Comparing shear wave elastography of breast tumors and axillary nodes in the axillary assessment after neoadjuvant chemotherapy in patients with node-positive breast cancer.

BACKGROUND: Accurately identifying patients with axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients remains challenging. PURPOSE: To compare the feasibility of shear wave elastography (SWE) performed on breast tumors and axillary lymph nodes (LNs) in predicting the axillary status after NAC. MATERIALS AND METHODS: This prospective study included a total of 319 breast cancer patients with biopsy-proven positive node who received NAC followed by axillary lymph node dissection from 2019 to 2022. The correlations between shear wave velocity (SWV) and pathologic characteristics were analyzed separately for both breast tumors and LNs after NAC. We compared the performance of SWV between breast tumors and LNs in predicting the axillary status after NAC. Additionally, we evaluated the performance of the most significantly correlated pathologic characteristic in breast tumors and LNs to investigate the pathologic evidence supporting the use of breast or axilla SWE. RESULTS: Axillary pCR was achieved in 51.41% of patients with node-positive breast cancer. In breast tumors, there is a stronger correlation between SWV and collagen volume fraction (CVF) (r = 0.52, p < 0.001) compared to tumor cell density (TCD) (r = 0.37, p < 0.001). In axillary LNs, SWV was weakly correlated with CVF (r = 0.31, p = 0.177) and TCD (r = 0.29, p = 0.213). No significant correlation was found between SWV and necrosis proportion in breast tumors or axillary LNs. The predictive performances of both SWV and CVF for axillary pCR were found to be superior in breast tumors (AUC = 0.87 and 0.85, respectively) compared to axillary LNs (AUC = 0.70 and 0.74, respectively). CONCLUSION: SWE has the ability to characterize the extracellular matrix, and serves as a promising modality for evaluating axillary LNs after NAC. Notably, breast SWE outperform axilla SWE in determining the axillary status in breast cancer patients after NAC.

Deep learning combining mammography and ultrasound images to predict the malignancy of BI-RADS US 4A lesions in women with dense breasts: a diagnostic study.

OBJECTIVES: The authors aimed to assess the performance of a deep learning (DL) model, based on a combination of ultrasound (US) and mammography (MG) images, for predicting malignancy in breast lesions categorized as Breast Imaging Reporting and Data System (BI-RADS) US 4A in diagnostic patients with dense breasts. METHODS: A total of 992 patients were randomly allocated into the training cohort and the test cohort at a proportion of 4:1. Another, 218 patients were enrolled to form a prospective validation cohort. The DL model was developed by incorporating both US and MG images. The predictive performance of the combined DL model for malignancy was evaluated by sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The combined DL model was then compared to a clinical nomogram model and to the DL model trained using US image only and to that trained MG image only. RESULTS: The combined DL model showed satisfactory diagnostic performance for predicting malignancy in breast lesions, with an AUC of 0.940 (95% CI: 0.874-1.000) in the test cohort, and an AUC of 0.906 (95% CI: 0.817-0.995) in the validation cohort, which was significantly higher than the clinical nomogram model, and the DL model for US or MG alone ( P <0.05). CONCLUSIONS: The study developed an objective DL model combining both US and MG imaging features, which was proven to be more accurate for predicting malignancy in the BI-RADS US 4A breast lesions of patients with dense breasts. This model may then be used to more accurately guide clinicians' choices about whether performing biopsies in breast cancer diagnosis.

Predicting the risk of axillary lymph node metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features and the use of nomograms: a prospective single-center observational study.

