Extracranial pressure (ECP) monitoring in severe traumatic brain injury (TBI): A prospective study validating intra-abdominal pressure (IAP) measurement for predicting intracranial pressure (ICP).

Background: Intracranial pressure (ICP)--guided therapy is the standard of care in the management of severe traumatic brain injury (TBI). Ideal ICP monitoring technique is not yet available, based on its risks associated with bleeding, infection, or its unavailability at major centers. Authors propose that ICP can be gauged based on measuring pressures of other anatomical cavities, for example, the abdominal cavity. Researchers explored the possibility of monitoring intra-abdominal pressure (IAP) to predict ICP in severe TBI patients. Methods: We measured ICP and IAP in severe TBI patients. ICP was measured using standard right frontal external ventricular drain (EVD) insertion and connecting it to the transducer. IAP was measured using a well-established technique of vesical pressure measurement through a manometer. Results: A total of 28 patients (n = 28) with an age range of 18-65 years (mean of 32.36 years ± 13.52 years [Standard deviation]) and the median age of 28.00 years with an interquartile range (21.00-42.00 years) were recruited in this prospective study. About 57.1% (n = 16) of these patients were in the age range of 18-30 years. About 92.9% (n = 26) of the patients were male. The most common mode of injury (78.6%) was road traffic accidents (n = 22) and the mean Glasgow Coma Scale at presentation was 4.04 (range 3-9). The mean ICP measured at the presentation of this patient cohort was 20.04 mmHg. This mean ICP (mmHg) decreased from a maximum of 20.04 at the 0 h' time point (at the time of insertion of EVD) to a minimum of 12.09 at the 96 hr time point. This change in mean ICP (from 0 h to 96 h) was found to be statistically significant (Friedman Test: χ2 = 87.6, P ≤ 0.001). The mean IAP (cmH2O) decreased from a maximum of 16.71 at the 0 h' time point to a minimum of 9.68 at the 96 h' time point. This change was statistically significant (Friedman Test: χ2 = 71.8, P ≤ 0.001). The per unit percentage change in IAP on per unit percentage change in ICP we observed was correlated to each other. The correlation coefficient between these variables varied from 0.71 to 0.89 at different time frames. It followed a trend in a directly proportional manner and was found to be statistically significant (P < 0.001) in each time frame of the study. The rise in one parameter followed the rise in another parameter and vice versa. Conclusion: In this study, we established that the ICP of severe TBI patients correlates well with IAP at presentation. This correlation was strong and constant, irrespective of the timeframe during the treatment and monitoring. This study also established that draining cerebrospinal fluid to decrease ICP in severe TBI patients is reflected in IAP. The study validates that IAP is a strong proxy of ICP in severe TBI patients.

Comparative Analysis of Balloon Angioplasty Alone versus Carotid Artery Stenting for Severe Extracranial Carotid Artery Stenosis: A Four-Year Retrospective Study.

BACKGROUND: This retrospective study aimed to compare the efficacy of balloon angioplasty alone (BAA) with carotid artery stenting (CAS) for severe extracranial carotid artery stenosis (ECAS). The primary outcomes assessed were restenosis requiring retreatment and symptomatic stroke occurrence within a four-year follow-up period. METHODS: A total of 77 patients with 89 carotid artery stenoses undergoing endovascular carotid revascularization (ECR) between January 2015 and December 2019 were included. Neuroradiological evaluations, including computed tomography angiography (CTA) or magnetic resonance angiography (MRA), were performed at defined intervals. Statistical analyses were conducted to compare patient characteristics, angiographic outcomes, and clinical outcomes between the BAA and CAS groups. RESULTS: The study demonstrated successful outcomes in both groups with low adverse event rates. The overall restenosis rate was 40.2%, but severe restenosis requiring retreatment occurred in only 10 cases (7 in BAA, 3 in CAS). No significant difference was found in retreatment rates between the two groups (p=0.53). Stroke occurrence within the four-year follow-up period was observed in three patients, with no statistically significant difference between BAA and CAS groups CONCLUSIONS: This study provides valuable insights into the comparative effectiveness of BAA and CAS for severe ECAS. Despite slightly shorter intervals to restenosis in the BAA group, there was no significant difference in retreatment or stroke occurrence rates between the two procedures. BAA offers advantages in terms of retreatment options.

