Worsen Outcomes Research Articles

Abstract TP391: CGRP Monoclonal Antibody Does Not Exacerbate Stroke Outcomes in Mice

Background: Calcitonin gene-related peptide (CGRP) is a potent vasodilator that plays a role in migraine. Monoclonal antibodies targeting CGRP, such as fremanezumab, is now widely used for migraine prevention. However, inhibition of CGRP system may also lead to vasoconstriction, raising concerns about whether the long-term treatment with these antibodies in migraine patients might increase the risk of stroke or worsen outcomes if a stroke occurs while taking these medications. Here, we aimed to investigate whether fremanezumab exacerbates stroke outcomes in a mouse model of ischemic stroke. Methods: Two middle cerebral artery occlusion (MCAO) models were used: a 12-minute occlusion simulating a transient ischemic attack (TIA) and a 60-minute occlusion representing a conventional stroke model. Fremanezumab was administered intraperitoneally at either 2 days or 7 days before MCAO induction in both models; one cohort received treatment 28 and 7 days before MCAO. On day 2 after reperfusion, brain tissues were harvested for TTC staining to evaluate infarct volume. Neurological function was assessed using a neuro score and corner test. Additionally, an angiogram using black ink was performed to visualize cerebral vasculature, and vessel diameters were measured to determine the impact of fremanezumab on vascular dimensions. Results: Angiographic arterial diameters in the fremanezumab arm did not differ from the saline arm, suggesting that fremanezumab does not cause vasoconstriction. In the TIA model, the fremanezumab group exhibited a trend towards increased infarct incidence and volume and hemorrhagic transformation, although these did not reach statistical significance. Additionally, there were no substantial changes in neurological scores and the corner test. In the 60-minute MCAO model, no significant changes or trends were observed in infarct volume or other outcomes between the two treatment arms. Outcomes were similar when fremanezumab was administered 2 or 7 days before MCAO. Conclusion: Despite previous concerns that long-term use of fremanezumab might exacerbate stroke risk by promoting vasoconstriction, our findings do not support this hypothesis and suggest that fremanezumab does not worsen stroke outcomes in these models. These findings have important implications for the management of stroke risk in patients using fremanezumab for migraine prevention, suggesting that it may be used with confidence regarding its impact on stroke risk.

Naegleria fowleri Infections: Bridging Clinical Observations and Epidemiological Insights.

Naegleria fowleri is the main etiologic agent implicated in primary amoebic meningoencephalitis (PAM). It is also known as the brain-eating amoeba because of the severe brain inflammation following infection, with a survival rate of about 5%. This review aims to identify Naegleria fowleri infections and evaluate patients' progression. This literature review emphasizes the importance of rapid diagnosis and treatment of infected patients because only prompt initiation of appropriate therapy can lead to medical success. Compared to other articles of this kind, this one analyzes a large number of reported cases and all the factors that affected patients' evolution. Two independent reviewers used "Naegleria fowleri" and "case report" as keywords in the Clarivate Analytics-Web of Science literature review, obtaining 163 results. The first evaluation step was article title analysis. The two reviewers determined if the title was relevant to the topic. The first stage removed 34 articles, leaving 129 for the second stage. Full-text articles were evaluated after reading the abstract, and 77 were eliminated. This literature review concluded with 52 articles. This review included 52 case report articles, 17 from the USA, eight from India, seven from China, four from Pakistan, two from the UK, and one each from Thailand, Korea, Japan, Italy, Iran, Norway, Turkey, Costa Rica, Zambia, Australia, Taiwan, and Venezuela, and Mexico. This study included 98 patients, with 17 women (17.4%) and 81 men (82.6%). The cases presented in this study show that waiting to start treatment until a diagnosis is confirmed can lead to rapid worsening and bad outcomes, especially since there is currently no drug that works very well as a treatment and the death rate is around 98%. The lack of case presentation standardization may lead to incomplete case information in the review since the cases did not follow a writing protocol. The small number of global cases may also lead to misleading generalizations, especially about these patients' treatment. Due to the small number of cases, there is no uniform sample of patients, making it difficult to determine the exact cause of infection.

