Citations

Background: There are limited oral treatment options available for resistant Gram-negative bacterial (GNB) infections. Minocycline, a second-generation tetracycline antibiotic, offers good bioavailability and broad-spectrum coverage that may be an option for GNB infections. Methods: We conducted a retrospective review of minocycline susceptibility testing performed on GNB isolates at the Mayo Clinic reference lab between 2013 and 2022. Minocycline susceptibility was evaluated with a focus on difficult-to-treat organisms and relevant anatomic source. Organisms included resistant isolates of Escherichia coli and Klebsiella pneumoniae ; high-risk ampC-derepressors, including Citrobacter freundii, Enterobacter cloacae, and K. aerogenes; and clinically challenging non-Enterobacterales, Acinetobacter species, Achromobacter species, and Stenotrophomonas maltophilia . Results: Of 217,206 GNB isolates, 18,148 Enterobacterales (EB) and 8,190 non- Enterobacter isolates were tested for minocycline susceptibility. Of these, 80% of all EB and 92% of non-EB isolates were susceptible. Among E. coli isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 78%, 76%, 70%, and 70.9%, respectively. Among the K. pneumoniae isolates with ceftriaxone, ciprofloxacin, meropenem, or multidrug resistance, minocycline susceptibility was 46%, 38%, 37%, and 39.3%, respectively. 85% of C. freundii , 81% of E. cloacae, and 85% of K. aerogenes isolates were susceptible to Minocycline. 83.5% of Achromobacter species isolates, 66% of Acinetobacter species isolates, and 99.1% of S. maltophilia isolates were susceptible. Conclusions: Our study reports the largest collection of minocycline susceptibility findings in GNB. Minocycline showed in vitro activity against many difficult-to-treat GNB isolates, including ceftriaxone- and multidrug-resistant E. coli and some K. pneumoniae isolates, common Amp-C-producing species, and non-fermenting GNB, including Stenotrophomonas , Acinetobacter , and Achromobacter .

Human diseases are complex and arise from the coordinated action of multiple genes and their protein products. Genes’ behaviors extend beyond genetic variants, mutations, and differential expressions. Their coordinated activity across biological scales (molecules, cells, tissues, organs) produces emergent behaviors that shape health and disease. These emergent behaviors span time and space and are often hard to measure directly from observation when using standard experimental measurements. Yet these “hidden” or latent gene characteristics can be powerful drivers of disease. We propose a Mini-Galaxy Model (MGM), a systems-level AI-driven network framework that models cells as “mini-galaxies” composed of multilayered biological information, with each layer encoding a different dimension of genes’ behavior. Here, we delineate a strategy on how to construct and compare MGMs across health and disease and map their etiological relatedness. We also operationalize the MGM as a discovery platform for translational medicine, offering modules to allow target prioritization and editing. By reframing human diseases as the result of emergent behavior of multilayered multimode biological networks and their perturbations, the MGM yields actionable rules to streamline biomarker discovery, guide target selection and enable rational design of combinatorial interventions, and accelerate drug repurposing.

Background Oral anti-cancer treatment is commonly used, and non-adherence can negatively affect outcomes. The Oral Oncolytic Non-Adherence Estimator (ORACLE) was designed to prospectively categorize patients into risk levels by considering constructs such as self-efficacy, health literacy, perception of treatment, quality of life, social support, and regimen complexity. Validating this estimator is essential. Methods A content validation survey evaluated representativeness, clarity, and factor structure of each construct in ORACLE. A multidisciplinary panel of 8 content experts and 4 lay experts completed the survey. Results were analyzed to evaluate inter-rater agreement, content validity index (CVI), and factorial validity index (FVI). Post-survey workgroup discussions reviewed results and considered tool adjustments. Results All 12 invited experts completed the survey. The average CVI for content experts was 0.88 for representativeness and 0.98 for clarity. The average CVI for lay experts was 0.95 for clarity. The average FVI was 0.88, with self-efficacy and negative perception constructs yielding the lowest scores (0.63 and 0.75, respectively). ORACLE revisions addressed survey results and expert feedback on health literacy, social support, and regimen complexity. Conclusions Strong CVI for content and lay experts (94% and 95%) and strong FVI for content experts (98%) verify that the tool is understandable and addresses non-adherence issues, establishing validity of construct clarity and representativeness. Content validity of the first pre-treatment oral oncolytic non-adherence risk estimator was established, providing a reliable tool to identify patients at higher risk of non-adherence.

