blood cells transfusion within 24 hours from injuries. The TBSS on admission was retrospectively calculated and its accuracy in predicting MT was analyzed by the area under the receiver operating characteristic curve (AUROC). To compare the predictive value between the TBSS and the pre-existing scores, the Trauma Associated Severe Hemorrhage score (TASH score) and the Assessment of Blood Consumption score (ABC score) on admission was similarly calculated, and the ROC comparison analysis was performed.

Results:
Totally, 1202 severely injured trauma patients were enrolled in the J-OCTET 2 study, and 889 patients were analyzed after the matching of the exclusion criteria. The median age was 66 years (IQR: 47-77), 71.4 % was male, 97.9% was blunt trauma, median ISS was 22 (IQR:16-29), and 13.8% received MT. The AUROC of the TBSS for was 0.848 (95% CI:0.81-0.88). According to the ROC comparison, the AUROC of the TASH score was 0.848 (95% CI: 0.81-0.88) and there was no significant difference between both prediction scores. (Bonferroni adjusted p=1.00). The AUROC of the ABC score was 0.751(95% CI: 0.70-0.80), which was significantly lower to TBSS’s (Bonferroni adjusted p<0.01).

Conclusion:
This TBSS external validation study showed that the accuracy of TBSS in the MT prediction was moderate accuracy. The predictive value of the TBSS was comparable to that of the TASH score and superior to the ABC score.
Abstract 377: Developing a Novel Oxygen Carrier for Resuscitation and Oxygen Delivery Through Targeted Mutations of Recombinant Heme-Proteins
Authors: Gandhi Alay , Tejero Jesus , DeMartino Anthony , Dent Matthew , Xu Qinzi , Hwang Hyon , Bocian Kaitlin , Huang XueYin , Chen Xiukai , Poropatich Ronald , Gladwin Mark , Rose Jason J
Published: December 2023

Introduction:
Hemorrhage is a leading cause of death in trauma patients. Interventions dedicated to hemostatic resuscitation have demonstrated benefit in decreasing mortality due to hemorrhagic injury. There remain significant limitations to donor-based blood transfusions. We have identified a heme-binding protein, the Bacterial Regulator of carbon monoxide metabolism (RcoM), with suitable properties to be a robust artificial oxygen carrier. We have engineered a variant that lacks a DNA binding domain and contains cysteine mutations for improved stability (RcoM HBD-CCC).

Hypothesis:
We hypothesize that engineered RcoM HBD-CCC can be used as an ideal artificial oxygen carrier due to the optimization of 4 factors: ligand binding, nitrite reduction rate, autoxidation rate, and thermal denaturation.

Methods:
Spectrophotometric methods were used to characterize RcoM HBD-CCC in terms of its biochemical properties for optimal oxygen transport and release. Specifically, ligand binding was tested by determination of the P50 (oxygen pressure for 50% saturation of the molecule) value indicating the affinity of RcoM HBD-CCC towards oxygen. Nitrite reduction assays were carried out to test the rate at which nitric oxide (NO) forms to counteract potential NO scavenging. The autoxidation rate determines how long a protein stays in the reduced state, where it is able to bind to oxygen. Thermal denaturation (T
m
) identifies the resistance of a protein to higher temperatures.

Results:
We determined that RcoM HBD-CCC’s P50 value was 4.2 mmHg which is within the ideal range for oxygen binding affinity given that optimal values for oxygen carriers to mimic hemoglobin oxygen dissociation are between 1 to 26 mmHg. Nitrite reductase rate was 5.6M
-1
s
-1
which is well above the rate for Hb (K = 0.12 M
-1
s
-1
). RcoM HBD-CCC has a low autoxidation rate at 0.016 min
-1
. RcoM HBD-CCC has a T
m
of 71°C which is well above all ambient environmental temperatures.

Conclusion:
We have designed and synthesized a variant of RcoM that we have demonstrated in
in vitro
spectrophotometric assays to have ideal biochemical properties for an artificial oxygen carrier. We next plan to test the efficacy of RcoM HBD-CCC in animal models of hemorrhage and assess safety in animal exposure models.
Abstract 382: The Effect of Stepstool Use on Chest Compression Quality During CPR in Young Children: Findings From the Videography in Pediatric Emergency Research (VIPER) Collaborative
Authors: O'Connell Karen J , Dutta Anuj , Sandler Alexis , Kerrey Benjamin , Myers Sage , Neubrand Tara , Donoghue Aaron
Published: December 2023

Background:
Delivering chest compressions (CC) of adequate depth and rate during pediatric cardiopulmonary resuscitation (CPR) has known beneficial hemodynamic consequences; however, chest compression quality in this population is often suboptimal. While common, the benefit of stepstool use during pediatric CPR has not been studied.

Objective:
To analyze the effect of step stool use on chest compression quality (depth, rate) in a pediatric emergency department (ED).

