2 Minute Medicine Rewind September 2, 2024

Repetitive Head Impacts and Perivascular Space Volume in Former American Football Players

1. In a cohort of former American football players and unexposed controls, repetitive head impacts (RHI) were associated with a larger perivascular space (PVS) volume, which was associated with worse cognitive performance.

Evidence Rating Level: 2 (Good)

Several studies in recent years have suggested an association between RHI exposure and an increased likelihood of developing neurodegenerative disorders later on in life. While the precise pathophysiological mechanisms surrounding the development of neurodegenerative diseases remain unclear, the role of the perivascular transport system in clearing proteins and waste products from the brain may be an important factor. This cross-sectional study therefore sought to investigate whether PVS volume, as measured on structural MRI, is associated with a history of RHI exposure. 224 participants (median age = 57) between the ages of 45 to 74 were included in the study and received MRI imaging and neuropsychological testing. 170 participants were former football players with experience in the National Football League or at the collegiate level while 54 participants were age-matched individuals without previous RHI exposure. Participants with football experience had significantly larger log-PVS than participants without previous RHI exposure (mean difference, 0.28 [95% CI, 0.00 to 0.76]; P = .05; n = 212). Among former football players, a significant association was found between larger log-PVS and worse performance on the Montreal Cognitive Assessment (MoCA) (β = −0.74 [95% CI, −1.35 to -0.13]; P = .04; n = 159). Overall, this study found that American football players had larger PVS volumes compared to age-matched individuals without previous RHI exposure, and that greater PVS volumes were associated with worse cognitive functioning.

First-Generation Antihistamines and Seizures in Young Children

1. Prescriptions of first-generation antihistamines in young children in Korea were associated with a 22.0% higher seizure risk.

Evidence Rating Level: 2 (Good)

First generation antihistamines remain widely used for the management of rhinorrhea or pruritus. While such medications can cross the blood brain barrier and have been shown to be capable of affecting brain waves, their impact on vulnerable age groups such as young children have not been well studied. This retrospective cohort study therefore sought to investigate the association between the prescription of first-generation antihistamines and seizures in young children. 11,729 children with seizure events and previous first generation antihistamine prescription were included from the National Health Insurance Service (NHIS) database in Korea and data was analyzed in a case-crossover approach. The main observational window, termed the hazard period, was defined as 15 days preceding the date of occurrence of a seizure event (the index date). The hazard period was then compared to prescriptions 31 to 45 days and 61 to 75 days prior to the index date, termed control periods 1 and 2 respectively. The risk of seizures within the hazard period was found to be elevated (adjusted OR [AOR], 1.22 [95% CI, 1.13-1.31]) compared to the control periods. An elevated risk of seizures was similarly found to be associated with antihistamine prescription with a time window adjusted to 1 to 5 days (AOR, 1.36 [95% CI, 1.23-1.51]) and 1 to 10 days (AOR, 1.25 [95% CI, 1.15-1.36]). When analyzing based on age subgroups, children aged 6 to 24 months had a significantly increased risk of seizure events compared to other age groups (AOR, 1.49 [95% CI, 1.31-1.70]). Overall, this study found that prescription of first generation antihistamines was associated with an increased risk of seizure events in young children, with a substantial increase in risk for children aged 6 to 24 months.

Endoscopic Skipping, Stricturing, and Penetrating Complications in Crohn’s Disease on Tandem Ileo-colonoscopy and Cross-sectional Imaging: A Retrospective Cohort Study

1. Approximately one-fifth of active Crohn’s disease (CD) cases were missed by ileo-colonoscopy due to endoscopic skipping, with such skip lesions being seen on cross-sectional imaging only.

2. Approximately one-third of cases of stricturing disease in adult CD patients were detected by cross-sectional imaging only.

