Endovascular thrombectomy for acute ischaemic stroke with established large infarct (TENSION): 12-month outcomes of a multicentre, open-label, randomised trial.

BACKGROUND: Long-term data showing the benefits of endovascular thrombectomy for stroke with large infarct are scarce. The TENSION trial showed the safety and efficacy of endovascular thrombectomy in patients with ischaemic stroke and large infarct at 90 days. We aimed to investigate the safety and efficacy at 12 months of endovascular thrombectomy in patients who were enrolled in the TENSION trial. METHODS: TENSION was an open-label, blinded endpoint, randomised trial done at 40 hospitals across Europe and one hospital in Canada. We included patients (aged ≥18 years) with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and who had a large infarct, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 on standard-of-care stroke imaging. We randomly assigned patients (1:1) to receive either endovascular thrombectomy with medical treatment or medical treatment only up to 12 h from stroke onset. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days. Here, we report the prespecified 12-month follow-up analyses for functional outcome (using the simplified modified Rankin Scale questionnaire), quality of life (using the Patient-Reported Outcomes Measurement Information System 10-item [PROMIS-10] and EQ-5D questionnaires), post-stroke anxiety and depression (using the Patient Health Questionnaire-4 [PHQ-4]), and overall survival. Outcomes (except survival) were assessed in the intention-to-treat population; the survival analysis was based on treatment received. This trial is registered with ClinicalTrials.gov, NCT03094715, and is completed. FINDINGS: We enrolled patients between July 17, 2018, and Feb 21, 2023, when the trial was stopped early for efficacy. 253 patients were randomly assigned, 125 (49%) to endovascular thrombectomy and 128 (51%) to medical treatment only. Median follow-up was 8·36 months (IQR 0·02-12·00). Endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better functional outcome at 12 months (adjusted common odds ratio 2·39 [95% CI 1·47-3·90]). Endovascular thrombectomy was also associated with a better quality of life compared with medical treatment only, as reflected by median scores on the EQ-5D questionnaire index (0·7 [IQR 0·4-0·9] vs 0·4 [0·2-0·7]), median scores for health status on the EQ-5D questionnaire visual analogue scale (50 [IQR 35-70] vs 30 [5-60]), and median global physical health scores on the PROMIS-10 questionnaire (T-score 39·8 [IQR 37·4-50·8] vs 37·4 [32·4-44·9]); although there was not enough evidence to suggest a difference between groups in global mental health scores on PROMIS-10 (41·1 [IQR 36·3-48·3] vs 38·8 [31·3-44·7]) or the numbers of patients reporting anxiety (13 [22%] of 58 vs 15 [42%] of 36) and depression (18 [31%] vs 18 [50%]) on PHQ-4. Overall survival was slightly better in the endovascular thrombectomy group compared with medical treatment only (adjusted hazard ratio 0·70 [95% CI 0·50-0·99]). INTERPRETATION: In patients with acute ischaemic stroke from large vessel occlusion with established large infarct, compared with medical treatment only, endovascular thrombectomy was associated at 12 months after stroke with better functional outcome, quality of life, and overall survival. These findings suggest that the benefits of endovascular thrombectomy in patients with an ischaemic stroke and a large infarct are sustained in the long term and support the use of endovascular thrombectomy in these patients. FUNDING: European Union Horizon 2020 Research and Innovation Programme.

Predictors of Outcome after Direct Aspiration of Basilar Artery Occlusion.

Background: Basilar artery occlusion (BAO) is a serious disease with a poor prognosis if left untreated. Endovascular therapy (EVT) is the most effective treatment that is able to reduce mortality and disability. Treatment results are influenced by a wide range of factors that have not been clearly identified. In the present study, direct aspiration was chosen as a first-line treatment. The safety and effectiveness of direct aspiration in BAO were determined, and factors affecting patient outcomes were identified. Methodology: Data for patients with BAO treated between November 2013 and December 2021 were evaluated using a database. The association between clinical and procedural parameters and functional outcome was assessed. Results: A total of 89 patients with BAO were identified. Full recanalization was achieved in 69.7% of cases and partial recanalization in 19.1%. Intracranial hemorrhage was detected in 11 (12.4%) patients, of which, eight (9.0%) patients experienced symptomatic intracranial hemorrhage. Patients with good outcomes presented with milder strokes (mean NIHSS score of 12.58 vs. 24.00, p < 0.001), had higher collateral scores (6.79 vs. 5.88, p = 0.016), more often achieved complete recanalization (87.9% vs. 58.9%, p = 0.009), and more often experienced early neurological improvement (66.7% vs. 26.8%, p < 0.001). On the contrary, patients with worse outcomes had higher serum glucose levels (p = 0.05), occlusion of the middle portion of the basilar artery (MAB) (30.3% vs. 53.6%, p = 0.033), longer thrombus lengths (10.51 vs. 16.48 mm, p = 0.046), and intracranial hemorrhage (p = 0.035). Conclusions: The present study results suggest that direct aspiration is a safe and effective treatment for patients with BAO. We identified several factors affecting the patients' outcome.

Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial.

BACKGROUND: Recent evidence suggests a beneficial effect of endovascular thrombectomy in acute ischaemic stroke with large infarct; however, previous trials have relied on multimodal brain imaging, whereas non-contrast CT is mostly used in clinical practice. METHODS: In a prospective multicentre, open-label, randomised trial, patients with acute ischaemic stroke due to large vessel occlusion in the anterior circulation and a large established infarct indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) of 3-5 were randomly assigned using a central, web-based system (using a 1:1 ratio) to receive either endovascular thrombectomy with medical treatment or medical treatment (ie, standard of care) alone up to 12 h from stroke onset. The study was conducted in 40 hospitals in Europe and one site in Canada. The primary outcome was functional outcome across the entire range of the modified Rankin Scale at 90 days, assessed by investigators masked to treatment assignment. The primary analysis was done in the intention-to-treat population. Safety endpoints included mortality and rates of symptomatic intracranial haemorrhage and were analysed in the safety population, which included all patients based on the treatment they received. This trial is registered with ClinicalTrials.gov, NCT03094715. FINDINGS: From July 17, 2018, to Feb 21, 2023, 253 patients were randomly assigned, with 125 patients assigned to endovascular thrombectomy and 128 to medical treatment alone. The trial was stopped early for efficacy after the first pre-planned interim analysis. At 90 days, endovascular thrombectomy was associated with a shift in the distribution of scores on the modified Rankin Scale towards better outcome (adjusted common OR 2·58 [95% CI 1·60-4·15]; p=0·0001) and with lower mortality (hazard ratio 0·67 [95% CI 0·46-0·98]; p=0·038). Symptomatic intracranial haemorrhage occurred in seven (6%) patients with thrombectomy and in six (5%) with medical treatment alone. INTERPRETATION: Endovascular thrombectomy was associated with improved functional outcome and lower mortality in patients with acute ischaemic stroke from large vessel occlusion with established large infarct in a setting using non-contrast CT as the predominant imaging modality for patient selection. FUNDING: EU Horizon 2020.

Effects of low-dose ionizing radiation on genomic instability in interventional radiology workers.

Interventional radiologists are chronically exposed to low-dose ionizing radiation (IR), which may represent a health risk. The aim of the present study was to evaluate genomic instability by analyzing chromosomal aberrations, micronuclei, and 53BP1 DNA repair foci in peripheral blood lymphocytes of radiologists. Based on the IAEA guidelines on biodosimetry using dicentrics, the average protracted whole-body dose in radiologists were estimated. Since preleukemic fusion genes (PFG) are the primary events leading to leukemia, we also studied their presence by RT-qPCR and FISH. No significant difference in 53BP1 foci and incidence of PFG (MLL-AF4, MLL-AF9, AML1-ETO, BCR-ABL p190) was found in cells of interventional radiologists in comparison to controls. However, our results showed an increased frequency of micronuclei and various types of chromosomal aberrations including dicentrics in interventional radiologists. The average protracted whole body estimated dose was defined at 452.63 mGy. We also found a significantly higher amplification of the MLL gene segment and increased RNA expression in cells of interventional radiologists in comparison to controls. In conclusion, our results showed that long-term low-dose IR induces genomic instability in interventional radiologists.

Dialysis vascular access restoration by a transcollateral approach using the Surfacer® Inside-Out® Access Catheter System.

