Catheter-Directed Thrombolysis for Acute Limb Ischemia in an Asian Population.

BACKGROUND: The incidence of peripheral arterial occlusions in Asian populations is likely to increase exponentially in the present and future decades due to the adapted Western lifestyle in metropolitan Asian life, extended life expectancies, and high rates of smoking. The literature on thrombolytic treatment of peripheral arterial occlusions in Asian populations is limited. Therefore, we evaluated the thrombolysis results in a real-world contemporary Asian cohort of patients with peripheral arterial occlusions. METHODS: Retrospective review of all electronic patient records of patients who underwent thrombolytic therapy for peripheral arterial occlusions between July 2011 and July 2016 was conducted. Outcomes were angiographic patency, clinical success, bleeding complications, amputation rates, and mortality rates. RESULTS: In total, 82 patients (median age 66 years, range 34-95) underwent catheter-directed thrombolysis. Median treatment duration was 26 hr (3-209). Angiographic patency and clinical success rates were 64% and 66%, respectively. Bleeding complications occurred in 12% of patients of which 6% were major. Amputation-free rates were 81%, 67%, and 63% for 30 days, 6 months, and 1 year, respectively. In-hospital mortality was 6%. CONCLUSIONS: This study demonstrates that thrombolytic treatment of peripheral arterial occlusions in an Asian patient cohort yields comparable treatment success rates to Western cohorts; however, higher rates of bleeding complications are hazardous and remain a detrimental drawback of this treatment.

Institutional Incentives for Mentoring at the U.S. Department of Veterans Affairs and Universities: Associations With Mentors' Perceptions and Time Spent Mentoring.

PURPOSE: Limited empirical attention to date has focused on best practices in advanced research mentoring in the health services research domain. The authors investigated whether institutional incentives for mentoring (e.g., consideration of mentoring in promotion criteria) were associated with mentors' perceptions of mentoring benefits and costs and with time spent mentoring. METHOD: The authors conducted an online survey in 2014 of a national sample of mentors of U.S. Department of Veterans Affairs (VA) Health Services Research and Development Service (HSR&D) mentored career development award recipients who received an award during 2000-2012. Regression analyses were used to examine institutional incentives as predictors of perceptions of benefits and costs of mentoring and time spent mentoring. RESULTS: Of the 145 mentors invited, 119 (82%) responded and 110 (76%) provided complete data for the study items. Overall, mentors who reported more institutional incentives also reported greater perceived benefits of mentoring (P = .03); however, more incentives were not significantly associated with perceived costs of mentoring. Mentors who reported more institutional incentives also reported spending a greater percentage of time mentoring (P = .02). University incentives were associated with perceived benefits of mentoring (P = .02), whereas VA incentives were associated with time spent mentoring (P = .003). CONCLUSIONS: Institutional policies that promote and support mentorship of junior investigators, specifically by recognizing and rewarding the efforts of mentors, are integral to fostering mentorship programs that contribute to the development of early-career health services researchers into independent investigators.

Cell transfer technique for constructing cytological microarrays for immunocytochemical analysis.

OBJECTIVE: To evaluate the utility of a proposed cell transfer technique for constructing cytological smear microarrays and its potential applications in multiplex immunocytochemical (ICC) staining. METHODS: Ninety-six cytology smears, including two pericardial effusions, 22 ascites and 72 pleural effusions, were transferred to a 33-plex cytological microarray. Paired staining of thyroid transcription factor-1 (TTF-1) and calretinin ICC was performed in duplicate slides. RESULTS: Most of the smeared cells selected for transfer could be removed from the original slides with a minimal loss of cells and with no change in morphological features or immunoreactivity. Comparison of the staining results with immunohistochemical staining results, clinical history and histopathological reports available for each patient revealed that TTF-1 was positive in 32/33 metastatic pulmonary adenocarcinomas (PACs), 1/15 non-pulmonary adenocarcinomas and 0/45 benign effusions. The ICC results for TTF-1 on a transferred cytological microarray revealed high (97%) sensitivity and high (96.7%) specificity for the detection of metastatic PAC. CONCLUSION: Cytology microarrays can be constructed by transferring cells from serous fluid cytological smears, and cells transferred to the microarray retain their morphological integrity and immunoreactivity. Researchers can use the technique for simultaneous immunostaining of multiple specimens in studies of neoplastic or non-neoplastic diseases when available tissue samples are limited.

