The Impact of Information Relevancy and Interactivity on Intensivists' Trust in a Machine Learning-Based Bacteremia Prediction System: Simulation Study.

Background: The exponential growth in computing power and the increasing digitization of information have substantially advanced the machine learning (ML) research field. However, ML algorithms are often considered "black boxes," and this fosters distrust. In medical domains, in which mistakes can result in fatal outcomes, practitioners may be especially reluctant to trust ML algorithms. Objective: The aim of this study is to explore the effect of user-interface design features on intensivists' trust in an ML-based clinical decision support system. Methods: A total of 47 physicians from critical care specialties were presented with 3 patient cases of bacteremia in the setting of an ML-based simulation system. Three conditions of the simulation were tested according to combinations of information relevancy and interactivity. Participants' trust in the system was assessed by their agreement with the system's prediction and a postexperiment questionnaire. Linear regression models were applied to measure the effects. Results: Participants' agreement with the system's prediction did not differ according to the experimental conditions. However, in the postexperiment questionnaire, higher information relevancy ratings and interactivity ratings were associated with higher perceived trust in the system (P<.001 for both). The explicit visual presentation of the features of the ML algorithm on the user interface resulted in lower trust among the participants (P=.05). Conclusions: Information relevancy and interactivity features should be considered in the design of the user interface of ML-based clinical decision support systems to enhance intensivists' trust. This study sheds light on the connection between information relevancy, interactivity, and trust in human-ML interaction, specifically in the intensive care unit environment.

Adherence to monitoring of patients treated with amiodarone: a nationwide study.

Objective: The aim of this study was to assess the adherence to monitoring guidelines regarding amiodarone treatment. Methods: This is a retrospective cohort study of data recorded in Clalit Health Services, the largest healthcare organization in Israel. Included were individuals aged >18 years; who were prescribed amiodarone and had a documented purchase of this drug, for a minimum of 200 consecutive days; and who had less than a 100-day gap between two consecutive purchases during 2013-2021. Adherence was assessed to testing for thyroid, liver function, and electrolytes, as determined by the performance of a test every 6 months. Results: The study included 24,094 individuals (mean age: 75 years, 53% male). The median follow-up was 2.3 years (total 73,727 person-years). The proportions of patients who performed baseline tests were: 43.4% for thyroid function, 58.3% for electrolytes, 48.6% for liver function, 20.6% for chest X-rays, and 14.9% for electrocardiograms. Adherence rates to semiannual monitoring of thyroid function, liver function, and electrolyte tests were: 70.4%, 79.4%, and 88.3%, respectively. In a multivariable analysis, the factors associated with higher adherence were male sex; older age; the presence of thyroid abnormalities, renal failure, and hypertension; and more frequent visits to the primary care physician. Conclusions: In our country, adherence is low to monitoring risk factors for adverse effects of amiodarone therapy, especially prior to treatment initiation. Patient and primary care physicians should be educated about the importance of monitoring, particularly prior to initiation of amiodarone treatment.

Exploring the association between serum phosphate levels and mortality in patients hospitalized with infectious diseases: a nationwide study.

Objective: The purpose of this study was to examine associations of serum phosphate levels with mortality, target organ damage and length of hospital stay in adults with infectious diseases hospitalized outside of the intensive care unit. Methods: This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. The main exposure variable was the first serum phosphate levels at admission (up to 1 week). The analysis included multivariable logistic regression models and quantile regression. Results: Of 126,088 patients (49% males, mean age: 69.3 years), 24,809 (19.7%) had decreased phosphate levels, 92,730 (73.5%) normal phosphate levels, and 8,549 (6.8%) elevated phosphate levels on admission. Overall- and in-hospital mortality rates were highest among those with hyperphosphatemia (74.5 and 16.4%, respectively), followed by those with normophosphatemia (57.0 and 6.6%), and lastly the hypophosphatemia group (48.7 and 5.6%); p < 0.001 for all. After adjusting for confounders, the lowest predicted mortality rate was observed in the normophosphatemia group. In the multivariable model, hyperphosphatemia conferred a higher probability of target organ damage (OR [95% CI]: 2.43 [2.06-2.86]), while moderate hypophosphatemia conferred a lower probability (OR [95% CI]: 0.73 [0.65-0.82]), compared to normal phosphate levels and extreme hypophosphatemia showed a non-significant association (OR [95% CI]: 0.87 [0.57-1.28]). The associations were independent of renal failure. In a multivariable model, hyperphosphatemia was associated with a slight increase of 0.33 days in length of stay compared to normal phosphate levels. Conclusion: A J-shaped relation was found between phosphate levels and prognosis in patients hospitalized with infectious diseases, regardless of their renal function.

