Outpatient Parenteral Antibiotic Therapy for Diabetic Foot Osteomyelitis in an Uninsured and Underinsured Cohort.

Background: Diabetic foot osteomyelitis (DFO) is usually treated with prolonged outpatient parenteral antibiotic therapy (OPAT). Evaluation and treatment of non-antibiotic aspects of DFO (e.g., peripheral artery disease [PAD]) are also recommended. There is limited data regarding OPAT practice patterns and outcomes for DFO. Methods: Single-center observational study of patients receiving OPAT for DFO in a large United States public hospital between January 2017 and July 2019. We abstracted data regarding microbiology test, antibiotics, clinical outcomes, and non-antibiotic DFO management. Results: Ninety-six patients were included and some had >1 DFO-OPAT course during the study period (106 DFO-OPAT courses included). No culture was obtained in 40 (38%) of courses. Methicillin-resistant S. aureus (MRSA) was cultured in 15 (14%) and P. aeruginosa in 1 (1%) of DFO-OPAT courses. An antibiotic with MRSA activity (vancomycin or daptomycin) was used in 79 (75%) of courses and a parenteral antibiotic with anti-pseudomonal activity was used in 7 (6%) of courses. Acute kidney injury occurred in 19 (18%) DFO-OPAT courses. An ankle-brachial index measurement was obtained during or 6 months prior to the first DFO-OPAT course for 44 (49%) of patients. Forty-two (44%) patients died or had an amputation within 12 months of their initial hospital discharge. Conclusions: We found high rates of empiric antibiotic therapy for DFO and low uptake of the non-antibiotic aspects of DFO care. Better implementation of microbiological tests for DFO in addition to stronger integration of infectious disease and non-infectious diseases care could improve DFO outcomes.

Cardiac Late Sodium Channel Current Is a Molecular Target for the Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin.

BACKGROUND: SGLT2 (sodium/glucose cotransporter 2) inhibitors exert robust cardioprotective effects against heart failure in patients with diabetes, and there is intense interest to identify the underlying molecular mechanisms that afford this protection. Because the induction of the late component of the cardiac sodium channel current (late-INa) is involved in the etiology of heart failure, we investigated whether these drugs inhibit late-INa. METHODS: Electrophysiological, in silico molecular docking, molecular, calcium imaging, and whole heart perfusion techniques were used to address this question. RESULTS: The SGLT2 inhibitor empagliflozin reduced late-INa in cardiomyocytes from mice with heart failure and in cardiac Nav1.5 sodium channels containing the long QT syndrome 3 mutations R1623Q or ΔKPQ. Empagliflozin, dapagliflozin, and canagliflozin are all potent and selective inhibitors of H2O2-induced late-INa (half maximal inhibitory concentration = 0.79, 0.58, and 1.26 µM, respectively) with little effect on peak sodium current. In mouse cardiomyocytes, empagliflozin reduced the incidence of spontaneous calcium transients induced by the late-INa activator veratridine in a similar manner to tetrodotoxin, ranolazine, and lidocaine. The putative binding sites for empagliflozin within Nav1.5 were investigated by simulations of empagliflozin docking to a three-dimensional homology model of human Nav1.5 and point mutagenic approaches. Our results indicate that empagliflozin binds to Nav1.5 in the same region as local anesthetics and ranolazine. In an acute model of myocardial injury, perfusion of isolated mouse hearts with empagliflozin or tetrodotoxin prevented activation of the cardiac NLRP3 (nuclear-binding domain-like receptor 3) inflammasome and improved functional recovery after ischemia. CONCLUSIONS: Our results provide evidence that late-INa may be an important molecular target in the heart for the SGLT2 inhibitors, contributing to their unexpected cardioprotective effects.

Characteristics of and reasons for electronic cigarette use among adult smokers with schizophrenia/schizoaffective disorder.