Endovascular Stent Graft Repair is an Effective and Safe Alternative Therapy for Arteriovenous Graft Pseudoaneurysms.

OBJECTIVE/BACKGROUND: Pseudoaneurysm formation occurs in 2-10% of hemodialysis arteriovenous grafts (AVGs). Surgical repair often requires pseudoaneurysm resection, interposition graft placement, and insertion of a catheter as a bridge. Endovascular stent graft repair is a controversial alternative therapy. This study was performed to examine the effectiveness and mid-term outcomes of stent graft repair for AVG pseudoaneurysms. METHODS: All patients who had undergone stent graft repair for AVG pseudoaneurysms between December 2012 and July 2015 were identified from hospital medical records for retrospective analysis. Outcome measures were technical success, early and late complications, and primary and secondary patency rates. RESULTS: A total of 37 stent graft repairs of AVG pseudoaneurysms were performed in 35 patients (42.9% men; mean age 66.9 years). The mean time from AVG creation to pseudoaneurysm repair was 69 months. The indications of treatment (as per the institutional policy) were large pseudoaneurysm (56.7%), impending rupture (27.1%), and bleeding (16.2%). Mean pseudoaneurysm diameter was 23.0 mm. The most common diameter and length of stent graft used were 7 mm (67.6%) and 50 mm (48.6%), respectively. Technical success was 100%. Only one early complication occurred after stent graft repair, which was due to recurrence of the pseudoaneurysm as a result of a short landing zone. Late complications included infection (17.1%) and thrombosis (37.1%). The 1, 6, and 12 month primary patency rates were 89.2%, 55.5%, and 22.0%, respectively. The 1, 6, and 12 month secondary patency rates were 100%, 88.6%, and 78.6%, respectively. The median follow up was 12.3 months. CONCLUSIONS: The study demonstrates that endovascular stent graft repair is an effective and safe alternative therapy for AVG pseudoaneurysms. However, the rate of thrombosis and infection was high and needs to be balanced against open surgery in future studies.

New Physics Opportunities in the Boosted Di-Higgs-Boson Plus Missing Transverse Energy Signature.

The Higgs field in the standard model may couple to new physics sectors related to dark matter and/or massive neutrinos. In this Letter we propose a novel signature, the boosted di-Higgs-boson plus E_{T} (which is either a dark matter or neutrino), to probe those new physics sectors. In a large class of models, in particular, the supersymmetric standard models and low scale seesaw mechanisms, this signature can play a key role. The signature has a clear background, and at the sqrt[s]=14 TeV high luminosity LHC, we can probe it with a production rate as low as ∼0.1 fb. We apply it to benchmark models, supersymmetry in the bino-Higgsino limit, the canonical seesaw model, and the little Higgs model, finding that the masses of the Higgsino, right-handed neutrino, and heavy vector boson can be probed up to ∼500, 650, and 900 GeV, respectively.

Emerging roles for lipids in non-apoptotic cell death.

Non-apoptotic regulated cell death (RCD) is essential to maintain organismal homeostasis and may be aberrantly activated during certain pathological states. Lipids are emerging as key components of several non-apoptotic RCD pathways. For example, a direct interaction between membrane phospholipids and the pore-forming protein mixed lineage kinase domain-like (MLKL) is needed for the execution of necroptosis, while the oxidative destruction of membrane polyunsaturated fatty acids (PUFAs), following the inactivation of glutathione peroxidase 4 (GPX4), is a requisite gateway to ferroptosis. Here, we review the roles of lipids in the initiation and execution of these and other forms of non-apoptotic cell death. We also consider new technologies that are allowing for the roles of lipids and lipid metabolism in RCD to be probed in increasingly sophisticated ways. In certain cases, this new knowledge may enable the development of therapies that target lipids and lipid metabolic processes to enhance or suppress specific non-apoptotic RCD pathways.

The Changing Faces of Mentorship: Application of a Developmental Network Framework in a Health Services Research Career Development Program.

Historically, mentorship has been conceived of as a dyadic relationship between a senior mentor and an early-career investigator. Models involving multiple mentors have gained favor in recent years, but empirical research on multiple-mentor models has been lacking. The current work aims to fill this gap by describing a long-standing health services research mentoring program at the U.S. Department of Veterans Affairs which has adopted a network-based approach to mentoring. As part of a broader project, we surveyed VA HSR&D Career Development Awardees who received an award between 2000 and 2012. In total, 133 awardees participated (84%). Awardees reported on the structure of mentoring relationships with their two most influential mentors. Awardees were mentored by teams consisting of one to five mentors (M = 2.7 mentors). Most often, one mentor served as primary mentor while one or more mentors played a supporting role. In most cases, an awardee's primary mentor was co-located with the awardee, with fewer secondary mentors co-located. More recently funded CDAs had more mentors and were less likely to be co-located with secondary mentors. The VA HSR&D CDA program incorporates current thinking about Developmental Network models of mentorship into a comprehensive program providing a rich mentorship experience for its awardees.

