Anti-CD19 and anti-BCMA CAR T cell therapy followed by lenalidomide maintenance after autologous stem-cell transplantation for high-risk newly diagnosed multiple myeloma.

Few prospective studies have examined posttransplant chimeric antigen receptor (CAR) T cell infusion as candidates for front-line consolidation therapy for high-risk multiple myeloma (MM) patients. This single-arm exploratory clinical trial is the first to evaluate the safety and efficacy of sequential anti-CD19 and anti-BCMA CAR-T cell infusion, followed by lenalidomide maintenance after autologous stem cell transplantation (ASCT), in 10 high-risk newly diagnosed multiple myeloma (NDMM) patients. The treatment was generally well tolerated, with hematologic toxicities being the most common grade 3 or higher adverse events. All patients had cytokine release syndrome (CRS), which was grade 1 in 5 patients (50%) and grade 2 in 5 patients (50%). No neurotoxicity was observed after CAR-T cell infusion. The overall response rate was 100%, with the best response being 90% for a stringent complete response (sCR), and 10% for a complete response (CR). At a median follow-up of 42 (36-49) months, seven (70%) of 10 patients showed sustained minimal residual disease (MRD) negativity for more than 2 years. The median progression-free survival (PFS) and overall survival (OS) were not reached. Although the sample size was small and there was a lack of control in this single-arm study, the clinical benefits observed warrant ongoing randomized controlled trials.

Insertable cardiac monitors for detection of atrial fibrillation after cryptogenic stroke: a meta-analysis.

BACKGROUND: In recent years, the implantable cardiac monitors (ICM) have enhanced the recognition ability of atrial fibrillation (AF), which makes ICM have a new application in AF detection. We conducted a meta-analysis to determine the total incidence of newly found AF detected by ICM after cryptogenic stroke and to evaluate the factors related to the detection of AF. METHODS: A literature search was conducted in the PubMed, EMBASE, Web of Science, and Cochrane library databases until March 1, 2020. Studies that reported the detection rate of AF using ICM in cryptogenic stroke patients with negative initial AF screening were analyzed. RESULTS: A total of 23 studies were included. The overall proportion of AF detected by ICM in cryptogenic stroke patients was 25% (95% confidence interval [CI], 22-29%). The rate of AF detected by ICM was independently related to both cardiac monitoring time (coefficient = 0.0003; 95% CI, 0.0001-0.0005; P = 0.0001) and CHA2DS2-VASc score (coefficient = 0.0834; 95% CI, 0.0339-0.1329; P = 0.001). In subgroup analysis, we found a significant difference in the detection rate of AF for monitoring duration (< 6 months: 9.6% [95% CI, 4.4-16.4%]; ≥ 6 and ≤ 12 months: 19.3% [95% CI, 15.9-23.0%]; > 12 and ≤ 24 months: 23.6% [95% CI, 19.9-27.5%]; > 24 months and ≤ 36 months: 36.5% [95% CI, 24.2-49.9%]; P < 0.001), and continent (Europe: 26.5% [95% CI, 22.2-31.0%]; North America: 16.0% [95% CI, 10.3-22.6%]; Asia: 17.4% [95% CI, 12.4-23.0%]; P = 0.005). CONCLUSIONS: The longer the time of ICM monitoring after cryptogenic stroke, the higher the detection rate of AF. Further research is still needed to determine the optimal duration of long-term cardiac monitoring.

The relationship between COVID-19's severity and ischemic stroke: a systematic review and meta-analysis.

OBJECTIVE: We aim to determine the risk of acute ischemic stroke in patients with severe and non-severe coronavirus disease 2019 (COVID-19). METHODS: A literature search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases until October 28, 2020. Studies covering COVID-19's severity classification data and COVID-19 patients with acute ischemic stroke were included. Two independent evaluators extracted data, and the random effects model was used to calculate the risk ratios (RR) and 95% confidence interval (95% CI) of acute ischemic stroke associated with COVID-19's severity. RESULTS: A total of 8 studies were included, involving 5266 patients. Among all COVID-19 patients, the total incidence of ischemic stroke was 1.76% (95% CI: 0.82-3.01). Severe patients have an increased risk of acute ischemic stroke compared with non-severe patients (RR = 3.53, 95% CI: 2.06-6.07, P < 0.0001; I2 = 12%). This association was also observed when COVID-19's severity was defined by clinical parameters (RR 2.91, 95% CI: 1.17-7.26, P = 0.02; I2 = 29%) and the need for intensive care (RR 4.47, 95% CI: 2.40-8.31, P < 0.0001; I2 = 0%). CONCLUSIONS: This meta-analysis shows that the severe course of COVID-19 is associated with an increased risk of acute ischemic stroke.

