Citations

ABSTRACT A total of 1,925 Corynebacterium isolates were tested for antimicrobial susceptibility at the Mayo Clinic Microbiology laboratory (Rochester, Minnesota) from January 2012 to March 2023, with C. striatum (35.6%) and C. amycolatum (24.4%) identified as the predominant species. Species known to potentially carry diphtheria toxin were excluded. Common sources of isolation included skin and soft tissue (56.8%), bone and/or native joint synovial fluid (14.2%), urine (13.1%), sputum (6.1%), and blood (5.9%). For penicillin, susceptibility decreased from 47.5% (58 of 122) in 2012 to 20.6% (14 of 68) in 2023. Isolates also showed a decrease in susceptibility to erythromycin from 22.4% (26 of 116) in 2012 to 13.2% (9 of 68) in 2023. Susceptibility to trimethoprim-sulfamethoxazole averaged around 50% throughout the period. Notably, linezolid and vancomycin were universally effective in vitro against all species. The highest susceptibility rates among tested oral agents were to linezolid and doxycycline for non- C . striatum species. Daptomycin minimal inhibitory concentrations (MICs) of >256 µg/mL were observed for one C. amycolatum isolate, one C. tuberculostearicum isolate, and for seven C. striatum isolates, all from patients with prior daptomycin exposure. Daptomycin MICs of 2 µg/mL (nonsusceptible) were observed in one C. striatum isolate recovered from a daptomycin-naïve patient and in six C. jeikeium isolates, from both daptomycin-exposed and non-exposed patients. Significant variation in susceptibility profiles across different Corynebacterium species underscores the importance of performing antimicrobial susceptibility testing to guide effective treatment. Moreover, multidrug resistance observed in C. striatum poses substantial therapeutic challenges especially in patients requiring prolonged or chronic antibiotic suppression.

Study Design: A meta-analysis approach to a systematic review. Objective: Perform a systematic review to identify all reports directly comparing outcomes of lateral lumbar interbody fusion (LLIF) using static versus expandable interbody cages. Specifically focusing on periprocedural complications, intraoperative morbidity, and fusion outcomes. Summary of Background Data: Minimally invasive surgical techniques, particularly LLIF, have gained popularity for their potential to reduce muscle and soft tissue dissection, leading to faster postoperative recovery. LLIF has been associated with fewer complications compared with open posterior approaches. The introduction of expandable lumbar interbody devices aims to further reduce surgical difficulty and potential complications. However, concerns include a small graft window due to the expansion mechanism and higher costs. Methods: The Web of Science, Scopus, and PubMed databases were systematically queried in accordance with PRISMA guidelines to identify articles comparing outcomes following LLIF using static and expandable interbodies. The Newcastle-Ottawa Scale (NOS) was employed to assess the risk of bias (ROB) in the selected studies. Extracted data underwent effect-size meta-analysis with the PyMARE library, using P<0.05 to define statistical significance. Results: Of the 77 identified articles, 4 studies comprising 283 patients (mean age: 67.1 y, 55.8% female) met the inclusion and exclusion criteria. A total of 150 patients (53%) were treated with static interbodies compared with 133 (47%) receiving expandable interbodies. The groups did not differ significantly with respect to operative time (P=0.59), blood loss (P=0.89), length of stay (P=0.78), subsidence (P=0.49), 24-month mean disc height (P=0.11), 24-month mean ODI (P=0.58), or 24-month mean visual analog scale (VAS) back pain (P=0.81). The expandable group saw a trend toward improved fusion rates (97% vs. 92%, P=0.06). Conclusions: The present meta-analysis suggests the use of expandable (vs. static) interbodies in LLIF surgery may result in similar surgical morbidity, subsidence, and decompression. Further prospective comparative studies are merited to validate these results.

