Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure.

OBJECTIVE: Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response. APPROACH: Retrospective analysis of 437 healthy subjects (aged 18-87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2 (EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCP temporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs. MAIN RESULTS: The reconstruction error for SRVMAP was the main determinant of SRVCrCP signal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCP showed highly significant (p<0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCP were the ARI and the mean CrCP for the entire five-minute baseline period. The early phase (2-3 s) of SRVCrCP response was influenced by heart rate whereas the late phase (10-14 s) was influenced by diastolic BP. SIGNIFICANCE: These results should allow better planning and quality of future research and clinical trials of novel metrics of cerebral blood flow regulation.

Influence of cardiometabolic medications on abdominal aortic aneurysm growth in the UK Aneurysm Growth Study: metformin and angiotensin-converting enzyme inhibitors associated with slower aneurysm growth.

BACKGROUND: There is a clinical need for treatments that can slow or prevent the growth of an abdominal aortic aneurysm, not only to reduce the need for surgery, but to provide a means to treat those who cannot undergo surgery. METHODS: Analysis of the UK Aneurysm Growth Study (UKAGS) prospective cohort was conducted to test for an association between cardiometabolic medications and the growth of an abdominal aortic aneurysm above 30 mm in diameter, using linear mixed-effect models. RESULTS: A total of 3670 male participants with data available on abdominal aortic aneurysm growth, smoking status, co-morbidities, and medication history were included. The mean age at recruitment was 69.5 years, the median number of surveillance scans was 6, and the mean(s.e.) unadjusted abdominal aortic aneurysm growth rate was 1.75(0.03) mm/year. In a multivariate linear mixed-effect model, smoking (mean(s.e.) +0.305(0.07) mm/year, P = 0.00003) and antiplatelet use (mean(s.e.) +0.235(0.06) mm/year, P = 0.00018) were found to be associated with more rapid abdominal aortic aneurysm growth, whilst metformin was strongly associated with slower abdominal aortic aneurysm growth (mean(s.e.) -0.38(0.1) mm/year, P = 0.00019), as were angiotensin-converting enzyme inhibitors (mean(s.e.) -0.243(0.07) mm/year, P = 0.0004), angiotensin II receptor antagonists (mean(s.e.) -0.253(0.08) mm/year, P = 0.00255), and thiazides/related diuretics (mean(s.e.) -0.307(0.09) mm/year, P = 0.00078). CONCLUSION: The strong association of metformin with slower abdominal aortic aneurysm growth highlights the importance of the ongoing clinical trials assessing the effectiveness of metformin with regard to the prevention of abdominal aortic aneurysm growth and/or rupture. The association of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and diuretics with slower abdominal aortic aneurysm growth points to the possibility that optimization of cardiovascular risk management as part of abdominal aortic aneurysm surveillance may have the secondary benefit of also reducing abdominal aortic aneurysm growth rates.

Editor's Choice - RANDOMisation Screening for Drug coated or Drug Eluting Device Randomised Trials Among Patients Undergoing Endovascular FemorOPopliteal Procedures (RANDOM-STOP study).

OBJECTIVE: The aim was to assess the proportion of patients undergoing endovascular therapy for femoropopliteal arterial disease (FP) who would be eligible to take part in seven major randomised controlled trials (RCTs) that investigated the efficacy of some of the currently available paclitaxel based (PTX) devices used in this clinical context. Various RCTs have shown a potential clinical benefit from the use of paclitaxel in FP endovascular therapy. Nonetheless, patients enrolled were highly selected and the generalisability of these findings in pragmatic cohorts is unclear. METHODS: Between 1 January and 31 December 2021, all consecutive patients who underwent endovascular procedures for symptomatic FP disease in 16 European centres were retrospectively screened and included in this analysis. The primary outcome measure was individual patient eligibility for inclusion into at least one of the seven RCTs. The reasons for exclusion (clinical and or radiological) as well as in hospital death and morbidity were also reported. RESULTS: A total of 1 567 consecutive patients (959 male, 61%), corresponding to 1 567 lower limbs, were included. Most patients (1 009 patients, 64.39%) were treated for chronic limb threatening ischaemia (CLTI). A total 1 280 patients (81.68%) were not eligible for inclusion in any of the evaluated RCTs. Of them, 741 (47.28%) were excluded for clinical and 1 125 (71.79%) for radiological reasons. CONCLUSION: The analysed RCTs assessing the efficacy or effectiveness of PTX based endovascular therapies do not seem representative of the patient population with FP disease receiving endovascular therapy in routine clinical practice.