Chronic thoracic venous occlusion (CTVO) as a result of repeated or prolonged central venous catheter insertion represents a significant problem in catheter-dependent patients. Different endovascular techniques techniques have been utilised for CTVO recanalization. The Surfacer® Inside-out® system represents a new approach to restore right-sided central venous access in CTVO by the inside-out recanalization technique. Standard approach for device implantation is through right femoral vein. In this case report, we report the first case to our knowledge of dialysis access restoration with Surfacer® system implantation via an unconventional and non-standard route by a transcollateral approach in a patient with exhausted vascular access options.

Radiation dose and image quality of CT coronary angiography in patients with high heart rate or irregular heart rhythm using a 16-cm wide detector CT scanner.

Aim of the study was to evaluate the effect of high and irregular heart rate on the image quality and on the radiation exposure using a 256-row, 16-cm wide detector computed tomography (CT) system. Between March and December 2019, 349 patients undergoing CT coronary angiography (CTCA) were prospectively enrolled. Patients were divided into 2 study groups; Group 1 included patients with a regular heart rate of ≤70 bpm, while Group 2 included patients with an irregular heart rhythm or heart rate of >70 bpm. In all patients, image quality score and radiation dose were analyzed and recorded. In Group 1, there were a total of 195 patients, while in Group 2, there were 154 patients. Of the 349 patients, 299 of them had a regular heart rhythm (85.7%) and 50 (14.3%) had an irregular heart rhythm. Mean heart rate during scanning was 59 ± 7 bpm in Group 1 and 80 ± 12 bpm in Group 2. Mean effective dose of CTCA in Group 1 (1.2 ± 0.8 mSv) was lower than in Group 2 (1.9 ± 1.2 mSv, P < .001). Mean image quality (Likert score) of Group 1 was significantly higher than in Group 2 (4.1 vs 3.4, P < .001). CT scanner with 16-cm wide detector enables low-radiation exposure during CTCA even at high heart rate or irregular heart rhythm. Good CTCA image quality and low dose are related to low heart rate.

DIAGNOSTIC REFERENCE LEVELS IN SCREENING MAMMOGRAPHY CENTERS IN SLOVAKIA.

Optimization in mammography remains the most important tool in practice. In the optimization process, we look for a balanced relationship between image quality and patient dose. For mammographic examinations, the diagnostic reference levels (DRLs) are expressed as the average glandular dose (AGD) based on the thickness of the compressed breast. The aim of this study was to analyse DRL compliance in diagnostic mammography at 16 mammography screening centres using an automated system for tracking patient doses during the period between January 2020 and December 2020 and to subsequently propose new DRLs for the screening mammography centres in Slovakia. The new DRLs were ~20% lower than the existing national DRLs in diagnostic mammography in Slovakia and significantly lower than the achievable AGD levels published in the fourth edition of the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis.

Response of Escherichia coli minimal ter operon to UVC and auto-aggregation: pilot study.

AIM: The study of minimal ter operon as a determinant of tellurium resistance (TeR) is important for the purpose of confirming the relationship of these genes to the pathogenicity of microorganisms. The ter operon is widespread among bacterial species and pathogens, implicated also in phage inhibition, oxidative stress and colicin resistance. So far, there is no experimental evidence for the role of the Escherichia coli (E. coli) minimal ter operon in ultraviolet C (UVC) resistance, biofilm formation and auto-aggregation. To identify connection with UVC resistance of the minimal ter operon, matched pairs of Ter-positive and -negative E. coli cells were stressed and differences in survival and whole genome sequence analysis were performed. This study was aimed also to identify differences in phenotype of cells induced by environmental stress. METHODS: In the current study, a minimal ter operon(terBCDEΔF) originating from the uropathogenic strain E. coli KL53 was used. Clonogenic assay was the method of choice to determine cell reproductive death after treatment with UVC irradiation at certain time intervals. Bacterial suspensions were irradiated with 254 nm UVC-light (germicidal lamp in biological safety cabinet) in vitro. UVC irradiance output was 2.5 mW/cm2 (calculated at the UVC device aperture) and plate-lamp distance of 60 cm. DNA damage analysis was performed using shotgun sequencing on Illumina MiSeq platform. Biofilm formation was measured by a crystal violet retention assay. Auto-aggregation assay was performed according to the Ghane, Babaeekhou & Ketabi (2020). RESULTS: A large fraction of Ter-positive E. coli cells survived treatment with 120-s UVC light (300 mJ/cm2) compared to matched Ter-negative cells; ∼5-fold higher resistance of Ter-positive cells to UVC dose (p = 0.0007). Moreover, UVC surviving Ter-positive cells showed smaller mutation rate as Ter-negative cells. The study demonstrated that a 1200-s exposure to UVC (3,000 mJ/cm2) was sufficient for 100% inhibition of growth for all the Ter-positive and -negative E. coli cells. The Ter-positive strain exhibited of 26% higher auto-aggregation activities and was able to inhibit biofilm formation over than Ter- negative strain (**** P < 0.0001). CONCLUSION: Our study shows that Ter-positive cells display lower sensitivity to UVC radiation, corresponding to a presence in minimal ter operon. In addition, our study suggests that also auto-aggregation ability is related to minimal ter operon. The role of the minimal ter operon (terBCDEΔF) in resistance behavior of E. coli under environmental stress is evident.