Methods:
We conducted a prospective observational cohort study involving patients <8 years of age receiving chest compressions in an ED for >2 minutes. Data was collecting via structured video review and from a CC monitoring device. Analysis was by compressor segment. We compared CC rate and depth by step stool use in each of 3 age groups: < 1 year, 1-8 years, 9-18 years. We also examined step stool and CC quality by compressor hand position: 1) two thumbs, hands encircling chest (2T), 2) two fingers, 2
nd
and 3
rd
digits, pressing on anterior sternum (2F), 3) one hand (1H), and4) two hands (2H).

Results:
46 patients received 390 CC segments (565 total minutes of CC). In patient <1 year and 1-8years of age, the majority of compressors utilized a step stool (73% <1 year; 83.3% 1-8 years). For <1year, there was no difference in mean CC rate or depth with or without step stool use. In children >1year of age, a step stool was associated with deeper chest compressions [3.63cm (IQR 3.07 - 4.17)versus 2.74 cm (IQR 2.39 - 3.24) without, p=0.000] and a mean CC rate more consistent with AHA guidelines [115 compressions per minute (IQR 115 - 128) versus 125 (IQR 110 - 121) without p=0.0037]. Stratified by hand placement technique, 1H compressions with a step stool achieved greater depth in children >1 years (p<0.01); 2H compressions with a step stool achieved a more compliant CC rate in children >1 years (p<0.05).

Conclusions:
CPR depth failed to reliably meet AHA guidelines regardless of stepstool use across all age categories. However, in children between 1 - 8 years of age, step stool use was significantly associated with higher quality chest compressions. Our findings of better CC depth and rate with one and two hand compressions should prompt further investigation and evaluation of CC technique in the pediatric population.
Abstract 390: Pre-Hospital Administered Adrenaline in the Presence of a Physician and Neurological Status of Patients With Out-of-Hospital Cardiac Arrest: A Multi-Center Prospective Cohort Study
Authors: Hatakeyama Toshihiro , Kiguchi Takeyuki , Sera Toshiki , Nachi Sho , Urushibata Nao , Ochiai Kanae , Kitamura Tetsuhisa , Ogura Shinji , Otomo Yasuhiro , Iwami Taku
Published: December 2023

Background:
Little is known about whether pre-hospital administered adrenaline with a physician present could improve the outcome of patients with cardiac arrest.

Hypothesis and Aim:
We aimed to test the hypothesis that pre-hospital administered adrenaline provided in the presence of a physician could improve neurological survival of patients with a specific type of first-confirmed cardiac rhythm following cardiac arrest compared with pre-hospital administered adrenaline provided in the absence of a physician.

Methods:
This prospective multi-center cohort study enrolled consecutive patients who were transported to 95 participating hospitals in Japan after out-of-hospital cardiac arrest and later underwent resuscitation at a hospital between June 1 2014 and December 31 2020. We included patients who were administered pre-hospital adrenaline under the presence or absence of a physician, and who were ≥18 years of age with cardiac arrest of a medical etiology. Primary outcome was a favorable neurological outcome (Cerebral Performance Category score of 1 or 2) one month after cardiac arrest. Whether the carotid artery was pulsating and 3-lead electrocardiogram monitor confirmed the first cardiac rhythm. Based on previous findings, those with the first-confirmed cardiac rhythm were subdivided into the non-shockable and shockable groups. Multivariable logistic regression analysis was performed on propensity score-matched patients.

Results:
We analyzed 11,711 patients. Among the 10,113 patients in the non-shockable group, 0.6% (N = 64) had a favorable neurological outcome. The adjusted odds ratio for a favorable neurologic outcome of pre-hospital administered adrenaline under the presence of a physician was 3.94 (95% confidence interval (CI): 1.58-11.4), compared with the absence of a physician. Of 1,598 patients in the shockable group, 10.3% (N = 164) had a favorable neurological outcome with an adjusted odds ratio of 1.30 (95% CI: 0.73-2.35).

Conclusion:
This prospective multi-center cohort study showed that pre-hospital administered adrenaline in the presence of a physician was significantly associated with a higher favorable neurological outcome in non-shockable patients with cardiac arrest.
Abstract 391: Association Between Defibrillation to Epinephrine Interval and Short-Term Outcomes in Out-of-Hospital Cardiac Arrest Patients With Shockable Rhythm
Authors: Kawakami Shoji , Tahara Yoshio , Noguchi Teruo , Yasuda Satoshi , Nishi Jun-ichiro , Nishimura Kunihiro , Yonemoto Naohiro W , Nonogi Hiroshi , Nagao Ken , Ikeda Takanori ,   JCS-ReSS group
Published: December 2023

Background:
The optimal timing of epinephrine administration after defibrillation in out-of-hospital cardiac arrest (OHCA) patients with shockable rhythm is unknown.

Aim:
We evaluated the association between defibrillation to epinephrine interval and short-term outcomes.

