Diffusion Tensor Imaging for Characterizing Changes in Triple-Negative Breast Cancer During Neoadjuvant Systemic Therapy.

BACKGROUND: Assessment of treatment response in triple-negative breast cancer (TNBC) may guide individualized care for improved patient outcomes. Diffusion tensor imaging (DTI) measures tissue anisotropy and could be useful for characterizing changes in the tumors and adjacent fibroglandular tissue (FGT) of TNBC patients undergoing neoadjuvant systemic treatment (NAST). PURPOSE: To evaluate the potential of DTI parameters for prediction of treatment response in TNBC patients undergoing NAST. STUDY TYPE: Prospective. POPULATION: Eighty-six women (average age: 51 ± 11 years) with biopsy-proven clinical stage I-III TNBC who underwent NAST followed by definitive surgery. 47% of patients (40/86) had pathologic complete response (pCR). FIELD STRENGTH/SEQUENCE: 3.0 T/reduced field of view single-shot echo-planar DTI sequence. ASSESSMENT: Three MRI scans were acquired longitudinally (pre-treatment, after 2 cycles of NAST, and after 4 cycles of NAST). Eleven histogram features were extracted from DTI parameter maps of tumors, a peritumoral region (PTR), and FGT in the ipsilateral breast. DTI parameters included apparent diffusion coefficients and relative diffusion anisotropies. pCR status was determined at surgery. STATISTICAL TESTS: Longitudinal changes of DTI features were tested for discrimination of pCR using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC). A P value <0.05 was considered statistically significant. RESULTS: 47% of patients (40/86) had pCR. DTI parameters assessed after 2 and 4 cycles of NAST were significantly different between pCR and non-pCR patients when compared between tumors, PTRs, and FGTs. The median surface/average anisotropy of the PTR, measured after 2 and 4 cycles of NAST, increased in pCR patients and decreased in non-pCR patients (AUC: 0.78; 0.027 ± 0.043 vs. -0.017 ± 0.042 mm2 /s). DATA CONCLUSION: Quantitative DTI features from breast tumors and the peritumoral tissue may be useful for predicting the response to NAST in TNBC. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

[Advances in the treatment of anti-HER-2 antibody drug conjugates in pan-tumor with low HER-2 expression].

Antibody-drug conjugates (ADCs) are drugs that combine monoclonal antibody drugs targeting specific antigens and small molecule cytotoxic drugs through linker molecules. ADCs combine the advantages of high specificity targeting and potent killing effects, achieving precise and efficient targeting of cancer cells. Nowadays, ADCs are one of the hotspots in cancer drug development. Human epidermal growth factor receptor 2 (HER-2) is a known oncogene that can drive the occurrence and development of various types of tumors. HER-2 is also an important tumor target for ADCs approved for solid tumors. Anti-HER-2 ADCs can not only be used to treat HER-2-positive tumors but also effectively target HER-2-low tumors. The emergence of ADCs has broken the traditional classification of HER-2 in tumors, bringing significant treatment breakthroughs for HER-2-low tumors. Anti-HER-2 ADCs are widely used in the treatment of solid tumors and have substantial evidence for HER-2-low tumors. This article presents the progress of various anti-HER-2 ADCs in HER-2-low tumors including breast cancer, gastrointestinal malignancies, urothelial carcinoma, lung cancer. And this article summarizes the current status of preclinical studies, clinical studies, and safety of anti-HER-2 ADCs in order to provide reference for the clinical use of HER-2-low tumors.

Challenging Contrast-Enhanced Mammography-Guided Biopsies: Practical Approach Using Real-Time Multimodality Imaging and a Proposed Procedural Algorithm.

Contrast-enhanced mammography (CEM) is an emerging functional breast imaging technique that entails the acquisition of dual-energy digital mammographic images after IV administration of iodine-based contrast material. CEM-guided biopsy technology was introduced in 2019 and approved by the U.S. FDA in 2020. This technology's availability enables direct sampling of suspicious enhancement seen only on or predominantly on recombined CEM images and addresses a major obstacle to the clinical implementation of CEM technology. The literature describing clinical indications and procedural techniques of CEM-guided biopsy is scarce. This article describes our initial experience in performing challenging CEM-guided biopsies and proposes a step-by-step procedural algorithm designed to proactively address anticipated technical difficulties and thereby increase the likelihood of achieving successful targeting.

