Examining the Impact of Median Arcuate Ligament-Induced Celiac Artery Compression on Target Vessel Patency and Long-term Survival and Device Integrity in Fenestrated and Branched Endovascular Repairs.

OBJECTIVE: To evaluate the impact of celiac artery (CA) compression by median arcuate ligament (MAL) on technical metrics and long-term CA patency in patients with complex aortic aneurysms (cAAs) undergoing fenestrated/branched endograft repairs (f/b-EVARs). METHODS: Single center, retrospective review of patients undergoing f/b-EVARs and requiring incorporation of the CA between 2013 and 2023. Patients were divided into two groups - those with (MAL+) and without (MAL-) CA compression - based on preoperative computed tomography angiography (CTA) findings. MAL was classified in three grades (A, B and C) based on the degree and length of stenosis. Patients with MAL grade A had ≤ 50% CA stenosis measuring ≤ 3 mm in length. Those with grade B had 50%-80% CA stenosis measuring 3-8 mm long while those with grade C had >80% stenosis measuring > 8 mm in length. Endpoints included device integrity, CA patency and technical success - defined as successful implantation of the f/b-device with perfusion of CA and no endoleak. RESULTS: 180 patients with cAAs (pararenal: 128; thoracoabdominal:52) required incorporation of the CA during f/b-EVAR. Majority (73%) were male, with a median age of 76 (69, 81) years and aneurysm size of 62 (57, 69) mm. Seventy-eight patients (43%) had MAL+ anatomy, including 33 patients with MAL grade A, 32 with grade B and 13 with grade C compression. The median length of CA stenosis was 7.0 (5.0 - 10.0) mm. CA was incorporated using fenestrations in 177 (98%) patients. Increased complexity led to failure in CA bridging stent placement in four MAL+ patients but completion angiography showed CA perfusion and no endoleak, accounting for a technical success of 100%. MAL+ patients were more likely to require bare metal stenting in addition to covered stents (p=.004). Estimated blood loss, median operating room time, contrast volume, fluoroscopy dose and time were higher (p<.001) in MAL+ group. Thirty-day mortality was 3.3%, higher (5.1%) in MAL+ patients compared to MAL- patients (2.0 %). At a median follow-up of 770 (198, 1525) days, endograft integrity was observed in all patients and CA events - kinking (7), thrombosis (1) and endoleak (2) - occurred in 10 (5.6%) patients. However, only two patients required reinterventions. MAL+ patients had overall lower long-term survival. CONCLUSIONS: CA compression by MAL is a predictor of increased procedural complexity during f/b-device implantation. However, technical success, long-term device integrity and CA patency are similar to that of patients with MAL- anatomy.

Twenty-five years of observations from the International Registry of Acute Aortic Dissection (IRAD) and its impact on the cardiovascular scientific community.

OBJECTIVE: The International Registry of Acute Aortic Dissection (IRAD) celebrated its 25th anniversary in January 2021. This study evaluated IRAD's role in promoting the understanding and management of acute aortic dissection (AD) over these years. METHODS: IRAD studies were identified, analyzed, and ranked according to their citations per year (c/y) to determine the most-cited IRAD studies and topics. A systematic search of the literature identified cardiovascular guidelines on the diagnosis and management of acute AD. Consequently, IRAD's presence and impact were quantified using these documents. RESULTS: Ninety-seven IRAD studies were identified, of which 82 obtained more than 10 cumulative citations. The median c/y index was 7.33 (25th-75th percentile, 4.01-16.65). Forty-two studies had a greater than median c/y index and were considered most impactful. Of these studies, most investigated both type A and type B AD (n = 17, 40.5%) and short-term outcomes (n = 26, 61.9%). Nineteen guideline documents were identified from 26 cardiovascular societies located in Northern America, Europe, and Japan. Sixty-nine IRAD studies were cited by these guidelines, including 38 of the 42 most-impactful IRAD studies. Among them, partial thrombosis of the false lumen as a predictor of postdischarge mortality and aortic diameters as a predictor of type A occurrence were determined as most-impactful specific IRAD topics by their c/y index. CONCLUSIONS: IRAD has had and continues to have an important role in providing observations, credible knowledge, and research questions to improve the outcomes of patients with acute AD.