OBJECTIVES: The purpose of this study was to establish two preoperative nomograms to evaluate the risk for axillary lymph node (ALN) metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features. METHODS: We prospectively evaluated 593 consecutive female participants who were diagnosed with cT1-3N0-1M0 breast cancer between March 2018 and May 2019 at Sun Yat-Sen Memorial Hospital. The participants were randomly classified into training and validation sets in a 4:1 ratio for the development and validation of the nomograms, respectively. Multivariate logistic regression analysis was performed to identify independent predictors of ALN status. We developed Nomogram A and Nomogram B to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2), respectively. RESULTS: A total of 528 participants were evaluated in the final analyses. Multivariable analysis revealed that the number of suspicious lymph nodes, long axis, short-to-long axis ratio, cortical thickness, tumor location, and histological grade were independent predictors of ALN status. The AUCs of nomogram A in the training and validation groups were 0.83 and 0.78, respectively. The AUCs of nomogram B in the training and validation groups were 0.87 and 0.87, respectively. Both nomograms were well-calibrated. CONCLUSION: We developed two preoperative nomograms that can be used to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2) in early breast cancer patients. Both nomograms are useful tools that will help clinicians predict the risk of ALN metastasis and facilitate therapy decision-making about axillary surgery. KEY POINTS: • We developed two preoperative nomograms to predict axillary lymph node status based on ultrasonographic-clinicopathologic features. • Nomogram A was used to predict axillary lymph node metastasis (presence vs. absence). The AUCs in the training and validation groups were 0.83 and 0.78, respectively. Nomogram B was used to estimate the number of metastatic lymph nodes ( ≤ 2 vs. > 2). The AUCs in the training and validation group were 0.87 and 0.87, respectively. • Our nomograms may help clinicians weigh the risks and benefits of axillary surgery more appropriately.

Determinants of quality of life in Parkinson's disease: a perspective of novel clinical subtypes.

OBJECTIVE: New subtyping classification systems of Parkinson's disease (PD) have been proposed for phenotyping patients into three different subtypes: mild motor-predominant (PD-MMP), intermediate (PD-IM) and diffuse malignant (PD-DM). The quality of life (QoL) underlying the novel PD clinical subtypes is unknown. This study aimed explore the feasibility of the classification in Chinese PD patients and to investigate the potential heterogeneous determinants of QoL among the three subtypes. METHODS: 298 PD patients were enrolled, including 129 PD-MMP patients, 121 PD-IM patients and 48 PD-DM patients. All patients completed the QoL assessment, clinical evaluations and neuropsychological tests. Univariate linear analysis and multiple stepwise regression analysis were performed to identify determinants of QoL. RESULTS: Compared to PD-MMP patients, PD-IM and PD-DM patients had more impaired QoL. The Geriatric Depression Rating Scale (GDS) score, Non-Motor Symptoms Questionnaire (NMSQ) score, Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score and Epworth Sleepiness Score (ESS) were independent contributors to QoL in PD-MMP patients. The GDS score, ESS and sniffin' sticks screening 12 test score were independent contributors to QoL in PD-IM patients. The GDS score and Mini Mental State Examination score were independent contributors to QoL in PD-DM patients. INTERPRETATION: The new novel subtyping classification is feasible for Chinese PD patients. Although depression was the most crucial determinant for QoL in PD-MMP, PD-IM and PD-DM patients, the other contributors of QoL in the three subtypes were heterogeneous. These findings may prompt clinicians to target specific factors for improving QoL depending on PD subtypes.

A new nomogram for predicting the malignant diagnosis of Breast Imaging Reporting and Data System (BI-RADS) ultrasonography category 4A lesions in women with dense breast tissue in the diagnostic setting.

BACKGROUND: Biopsy has been recommended for Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. However, the malignancy rate of category 4A lesions is very low (2-10%). Therefore, most biopsies of category 4A lesions are benign, and the results will generally cause additional health care costs and patient anxiety. METHODS: A prediction model was developed based on an analysis of 418 BI-RADS ultrasonography (US) category 4A patients at Sun Yat-sen Memorial Hospital. Univariate and multivariate logistic regression analyses were applied to identify significant variables for inclusion in the final nomogram. The predictive accuracy and discriminative ability were evaluated using the concordance index (C-index) and calibration curves. An independent cohort of 97 patients from the Second Affiliated Hospital of Guangzhou Medical University was used for external validation. RESULTS: The independent risk factors from the multivariate analysis for the training cohort were family history of breast cancer (OR =4.588, P=0.004), US features [margin (OR =2.916, P=0.019), shape (irregular vs. oval, OR =2.474, P=0.044; round vs. oval, OR =1.935, P=0.276), parallel orientation vs. not parallel (OR =2.204, P=0.040)], low suspicious lymph nodes (OR =7.664, P=0.019), and suspicious calcifications on mammography (MG) (OR =6.736, P=0.001). The C-index was good in the training [0.813, 95% confidence interval (95% CI), 0.733 to 0.893] and validation cohorts (0.765, 95% CI, 0.584 to 0.946). The calibration curves showed optimal agreement between the nomogram prediction and actual observations for the probability of malignancy. Also, the cutoff score was set to 100 for discriminating high and low risk. The model performed well in discerning different risk groups. CONCLUSIONS: We developed a well-discriminated and calibrated nomogram to predict the malignancy of BI-RADS US category 4A lesions in dense breast tissue, which may help clinicians identify patients at lower or higher risk.

