Comparison of head positioning using the Mayfield skull clamp versus padded headrest in anterior cervical discectomy and fusion surgery.

Background: Anterior cervical discectomy and fusion (ACDF) is a commonly implemented surgical intervention for a variety of pathologies affecting the cervical spine. The current literature and daily practice reveal variations on patient head positioning for this procedure with both rigid fixations in the Mayfield skull clamp as well as use of a padded headrest being used. In this study, we therefore examine whether patients undergoing surgery using head positioning in the Mayfield skull clamp versus a padded headrest differ in regard to adverse events, surgical parameters and clinical outcome. Methods: A single-center, retrospective analysis of 121 patients treated with ACDF for degenerative disease, traumatic cervical spine injury and infectious disease between November 2019 and March 2023 was performed. Clinical and imaging data for 59 patients positioned in the Mayfield skull clamp and 62 patients positioned in a padded headrest were evaluated using electronic medical records. In addition to demographic data, surgical indications, procedures performed were analyzed for both groups. Level of training (chief, attending and resident), length of surgery and intraoperative radiation exposure (measured by dose area product and total radiation time) were also examined. Finally, modified Rankin Scale (mRS) preoperatively and at last follow-up as well as adverse events were compared between groups. Results: We found no statistically significant differences between the Mayfield and headrest groups regarding surgical indications (P=0.583), procedures performed (P=0.069), level of training of the surgeon (P=0.218), length of surgery (P=0.752), adverse events (P=0.619) or neurological impairment (P=0.080) following surgical intervention. There was a significant difference regarding dose area product between both groups with patients positioned in the Mayfield skull clamp showing lower mean levels of radiation than those in the headrest group (99 versus 131 cGy/cm2; P=0.003). Conclusions: Patient positioning using the Mayfield skull clamp may reduce required radiation exposure during ACDF procedures versus use of a padded headrest.

Influence of Blood Components on Neuroinflammation, Blood-Brain Barrier Breakdown, and Functional Damage After Acute Subdural Hematoma in Rats.

A central component of injury development after acute subdural hematoma (ASDH) is the increased intracranial pressure and consecutive mechanical reduction of cerebral blood flow (CBF). However, the role of different blood constituents in ASDH as additional lesioning factors remains unclear. This study examines the influence of blood components on neuroinflammation, blood-brain barrier (BBB) breakdown, and functional deficits in a rat model of ASDH. We infused corpuscular (whole blood, whole blood lysate, and red cell blood) and plasmatic (blood plasma, anticoagulated blood plasma, and aqueous isotonic solution) blood components into the subdural space while CBF was monitored. Rats then underwent behavioral testing. Lesion analysis and immunohistochemistry were performed 2 days after ASDH. Inflammatory reaction was assessed using staining for ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein, interleukin-1ß, tumor necrosis factor-alpha, and membrane attack complex. Integrity of the BBB was evaluated with albumin and matrix metalloproteinase 9 (MMP9) staining. We observed a significant drop in CBF in the corpuscular group (75% ± 7.5% of baseline) with distinct post-operative deficits and larger lesion volume compared to the plasmatic group (13.6 ± 5.4 vs. 1.3 ± 0.4 mm3). Further, inflammation was significantly increased in the corpuscular group with stronger immunoreaction. After whole blood infusion, albumin and MMP9 immunoreaction were significantly increased, pointing toward a disrupted BBB. The interaction between corpuscular and plasmatic blood components seems to be a key factor in the detrimental impact of ASDH. This interaction results in neuroinflammation and BBB leakage. These findings underscore the importance of performing surgery as early as possible and also provide indications for potential pharmacological targets.

The Role of Tumor-Associated Hypothalamic Involvement in Surgical Treatment and Long-Term Outcome in Adult Patients with Craniopharyngioma.

