Balloon-Assisted Catheterization of Occluded Carotid Artery (BOCA) Technique in Acute Stroke.

BACKGROUND: Acute ischemic stroke from tandem occlusion of internal carotid artery (ICA) poses a technical challenge to neurointerventionalists. OBJECTIVE: To present a novel balloon-assisted catheterization of occluded carotid artery (BOCA) technique used for rapid and effective catheterization of occluded/critically stenosed ICA in tandem occlusion. METHODS: A retrospective review of 10 patients with tandem carotid occlusion, treated with BOCA technique for revascularization between July 2020 and June 2021, was performed. Clinical, radiographic, and procedural data; details of BOCA technique; complications; and outcomes were reviewed. RESULTS: Of the 10 patients, 8 (80%) had complete occlusion of the cervical ICA and the remaining 2 had high-grade stenosis with poor intracranial flow. The mean age was 63.2 years. The mean presenting NIH Stroke Scale was 13.4. The BOCA technique resulted in recanalization of ICA in all patients and allowed mechanical thrombectomy of middle cerebral artery. Thrombolysis in cerebral infarction grade 2b/3 was achieved in all 10 patients. The mean groin-to-reperfusion time was 41.4 minutes. The mean internal carotid artery stenosis was 99.7% preoperatively and 41.1% postoperatively. Only one patient needed stent at the end of the procedure because of dissection. CONCLUSION: The BOCA technique can be used in distal first approach for acute stroke from tandem ICA occlusion. This technique allows direct guide catheterization of occluded ICA by tracking over a partially inflated balloon.

Clopidogrel Bolus is Inferior to Sustained Clopidogrel Pretreatment in Patients Undergoing Carotid Artery Stent Placement.

BACKGROUND: Clopidogrel bolus is an option used before carotid artery stent (CAS) placement when sustained clopidogrel pretreatment is not used. OBJECTIVE: To compare the effect of clopidogrel bolus (450 mg administered ≥4 hours) with sustained clopidogrel pretreatment (48 hours or greater) before CAS among patients recruited in the Carotid Revascularization Endarterectomy versus Stenting Trial. METHODS: We compared the rates of primary end point (either any stroke, myocardial infarction, or death during the periprocedural period or any ipsilateral stroke within 4 years) between patients who received clopidogrel bolus and those who received sustained clopidogrel pretreatment using Cox proportional hazards analysis after adjusting for age, sex, symptomatic status, and initial severity of stenosis (≥70% vs <70%) over 4 years. RESULTS: The rate of periprocedural stroke (7.3% vs 3.4%, P = .03) and primary end point (11.3% vs 5.9%, P = .02) was significantly higher among patients who received clopidogrel bolus. The risk of primary end point was significantly higher in patients who received clopidogrel bolus (hazards ratio 1.9, 95% CI 1.1-3.4, P = .02) after adjusting for potential confounders. The overall mean (±standard deviation) primary end point-free survival based on Kaplan-Meier analysis was 7.0 ± 0.2 years for patients who received clopidogrel bolus and 8.9 ± 0.1 years for those who received sustained clopidogrel pretreatment (log-rank test P = .011). CONCLUSION: Clopidogrel bolus was associated with higher rates of adverse outcomes compared with sustained clopidogrel pretreatment in patients who underwent CAS. Therefore, clopidogrel bolus may not be equivalent to sustained clopidogrel pretreatment.

Repeat Revascularization over 10 Years Following Carotid Endarterectomy or Carotid Stent Placement: An Analysis of Carotid Revascularization Endarterectomy Versus Stenting Trial.