Quantitative evaluation of bone marrow infiltration using dual-energy spectral computed tomography in patients with multiple myeloma.

OBJECTIVE: To explore the potential value of quantitative parameters derived from dual-energy spectral computed tomography (DESCT) as comparing to the parameters derived from magnetic resonance imaging (MRI) in detecting bone marrow (BM) infiltration and distinguishing different patterns of BM infiltration in patients diagnosed with Multiple myeloma (MM). METHODS: This study involved 35MM patients and 15 healthy control subjects who had undergone spinal DESCT and MRI. Pattern assignment was based on visual assessment of MR images, and the regions of interest were defined on both DESCT and apparent diffusion coefficient maps. Quantitative values of DESCT parameters were measured and compared between infiltrated and healthy bone marrow. Receiver operating characteristic (ROC) analysis was performed to determine potential utility of DESCT parameters in identifying BM infiltration and different patterns defined by MRI. Sensitivity and specificity under the optimal thresholds determined by the Youden Index were also calculated. RSULTS: Statistical differences were observed between the DESCT parameters including Ca(Water), Water(Ca), HAP(Fat), Fat(HAP) and Effective atomic number (Eff-Z) but not for the 70-keV CT value between the infiltrated and healthy BM (all P < 0.001). The 70keV CT value and Ca(Water), HAP(Fat) and Eff-Z values were also found to be statistically different in comparing different infiltration patterns (all P < 0.05). Performance of the model-based parameter Ca/Water was superior in differentiating between infiltrated and healthy BM in which the area under ROC curve, AUC = 0.856 [95% CI, 81.4-89.1%] with sensitivity = 0.841 and specificity = 0.768, as well as between MM patients and control subjects (AUC = 0.910 [95% CI, 79.5-97.3%], sensitivity = 0.829 and specificity = 1.000). CONCLUSIONS: Analysis of DESCT offers potential as a quantitative method to detect infiltrated BM and evaluate infiltration patterns of BM in patients diagnosed with MM.

Computed tomography perfusion software pipelines to assess parameter maps and ischemic volumes: A comparative study.

BACKGROUND AND PURPOSE: This study was dedicated to investigating the agreement of the calculated results of two CT perfusion (CTP) postprocessing software packages, including parameter maps and ischemic volume, focusing on the infarct core volume (ICV) and penumbra volume (PV). METHODS: A retrospective collection of 235 patients with acute ischemic stroke who underwent CTP examination were enrolled. All images had been analyzed with two software pipelines, RAPID CTP and AccuCTP, and the comparative analysis was based on ICV and PV results calculated by both software packages. The agreement of parameter maps was evaluated by root mean square error and Bland-Altman analysis. The ICV and PV agreement was evaluated by intraclass correlation coefficient (ICC) and Bland-Altman analysis. The accuracy of ICV and PV based on multiple thresholds was also analyzed. RESULTS: The ICV and PV of AccuCTP and RAPID CTP show excellent agreement. The relative differences of the parameter maps were all within 10% and the Bland-Altman analysis also showed a strong agreement. From ordinary least squares fitting results, both ICV and PV had a remarkably high goodness of fit (ICV, R2 = 0.975 [p<.001]; PV, R2 = 0.964 [p<.001]). For the ICC analysis, both had high ICC scores (ICV ICC 0.984, 95% CI [confidence interval] 0.973-0.989; PV ICC 0.955, 95% CI 0.947-0.964). Furthermore, multi-threshold analysis on the basis of ICV and PV also achieved reliable analytical accuracy. CONCLUSIONS: The image analysis results of AccuCTP are in excellent agreement with RAPID CTP and can be used as an alternative analysis tool to RAPID CTP software in stroke clinical practice.

Intracranial hemorrhage in large vessel occlusion patients receiving endovascular thrombectomy with or without intravenous alteplase: a secondary analysis of the DIRECT-MT trial.