INTRODUCTION: Hypothalamic invasion in pediatric patients with craniopharyngioma negatively influences clinical outcomes. It has been shown that radiologic classification of hypothalamic invasion can effectively predict surgical strategies to minimize postoperative comorbidities in pediatric patients. However, no comparative analysis has been performed in adult patients with craniopharyngioma. This study implements the previously established radiologic classification to characterize postoperative morbidity, surgical outcome, and distress in adult patients with craniopharyngioma. METHODS: Electronic medical records of 22 adult patients with craniopharyngioma were used to analyze patient demographics, surgical data, endocrinologic and ophthalmologic status, and histopathology in a retrospective single-center study. Questionnaires regarding postoperative distress (National Comprehensive Cancer Network Distress Thermometer and Problem List), comorbidities (Charlson Comorbidity Index), employment status, and need for supportive care were distributed. Magnetic resonance imaging scans were categorized according to Puget et al. RESULTS: Patients with hypothalamic involvement show significantly higher rates of postoperative diabetes insipidus and higher scores on the National Comprehensive Cancer Network Distress Thermometer. This significant difference was lost when considering postoperative Puget grades. Puget grades 1 and 2 were found to be associated with the use of a subfrontal surgical approach (hazard ratio, 4.080; confidence interval, 1.153-14.431; P = 0.029). CONCLUSIONS: Our results point toward a possible predictive role of preoperative hypothalamic invasion for postoperative diabetes insipidus as well as higher perceived levels of distress after surgery, which may be established in larger patient cohorts. Furthermore, a subfrontal surgical approach seems to be predicted by tumors with hypothalamic invasion. In this case, preoperative magnetic resonance imaging grading may help guide the planning of an optimal surgical strategy for adults with craniopharyngioma to reduce postoperative morbidity.

Early Onset of Rapid Lesion Growth in an Acute Subdural Hematoma Model in Rats.

OBJECTIVE: Acute subdural hematoma (ASDH) leads to the highest mortality rates of all head injuries with secondary brain damage playing a pivotal role in terms of morbidity and mortality. In patients with ASDH, a delay in surgery leads to disproportional mortality. The benefit of (very) early therapy is therefore, a target of ongoing research. As the process of delayed brain damage in ASDH has not yet been described, this study therefore aimed to examine secondary lesion growth in an experimental rat model of ASDH to define the ideal timing for testing potential neuroprotective therapies. METHODS: Cerebral blood flow was monitored during ASDH induction with 300 µl of autologous blood. Lesion growth was characterized using Hematoxylin-Eosin- , Cresyl-Violet-, and Fluoro-Jade B-staining for early signs of neuronal degeneration. Histological evaluations were performed between 15 minutes and 24 hours after ASDH. RESULTS: There was a significant reduction of cerebral blood flow after ASDH. Fluoro-Jade B-positive cells were visible 15 minutes after ASDH in the lesioned hemisphere. Nonlinear growth of lesion volume from 3.7 ± 0.4 mm3 to 17.5 ± 0.6 mm3 was observed at 24 hours in Hematoxylin-Eosin-staining. CONCLUSIONS: The most damage develops between 15 minutes and 1 hour and again between 2 and 6 hours after ASDH. The time course of lesion growth supports the approach of early surgery for patients. It furthermore constitutes a basis for further ASDH research with more clearly defined time windows for therapy in animal models.

The Development and Effect of Systemic Hypertension on Clinical and Radiological Outcome in Adult Moyamoya Angiopathy Following Revascularization Surgery: Experience of a Single European Institution.

Patients with Moyamoya Angiopathy (MMA) display structurally altered vessels with decreased cerebral autoregulatory capacity, so aggressive lowering of systemic hypertension may aggravate ischemic symptoms, whereas uncontrolled hypertension may promote hemorrhage. This study provides an in-depth analysis of the role of hypertension in adult MMA patients including long-term analysis of clinical and radiological development. In this single-center retrospective analysis of 137 adult MMA patients with 206 surgically treated hemispheres angiographic images, clinical/operative data were reviewed and scored. Univariate Cox-regression analysis was performed to evaluate hypertension as a predictor for negative angiographic and clinical outcomes following revascularization surgery. A total of 50% of patients were being treated for hypertension prior to the first surgery. Patients with and without hypertension did not differ in terms of age, gender, diagnosis, symptom onset or disease severity (Berlin and Suzuki Grades). Although hypertension did not statistically significantly affect postoperative collaterals, moyamoya vessels or STA-MCA bypass patency, patients with hypertension showed higher rates of bypass patency and better bypass filling compared to those without hypertension. No significant differences in adverse events were found in patients with and without systemic hypertension and the presence of systemic hypertension was not found to predict negative clinical or radiological outcomes. In conclusion, the rate of systemic hypertension in MMA patients appears to be higher than the general population; however, this is not associated with an increased risk of postoperative complications or negative angiographic development following revascularization procedures. Systemic hypertension may also positively influence the rate of bypass patency and filling following revascularization procedures.

