Impact of storage conditions and duration on function of native and cargo-loaded mesenchymal stromal cell extracellular vesicles.

BACKGROUND AIMS: As evidenced by ongoing clinical trials and increased activity in the commercial sector, extracellular vesicle (EV)-based therapies have begun the transition from bench to bedside. As this progression continues, one critical aspect of EV clinical translation is understanding the effects of storage and transport conditions. Several studies have assessed the impact of storage on EV characteristics such as morphology, uptake and component content, but effects of storage duration and temperature on EV functional bioactivity and, especially, loaded cargo are rarely reported. METHODS: The authors assessed EV outcomes following storage at different temperatures (room temperature, 4°C, -20°C, -80°C) for various durations as well as after lyophilization. RESULTS: Mesenchymal stromal cell (MSC) EVs were observed to retain key aspects of their bioactivity (pro-vascularization, anti-inflammation) for up to 4-6 weeks at -20°C and -80°C and after lyophilization. Furthermore, via in vitro assays and an in vivo wound healing model, these same storage conditions were also demonstrated to enable preservation of the functionality of loaded microRNA and long non-coding RNA cargo in MSC EVs. CONCLUSIONS: These findings extend the current understanding of how EV therapeutic potential is impacted by storage conditions and may inform best practices for handling and storing MSC EVs for both basic research and translational purposes.

Chitosan Particles Complexed with CA5-HIF-1α Plasmids Increase Angiogenesis and Improve Wound Healing.

Wound therapies involving gene delivery to the skin have significant potential due to the advantage and ease of local treatment. However, choosing the appropriate vector to enable successful gene expression while also ensuring that the treatment's immediate material components are conducive to healing itself is critical. In this study, we utilized a particulate formulation of the polymer chitosan (chitosan particles, CPs) as a non-viral vector for the delivery of a plasmid encoding human CA5-HIF-1α, a degradation resistant form of HIF-1α, to enhance wound healing. We also compared the angiogenic potential of our treatment (HIF/CPs) to that of chitosan particles containing only the plasmid backbone (bb/CPs) and the chitosan particle vector alone (CPs). Our results indicate that chitosan particles exert angiogenic effects that are enhanced with the human CA5-HIF-1α-encoded plasmid. Moreover, HIF/CPs enhanced wound healing in diabetic db/db mice (p < 0.01), and healed tissue was found to contain a significantly increased number of blood vessels compared to bb/CPs (p < 0.01), CPs (p < 0.05) and no-treatment groups (p < 0.01). Thus, this study represents a method of gene delivery to the skin that utilizes an inherently pro-wound-healing polymer as a vector for plasmid DNA that has broad application for the expression of other therapeutic genes.

The Preferred Reconstructive Choice for a Lower Third Tibial Exposure Defect: An Online Survey of 356 Microsurgeons.

BACKGROUND: One of the most challenging yet common areas in reconstructive surgery is the closure of defects in the lower leg. Surgeons can choose from several reconstructive options including local and free flaps. The aim of this study was to understand the reconstructive strategy for lower leg defects of different microsurgeons around the world by harnessing the power of social media and online questionnaires. METHODS: A case of a patient with an exposed plate over distal tibial fracture was presented via an online questionnaire distributed on various social media platforms. A total of 369 international microsurgeons replied with their preferred treatment choice. The data were analyzed according to geographic area, microsurgical training, seniority, and subspecialty. RESULTS: Among all the respondents (n = 369), 64% would have opted for a free flap reconstruction, while the remaining 36% would have opted for a local/pedicle flap. In the group that would have opted for a free flap, 63% would reconstruct the defect using a free fasciocutaneous flap, while the remaining 37% would have used a free muscle flap. In the local flap group, 60% would have used a local perforator while 30% would have chosen a conventional local flap. While North American and European microsurgeons had a clear preference toward free flaps, Asian, Middle Eastern, African, and South American surgeons were evenly divided between local and free flaps. CONCLUSION: In this study, we provide a current global overview of the reconstructive strategies for a lower limb with skin defect and bone or prosthesis exposure. We hope that this will be able to help global microsurgeons and patients worldwide.

