The Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Antibiotic and Anticancer Agent Marinomycin.

With the rise in antimicrobial resistance, there is an urgent need for new classes of antibiotic with which to treat infectious disease. Marinomycin, a polyene antibiotic from a marine microbe, has been shown capable of killing methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF), as well as having promising activity against melanoma. An attractive solution to the photoprotection of this antibiotic has been demonstrated. Here, we report the identification and analysis of the marinomycin biosynthetic gene cluster (BGC), and the biosynthetic assembly of the macrolide. The marinomycin BGC presents a challenge in heterologous expression due to its large size and high GC content, rendering the cluster prone to rearrangement. We demonstrate the transformation of Streptomyces lividans using a construct containing the cluster, and the heterologous expression of the encoded biosynthetic machinery and production of marinomycin B.

Minimally Invasive Liquid Microjunction Sampling to Identify Dye on a 17th Century Spanish Illuminated Manuscript.

Common sampling methods for mass spectrometry such as sectioning are undesirably damaging to cultural heritage objects. A liquid microjunction sampling technique is developed that uses minimal solvent volume for analysis. Painted illustrations on a 17th century parchment manuscript from Spain were analyzed to identify the organic red pigment throughout its pages. By extracting with 0.1 µL solvent, the pigment was supplied for direct infusion electrospray MS, and the resulting disruption to the object surface was practically invisible to the naked eye.

Antithrombotic Therapy and Hematoma Risk during Image-guided Core-Needle Breast Biopsy.

Background For image-guided core-needle breast biopsy (CNBB), it remains unclear whether antithrombotic medication should be withheld because of hematoma risk. Purpose To determine hematoma risk after CNBB in patients receiving antithrombotic medication and to stratify risk by antithrombotic type. Materials and Methods This HIPAA-compliant retrospective study included US-, stereotactic-, or MRI-guided CNBBs performed across six academic and six private practices between April 2019 and April 2021. Patients were instructed to continue antithrombotic medications, forming two groups: antithrombotic and nonantithrombotic. Hematomas were defined as new biopsy-site masses with a diameter of 2 cm or larger on postprocedure mammograms. Hematomas were considered clinically significant if management involved an intervention other than manual compression. Patient age, type of antithrombotic medication, practice type, image guidance modality, needle gauge and type, and outcome of pathologic analysis were recorded. Multivariable logistic regression analysis was used to analyze variables associated with hematomas. Results A total of 3311 biopsies were performed in 2664 patients (median age, 60 years; IQR, 48-70 years; 2658 women). The nonantithrombotic group included 2788 biopsies, and the antithrombotic group included 523 biopsies (328 low-dose aspirin, 73 full-dose antiplatelet drugs, 51 direct oral anticoagulants, 36 warfarin, 32 daily nonsteroidal anti-inflammatory drugs, three heparin or enoxaparin). The antithrombotic group had a higher overall hematoma rate (antithrombotic group: 49 of 523 biopsies [9.4%], nonantithrombotic group: 172 of 2788 biopsies [6.2%]; P = .007), but clinically significant hematoma rates were not different (antithrombotic group: two of 523 biopsies [0.4%], nonantithrombotic group: one of 2788 biopsies [0.04%]; P = .07). At multivariable analysis, age (odds ratio [OR], 1.02; 95% CI: 1.01, 1.03; P < .001), 9-gauge or larger needles (OR, 2.1; 95% CI: 1.28, 3.3; P = .003), and full-dose antiplatelet drugs (OR, 2.5; 95% CI: 1.29, 5.0; P = .007) were associated with higher hematoma rates. US guidance (OR, 0.26; 95% CI: 0.17, 0.40; P < .001) and 10-14-gauge needles (OR, 0.53; 95% CI: 0.36, 0.79; P = .002) were predictive of no hematoma. Conclusion Because clinically significant hematomas were uncommon, withholding antithrombotic medications before core-needle breast biopsy may be unnecessary. Postbiopsy hematomas were associated with full-dose antiplatelet drugs, patient age, and 9-gauge or larger needles. No association was found with other types of antithrombotic medication. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chang and Yoen in this issue.

Quality Improvement Intervention for Reduction of Redundant Testing.

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (-) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P < .001) in services not receiving peer leader intervention and to >80% (P < .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care.

Outcomes of benign breast papillomas diagnosed at image-guided vacuum-assisted core needle biopsy.

PURPOSE: To determine the upgrade rate of benign papillomas diagnosed at image-guided vacuum-assisted core needle biopsy (VACNB) and to compare our results with the summarized literature. MATERIALS AND METHODS: A database search was performed to identify patients older than 18 years of age with benign papillomas diagnosed at VACNB between 2004 and 2013. A total of 199 papillomas in 184 patients were identified. Clinical, imaging, and pathological features for each were analyzed. Patients who were subsequently diagnosed with malignancy at the site of papilloma, either at surgical excision or upon imaging follow-up, were compared with those not upgraded. Upgrade was defined as a diagnosis of invasive carcinoma or ductal carcinoma in situ (DCIS). RESULTS: Of 199 papillomas, 110 (55.3%) were diagnosed at ultrasound-guided VACNB, 78 (39.2%) were diagnosed at stereotactic-guided VACNB, and 11 (5.5%) were diagnosed at magnetic resonance imaging-guided VACNB. Surgical excision was performed for 89 (44.7%), and the remaining 110 (55.3%) underwent imaging follow-up. Two patients were subsequently diagnosed with invasive carcinoma and 4 were found with DCIS. The upgrade rate across both groups was 3% (6 of 199). Masses with calcifications (P=.001) and smaller needle gauge at VACNB (P=.02) had a significant association with upgrade. CONCLUSION: Benign papillomas diagnosed with VACNB demonstrated a 3% upgrade rate to malignancy, which is similar to the 2.9% upgrade rate calculated by compiling applicable published literature. Conservative management with imaging follow-up as opposed to surgical excision may be appropriate in cases where an initial diagnosis of benign papilloma is made with VACNB. Benign papillomas associated with calcifications on imaging should be considered for surgical excision given their increased association with malignancy.