Comparative transcriptional and functional profiling defines conserved programs of intestinal DC differentiation in humans and mice.

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterized human gut DC populations and defined their relationship to previously studied human and mouse DCs. CD103(+)Sirpα(-) DCs were related to human blood CD141(+) DCs and to mouse intestinal CD103(+)CD11b(-) DCs and expressed markers of cross-presenting DCs. CD103(+)Sirpα(+) DCs aligned with human blood CD1c(+) DCs and mouse intestinal CD103(+)CD11b(+) DCs and supported the induction of regulatory T cells. Both CD103(+) DC subsets induced the TH17 subset of helper T cells, while CD103(-)Sirpα(+) DCs induced the TH1 subset of helper T cells. Comparative analysis of transcriptomes revealed conserved transcriptional programs among CD103(+) DC subsets and identified a selective role for the transcriptional repressors Bcl-6 and Blimp-1 in the specification of CD103(+)CD11b(-) DCs and intestinal CD103(+)CD11b(+) DCs, respectively. Our results highlight evolutionarily conserved and divergent programming of intestinal DCs.

Spin-enhanced nanodiamond biosensing for ultrasensitive diagnostics.

The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity5 and frequency-domain analysis6 to separate the signal from background autofluorescence7, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10-19 molar for a biotin-avidin model, 105 times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.

Probabilistic Interpolation of Quantum Rotation Angles.

Quantum computing requires a universal set of gate operations; regarding gates as rotations, any rotation angle must be possible. However a real device may only be capable of B bits of resolution, i.e., it might support only 2^{B} possible variants of a given physical gate. Naive discretization of an algorithm's gates to the nearest available options causes coherent errors, while decomposing an impermissible gate into several allowed operations increases circuit depth. Conversely, demanding higher B can greatly complexify hardware. Here, we explore an alternative: probabilistic angle interpolation (PAI). This effectively implements any desired, continuously parametrized rotation by randomly choosing one of three discretized gate settings and postprocessing individual circuit outputs. The approach is particularly relevant for near-term applications where one would in any case average over many runs of circuit executions to estimate expected values. While PAI increases that sampling cost, we prove that (a) the approach is optimal in the sense that PAI achieves the least possible overhead and (b) the overhead is remarkably modest even with thousands of parametrized gates and only seven bits of resolution available. This is a profound relaxation of engineering requirements for first generation quantum computers where even 5-6 bits of resolution may suffice and, as we demonstrate, the approach is many orders of magnitude more efficient than prior techniques. Moreover we conclude that, even for more mature late noisy intermediate-scale quantum era hardware, no more than nine bits will be necessary.

Ventral hernia repair with permanent mesh for non-Hispanic black versus white patients: access and post-operative outcomes in the era of robotic surgery.

BACKGROUND: Robotic ventral hernia surgery may provide better patient outcomes. Whether it is provided equitably based on race remains unknown. METHODS: We examined whether patients from the Abdominal Core Health Quality Collaborative who were Black had equitable access to robotic surgery for ventral hernia repair with permanent mesh compared to white counterparts from 2013 to 2023. We performed propensity-score matching to address confounding and then chi-squared testing to examine access to robotic, laparoscopic, and open approaches. Secondary outcomes included 30-day readmissions, complications, and death and 1- and 2-year hernia recurrence and quality of life measured by HerQLes Summary and PROMIS Pain T-Scores analyzed with chi-squared, Fisher exact, and Wilcoxon testing. RESULTS: 2397 patients identified as Black, and 21,900 identified as white. Our propensity-score matched cohort included 2374 Black patients and 7122 white. Black and white groups had the same rates of laparoscopy (15% vs 15%). Patients who identified as Black were more likely to undergo robotic surgery (36% vs 32%). Open approach was 49% for Black and 53% for white (p = 0.005). For 30-day complications, we found Black patients were more likely to experience reoperation (2% vs 1%, p = 0.005) and less likely surgical site infection (1% vs 2%, p < 0.001). Hernia recurrence scores and perceived abdominal health based on HerQLes were not statistically significantly different. At 2 years, absolute reported T-Scores were higher for Black patients (median 40 (IQR 31-49) vs 36 (31-46), p = 0.031). CONCLUSIONS: This is the first large-scale study examining access to robotic surgery, complications, and quality of life measures. We found patients who identified as Black were more likely than white counterparts to undergo robotic surgery, but they were more likely to require reoperation and had higher pain scores. Our data suggest equitable access still may not translate to equitable patient outcomes.