Specimen number based diagnostic yields of suspicious axillary lymph nodes in core biopsy in breast cancer: clinical implications from a prospective exploratory study.

BACKGROUND: Ultrasound (US)-guided core needle biopsy (CNB) is widely applied in the pathological diagnosis of suspicious axillary lymph nodes (ALNs) in breast cancer. However, the number of specimens removed during biopsy is currently based on the preference of the individual radiologist. This study aims to analyze the specimen number based diagnostic yields of US guided CNB of suspicious ALNs in breast cancer. METHODS: Core biopsy specimens of suspicious lymph nodes were prospectively obtained from breast cancer patients treated at our hospital between November, 2018, and July, 2019. Four specimens were obtained from each patient and labeled 1-4 in the order they were removed. Each specimen underwent pathological evaluation to determine whether metastasis had occurred. The diagnostic yields of the specimens were calculated and differences in diagnostic accuracy according to the number of specimens were evaluated by McNemar's test. RESULTS: A total of 167 patients were enrolled, and 139 (83.2%) cases were identified as metastasis by CNB. The diagnostic yields were: 74.2% (specimen 1), 87.8% (specimens 1-2), 91.2% (specimens 1-3), and 94.6% (specimens 1-4). The increases in diagnostic yield from specimen 1 to 1-2 and from specimens 1-2 to 1-4 were significant; however, no significant differences were detected between specimens 1-3 and the first two, or between specimens 1-4 and the first three in this sample size. The lower diagnostic abilities for the first two specimens were associated with shorter long- and short-axis lengths of lymph nodes on US. CONCLUSIONS: Although the second specimen contributed significant diagnostic yield of suspicious axillary lymph nodes in core biopsy in breast cancer, a minimum number cannot be determined by this study. Additional specimens may improve diagnostic yield particularly in patients with small nodes.

Neuroprotection of Exendin-4 by Enhanced Autophagy in a Parkinsonian Rat Model of α-Synucleinopathy.

Glucagon-like peptide-1 (GLP-1) receptor stimulation ameliorates parkinsonian motor and non-motor deficits in both experimental animals and patients; however, the disease-modifying mechanisms of GLP-1 receptor activation have remained unknown. The present study investigated whether exendin-4 (a GLP-1 analogue) can rescue motor deficits and exert disease-modifying effects in a parkinsonian rat model of α-synucleinopathy. This model was established by unilaterally injecting AAV-9-A53T-α-synuclein into the right substantia nigra pars compacta, followed by 4 or 8 weeks of twice-daily intraperitoneal injections of exendin-4 (5 µg/kg/day) starting at 2 weeks after AAV-9-A53T-α-synuclein injections. Positron emission tomography/computed tomography (PET/CT) scanning and immunostaining established that treatment with exendin-4 attenuated tyrosine-hydroxylase-positive neuronal loss and terminal denervation and mitigated the decrease in expression of vesicular monoamine transporter 2 within the nigrostriatal dopaminergic systems of rats injected with AAV-9-A53T-α-synuclein. It also mitigated the parkinsonian motor deficits assessed in behavioral tests. Furthermore, through both in vivo and in vitro models of Parkinson's disease, we showed that exendin-4 promoted autophagy and mediated degradation of pathological α-synuclein, the effects of which were counteracted by 3-methyladenine or chloroquine, the autophagic inhibitors. Additionally, exendin-4 attenuated dysregulation of the PI3K/Akt/mTOR pathway in rats injected with AAV-9-A53T-α-synuclein. Taken together, our results demonstrate that exendin-4 treatment relieved behavioral deficits, dopaminergic degeneration, and pathological α-synuclein aggregation in a parkinsonian rat model of α-synucleinopathy and that these effects were mediated by enhanced autophagy via inhibiting the PI3K/Akt/mTOR pathway. In light of the safety and tolerance of exendin-4 administration, our results suggest that exendin-4 may represent a promising disease-modifying treatment for Parkinson's disease.

