Predictors of hospital length of stay and long-term care facility placement in aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is frequently associated with complications, extended hospital length of stay (LOS) and high health care related costs. We sought to determine predictors for hospital LOS and discharge disposition to a long-term care facility (LTCF) in aSAH patients. Methods: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic referral center from 2016 to 2021. Multiple linear regression was performed to identify predictors for hospital LOS. We then created a 10-point scoring system to predict discharge disposition to a LTCF. Results: In a cohort of 318 patients with confirmed aSAH, mean age was 57 years (SD 13.7), 61% were female and 70% were white. Hospital LOS was longer for survivors (median 19 days, IQR 14-25) than for non-survivors (median 5 days, IQR 2-8; p < 0.001). Main predictors for longer LOS for this cohort were ventriculoperitoneal shunt (VPS) requirement (p < 0.001), delayed cerebral ischemia (p = 0.026), and pneumonia (p = 0.014). The strongest predictor for LTCF disposition was age older than 60 years (OR 1.14, 95% CI 1.07-1.21; p < 0.001). LTCF score had high accuracy in predicting discharge disposition to a LTCF (area under the curve [AUC] 0.83; 95% CI 0.75-0.91). Forty-one percent of patients who were discharged to a LTCF had significant functional recovery at 3 months post-discharge. Conclusions: VPS requirement and aSAH related complications were associated with longer hospital LOS compared to other factors. LTCF score has high accuracy in predicting discharge disposition to a LTCF.

Arm Health in Elite Collegiate Summer League Baseball Players Assessed by the Kerlan-Jobe Orthopaedic Clinic Score.

CONTEXT: Collegiate baseball players with professional aspirations often participate in summer leagues; foremost among them is the Cape Cod Baseball League (CCBL). Injuries acquired during the collegiate baseball season can be carried into the CCBL season and vice versa. OBJECTIVE: To assess the history of throwing arm injury and current functionality in midseason CCBL players. DESIGN: Cross-sectional study. SETTING: Online questionnaire. PATIENTS OR OTHER PARTICIPANTS: A total of 123 CCBL players participated. Qualifying athletes were ≥18 years old and were rostered CCBL players with remaining collegiate eligibility. MAIN OUTCOME MEASURE(S): After collecting background information, we used the Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow questionnaire to assess the history of throwing arm injury and current functionality. The maximum KJOC score is 100.0; higher scores correspond with greater functionality. RESULTS: The mean KJOC score was 86.6 ± 14.5 (n = 92); 24.5% (23/94) of players reported a prior diagnosis of throwing arm injury other than a strain or sprain. A total of 49 (49/96, 51.0%) players had undergone rehabilitation for a throwing arm injury, and 7 (7/96, 7.3%) had experienced a medical procedure. Players with no previous treatment (n = 41, mean KJOC score = 88.9 ± 19.0) more frequently demonstrated KJOC scores of ≥90 than players with such treatment (n = 55, 80.9 ± 17.1; P < .001). The 18 players with time-loss arm injury in the last year had lower mean KJOC scores (71.3 ± 20.0) than players with no injury or time loss (90.3 ± 9.8; P < .001). Similarly, players who reported current arm trouble (n = 15) had lower KJOC scores (71.6 ± 17.5) than players with healthy arms (89.5 ± 11.9; P < .001). CONCLUSIONS: The average KJOC score of the CCBL players was <90, with particularly low scores in athletes with prior arm injury and treatment.

Evaluation of an in vitro experimental platform of human polarized intestinal epithelial monolayers for the hazard assessment of insecticidal proteins.

Previous work demonstrated the utility of using human-derived intestinal epithelial cell (IEC) lines cultured as polarized monolayers on Transwell® filters to differentiate between hazardous and non-hazardous proteins. The current study seeks to further resolve appropriate concentrations for evaluating proteins of unknown hazard potential using the IEC experimental platform and leverages these parameters for evaluating the potential toxicity of insecticidal proteins characteristic of those expressed in genetically modified (GM) agricultural biotechnology crops. To establish optimal test protein concentrations, effects of several known hazardous (C. perfringens epsilon toxin, Listeriolysin O, Phaseolus vulgaris erythroagglutinin, E. coli Shiga toxin 1, C. difficile Toxin B and wheat germ agglutinin) and non-hazardous (Ara-h2, ß-lactoglobulin, fibronectin and Rubisco) proteins on IEC barrier integrity and cell viability were evaluated at concentration ranges. Two insecticidal proteins (AfIP-1A and AfIP-1B) were evaluated for effects in the IEC assay, a seven-day insecticidal bioassay, and assessed in a high-dose 14-day acute oral toxicity study in mice. The results obtained from the human in vitro IEC assay were consistent with results obtained from an in vivo acute oral toxicity study, both demonstrating that the combination of AfIP-1A and AfIP-1B do not exhibit any identifiable harmful impacts on mammalian cells.

