Patients Requiring Conversion to General Anesthesia during Endovascular Therapy Have Worse Outcomes: A Post Hoc Analysis of Data from the SAGA Collaboration.

BACKGROUND AND PURPOSE: Endovascular therapy for acute ischemic stroke is often performed with the patient under conscious sedation. Emergent conversion from conscious sedation to general anesthesia is sometimes necessary. The aim of this study was to assess the functional outcome in converted patients compared with patients who remained in conscious sedation and to identify predictors associated with the risk of conversion. MATERIALS AND METHODS: Data from 368 patients, included in 3 trials randomizing between conscious sedation and general anesthesia before endovascular therapy (SIESTA, ANSTROKE, and GOLIATH) constituted the study cohort. Twenty-one (11%) of 185 patients randomized to conscious sedation were emergently converted to general anesthesia. RESULTS: Absence of hyperlipidemia seemed to be the strongest predictor of conversion to general anesthesia, albeit a weak predictor (area under curve = 0.62). Sex, hypertension, diabetes, smoking status, atrial fibrillation, blood pressure, size of the infarct, and level and side of the occlusion were not significantly associated with conversion to general anesthesia. Neither age (mean age, 71.3 ± 13.8 years for conscious sedation versus 71.6 ± 12.3 years for converters, P = .58) nor severity of stroke (mean NIHSS score, 17 ± 4 versus 18 ± 4, respectively, P = .27) were significantly different between converters and those who tolerated conscious sedation. The converters had significantly worse outcome with a common odds ratio of 2.67 (P = .015) for a shift toward a higher mRS score compared with the patients remaining in the conscious sedation group. CONCLUSIONS: Patients undergoing conversion had significantly worse outcome compared with patients remaining in conscious sedation. No factor was identified that predicted conversion from conscious sedation to general anesthesia.

A novel approach to genetic engineering of T-cell subsets by hematopoietic stem cell infection with a bicistronic lentivirus.

Lentiviral modification of hematopoietic stem cells (HSCs) paved the way for in vivo experimentation and therapeutic approaches in patients with genetic disease. A disadvantage of this method is the use of a ubiquitous promoter leads not only to genetic modification of the leukocyte subset of interest e.g. T-cells, but also all other subsequent leukocyte progeny of the parent HSCs. To overcome this limitation we tested a bicistronic lentivirus, enabling subset specific modifications. Designed novel lentiviral constructs harbor a global promoter (mPGK) regulating mCherry for HSCs selection and a T-cell specific promoter upstream of eGFP. Two T-cell specific promoters were assessed: the distal Lck-(dLck) and the CD3δ-promoter. Transduced HSCs were FACS sorted by mCherry expression and transferred into sublethally irradiated C57/BL6 mice. Successful transplantation and T-cell specific expression of eGFP was monitored by peripheral blood assessment. Furthermore, recruitment response of lentiviral engineered leukocytes to the site of inflammation was tested in a peritonitis model without functional impairment. Our constructed lentivirus enables fast generation of subset specific leukocyte transgenesis as shown in T-cells in vivo and opens new opportunities to modify other HSCs derived subsets in the future.

Precision and reproducibility of automated computer-guided Psoriasis Area and Severity Index measurements in comparison with trained physicians.

BACKGROUND: The Psoriasis Area and Severity Index (PASI) represents the gold standard for psoriasis severity assessments but is limited by its subjectivity and low intra- and inter-rater consistency. OBJECTIVES: To investigate the precision and reproducibility of automated, computer-guided PASI measurements (ACPMs) in comparison with three trained physicians. METHODS: This was a comparative observational study assessing ACPMs attained by automated total-body imaging and computerized digital image analysis in a cohort of 120 patients affected by plaque psoriasis of various severities. The level of agreement between ACPMs and physicians' PASI measurements was calculated by the intraclass correlation coefficient (ICC). The reproducibility of ACPMs in comparison with physicians' PASI measurements was investigated by performing two successive 'repeat PASI calculations' in the same patients. RESULTS: The agreement between ACPMs and physicians' PASI calculations in 120 fully evaluable patients was high (ICC 0·86, 95% confidence interval 0·80-0·90, mean absolute difference 2·5 PASI points). Repeat ACPMs to measure the reproducibility showed an excellent ICC of 0·99 (95% confidence interval 0·98-0·99) with a mean absolute difference of 0·5 PASI points. The ACPMs thus outperformed the three physicians for intrarater reliability (mean ICC 0·86). CONCLUSIONS: The results of this first clinical study investigating ACPMs in 120 patients with psoriasis indicate a similar precision and higher reproducibility in comparison with trained physicians. Limitations arise from poorly observable body sites and from patients unable to attain predefined postures during automated image acquisition.