Predictors of clinical outcomes in space-occupying cerebellar infarction undergoing suboccipital decompressive craniectomy.

Introduction: Despite current clinical guidelines recommending suboccipital decompressive craniectomy (SDC) in cerebellar infarction when patients present with neurological deterioration, the precise definition of neurological deterioration remains unclear and accurate timing of SDC can be challenging. The current study aimed at characterizing whether clinical outcomes can be predicted by the GCS score immediately prior to SDC and whether higher GCS scores are associated with better clinical outcomes. Methods: In a single-center, retrospective analysis of 51 patients treated with SDC for space-occupying cerebellar infarction, clinical and imaging data were evaluated at the time points of symptom onset, hospital admission, and preoperatively. Clinical outcomes were measured by the mRS. Preoperative GCS scores were stratified into three groups (GCS, 3-8, 9-11, and 12-15). Univariate and multivariate Cox regression analyses were performed using clinical and radiological parameters as predictors of clinical outcomes. Results: In cox regression analysis GCS scores of 12-15 at surgery were significant predictors of positive clinical outcomes (mRS, 1-2). For GCS scores of 3-8 and 9-11, no significant increase in proportional hazard ratios was observed. Negative clinical outcomes (mRS, 3-6) were associated with infarct volume above 6.0 cm3, tonsillar herniation, brainstem compression, and a preoperative GCS score of 3-8 [HR, 2.386 (CI, 1.160-4.906); p = 0.018]. Conclusion: Our preliminary findings suggest that SDC should be considered in patients with infarct volumes above 6.0 cm3 and with GCS between 12 and 15, as these patients may show better long-term outcomes than those in whom surgery is delayed until a GCS score below 11.

Implementation of the "No ICU - Unless" approach in postoperative neurosurgical management in times of COVID-19.

Following elective craniotomy, patients routinely receive 24-h monitoring in an intensive care unit (ICU). However, the benefit of intensive care monitoring and treatment in these patients is discussed controversially. This study aimed to evaluate the complication profile of a "No ICU - Unless" strategy and to compare this strategy with the standardized management of post-craniotomy patients in the ICU. Two postoperative management strategies were compared in a matched-pair analysis: The first cohort included patients who were managed in the normal ward postoperatively ("No ICU - Unless" group). The second cohort contained patients routinely admitted to the ICU (control group). Outcome parameters contained detailed complication profile, length of hospital and ICU stay, duration to first postoperative mobilization, number of unplanned imaging before scheduled postoperative imaging, number and type of intensive care interventions, as well as pre- and postoperative modified Rankin scale (mRS). Patient characteristics and clinical course were analyzed using electronic medical records. The No ICU - Unless (NIU) group consisted of 96 patients, and the control group consisted of 75 patients. Complication rates were comparable in both cohorts (16% in the NIU group vs. 17% in the control group; p = 0.123). Groups did not differ significantly in any of the outcome parameters examined. The length of hospital stay was shorter in the NIU group but did not reach statistical significance (average 5.8 vs. 6.8 days; p = 0.481). There was no significant change in the distribution of preoperative (p = 0.960) and postoperative (p = 0.425) mRS scores in the NIU and control groups. Routine postoperative ICU management does not reduce postoperative complications and does not affect the surgical outcome of patients after elective craniotomies. Most postoperative complications are detected after a 24-h observation period. This approach may represent a potential strategy to prevent the overutilization of ICU capacities while maintaining sufficient postoperative care for neurosurgical patients.

Improved pasireotide response in USP8 mutant corticotroph tumours in vitro.

