Cell-Based Therapies Induce Tolerance of Vascularized Composite Allotransplants: A Systematic Review.

INTRODUCTION: Vascularized composite allotransplantation (VCA) is the transplantation of multiple tissue types as a solution for devastating injuries. Despite the highly encouraging functional outcomes of VCA, the consequences of long-term immunosuppression remain the main obstacle in its application. In this review, we provide researchers and surgeons with a summary of the latest advances in the field of cell-based therapies for VCA tolerance. METHODS: Four electronic databases were searched: PubMed, Scopus, Cumulative Index to Nursing and Allied Health Literature , and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as the basis of our organization. RESULTS: Hematopoietic stem cells prolonged VCA survival. A combination of immature dendritic cells and tacrolimus was superior to tacrolimus alone. T cell Ig domain and mucin domain modified mature dendritic cells increased VCA tolerance. Bone marrow-derived mesenchymal stem cells prolonged survival of VCAs. A combination of adipose-derived mesenchymal stem cells, cytotoxic T-lymphocyte antigen 4 immunoglobulin, and antilymphocyte serum significantly improved VCA tolerance. Ex-vivo allotransplant perfusion with recipient's bone marrow-derived mesenchymal stem cells increased VCA survival. Recipient's adipose-derived mesenchymal stem cells and systemic immunosuppression prolonged VCA survival more than any of those agents alone. Additionally, a combination of peripheral blood mononuclear cells shortly incubated in mitomycin and cyclosporine significantly improved VCA survival. Finally, a combination of donor recipient chimeric cells, anti-αß-T cell receptor (TCR), and cyclosporine significantly prolonged VCA tolerance. CONCLUSIONS: Evidence from animal studies shows that cell-based therapies can prolong survival of VCAs. However, there remain many obstacles for these therapies, and they require rigorous clinical research given the rarity of the subjects and the complexity of the therapies. The major limitations of cell-based therapies include the need for conditioning with immunosuppressive drugs and radiation, causing significant toxicity. Safety concerns also persist as most research is on animal models. While completely replacing traditional immunosuppression with cell-based methods is unlikely soon, these therapies could reduce the need for high doses of immunosuppressants and improve VCA tolerance.

The impact of moderate aortic stenosis in acute myocardial infarction: A multicenter retrospective study.

BACKGROUND: Aortic stenosis (AS) is associated with myocardial ischemia through different mechanisms and may impair coronary arterial flow. However, data on the impact of moderate AS in patients with acute myocardial infarction (MI) is limited. AIMS: This study aimed to investigate the impact of moderate AS in patients presenting with acute myocardial infarction (MI). METHODS: We conducted a retrospective analysis of all patients who presented with acute MI to all Mayo Clinic hospitals, using the Enterprise Mayo PCI Database from 2005 to 2016. Patients were stratified into two groups: moderate AS and mild/no AS. The primary outcome was all cause mortality. RESULTS: The moderate AS group included 183 (13.3%) patients, and the mild/no AS group included 1190 (86.7%) patients. During hospitalization, there was no difference between both groups in mortality. Patients with moderate AS had higher in-hospital congestive heart failure (CHF) (8.2% vs. 4.4%, p = 0.025) compared with mild/no AS patients. At 1-year follow-up, patients with moderate AS had higher mortality (23.9% vs. 8.1%, p < 0.001) and higher CHF hospitalization (8.3% vs. 3.7%, p = 0.028). In multivariate analysis, moderate AS was associated with higher mortality at 1-year (odds ratio 2.4, 95% confidence interval [1.4-4.1], p = 0.002). In subgroup analyses, moderate AS increased all-cause mortality in STEMI and NSTEMI patients. CONCLUSION: The presence of moderate AS in acute MI patients was associated with worse clinical outcomes during hospitalization and at 1-year follow-up. These unfavorable outcomes highlight the need for a close follow-up of these patients and for timely therapeutic strategies to best manage these coexisting conditions.

High Satisfaction With a Virtual Assistant for Plastic Surgery Frequently Asked Questions.