Methods:
Between 2011 and 2020, we enrolled 1,259,960 OHCA patients from a nationwide prospective population-based registry in Japan. After applying exclusion criteria, 20,905 patients with shockable rhythm as the first documented rhythm at emergency medical services (EMS) arrival who received epinephrine after defibrillation were eligible for the study. Clinical outcomes included prehospital return of spontaneous circulation (ROSC), survival, and favorable neurological outcome at 30 days. To examine whether each variable predicted a good short-term outcome, multivariable logistic regression models were constructed using age, gender, year, district, origin of cardiac arrest, witnessed arrest, bystander-initiated cardiopulmonary resuscitation, call to EMS arrival interval, EMS arrival to defibrillation interval, and defibrillation to epinephrine interval.

Results:
At 30 days, 1,618 patients (8%) had a favorable neurological outcome. The defibrillation to epinephrine interval in these patients was significantly shorter than the interval in patients with an unfavorable neurological outcome [8 (5-12) vs 11 (7-16) min; P<0.001]. The proportion of patients who achieved prehospital ROSC, survived, or had a favorable neurological outcome at 30 days decreased as time to epinephrine after defibrillation increased (P<0.001 for trend). Multivariable analysis showed that shorter defibrillation to epinephrine interval independently predicted good outcomes (
Table
).

Conclusion:
A shorter defibrillation to epinephrine interval is significantly associated with good short-term outcomes in OHCA patients with shockable rhythm.
Abstract 396: A Novel Machine Learning Approach for Identifying Subgroups With Differential Responses to Amiodarone in Patients With Cardiac Arrest With Shockable Rhythm
Authors: Nishikimi Mitsuaki , Emoto Ryo , Ohshimo Shinichiro , Matsui Shigeyuki , Shime Nobuaki
Published: December 2023

Introduction:
Although there is a possibility that the effectiveness of amiodarone may differ among a particular subgroup, there are few studies on the differential effects of amiodarone for the out-of-hospital cardiac arrest (OHCA) patients with a shockable rhythm.

Objective:
To identify subgroups with differential responses to amiodarone in OHCA with shockable rhythm by a novel machine learning approach.

Methods:
We used data from the Japanese nationwide OHCA registry of the Japanese Association for Acute Medicine. The OHCA patients who had initial shockable rhythm upon hospital arrival were included. The primary outcome was a good neurological outcome at 30 days, defined as a Cerebral Performance Categories score ≤2. We developed a linear score by outcome weighting learning (OWL) method with logistic loss to identify subgroups with differential effects of amiodarone. The difference in the effect of amiodarone between subgroups based on the developed score was evaluated by repeated cross-validation (RCV), and hypothesis testing was performed by the permutation method.

Results:
Among 68,111 OHCA patients in the registry, data of 2333 patients with initial shockable rhythm upon hospital arrival were analyzed. Our developed score showed that the longer duration from call to EMS to hospital arrival, hypothermia at hospital arrival, and no defibrillation until hospital arrival were important variables that had a trend of increasing the beneficial effect of amiodarone (Table). The effect of amiodarone on neurological outcomes varied significantly among the subgroups identified by the developed scores (OR: 1.05 (95%CI: 0.99-1.13), P
[RCV]
= 0.038).

Conclusions:
We successfully developed a model that discriminates between the patients for whom amiodarone had a harmful effect on their neurological outcome from those for whom amiodarone had a beneficial effect. In the patients for whom amiodarone had a harmful effect, the other treatment approaches may be needed.
Abstract 411: Characterization of Pediatric In-Hospital Cardiac Arrest in Denmark
Authors: Lauridsen Kasper G , Naveendran Elakiya , Brix Bea , Lofgren Bo
Published: December 2023

Background:
Pediatric in-hospital cardiac arrest occurs frequently and is associated with high mortality. However, the epidemiology of pediatric in-hospital cardiac arrest outside of the US is poorly characterized.

Aim:
We aimed to characterize pediatric in-hospital cardiac arrests in Denmark.

Methods:
This is a nationwide cohort study. We collected data from the Danish in-hospital cardiac arrest registry (DANARREST) from 2013-2021. We included all pediatric in-hospital cardiac arrests (<18 years of age) with a clinical indication for CPR. Neonatal cardiac arrests were excluded.

Results:
We identified 318 cases of which 137 had a cardiac arrest with an indication for CPR and complete data. Overall, the median (quartile 1; quartile 3) age was 2 (0; 13) years and 90 (66%) were male. In total, 34 (25%) occurred in the pediatric intensive care unit, 79 (58%) were monitored, 121 (90%) were witnessed, and 42 (31%) were intubated prior to the cardiac arrest. The initial rhythm was PEA (51%), asystole (19%), VF/ VT (13%) and pulse generating rhythm (17%). The cause of arrest was cardiac (23%) vs. non-cardiac (77%). Median time to first rhythm check was 1 (0;3) minutes and median time to arrival of the cardiac arrest team was 3 (2; 5) minutes. Overall, 81% achieved return of spontaneous circulation or return of circulation on ECMO, whereas 49% survived to 30 days, and 43% survived to one year.