BACKGROUND: The objective of our study was to determine lifetime and current e-cigarette use among adult cigarette smokers with schizophrenia or schizoaffective disorder, and to describe characteristics of these e-cigarette users. METHODS: Adult daily tobacco smokers with schizophrenia who were psychiatrically stable in outpatient treatment (n = 162) were enrolled in a motivational intervention study from 2013 to 2015 and followed for 6 months. Approximately 80% (n = 140) completed a 6-month follow-up, including the Population Assessment of Tobacco and Health survey. RESULTS: Among the 140 participants, 46% (n = 64) reported ever using e-cigarettes and 15% (n = 21) reported current use. Participants were significantly more likely to report ever-use if they were younger (Chi-square = 11.7, P < .01), lesbian/gay/bisexual (LGB) (Chi-square = 4.8, P = .03), or reported recent drug use (Chi-square = 6.5, P = .01). In a multivariate model, only age remained a significant predictor of ever-use (coefficient: 0.03; P = .02). The most common reasons for using e-cigarettes were "helps people quit cigarettes" and "less harmful to me or to people around me than cigarettes." Current e-cigarette users had significantly lower carbon monoxide levels than past e-cigarettes users (T = 2.08, P = .04). CONCLUSIONS: Almost one-half of smokers with schizophrenia or schizoaffective disorder reported ever using e-cigarettes. Interventions for tobacco use among this demographic should incorporate recognition of e-cigarette use, particularly among younger adults, illicit drug users, and LGB individuals.

Impact of Clinical Decision Support on Azithromycin Prescribing in Primary Care Clinics.

BACKGROUND: Inappropriate use of antibiotics in the outpatient setting is a common problem, yet literature evaluating best practices for stewardship interventions in this setting is sparse. OBJECTIVE: To evaluate the impact of clinical decision support (CDS) order panels for azithromycin prescribing on the percentage of inappropriate azithromycin prescriptions in primary care clinics. DESIGN: Single-center, retrospective analysis of azithromycin prescribing within nine primary care clinics. Pre-intervention and post-intervention data included azithromycin prescriptions from November 2016 to April 2017 and February 2019 to July 2019, respectively. Key exclusion criteria included prescriptions for the treatment of a sexually transmitted infection or for prophylaxis against Mycobacterium avium complex. INTERVENTION: The azithromycin CDS panel was created to provide point-of-care information on appropriate use of azithromycin along with recommended alternatives based on indications. CDS panels were implemented on January 10, 2019. MAIN MEASURES: The primary composite outcome was the change in the percentage of inappropriate azithromycin prescribing before and after implementation of CDS panels. The composite outcome included prescriptions with inappropriate indications for azithromycin, unnecessary prescriptions, inappropriate treatment durations, and/or inappropriate dose. KEY RESULTS: There were 306 and 263 prescriptions for azithromycin prescriptions included for analysis in the pre- and post-intervention periods, respectively. Inappropriate prescriptions decreased by 12.6% from the pre- to post-intervention period (81.4% vs. 68.8%; P < 0.001). In both the pre- and post-intervention period, bronchitis and unspecified upper respiratory tract infections (URI) were the two most common indications where azithromycin was prescribed inappropriately. CONCLUSIONS: Implementation of CDS order panels resulted in a reduction in inappropriate azithromycin prescribing. However, additional improvement in azithromycin prescribing is needed especially for the indications of bronchitis and unspecified URI.

Effectiveness of an Automated Error Checking and Feedback System to Improve Text Message Reporting for Disease Surveillance in Viet Nam.

Purpose: Viet Nam currently relies on a manual paper-based system to track and monitor 28 major infectious diseases. This inefficient system takes 2 or more months to complete. Method: We designed and pilot tested the use of text messaging to report certain infectious disease symptoms in rural areas of northern Viet Nam. The project was divided into three 6-month phases carried out in two provinces. The current analysis focuses on the implementation of a two-way feedback system between Phases II and III, which aims at (1) evaluating whether this system improves efficiency by determining the number of correctly (vs. incorrectly) formatted text messages; (2) assessing this system's influence on accuracy by comparing text messages with their respective official paper-based documented forms; and (3) determining whether the amount of information required to report through text messages influences the efficiency and accuracy of the text messages. Results: Between Phases II and III, results revealed a significant improvement in correctly formatted texts in comparison to incorrectly formatted texts. As the number of fields required to report increased, the number of correctly formatted texts (efficiency) as well as the number of matched text messages (accuracy) decreased. Conclusion: Our research demonstrates that an automated error bidirectional feedback system can significantly improve both the efficiency and accuracy of a Short Message Service-based method for disease surveillance. Also, our data may suggest that two-way communication has better engaged health care staff to follow reporting protocols as well as to maintain accuracy from their clinic's own data.