Decreasing Readmissions After Ileostomy Creation Through a Perioperative Quality Improvement Program.

BACKGROUND: Readmission after ileostomy creation in patients undergoing colorectal surgery creates a significant burden on health care cost and patient quality of care, with a 30-day readmission rate of 40%. OBJECTIVE: This study aimed to evaluate the implementation of our perioperative quality improvement program, Decreasing Readmissions After Ileostomy Creation. DESIGN: Perioperative interventions were administered to patients who underwent ileostomy creation. SETTINGS: A single tertiary care academic center. PATIENTS: Eighty patients participated in this program from February 2020 to January 2021. MAIN OUTCOME MEASURES: The primary outcomes measured were 30-day readmission rates and causes of readmission, which were compared to a historical national database. Descriptive statistics were used to evaluate the effectiveness of this quality improvement program. RESULTS: Eighty patients were enrolled in this prospective quality improvement program. The mean age was 52 (±15.06) years. The most common indication for patients undergoing creation of an ileostomy was colorectal cancer (40%; n = 32). The overall 30-day readmission rate was 8.75% (n = 7) throughout the study period, which was significantly lower than historical cohort data (20.10%; p = 0.01). Among the 7 readmitted patients, 3 (3.75%) were readmitted due to dehydration. The most significant associated risk factor for all-cause readmission was urgent/emergent operative status, which was associated with an increased risk of readmission ( p = 0.01). The 3 readmitted patients with dehydration had a mean Dehydration Readmission After Ileostomy Prediction risk score of 11.71 points, compared to 9.59 points in nondehydrated patients, who did not require readmission ( p = 0.38). LIMITATIONS: This study is limited by its small sample size (N = 80). CONCLUSIONS: The Decreasing Readmissions After Ileostomy Creation program has been successful in reducing both the all-cause readmission rate and readmission due to dehydration both within an academic tertiary care referral center and in comparison with historical readmission rates. See Video Abstract at http://links.lww.com/DCR/B894 . DISMINUCIN DE LA READMISIN DESPUS DE LA CREACIN DE UNA ILEOSTOMA MEDIANTE UN PROGRAMA DE MEJORA DE LA CALIDAD PERIOPERATORIA: ANTECEDENTES:La readmisión después de la creación de una ileostomía en pacientes de cirugía colorrectal crea una carga significativa sobre el costo de la atención médica y la calidad de la atención del paciente, con una tasa de readmisión a los 30 días que llega al 40%.OBJETIVO:Este estudio tiene como objetivo evaluar la implementación de nuestro programa de mejora de la calidad perioperatoria que disminuyen los reingresos después de la creación de ileostomía.DISEÑO:Se administraron intervenciones perioperatorias a pacientes que se sometieron a la creación de una ileostomía.AJUSTE:Se trataba de un único centro académico de atención terciaria.PACIENTES:Participaron 80 pacientes en este programa desde febrero de 2020 hasta enero de 2021.PRINCIPALES MEDIDAS DE RESULTADO:Los principales resultados medidos fueron las tasas de reingreso a los 30 días y las causas de reingreso, que se compararon con una base de datos histórica nacional. Se utilizaron estadísticas descriptivas para evaluar la eficacia de este programa de mejora de la calidad.RESULTADOS:Ochenta pacientes se inscribieron en este programa prospectivo de mejora de la calidad. La edad media fue de 52 (± 15,06) años. La indicación más común para los pacientes que se sometieron a la creación de una ileostomía fue el cáncer colorrectal (40%, n = 32). La tasa general de reingreso a los 30 días fue del 8,75% (n = 7) durante todo el período de estudio, lo que fue significativamente más bajo que los datos históricos de la cohorte (20,10%, p = 0,01). Entre los 7 pacientes readmitidos, tres (3,75%) fueron readmitidos por deshidratación. El factor de riesgo asociado más significativo para la readmisión por todas las causas fue el estado operatorio urgente / emergencia, que se asoció con un mayor riesgo de readmisión (p = 0,01). Los tres pacientes readmitidos con deshidratación tuvieron una puntuación de riesgo promedio de readmisión por deshidratación después de la predicción de ileostomía de 11,71 puntos, en comparación con los pacientes no deshidratados, que no requirieron readmisión (media, 9,59 puntos, p = 0,38).LIMITACIONES:Este estudio está limitado por su pequeño tamaño de muestra (n = 80).CONCLUSIONES:El programa de disminución de las readmisiones después de la creación de una ileostomía ha logrado reducir tanto la tasa de readmisión por todas las causas como la readmisión por deshidratación, tanto dentro de un centro académico de referencia de atención terciaria como en comparación con las tasas históricas de readmisión. Consulte Video Resumen en http://links.lww.com/DCR/B894 . (Traducción-Dr Yolanda Colorado ).

