Sex differences in the extent of acute axonal pathologies after experimental concussion.

Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.

Reality of DCD donor use in pediatric thoracic transplantation in the United States.

In the US, the first pediatric donation after circulatory death (DCD) thoracic transplant was done in 2004; however, ethical controversy led to minimal utilization of these donors. The present study was performed to characterize the current state of pediatric DCD heart and lung transplantation (HTx, LTx). Children (<18 year old) who underwent HTx or LTx using DCD donors from June 2004 to June 2022 were identified in the United Network for Organ Sharing registry. A total of 14 DCD recipients were identified: 7 (50%) HTx and 7 (50%) LTx. Donor and recipient demographics are described in Table 1. One and 5-year post-transplant survival were as follows: HTx recipients (64% for each) and LTx recipients (86%, 55%). Although often discussed, the national experience with DCD donors for pediatric HTx and LTx remains limited and not being practiced consistently by any pediatric program. Given the critical organ shortage, DCD use in the field of pediatric thoracic transplantation should be strongly considered.

Later Brain Death Declaration Correlates to Favorable Donor Characteristics but Decreased Heart Acceptance.

BACKGROUND: With rates of potential donor heart discard as high as 66% nationally, quality improvement efforts must seek to optimize donor utilization. Whether the timing of donor brain death declaration (BDD) influences organ acceptance is understudied. The authors sought to characterize the impacts of time between donor hospital admission and BDD on heart utilization and posttransplant outcomes. METHODS: All potential heart donors and recipients in the United Network for Organ Sharing database were identified (2006-2021). Admission-to-BDD cohorts were: 1 to 2 d (n = 52 469), 3 to 4 d (n = 44 033), 5 to 7 d (n = 24 509), and 8 to 10 d (n = 8576). Donor clinical characteristics were compared between cohorts, and donor acceptance was assessed using multivariable binary logistic regression. Recipient posttransplant survival was assessed with the Kaplan-Meier method. RESULTS: Donor demographics and comorbidity profiles (diabetes and hypertension) were comparable across cohorts. Anoxia/overdose deaths were more common (10% > 21% > 24% > 18%, respectively) and cardiopulmonary resuscitation requirements were higher (37% > 52% > 58% > 47%) when BDD occurred longer after admission. Renal dysfunction (44% > 44% > 35% > 29%) and inotrope requirements (52% > 25% > 36% > 29%) were lower in the later BDD cohorts. Proportions of hepatic dysfunction (18%-21%) and left ventricular ejection fraction <50% (13%-16%) were clinically equivalent. Donor acceptance differed by admission-to-BDD cohort (36% [1-2 d], 34% [3-4 d], 30% [5-7 d], and 28% [8-10 d]). Admission-to-BDD >4 d was independently associated with lower odds of acceptance on multivariable analysis (odds ratio 0.79, P < 0.001). Recipients experienced equivalent posttransplant survival for all donor admission-to-BDD cohorts ( P = 0.999 adults and P = 0.260 pediatrics). CONCLUSIONS: Heart donors with later BDD were disproportionately discarded despite similar-to-favorable overall clinical profiles, resulting in nearly 3000 fewer transplants during the study. Increased utilization of donors with later BDD and "high-risk" characteristics (eg, anoxia/overdose, cardiopulmonary resuscitation requirement) can improve rates of transplantation without compromising outcomes.

Cariprazine in Youth with Bipolar and Psychotic Disorders: A Retrospective Chart Review.

Objective: To examine the potential effectiveness and tolerability of cariprazine in pediatric bipolar and psychotic disorders. Methods: We retrospectively reviewed the electronic health records of patients <21 years of age prescribed cariprazine to treat bipolar and psychotic disorders. Adverse effects, tolerability, therapeutic response (Clinical Global Impression-Improvement [CGI-I]), and severity of illness (Clinical Global Impression-Severity [CGI-S]) were determined through manual chart review. Results: We identified 16 patients aged 6-20 years who were treated with cariprazine (initial dose: 1.5 mg/day, interquartile range [IQR], 1.5-1.5; endpoint dose: 3 mg/day, IQR, 1.5-4.5). No serious adverse events were reported, but the most commonly reported side effect was weight gain (n = 3, 19%). Of the 14 patients for whom baseline and endpoint body mass index (BMI) data were available, neither changes in BMI (p = 0.391; 0.54 kg/m2, IQR, -0.33 to 1.38) nor BMI percentile (p = 0.71; 0.36%, IQR, -0.49 to 3.97) significantly differed between baseline and endpoint. However, patients receiving ≥4.5 mg/day had a significantly greater BMI increases during the course of treatment compared with those receiving ≤3 mg/day (p = 0.034; -1.14 kg/m2, IQR, -3.65 to 0.53 vs. 1.01 kg/m2, IQR, 0.17-4.88). CGI-S scores (p = 0.016; 4.5, IQR, 4-5 vs. 4, IQR, 3-4) significantly differed from baseline to endpoint. The response rate was 44% (n = 7/16), with responders being prescribed higher doses (p = 0.005; 6 mg/day, IQR, 4.875-6 vs. 3 mg/day, IQR, 3-4.125). Conclusions: Cariprazine may be well tolerated and effective for pediatric bipolar and psychotic disorders; however, compared with higher doses, total daily doses ≤3 mg/day appear to be more tolerable. Prospective controlled studies to further evaluate cariprazine in youth are needed.