Prognostic value of atherogenic index of plasma in pulmonary hypertension.

The atherogenic index of plasma (AIP) is a brand-new lipid parameter that has been used to assess various cardiovascular events. This study aimed to investigate the prognostic value of AIP in patients with pulmonary hypertension (PH). This retrospective study was conducted at Shanghai Jiao Tong University School of Medicine affiliated Renji Hospital, and included data from 125 PH patients treated during 2014-2018. The endpoint events of this study were clinical worsening outcomes. PH patients include those from group 1 and group 4. AIP was determined as the logarithm of the blood triglycerides ratio to high-density lipoprotein cholesterol. The 1-year, 3-year, and 5-year incidence rates of clinical worsening outcomes in PH patients in this study were 20.0, 44.8, and 54.4%, respectively. The median age of the PH patients was 38.00 years, with females accounting for 90.4%. After controlling for multivariable factors, the results of Cox regression analysis indicated that AIP was an independent predictor of adverse outcomes with a hazard ratio and 95% confident interval (CI) of 2.426 (1.021-5.763). The positive linear relationship of AIP was evaluated using restricted cubic spline analysis. Kaplan-Meier curves showed a significantly higher events rate in patients with AIP ≥ 0.144 compared to those with AIP < 0.144 (p = 0.002). Four potential prognostic variables, including AIP, were identified by LASSO regression to construct a nomogram. Compared to the model minus AIP, the AUC of the nomogram displayed a non-significant improvement (0.749 vs. 0.788, p = 0.298). In contrast, the results of net reclassification improvement (0.306, 95% CI: 0.039-0.459, p < 0.001) and integrated discrimination improvement (0.049, 95% CI: 0.006-0.097, p = 0.020) demonstrated significant enhancements in the predictive ability of the model when AIP was added to the clinical model. AIP is an independent predictor of long-term clinical worsening in PH patients, and its inclusion in prognostic models could improve risk stratification and management.

Neutrophil Extracellular Traps Induce Brain Edema Around Intracerebral Hematoma via ERK-Mediated Regulation of MMP9 and AQP4.

Perihematomal edema (PHE) significantly aggravates secondary brain injury in patients with intracerebral hemorrhage (ICH), yet its detailed mechanisms remain elusive. Neutrophil extracellular traps (NETs) are known to exacerbate neurological deficits and worsen outcomes after stroke. This study explores the potential role of NETs in the pathogenesis of brain edema following ICH. The rat ICH model was created, immunofluorescence and Western blot were used to examine neutrophil accumulation, NET markers citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), tight junction proteins (ZO-1 and Occludin), Aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), and ERK phosphorylation (p-ERK) in brain tissues surrounding the hematoma. TUNEL staining and behavioral tests were employed to evaluate neuronal apoptosis and neurological dysfunction, while blood-brain barrier (BBB) permeability and brain edema were also measured by Evans blue and brain water content. Furthermore, the molecular mechanisms related to NETs-induced PHE were investigated using NETs, ERK, MMP-9 and AQP4 regulators, respectively. Ly6G+ neutrophils surrounding the hematoma developed NETs within 3days post-ICH. NETs decreased tight junction proteins, destroyed BBB integrity, promoted brain edema, increased neuronal apoptosis, and exacerbated neurological deficits. Conversely, inhibition of NETs mitigated PHE, reduced neuronal apoptosis, and improved neurological functions. Mechanistically, NET-induced PHE was originated from impairment of BBB tight junction via ERK/MMP9 pathway, coupled with ERK-mediated AQP4 downregulation in perihematomal regions. These findings elucidated the effects of NETs on PHE, which offered promising insights for targeting NETs to relieve brain edema and secondary brain injury post-ICH.

Endothelial Cell Senescence Effect on the Blood-Brain Barrier in Stroke and Cognitive Impairment.