BACKGROUND: Alteplase before thrombectomy for patients with large vessel occlusion stroke raises concerns regarding an increased risk of intracranial hemorrhage (ICH), but the details of this relationship are not well understood. METHODS: This was a secondary analysis of the DIRECT-MT trial. ICH and its subtypes were independently reviewed and classified according to the Heidelberg Bleeding Classification. The effects of alteplase before thrombectomy on ICH and ICH subtypes occurrence were evaluated using logistic regression. Clinical and imaging characteristics that may modify these effects were exploratorily tested. RESULTS: Among 591 patients, any ICH occurred in 254 (43.0%), including hemorrhagic infarction type 1 in 12 (2.1%), hemorrhagic infarction type 2 in 127 (21.7%), parenchymal hematoma type 1 in 34 (5.8%), parenchymal hematoma type 2 in 50 (8.6%), and other hemorrhage types (3a-3c) in 24 (4.1%). Similar ICH frequencies were observed with combined alteplase and thrombectomy versus thrombectomy only (134/292 (45.9%) vs 120/299 (40.1%); OR 1.27, 95% CI 0.91 to 1.75, P=0.16), but patients treated with alteplase had a higher parenchymal hematoma rate (51/287 (17.8%) vs 33/297 (11.1%); OR 1.75, 95% CI 1.08 to 2.85, P=0.024). In the adjusted model, difference in parenchymal hematoma occurrence between groups remained significant (adjusted OR 1.71, 95% CI 1.00 to 2.92, P=0.049). Patients with history of diabetes (Pinteraction=0.048), hypertension (Pinteraction=0.02), antiplatelet therapy (Pinteraction=0.02), anticoagulation therapy (Pinteraction=0.04), and statin administration (Pinteraction=0.02) harbored a higher ICH rate when they received combination therapy. CONCLUSIONS: Our data showed that in the DIRECT-MT trial, alteplase did not increase overall ICH for large vessel occlusion patients treated with thrombectomy, but it increased the parenchymal hematoma rate.

Pre-treatment spectral CT combined with CT perfusion can predict hemorrhagic transformation after thrombolysis in patients with acute ischemic stroke.

OBJECTIVE: To investigate the value of pre-treatment spectral CT angiography (CTA) in predicting hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) treatment in acute ischemic stroke (AIS) patients. MATERIALS AND METHODS: AIS patients who underwent IVT with recombinant tissue plasminogen activator and pre-treatment head and neck spectral CTA and head CT perfusion (CTP) from January 2018 to June 2020 were reviewed retrospectively. Finally, 20 patients were included in the HT group and 22 age-matched patients were included in the non-HT group. Spectral and CTP parameters of the region of interest on pre-treatment CTA axial raw images and CTP images, including the infarct core (IC) and ischemic penumbral (IP) regions, were recorded. The differences in clinical variables, CTP, collateral scores and spectral parameters between the two groups were analyzed. Three multivariate logistic regression models were then developed, where model 1 included clinical and spectral parameters, model 2 included clinical and CTP parameters and a combined model included clinical, CTP, and spectral parameters. Receiver operating characteristic analysis was used to evaluate the performance of the multivariate model. RESULTS: Patients with HT had higher Safe Implementation of Treatments in Stroke (SITS) score (p = 0.023), the volume of perfusion lesions (p = 0.005), the volume of IP (p = 0.003), the mean transit time (MIT) in the IC area (p = 0.012), as well as the TTP in IP area (p = 0.015) compared with patients without HT. The HT group showed significantly lower CBF in the IC area (p = 0.019), iodine concentration (p = 0.017) and the effective atomic number (p = 0.024) in the IP area than non-HT group. And the slope of the spectral curve of the HT group in the IP region was larger than that of the non-HT group (p = 0.023). Gender, age, SITS score, the volume of entire perfusion lesion, CBF and MIT in the IC area, TTP in the IP area, as well as iodine concentration in the IP area were included in the final multivariate model for predicting HT. And CBF in the IC area (OR = 0.779, 95 % CI:0.609-0.996, p = 0.046) as well as the iodine concentration of IP area (OR = 0.343, 95 % CI: 0.131-0.901, p = 0.030) were proved to be independent predictors for HT. The combined model including clinical, spectral, and CTP parameters, showed improved accuracy compared to the other two models, while the Delong test did not suggest a statistically significant difference (both p values > 0.05). CONCLUSIONS: The iodine concentration of IP area derived from pre-treatment spectral CTA was an independent predictor of HT after IVT treatment for AIS patients. Moreover, multivariate models combined with clinical, spectral, and CTP parameters may be able to predict HT.

[The Role of Whole Body DWI in the Evaluation of Bone Disease in Multiple Myeloma].