Ultrasound-Guided Vacuum-assisted Biopsy Versus Surgical Resection in Patients With Breast Desmoid Tumor.

BACKGROUND: Recent studies suggest that desmoid tumors can be managed more conservatively rather than undergoing wide surgical resection (SR). Ultrasound-guided vacuum-assisted biopsy (UGVAB) is a minimally invasive technique. This retrospective study aimed to compare the outcome in patients with breast desmoid tumor (BDT) who received UGVAB alone versus SR. MATERIALS AND METHODS: The pathology database was searched for patients diagnosed with BDT ≤ 3 cm from 2007 to 2019. All patients underwent breast ultrasound examination and were then performed UGVAB alone or local SR. The Kaplan-Meier method with a log-rank test was used as a univariate analysis to compare the relapse-free survival (RFS) rates between UGVAB and SR groups. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 39 patients were included. The median follow-up was 41 mo (range, 5-110 mo). The incidence of tumor recurrence was 23.1% (9/39). The 3-y cumulative RFS was 83.1% and 95.8% in the UGVAB and SR group, respectively, which was not significantly different between the two groups (P = 0.131, log-rank test). Multivariate analysis also revealed that treatment strategy (UGVAB versus SR) was not associated with an increased risk of relapse events (P = 0.274). CONCLUSIONS: Small desmoid tumors (≤3 cm) after UGVAB alone did not have a significantly compromised RFS compared with those who underwent SR. UGVAB may be an alternative and relatively conservative method for the diagnosis and local control of BDT with a smaller size. A prospective, randomized study with large sample size is needed to confirm this observation.

Diagnosis and surgical treatment of non-lesional temporal lobe epilepsy with unilateral amygdala enlargement.

OBJECTIVE: Exploring the role of amygdala enlargement (AE) in temporal lobe epilepsy (TLE) without ipsilateral mesial temporal sclerosis (MTS) using comprehensive presurgical workup tools including traditional tools, automatically volumetric analysis, high-density EEG (HD-EEG) source imaging (HD-ESI), and stereoelectroencephalography (SEEG). METHODS: Nine patients diagnosed with TLE-AE who underwent resective surgeries encompassing the amygdala were retrospectively studied. HD-ESI was obtained using 256-channel HD-EEG on the individualized head model. For automatic volumetric analysis, 48 matched controls were enrolled. Diagnosis and surgical strategies were based on a comprehensive workup following the anatomo-electro-clinical principle. RESULTS: At post-operative follow-up (average 30.9 months), eight patients had achieved Engel class I and one Engel class II recovery. HD-ESI yielded unifocal source estimates in anterior mesial temporal region in 85.7% of cases. Automatic volumetric analysis showed the AE sides were consistent with the values determined through other preoperative workup tools. Furthermore, the amygdala volume of the affected sides in AE was significantly greater than that of the larger sides in controls (p < 0.001). Meanwhile, the amygdala volume lateral index (LI) of AE was significantly higher than in controls (p < 0.001). SEEG analysis showed that ictal onsets arose from the enlarged amygdala (and hippocampus) in all cases. CONCLUSION: In addition to traditional workup tools, automatic volumetric analysis, HD-ESI on individualized head model, and invasive SEEG can provide evidence of epileptogenicity in TLE-AE. Resective surgical strategies encompassing the amygdala result in better prognosis. In suspected TLE cases, more attention should be focused on detecting enlargement of amygdala which sometimes is "hidden" in "MR-negative" non-MTS cases.

Circulating Tumor DNA Predicts the Response and Prognosis in Patients With Early Breast Cancer Receiving Neoadjuvant Chemotherapy.