Evidence Rating Level: 2 (Good)

CD involves inflammation that can occur anywhere along the intestinal tract and often in a discontinuous manner. As such, cross-sectional imaging alongside ileo-colonoscopy in the form of computerized tomography enterography (CTE) or magnetic resonance enterography (MRE) are required for comprehensive assessment. Indeed, when inflammation occurs more proximally than the terminal ileum (TI), such cases are referred to as endoscopic skipping of the TI as these lesions are out of reach of the colonoscope. This retrospective study therefore sought to investigate the prevalence of endoscopic skipping of the TI and stricturing and penetrating complications in adult patients with CD. 202 adult patients (mean age = 45.2 years) with a confirmed diagnosis of CD and previous ileo-colonoscopy and cross-sectional imaging (CTE or MRE) done within 6 months of each other from London, Canada were included in the study. 22.3% (45/202) patients had evidence of endoscopic skipping, defined as small bowel lesions detected on cross-sectional imaging but not ileo-colonoscopy. 24.7% (50/202) of patients had evidence of skip lesions, defined as discontinuous inflammation of the small bowel, of which the majority occurred in the ileum (42/202). 36.2% (21/58) of cases of stricturing disease were identified only on cross-sectional imaging, while 5.1% (3/58) were identified exclusiely by ileo-colonoscopy. Overall, this study found that approximately one-fifth of CD patients exhibited endoscopic skipping of the TI requiring cross-sectional imaging for detection, and that over one-third of cases of stricturing disease required cross-sectional imaging for detection.​​

Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update

1. The use of tarlatamab, a bispecific T-cell engager targeting delta-like ligand 3, in patients with previously treated small cell lung cancer (SCLC) showed a sustained clinical benefit in extended follow-up, demonstrating an unprecedent overall survival (OS).

Evidence Rating Level: 1 (Excellent)

Tarlatamab is a novel bispecific T-cell engager (BiTE) immunotherapy which directs cytotoxic T cells against tumour cells expressing delta-like ligand 3 (DLL3). Tarlatamab has been approved in the United States for extensive-stage SCLC with disease progression on or after platinum-based chemotherapy based on data from the previous DeLLphi-300 phase I and phase II trials, in which tarlatamab demonstrated durable anticancer activity and a manageable safety profile. This extended follow-up of the DeLLphi-300 phase I trial was conducted with a data cut-off of 14.5 months beyond the initial report. The follow-up included 72 patients from the initial report and 80 patients not included in the initial report for a total of 152 patients receiving clinically relevant doses of tarlatamab for previously treated SCLC, with the primary endpoint being safety and secondary end points including progression-free survival (PFS) and overall survival (OS). Compared to previous reports, no new safety signals were found, with the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) being similar in patients with and without brain metastases (any grade: 10.5% [4 of 38] v 12.3% [14 of 114]). Median time to resolution for events of interest, including cytokine release syndrome (CRS), ICANS and neutropenia was 4, 5 and 9 days respectively. The overall response rate (ORR) was 25.0% (95% CI, 18.3 to 32.7) with a PFS of 3.5 months (95% CI, 2.7 to 3.8) and OS of 17.5 months (95% CI, 11.4 to not estimable [NE]). Overall, this study found that tarlatamab demonstrated a sustained clinical benefit in patients with previously treated SCLC, with no new safety signals and an unprecented OS. 

Risk of dementia after initiation of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors in adults aged 40-69 years with type 2 diabetes: population based cohort study

1. In a population of adults aged 40-69 years with type 2 diabetes (T2D), use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors was associated with a 35% reduction in the risk of dementia compared to the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.

Evidence Rating Level: 2 (Good)

In recent years, a mounting body of evidence has suggested that T2D is associated with an increased risk of dementia with some studies showing that certain antihyperglycemic drugs may exert neuroprotective effects in patients with T2D. While SGLT-2 inhibitors and DPP-4 inhibitors are newer classes of antihyperglycemic drugs, direct comparisons on the neuroprotective effects of the medications in some age groups have not yet been conducted. This population-based cohort study therefore sought to compare the risk of dementia in adults with T2D under the age of 70 using SGLT-2 inhibitors or DPP-4 inhibitors. 110,885 pairs of adults between the ages of 40 and 69 were identified from the Korean National Health Insurance Service database and matched using a propensity score matched active comparator new user cohort study design. The primary outcome of interest was incident dementia based on ICD-10 diagnosis codes. The incidence rate of dementia per 100 person years was 0.22 for patients receiving SGLT-2 inhibitors and 0.35 for patients receiving DPP-4 inhibitors, with a corresponding hazard ratio of 0.65 (95% CI 0.58 to 0.73). This association was observed across several subgroups, with SGLT-2 inhibitors being associated with a lower risk of dementia when analysis was stratified based on age, sex and baseline cardiovascular risk. Overall, this study found that the use of SGLT-2 inhibitors in a population of adults aged 40-69 years with T2D was associated with a lower risk of dementia compared to adults with similar characteristics receiving DPP-4 inhibitors.

Image: PD

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