Introduction: Identifying patients at risk for ischemic events after percutaneous coronary intervention (PCI) relies on traditional analysis of limited clinical and imaging variables. Machine learning (ML) has shown promise in effectively predicting cardiovascular risk in population studies. While existing ML models mainly predict mortality and incorporate clinical variables, there is a lack of tools that have utilized genetic data and that predict ischemic events. Aims: This study aims to develop and validate a ML model incorporating genotyping and clinical data to enhance prediction of ischemic outcomes for PCI patients utilizing large prospectively derived diverse datasets. Methods: Patients from the TAILOR-PCI trial (n=5302) were utilized for model development. 50% of the sample was utilized for Boruta feature selection and 50% for training and testing using cross validation. Features included demographics, medical history, medications, PCI characteristics, and genetic data (specifically, CYP2C19 *2, *3, *17 alleles). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. Multiple ML classification algorithms, including Support Vector Machine (SVM) polynomial, Random Forest, Light gradient boost, XG Boost, among others, were benchmarked for their prediction performance on rare events. The top performing classifiers were externally validated on an independent dataset from the PRECISION PCI study (n=3,745). Results: Mean participant age of the training set was 64.2 ± 11.0 years, with 75.4% being male. During follow-up of 12 months, among 4,572 patients in the entire cohort 343 (7.5%) met the primary outcome. The SVM polynomial model demonstrated the highest area under the curve (AUC) of 0.67 for predicting the primary outcome with test dataset. The sensitivity, specificity, precision, and recall were 0.87, 0.28, 0.07, and 0.87 respectively (Figure). Peripheral arterial disease, body mass index, and age were among the top variables by feature importance. Conclusion: ML models incorporating both clinical and genetic data are feasible and highly promising in predicting major adverse cardiac events that may help guide use of anti-platelet drug therapy. The AUC values are reasonable given imbalances and misclassifications in datasets, and further model optimization with prospective utilization of the model will be paramount.

Background: VICTORION-INITIATE (NCT04929249) showed significantly greater LDL-C lowering in patients (pts) with ASCVD with an inclisiran first (IF) strategy (adding inclisiran immediately on failure to achieve LDL-C <70 mg/dL on maximally tolerated statin therapy) vs usual care (UC). Tokenization can be leveraged to link clinical trial data to pt-level real-world data (RWD) to provide a comprehensive overview of the pt journey pre- and post-trial and enhance understanding of clinical trial and long-term pt outcomes. Aim: To utilize tokenization and linked RWD to characterize the pt journey pre-VICTORION-INITIATE enrollment. Methods: Eligible pts from VICTORION-INITIATE were deidentified and tokenized with unique IDs, allowing linking to RWD (EMR, claims, hospital, and lab records) to follow the pt journey in the 3-year pre-trial and 2-year post-trial periods. Here we present demographics, clinical characteristics, and lipid-lowering therapy (LLT) use of pts with linked pre-trial RWD. Results: Of 450 pts randomized, 383 (85.1%) were linked with pre-trial RWD (IF arm, n=193; UC arm, n=190); 26.9% were female, first available recorded mean (SD) age was 64 (9.36) years. Among the 74.2% (n=284) of pts with linked, pre-trial, lipid test RWD, mean (SD) earliest and latest LDL-C values were 100.1 mg/dL (35.70) and 99.3 mg/dL (30.06), respectively, for pts in the IF arm vs 97.3 mg/dL (40.43) and 97.8 mg/dL (27.60) for pts in the UC arm ( Table ). Overall, in the pre-trial period, LLT was dispensed/prescribed to 66.1% of pts, statins to 64.5%, ezetimibe to 4.4%, and PCSK9i to 4.4%. Of pts with ≥1 recorded ASCVD events in the pre-trial period (n=141), 53.2% and 68.8% had available LLT dispensing/prescription records pre- and post-event, respectively. Conclusions: In the 3 years pre-VICTORION-INITIATE, mean LDL-C levels were above recommended goals, non-statin LLT prescription was infrequent, and ~31% of pts with ≥1 recorded ASCVD event had no evidence of post-event LLT use, highlighting a need for more aggressive LDL-C management. Full data visibility for each pt is a limitation of this approach. Tokenization post-trial will allow for long-term evaluation of LLT practices.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell–engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