The ZFP36 family of RNA binding proteins regulates homeostatic and autoreactive T cell responses.

RNA binding proteins are important regulators of T cell activation, proliferation, and cytokine production. The zinc finger protein 36 (ZFP36) family genes (Zfp36, Zfp36l1, and Zfp36l2) encode RNA binding proteins that promote the degradation of transcripts containing AU-rich elements. Numerous studies have demonstrated both individual and shared functions of the ZFP36 family in immune cells, but their collective function in T cells remains unclear. Here, we found a redundant and critical role for the ZFP36 proteins in regulating T cell quiescence. T cell-specific deletion of all three ZFP36 family members in mice resulted in early lethality, immune cell activation, and multiorgan pathology characterized by inflammation of the eyes, central nervous system, kidneys, and liver. Mice with T cell-specific deletion of any two Zfp36 genes were protected from this spontaneous syndrome. Triply deficient T cells overproduced proinflammatory cytokines, including IFN-γ, TNF, and GM-CSF, due to increased mRNA stability of these transcripts. Unexpectedly, T cell-specific deletion of both Zfp36l1 and Zfp36l2 rendered mice resistant to experimental autoimmune encephalomyelitits due to failed priming of antigen-specific CD4+ T cells. ZFP36L1 and ZFP36L2 double-deficient CD4+ T cells had poor proliferation during in vitro T helper cell polarization. Thus, the ZFP36 family redundantly regulates T cell quiescence at homeostasis, but ZFP36L1 and ZFP36L2 are specifically required for antigen-specific T cell clonal expansion.

Iatrogenic aortic dissection of the descending aorta after percutaneous coronary intervention.

Aortic dissection is a rare and potentially fatal complication of coronary angiography. We report a case of a woman in her late 80s who underwent a left femoral approach coronary angiogram for evaluation of a transcatheter aortic valve replacement (TAVR). Following the procedure, she had a cardiac arrest and was found to have a descending aortic dissection on transoesophageal echocardiogram. Autopsy showed an acute intimal tear of the descending aorta, most likely related to catheter manipulation. Patients undergoing evaluation for TAVR, who tend to be elderly with concomitant atherosclerosis, are at risk for complications following cardiac catheterisation including aortic dissection.

Involvement of TLR2-TLR4, NLRP3, and IL-17 in pain induced by a novel Sprague-Dawley rat model of experimental autoimmune encephalomyelitis.

Up to 92% of patients suffering from multiple sclerosis (MS) experience pain, most without adequate treatment, and many report pain long before motor symptoms associated with MS diagnosis. In the most commonly studied rodent model of MS, experimental autoimmune encephalomyelitis (EAE), motor impairments/disabilities caused by EAE can interfere with pain testing. In this study, we characterize a novel low-dose myelin-oligodendrocyte-glycoprotein (MOG)-induced Sprague-Dawley (SD) model of EAE-related pain in male rats, optimized to minimize motor impairments/disabilities. Adult male SD rats were treated with increasing doses of intradermal myelin-oligodendrocyte-glycoprotein (MOG1-125) (0, 4, 8, and 16 µg) in incomplete Freund's adjuvant (IFA) vehicle to induce mild EAE. Von Frey testing and motor assessments were conducted prior to EAE induction and then weekly thereafter to assess EAE-induced pain and motor impairment. Results from these studies demonstrated that doses of 8 and 16 µg MOG1-125 were sufficient to produce stable mechanical allodynia for up to 1 month in the absence of hindpaw motor impairments/disabilities. In the follow-up studies, these doses of MOG1-125, were administered to create allodynia in the absence of confounded motor impairments. Then, 2 weeks later, rats began daily subcutaneous injections of the Toll-like receptor 2 and 4 (TLR2-TLR4) antagonist (+)-naltrexone [(+)-NTX] or saline for an additional 13 days. We found that (+)-NTX also reverses EAE-induced mechanical allodynia in the MOG-induced SD rat model of EAE, supporting parallels between models, but now allowing a protracted timecourse to be examined completely free of motor confounds. Exploring further mechanisms, we demonstrated that both spinal NOD-like receptor protein 3 (NLRP3) and interleukin-17 (IL-17) are necessary for EAE-induced pain, as intrathecal injections of NLRP3 antagonist MCC950 and IL-17 neutralizing antibody both acutely reversed EAE-induced pain. Finally, we show that spinal glial immunoreactivity induced by EAE is reversed by (+)-NTX, and that spinal demyelination correlates with the severity of motor impairments/disabilities. These findings characterize an optimized MOG-induced SD rat model of EAE for the study of pain with minimal motor impairments/disabilities. Finally, these studies support the role of TLR2-TLR4 antagonists as a potential treatment for MS-related pain and other pain and inflammatory-related disorders.