OBJECTIVE: To identify rates of and factors associated with repeat revascularization in a large cohort of patients prospectively followed over 10 years in Carotid Revascularization Endarterectomy versus Stenting Trial. METHODS: We compared the effect of carotid angioplasty and stenting (CAS) versus carotid endarterectomy (CEA) on risk of repeat revascularization after adjusting for age, sex, symptomatic status, and initial severity of stenosis (≥70% vs. <70%) using Cox proportional hazards analysis. We used Kaplan-Meier analysis to assess repeat revascularization-free survival for the overall cohort. RESULTS: Repeat revascularization was performed in 90 (3.9%, 95% confidence interval [CI] 3.1%-4.8%) of 2318 patients; 6 (6.7%, 95% CI 2.5%-14.0%) patients experienced the composite end point of any stroke, myocardial infarction, or death within 30 days after repeat revascularization. There was no difference in risk of repeat revascularization in patients who underwent CAS (compared with CEA) as the index procedure (hazard ratio 0.92, 95% CI 0.69-1.23, P = 0.5765). Patient's age (hazard ratio 1.01, 95% CI 1.01-1.02, P < 0.0001) was associated with performance of repeat revascularization. Mean ± SD repeat revascularization-free survival was 8.2 ± 0.1 years and 8.0 ± 0.1 years for CAS and CEA, respectively (log-rank test P = 0.0823). CONCLUSIONS: A low rate of repeat revascularization was seen without any significant difference among patients who underwent CEA or CAS over 10 years. The 6.7% rate of composite end point within 30 days after procedure highlights the need for standardizing the indications for repeat revascularization.

Baicalin attenuates endometritis in a rabbit model induced by infection with Escherichia coli and Staphylococcus aureus via NF-κB and JNK signaling pathways.

In this study, a rabbit endometritis model was developed to study cow endometritis. In addition, the protective effects of baicalin (a flavonoid) against endometritis were investigated. Clinical symptoms, differential leukocyte counting, uterine secretion smear microscopy and chemical examination, urine testing, and signs of necropsy showed abnormal changes and inflammatory responses in the uterus of rabbits. Histopathological results revealed visible inflammatory exudates and blood spots between intercellular spaces which confirmed that the rabbit endometritis model was successfully developed. Most importantly, these inflammatory signs were partially attenuated with baicalin treatment. The data revealed that the increased body temperature and leukocyte cells, pus, and the detachment of epithelial cells were alleviated with baicalin administration in a dose-dependent manner. Histopathological tissue changes such as inflammatory cells infiltrates, hyperemia, hemorrhages, and shedding of epithelial cells were partially attenuated with baicalin treatment. In addition, the mRNA expression of inflammation-related genes (iNOS, IL-1ß, TNF-α, IL-10, IL-4, and IL-6) was significantly altered in RAW264.7 cells after LPS treatment. Further, the phosphorylated protein expression of JNK, p65, and IκBα were significantly reduced with LPS treatment. Intriguingly, baicalin pretreatment reversed the alteration in mRNA expression of inflammation-related genes and significantly reduced the phosphorylation of JNK, p65, and IκBα. In summary, our results suggest that baicalin has protective effects on bacterial-induced endometritis in rabbits that involve the suppression of NF-κB and JNK signaling pathways and pro-inflammatory cytokines.

Comparison of Experimental Infection of Normal and Immunosuppressed Chickens with Mycoplasma gallisepticum.

Four different models of infection of chickens with Mycoplasma gallisepticum (MG) were evaluated. Normal or immunosuppressed chicks (10 days old) were infected with the MG Rlow strain via eye and nasal drops or by direct air sac injection. Bacterial load in the lungs was quantified and air sac and tracheal lesion scores, tracheal mucosal thickness and humoral immune responses were assessed. Serum antibody responses were assessed by use of a serum plate agglutination test. Three days post infection (dpi), all immunosuppressed chicks had developed significant respiratory signs. Chicks infected via air sac injection had significant differences in serum antibody and gross lesion scores at 5 dpi. All chicks had developed pathological changes by 7 dpi. Air sac inoculation of immunosuppressed chicks produced more significant (P ≤0.05) lesions, and these birds had the highest bacterial load in the lungs compared with other groups.

Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Endovascular Treatment versus Best Medical Treatment in Patients with Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND PURPOSE: Endovascular treatment has emerged as a minimally invasive technique for patients with acute ischemic stroke to achieve recanalization. Our aim was to determine the effects of endovascular treatment on clinical and safety outcomes compared with best medical treatment. MATERIALS AND METHODS: Fifteen randomized trials that compared endovascular treatment with best medical treatment in patients with acute ischemic stroke met the inclusion criteria. We calculated pooled odds ratios and 95% CIs by using random-effects models. The primary end point was a favorable outcome defined by a modified Rankin Scale score of 0 (no symptoms), 1 (no significant disability), or 2 (slight disability) at 90 days postrandomization. RESULTS: Of the 2980 subjects randomized, the proportion of subjects who achieved a favorable outcome was significantly greater among those randomized to endovascular treatment compared with best medical treatment (2949 subjects analyzed; odds ratio, 1.82; 95% CI, 1.38-2.40; P < .001). Excellent outcome (modified Rankin Scale score of 0 or 1) was also significantly greater among those randomized to endovascular treatment (2791 subjects analyzed; odds ratio, 1.77; 95% CI, 1.29-2.43, P < .001). Risk of symptomatic intracranial hemorrhage was similar between endovascular treatment and best medical treatment (2906 subjects analyzed; odds ratio, 1.19; 95% CI, 0.84-1.68; P = .34). CONCLUSIONS: Compared with best medical treatment, the odds of achieving a favorable outcome or excellent outcome at 3 months postrandomization are approximately 80% higher with endovascular treatment among patients with acute ischemic stroke.

Novel SYK gene variations and changes in binding sites of miRs in breast cancer patients.

BACKGROUND: Spleen Tyrosine Kinase (SYK) belongs to non-receptor tyrosine Kinase family, which normally expresses in epithelial breast tissues and acts as a tumor suppressor gene. OBJECTIVE: Analysis of mutations in the SYK gene and deregulation of SYK transcripts by miRNA in breast cancer was studied. METHODS: All exons and exon/intron boundaries of SYK gene were amplified and sequenced in blood samples of 207 breast cancer cases and 200 matched controls using PCR-single stranded conformational polymorphism method. RESULTS: Sequence analysis revealed 10 novel mutations in breast cancer patients. Among these 6 mutations (Ala 161Pro, His162Tyr, Phe191Tyr, Val 535Gly, Ser 556lIe and Lys536Gln) were found in exonic region and 4 (26249 T>A, 63941 G>A, 63981G>C and 86548T>A) were found in intronic region. All of these mutations are associated with ∼ 5 folds (p< 0.0001) increase in breast cancer risk in present study cohort. Regulation of SYK transcripts by miRNA was also analyzed using in silico bioinformatics tools, exon 6's mutation (Phe191Tyr) was found to have altered interaction with miR-873. CONCLUSION: Overall novel mutations in SYK gene and in silico analysis revealed that these mutations are crucial and might be responsible for altered expression of SYK.

Interferon-gamma reduces the proliferation of M-tuberculosis within macrophages from a patient with a novel hypomorphic NEMO mutation

X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by mutations in the nuclear factor-kappa B essential modulator (NEMO) gene. Here, we report the clinical and genetic features of a XL-EDA-ID patient who developed bacillus Calmette-Guerin infection. Patient lymphocytes failed to degrade IB-, and sequencing of NEMO identified the novel mutation c.1238A>C/p.H413P. Furthermore, patient monocyte-derived macrophages ingested Mycobacterium tuberculosis normally, but failed to control the intracellular proliferation of bacilli, a defect which was improved in the presence of interferon-gamma (IFN-). This work expands the genetic spectrum of XL-EDA-ID and demonstrates improvement in macrophage function in a NEMO-deficient patient by IFN-

Preparation and pre-clinical study of 177Lu-labelled hydroxyapatite for application in radiation synovectomy of small joints.