PURPOSE: Many patients with breast cancer still relapse after curative treatment. How to identify the ones with high relapse risk remains a critical problem. Circulating tumor DNA (ctDNA) has recently become a promising marker to monitor tumor burden. Whether ctDNA can be used to predict the response and prognosis in patients with breast cancer receiving neoadjuvant chemotherapy (NAC) is unknown. Our study aimed to evaluate the clinical value of the presence and dynamic change of ctDNA to predict the tumor response and prognosis in patients with breast cancer treated with NAC. MATERIALS AND METHODS: Fifty-two patients with early breast cancer who underwent NAC were prospectively enrolled. Serial plasma samples before, during, and after NAC and paired tumor biopsies were harvested and subjected to deep targeted sequencing using a large next-generation sequencing panel that covers 1,021 cancer-related genes. RESULTS: Positive baseline ctDNA was detected in 21 of 44 patients before NAC. Most patients with positive ctDNA had one or more mutations confirmed in paired primary tumor. The ctDNA level after 2 cycles of NAC was predictive of local tumor response after all cycles of NAC (area under the curve, 0.81; 95% CI, 0.61 to 1.00). ctDNA tracking during NAC outperformed imaging in predicting the overall response to NAC. More importantly, positive baseline ctDNA is significantly associated with worse disease-free survival (P = .011) and overall survival (P = .004) in patients with early breast cancer, especially in estrogen receptor-negative patients. CONCLUSION: Our study demonstrated that ctDNA can be used to predict tumor response to NAC and prognosis in early breast cancer, providing information to tailor an individual's therapeutic regimen.

Ictal stereo-electroencephalography onset patterns of mesial temporal lobe epilepsy and their clinical implications.

OBJECTIVE: The differences in mesial temporal epilepsy (MTE) stereo-electroencephalography (SEEG) seizure-onset patterns and their clinical implications remains unclear. METHODS: We analyzed consecutive patients with MTE undergoing non-invasive workup, SEEG evaluation and resective surgery. Cases were classified into either mesial temporal sclerosis (MTS) group or non-MTS group based on magnetic resonance imaging (MRI). Seizure-onset patterns of SEEG were classified to analyze their correlation with surgical outcome and clinical subtypes. RESULTS: Twenty-eight patients were studied. Twenty (71.4%) patients had Engel I outcome. Thirteen patients had one seizure-onset pattern, 15 had two or more patterns. Five patterns of seizure-onset were identified and seizure-onset zones differed significantly across the 5 patterns. No difference was observed in surgical outcome between patients with single or multiple seizure-onset patterns. Periodic spike-onset pattern was associated with MTS (P = 0.003) while burst-onset was associated with non-MTS lesions (P = 0.003). Patients with seizure-onsets outside the resected temporal lobe (multiple onsets) had poorer prognosis (P = 0.0046). CONCLUSION: We identified 5 distinct onset patterns of MTE and correlated two of them with MRI findings. Multiple seizure-onset patterns in MTE may not necessarily suggest poor outcome. Patients with multi-focal seizure-onsets including seizures originating outside the resected temporal lobe have poorer outcome. SIGNIFICANCE: This study identifies distinct onset patterns of MTE and their clinical implications.

Fasudil Promotes α-Synuclein Clearance in an AAV-Mediated α-Synuclein Rat Model of Parkinson's Disease by Autophagy Activation.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, but the disease-modifying therapies focusing on the core pathological changes are still unavailable. Rho-associated protein kinase (ROCK) has been suggested as a promising target for developing neuroprotective therapies in PD. OBJECTIVE: We aimed to explore the promotion of α-synuclein (α-syn) clearance in a rat model. METHODS: In a rat model induced by unilateral injection of adeno-associated virus of serotype 9 (AAV9) expressing A53T α-syn (AAV9-A53T-α-syn) into the right substantia nigra, we aimed to investigate whether Fasudil could promote α-syn clearance and thereby attenuate motor impairments and dopaminergic deficits. RESULTS: In our study, treatment with Fasudil (5 mg/kg rat weight/day) for 8 weeks significantly improved the motor deficits in the Cylinder and Rotarod tests. In the in vivo positron emission tomography imaging with the ligand 18F-dihydrotetrabenazine, Fasudil significantly enhanced the dopaminergic imaging in the injected striatum of the rat model (p < 0.05 vs. vehicle group, p < 0.01 vs. left striatum in Fasudil group). The following mechanistic study confirmed that Fasudil could promote the autophagic clearance of α-syn by Becline 1 and Akt/mTOR pathways. CONCLUSION: Our study suggested that Fasudil, the ROCK2 inhibitor, could attenuate the anatomical and behavioral lesions in the Parkinsonian rat model by autophagy activation. Our results identify Fasudil as a drug with high translational potential as disease-modifying treatment for PD and other synucleinopathies.