Acute Kidney Injury in Patients with Acute Type B Aortic Dissection.

OBJECTIVE: Acute kidney injury (AKI) is common in patients with aortic diseases; however, it has not been extensively studied in acute type B aortic dissection (TBAD). AKI is known to be associated with adverse kidney outcomes and premature death. This study investigated the incidence and impact of AKI in patients with acute TBAD. METHODS: This was a retrospective study including data from two tertiary vascular centres in the UK. Case notes and electronic records were reviewed for consecutive patients presenting with acute symptomatic TBAD. Patients were managed according to a uniform clinical protocol; both patients who underwent surgery and those managed conservatively were included in this analysis. Serum creatinine values were used to calculate the number of patients who developed AKI, based on validated Kidney Disease Improving Global Outcomes definitions. Associations between incidence of AKI, death, and Major Adverse Kidney Events (MAKE; defined as death, dialysis and/or drop in estimated glomerular filtration rate > 25%) were explored. RESULTS: Overall, 66 (42.6%) of 155 patients developed AKI within one week of presenting with TBAD. Of these, 23 patients (34.8%) had stage 1, 26 patients (39.4%) stage 2, and 17 patients (25.8%) stage 3 AKI. MAKE at 30 and 90 days occurred in 17 (11.0%) and 12 patients (7.7%), respectively. AKI was associated with significantly worse outcomes, with a 24.2% mortality rate in the AKI group compared with 7.8% among those with no AKI (p <.001); this association was also significant in adjusted analyses, both in patients who did and did not undergo surgery. CONCLUSION: AKI is very common among patients presenting with acute TBAD, even in clinically uncomplicated disease. There was a significant association with mortality and MAKE, whether patients underwent surgery or not. This warrants further investigation to better understand the underlying causes of the AKI and investigate management strategies which may improve outcomes.

Different endovascular modalities of treatment for isolated atherosclerotic popliteal artery lesions (EMO-POP) registry.

BACKGROUND: The mid-term results after treatment of isolated popliteal lesions have been limited. The aim of the present study was to report the mid-term outcomes after endovascular treatment of isolated atherosclerotic popliteal artery lesions. METHODS: A multicenter (15 hospitals in five countries) retrospective cohort study was performed. Between June 2016 and June 2021, 651 consecutive patients who had been treated for isolated popliteal lesions using endovascular methods exclusively were included in the present study. Six techniques were identified, including plain balloon angioplasty (PTA; n = 286; 43.9%), drug-coated balloon angioplasty (n = 98; 15.1%), stenting with low-chronic outward force (COF) stents (n = 84; 12.9%), stenting with high-COF stents (n = 76; 11.7%), atherectomy alone (n = 17; 2.6%), and directional atherectomy with drug-coated balloons (n = 90; 13.8%). The primary outcomes measures were primary and secondary patency and freedom from clinically driven target lesion revascularization (F-CDTLR). RESULTS: The mean patient age was 74.5 years. Most of the patients (n = 409; 62.9%) had had chronic limb-threatening ischemia. Popliteal occlusion was found in 400 cases (61.4%). High-grade calcification was present in 36.7% of cases. Immediate technical success was 94.8%. The median follow-up was 26 months (range, 6-42 months). The actuarial rate for all patients at 26 months (per outcome measure) was as follows: primary patency, 73.9%; secondary patency, 88%; and F-CDTLR, 76.5%. When comparing PTA vs all other treatments in an adjusted regression analysis, the F-CDTLR was 75.2% for PTA vs 76.5% for all other treatment (hazard ratio, 1.06; 95% confidence interval, 0.75-1.48; P = .46, adjusted regression). The difference in secondary patency also was not statistically significant (85.7% for PTA vs 88%; P = .20). Adjusted Kaplan-Meier analysis revealed that the estimated primary patency was inferior for PTA in pairwise comparisons vs other treatments (P < .001 vs atherectomy; P = .002 vs directional atherectomy with drug-coated balloons; and P = .002 vs low-COF stenting). CONCLUSIONS: The results from our study have shown that endovascular treatment of isolated popliteal lesions is safe and associated with acceptable patency and F-CDTLR in the mid-term.

