Placenta Accreta Spectrum Part I: anesthesia considerations based on an extended review of the literature.

"Placenta Accreta Spectrum" (PAS) describes abnormal placental adherence to the uterine wall without spontaneous separation at delivery. Though relatively rare, PAS presents a particular challenge to anesthesiologists, as it is associated with massive peripartum hemorrhage and high maternal morbidity and mortality. Standardized evidence-based PAS management strategies are currently evolving and emphasize: "PAS centers of excellence", multidisciplinary teams, novel diagnostics/pharmaceuticals (especially regarding hemostasis, hemostatic agents, point-of-care diagnostics), and novel operative/interventional approaches (expectant management, balloon occlusion, embolization). Though available data are heterogeneous, these developments affect anesthetic management and must be considered in planed anesthetic approaches. This two-part review provides a critical overview of the current evidence and offers structured evidence-based recommendations to help anesthesiologists improve outcomes for women with PAS. This first part discusses PAS management in centers of excellence, multidisciplinary care team, anesthetic approach and monitoring, surgical approaches, patient safety checklists, temperature management, interventional radiology, postoperative care and pain therapy. The diagnosis and treatment of hemostatic disturbances and preoperative prepartum anemia, blood loss, transfusion management and postpartum venous thromboembolism will be addressed in the second part of this series.

Placenta Accreta Spectrum Part II: hemostatic considerations based on an extended review of the literature.

"Placenta Accreta Spectrum" (PAS) is a rare but serious pregnancy condition where the placenta abnormally adheres to the uterine wall and fails to spontaneously release after delivery. When it occurs, PAS is associated with high maternal morbidity and mortality - as PAS management can be particularly challenging. This two-part review summarizes current evidence in PAS management, identifies its most challenging aspects, and offers evidence-based recommendations to improve management strategies and PAS outcomes. The first part of this two-part review highlighted the general anesthetic approach, surgical and interventional management strategies, specialized "centers of excellence," and multidisciplinary PAS treatment teams. The high rates of PAS morbidity and mortality are often provoked by PAS-associated coagulopathies and peripartal hemorrhage (PPH). Anesthesiologists need to be prepared for massive blood loss, transfusion, and to manage potential coagulopathies. In this second part of this two-part review, we specifically reviewed the current literature pertaining to hemostatic changes, blood loss, transfusion management, and postpartum venous thromboembolism prophylaxis in PAS patients. Taken together, the two parts of this review provide a comprehensive survey of challenging aspects in PAS management for anesthesiologists.

Ankle-Brachial Index and Recurrent Stroke Risk: Meta-Analysis.

BACKGROUND AND PURPOSE: The ankle-brachial index (ABI) is a fast, cheap, noninvasive indicator of atherosclerotic burden that may also be a predictor of stroke recurrence. In this systematic review and meta-analysis, we sought to explore ABI's merit as a marker for stroke recurrence and vascular risk by synthesizing the data currently available in stroke literature. METHODS: We searched Embase, MEDLINE, and Pubmed databases for prospective cohort studies that included consecutive patients with stroke and transient ischemic attack, measured ABI at baseline, and performed a follow-up assessment at least 12 months after initial stroke or transient ischemic attack. The following end points were chosen for our analysis: recurrent stroke and combined vascular end point (recurrent vascular event or vascular death). Crude risk ratios and adjusted Cox proportional hazard ratios were combined separately using the random-effects model. Study-level characteristics (eg, percent of cohort with a history of hypertension, average cohort age, level of adjustment, and mean follow-up duration) were included as covariates in a metaregression analysis. RESULTS: We identified 11 studies (5374 patients) that were not significantly heterogeneous. Pooling adjusted hazard ratios showed that low ABI was associated with both an increased hazard of recurrent stroke (hazard ratio, 1.70; 95% confidence interval, 1.10-2.64) and an increased risk of vascular events or vascular death (hazard ratio, 2.22; 95% confidence interval, 1.67-2.97). CONCLUSION: Our results confirm the positive association between ABI and stroke recurrence. Further studies are needed to see whether inclusion of ABI will help improve the accuracy of prediction models and management of stroke patients.