[EC-IC bypass for occlusion of the internal carotid artery]. / EC-IC-Bypass bei Verschluss der A. carotis interna.

BACKGROUND: There are barely any alternative treatment options to the drug treatment of hemodynamically caused cerebral ischemia, as in occlusion of the internal carotid artery. OBJECTIVE: For secondary prevention of an ischemic stroke due to carotid occlusion and hemodynamic instability, extracranial-intracranial (EC-IC) bypass surgery can be an important option in selected patients. MATERIAL AND METHODS: The development, study situation, indications and surgical technique for placement of an EC-IC bypass in cases of occlusion of the internal carotid artery are presented. RESULTS: With appropriate expertise and strict selection of patients, the placement of an EC-IC bypass enables stabilization of cerebral perfusion with a low rate of complications. CONCLUSION: The study situation is controversially discussed; nevertheless, surgical treatment in a specialized neurovascular center should at least be considered.

Differential distribution of plasma apoA-I and apoB levels and clinical significance of apoB/apoA-I ratio in ischemic stroke subtypes.

Background and purpose: Ischemic stroke (IS) is classified into clinical subtypes and likely influenced by various lipid components. Nevertheless, the roles of apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and apoB/apoA-I ratio in different IS subtypes remain underexplored. This study aimed to investigate the differential distribution of plasma apoA-I and apoB levels among IS subtypes and to evaluate the predictive value of the apoB/apoA-I ratio in assessing IS subtypes and disease severity. Methods: In this study, 406 IS patients were categorized into three IS-subtypes based on clinical manifestations and imaging assessment, including intracranial atherosclerosis-related IS patients (ICAS, n = 193), extracranial atherosclerosis-related IS patients (ECAS, n = 111), and small artery occlusion-related IS patients (SAO, n = 102). Plasma apoA-I and apoB levels were measured upon hospital admission. Random forest (RF) models were performed to assess predictive values of these apolipoproteins apoB, apoA-I and their ratio in assessing IS subtype stratification and disease severity. Results: Serum apoA-I levels were significantly lower in ICAS compared to ECAS and SAO patients (p < 0.0001), while apoB levels were higher in ICAS patients (p < 0.0001). The apoB/apoA-I ratio was significantly higher in ICAS compared to ECAS and SAO patients (p < 0.0001). Correlation analyses found a significant correlation between the apoB/apoA-I ratio and conventional lipid components. Additionally, RF models and plots of variable importance and distribution of minimal depth revealed that the apoB/apoA-I ratio played the most influential predictor in predicting IS subtypes and stenosis severity. Conclusion: Our study shows the differential distribution of apoA-I and apoB IS subtypes and reveals the significance of the apoB/apoA-I ratio in assessing IS subtypes and arterial stenosis severity. Further studies are warranted to validate these findings and enhance their clinical applicability.

Multidisciplinary Management of an Internal Carotid Artery Aneurysm Near the Skull Base.

Extracranial carotid artery aneurysms (ECAAs) are rare in comparison to the total number of peripheral artery aneurysms. Although there are multiple treatment modalities, no clear guidelines exist for the optimal management of ECAA. We describe a case of a 59-year-old female with an incidental finding of a 2.6 cm right internal carotid artery (ICA) aneurysm on computed tomography (CT) that was eventually excised via transcervical approach followed by end-to-end anastomosis with great saphenous vein (GSV) graft. To our knowledge, this case demonstrates a novel multidisciplinary approach to an ECAA near the skull base involving head and neck surgery (HNS), vascular surgery (VS), and neuro-interventional radiology (NIR).

