Trials of endovascular thrombectomy of basilar-artery occlusion compared to real-life data.

BACKGROUND: Two recent clinical trials showed mechanical thrombectomy (MT) of basilar-artery occlusions (BAO) in stroke to be safe and effective: Endovascular Treatment for Acute BAO (ATTENTION) and BAO Chinese Endovascular (BAOCHE). The trials restricted patient inclusion on both age and pre-stroke mRS, and with both trials conducted in China, population differences may affect generalisability of the trial results. METHODS: Consecutive patients with BAO undergoing MT were registered from 2017 to 2021 with retrospective data collection at a single centre with a predominantly Caucasian catchment population of 2.7 million. Age and pre-stroke modified Rankin Scale (mRS) were not absolute contraindications for MT. We present functional outcome as mRS at 90 days, patient characteristics and procedural safety compared to the trial intervention groups. RESULTS: Of the 108 included patients, 50 % achieved mRS 0-3 at 90 days and mortality was 32 %, which was no different from ATTENTION (46 %, p = 0.40, 37 %, p = 0.31, respectively) and BAOCHE (46 %, p = 0.50, 31 %, p = 0.93). Pre-stroke mRS 0 was seen in 62 %, 89 %, and 77 % of the study patients, ATTENTION, and BAOCHE, respectively. Proximal segment BAO was less common (22 % vs. 31 %, p = 0.04, and 65 %, p < 0.01) and intracranial stenting less frequently used (9 % vs. 40 % and 55 %, p < 0.01) in study patients compared to ATTENTION and BAOCHE, respectively. CONCLUSION: Outcome of MT in BAO stroke in a clinical patient cohort was similar to recent trials, despite broader patient inclusion and differences in both occluded BAO segment and use of stenting. Our study suggest that MT is safe and effective in a Caucasian population.

Identification of gene expression biomarkers to predict clinical response to methotrexate in patients with rheumatoid arthritis.

OBJECTIVES: To identify biomarkers at the gene expression level to predict response to methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: MTX-naïve patients with RA were started on MTX and followed up over three months. The disease activity score 28 (DAS28) was used to classify patients into responders and non-responders. Genome-wide gene expression analysis was performed in CD4 + and CD14 + mononuclear cells sampled from whole blood at baseline to identify differentially expressed genes in responders versus non-responders. Gene selection methods and prediction modelling obtained the most relevant differentially expressed genes. A logistic regression prediction model was subsequently constructed and validated via bootstrapping. The area under the receiver operating characteristic (AUC) curve was calculated to judge model quality. RESULTS: Seventy-nine patients with RA (53.4 ± 13.9 years, 74.7% females) were enrolled, and 70 finished the study with a documented treatment EULAR response (77.1% responders). Forty-six differentially expressed genes were found. The most promising genes were KRTAP4-11, LOC101927584, and PECAM1 in CD4 + cells and PSMD5 and ID1 in CD14 + cells. The final prediction model using these genes reached an AUC of 90%; the validation set's AUC was 82%. CONCLUSIONS: Our prediction model constructed via genome-wide gene expression analysis in CD4 + and CD14 + mononuclear cells yielded excellent predictions. Our findings necessitate confirmation in other cohorts of MTX-naïve RA patients. Especially if used in conjunction with previously identified clinical and laboratory (bio)markers, our results could help predict response to MTX in RA to guide treatment decisions. Key Points • Patients with rheumatoid arthritis may or may not respond to treatment with methotrexate, which is the recommended first-line drug in guidelines around the world. • In non-responders, valuable time is lost until second-line treatments are started. • This study aimed at predicting response to methotrexate by identifying differentially expressed genes from peripheral blood samples. • The final prediction model yielded excellent prognostic values, but validation in other cohorts is necessary to corroborate these findings.

[Evaluation of Psychological Distress in Obstetric Patients during the Visit Ban in Hospitals in the SARS-CoV-2 Pandemic: A Prospective, Multicentre, Controlled Study]. / Evaluation der psychischen Belastung geburtshilflicher Patientinnen während des Besuchsverbots der Kliniken im Rahmen der SARS-CoV-2-Pandemie: Eine prospektive, multizentrische, kontrollierte Studie.