Potential Role of Silencing Ribonucleic Acid for Esophageal Cancer Treatment.

INTRODUCTION: Esophageal cancer is an aggressive malignancy with high mortality. Optimal treatment of esophageal cancer remains an elusive goal. Ribonucleic acid (RNA) interference is a novel potential targeted approach to treat esophageal cancer. Targeting oncogenes that can alter critical cellular functions with silencing RNA molecules is a promising approach. The silencing of specific oncogenes in esophageal cancer cells in the experimental setting has been shown to decrease the expression of oncogenic proteins. This has resulted in cell apoptosis, reduction in cell proliferation, reduced invasion, migration, epithelial-mesenchymal transition, decrease in tumor angiogenesis and metastasis, and overcoming drug resistance. The Hedgehog (Hh) signaling pathway has been shown to be involved in esophageal adenocarcinoma formation in a reflux animal model. In addition to Hh, we will focus on other targets with clinical potential in the treatment of esophageal cancer. MATERIALS AND METHODS: We searched for articles published from 2005 to August 2020 that studied the siRNA effects on inhibiting esophageal cancer formation in experimental settings. We used combinations of the following terms for searching: "esophageal cancer," "RNA interference," "small interfering RNA," "siRNA," "silencing RNA," "Smoothened (Smo)," "Gli," "Bcl-2," "Bcl-XL," "Bcl-W,″ "Mcl-1," "Bfl-1," "STAT3,"and "Hypoxia inducible factor (HIF)". A total of 21 relevant articles were found. RESULTS AND CONCLUSIONS: Several proto-oncogenes/oncogenes including Hh pathway mediators, glioma-associated oncogene homolog 1 (Gli-1), Smoothened (Smo), and antiapoptotic Bcl-2 have potential as targets for silencing RNA in the treatment of esophageal cancer.

Metformin use and the risk of anal intraepithelial neoplasia in type II diabetic patients.

AIM: Emerging evidence has suggested that metformin may be protective against the development of human-papillomavirus-related cancers. Anal intraepithelial neoplasia (AIN) is highly associated with human papillomavirus infection and a precancerous status of anal cancer. The aim of this study was to investigate the relationship between metformin usage and the development of AIN in a large national sample. METHODOLOGY: The IBM MarketScan dataset was used to design a nested case-control study from 2010 to 2017. Patients aged 18-65 years with type 2 diabetes mellitus (DM) were evaluated, and cases of AIN were identified. Four controls were randomly selected in the risk set of each case by using incidence density sampling. The association between metformin usage and AIN was assessed using multivariate logistic regression modelling. RESULTS: A total of 258 patients with type 2 DM were diagnosed with AIN during the study interval, and these were matched to 1032 control patients without a diagnosis of AIN. Patients who developed AIN had 38% lower odds of prior metformin use compared to those without a history of AIN (P < 0.01) and this finding remained robust after adjusting for age, sex, human immunodeficiency virus infection and DM complications (P = 0.02). Patients with AIN had 56% lower odds of long-term metformin use compared to control patients (P = 0.01). CONCLUSIONS: An AIN diagnosis in patients with DM is associated with 56% lower likelihood of prior metformin use. This relationship suggests that metformin could potentially play a protective role against AIN. Prospective studies in non-diabetic patients are warranted to examine these findings further.

