Validation of Noninvasive Detection of Hyperkalemia by Artificial Intelligence-Enhanced Electrocardiography in High Acuity Settings.

Background: Artificial intelligence (AI) electrocardiogram (ECG) analysis can enable detection of hyperkalemia. In this validation, we assessed the algorithm's performance in two high acuity settings. Methods: An emergency department (ED) cohort (February to August 2021) and a mixed intensive care unit (ICU) cohort (August 2017 to February 2018) were identified and analyzed separately. For each group, pairs of laboratory-collected potassium and 12 lead ECGs obtained within 4 hours of each other were identified. The previously developed AI ECG algorithm was subsequently applied to leads 1 and 2 of the 12 lead ECGs to screen for hyperkalemia (potassium >6.0 mEq/L). Results: The ED cohort (N=40,128) had a mean age of 60 years, 48% were male, and 1% (N=351) had hyperkalemia. The area under the curve (AUC) of the AI-enhanced ECG (AI-ECG) to detect hyperkalemia was 0.88, with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive likelihood ratio (LR+) of 80%, 80%, 3%, 99.8%, and 4.0, respectively, in the ED cohort. Low-eGFR (<30 ml/min) subanalysis yielded AUC, sensitivity, specificity, PPV, NPV, and LR+ of 0.83, 86%, 60%, 15%, 98%, and 2.2, respectively, in the ED cohort. The ICU cohort (N=2636) had a mean age of 65 years, 60% were male, and 3% (N=87) had hyperkalemia. The AUC for the AI-ECG was 0.88 and yielded sensitivity, specificity, PPV, NPV, and LR+ of 82%, 82%, 14%, 99%, and 4.6, respectively in the ICU cohort. Low-eGFR subanalysis yielded AUC, sensitivity, specificity, PPV, NPV, and LR+ of 0.85, 88%, 67%, 29%, 97%, and 2.7, respectively in the ICU cohort. Conclusions: The AI-ECG algorithm demonstrated a high NPV, suggesting that it is useful for ruling out hyperkalemia, but a low PPV, suggesting that it is insufficient for treating hyperkalemia.

Host-specific effects of a generalist parasite of mosquitoes.

Microsporidians are obligate parasites of many animals, including mosquitoes. Some microsporidians have been proposed as potential agents for the biological control of mosquitoes and the diseases they transmit due to their detrimental impact on larval survival and adult lifespan. To get a more complete picture of their potential use as agents of biological control, we measured the impact of Vavraia culicis on several life-history traits of Aedes aegypti and Anopheles gambiae. We measured the infection dynamics and clearance rate for the two species, and we assessed sexual dimorphism in infection dynamics within each species. Our results show differences in infection dynamics, with Ae. aegypti life-history traits being more affected during its aquatic stage and exhibiting higher clearance of the infection as adults. In contrast, An. gambiae was unable to clear the infection. Additionally, we found evidence of sexual dimorphism in parasite infection in An. gambiae, with males having a higher average parasite load. These findings shed light and improve our knowledge of the infection dynamics of V. culicis, a microsporidian parasite previously recognized as a potential control agent of malaria.

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis.

BACKGROUND: Juvenile dermatomyositis (JDM) is a systemic vasculopathy associated with metabolic derangements and possible increased risk for premature atherosclerosis. Oxidation of low-density lipoprotein (LDL) in the endothelium is an early step in atherosclerotic plaque formation. It is not known if oxidized LDL is altered in children with untreated JDM. The deposition of oxidized LDL in the vasculature of muscle biopsies (MBx) from patients with untreated JDM and pediatric controls was assessed. FINDINGS: Frozen tissue sections of MRI-directed MBx from 20 female children with untreated JDM and 5 female controls were stained with DAPI and fluorescently labeled antibodies against von Willebrand factor (vWF) and LDL oxidized by copper (oxLDL). Blood vessels were identified by positive vWF staining, and total fluorescence of oxLDL within the vessel walls was measured. Children with untreated JDM had increased deposition of oxLDL in the walls of muscle vasculature compared to healthy children (difference in means ± SEM = 19.86 ± 8.195, p = 0.03). Within the JDM cohort, there was a trend towards increased oxLDL deposition with longer duration of untreated disease (r = 0.43, p = 0.06). There was no significant correlation found between oxLDL deposition and markers of acute JDM disease activity including disease activity scores or muscle enzymes. CONCLUSIONS: This study found increased deposition of oxLDL within blood vessels of children with untreated JDM supporting the concern that these children are at increased risk for premature atherosclerosis from chronic exposure to vascular oxLDL. This study highlights the importance of early diagnosis and treatment initiation to ameliorate cardiovascular damage.