A nomogram and risk classification system for predicting cancer-specific survival in tall cell variant of papillary thyroid cancer: a SEER-based study.

BACKGROUND: Tall cell variant (TCV) of papillary thyroid cancer (PTC) is the most common aggressive subtype of PTC. The factors that affect survival of patients with TCV remain unclear. We aimed to develop a model to predict the cancer-specific survival (CSS). METHODS: A total of 1615 patients diagnosed with TCV between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database and randomized into training and validation cohorts (7:3). A predictive nomogram for predicting CSS was constructed by Cox proportional hazards regression and validated by concordance index (C-index), calibration curve, and decision curve analyses (DCA). A risk classification system was built based on the total nomogram scores of each case. RESULTS: A nomogram was constructed including five independent prognostic factors (age, tumor size, T stage, M stage, and extent of surgery) associated with CSS in TCV patients. Various validations proved that the nomogram model had good consistency and discrimination for TCV prognosis. The risk classification system could perfectly classify TCV patients into three risk groups with significantly different CSS. Compared with traditional AJCC TNM staging system, the nomogram could better predict CSS in TCV patients. CONCLUSIONS: A nomogram and corresponding risk classification system were developed for predicting CSS in TCV patients. The model has excellent performance and can be used to help clinicians make accurate prognostic assessment and individualized treatment.

Mesobiliverdin IXα-enriched microalgae feed additive eliminates reliance on antibiotic tylosin to promote intestinal health of weaning piglets.

Weaning is a critical period in raising pigs. Novel animal feed additives that promote gut health and regulate immune function of piglets without antibiotics are needed. In this study, we aimed to test the ability of mesobiliverdin IXα-enriched microalgae (MBV IXα-enriched microalgae) to eliminate reliance on antibiotics to promote intestinal health in piglets. Eighty 28-day-old weaned piglets were randomly allocated to four groups each with four replicate pens and five piglets per pen. The dietary treatments were a basal diet as control (NC), basal diet plus 0.05% tylosin (PC), basal diet plus 0.1% or 0.5% MBV IXα-enriched microalgae as low (MBV-SP1) or high (MBV-SP2) dose respectively. All treated animals showed no significant differences in live weight, average daily gain and feed efficiency compared to control animals. Histological examination showed that MBV-SP1 and particularly MBV-SP2 increased the ratio of villus height to crypt depth in the jejunum and ileum compared to NC (p < 0.05). Similarly, tylosin treatment also increased villi lengths and the ratio of villus height to crypt depth in the jejunum and ileum compared to the NC (p < 0.05). MBV-SP1 and particularly MBV-SP2 reduced the levels of inflammatory cytokines interleukin-6 and tumour necrosis factor-alpha in the small intestine. MBV-SP2 and tylosin similarly reduced the lipid peroxidation marker (TBARS value) in the duodenum and ileum. In conclusion, feed supplementation with MBV IXα-enriched microalgae improved gut health by villus height and production of immunomodulators that correlated with down-regulated secretion of inflammatory cytokines.

[Analysis of suspected occupational diseases cases and subsequent diagnosis follow-up investigation in Hubei Province from 2020 to 2021].