Predictors of Good Functional Outcome in Patients with Tandem Occlusion After Revascularization Treatment: Single-Center Experience with 12-Month Follow-Up.

OBJECTIVE: The optimal management and procedural strategy for tandem occlusion (TO) in acute ischemic stroke are still unclear, as is the long-term outcome of these patients. The aim of this study was to evaluate predictors of good functional outcome in patients with TO through the analysis of demographics, clinical, and radiological data with a 1-year follow-up. METHODS: We collected data on 100 patients with TO who underwent revascularization treatments in our comprehensive stroke center. We divided patients into 2 groups: those with good functional outcome, defined as a modified Rankin Scale 0-2, and those with poor functional outcome, defined as a modified Rankin Scale 3-6 at 3, 6, and 12-month follow-up. Moreover, we investigated which variables were able to influence mortality. RESULTS: At multivariate analysis, endovascular treatment with mechanical thrombectomy combined with emergent cervical carotid artery stenting was an independent predictor of good functional outcome at 6 and 12 months (adjusted odds ratio [aOR] 4.3, confidence interval [CI] 1.49-12.31, P = 0.007) (aOR 3.5, CI 1.25-9.61, P = 0.017) and was associated with a lower rate of mortality at 3 and 6 months follow-up (aOR 0.14, CI 0.04-0.57, P = 0.006 and aOR 0.296, CI 0.97-0.902, P = 0.032, respectively). Furthermore, smoking habit was associated with a better outcome at 3-month follow-up (aOR 10.7, CI 2.2-51.6, P = 0.003) but not at 6- and 12-month. CONCLUSIONS: Our research, conducted in a small sample size of patients with acute ischemic stroke due to TO of anterior circulation, found that acute stent placement seems to be safe, improving clinical outcome, and it is associated with low rate of mortality at long-term follow-up.

Anatomical variations of the extracranial internal carotid artery: prevalence, risk factors, and imaging insights from CT-angiography.

PURPOSE: To determine the prevalence of different extracranial internal carotid artery (EICA) variations in CT angiography (CTA) of the neck and its predisposing factors. METHODS: In this retrospective study from 2021 to 2023 conducted in the radiology department of Shafa Hospital, Kerman, Iran, all patients who had undergone neck CTA were included. Expert radiologists blindly examined each CTA image for the following: EICA variations-coiling, kinking, straight morphology, and tortuosity-and the distance between the internal carotid artery and the apex of the epiglottis and the C2 lower margin. RESULTS: Of the 106 patients, the mean age was 55.9 ± 16.9 years. 64.2% were men, and 35.8% were women. Considering each patient's bilateral anatomy, the reported 70.28% (149/212) frequency of EICA variations of all arteries. Tortuosity, kinking, and coiling variation were found in 61.8%, 4.2%, and 4.2% of arteries, respectively. Also, 54.72%, 1.89%, and 0.94% of the participants had bilateral tortuosity, kinking, and coiling, respectively. There was a significant relationship between the prevalence of EICA variations and female sex, age, and hypertension. CONCLUSION: The frequency of EICA variations in arteries and patients was 70.28% and 73.58%, respectively. Tortuosity was the most common variation. Female sex, old age, and hypertension were significant risk factors for EICA variations.

3D exoscopic versus microscopic superficial temporal artery to middle cerebral artery bypass surgery for moyamoya disease - a comparative series.