Early Mortality in Type A Acute Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection.

Importance: Early data revealed a mortality rate of 1% to 2% per hour for type A acute aortic dissection (TAAAD) during the initial 48 hours. Despite advances in diagnostic testing and treatment, this mortality rate continues to be cited because of a lack of contemporary data characterizing early mortality and the effect of timely surgery. Objective: To examine early mortality rates for patients with TAAAD in the contemporary era. Design, Setting, and Participants: This cohort study examined data for patients with TAAAD in the International Registry of Acute Aortic Dissection between 1996 and 2018. Patients were grouped according to the mode of their intended treatment, surgical or medical. Exposure: Surgical treatment. Main Outcomes and Measures: Mortality was assessed in the initial 48 hours after hospital arrival using Kaplan-Meier curves. In-hospital complications were also evaluated. Results: A total of 5611 patients with TAAAD were identified based on intended treatment: 5131 (91.4%) in the surgical group (3442 [67.1%] male; mean [SD] age, 60.4 [14.1] years) and 480 (8.6%) in the medical group (480 [52.5%] male; mean [SD] age, 70.9 [14.7] years). Reasons for medical management included advanced age (n = 141), comorbidities (n = 281), and patient preference (n = 81). Over the first 48 hours, the mortality for all patients in the study was 5.8%. Among patients who were medically managed, mortality was 0.5% per hour (23.7% at 48 hours). For those whose intended treatment was surgical, 48-hour mortality was 4.4%. In the surgical group, 51 patients (1%) died before the operation. Conclusions and Relevance: In this study, the overall mortality rate for TAAAD was 5.8% at 48 hours. For patients in the medical group, TAAAD had a mortality rate of 0.5% per hour (23.7% at 48 hours). However, among those in the surgical group, 48-hour mortality decreased to 4.4%.

Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy.

Over the past several decades, alcohol septal ablation has become an established therapy for selected patients, in whom there is clinical improvement in symptoms as well as objective functional capacity. Patient selection is essential to success, with continued emphasis on the procedure being performed by experienced operators as part of a multidisciplinary team. In many patients, the outcomes of alcohol septal ablation are comparable to the standard of surgical myectomy. The optimization of the outcomes of alcohol septal ablation is essential for the longitudinal care of patients with hypertrophic cardiomyopathy.

Location of Aortic Enlargement and Risk of Type A Dissection at Smaller Diameters.

BACKGROUND: Previous work has demonstrated that more than one-half of acute type A aortic dissections (ATADs) occur at a maximal aortic diameter (MAD) of <5.5 cm. However, no analysis has investigated whether ATAD risk at smaller MADs is more common with modest dilation of the aortic root (AR) or supracoronary ascending aorta (AA) in patients without genetically triggered aortopathy. OBJECTIVES: This study sought to determine if the segment of modest aortic dilation affects risk of ATAD. METHODS: Using the International Registry of Acute Aortic Dissection (IRAD) database from May 1996 to October 2016, we identified 667 ATAD patients with MAD <5.5 cm. Patients were stratified by location of the largest proximal aortic segment (AR or AA). Patients with known genetically triggered aortopathy were excluded. MADs at time of dissection were compared between AR and AA groups. Secondary outcomes included operation, postoperative outcomes, and long-term survival. RESULTS: Of patients with ATAD at an MAD <5.5 cm, 79.5% (n = 530) were in the AA group and 20.5% (n = 137) in the AR group. Modestly dilated ARs (median MAD 4.6 cm [IQR: 4.1-5.0 cm]) dissected at a significantly smaller diameter than modestly dilated AAs (median MAD 4.8 cm [IQR: 4.4-5.1 cm]) (P < 0.01). AR patients were significantly younger than AA patients (58.5 ± 13.0 years vs 63.2 ± 13.3 years; P < 0.01) and more commonly male (78% vs 65%; P < 0.01). Postoperative and long-term outcomes did not differ between groups. CONCLUSIONS: ATAD appears to occur at smaller diameters in patients with modest dilation in the AR vs the AA (4.6 vs 4.8 cm). These findings may have implications for future consensus guidelines regarding the management of patients with aortic disease.