OBJECTIVE: To explore the characteristics of ADC value changes in DWI of newly diagnosed symptomatic MM patients and its correlation with R-ISS stage. METHODS: The data of 148 newly diagnosed symptomatic MM patients treated by whole-body DWI scan at The First Affiliated Hospital of Soochow University from June 2016 to June 2019 were selected and retrospectively analyzed and 30 cases of age-matched healthy people were selected as controls. The differences of ADC values between the patients in normal control group, DWI- group and DWI+ group were compared, and the relationship between ADC values and R-ISS stage in MM patients was compared. RESULTS: The plasma cell percentage of the patients in DWI+ group was higher than those in DWI- group. ADC values of vertebra, sternum, rib, pectoral girdle, pelvic girdle of the patients in DWI+ group were significantly higher than those in DWI- group and normal control group. The ADC values of each part of the patients in DWI- group were higher than those in normal control group. ADC values of sternum, rib and pectoral girdle in the patients at R-ISS stage III were higher than those at R-ISS stage I and II, while, there was no statistical difference between R-ISS stage I and II groups. And there was no significant difference in ADC values of other bone parts such as vertebra and pelvic girdle in patients at R-ISS stage Ⅰ-Ⅲ. CONCLUSION: DWI+ in MM patients is related to higher tumor invasion. The ADC values of the DWI+ group are higher than those of the DWI- group; the bone ADC values of the DWI- patients are still higher than the normal ones. And there is a certain relationship between ADC value and R-ISS stage.

Evaluation of Revascularization in Different Suzuki Stages of Ischemic Moyamoya Disease by Whole-Brain CT Perfusion.

Objective: This study compared the clinical features and hemodynamic characteristics of patients in different Suzuki stages of ischemic moyamoya disease (iMMD) before and after treatment with extracranial-intracranial (EC-IC) bypass surgery combined with encephalo-duro-myo-synangiosis and whole-brain computed tomography perfusion (WB-CTP). Methods: A total of 126 patients in different Suzuki stages (II, III, IV, and V) of iMMD who underwent bypass surgery from April 2013 to August 2020 were included in this retrospective study. MIStar automatic analysis of Whole brain CT perfusion imaging software (WB-CTP, Apollo Medical Imaging Technology, Melbourne, Australia) was used. The patients also underwent WB-CTP 1 day before and 1 week and 3 months after the surgery. The relationships between hemodynamic parameters in WB-CTP including delay time (DT) > 3 s, relative cerebral blood flow (rCBF) < 30%, mismatch and mismatch ratio, and clinical outcomes were evaluated for different Suzuki stages, with comparisons between early (II and III) and late (IV and V) stages. Results: Combined bypass surgery was performed in 161 hemispheres of 126 patients with iMMD. Brain volume with DT > 3 s was decreased 1 week (51.5 ± 11.8 ml, P < 0.05) and 3 months (41.5 ± 10.7 ml, P < 0.05) after bypass compared to 1 day before bypass (104.7 ± 15.1 ml) in early-stage patients. In late-stage patients, the volume was increased 1 week after bypass compared to the preoperative value (154.3 ± 14.7 vs. 118.3 ± 19.1 ml, P < 0.05). Preoperative brain volume with rCBF < 30% was lower (9.8 ± 3.9 vs. 33.5 ± 11.0 ml) whereas preoperative mismatch ratio was higher (11.2 ± 2.8 vs. 3.6 ± 1.6) in early-stage as compared to late-stage patients (both P < 0.05). A higher modified Rankin scale score (0-1) was achieved by early-stage patients than by those in the late stage (93.8 vs. 80.4%, P < 0.05) at the 3-month follow-up. Conclusions: WB-CTP is useful for assessing the effectiveness of combined bypass/revascularization in different Suzuki stages of iMMD. Patients in the early stage of disease with higher preoperative brain volume with DT > 3 s and mismatch ratio show greater improvements in hemodynamic parameters and fewer postoperative complications associated with hemodynamic disturbance following bypass than patients in the late stage. Preoperative mismatch ratio can serve as a marker for assessing the status of collateral circulation in different Suzuki stages of iMMD.

Assessment of Transient Cerebral Hemodynamic Disturbance via Whole-Brain Computed Tomography Perfusion After Extracranial-Intracranial Bypass in Ischemic Moyamoya Disease.

OBJECTIVE: To assess the cerebral hemodynamic data associated with transient cerebral hemodynamic disturbance (TCHD), including cerebral hyperperfusion syndrome (CHS) and watershed shift ischemia (WSI), by whole-brain (WB) computed tomography perfusion (CTP) before and after revascularization for ischemic moyamoya disease. METHODS: A total of 115 consecutive patients with ischemic moyamoya disease underwent revascularization. All patients underwent WB-CTP 24 hours before operation and on the day of onset of TCHD and 6 months after revascularization. The volumes of delay time (DT) >3 seconds and mismatch and relative cerebral blood flow <30% were calculated in 3 time points. RESULTS: Of the 115 patients, 18 115 had TCHD, comprising 10 with CHS and 8 with WSI. Compared with the brain volume of DT >3 seconds before revascularization, the volume decreased significantly (P < 0.05) on the day of CHS. The volume of mismatch in 3 time points indicated no significant differences (P > 0.05). The volume of relative cerebral blood flow <30% showed obvious differences of significance among 10 patients with CHS (P < 0.05) at 3 time points. In the WSI group, the volume of DT >3 seconds, mismatch, and DT >3 seconds showed significant differences, relatively (P < 0.05), at 3 time points. At the time of onset of TCHD, DT >3 seconds and mismatch in the CHS group were dramatically lower than those in the WSI group (P < 0.05). DT >3 seconds in the no-TCHD group showed significant differences (P < 0.05) at 3 time points. CONCLUSIONS: WB-CTP could be used to assess the cerebral hemodynamic characteristics before and after revascularization. DT >3 seconds and mismatch played important roles in evaluating distinct features of TCHD.