Cushing's disease is a rare but devastating and difficult to manage condition. The somatostatin analogue pasireotide is the only pituitary-targeting pharmaceutical approved for the treatment of Cushing's disease but is accompanied by varying efficacy and potentially severe side effects. Finding means to predict which patients are more likely to benefit from this treatment may improve their management. More than half of corticotroph tumours harbour mutations in the USP8 gene, and there is evidence of higher somatostatin receptor 5 (SSTR5) expression in the USP8-mutant tumours. Pasireotide has a high affinity for SSTR5, indicating that these tumours may be more sensitive to treatment. To test this hypothesis, we examined the inhibitory action of pasireotide on adrenocorticotrophic hormone synthesis in primary cultures of human corticotroph tumour with assessed USP8 mutational status and in immortalized murine corticotroph tumour cells overexpressing human USP8 mutants frequent in Cushing's disease. Our in vitro results demonstrate that pasireotide exerts a higher antisecretory response in USP8-mutant corticotroph tumours. Overexpressing USP8 mutants in a murine corticotroph tumour cell model increased endogenous somatostatin receptor 5 (Sstr5) transcription. The murine Sstr5 promoter has two binding sites for the activating protein 1 (AP-1) and USP8 mutants possibly to mediate their action by stimulating AP-1 transcriptional activity. Our data corroborate the USP8 mutational status as a potential marker of pasireotide response and describe a potential mechanism through which USP8 mutants may regulate SSTR5 gene expression.

Endothelial EphrinB2 Regulates Sunitinib Therapy Response in Murine Glioma.

Vascular guidance is critical in developmental vasculogenesis and pathological angiogenesis. Brain tumors are strongly vascularized, and antiangiogenic therapy was anticipated to exhibit a strong anti-tumor effect in this tumor type. However, vascular endothelial growth factor A (VEGFA) specific inhibition had no significant impact in clinical practice of gliomas. More research is needed to understand the failure of this therapeutic approach. EphrinB2 has been found to directly interact with vascular endothelial growth factor receptor 2 (VEGFR2) and regulate its activity. Here we analyzed the expression of ephrinB2 and EphB4 in human glioma, we observed vascular localization of ephrinB2 in physiology and pathology and found a significant survival reduction in patients with elevated ephrinB2 tumor expression. Induced endothelial specific depletion of ephrinB2 in the adult mouse (efnb2i∆EC) had no effect on the quiescent vascular system of the brain. However, we found glioma growth and perfusion altered in efnb2i∆EC animals similar to the effects observed with antiangiogenic therapy. No additional anti-tumor effect was observed in efnb2i∆EC animals treated with antiangiogenic therapy. Our data indicate that ephrinB2 and VEGFR2 converge on the same pathway and intervention with either molecule results in a reduction in angiogenesis.

LPPR5 Expression in Glioma Affects Growth, Vascular Architecture, and Sunitinib Resistance.

Despite intensive research, glioblastoma remains almost invariably fatal. Various promising drugs targeting specific aspects of glioma biology, in addition to or as an alternative to antiproliferative chemotherapy, were not successful in larger clinical trials. Further insights into the biology of glioma and the mechanisms behind the evasive-adaptive response to targeted therapies is needed to help identify new therapeutic targets, prognostics, or predictive biomarkers. As a modulator of the canonically oncogenic Rho-GTPase pathway, Lipid phosphate phosphatase-related protein type 5 (LPPR5) is pivotal in influencing growth, angiogenesis, and therapeutic resistance. We used a GL261 murine orthotopic allograft glioma model to quantify the tumor growth and to obtain tissue for histological and molecular analysis. Epicortical intravital epi-illumination fluorescence video microscopy of the tumor cell spheroids was used to characterize the neovascular architecture and hemodynamics. GL261-glioma growth was delayed and decelerated after LPPR5 overexpression (LPPR5OE). We observed increased tumor cell apoptosis and decreased expression and secretion of vascular endothelial growth factor A in LPPR5OE glioma. Hence, an altered micro-angioarchitecture consisting of dysfunctional small blood vessels was discovered in the LPPR5OE tumors. Sunitinib therapy eliminated these vessels but had no effect on tumor growth or apoptosis. In general, LPPR5 overexpression generated a more benign, proapoptotic glioma phenotype with delayed growth and a dysfunctional vascular architecture.

