Health Digital Twins in Life Science and Health Care Innovation.

Health digital twins (HDTs) are virtual representations of real individuals that can be used to simulate human physiology, disease, and drug effects. HDTs can be used to improve drug discovery and development by providing a data-driven approach to inform target selection, drug delivery, and design of clinical trials. HDTs also offer new applications into precision therapies and clinical decision making. The deployment of HDTs at scale could bring a precision approach to public health monitoring and intervention. Next steps include challenges such as addressing socioeconomic barriers and ensuring the representativeness of the technology based on the training and validation data sets. Governance and regulation of HDT technology are still in the early stages.

The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction.

BACKGROUND: Autologous fat transfer in the form of lipoaspirates for the reconstruction of the breast after breast cancer surgery is a commonly used procedure in plastic surgery. However, concerns regarding the oncologic risk of nutrient-rich fat tissue are widely debated. Previous studies have primarily focused on studying the interaction between adipose-derived stem cells (ASCs) and breast cancer cells. METHODS: In this study, we performed a comprehensive analysis of the paracrine- and contact-based interactions between lipoaspirates, ASCs and breast cancer cell lines. An inverted flask culture method was used to study the contact-based interaction between lipoaspirates and breast cancer cells, while GFP-expressing breast cancer cell lines were generated to study the cell-cell contact interaction with ASCs. Three different human breast cancer cell lines, MCF-7, MDA-MB-231 and BT-474, were studied. We analyzed the impact of these interactions on the proliferation, cell cycle and epithelial-to-mesenchymal (EMT) transition of the breast cancer cells. RESULTS: Our results revealed that both lipoaspirates and ASCs do not increase the proliferation rate of the breast cancer cells either through paracrine- or contact-dependent interactions. We observed that lipoaspirates selectively inhibit the proliferation of MCF-7 cells in contact co-culture, driven by the retinoblastoma (Rb) protein activity mediating cell cycle arrest. Additionally, ASCs inhibited MDA-MB-231 breast cancer cell proliferation in cell-cell contact-dependent interactions. Quantitative real-time PCR revealed no significant increase in the EMT-related genes in breast cancer cells upon co-culture with ASCs. CONCLUSION: In conclusion, this study provides evidence of the non-oncogenic character of lipoaspirates and supports the safety of clinical fat grafting in breast reconstruction after oncological surgical procedures. In vivo studies in appropriate animal models and long-term post-operative clinical data from patients are essential to reach the final safety recommendations.

Head and Neck Microsurgeon Practice Patterns and Perceptions Regarding Venous Thromboembolism Prophylaxis.

BACKGROUND: Patients undergoing head and neck (H&N) microvascular reconstruction comprise a population at high risk for venous thromboembolism (VTE). Free flap and VTE thromboprophylaxis may coincide but tend to vary from surgeon to surgeon. This study identifies VTE prophylaxis patterns and perceptions among H&N microsurgeons in the United States. METHODS: An online survey on VTE prophylaxis practice patterns and perceptions was emailed to 172 H&N microsurgeons in the United States using an anonymous link. RESULTS: There were 74 respondents (43% response rate). These surgeons completed residencies in otolaryngology (59%), plastic surgery (31%), and oral maxillofacial surgery (7%). Most underwent fellowship training (95%) and have practiced at an academic center (97%) for at least 6 years (58%), performing an average of 42 ± 31 H&N free flap cases per year (range = 1-190). Most adhered to general VTE prophylaxis guidelines (69%) while 11% did not and 20% were unsure. Nearly all surgeons (99%) would provide prophylactic anticoagulation, mostly in the form of subcutaneous heparin (51%) or enoxaparin (44%); 64% additionally used aspirin, while 4% used aspirin alone. The majority of surgeons (68%) reported having postoperative VTE complications, with six surgeons (8%) reporting patient deaths due to pulmonary embolism. A third of the surgeons have encountered VTE prophylaxis-related adverse bleeding events, but most still believe that chemoprophylaxis is important for VTE prevention (92%). While 35% of surgeons were satisfied with their current practice, most would find it helpful to have official prophylactic anticoagulation guidelines specific to H&N free flap cases. CONCLUSION: The majority of microsurgeons experienced postoperative VTE complications after H&N free flap reconstruction despite the routine use of prophylactic anticoagulation. Though bleeding events are a concern, most surgeons believe chemoprophylaxis is important for VTE prevention and would welcome official guidelines specific to this high-risk population.

Has increased telehealth access during COVID-19 led to over-utilization of primary care?

Telehealth use for primary care has skyrocketed since the onset of the COVID-19 pandemic. Enthusiasts have praised this new medium of delivery as a way to increase access to care while potentially reducing spending. Over two years into the pandemic, the question of whether telehealth will lead to an increase in primary care utilization and spending has been met with contradictory answers. Some evidence suggests that telehealth may be used as an addition to in-person visits. Others like Dixit et al. have found that telehealth can actually substitute for in-person care rather than contribute to overutilization. As telehealth continues to evolve, outcomes, utilization, and quality of care should be closely monitored.

Intelligent risk prediction in public health using wearable device data.

The importance of infection risk prediction as a key public health measure has only been underscored by the COVID-19 pandemic. In a recent study, researchers use machine learning to develop an algorithm that predicts the risk of COVID-19 infection, by combining biometric data from wearable devices like Fitbit, with electronic symptom surveys. In doing so, they aim to increase the efficiency of test allocation when tracking disease spread in resource-limited settings. But the implications of technology that applies data from wearables stretch far beyond infection monitoring into healthcare delivery and research. The adoption and implementation of this type of technology will depend on regulation, impact on patient outcomes, and cost savings.