PURPOSE: Superficial temporal artery to middle cerebral artery (STA-MCA) direct bypass surgery is the most common surgical procedure to treat moyamoya disease (MMD). Here, we aim to compare the performance of the 3D exoscope in bypass surgery with the gold standard operative microscope. METHODS: All direct STA-MCA bypass procedures performed at a single university hospital for MMD between 2015 and 2023 were considered for inclusion. Data were retrospectively collected from patient files and surgical video material. From 2020 onwards, bypass procedures were exclusively performed using a digital three-dimensional exoscope as visualization device. Results were compared with a microsurgical bypass control group (2015-2019). The primary endpoint was defined as total duration of surgery, duration of completing the vascular anastomosis (ischemia time), bypass patency, number of stiches to perform the anastomosis, added stiches after leakage testing of the anastomosis and the Glasgow outcome scale (GOS) at last follow-up as secondary outcome parameter. RESULTS: A total of 16 consecutive moyamoya patients underwent 21 STA-MCA bypass procedures. Thereof, six patients were operated using a microscope and ten patients using an exoscope (ORBEYE® n = 1; AEOS® n = 9). Total duration of surgery was comparable between devices (microscope: 313 min. ± 116 vs. exoscope: 279 min. ± 42; p = 0.647). Ischemia time also proved similar between groups (microscope: 43 min. ± 19 vs. exoscope: 41 min. ± 7; p = 0.701). No differences were noted in bypass patency rates. The number of stiches per anastomosis was similar between visualization devices (microscope: 17 ± 4 vs. exoscope: 17 ± 2; p = 0.887). In contrast, more additional stiches were needed in microscopic anastomoses after leakage testing the bypass (p = 0.035). CONCLUSION: Taking into account the small sample size, end-to-side bypass surgery for moyamoya disease using a foot switch-operated 3D exoscope was not associated with more complications and led to comparable clinical and radiological results as microscopic bypass surgery.

Optimal medical therapy is lacking in patients undergoing intervention for symptomatic carotid artery stenosis and protects against larger areas of cerebral infarction.

OBJECTIVES: Carotid interventions are indicated for both patients with symptomatic and a subset of patients with severe asymptomatic carotid artery stenosis (CAS). Symptomatic CAS accounts for up to 12%-25% of overall carotid interventions, but predictors of symptomatic presentation remain poorly defined. The aim of this study was to identify factors associated with symptomatic CAS in our patient population. METHODS: Between January 2015 and February 2022, an institutional retrospective cohort study of prospectively collected data on patients undergoing interventions for CAS was performed. Procedures included carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TF-CAS). Demographic data, comorbidities, procedural details, and anatomic features from various imaging modalities were collected. Comparisons were made between symptomatic (symptoms within the prior 6 months) and asymptomatic patients. RESULTS: During the study period, 279 patients who underwent intervention for symptomatic CAS were paired with a randomly selected cohort of 300 patients who underwent intervention for asymptomatic CAS from a total patient cohort of 1143 patients undergoing interventions for asymptomatic CAS. Demographic data did not differ between groups. Patients with symptomatic CAS more frequently had prior TIA/stroke (>6 months remote to the current event), but less frequently had coronary artery disease or chronic kidney disease and were less likely to receive adequate medical management including antihypertensive agents, lipid-lowering agents, and anti-platelet therapy. On multivariate analysis, remote prior TIA/stroke and lack of anti-platelet therapy remained significant. Among symptomatic patients presenting with stroke, lack of anti-platelet therapy was associated with an overall larger area of parenchymal involvement. No difference was observed with single versus dual anti-platelet therapy. Furthermore, symptomatic patients were more likely to have ulcerated plaques (30.9% vs 18%, p < .001), and symptomatic patients with ulcerated plaques more frequently had less than 50% compared to moderate/severe CAS. Nine patients who presented with symptoms had mild CAS and underwent intervention. CONCLUSIONS: Symptomatic CAS was associated with a history of remote prior symptoms and lack of anti-platelet therapy at time of presentation. Furthermore, symptomatic patients not on anti-platelet agents were more likely to have a greater area of parenchymal involvement when presenting with stroke and symptomatic patients with ulcerated plaques were more likely to have mild CAS, suggesting the role of plaque instability in symptomatic presentation. These findings underscore the importance of appropriate medical management and adherence in all patients with CAS and perhaps a role for more frequent surveillance in those with potentially unstable plaque morphology.