Objective: To understand the epidemiological characteristics of suspected occupational diseases cases, and to track the subsequent diagnosis of suspected cases in Hubei Province from 2020 to 2021, and to provide theoretical basis for the supervision of suspected occupational diseases. Methods: In April 2022, the data of suspected occupational diseases cases and occupational diseases in Hubei Province from 2020 to 2021 were collected by the Occupational Diseases and Health Risk Factors Information Surveillance System. The distribution and diagnosis of suspected occupational diseases cases were analyzed. We investigated undiagnosed suspected occupational diseases by telephone. Results: From 2020 to 2021, a total of 1872 cases of suspected occupational diseases in 6 categories and 18 species were reported in Hubei Province. The top three suspected occupational diseases were suspected occupational noise deafness (36.75%, 688/1872), suspected coal worker's pneumoconiosis (33.07%, 619/1872) and suspected silicosis (20.99%, 393/1872). The diagnosis rate of suspected occupational diseases was 33.60% (629/1872). The rate of confirmed diagnosis was 63.59% (400/629). The diagnosis rate (26.86%, 456/1698) and rate of confirmed diagnosis (55.48%, 253/456) of suspected occupational diseases detected by occupational health examination were the lowest. The diagnosis rate of suspected occupational diseases detected by comprehensive medical institutions and private medical institutions were lower than disease prevention and control institutions and occupational disease prevention center (P<0.05). The main reasons for not entering the diagnostic procedure included that workers were not informed that they were diagnosed as suspected occupational diseases (31.55%, 124/393), workers were unwilling to apply for occupational disease diagnosis (18.56%, 73/393), and some workers planned to apply for diagnosis but had not yet applied (10.69%, 42/393) . Conclusion: Occupational noise deafness, coal worker's pneumoconiosis and silicosis are the main diseases of suspected occupational diseases in Hubei Province. In order to increase the diagnosis rate and confirmed diagnosis rate of suspected occupational diseases, it is suggested to strengthen management and supervision from the aspects of case management, information warning and worker notification.

Eliminating breast surgery for invasive breast cancer in exceptional responders to neoadjuvant systemic therapy: a multicentre, single-arm, phase 2 trial.

BACKGROUND: Neoadjuvant systemic therapy (NST) for triple-negative breast cancer and HER2-positive breast cancer yields a pathological complete response in approximately 60% of patients. A pathological complete response to NST predicts an excellent prognosis and can be accurately determined by percutaneous image-guided vacuum-assisted core biopsy (VACB). We evaluated radiotherapy alone, without breast surgery, in patients with early-stage triple-negative breast cancer or HER2-positive breast cancer treated with NST who had an image-guided VACB-determined pathological complete response. METHODS: This multicentre, single-arm, phase 2 trial was done in seven centres in the USA. Women aged 40 years or older who were not pregnant with unicentric cT1-2N0-1M0 triple-negative breast cancer or HER2-positive breast cancer and a residual breast lesion less than 2 cm on imaging after clinically standard NST were eligible for inclusion. Patients had one biopsy (minimum of 12 cores) obtained by 9G image-guided VACB of the tumour bed. If no invasive or in-situ disease was identified, breast surgery was omitted, and patients underwent standard whole-breast radiotherapy (40 Gy in 15 fractions or 50 Gy in 25 fractions) plus a boost (14 Gy in seven fractions). The primary outcome was the biopsy-confirmed ipsilateral breast tumour recurrence rate determined using the Kaplan-Meier method assessed in the per-protocol population. Safety was assessed in all patients who received VACB. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02945579. FINDINGS: Between March 6, 2017, and Nov 9, 2021, 58 patients consented to participate; however, four (7%) did not meet final inclusion criteria and four (7%) withdrew consent. 50 patients were enrolled and underwent VACB following NST. The median age of the enrolled patients was 62 years (IQR 55-77); 21 (42%) patients had triple-negative breast cancer and 29 (58%) had HER2-positive breast cancer. VACB identified a pathological complete response in 31 patients (62% [95% CI 47·2-75·4). At a median follow-up of 26·4 months (IQR 15·2-39·6), no ipsilateral breast tumour recurrences occurred in these 31 patients. No serious biopsy-related adverse events or treatment-related deaths occurred. INTERPRETATION: Eliminating breast surgery in highly selected patients with an image-guided VACB-determined pathological complete response following NST is feasible with promising early results; however, additional prospective clinical trials evaluating this approach are needed. FUNDING: US National Cancer Institute (National Institutes of Health).

Mesobiliverdin IXα ameliorates osteoporosis via promoting osteogenic differentiation of mesenchymal stem cells.