BACKGROUND: Most of a surgeon's office time is dedicated to patient education, preventing an appropriate patient-physician relationship. Telephone-accessed artificial intelligent virtual assistants (AIVAs) that simulate a human conversation and answer preoperative frequently asked questions (FAQs) can be effective solutions to this matter. An AIVA capable of answering preoperative plastic surgery-related FAQs has previously been described by the authors. OBJECTIVES: The aim of this paper was to determine patients' perception and satisfaction with an AIVA. METHODS: Twenty-six adult patients from a plastic surgery service answered a 3-part survey consisting of: (1) an evaluation of the answers' correctness, (2) their agreement with the feasibility, usefulness, and future uses of the AIVA, and (3) a section on comments. The first part made it possible to measure the system's accuracy, and the second to evaluate perception and satisfaction. The data were analyzed with Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA). RESULTS: The AIVA correctly answered the patients' questions 98.5% of the time, and the topic with the lowest accuracy was "nausea." Additionally, 88% of patients agreed with the statements of the second part of the survey. Thus, the patients' perception was positive and overall satisfaction with the AIVA was high. Patients agreed the least with using the AIVA to select their surgical procedure. The comments provided improvement areas for subsequent stages of the project. CONCLUSIONS: The results show that patients were satisfied and expressed a positive experience with using the AIVA to answer plastic surgery FAQs before surgery. The system is also highly accurate.

Simulation and Artificial Intelligence in Rhinoplasty: A Systematic Review.

BACKGROUND: Rhinoplasty is one of the most popular cosmetic procedures. The complexity of the nasal structure and the substantial aesthetic and functional impact of the operation make rhinoplasty very challenging. The past few years have witnessed an increasing implementation of artificial intelligence (AI) and simulation systems into plastic surgery practice. This review explores the potential uses of AI and simulation models in rhinoplasty. METHODS: Five electronic databases were searched: PubMed, CINAHL, EMBASE, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as our basis of organization. RESULTS: Several simulation models were described to predict the nasal shape that aesthetically matches the patient's face, indicate the implant size in augmentation rhinoplasty and construct three-dimensional (3D) facial images from two-dimensional images. Machine learning was used to learn surgeons' rhinoplasty styles and accurately simulate the outcomes. Deep learning was used to predict rhinoplasty status accurately and analyze the factors associated with increased facial attractiveness after rhinoplasty. Finally, a deep learning model was used to predict patients' age before and after rhinoplasty proving that the procedure made the patients look younger. CONCLUSION: 3D simulation models and AI models can revolutionalize the practice of functional and aesthetic rhinoplasty. Simulation systems can be beneficial in preoperative planning, intra-operative decision making, and postoperative evaluation. In addition, AI models can be trained to carry out tasks that are either challenging or time-consuming for surgeons. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Machine Learning Algorithms Predict Long-Term Postoperative Opioid Misuse: A Systematic Review.

INTRODUCTION: A steadily rising opioid pandemic has left the US suffering significant social, economic, and health crises. Machine learning (ML) domains have been utilized to predict prolonged postoperative opioid (PPO) use. This systematic review aims to compile all up-to-date studies addressing such algorithms' use in clinical practice. METHODS: We searched PubMed/MEDLINE, EMBASE, CINAHL, and Web of Science using the keywords "machine learning," "opioid," and "prediction." The results were limited to human studies with full-text availability in English. We included all peer-reviewed journal articles that addressed an ML model to predict PPO use by adult patients. RESULTS: Fifteen studies were included with a sample size ranging from 381 to 112898, primarily orthopedic-surgery-related. Most authors define a prolonged misuse of opioids if it extends beyond 90 days postoperatively. Input variables ranged from 9 to 23 and were primarily preoperative. Most studies developed and tested at least two algorithms and then enhanced the best-performing model for use retrospectively on electronic medical records. The best-performing models were decision-tree-based boosting algorithms in 5 studies with AUC ranging from .81 to .66 and Brier scores ranging from .073 to .13, followed second by logistic regression classifiers in 5 studies. The topmost contributing variable was preoperative opioid use, followed by depression and antidepressant use, age, and use of instrumentation. CONCLUSIONS: ML algorithms have demonstrated promising potential as a decision-supportive tool in predicting prolonged opioid use in post-surgical patients. Further validation studies would allow for their confident incorporation into daily clinical practice.