Vascular architecture characters and risk factors analysis of unstable moyamoya disease.

Background: In some MMD patients, the digital subtraction angiography (DSA) examination found, occlusion in the ipsilateral internal carotid artery or middle cerebral artery, accompanied by the formation of numerous moyamoya vessels. Conversely, the contralateral internal carotid artery or middle cerebral artery shows signs of stenosis without the presence of moyamoya vessels. Notably, cerebral perfusion studies reveal a similar or even more severe reduction in perfusion on the occluded side compared to the stenotic side. Importantly, clinical symptoms in these patients are typically attributed to ischemia caused by the stenotic side. This condition is referred to as unstable moyamoya disease (uMMD). Objective: This clinical research focuses on evaluating risk factors related to MMD and developing strategies to minimize postoperative complications. The study aims to analyze vascular characteristics and identify potential risk factors in patients with uMMD. Methods: The authors reviewed consecutive cases with complete clinical and radiological documentation of patients who underwent surgery between January 2018 and June 2023. Univariate analysis and multivariate logistic regression analysis were employed to understand the risk factors and prognosis of postoperative complications in uMMD. Results: Postoperative complications were retrospectively analyzed in 1481 patients (aged 14 to 65). Among them, 1,429 patients were assigned to the conventional treatment group, while 52 were in the unstable moyamoya disease group. The uMMD treatment group showed a significantly higher incidence of early postoperative complications such as RIND, cerebral infarction, and cerebral hemorrhage (p < 0.05). Univariate and multivariate logistic regression analyses were conducted on the postoperative complications of 52 uMMD patients. Initial symptoms of stenosis ≤50% (univariate: p = 0.008, multivariate: p = 0.015; OR [95% CI] =23.149 [1.853-289.217]) and choosing occluded side surgery (univariate: p = 0.043, multivariate: p = 0.018; OR [95% CI] =0.059 [0.006-0.617]) were identified as significant risk factors for postoperative neurological complications. Conclusion: Compared to the conventional treatment group, uMMD has higher complication rates, with vascular stenosis degree and surgical side selection identified as significant risk factors. A comprehensive understanding of preoperative clinical symptoms and vascular characteristics in moyamoya disease patients, coupled with the formulation of rational surgical plans, contributes positively to decreasing postoperative mortality and disability rates in uMMD.

Which is a more appropriate recipient for posterior circulation bypass surgery: V3 or V2? Differences in underlying disease and lesion sites between extracranial vertebral artery dissection and atherosclerotic changes. Illustrative cases.

BACKGROUND: Revascularization for extracranial vertebral artery dissection or vertebral artery atherosclerotic occlusive lesions caused by vertebrobasilar insufficiency or posterior circulation infarction is relatively rare. When bypassing the cervical external carotid artery (ECA) or common carotid artery (CCA) using a radial artery (RA) or saphenous vein (SV) graft, it is difficult to determine whether the recipient site should be the V2 or V3 portion. OBSERVATIONS: In case 1, cervical ECA-RA-V3 bypass was performed for bilateral extracranial vertebral artery dissection with the onset of ischemia, and cervical CCA-SV-V3 bypass was added 12 days later. Nine years after surgery, the bilateral vertebral artery dissection had improved, and the patient still had a patent bypass. In case 2, cervical ECA-RA-V2 bypass was performed for arteriosclerotic bilateral extracranial vertebral artery occlusion. The bypass was patent 5 years after surgery. The postoperative course was uneventful in both patients. LESSONS: The authors present cases of posterior fossa revascularization using the vertebral artery V3 and V2 portions via skull base surgery and note that it is important to consider each patient's individual characteristics when selecting the V3 or V2 portion.