Heme oxygenase-1 (HO-1) expression promotes osteogenesis, but the mechanisms remain unclear and therapeutic strategies using it to target bone disorders such as osteoporosis have not progressed. Mesobiliverdin IXα is a naturally occurring bilin analog of HO-1 catalytic product biliverdin IXα. Inclusion of mesobiliverdin IXα in the feed diet of ovariectomized osteoporotic mice was observed to increase femur bone volume, trabecular thickness and osteogenesis serum markers osteoprotegrin and osteocalcin and to decrease bone resorption serum markers cross-linked N-teleopeptide and tartrate-resistant acid phosphatase 5b. Moreover, in vitro exposure of human bone marrow mesenchymal stem cells to mesobiliverdin IXα enhanced osteogenic differentiation efficiency by two-fold over non-exposed controls. Our results imply that mesobiliverdin IXα promotes osteogenesis in ways that reflect the potential therapeutic effects of induced HO-1 expression in alleviating osteoporosis.

Quantitative Apparent Diffusion Coefficients From Peritumoral Regions as Early Predictors of Response to Neoadjuvant Systemic Therapy in Triple-Negative Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC. PURPOSE: To determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC. STUDY TYPE: Prospective. POPULATION/SUBJECTS: A total of 108 patients with biopsy-proven TNBC who underwent NAST and definitive surgery during 2015-2020. FIELD STRENGTH/SEQUENCE: A 3.0 T/rFOV single-shot diffusion-weighted echo-planar imaging sequence (DWI). ASSESSMENT: Three scans were acquired longitudinally (pretreatment, after two cycles of NAST, and after four cycles of NAST). For each scan, 11 ADC histogram features (minimum, maximum, mean, median, standard deviation, kurtosis, skewness and 10th, 25th, 75th, and 90th percentiles) were extracted from tumors and from PTRs of 5 mm, 10 mm, 15 mm, and 20 mm in thickness with inclusion and exclusion of fat-dominant pixels. STATISTICAL TESTS: ADC features were tested for prediction of pCR, both individually using Mann-Whitney U test and area under the receiver operating characteristic curve (AUC), and in combination in multivariable models with k-fold cross-validation. A P value < 0.05 was considered statistically significant. RESULTS: Fifty-one patients (47%) had pCR. Maximum ADC from PTR, measured after two and four cycles of NAST, was significantly higher in pCR patients (2.8 ± 0.69 vs 3.5 ± 0.94 mm2 /sec). The top-performing feature for prediction of pCR was the maximum ADC from the 5-mm fat-inclusive PTR after cycle 4 of NAST (AUC: 0.74; 95% confidence interval: 0.64, 0.84). Multivariable models of ADC features performed similarly for fat-inclusive and fat-exclusive PTRs, with AUCs ranging from 0.68 to 0.72 for the cycle 2 and cycle 4 scans. DATA CONCLUSION: Quantitative ADC features from PTRs may serve as early predictors of the response to NAST in TNBC. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

[Clinical efficacy of transjugular intrahepatic portosystemic shunt for gastrointestinal hemorrhage in patients with idiopathic noncirrhotic portal hypertension].

Objective: To explore the medium-long term efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for gastrointestinal hemorrhage in patients with idiopathic non-cirrhotic portal hypertension (INCPH). Methods: From March 2013 to July 2018, clinical data of 13 INCPH patients, including 5 males, 8 females,with gastrointestinal hemorrhage were retrospectively analyzed, who were diagnosed at the First Affiliated Hospital of Zhengzhou University, Anyang Fifth People' s Hospital and Yuncheng Central Hospital. All patients received TIPS treatment. The general information, postoperative survival rate, the incidence of rebleeding, shunt dysfunction rate, and incidence of hepatic encephalopathy were analyzed. Results: All 13 patients with INCPH completed TIPS successfully with an average age of 45±8 (33 to 59) years. The hepatic venous pressure gradient (HVPG) decreased from 20.0-26.0 (22.6±1.9) mmHg before procedure to 8.0-14.0 (9.4±3.2) mmHg after. The median follow-up time was 44±7 (31 to 53) months. One patient died of liver failure 27 months after TIPS. Hepatic encephalopathy occurred cumulatively in 1 case (1/13), 1 case (1/13) and 1 case (1/13) in 12, 24 and 36 months after TIPS. Stent restenosis occurred cumulatively in 2 cases (2/13), 3 cases (3/13) and 3 cases (3/13) in 12, 24 and 36 months after TIPS. Portal vein thrombosis occurred cumulatively in 2 cases (2/13), and no primary liver cancer developed. Conclusions: TIPS is safe and effective in the treatment of INCPH with gastrointestinal bleeding with favorable medium-long term outcome.