Cerebral arteriosclerosis stenosis predicts poor short-term prognosis in non-valvular atrial fibrillation related cardioembolic stroke treated by reperfusion therapy.

BACKGROUND AND PURPOSE: We aimed to investigate the association between cerebral arteriosclerosis stenosis (CAS) and the short-term prognosis of non-valvular atrial fibrillation (NVAF) related cardioembolic stroke treated by reperfusion therapy. METHODS: The data of 195 consecutive NVAF related cardioembolic stroke patients were retrospectively collected. We defined poor functional outcome as a modified Rankin scale (mRS) score of > 2 at 90 days. RESULTS: Patients with CAS were more likely to be older (75.5 ± 6.8 vs. 72.5 ± 9.2 years, p = 0.001), more current smokers (35.6% vs. 24.1%, p = 0.018), with hypertension (88.1% vs. 65.6%, p < 0.001), diabetes mellitus (50.0% vs. 20.0%, p = 0.020), dyslipidemia (33.9% vs. 23.6%, p = 0.029), previous history of stroke (30.5% vs. 19.5%, p = 0.012), and congestive heart failure (32.2% vs. 22.6%, p = 0.041). Patients with CAS had higher National Institutes of Health Stroke Scale (NIHSS) (18 [13, 22] vs. 15 [9, 19], p < 0.001), and 90-day mRS scores (5 [3, 6] vs. 3[2, 5], p < 0.001). Multivariate logistic regression analysis showed that CAS (odds ratio [OR] 3.184, 95% confidence interval [CI] 1.314-7.713, p = 0.01), NIHSS score on admission (OR 1.228 [per 1 point], 95% CI 1.146-1.316, p < 0.001), congestive heart failure (OR 2.850, 95% CI 1.108-7.331, p = 0.030), and current smokers (OR 2.841, 95% CI 1.102-7.326, p = 0.031) were independent predictors of a poor functional outcome at 90 days. CONCLUSION: We should give the coexistence of CAS and NVAF related cardioembolic stroke proper attention. CAS was an independent factor for predicting the short-term prognosis of NVAF associated cardioembolic stroke patients treated by reperfusion therapy.

Utility of preoperative three-dimensional CT bronchography and angiography in uniportal video-assisted thoracoscopic anatomical lobectomy: a retrospective propensity score-matched analysis.

BACKGROUND: Personalized three-dimensional (3D) reconstruction can help surgeons to overcome technical challenges and variations of pulmonary anatomic structures in the performance of uniportal video-assisted thoracoscopic surgery (UVATS), thus improving the safety and efficacy of the procedure. This study aims to evaluate the utility of preoperative 3D-CT bronchography and angiography (3D-CTBA) with Exoview software in the assessment of anatomical variations of pulmonary vessels, and to analyze short-term surgical outcomes in patients undergoing UVATS lobectomy. METHODS: We retrospectively analyzed the data of 198 consecutive patients who underwent curative UVATS lobectomy between November 2019 and September 2020. The patients were divided into an "Exoview" group (n=53) and a "non-Exoview" group (n=145). We performed 1:1 propensity score matching and compared intraoperative and postoperative outcomes between the two groups. A subgroup analysis of 74 patients who underwent single-direction uniportal lobectomy was also conducted. Aberrant pulmonary vessel patterns related to the surgery were also examined. RESULTS: The operative time in the Exoview group was significantly shorter than that in the non-Exoview group, both before (145.7±33.9 vs. 159.5±41.6 minutes, P=0.032) and after (145.7±33.9 vs. 164.2±41.8 minutes, P=0.014) propensity score matching. The number of mediastinal lymph nodes dissected was higher in the Exoview group than in the non-Exoview group (8.19±6.89 vs. 5.78±3.3, P=0.024) after propensity score matching. Intraoperative blood loss showed a statistical difference between the Exoview and non-Exoview groups (60.4±45.4 vs. 100.8±83.9, P=0.009). Four types of arterial variations and 2 types of venous variations related to the surgery were observed among 8 patients (15%), which have rarely been reported before. CONCLUSIONS: Personalized preoperative 3D-CT bronchography and angiography helped to clearly visualize the pulmonary anatomical structures and could contribute to the safe and efficient performance of UVATS anatomical lobectomy.

