Radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal sarcomatosis: Results from a reference center and considerations based on current evidence.

INTRODUCTION: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. METHODS: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. RESULTS: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. CONCLUSIONS: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.

Analytical strategy to assess the microbial degradation of poly(butylene-adipate-co-terephthalate)/poly(lactic acid) films.

Plastic is widely used in agricultural applications, but its waste has an adverse environmental impact and a long-term detrimental effect. The development of biodegradable plastics for agricultural use is increasing to mitigate plastic waste. The most commonly used biodegradable plastic is poly(butylene adipate co-terephthalate)/poly(lactic acid) (PBAT/PLA) polymer. In this study, an analytical procedure based on dispersive liquid-liquid microextraction (DLLME) followed by gas chromatography-mass spectrometry (GC-MS) in combination with chemometrics has been optimized to assess the degradation level of PBAT/PLA films by monitoring their characteristic degradation products. Carboxylic acids (benzoic, phthalic, adipic, heptanoic, and octadecanoic acids) and 1,4-butanediol have been found to be potential markers of PBAT/PLA degradation. The DLLME-GC-MS analytical approach has been applied for the first time to assess the degradation efficiency of several microorganisms used as degradation accelerators of PBAT/PLA based on the assigned potential markers. This analytical strategy has shown higher sensitivity and precision than standard techniques, such as elemental analysis, allowing us to detect low degradation levels.

Cancer-associated stroke from progressive acinic cell carcinoma.

Cancer-associated stroke is an evolving subgroup of embolic strokes of undetermined source. A man in his mid-20s with progressive follicular variant acinic cell carcinoma of the parotid was admitted because of new onset left-sided weakness. Neuroimaging confirmed a right middle cerebral artery infarction. After extensive diagnostics, stroke aetiology was deemed from cancer-induced hypercoagulability. Questions which arose regarding his management included (1) What was the best antithrombotic for secondary stroke prevention? (2) What was his risk for intracranial or tumorous bleeding once antithrombotics had been started? (3) How many days post-stroke could the antithrombotic be initiated? and (4) When could he be cleared for palliative chemotherapy and whole brain irradiation? The approach to address the abovementioned questions in the management of a rare cancer complicated by stroke is presented. Although treatments are guided by known pathomechanisms, additional studies are needed to further support current treatment strategies for this subgroup of patients.

Daily quetiapine after severe TBI improves learning and memory.

BACKGROUND: Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI. METHODS: CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction (p < 0.05). RESULTS: On day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 (p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 (p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones (p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones (p < 0.05). CONCLUSION: Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.

Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

Tuneable Current Rectification Through a Designer Graphene Nanoribbon.

Unimolecular current rectifiers are fundamental building blocks in organic electronics. Rectifying behavior has been identified in numerous organic systems due to electron-hole asymmetries of orbital levels interfaced by a metal electrode. As a consequence, the rectifying ratio (RR) determining the diode efficiency remains fixed for a chosen molecule-metal interface. Here, a mechanically tunable molecular diode exhibiting an exceptionally large rectification ratio (>105) and reversible direction is presented. The molecular system comprises a seven-armchair graphene nanoribbon (GNR) doped with a single unit of substitutional diboron within its structure, synthesized with atomic precision on a gold substrate by on-surface synthesis. The diboron unit creates half-populated in-gap bound states and splits the GNR frontier bands into two segments, localizing the bound state in a double barrier configuration. By suspending these GNRs freely between the tip of a low-temperature scanning tunneling microscope and the substrate, unipolar hole transport is demonstrated through the boron in-gap state's resonance. Strong current rectification is observed, associated with the varying widths of the two barriers, which can be tuned by altering the distance between tip and substrate. This study introduces an innovative approach for the precise manipulation of molecular electronic functionalities, opening new avenues for advanced applications in organic electronics.

Ongoing CPR with an onboard physician.

Introduction: Recent data are not available on ongoing CPR for emergency services with an onboard physician. The aim of the present study was to identify factors associated with the decision to transport patients to hospital with ongoing CPR and examine their survival to hospital discharge with good neurological status. Methods: An observational study based on a registry of out-of-hospital cardiac arrests attended to by emergency services with an onboard physician. All OHCA cases occurring between the 1st of January and the 31st of December 2022 were included. Patients receiving ongoing CPR during transport to the hospital were compared with patients pronounced dead at the scene following arrival of the care team. The dependent variable was ongoing CPR during transport to the hospital. The main characteristics and the neurological status of patients surviving to discharge were described. Results: A total of 9321 cases were included, of which 350 (3.7%) were transported to hospital with ongoing CPR. Such patients were young (59.9 ± 20.1 years vs 64.6 ± 16.9 years; p < 0.001; 95%CI: 0.98 [0.98; 0.99]) with arrest taking place outside of the home (151 [44.5%] vs 4045 [68.01%]; p < 0.001; 95%CI: 0.41 [0.31; 0.54]) and being witnessed by EMS (126 [36.0%] vs 667 [11.0%]; p < 0.001; 95%CI: 4.31 [3.19; 5.80]), whilst initial rhythm differed from asystole (164 [47.6%] vs 4325 [73.0%]; p < 0.01; 95%CI: 0.44 [0.33; 0.60]) and a mechanical device was more often employed during resuscitation and transport to hospital (199 [56.9%] vs 2050 [33.8%]; p < 0.001; 95%CI: 2.75 [2.10; 3.59]). Seven patients (2%) were discharged alive from hospital, five with ad integrum neurological recovery (CPC1) and two with minimally impaired neurological function (CPC2). Conclusions: The strategy of ongoing CPR is uncommon in EMS with an onboard physician. Despite their limited efficacy, the availability of mechanical chest compression devices, together with the possibility of specific hospital treatments, mainly ICP and ECMO, opens up the possibility of this approach with determined patients.