Conclusion:
Most pediatric in-hospital cardiac arrests in Denmark occurred outside of the pediatric intensive care units, and almost half were not monitored. However, almost half survived to 30 days.
Abstract 417: Advanced vs. Basic Life Support Outcome Variation in the Treatment of Out-of-Hospital-Cardiac-Arrest in Detroit
Authors: Silvagi Ryan , Reece Ryan , Cranford James , Mathew Shobi , Byrd Mitchell , Pum John , Gorelick Damon , Mika Valerie H , Dunne Robert B , O'Neil Brian
Published: December 2023

Background:
Out-of-Hospital-Cardiac-Arrest (OHCA) may be treated with Advanced Life Support (ALS) and Basic Life Support (BLS). Previous literature has indicated that ALS provides no additional benefit to OHCA patients. This study compared OHCA outcomes between prehospital ALS or BLS care in a city with a preponderance of BLS only care.

Study Objectives:
To test for associations between prehospital ALS or BLS care stratified by initial cardiac rhythm on ROSC, discharged alive from the hospital, and on favorable neurological outcome at hospital discharge in OHCA of a presumed cardiac origin.

Methods:
A retrospective cohort of 6746 patients with non-traumatic OHCA who received CPR from a transporting EMS agency was collected using the Cardiac Arrest Registry to Enhance Survival (CARES) database. Patients were sorted into 4 cohorts based on ALS vs BLS care and initial shockable vs non-shockable cardiac rhythms. Cohorts were compared utilizing chi-squared and multivariable logistic regression analysis against the outcome variables of sustained ROSC, discharged alive from the hospital, and a favorable neurological outcome at hospital discharge.

Results:
After controlling for covariates, the odds of sustained ROSC were statistically significantly higher for S-ALS vs. NS-BLS (OR=4.4, p.001), S-BLS vs. NS-BLS (OR=1.8, p.001), and NS-ALS vs. NS-BLS (OR=2.2, p.001). The association between cohort and discharged alive from the hospital was also statistically significant (p.001), and discharged alive rates were S-ALS (17.9%); S-BLS (11.8%); NS-ALS (3.7%); NS-BLS (4.0%). The association between cohort and favorable neurological outcome was also statistically significant (p.001), and outcome rates were S-ALS (74.6%); S-BLS (58.2%); NS-ALS (36.5%); NS-BLS (41.6%). The odds of favorable neurological outcome were higher for S-ALS vs. NS-BLS (OR=2.6, p.001).

Conclusion:
In contrast to previous literature, ALS care in the study was superior to BLS care. ALS care was associated with higher rates of ROSC in OHCA patients regardless of rhythm. Further, ALS care was associated with higher rates of being discharged alive from the hospital and favorable neurological outcomes among patients with a shockable rhythm.
Abstract 421: Automated External Defibrillator Implementation Gaps in Three Non-Urban U.S. Communities
Authors: Coute Ryan A , Grady Jason , Dupont Allison G , Ruby Megan A , Leaming James M , Fountain James , Revelle Michael A , Kaviyarasu Aarthi , Ghorbani Anahita , Buckingham Julie , Hansen Peter Z , Abella Benjamin S , Kurz Michael C
Published: December 2023

Introduction:
Automated external defibrillators (AEDs) represent a crucial component of bystander response to out-of-hospital cardiac arrest (OHCA), yet epidemiologic evidence suggests that AEDs are deployed by laypersons in less than 5% of OHCA events in the US. The reasons for low utilization remain poorly characterized, especially in rural/suburban environments. We hypothesized that in these non-urban environments, layperson AED use is mostly in commercial or public locations despite most arrests occuring in private residences.

Methods:
We conducted an analysis of EMS-treated atraumatic OHCA events from 3 non-urban US regions (Cumberland County, PA; Jackson, TN; Forsyth County, GA), abstracted from EMS patient care reports. Data included Utstein reporting elements, arrest location type, and response intervals as calculated by dispatch and EMS arrival times. We excluded events in skilled nursing facilities and prisons. CPR and AED delivery by laypersons was measured.

Results:
Between 12/8/17-12/31/21, we identified 1542 adult OHCA patients with median age 66.5 y (IQR 22.5), 37% female, 18% had initial shockable rhythms, and 75% occurred in private residences. Return of spontaneous circulation was obtained in 19% of cases. Bystander CPR was performed in 23% and AEDs were deployed by laypersons in 3%. Laypersons applied AEDs in 12% of OHCA in commercial locations, 6% of OHCA in public, and 3% of OHCA in private residences. EMS response times were 4% less than 4 min, 48% 4-9 min, and 48% >9 min; prevalence of AED use was indistinguishable between time intervals of EMS response. 16% OHCA victims still had initial shockable rhythms even among the >9 min EMS response cases; of these, 1% received AED use from laypersons.