[Clinical analysis of pulmonary nocardiosis associated with bronchiectasis].

Objective: To better understand the clinical characteristics of pulmonary nocardiosis associated with bronchiectasis. Methods: Patients diagnosed as bronchiectasis complicated with pulmonary nocardiosis in 9 tertiary general hospitals in China were enrolled from March 2016 to March 2020, with the record of general data, imaging performance and pathogen. The literature was reviewed. Results: Totally 17 patients were included. There were 12 females and 5 males. The ages ranged from 45 to 79 years, with an average of (63±9) years. There were 15 nonsmokers and 2 smokers, all of whom with chronic course. The clinical manifestations were mostly cough, expectoration, hemoptysis, fever, and dyspnea. The imaging manifestation was bronchiectasis in both lungs, with the most common involvement in the left lower lung, right middle lobe and left lingual lobe. Sputum cultures were positive in 10 cases, bronchoalveolar lavage fluid (BALF) cultures were positive in 6 cases, and next generation gene sequencings were positive in 4 cases, including 2 cases of Nocardia gelsenkii, 2 cases of Nocardia abscess, 2 cases of Nocardia stellate, 1 case of Nocardia mexicana, 1 case of Nocardia otitis caviae, and 9 cases of undetermined Nocardia. There were 3 cases of Klebsiella pneumoniae, 2 cases of Pseudomonas aeruginosa and 2 cases of Aspergillus. The symptoms and imaging of all patients were improved after anti Nocardia therapy. Conclusions: Bronchiectasis combined with nocardiosis is more common in middle-aged and elderly women without smoking, which is similar to the clinical manifestations of Lady Windermere syndrome. Bronchiectasis often involves the left lower lobe, right middle lobe and left lingual lobe. Nocardia infection might further precipitate the initiation and progression of bronchiectasis.

RE-EVALUATION OF SYMPOVENTURIACEAE.

Abstract Sympoventuriaceae (Venturiales, Dothideomycetes) comprises genera including saprophytes, endophytes, plant pathogens, as well as important animal or human opportunistic pathogens with diverse ecologies and wide geographical distributions. Although the taxonomy of Sympoventuriaceae has been well studied, generic boundaries within the family remain poorly resolved due to the lack of type materials and molecular data. To address this issue and establish a more stable and reliable classification system in Sympoventuriaceae, we performed multi-locus phylogenetic analyses using sequence data of seven genes (SSU, ITS, LSU, act1, tub2, tef1 and rpb2) with increased taxon sampling and morphological analysis. The molecular data combined with detailed morphological studies of 143 taxa resolved 22 genera within the family, including one new genus, eight new species, five new combinations and one new name. Finally, we further investigated the evolutionary history of Sympoventuriaceae by reconstructing patterns of lifestyle diversification, indicating the ancestral state to be saprophytic, with transitions to endophytic, animal or human opportunistic and plant pathogens. Citation: Wei TP, Zhang H, Zeng XY, et al. 2022. Re-evaluation of Sympoventuriaceae. Persoonia 48: 219-260. https://doi.org/10.3767/persoonia.2022.48.07.. Effectively published online: 17 June 2022 [Received: 2 February 2022; Accepted: 27 April 2022].

[Epidemiological characteristics and trend of new cases of occupational pneumoconiosis in Hubei Province from 2011 to 2020].