Age is an important risk factor of stroke, cognitive decline, and dementia. Senescent endothelial cells (ECs) accumulate with advancing age through exposure to cellular stress, such as that exerted by hypertension and diabetes. These senescent ECs have altered characteristics, such as altered tight junction proteins, use of a more indiscriminate transcellular transport system, increased inflammation, and increased immune cell interactions. ECs are the main component of the blood-brain barrier (BBB), separating the brain from systemic circulation. As senescent ECs accumulate in the BBB, their altered functioning results in the disruption of the barrier. They have inadequate barrier-forming properties, disrupted extracellular matrix, and increased transcytosis, resulting in an overly permeable barrier. This disruption of the BBB can have important effects in stroke and cognitive impairment, as presented in this review. Besides increasing the permeability of the BBB, senescent ECs can also impair angiogenesis and vascular remodeling, which in ischemic stroke may increase risk of hemorrhagic transformation and worsen outcomes. Senescent ECs may also contribute to microvascular dysfunction, with disruption of cerebral perfusion and autoregulation. These may contribute to vascular cognitive impairment along with increased permeability. With an aging population, there is growing interest in targeting senescence. Several ongoing trials have been evaluating whether senolytics can slow aging, improve vascular health, and reduce the risk of stroke and cognitive decline.

Racial Bias in Clinical and Population Health Algorithms: A Critical Review of Current Debates.

Among health care researchers, there is increasing debate over how best to assess and ensure the fairness of algorithms used for clinical decision support and population health, particularly concerning potential racial bias. Here we first distill concerns over the fairness of health care algorithms into four broad categories: (a) the explicit inclusion (or, conversely, the exclusion) of race and ethnicity in algorithms, (b) unequal algorithm decision rates across groups, (c) unequal error rates across groups, and (d) potential bias in the target variable used in prediction. With this taxonomy, we critically examine seven prominent and controversial health care algorithms. We show that popular approaches that aim to improve the fairness of health care algorithms can in fact worsen outcomes for individuals across all racial and ethnic groups. We conclude by offering an alternative, consequentialist framework for algorithm design that mitigates these harms by instead foregrounding outcomes and clarifying trade-offs in the pursuit of equitable decision-making.

Gut microbiota-derived 3-indoleacetic acid confers a protection against sepsis-associated encephalopathy through microglial aryl hydrocarbon receptors

The gut microbiota significantly contributes to the pathogenesis of central nervous system disorders. Among the bioactive molecules produced by the gut microbiota, 3-indoleacetic acid (IAA) has been shown to attenuate oxidative stress and inflammatory responses. This experiment aimed to determine the impacts of IAA on sepsis-associated encephalopathy (SAE) and the underlying mechanisms. A total of 34 septic patients and 24healthy controls were included in the analysis of the clinical correlation between fecal IAA and septic encephalopathy. Fecal microbiota transplantation was used to verify the role of the gut microbiota and its metabolites in SAE. Male C57BL/6 mice aged six to eight weeks, pre-treated with IAA via oral gavage, were subjected to the cecal ligation and puncture (CLP) procedures. This treatment was administered either in combination with an aryl hydrocarbon receptor (AhR) antagonist, CH223191, or a CSF1R inhibitor, PLX3397, to eliminate microglia. Both immunofluorescence staining and enzyme-linked immunosorbent assays were used to evaluate microglia activation and inflammatory cytokine secretion. Behavioral assessments were conducted to quantify neurological deficits. A decreased fecal level of IAA was observed in the patients with sepsis-associated delirium (SAD), a manifestation of SAE. A reduced IAA level was significantly associated with worsen clinical outcomes. Fecal microbiota transplantation from the SAD patients induced an SAE-like phenotype in mice, but supplementing exogenous IAA improved the SAE-like phenotype, mediated by microglia. IAA effectively binded with the aryl hydrocarbon receptor (AhR). Furthermore, IAA increased the nuclear activity of AhR in the lipopolysaccharide (LPS)-treated microglial cells, leading to reduced secretion of inflammatory cytokines. The AhR inhibitor CH223191 counteracted the protective effect of IAA against SAE in mice. Gut microbiota-derived IAA confers a protection against SAE by activating AhR in microglia, improving neuronal and cognitive impairments. Thus, IAA holds the promise as a potential therapeutic agent for managing SAE.

Advances in the restoration of CFTR in children and pwCF with "mild disease".