Aspiration Thrombectomy in Patients with Large Vessel Occlusion and Mild Stroke: A Single-Center Experience.

BACKGROUND The purpose of this study was to evaluate outcomes of patients with mild stroke, defined by National Institutes of Health Stroke Scale (NIHSS) score <6, caused by large vessel occlusion treated with aspiration thrombectomy. MATERIAL AND METHODS Data from the endovascular stroke registry of our center were retrospectively analyzed. Anterior or posterior circulation strokes with NIHSS score <6 upon admission were analyzed. The assessment of a good clinical outcome (modified Rankin scale score 0-2) at day 90 was the primary endpoint. Symptomatic intracranial hemorrhage, defined in European Cooperative Acute Stroke Study grade III, and mortality at day 90 were the safety measures. A successful endovascular procedure was defined as a Thrombolysis in Cerebral Infarction (TICI) score of 2b or 3. RESULTS We included 27 patients treated with immediate mechanical thrombectomy, 19 (70.4%) in the anterior circulation and 8 (29.6%) in the posterior circulation. The mean age was 69.8±12.3 years and 40.7% were male. Thirteen patients (48.1%) received bridging intravenous thrombolysis before endovascular thrombectomy. Twenty-five patients (92.6%) underwent the direct aspiration first-pass technique "ADAPT" as the first choice of endovascular procedure. Successful recanalization was achieved in 25 patients (92.6%). Twenty-one patients (77.8%) had a good functional outcome at the 3-month follow-up, 1 (3.7%) symptomatic intracranial hemorrhage was observed, and 2 patients (7.4%) died. CONCLUSIONS Immediate aspiration thrombectomy may be a safe and feasible first-line treatment option in patients suffering from mild stroke due to large vessel occlusion in the anterior and posterior circulation.

Aspiration thrombectomy as the first-line treatment of M2 occlusions.

PURPOSE: The aim of the present study was (i) to evaluate the safety and efficacy of aspiration thrombectomy in patients with M2 occlusions and (ii) to compare outcome of treatment of occlusion of different M2 segments. MATERIALS AND METHODS: Between March 2016 and June 2019, 82 patients with acute ischemic stroke and isolated M2 occlusions were treated in cerebrovascular stroke center with aspiration thrombectomy as the first-line treatment. Functional outcomes of patients with different types of M2 occlusions were statistically compared. Multivariable logistic regression analysis was performed to determine the factors associated with good clinical outcome. RESULTS: The mean age was 71.9 ± 13.4 years, 47.6% were men. Aspiration thrombectomy alone was utilized in 72.5% of patients, with 27.5% of patients being treated with a combination of aspiration thrombectomy and stent retriever. At the three-month follow-up, there was no statistically significant difference in functional outcome between different types of M2 occlusions (p = 0.662), however in the underpowered analysis because of the small sample size of patients, with good clinical outcome mRS 0-2 in 50% of all treated patients. Symptomatic intracranial hemorrhage was found in 6.1% of patients. Lower age (OR 0.932, 95% CI 0.878-0.988) and lower NIHSS score upon admission (OR 0.893, 95% CI 0.805-0.991) were independent predictors of good clinical outcome. CONCLUSION: Aspiration thrombectomy appeared to be a safe and effective first-line treatment option for patients with M2 occlusion, being the first-line option for almost three-quarters of patients.