Evaluation of a Novel Three-Dimensional Robotic Digital Microscope (Aeos) in Neurosurgery.

OBJECTIVE: Current literature debates the role of newly developed three-dimensional (3D) Exoscopes in the daily routine of neurosurgical practice. So far, only a small number of cadaver lab studies or case reports have examined the novel Aesculap Aeos Three-Dimensional Robotic Digital Microscope. This study aims to evaluate the grade of satisfaction and intraoperative handling of this novel system in neurosurgery. METHODS: Nineteen neurosurgical procedures (12 cranial, 6 spinal and 1 peripheral nerve) performed over 9 weeks using the Aeos were analyzed. Ten neurosurgeons of varying levels of training were included after undergoing device instruction and training. Following every surgery, a questionnaire consisting of 43 items concerning intraoperative handling was completed. The questionnaires were analyzed using descriptive statistics. RESULTS: No intraoperative complications occurred. Surgical satisfaction was ranked high (78.95%). In total, 84.21% evaluated surgical ergonomics as satisfactory, while 78.95% of the surgeons would like to use this system frequently. Image quality, independent working zoom function and depth of field were perceived as suboptimal by several neurosurgeons. CONCLUSION: The use of Aeos is feasible and safe in microsurgical procedures, and surgical satisfaction was ranked high among most neurosurgeons in our study. The system might offer advanced ergonomic conditions in comparison to conventional ocular-based microscopes.

Surgical Management of Failed Revascularization in Moyamoya Vasculopathy.

Objectives: Moyamoya vasculopathy (MMV) is a rare stenoocclusive cerebrovascular disease associated with increased risk of ischemic and hemorrhagic stroke, which can be treated using surgical revascularization techniques. Despite well-established neurosurgical procedures performed in experienced centers, bypass failure associated with neurological symptoms can occur. The current study therefore aims at characterizing the cases of bypass failure and repeat revascularization at a single center. Methods: A single-center retrospective analysis of all patients treated with revascularization surgery for MMV between January 2007 and December 2019 was performed. Angiographic data, cerebral blood flow analysis [H2O PET or single-photon emission CT (SPECT)], MRI, and clinical/operative data including follow-up assessments were reviewed. Results: We identified 308 MMV patients with 405 surgically treated hemispheres. Of the 405 hemispheres treated, 15 patients (3.7%) underwent repeat revascularization (median age 38, time to repeat revascularization in 60% of patients was within 1 year of first surgery). The most common cause of repeat revascularization was a symptomatic bypass occlusion (80%). New ischemic lesions were found in 13% of patients prior to repeat revascularization. Persistence of reduced or progressive worsening of cerebrovascular reserve capacity (CVRC) compared with preoperative status was observed in 85% of repeat revascularization cases. Intermediate-flow bypass using a radial artery graft was most commonly used for repeat revascularization (60%) followed by re-superficial temporal artery to middle cerebral artery (re-STA-MCA) bypass (26%). High-flow bypass using a saphenous vein graft and using an occipital artery to MCA bypass was each used once. Following repeat revascularization, no new ischemic events were recorded. Conclusion: Overall, repeat revascularization is needed only in a small percentage of the cases in MMV. A rescue surgery should be considered in those with neurological symptoms and decreased CVRC. Intermediate-flow bypass using a radial artery graft is a reliable technique for patients requiring repeat revascularization. Based on our institutional experience, we propose an algorithm for guiding the decision process in cases of bypass failure.

Health-Related Quality of Life in Adult Patients with Craniopharyngioma.