Objective: The epidemiological characteristics and trend of occupational pneumoconiosis in Hubei Province from 2011 to 2020 were analyzed to provide a theoretical basis for the development of prevention and control strategies for occupational pneumoconiosis. Methods: In March 2021, the data of newly occupational pneumoconiosis in Hubei Province from 2011 to 2020 were collected by the Occupational Diseases and Health Risk Factors Information Surveillance System. Descriptive statistics were adopted to analyze basic situation, region, industry, type of disease, year of diagnosis, age of onset and dust exposureduration of the cases. Results: From 2011 to 2020, a total of 7203 new cases of occupational pneumoconiosis were reported in Hubei Province, including 7125 (98.92%) men and 78 (1.08%) women. The average age of onset was (54.03±10.12) years old. The average duration of dust exposure was (13.80±9.56) years. The mainly types of pneumoconiosis were coal worker's pneumoconiosis (3593 cases, 49.88%) and silicosis (3301 cases, 45.83%). The cases included 4814 cases (66.83%) of stage Ⅰ pneumoconiosis, 1270 cases (17.63%) of stage Ⅱ and 1119 cases (15.54%) of stage Ⅲ. New cases mainly distributed in Yichang City (1586 cases, 22.02%), Shiyan City (1257 cases, 17.45%), Enshi Tujia and Miao Autonomous Prefecture (1050 cases, 14.58%) and Huangshi City (1009 cases, 14.01%), and occurred most frequently in coal mining and washing industry (3743 cases, 51.96%) and nonmetallic mining industry (582 cases, 8.08%). Pneumoconiosis patients of stage Ⅲ were mainly distributed in small enterprises (401 cases, 50.25%) and domestic enterprises (796 cases, 99.75%) . Conclusion: Coal worker's pneumoconiosis and silicosis accounted for the vast majority pneumoconiosis in Hubei Province. The new cases show obvious regions, industries and type of disease distribution. We should strengthen occupational health supervision in small and domestic enterprises.

Early ultrasound evaluation identifies excellent responders to neoadjuvant systemic therapy among patients with triple-negative breast cancer.

BACKGROUND: Heterogeneity exists in the response of triple-negative breast cancer (TNBC) to standard anthracycline (AC)/taxane-based neoadjuvant systemic therapy (NAST), with 40% to 50% of patients having a pathologic complete response (pCR) to therapy. Early assessment of the imaging response during NAST may identify a subset of TNBCs that are likely to have a pCR upon completion of treatment. The authors aimed to evaluate the performance of early ultrasound (US) after 2 cycles of neoadjuvant NAST in identifying excellent responders to NAST among patients with TNBC. METHODS: Two hundred fifteen patients with TNBC were enrolled in the ongoing ARTEMIS (A Robust TNBC Evaluation Framework to Improve Survival) clinical trial. The patients were divided into a discovery cohort (n = 107) and a validation cohort (n = 108). A receiver operating characteristic analysis with 95% confidence intervals (CIs) and a multivariate logistic regression analysis were performed to model the probability of a pCR on the basis of the tumor volume reduction (TVR) percentage by US from the baseline to after 2 cycles of AC. RESULTS: Overall, 39.3% of the patients (42 of 107) achieved a pCR. A positive predictive value (PPV) analysis identified a cutoff point of 80% TVR after 2 cycles; the pCR rate was 77% (17 of 22) in patients with a TVR ≥ 80%, and the area under the curve (AUC) was 0.84 (95% CI, 0.77-0.92; P < .0001). In the validation cohort, the pCR rate was 44%. The PPV for pCR with a TVR ≥ 80% after 2 cycles was 76% (95% CI, 55%-91%), and the AUC was 0.79 (95% CI, 0.70-0.87; P < .0001). CONCLUSIONS: The TVR percentage by US evaluation after 2 cycles of NAST may be a cost-effective early imaging biomarker for a pCR to AC/taxane-based NAST.

Tumor necrosis by pretreatment breast MRI: association with neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC).