INTRODUCTION: Risk factors for postpartum depression include a lack of social support and perceived social isolation. We would like to determine whether the isolation of inpatients on the maternity wards during Covid-19 leads to increased psychological stress. METHODS: This is a multicentre, controlled study of obstetric patients who gave birth during an inpatient stay. Patients were included during the visitation ban (study group) and after the visitation ban (control group). Psychological stress was evaluated with the Edinburgh Postnatal Depression Scale (EPDS) during the inpatient stay and six to eight weeks postpartum. RESULTS: A total of 194 women were included, 107 in the study group and 87 in the control group. The overall result of the first EPDS shows a higher score in the study group compared to the control group (7.0 vs. 4.9 points). Primipara show a higher score in the first EPDS compared to multipara (7.28 vs. 4.82). Caesarean section, regardless of isolation, shows a higher score in the first EPDS than vaginal birth (8.42 vs. 5.11). Comparison of vaginal birth shows a higher score only in the study group (5.97 vs. 4.07). CONCLUSION: In the context of Covid-19, women giving birth and new mothers, especially primipara, are exposed to increased psychological stress in the clinics. Caesarean section leads to increased psychological stress.

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors.

Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This kinase is translated from the Philadelphia chromosome in chronic myeloid leukemia (CML). Marketing authorization for asciminib was granted on August 25, 2022 by the European Commission. The approved indication was for patients with Philadelphia chromosome-positive CML in the chronic phase which have previously been treated with at least 2 TKIs. Clinical efficacy and safety of asciminib were evaluated in the open-label, randomized, phase III ASCEMBL study. The primary endpoint of this trial was major molecular response (MMR) rate at 24 weeks. A significant difference in MRR rate was shown between the asciminib treated population and the bosutinib control group (25.5% vs. 13.2%, respectively, P = .029). In the asciminib cohort, adverse reactions of at least grade 3 with an incidence ≥ 5% were thrombocytopenia, neutropenia, increased pancreatic enzymes, hypertension, and anemia. The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the European Medicines Agency's Committee for Medicinal Products for Human Use.

Multimodality Imaging in Cranial Giant Cell Arteritis: First Experience with High-Resolution T1-Weighted 3D Black Blood without Contrast Enhancement Magnetic Resonance Imaging.

In order to support or refute the clinical suspicion of cranial giant cell arteritis (GCA), a supplemental imaging modality is often required. High-resolution black blood Magnetic Resonance Imaging (BB MRI) techniques with contrast enhancement can visualize artery wall inflammation in GCA. We compared findings on BB MRI without contrast enhancement with findings on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/low-dose computed tomography (2-[18F]FDG PET/CT) in ten patients suspected of having GCA and in five control subjects who had a 2-[18F]FDG PET/CT performed as a routine control for malignant melanoma. BB MRI was consistent with 2-[18F]FDG PET/CT in 10 out of 10 cases in the group with suspected GCA. In four out of five cases in the control group, the BB MRI was consistent with 2-[18F]FDG PET/CT. In this small population, BB MRI without contrast enhancement shows promising performance in the diagnosis of GCA, and might be an applicable imaging modality in patients.

Mechanical thrombectomy in stroke patients of advanced age with score-based prediction of outcome.

