Intraoperative near infrared functional imaging of rectal cancer using artificial intelligence methods - now and near future state of the art.

Colorectal cancer remains a major cause of cancer death and morbidity worldwide. Surgery is a major treatment modality for primary and, increasingly, secondary curative therapy. However, with more patients being diagnosed with early stage and premalignant disease manifesting as large polyps, greater accuracy in diagnostic and therapeutic precision is needed right from the time of first endoscopic encounter. Rapid advancements in the field of artificial intelligence (AI), coupled with widespread availability of near infrared imaging (currently based around indocyanine green (ICG)) can enable colonoscopic tissue classification and prognostic stratification for significant polyps, in a similar manner to contemporary dynamic radiological perfusion imaging but with the advantage of being able to do so directly within interventional procedural time frames. It can provide an explainable method for immediate digital biopsies that could guide or even replace traditional forceps biopsies and provide guidance re margins (both areas where current practice is only approximately 80% accurate prior to definitive excision). Here, we discuss the concept and practice of AI enhanced ICG perfusion analysis for rectal cancer surgery while highlighting recent and essential near-future advancements. These include breakthrough developments in computer vision and time series analysis that allow for real-time quantification and classification of fluorescent perfusion signals of rectal cancer tissue intraoperatively that accurately distinguish between normal, benign, and malignant tissues in situ endoscopically, which are now undergoing international prospective validation (the Horizon Europe CLASSICA study). Next stage advancements may include detailed digital characterisation of small rectal malignancy based on intraoperative assessment of specific intratumoral fluorescent signal pattern. This could include T staging and intratumoral molecular process profiling (e.g. regarding angiogenesis, differentiation, inflammatory component, and tumour to stroma ratio) with the potential to accurately predict the microscopic local response to nonsurgical treatment enabling personalised therapy via decision support tools. Such advancements are also applicable to the next generation fluorophores and imaging agents currently emerging from clinical trials. In addition, by providing an understandable, applicable method for detailed tissue characterisation visually, such technology paves the way for acceptance of other AI methodology during surgery including, potentially, deep learning methods based on whole screen/video detailing.

Technical and functional design considerations for a real-world interpretable AI solution for NIR perfusion analysis (including cancer).

Near infrared (NIR) analysis of tissue perfusion via indocyanine green fluorescence assessment is performed clinically during surgery for a range of indications. Its usefulness can potentially be further enhanced through the application of interpretable artificial intelligence (AI) methods to improve dynamic interpretation accuracy in these and also open new applications. While its main use currently is for perfusion assessment as a tissue health check prior to performing an anastomosis, there is increasing interest in using fluorophores for cancer detection during surgical interventions with most research being based on the paradigm of static imaging for fluorophore uptake hours after preoperative dosing. Although some image boosting and relative estimation of fluorescence signals is already inbuilt into commercial NIR systems, fuller implementation of AI methods can enable actionable predictions especially when applied during the dynamic, early inflow-outflow phase that occurs seconds to minutes after ICG (or indeed other fluorophore) administration. Already research has shown that such methods can accurately differentiate cancer from benign tissue in the operating theatre in real time in principle based on their differential signalling and could be useful for tissue perfusion classification more generally. This can be achieved through the generation of fluorescence intensity curves from an intra-operative NIR video stream. These curves are processed to adjust for image disturbances and curve features known to be influential in tissue characterisation are extracted. Existing machine learning based classifiers can then use these features to classify the tissue in question according to prior training sets. The use of this interpretable methodology enables accurate classification algorithms to be built with modest training sets in comparison to those required for deep learning modelling in addition to achieving compliance with medical device regulations. Integration of the multiple algorithms required to achieve this classification into a desktop application or medical device could make the use of this method accessible and useful to (as well as useable by) surgeons without prior training in computer technology. This document details some technical and functional design considerations underlying such a novel recommender system to advance the foundational concept and methodology as software as medical device for in situ cancer characterisation with relevance more broadly also to other tissue perfusion applications.

A feasibility study assessing quantitative indocyanine green angiographic predictors of reconstructive complications following nipple-sparing mastectomy.