Network meta-analysis of topical haemostatic agents in thyroid surgery.

BACKGROUND: The objective of this study was to investigate the potential benefit of local haemostatic agents for the prevention of postoperative bleeding after thyroidectomy. METHODS: A systematic literature search was performed, and RCTs involving adult patients who underwent thyroid surgery using either active (AHA) or passive (PHA) haemostatic agents were included in the review. The main outcome was the rate of cervical haematoma that required reoperation. A Bayesian random-effects model was used for network meta-analysis with minimally informative prior distributions. RESULTS: Thirteen RCTs were included. The rate of cervical haematoma requiring reoperation ranged from 0 to 9·1 per cent, and was not reduced by haemostatic agents: AHA versus control (odds ratio (OR) 1·53, 95 per cent credibility interval 0·21 to 10·77); PHA versus control (OR 2·74, 0·41 to 16·62) and AHA versus PHA (OR 1·77, 0·12 to 25·06). No difference was observed in the time required for drain removal, duration of hospital stay, and the rate of postoperative hypocalcaemia or recurrent nerve palsy. AHA led to a significantly lower total postoperative blood loss and reduced operating time in comparison with both the control and PHA groups. CONCLUSION: The general use of local haemostatic agents has not been shown to reduce the rate of clinically relevant bleeding.

Man against machine: diagnostic performance of a deep learning convolutional neural network for dermoscopic melanoma recognition in comparison to 58 dermatologists.

Background: Deep learning convolutional neural networks (CNN) may facilitate melanoma detection, but data comparing a CNN's diagnostic performance to larger groups of dermatologists are lacking. Methods: Google's Inception v4 CNN architecture was trained and validated using dermoscopic images and corresponding diagnoses. In a comparative cross-sectional reader study a 100-image test-set was used (level-I: dermoscopy only; level-II: dermoscopy plus clinical information and images). Main outcome measures were sensitivity, specificity and area under the curve (AUC) of receiver operating characteristics (ROC) for diagnostic classification (dichotomous) of lesions by the CNN versus an international group of 58 dermatologists during level-I or -II of the reader study. Secondary end points included the dermatologists' diagnostic performance in their management decisions and differences in the diagnostic performance of dermatologists during level-I and -II of the reader study. Additionally, the CNN's performance was compared with the top-five algorithms of the 2016 International Symposium on Biomedical Imaging (ISBI) challenge. Results: In level-I dermatologists achieved a mean (±standard deviation) sensitivity and specificity for lesion classification of 86.6% (±9.3%) and 71.3% (±11.2%), respectively. More clinical information (level-II) improved the sensitivity to 88.9% (±9.6%, P = 0.19) and specificity to 75.7% (±11.7%, P < 0.05). The CNN ROC curve revealed a higher specificity of 82.5% when compared with dermatologists in level-I (71.3%, P < 0.01) and level-II (75.7%, P < 0.01) at their sensitivities of 86.6% and 88.9%, respectively. The CNN ROC AUC was greater than the mean ROC area of dermatologists (0.86 versus 0.79, P < 0.01). The CNN scored results close to the top three algorithms of the ISBI 2016 challenge. Conclusions: For the first time we compared a CNN's diagnostic performance with a large international group of 58 dermatologists, including 30 experts. Most dermatologists were outperformed by the CNN. Irrespective of any physicians' experience, they may benefit from assistance by a CNN's image classification. Clinical trial number: This study was registered at the German Clinical Trial Register (DRKS-Study-ID: DRKS00013570; https://www.drks.de/drks_web/).

Intra- and interobserver variability of image-based PASI assessments in 120 patients suffering from plaque-type psoriasis.