Conclusion:
In three non-urban US regions, most arrests occurred in private residences while AED use was much more likely in public or commercial locales, suggesting an important gap in AED deployment. Even in cases with prolonged response times, many patients had shockable rhythms, suggesting an important opportunity for earlier AED deployment. Future work will test whether placement of AEDs in residential areas using trained volunteer responders in these same communities will improve OHCA response and survival outcomes.
Abstract 427: Differential Gene Expression in Survivors versus Non-Survivors of In-Hospital Cardiac Arrest
Authors: Patel Jignesh K
Published: December 2023

Background:
While association of inflammatory cytokines with outcomes in cardiac arrest have become increasingly studied in both animal and human models, sparse published literature exists regarding gene expression and outcomes in adults with cardiac arrest. Accordingly, the goal of the current investigation was to identify proteins that are associated with survival, gender, and time and in what direction these proteins are associated in patients resuscitated from IHCA.

Methods:
In this prospective study, we assessed blood samples from adult patients with IHCA who underwent ACLS-guided resuscitation between 2014 and 2019 at an academic tertiary care medical center. Blood obtained at 0, 6, and 24 hours of IHCA) was sent for proteomic analysis. The primary outcome of interest was survival to hospital discharge.

Results:
Of the 95 patients, 22 (23.2%) survived to hospital discharge while 73 (76.8%) did not. A total of 206 samples were obtained from 95 patients, where each patient was measured at up to 6 time points. Given higher number of samples at 0, 6, and 24 hours following IHCA, modeling data was restricted to these time points. Volcano plot and heat map were generated for significant proteins for the survivor versus non-survivor analysis at each of the listed time points. Gene set enrichment analysis was also utilized to identify the top 10 gene sets associated with survivorship at T0, T6, and T12, and visualized via heatmap and a bar graph.

Conclusions:
In this contemporary proteomic study of 95 adults with IHCA receiving ACLS-guided resuscitative and post-resuscitative care, gene sets associated with survival exist and significant proteins associated with survivorship can be identified. To our knowledge, this is one of the first studies to assess differential gene expression in men and women with IHCA with respect to survival.
Potential biomarkers and therapeutic targets for obsessive compulsive disorder
Authors: Ravi Sudesh , Vashishth Rahul , Rajesh Keerthna , Batra Dhruv Rishb , Venkatesan Shashank , Sultania Aarushi , Ahmad Faraz
Published: December 2023

Obsessive compulsive disorder (OCD) is a prevalent behavioral disorder with a complex etiology. However, the underlying pathogenic molecular pathways and the associated risk factors are largely obscure. This has hindered both the identification of relevant prognostic biomarkers and the development of effective treatment strategies. Because of the diverse range of clinical manifestations, not all patients benefit from therapies currently practiced in the clinical setting. Nevertheless, several lines of evidence indicate that neurotrophic, neurotransmitter, and oxidative signaling are involved in the pathophysiology of OCD. Based upon evidences from clinical (and pre-clinical studies), the present review paper sets out to decipher the utilities of three parameters (i.e. brain-derived neurotrophic factor; BDNF, noradrenalin-synthesizing enzyme dopamine beta-hydroxylase; DBH; and oxidative damage marker malondialdehyde; MDA) as diagnostic peripheral biomarkers as well as bio-targets for therapeutic strategies. While the data indicates promising results, there is necessitation for future studies to further confirm and establish these. Further, based again on the available clinical data, we investigated the possibilities of exploiting the etiological links between disruptions in the sleep-wake cycle and insulin signaling, and OCD for the identification of potential anti-OCD ameliorative agents with the ability to elicit multimodal effects, including attenuation of the alterations in BDNF, noradrenergic and redox pathways. In this respect, agomelatine and metformin may represent particularly interesting candidates; however, further clinical studies are warranted to establish these as singular or complementary medications in OCD subjects.
Point of care testing in Croatia: a survey of the Working group for point of care testing of the Croatian society of medical biochemistry and laboratory medicine
Authors: Kuštro Maja , Grdić Rajković Marija , Ruljančić Nedjeljka , Milevoj Kopčinović Lara , Baršić Lapić Ivana
Published: December 2023