Gadolinium enhancement of atherosclerotic plaque in the intracranial artery.

Background: Gadolinium enhancement on high resolution magnetic resonance imaging (HR-MRI) has been considered a sign of instability and inflammation of intracranial atherosclerotic plaques. Our research objective was to explore the relationship between the extent of plaque enhancement (PE), the degree of intracranial artery stenosis, and acute ischemic stroke events.Methods: HR-MRI was performed in 91 patients with intracranial vascular stenosis to determine the existence and intensity of PE.Results: Among 91 patients enrolled in the trial, there were 43 patients in the acute/subacute group (≤1 month from ischemic stroke event), 15 patients in the chronic group (>1 month from ischemic stroke event), and 33 patients in the non-culprit plaques group (no ischemic stroke event). A total of 105 intracranial atherosclerotic plaques were detected in 91 patients. 14 (13.3%) were mild-stenosis plaques, 22 (21.0%) were moderate-stenosis plaques, and 69 (65.7%) were severe-stenosis plaques. There were 12 (11.4%), 18 (17.1%), and 75 (71.4%) plaques in the non-enhanced plaque group, the mild-enhancement group, and the significant-enhancement group, respectively. The degree of PE among the acute/subacute group, the chronic group, and the non-culprit plaque group had a significant difference (P = 0.005). Enhanced plaques were more often observed in culprit plaques (acute/subacute group and chronic group) than non-culprit plaques (96.7% vs 77.3%). Non-enhanced plaques were more often observed in non-culprit plaques than culprit plaques (acute/subacute group and chronic group) (22.7% vs 3.3%). And 36.6% of the enhanced plaques were non-culprit plaques. After performing univariate and multivariate logistic regression analysis, the results showed that strong plaque enhancement (P = 0.025, odds ratio [OR] 3.700, 95% confidence interval [95% CI] 1.182-11.583) and severe stenosis (P = 0.008, OR 4.393, 95%CI 1.481-13.030) were significantly associated with acute ischemic events.Conclusion: Enhanced plaques were more often observed in culprit plaques, and non-enhanced plaques were more often observed in non-culprit plaques. Moreover, significant plaque enhancement and severe ICAS were closely associated with acute ischemic events.

Combining inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) treatment improves motor function by modulating GABA in acute ischemic stroke patients.

BACKGROUND: The combination of inhibitory and facilitatory repetitive transcranial magnetic stimulation (rTMS) can improve motor function of stroke patients with undefined mechanism. It has been demonstrated that rTMS exhibits a neuro-modulatory effect by regulating the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) in other diseases. OBJECTIVES: To evaluate the effect of combined inhibitory and facilitatory rTMS on GABA in the primary motor cortex (M1) for treating motor dysfunction after acute ischemic stroke. METHODS: 44 ischemic stroke patients with motor dysfunction were randomly divided into two groups. The treatment group was stimulated with 10 Hz rTMS at the ipsilesional M1 and 1 Hz rTMS at the contralesional M1. The sham group received bilateral sham stimulation at the motor cortices. The GABA level in the bilateral M1 was measured by proton magnetic resonance spectroscopy (1H-MRS) at 24 hours before and after rTMS stimulation. Motor function was measured using the Fugl-Meyer Assessment (FMA). The clinical assessments were performed before and after rTMS and after 3 months. RESULTS: The treatment group exhibited a greater improvement in motor function 24 hours after rTMS compared to the sham group. The increased improvement in motor function lasted for at least 3 months after treatment. Following 4 weeks of rTMS, the GABA level in the ipsilesional M1 of the treatment group was significantly decreased compared to the sham group. Furthermore, the change of FMA score for motor function was negatively correlated to the change of the GABA:Cr ratio. Finally, the effect of rTMS on motor function outcome was partially mediated by GABA level change in response to the treatment (27.7%). CONCLUSIONS: Combining inhibitory and facilitatory rTMS can decrease the GABA level in M1, which is correlated to the improvement of motor function. Thus, the GABA level in M1 may be a potential biomarker for treatment strategy decisions regarding rTMS neuromodulatory interventions.

Diagnostic performance of deep learning-based vascular extraction and stenosis detection technique for coronary artery disease.