High photosensitivity few-layered MoSe2 back-gated field-effect phototransistors.

In this paper, we report on the fabrication and optoelectronic properties of high sensitive phototransistors based on few-layered MoSe2 back-gated field-effect transistors, with a mobility of 19.7 cm² V⁻¹ s⁻¹ at room temperature. We obtained an ultrahigh photoresponsivity of 97.1 AW⁻¹ and an external quantum efficiency (EQE) of 22 666% using 532 nm laser excitation at room temperature. The photoresponsivity was improved near the threshold gate voltage; however, the selection of the silicon dioxide as a gate oxide represents a limiting factor in the ultimate performance. Thanks to their high photoresponsivity and external quantum efficiency, the few-layered MoSe2-based devices are promising for photoelectronic applications.

[The use of SPECT-CT in the diagnosis of cancerous lesions of axillary lymph nodes in patients with breast cancer].

The purpose of the study was to explore the possibilities of a new hybrid technology of SPECT-CT in the diagnosis of metastatic regional lymph nodes (LN) in patients with breast cancer (BC). There were examined 57 primary patients. All patients underwent axillary lymph node dissection and /or biopsy of sentinel LN followed by histological examination of the material. Metastases in LN were verified in 20 (35%) of 57 examined patients. Sensitivity, specificity and overall accuracy of SPECT-CT in the combined use of anatomical and functional criteria for assessing the state of LN accounted for 75%, 89% and 84%, respectively. Sensitivity of SPECT-CT in the diagnosis of massive axillary LN lesion (more than two) in breast cancer patients was 95%. Thus, the new hybrid technology of SPECT-CT, combining functional and anatomical techniques for assessing of pathological changes, is highly informative in the diagnosis of metastatic lesions of regional LN in patients with breast cancer.

[Adjuvant chemotherapy for breast cancer: search for new ways of planning].

A decision regarding adjuvant chemotherapy in early (operable) breast cancer in the past was made entirely on the basis of clinical and pathological features. However with the growing awareness of tumor biology and the possibility of the genomic analysis to determine the molecular subtypes of breast cancer it is getting real to identify patients whose tumors are resistant to chemotherapy or vice versa benefit from its addition. Despite the fact that genomic analysis allows some patients avoiding chemotherapy (especially patients with localized breast cancer), such studies do not indicate the most appropriate chemotherapy regimens. Therefore treatment decisions should be based on a combination of biological features of the tumor, its stage and signs that characterize the patient such as age and tolerance to the side effects of therapy.

[Functional dissociation of parts of the "sensorimotor complex" in the human cortex with the method of magnetoencephalography].

A method of non-invasive human primary motor cortex mapping has been developed. In 18 healthy right-handed subjects magnetic brain responses caused by repeated voluntary left or right index finger movements were studied. Movement onsets were derived from the accelerometer signal. Recordings of magnetic activity throughout whole experimental sessions in all subjects were concatenated into a single sequence, which was separated into independent components using independent component analysis and ranked according to the amount of mutual information with the modified accelerometer signal. Independent components that demonstrated maximum relation to the finger movement were averaged relative to the movement onset. The results of the distributed brain source modeling of the two independent components that manifested maximum amount of mutual information has demonstrated that their sources localize in the cortical areas corresponding to anatomical markers of hand representation in the primary motor and the primary sensory cortices contralateral to the movement. The method developed has demonstrated the fundamental possibility of localizing the M1 area in healthy subjects.

[The use of SPECT-CT with 99mTc-labeled phosphates in patients with suspected skeletal metastases in planar bone scintigraphy].