BACKGROUND: Stroke patients ≥80 years constituted only 15% in randomised trials on mechanical thrombectomy (MT), but is a considerable higher proportion in clinical practice. Association of clinical variables collected before MT with functional outcome has not been independently described in these patients, while being important in the decision of patient eligibility for MT. METHODS: We included patients consecutively at a single centre (2017-2021) categorised as octogenarians (age: 80-89 years) or nonagenarians (age: 90-99 years). Functional outcome at 90 days was defined as fair (modified Rankin Scale (mRS) 0-3) or poor (mRS 4-6). Clinical variables collected before MT were analysed for association with shift of mRS in a poor direction. Significant predictors were used to produce a risk score of fair outcome. Significance was set at the p < 0.05 level. RESULTS: Nonagenarians (n = 43, 15.5%) compared to octogenarians (n = 235, 84.5%) less likely achieved fair outcome (20.9% vs. 46.0%, p < 0.01) with higher mortality (65.1% vs. 31.9%, p < 0.01). Significant predictors of outcome were: age, adjusted odds ratio (aOR) = 0.91 (95% confidence interval (CI): 0.86-0.97); pre-stroke mRS, aOR = 0.57 (95% CI: 0.44-0.73); National Institute of Health Stroke Scale at admission, aOR = 0.91 (95% CI: 0.87-0.95); Alberta Stroke Program Early Computed Tomography, aOR = 1.23 (95% CI: 1.05-1.45). After bootstrap validation, the area under the curve of the risk score was 0.74 and the optimal cut-off for fair outcome was a score of >7 points. CONCLUSIONS: One in two octogenarians achieved fair outcome, however, only one in five nonagenarians had fair outcome. The clinical risk score could be considered as guidance when deciding patient eligibility for MT.

Non-intubated Uniportal Subxiphoid Video-Assisted Thoracoscopic Surgery for Extended Thymectomy in Myasthenia Gravis Patients: A Case Series.

Minimally invasive strategies are increasingly popular in patients with myasthenia gravis (MG)-associated thymomas. Within the context of video-assisted thoracoscopic surgery (VATS) as a widely known minimally invasive option, the most recent achievement is uniportal subxiphoid VATS. In MG patients, it is mandatory (1) to minimize perioperative interference with administered anesthetics to avoid complications and (2) to achieve a complete surgical resection, as the prognosis essentially depends on radical tumor resection. In order to fulfill these criteria, we merged this surgical technique with its anesthesiologic counterpart: regional anesthesia with the maintenance of spontaneous ventilation via a laryngeal mask. Non-intubated uniportal subxiphoid VATS for extended thymectomy allowed radical thymectomy in all MG patients with both rapid symptom control and fast recovery.

Lanthanum Carbonate Opacities-A Systematic Review.

BACKGROUND: Lanthanum carbonate is a phosphate binder used in advanced kidney disease. Its radiopaque appearance has been described in many case studies and case series. Misinterpretation of this phenomenon leads to unnecessary diagnostic tests and procedures. The objectives of this study were to summarize the literature on lanthanum carbonate opacities and present a visual overview. METHODS: A systematic search was conducted using MEDLINE, Embase, and Web of Science. We included all types of studies, including case reports/studies, describing radiological findings of lanthanum carbonate opacities in patients with chronic kidney disease. No filter for time was set. RESULTS: A total of 36 articles were eligible for data extraction, and 33 articles were included in the narrative synthesis. Lanthanum carbonate opacities were most commonly reported in the intestines (26 studies, 73%), stomach (8 studies, 21%), and the aerodigestive tract (2 studies, 6%). The opacities in the intestine were most frequently described as multiple, scattered radiopaque densities, compared with the aerodigestive tract, where the opacities were described as a single, round foreign body. Suspicion of contrast medium or foreign bodies was the most common differential diagnosis. LC opacities in patients with CKD are commonly misinterpreted as foreign bodies or suspect contrast media. CONCLUSIONS: CKD patients treated with LC may have opacities throughout the digestive tract that can vary in appearance. Stopping LC treatment or changing to an alternative phosphate binder prior to planned image studies can avoid diagnostic confusion. If this is not an option, knowledge of the presentation of LC opacities is important.

Common Carotid Artery Volume Flow: A Comparison Study between Ultrasound Vector Flow Imaging and Phase Contrast Magnetic Resonance Imaging.

Volume flow estimation in the common carotid artery (CCA) can assess the absolute hemodynamic effect of a carotid stenosis. The aim of this study was to compare a commercial vector flow imaging (VFI) setup against the reference method magnetic resonance phase contrast angiography (MRA) for volume flow estimation in the CCA. Ten healthy volunteers were scanned with VFI and MRA over the CCA. VFI had an improved precision of 19.2% compared to MRA of 31.9% (p = 0.061). VFI estimated significantly lower volume flow than MRA (mean difference: 63.2 mL/min, p = 0.017), whilst the correlation between VFI and MRA was strong (R2 = 0.81, p < 0.0001). A Bland-Altman plot indicated a systematic bias. After bias correction, the percentage error was reduced from 41.0% to 25.2%. This study indicated that a VFI setup for volume flow estimation is precise and strongly correlated to MRA volume flow estimation, and after correcting for the systematic bias, VFI and MRA become interchangeable.