IntroductionThe aim of this study was to investigate attitudes and routine procedures in point of care testing (POCT) among non-laboratory and laboratory healthcare professionals in Croatia.Materials and methodsThe Working Group (WG) for POCT of the Croatian society of medical biochemistry and laboratory medicine has designed two anonymous surveys for laboratory staff and non-laboratory staff with a total of 44 questions/statements on POCT (27 questions for non-laboratory staff and 17 for laboratory staff). Surveys were sent to 184 medical biochemistry laboratory (MBL) managers, the Croatian medical chamber and the Croatian chamber of nurses. The survey was disseminated using the online survey platform SurveyMonkey.ResultsA total of 112 non-laboratory healthcare professionals and 50 laboratories participated in the survey, which represents a response rate of 0.25% for non-laboratory professionals and 27% for MBLs. The majority of non-laboratory staff stated that POCT enables better medical care for the patient (90/112) and that the implementation of new POCT devices should be the responsibility of a POCT team comprising laboratory and clinical healthcare professionals. The great majority of responding MBLs (42/50) acknowledge that POCT is necessary for better patient care, and also realize that validation of POCT devices and comparison to the central laboratory is necessary before implementation (49/50).ConclusionsThe majority of participants consider POCT as a medical tool that enables better patient care but there is still a lack of communication between laboratory and clinical staff. The study identified some critical spots that will help to create national guidelines to ensure high patient safety when using POCT devices.
Syndrome of inappropriate antidiuretic hormone secretion as an adverse reaction of ciprofloxacin: a case report and literature review
Authors: Mandić Sanja , Canecki-Varžić Silvija , Bilić-Ćurčić Ines , Lišnjić Dubravka , Zlosa Mihaela , Sabadi Dario , Švitek Luka , Grubišić Barbara , Schonberger Ema
Published: December 2023

Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland. Unsuppressed release of ADH leads to hyponatremia. This condition is referred to as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hereby, a case report is presented on ciprofloxacin-induced SIADH. A 67-year-old male patient was examined in the emergency room with symptoms of lethargy, headache, lack of attention, and a generally depressed mood lasting for three days. One week prior, empirical antimicrobial therapy involving ciprofloxacin for prostatitis was initiated. Laboratory analysis showed no relevant abnormalities except for hyponatremia (Na = 129 mmol/L). Chronic hyponatremia, thyroid dysfunction, and adrenal dysfunction were ruled out. Serum osmolality was 263 mOsmol/kg, urine osmolality was 206 mOsmol/kg, and urine sodium was 39 mmol/L. Given that all criteria for SIADH were met, ciprofloxacin was discontinued, and fluid restriction was advised. Four days later, the patient’s serum sodium concentrations nearly normalized (Na = 135 mmol/L), and all symptoms resolved. The Naranjo Scale yielded a score of 8, supporting the likelihood of a probable adverse reaction to ciprofloxacin. This case is presented to raise awareness among clinicians about the potential of ciprofloxacin to cause even mild hyponatremia.
Beckett personnage de roman
Authors: Mével Yann
Published: December 2023

Cet article vise à rendre compte des représentations de Samuel Beckett, en tant qu’homme et écrivain, et des usages fictionnels de sa vie, dans trois romans publiés en France, entre 2013 et 2020 : Gaby et son maître, d’Arthur Bernard, L’Apiculture selon Samuel Beckett, de Martin Page, et Le Tiers Temps, de Maylis Besserie. Ces fictions biographiques prennent plus ou moins ouvertement Samuel Beckett pour objet tout en recourant à l’imagination dans des proportions et selon des modalités variables. Notre étude, diachronique, se veut sensible à la singularité du projet porté par chacun de ces romans.
Ratio emblematum: Characteristic Features of the Jesuit Emblem
Authors: Melion Walter S.
Published: December 2023

The introductory essay examines the principles of Jesuit emblematic usage, as codified by Antonio Possevino, S.J. (1533–1611) in his educational treatise Bibliotheca selecta de ratione studiorum of 1603 and developed by two of the Society’s key emblematists: Jan David, S.J. (1545–1613) in his Duodecim specula of 1610 and Herman Hugo, S.J. (1588–1629) in his Pia desideria of 1624. The essay concludes by summarizing the five articles contained in this issue of the Journal of Jesuit Studies and then, on that basis, offering a brief account of the state of the question in the study of Jesuit emblematics.
The Emblematic Decoration of the Staircase at the Former Jesuit College of Győr in the Context of Jesuit Marian Iconography
Authors: Kusler Ágnes
Published: December 2023

This article contextualizes the emblematic decoration of the main staircase at the Jesuit College in Győr, northwestern Hungary. Painted in 1697, this fresco cycle visualizes the prayer of Salve Regina. The staircase emblems were designed as a visual aid to the Jesuits who wished to meditate on the significance of the Virgin Mary. Earlier scholarship has connected the decorative scheme to Jesuit emblem literature in general. In this article, I argue that the visual source of the program can be identified as the Salve Regina print series by Anton Wierix (1598). The emblems and their program, key examples of applied emblematics, demonstrate how and to what degree Jesuit meditative praxis underlay the decoration of Győr college. Focusing on the practical function of the decorative program also expands our knowledge of early modern practices of emblematic meditation in religious communities. This article is part of the special issue of the Journal of Jesuit Studies on Jesuit emblems and emblematic edited by Walter S. Melion.
Kurdish Queer Studies
Authors: Sandal-Wilson Hakan
Published: December 2023