The relative risk of ischemic cerebrovascular accident in patients with Von Willebrand disease.

Cerebrovascular accident (CVA) is one of the leading causes of death in the United States. Von Willebrand factor plays an important role in platelet activation and adhesion. It remains unclear whether Von Willebrand disease (vWD) is associated with a decreased risk of developing CVA. The study aimed to compare the relative risk (RR) of CVA in patients with and without vWD. We queried the National Inpatient Sample from 2009 to 2014 for discharge data and records for vWD and CVA using International Classification of Diseases, Ninth-Revision codes. The unadjusted and adjusted RR of CVA in patients with and without vWD were estimated using log-binomial model. Descriptive measures including means, medians, standard deviations, and range were presented based on normality test of continuous data. The prevalence of CVA was lower in patients with vWD than in those without vWD (1.31% vs 2.04%), with a RR of 0.64 (95% confidence interval (CI): 0.60-0.68). After adjusting for common CVA risk factors, the RR remained lower in vWD patients: 0.81 (95% CI: 0.76-0.86). vWD is associated with a lower RR of developing CVA. This suggests that deficiency of Von Willebrand factor is potentially protective against the development of CVA. To the best of our knowledge, this is the first study in humans to compare the RR of CVA in patients with and without vWD. Future studies are needed to explore causal relationships and therapeutic benefits.

Modulation of Burn Hypermetabolism in Preclinical Models.

Severe burns elicit a state of physiological stress and increased metabolism to help the body compensate for the changes associated with the traumatic injury. However, this hypermetabolic state is associated with increased insulin resistance, cardiovascular dysfunction, skeletal muscle catabolism, impaired wound healing, and delayed recovery. Several interventions were attempted to modulate burn hypermetabolism, including nutritional support, early excision and grafting, and growth hormone application. However, burn hypermetabolism still imposes significant morbidity and mortality in burn patients. Due to the limitations of in vitro models, animal models are indispensable in burn research. Animal models provide researchers with invaluable tools to test the safety and efficacy of novel treatments or advance our knowledge of previously utilized agents. Several animal studies evaluated novel therapies to modulate burn hypermetabolism in the last few years, including recombinant human growth hormone, erythropoietin, acipimox, apelin, anti-interleukin-6 monoclonal antibody, and ghrelin therapies. Results from these studies are promising and may be effectively translated into human studies. In addition, other studies revisited drugs previously used in clinical practice, such as insulin and metformin, to further investigate their underlying mechanisms as modulators of burn hypermetabolism. This review aims to update burn experts with the novel therapies under investigation in burn hypermetabolism with a focus on applicability and translation. Furthermore, we aim to guide researchers in selecting the correct animal model for their experiments by providing a summary of the methodology and the rationale of the latest studies.

Transcatheter Aortic Valve Replacement: Variations in Use, Charges, and Geography in the United States.

The use of transcatheter aortic valve replacement (TAVR) in the United States has been increasing but with variability. We used a 100% sample of Medicare beneficiaries (MBs), from the Centers for Medicare and Medicaid Services database, who underwent TAVR by cardiologists between 2015 and 2019. We stratified data by geographic region, rural/urban areas, and provider's gender. We examined the average number of TAVRs performed per 100,000 MBs, the average number of TAVRs performed per individual cardiologist, and the average submitted charge (ASC) per procedure. The number of TAVR per 100,000 MBs was significantly variable among regions in all years (all P≤0.028), except in 2015 (P=0.103), with the highest rates being in the Northeast and the lowest being in the West. The number of TAVRs per cardiologist was significantly different among regions only in 2019 (P=0.04), with the Northeast showing the highest numbers and the South showing the lowest. The ASC was also significantly variable among regions in all years (all P≤0.01). The highest ASC was in the Midwest for all years, whereas the lowest was in the West in 2015 to 2016 and in the South in 2017 to 2019. In all years, the number of TAVRs per cardiologist was higher in urban areas than in rural areas (all P<0.05); however, rural cardiologists had higher ASCs (all P<0.05). The number of TAVR procedures per cardiologist was not significantly different between male and female cardiologists (all P>0.1). Female cardiologists had a significantly higher ASC only in 2015 (P=0.034). In conclusion, there are variations in TAVR use and charges for MBs according to geographic, urban, and rural regions and the performing cardiologist's gender.

