Sex differences in aneurysmal subarachnoid haemorrhage (aSAH): aneurysm characteristics, neurological complications, and outcome.

BACKGROUND: Women are over-represented in aSAH cohorts, but whether their outcomes differ to men remains unclear. We examined if sex differences in neurological complications and aneurysm characteristics contributed to aSAH outcomes. METHODS: In a retrospective cohort (2010-2016) of all aSAH cases across two hospital networks in Australia, information on severity, aneurysm characteristics and neurological complications (rebleed before/after treatment, postoperative stroke < 48 h, neurological infections, hydrocephalus, seizures, delayed cerebral ischemia [DCI], cerebral infarction) were extracted. We estimated sex differences in (1) complications and aneurysm characteristics using chi square/t-tests and (2) outcome at discharge (home, rehabilitation or death) using multinomial regression with and without propensity score matching on prestroke confounders. RESULTS: Among 577 cases (69% women, 84% treated) aneurysm size was greater in men than women and DCI more common in women than men. In unadjusted log multinomial regression, women had marginally greater discharge to rehabilitation (RRR 1.15 95% CI 0.90-1.48) and similar likelihood of in-hospital death (RRR 1.02 95% CI 0.76-1.36) versus discharge home. Prestroke confounders (age, hypertension, smoking status) explained greater risk of death in women (rehabilitation RRR 1.13 95% CI 0.87-1.48; death RRR 0.75 95% CI 0.51-1.10). Neurological complications (DCI and hydrocephalus) were covariates explaining some of the greater risk for poor outcomes in women (rehabilitation RRR 0.87 95% CI 0.69-1.11; death RRR 0.80 95% CI 0.52-1.23). Results were consistent in propensity score matched models. CONCLUSION: The marginally poorer outcome in women at discharge was partially attributable to prestroke confounders and complications. Improvements in managing complications could improve outcomes.

Nellix Endobag rupture associated with a fatal outcome.

Endovascular treatment of a type IA endoleak was conducted using a Nellix chimney graft technique for an expanding abdominal aortic aneurysm in an 84-year-old man. During the procedure, a polymer leak occurred from one of the endobags. Postoperatively, the patient developed hemodynamic instability and a swollen leg on the side of the leaking endobag, resulting in a fatal outcome.

Barriers and facilitators to more timely treatment of aneurysmal subarachnoid haemorrhage across two tertiary referral centres in Australia: A thematic analysis.

BACKGROUND: Delays in treatment of aSAH appear to be common but the causes are not well understood. We explored facilitators and barriers to timely treatment of aSAH. METHODS: We used a multiple case study with cases of aSAH surviving> 1 day identified prospectively. We conducted semi-structured interviews with the patient, their next-of-kin and health professionals involved in the case. Within-case analysis identified barriers and facilitators in 4 phases (pre-hospital, presentation, transfer, in-hospital) followed by thematic analysis across cases using a case-study matrix. RESULTS: Twenty-seven cases with 90 interviewees yielded five themes related to facilitators or barriers of timely treatment. "Early recognition" led to urgent response. "Accessibility to health care" depended on patient's location, transport, and environmental conditions. Good "Coordination" between and within health services was a key facilitator. "Complexity" of patient's condition affected time to treatment in multiple time periods. "Availability of resources" was identified most frequently during the diagnostic and treatment phases as both barrier and facilitator. CONCLUSIONS: The identified themes may be modifiable at the patient/health professional level and health system level and may improve timely treatment of aSAH through targeted interventions, subsequently contributing to improve morbidity and mortality of patients with aSAH.

Association of Onset-to-Treatment Time With Discharge Destination, Mortality, and Complications Among Patients With Aneurysmal Subarachnoid Hemorrhage.