Impact of a multidisciplinary acute aortic dissection program: Improved outcomes with a comprehensive initial surgical repair strategy.

OBJECTIVE: As part of a multidisciplinary aortic dissection (AD) program, a more comprehensive repair strategy for patients with acute type A aortic dissection (ATAAD) and frequent endografting for suitable patients with type B aortic dissection (ATBAD) was adopted in 2015. The aim of this study was to evaluate the impact of these changes. METHODS: This study is a retrospective review of a prospective database containing all patients treated for acute AD between 2003 and 2020. Patients were grouped based on differing repair strategies (pre 2015 vs post 2015). Clinical characteristics, procedural details, and survival data were analyzed. RESULTS: During this time, 323 patients (210 pre, 113 post) were treated for acute AD at our institution. There were 221 patients with ATAAD (149 pre, 72 post) and 102 patients with ATBAD (61 pre, 41 post). The majority (60%) were males, with a mean age of 65.9 ± 15.2 years. There were no differences in cardiovascular risk factors or demographics between the groups. After 2015, fewer patients with ATAAD underwent medical management alone (15% pre vs 4% post; P = .014), and most that underwent surgical intervention had a total arch or aggressive hemiarch repair (27% pre vs 78% post; P < .001). Seventy-four patients (73%) with ATBAD were treated medically, whereas 28 underwent medical management and endografting (23% pre, 34% post; P = .214). For all patients with AD, 30-day mortality was significantly improved (26% pre vs 10% post; P < .001) especially among patients who underwent ATAAD surgery (23% pre vs 9% post; P = .018). Three-year Kaplan-Meier survival estimates showed survival improvement among patients with ATAAD (Log rank P-value = .019); however, this improvement does not extend to type B dissections or the overall cohort. A survival analysis landmarked to 30 days after initial presentation showed no statistical difference in survival from 30 days to 3 years post-presentation. CONCLUSIONS: A more comprehensive repair strategy in the management of patients with acute AD resulted in improved overall patient outcomes and significantly decreased 30-day mortality, even though more complex repairs were performed. The long-term impact of the changes made to our program remains to be evaluated.

Type A Acute Aortic Dissection Presenting With Cerebrovascular Accident at Advanced Age.

Our aim was to analyze outcomes of patients aged 70 years or above presenting with type A acute aortic dissection (TAAAD) and cerebrovascular accident (CVA). A retrospective analysis of the International Registry of Acute Aortic Dissection (IRAD) was conducted. Patients aged 70 years or above (n = 1449) were stratified according to presence or absence of CVA before surgery (CVA: n = 110, 7.6%). In-hospital outcomes and mortality up to 5 years were analyzed. Additionally, in-hospital outcomes of patients who received medical management were described. No patient presenting with CVA over the age of 87 years underwent surgery. The rates of in-hospital mortality and post-operative CVA were significantly higher in patients presenting with CVA (in-hospital mortality: 32.7% vs 21.7%, P = 0.008; post-operative CVA: 23.4% vs 8.3%, P < 0.001). Presence of CVA was independently associated with significantly increased in-hospital mortality (odds ratio 2.99, 95% confidence interval 1.35 - 6.60, P = 0.007). In survivors of the hospital stay, presenting CVA had no independent influence on mortality up to 5 years (hazard ratio 1.52, 95% confidence interval 0.99 - 2.31, P = 0.54). In medically managed patients, exceedingly high rates of in-hospital mortality (71.4%) and CVA (90.9%) were noted. Patients presenting with TAAAD and CVA at ≥ 70 years of age are at significantly increased risk of in-hospital mortality, although long-term mortality is not affected in hospital survivors. Medical management is associated with poor outcomes. We believe that surgical management should be offered after critical assessment of comorbidities.