Endovascular treatment of acute ischemic stroke in patients with recurrent intracranial large vessel occlusion.

BACKGROUND: Data on the treatment with recurrent mechanical thrombectomy of patients with acute ischemic stroke with recurrent large vessel occlusion are limited. We report our experience with recurrent mechanical thrombectomy for recurrent large vessel occlusion. METHODS: During the period between May 2013 and August 2018, data on patients with recurrent large vessel occlusion were collected. Baseline clinical characteristics, recanalization technique, recanalization rates and clinical outcomes of patients with recurrent large vessel occlusion treated with mechanical thrombectomy were analyzed. Patients with recurrent large vessel occlusion treated with mechanical thrombectomy were compared with patients who underwent single mechanical thrombectomy. RESULTS: During the study period, 7 of 474 patients (1.5%) were treated with mechanical thrombectomy for recurrent large vessel occlusion. The mean age of these patients was 64.4 (±7.9) years, and the mean time interval between thrombectomies was 47 (±48) h. The median baseline National Institutes of Health Stroke Scale (NIHSS) was 12 (range 5-24) before the first and 20 (range 3-34) before the second procedure; the mean NIHSS at discharge was 5 (range 2-25). Good clinical outcome after repeated mechanical thrombectomy defined as modified Rankin scale of 0-2 was achieved in 29% of patients at three months of follow-up. CONCLUSIONS: Repeat mechanical thrombectomy is a rare procedure, but appears to be a feasible, safe and effective treatment option in patients with acute ischemic stroke and early recurrent large vessel occlusion.

CT protocols and radiation doses for hematuria and urinary stones: Comparing practices in 20 countries.

PURPOSE: Patients with hematuria and renal colic often undergo CT scanning. The purpose of our study was to assess variations in CT protocols and radiation doses for evaluation of hematuria and urinary stones in 20 countries. METHOD: The International Atomic Energy Agency (IAEA) surveyed practices in 51 hospitals from 20 countries in the European region according to the IAEA Technical cooperation classification and obtained following information for three CT protocols (urography, urinary stones, and routine abdomen-pelvis CT) for 1276 patients: patient information (weight, clinical indication), scanner information (scan vendor, scanner name, number of detector rows), scan parameters (such as number of phases, scan start and end locations, mA, kV), and radiation dose descriptors (CTDIvol, DLP). Two radiologists assessed the appropriateness of clinical indications and number of scan phases using the ESR Referral Guidelines and ACR Appropriateness Criteria. Descriptive statistics and Student's t tests were performed. RESULTS: Most institutions use 3-6 phase CT urography protocols (80 %, median DLP 1793-3618 mGy.cm) which were associated with 2.4-4.9-fold higher dose compared to 2-phase protocol (20 %, 740 mGy.cm) (p < 0.0001). Likewise, 52 % patients underwent 3-5 phase routine abdomen- pelvis CT (1574-2945 mGy.cm) as opposed to 37 % scanned with a single-phase routine CT (676 mGy.cm). The median DLP for urinary stones CT (516 mGy.cm) were significantly lower than the median DLP for the other two CT protocols (p < 0.0001). CONCLUSIONS: Few institutions (4/13) use low dose CT for urinary stones. There are substantial variations in CT urography and routine abdomen-pelvis CT protocols result in massive radiation doses (up to 2945-3618 mGy.cm).

Neurointerventionalist and Patient Radiation Doses in Endovascular Treatment of Acute Ischemic Stroke.

PURPOSE: To evaluate the patient and the neurointerventionalist radiation dose levels during endovascular treatment of acute ischemic stroke, and to analyze factors affecting doses. MATERIALS AND METHODS: From October 2017 to January 2019, we prospectively collected patient radiation data and neurointerventionalist data from real-time dosimetry from all consecutive thrombectomies. Multivariate analysis was performed to analyze patient total dose area product (DAP) and neurointerventionalist dose variability in terms of clinical characteristics and the technical parameters of thrombectomies. Local dose reference levels (RL) were derived as the 75th percentile of the patient dose distributions. RESULTS: A total of 179 patients were treated during the study period and included in this study. Local dose RL for thrombectomy was derived for total DAP to 34 Gy cm2, cumulative air kerma of 242 mGy and fluoroscopy time of 12 min. The mean neurointerventionalist dose for thrombectomy was 7.7 ± 7.4 µSv. Height (P = 0.018), weight (P = 0.004), body mass index (P = 0.015), puncture to recanalisation (P < 0.001), fluoro time (P < 0.001), number of passes (P < 0.001), thrombolysis in cerebral infarction 2b/3 recanalisation (P = 0.034) and aspiration thrombectomy (P < 0.001) were independent factors affecting patient total DAP, whereas baseline National Institutes of Health Stroke Scale (P = 0.043), puncture to recanalisation (P = 0.003), fluoroscopy time (P = 0.009) and number of passes (P = 0.009) were factors affecting the neurointerventionalist dose. CONCLUSION: New reference patient doses lower than those in previously published studies were defined. However, the operator's doses were higher than those in the only available study reporting on operator's dose during cerebral interventions.