Veno-venous ECLS rescue for a heart transplant recipient with COVID-19, a case report.

The potential for increased rates of morbidity of SARS-CoV-2 within immunocompromised populations has been of concern since the pandemic's onset. Transplant providers and patients can face particularly challenging situations, in the current settings as data continues to emerge for the prevention and treatment of the immunocompromised subpopulation. This case report details a patient 9-months post orthotopic heart transplant that developed SARS-CoV-2 infection despite two prior doses of the Pfizer-BioNtech COVID-19 vaccine, and had successful rescue from refractory hypoxemia with veno-venous extracorporeal membrane oxygenation (VV ECLS).

Generation of functional human thymic cells from induced pluripotent stem cells.

BACKGROUND: The thymus is a glandular organ that is essential for the formation of the adaptive immune system by educating developing T cells. The thymus is most active during childhood and involutes around the time of adolescence, resulting in a severe reduction or absence of naive T-cell output. The ability to generate a patient-derived human thymus would provide an attractive research platform and enable the development of novel cell therapies. OBJECTIVES: This study sought to systematically evaluate signaling pathways to develop a refined direct differentiation protocol that generates patient-derived thymic epithelial progenitor cells from multiple induced pluripotent stem cells (iPSCs) that can further differentiate into functional patient-derived thymic epithelial cells on transplantation into athymic nude mice. METHODS: Directed differentiation of iPSC generated TEPs that were transplanted into nude mice. Between 14 and 19 weeks posttransplantation, grafts were removed and analyzed by flow cytometry, quantitative PCR, bulk RNA sequencing, and single-cell RNA sequencing for markers of thymic-cell and T-cell development. RESULTS: A direct differentiation protocol that allows the generation of patient-derived thymic epithelial progenitor cells from multiple iPSC lines is described. On transplantation into athymic nude mice, patient-derived thymic epithelial progenitor cells further differentiate into functional patient-derived thymic epithelial cells that can facilitate the development of T cells. Single-cell RNA sequencing analysis of iPSC-derived grafts shows characteristic thymic subpopulations and patient-derived thymic epithelial cell populations that are indistinguishable from TECs present in primary neonatal thymus tissue. CONCLUSIONS: These findings provide important insights and resources for researchers focusing on human thymus biology.

Near-Surface

Impurity spins in crystal matrices are promising components in quantum technologies, particularly if they can maintain their spin properties when close to surfaces and material interfaces. Here, we investigate an attractive candidate for microwave-domain applications, the spins of group-VI ^{125}Te^{+} donors implanted into natural Si at depths as shallow as 20 nm. We show that surface band bending can be used to ionize such near-surface Te to spin-active Te^{+} state, and that optical illumination can be used further to control the Te donor charge state. We examine spin activation yield, spin linewidth, and relaxation (T_{1}) and coherence times (T_{2}) and show how a zero-field 3.5 GHz "clock transition" extends spin coherence times to over 1 ms, which is about an order of magnitude longer than other near-surface spin systems.

Successful recovery with venovenous ECMO for ARDS after LVAD HeartMate 3 implantation: A case report.

Acute respiratory distress syndrome (ARDS) following left ventricular assist device (LVAD) implantation is a rare complication. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is used as a treatment for severe ARDS and pneumonia. We report the successful use of VV ECMO for ARDS Klebsiella pneumonia following urgent LVAD HeartMate 3 implantation.

Impella 5.0: An intermediate strategy for bridging a patient from infected durable LVAD to cardiac transplant.