Introduction: Immediate post-mastectomy breast reconstruction offers benefits; however, complications can compromise outcomes. Intraoperative indocyanine green fluorescence angiography (ICGFA) may mitigate perfusion-related complications (PRC); however, its interpretation remains subjective. Here, we examine and develop methods for ICGFA quantification, including machine learning (ML) algorithms for predicting complications. Methods: ICGFA video recordings of flap perfusion from a previous study of patients undergoing nipple-sparing mastectomy (NSM) with either immediate or staged immediate (delayed by a week due to perfusion insufficiency) reconstructions were analysed. Fluorescence intensity time series data were extracted, and perfusion parameters were interrogated for overall/regional associations with postoperative PRC. A naïve Bayes ML model was subsequently trained on a balanced data subset to predict PRC from the extracted meta-data. Results: The analysable video dataset of 157 ICGFA featured females (average age 48 years) having oncological/risk-reducing NSM with either immediate (n=90) or staged immediate (n=26) reconstruction. For those delayed, peak brightness at initial ICGFA was lower (p<0.001) and significantly improved (both quicker-onset and brighter p=0.001) one week later. The overall PRC rate in reconstructed patients (n=116) was 11.2%, with such patients demonstrating significantly dimmer (overall, p=0.018, centrally, p=0.03, and medially, p=0.04) and slower-onset (p=0.039) fluorescent peaks with shallower slopes (p=0.012) than uncomplicated patients with ICGFA. Importantly, such relevant parameters were converted into a whole field of view heatmap potentially suitable for intraoperative display. ML predicted PRC with 84.6% sensitivity and 76.9% specificity. Conclusion: Whole breast quantitative ICGFA assessment reveals statistical associations with PRC that are potentially exploitable via ML.

Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis.

BACKGROUND: Postoperative ileus (POI) remains a common phenomenon following loop ileostomy closure. Our aim was to determine whether preoperative physiological stimulation (PPS) of the efferent limb reduced POI incidence. METHODS: A PRISMA-compliant meta-analysis searching PubMed, EMBASE and CENTRAL databases was performed. The last search was carried out on 30 January 2023. All randomized studies comparing PPS versus no stimulation were included. The primary endpoint was POI incidence. Secondary endpoints included the time to first passage of flatus/stool, time to resume oral diet, need for nasogastric tube (NGT) placement postoperatively, length of stay (LOS) and other complications. Random effects models were used to calculate pooled effect size estimates. Trial sequential analyses (TSA) were also performed. RESULTS: Three randomized studies capturing 235 patients (116 PPS, 119 no stimulation) were included. On random effects analysis, PPS was associated with a quicker time to resume oral diet (MD - 1.47 days, 95% CI - 2.75 to - 0.19, p = 0.02), shorter LOS (MD - 1.47 days, 95% CI - 2.47 to - 0.46, p = 0.004) (MD - 1.41 days, 95% CI - 2.32 to - 0.50, p = 0.002, I2 = 56%) and fewer other complications (OR 0.42, 95% CI 0.18 to 1.01, p = 0.05). However, there was no difference in POI incidence (OR 0.35, 95% CI 0.10 to 1.21, p = 0.10), the requirement for NGT placement (OR 0.50, 95% CI 0.21 to 1.20, p = 0.12) or time to first passage of flatus/stool (MD - 0.60 days, 95% CI - 1.95 to 0.76, p = 0.39). TSA revealed imprecise estimates for all outcomes (except LOS) and further studies are warranted to meet the required information threshold. CONCLUSIONS: PPS prior to stoma closure may reduce LOS and postoperative complications albeit without a demonstrable beneficial effect on POI. Further high-powered studies are required to confirm or refute these findings.

CLASSICA: Validating artificial intelligence in classifying cancer in real time during surgery.

AIM: Treatment pathways for significant rectal polyps differ depending on the underlying pathology, but pre-excision profiling is imperfect. It has been demonstrated that differences in fluorescence perfusion signals following injection of indocyanine green (ICG) can be analysed mathematically and, with the assistance of artificial intelligence (AI), used to classify tumours endoscopically as benign or malignant. This study aims to validate this method of characterization across multiple clinical sites regarding its generalizability, usability and accuracy while developing clinical-grade software to enable it to become a useful method. METHODS: The CLASSICA study is a prospective, unblinded multicentre European observational study aimed to validate the use of AI analysis of ICG fluorescence for intra-operative tissue characterization. Six hundred patients undergoing transanal endoscopic evaluation of significant rectal polyps and tumours will be enrolled in at least five clinical sites across the European Union over a 4-year period. Video recordings will be analysed regarding dynamic fluorescence patterns centrally as software is developed to enable analysis with automatic classification to happen locally. AI-based classification and subsequently guided intervention will be compared with the current standard of care including biopsies, final specimen pathology and patient outcomes. DISCUSSION: CLASSICA will validate the use of AI in the analysis of ICG fluorescence for the purposes of classifying significant rectal polyps and tumours endoscopically. Follow-on studies will compare AI-guided targeted biopsy or, indeed, AI characterization alone with traditional biopsy and AI-guided local excision versus traditional excision with regard to marginal clearance and recurrence.