3 Year outcome after treatment of uterovaginal prolapse with a 6-point fixation mesh.

INTRODUCTION: The aim of this study was to describe the intermediate outcome of a single-incision 6-point fixation transvaginal mesh for the treatment of primary and recurrent pelvic organ prolapse (POP). STUDY DESIGN: This was a prospective cohort study including consecutive patients undergoing POP repair with the InGYNious anterior transvaginal mesh. Inclusion criteria were women with symptomatic stage II POP or higher. Exclusion criteria were the unwillingness or inability to give written informed consent, malignant diseases, neuro-muscular disorders, chronic pain syndrome or previous radiation in the pelvis. Every study participant completed a structured questionnaire, a urogynecological examination according to the IUGA-ICS POP-Q staging system and the validated P-QoL questionnaire before the operation and three years postoperatively. RESULTS: 254 patients were included into the study, 179 were available for the three-year follow-up (70 %). Sixteen patients (8.2 %) had undergone reoperation for recurrent or de novo prolapse (12/16 patients underwent reoperation in the posterior compartment) and were excluded from the objective outcome analysis. In the final study group, all POP-Q measurements, urge urinary incontinence and voiding dysfunction were significantly improved. The de novo SUI rate was 27/ 120 (23 %) in women without reoperation for SUI and/ or POP and without primary SUI. No serious adverse events occurred. Four (1.5 %) patients had mesh exposure at the one-year follow-up and been treated with local oestrogen. At three-year follow-up, no new mesh exposure was seen. De novo dyspareunia rate was low (n = 5 (3 %)). CONCLUSIONS: In this study, the objective outcome three years after anterior POP repair with the InGYNious transvaginal mesh was good. The reoperation rate both for mesh related problems or prolapse were rare.

Carotid Stenosis Assessment with Vector Concentration before and after Stenting.

Digital subtraction angiography (DSA) is considered the reference method for the assessment of carotid artery stenosis; however, the procedure is invasive and accompanied by ionizing radiation. Velocity estimation with duplex ultrasound (DUS) is widely used for carotid artery stenosis assessment since no radiation or intravenous contrast is required; however, the method is angle-dependent. Vector concentration (VC) is a parameter for flow complexity assessment derived from the angle independent ultrasound method vector flow imaging (VFI), and VC has shown to correlate strongly with stenosis degree. The aim of this study was to compare VC estimates and DUS estimated peak-systolic (PSV) and end-diastolic velocities (EDV) for carotid artery stenosis patients, with the stenosis degree obtained with DSA. Eleven patients with symptomatic carotid artery stenosis were examined with DUS, VFI, and DSA before and after stent treatment. Compared to DSA, VC showed a strong correlation (r = -0.79, p < 0.001), while PSV (r = 0.68, p = 0.002) and EDV (r = 0.51, p = 0.048) obtained with DUS showed a moderate correlation. VFI using VC calculations may be a useful ultrasound method for carotid artery stenosis and stent patency assessment.

Flow Complexity Estimation in Dysfunctional Arteriovenous Dialysis Fistulas using Vector Flow Imaging.

Non-invasive assessment is preferred for monitoring arteriovenous dialysis fistulas (AVFs). Vector concentration assesses flow complexity, which may correlate with stenosis severity. We determined whether vector concentration could assess stenosis severity in dysfunctional AVFs. Vector concentration was estimated in four stenotic phantoms at different pulse repetition frequencies. Spectral Doppler peak velocity and vector concentration were measured in 12 patients with dysfunctional AVFs. Additionally, 5 patients underwent digital subtraction angiography (DSA). In phantoms, vector concentration exhibited an inverse relationship with stenosis severity and was less affected by aliasing in severe stenoses. In nine stenoses of 5 patients undergoing DSA, vector concentration correlated strongly with stenosis severity (first stenosis: r = -0.73, p = 0.04; other stenoses; r = -0.69, p = 0.02) and mid-stenotic diameter (first stenosis: r = 0.87, p = 0.006; other stenoses: r = 0.70, p = 0.02) as opposed to peak velocities (p > 0.05). Vector concentration is less affected by aliasing in severe stenoses and correlates with DSA in patients with dysfunctional AVF.