Establishing a 3-Tesla Magnetic Resonance Imaging Method for Assessing Diffuse Axonal Brain Injury in Rats.

Traumatic brain injury (TBI) significantly contributes to death and disability worldwide. However, treatment options remain limited. Here, we focus on a specific pathology of TBI, diffuse axonal brain injury (DABI), which describes the process of the tearing of nerve fibers in the brain after blunt injury. Most protocols to study DABI do not incorporate a specific model for that type of pathology, limiting their ability to identify mechanisms and comorbidities of DABI. In this study, we developed a magnetic resonance imaging (MRI) protocol for DABI in a rat model using a 3-T clinical scanner. We compared the neuroimaging outcomes with histologic and neurologic assessments. In a sample size of 10 rats in the sham group and 10 rats in the DABI group, we established neurological severity scores before the intervention and at 48 h following DABI induction. After the neurological evaluation after DABI, all rats underwent MRI scans and were subsequently euthanized for histological evaluation. As expected, the neurological assessment showed a high sensitivity for DABI lesions indicated using the ß-APP marker. Surprisingly, however, we found that the MRI method had greater sensitivity in assessing DABI lesions compared to histological methods. Out of the five MRI parameters with pathological changes in the DABI model, we found significant changes compared to sham rats in three parameters, and, as shown using comparative tests with other models, MRI was the most sensitive parameter, being even more sensitive than histology. We anticipate that this DABI protocol will have a significant impact on future TBI and DABI studies, advancing research on treatments specifically targeted towards improving patient quality of life and long-term outcomes.

Methemoglobinemia screening and treatment in tank warfare survivors.

INTRODUCTION: Methemoglobinemia, characterized by the conversion of functional hemoglobin to methemoglobin, can significantly impede tissue oxygenation. Prompt diagnosis and treatment of methemoglobinemia are critical to optimizing clinical outcomes. Although the underlying etiology of methemoglobinemia is often attributed to a medication reaction or chemical exposure, its association with battlefield trauma remains underexplored. This case series explores the presence of methemoglobinemia in nine soldiers evacuated from tanks targeted by explosives, shedding new light on screening needs and treatment strategies. CASES DESCRIPTION: Nine combat trauma patients with methemoglobinemia were admitted to Soroka Medical Center over a two-month period. Detailed case descriptions illustrate the diverse presentations and treatment responses. Notably, the administration of methylene blue resulted in rapid methemoglobin reductions and an improvement in oxygenation without any observed side effects. DISCUSSION: This series highlights an unexpected consequence of an explosion within an armored fighting vehicle and the challenges related to standard pulse oximetry interpretation and accuracy in the presence of methemoglobinemia, emphasizing the need for vigilant monitoring and co-oximetry utilization. Additionally, the coexistence of carboxyhemoglobin further warrants attention due to its synergistic and deleterious effects on oxygen delivery. Collaborative efforts with military authorities should aim to explore the underlying mechanisms associated with trauma and methemoglobinemia and optimize battlefield care. CONCLUSION: This case series underscores the significance of methemoglobinemia screening in combat trauma patients, and advocates for systematic co-oximetry utilization and methylene blue availability in combat zones. Early detection and intervention of methemoglobinemia in combat soldiers are often difficult in the context of battlefield injuries but are necessary to mitigate the potentially fatal consequences of this condition.

The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review.