T cell transgressions: Tales of T cell form and function in diverse disease states.

Insights into T cell form, function, and dysfunction are rapidly evolving. T cells have remarkably varied effector functions including protecting the host from infection, activating cells of the innate immune system, releasing cytokines and chemokines, and heavily contributing to immunological memory. Under healthy conditions, T cells orchestrate a finely tuned attack on invading pathogens while minimizing damage to the host. The dark side of T cells is that they also exhibit autoreactivity and inflict harm to host cells, creating autoimmunity. The mechanisms of T cell autoreactivity are complex and dynamic. Emerging research is elucidating the mechanisms leading T cells to become autoreactive and how such responses cause or contribute to diverse disease states, both peripherally and within the central nervous system. This review provides foundational information on T cell development, differentiation, and functions. Key T cell subtypes, cytokines that create their effector roles, and sex differences are highlighted. Pathological T cell contributions to diverse peripheral and central disease states, arising from errors in reactivity, are highlighted, with a focus on multiple sclerosis, rheumatoid arthritis, osteoarthritis, neuropathic pain, and type 1 diabetes.

Is Compliance With Guideline Recommended Follow-Up After Aortic Dissection Associated With Survival?

BACKGROUND: Patients with acute aortic dissection (AD) remain at risk for long-term complications and thus are recommended to adhere closely to American College of Cardiology and American Heart Association aorta guideline-based follow-up imaging and clinic visits. The long-term outcomes of compliance with such a model are not well understood. METHODS: This was a retrospective cohort study of patients at a regional AD center who survived hospital discharge for AD and who were analyzed by compliance with initial follow-up at 3 months and long term after AD. The primary end point was death. RESULTS: A total of 172 (66% type A; 33% type B) patients survived hospitalization and were followed up over 48 months (interquartile range [IQR], 21, 88 months). Of these patients, 122 (71%) attended the first follow-up appointment, and 90 (52%) attended more than two-thirds of recommended appointments. Patients who attended the first follow-up visit had improved long-term follow-up compliance (75% [IQR, 50%, 91%]) compared with patients who did not attend the first visit (18% [IQR, 0%, 57%]). Noncompliance with the scheduled long-term follow-up was associated with a 50% increase in the risk of death (hazard ratio, 1.6; 95% confidence interval, 1.2, 2.1; P < .001). Furthermore, in patients with low compliance (consistently attending less than one-third of follow-up appointments), the lifetime risk of death after AD was more than double that of patients with high compliance (consistently attending more than two-thirds of appointments) (hazard ratio, 2.2; 95% confidence interval, 1.5, 3.1; P < .001). CONCLUSIONS: Nearly one-third of patients with AD do not attend the first recommended follow-up visit, and such failure was associated with later noncompliance with subsequent follow-up. Low-compliant patients have double the lifetime risk of death after AD than do high-compliant patients.

Aortic Size and Clinical Care Pathways Before Type A Aortic Dissection.

Patients with aortic enlargement are recommended to undergo serial imaging and clinical follow-up until they reach surgical thresholds. This study aimed to identify aortic diameter and care of patients with aortic imaging before aortic dissection (AD). In a retrospective cohort of AD patients, we evaluated previous imaging results in addition to ordering providers and indications. Imaging was stratified as >1 or <1 year: 62 patients (53% men) had aortic imaging before AD (most recent test: 82% echo, 11% computed tomography, 6% magnetic resonance imaging). Imaging was ordered most frequently by primary care physicians (35%) and cardiologists (39%). The most frequent imaging indications were arrhythmia (11%), dyspnea (10%), before or after aortic valve surgery (8%), chest pain (6%), and aneurysm surveillance in 13%. Of all patients, 94% had aortic diameters below the surgical threshold before the AD. Imaging was performed <1 year before AD in 47% and aortic size was 4.4 ± 0.8 cm in ascending aorta and 4.0 ± 0.8 cm in sinus. In patients whose most recent imaging was >1 year before AD (1,317 ± 1,017 days), the mean ascending aortic diameter was 4.2 ± 0.4 cm. In conclusion, in a series of patients with aortic imaging before AD, the aortic size was far short of surgical thresholds in 94% of the group. In >50%, imaging was last performed >1 year before dissection.