Stereoselective Synthesis of anti-2,4-Disubstituted Tetrahydrofurans via a Pd-Catalyzed Hayashi-Heck Arylation and Rh-Catalyzed Hydroformylation Sequence.

A catalytic, two-step protocol for the expedient synthesis of anti-2,4-disubstituted tetrahydrofurans is described. In the first step, an enantioselective and regioselective Pd-catalyzed Hayashi-Heck arylation was developed using (R)-hexaMeOBiphep to generate 5-aryl-2,3-dihydrofurans. A subsequent Rh-catalyzed hydroformylation step proceeds at low Rh loading with high regio- and diastereoselectivity for the anti-2,4-disubstituted tetrahydrofuran isomer. Key to the development of the hydroformylation reaction was the utilization of either (R)-Me-i-Pr-INDOLphos or (R,R)-Ph-BPE to control the regioselectivity and provide the kinetic product isomer.

Modeling Tumor Cell Dormancy in an Ex Vivo Liver Metastatic Niche.

Despite decades of research into metastatic disease, our knowledge of the mechanisms governing dormancy are still limited. Unraveling the process will aid in developing effective therapies to either maintain or eliminate these dormant cells and thus prevent them from emerging into overt metastatic disease. To study the behavior of dormant tumor cells-mechanisms that promote, maintain, and disrupt this state-we utilize the Legacy LiverChip®, an all-human ex vivo hepatic microphysiological system. This complex, bioengineered system is able to recreate metastatic disease that is reflective of the human situation and is among only a handful of systems able to mimic spontaneous tumor cell dormancy. The dormant subpopulation reflects the defining traits of cellular dormancy-survival in a foreign microenvironment, chemoresistance, and reversible growth arrest. This microphysiological system has and continues to provide critical insights into the biology of dormant tumor cells. It also serves as an accessible tool to identify new therapeutic strategies targeting dormancy and concurrently evaluate the efficacy of therapeutic agents as well as their metabolism and dose-limiting toxicity.

Effects of high dose aspartame-based sweetener on the gut microbiota and bone strength in young and aged mice.

In a recent study examining the effects of manipulating the gut microbiome on bone, a control group of mice in which the microbiome was altered using a non-caloric, aspartame-based sweetener resulted in whole bone strength being 40% greater than expected from geometry alone, implicating enhanced bone tissue strength. However, the study was not designed to detect changes in bone in this control group and was limited to young male mice. Here we report a replication study examining how changes in the gut microbiome caused by aspartame-based sweetener influence bone. Male and female C57Bl/6 J mice were untreated or treated with a high dose of sweetener (10 g/L) in their drinking water from either 1 to 4 mo of age (young cohort; n = 80) or 1 to 22 mo of age (aged cohort; n = 52). Sweetener did not replicate the modifications to the gut microbiome observed in the initial study and did not result in an increase in bone tissue strength in either sex at either age. Aged male mice dosed with sweetener had larger bones (+17% femur section modulus, p<.001) and greater whole bone strength (+22%, p=.006) but the increased whole bone strength was explained by the associated increase in body mass (+9%, p<.001). No differences in body mass, whole bone strength, or femoral geometry were associated with sweetener dosing in males from the young cohort or females at either age. As we were unable to replicate the gut microbiota observed in the initial experiment, it remains unclear if changes in the gut microbiome can enhance bone tissue strength. Although prior work studying gut microbiome-induced changes in bone with oral antibiotics has been highly repeatable, the current study highlights the variability of nutritional manipulations of the gut microbiota in mice.