Cystic fibrosis (CF) is a progressive genetic disorder, with lung disease being the main cause of morbidity and mortality. While advances in treatment have extended life expectancy, lung function still declines over time. Early inflammation and chronic infection, particularly with pseudomonas, worsen outcomes. Current management focuses on nutrition, airway clearance and infection control, but CFTR modulators directly target the genetic defect, improving lung function and reducing pulmonary exacerbations. Early use of CFTR modulators can alter the course of the disease.

Bypassing Emergency Service: Decoding the Drivers of Self-Referral During Acute Myocardial Infarction on Rural Areas in Sachsen-Anhalt, Germany.

Background/Objectives: the timely and effective management of acute myocardial infarction (AMI) is crucial to improve patient outcomes. 'Self-Referral' is defined as instances either where patients arrive at the hospital by their own means or are transported by someone else, rather than through professional emergency medical services. This approach can lead to treatment delays and potentially worsen outcomes. This study aims to identify the factors associated with the choice of self-referral among patients with AMI in Saxony-Anhalt, Germany. Methods: We used the data from the Regional Myocardial Infarction Registry of Saxony-Anhalt (RHESA), which included 4044 patients with confirmed acute myocardial infarction (AMI), including 48.7% from urban areas (city of Halle) and 51.3% from rural areas (Altmark). The gender distribution was 65% male and 35% female, covering an age range from 25 to over 80 years. Multivariable logistic regression identified factors associated with self-referral and its impact on reaching a hospital with percutaneous coronary intervention (PCI) capability. Results: Rural residents were more likely to self-refer compared to those in urban settings (adjusted odds ratio 2.43 [95% CI: 2.00-2.94]). Odds of self-referral decreased with age, while metabolic factors, including hypertension, high body mass index (BMI), and diabetes, as well as sex were not associated with self-referral. Self-referral did not increase the odds of arriving in a hospital without PCI capability. (Adjusted odds ratio 1.12 [95% CI: 0.85-1.47]). Furthermore, in cases of self-referral, women did not have a disadvantage in reaching a hospital with PCI (0.91; 0.59-1.41) compared to men. However, in medically attended transports, women were at a disadvantage (odds ratio: 1.33; 95% CI: 1.06-1.67). Conclusions: These findings highlight the need for public education on self-referral and for medical personnel training to prevent gender bias in AMI transport to PCI-capable hospitals.

Prognostic value of left atrial strain for outcome of catheter ablation in patients with atrial fibrillation and moderately enlarged left atrium

Abstract Background Atrial fibrillation catheter ablation (AFCA) is an effective rhythm control method for patients with AF, but AF recurrence is higher in patients with a large left atrium (LA). We explored whether pre-procedural LA strain has incremental prognostic value for the long-term rhythm outcomes of AFCA in patients with AF and moderately enlarged LA size (45≤LA diameter&amp;lt;50mm). Methods We included 2,269 patients who underwent de novo AF catheter ablation (men 72.2%, 59.1[±10.7] years, paroxysmal AF 64.0%). We divided grouped into 5 mm increments and determined the appropriate cut-off of LA diameter (45mm) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. Patients with moderately enlarged LA size (45≤LA diameter&amp;lt;50mm, n=413) with borderline rhythm outcomes were used for analysis. Results In the cohort of 413 patients who underwent AFCA with moderately enlarged LA size, AF was recurred in 208 patients (43.7%) after AFCA. We determined the appropriate cut-off of LA strain (12.5) predicting the difference in long-term rhythm outcome by the log-likelihood values of multivariate Cox proportional hazard models. During 24 months [10-50] follow-up, patients with low LA strain (&amp;lt;12.5) were showed worsen rhythm outcome than high LA strain (Log-rank p&amp;lt;0.001). Patients with AF recurrence after AFCA were independently associated with low LA strain (HR 1.539 [1.130-2.094], p=0.006), and paroxysmal AF (OR 0.651 [0.469-0.905], p=0.011). Furthermore, the likelihood ratio test demonstrated a significant influence of adding LA strain by TTE (χ2 = 13.90 [P &amp;lt; 0.001]). Conclusions LA strain using baseline echocardiography has a predictive power for AF recurrence after AFCA in patients with moderately enlarged LA size (45≤LA diameter&amp;lt;50mm).