Comparative Outcomes of Sacubitril/Valsartan Use After Hospitalization for Heart Failure Among Medicare Beneficiaries Naïve to Renin-Angiotensin System Inhibitors.

Sacubitril/valsartan improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with angiotensin-converting enzyme inhibitors (ACEis). However, data on postdischarge outcomes in renin-angiotensin system inhibitor (RASi)-naïve patients are limited. We included Medicare beneficiaries aged ≥65 years who were hospitalized for HFrEF in the Get With The Guidelines-Heart Failure registry between October 2015 and June 2019, had part D prescription coverage, and were not on RASi therapy during the 6 months before hospital admission. We examined the associations between sacubitril/valsartan prescription at hospital discharge and outcomes at 30 days and 1 year after discharge using overlap-weighted median regression and Cox proportional hazards models. The end points included "home time" (defined as days alive and out of any health care institution), mortality, and rehospitalization. Among 3,572 patients with HFrEF and who are naïve to RASi therapy, at discharge, 290 (8.1%) were prescribed sacubitril/valsartan and 1,390 (38.9%) were prescribed ACEis and angiotensin receptor blockers. After adjusting for baseline characteristics, patients prescribed sacubitril/valsartan had a longer median home time (parameter estimate 27.0 days, 95% confidence interval [CI] 12.40 to 41.6, p <0.001) and lower all-cause mortality (hazard ratio [HR] 0.74, 95% CI 0.61 to 0.91, p = 0.004) at 1 year than patients not prescribed sacubitril/valsartan. The prescription of sacubitril/valsartan was not significantly associated with all-cause rehospitalization (HR 0.87, 95% CI 0.74 to 1.03, p = 0.10) or heart failure rehospitalization (HR 0.87, 95% CI 0.70 to 1.07, p = 0.19). In a restricted comparison of patients discharged on sacubitril/valsartan versus ACEis and angiotensin receptor blockers, there were no significant differences in the outcomes. In conclusion, in this contemporary population of RASi-naïve patients with HFrEF from routine clinical practice, compared with not initiating, the initiation of sacubitril/valsartan at discharge was associated with longer home time and improvements in overall survival.

Population well-being and the COVID-19 vaccination program in Chile: evidence from Google Trends.

OBJECTIVE: We analyze the dynamics of the mental well-being of the Chilean population in response to the progress of the vaccination strategy implemented by the government. STUDY DESIGN: This study aims at investigating the possibility of using Google Trends as an instrument for tracking mental well-being of the Chilean population. METHODS: We use the volume of searches for keywords in Google Trends (GT) related to Anguish, Anxiety, Depression, and Stress as a proxy for population well-being. Using event study methods, we analyze social attention reactions to news about the vaccination program. We implement a Difference-in-Difference-in-Differences estimation to estimate changes in population welfare by socio-economic status induced by the progress of inoculation. RESULTS: We show that social attention to mental health problems is sensitive to news about the vaccination program. Moreover, and most importantly, we find that mental well-being responds positively to the percentage of inoculated people. This phenomenon appear to be permanent and affected by socio-economic status, with the wealthier population experiencing greater improvements than the less wealthy. CONCLUSIONS: During the COVID-19 vaccination program in Chile, social attention to mental health problems appears to be sensitive to news about the vaccination program. There is also strong evidence of socio-economic status-induced heterogeneity in population responses to program implementation. The above phenomena appears to be permanent and cannot be attributed to either socio-economic segregation in access to vaccines or to the highly stratified schedule of the vaccination program.

Initial Thoracic Endovascular Aortic Repair vs Medical Therapy for Acute Uncomplicated Type B Aortic Dissection.