Cardiac transplant remains the gold-standard treatment for end-stage heart failure more than 50 years after the procedure was first pioneered. The number of transplant operations performed annually has been limited by the global imbalance of donor organs to recipients. This imbalance helped fuel the development of left ventricular assist devices (LVADs) first as a bridge to cardiac transplant and subsequently as destination therapy. Driveline infection is one of several problems that continue to plague LVADs through several generations of improvement. We present a patient with an infected LVAD driveline exit site that progressed to mediastinitis, pericardial and pump infection. The device was explanted, and the patient supported with an axillary Impella 5.0 as a bridge until the time of transplant. An Impella 5.0 (or 5.5) can be used as an intermediate tool to be able to explant an infected LVAD, with mediastinitis, allowing the patient to clear the infection, and prepare the patient for transplant free of infection. METHODS: The patient consented to the study and case report. The patient signed an informed consent and permission for publication.

Correlating actual one-year weight loss with predicted weight loss by the MBSAQIP: bariatric surgical risk/benefit calculator.

BACKGROUND: The American Society for Metabolic and Bariatric Surgery has released a Bariatric Surgical Risk/Benefit Calculator, an online tool with which patients and providers can input patient preoperative information and predict their 1-year weight loss. We seek to validate our institutional data with the national database and investigated patient factors that influence lack of treatment effect after bariatric surgery. MATERIALS AND METHODS: A retrospective review of all prospectively collected data of bariatric surgeries performed at Yale New Haven Hospital from 2017 to 2018 was conducted. By entering data into the MBSAQIP Calculator, the 1-year predicted Body Mass Index was calculated and compared to the actual weight loss. Statistical analysis was performed using an unpaired t-test with Welch's correction (Prism 8, GraphPad). RESULTS: The average difference between the actual and predicted weight loss at 1-year for 327 patients was 3.6 BMI points. When the actual weight loss was compared to predicted BMI at 1 year, a high correlation was found (R = 0.6, P = 0.003). We examined the outliers with a comparison of weight loss for those patients who's BMI fell within 5 points of the predicted versus those whose BMI recorded above 5. It was discovered those patients who had higher than 5 BMI points than predicted, had higher preoperative BMI (46.1 vs 43.6, P = 0.008). CONCLUSIONS: The MBSAQIP calculator is a useful tool to guide surgeons with decision-making and informed consent. Our institution's 1-year weight loss data correlated closely with that predicted. From the outliers, we found that patients who did not meet the predicted weight loss had significantly higher preoperative BMI. This may alter preoperative discussions with class 3 or over obese patients regarding expected weight loss and warrant investigations with the national database to develop modifications of the calculator.

Association between preoperative gonioscopic status and postoperative glaucoma after phacoemulsification in dogs: A retrospective cohort study of 505 eyes.

OBJECTIVE: To assess whether preoperative gonioscopy status is associated with the development of postoperative glaucoma after phacoemulsification. PROCEDURE: Eligible dogs and eyes were selected from medical records (2007-2017), and each eye was classified as having normal or abnormal gonioscopy status. Records were examined for postoperative glaucoma, and data were collected for baseline variables including patient signalment, surgical factors, and pre, intra, and postoperative medications. RESULTS: Of 305 dogs (505 eyes) selected for review in this study, 111 dogs (163 eyes) had abnormal gonioscopy findings, and 194 dogs (342 eyes) had normal gonioscopy findings. Postoperative glaucoma occurred in 24% (39/163) of eyes with abnormal gonioscopy and in 14% (49/342) eyes with normal gonioscopy. Eyes with abnormal gonioscopy status were at higher risk of postoperative glaucoma compared to normal eyes (P = .025). There was no important confounding due to the numerous baseline variables summarised above. Regardless of gonioscopy status, the risk of glaucoma was highest during the first 2 months after surgery. CONCLUSIONS: Eyes with abnormal gonioscopy findings are at increased risk of postoperative glaucoma compared with eyes with normal gonioscopy findings. Gonioscopy is recommended as a part of presurgical assessment in all dogs prior to phacoemulsification. Further study is needed to assess whether the incidence of postoperative glaucoma can be reduced by increased monitoring or altered treatment protocols in cases that are known to have abnormal gonioscopy findings prior to cataract surgery.