This special issue introduction aims to map out encounters between Kurdish Studies and Queer Studies. While the growing scholarship on Queer Studies in the Middle East offers theoretically and politically significant frameworks and analyses, Kurdish experiences and interventions are notably absent from this picture. As well as outlining the contributions to the special issue, this introduction offers reflections on how Kurdish Studies, Middle East Studies, and Queer Studies would benefit from a “Kurdish Queer” perspective. In doing so, the introduction and this special issue more widely mark a shift from “queer encounters in Kurdish Studies” to “Kurdish Queer Studies” as an emerging field of inquiry, without setting rigid boundaries around it.
2. Sappho to Phaon
Authors: Hutchings William
Published: December 2023

Chapter 2. Sappho to Phaon is Pope’s early venture into the world of Ovid’s Heroides, verse epistles from heroines. An erotically charged beginning is gradually softened by its writer, the sixth century BCE Greek lyricist Sappho, adopting the gentler, more peaceful language of the Pastorals.
7. Eloisa to Abelard
Authors: Hutchings William
Published: December 2023

Chapter 7. Eloisa to Abelard is a striking and powerful development of the Ovidian verse epistle, resulting in a poem of intense and unremitting eroticism. The voice of Eloisa is flexible in language but firm in commitment to a love which grows stronger as its circumstances tragically deny its resolution. Love conquers all in its all-consuming fires.
15. Epistle to Miss Blount with the Works of Voiture; Epistle to Miss Blount, on her Leaving the Town after the Coronation; An Epistle to a Lady
Authors: Hutchings William
Published: December 2023

Chapter 15. An Epistle to a Lady is the culmination of Pope’s growing concern for the nature and social positioning of women, set within his recurrent emphasis on the power of friendship. Its finale joyfully and respectfully celebrates its addressee, Martha Blount, whom he has known for over twenty years. The shorter Epistle to Miss Blount with the Works of Voiture and Epistle to Miss Blount, on her Leaving the Town after the Coronation emerge from the early years of Pope’s friendship with the sisters Teresa and Martha Blount. The span of these friendships, matched by the arc of the poems themselves, embodies enduring respect and love. A recurrent counterpoint of Pope’s characteristically satirical sketches absorbs these poems within the texture of his broad ethical vision.
16. The First Satire of the Second Book of Horace Imitated
Authors: Hutchings William
Published: December 2023

Chapter 16 begins by locating The First Satire of the Second Book of Horace Imitated as the first of Pope’s seven Imitations of Horace’s satires and epistles. It then restates from the Introduction the importance of respecting the layout of the original printings of these poems (Latin text on the verso, English version on the recto) for a full appreciation of how the parallel texts affect our reading. (For the non-Latinist, a good modern translation of Horace’s poems will serve.) Pope’s choice of William Fortescue as his eighteenth-century equivalent of Horace’s interlocutor is also discussed. The main body of the chapter examines in detail seven significant extracts to show how Pope’s Imitation addresses the complex moral, political and social questions involved in the writing of satires. What constitutes ethically responsible action? How should it adapt to the changing public circumstances within which it has to operate? Pope’s investigation is searching, yet humorous in much of its tone; but it does not flinch from asserting the role of poetry (and printing) as a force for good.
22. The First Epistle of the Second Book of Horace Imitated. To Augustus
Authors: Hutchings William
Published: December 2023

Chapter 22. The First Epistle of the Second Book of Horace Imitated. To Augustus is the longest of Pope’s Imitations of Horace, and it is a magnificent example of sustained double-meaning masquerading as a humble address to his monarch, George II, whom Pope regarded as irredeemably uncultivated. George’s second name was Augustus, identical with the emperor for whom Horace wrote. Several extracts are then read in detail to mark the progress of Pope’s ironic argument. Why do people consider writers of earlier times superior to those of the present? But those supposed greats had their faults. Anyway, there is no need for you to be concerned, because poets are harmless creatures. May I, though, respectfully propose that we poets may be of some use? Some monarchs have indeed encouraged the arts. I would dearly love to be good enough to rise to a level fit for your great status. Alas, I fear I may not be.
Quotations for Lexical Lists and Other Texts in Later Mesopotamian Commentaries
Authors: Jiménez Enrique
Published: December 2023

Lists represent the oldest, and most pervasive, scholarly genre in ancient Mesopotamia. Cuneiform commentaries, first attested in the first millennium BCE, can be regarded as a genre derived from lexical lists. The contribution by Enrique Jiménez studies the ways in which lexical lists are cited in commentaries, and compares them with quotations from texts other than lexical lists.
Chapter Lists in Giant and Beneventan Bibles
Authors: Maniaci Marilena
Published: December 2023