Variations in Atrial Fibrillation Ablation Use and Charges in a Modern Cohort of Medicare Beneficiaries.

Catheter ablation of atrial fibrillation (CAF) is increasingly being used in the United States. This study aimed to identify variations in CAF use among Medicare beneficiaries (MBs) over a 6-year period (2013 to 2019). Using the Center of Medicare and Medicaid Services database, a 100% sample of MBs who underwent CAF from 2013 to 2019 was included. We stratified CAF use data geographically (Northeast, South, West, and Midwest) and identified the number of CAFs per 100,000 MBs, number of electrophysiologists performing CAFs per 100,000 MBs, number of CAFs per individual electrophysiologist, and average submitted charge for CAF. In addition, we stratified the data per urban versus rural areas and gender of the operator. We found that the mean atrial fibrillation (AF) prevalence, rates of CAFs, number of electrophysiologists performing CAFs, and number of CAFs per electrophysiologist have increased steadily in all regions. The mean AF prevalence was different among regions, with the highest prevalence in the Northeast (p <0.001); however, there was a pattern of higher CAFs rates in the West and the South (p ≥0.057). The number of electrophysiologists performing CAFs was not different among regions; however, the number of CAFs per electrophysiologist was higher in the West and the South (p <0.001). The average submitted charge for CAF has decreased over years and was the lowest in the West and the South (p <0.001). There was no major difference in these variables regarding operator gender. In conclusion, there are significant variations in CAF use among MBs in the United States according to geographic and urban versus rural regions. These variations have the potential to impact the outcomes in MBs diagnosed with AF.

Radiomics and Artificial Intelligence in Predicting Axillary Lymph Node Metastasis in Breast Cancer: A Systematic Review.

BACKGROUND: Breast cancer is the most common malignancy and the second most common cause of death in women worldwide. Axillary lymph node metastasis (ALNM) is the most significant prognostic factor in breast cancer. Under the current guidelines, sentinel lymph node biopsy (SLNB) is the standard of axillary staging in patients with clinically-node negative breast cancer. Despite the minimally invasive nature of SLNB, it can cause short and long-term morbidities, including pain, sensory impairment, and upper limb motor dysfunction. However, lymphedema remains the most feared adverse event, and it affects 7% of patients within 36 months of follow-up. Recently, we have witnessed the implication of radiomics and artificial intelligence domains in the diagnosis and follow-up of many malignancies with promising results. Therefore, we have conducted a systematic search to investigate the potential of radiomics and artificial intelligence in predicting ALNM. METHODS: Four electronic databases were searched: PubMed, Scopus, CINAHL, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as our basis of organization. RESULTS: For radiomics, the area under the curve (AUC) for the included studies ranged from 0.715 to 0.93. Accuracy ranged from 67.7% to 98%. Sensitivity and specificity ranged from 70.3% to 97.8% and 58.4% to 98.2%, respectively. For other artificial intelligence methods, AUC ranged from 0.68 to 0.98, while accuracy ranged from 55% to 89%. CONCLUSION: The results of radiomics and artificial intelligence in predicting ALNM are promising. However, validation as a substitute for SLNB requires more substantial evidence from large randomized trials.

Bone Morphogenic Protein and Mesenchymal Stem Cells to Regenerate Bone in Calvarial Defects: A Systematic Review.