Triglycerides and carotid intima-media thickness in ischemic stroke patients.

BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) is an established marker for atherosclerosis. The role of triglycerides in CCA-IMT remains controversial. We sought to determine if elevated fasting and post-challenge triglycerides are associated with CCA-IMT. METHODS: All acute ischemic stroke patients who participated in the Berlin "Cream & Sugar" study in the Charité Virchow and Charité Mitte Campuses between January 2009 and January 2014 and underwent carotid artery ultrasound studies were eligible for inclusion. A combined oral glucose and triglyceride tolerance test was performed 3-7 days after first ever ischemic stroke. Patients were classified according to triglyceride metabolism-namely, (1) patients reaching a maximum triglyceride levels 3 h post-challenge ("fast metabolizers," n = 37), (2) patients with increasing triglycerides 4 (medium metabolizers, n = 64), and (3) 5 h post-challenge ("slow metabolizers," n = 44; 13 missing). RESULTS: We included 158 patients (34% female; mean age 63 years, SD 14). Absolute non-fasting triglyceride levels were positively associated with CCA-IMT. A final multiple regression model revealed that older age, more severe strokes, and higher levels of fasting triglycerides were significantly and independently associated with higher mean CCA-IMT. Older age, higher waist-to-hip ratio, and higher levels of thyroid-stimulating hormone were independently associated with higher maximum CCA-IMT. CONCLUSION: Fasting triglycerides but not post-challenge triglycerides associate with CCA-IMT. An oral fat challenge may not add information on atherosclerotic status in ischemic stroke patients. CLINICAL TRIAL REGISTRATION INFORMATION: The Berlin "Cream & Sugar" study is registered with EudraCT (2009-010356-97) and clinicaltrials.gov (NCT 01378468).

Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis.

OBJECTIVE: Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. METHODS: A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. RESULTS: A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. CONCLUSION: Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted.

Risk and Outcome of Aortic Valve Surgery in the Transcatheter Valve Era: The Gender Aspect.

OBJECTIVES: In 2009, a transcatheter valve intervention program was introduced at our centre. The aim of this single-centre retrospective study was to evaluate gender-specific risk profiles and outcome of patients undergoing surgical aortic valve replacement before and after 2009. METHODS: We assessed the preoperative logistic EuroSCORE and age, gender and 30-day-survival of 357 patients diagnosed with symptomatic severe aortic stenosis that underwent primary isolated surgical aortic valve replacement in 2007-2008 (group I, n = 191, 47% female) and 2010-2011 (group II, n = 166, 40% female). Survival follow up data was 100% complete. RESULTS: Women in group II were significantly younger (71.6 ± 9.0 years; p = 0.004) and showed significantly lower risk profiles (logistic EuroSCORE: 9.6 ± 9.9%; p = 0.04) than women in group I (age: 75.6 ± 8.5 years, logistic EuroSCORE: 13.9 ± 15.9). Men's age and risk profiles remained similar in both groups. Observed survival at 30 days was 98.8% in group II and 95.8% in group I which represented a statistical trend (p = 0.09). Female survival in group I was 92.2% and significantly worse as compared to 99% male survival in group I (p = 0.03). This significant difference in gender ratio of mortality was not detected in group II (female survival 97%, male survival 100%; p = 0.2). Being female was a significant risk factor in group I (odds ratio; 8.4; p = 0.03) but not in group II any longer (odds ratio: 1.0; p = 0.2). CONCLUSIONS: The possibility of transcatheter aortic valve replacement for therapy of aortic stenosis has led to a lower risk and improved outcome of surgical aortic valve replacement especially for women.

White matter lesions and depression: a systematic review and meta-analysis.