There is a growing body of evidence that suggests a connection between traumatic brain injury (TBI) and subsequent post-traumatic stress disorder (PTSD). While the exact mechanism is unknown, we hypothesize that chronic glutamate neurotoxicity may play a role. The consumption of dietary glutamate is a modifiable factor influencing glutamate levels in the blood and, therefore, in the brain. In this systematic review, we explored the relationship between dietary glutamate and the development of post-TBI PTSD. Of the 1748 articles identified, 44 met the inclusion criteria for analysis in this review. We observed that individuals from countries with diets traditionally high in glutamate had greater odds of developing PTSD after TBI (odds ratio = 15.2, 95% confidence interval 11.69 to 19.76, p < 0.01). These findings may support the hypothesis that chronically elevated blood glutamate concentrations caused by high dietary intake invoke neurodegeneration processes that could ultimately result in PTSD. Further studies will clarify whether lowering glutamate via diet would be an effective strategy in preventing or treating post-TBI PTSD.

Vasopressors and Mean Arterial Pressure in Septic Shock: Do We Bend the Rules for Young Adults?

BACKGROUND: Younger patient age and relatively good prognosis have been described as factors that may increase caregiver motivation in treating patients with septic shock in the intensive care unit (ICU). OBJECTIVES: To examine whether clinical teams tended to achieve unnecessarily higher map arterial pressure (MAP) values in younger patients. METHODS: We conducted a population-based retrospective cohort study of patients presenting with septic shock who were treated with noradrenaline and hospitalized in a general ICU between 2006 and 2018. The patients were classified into four age groups: 18-45 (n=129), 46-60 (n=96), 61-75 (n=157), and older than 75 years (n=173). Adjusted linear mixed models and locally weighted scatterplot smoothing (LOWESS) curves were used to assess associations and potential non-linear relationships, respectively, of age group with MAP and noradrenaline dosage. RESULTS: The cohort included 555 patients. An inverse relation was observed between average MAP value and age. Among patients aged 18-45 years, the average MAP was 4.7 mmHg higher (95% confidence interval 3.4-5.9) than among patients aged > 75 years (P-value <0.001) after adjustment for sex, death in the intensive care unit, and Sequential Organ Failure Assessment scores. CONCLUSIONS: Among patients with septic shock, the titration of noradrenaline by staff led to a higher average MAP for younger patients. Although the MAP target is equal for all age groups, staff may administer noradrenaline treatment according to a higher target of MAP due to attitudes toward patients of different ages, despite any evidence that such practice is beneficial.

Prophylactic Administration of Tranexamic Acid Reduces Blood Products' Transfusion and Intensive Care Admission in Women Undergoing High-Risk Cesarean Sections.

Postpartum hemorrhage (PPH) remains a major cause of maternal mortality. Tranexamic acid (TxA) has shown effectiveness in reducing PPH-related maternal bleeding events and deaths. We conducted a cohort study including parturient women at high risk of bleeding after undergoing a cesarean section (CS). Participants were divided into two groups: the treatment group received prophylactic 1-g TxA before surgery (n = 500), while the comparison group underwent CS without TxA treatment (n = 500). The primary outcome measured increased maternal blood loss following CS, defined as more than a 10% drop in hemoglobin concentration within 24 h post-CS and/or a drop of ≥2 g/dL in maternal hemoglobin concentration. Secondary outcomes included PPH indicators, ICU admission, hospital stay, TxA complications, and neonatal data. TxA administration significantly reduced hemoglobin decrease by more than 10%: there was a 35.4% decrease in the TxA group vs. a 59.4% decrease in the non-TxA group, p < 0.0001 and hemoglobin decreased by ≥2 g/dL (11.4% in the TxA group vs. 25.2% in non-TxA group, p < 0.0001), reduced packed red blood cell transfusion (p = 0.0174), and resulted in lower ICU admission rates (p = 0.034) and shorter hospitalization (p < 0.0001). Complication rates and neonatal outcomes did not differ significantly. In conclusion, prophylactic TxA administration during high-risk CS may effectively reduce blood loss, providing a potential intervention to improve maternal outcomes.