OBJECTIVE: To investigate the diagnostic performance of deep learning (DL)-based vascular extraction and stenosis detection technology in assessing coronary artery disease (CAD). METHODS: The diagnostic performance of DL technology was evaluated by retrospective analysis of coronary computed tomography angiography in 124 suspected CAD patients, using invasive coronary angiography as reference standard. Lumen diameter stenosis ≥50% was considered obstructive, and the diagnostic performances were evaluated at per-patient, per-vessel and per-segment levels. The diagnostic performances between DL model and reader model were compared by the areas under the receiver operating characteristics curves (AUCs). RESULTS: In patient-based analysis, AUC of 0.78 was obtained by DL model to detect obstructive CAD [sensitivity of 94%, specificity of 63%, positive predictive value of 94%, and negative predictive value of 59%], While AUC by reader model was 0.74 (sensitivity of 97%, specificity of 50%, positive predictive value of 93%, negative predictive value of 73%). In vessel-based analysis, the AUCs of DL model and reader model were 0.87 and 0.89 respectively. In segment-based analysis, the AUCs of 0.84 and 0.89 were obtained by DL model and reader model respectively. It took 0.47 min to analyze all segments per patient by DL model, which is significantly less than reader model (29.65 min) (p < 0.001). CONCLUSION: The DL technology can accurately and effectively identify obstructive CAD, with less time-consuming, and it could be a reliable diagnostic tool to detect CAD. ADVANCES IN KNOWLEDGE: The DL technology has valuable prospect with the diagnostic ability to detect CAD.

Cyclic RGD-Functionalized and Disulfide-Crosslinked Iodine-Rich Polymersomes as a Robust and Smart Theranostic Agent for Targeted CT Imaging and Chemotherapy of Tumor.

There is tremendous interest in integrating CT imaging with chemotherapy; however, reported iodine-based nanosystems such as nanogels and nano-emulsions display typically reduced contrast coefficient, low drug loading and stability, and poor targetability. Here, cRGD-functionalized disulfide-crosslinked iodine-rich polymersomes (cRGD-XIPs) were designed as a novel, robust and smart theranostic agent and investigated for targeted CT imaging and chemotherapy of malignant tumors. Methods: cRGD-XIPs were prepared from co-self-assembly of poly(ethylene glycol)-b-poly(dithiolane trimethylene carbonate-co-iodinated trimethylene carbonate) (PEG-P(DTC-IC)) and cRGD-PEG-P(DTC-IC) block copolymers. In vitro and in vivo CT contrast effect of cRGD-XIPs was studied using αvß3-overexpressing B16 melanoma as a tumor model in comparison with clinical agent iohexol. The therapeutic efficacy of doxorubicin-loaded cRGD-XIPs (cRGD-XIPs-Dox) to B16 melanoma was investigated and compared with XIPs-Dox (non-targeted), cRGD-IPs-Dox (non-crosslinked) and free Dox. Results: cRGD-XIPs were formed with 55.5 wt.% iodine and ca. 90 nm in diameter. cRGD-XIPs-Dox with a Dox loading of 15.3 wt.% bared superior colloidal stability and reduction-responsive drug release. Notably, blank cRGD-XIPs showed a maximum-tolerated dose (MTD) > 400 mg iodine equiv./kg while cRGD-XIPs-Dox had an MTD > 150 mg Dox equiv./kg, ca. 15-fold improvement over free Dox. cRGD-XIPs revealed superior CT contrast effect and achieved 46.5- and 24.0-fold better enhancement of CT imaging of B16 melanoma than iohexol at 4 h following intratumoral and intravenous injection, respectively. cRGD-XIPs-Dox displayed an elimination half-life of 6.5 h and an elevated accumulation of 6.68% ID/g in the tumors. Furthermore, cRGD-XIPs-Dox was significantly more effective than XIPs-Dox and cRGD-XPs-Dox in inhibiting growth of B16 melanoma model. Conclusion: This proof-of-concept study demonstrates that cRGD-XIPs are a robust, non-toxic and smart polymeric theranostic agent that can not only significantly enhance CT imaging of tumors but also mediate efficient tumor-targeted chemotherapy. XIPs offer a unique and safe platform for theranostic polymersomes that pre-select patients using CT imaging prior to targeted chemotherapy with the same system.

Whole-body diffusion-weighted MRI for evaluation of response in multiple myeloma patients following bortezomib-based therapy: A large single-center cohort study.