We sought to determine if an association exists between overall, deep, and periventricular white matter hyperintensities and depression. We searched PubMed (Medline) and Scopus (Embase) from April-October 2012 using the MeSH terms: "White matter lesions" OR "white matter disease" OR "Cerebrovascular Disease" OR "Leukoencephalopathies" AND "Depressive Disorder" AND "magnetic resonance imaging," and "Depression" AND "leukoaraiosis." No language limits were implemented. Hand searching was performed of all included studies and relevant review articles. 913 PubMed and 188 Scopus citations were identified. Relevant, human, non-overlapping magnetic resonance imaging studies were eligible for inclusion if they reported generic data. We extracted the most adjusted odds ratios reported generated from comparing depression across severe (determined either volumetrically or visually) and mild/no white matter lesion groups. 19 reports were included. Cross-sectional subgroup analyses showed that deep white matter hyperintensities significantly associated with depression (N = 2261, odds ratio 1.02, 95% confidence interval 1.00-1.04, p = 0.02), whereas periventricular (N = 3813, odds ratio 1.08, 95% confidence interval 0.99-1.17, p = 0.07) and overall did not (N = 5876, odds ratio 1.12, 95% confidence interval 0.96-1.30, p = 0.14). Overall longitudinal analysis revealed a pooled odds ratio of 1.12 (N = 2015; 95% confidence interval 0.97-1.29; p = 0.13; Q = 7.19, p = 0.07; I2 = 58.3%). Longitudinal subgroup analyses revealed that overall white matter hyperintensities (N = 1882, odds ratio 1.22, 95% confidence interval, 1.06-1.4, p < 0.01) significantly associated with depression but deep did not (N = 660, odds ratio 2.02, 95% confidence interval, 0.56-7.22, p = 0.281). No significant heterogeneity was present in subgroup analyses. In conclusion, we found a significant, but weak association between white matter hyperintensities and depression.

Thyroid-stimulating hormone, white matter hyperintensities, and functional outcome in acute ischemic stroke patients.

BACKGROUND: Thyroid-stimulating hormone (TSH) concentrations are frequently altered in acute ischemic stroke patients. It is becoming increasingly apparent that various hormones in the hypothalamus-pituitary-thyroid axis may be associated with functional stroke outcome. We have previously shown that white matter hyperintensities (WMH) of presumed vascular origin are strong indicators of functional outcome. It is unclear whether an association exists between WMH and TSH. We therefore sought to determine whether TSH levels, measured in acute ischemic stroke patients, are associated with WMH and functional outcome. METHODS: We analyzed all first ischemic stroke patients who participated in the Berlin 'Cream & Sugar' Study (NCT 01378468) and completed a 1-year follow-up assessment from January 2009 to March 2013. Patients were stratified into 3 groups: (1) low TSH (0.1-0.44 µU/ml); (2) normal TSH (0.44-2.5 µU/ml), and (3) high TSH (2.5-20 µU/ml). WMH were assessed using the Fazekas and Wahlund visual rating scales. Functional outcome was assessed using the modified Rankin Scale and was performed via telephone at 1 year by a certified rater. RESULTS: 183 patients were included [median age 66, interquartile range (IQR) 54-75; 33% females; median National Institute of Health Stroke Scale 3, IQR 1-4, range 0-24]. Venous samples were collected a median of 4 days (IQR 3-5) following initial symptom onset between 8 and 9 a.m. following a 10-hour fast. Patients with normal TSH levels (n = 132; 72%) had significantly higher rates of prestroke diabetes than patients with high TSH levels (normal TSH 17%; high TSH 1%; p = 0.03). Additionally, patients with normal TSH levels tended to have higher estimated glomerular filtration rates than patients with high and low TSH concentrations (normal TSH median estimated glomerular filtration rates: 83 ml/min/1.73 m(2); high TSH median estimated glomerular filtration rates: 76 ml/min/1.73 m(2); low TSH median: 78 ml/min/1.73 m(2); p = 0.068). Logistical regression analysis force-adjusted for age (quartiles), NIHSS (quartiles), prestroke diabetes status, and stroke subtype revealed significant associations between WMH and TSH [Wahlund scores: odds ratio 2.547, 95% confidence interval (CI) 1.159-5.598, p = 0.020; Fazekas scores: odds ratio 2.530, 95% CI 1.115-5.741, p = 0.003]. Functional outcome was not significantly associated with TSH levels in univariate or multivariate models. CONCLUSION: TSH levels are independently associated with WMH in acute ischemic stroke patients. Based on our findings, we cannot recommend assessing TSH to estimate the 1-year functional outcome following ischemic stroke.