Emergency Department Admission Rates, Waiting Times, and Mortality: An Observational Study in the Tertiary Center Most Proximal to Gaza During a Military Conflict.

OBJECTIVES: Military conflicts may be ongoing and encompass multiple medical facilities. This study investigated the impact of a military conflict ("Protective Edge" PE) on emergency department (ED) function in a tertiary medical center. METHODS: Visits to the ED during PE (July-August 2014) were compared with ED visits during July-August 2013 and 2015 with regard to admission rates, waiting times and 30-d mortality. Odds ratios (ORs) adjusted for confounders were used for the multivariable regression models. RESULTS: There were 32,343 visits during PE and 74,279 visits during the comparison periods. A 13% decrease in the daily number of visits was noted. During PE, longer waiting times were found, on average 0.25 h longer, controlling for confounders. The difference in waiting times was greater in medicine and surgery. Admission rates were on average 10% higher during PE military conflict, controlling for confounders. This difference decreased to 7% controlling for the daily number of visits. Thirty-day mortality was significantly increased during PE (OR = 1.42; 95% CI: 1.18-1.70). ORs for mortality during PE were significantly higher in medicine (OR = 1.45; 95% CI: 1.15-1.81) and pediatrics (OR = 4.40; 95% CI: 1.33-14.5). CONCLUSIONS: During an ongoing military conflict, waiting times, admission rates, and mortality were statistically significantly increased.

Challenging the Interpretation of White Blood Cell Counts in Patients with Sepsis Following Packed Cell Transfusion.

Critically ill patients with sepsis often require packed cell transfusions (PCT). However, PCT may affect white blood cell (WBC) counts. We conducted a population-based retrospective cohort study to trace changes in WBC count following PCT in critically ill patients with sepsis. We included 962 patients who received one unit of PCT while hospitalized in a general intensive care unit, and 994 matched patients who did not receive PCT. We calculated the mean values of WBC count for the 24 h before and 24 h after PCT. Multivariable analyses using a mixed linear regression model were performed. The mean WBC count decreased in both groups, but more in the non-PCT group (from 13.9 × 109/L to 12.2 × 109/L versus 13.9 × 109/L to 12.8 × 109/L). A linear regression model showed a mean decrease of 0.45 × 109/L in WBC count over the 24 h following the start of PCT. Every 1.0 × 109/L increase in the WBC count prior to PCT administration showed a corresponding decrease of 0.19 × 109/L in the final WBC count. In conclusion, among critically ill patients with sepsis, PCT causes only mild and clinically non-prominent changes in WBC count.

The use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in Civilian Trauma in an Israeli Level 1 Trauma Center.

BACKGROUND: Massive, non-compressible bleeding is a leading cause of preventable trauma mortality. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is a minimally invasive procedure in which a balloon catheter is maneuvered into the aorta to temporarily occlude large vessels and enable stabilization of the exsanguinating patient. OBJECTIVES: To present experiences in assimilating REBOA at a single level 1 trauma center in Israel, to evaluate the technical aspects of the procedure, and to describe patient characteristics and outcomes. METHODS: This retrospective cohort study comprised civilians admitted with hemorrhagic shock to our trauma department who were treated with REBOA between November 2017 and July 2021. Descriptive statistics of the patients, characteristics of the injuries and patient outcomes are presented. RESULTS: The study included 22 patients (median age 30.1 years, 21 male). The mean systolic blood pressure (SBP) before REBOA inflation was 59.6 ± 11.4 mmHg, and the mean SBP measured after the procedure was 115.2 ± 26.3 mmHg. In 20 patients (91%), the SBP was normalized (> 90 mmHg) shortly after inflation of the balloon, and they survived the treatment in the trauma department; 15 (75%) survived the first 30 days. CONCLUSIONS: REBOA is an effective method for the initial resuscitation and hemorrhage control of patients with massive, non-compressible bleeding and is relatively easy to assimilate in a hospital. The achievement of immediate normalization of SBP enables medical personnel to correct physiological parameters and obtain accurate imaging before proceeding to the operating theater.