Acute Myocardial Infarction-Like Events in Related Patients With a Desmoplakin-Associated Arrhythmogenic Cardiomyopathy.

Patients with familial arrhythmogenic cardiomyopathy typically present with ventricular arrhythmias or progressive heart failure. This paper characterizes a rare presentation of an underlying genetic cardiomyopathy with clinical manifestations mimicking an acute myocardial infarction in 2 siblings, each with the same mutation in the desmoplakin (DSP) gene. (Level of Difficulty: Advanced.).

Relation of Guideline Adherence to Outcomes in Patients With Asymptomatic Severe Primary Mitral Regurgitation.

Current guidelines empirically recommend serial clinical evaluations for asymptomatic patients with severe mitral regurgitation (MR). However, there is a paucity of data on the effectiveness of such monitoring. This study sought to examine the potential benefit of guideline adherence among asymptomatic patients with severe primary MR. Asymptomatic patients with severe primary MR who had been evaluated in the Allina Health system between January 1, 2012 and May 30, 2018 were examined. The medical records were manually reviewed for demographics, comorbidities, echocardiographic data, subsequent interventions, and clinical outcomes. Patients were grouped according to occurrence of guideline adherence, which was defined as a serial clinical evaluation with echocardiography every 12 ± 1 month until mitral valve surgery, or death. Over the study period, 246 patients (67.3 ± 15.5 years, 61.4% men) with severe, asymptomatic primary MR were identified, including 154 patients (62.6%) with and 92 patients (37.4%) without guideline adherence. Overall, there were no differences in demographics, morbidities, MR severity, or left ventricular function between patient adherence groups. During follow-up (40.9; 21.2, 58.3 months), patients with adherence more frequently had surgery or transcatheter therapy performed (64.3% vs 18.5%; p <0.001) and the time to intervention was earlier (13.6 [3.9-22.7] vs 44.2[25.6-57.3] months; p <0.001). Compared to non-adherent patients, those with guideline adherence had a significantly higher five-year survival free from all-cause mortality (92.0% vs 74.3%, p = 0.002), and freedom from death or hospitalization for heart failure (90.1% vs 69.3%, p = 0.001). Adherent patients also had a significantly better survival free from combined endpoint of death, re-hospitalization for heart failure, myocardial infarction, and stroke (84.5% vs 63.2%, p = 0.002). In patients with asymptomatic severe primary MR, guideline adherence with serial evaluations every 12 months or less is associated with earlier therapy and improved long-term outcomes. These data support educational efforts to promote guideline adherence.

Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection.

Importance: Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs. Objective: To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection. Design, Setting, and Participants: A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018). The multicenter referral center study included 29 women with aortic dissection during pregnancy or less than 12 weeks post partum in IRAD from 1998 to 2018. Main Outcomes and Measures: Clinical features of pregnancy-related aortic dissection to be studied included underlying aortopathy, aortic size, type of aortic dissection, timing of dissection, hypertension, and previous aortic surgery. Results: A total of 29 women (mean [SD] age, 32 [6] years) had pregnancy-related aortic dissection, representing 0.3% of all aortic dissections and 1% of aortic dissection in women in the IRAD. Among women younger than 35 years, aortic dissection was related to pregnancy in 20 of 105 women (19%). Thirteen women (45%) had type A aortic dissection, and 16 women (55%) had type B. Aortic dissection onset was known in 27 women (93%): 15 during pregnancy, 4 in the first trimester, and 11 in the third trimester; 12 were post partum, occurring a mean (SD) of 12.5 (14) days post partum. At type A aortic dissection diagnosis, the mean (SD) aortic diameters were sinus of Valsalva, 54.5 (5) mm and ascending aorta, 54.7 (6) mm. At type B aortic dissection diagnosis, the mean (SD) descending aortic diameter was 32.5 (5) mm. Twenty women (69%) had an aortopathy condition or a positive family history: 13 women (65%) with Marfan syndrome, 2 women (10%) with Loeys-Dietz syndrome, 2 women (10%) with bicuspid aortic valves, 2 women (10%) with a family history of aortic disease, and 1 woman (5%) with familial thoracic aortic aneurysm. Aortopathy was not recognized until after aortic dissection in 47% of the women. Twenty-eight women (97%) survived aortic dissection hospitalization. Conclusions and Relevance: Aortic dissection complicating pregnancy is rare. Most pregnancy-related aortic dissection is due to an aortopathy often not diagnosed until after aortic dissection. In this study, type A aortic dissections were associated with a dilated aorta, and type B aortic dissections often were not. Recognition of underlying conditions and risks for aortic dissection may improve management of pregnancy in women with aortopathy.