Long-Term Effects of Acute Kidney Injury Following Endovascular Femoropopliteal Intervention: Insights From a Multicenter Trial.

PURPOSE: To examine the association between acute kidney injury (AKI) severity and duration with cardiovascular mortality, following endovascular treatment of femoropopliteal disease, and whether it is AKI in itself that confers an increased risk of cardiovascular mortality. METHODS: A retrospective analysis of prospectively collected data obtained between 2014 and 2019 from 3 vascular centers. Renal function was followed up for a minimum of 90 days. Electronic records were queried to establish a cause of death, where applicable. Patients were excluded if unable to provide written informed consent or if presenting with acute limb ischemia. Primary outcomes were the hazard ratios for cardiovascular death (AKI patients vs no AKI; no AKI vs stage 1 AKI vs stage 3 AKI; and no AKI vs transient AKI vs established AKI). Propensity score-matched analysis was used to establish whether developing AKI, in patients with similar demographics and procedural characteristics, is associated with a higher risk of cardiovascular death. RESULTS: Overall 239 patients developed AKI, and this was associated with an increased risk of cardiovascular mortality (hazard risk [HR]: 4.3, 95% confidence intervals [CIs]: 2.1-6.8, pairwise comparison p value=0.006]. This was dependent on the severity of the AKI stage (HR 5.4, 95% CI: 2.4-7.3, pairwise comparison p value=0.01) and duration (HR 4.2, 95% CI: 2.3-6.2, pairwise comparison p value=0.04). The propensity score-matched analysis showed that even when patients are matched for comorbidity and procedural characteristics, AKI confers an increased risk of mortality (p=0.04). CONCLUSIONS: Acute kidney injury is common after femoropopliteal endovascular therapy. It confers an increased risk of long-term cardiovascular mortality, which is still present when renal decline is transient, and highest for patients with established decline in renal function. CLINICAL IMPACT: This is the first study in the setting of peripheral arterial disease to show that acute kidney injury has an adverse effect on cardiovascular mortality, in the long-term, that is dependent on its severity, and present even when the AKI is transient. We have also shown that this difference in cardiovascular mortality becomes more pronounced from the medium-term, and thus closer follow-up of these patients is required.

Selecting Portable Ankle/Toe Brachial Pressure Index Systems for a Peripheral Arterial Disease Population Screening Programme: a Systematic Review, Clinical Evaluation Exercise, and Consensus Process.

OBJECTIVE: To provide an overview of systems available for peripheral arterial disease (PAD) screening, together with respective accuracies and a clinical evaluation to identify a system suitable for use in a community screening programme. METHODS: A systematic review of the diagnostic accuracy of six ankle brachial pressure index (ABPI) and toe brachial pressure index (TBPI) devices deemed to be portable, which were Conformité Européenne (CE) marked, and were automated or semi-automated was carried out compared with gold standard handheld Doppler and duplex ultrasound. The devices were MESI-ABPI-MD, Huntleigh Dopplex Ability, Huntleigh ABPI and TBPI systems, Systoe TBPI system, and BlueDop. Seven databases (MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) were searched, and 11 studies were identified as eligible for review. This was followed by hands on clinical evaluation by abdominal aortic aneurysm (AAA) screening staff (n = 39). During this, devices were demonstrated to staff which they then tested on volunteers and gave feedback using pre-designed questionnaires on their suitability for use in a screening programme. Finally, accuracy data and staff preferences were combined during a consensus conference that was held between study and screening staff to determine the most appropriate device to use in a community screening programme. RESULTS: Generally, the evaluated systems have a moderate level of sensitivity and a high level of specificity: Dopplex ability sensitivity 20% - 70%, specificity 86% - 96%; MESI sensitivity 57% - 74%, specificity 85% - 99%; BlueDop sensitivity 95%, specificity 89%; and Systoe sensitivity 71%, specificity 77%. Clinical evaluation by screening staff identified a preference for the MESI system. The consensus conference concluded that the MESI device was a good candidate for use in a community PAD screening programme. CONCLUSION: The MESI system is a good candidate to consider for community PAD screening.

Drug-eluting stents for the treatment of complex femoro-popliteal disease: a systematic review and meta-analysis.