Prognostic Value of Modified IHC4 Score in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer.

BACKGROUND: This study aimed to investigate whether an immunohistochemical prognostic model (IHC4 score) can predict the prognosis and the chemotherapy benefit in patients with estrogen receptor-positive (ER+)/human epidermal growth receptor 2-negative (HER2-) metastatic breast cancer (MBC). MATERIALS AND METHODS: We developed a method to calculate the modified IHC4 (mIHC4) scores based on routine pathological reports and compared them with the original IHC4 scores that were much more difficult to calculate. Univariate and multivariate analyses were used to study the prognostic factors of progression-free survival (PFS) and overall survival (OS). The predictive value of mIHC4 score was also investigated. RESULTS: The Sun Yat-sen Memorial Hospital data set included 315 patients with newly diagnosed ER+ MBC with a median follow-up of 25.6 months. Univariate and multivariate analysis showed that higher mIHC4 scores in metastatic lesions, but not the ones in primary tumors, were significantly associated with worse PFS and OS. The prognostic value of mIHC4 scores for PFS was validated using an independent Chinese Society of Clinical Oncology- Breast Cancer (CSCO-BC) data set. More importantly, subpopulation treatment effect pattern plot analysis showed that first-line endocrine therapy achieved better PFS and OS than chemotherapy in low-risk patients with ER+/HER2- MBC, whereas first-line chemotherapy was associated with improved PFS and OS compared with endocrine therapy in high-risk ones. The predictive value of mIHC4 score for PFS in selecting first-line endocrine therapy versus chemotherapy was also confirmed in the CSCO-BC data set. CONCLUSION: mIHC4 scores in metastatic lesions are prognostic for the PFS and OS in patients with ER+ MBC. Low or high mIHC4 score may indicate the survival benefit in choosing first-line endocrine therapy or chemotherapy in patients with ER+/HER2- MBC, respectively. IMPLICATIONS FOR PRACTICE: The modified IHC4 (mIHC4) score is easy to implement and able to predict patients with advanced and/or metastatic breast cancer. In addition, with the help of the mIHC4 score, physicians might be able to recommend chemotherapy or endocrine therapy as the first-line treatment for patients with high and low risk as predicted by the mIHC4 score.

Recent advance in the development of novel, selective and potent FGFR inhibitors.

Mutation or abnormal expression of protein tyrosine kinases (PTKs) is one of the main causes of cancer. Fibroblast growth factor receptors (FGFRs) are a subfamily of tyrosine kinase receptors, which have four subtypes including FGFR1, FGFR2, FGFR3 and FGFR4. Their abnormal expression in cells is considered to be the main cause of tumorigenesis, so inhibiting FGFRs is thought to be important targets for cancer treatment. This article mainly summarizes the recent development of FGFR inhibitors in the past 5 years, and hopes to guide the future research on the design and synthesis of FGFR inhibitors.

Imaging features that distinguish pure ductal carcinoma in situ (DCIS) from DCIS with microinvasion.

Patients with ductal carcinoma in situ with microinvasion (DCISM) have worse cancer-specific survival, disease-free survival and overall survival, and a higher mortality rate compared with patients with ductal carcinoma in situ (DCIS). Distinguishing DCISM from DCIS via preoperative imaging could help to predict the prognosis of patients. The present study compared the sonographic and mammographic features of patients with DCIS and DCISM. A total of 147 women (94 patients with DCIS and 53 patients with DCISM) were retrospectively included. The sonographic lesions were classified as either masses or non-mass abnormalities. The lesions observed on mammography were classified as calcifications only, mass, asymmetry or architectural distortion. Statistical comparisons were performed using the Mann-Whitney U test, χ2 test, Fisher's exact test and multiple logistic regression analysis. Univariate and multivariate analyses showed that the presence of calcifications (P=0.038) and vascularity (P=0.025) on sonography were associated with DCISM. Furthermore, a lager distribution of calcifications was associated with a higher likelihood of DCISM (P=0.002). In conclusion, the presence of calcifications and vascularity on sonography or a lager distribution of calcifications on mammography may suggest DCISM.