Importance: Rapid access to specialized care is recommended to improve outcomes after aneurysmal subarachnoid hemorrhage (SAH), but understanding of the optimal onset-to-treatment time for aneurysmal SAH is limited. Objective: To assess the optimal onset-to-treatment time for aneurysmal SAH that maximized patient outcomes after surgery. Design, Setting, and Participants: This cohort study assessed 575 retrospectively identified cases of first-ever aneurysmal SAH occurring within the referral networks of 2 major tertiary Australian hospitals from January 1, 2010, to December 31, 2016. Individual factors, prehospital factors, and hospital factors were extracted from the digital medical records of eligible cases. Data analysis was performed from March 1, 2020, to August 31, 2021. Exposures: Main exposure was onset-to-treatment time (time between symptom onset and aneurysm surgical treatment in hours) derived from medical records. Main Outcomes and Measures: Clinical characteristics, complications, and discharge destination were extracted from medical records and 12-month survival obtained from data linkage. The associations of onset-to-treatment time (in hours) with (1) discharge destination of survivors (home vs rehabilitation), (2) 12-month survival, and (3) neurologic complications (rebleed, delayed cerebral ischemia, meningitis, seizure, hydrocephalus, and delayed cerebral injury) were investigated using natural cubic splines in multivariable Cox proportional hazards and logistic regression models. Results: Of the 575 patients with aneurysmal SAH, 482 patients (mean [SD] age, 55.0 [14.5] years; 337 [69.9%] female) who received endovascular coiling or neurosurgical clipping were studied. A nonlinear association of treatment delay was found with the odds of being discharged home vs rehabilitation (effective df = 3.83 in the generalized additive model, χ2 test P = .002 for the 4-df cubic spline), with a similar nonlinear association remaining significant after adjustment for sex, treatment modality, severity, Charlson Comorbidity Index, history of hypertension, and hospital transfer (likelihood ratio test: df = 3, deviance = 9.57, χ2 test P = .02). Both unadjusted and adjusted cox regression models showed a nonlinear association between time to treatment and 12-month mortality with the lowest hazard of death with receipt of treatment at 12.5 hours after symptom onset, although the nonlinear term became nonsignificant upon adjustment. The odds of being discharged home were higher with treatment before 20 hours after onset, with the probability of being discharged home compared with rehabilitation or other hospital increased by approximately 10% when treatment was received within the first 12.5 hours after symptom onset and increased by an additional 5% from 12.5 to 20 hours. Time to treatment was not associated with any complications. Conclusions and Relevance: This cohort study found evidence that more favorable outcomes (discharge home and survival at 12 months) were achieved when surgical treatment occurred at approximately 12.5 hours. These findings provide more clarity around optimal timelines of treatment with people with aneurysmal SAH; however, additional studies are needed to confirm the findings.

Adherence to evidence-based processes of care reduces one-year mortality after aneurysmal subarachnoid hemorrhage (aSAH).

BACKGROUND: There is limited research on the provision of evidence-based care and its association with outcomes after aneurysmal subarachnoid hemorrhage (aSAH). AIMS: We examined adherence to evidence-based care after aSAH and associations with survival and discharge destination. Also, factors associated with evidence-based care including age, sex, Charlson comorbidity index, severity scores, and delayed cerebral ischemia and infarction were examined for association with survival and discharge destination. METHODS: In a retrospective cohort (2010-2016) of all aSAH cases across two comprehensive cerebrovascular centres, we extracted 3 indicators of evidence-based aSAH care from medical records: (1) antihypertensives prior to aneurysm treatment, (2) nimodipine, and (3) aneurysm treatment (coiling/clipping). We defined 'optimal care' as receiving all eligible processes of care. Survival at 1 year was obtained by data linkage. We estimated (1) proportion of patients and characteristics associated with receiving processes of care, (2) associations between processes of care with 1-year mortality using cox-proportional hazard model and discharge destination with log binomial regression adjusting for age, sex, severity of aSAH, delayed cerebral ischemia and/or cerebral infarction and comorbidities. Sensitivity analyses explored effect modification of the association between processes of care and outcome by management type (active versus comfort measures). RESULTS: Among 549 patients (69% women), 59% were managed according to the guidelines. Individual indicators were associated with lower 1-year mortality but not discharge destination. Optimal care reduced mortality at 1 year in univariable (HR 0.24 95% CI 0.17-0.35) and multivariable analyses (HR 0.51 95% CI 0.34-0.77) independent of age, sex, severity, comorbidities, and hospital network. CONCLUSION: Adherence to processes of care reduced 1-year mortality after aSAH. Many patients with aSAH do not receive evidence-based care and this must be addressed to improve outcomes.