The impact of an automated antibiotic stewardship intervention for the management of Staphylococcus aureus bacteraemia utilizing the electronic health record.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) management bundles have been shown to improve performance measures and clinical outcomes. SAB bundles often require direct intervention by infectious diseases (ID) physicians or antibiotic stewardship programme (ASP) members or pharmacists. The purpose of this study was to evaluate an automated, real-time ASP intervention utilizing clinical decision support (CDS) in the electronic health record (EHR) for the management of SAB. METHODS: A retrospective, single-centre quasi-experimental study of hospitalized patients with known SAB was conducted. The intervention was the implementation of a hard-stop best practice advisory (BPA) alert that would prompt physicians to use an electronic order set, on identification of SAB, with management recommendations, including ID consultation. The primary outcome was overall adherence to six institutional ASP SAB bundle elements. Secondary outcomes included both clinical and process outcomes. RESULTS: A total of 227 patients were included, 111 in the pre-intervention and 116 in the post-intervention period. Completion of all six bundle elements improved by 27.2% in the post-intervention group (29.7% versus 56.9%, P < 0.001). BPA activation and order-set utilization occurred in 95.7% and 57.8% in the post-intervention group, respectively. Composite outcome of 30 day mortality or 90 day readmission with SAB complication decreased in the post-intervention group by 9.6% (24.3% versus 14.7%, P = 0.092). CONCLUSIONS: Optimization of CDS within the EHR, using real-time BPA alert and order set, demonstrated an immediate, sustainable intervention that improved adherence to institutional performance measures for SAB management without direct prospective audit with intervention and feedback.

Long term toxicity of intracranial germ cell tumor treatment in adolescents and young adults.

PURPOSE: The purpose of this study is to describe the long-term toxicities of intracranial germ cell tumor (IGCT) in the adolescent and young adult (AYA) population. METHODS: We report late toxicities of a multi-center cohort of AYA patients treated for IGCT between 1975 and 2015. Charts were retrospectively reviewed for hormone deficiency, ototoxicity, seizure disorder, visual deterioration, cerebrovascular events, second neoplasm, psychiatric illness, and neurocognitive impairment. Statistical analysis was performed for late toxicities to evaluate the influence of select factors. RESULTS: Our patient cohort included 112 patients with IGCTs; 84% of patients had a germinoma as opposed to a non-germinomatous germ cell tumor (NGGCT), median age at radiotherapy (RT) was 19 years, and median follow-up was 8.3 years. Of the 94 patients with germinoma, 32 (34%) received both chemotherapy and RT as part of their upfront treatment, while 62 (66%) received RT alone. All 18 patients with NGGCT received chemotherapy and RT. The most common late toxicity following IGCT treatments was physician-reported neurocognitive impairment, with a 10-year cumulative incidence (CI) of 38.5%. Ten-year CI of treatment-induced ototoxicity was 39.2% for patients who received cisplatin, compared to 3.6% for those who received carboplatin but no cisplatin (p < 0.005). Suprasellar/hypothalamic tumor location was associated with 10-year CI of treatment-induced hormone deficiency (36.1 vs 6.2%, p < 0.005). CONCLUSIONS: A significant proportion of AYAs treated for IGCTs experience late effects from treatment, including neurocognitive impairment, ototoxicity, and hormone deficiency. Suprasellar/hypothalamic tumor location and cisplatin were associated with a higher risk of treatment-induced hormone deficiency and ototoxicity, respectively.

The TEACHH model to predict life expectancy in patients presenting for palliative spine radiotherapy: external validation and comparison with alternate models.

INTRODUCTION: The TEACHH score was developed to identify patients with predicted short (< 3 months) and long (> 1 year) life expectancy. We aimed to validate this model in an independent group of patients presenting for palliative spine radiotherapy and to compare it to alternate prognostic models. METHODS: We retrospectively reviewed charts of 195 consecutive patients referred for palliative spine radiotherapy. Patients were grouped according to the number of risk factors from the TEACHH model, Chow model, and Oswestry Risk Index. RESULTS: One hundred and eighty patients with a median age of 65 years were included. Follow-up was 5.8 months in all patients and 31.8 months in living patients. For the TEACHH model, patients in groups 1, 2, and 3 had a median (95% CI) overall survival (OS) of 22.3 (15.7-36.1), 4.9 (3.8-6.6), and 1.5 (0.8-5.4) months, respectively. Wilcoxon pairwise comparisons showed statistically different survival between groups 1 and 2, and 1 and 3. In the Chow model, patients in groups 1, 2, and 3 had a median (95% CI) OS of 16.1 (10.0-22.3), 5.9 (3.8-9.2), and 1.9 (1.2-2.5) months, respectively. There was a significant difference between all groups. The Oswestry Risk Index identified five prognostic groups with median OS (95% CI) ranging from 22.2 (12.9-30.2) to 2.1 (0.8-4.0) months. Only group 1 was statistically different from the others. Although the effect of age was small, the TEACHH model performed best with the inclusion of all parameters. CONCLUSIONS: The TEACHH model is useful to identify patients with spinal metastases with predicted short, intermediate, and long LE. Its prognostic ability is similar to the Chow model.

Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease.

Hyaluronan (HA), a major component of the extracellular matrix, is secreted by airway structural cells. Airway fibroblasts in allergic asthma secrete elevated levels of HA in association with increased HA synthase 2 (HAS2) expression. Thus, we hypothesized that HA accumulation in the airway wall may contribute to airway remodeling and hyperresponsiveness in allergic airways disease. To examine this hypothesis, transgenic mice in which the α-smooth muscle actin (α-SMA) promoter drives HAS2 expression were generated. Mixed male and female α-SMA-HAS2 mice (HAS2+ mice, n = 16; HAS2- mice, n = 13) were sensitized via intraperitoneal injection and then chronically challenged with aerosolized ovalbumin (OVA) for 6 weeks. To test airway responsiveness, increasing doses of methacholine were delivered intravenously and airway resistance was measured using the forced oscillation technique. HA, cytokines, and cell types were analyzed in bronchoalveolar lavage fluid, serum, and whole lung homogenates. Lung sections were stained using antibodies specific for HA-binding protein (HABP) and α-SMA, as well as Masson's trichrome stain. Staining of lung tissue demonstrated significantly increased peribronchial HA, α-SMA, and collagen deposition in OVA-challenged α-SMA-HAS2+ mice compared with α-SMA-HAS2- mice. Unexpectedly, OVA-challenged α-SMA-HAS2+ mice displayed significantly reduced airway responsiveness to methacholine compared with similarly treated α-SMA-HAS2- mice. The total numbers of inflammatory cell types in the bronchoalveolar lavage fluid did not differ significantly between OVA-challenged α-SMA-HAS2+ mice and α-SMA-HAS2- mice. We conclude that allergen-challenged mice that overexpress HAS2 in myofibroblasts and smooth muscle cells develop increased airway fibrosis, which lessens airway hyperresponsiveness to bronchoconstrictors.

Smoking-related correlates of psychomotor restlessness and agitation in a community sample of daily cigarette smokers.

BACKGROUND AND OBJECTIVES: Psychomotor restlessness and agitation (PMA) is a putatively important, yet understudied, psychopathologic correlate of smoking. The scant smoking research on PMA previously conducted has been narrow in scope and conducted among psychiatric patients. To examine the generalizability and relevance of PMA to smoking, this cross-sectional study investigated associations between PMA and a variety of smoking processes in a community sample. METHODS: Participants in this study were non-treatment-seeking smokers (N = 254, ≥10 cig/day, M age = 44 years) from the community without an active mood disorder. At baseline, they completed a PMA symptom checklist, a composite depressive symptom index, and a battery of smoking questionnaires. RESULTS: Linear regression models adjusting for depressive symptoms and demographics indicated that PMA level was positively associated with severity of nicotine withdrawal symptoms during prior quit attempts (ß = .18, p < .05), anticipated likelihood of withdrawal in a future quit attempt (ß = .19, p < .05), motivation to smoke for negative reinforcement (ß = .14, p < .05), and smoking expectancies for negative reinforcement (ß = .17, p < .05), negative consequences (ß = .22, p < .01), and positive reinforcement (ß = .14, p < .05). PMA was not significantly associated with smoking chronicity, frequency, or dependence severity. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Smokers with elevated PMA appear to experience greater smoking-induced affect modulation and nicotine withdrawal than the average smoker, regardless of other depressive symptoms. Given that PMA differentiates a qualitatively unique profile of smoking characteristics, PMA warrants consideration in tobacco addiction research and practice.

Cortisol levels decrease after acute tobacco abstinence in regular smokers.