Does establishing a preoperative nomogram including ultrasonographic findings help predict the likelihood of malignancy in patients with microcalcifications?

BACKGROUND: Mammography (MG) is highly sensitive for detecting microcalcifications, but has low specificity. This study investigates whether establishing a preoperative nomogram including ultrasonographic findings can help predict the likelihood of malignancy in patients with mammographic microcalcification. METHODS: Between May 2012 and January 2017, 475 patients with suspicious microcalcifications detected on MG underwent ultrasonography (US). The χ2 test was used to screen risk factors among the variables. Then, a multivariate logistic regression analysis was performed to identify independent predictors of malignant microcalcifications. A mammographic nomogram (M nomogram) and mammographic-ultrasonographic nomogram (M-U nomogram) were established based on multivariate logistic regression models. The discriminatory ability and clinical utility of both nomograms were compared by the receiver operating characteristics curve and decision curve analysis. The calibration ability was evaluated using a calibration curve. RESULTS: Among the cases, 68.2% (324/475) were pathologically diagnosed as breast cancer and 31.8% (151/475) were benign lesions. Based on multivariate logistic regression analysis, age, clinical manifestation, morphology and distribution of microcalcifications on MG and lesions associated with microcalcifications on US were confirmed as independent predictors of malignant microcalcifications. In terms of discrimination ability, the C-index of the M-U nomogram was significantly higher than that of the M nomogram (0.917 vs 0.897, p = 0.006). The bias-corrected curve was close to the ideal line in the calibration curve. Decision curve analysis suggested that the M-U nomogram was superior to M nomogram. CONCLUSIONS: Combining mammographic parameters with ultrasonographic findings in a nomogram provided better performance than an M nomogram alone, especially for dense breasts, which suggests the value of ultrasonographic finding for individualized prediction of malignancy in patients with microcalcifications.

Does the radiologist need to rescan the breast lesion to validate the final BI-RADS US assessment made on the static images in the diagnostic setting?

Purpose: To assess whether radiologist needs to rescan the breast lesion to validate the final American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) ultrasonography (US) assessment made on the static images in the diagnostic setting. Patients and methods: Image data on 1,070 patients with 1,070 category 3-5 breast lesions with a pathological diagnosis scanned between January and June 2016 were included. Both real-time and static image assessments were acquired for each lesion. The diagnostic performance was evaluated by receiver operating characteristic (ROC) curves. The positive predictive values (PPVs) of each category in the two groups were calculated according to the ACR BI-RADS manual and compared. Kappas were determined for agreement on two assessment approaches. Results: The sensitivity, specificity, PPV, and negative predictive value for real-time US were 98.9%, 58.2%, 44.8% and 99.4%, and for static images were 98.9%, 57.1%, 44.1% and 99.3%, respectively. The performance of the two groups was not significantly different (areas under ROCs: 0.786 vs 0.780, P=0.566) if the final assessment was only dichotomized as negative (category 3) and positive (categories 4 and 5). All PPVs of each category for each assessment were within the reference range provided by the ACR in 2013 except subcategory 4B (reference range: >10% and ≤50%) of static image evaluation, which was also significantly higher than that of real-time assessment (54.8% vs 40.7%, P=0.037). The overall agreement of the two approaches was moderate (κ=0.43-0.56 according to different detailed assessment). Conclusion: Both static image and real-time assessment had similar diagnostic performance if only the treatment recommendations were considered, that is, follow-up or biopsy. However, as for subcategory 4B lesions without obviously benign or malignant US features, real-time scanning by the interpreter is recommended to obtain a more accurate BI-RADS assessment after assessing static images.