Importance: Thoracic endovascular aortic repair (TEVAR) has increasingly been used for uncomplicated type B aortic dissection (uTBAD) despite limited supporting data. Objective: To assess whether initial TEVAR following uTBAD is associated with reduced mortality or morbidity compared with medical therapy alone. Design, Setting, and Participants: This cohort study included Centers for Medicare & Medicaid Services inpatient claims data for adults aged 65 years or older with index admissions for acute uTBAD from January 1, 2011, to December 31, 2018, with follow-up available through December 31, 2019. Exposures: Initial TEVAR was defined as TEVAR within 30 days of admission for acute uTBAD. Main Outcomes and Measures: Outcomes included all-cause mortality, cardiovascular hospitalizations, aorta-related and repeated aorta-related hospitalizations, and aortic interventions associated with initial TEVAR vs medical therapy. Propensity score inverse probability weighting was used. Results: Of 7105 patients with eligible index admissions for acute uTBAD, 1140 (16.0%) underwent initial TEVAR (623 [54.6%] female; median age, 74 years [IQR, 68-80 years]) and 5965 (84.0%) did not undergo TEVAR (3344 [56.1%] female; median age, 76 years [IQR, 69-83 years]). Receipt of TEVAR was associated with region (vs South; Midwest: adjusted odds ratio [aOR], 0.66 [95% CI, 0.53-0.81]; P < .001; Northeast: aOR, 0.63 [95% CI, 0.50-0.79]; P < .001), Medicaid dual eligibility (aOR, 0.76; 95% CI, 0.63-0.91; P = .003), hypertension (aOR, 1.26; 95% CI, 1.03-1.54; P = .03), peripheral vascular disease (aOR, 1.24; 95% CI, 1.02-1.49; P = .03), and year of admission (2012, 2013, 2014, and 2015 were associated with greater odds of TEVAR compared with 2011). After inverse probability weighting, mortality was similar for the 2 strategies up to 5 years (hazard ratio [HR], 0.95; 95% CI, 0.85-1.06), as were aorta-related hospitalizations (HR, 1.12; 95% CI, 0.99-1.27), aortic interventions (HR, 1.01; 95% CI, 0.84-1.20), and cardiovascular hospitalizations (HR, 1.05; 95% CI, 0.93-1.20). In a sensitivity analysis that included deaths within the first 30 days, initial TEVAR was associated with lower mortality over a period of 1 year (adjusted HR [aHR], 0.86; 95% CI, 0.75-0.99; P = .03), 2 years (aHR, 0.85; 95% CI, 0.75-0.96; P = .008), and 5 years (aHR, 0.87; 95% CI, 0.80-0.96; P = .004). Conclusions and Relevance: In this study, 16.0% of patients underwent initial TEVAR within 30 days of uTBAD, and receipt of initial TEVAR was associated with hypertension, peripheral vascular disease, region, Medicaid dual eligibility, and year of admission. Initial TEVAR was not associated with improved mortality or reduced hospitalizations or aortic interventions over a period of 5 years, but in a sensitivity analysis that included deaths within the first 30 days, initial TEVAR was associated with lower mortality. These findings, along with cost-effectiveness and quality of life, should be assessed in a prospective trial in the US population.

Impact of risk factor control on peripheral artery disease outcomes and health disparities.

BACKGROUND: Peripheral artery disease (PAD) is associated with modifiable atherosclerotic risk factors like hypertension, diabetes, hyperlipidemia, and smoking. However, the effect of risk factor control on outcomes and disparities in achieving control is less well understood. METHODS: All patients in an integrated, regional health system with PAD-related encounters, fee-for-service Medicare, and clinical risk factor control data were identified. Component risk factors were dichotomized into controlled and uncontrolled categories (control defined as low-density lipoprotein < 100 mg/dL, hemoglobin A1c < 7.0%, SBP < 140 mmHg, and current nonsmoker) and composite categories (none, 1, ⩾ 2 uncontrolled RFs) created. The primary outcome was major adverse vascular events (MAVE, a composite of all-cause mortality, myocardial infarction, stroke, and lower-extremity revascularization and amputation). RESULTS: The cohort included 781 patients with PAD, average age 72.5 ± 9.8 years, of whom 30.1% were Black, and 19.1% were Medicaid dual-enrolled. In this cohort, 260 (33.3%) had no uncontrolled risk factors and 200 (25.6%) had two or more uncontrolled risk factors. Patients with the poorest risk factor control were more likely to be Black (p < 0.001), Medicaid dual-enrolled (p < 0.001), and have chronic limb-threatening ischemia (p = 0.009). Significant differences in MAVE by degree of risk factor control were observed at 30 days (none uncontrolled: 5.8%, 1 uncontrolled: 11.5%, ⩾ 2 uncontrolled: 13.6%; p = 0.01) but not at 1 year (p = 0.08). risk factor control was not associated with outcomes at 1 year after adjustment for patient and PAD-specific characteristics. CONCLUSIONS: risk factor control is poor among patients with PAD. Significant disparities in achieving optimal risk factor control represent a potential target for reducing inequities in outcomes.