OBJECTIVE: The aim of this study was to examine the effect of acute tobacco abstinence on cortisol levels in regular smokers, and whether abstinence-induced changes in cortisol levels are correlated with various signs and symptoms of the tobacco withdrawal syndrome. METHODS: Smokers (N = 77, ≥15 cigarettes/day) attended two counterbalanced sessions (avg = 1 h), one following 12-20 h of abstinence and the other following ad lib smoking. At both sessions, salivary cortisol levels were measured at three time points. Additionally, a battery of self-report questionnaires, physiological assessments, and cognitive performance tasks were administered to measure signs and symptoms of tobacco withdrawal. RESULTS: Salivary cortisol levels were significantly lower during the abstinent session versus the non-abstinent session. No significant associations were found between abstinence-induced changes in cortisol and other tobacco withdrawal measures, although there was suggestive evidence that abstinence-induced changes in cortisol levels and hunger were inversely associated to a modest degree. CONCLUSION: Acute tobacco abstinence was associated with decreased cortisol levels. Cortisol dampening during acute tobacco abstinence may reflect nicotine-mediated modulation of hypothalamic-pituitary-adrenal axis activity, which may be relevant to the maintenance of tobacco dependence. Tobacco-withdrawal cortisol changes do not appear to be a cause or consequence of many manifestations of acute tobacco withdrawal with the possible exception of hunger.

HumanIslets: An integrated platform for human islet data access and analysis.

Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibility, usability, and integration of data from human islets isolated from donors with and without diabetes at the Alberta Diabetes Institute (ADI) IsletCore. Here we introduce HumanIslets.com , an open resource for the research community. This platform, which presently includes data on 547 human islet donors, allows users to access linked datasets describing molecular profiles, islet function and donor phenotypes, and to perform various statistical and functional analyses at the donor, islet and single-cell levels. As an example of the analytic capacity of this resource we show a dissociation between cell culture effects on transcript and protein expression, and an approach to correct for exocrine contamination found in hand-picked islets. Finally, we provide an example workflow and visualization that highlights links between type 2 diabetes status, SERCA3b Ca 2+ -ATPase levels at the transcript and protein level, insulin secretion and islet cell phenotypes. HumanIslets.com provides a growing and adaptable set of resources and tools to support the metabolism and diabetes research community.

Long-Term Survival and Induction of Operational Tolerance to Murine Islet Allografts by Co-Transplanting Cyclosporine A Microparticles and CTLA4-Ig.

One strategy to prevent islet rejection is to create a favorable immune-protective local environment at the transplant site. Herein, we utilize localized cyclosporine A (CsA) delivery to islet grafts via poly(lactic-co-glycolic acid) (PLGA) microparticles to attenuate allograft rejection. CsA-eluting PLGA microparticles were prepared using a single emulsion (oil-in-water) solvent evaporation technique. CsA microparticles alone significantly delayed islet allograft rejection compared to islets alone (p < 0.05). Over 50% (6/11) of recipients receiving CsA microparticles and short-term cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig) therapy displayed prolonged allograft survival for 214 days, compared to 25% (2/8) receiving CTLA4-Ig alone. CsA microparticles alone and CsA microparticles + CTLA4-Ig islet allografts exhibited reduced T-cell (CD4+ and CD8+ cells, p < 0.001) and macrophage (CD68+ cells, p < 0.001) infiltration compared to islets alone. We observed the reduced mRNA expression of proinflammatory cytokines (IL-6, IL-10, INF-γ, and TNF-α; p < 0.05) and chemokines (CCL2, CCL5, CCL22, and CXCL10; p < 0.05) in CsA microparticles + CTLA4-Ig allografts compared to islets alone. Long-term islet allografts contained insulin+ and intra-graft FoxP3+ T regulatory cells. The rapid rejection of third-party skin grafts (C3H) in islet allograft recipients suggests that CsA microparticles + CTLA4-Ig therapy induced operational tolerance. This study demonstrates that localized CsA drug delivery plus short-course systemic immunosuppression promotes an immune protective transplant niche for allogeneic islets.

Recent Developments in Islet Biology: A Review With Patient Perspectives.

Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more than 2,000 peer-reviewed articles on islet biology were published in 2021. Herein, we highlight noteworthy advances in islet research between January 2021 and April 2022, focussing on 5 areas. First, we discuss new insights into the role of glucokinase, mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase and mitochondrial function on insulin secretion from the pancreatic ß cell, provided by new genetically modified mouse models and live imaging. We then discuss a new connection between lipid handling and improved insulin secretion in the context of glucotoxicity, focussing on fatty acid-binding protein 4 and fetuin-A. Advances in high-throughput "omic" analysis evolved to where one can generate more finely tuned genetic and molecular profiles within broad classifications of type 1 diabetes and type 2 diabetes. Next, we highlight breakthroughs in diabetes treatment using stem cell-derived ß cells and innovative strategies to improve islet survival posttransplantation. Last, we update our understanding of the impact of severe acute respiratory syndrome-coronavirus-2 infection on pancreatic islet function and discuss current evidence regarding proposed links between COVID and new-onset diabetes. We address these breakthroughs in 2 settings: one for a scientific audience and the other for the public, particularly those living with or affected by diabetes. Bridging biomedical research in diabetes to the community living with or affected by diabetes, our partners living with type 1 diabetes or type 2 diabetes also provide their perspectives on these latest advances in islet biology.

Antimicrobial stewardship pharmacist interventions for coagulase-negative staphylococci positive blood cultures using rapid polymerase chain reaction.

BACKGROUND: No studies exist regarding the value of pharmacist interventions using rapid identification of coagulase-negative staphylococci (CoNS) by rapid polymerase chain reaction (rPCR) from blood cultures. OBJECTIVE: To evaluate the impact of interventions by infectious diseases pharmacists (ID PharmDs) on blood cultures positive for CoNS using rPCR and assess the duration of antistaphylococcal antibiotic therapy, hospital length of stay (LOS), and related costs. METHODS: A quasi-experimental, pre- and postintervention study of patients with positive blood cultures for CoNS, identified using rPCR, was conducted. Patients were included if there was a blood culture for CoNS from January 1, 2011, to March 31, 2011 (preintervention), or October 1, 2011, to January 18, 2012 (postintervention). Exclusion criteria included age younger than 18 years or 89 years or older, neutropenia, incomplete records, and duplicate or mixed blood cultures. The setting was a 1200-bed academic medical center. The ID PharmD intervened on blood cultures identified in the postintervention group as CoNS after notification from the microbiology laboratory. The pre- and postintervention groups were compared to analyze the effect of the intervention. The primary outcome was time to discontinuation of antistaphylococcal antibiotics by the pharmacist intervention in patients with a positive blood culture for CoNS that was determined to be a contaminant. RESULTS: We analyzed 53 patients (31 preintervention, 22 postintervention) with CoNS blood culture contaminants. In the postintervention group, antistaphylococcal antibiotics were discontinued 32.0 hours sooner from time of rPCR result (median 57.7 vs 25.7 hours; p = 0.005), total antibiotic exposure decreased 43.5 hours (97.6 vs 54.1 hours; p = 0.011), infection-related LOS decreased 4.5 days (10 vs 5.5 days; p = 0.018), and infection-related costs decreased $8338 ($28,973 vs $20,635; p = 0.144). The pharmacist initiated vancomycin in 7 (21.9%) patients with CoNS bloodstream infections. CONCLUSIONS: Timely interventions by ID PharmDs using rPCR are required to impact the outcomes of patients with positive blood cultures for CoNS.

Training and Validation of Deep Learning-Based Auto-Segmentation Models for Lung Stereotactic Ablative Radiotherapy Using Retrospective Radiotherapy Planning Contours.

PURPOSE: Deep learning-based auto-segmented contour (DC) models require high quality data for their development, and previous studies have typically used prospectively produced contours, which can be resource intensive and time consuming to obtain. The aim of this study was to investigate the feasibility of using retrospective peer-reviewed radiotherapy planning contours in the training and evaluation of DC models for lung stereotactic ablative radiotherapy (SABR). METHODS: Using commercial deep learning-based auto-segmentation software, DC models for lung SABR organs at risk (OAR) and gross tumor volume (GTV) were trained using a deep convolutional neural network and a median of 105 contours per structure model obtained from 160 publicly available CT scans and 50 peer-reviewed SABR planning 4D-CT scans from center A. DCs were generated for 50 additional planning CT scans from center A and 50 from center B, and compared with the clinical contours (CC) using the Dice Similarity Coefficient (DSC) and 95% Hausdorff distance (HD). RESULTS: Comparing DCs to CCs, the mean DSC and 95% HD were 0.93 and 2.85mm for aorta, 0.81 and 3.32mm for esophagus, 0.95 and 5.09mm for heart, 0.98 and 2.99mm for bilateral lung, 0.52 and 7.08mm for bilateral brachial plexus, 0.82 and 4.23mm for proximal bronchial tree, 0.90 and 1.62mm for spinal cord, 0.91 and 2.27mm for trachea, and 0.71 and 5.23mm for GTV. DC to CC comparisons of center A and center B were similar for all OAR structures. CONCLUSIONS: The DCs developed with retrospective peer-reviewed treatment contours approximated CCs for the majority of OARs, including on an external dataset. DCs for structures with more variability tended to be less accurate and likely require using a larger number of training cases or novel training approaches to improve performance. Developing DC models from existing radiotherapy planning contours appears feasible and warrants further clinical workflow testing.