RISK EVALUATION IN THE LOW-DOSE RANGE CT FOR RADIATION-EXPOSED CHILDREN, BASED ON DNA DAMAGE.

One of the most common usages of radiation in current medical diagnosis is computed tomography (CT) using X-rays. The potential health risk of CT scans has been discussed in various studies to determine whether low-dose radiation from CT could enhance the chromosome aberration yields in pediatric patients and increase their risk of carcinogenesis. For this reason, it is of great interest to study the effects of low-dose radiation. The induction of DNA damage by a CT scan examination has been demonstrated in several reports by the γ-H2AX assay, the micronuclei assay and dicentrics measurements. However, the results of most studies showed limitations. On the other hand, epidemiological studies give contradictory results for post-natal radiation exposure in the low-dose range, so it is still difficult to draw conclusions about the effects of CT examinations and risk of carcinogenesis. This article provides an overview of previously published data and summarizes the current state of knowledge.

Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia.

BACKGROUND: The present study investigated factors associated with therapeutic benefits after autologous bone marrow cell (BMC) therapy in patients with "no-option" critical limb ischemia (CLI). METHODS AND RESULTS: Sixty-two patients with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were randomized to treatment with 40 ml of autologous BMCs (SmartPreP2) by local intramuscular (n = 32) or intra-arterial (n = 30) application. The primary endpoint was limb salvage and wound healing at 12 months. Seven patients (11 %) died during the follow-up from reasons unrelated to stem cell therapy. The BMC product of patients with limb salvage and wound healing (33/55) was characterized by a higher CD34(+) cell count (p = 0.001), as well as a higher number of total bone marrow mononuclear cells (BM-MNCs) (p = 0.032), than that of nonresponders (22/55). Patients with limb salvage and wound healing were younger (p = 0.028), had lower C-reactive protein levels (p = 0.038), and had higher transcutaneous oxygen pressure (tcpO2) (p = 0.003) before cell application than nonresponders. All patients with major tissue loss at baseline (Rutherford 6 stage of CLI, n = 5) showed progression of limb ischemia and required major limb amputation. In the multiple binary logistic regression model, the number of applied CD34(+) cells (p = 0.046) and baseline tcpO2 (p = 0.031) were independent predictors of limb salvage and wound healing. The number of administrated BM-MNCs strongly correlated with decreased peripheral leukocyte count after 6 months in surviving patients with limb salvage (p = 0.0008). CONCLUSION: Patients who benefited from autologous BMC therapy for "no-option" CLI were treated with high doses of CD34(+) cells. The absolute number of applied BM-MNCs correlated with the improvement of inflammation. We hypothesize that the therapeutic benefit of cell therapy for peripheral artery disease is the result of synergistic effects mediated by a mixture of active cells with regenerative potential. Patients at the most advanced stage of CLI do not appear to be suitable candidates for cell therapy. TRIAL REGISTRATION: The study was approved and registered by the ISRCTN registry. TRIAL REGISTRATION: ISRCTN16096154 . Registered: 26 July 2016.

Pharmacomechanical thrombectomy for treatment of acute transplant renal artery thrombosis.

Acute transplant renal artery thrombosis is a rare complication in kidney transplantation that often leads to renal allograft loss. We present the first case of acute renal artery thrombosis 3 months after kidney transplantation, treated with pharmacomechanical thrombectomy with adjunctive catheter-directed thrombolysis and stent placement. The graft was salvaged with restoration of renal function and renal artery patency at the 3-year follow-up point.