Ethanol drinking sex-dependently alters cortical IL-1β synaptic signaling and cognitive behavior in mice.

Individuals with alcohol use disorder (AUD) struggle with inhibitory control, decision making, and emotional processing. These cognitive symptoms reduce treatment adherence, worsen clinical outcomes, and promote relapse. Neuroimmune activation is a key factor in the pathophysiology of AUD, and targeting this modulatory system is less likely to produce unwanted side effects compared to directly targeting neurotransmitter dysfunction. Notably, the cytokine interleukin-1β (IL-1β) has been broadly associated with the cognitive symptoms of AUD, though the underlying mechanisms are not well understood. Here we investigated how chronic intermittent 24-hour access two bottle choice ethanol drinking affects medial prefrontal cortex (mPFC)-related cognitive function and IL-1 synaptic signaling in male and female C57BL/6J mice. In both sexes, ethanol drinking decreased reference memory and increased mPFC IL-1 receptor 1 (IL-1R1) mRNA levels. In neurons, IL-1β can activate either pro-inflammatory or neuroprotective intracellular pathways depending on the isoform of the accessory protein (IL-1RAcP) recruited to the IL-1R1 complex. Moreover, ethanol drinking sex-dependently shifted mPFC IL-1RAcP isoform gene expression and IL-1β regulation of mPFC GABA synapses, both of which may contribute to female mPFC resiliency and male mPFC susceptibility. This type of signaling bias has become a recent focus of rational drug development. Therefore, in addition to increasing our understanding of how IL-1β sex-dependently contributes to mPFC dysfunction in AUD, our current findings also support the development of a new class of pharmacotherapeutics based on biased IL-1 signaling.

Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study

BackgroundPreventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2–5 years...

Outcomes of Pilon Fractures

Category: Trauma; Ankle Introduction/Purpose: Pilon fractures are debilitating injuries with consequences affecting patients long-term and require unplanned surgical interventions. Post-operative complications such as infection, non-union, and post traumatic osteoarthritis require unplanned surgical interventions and further worsen outcomes. The primary aim of this study was to determine survivorship of the native ankle joint through evaluation of subsequent procedures and complications. Methods: A retrospective chart review of pilon fractures was performed within a large healthcare system, including a level one trauma center, from 2010 to 2022. Patients with less than 6 months of follow-up were excluded. The primary outcome, survivorship of the native ankle joint, was determined by collecting ankle fusion, arthroplasty, and amputation data. Demographics, injury characteristics, and comorbidities (diabetes mellitus (DM), vascular disease, smoking status) were collected. Results: Our cohort included 386 patients with an average age of 48.5 years, 51.6% were male. 11.4% had DM and 45.1% were smokers. 61.4% had a high energy mechanism and 23.6% were open fractures. Patients had an average of 2.8 operations, including irrigation and debridement, ORIF, bone graft, free flap, hardware removal, and definitive management with arthrodesis, arthroplasty, and amputation. Nonunion, high energy, open fracture, and infection were all associated with unplanned procedures (p&lt; 0.01). 31 patients lost their native ankle, with 11 ankle fusions, 6 total ankle arthroplasty, and 14 amputations. Infection was associated with ankle fusion and amputation (p&lt; 0.01). Those with infection were 15.6x more likely to undergo fusion. Open fractures were associated with amputation (p&lt; 0.01). Diabetes and vascular disease were associated with amputation (p&lt; 0.05). Conclusion: This study demonstrates the burden pilon fractures place on patients, with an average of 2.8 operations per patient. With modern surgical technique, joint survivorship is likely for most patients at 92%. Notably, the presence of diabetes, vascular disease, open fracture, and infection were all significantly associated with loss of the native joint. Injury characteristics, such as high energy and open fractures, significantly affect the need for unplanned procedures following these devastating injuries.

Impact of antibiotic changes on hospital stay and treatment duration in community-acquired pneumonia.