Remote Capacitive Sensing in Two-Dimensional Quantum-Dot Arrays.

We investigate gate-induced quantum dots in silicon nanowire field-effect transistors fabricated using a foundry-compatible fully depleted silicon-on-insulator (FD-SOI) process. A series of split gates wrapped over the silicon nanowire naturally produces a 2 × n bilinear array of quantum dots along a single nanowire. We begin by studying the capacitive coupling of quantum dots within such a 2 × 2 array and then show how such couplings can be extended across two parallel silicon nanowires coupled together by shared, electrically isolated, "floating" electrodes. With one quantum dot operating as a single-electron-box sensor, the floating gate serves to enhance the charge sensitivity range, enabling it to detect charge state transitions in a separate silicon nanowire. By comparing measurements from multiple devices, we illustrate the impact of the floating gate by quantifying both the charge sensitivity decay as a function of dot-sensor separation and configuration within the dual-nanowire structure.

Development and Evaluation of a Novel Instrument to Measure Severity of Intraoperative Events Using Video Data.

OBJECTIVE: To develop and evaluate a novel instrument to measure SEVERE processes using video data. BACKGROUND: Surgical video data can serve an important role in understanding the relationship between intraoperative events and postoperative outcomes. However, a standard tool to measure severity of intraoperative events is not yet available. METHODS: Items to be included in the instrument were identified through literature and video reviews. A committee of experts guided item reduction, including pilot tests and revisions, and determined weighted scores. Content validity was evaluated using a validated sensibility questionnaire. Inter-rater reliability was assessed by calculating intraclass correlation coefficient. Construct validity was evaluated on a sample of 120 patients who underwent laparoscopic Roux-en-Y gastric bypass procedure, in which comprehensive video data was obtained. RESULTS: SEVERE index measures severity of 5 event types using ordinal scales. Each intraoperative event is given a weighted score out of 10. Inter-rater reliability was excellent [0.87 (95%-confidence interval, 0.77-0.92)]. In a sample of consecutive 120 patients undergoing gastric bypass procedures, a median of 12 events [interquartile range (IQR) 9-18] occurred per patient and bleeding was the most frequent type (median 10, IQR 7-14). The median SEVERE score per case was 11.3 (IQR 8.3-16.9). In risk-adjusted multivariable regression models, history of previous abdominal surgery (P = 0.02) and body mass index (P = 0.005) were associated with SEVERE scores, demonstrating construct validity evidence. CONCLUSION: The SEVERE index may prove to be a useful instrument in identifying patients with high risk of developing postoperative complications.

Results of COVID-minimal Surgical Pathway During Surge-phase of COVID-19 Pandemic.

OBJECTIVE: The outcomes of patients treated on the COVID-minimal pathway were evaluated during a period of surging COVID-19 hospital admissions, to determine the safety of continuing to perform urgent operations during the pandemic. SUMMARY OF BACKGROUND DATA: Crucial treatments were delayed for many patients during the COVID-19 pandemic, over concerns for hospital-acquired COVID-19 infections. To protect cancer patients whose survival depended on timely surgery, a "COVID-minimal pathway" was created. METHODS: Patients who underwent a surgical procedure on the pathway between April and May 2020 were evaluated. The "COVID-minimal surgical pathway" consisted of: (A) evolving best-practices in COVID-19 transmission-reduction, (B) screening patients and staff, (C) preoperative COVID-19 patient testing, (D) isolating pathway patients from COVID-19 patients. Patient status through 2 weeks from discharge was determined as a reflection of hospital-acquired COVID-19 infections. RESULTS: After implementation, pathway screening processes excluded 7 COVID-19-positive people from interacting with pathway (4 staff and 3 patients). Overall, 122 patients underwent 125 procedures on pathway, yielding 83 admissions (42 outpatient procedures). The median age was 64 (56-79) and 57% of patients were female. The most common surgical indications were cancer affecting the uterus, genitourinary tract, colon, lung or head and neck. The median length of admission was 3 days (1-6). Repeat COVID-19 testing performed on 27 patients (all negative), including 9 patients evaluated in an emergency room and 8 readmitted patients. In the postoperative period, no patient developed a COVID-19 infection. CONCLUSIONS: A COVID-minimal pathway comprised of physical space modifications and operational changes may allow urgent cancer treatment to safely continue during the COVID-19 pandemic, even during the surge-phase.