Health digital twins as tools for precision medicine: Considerations for computation, implementation, and regulation.

Health digital twins are defined as virtual representations ("digital twin") of patients ("physical twin") that are generated from multimodal patient data, population data, and real-time updates on patient and environmental variables. With appropriate use, HDTs can model random perturbations on the digital twin to gain insight into the expected behavior of the physical twin-offering groundbreaking applications in precision medicine, clinical trials, and public health. Main considerations for translating HDT research into clinical practice include computational requirements, clinical implementation, as well as data governance, and product oversight.

Watching Parkinson's disease with wrist-based sensors.

Parkinson's disease (PD) lacks sensitive, objective, and reliable measures for disease progression and response. This presents a challenge for clinical trials given the multifaceted and fluctuating nature of PD symptoms. Innovations in digital health and wearable sensors promise to more precisely measure aspects of patient function and well-being. Beyond research trials, digital biomarkers and clinical outcome assessments may someday support clinician-initiated or closed-loop treatment adjustments. A recent study from Verily Life Sciences presents results for a smartwatch-based motor exam intended to accelerate the development and evaluation of therapies for PD.

Defining digital surgery for the future.

Innovations in robotics, virtual and augmented reality, and artificial intelligence are being rapidly adopted as tools of "digital surgery". Despite its quickly emerging role, digital surgery is not well understood. A recent study defines the term itself, and then specifies ethical issues specific to the field. These include privacy and public trust, consent, and litigation.

Leveraging reimbursement strategies to guide value-based adoption and utilization of medical AI.

With the increasing number of FDA-approved artificial intelligence (AI) systems, the financing of these technologies has become a primary gatekeeper to mass clinical adoption. Reimbursement models adapted for current payment schemes, including per-use rates, are feasible for early AI products. Alternative and complementary models may offer future payment options for value-based AI. A successful reimbursement strategy will align interests across stakeholders to guide value-based and cost-effective improvements to care.

Adipose Stem Cells Enhance Nerve Regeneration and Muscle Function in a Peroneal Nerve Ablation Model.

Severe peripheral nerve injuries have devastating consequences on the quality of life in affected patients, and they represent a significant unmet medical need. Destruction of nerve fibers results in denervation of targeted muscles, which, subsequently, undergo progressive atrophy and loss of function. Timely restoration of neural innervation to muscle fibers is crucial to the preservation of muscle homeostasis and function. The goal of this study was to evaluate the impact of addition of adipose stem cells (ASCs) to polycaprolactone (PCL) nerve conduit guides on peripheral nerve repair and functional muscle recovery in the setting of a critical size nerve defect. To this end, peripheral nerve injury was created by surgically ablating 6 mm of the common peroneal nerve in a rat model. A PCL nerve guide, filled with ASCs and/or poloxamer hydrogel, was sutured to the nerve ends. Negative and positive controls included nerve ablation only (no repair), and reversed polarity autograft nerve implant, respectively. Tibialis anterior (TA) muscle function was assessed at 4, 8, and 12 weeks postinjury, and nerve and muscle tissue was retrieved at the 12-week terminal time point. Inclusion of ASCs in the PCL nerve guide elicited statistically significant time-dependent increases in functional recovery (contraction) after denervation; ∼25% higher than observed in acellular (poloxamer-filled) implants and indistinguishable from autograft implants, respectively, at 12 weeks postinjury (p < 0.05, n = 7-8 in each group). Analysis of single muscle fiber cross-sectional area (CSA) revealed that ASC-based treatment of nerve injury provided a better recapitulation of the overall distribution of muscle fiber CSAs observed in the contralateral TA muscle of uninjured limbs. In addition, the presence of ASCs was associated with improved features of re-innervation distal to the defect, with respect to neurofilament and S100 (Schwann cell marker) expression. In conclusion, these initial studies indicate significant benefits of inclusion of ASCs to the rate and magnitude of both peripheral nerve regeneration and functional recovery of muscle contraction, to levels equivalent to autograft implantation. These findings have important implications to improved nerve repair, and they provide input for future work directed to restoration of nerve and muscle function after polytraumatic injury. Impact Statement This works explores the application of adipose stem cells (ASCs) for peripheral nerve regeneration in a rat model. Herein, we demonstrate that the addition of ASCs in poloxamer-filled PCL nerve guide conduits impacts nerve regeneration and recovery of muscle function, to levels equivalent to autograft implantation, which is considered to be the current gold standard treatment. This study builds on the importance of a timely restoration of innervation to muscle fibers for preservation of muscle homeostasis, and it will provide input for future work aiming at restoring nerve and muscle function after polytraumatic injury.

Systemic Contact Dermatitis: A review.

Systemic contact dermatitis (SCD) is a broad category of syndromes characterized by a variety of clinical presentations and offending agents. There exists general consensus that SCD and its subcategories are due to type IV (and less commonly type III) hypersensitivity reactions, in which a previously sensitized individual undergoes a cytotoxic CD8+ T-cell response upon systemic reexposure. There are various linked allergens, generally grouped into plants, foods, metals, and medications. Diagnosis is relatively successful through epicutaneous patch testing utilizing standard series and customized panels. Treatment consists of allergen avoidance diets as determined by clinical history and patch testing.