OBJECTIVE: Craniopharyngiomas (CPs) are benign, dysontogenetic tumors associated with complex endocrinologic and neurologic symptoms and high morbidity. The aim of this study is to elucidate modifiable effectors of health-related quality of life (HrQoL) of adult patients with CP following neurosurgical intervention using standardized instruments as well as descriptive analysis. METHODS: HrQoL (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 and BN20) was evaluated in 20 adult patients with CP. We examined pre- as well as postoperative radiologic, hormonal, and symptom-oriented data in a retrospective analysis. Surgical approach, postoperative complications, and extent of resection were recorded. Additional descriptive analysis was performed on case records of all patients with HrQoL results. RESULTS: Long-term follow-up of HrQoL (mean of 75 months) was lower than the in healthy reference group (CP = 58, reference = 75). The most common postoperative complaints were endocrinologic disturbances (88%). Overall, univariate and multivariate logistic regression analysis revealed no significant predictors of reduced postoperative HrQoL. Descriptive analysis did, however, reveal a cluster of patients among those with the lowest global HrQoL which reported new postoperative anosmia and ageusia. CONCLUSIONS: The global HrQoL of our cohort showed a substantial reduction compared with a healthy reference population. Postoperative hyposmia and ageusia is found in patients with the lowest postoperative HrQoL who otherwise had no new significant endocrinologic or neurologic complications. As these symptoms are not regularly accounted for in the HrQoL instruments used in this study, further analysis is needed to determine the possible significance of this complication in CP surgery, and it may affect the choice of surgical approach as well as the information patients receive before consenting to surgery.

Spinal Cord Stimulation: A Reasonable Alternative Treatment in Patients With Symptomatic Adult Scoliosis for Whom Surgical Therapy Is Not Suitable? A Pilot Study.

INTRODUCTION: In adult scoliosis, dorsal instrumentation and fusion can provide significant improvement of pain and disability scores (Owestry Index); however, complication rates of up to 39% have been reported. As such, recent attempts have been made at expanding the surgical spectrum to include less invasive techniques in patients such as neuromodulation, specifically spinal cord stimulation (SCS). We therefore aimed to evaluate its use in a larger cohort of adult scoliosis patients in the form of a pilot study. MATERIALS AND METHODS: We analyzed prospectively collected data from 18 adult scoliosis patients receiving SCS treatment in our institution between February 2019 and May 2020. Clinical follow-up was performed at 3, 6, and 12 months following implantation of an epidural SCS System. Patients reported numeric rating scale (NRS) values for the categories of lower back pain (LBP) and regional pain (RP) both at rest and in motion. Further, SF-36, ADS-K, PSQI, and ODI forms were completed. The study was approved by the institutional Ethics Committee (EA2/093/13). RESULTS: Initial preoperative NRS of LBP at rest was significantly reduced following SCS at three (45% reduction, p = 0.005) and six (43% reduction, p = 0.009) months follow-up. LBP in motion was also reduced at three (27% reduction, p = 0.002) and six (33% reduction vs. preoperative, p = 0.005) months. RP at rest was reduced at three (38% reduction, p = 0.003) and six (37% reduction, p = 0.007) and in movement at three (29% reduction, 0.006) and six (32% reduction, p = 0.011). Loss of thoracic kyphosis and increased pelvic incidence were associated with worse NRS response to SCS stimulation at six months follow-up. DISCUSSION: In overweight, older adults for whom the risks of corrective surgery must be carefully considered, neuromodulation can significantly reduce LBP as well as regional pain in the first six months following implantation. These findings may provide a reasonable alternative in patients not willing or eligible to undergo extensive corrective surgery.

Quality Assurance and Continuing Education: A Cyclic Approach for Maintaining High Quality Data in a High Volume Cancer Registry.

Quality Assurance and Education are 2 areas of the Cancer Registry that go hand in hand. High-quality data can only be maintained through routine surveillance of data quality coupled with tailored continuing education of certified tumor registrars (CTRs). However, the magnitude of information a CTR is required to know, the rapid frequency with which standards change, and growing demands on the time of the CTRs can be roadblocks to maintaining quality in the Cancer Registry. Here we describe a robust approach to quality assurance in a high-volume hospital-based Cancer Registry, leveraging a repeated cycle of quality assessment and educational activities targeting identified opportunities for improvement. Establishing such an approach encourages the professional development of CTRs while simultaneously ensuring the highest quality data for use in population-based cancer surveillance, cancer research, and patient care.

Hypoxia and the hypoxia inducible factor 1α activate protein kinase A by repressing RII beta subunit transcription.