Experimental autoimmune encephalopathy (EAE)-induced hippocampal neuroinflammation and memory deficits are prevented with the non-opioid TLR2/TLR4 antagonist (+)-naltrexone.

Multiple sclerosis (MS) is associated with burdensome memory impairments and preclinical literature suggests that these impairments are linked to neuroinflammation. Previously, we have shown that toll-like receptor 4 (TLR4) antagonists, such as (+)-naltrexone [(+)-NTX], block neuropathic pain and associated spinal inflammation in rats. Here we extend these findings to first demonstrate that (+)-NTX blocks TLR2 in addition to TLR4. Additionally, we examined in two rat strains whether (+)-NTX could attenuate learning and memory disturbances and associated neuroinflammation using a low-dose experimental autoimmune encephalomyelitis (EAE) model of MS. EAE is the most commonly used experimental model for the human inflammatory demyelinating disease, MS. This low-dose model avoided motor impairments that would confound learning and memory measurements. Fourteen days later, daily subcutaneous (+)-NTX or saline injections began and continued throughout the study. Contextual and auditory-fear conditioning were conducted at day 21 to assess hippocampal and amygdalar function. With this low-dose model, EAE impaired long-term, but not short-term, contextual fear memory; both long-term and short-term auditory-cued fear memory were spared. This was associated with increased mRNA for hippocampal interleukin-1ß (IL-1ß), TLR2, TLR4, NLRP3, and IL-17 and elevated expression of the microglial marker Iba1 in CA1 and DG regions of the hippocampus, confirming the neuroinflammation observed in higher-dose EAE models. Importantly, (+)-NTX completely prevented the EAE-induced memory impairments and robustly attenuated the associated proinflammatory effects. These findings suggest that (+)-NTX may exert therapeutic effects on memory function by dampening the neuroinflammatory response in the hippocampus through blockade of TLR2/TLR4. This study suggests that TLR2 and TLR4 antagonists may be effective at treating MS-related memory deficits.

Sudden Unexpected Death Due to Myocarditis in Young People, Including Athletes.

Sudden deaths in young active people and athletes are distinctly uncommon and frequently related to highly visible cardiovascular conditions including hypertrophic cardiomyopathy and congenital coronary anomalies. Myocarditis is also a cause of sudden death in the young, but frequently under-recognized clinically, and therefore deserving of the present analysis. Two large registries were interrogated for cases of myocarditis, and clinical, demographic, and pathologic findings were assessed. Of 97 cases of myocarditis identified, ages were 19.3 ± 6.2 years, 76% male, and 58 were physically active at or near the time of death. Almost one-half of the 97 cases (47%) had a viral prodrome or symptoms (i.e., syncope, malaise, chest pain or palpitations). Nine were evaluated by cardiologists, but in none was a diagnosis of myocarditis established before death. The inflammatory cellular infiltrate was predominantly lymphocytic (67%), was most frequently multifocal (59%) and involved the conduction system (including atrioventricular node), 38%. In conclusion, myocarditis is an important but under-recognized cause of sudden death in young people including competitive athletes. Clinical diagnosis is difficult because symptoms are nonspecific and often ignored, requiring high index of suspicion for diagnosis. Our data support the ACC/AHA consensus guidelines recommending removal of individuals with myocarditis from competitive sports during recovery. Selective examination of conduction systems showed a number of cases with involvement of myocarditis, suggesting a novel mechanism for sudden death.