BACKGROUND: The Psoriasis Area and Severity Index (PASI) is the standard for psoriasis severity assessment. However, PASI measurement is complex and subjective, frequently leading to a high intra- and interobserver variability. To date, the precise extent of variability in PASI measurements and its underlying causes remain unknown. OBJECTIVE: To determine the inter- and intrarater variability of image-based PASI measurements by calculating Intra-Class-Correlation-Coefficients (ICCs) and to investigate the impact of the different PASI components and specific anatomic regions on the extent of variability. METHODS: First, the methodology of 'image-based' vs. commonly used 'live' PASI measurements was validated in a pilot study. Next, in an observational cohort study, PASI scores of 120 patients affected by plaque psoriasis were prospectively evaluated by three formally trained physicians by means of total body images (TBI). Each observer independently performed two rounds of image-based PASI calculations in all patients at two different time points. RESULTS: Overall, 720 image-based PASI scores were calculated with a mean PASI of 8.8 (range 0.7-34.8). An interrater variability with an ICC of 0.895 and mean absolute difference (MAD) of 3.3 PASI points were observed. Intrarater variability showed a mean ICC of 0.877 and a MAD of 2.2 points. When considering specific PASI components, the highest agreement was found for the assessment of the involved body surface area (BSA), while the lowest ICCs were calculated for severity scoring of 'scaling' and 'induration'. As BSA scores serve as a multiplier in the calculation of PASI, minor inaccuracies were capable of inducing a large share of variability. CONCLUSION: The overall inter- and intrarater reliability of image-based PASI measurements in this study was good. However, physicians were formally trained and experienced, which frequently is not the case in a real-life clinical setting. Therefore, new strategies for higher standardization and objectivity of PASI calculations are needed.

Predictors of symptomatic intracranial haemorrhage in off-label thrombolysis: an analysis of the Safe Implementation of Treatments in Stroke registry.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. METHODS: This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. RESULTS: Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. CONCLUSIONS: Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.

The Impact of Conscious Sedation versus General Anesthesia for Stroke Thrombectomy on the Predictive Value of Collateral Status: A Post Hoc Analysis of the SIESTA Trial.

BACKGROUND AND PURPOSE: Radiologic selection criteria to identify patients likely to benefit from endovascular stroke treatment are still controversial. In this post hoc analysis of the recent randomized Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA) trial, we aimed to investigate the impact of sedation mode (conscious sedation versus general anesthesia) on the predictive value of collateral status. MATERIALS AND METHODS: Using imaging data from SIESTA, we assessed collateral status with the collateral score of Tan et al and graded it from absent to good collaterals (0-3). We examined the association of collateral status with 24-hour improvement of the NIHSS score, infarct volume, and mRS at 3 months according to the sedation regimen. RESULTS: In a cohort of 104 patients, the NIHSS score improved significantly in patients with moderate or good collaterals (2-3) compared with patients with no or poor collaterals (0-1) (P = .011; mean, -5.8 ± 7.6 versus -1.1 ± 10.7). Tan 2-3 was also associated with significantly higher ASPECTS before endovascular stroke treatment (median, 9 versus 7; P < .001) and smaller mean infarct size after endovascular stroke treatment (median, 35.0 versus 107.4; P < .001). When we differentiated the population according to collateral status (0.1 versus 2.3), the sedation modes conscious sedation and general anesthesia were not associated with significant differences in the predictive value of collateral status regarding infarction size or functional outcome. CONCLUSIONS: The sedation mode, conscious sedation or general anesthesia, did not influence the predictive value of collaterals in patients with large-vessel occlusion anterior circulation stroke undergoing thrombectomy in the SIESTA trial.

A prospective randomized controlled trial for assessment of perineal hydrodissection technique for nervesparing robot assisted radical prostatectomy.