AIM: We present in this paper, the preparation and pre-clinical study of 177Lu-labelled hydroxyapatite for the application in radiation synovectomy of small sized joints. METHODS: 177Lu is an adequate radionuclide for therapy, having ability of simultaneously showing therapeutic effects and depicting images. Both hydroxyapatite particulates and 177Lu were prepared indigenously. RESULTS AND CONCLUSION: Analysis of the gamma ray spectrum showed the radionuclide purity of 177Lu more than 99%. HA particles were synthesized and characterized by FTIR-ATR and X-ray diffractometry. XRD-Pattern generated by the product indicated that the chief inorganic phase of the sample is hydroxyapatite crystal. FTIR spectrum of HA powder calcined at 800°C for 1h showed all the bands that can be assigned to phosphate and hydroxyl groups in an apatite environment. Ca/P ratio was determined by ICP-OES. The Ca/P ratio of 1.68 determined for HA was about 0.6% above the stoichiometric ratio of 1.67. Particle size distribution pattern was obtained with the help of laser particle size analyzer and results showed that more than 80% of the particles bear the size in the range ideal for radiosynovectomy. 177Lu-labelled hydroxyapatite particulates were prepared with high radiochemical purity and yield. >95% labeling yield was achieved at pH 7. Labeled specie remained stable up to 18 days. In vitro stability >99% remained up to >one half life of 177Lu. Bio-evaluation of the 177Lu-HA particles was carried out by injecting approximate activities of 10 and 5 MBq (in 0.1 mL suspension) as intra-articular injection in the right knee joints of rabbit 1 and 2 respectively. Retention of activity was studied using images of the injected joints with the help of a gamma camera at various intervals. In all images no activity was visible in any organ other than knee joints. The retention of the 177Lu activity was followed for 772 hours (30.01 days). Leakage of activity was also assessed indirectly by estimating the residing time of radiopharmaceutical in the synovium. Half life of 177Lu-HA residing time in the knees was estimated to be 154 hours and 158 hours for rabbit-1 and rabbit-2 respectively. No significant extra articular leakage of the injected activity was observed over a period of one month post injection. Pre-clinical study of 177Lu-labelled hydroxyapatite indicated its potential for application in radiation synovectomy of small joints.

Experience on the neutron activation of natural/enriched Re, Sm, and Ho nuclides in a reactor for the production of radiotherapeutic radionuclides.

In recent years, much effort has been concentrated on the use of beta-emitting radionuclides for the treatment of various cancers. The reports suggested the application of 186Re and 153Sm as radiotherapeutic radionuclides for the treatment of palliative widespread skeletal metastases, whereas 166Ho was suggested as an agent for radiation synovectomy. Hence, a study on the production of 186Re, 153Sm, and 166Ho radionuclides was carried out by neutron activation of the appropriate target materials using a Pakistan Atomic Research Reactor (PARR-1) at a neutrons flux of 1 x 10(4) n/cm2 s. These radionuclides were then converted to appropriate radiopharmaceuticals for their use on animals and patients. The targets of natural Re (metal), natural Sm2O3, enriched Sm2O3 (99.06%), Sm(NO3)3 (solid), Sm(NO3)3 (liquid), and Ho2O3 were irradiated in the PARR-1. After irradiation, the purity of these radionuclides were checked by a multichannel analyzer, Canberra series 85 (MCA) coupled with HPGe detector and then measured in radioisotope calibrator Capintec ionization chamber model CRC-5RH. The effect of the irradiation time and amount of target material was investigated on the production yields of the radionuclides. The results showed an increase in the specific activity of Re with an increase in the irradiation time from 1 to 72 h, whereas a decrease in the specific activity was observed with increase in the amount of Re from 10 to 100 mg. Similar results were obtained for 153Sm and 166Ho radionuclides. The results further indicated that the specific activity of powder target was much less than the liquid targets for 153Sm. Their conversion to the appropriate radiotherapeutic radiopharmaceuticals were also carried out by investigating the experimental conditions and acceptable quality of 186Re-HEDP and 153Sm-EDTMP complexes were prepared. These complexes were then used on animals and patients which showed good performance.

A simple radioaerosol generator and delivery system for pulmonary ventilation studies.

Details of a simple radioaerosol generator and delivery system are presented. Aerosol streams of 99mTc-DTPA solution of different distributions were produced. The most useful distribution had an activity median aerodynamic diameter (AMAD) of 0.9 micron with a geometric standard deviation of 1.5. This distribution also had more than 96% of aerosol particles with aerodynamic diameter less than 2 micron. The system has been used for patient lung ventilation studies. The aerosol breathing-in period to achieve a satisfactory count rate was 1.8 +/- 0.38 min. The radioaerosol images were excellent and comparable to those obtained with 81mKr gas.