Clinician Specialty, Access to Care, and Outcomes Among Patients with Peripheral Artery Disease.

BACKGROUND: Understanding the relationship between patterns of peripheral artery disease and outcomes is an essential step toward improving care and outcomes. We hypothesized that clinician specialty would be associated with occurrence of major adverse vascular events (MAVE). METHODS: Patients with at least 1 peripheral artery disease-related encounter in our health system and fee-for-service Medicare were divided into groups based on the specialty of the clinician (ie, cardiologist, surgeon, podiatrist, primary care, or other) providing a plurality of peripheral artery disease-coded care in the year prior to index encounter. The primary outcome was MAVE (a composite of all-cause mortality, myocardial infarction, stroke, lower extremity revascularization, and lower extremity amputation). RESULTS: The cohort included 1768 patients, of whom 30.0% were Black, 23.9% were Medicaid dual-enrollment eligible, and 31.1% lived in rural areas. Patients receiving a plurality of their care from podiatrists had the highest 1-year rates of MAVE (34.4%, P <.001), hospitalization (65.9%, P <.001), and amputations (22.6%, P <.001). Clinician specialty was not associated with outcomes after adjustment. Patients who were Medicaid dual-eligible had higher adjusted risks of mortality (adjusted hazard ratio [HRadj] 1.54, 95% confidence interval [CI] 1.11-2.14) and all-cause hospitalization (HRadj 1.20, 95% CI 1.03-1.40) and patients who were Black had a higher adjusted risk of amputation (HRadj 1.49, 95% CI 1.03-2.15). CONCLUSIONS: Clinician specialty was not associated with worse outcomes after adjustment, but certain socioeconomic factors were. The effects of clinician specialty and socioeconomic status were likely attenuated by the fact that all patients in this study had health insurance; these analyses require confirmation in a more representative cohort.

Sacubitril/Valsartan Adherence and Postdischarge Outcomes Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction.

OBJECTIVES: The authors sought to investigate associations between sacubitril/valsartan adherence and clinical outcomes after hospitalization for heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Sacubitril/valsartan improves outcomes in HFrEF, though the extent to which medication adherence is associated with outcomes in routine care is less well characterized. METHODS: The authors analyzed patients aged ≥65 years hospitalized for HFrEF within the Get With the Guidelines-Heart Failure registry linked with Medicare claims between October 2015 and September 2018 who were discharged with sacubitril/valsartan. Sacubitril/valsartan adherence was assessed using medication fills to calculate proportion of days covered (PDC) through 90 days postdischarge. Associations between postdischarge adherence (PDC < or ≥80%) and risk of readmission and death within 1 year were examined by comparing cumulative incidences and adjusted event rates. RESULTS: Among 897 patients prescribed sacubitril/valsartan at discharge, 295 (32.9%) had PDC ≥80% and 602 (67.1%) had PDC <80%. Baseline characteristics were balanced between groups. Compared with patients with PDC <80%, patients with PDC ≥80% had a significantly lower adjusted hazard of all-cause rehospitalization (HR: 0.66 [95% CI: 0.48-0.89]) and death (HR: 0.42 [95% CI: 0.22-0.79]) at 90 days and at 1 year (HR: 0.69 [95% CI: 0.56-0.86] and HR: 0.53 [95% CI: 0.38-0.74], respectively). For every 5 percentage point increase in PDC, patients experienced a significant reduction in rehospitalization (HR: 0.98 [95% CI: 0.97-0.99]) and death (HR: 0.96 [95% CI: 0.94-0.97]) at 1 year. CONCLUSIONS: In patients hospitalized for HFrEF and discharged on sacubitril/valsartan, high adherence to sacubitril/valsartan within 90 days after discharge was associated with substantially lower rates of readmission and death. Additional efforts to improve adherence with sacubitril/valsartan and other guideline-directed medical therapies in HFrEF are warranted.