BODY TEMPERATURE VARIATION AFTER PACKED CELL TRANSFUSION IN ADULT PATIENTS WITH SEPSIS-WHERE WILL THE PENDULUM STOP?

ABSTRACT: Background : Critically ill patients with sepsis often require packed cell transfusions (PCTs). Packed cell transfusion causes changes in body's core temperature. Objective : To trace the course and amplitude of body core temperature after PCT in adults with sepsis. Methods : We conducted a population-based retrospective cohort study of patients with sepsis who received one unit of PCT during their hospitalization in a general intensive care unit during 2000-2019. A control group was established by matching each of these patients to a patient who did not receive PCT. We calculated the mean values of urinary bladder temperature for the 24 h before and 24 h after PCT. To evaluate the effect of PCT on body core temperature, multivariable analyses using a mixed linear regression model were performed. Results : The study comprised 1,100 patients who received one unit of PCT and 1,100 matched patients. The mean temperature before PCT was 37.3°C. Immediately from initiation of PCT, body temperature decreased, to a minimum of 37.0°C. During the 24 subsequent hours, the temperature increased gradually and consistently, until a peak temperature of 37.4°C. In a linear regression model, body core temperature increased by a mean 0.06°C in the first 24 h after PCT and decreased by a mean 0.65°C for every 1.0°C increase before PCT. Conclusions : Among critically ill patients with sepsis, PCT itself causes only mild and clinically insignificant temperature changes. Thus, significant changes in core temperature during the 24 h after PCT may indicate an unusual clinical event that requires clinicians' immediate attention.

The role of lactate dehydrogenase in hospitalized patients, comparing those with pulmonary versus non-pulmonary infections: A nationwide study.

BACKGROUND: Lactic dehydrogenase reflects target organ damage, and is associated with mortality in patients with infectious diseases. OBJECTIVE: The purpose of this study was to examine associations of serum lactic dehydrogenase levels with mortality, target organ damage and length of hospital stay in adults with pulmonary and non-pulmonary infections. METHODS: This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. Patients with available serum lactic dehydrogenase levels on admission and one week after were included, and stratified by the source of their infection: pulmonary vs. non-pulmonary. Associations of lactic dehydrogenase levels with mortality and target organ damage were analyzed using multivariable logistic regression models. Quantile regression was used for multivariable analysis of the median length of stay. RESULTS: The study included 103,050 patients (45.4% male, median age: 69 years); 44,491 (43.1%) had pulmonary infections. The median serum lactic dehydrogenase levels on admission were higher in patients with pulmonary than non-pulmonary infections (418 vs. 385 units per liter (U/L), p<0.001). In a multivariable logistic regression model, elevated serum lactic dehydrogenase levels (480-700 U/L, 700-900 U/L and >900 U/L), compared with <480 U/L, were associated with in-hospital mortality (OR = 1.81, 2.85 and 3.69, respectively) and target organ damage (OR = 1.19, 1.51 and 1.80, respectively). The median stay increased with increasing elevated lactic dehydrogenase levels (+0.3, +0.5 and +0.4 days, respectively). Among patients with lactic dehydrogenase levels >900 U/L, mortality, but none of the other examined outcomes, was greater among those with pulmonary than non-pulmonary infections. CONCLUSIONS: Among hospitalized patients with infectious diseases, lactic dehydrogenase levels were associated with mortality and target organ damage, and were similar in patients with pulmonary and non-pulmonary infections. Among patients with lactic dehydrogenase levels >900 U/L, mortality was prominently higher among those with pulmonary than non-pulmonary infections.

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment.

Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate's concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.

Ivabradine for Uncontrolled Sinus Tachycardia in Thyrotoxic Cardiomyopathy - Case Report.