BACKGROUND: The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach. METHODS: We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins. Eligible studies included animal studies that used BMP therapy and mesenchymal stem cells to promote bone regeneration in calvarial defects. Reviews, conference articles, book chapters, and non-English language studies were excluded. Two independent investigators conducted the search and data extraction. RESULTS: Twenty-three studies published between 2010 and 2022 met our inclusion criteria after a full-text review of the forty-five records found in the search. Eight of the 23 studies used mice as models, while 15 used rats. The most common mesenchymal stem cell was bone marrow-derived, followed by adipose-derived. BMP-2 was the most popular. Stem cells were embedded in Scaffold (13), Transduction (7), and Transfection (3), and they were delivered BMP to cells. Each treatment used 2 × 104-1 × 107 mesenchymal stem cells, averaging 2.26 × 106. Most BMP-transduced MSC studies used lentivirus. CONCLUSIONS: This systematic review examined BMP and MSC synergy in biomaterial scaffolds or alone. BMP therapy and mesenchymal stem cells in calvarial defects, alone, or with a scaffold regenerated bone. This method treats skull defects in clinical trials. The best scaffold material, therapeutic dosage, administration method, and long-term side effects need further study.

Benefits and Challenges of Remote Patient Monitoring as Perceived by Health Care Practitioners: A Systematic Review.

BACKGROUND: Remote patient monitoring (RPM), or telemonitoring, offers ways for health care practitioners to gather real-time information on the physiological conditions of patients. As telemedicine, and thus telemonitoring, is becoming increasingly relevant in today's society, understanding the practitioners' opinions is crucial. This systematic review evaluates the perspectives and experiences of health care practitioners with telemonitoring technologies. METHODS: A database search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for the selection of articles measuring health care practitioners' perspectives and experiences with RPM technologies published between 2017 and 2021. Only articles written in English were included. No statistical analysis was performed and thus this is a qualitative review. RESULTS: A total of 1605 studies were identified after the initial search. After applying the inclusion and exclusion criteria of this review's authors, 13 articles were included in this review. In all, 2351 practitioners' perspectives and experience utilizing RPM technology in a variety of medical specialties were evaluated through close- and open-ended surveys. Recurring themes emerged for both the benefits and challenges. Common benefits included continuous monitoring of patients to provide prompt care, improvement of patient self-care, efficient communication, increased patient confidence, visualization of health trends, and greater patient education. Challenges comprised increased workload, higher patient anxiety, data inaccuracy, disorienting technology, financial issues, and privacy concerns. CONCLUSION: Health care practitioners generally believe that RPM is feasible for application. Additionally, there is a consensus that telemonitoring strategies will become increasingly relevant. However, there are still drawbacks to the technology that need to be considered.

Mesenchymal Stromal Cell Healing Outcomes in Clinical and Pre-Clinical Models to Treat Pressure Ulcers: A Systematic Review.

BACKGROUND: Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers. METHODS: A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL. Our search yielded 52 articles, narrowed to 44 after excluding duplicates. RESULTS: Out of 52 articles collected from four databases, 11 met the inclusion criteria. A total of 11 articles published between 2008 and 2020 met the inclusion criteria. Eight studies were observational descriptive papers in animal models, and three were prospective. Six studies used autologous MSCs, while five used allogenic MSCs. Three studies were conducted in humans, and the remaining eight were conducted in animals. The most common method of cell delivery was an intradermal injection in the margins of the ulcer. All studies reported positive results, including improved wound healing, reduced inflammation, and improved tissue regeneration. CONCLUSIONS: MSCs have shown promising results in treating pressure ulcers in animal and clinical trials. The combination of MSCs and scaffold materials has also been studied and found to be effective in wound healing. A standardized human wound model has been proposed further to investigate the efficacy of cell-based therapies for chronic wounds. However, more research is needed to determine the best quantity of cells to apply for pressure ulcers and to ensure the safety and efficacy of these treatments in clinical settings.

Artificial intelligence and lymphedema: State of the art.