Effect of pre-incident antiplatelet therapy on sudden sensorineural hearing loss.

OBJECTIVE: Identify if pre-incident aspirin influences severity and outcome of idiopathic sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospective review. SETTING: Tertiary care center. METHODS: Patients with idiopathic SSNHL were identified and separated into aspirin and non-aspirin groups. Variables, including demographics, comorbid conditions, audiologic outcomes were identified and compared between groups. RESULTS: One hundred forty-eight patients were included that met inclusion criteria. There were 38 patients who were on pre-incident aspirin therapy and 110 patients not on aspirin prior to the onset of SSNHL. Pre- and post-treatment audiologic status was worsened in the aspirin group. Other comorbid conditions, including hyperlipidemia, coronary artery disease (CAD), cerebrovascular accident (CVA), and vertigo symptoms had an effect as well. With multivariate analysis, CAD, CVA, and vertigo symptoms appeared to have an effect more than aspirin. CONCLUSIONS: Patients on aspirin have a worsened pre- and post-treatment audiologic status. This appears to be more due to the underlying CAD or history of CVA rather than aspirin use itself.

Laparoscopic-Assisted Colonic Derotation in Patients With Hirschsprung Disease.

BACKGROUND: Children with Hirschsprung disease (HSCR) proximal to the splenic flexure or those needing a redo pull-through (PT) are at risk for tension and ischemia of the PT which could result in leak, stricture, or loss of ganglionated bowel. Colonic derotation is a technique used to minimize tension and avoid duodenal obstruction. The aim of this study was to describe this technique and outcomes in a series of patients requiring this intervention. METHODS: All patients underwent initial diversion and colonic mapping. The derotation procedure involves mobilization of the remaining colon, counterclockwise rotation via the stoma closure site, placement of the pull through (the right colon) lying on the right of the pelvis, and ligation of the middle colic artery with preservation of the marginal branch running from the ileocolic artery. This maneuver prevents compression of the duodenum by the mesenteric vessels and allows for an isoperistaltic, tension-free anastomosis. Intraoperative indocyanine green fluorescence angiography (ICG-FA) was utilized in many of the cases to map the blood supply of the pull-through colon. We reviewed outcomes for all children with HSCR who underwent colonic derotation from 2014 to 2023. Descriptive statistics were performed. RESULTS: There were 37 children included. Most were male (67.5%) with the original transition zone proximal to the rectosigmoid (81.1%). The median age at PT was 9.3 months [6.1-39.7]. Median operative time was 6.6 h [4.9-7.4] and 19 cases (51.4%) used ICG-FA. Most children had no 30-day postoperative complications (67.6%); in those who did develop complications, readmissions for electrolyte imbalance was most common (50.0%). There were zero cases of anastomotic leak at PT anastomosis. At long-term follow up, median 4.4 years [2.3-7.0], three children (8.1%) developed an anastomotic stricture, all were amenable to anal dilation, and five experienced episodes of enterocolitis (14.7%). Most children had between 1 and 4 stools per day (58.8%). CONCLUSION: Colonic derotation is a useful strategy to ensure well-perfused colonic length, protect the marginal artery blood supply, avoid duodenal compression, and ensure a tension-free anastomosis with minimal complications. TYPE OF STUDY: Original research, retrospective cohort. LEVEL OF EVIDENCE: III.

Endovascular (stent-graft)-assisted open vascular anastomosis.

Endovascular and open surgical approaches are an integral part of treating patients with complex vascular disease and are often considered separately. In some situations, traditional open surgical techniques can be used to facilitate an endovascular approach, as example: iliac conduit use for EVAR/TEVAR, subclavian or axillary conduits for complex endovascular aortic repairs (chimney, B-FEVAR), and bypass to great vessels or visceral artery (celiac, superior mesenteric and renal arteries) debranching. As devices and techniques evolve, the open and endovascular approaches can be utilized in more complimentary fashion. This paper describes the use of endovascular procedures to assist difficult open surgical situations such as iliofemoral bypass, aortic arch debranching involving the left subclavian artery, and distal right iliac artery management during open thoracoabdominal aortic aneurysm (TAAA) repair.

Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation.

The memory CD8+ T cell pool contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. Here, we examined the epigenetic landscape of CD8+ T cells isolated from seven non-lymphoid organs across four distinct infection models, alongside their circulating T cell counterparts. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), we found that tissue-resident memory T (TRM) cells and circulating memory T (TCIRC) cells develop along distinct epigenetic trajectories. We identified organ-specific transcriptional regulators of TRM cell development, including FOSB, FOS, FOSL1, and BACH2, and defined an epigenetic signature common to TRM cells across organs. Finally, we found that although terminal TEX cells share accessible regulatory elements with TRM cells, they are defined by TEX-specific epigenetic features absent from TRM cells. Together, this comprehensive data resource shows that TRM cell development is accompanied by dynamic transcriptome alterations and chromatin accessibility changes that direct tissue-adapted and functionally distinct T cell states.

Plasmacytoid Dendritic Cells Mediate CpG-ODN Induced Increase in Survival in a Mouse Model of Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a devastating disease primarily found in women of reproductive age that leads to cystic destruction of the lungs. Recent work has shown that LAM causes immunosuppression and that checkpoint inhibitors can be used as LAM treatment. Toll-like receptor (TLR) agonists can also re-activate immunity and the TLR9 agonist, CpG-ODN, has been effective in treating lung cancer in animal models. Here we investigate the use of TLR9 agonist CpG-ODN as LAM immunotherapy in combination with checkpoint inhibitor, anti-PD1, standard of care rapamycin and determine the immune mechanisms underlying therapeutic efficacy. We used survival studies, flow cytometry, ELISA, and histology to assess immune response and survival after intranasal treatment with CpG-ODN in combination with rapamycin or anti-PD1 therapy in a mouse model of metastatic LAM. We found that local administration of CpG-ODN enhances survival in a mouse model of LAM. We found that a lower dose led to longer survival likely due to fewer local side effects but increased LAM nodule count and size compared to the higher dose. CpG-ODN treatment also reduced regulatory T cells and increased the number of Th17 helper T cells as well as cytotoxic T cells. These effects appear to be mediated in part by plasmacytoid dendritic cells (pDCs), as depletion of pDCs reduces survival and abrogates Th17 T cell response. Finally, we found that CpG-ODN treatment is effective in early stage and progressive disease and is additive with anti-PD1 therapy and rapamycin. In summary, we have found that TLR9 agonist CpG-ODN can be used as LAM immunotherapy and effectively synergizes with rapamycin and anti-PD1 therapy in LAM.

Superelectrophilic Nonclassical Carbocations.

The chemistry of dicationic and tricationic 2-norbornyl cations has been studied. A series of N-heterocyclic functionalized norborneol substrates were prepared and ionization of these compounds in superacid provided superelectrophilic species. These highly charged 2-norbornyl cations were found to react with arene nucleophiles in high yields and stereoselectivity. Density functional theory computational studies suggest that increasing positive charge on the structures tends to enhance the degree of nonclassical (or 3-center-2-electron) bonding through separation of the cationic charges.

Effect of Preoperative Motor Weakness on Postoperative Clinical Outcomes in Patients Undergoing Cervical Disk Replacement.