1-year outcome after treatment of uterovaginal prolapse with a 6-point fixation mesh.

INTRODUCTION: The aim of this study was to describe the safety and anatomical results of a surgical approach with a single-incision 6-point fixation vaginal mesh for the treatment of pelvic organ prolapse at perioperatively and at 1-year follow-up. MATERIALS AND METHODS: This was a prospective observational study of patients who underwent operation receiving an InGYNious anterior transvaginal mesh. All patients with symptomatic stage II prolapse or higher were included in the study. Exclusion criteria were the unwillingness or inability to give written informed consent, neuromuscular disorders, malignant diseases, previous radiation in the pelvis, or chronic pain syndrome. Every patient completed a structured questionnaire and a full physical examination according to the IUGA-ICS POP-Q staging system before the operation and at 1-year follow-up. RESULTS: Two hundred fifty-four patients (91%) were included in the study. The intraoperative complication rate was 7% with hemorrhage being the most common complication. Six patients (2.4%) had undergone reoperation for prolapse (four out of the six patients had reoperation in the posterior compartment) and were excluded from the objective outcome analysis. In the remaining 248 patients all POP-Q measurements were significantly improved in the anterior and apical compartments. Similarly, urge urinary incontinence and voiding dysfunction improved significantly. CONCLUSIONS: In this series, the objective outcome one year after the InGYNious mesh was good with low numbers of mesh-related problems or reoperation for prolapse.

Summary report of second EUFEPS/AAPS conference on global harmonization in bioequivalence.

The Global Bioequivalence Harmonization Initiative (GBHI) was launched by the Network on Bioavailability and Biopharmaceutics (BABP) under the auspices of European Federation for Pharmaceutical Sciences (EUFEPS) several years ago. Since 2015, EUFEPS in collaboration with the American Association of Pharmaceutical Scientists (AAPS) has organized three international conferences to support global harmonization of regulatory requirements for bioequivalence (BE) assessment. These conferences provided an open forum for pharmaceutical scientists from academia, industry and regulatory agencies to discuss various BE topics at issue. The current report summarizes the discussion of BE issues at the 2nd GBHI conference held in 2016, Rockville, USA. Three important BE topics were discussed at the meeting: (a) prodrugs and compounds with pre-systemic extraction, (b) scaling procedures and two-stage designs, and (c) exclusion of pharmacokinetic data in BE assessment. The presentations and discussions of these issues have enhanced the mutual understanding of scientific background for BE evaluation and further facilitated harmonization of regulatory approaches for establishing BE of multisource drug products.

Risk markers for later cardiovascular diseases in liver-transplanted children and adolescents.

BACKGROUND: Increased risk of cardiovascular diseases is well described after adult liver transplantation, whereas the risk in the pediatric population still is discussed. The aim of this study was to investigate the prevalence of metabolic syndrome in pediatric liver transplant recipients and whether measurements of carotid intima media thickness and pulse wave velocity were increased compared to healthy controls. METHODS: We included 42 pediatric liver transplantation recipients and examined them for markers of metabolic syndrome, liver fibrosis measured by shear wave velocity, body fat measured by DXA scans and carotid intima-media thickness, and pulse wave velocity (n = 41 for the carotid scans). The ultrasound measurements of carotid intima-media thickness and pulse wave velocity were also conducted on 82 healthy children and adolescents matched on height and age, respectively. RESULTS: Participants had a median age of 13.03 years, and median time since transplantation was 8.54 years. Compared to healthy controls, liver-transplanted patients had significantly increased intima-media thickness measurements in both control groups whereas there was no significant difference with regard to pulse wave velocity. Two patients (6.25%) were diagnosed with metabolic syndrome. Within the group of liver-transplanted pediatric patients, only elevated body mass index was associated with elevated carotid intima-media thickness measurement. Elevated pulse wave velocity was only associated with abdominal obesity. Factors not significantly correlated with either were age, sex, metabolic syndrome, hyperglycemia, triglycerides, years since transplantation, fibrosis of the liver, body fat content, smoking habits, HDL cholesterol levels, hypertension, and mono-drug versus multi-drug therapies. CONCLUSION: Pediatric liver transplant recipients do have an increased risk of increased carotid intima-media thickness.