Background: Lymphedema practice is facing many challenges. Some of these challenges include eradication of tropical lymphedema, preclinical diagnosis of cancer-related lymphedema, and delivery of appropriate individualized care. The past two decades have witnessed an increasing implementation of artificial intelligence (AI) in health-care services. The nature of the challenges facing the lymphedema practice is suitable for AI applications. Aim: The aim of this study was to explore the current AI applications in lymphedema prevention, diagnosis, and management and investigate the potential future applications. Methods and Results: Four databases were searched: PubMed, Scopus, Web of Science, and EMBASE. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as our basis of organization. Our analysis showed that several domains of AI, including machine learning (ML), fuzzy models, deep learning, and robotics, were successfully implemented in lymphedema practice. ML can guide the eradication campaigns of tropical lymphedema by estimating disease prevalence and mapping the risk areas. Robotic-assisted surgery for gynecological cancer was associated with a lower risk for the lower limb lymphedema. Several feasible models were described for the early detection and diagnosis of lymphedema. The proposed models are more accurate, sensitive, and specific than current methods in practice. ML was also used to guide and monitor patients during the rehabilitation exercises. Conclusion: AI offers a variety of solutions to the most challenging problems in lymphedema practice. Further, implementation into the practice can revolutionize many aspects of lymphedema prevention, diagnosis, and management. Relevance to Patients: Lymphedema is a chronic debilitating disease that is affecting millions of patients. Developing new modalities for prevention, early diagnosis, and treatment are critical to improve the outcomes. AI offers a variety of solutions for some of the complexities of lymphedema management. In this systematic review, we summarize and discuss the latest AI advances in lymphedema practice.

Colectomy Complicated by High-Output Ileostomy Managed in a Virtual Hybrid Hospital-at-Home Program.

Chronically ill patients with superimposed acute illness requiring hospitalization are more likely to develop an extended length of stay, hospital-acquired infections, and adverse events throughout their hospitalization. An excellent alternative to managing this population of patients in the traditional bricks-and-mortal (BAM) hospital is the hospital-at-home (HaH) model. The Advanced Care at Home (ACH) program is Mayo Clinic's HaH model that provides acute and postacute care to high-acuity patients in their homes rather than in the traditional hospital and skilled nursing facility. We report a case of postoperative care through the ACH program of a patient suffering from short gut syndrome, high-output ileostomy, and severe protein-calorie malnutrition in the setting of previously diagnosed triple-negative invasive ductal carcinoma (IDC) of the right breast complicated by lung and brain metastasis. The patient had multiple complications that required repeated scare escalations directed by a multidisciplinary virtual care. Despite these complications, the ACH model of care was able to keep the patient in the home setting the majority of the time, limiting BAM hospital days, and eliminating the need to use the emergency department for acute escalation for 3 months. The patient was able to recover during this time period and proceed to successful take-down of the ileostomy. This case highlights the benefits of the ACH program by offering high-acuity hospital-level care to severely ill patients in the comfort of their homes. Highly qualified providers paired with curated technology in the home allowed for prompt identification of patient decompensation and timely initiation of treatment while avoiding institutionalization.

Systemic anti-inflammatory effects of mesenchymal stem cells in burn: A systematic review of animal studies.