Platelet Function Testing in Neurovascular Procedures: Tool or Gimmick?

BACKGROUND: Platelet inhibitors are used to prevent thromboembolic complications related to neurovascular stenting (NVS) procedures. Despite substantial inter-individual variability of functional platelet inhibition, the value of platelet function tests (PFT) to assess inhibition remains controversial. OBJECTIVE: This study was conducted to compare differences in thromboembolic complication rates associated with NVS in platelet-inhibited patients with and without PFT. Clinical neurological outcomes were assessed by differences in the modified Rankin Scale (mRS). MATERIALS AND METHODS: One hundred seventeen consecutive patients underwent elective NVS procedures within a 7-year period. All patients received aspirin and clopidogrel 8 days before the procedure. Fifty-two patients were treated without assessment of platelet inhibition, and 65 patients were tested for clopidogrel resistance. When clopidogrel resistance was revealed, corresponding patients were converted to ticagrelor. Changes in mRS and thromboembolic event rates were compared between the 2 cohorts. RESULTS: Thirty-five percent of patients from the cohort subjected to PFT tests showed inadequate platelet inhi-bition under clopidogrel and were converted to ticagrelor. Compared to the non-PFT test -cohort, neurological deficits were significantly reduced (12 vs. 0%; p = 0.009) and a lower number of thromboembolic events was found (12 vs. 3%; p > 0.05) within the test cohort. CONCLUSION: PFT appears to identify patients with clopidogrel resistance prior to NVS procedures. When non-responders are converted to alternative platelet inhibitors, neurological outcomes and thromboembolic complication rates may improve. Consequently, this study provides preliminary evidence that PFT may be a useful clinical tool to enhance procedural safety and improve clinical outcomes in NVS procedures.

Residuals, recurrences and re-treatment after endovascular repair of intracranial aneurysms: A retrospective methodological comparison.

OBJECTIVE: Incomplete aneurysm occlusions and re-treatment rates of 52 and 10-30%, respectively, have been reported following endovascular treatment of intracranial aneurysms, raising clinical concerns regarding procedural efficacy. We compare residual, recurrence and re-treatment rates subject to different endovascular techniques in both ruptured and unruptured intracranial aneurysms at a comprehensive state-wide tertiary neurovascular centre in Australia. METHODS: Medical records, procedural and follow-up imaging studies of all patients who underwent endovascular treatment for intracranial aneurysms between July 2010 and July 2017 were reviewed retrospectively. Residuals, recurrences and re-treatment rates were assessed regarding initial aneurysm rupture status and applied endovascular technique: primary coiling, balloon- and stent-assisted coiling and flow diversion. RESULTS: Among 233 aneurysms, residual, recurrence and re-treatment rates were 27, 11.2 and 9.4%, respectively. Compared with unruptured aneurysms, similar residual and recurrence (p > .05), but higher re-treatment rates (4.5% vs. 19%; p < .001) were found for ruptured aneurysms. Residual, recurrence and re-treatment rates were: 13.3, 16 and 12% for primary coiling; 12, 12 and 10.7% for balloon-assisted coiling; 14.9, 7.5 and 4.5% for stent-assisted coiling; 91.9, 0 and 5.4% for flow diversion. Stent-assistance and flow-diversion were associated with lower recurrence and re-treatment rates, when compared with primary- and balloon-assisted coiling (p < .05). CONCLUSIONS: Residuals and recurrences after endovascular treatment of intracranial aneurysms are less common than previously reported. Stent assistance and flow diversion seem associated with reduced recurrence- and re-treatment rates, when compared with primary- and balloon-assisted coiling. Restrained use of stents in ruptured aneurysms may be a contributing factor for higher recurrence/retreatment rates compared to unruptured aneurysms.