INTRODUCTION: Endovascular methods have emerged as an appealing alternative to bypass for the treatment of patients not suitable for surgery. Drug eluting stents (DES) have been developed to address the limitations of angioplasty and stenting. There is a paucity of data in the literature on their performance for the treatment of patients with long femoro-popliteal segment lesions. We aimed to analyze the evidence supporting the use of DES in patients with complex femoro-popliteal disease. EVIDENCE ACQUISITION: A systematic review and meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: A total of 1255 potentially relevant articles were initially selected. After reviewing at title or abstract level, 22 articles were read in full and 10 were included. These studies reported on the use of DES for 1539 patients. In all studies the DES that was employed was a paclitaxel-eluting stent (Zilver PTX, Cook Medical; Bloomington, IN, USA). Average lesion length ranged from 114 mm to 400 mm. The pooled technical success rate was 0.964 (95% confidence interval [CI]: 0.936-0.980). The pooled estimate of limb loss at 12 months was 0.019 (95% CI: 0.012-0.030), stent fracture at 12 months was 0.035 (95% CI: 0.007-0.155), primary patency at 12 months was 0.705 (95% CI: 0.576-0.807) and secondary patency at 12 months was 0.898 (95% CI: 0.815-0.946). CONCLUSIONS: The short-term outcomes of DES for TASC C & D femoro-popliteal lesions are encouraging. Caution is advised in extrapolating the results of the included studies due to the large heterogeneity and lack of reporting of subgroup specific outcomes.

Superior Fitting of Arterial Resistance and Compliance Parameters With Genetic Algorithms in Models of Dynamic Cerebral Autoregulation.

OBJECTIVE: The capacity of discriminating between normal and impaired dynamic cerebral autoregulation (dCA), based on spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF), has considerable clinical relevance. This study aimed to quantify the separate contributions of vascular resistance and compliance as parameters that could reflect myogenic and metabolic mechanisms to dCA. METHODS: Forty-five subjects were studied under normo and hypercapnic conditions induced by breathing a mixture of 5% carbon dioxide in air. Dynamic cerebrovascular resistance and compliance models with ABP as input and CBFV as output were fitted using Genetic Algorithms to identify parameter values for each subject, and respiratory condition. RESULTS: The efficiency of dCA was assessed from the model's generated CBFV response to an ABP step change, corresponding to an autoregulation index of 5.56 ± 1.57 in normocapnia and 2.38 ± 1.73 in hypercapnia, with an area under the ROC curve (AUC) of 0.9 between both conditions. Vascular compliance increased from 0.75 ± 0.7 ml/mmHg in normocapnia to 5.82 ± 12.0 ml/mmHg during hypercapnia, with an AUC of 0.88. CONCLUSION: Further work is needed to validate this approach in clinical applications where individualised model parameters could provide relevant diagnostic and prognostic information about dCA impairment.

Editor's Choice - Infra-Renal Aortic Diameter and Cardiovascular Risk: Making Better Use of Abdominal Aortic Aneurysm Screening Outcomes.

OBJECTIVE: Aortic diameter (AD), used traditionally for abdominal aortic aneurysm (AAA) screening may have a role in assessing cardiovascular risk. Unfortunately, AD estimates for those without AAA are underutilised, whilst cardiovascular risk is sub-optimally managed in those with AAA. Our objective was to examine the association between AD measurements and future cardiovascular risk. METHODS: Retrospective analysis of three databases of male participants screened for aortic aneurysm disease. Imaging and clinical data were obtained from three independent sources: 1) the Multi-centre Aneurysm Screening Study (MASS) trial (n = 26 882 men); 2) the 2013/14 cohort of the English NHS AAA Screening Programme (NAAASP) (n = 237 441 men) linked with NHS hospital admission and death registry data; and 3) the Framingham Heart Study (FHS) offspring cohort (n = 649). Associations between maximal aortic diameter, as measured on ultrasound or computed tomography, and cardiovascular outcomes were examined. RESULTS: Cardiovascular mortality in the MASS trial, was higher in men with AAA at 13 years of follow up, compared to those without (Hazard Ratio [HR] 2.22, 95% CI 1.97-2.50, p < .001). Contemporary risk of major adverse cardiovascular events in the NAAASP was highest in those with an AAA (HR 2.91, 95% CI 2.00-4.25), whilst, extremes of aortic diameter were associated with increased risk for cardiovascular events. Aortic diameter was an independent risk factor for cardiovascular events in the FHS dataset. CONCLUSION: Irrespective of the diagnosis of AAA, men attending for AAA screening who are found to have an abnormal aortic diameter are at high risk of future cardiovascular events. This currently unutilised data from AAA screening programmes has the potential to improve preventative management of cardiovascular risk.