Fasting versus post-challenge triglycerides and pre-existing cavitating lacunes: a berlin "cream & sugar" substudy.

BACKGROUND AND PURPOSE: Although the presence of cavitating lacunes on brain imaging may have prognostic implications, the modifiable risk factors underlying these frequently observed lesions are not completely understood. We sought to determine if fasting and post-challenge triglycerides associate with cavitating lacunes. METHODS: All first ischemic stroke patients who completed a novel combined oral triglyceride and glucose tolerance test and MRI between January 2009 and June 2012 were included. Fluid-attenuated inversion recovery or T2 MRI sequences were used to visualize cavitating lacunes and white matter hyperintensities, which were graded using the Wahlund visual scale. RESULTS: One hundred and ninety patients were included (median age 66, IQR 52-73; 33% female; median National Institute of Health Stroke Scale 2, IQR 1-4). A forward stepwise binary logistical regression analysis applying the Hosmer-Lemeshow goodness of fit test adjusted for parameters significant in univariate analyses (at the p < 0.10 level) revealed that Wahlund scores (Wahlund 0-4: reference; Wahlund 5-10: adjusted odds ratio, 5.1; 95% confidence interval, 1.3-20.0, p = 0.019; Wahlund>10: adjusted odds ratio 9.6; 95% CI, 1.55-59.35; p = 0.015) and the highest quartile of post-challenge triglycerides (>295 mg/dL; adjusted odds ratio, 7.36; 95% confidence interval 1.24-43.70; p = 0.028) independently associated with the presence of cavitating lacunes. CONCLUSION: Post-challenge serum triglycerides are independently associated with the presence of cavitating lacunes.

White matter lesion severity in mild acute ischemic stroke patients and functional outcome after 1 year.

BACKGROUND AND PURPOSE: To determine if severity of visually assessed white matter disease is associated with disability after ischemic stroke. METHODS: In this Berlin "Cream & Sugar" substudy, all first ischemic stroke patients who received magnetic resonance imaging and completed follow-up between January 2009 and December 2010, were enrolled. Severity of white matter disease was assessed on fluid-attenuated inversion recovery or T2-weighted sequences using the Wahlund and Fazekas visual scales. Functional outcome was assessed after 1 year using the modified Rankin Scale (follow-up [FU] modified Rankin Scale [mRS]). RESULTS: Of 101 patients (37% female; median age, 67 years; interquartile range, 54-75; National Institutes of Health Stroke Scale score, 1; interquartile range, 0-2), median FU mRS was 1 (interquartile range, 0-2). Binary logistical regression adjusted for age (at 5-year intervals), acute National Institutes of Health Stroke Scale scores, fasting glucose, insulin, glycosylated hemoglobin, creatinine, C-reactive protein quartiles, waist circumference, and systolic blood pressure revealed that Fazekas scores of 2 and 3 independently associated with FU mRS (Fazekas score 2: adjusted odds ratio, 8.4; 95% confidence interval, 2.35-30.09; P=0.001; Fazekas score 3: adjusted odds ratio, 4.2; 95% confidence interval, 1.04-16.96; P=0.044). Wahlund scores>10 were significantly associated with FU mRS when fasting glucose levels were removed from the regression analysis (adjusted odds ratio, 12.17; 95% confidence interval, 1.91-77.54; P=0.008). CONCLUSIONS: Severe white matter disease defined by standard criteria in acute ischemic stroke patients is associated with disability at 1 year and can be assessed quickly using visual rating scales. CLINICAL TRIAL REGISTRATION INFORMATION: URLs: http://www.clinicaltrials.gov and https://eudract.ema.europa.eu. Unique identifiers: NCT 01378468 and 2009-010356-97.