STUDY DESIGN: This is a retrospective review. OBJECTIVE: To examine the effect of preoperative motor weakness on clinical outcomes in patients undergoing cervical disk replacement (CDR). SUMMARY OF BACKGROUND DATA: Studies examining the effect of preoperative motor weakness on postoperative clinical outcomes in CDR are limited. METHODS: Patient cohorts were based on documented upper-extremity motor weakness on physical exam versus no motor weakness. Demographics, perioperative characteristics, and preoperative patient-reported outcome measures (PROMs) were compared using univariate inferential statistics. PROMs consisted of Visual Analog Pain Scale-Neck (VAS-N), Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS-PF), VAS-Arm (VAS-A), 12-Item Short Form (SF-12) Physical Component Score (PCS), Oswestry Neck Disability Index (NDI), and SF-12 Mental Component Score (MCS). Postoperative PROMs were collected at the 6-week, 12-week, 6-month, and final follow-up up to 1-yeartime points, and intercohort minimum clinically important difference (MCID) achievement was compared through multivariable linear logistic regression adjusting for significant differences in preoperative characteristics. RESULTS: A total of 118 patients formed cohorts based on documented upper-extremity weakness (n=73) versus no weakness (n=45). The average time to postoperative follow-up was 9.7±7.0 mo. The differences in insurance type between the 2 cohorts were significant (P<0.042). Perioperative diagnosis of foraminal stenosis was significantly more common in the motor weakness cohort (P<0.013). There were no differences in reported PROMs between cohorts. Patients with motor weakness reported significant MCID achievement for PROMIS-PF at 6-/12-weeks (P<0.012, P<0.041 respectively), SF-12 PCS at 6-months (P<0.042), VAS-N at final follow-up (P<0.021), and NDI at final follow-up (P<0.013). CONCLUSIONS: CDR patients with preoperative muscle weakness achieved MCID across several PROMs compared with patients without muscle weakness. Patients with motor weakness reported greater improvement in mental health, pain, and disability as early as 6 weeks and up to 1 year after CDR. This information serves to inform physicians that motor weakness may not indicate a negative overall outcome.

Clinical Outcomes Associated with a Remote Postpartum Hypertension Monitoring Program.

OBJECTIVE: To evaluate differences in health care utilization and guideline adherence for postpartum individuals with hypertensive disorders of pregnancy (HDP) who are engaged in a remote monitoring program, compared with usual care. METHODS: This was a retrospective cohort study of postpartum individuals with HDP who delivered between March 2019 and June 2023 at a single institution. The primary exposure was enrollment in a remote hypertension management program that relies on patient home blood pressure (BP) measurement and centralized nursing team management. Patients enrolled in the program were compared with those receiving usual care. Outcomes included postpartum readmission, office visit within 6 weeks postpartum, BP measurement within 10 days, and initiation of antihypertensive medication. We performed multivariable logistic and conditional regression in a propensity score matched cohort. Propensity scores, generated by modeling likelihood of program participation, were assessed for even distribution by group, ensuring standardized bias of less than 10% after matching. RESULTS: Overall, 12,038 eligible individuals (6,556 participants, 5,482 in the control group) were included. Program participants were more likely to be White, commercially insured, be diagnosed with preeclampsia, and have higher prenatal and inpatient postpartum BPs. Differences in baseline factors were well-balanced after implementation of propensity score. Program enrollment was associated with lower 6-week postpartum readmission rates, demonstrating 1 fewer readmission for every 100 individuals in the program (propensity score-matched adjusted risk difference [aRD] -1.5, 95% CI, -2.6 to -0.46; adjusted risk ratio [aRR] 0.78, 95% CI, 0.65-0.93). For every 100 individuals enrolled in the program, 85 more had a BP recorded within 10 days (propensity score-matched aRD 85.4, 95% CI, 84.3-86.6), and six more had a 6-week postpartum office visit (propensity score-matched aRD 5.7, 95% CI, 3.9-7.6). Program enrollment was also associated with increased initiation of an antihypertensive medication postpartum (propensity score-matched aRR 4.44, 95% CI, 3.88-5.07). CONCLUSION: Participation in a postpartum remote BP monitoring program was associated with fewer postpartum hospital readmissions, higher attendance at postpartum visits, improved guideline adherence, and higher rates of antihypertensive use.

Primary Care Considerations for the Adolescent Wrestler.