Potentially actionable FGFR2 high-level amplification in thymic sebaceous carcinoma.

Our aim was to investigate sebaceous differentiation in thymus tumours and to identify new actionable genomic alterations. To this end we screened 35 normal and 23 hyperplastic thymuses, 127 thymomas and 41 thymic carcinomas for the presence of sebaceous differentiation as defined by morphology and expression of adipophilin and androgen receptor (AR). One primary thymic carcinoma showed morphology of sebaceous carcinomas (keratinizing and foam cells, calcifications, giant cells), a strong expression of adipophilin and AR together with squamous markers. NGS revealed high-level amplification of fibroblast growth factor receptor 2 (FGFR2). In thymuses and thymomas, no cells with sebaceous morphology were present. Occasionally, macrophages or epithelial cells showed adipophilin-positivity, however, without co-expression of AR. Thymic sebaceous carcinoma should be considered if a thymic carcinoma shows clear or foamy features. Testing for FGFR2 amplification might be warranted when searching for actionable genomic alterations in sebaceous carcinomas in the mediastinum and in other locations.

Relationship between pulmonary artery volumes at computed tomography and pulmonary artery pressures in patients with- and without pulmonary hypertension.

OBJECTIVES: This study was designed to determine the relationship between pulmonary artery (PA) volumes at computed tomography (CT) and PA pressures at right-sided heart catheterization in patients with and without pulmonary hypertension (PAH) to develop a noninvasive CT method of PA pressure quantification. MATERIALS AND METHODS: Sixteen patients with chronic sleep apnea syndrome underwent contrast enhanced helical CT (slice thickness 3mm; pitch 2; increment 2mm) at inspiration. Eight patients had PAH while cardiopulmonary disease has been excluded in eight other patients. Vascular volumes were determined using a 3D technique (threshold seeded vascular tracing algorithm; thresholds -600 H [lower] and 3,000 H [upper]). Right-sided heart catheterization measurements were available for linear regression analysis of PA volumes and pressures. RESULTS: Correlation between PA pressures and volumes (normalized for BMI), was high in both groups (without PAH: r=.85; with PAH .90, Pearson). Compared to elevated PA pressures in patients with pulmonary hypertension (p<.005), PA volumes also were significantly increased (p<.05) among the groups. CONCLUSIONS: High correlation was found between PA volumes and mean PA pressures in patients with- and without PAH. Significant differences in PA volumes at CT-volumetry may admit non-invasive determination of pulmonary hypertension.

[Refined staging in Hilar bronchial neoplasms with ECG-gated multislice-CT---case report]. / Verfeinertes Staging von hilusnahen Bronchialkarzinomen durch EKG-gegatete Mehrschicht-Spiral-CT--Fallbeschreibung.

Equivocal initial CT-based staging in 2 patients with hilar bronchial neoplasms was reassessed with retrospective ECG-gated Multislice-CT and optimized examination parameters prior to definition of treatment. An initially suspected irresectable T4 tumor with mediastinal infiltration was downstaged to T2 in one case, while tumor infiltration into the left atrium could be confirmed in the other case. In doubtful conditions, ECG-gated multislice CT with optimized examination parameters may be helpful for refined staging in patients with hilar bronchial neoplasms, thus possibly influencing treatment strategies.

Radiation exposure, and procedure and fluoroscopy times in endovascular treatment of intracranial aneurysms: a methodological comparison.