The misuse and overtreatment of antibiotics in hospitalized patients with community-acquired pneumonia (CAP) can cause multi-drug resistance and worsen clinical outcomes. We aimed to analyze the trends and appropriateness of antibiotic changes in hospitalized patients with CAP and their impact on clinical outcomes. This retrospective study enrolled patients with CAP, aged > 18 years, admitted from January 2017 to December 2021 at Seoul National University Bundang Hospital, South Korea. We examined the pathogens identified, antibiotics prescribed, and the appropriateness of antibiotic changes as reviewed by infectious disease specialists. Antibiotic appropriateness was assessed based on adherence to the 2019 ATS/IDSA guidelines and the 2018 Korean national guidelines for CAP, targeting appropriate pathogens, proper route, dosage, and duration of therapy. Outcomes measured included time to clinical stability (TCS), length of hospital stay, duration of antibiotic treatment, and in-hospital mortality. The study included 436 patients with a mean age of 72.11 years, of whom 35.1% were male. The average duration of antibiotic treatment was 13.5 days. More than 55% of patients experienced at least one antibiotic change, and 21.7% had consecutive changes. Throughout their hospital stay, 273 patients (62.6%) received appropriate antibiotic treatment, while 163 patients (37.4%) received at least one inappropriate antibiotic prescription. Those who received at least one inappropriate prescription experienced longer antibiotic treatment durations and extended hospital stays, despite having similar TCS. In conclusion, inappropriate antibiotic prescribing in hospitalized patients with CAP is associated with prolonged antibiotic treatment and increased length of stay. Emphasizing the appropriate initial antibiotic selection may help mitigate these negative effects.

Cardiogenic shock in general intensive care unit: a nationwide prospective analysis of epidemiology and outcome.

Cardiogenic shock (CS) is a life-threatening disease burdened by a mortality up to 50%. The epidemiology has changed with non-ischaemic aetiologies being predominant, although data were mainly derived from patients admitted to dedicated acute cardiac care. We report the epidemiology and outcome of patients with CS admitted to general intensive care unit (ICU). Prospective multicentric epidemiological study including 314 general ICU adhering to the GiViTI nationwide registry from 2011 to 2018, excluding cardiac arrest. The primary endpoint of the study was mortality. The association between clinical factors and mortality was evaluated using a logistic regression model. The odds ratios (ORs) of the covariates quantify their association with mortality during hospitalization. A total of 11 052 patients admitted to general ICU {incidence 2.17%; median age 72 [interquartile range (66-81)], 38.7% were women} with CS were included. Forty-seven per cent of patients had more than three organ insufficiency at the time of admission. The most common CS aetiologies were left heart failure (LHF, 5247-47.5%); acute myocardial infarction (3612-32.6%); right heart failure (RHF, 515-4.6%); and biventricular failure (532-4.8%). A total of 85.5% were mechanically ventilated during the ICU hospitalization. The overall ICU mortality was 44.8%, increasing to 53.4% during the hospitalization in the index hospital and to 54.3% at the latest hospital. Right heart failure-cardiogenic shock patients exhibited the highest mortality risk [OR: 1.19, 95% confidence interval (CI) (0.94-1.50); P < 0.001], followed by biventricular CS [OR 1.04, 95% CI (0.82-1.32)]. Respiratory failure [OR 1.13 (95% CI 1.08-1.19)], coagulation disorder [1.17 (95% CI 1.1-1.24)], renal dysfunction [OR 1.55 (95% CI 1.50-1.61)], and neurological alteration [OR 1.45 (95% CI 1.39-1.50)] were associated with worsen outcome along with severe hypotension [systolic blood pressure < 70 mmHg-OR 2.35, 95% CI (2.06-2.67)], increasing age [OR 2.21 95% CI (2.01-2.42)], and longer ICU stay prior to admission (two-fold increase for each 4.7 days). In the general ICU, the aetiology of CS, excluding cardiac arrest, remains characterized mostly by LHF with RHF-CS burdened by higher mortality. Multiorgan failure at admission and longer hospital stay before ICU admission predispose to worsen outcome.

Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer's disease-related genes in mice

Hypoxic-ischemic encephalopathy (HIE) in neonates causes mortality and neurologic morbidity, including poor cognition with a complex neuropathology. Injury to the cholinergic basal forebrain and its rich innervation of cerebral cortex may also drive cognitive pathology. It is uncertain whether genes associated with adult cognition-related neurodegeneration worsen outcomes after neonatal HIE. We hypothesized that neocortical damage caused by neonatal HI in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer's disease. We subjected non-transgenic (nTg) C57Bl6 mice and mice transgenically (Tg) expressing human mutant amyloid precursor protein (APP-Swedish variant) and mutant presenilin (PS1-ΔE9) to the Rice-Vannucci HI model on postnatal day 10 (P10). nTg and Tg mice with sham procedure were controls. Visual discrimination (VD) was tested for cognition. Cortical and hippocampal cholinergic axonal and IN pathology and Aβ plaques, identified by immunohistochemistry for choline acetyltransferase (ChAT) and 6E10 antibody respectively, were counted at P210. Simple ChAT+ axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings in APP/PS1 Tg mice. In contrast, complex ChAT+ neuritic clusters (NC) occurred only in Tg mice; HI increased that burden. The abundance of ChAT+ clusters in specific regions correlated with decreased VD. The frequency of attritional ChAT+ INs in the entorhinal cortex (EC) was increased in Tg shams relative to their nTg counterparts, but HI obviated this difference. Cholinergic IN pathology in EC correlated with NC number. The Aβ deposition in APP/PS1 Tg mice was not exacerbated by HI, nor did it correlate with other metrics. Adult APP/PS1 Tg mice have significant cortical cholinergic axon and EC ChAT+ IN pathologies; some pathology was exacerbated by neonatal HI and correlated with VD. Mechanisms of neonatal HI induced cognitive deficits and cortical neuropathology may be modulated by genetic risk, perhaps accounting for some of the variability in outcomes.

Comparing pharmacotherapy and transcranial magnetic stimulation for the treatment of anxiety and depression after aortic dissection surgery.

Aortic coarctation is a potentially fatal condition that is primarily treated surgically. Despite successful procedures, patients frequently experience postoperative anxiety and depression, which can hinder recovery and worsen outcomes. Pharmacological interventions, such as 5-hydroxytryptamine (5-HT) and norepinephrine reuptake inhibitors, are commonly prescribed; however, their efficacy alone or in combination with non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation (TMS), remains unclear. To assess the effect of medications and TMS on post-aortic surgery anxiety and depression. We analyzed the outcomes of 151 patients with anxiety and depression who were hospitalized for aortic dissection between January 2020 and September 2022. Using the random number table method, 75 and 76 patients were allocated to the normal control and study groups, respectively. All the patients were treated using routine procedures. The control group was administered anti-anxiety and anti-depression drugs, whereas the study group was treated with TMS in addition to these medications. The patients in both groups showed improvement after two courses of treatment. The Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) were used to assess anxiety and depression, respectively. The serum levels of brain-derived neurotrophic factor (BDNF) and 5-HT were determined using enzyme-linked immunosorbent assay. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. The HAMD and HAMA scores reduced in 2 groups, with the study group achieving a lower level than control (P < 0.05). In the control group, 43 patients recovered, 17 showed improvement, and 15 were deemed invalid. In the study group, 52 recovered, 20 improved, and four were invalid. The efficacy rate in study group was 94.74% compared to 80.00% in control (P < 0.05). The BDNF and 5-HT levels increased in both groups, with higher levels observed in the experimental group (P < 0.05). Moreover, the PSQI scores decreased in 2 groups, but were lower in the intervention group than control (P < 0.05). The scores of the RBANS items increased, with the study group scoring higher than control (P < 0.05). Combining anti-anxiety and anti-depressive drugs with repetitive TMS after aortic surgery may enhance mood and treatment outcomes, offering a promising clinical approach.