Marilena Maniaci examines the so-called capitula, or chapter lists, that introduce the single biblical books in the majority of Latin Bibles, particularly prior to the 13th century, when the “Paris Bible” made its appearance and brought with it a new chapter subdivision of the biblical text. The Latin capitula briefly summarize, chapter by chapter, the contents of each section of the biblical text or reproduce the words or the section’s initial sentence. Several sequences or “families” of lists are attested, which differ (even significantly) in the number, extension and wording of the individual tituli, but also in the way they are arranged on the manuscript’s page and distinguished from the main text. Maniaci’s contribution aimes to provide some examples of the potential interest of an in-depth analysis of the chapters, not only as a tool to highlight relationships between individual codices or operate groupings within specific strands of textual tradition, but also to deepen our knowledge of the practices of manufacture and transcription of the biblical text and of its accompanying paratexts.
A phase 2 study of the PI3Kδ inhibitor parsaclisib in relapsed and refractory marginal zone lymphoma (CITADEL-204)
Authors: Phillips Tycel J. , Avigdor Abraham , Gurion Ronit , Patti Caterina , Corradini Paolo , Tani Monica , Mehta Amitkumar , Lossos Izidore S. , Zinzani Pier Luigi , Thieblemont Catherine , Jurczak Wojciech , Zheng Fred , Rappold Erica , Zhao Wanying , Jiang Ping , Johnson Peter
Published: December 2023

Parsaclisib, a potent and highly selective PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory (R/R) B-cell lymphomas. The phase 2 CITADEL-204 study (NCT03144674, EudraCT 2017-000970-12) assessed efficacy and safety of parsaclisib in Bruton tyrosine kinase (BTK) inhibitor–experienced (cohort 1) or BTK inhibitor–naive (cohort 2) patients with R/R marginal zone lymphoma (MZL). Patients aged ≥18 years with histologically confirmed R/R MZL, treated with ≥1 prior systemic therapy (including ≥1 anti-CD20 antibody) received parsaclisib 20 mg once daily for 8 weeks then 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg once daily for 8 weeks then 2.5 mg once daily (daily dosing group [DG]); DG was selected for further assessment. Primary end point of the study was objective response rate (ORR). Owing to slower than expected recruitment, cohort 1 was closed with 10 patients (WG, n = 4; DG, n = 6) enrolled. Based on a planned interim analysis in cohort 2, the futility boundary was not crossed, and enrollment continued to study completion. At data cutoff (15 January 2021), 100 patients were enrolled and treated in cohort 2 (WG, n = 28; DG, n = 72). In the DG, the ORR was 58.3% (95% confidence interval [CI], 46.1-69.8), with a complete response rate of 4.2% (95% CI, 0.9-11.7); the lower bound of the ORR 95% CI exceeded the protocol-defined threshold of 40%. The median duration of response was 12.2 months (95% CI, 8.1-17.5) and progression-free survival was 16.5 months (95% CI, 11.5-20.6); median overall survival was not reached. The most common treatment-emergent adverse events (TEAEs) among all patients were diarrhea (47.0%), cough (23.0%), and rash (18.0%); the most common grade ≥3 TEAEs included diarrhea (12.0%), neutropenia, and pneumonia (9.0% each). TEAEs led to dose interruptions, reductions, and discontinuations in 56.0%, 16.0%, and 29.0% of all patients, respectively. Durable responses and an overall manageable safety profile were demonstrated in patients with R/R MZL treated with parsaclisib monotherapy.
Choosing the right mouse model: comparison of humanized NSG and NBSGW mice for in vivo HSC gene therapy
Authors: Choo Seunga , Wolf Carl B. , Mack Heather M. , Egan Mitchell J. , Kiem Hans-Peter , Radtke Stefan
Published: December 2023

In vivo hematopoietic stem cell (HSC) gene therapy is an emerging and promising area of focus in the gene therapy field. Humanized mouse models are frequently used to evaluate novel HSC gene therapy approaches. Here, we comprehensively evaluated 2 mouse strains, NSG and NBSGW. We studied human HSC engraftment in the bone marrow (BM), mobilization of BM-engrafted HSCs into circulation, in vivo transduction using vesicular stomatitis virus glycoprotein–pseudotyped lentiviral vectors (VSV-G LVs), and the expression levels of surface receptors needed for transduction of viral vectors. Our findings reveal that the NBSGW strain exhibits superior engraftment of human long-term HSCs compared with the NSG strain. However, neither model resulted in a significant increase in circulating human HSCs after mobilization. We show that time after humanization as well as human chimerism levels and platelet counts in the peripheral blood can be used as surrogates for human HSC engraftment in the BM. Furthermore, we observed low expression of the low-density lipoprotein receptor, a requirement for VSV-G LV transduction, in the human HSCs present in the murine BM. Our comprehensive characterization of humanized mouse models highlights the necessity of proper validation of the model and methods to study in vivo HSC gene therapy strategies.