PURPOSE: To determine if tumor necrosis by pretreatment breast MRI and its quantitative imaging characteristics are associated with response to NAST in TNBC. METHODS: This retrospective study included 85 TNBC patients (mean age 51.8 ± 13 years) with MRI before NAST and definitive surgery during 2010-2018. Each MRI included T2-weighted, diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging. For each index carcinoma, total tumor volume including necrosis (TTV), excluding necrosis (TV), and the necrosis-only volume (NV) were segmented on early-phase DCE subtractions and DWI images. NV and %NV were calculated. Percent enhancement on early and late phases of DCE and apparent diffusion coefficient were extracted from TTV, TV, and NV. Association between necrosis with pathological complete response (pCR) was assessed using odds ratio (OR). Multivariable analysis was used to evaluate the prognostic value of necrosis with T stage and nodal status at staging. Mann-Whitney U tests and area under the curve (AUC) were used to assess performance of imaging metrics for discriminating pCR vs non-pCR. RESULTS: Of 39 patients (46%) with necrosis, 17 had pCR and 22 did not. Necrosis was not associated with pCR (OR, 0.995; 95% confidence interval [CI] 0.4-2.3) and was not an independent prognostic factor when combined with T stage and nodal status at staging (P = 0.46). None of the imaging metrics differed significantly between pCR and non-pCR in patients with necrosis (AUC < 0.6 and P > 0.40). CONCLUSION: No significant association was found between necrosis by pretreatment MRI or the quantitative imaging characteristics of tumor necrosis and response to NAST in TNBC.

Mean Apparent Diffusion Coefficient Is a Sufficient Conventional Diffusion-weighted MRI Metric to Improve Breast MRI Diagnostic Performance: Results from the ECOG-ACRIN Cancer Research Group A6702 Diffusion Imaging Trial.

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Prospective Registry Trial Assessing the Use of Magnetic Seeds to Locate Clipped Nodes After Neoadjuvant Chemotherapy for Breast Cancer Patients.

BACKGROUND: Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. METHODS: This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. RESULTS: Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. CONCLUSIONS: Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds.

Functional Tumor Volume by Fast Dynamic Contrast-Enhanced MRI for Predicting Neoadjuvant Systemic Therapy Response in Triple-Negative Breast Cancer.

BACKGROUND: Dynamic contrast-enhanced (DCE) MRI is useful for diagnosis and assessment of treatment response in breast cancer. Fast DCE MRI offers a higher sampling rate of contrast enhancement curves in comparison to conventional DCE MRI, potentially characterizing tumor perfusion kinetics more accurately for measurement of functional tumor volume (FTV) as a predictor of treatment response. PURPOSE: To investigate FTV by fast DCE MRI as a predictor of neoadjuvant systemic therapy (NAST) response in triple-negative breast cancer (TNBC). STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty patients with biopsy-confirmed TNBC between December 2016 and September 2020. FIELD STRENGTH/SEQUENCE: A 3.0 T/3D fast spoiled gradient echo-based DCE MRI ASSESSMENT: Patients underwent MRI at baseline and after four cycles (C4) of NAST, followed by definitive surgery. DCE subtraction images were analyzed in consensus by two breast radiologists with 5 (A.H.A.) and 2 (H.S.M.) years of experience. Tumor volumes (TV) were measured on early and late subtractions. Tumors were segmented on 1 and 2.5-minute early phases subtractions and FTV was determined using optimized signal enhancement thresholds. Interpolated enhancement curves from segmented voxels were used to determine optimal early phase timing. STATISTICAL TESTS: Tumor volumes were compared between patients who had a pathologic complete response (pCR) and those who did not using the area under the receiver operating curve (AUC) and Mann-Whitney U test. RESULTS: About 26 of 60 patients (43%) had pCR. FTV at 1 minute after injection at C4 provided the best discrimination between pCR and non-pCR, with AUC (95% confidence interval [CI]) = 0.85 (0.74,0.95) (P < 0.05). The 1-minute timing was optimal for FTV measurements at C4 and for the change between C4 and baseline. TV from the early phase at C4 also yielded a good AUC (95%CI) of 0.82 (0.71,0.93) (P < 0.05). DATA CONCLUSION: FTV and TV measured at 1 minute after injection can predict response to NAST in TNBC. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 4.

Survival of Clostridioides difficile in finished dairy compost under controlled conditions.