PURPOSE OF REVIEW: Adolescent wrestlers undergo intense physical combat. While guidelines are effective in keeping the sport safer, concerns specific to the adolescent wrestler may be missed at primary care visits without knowledge of the unique challenges faced by these athletes. The following review highlights important characteristics of the adolescent wrestler which are of interest to primary care providers. RECENT FINDINGS: Recommendations for concussion management are evolving to gradual return-to-sport after physician clearance rather than total sport removal. Prolonged skin-to-skin contact also places athletes at greater risk of dermatologic infections, which often require removal from competition, treatment, and/or coverage. Finally, adolescent nutritional literature recommends limiting pre-match weight loss to 3-5% body weight due to noted kidney damage that may result from larger deficits. Adolescent wrestlers are more prone to acute injuries than chronic overuse injuries, with most injuries occurring above the trunk. Primary care providers should consider obtaining imaging to rule out severe injuries or referring to specialist providers. Current guidelines for skin infections require frequent pre-match skin checks and mandatory waiting periods when certain infections are identified. However, the primary care provider is well-equipped for more in-depth skin examination, discussion of skin hygiene, and appropriate treatment of skin infections. Athletes attempting to meet lower weight classes may put themselves at risk of acute kidney damage, under-fueling, and eating disorders. Current guidelines attempt to mitigate excessive weight changes in the adolescent wrestler during competition season, but primary care providers should emphasize healthier methods of weight fluctuation and look for indicators of physiological or psychological effects.

Chronic Deltoid Insufficiency in Stage IV Adult Acquired Flatfoot Deformity: Do We Have a Good Answer?

Stage IV adult acquired flatfoot deformity (AAFD) with secondary chronic deltoid ligament insufficiency is a challenging deformity to treat, with minimal consensus in the literature concerning its surgical management. Many surgical treatment options have been described, including joint-sparing techniques, fusions, osteotomies, and even arthroplasties. However, questions remain as to what, if any, treatment is optimal. This contribution reviews studies on surgical treatments for stage IV AAFD with deltoid ligament failure and provides a critical analysis regarding the quality of outcomes reported for those different treatment options. PubMed and Google Scholar databases were searched between June 1, 2022, and August 15, 2022, for studies published between 1990 and 2022 that describe the treatment of stage IV AAFD with deltoid ligament insufficiency. Articles included in the study focused on subjects with stage IV AAFD and associated deltoid ligament insufficiency undergoing surgical correction. Exclusion criteria included stage I, II, and III AAFD, as well as deltoid ligament repair following acute injury/rupture. Nine studies covering five different treatment options for patients with stage IV AAFD and chronic deltoid insufficiency were included, with minimal overlap in outcome measures used to assess the efficacy of the procedure. Triple arthrodesis with deltoid ligament reconstruction resulted in a 62.5% (5/8) success rate with a residual tibiotalar (TT) angulation of 2° (success defined as <3°). Tibiotalar arthrodesis of four patients resulted in an average post-operative tibiotalar angulation of 4.8° with all patients showing progressive destabilization of the hindfoot complex at 12-18 year follow-ups. Deltoid arthroscopic laminoplasty (Brostrom) resulted in an increased American Orthopaedic Foot and Ankle Society (AOFAS) score from 49.7 pre-op to 91.9 post-op. There was no long-term follow-up of these patients. Deltoid ligament reconstruction using autografts of the peroneus longus resulted in a post-operative valgus of 2.1° in one study and <5° in another. Deltoid ligament reconstruction using an anterior tibial tendon autograft resulted in a gain of 126.4 + 40.2% in stiffness compared to an intact ligament. Twinfix suture anchors resulted in a post-operative hindfoot angle averaging 5.3°. Combined deltoid and spring ligament reconstruction resulted in a 5.1° valgus angulation. There is currently no standard of care or clinical consensus regarding surgical treatment for stage IV AAFD with deltoid insufficiency. Several studies imply that mild valgus malalignment around the tibiotalar joint can result in satisfactory outcomes. A few studies even deemed <5° of valgus tilt post-operatively successful. However, it has been described that any imbalance in tibiotalar tilt is a significant risk factor for progressive arthritis and future ligamentous failure. No treatment option was able to correct valgus tilt to an anatomical standard (i.e., to normal anatomy). These varied findings, along with the lack of consensus on post-surgical measures to assess efficacy, are worrisome and emphasize the need for better surgical options. Moreover, there is a critical need for additional research on the long-term outcomes following stage IV AAFD and deltoid insufficiency repair, particularly, as over five million people in the United States and 10% of the geriatric population are affected by AAFD with a risk of progressing to stage IV.

Arterial hyperoxia and mortality in the cardiac intensive care unit.