We assessed the diagnostic capabilities of SPECT-CT in patients with unclear and suspicious on the secondary lesion with bone scintigraphy background in planar mode (227 patients (mean age - 57 years) with various primary malignancies). All patients underwent planar scintigraphy with 99mTc-labeled phosphates in the "whole body" mode and then - bizonal single-photon-emission computed tomography combined with X-ray computed tomography (SPECT-CT). In patients with the presence of lesions in the skeleton, suspicious on metastases, there was conducted comparison with the data of SPECT-CT. During planar investigation the suspicion on metastases was detected in 41 patients (18%). The use of SPECT-CT allowed excluding metastases in 29 (71%) and confirmed in 7 (17%) of them. In 5 (12%) cases the nature of the changes remained unclear. Thus, in cancer patients with revealed by planar bone scintigraphy unclear or suspicious for metastatic foci in the skeleton, the use of SPECT-CT allowed in most cases (88%) to clarify the nature of these changes.

[Effectiveness of mammary scintigraphy for determining the results of neoadjuvant polychemotherapy in breast cancer].

Analysis of mammoscintigraphy is presented to assess the effectiveness of neoadjuvant polychemotherapy for locally advanced breast cancer. In 90% of patients there is defined conformity of scintigraphy data on the effectiveness of performed polychemotherapy to the results of histologic examination of the postoperative material. The sensitivity of scintigraphy in assessing the effectiveness of neoadjuvant polychemoterapy was 83.3%, specificity--87.9%, accuracy--86.3%, predictive value of positive and negative results-78.9% and 90.1%, respectively. Mammoscintigraphy is an effective method to control the response of locally advanced breast cancer to neoadjuvant polychemotherapy.

[Markers of effectiveness of preoperative taxane-based chemotherapy for locally advanced breast cancer].

The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.

[Methodological issues of sentinel lymph nodes biopsy in patients with breast cancer].

Radionuclide imaging of sentinel lymph nodes (SLN) was performed in 122 breast cancer patients, which before the biopsy of lymph nodes it was performed intratumoral injection of colloidal radiopharmaceuticals (RFP): in 89 patients--nanocolloidal (NC) and in 33--colloidal with particle size from 200 to 1000 nm. After the introduction of NC the SLN image was obtained in 83 of 89 women. (93.3%). After the introduction of large colloids (200-1000 nm or more) SLN visualization in this group was achieved in 27 of 33 patients, i.e., in 81.8% of cases (p < 0.05). Along with the axillary SLN, in 55.8% of cases SLN image was obtained in parasternal area and/or lymph nodes of the second and higher orders in axillary as well as under-and supraclavicular regions. On the contrary while using larger colloids, RFP accumulated only in SLN of axillary region in 85.1%. These differences in the topography of the absorption of various diameters radiocolloids were reliable (p = 0.01). Using the NC RFN compared with colloidal RFP of larger diameter can reliably improve SLN visualization till 98.9% however leads to a concomitant accumulation of RFP in lymph nodes of the second order in 55.8% of patients.

[Combined use of 99mTc-MIBI scintigraphy and ultrasonography (US) in the diagnosis of axillary lymphatic metastasis in patients with breast cancer].

We aimed to evaluate different imaging strategies for diagnosis of axillary LNMs in patients with primary breast cancer (BC). 168 consecutive patients with primary BC were included in the study. Functional imaging by scintigraphy (AxSc) with 99mTc-MIBI was performed in static and tomography modes 15 min after i/v injection. Focal areas of tracer accumulation in axial region were considered as sings of LNMs. Ultrasound (US) examination of axillary region was performed on 7.5 kH scanner. Nodes with diameter more than 1 cm were considered abnormal. All patients were operated with axial LN dissection and subsequent histological evaluation. Scintigraphic signs of LNMs revealed in 65 patients: 48--true positive, 17--false positive. Among 103 women with normal AxSc results 27 had LNMs and 76--uninvolved nodes. Sensitivity (Sen), Specificity (Sp) and Accuracy (Ac) of AxSc were as follows: 64%, 82% and 74%. Sonography diagnosed LNMs in 74 women: 56 were metastatic on histology while other 18--uninvolved. On the contrary, 19 of 94 US normal sized nodes were metastatic on histology. US had following values when used for diagnosis of axillary LNMs: Sen--75%, Sp--81%, Ac--78%. When LNMs were diagnosed as the combination of concordantly abnormal US and AxSc examinations Sp reached 95%, Sen dropped down to 56% and Ac--to 77%. Another model was based on the assumption that LNMs must be diagnosed in all patients with abnormal US or AxSc examinations. According to this strategy Sen reached 83%, Sp--68% and Ac--74%. Thus, we found comparative accuracy of US and AxSc in diagnosis of axillary LNMs in patients with primary BC. Combination of both modalities can significantly improve sensitivity (83%) or specificity (95%) of final conclusion which is determined by established diagnostic strategy and criteria's that are used for BC diagnosis.