Incidence, treatment, and factors associated with survival of out-of-hospital cardiac arrest attended by Spanish emergency services: report from the Out-of-Hospital Spanish Cardiac Arrest Registry for 2022. / Incidencia, tratamiento y factores asociados con la supervivencia de la parada cardiaca extrahospitalaria atendida por los servicios de emergencias en España: informe 2022 del registro OHSCAR.

SUMMARY: Out-of-hospital cardiac arrest is a serious public health problem worldwide. The annual incidence is estimated at around 400 000 cases in Europe and the United States, and survival rates scarcely reach 10%. However, there is considerable variation between countries and even between regions that share a similar health care system within a single country. Information recorded by the Out-of-Hospital Spanish Cardiac Arrest Registry (OHSCAR) provides information on care provided by emergency ambulance services, final health outcomes after cardiac arrest cases (including variations), the possibility of organ donation, and the impact of the COVID-19 pandemic. This paper presents the OHSCAR report for Spanish emergency services for the year 2022.

RESUMEN: La parada cardiorrespiratoria extrahospitalaria (PCREH) es un grave problema de salud pública mundial, con una incidencia anual estimada entorno a entorno a los 350.000 y 400.000 casos de PCERH en Europa y Estados Unidos, respectivamente. La supervivencia final se sitúa en porcentajes que apenas alcanzan el 10%, aunque existe una importante variabilidad entre países e incluso entre regiones del mismo país con modelos de atención similares. En España, el Registro Español de Parada Cardiaca Extrahospitalaria (acrónimo OHSCAR) ha ofrecido información sobre la asistencia a la PCRE prestada por los servicios de emergencias (SEM) y sus resultados finales en salud, así como sobre variabilidad, posibilidades de programas de donación o impacto de la pandemia COVID-19. A continuación se presenta el informe OHSCAR correspondiente a la asistencia a la PCRE por los SEM españoles durante el año 2022.

Ferromagnetic Order in 2D Layers of Transition Metal Dichlorides.

Magnetism in two dimensions is traditionally considered an exotic phase mediated by spin fluctuations, but far from collinearly ordered in the ground state. Recently, 2D magnetic states have been discovered in layered van der Waals compounds. Their robust and tunable magnetic state by material composition, combined with reduced dimensionality, foresee a strong potential as a key element in magnetic devices. Here, a class of 2D magnets based on metallic chlorides is presented. The magnetic order survives on top of a metallic substrate, even down to the monolayer limit, and can be switched from perpendicular to in-plane by substituting the metal ion from iron to nickel. Using functionalized STM tips as magnetic sensors, local exchange fields are identified, even in the absence of an external magnetic field. Since the compounds are processable by molecular beam epitaxy techniques, they provide a platform with large potential for incorporation into current device technologies.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study.

BACKGROUND: Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery. METHODS: CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury. RESULTS: I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group. CONCLUSIONS: Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

Sex Differences in Response Inhibition-Related Neural Predictors of Posttraumatic Stress Disorder in Civilians With Recent Trauma.

BACKGROUND: Females are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma. METHODS: Participants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months. RESULTS: Lower response inhibition-related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition-related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus. CONCLUSIONS: There are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.

To close or not to close? Wound management in emergent colorectal surgery, an EAST multicenter prospective cohort study.

BACKGROUND: This study aimed to determine the clinical impact of wound management technique on surgical site infection (SSI), hospital length of stay (LOS), and mortality in emergent colorectal surgery. METHODS: A prospective observational study (2021-2023) of urgent or emergent colorectal surgery patients at 15 institutions was conducted. Pediatric patients and traumatic colorectal injuries were excluded. Patients were classified by wound closure technique: skin closed (SC), skin loosely closed (SLC), or skin open (SO). Primary outcomes were SSI, hospital LOS, and in-hospital mortality rates. Multivariable regression was used to assess the effect of wound closure on outcomes after controlling for demographics, patient characteristics, intensive care unit admission, vasopressor use, procedure details, and wound class. A priori power analysis indicated that 138 patients per group were required to detect a 10% difference in mortality rates. RESULTS: In total, 557 patients were included (SC, n = 262; SLC, n = 124; SO, n = 171). Statistically significant differences in body mass index, race/ethnicity, American Society of Anesthesiologist scores, EBL, intensive care unit admission, vasopressor therapy, procedure details, and wound class were observed across groups. Overall, average LOS was 16.9 ± 16.4 days, and rates of in-hospital mortality and SSI were 7.9% and 18.5%, respectively, with the lowest rates observed in the SC group. After risk adjustment, SO was associated with increased risk of mortality (OR, 3.003; p = 0.028) in comparison with the SC group. Skin loosely closed was associated with increased risk of superficial SSI (OR, 3.439; p = 0.014), after risk adjustment. CONCLUSION: When compared with the SC group, the SO group was associated with mortality but comparable when considering all other outcomes, while the SLC was associated with increased superficial SSI. Complete skin closure may be a viable wound management technique in emergent colorectal surgery. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

This study examines the association between brain dynamic functional network connectivity (dFNC) and current/future posttraumatic stress (PTS) symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.179, pcorrected= 0.021) and future (r=-0.166, pcorrected= 0.029) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.192, pcorrected = 0.021). We additionally observed that the association between the network dynamics of the inter-network brain state with symptom severity is more pronounced in females (r=-0.244, pcorrected = 0.014). Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger protective effect of inter-network brain states against symptom severity in females, underscoring the importance of sex differences.

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.