Background: Despite the advances in burn care, severe burns still impose significant morbidity and mortality. Severe burns are associated with an inflammatory response that ranges from alterations in vital signs to shock, multiorgan failure, and death. Mesenchymal stem cells (MSCs) are known for their anti-inflammatory and immunomodulatory effects. Therefore, MSCs were investigated for their potential benefits in modulating burn-induced inflammation and organ damage in several studies. Aim: We have conducted a systematic review of the literature to evaluate the efficacy of MSCs in modulating burn-induced systemic inflammation and organ damage in animal models. Methods: Four databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as our basis of organization. Results: Eight studies were included in the study. Bone marrow derived MSCs, umbilical cord derived MSCs (UC-MSCs), and UC-MSCs exosomes were used to modulate the burn-induced inflammation. MSCs therapy reduced serum levels of pro-inflammatory cytokines, improved renal function, inhibited tissue damage, and improved survival after burn. Furthermore, MSCs reversed all the burn-induced pathological changes in blood brain barrier (BBB). Conclusion: MSCs may attenuate the burn-induced inflammation by decreasing serum levels of inflammatory cytokines. However, the effect on anti-inflammatory cytokines is conflicting and mandates more substantial evidence. Furthermore, MSCs reduce tissue inflammation, tissue damage, and apoptosis in the lungs and kidneys. In addition, MSCs reversed the burn-induced pathophysiologic changes in the BBB. The underlying mechanisms of these effects are poorly understood and should be the focus of future stem cell research. Relevance to Patients: Severe burn patients are liable to systemic inflammation due to the release of inflammatory cytokines into the circulation. This inflammatory response has a broad spectrum of severity that ranges from alterations in vital signs to multiorgan failure and death. Despite the advances in burn care, burn-induced inflammation still imposes significant morbidity and mortality. This systematic review evaluates the potential benefits of stem cells in modulating burn-induced systemic inflammation in animal burn models.

Animal models in lymph node transfer surgery: A systematic review.

Background and Aim: Lymph node transfer surgery (LNTS) is indicated in secondary lymphedema (LE) patients who do not respond to conservative therapy. Animal models are the spearhead of LE research and were used to pioneer most of the surgical interventions currently in practice. We conducted a systematic review of the literature to explore animal models dedicated to LNTS to compare different species, techniques, and outcomes. Methods: Four databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis as our basis of organization. Results: Avascular lymph node graft (ALNG) and vascularized lymph node transfer (VLNT) effectively treated LE and lead to better outcomes than controls. Whole ALNGs are superior to fragmented ALNGs. Larger fragments are more likely to be reintegrated into the lymphatic system than small fragments. VLNT was superior to whole and fragmented ALNG. Increasing the number of VLNT resulted in better outcomes. Adipose-derived stem cells improved outcomes of VLNT; vascular endothelial growth factor C and D and platelet-rich plasma improved outcomes for ALNG. Cryopreservation of lymph nodes (LNs) did not affect outcomes for ALNG. The critical ischemia and venous occlusion time for LN flaps were 4-5 and 4 h, respectively. The critical time for reperfusion injury was 2 h. Some of the novel models included venous LNT, and cervical adipocutaneous flap to groin. Conclusion: Current evidence from animals favors VLNT over other surgical interventions. Several pharmacological therapies significantly improved outcomes of ALNG and VLNT. Relevance to Patients: LE is a chronic condition affecting millions of patients worldwide. LNTS is becoming more popular as a LE treatment. Animal models have led the LE research for decades and developing new models for LE are essential for LE research. This systematic review aims to summarize the existing animal models dedicated to LNTS. We believe that this review is critical to guide researchers in the selection of the model that is best fit for their hypothesis-driven experiments.

Provider Evaluation of a Novel Virtual Hybrid Hospital at Home Model.

BACKGROUND: Healthcare provider's experience with new models of care is crucial for long-term success. In July 2020, Mayo Clinic implemented a novel virtual hybrid hospital at home program called Advanced Care at Home (ACH). This model allows virtual providers in a command center to care for high-acuity patients in the home setting through collaboration with a vendor-mediated supply chain. This study aims to describe the outcomes obtained from a survey applied to the ACH providers to determine their acceptance of the quality and safety of the virtual hybrid care model, their perception towards the decision-making and teamwork between the command center and supplier network, and determine if the overall experience with ACH was rewarding. METHODS: A 15-question anonymous survey was distributed via email quarterly to all the physicians and nurse practitioners registered in ACH program at Mayo Clinic. The survey encompassed questions related to the overall experience in ACH concerning work environment, quality of care, service reliability, teamwork, decision-making, and satisfaction. All the questions were Likert-like scale choice, and a descriptive analysis using frequency distribution and percentages of the data was performed. RESULTS: Between September 1, 2020 and April 30, 2021, three quarterly surveys were sent to a total of 21 physicians and nurse practitioners caring for patients virtually in ACH. The response rate reported was 72%, 33%, and 66%, respectively, at the first, second, and third quarters. Eighty percent or more of providers consistently gave positive scores to all three areas analyzed throughout the 8-month study. CONCLUSION: Providers found the ACH virtual hybrid model of home hospital care very rewarding. They were able to deliver high-quality and safe care to their patients through positive teamwork with a vendor-mediated supply chain. This novel model of hospital at home has the potential to be a great provider satisfier moving forward.