Clinical Effectiveness of Sacubitril/Valsartan Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction.

Background Sacubitril/Valsartan has been highly efficacious in randomized trials of heart failure with reduced ejection fraction (HFrEF). However, the effectiveness of sacubitril/valsartan in older patients hospitalized for HFrEF in real-world US practice is unclear. Methods and Results This study included Medicare beneficiaries age ≥65 years who were hospitalized for HFrEF ≤40% in the Get With The Guidelines-Heart Failure registry between October 2015 and December 2018, and eligible for sacubitril/valsartan. Associations between discharge prescription of sacubitril/valsartan and clinical outcomes were assessed after inverse probability of treatment weighting and adjustment for other HFrEF medications. Overall, 1551 (10.9%) patients were discharged on sacubitril/valsartan. Of those not prescribed sacubitril/valsartan, 7857 (62.0%) were prescribed an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Over 12-month follow-up, compared with a discharge prescription of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, sacubitril/valsartan was independently associated with lower all-cause mortality (adjusted hazard ratio [HR], 0.82; 95% CI, 0.72-0.94; P=0.004) but not all-cause hospitalization (adjusted HR, 0.97; 95% CI, 0.89-1.07; P=0.55) or heart failure hospitalization (adjusted HR, 1.04; 95% CI, 0.91-1.18; P=0.59). Patients prescribed sacubitril/valsartan versus those without a prescription had lower risk of all-cause mortality (adjusted HR, 0.69; 95% CI, 0.60-0.79; P<0.001), all-cause hospitalization (adjusted HR, 0.90; 95% CI, 0.82-0.98; P=0.02), but not heart failure hospitalization (adjusted HR, 0.94; 95% CI, 0.82-1.08; P=0.40). Conclusions Among patients hospitalized for HFrEF, prescription of sacubitril/valsartan at discharge was independently associated with reduced postdischarge mortality compared with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, and reduced mortality and all-cause hospitalization compared with no sacubitril/valsartan. These findings support the use of sacubitril/valsartan to improve postdischarge outcomes among older patients hospitalized for HFrEF in routine US clinical practice.

Sacubitril/Valsartan Initiation and Postdischarge Adherence Among Patients Hospitalized for Heart Failure.

BACKGROUND: We investigated associations between timing of sacubitril/valsartan initiation and postdischarge adherence among patients hospitalized for heart failure with reduced ejection fraction (HFrEF). Clinical trials support initiation of sacubitril/valsartan among patients hospitalized with HFrEF. The association between timing of initiation and postdischarge adherence is unknown. METHODS AND RESULTS: We analyzed patients hospitalized for HFrEF (EF of ≤40%) within the Get With The Guidelines Heart Failure registry linked with Medicare claims between October 2015 and September 2017 who were eligible for sacubitril/valsartan. Follow-up was through December 2018. Patients were grouped by timing of sacubitril/valsartan initiation. Sacubitril/valsartan adherence at 90 and 365 days after discharge was assessed by calculating proportion of days covered (PDC) using medication fills. Among 4666 patients, 108 (2.3%) were continued on sacubitril/valsartan (on sacubitril/valsartan at admission and discharge), 191 (4.1%) were initiated as inpatients, 130 (2.8%) were initiated at discharge, and 4237 (90.1%) were discharged without sacubitril/valsartan. Median (25th, 75th) proportion of days covered through 90 days among those continued, initiated as inpatients, and initiated at discharge was 0.9 (0.6-0.1), 0.3 (0.0-0.7), and 0.0 (0.0-0.7), respectively (P < .001). Patients discharged without sacubitril/valsartan had very low rates of any sacubitril/valsartan fills within 90 and 365 days of discharge (2.1% and 7.7% of surviving patients, respectively). CONCLUSIONS: In 2015-2017 US clinical practice, more than 90% of eligible patients hospitalized for HFrEF were discharged without sacubitril/valsartan. Patients initiated as inpatients had a higher postdischarge proportion of days covered than patients initiated at discharge. Patients discharged without sacubitril/valsartan were unlikely to receive it during follow-up. These findings highlight the importance of initiating sacubitril/valsartan during hospitalization to improve the quality of care.