Objective To describe the immediate clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) in treating long COVID symptoms. Long COVID currently impacts approximately 5.3% of US adults, presenting with persistent fatigue, depression, anxiety, cognitive impairments, and social function decline. Repetitive transcranial magnetic stimulation targeting the left dorsolateral prefrontal cortex has improved these symptoms in some studies. Methods Five patients (ages 52–63 years, 3 female patients) underwent accelerated rTMS using intermittent theta burst stimulation (600 pulses over 3 minutes 20 seconds, 80%–120% of resting motor threshold) to the left dorsolateral prefrontal cortex. The treatment consisted of twice-daily sessions over 20–30 treatments. Outcomes were measured using the Patient-Reported Outcomes Measurement and Information System (PROMIS) questionnaires, assessing fatigue, depression, anxiety, cognitive function, and social function at baseline and immediately posttreatment. Results One patient discontinued immediately due to intolerable scalp pain. Posttreatment PROMIS scores showed the following: fatigue decreased from 74.5 to 61.8, depression from 60.3 to 51.5, and anxiety from 62.0 to 54.0. Scores increased for cognitive (26.8 to 32.3) and social (31.0 to 32.5) function. These changes, although not statistically significant, indicate a trend toward symptom reduction. Subjectively, 3 of 4 patients who completed the rTMS course reported improvements. Conclusion This case series suggests that rTMS may offer symptomatic relief in long COVID patients. Although the observed improvements in PROMIS were not statistically significant, even minimal improvements are clinically significant for patients enduring prolonged suffering. These preliminary findings are encouraging and underscore the need for further research with larger cohorts to validate the efficacy of rTMS in long COVID symptom relief.

AbstractBackgroundMotion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.PurposeProton radiography uses the treatment beam, at an energy high enough to traverse the patient, to produce a radiograph. This work shows the first results of using an integrated‐mode proton radiography system to track the position of moving objects in an experimental phantom study; demonstrating the potential of using this method for measuring tumor motion.MethodsProton radiographs of an anthropomorphic lung phantom, with a motor‐driven tumor insert, were acquired approximately every 1 s, using tumor inserts of 10, 20, and 30 mm undergoing a known periodic motion. The proton radiography system used a monolithic scintillator block and digital cameras to capture the residual range of each pencil beam passing through the phantom. These ranges were then used to produce a water equivalent thickness map of the phantom. The centroid of the tumor insert in the radiographs was used to determine its position. This measured position was then compared to the known motion of the phantom to determine the accuracy.ResultsSubmillimeter accuracy on the measurement of the tumor insert was achieved when using a 30 mm tumor insert with a period of 24 s and was found to be improved for decreasing motion amplitudes with a mean absolute error (MAE) of 1.0, 0.9, and 0.7 mm for 20, 15, and 10 mm respectively. Using smaller tumor inserts reduced the accuracy with a MAE of 1.8 and 1.9 mm for a 20 and 10 mm insert respectively undergoing a periodic motion with an amplitude of 20 mm and a period of 24 s. Using a shorter period resulted in significant motion artifacts reducing the accuracy to a MAE of 2.2 mm for a 12 s period and 3.1 mm for a 6 s period for the 30 mm insert with an amplitude of 20 mm.ConclusionsThis work demonstrates that the position of a lung tumor insert in a realistic anthropomorphic phantom can be measured with high accuracy using proton radiographs. Results show that the accuracy of the position measurement is the highest for slower tumor motions due to a reduction in motion artifacts. This indicates that the primary obstacle to accurate measurement is the speed of the radiograph acquisition. Although the slower tumor motions used in this study are not clinically realistic, this work demonstrates the potential for using proton radiography for measuring tumor motion with an increased scanning speed that results in a decreased acquisition time.