Opioids are often the first-line approach to treat moderate to severe cancer-related pain. However, opioids can cause conflict and distress to cancer survivors when prescribed for pain. The objective of this multi-methods study was to explore the psychosocial factors that affect the use or refusal of opioids among breast cancer survivors. We recruited 20 breast cancer survivors treated with opioids to participate in a free-listing exercise and semi-structured interview. Results revealed that survivors felt unprepared for the intensity of pain following cancer treatments, which contributed to the use of opioids. The adverse side effects often influenced their decision to discontinue them from their pain management strategy. Finally, the addictive properties of the medication affected survivors’ use of the medication. Findings identify and recognize clinicians and researchers can promote safer, more personalized approaches to pain management to inform interventions that integrate behavioral health support and improve patient-provider communication.

Abstract Introduction The effectiveness of temporary uterine artery ligation (TUAL) in reducing blood loss during laparoscopic myomectomy (LM) is uncertain, despite increased use as an adjunct to improve surgical safety. This study aims to evaluate the safety and efficacy of TUAL in LM for the management of uterine myomas. Material and Methods We conducted a systematic review and meta‐analysis of comparative studies evaluating LM with and without TUAL. Electronic databases were searched up to October 7, 2024. Eligible studies were randomized controlled trials or observational comparative studies published in English that reported at least one primary outcome. The primary outcomes were intraoperative estimated blood loss and perioperative change in hemoglobin. Secondary outcomes included operative time, number and size of myomas removed, length of hospital stay, recurrence, and complication rates. Data extraction and analysis were performed using a random‐effects model. This review was registered prospectively with PROSPERO (CRD42024595684). Results Seven studies met the inclusion criteria, comprising five randomized controlled trials and two retrospective case–control studies, with a total of 857 women (352 undergoing LM with TUAL and 505 undergoing LM alone). TUAL was associated with a reduction in intraoperative estimated blood loss (mean difference [MD]: −84.7 mL; 95% Cl: −89.0; −80.0) and postoperative reduction in hemoglobin level (MD: −0.4 g/dL; 95% Cl: −0.7; −0.2) compared with LM without TUAL. However, TUAL was associated with increased operative time (MD: 16.5 min; 95% Cl: 3.4; 29.6). Conclusions TUAL appears to be a possible adjunct to LM for selected patients in the management of uterine myomas. Our study demonstrated that TUAL with LM could be associated with a reduction in estimated blood loss, despite an increase in operative time. Nonetheless, further studies with a larger sample size and long‐term follow‐up, as well as stratification of outcomes based on ligation technique, are warranted to elucidate the benefits of TUAL.

Background: Chronic venous insufficiency (CVI) can be evaluated using Duplex ultrasonography (US) and air plethysmography (PG), yet comparative performance remains unclear. Methods: We retrospectively identified patients who underwent venous insufficiency US and PG within a 90-day interval from March 1, 2015 through July 31, 2024. CVI severity was classified by the clinical (C) component of the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification system and categorized as mild (C0–2), moderate (C3), or severe (C4–6). PG and insufficiency US findings were compared across categories and machine learning models were trained to predict severe CVI. Results: We analyzed 1478 limbs from 839 patients who were predominantly women (62%) with a mean age of 61 years (± 14 years). Severe CVI was present in 32.3% of limbs. US detected venous incompetence in 67.4% of limbs overall and in 75.3% of severe CVI limbs. Abnormal PG findings occurred in 72.9% of limbs overall and in 88.5% of severe CVI limbs. PG parameters in machine learning models outperformed US parameters in predicting severe CVI (area under the receiver operating characteristic curve [AUROC] 0.82 vs 0.65). The top PG model (multilayer perceptron [MLP]) achieved an AUROC of 0.82, versus the best US model (gradient boosting) with an AUROC of 0.65. Limiting PG data to incompetence and obstruction parameters modestly reduced performance but remained higher than US (logistic regression AUROC 0.72). Conclusion: Our findings indicate that PG assessment in CVI offers superior performance compared to US. Overall, these results validate the quantitative whole-limb hemodynamic approach using PG, which provides a more complete understanding of the pathology behind CVI.