Comparison of stroke process measures and clinical outcomes between English and Non-English preferring patients

In the United States, limited English proficiency may reduce the quality of care and worsen outcomes after stroke. The aim was to compare stroke process measures and clinical outcomes between English preferring and non-English preferring stroke patients. This single-center retrospective cohort study evaluated patients from one United States hospital with acute ischemic stroke between July 2013 and June 2022. The primary outcomes were defect-free care, a composite of 7 stroke process measures, and independent ambulation at hospital discharge. Multivariate logistic regression models quantified the association between language preference and outcomes. Secondary outcomes included individual components of defect-free care, discharge modified Rankin scale, and discharge disposition. There were 4,030 patients with acute ischemic stroke identified, of which 2,965 were matched with language data from the electronic medical record. There were 373 non-English preferring patients, among which 76.9% preferred Spanish and 23.1% were non-English, non-Spanish preferring. In the multivariable model, there was no significant association between non-English preference and defect-free care (OR=0.64, 95% CI=0.26-1.59) or independent ambulation at discharge (OR=0.89, 95% CI=0.67-1.17). When compared to Spanish preferring patients, non-English, non-Spanish preferring patients had more severe strokes (P<0.001) but there was no difference in defect-free care or independent ambulation after adjustment. Our results suggest that process and clinical outcomes are similar regardless of language preference; although, our data are limited by small numbers of non-English, non-Spanish preferring patients. Additional research is needed among this population.

Analysis of How Obesity Affects the Severity of Covid-19 Second Wave on Hospitalized Patients at RSUD Dr. Saiful Anwar Malang

Background : Based on WHO data, Covid-19 has officially been declared a pandemic because its spread has reached more than 100 infected countries. Several risk factors can affect the severity of Covid-19 patients, one of which is comorbid obesity. The Covid-19 pandemic occurred when the prevalence of overweight/obesity was increasing in almost every country in the world. Chronic inflammation associated with obesity, impaired immune function, and increased expression of ACE 2 contribute to disease severity and worsen clinical outcomes in obese patients with Covid-19 infection. Aim : This study aims to analyse the effect of obesity on the severity of the second wave of Covid-19 patients who were hospitalized at RSUD dr. Saiful Anwar Malang. Methods : This research is an analytic observational study with cross sectional approach. The sample consisted of 46 Covid-19 patients with obesity who were hospitalized at RSUD dr. Saiful Anwar Malng. The data acquired will be analysed using Mann Whitney non-parametric analysis test. Results : In the obese and non-pbese groups, the p-value was 0,042 and the odds ratio was 1,23. In the distribution of age and sex groups, each group obtained a p-value of 0,363 and 0,592. Conclusion : There is a significant difference in obesity among patients, with a 1,23-fold increased risk of experiencing severity compared to those who are not obese. Meanwhile, for the distribution based on age and sex, there was no significant difference, but it tended to have a more critical degree of severity towards men and older age.

Modeling longitudinal relationships between sleep disturbances and depressed mood in postpartum: A cross-lagged panel design

This short communication explores the interrelationships between depressed mood and sleep disturbances in one-year postpartum period. Utilizing data from the Interaction of Gene and Environment of Depression during PostPartum Cohort (IGEDEPP) involving 3310 French postpartum women, we employed a cross-lagged panel model (CLPM) to analyze the relationships between these two symptoms, across three time points (immediate postpartum [<1week after delivery], early postpartum [<2months after delivery], and late postpartum [2months to 1years after delivery]). Depressed mood significantly influences sleep disturbances in late postpartum (β=0.096, z-value=7.4; p<0.001) but not in early postpartum (p-value=0.9). We found no cross-lagged influence of sleep disturbances on depressed mood in early (p=0.066) or in late postpartum (p=0.060). Moreover, depressed mood and sleep disturbances in immediate postpartum are predictive of similar symptoms in the two other postpartum periods (between each of the three periods, p=0.006 and p<0.001 for depressed mood, and p=0.039 and p<0.001 for sleep disturbances), thus demonstrating the stability of these symptoms over time. Although conducted with a prospectively assessed cohort, this study faces limitations due to potential methodological biases. This study is a pioneering analysis of mutual causal interactions between depressed mood and sleep disturbances in the postpartum period, highlighting the need for vigilant monitoring, early detection, prevention of worsen outcomes and intervention on these symptoms.