BACKGROUND: Limited data are available for radiation exposure, and procedure and fluoroscopy times in neuroendovascular treatment (NET) strategies. OBJECTIVE: This study establishes and compares related parameters between coil embolization (COIL), balloon assisted coil embolization (BAC), stent assisted coil embolization (SAC), and flow diverting technology (FDT) in NET of intracranial aneurysms. MATERIALS AND METHODS: Between 2010 and 2017, 249 consecutive intracranial aneurysms underwent NET at a single center, all performed by the same operator. Dose area products (DAP), and procedure and fluoroscopy times were recorded and compared between COIL, BAC, SAC, and FDT techniques. Differences in parameters between cohorts were analyzed for significance using the Mann-Whitney U test, unpaired t test and χ2test. Additional subgroup analysis was performed for emergency and elective cases. RESULTS: 83 aneurysms were treated with COIL (33%), 72 with BAC (29%), 61 with SAC (25%), and 33 with FDT (13%). Baseline characteristics were largely similar within these groups (P>0.05). Among COIL, BAC, and FDT cohorts, no significant difference was found for mean DAP, or procedure and fluoroscopy times (P>0.05). However, compared with all other cohorts, SAC was associated with a significantly higher DAP and longer procedure and fluoroscopy times (P<0.005). No significant difference was recorded for emergency and elective case subgroups. CONCLUSION: Compared with other NET strategies, SAC was associated with a significantly higher DAP, and longer procedure and fluoroscopy times. This study provides an initial dataset regarding radiation exposure, and procedure and fluoroscopy times for common NET, and may assist ALARA (As Low As Reasonably Achievable) principles to reduce radiation risks.

Size and Location of Ruptured Intracranial Aneurysms: A 5-Year Clinical Survey.

BACKGROUND: Prospective international cohort trials have suggested that incidental cerebral aneurysms with diameters less than 10 mm are unlikely to rupture. Consequently, small ruptured cerebral aneurysms should rarely be seen in clinical practice. To verify this theory, dimensions and locations of ruptured cerebral aneurysms were analyzed across the state of Tasmania, Australia. METHODS: We retrospectively reviewed medical records and diagnostic tests of all patients admitted with ruptured cerebral aneurysms during a 5-year interval. Aneurysm location, maximum size, dome-to-neck ratio, volume, and presence of daughter sacs were determined by preoperative digital subtraction angiography or computed tomography angiography. RESULTS: A total of 131 ruptured cerebral aneurysms were encountered and treated by microsurgical clipping (n = 59) or endovascular techniques (n = 72). The mean maximum aneurysm diameter was 6.4 ± 3.7 mm, dome-to-neck ratio 2 ± 0.8, aneurysm volume 156 ± 372 mm(3), and daughter sacs were present in 70 aneurysms (53.4%). The anterior communicating artery was the most common location (37.4%). Cumulative maximum diameters of ruptured aneurysms were ≤5 mm in 49%, ≤7 mm in 73%, and ≤10 mm in 90%. CONCLUSIONS: Despite findings from prospective international cohort trials, small ruptured intracranial aneurysms are common in clinical practice. In consequence, it seems important to identify those patients with small but vulnerable unruptured aneurysms before conservative management is considered.

Evaluation of hemolysis in microcatheter directed blood infusion at different flow rates for transarterial salvage reperfusion: In-vitro study.

BACKGROUND: Microcatheter directed blood reperfusion is an endovascular salvage option for acute cerebral artery occlusions. It has not been investigated whether this technique may be associated with hemolysis. OBJECTIVE: Analysis of hemolysis during blood infusion through different microcatheters and infusion rates to assess related risks. METHODS: Four microcatheters with different inner diameters were perfused with blood samples at three infusion rates. Hemolytic markers including lactate-dehydrogenase (LDH) and haptoglobin were analyzed. Samples before and after blood infusion were compared using Student's t-test. Flow-related degree of hemolysis was analyzed with regression analysis. Resulting shear stress was calculated and correlated with LDH and haptoglobin. RESULTS: Significant increase of LDH and decrease of haptoglobin was found after blood reperfusion through small microcatheters at progressive flow rates (p<0.05). No hemolysis was found with larger diameter microcatheters at all flow rates (p>0.05). Correlation between shear stress, LDH and haptoglobin was r=0.86 and r=0.75, respectively. CONCLUSIONS: Progressive hemolysis occurs during blood perfusion of small lumen microcatheters at increasing flow rates. This phenomenon may be related to turbulent flow, exposure time and increased shear stress. Larger microcatheters did not induce hemolysis and may be the preferred choice for stroke reperfusion.