BACKGROUND: Arterial hyperoxia (hyperoxemia), defined as a high arterial partial pressure of oxygen (PaO2), has been associated with adverse outcomes in critically ill populations, but has not been examined in the cardiac intensive care unit (CICU). We evaluated the association between exposure to hyperoxia on admission with in-hospital mortality in a mixed CICU cohort. METHODS: We included unique Mayo Clinic CICU patients admitted from 2007 to 2018 with admission PaO2 data (defined as the PaO2 value closest to CICU admission) and no hypoxia (PaO2 < 60mmHg). The admission PaO2 was evaluated as a continuous variable and categorized (60-100 mmHg, 101-150 mmHg, 151-200 mmHg, 201-300 mmHg, >300 mmHg). Logistic regression was used to evaluate predictors of in-hospital mortality before and after multivariable adjustment. RESULTS: We included 3,368 patients with a median age of 70.3 years; 70.3% received positive-pressure ventilation. The median PaO2 was 99 mmHg, with a distribution as follows: 60-100 mmHg, 51.9%; 101-150 mmHg, 28.6%; 151-200 mmHg, 10.6%; 201-300 mmHg, 6.4%; >300 mmHg, 2.5%. A J-shaped association between admission PaO2 and in-hospital mortality was observed, with a nadir around 100 mmHg. A higher PaO2 was associated with increased in-hospital mortality (adjusted OR 1.17 per 100 mmHg higher, 95% CI 1.01-1.34, p = 0.03). Patients with PaO2 >300 mmHg had higher in-hospital mortality versus PaO2 60-100 mmHg (adjusted OR 2.37, 95% CI 1.41-3.94, p < 0.001). CONCLUSIONS: Hyperoxia at the time of CICU admission is associated with higher in-hospital mortality, primarily in those with severely elevated PaO2 >300 mmHg.

Acute social defeat during adolescence promotes long-lasting aggression through activation of the medial amygdala.

Traumatic stress, particularly during critical developmental periods such as adolescence, has been strongly linked to an increased propensity and severity of aggression. Existing literature underscores that being a victim of abuse can exacerbate aggressive behaviors, with the amygdala playing a pivotal role in mediating these effects. Historically, animal models have demonstrated that traumatic stressors can increase attack behavior, implicating various amygdala nuclei. Building on this foundation, our previous work has highlighted how traumatic stress invokes long-lasting aggression via an excitatory pathway within the posterior ventral medial amygdala (MeApv). In the current study, we sought to further delineate this mechanism by examining the effects of acute social defeat during adolescence on aggressive behaviors and neural activation in mice. Using a common social defeat paradigm, we first established that acute social defeat during late adolescence indeed promotes long-lasting aggression, measured as attack behavior 7 days after the defeat session. Immunolabeling with c-Fos demonstrated that acute social defeat activates the MeApv and ventrolateral aspect of the ventromedial hypothalamus (VmHvl), consistent with our previous studies that used foot shock as an acute stressor. Finally, chemogenetically inhibiting excitatory MeApv neurons during social defeat significantly mitigated the aggression increase without affecting non-aggressive social behavior. These results strongly suggest that the MeApv plays a critical role in the onset of aggression following traumatic social experience, and offer the MeA as a potential target for therapeutic interventions.

Worse Preoperative 12-Item Veterans Rand Physical Component Scores Prognosticate Inferior Outcomes Following Outpatient Lumbar Decompression.