Hypoxia-preconditioning of human adipose-derived stem cells enhances cellular proliferation and angiogenesis: A systematic review.

BACKGROUND: Human adipose-derived stem cells (hADSCs) have gained attention lately because of their ease of harvesting and ability to be substantially multiplied in laboratory cultures. Stem cells are usually cultured under atmospheric conditions; however, preconditioning stem cells under hypoxic conditions seems beneficial. AIM: This systematic review aims to investigate the effect of hypoxia preconditioning and its impact on the proliferation and angiogenic capacity of the hADSCs. METHODS: We performed a systematic review by searching PubMed, Scopus, Embase, and Google Scholar databases from all years through March 22, 2021, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medical Subject Headings terms "adipose-derived stem cell," "Hypoxia," "cell proliferation," and "angiogenesis" guided our search. Only articles written in English using experimental models comparing a preconditioned group against a control group of hADSCs with data on proliferation and angiogenic capacity were included. RESULTS: Our search yielded a total of 321 articles. 11 articles met our inclusion criteria and were ultimately included in this review. Two studies induced hypoxia using hypoxia-inducible factor-1 alpha stabilizing agents, while nine reached hypoxia by changing oxygen tension conditions around the cells. Four articles conducted in-vivo studies to correlate their in-vitro findings, which proved to be consistent. Although 1 article indicated cell proliferation inhibition with hypoxia preconditioning, the remaining 10 found enhanced proliferation in preconditioned groups compared to controls. All articles showed an enhanced angiogenic capacity of hADSCs after hypoxia preconditioning. CONCLUSION: In this review, we found evidence to support hypoxia preconditioning of hADSCs before implantation. Benefits include enhanced cell proliferation with a faster population doubling rate and increased secretion of multiple angiogenic growth factors, enhancing angiogenesis capacity. RELEVANCE FOR PATIENTS: Although regenerative therapy is a promising field of study and treatment in medicine, much is still unknown. The potential for angiogenic therapeutics with stem cells is high, but more so, if we discover ways to enhance their natural angiogenic properties. Procedures and pathologies alike require the assistance of angiogenic treatments to improve outcome, such is the case with skin grafts, muscle flaps, skin flaps, or myocardial infarction to mention a few. Enhanced angiogenic properties of stem cells may pave the way for better outcomes and results for patients.

85-Year-Old Postsurgical Complex Patient Successfully Managed Remotely at the Novel Mayo Clinic's Hospital at Home.

An 85-year-old male presented to the podiatry clinic following a 1st to 5th left toe amputation as a complication of severe peripheral arterial disease and nonhealing wound despite endovascular intervention with an angiogram. At the visit, cellulitis with gangrene of the surgical site was noted. The patient was admitted to the brick and mortar (BAM) hospital and taken to surgery for a transmetatarsal amputation of the left limb. In the immediate postoperative period, the incisional margins appeared dusky creating concern for flap viability. The medical team recommended a vascular bypass versus a below-knee amputation. However, given the age, comorbidities, and nutritional status, the family refused further surgical intervention. As such, Mayo Clinic's home hospital program, Advanced Care at Home (ACH), was consulted for continued nonsurgical acute management at home. The patient was transferred to ACH and transported home three days after BAM admission to continue IV antibiotic therapy and wound care. Discharge from ACH occurred 11 days after admission to the BAM hospital. This case highlights the importance of developing health care alternatives to traditional hospitalization and demonstrates that ACH can manage highly complex, elder postoperative patients from the comfort of their homes.