The association of healthcare disparities and patient-specific factors on clinical outcomes in peripheral artery disease.

BACKGROUND: PAD increases the risk of cardiovascular mortality and limb loss, and disparities in treatment and outcomes have been described. However, the association of patient-specific characteristics with variation in outcomes is less well known. METHODS: Patients with PAD from Duke University Health System (DUHS) between January 1, 2015 and March 31, 2016 were identified. PAD status was confirmed through ground truth adjudication and predictive modeling using diagnosis codes, procedure codes, and other administrative data. Symptom severity, lower extremity imaging, and ankle-brachial index (ABI) were manually abstracted from the electronic health record (EHR). Data was linked to Centers for Medicare and Medicaid Services data to provide longitudinal follow up. Primary outcome was major adverse vascular events (MAVE), a composite of all-cause mortality, myocardial infarction (MI), stroke, lower extremity revascularization and amputation. RESULTS: Of 1,768 patients with PAD, 31.6% were asymptomatic, 41.2% had intermittent claudication (IC), and 27.3% had chronic limb-threatening ischemia (CLTI). At 1 year, patients with CLTI had higher rates of MAVE compared with asymptomatic or IC patients. CLTI and Medicaid dual eligibility were independent predictors of mortality. CLTI and Black race were associated with amputation. CONCLUSIONS: Rates of MAVE were highest in patients with CLTI, but patients with IC or asymptomatic disease also had high rates of adverse events. Black and Medicaid dual-eligible patients were disproportionately present in the CLTI subgroup and were at higher risk of amputation and mortality, respectively. Future studies must focus on early identification of high-risk patient groups to improve outcomes in patients with PAD.

Aerosols, airflow, and airspace contamination during laparoscopy.

Laparoscopic surgery has been undermined throughout the COVID-19 pandemic by concerns that it may generate an infectious risk to the operating team through aerosolization of peritoneal particles. There is anyway a need for increased awareness and understanding of the occupational hazard for surgical teams regarding unfiltered escape of pollutants generated by surgical smoke and other microbials. Here, the aerosol-generating nature of this access modality was confirmed through repeatable real-time methodology both qualitatively and quantitively to inform best practice and additional engineering solutions to optimize the operating room environment.

Laparoscopic surgery has been undermined throughout the COVID-19 pandemic by concerns that it may generate an infectious risk to the operating team through aerosolization of peritoneal particles. There is anyway a need for increased awareness and understanding of the occupational hazard for surgical teams regarding unfiltered escape of pollutants generated by surgical smoke and other microbials. Here, the aerosol-generating nature of this access modality was confirmed through repeatable real-time methodology both qualitatively and quantitively to inform best practice and additional engineering solutions to optimize the operating room environment.

Relationship between intramammary infection and antibody concentrations in Jersey and Holstein colostrum.

Feeding calves a high-quality and antibody-rich colostrum is an important management practice for supporting calf health and productivity. Colostrum quality and antibody concentrations are highly variable between cows and among quarters within a cow. Intramammary infections often occur during the time of colostrum formation; however, it is unknown if these infections ultimately affect colostrum quality and antibody concentrations. The objective of this study was to determine if antibody concentrations and Brix percentage in colostrum from infected mammary glands (quarters) differed from uninfected. In 2 cross-sectional studies, colostrum samples were aseptically collected at first milking from 110 Holstein and 89 Jersey cows at 3 Holstein and 4 Jersey commercial dairy farms in Ohio. A total of 771 quarter samples were collected, underwent bacteriological culture, and were measured for Brix percentage with a digital refractometer. When 1 infected and 1 uninfected quarter existed among the fore or rear quarters within a cow, IgG1, IgG2, IgA, and IgM antibody concentrations were determined via ELISA for the paired quarters (n = 82). Overall, for Holstein cows, Brix percentages were greater in multiparous than primiparous cows (30.5 vs. 23.7 ± 2.1 SEM), but an opposite pattern was observed for Jersey cows (24.3 vs. 27.2 ± 1.2 SEM). Uninfected quarters in both Holstein and Jersey multiparous cows had greater Brix percentage than colostrum from infected quarters; this pattern was absent for Holstein and Jersey primiparous cows. For Holstein cows, concentrations of IgG1, IgG2, and IgA were greater in multiparous cows than primiparous cows; quarter-infection status did not significantly influence antibody concentrations. For Jersey samples, antibody concentrations did not differ between primiparous and multiparous cows and were not significantly affected by quarter-infection status. The results of these works indicate that infection status at parturition does not markedly affect colostrum antibody concentrations and quality, and that other factors at the local level of the mammary gland more greatly influence colostrogenesis and antibody transport into the mammary gland during colostrogenesis.