Cervicocerebral Atherosclerosis Burden Increases Long-Term Mortality in Patients With Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND: The influence of burden of atherosclerosis in the brain supplying arteries on mortality in patients with acute ischemic stroke or transient ischemic attack is poorly known. We assessed whether total burden of atherosclerosis within cervicocerebral arteries is associated with long-term mortality. METHODS AND RESULTS: A total of 406 patients (median age, 71.8 years; 57.9% male) with acute ischemic stroke or transient ischemic attack were included and their cervicocerebral arteries imaged with computed tomography angiography. The presence of atherosclerotic findings was scored for 25 artery segments and points were summed as a Cervicocerebral Atherosclerosis Burden (CAB) score, analyzed as quartiles. Data on all-cause mortality came from Statistics Finland. After a median follow-up of 7.3 years, 147 (33.5%) patients had died. Compared with surviving patients, those who died had a higher median CAB score (5, interquartile range 2-10 versus 11, 7-16; P<0.001). Cumulative mortality increased from 8.9% (95% CI, 7.0-10.8) in the lowest to 61.4% (95% CI, 55.4-67.4) in the highest quartile of CAB score. Adjusted for demographics, cardiovascular risk factors, secondary preventive medication, and admission National Institute of Health Stroke Scale score, every CAB score point increased probability of death by 3%. Analyzed in quartiles, the highest CAB quartile was associated with a 2.5-fold likelihood of all-cause mortality. CONCLUSIONS: The main findings of our study were the increasing mortality with the total burden of computed tomography angiography-defined atherosclerosis in the brain supplying arteries after ischemic stroke or transient ischemic attack and that the CAB score-integrating this pathology-independently increased all-cause mortality.

Correlation Between Optical Coherence Tomography Angiography Findings at 3 to 6 Weeks and Functional Outcome at 3 Months Following Acute Ischaemic Stroke Due to Extracranial Carotid Artery Atherosclerotic Disease.

We wanted to evaluate if optical coherence tomography angiography OCTA findings could predict the functional outcome in extracranial carotid artery atherosclerotic disease (ECAD) associated stroke. This exploratory study was performed on adults with acute ischaemic stroke due to ECAD at 3-6 weeks following stroke onset with risk factor matched controls without carotid artery stenosis. Twenty-three stroke patients (cases) and 23 controls were enrolled. There was significant difference between cases and controls in deep vessel density at the macula (p = .0007) and in radial peripapillary capillary perfusion density (RPCPD) at the optic nerve head (ONH) (p = .0007). Statistically significant difference was noted in the total superficial vessel density (SVD) at the macula (SVD within 1 standard deviation [SD] versus SVD beyond 1 SD of control data) in the ipsilateral eye and functional outcome at 3 months (poor versus very good outcome, modified Rankin scale [mRS] 0-1 versus mRS 2-6, respectively; p = .0361). There was statistically insignificant correlation between the RPCPD at the ONH and the National Institutes of Health Stroke Scale score at admission, mRS at discharge, and mRS at 3 months following stroke onset (r = .33, r = .35, r = .39; p = .11, p = .09, p = .06, respectively). The findings of this exploratory study suggested that OCTA findings may predict 3 month outcomes in cases of ECAD-related stroke and could be useful in decision making in future intervention studies as to whether intervene or not in patients having critical or non-critical ECAD for preventing stroke.

A case report of Extra-neurologic metastasis of ventricular meningioma with literature review.

Ventricular meningiomas are neoplastic cells originating from the ependymal lining of the central canal of the spinal cord and the ventricles of the brain. These tumorigenic cells predominantly manifest in the fourth ventricle, followed by the spinal cord. Most intraparenchymal ventricular meningiomas are located within the brain tissue, exhibiting a higher degree of malignancy compared to their intracerebroventricular counterparts. While intracranial dissemination and metastasis to the spinal cord can occur, extra-neurologic metastasis is an exceedingly rare phenomenon that lacks a clear elucidation regarding its underlying mechanism. The authors presented a case of supratentorial brain parenchymal type ventricular meningioma surgical treatment in a young female patient, occurring two years after the development of multiple metastases in both lungs, pleura, and mediastinum. This may be attributed to the high malignancy degree and strong invasiveness of this lesion, as well as its proximity to the dura mater and venous sinus. The craniotomy provided an opportunity for tumor cells to invade the adjacent venous sinus, leading to dissemination through the blood system. Additionally, postoperative radiation and chemotherapy were administered to inhibit tumor angiogenesis; however, these treatments also increased the likelihood of tumor cell invasion into neighboring brain tissues and distant metastasis.