Implementation of deep learning-based auto-segmentation for radiotherapy planning structures: a workflow study at two cancer centers.

PURPOSE: We recently described the validation of deep learning-based auto-segmented contour (DC) models for organs at risk (OAR) and clinical target volumes (CTV). In this study, we evaluate the performance of implemented DC models in the clinical radiotherapy (RT) planning workflow and report on user experience. METHODS AND MATERIALS: DC models were implemented at two cancer centers and used to generate OAR and CTVs for all patients undergoing RT for a central nervous system (CNS), head and neck (H&N), or prostate cancer. Radiation Therapists/Dosimetrists and Radiation Oncologists completed post-contouring surveys rating the degree of edits required for DCs (1 = minimal, 5 = significant) and overall DC satisfaction (1 = poor, 5 = high). Unedited DCs were compared to the edited treatment approved contours using Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD). RESULTS: Between September 19, 2019 and March 6, 2020, DCs were generated on approximately 551 eligible cases. 203 surveys were collected on 27 CNS, 54 H&N, and 93 prostate RT plans, resulting in an overall survey compliance rate of 32%. The majority of OAR DCs required minimal edits subjectively (mean editing score ≤ 2) and objectively (mean DSC and 95% HD was ≥ 0.90 and ≤ 2.0 mm). Mean OAR satisfaction score was 4.1 for CNS, 4.4 for H&N, and 4.6 for prostate structures. Overall CTV satisfaction score (n = 25), which encompassed the prostate, seminal vesicles, and neck lymph node volumes, was 4.1. CONCLUSIONS: Previously validated OAR DC models for CNS, H&N, and prostate RT planning required minimal subjective and objective edits and resulted in a positive user experience, although low survey compliance was a concern. CTV DC model evaluation was even more limited, but high user satisfaction suggests that they may have served as appropriate starting points for patient specific edits.

Delirious Mania: An Approach to Diagnosis and Treatment.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Efficacy of Palliative Radiation Therapy (RT) for Chemotherapy Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Population-Based Retrospective Review.

PURPOSE: The study objective was to investigate the effectiveness of palliative radiation therapy (RT) for patients with diffuse large B-cell lymphoma (DLBCL) and to identify factors, such as chemotherapy relapsed/refractory (R/R) disease, that may influence RT outcomes. METHODS AND MATERIALS: Patients with DLBCL who received palliative RT from 2001 to 2015 in British Columbia were reviewed for patient characteristics, treatment details, and outcomes. Univariable and multivariable analyses for response and local progression were performed. RESULTS: Three-hundred and seventy courses of palliative RT in 217 patients were identified. Median equivalent dose in 2 Gy fractions was 19 Gy (range, 2-42 Gy). Clinical and/or radiologic response occurred in 230 (83%) of the 276 courses with response data available. Local control following palliative RT at 6 months was 66.7%. On univariable analysis, R/R disease was not associated with lower clinical response rates but had higher risk of progression (hazard ratio [HR], 0.5; P = .040). On multivariable analyses, patients with R/R disease who did not require concurrent steroids had greater response compared with those who received upfront palliative RT (odds ratio, 3.5; P = .011). Response to first-line chemotherapy and smaller lesion size were associated with improved local progression rates (HR, 0.2; P < .001 and HR, 0.5; P = .020, respectively). RT dose fractionation factors were not significant on any analyses. CONCLUSIONS: Palliative RT for DLBCL is effective for symptom improvement, including in the chemotherapy R/R setting. Not requiring concurrent steroids, response to first-line chemotherapy, and smaller lesion size predicted better RT outcomes. There was no association between dose fractionation and response rates or local control to suggest that higher RT doses are more effective for palliation.