[Diagnostic accuracy of mammography and mammoscintigraphy in multifocal breast cancer].

The aim of the study was to compare accuracy of conventional mammography and mammoscintigraphy with the 99mTc-Technetril in the detection of multicentric (MC) breast cancer. A total of 135 women (mean age 52 years) with unilateral simple breast lesions at clinical examination underwent preoperative mammography and mammoscintigraphy. Data of diagnostic procedure were compared with histopathologic analysis in all cases. The present of MC breast cancer was proven in 11 of 135 cases (8%). Mammography detected only one of 11 multicentric cases, while mammoscintigraphy-9 of 11 cases. Mammography showed a 9.1% and 93.5% sensitivity and specificity rates for the detection of multicentric breast cancer, respectively. The overall sensitivity and specificity rates for the detection of the form were 81.8% and 91.1% for mammoscintigraphy, respectively. Confirmation of the distinction between two methods has been attained by Bayesian probability calculation. Mammoscintigraphy proved a more highly sensitive diagnostic method than mammography in the detection and preoperative assessment of MC breast cancer and may contribute to changing surgical management in some cases.

Adaptive femtosecond laser-induced breakdown spectroscopy of uranium.

Laser-induced breakdown spectroscopy (LIBS) is an established technique for material characterization applicable to a variety of problems in research, industry, environmental studies, and security. LIBS conducted with femtosecond laser pulses exhibits unique properties, arising from the characteristics of laser-matter interactions in this pulse width regime. The time evolution of the electric field of the pulse determines its interaction with sample materials. We present the design and performance of a femtosecond LIBS system developed to systematically optimize the technique for detection of uranium. Sample analysis can be performed in vacuum environment, and the spectral and temporal diagnostics are coupled through an adaptive feedback loop, which facilitates optimization of the signal-to-noise ratio by pulse shaping. Initial experimental results of LIBS on natural uranium are presented.

[Nuclear medicine in radiotherapy planning for patients with malignant neoplasms of different locations].

The performance of nuclear medicine methods in radiation therapy tactics determination was analyzed in patients receiving therapy for Hodgkin lymphoma (HL, n=556), breast cancer (BC, n=230), treatment-naive patients with non-small cell lung cancer (NSCLC, n=86). In HL patients the nuclear medicine methods were used to determine the irradiation fields for spleen irradiation (67%) and abdominal lymph nodes (27%). The bone marrow scan data had significant influence on radiation therapy tactics in 10-27% of cases. The visualization of primary tumor lymphatic drainage lead to changing the irradiation field topography in 75% cases of external BC and 85% of internal BC localization. Tumorotropic isotope mammal scan data lead to the changes in planned irradiation volume in 16% of BC patietns. In NSLC patients the results of "positive" scintigraphy with lipophilic 99mTc-marked cations lead to the change in irradiation tactics in 16% of cases. Therefore, the results of diagnostic investigations suggest the important role of nuclear medicine diagnostic methods in patients with various tumors of different localizations.

Risk factors and possible mechanisms of intravenous port catheter migration.

OBJECTIVE: To identify the risk factors for catheter migration and demonstrate possible mechanisms of this migration. DESIGN: Retrospective study. SETTING: Chang Gung Memorial Hospital, a tertiary medical centre in Taiwan. PATIENTS: Patients who underwent implantation of intravenous ports via the superior vena cava (SVC). INTERVENTIONS: Procedures involving catheter placement and re-intervention for catheter migration. MAIN OUTCOME MEASURES: The anatomic location of the catheter tip was confirmed by plain chest X-rays (postero-anterior view). From these plain radiographs, the distance (in cm) between the carina and catheter tip and the angle (in degrees) between the locking nut and catheter were measured. METHODS: A total of 1542 procedures related to intravenous port implantation were retrospectively reviewed but only procedures involving implantation via the SVC were included in the analysis. The study group was composed of 31 interventions because of catheter migration, while the control group consisted of 1475 implantation and re-intervention procedures except those involving catheter migrations. RESULTS: Shallow catheter-tip location (p < 0.0001) and the presence of lung cancer (p = 0.006) were risk factors for catheter migration. CONCLUSIONS: Shallow catheter-tip location and the presence of lung cancer are risk factors for catheter migration. Strategies that ensure low catheter-tip location and avoid increased thoracic pressure may be useful preventive measures.