Characterization of mesenchymal stem cells of "no-options" patients with critical limb ischemia treated by autologous bone marrow mononuclear cells.

BACKGROUND: Application of autologous bone marrow mononuclear cells to "no option" patients with advanced critical limb ischemia (CLI) prevented major limb amputation in 73% patients during the 6-month follow-up. We examined which properties of bone marrow stromal cells also known as bone-marrow derived mesenchymal stem cells of responding and non-responding patients are important for amputation-free survival. METHODS AND FINDINGS: Mesenchymal stem cells of 41 patients with CLI unsuitable for revascularisation were isolated from mononuclear bone marrow concentrate used for their treatment. Based on the clinical outcome of the treatment, we divided patients into two groups: responders and non-responders. Biological properties of responders' and non-responders' mesenchymal stem cells were characterized according to their ability to multiply, to differentiate in vitro, quantitative expression of cell surface markers, secretion of 27 cytokines, chemokines and growth factors, and to the relative expression of 15 mesenchymal stem cells important genes. Secretome comparison between responders (n=27) and non-responders (n=14) revealed significantly higher secretion values of IL-4, IL-6 and MIP-1b in the group of responders. The expression of cell markers CD44 and CD90 in mesenchymal stem cells from responders was significantly higher compared to non-responders (p<0.01). The expression of mesenchymal stem cells surface markers that was analyzed in 22 patients did not differ between diabetic (n=13) and non-diabetic (n=9) patient groups. Statistically significant higher expression of E-cadherin and PDX-1/IPF1 genes was found in non-responders, while expression of Snail was higher in responders. CONCLUSIONS: The quality of mesenchymal stem cells shown in the expression of cell surface markers, secreted factors and stem cell genes plays an important role in therapeutic outcome. Paracrine mechanisms are main drivers in the induction of reparatory processes in CLI patients. Differences in mesenchymal stem cells properties are discussed in relation to their involvement in the reparatory process.

Intra-arterial autologous bone marrow cell transplantation in a patient with upper-extremity critical limb ischemia.

Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia.

Stem cell therapy has been proposed to be an alternative therapy in patients with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization. We compared the therapeutic effects of intramuscular (IM) and intra-arterial (IA) delivery of bone marrow cells (BMCs) and investigated the factors associated with therapeutic benefits. Forty-one patients (mean age, 66 ± 10 years; 35 males) with advanced CLI (Rutherford category, 5 and 6) not eligible for revascularization were randomized to treatment with 40 ml BMCs using local IM (n = 21) or selective IA infusion (n = 20). Primary endpoints were limb salvage and wound healing. Secondary endpoints were changes in transcutaneous oxygen pressure (tcpO(2)), quality-of-life questionnaire (EQ5D), ankle-brachial index (ABI), and pain scale (0-10). Patients with limb salvage and wound healing were considered to be responders to BMC therapy. At 6-month follow-up, overall limb salvage was 73% (27/37) and 10 subjects underwent major amputation. Four patients died unrelated to stem cell therapy. There was significant improvement in tcpO(2) (15 ± 10 to 29 ± 13 mmHg, p < 0.001), pain scale (4.4 ± 2.6 to 0.9 ± 1.4, p < 0.001), and EQ5D (51 ± 15 to 70 ± 13, p < 0.001) and a significant decrease in the Rutherford category of CLI (5.0 ± 0.2 to 4.3 ± 1.6, p < 0.01). There were no differences among functional parameters in patients undergoing IM versus IA delivery. Responders (n = 27) were characterized by higher CD34(+) cell counts in the bone marrow concentrate (CD34(+) 29 ± 15×10(6) vs. 17 ± 12×10(6), p < 0.05) despite a similar number of total nucleated cells (4.3 ± 1.4×10(9) vs. 4.1 ± 1.2×10(9), p = 0.66) and by a lower level of C-reactive protein (18 ± 28 vs. 100 ± 96 mg/L, p < 0.05) as well as serum leukocytes (8.3 ± 2.1×10(9)/L vs. 12.3 ± 4.5×10(9)/L, p < 0.05) as compared with nonresponders (10 patients). Both IM and IA delivery of autologous stem cells are effective therapeutic strategies in patients with CLI. A higher concentration of CD34(+) cells and a lower degree of inflammation are associated with better clinical therapeutic responses.