BACKGROUND: This study prospectively evaluated the safety and efficacy of perineal hydrodissection in robot assisted nervesparing prostatectomy. METHODS: Patients were randomized for perineal, ultrasound guided hydrodissection (HD) before radical prostatectomy and compared with standard treatment (ST). Follow-up was done every 3 months, including erectile function (IIEF5-score), reported grade of erection, ability for sexual intercourse, continence, PSA. RESULTS: 21 patients were enrolled to this prospective study, 10 for ST and 11 for HD. No significant differences in demographic and preoperative oncological data between both groups were identified. Blood loss and time for surgery did not differ significantly. HD resulted in 66% (4/6) rate of positive surgical margins (PSM) in pT3 tumors vs 50% in ST (1/2; P = 0.67). Follow-up revealed higher IIEF scores, better ability for sexual intercourse and early continence in HD. CONCLUSIONS: Erectile function after radical prostatectomy was improved by perineal hydrodissection in this proof of principal study. However, careful patient selection and further studies are needed as perineal hydrodissection could result in increased positive surgical margins in pT3a tumors.

Pain management in photodynamic therapy using a nitrous oxide/oxygen mixture: a prospective, within-patient, controlled clinical trial.

BACKGROUND: Photodynamic therapy is an effective treatment for actinic keratoses. Nevertheless, severe pain during the procedure is a serious adverse effect, which leads to interruption or even termination. Complete pain relief remains a difficult challenge. OBJECTIVE: To evaluate the effect of a nitrous oxide/oxygen mixture on pain intensity during photodynamic therapy. METHODS: This clinical trial has been designed as a prospective, single-centre, explorative, controlled, observational study. RESULTS: We were able to detect a significant overall pain reduction of 55.2% after application of a nitrous oxide/oxygen mixture by means of an intra-individual comparison. Furthermore, the total number of therapy interruption significantly decreased by 82% after the inhalation analgesia. Additionally, treatment satisfaction ranged from 'extremely to very satisfied'. CONCLUSIONS: This study shows that analgesia by means of a nitrous oxide/oxygen mixture is a very effective and well-tolerated method for achieving significant pain reduction during photodynamic therapy.

Meta-analysis of reconstruction techniques after low anterior resection for rectal cancer.

BACKGROUND: Options for reconstruction after low anterior resection (LAR) for rectal cancer include straight or side-to-end coloanal anastomosis (CAA), colonic J pouch and transverse coloplasty. This systematic review compared these techniques in terms of function, surgical outcomes and quality of life. METHODS: A systematic literature search (MEDLINE, Embase and the Cochrane Library, from inception of the databases until November 2014) was conducted to identify randomized clinical trials comparing reconstructive techniques after LAR. Random-effects meta-analyses were carried out, and results presented as weighted odds ratios or mean differences with corresponding 95 per cent c.i. A network meta-analysis was conducted for the outcome anastomotic leakage. RESULTS: The search yielded 965 results; 21 trials comprising data from 1636 patients were included. Colonic J pouch was associated with lower stool frequency and antidiarrhoeal medication use for up to 1 year after surgery compared with straight CAA. Transverse coloplasty and side-to-end CAA had similar functional outcomes to the colonic J pouch. No superiority was found for any of the techniques in terms of anastomotic leak rate. CONCLUSION: Colonic J pouch and side-to-end CAA or transverse coloplasty lead to a better functional outcome than straight CAA for the first year after surgery.

Volatile sedation with sevoflurane in intensive care patients with acute stroke or subarachnoid haemorrhage using AnaConDa®: an observational study.

BACKGROUND: The anaesthetic conserving device, AnaConDa(®), allows use of inhaled anaesthetics for sedation in the intensive care unit. We prospectively measured cerebral and cardiopulmonary parameters in patients with acute stroke or subarachnoid haemorrhage during a switch from i.v. to inhalative sedation. METHODS: 25 patients were switched from i.v. to an indefinite period of inhaled sedation with sevoflurane. Mean arterial (MAP), intracranial (ICP), and cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (MFV) and fractional tissue oxygen extraction (FTOE), systemic cardiopulmonary parameters, and administered drugs were assessed before and after the change (-6 to +12 h). RESULTS: In 8 patients, critically reduced MAP or ICP crisis led to premature termination of sevoflurane sedation. In the other 17 patients, after the first hour, mean ICP increased [2.4 (4.5) mm Hg; P=0.046], MAP decreased [7.8 (14.1) mm Hg; P=0.036] and thus CPP decreased also [-10.2 (15.1) mm Hg; P=0.014]. MFV and FTOE did not change. Over a 12 hour post switch observational period, [Formula: see text] increased slightly [0.3 (0.8) kPa; P=0.104], ICP did not change [0.2 (3.9) mm Hg; P=0.865], but MAP [-6 (6.9) mm Hg; P=0.002] and thus CPP decreased [-6 (8.5) mm Hg; P=0.010]. CONCLUSION: Sevoflurane led to sufficient sedation, but decreased MAP and CPP in a selected cerebrovascular neurocritical care population. In about a third of these patients, severe adverse reactions, including intolerable ICP increases, were observed.