Cerebral critical closing pressure and resistance-area product: the influence of dynamic cerebral autoregulation, age and sex.

Instantaneous arterial pressure-flow (or velocity) relationships indicate the existence of a cerebral critical closing pressure (CrCP), with the slope of the relationship expressed by the resistance-area product (RAP). In 194 healthy subjects (20-82 years, 90 female), cerebral blood flow velocity (CBFV, transcranial Doppler), arterial blood pressure (BP, Finapres) and end-tidal CO2 (EtCO2, capnography) were measured continuously for five minutes during spontaneous fluctuations of BP at rest. The dynamic cerebral autoregulation (CA) index (ARI) was extracted with transfer function analysis from the CBFV step response to the BP input and step responses were also obtained for the BP-CrCP and BP-RAP relationships. ARI was shown to decrease with age at a rate of -0.025 units/year in men (p = 0.022), but not in women (p = 0.40). The temporal patterns of the BP-CBFV, BP-CrCP and BP-RAP step responses were strongly influenced by the ARI (p < 0.0001), but not by sex. Age was also a significant determinant of the peak of the CBFV step response and the tail of the RAP response. Whilst the RAP step response pattern is consistent with a myogenic mechanism controlling dynamic CA, further work is needed to explore the potential association of the CrCP step response with the flow-mediated component of autoregulation.

Endovascular Aneurysm Repair Assisted by CO2 Digital Subtraction Angiography and Intraoperative Contrast-Enhanced Ultrasonography: Single-Center Experience.

BACKGROUND: Allergy to iodinated contrast (IC) agent and advanced chronic kidney disease are major limitations to endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs). We describe our experience combining CO2-assisted EVAR with intraoperative contrast-enhanced ultrasound (CEUS) in an attempt to avoid contrast-induced allergy or nephropathy. METHODS: Observational cohort study using prospectively acquired data on patients undergoing CO2-assisted EVAR in single institution. EVAR planning was performed using computed tomographic angiography or magnetic resonance aortography in patients contraindicated for IC. Patients were considered if their estimated glomerular filtration rate was <40 mL/min and anatomically suitable for conventional infrarenal EVAR. Outcomes of interest included technical success rate and reintervention rates, total radiation dose, length of hospital stay, and graft kinking or migration. RESULTS: Fifteen patients (10 male) were treated across a 5-year period. Technical success was achieved in all cases. Completely IC-free EVAR was performed in 9 cases, whereas the remaining 6 required IC administration for adjunct procedures. CO2 completion angiography detected all type I endoleaks (2 Ia and 1 Ib) but was less sensitive to type II. Intraoperative CEUS confirmed all type I and 2 cases of type II endoleaks. Median hospital stay was 4 days. No significant deterioration in renal function was seen postoperatively. CONCLUSIONS: In patients with abdominal aortic aneurysms and with contraindication for IC, a combined approach of using CO2 digital subtraction angiography and CEUS can be used safely and efficiently to minimize or obviate the need for IC agents with satisfactory mid-term results.

Effects of Left Renal Vein Ligation During Open Abdominal Aortic Aneurysm Repair on Renal Function.

OBJECTIVE: Left renal vein (LRV) ligation is performed during open abdominal aortic aneurysm (AAA) repair to facilitate proximal anastomosis. Its impact on short, medium, and long term renal function has not been investigated in detail using appropriately validated endpoints. METHODS: This was a nested case control study using data from a prospectively maintained AAA institutional dataset (tertiary centre). A total of 76 patients who underwent elective open AAA repair and had LRV ligation (1 January 2012 to 1 January 2018) were individually case matched based on age (within two years), sex, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologist (ASA) score, chronic kidney disease (CKD) stage, and history of diabetes with 76 patients who had open AAA repair without LRV ligation. Renal outcomes were compared between groups, including proportion of patients developing acute kidney injury (AKI) using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, proportion developing major adverse kidney events (MAKE90) at 90 days (comprising mortality and/or decrease in eGFR >25%), and absolute decrease in eGFR at latest follow up. RESULTS: A higher proportion of patients developed AKI and MAKE90 in the LRV ligation group (AKI: 11 patients [14.8%] vs. 2 [2.6%], p = .009; MAKE90: 6 [7.9%] vs. 1 [1.3%] p = .053, in the LRV ligation and the non-LRV ligation groups, respectively) - even though the difference in the MAKE90 endpoint was not statistically significant. Changes in eGFR were not statistically different in the LRV ligation group at 90 days (4.0 ± 1.1 mL/min/1.73 m2vs. 4.4 ± 2.1, p = .64) or by the time of latest follow up (median: 28 months; 3.7 ± 1.6 vs. 2.6 ± 2.0, p = .55). CONCLUSION: Ligation of the LRV is associated with increased levels of AKI and renal deterioration in the early post-operative phase using validated reporting criteria; however, long term renal function does not seem to be affected.