PURPOSE: To determine the feasibility of whole-body diffusion-weighted imaging (WB-DWI) MRI for evaluation of response in patients with multiple myeloma (MM) following bortezomib-based therapy and to explore the direction of apparent diffusion coefficient (ADC) changes upon treatment. METHOD: Seventy-two MM patients who underwent WB-DWI MRI before and after bortezomib-based chemotherapy (21 weeks) were evaluated retrospectively. The estimated tumor volume (eTV) and ADCmean values before and after chemotherapy were calculated and compared between deep and non-deep responders. Predictive value of baseline ADCmean was calculated to predict the trend of ADCmean change following treatment. RESULTS: Fifty-five patients were classified as deep responders, and 17 cases were assigned as non-deep responders. For 327 focal lesions (FLs), the ADCmean value was significantly increased from baseline to post-treatment. However, the ADCmean value was significantly decreased following treatment in 846 representative diffuse lesions. Diffuse lesions showed a significantly decreased ADCmean value in deep responders, whereas no significant variation in ADCmean value in FLs was found between deep and non-deep responders. Baseline ADCmean at a specific value (0.808 × 10-3 mm2/s) yielded a maximum specificity (68.05%) and sensitivity (54.09%) in predicting increase of post-treatment ADCmean. CONCLUSIONS: The ADCmean value was significantly decreased in MM patients with diffuse pattern, while it was significantly increased in those with focal pattern following bortezomib-based treatment. WB-DWI MRI could be used to discriminate deep response to induction treatment in MM patients with diffuse infiltration pattern. Baseline ADCmean value might have a potential to predict the trend of ADCmean change following treatment.

[Diagnostic Utility of Electromagnetic Navigation Bronchoscopy Combined with 
Radial Probe Endobronchial Ultrasound in Peripheral Pulmonary Lesions].

BACKGROUND: With the application of high resolution computed tomography (CT), a large number of peripheral lung lesions were found. It put forward new challenge on clinical diagnosis and treatment for these peripheral lung lesions. Electromagnetic navigation bronchoscopy (ENB) and radial endobronchial ultrasound probe (R-EBUS) are new technologies used for the diagnosis of peripheral lung lesions. The aim of this study is to explore the application value of ENB combined with R-EBUS in the diagnosis of peripheral pulmonary lesions. METHODS: From September 2016 to November 2017, eighteen patients with thirty peripheral pulmonary lesions in the First Affiliated Hospital of Soochow University were enrolled. The ENB was performed on these patients who were detected peripheral lung lesions by chest HR-CT. After successful navigation, the lesion's location was confirmed by R-EBUS, and specimens were acquired by needle aspiration, endoscopic cell brush and biopsy forceps. RESULTS: A total of eighteen patients with thirty lesions were enrolled in this study, the navigation success rate was 100%, the positive rate was 90%. The mean operation time was (95.61±28.74) min, and navigation time for each lesion was (25.90±11.29) min, and pneumothorax was observed in 1 case. CONCLUSIONS: ENB combined with R-EBUS for the diagnosis of peripheral pulmonary lesions is safe and effective. This technique is worth promoting.

High-resolution melting analysis for rapid and sensitive NOTCH1 screening in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a biological and clinical heterogeneous disease. Activating mutations of NOTCH1 have been implicated to be associated with adverse prognosis in CLL. The objective of the present study was to develop an effective high-resolution melting (HRM) assay for detecting NOTCH1 mutations. Genomic DNA (gDNA) extracted from 133 CLL patients was screened by HRM assay, and the results were compared with the data obtained using direct sequencing. The relative sensitivity of the HRM assay and direct sequencing was evaluated using diluted gDNA with different NOTCH1 mutational frequencies. The HRM assay was able to detect and discriminate samples with NOTCH1 mutations from the wild-type template in CLL. Eight of the 133 CLL patients (6.02%) were scored positively for NOTCH1 mutations in the HRM assay. The results of the NOTCH1 mutations detected by HRM analysis achieved 100% concordance with those determined from direct sequencing. HRM had a higher sensitivity (1%) and shorter turn-around time (TAT), compared to direct sequencing. In conclusion, the HRM assay developed by us was confirmed to be a rapid, sensitive, and promising approach for high-throughput prognostic NOTCH1 screening in CLL. It enables real-time NOTCH1 evaluation, which is of great significance in clinical practice and may facilitate the decision-making of clinicians in CLL.

Primary chondrosarcoma presenting as an intrathoracic mass: A report of three cases.

Primary intrathoracic chondrosarcomas are rare tumors. The present study reports three cases of primary intrathoracic chondrosarcomas in two males and one female aged between 45 and 64 years. Clinically, one case presented with cough and blood sputum, while the other two cases of primary intrathoracic chondrosarcoma were found incidently during a routine health examination. Radiologically, the chondrosarcomas presented as large masses with intratumoral calcification. Chondrosarcoma should be distinguished from other calcified pulmonary lesions. In this study, all three cases underwent surgical treatment, and in one case, the surgery was accompanied by radiotherapy. To date, all patients have been followed up for between two and three years and are alive.