Self-Stimulated Pulse Echo Trains from Inhomogeneously Broadened Spin Ensembles.

We show experimentally and describe theoretically how a conventional magnetic resonance Hahn echo sequence can lead to a self-stimulated pulse echo train when an inhomogeneously broadened spin ensemble is coupled to a resonator. Effective strong coupling between the subsystems assures that the first Hahn echo can act as a refocusing pulse on the spins, leading to self-stimulated secondary echoes. Within the framework of mean field theory, we show that this process can continue multiple times leading to a train of echoes. We introduce an analytical model that explains the shape of the first echo and numerical results that account well for the experimentally observed shape and strength of the echo train and provides insights into the collective effects involved.

Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting.

This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.

On the susceptibility and vulnerability of agricultural value chains to COVID-19.

In the context of the major potential impacts of COVID-19 on agriculture and agricultural trade in developing countries, this Viewpoint discusses the advantages of adopting a conceptual framework previously used to discuss the impact of the HIV/AIDS pandemic on agriculture and rural livelihoods. The framework is made up of two pairs of linked concepts: 1) Susceptibility or the chance of an individual becoming infected; 2) Resistance or the ability of an individual to avoid infection; 3) Vulnerability or the likelihood of significant impacts occurring at individual, household or community level; and 4) Resilience: the active responses that enable people to avoid the worst impacts of an epidemic at different levels or to recover faster to a level accepted as normal. This framework allows the clear formulation of key questions for COVID-19: factors in the labor process itself that make people more or less susceptible; broader socio-economic and biophysical determinants of susceptibility; factors that make farm households, food enterprises and value chains more vulnerable to the impacts of the pandemic; and aspects of COVID-19 responses by governments and the private sector that might increase vulnerability. Brief examples of susceptibility of value chain operations and of their vulnerability to COVID-19 lockdown measures are given. A focus on resistance and resilience encourages investigation of local-level responses by communities and NGOs, which with appropriate monitoring and learning could be scaled up.

Wnt signaling dynamics in head and neck squamous cell cancer tumor-stroma interactions.

Wnt pathway activation maintains the cancer stem cell (CSC) phenotype and promotes tumor progression, making it an attractive target for anti-cancer therapy. Wnt signaling at the tumor and tumor microenvironment (TME) front have not been investigated in depth in head and neck squamous cell carcinoma (HNSCC). In a cohort of 48 HNSCCs, increased Wnt signaling, including Wnt genes (AXIN2, LGR6, WISP1) and stem cell factors (RET, SOX5, KIT), were associated with a more advanced clinical stage. Key Wnt pathway proteins were most abundant at the cancer epithelial-stromal boundary. To investigate these observations, we generated three pairs of cancer-cancer associated fibroblast (CAF) cell lines derived from the same HNSCC patients. 3D co-culture of cancer spheres and CAFs mimicked these in vivo interactions, and using these we observed increased expression of Wnt genes (eg, WNT3A, WNT7A, WNT16) in both compartments. Of these Wnt ligands, we found Wnt3a, and less consistently Wnt16, activated Wnt signaling in both cancer cells and CAFs. Wnt activation increased CSC characteristics like sphere formation and invasiveness, which was further regulated by the presence of CAFs. Time lapse microscopy also revealed preferential Wnt activation of cancer cells. Wnt inhibitors, OMP-18R5 and OMP-54F28, significantly reduced growth of HNSCC patient-derived xenografts and suppressed Wnt activation at the tumor epithelial-stromal boundary. Taken together, our findings suggest that Wnt signaling is initiated in cancer cells which then activate CAFs, and in turn perpetuate a paracrine signaling loop. This suggests that targeting Wnt signaling in the TME is essential.