Modifiable risk factors for cognitive impairment in Parkinson's disease: A systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Cognitive impairment is a common and devastating manifestation in Parkinson's disease (PD). We aimed to identify modifiable risk factors for PD with cognitive impairment. METHODS: We systematically searched PubMed and the Cochrane Library from June 1937 to September 2018 and included prospective cohort studies with random-effects model used to combine estimates. Primary analyses for all types of cognitive impairments and subgroup analyses for separate outcomes were conducted. RESULTS: A total of 31,298 articles were identified, of which 32 articles with 18 factors met the inclusion criteria for meta-analysis. In the primary analysis, 9 modifiable risk factors were found to increase the risk of PD with cognitive impairment, including postural-instability-gait disorder (relative risk = 3.76, 95% confidence interval = 1.36-10.40), hallucinations (relative risk = 3.09, 95% confidence interval = 1.61-5.93), orthostatic hypotension (relative risk = 2.98, 95% confidence interval = 1.41-6.28), cerebrovascular disease (relative risk = 1.52, 95% confidence interval = 1.01-2.28), diabetes mellitus (relative risk = 1.47, 95% confidence interval = 1.13-1.92), obesity (relative risk = 1.38, 95% confidence interval = 1.15-1.65), cardiac disease (relative risk = 1.35, 95% confidence interval = 1.17-1.56), alcohol consumption (relative risk = 1.32, 95% confidence interval = 1.15-1.52), and smoking (relative risk = 1.31, 95% confidence interval = 1.14-1.50). In the subgroup analysis, postural-instability-gait disorder subtype, orthostatic hypotension and hallucinations may increase the risk of dementia in PD. A total of 37 articles were included in the systematic review, in which 9 risk factors and 1 protective factor were additionally associated in single studies with the risk of PD with cognitive impairment, and 5 factors were associated with specific cognition domains. CONCLUSIONS: Effective interventions in the management of PD symptoms, comorbidities, and lifestyles may be promising to reduce PD with cognitive impairment risk. © 2019 International Parkinson and Movement Disorder Society.

Predictors to quality of life improvements after subthalamic stimulation in Parkinson's disease.

INTRODUCTION: Subthalamic deep brain stimulation (STN DBS) has been reported to improve the quality of life (QoL) related to Parkinson's disease (PD). However, not all subjects are satisfied with the postsurgical QoL outcome. We aimed to detect the related factors and possible predictors to QoL improvement for those PD patients one year after STN DBS. MATERIALS AND METHODS: A total of 45 PD patients with bilateral STN DBS surgery were included and followed up for 1 year. The Reliable Change Index (RCI) was adapted to determine the individual postsurgical QoL outcome. The changes of QoL were correlated with baseline parameters and the changes of progression parameters using Pearson's correlation. The exploratory stepwise regressions were adopted to detect the extents of baseline variables and progression parameters. The predictors to QoL outcome were detected using the logistic regression analysis. RESULTS: A total of 51.1% of the patients reported a better QoL, 40.0% of patients reported an unchanged QoL, while 8.9% of patients reported a worsening of QoL. The subdomains of mobility, activity of daily living, cognition, and bodily discomfort improved significantly after the surgery. The presurgical factors including QoL, dopaminergic medication burden, disease stages, depression scores, and postsurgical reductions in depression and nonmotor scores were found to correlate with QoL changes. Furthermore, the greater presurgical QoL burden, lesser dopaminergic medication exposure, and earlier disease stages were predictors to QoL improvements. CONCLUSION: The clinicians should carefully evaluate the nonmotor symptoms and life quality in those patients at relatively earlier stages and with lower medicine dosage to get more successful DBS outcomes.

Design, synthesis and structure-activity relationship of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure as multi-target inhibitors against receptor tyrosine kinase.

Inspired by that the multi-target inhibitors against receptor tyrosine kinases (RTKs) have significantly improved the effect of clinical treatment for cancer, and based on the chemical structure of Linifanib (ABT-869, Abbott), two series of diaryl-ureas with novel isoxazol[3,4-b]pyridine-3-amino-structure were designed and synthesized as multi-target inhibitors against RTKs. The preliminary biological evaluation showed that several compounds exhibited comparable potency with Linifanib. Compound S21 was identified as the most potent inhibitor against Fms-like tyrosine kinase 3 (FLT-3), kinase insert domain containing receptor (KDR) and platelet-derived growth factor receptor ß (PDGFR-ß) with its IC50 values were 4 nM, 3 nM and 8 nM respectively, it also showed potent inhibitory activities against several cancer cells.