The critical closing pressure contribution to dynamic cerebral autoregulation in humans: influence of arterial partial pressure of CO2.

KEY POINTS: Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia. ABSTRACT: Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70 years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO2 (capnography) and heart rate (ECG) were performed for 5 min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis. The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP made a highly significant contribution during normocapnia (P < 0.0001) and was the sole determinant of changes in the CBFV response, resulting from hypercapnia, which led to a reduction in the autoregulation index from 5.70 ± 1.58 (normocapnia) to 4.14 ± 2.05 (hypercapnia; P < 0.0001). In conclusion, CrCP makes a very significant contribution to the dynamic CBFV response to changes in MAP and plays a major role in explaining the deterioration of dynamic CA induced by hypercapnia. Further studies are needed to assess the relevance of CrCP contribution in physiological and clinical studies.

COHmax: an algorithm to maximise coherence in estimates of dynamic cerebral autoregulation.

OBJECTIVE: The reliability of dynamic cerebral autoregulation (dCA) parameters, obtained with transfer function analysis (TFA) of spontaneous fluctuations in arterial blood pressure (BP), require statistically significant values of the coherence function. A new algorithm (COHmax) is proposed to increase values of coherence by means of the automated, selective removal of sub-segments of data. APPROACH: Healthy subjects were studied at baseline (normocapnia) and during 5% breathing of CO2 (hypercapnia). BP (Finapres), cerebral blood flow velocity (CBFV, transcranial Doppler), end-tidal CO2 (EtCO2, capnography) and heart rate (ECG) were recorded continuously during 5 min in each condition. TFA was performed with sub-segments of data of duration (SEGD) 100 s, 50 s or 25 s and the autoregulation index (ARI) was obtained from the CBFV response to a step change in BP. The area-under-the curve (AUC) was obtained from the receiver-operating characteristic (ROC) curve for the detection of changes in dCA resulting from hypercapnia. MAIN RESULTS: In 120 healthy subjects (69 male, age range 20-77 years), CO2 breathing was effective in changing mean EtCO2 and CBFV (p < 0.001). For SEGD = 100 s, ARI changed from 5.8 ± 1.4 (normocapnia) to 4.0 ± 1.7 (hypercapnia, p < 0.0001), with similar differences for SEGD = 50 s or 25 s. Depending on the value of SEGD, in normocapnia, 15.8% to 18.3% of ARI estimates were rejected due to poor coherence, with corresponding rates of 8.3% to 13.3% in hypercapnia. With increasing coherence, 36.4% to 63.2% of these could be recovered in normocapnia (p < 0.001) and 50.0% to 83.0% in hypercapnia (p < 0.005). For SEGD = 100 s, ROC AUC was not influenced by the algorithm, but it was superior to corresponding values for SEGD = 50 s or 25 s. SIGNIFICANCE: COHmax has the potential to improve the yield of TFA estimates of dCA parameters, without introducing a bias or deterioration of their ability to detect impairment of autoregulation. Further studies are needed to assess the behaviour of the algorithm in patients with different cerebrovascular conditions.

Chasing the evidence: the influence of data segmentation on estimates of dynamic cerebral autoregulation.