Evaluation of Peak Reflux Velocities with Vector Flow Imaging and Spectral Doppler Ultrasound in Varicose Veins.

Purpose Spectral Doppler ultrasound (SDUS) is used for quantifying reflux in lower extremity varicose veins. The technique is angle-dependent opposed to the new angle-independent Vector Flow Imaging (VFI) method. The aim of this study was to compare peak reflux velocities obtained with VFI and SDUS in patients with chronic venous disease, i. e., pathological retrograde blood flow caused by incompetent venous valves. Materials and Methods 64 patients with chronic venous disease were scanned with VFI and SDUS in the great or the small saphenous vein, and reflux velocities were compared to three assessment tools for chronic venous disease. A flow rig was used to assess the accuracy and precision of the two methods. Results The mean peak reflux velocities differed significantly (VFI: 47.4 cm/s vs. SDUS: 62.0 cm/s, p<0.001). No difference in absolute precision (p=0.18) nor relative precision (p=0.79) was found. No correlation to disease severity, according to assessment tools, was found for peak reflux velocities obtained with either method. In vitro, VFI was more accurate but equally precise when compared to SDUS. Conclusion Both VFI and SDUS detected the pathologic retrograde flow in varicose veins but measured different reflux velocities with equal precision. VFI may play a role in evaluating venous disease in the future.

Respiratory variability of peak velocities in the common femoral vein estimated with vector flow imaging and Doppler ultrasound.

Respiratory variability of peak velocities (RVPV) in the common femoral vein measured with ultrasound can reveal venous outflow obstruction. Pulse wave (PW) Doppler is the gold standard for venous velocity estimation of the lower extremities. PW Doppler measurements are angle dependent, whereas vector flow imaging (VFI) can yield angle-independent measures. The hypothesis of the present study was that VFI can provide RVPV estimations without the angle dependency of PW Doppler for an improved venous disease assessment. Sixty-seven patients with symptomatic chronic venous disease were included in the study. On average, VFI measured a lower RVPV than PW Doppler (VFI: 14.11 cm/s; PW: 17.32 cm/s, p = 0.002) with a non-significant improved precision compared with PW Doppler (VFI: 21.09%; PW: 26.49%, p = 0.08). In a flow phantom, VFI had improved accuracy (p < 0.01) and equal precision compared with PW Doppler. The study indicated that VFI can characterize the hemodynamic fluctuations in the common femoral vein.

A Comparison Study of Vector Velocity, Spectral Doppler and Magnetic Resonance of Blood Flow in the Common Carotid Artery.

Magnetic resonance phase contrast angiography (MRA) is the gold standard for blood flow evaluation. Spectral Doppler ultrasound (SDU) is the first clinical choice, although the method is angle dependent. Vector flow imaging (VFI) is an angle-independent ultrasound method. The aim of the study was to compare VFI- and SDU-estimated peak systolic velocities (PSV) of the common carotid artery (CCA) with PSV obtained by MRA. Furthermore, intra- and inter-observer agreement was determined. MRA estimates were significantly different from SDU estimates (left CCA: p < 0.001, right CCA: p < 0.001), but not from VFI estimates (left CCA: p = 0.28, right CCA: p = 0.18). VFI measured lower PSV in both CCAs compared with SDU (p < 0.001) with improved precision (VFI: left: 24%, right: 18%; SDU: left 38%, right: 23%). Intra- and inter-observer agreement was almost perfect for VFI and SDU (inter-observer correlation coefficient: VFI 0.88, SDU 0.91; intra-observer correlation coefficient: VFI 0.96, SDU 0.97). VFI is more accurate than SDU in evaluating PSV compared with MRA.