Guidance of percutaneous pulmonary biopsies with real-time CT fluoroscopy.

OBJECTIVE: Clinical evaluation of computed tomography (CT) fluoroscopy and comparison with conventional CT guidance for monitoring of percutaneous pulmonary biopsy procedures. METHODS: Twenty CT-guided pulmonary biopsy procedures were conducted. The interventions have prospectively been performed either with CT fluoroscopy or with conventional CT guidance. About 120 kV and 50 mA with a frame-rate of eight images per second were used for CT fluoroscopy. Number of pleural needle passages, procedure times, radiation doses and histologic results were analyzed separately for both methods. RESULTS: Compared with conventional CT guidance, CT fluoroscopy was associated with less pleural needle passages (1.8+/-0.6 vs. 1.1+/-0.3; P=0.003, t-test) and procedure times were shorter than for conventional CT guidance (12.7+/-2.2 min vs. 26.7+/-16.4 min; P=0.02). Analysis of estimated patient related radiation exposure and histologic outcome showed no significant difference between conventional and fluoroscopic CT-guided procedures (P>0.05). CONCLUSION: CT fluoroscopy facilitates guidance of percutaneous pulmonary biopsy procedures. Compared with conventional CT assistance, procedure times are decreased and less pleural needle passages are required. While patient-related radiation exposure is similar, operator-related radiation exposure remains a disadvantage associated with CT fluoroscopy.

Cardiovascular risk factors do not predict clinically defined restenosis after percutaneous transluminal angioplasty for lower limb ischemia.

The purpose of this study was to evaluate risk factors predicting restenosis and primary patency after percutaneous transluminal angioplasty. Follow-up data (including cardiovascular risk factor scores according to SCVIR criteria, preinterventional and postinterventional clinical data and patient history) of all patients who underwent successful percutaneous transluminal angioplasty for lower limb ischemia were analyzed retrospectively and patients, relatives, or referring physicians underwent a telephone interview. Patients with incomplete follow-up data were examined by means of a clinical examination, including Doppler measurements and treadmill test. Additionally all angiograms were evaluated to calculate lesion length, number of treated lesions, lesion type (SCVIR score), and runoff. The outcome was categorized into four groups: early recurrence (< 1 month, group I), mean recurrence (1-6 months, group II), late recurrence (>6 months, group III), and no recurrence (group IV). According to common concepts group I was defined as early (thrombotic) reocclusion, group II as clinically defined restenosis, and group III as progression of atherosclerosis. One hundred thirty-seven patients underwent percutaneous transluminal angioplasty of 148 extremities. The groups differ significantly only with respect to a higher diabetes score for group I in comparison to group IV (p=0.002, Kruskal-Wallis test), and a worse runoff of group I compared with group IV (p =0.008). There was a trend toward a higher diabetes score for group II in comparison to group IV (p = 0.014). There were no differences with regard to hyperlipemia, hypertension, and tobacco use between patient groups. Mean primary patency was 436 days. Predictors for lower patency rates were diabetes mellitus (p<0.001), runoff (p=0.005), and number of treated lesions (p=0.007) in a stepwise, multiple regression analysis. Patients with clinically defined restenosis showed no specific risk factor profile in this study. Predictors for lower primary patency were diabetes mellitus, number of treated lesions, and runoff.