Reversal of thoracic sympathectomy through robot-assisted microsurgical sympathetic trunk reconstruction with sural nerve graft and additional end-to-side coaptation of the intercostal nerves: A case report.

Thoracic sympathectomy to treat palmar hyperhidrosis (PH) has widely been performed. Many patients regret the surgery due to compensatory hyperhidrosis (CH), gustatory hyperhidrosis, arrhythmia, hypertension, gastrointestinal disturbances, and emotional distress. Robotic applications in microsurgery are very limited. We report the technique and long-term patient-reported outcomes of bilateral robot-assisted microsurgical sympathetic trunk reconstruction with a sural nerve graft in an interdisciplinary setting. A 59-year-old female suffered from severe adverse effects after endoscopic thoracic sympathectomy (ETS) for PH 25 years ago. She reported CH over the whole trunk, gustatory hyperhidrosis, excessive dry hands, and emotional distress. An interdisciplinary surgical team performed a bilateral sympathetic trunk reversal reconstruction with an interpositional sural nerve graft per side by a da Vinci® Robot. The nerve graft was microsurgically coapted using 9-0 sutures end-to-end to the sympathetic trunk stumps and side-to-end to the intercostal nerves T2-T4. At 24, 33 and 42 months, palmar dryness and emotional distress were strongly reduced. A highly specialized interdisciplinary setting may provide a precise, safe, and efficient treatment for ETS sequelae. A clinical study is initiated to validate this new therapy.

International Microsurgery Club: An Effective Online Collaboration System.

BACKGROUND: This study aimed to determine if International Microsurgery Club (IMC) is an effective online resource for microsurgeons worldwide, in providing an avenue for timely group discussions and advice regarding complicated cases, and an avenue for collaboration and information sharing. METHODS: All posts on the IMC Facebook group from member 1 to 8,000 were analyzed according to inclusion criteria and categorized into three categories-case discussion, question, and information sharing. Posts were retrospectively analyzed for number of responses, time of responses, number of "likes," number of treatment options, time of day, and demographics of authors and responders. RESULTS: A retrospective analysis of 531 cases showed an average response rate of 75.7% within 1 hour and as membership grew. The response rate stabilized averaging between 72.5 and 78% across all times of the day. An average of 11.8 microsurgeons was involved per case discussion, and 5.7 treatment options were provided per case. CONCLUSION: IMC is shown to be an effective resource to allow microsurgeons to access timely advice from other microsurgeons without time and distance limitation, and to have interactive group discussions on complicated cases.

The Preferred Management of a Single-Digit Distal Phalanx Amputation.

BACKGROUND: Replantation of a single digit at the distal phalanx level is not routinely performed since it is technically challenging with questionable cost-effectiveness. The purpose of this study was to analyze international microsurgeons' clinical decisions when faced with this common scenario. METHODS: A survey of a right-middle finger distal phalanx transverse complete amputation case was conducted via online and paper questionnaires. Microsurgeons around the world were invited to provide their treatment recommendations. In total, 383 microsurgeons replied, and their responses were stratified and analyzed by geographical areas, specialties, microsurgery fellowship training, and clinical experiences. RESULTS: Among 383 microsurgeons, 170 (44.3%) chose replantation as their preferred management option, 137 (35.8%) chose revision amputation, 62 (16.2%) chose local flap coverage, 8 (2.1%) chose composite graft, and 6 (1.6%) favored other choices as their reconstruction method for the case study. Microsurgeons from the Asia-Pacific, Middle East/South Asia, and Central/South America regions tend to perform replantation (70.7, 68.8, and 67.4%, respectively) whereas surgeons from North America and Europe showed a lower preference toward replantation (20.5 and 26.8%, respectively p < 0.001). Having completed a microsurgery fellowship increased the attempt rate of replantation by 15.3% (p = 0.004). Clinical experience and the surgeons' specialties did not show statistical significance in clinical decision making. CONCLUSION: From the present study, the geographic preferences and microsurgery fellowship experience influence the method of reconstruction for distal phalanx amputation. Multiple factors are taken into consideration in selecting the most suitable reconstructive method for each case scenario. In addition to the technical challenges of the proposed surgery, the cost of the procedure and the type of facility needed are important variables in the decision making process.