Organization of mammary blood vessels as affected by mammary parenchymal region and estradiol administration in Holstein heifer calves.

Mammary blood flow is central to mammary growth, development, and productivity, but the development of the vasculature network is poorly understood. The objective of this study was to determine how the vascular system adapts to mammary growth by inducing different levels of mammary growth and examining 2 regions of mammary parenchymal tissue. Holstein heifer calves (n = 12) received daily injections on the days immediately preceding euthanasia at 82 d of age. Treatments were control (CON), short-term estradiol (STE), and long-term estradiol (LTE). The CON calves received corn oil injections, the STE calves received 9 injections of corn oil followed by 3 injections of estradiol, and the LTE calves received 12 estradiol injections. Mammary tissues were collected from the center and edge parenchymal regions of all right rear mammary glands to quantify the tissue area of various tissue structures, the percentage of proliferating epithelial cells, and the number and form of blood vessels. Results showed that LTE calves had a greater tissue area occupied by epithelium than CON and STE calves, and the epithelial area in CON and STE calves was similar. Edge parenchyma had a greater percentage of proliferating epithelial cells than center parenchyma across all treatment groups. In the edge region, LTE calves had the greatest percentage of proliferating epithelial cells, coinciding with greater epithelial area. The number of blood vessels per unit of tissue area was greater in center than in edge parenchyma; the corresponding vessel surface area per unit of tissue area followed the same pattern. Mammary blood vessel measures were not markedly influenced by estradiol treatment. These results highlight the marked difference in the number and organization of blood vessels in different mammary parenchyma regions but indicate that the effects of estradiol on stimulating mammary epithelial proliferation does not directly translate to increasing numbers of blood vessels.

Model-Based Algorithms for Detecting Peripheral Artery Disease Using Administrative Data From an Electronic Health Record Data System: Algorithm Development Study.

BACKGROUND: Peripheral artery disease (PAD) affects 8 to 10 million Americans, who face significantly elevated risks of both mortality and major limb events such as amputation. Unfortunately, PAD is relatively underdiagnosed, undertreated, and underresearched, leading to wide variations in treatment patterns and outcomes. Efforts to improve PAD care and outcomes have been hampered by persistent difficulties identifying patients with PAD for clinical and investigatory purposes. OBJECTIVE: The aim of this study is to develop and validate a model-based algorithm to detect patients with peripheral artery disease (PAD) using data from an electronic health record (EHR) system. METHODS: An initial query of the EHR in a large health system identified all patients with PAD-related diagnosis codes for any encounter during the study period. Clinical adjudication of PAD diagnosis was performed by chart review on a random subgroup. A binary logistic regression to predict PAD was built and validated using a least absolute shrinkage and selection operator (LASSO) approach in the adjudicated patients. The algorithm was then applied to the nonsampled records to further evaluate its performance. RESULTS: The initial EHR data query using 406 diagnostic codes yielded 15,406 patients. Overall, 2500 patients were randomly selected for ground truth PAD status adjudication. In the end, 108 code flags remained after removing rarely- and never-used codes. We entered these code flags plus administrative encounter, imaging, procedure, and specialist flags into a LASSO model. The area under the curve for this model was 0.862. CONCLUSIONS: The algorithm we constructed has two main advantages over other approaches to the identification of patients with PAD. First, it was derived from a broad population of patients with many different PAD manifestations and treatment pathways across a large health system. Second, our model does not rely on clinical notes and can be applied in situations in which only administrative billing data (eg, large administrative data sets) are available. A combination of diagnosis codes and administrative flags can accurately identify patients with PAD in large cohorts.