Highs and Lows: Dysnatremia and Patient Outcomes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Disturbances in serum sodium concentration (dysnatremia) are common following aneurysmal subarachnoid hemorrhage (aSAH), but its direct impact on outcomes is not well understood. This study aimed to examine the association between dysnatremia following aSAH and patient outcomes. METHODS: A retrospective cohort study of consecutive patients with aSAH who were admitted to an academic referral center between 2015 and 2021 was performed. Multivariate logistic regression was used to test the association of dysnatremia and outcomes including modified Rankin Scale score at 3 months after discharge and vasospasm. Multiple linear regression was used to test the association of hospital length of stay and dysnatremia. RESULTS: We included 320 patients with confirmed aneurysmal etiology (mean [SD] age = 57.8 [14.3] years; 61% female; 70% White). No independent associations were found between hyponatremia or hypernatremia and functional outcome or vasospasm. However, hospital length of stay was longer in patients with hypernatremia (7 more days; 95% confidence interval = 4.4-9.6, P < 0.001) independent of age, Hunt and Hess grade, modified Fisher score, delayed cerebral ischemia, and other hospital complications. CONCLUSIONS: Although dysnatremia may not directly impact functional outcome or vasospasm risk, hypernatremia may prolong hospital length of stay. Judicious use of hypertonic saline solutions and avoidance of unnecessary dysnatremia in patients with aSAH should be considered.

Association of hemoglobin trend and outcomes in aneurysmal subarachnoid hemorrhage: A single center cohort study.

BACKGROUND: Anemia has been linked to delayed cerebral ischemia (DCI) and worse outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the association of hemoglobin (Hb) trend and outcomes is not well studied. We investigated predictors of Hb trend and its association with outcomes in patients with aSAH. Our hypothesis was that a negative Hb trend is associated with poorer outcomes independent of Hb values. METHODS: We conducted a retrospective study of a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center (2016-2021). We tested the association of Hb trend and values with measures including DCI and poor functional outcome defined as modified Rankin scale 4-6 at 3 months after discharge. Multiple linear regression analysis was used to identify factors associated with Hb difference from admission to discharge. RESULTS: We included 310 patients with confirmed aneurysmal etiology (mean age 57 years, SD13.6; 62 % female). Greater Hb decrement from admission to discharge was independently associated with higher likelihood of both DCI (OR 1.28 per 1 g/dl decrease in Hb, 95 % CI 1.08-1.47; p = 0.003) and poor functional outcome (OR 1.27 per 1 g/dl decrease in Hb, 1.03-1.53; p = 0.026) independent of any absolute Hb values. Predictors of Hb decrement from admission to discharge were hospital length of stay, Hunt and Hess grades, female sex and age. CONCLUSION: Greater Hb decrement can be associated with higher likelihood of DCI and poor functional outcome in aSAH. More evidence is needed to use Hb trend to guide transfusion threshold in aSAH patients.

ATP Synthase and Mitochondrial Bioenergetics Dysfunction in Alzheimer's Disease.

Alzheimer's Disease (AD) is the most common neurodegenerative disorder in our society, as the population ages, its incidence is expected to increase in the coming decades. The etiopathology of this disease still remains largely unclear, probably because of the highly complex and multifactorial nature of AD. However, the presence of mitochondrial dysfunction has been broadly described in AD neurons and other cellular populations within the brain, in a wide variety of models and organisms, including post-mortem humans. Mitochondria are complex organelles that play a crucial role in a wide range of cellular processes, including bioenergetics. In fact, in mammals, including humans, the main source of cellular ATP is the oxidative phosphorylation (OXPHOS), a process that occurs in the mitochondrial electron transfer chain (ETC). The last enzyme of the ETC, and therefore the ulterior generator of ATP, is the ATP synthase. Interestingly, in mammalian cells, the ATP synthase can also degrade ATP under certain conditions (ATPase), which further illustrates the crucial role of this enzyme in the regulation of cellular bioenergetics and metabolism. In this collaborative review, we aim to summarize the knowledge of the presence of dysregulated ATP synthase, and of other components of mammalian mitochondrial bioenergetics, as an early event in AD. This dysregulation can act as a trigger of the dysfunction of the organelle, which is a clear component in the etiopathology of AD. Consequently, the pharmacological modulation of the ATP synthase could be a potential strategy to prevent mitochondrial dysfunction in AD.

Variation of anti-A and anti-B titers in group O potential blood donors: A pilot study.