Endovascular Management of a Ruptured Aneurysm on a Posterior Inferior Cerebellar Artery with Extradural C2-Origin: Case Report and Literature Review.

Extracranial vascular pathology uncommonly causes intracranial subarachnoid hemorrhage (SAH). Among possible lesions are aneurysms at the craniocervical junction arising from a posterior inferior cerebellar artery (PICA) with an extradural origin. We describe a case of a 55-year-old female presenting with a sudden and severe headache. A computed tomography scan revealed a SAH within the fourth ventricle and cervical spinal canal, and a ruptured saccular aneurysm on a PICA with extradural C2-origin. Despite difficult access anatomy, endovascular treatment was feasible and resulted in subtotal initial occlusion and preservation of distal PICA flow. Upon 3-month follow-up, the aneurysm was completely occluded with a patent PICA. The patient's clinical status remained stable at the 1.5-year follow-up. In conclusion, we present a rare case of an aneurysm originating from a PICA with extradural C2-origin that was treated endovascularly with preservation of the PICA.

Cranial and extracranial manifestations of giant cell arteritis: a single-center observational study.

INTRODUCTION: Giant cell arteritis (GCA) presents two major phenotypes - cranial (cGCA) and extracranial (exGCA). exGCA may be overlooked. The study aimed to compare the clinical characteristics between cGCA and exGCA. METHODS: Electronic medical records of patients treated between January 2015 and July 2023 at the Department of Rheumatology were searched for the diagnosis of GCA. The clinical characteristics of patients with cGCA, exGCA, and overlapping GCA manifestations were compared. RESULTS: Out of 32 patients with GCA, 20 had cGCA, 7 had exGCA, and 5 had overlap manifestations. The groups did not differ significantly in demographics, clinical signs/symptoms, or laboratory test results. Importantly, the combined group of patients with exGCA and overlap GCA had a statistically significant delay in initiating treatment (median 12 weeks) compared to patients with cGCA (median 4 weeks; p = 0.008). CONCLUSION: Our study confirmed the insidious nature of exGCA, which lacks distinctive clinical symptoms and consequently leads to delayed treatment.

Therapeutic Targeting of DNA Repair Pathways in Pediatric Extracranial Solid Tumors: Current State and Implications for Immunotherapy.

DNA damage is fundamental to tumorigenesis, and the inability to repair DNA damage is a hallmark of many human cancers. DNA is repaired via the DNA damage repair (DDR) apparatus, which includes five major pathways. DDR deficiencies in cancers give rise to potential therapeutic targets, as cancers harboring DDR deficiencies become increasingly dependent on alternative DDR pathways for survival. In this review, we summarize the DDR apparatus, and examine the current state of research efforts focused on identifying vulnerabilities in DDR pathways that can be therapeutically exploited in pediatric extracranial solid tumors. We assess the potential for synergistic combinations of different DDR inhibitors as well as combinations of DDR inhibitors with chemotherapy. Lastly, we discuss the immunomodulatory implications of targeting DDR pathways and the potential for using DDR inhibitors to enhance tumor immunogenicity, with the goal of improving the response to immune checkpoint blockade in pediatric solid tumors. We review the ongoing and future research into DDR in pediatric tumors and the subsequent pediatric clinical trials that will be critical to further elucidate the efficacy of the approaches targeting DDR.