OBJECTIVE: Transfer function analysis (TFA) of dynamic cerebral autoregulation (dCA) requires smoothing of spectral estimates using segmentation of the data (SD). Systematic studies are required to elucidate the potential influence of SD on dCA parameters. APPROACH: Healthy subjects (HS, n = 237) and acute ischaemic stroke patients (AIS, n = 98) were included. Cerebral blood flow velocity (CBFV, transcranial Doppler ultrasound) was recorded supine at rest with continuous arterial blood pressure (BP, Finometer) for a minimum of 5 min. TFA was performed with durations SD = 100, 50 or 25 s and 50% superposition to derive estimates of coherence, gain and phase for the BP-CBFV relationship. The autoregulation index (ARI) was estimated from the CBFV step response. Intrasubject reproducibility was expressed by the intraclass correlation coefficient (ICC). MAIN RESULTS: In HS, the ARI, coherence, gain, and phase (low frequency) were influenced by SD, but in AIS, phase (very low frequency) and ARI were not affected. ICC was excellent (>0.75) for all parameters, for both HS and AIS. For SD = 100 s, ARI was different between HS and AIS (mean ± sdev: 5.70 ± 1.61 vs 5.1 ± 2.0; p < 0.01) and the significance of this difference was maintained for SD = 50 s and 25 s. Using SD = 100 s as reference, the rate of misclassification, based on a threshold of ARI ⩽ 4, was 6.3% for SD = 50 s and 8.1% for SD = 25 s in HS, with corresponding values of 11.7% and 8.2% in AIS patients, respectively. SIGNIFICANCE: Further studies are warranted with SD values lower than the recommended standard of SD = 100 s, to explore possibilities of improving the reproducibility, sensitivity and prognostic value of TFA parameters used as metrics of dCA.

Can we use short recordings for assessment of dynamic cerebral autoregulation? A sensitivity analysis study in acute ischaemic stroke and healthy subjects.

OBJECTIVE: It is unclear whether the duration of recordings influences estimates of dynamic cerebral autoregulation (dCA). Therefore, we performed a retrospective study of the effects of reducing recording durations on dCA estimates; with the potential to inform recording duration for reliable estimates in challenging clinical populations. APPROACH: Seventy-eight healthy control subjects and 79 acute ischaemic stroke (AIS) patients were included. Cerebral blood flow (CBF) velocity was recorded with transcranial Doppler (TCD) and continuous blood pressure (BP) with a Finapres device. The autoregulation index (ARI), derived with transfer function analysis (TFA), was calculated for recording durations at one-minute intervals between 1 and 5 min using the same starting point of each recording. MAIN RESULTS: Though recording duration did not affect the overall ARI value, when compared to control subjects, AIS patients had significantly lower ARI values for durations between 3 and 5 min (p  < 0.0001), but not 1 and 2 min. The intraclass correlation coefficient of all participants, for reproducibility of the five recording durations, was 0.69. AIS patients classified as having impaired cerebral autoregulation (CA; ARI ⩽ 4) at 5 min, had a 7.1% rate of false negatives for both 4 and 3 min recordings, reaching 42.9% for 1 min recording. The percentage of false-positives also increased with reduced recording durations (from 0% at 5 to 16.2% at 1 min). SIGNIFICANCE: Reducing recording durations from 5 to 3 min can still provide reliable estimates of ARI, and may facilitate CA studies in potentially medically unstable AIS patients, as well as in other patient groups.

The role of sartorius muscle flaps in the management of complex groin wounds.

A best evidence topic in vascular surgery was written according to a structured protocol. The question addressed was whether sartorius muscle flaps (SMF) can be effectively used in the setting of complex groin wounds with exposed prosthetic grafts for graft salvage and limb salvage. The literature review identified 33 articles reporting on the use of SMF for complex vascular wounds. Of these, 7 articles reporting on the use of 539 SMFs were considered the best evidence to answer the clinical question. Indications included surgical site infections with or without wound dehiscence, lymph leaks, graft infection and groin pseudoaneurysms, whereas in 98 of the included 539 cases, the flaps were performed prophylactically. Vacuum-assisted closure systems were used in 25 cases to promote healing. The use of an SMF is associated with low rates of muscle flap and graft complications, whereas outcomes seem to be independent of the presence of occlusive disease in the superficial femoral artery. They can be effectively combined with aggressive debridement strategies and vacuum-assisted closure devices to optimize outcomes. The published literature supports the use of SMF in the management of complex groin wounds following vascular reconstruction and is associated with encouraging flap, limb and graft salvage rates.

Merkel-cell carcinoma of the upper limb.

Merkel-cell carcinoma is a rare form of aggressive cutaneous cancer that is associated with a poor prognosis. Despite significant advances, its pathogenesis is still poorly understood, and treatment remains controversial. Timely diagnosis and early management is essential in improving survival rate. We present a case of a 63-year-old patient with a rapidly growing upper limb Merkel-cell carcinoma. It was treated with wide-local excision and adjuvant radiotherapy.