BACKGROUND: Beta-blockers, mainly propranalol, are usually administered to control heart rate in patients with thyrotoxicosis, especially when congestive heart failure presents. However, when thyrotoxicosis is not controlled, heart rate may be difficult to control even with maximal doses of propranolol. This presentation alerts physicians to the possibility of using ivabradine, a selective inhibitor of the sinoatrial pacemaker, for the control of heart rate. CASE PRESENTATION: We present a 37-year-old woman with thyrotoxicosis and congestive heart failure whose heart rate was not controlled with a maximal dose of beta blockers during a thyroid storm. The addition of ivabradine, a selective inhibitor of the sinoatrial pacemaker, controlled her heart rate within 48 hours. CONCLUSION: Ivabradine should be considered in patients with thyrotoxicosis, including those with heart failure, in whom beta blockers are insufficient to control heart rate.

Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review.

Post-stroke depression (PSD) is a biopsychosocial disorder that affects individuals who have suffered a stroke at any point. PSD has a 20 to 60 percent reported prevalence among stroke survivors. Its effects are usually adverse, can lead to disability, and may increase mortality if not managed or treated early. PSD is linked to several other medical conditions, including anxiety, hyper-locomotor activity, and poor functional recovery. Despite significant awareness of its adverse impacts, understanding the pathogenesis of PSD has proved challenging. The exact pathophysiology of PSD is unknown, yet its complexity has been definitively shown, involving mechanisms such as dysfunction of monoamine, the glutamatergic systems, the gut-brain axis, and neuroinflammation. The current effectiveness of PSD treatment is about 30-40 percent of all cases. In this review, we examined different pathophysiological mechanisms and current pharmacological and non-pharmacological approaches for the treatment of PSD.

Can the Duration of In-Hospital Ventilation in Patients with Sepsis Help Predict Long-Term Survival?

Mechanical ventilation is a cornerstone in the treatment of critical illness, especially sepsis. Prolonged mechanical ventilation, for a duration exceeding 21 days, is associated with higher rates of in-hospital and post-discharge mortality. Our aim was to assess the association between in-hospital ventilation duration and long-term life expectancy in patients ventilated in intensive care units specifically due to sepsis of any origin. We conducted a population-based retrospective cohort study of adults hospitalized in a general intensive care unit for 24 h or more during 2007-2017, who were diagnosed with sepsis or septic shock, treated with invasive mechanical ventilation for a maximum of 60 days and survived hospitalization. The primary exposure was the length of invasive mechanical ventilation. In an adjusted multivariable regression model, survival rates at 1, 2, 3 and 4 years post-hospitalization did not differ significantly between patients who were ventilated for 3-8 days (n = 169), 9-21 days (n = 160) or 22-60 days (n = 170), and those who were ventilated for 1-2 days (n = 192). We concluded that the duration of in-hospital ventilation in patients with sepsis cannot serve as a predictor for long-term survival. Thus, the duration of ventilation in itself should not guide the level of care in ventilated patients with sepsis.

Glutamate Neurotoxicity and Destruction of the Blood-Brain Barrier: Key Pathways for the Development of Neuropsychiatric Consequences of TBI and Their Potential Treatment Strategies.

Traumatic brain injury (TBI) is associated with significant cognitive and psychiatric conditions. Neuropsychiatric symptoms can persist for years following brain injury, causing major disruptions in patients' lives. In this review, we examine the role of glutamate as an aftereffect of TBI that contributes to the development of neuropsychiatric conditions. We hypothesize that TBI causes long-term blood-brain barrier (BBB) dysfunction lasting many years and even decades. We propose that dysfunction in the BBB is the central factor that modulates increased glutamate after TBI and ultimately leads to neurodegenerative processes and subsequent manifestation of neuropsychiatric conditions. Here, we have identified factors that determine the upper and lower levels of glutamate concentration in the brain after TBI. Furthermore, we consider treatments of disruptions to BBB integrity, including repairing the BBB and controlling excess glutamate, as potential therapeutic modalities for the treatment of acute and chronic neuropsychiatric conditions and symptoms. By specifically focusing on the BBB, we hypothesize that restoring BBB integrity will alleviate neurotoxicity and related neurological sequelae.