Overactivation of the cAMP signal transduction pathway plays a central role in the pathogenesis of endocrine tumors. Genetic aberrations leading to increased intracellular cAMP or directly affecting PKA subunit expression have been identified in inherited and sporadic endocrine tumors, but are rare indicating the presence of nongenomic pathological PKA activation. In the present study, we examined the impact of hypoxia on PKA activation using human growth hormone (GH)-secreting pituitary tumors as a model of an endocrine disease displaying PKA-CREB overactivation. We show that hypoxia activates PKA and enhances CREB transcriptional activity and subsequently GH oversecretion. This is due to a previously uncharacterized ability of HIF-1α to suppress the transcription of the PKA regulatory subunit 2B (PRKAR2B) by sequestering Sp1 from the PRKAR2B promoter. The present study reveals a novel mechanism through which the transcription factor HIF-1α transduces environmental signals directly onto PKA activity, without affecting intracellular cAMP concentrations. By identifying a point of interaction between the cellular microenvironment and intracellular enzyme activation, neoplastic, and nonneoplastic diseases involving overactivated PKA pathway may be more efficiently targeted.

Impact of histological thrombus composition on preinterventional thrombus migration in patients with acute occlusions of the middle cerebral artery.

Purpose The occurrence of thrombus migration (TM) in middle cerebral arteries (MCAs) prior to mechanical thrombectomy (MT) in patients suffering from acute ischemic strokes is a crucial aspect as TM is associated with lower rates of complete reperfusion and worse clinical outcomes. In this study, we sought to clarify whether histological thrombus composition influences TM. Methods We included 64 patients with acute MCA occlusions who had undergone MT. In 11 of the cases (17.2%) we identified TM prior to the interventions. The extracted clots were collected and histologically examined. The hematoxylin and eosin-stained specimens were quantitatively analyzed in terms of the relative fractions of the main constituents (red and white blood cells and fibrin/platelets). The histologic patterns were correlated with the occurrence of TM. Results Patients in whom TM could be observed were more often treated in a drip-and-ship fashion (90.9% vs 41.5%, p = 0.003). Stroke etiology did not differ between migrated and stable thrombi. A weak tendency for higher RBC and lower F/P content could be observed in thrombi that had migrated when compared with stable thrombi (RBC: median 41% vs 37%, p = 0.022 and F/P: median 54% vs 57%, p = 0.024). When using a cut-off of 60% RBC content for the definition of RBC-rich thrombi, a higher portion of RBC-rich thrombi could be identified in the migrated group as opposed to the stable group (36.4% vs 5.7%, p = 0.003). Conclusion Preinterventional TM may be influenced by the histological thrombus composition in a way that RBC-rich thrombi are more prone to migrate.

Intraprocedural Thrombus Fragmentation During Interventional Stroke Treatment: A Comparison of Direct Thrombus Aspiration and Stent Retriever Thrombectomy.

PURPOSE: The aim of this study was to compare the rates of intraprocedural thrombus fragmentation between the exclusive thrombus aspiration technique (ADAPT) and the use of stent retrievers. MATERIALS AND METHODS: Cases with successful recanalization of the primary occlusion site (POS) with either of the techniques were analyzed (n = 36 ADAPT, n = 61 stent retriever). The primary endpoint was the evaluation of intraprocedural thrombus fragmentation before applying additional maneuvers to enhance reperfusion success. Grading was performed using the modified thrombolysis in cerebral infarction (mTICI) perfusion scale grade with the implementation of an additional TICI 2c grade. Secondary endpoints were procedural complications and clinical data. RESULTS: After opening of the POS, 83.3% successful reperfusions were reached using the ADAPT technique and 88.5% using stent retrievers (p = 0.47). Subarachnoid hemorrhages (SAH) appeared only when using stent retrievers (16.4 vs. 0%, p = 0.010). The number of maneuvers was significantly higher (median 2 vs. 1, p = 0.006), and procedural time was longer in the stent retriever group (median 30 vs. 13 min, p < 0.0001). There was no significant difference between both techniques with regard to the occurrence of embolizations to new territories (2.8 vs. 8.2%, p = 0.28). CONCLUSION: When retrieving of the primary thrombus is possible, ADAPT results in comparable reperfusion grades as do stent retrievers. This suggests that comparable distraction forces act on the thrombus and that both techniques possess a comparable risk of periprocedural thrombus fragmentation. SAH exclusively occurred after using stent retrievers, which may further promote ADAPT as safe and fast initial front-line approach.