The Impact of Ethnicity on Metabolic Outcomes After Bariatric Surgery.

BACKGROUND: Previous studies have demonstrated that ethnic minority patients experience significant metabolic improvements after bariatric surgery but less so than non-Hispanic whites. Previous research has primarily investigated differences between non-Hispanic white and black patients. Thus, there remains a need to assess differences in diabetic outcomes among other ethnic groups, including Hispanic and Asian patient populations. MATERIALS AND METHODS: A retrospective analysis including 650 patients with type II diabetes mellitus (T2DM), who underwent either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy (LSG) procedures, was conducted to understand ethnic disparities in diabetic metabolic outcomes, including weight loss, serum concentrations of glucose, fasting insulin, and hemoglobin A1c (HbA1c). Data were from a single academic institution in northern California. Ethnicity data were self reported. T2DM was defined as having one or more of the following criteria: a fasting glucose concentration >125 mg/dL, HbA1c >6.5%, or taking one or more diabetic oral medications. Diabetes resolution was defined as having a fasting glucose <125 mg/dL, a HbA1c <6.5%, and discontinuation of diabetic oral medications. RESULTS: Within-group comparisons in all ethnic groups showed significant reductions in body mass index, body weight, fasting insulin, fasting glucose, and HbA1c by 6 mo, but Asian patients did not experience further improvement in body mass index or diabetic outcomes at the 12-mo visit. Black patients did not experience additional reductions in fasting insulin or glucose between the 6- and 12-mo visit and their HbA1c significantly increased. Nevertheless, the majority of patients had diabetes remission by the 12-mo postoperative visit (98%, 97%, 98%, and 92% in Non-Hispanic, Hispanic, black, and Asian, respectively). CONCLUSIONS: The results of this study demonstrate that bariatric surgery serves as an effective treatment for normalizing glucose metabolism among patients with T2DM. However, this study suggests that additional interventions that support black and Asian patients with achieving similar metabolic outcomes as non-Hispanic white and Hispanic patients warrant further consideration.

Using Machine Learning Applied to Real-World Healthcare Data for Predictive Analytics: An Applied Example in Bariatric Surgery.

OBJECTIVES: Laparoscopic metabolic surgery (MxS) can lead to remission of type 2 diabetes (T2D); however, treatment response to MxS can be heterogeneous. Here, we demonstrate an open-source predictive analytics platform that applies machine-learning techniques to a common data model; we develop and validate a predictive model of antihyperglycemic medication cessation (validated proxy for A1c control) in patients with treated T2D who underwent MxS. METHODS: We selected patients meeting the following criteria in 2 large US healthcare claims databases (Truven Health MarketScan Commercial [CCAE]; Optum Clinformatics [Optum]): underwent MxS between January 1, 2007, to October 1, 2013 (first = index); aged ≥18 years; continuous enrollment 180 days pre-index (baseline) to 730 days postindex; baseline T2D diagnosis and treatment. The outcome was no antihyperglycemic medication treatment from 365 to 730 days after MxS. A regularized logistic regression model was trained using the following candidate predictor categories measured at baseline: demographics, conditions, medications, measurements, and procedures. A 75% to 25% split of the CCAE group was used for model training and testing; the Optum group was used for external validation. RESULTS: 13 050 (CCAE) and 3477 (Optum) patients met the study inclusion criteria. Antihyperglycemic medication cessation rates were 72.9% (CCAE) and 70.8% (Optum). The model possessed good internal discriminative accuracy (area under the curve [AUC] = 0.778 [95% CI = 0.761-0.795] in CCAE test set N = 3527) and transportability (external AUC = 0.759 [95% CI = 0.741-0.777] in Optum N = 3477). CONCLUSION: The application of machine learning techniques to real-world healthcare data can yield useful predictive models to assist patient selection. In future practice, establishment of prerequisite technological infrastructure will be needed to implement such models for real-world decision support.