BACKGROUND: Resuscitation with fresh whole blood is vital to preserving life on the battlefield. Transfusing low titer O whole blood (LTOWB), defined as anti-A and anti-B titer levels of <1:256, is safe because LTOWB alleviates the risk for hemolytic transfusion reactions. Because of possible variations in titer levels over time, a study was needed using US Navy and Marine Corps personnel to assess how these titers change across two assessments. METHODS: Retrospective data from group O marines and sailors (M = 25 years of age; range, 19-35 years) stationed in the San Diego region were acquired from the Armed Services Blood Program and the Composite Health Care System. Of 972 group O donors between January 2016 and November 2019, 55 donors with 2 samples were identified (N = 55). Analysis included contrasting rates of high (≥1:256) and low (<1:256) anti-A and anti-B titers on the initial and second blood tests, along with the time between testings. RESULTS: The average time between testing was 332 days (range, 35-1,121 days), which far exceeded the recommended 90-day interval (p < 0.00001). Only 45% met the 90-day recommendation. Titer status changed frequently, from low to high (anti-A, 18%; anti-B, 13%; LTOWB to not LTOWB, 21%) or from high to low (anti-A, 62%; anti-B, 78%; not LTOWB to LTOWB, 62%). CONCLUSIONS: Anti-A and anti-B titers change frequently enough to warrant testing immediately before deployment and even during deployment. The observed time elapsed between testing is unacceptably long. The present pilot study provides a foundation for a larger formal study to more fully characterize titer changes over repeated testing. LEVEL OF EVIDENCE: Diagnostic test, level IV.

Aspergillus fumigatus Cell Wall Promotes Apical Airway Epithelial Recruitment of Human Neutrophils.

Aspergillus fumigatus is a ubiquitous fungal pathogen capable of causing multiple pulmonary diseases, including invasive aspergillosis, chronic necrotizing aspergillosis, fungal colonization, and allergic bronchopulmonary aspergillosis. Intact mucociliary barrier function and early airway neutrophil responses are critical for clearing fungal conidia from the host airways prior to establishing disease. Following inhalation, Aspergillus conidia deposit in the small airways, where they are likely to make their initial host encounter with epithelial cells. Challenges in airway infection models have limited the ability to explore early steps in the interactions between A. fumigatus and the human airway epithelium. Here, we use inverted air-liquid interface cultures to demonstrate that the human airway epithelium responds to apical stimulation by A. fumigatus to promote the transepithelial migration of neutrophils from the basolateral membrane surface to the apical airway surface. Promoting epithelial transmigration with Aspergillus required prolonged exposure with live resting conidia. Swollen conidia did not expedite epithelial transmigration. Using A. fumigatus strains containing deletions of genes for cell wall components, we identified that deletion of the hydrophobic rodlet layer or dihydroxynaphthalene-melanin in the conidial cell wall amplified the epithelial transmigration of neutrophils, using primary human airway epithelium. Ultimately, we show that an as-yet-unidentified nonsecreted cell wall protein is required to promote the early epithelial transmigration of human neutrophils into the airspace in response to A. fumigatus Together, these data provide critical insight into the initial epithelial host response to Aspergillus.

Pepsin Triggers Neutrophil Migration Across Acid Damaged Lung Epithelium.

Pepsin represents a potential biomarker for extraesophageal reflux disease when detected in airways, however a direct role for pepsin in lung dysfunction has not been clearly established. Children experiencing gastroesophageal and extraesophageal reflux are often prescribed proton pump inhibitors (PPIs) to reduce gastric acid associated damage to esophageal and airway mucosa. The potential of pepsin and gastric fluid, from children that were either on or off PPI therapy, to cause inflammation and damage using a human in vitro co-culture model of the airway mucosa was evaluated herein. Exposure of the airway model to acidic solutions caused cellular damage and loss of viability, however, acid alone did not disrupt barrier integrity or instigate neutrophil trans-epithelial migration without pepsin. Gastric fluid from patients on PPI therapy exhibited only a slightly higher pH yet had significantly higher concentrations of pepsin and elicited more barrier disruption and neutrophil trans-epithelial migration compared to gastric fluid from patients off PPIs. Inflammatory and damaging responses observed with gastric fluid from patients on PPIs were largely driven by pepsin. These results indicate the potential for PPI usage to raise concentrations of pepsin in gastric fluid, which may enhance the pathological impact of micro-aspirations in children with extraesophageal reflux.

Benefit of Critical Care Flight Paramedic-Trained Search and Rescue Corpsmen in Treatment of Severely Injured Aviators.

During routine aircraft start-up procedures at a US Naval Air Station, an aviation mishap occurred, resulting in the pilot suffering a traumatic brain injury and the copilot acquiring bilateral hemopneumothoraces, a ruptured diaphragm, and hepatic and splenic contusions. The care of both patients, including at point of injury and en route to the closest trauma center, is presented. This case demonstrates a benefit from advanced life-saving interventions and critical care skills beyond the required scope of practice of search and rescue medical technicians as dictated by relevant instructions.