[GP-centered health care in Baden-Württemberg, Germany: Results of a quantitative and qualitative evaluation]. / Hausarztzentrierte Versorgung in Baden-Württemberg : Ergebnisse einer qualitativen und querschnittlich quantitativen Evaluation.

BACKGROUND: GP-centered health care ("Hausarztzentrierte Versorgung", HzV)-the terms of which are described in § 73b of the Social Code Book V-came into effect in Baden-Württemberg, Germany, on 1 July 2008. The HzV is aimed at enhancing health care for patients with chronic diseases and complex health care needs (e.g., those requiring long-term care). OBJECTIVES: On the basis of four working packages (WP I-WP IV), the present paper examines the impact that GP-centered health care has had on patients insured by the "AOK" regional sickness fund and their GPs. WP I addresses the association between HzV participation and the corresponding health care utilization of patients on the basis of claims data. WP II looks at any changes that GPs and patients noticed were potentially attributable to HzV participation. WP III focuses on health care assistants in primary care ("Versorgungsassistenten in der Hausarztpraxis", VERAH). These assistants play a special role within the framework of the HzV. WP IV analyzes the quality of health care for patients aged 65 years and over, also on the basis of claims data. MATERIALS AND METHODS: A mixed methods design was used for this evaluation, and quantitative and qualitative approaches taken. This design enabled insights into the implementation of the HzV in regular health care to be obtained from different perspectives. RESULTS: Numerous positive associations between HzV participation and the variables of interest were observed for all WPs. These are presented in detail in the paper. CONCLUSION: The results obtained so far clearly support the continuation of HzV and associated evaluations.

The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus.

Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3(+)) T(reg) pool consists of four different T(reg) subsets: naive CD45RA(+) T(regs), HLA-DR(-) CD45RA(-) memory T(regs) (DR(-) T(regs)) and the highly differentiated and activated HLA-DR(low+) CD45RA(-) and HLA-DR(high+) CD45RA(-) memory T(regs) (DR(low+) and DR(high+) T(regs)). Compared to healthy pregnancies, the percentage of CD4(+) CD127(low+/-) CD25(+) FoxP3(+) T(regs) within the total CD4(+) T helper cell pool was not different in patients affected by GDM. However, the suppressive activity of the total CD4(+) CD127(low+/-) CD25(+) T(reg) pool was significantly reduced in GDM patients. The composition of the total T(reg) pool changed in the way that its percentage of naive CD45RA(+) T(regs) was decreased significantly in both patients with dietary-adjusted GDM and patients with insulin-dependent GDM. In contrast, the percentage of DR(-) -memory T(regs) was increased significantly in patients with dietary-adjusted GDM, while the percentage of DR(low+) and DR(high+) memory T(regs) was increased significantly in patients with insulin-dependent GDM. Hence, our findings propose that alterations in homeostatic parameters related to the development and function of naive and memory T(regs) may cause the reduction of the suppressive capacity of the total T(reg) pool in GDM patients. However, as this is an exploratory analysis, the results are only suggestive and require further validation.

Electron collisions with laser cooled and trapped metastable helium atoms: total scattering cross sections.

Absolute measurements of total scattering cross sections for low energy (5-70 eV) electrons by metastable helium (2(3)S) atoms are presented. The measurements are performed using a magneto-optical trap which is loaded from a laser-cooled, bright beam of slow He(2(3)S) atoms. The data are compared with predictions from convergent close coupling and R matrix with pseudostate calculations, and we find good agreement between experiment and theory.