STUDY DESIGN: Retrospective Review. OBJECTIVE: Evaluate the influence of the 12-Item veterans Rand (VR-12) physical component score (PCS) on patient-reported outcome measures (PROMs) in an outpatient lumbar decompression (LD) cohort. SUMMARY OF BACKGROUND DATA: The influence of baseline VR-12 PCS on postoperative clinical outcomes has not been evaluated in patients undergoing outpatient LD. METHODS: Patients undergoing primary, elective, 1/2-level outpatient LD with baseline VR-12 PCS scores were retrospectively identified from a prospectively maintained single-surgeon database. Cohorts were preoperative VR-12 PCS<30 and VR-12 PCS≥30. Patient/perioperative characteristics and preoperative/postoperative 6-week/final follow-up (FF) PROMs were collected. Physical health PROMs included the VR-12 PCS, 12-Item Short Form (SF-12) PCS, patient-reported outcome measure information system-physical function (PROMIS-PF), visual analog scale (VAS)-back/leg, and Oswestry disability index (ODI). Mental health PROMs included the VR-12/SF-12 mental component score (MCS) and the patient-health questionnaire-9 (PHQ-9). Average FF was 13.8±8.9 months postoperatively. PROM improvements at 6 weeks/FF and minimal clinically important difference (MCID) achievement rates were determined. χ2 analysis and the Student's t tests compared demographics, perioperative data, and preoperative PROMs. Multivariate linear/logistic regression compared postoperative PROMs, PROM improvements, and MCID achievement rates. RESULTS: Six weeks postoperatively, VR-12 PCS<30 reported worse baseline PROMs (P≤0.042, all) and worse scores except VR-12/SF-12 MCS (P≤0.043, all). Compared with VR-12 PCS≥30, VR-12 PCS<30 had worse FF VR-12 PCS, SF-12 PCS/MCS, PROMIS-PF, PHQ-9, and VAS-Back (P≤0.033, all). VR-12 PCS<30 experienced greater 6-week improvements in VR-12/SF-12 PCS, PHQ-9, VAS-Back, and ODI (P≤0.039, all). VR-12 PCS<30 had greater FF improvements in VR-12/SF-12 PCS, PHQ-9, and ODI (P≤0.001, all) and greater overall MCID achievement in VR-12 PCS/MCS, SF-12 PCS, PHQ-9, and ODI (P≤0.033, all). CONCLUSIONS: VR-12 PCS<30 patients-reported worse baseline/postoperative mental/physical health scores. However, they reported greater improvements in physical function, depressive burden, back pain, and disability by 6 weeks and FF and experienced greater MCID achievement for physical functioning, mental health, and disability scores.

Impact of Early Depressive Burden on Patient-Reported Outcomes Following Minimally Invasive Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate mental health influence on minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) patients. SUMMARY OF BACKGROUND DATA: Poor mental health has been postulated to indicate inferior patient perceptions of surgical outcomes in spine literature. Few studies have assessed mental health as a dynamic metric throughout the perioperative period. METHODS: A single-surgeon database was retrospectively searched for patients who underwent primary, elective MIS-TLIF for degenerative or isthmic spondylolisthesis. Summative depressive burden (SDB) was defined by the sum of preoperative and 6-week postoperative 9-item Patient Health Questionnaire (PHQ-9), with Lesser Burden (LB, SDB<10) and Greater Burden (GB, SDB≥10) cohorts. Patient-reported outcomes measures (PROMs) were compared preoperatively, at 6 weeks, and at final postoperative follow-up (11.4±10.9 mo), using Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), Oswestry disability index (ODI), visual analog scale-back (VAS-B), VAS-leg (VAS-L), and PHQ-9. Improvements at 6-week (∆PROM-6W), final follow-up (∆PROM-FF), and minimum clinically important difference (MCID) achievement were compared. RESULTS: The GB cohort consisted of 44 of 105 patients. Demographic variations included older age, higher Charlson comorbidity index, increased hypertension prevalence, and private insurance in the LB cohort (P≤0.018). The LB cohort demonstrated better baseline and 6-week PROMIS-PF/ODI/VAS-L (P≤0.032) and better final PROMIS-PF/ODI/VAS-L/PHQ-9 (P≤0.031). Both cohorts improved in all PROMs at 6 weeks and final follow-up (P≤0.029), except for PROMIS-PF at 6 weeks in the GB cohort. ∆PROM-6W, ∆PROM-FF, and MCID achievement rate for PHQ-9 were greater in the GB cohort (P≤0.001). CONCLUSION: On average, patients undergoing MIS-TLIF for degenerative or isthmic spondylolisthesis improved in all PROMs by final follow-up. Patients with GB suffered inferior perceptions of physical function, disability, and leg pain. MCID rates in mental health were higher for GB cohort. Surgeons are encouraged to adopt a compassionate understanding of depressive burden and educate the patient on possible consequential postoperative outcomes.