AIM: The survival of Clostridioides difficile (previously Clostridium difficile) vegetative cells and endospores was compared at different levels of indigenous microflora using autoclaved and unautoclaved dairy composts with different moisture contents (MCs). METHODS AND RESULTS: Both types of composts adjusted to 20, 30 and 40% MCs were inoculated with a suspension of C. difficile that contained both vegetative cells (c. 5-6 log CFU per gram) and endospores (c. 5·0 CFU per gram), and then stored aerobically inside a humidity-controlled chamber at room temperature 22·5 ± 0·8°C for 1 year. The level of indigenous microflora was very stable during the storage after day 7 in both types of compost. The greatest reductions of C. difficile vegetative cell counts occurred during the first 24 h of storage in autoclaved and unautoclaved composts, which had 4·7 and 5·5 log CFU per gram with 20% MC, 1·8 and 2·1 log CFU per gram with 30% MC, and 2·3 and 1·3 log CFU per gram with 40% MC, respectively. Both MC and the duration of storage have significant (P < 0·05) effects on the survival of vegetative cells for first 120 days of storage. The slow inactivation of C. difficile vegetative cells at higher MCs during aerobic storage was confirmed by exponentially decaying modelling data during the early stage of aerobic exposure. The reduction of endospore counts (<1·0 log CFU per gram) during the storage for both types of compost at all MCs was not significant (P > 0·05) except for the autoclaved compost with 30% MC. CONCLUSION: The highly resistant C. difficile endospores to the unfavourable environmental conditions survived for more than a year while vegetative cells died off exponentially upon the initial aerobic exposure. SIGNIFICANCE AND IMPACT OF THE STUDY: The long-term survival of C. difficile endospores in contaminated compost may transmit the pathogen to fresh produce, animals or water in pre-harvest conditions.

[Analysis of the clinical effects and outcome of patients with double-hit high-risk multiple myeloma].

Objective: To compare the clinical features, clinical efficacy, and prognosis of patients with double-hit and non-double-hit high-risk multiple myeloma (MM) and explored the clinical significance of high-risk cell karyotype in MM development. Methods: The clinical data of 73 high-risk MM patients admitted to the Department of Hematology of Fujian Provincial Hospital from January 2011 to February 2019 were retrospectively analyzed. Interphase fluorescence in situ hybridization was used to detect their karyotypes. Based on mSMART 3.0 risk stratification, we divided the patients into a double-hit group (28 cases) and a non-double-hit group (45 cases). Results: Fifteen patients in the double-hit group and 26 in the non-double-hit group received bortezomib-based chemotherapy. The median progression-free survival (PFS) in the double-hit and the non-double-hit groups was 8.0 months and 22.0 months, and the median overall survival (OS) was 10.0 months and not reached, respectively. Ten patients in the double-hit group and 12 in the non-double-hit group received bortezomib combined with lenalidomide (RVD) chemotherapy. The median PFS in the double-hit group and the non-double-hit group was 12.0 months and 24.0 months, and the median OS was 14.0 months and not reached, correspondingly. Both the PFS and OS of the double-hit group were significantly shorter than those of the non-double-hit group (P<0.05). Univariate analysis results indicated that cytogenetic abnormalities, revised-international staging system (R-ISS), ß2 microglobulin, and calcium had significant effects on PFS in high-risk MM patients (P<0.05). The cytogenetic abnormalities, R-ISS, and ß2 microglobulin were associated with OS in high-risk MM patients (P=0.001). Multivariate Cox regression analysis showed that the cytogenetic grouping was an independent prognostic factor for OS and PFS in high-risk MM patients. The risk of disease progression was 3.160 times (95% CI: 1.364-7.318) and the risk of death was 2.966 times higher (95%CI: 1.205-7.306) in the double-hit group than those in the non-double-hit group. Calcium was an independent risk factor for PFS in the high-risk MM patients. Notably, the risk of disease progression in patients with calcium levels≥ 2.75 mmol/L was 2.667 times higher than that in patients with calcium<2.75 mmol/L (95% CI: 1.209-5.883). Conclusions: Double-hit patients are a highly specific group with worse high-risk MM prognosis. In such patients, the relapse is more common, the disease progression is faster, and the survival time is shorter than those in the non-double-hit patients.