Abstract Background Minimally invasive colorectal surgery is characterized by significant procedural variability, a difficult learning curve, and complications that affect patient outcomes. Video-based assessment offers an opportunity to generate data-driven insights to reduce variability, optimize training, and improve surgical performance. This mixed-methods study aimed to develop and validate a video-based assessment tool for workflow analysis across minimally invasive colorectal procedures. Methods An international steering committee panel of seven members coordinated a three-round modified Delphi process. Experts in colorectal surgery and video-based assessment were invited to reach consensus (≥ 70% agreement) on the phases and steps that describe workflows across colorectal surgery procedural videos. The resulting framework informed the development of ColoWorkflow. Four independent raters then applied ColoWorkflow to a multicentre video data set of laparoscopic and robotic colorectal procedures. Applicability and inter-rater reliability were evaluated. Results Of 66 invited experts, 41 (62%) from 11 countries completed round 1, 40 (98%) completed round 2, 20 attended the final online consensus meeting, and all (40 of 40) approved the final workflow descriptors. Consensus was achieved on nine procedure-agnostic phases (port placement and abdomen exploration; vascular dissection and ligation, mesocolon/mesorectum dissection, additional lymphadenectomy; colon and/or rectum mobilization; colorectal transection; anastomosis; completion of operation; preplanned additional procedures; unplanned procedures; extracorporeal procedures) and 34 procedure-specific steps that describe colorectal surgery workflows. ColoWorkflow was developed and applied to 54 colorectal surgery videos (left and right hemicolectomies, sigmoid and rectosigmoid resections, and total proctocolectomies) from five centres in four countries. The tool demonstrated broad applicability, as all phase and step labels, except one, were represented in at least one video. Inter-rater reliability was moderate, with a mean Cohen’s κ value of 0.72 for phases and 0.67 for steps. Most discrepancies arose at phase transitions and step boundary definitions. Conclusion Based on this preliminary work, ColoWorkflow is a promising tool for workflow analysis across minimally invasive colorectal procedures. Its adoption may help standardize training, accelerate competency acquisition, and advance data-informed surgical quality improvement.

Objectives: To assess how social risk factors and socioeconomic status (SES) affect health care costs at a large, integrated health system of 45 clinics in Iowa, Minnesota, and Wisconsin. Methods: We retrospectively reviewed administrative patient cost data from January 1 through December 31, 2022. Social risk factors (lack of financial resources, food insecurity, intimate partner violence, unmet transportation needs, and housing instability) were determined with patient questionnaires. Cost z -scores were compared across all risk-factor quartiles. We used a housing-based measure to objectively determine SES. Results: We analyzed data from 410 624 patients empaneled with 689 family medicine clinicians. Self-reported risk factor data were incomplete for 219 321 patients. Costs were higher for those with higher social risk (mean cost z -score: high risk = 0.38, low risk = 0.11; P < .001). In addition, higher costs were associated with increasing age, greater medical complexity (higher Adjusted Clinical Group scores), White race, and lack of financial resources. Although we observed geographic variations in cost, urban and rural locations did not have significant cost differences. Costs were similar across all quartiles of SES, and the absolute difference in cost z -scores between the highest and lowest SES quartiles was only 0.04. The multivariate analysis, which adjusted for age, medical complexity, race, sex, and objective SES, showed that these specific associations were substantially decreased and no longer significantly associated with mean cost z -scores. Conclusions: Patient-reported social risk factors were significantly associated with increased cost of care in a large, multispecialty health system in the midwestern US. These associations were decreased in the multivariate analysis. Results should be interpreted cautiously for readers outside the midwestern US, given potential responder bias and the racial homogeneity (92% White) of the study cohort.