Impact of Social Media on Current Medical Conferences.

BACKGROUND: Medical conferences are forums for research, continuing medical education, and networking. Social media is increasingly used for communication and networking due to its low cost and ability to overcome large distances. This study investigates the impact that social media brings to the current conference system. METHODS: There are three parts of this study: (1) comparing two similar brachial plexus injuries (BPIs) courses without (2009) and with (2017) social media support, and the participants' feedback; (2) sharing our experiences in the management of the 2018 International Course on SuperMicrosurgery (ICSM) conference; and (3) evaluating the studies from the social media platform International Microsurgery Club (IMC), for the consensus pertaining to social media and conference system. RESULTS: With the help of social media, international attendance increased during the 2017 BPI conference compared with the 2009 BPI course (25 nationalities in 2009 vs. 35 in 2017). At least 23% obtained their meeting information through social media. Live surgery was the overall main attraction (79%). The 2018 ICSM meeting revealed that video posts increased attendance; videos that were the most effective in attracting (viewership) were either short or pertained to surgical procedures. Facebook, Messenger, and WeChat smartphone applications were effective for immediate communication and troubleshooting among the participants. From the IMC polls, 78% believe that the social media and the conference complemented each other. 97% attended the conference to update their skills and knowledge. CONCLUSION: Social media is a quick and economic tool in promoting medical conferences and instant messenger systems offer immediate communication amongst associates. Despite the popularity of social media, the conference still has its irreplaceable role. The combination of the conference and the social media enhances the training and education of microsurgeons.

Use of Social Media and an Online Survey to Discuss Complex Reconstructive Surgery: A Case of Upper Lip Reconstruction with 402 Responses from International Microsurgeons.

BACKGROUND: The best reconstructive strategy for upper lip defects is still in debate. The purpose of this study was to analyze the decisions made by international microsurgeons, who were participated through online questionnaire, distributed by email and social media network. MATERIALS AND METHODS: A case of a two-thirds upper lip oncologic defect was presented via an online questionnaire and 402 microsurgeons replied their treatment options. The data were then analyzed according to the geographic area, microsurgical fellowship, seniority, and subspecialty. All the data were analyzed using SPSS 22. RESULTS: A total of 27.7% of microsurgeons chose a free flap, while 72.3% chose a local/pedicle flap as their preferred method for reconstruction. The most common choice of free and local/pedicle flaps was radial forearm (73.6%) and Abbé (36.2%), respectively. The microsurgeons in Europe preferred local/pedicle flaps than free flap when compared with Middle/South America, Asia-Pacific, Africa and South Asia/Middle East (11.6% versus 50%, 43.4%, 29.3% and 27.3%, respectively, multivariant p < 0.05). The microsurgeons with microsurgical fellowships preferred to use free flaps (32.9% versus 17.5%, multivariant p = 0.021). There was no difference for the seniority and specialty of the microsurgeons. CONCLUSIONS: The online questionnaire is valuable and feasible for obtaining experts' opinions. This study provides a current global overview of surgical preferences for this common complicated clinical scenario.

Adjuvant chemotherapy in stage 1 colon cancer: Patient characteristics and survival analysis from the national cancer database.

BACKGROUND: A subset of patients in ACS-NCDB with stage-1 colon cancer received adjuvant chemotherapy (AC), in contrast to national guidelines. This study aimed to define this population and evaluate associations between AC and survival. METHODS: Patients with T1-2N0 colon cancer from 2004 to 2016 were separated into AC and non-AC groups. Adverse pathological features (APF) included T2, poor differentiation, lymphovascular invasion, positive margin, and inadequate lymph nodes (<12). Cox proportional hazard models were used to estimate prognostic factors for overall survival (OS). RESULTS: A total of 1745 of 139,857 patients (1.2 %) received AC. Receiving AC was associated with male sex (p = 0.02), uninsured (p < 0.01), low income (p = 0.02), or having ≥2 APFs (p < 0.001). In the total cohort, AC was associated with increased mortality (HR 1.14 [1.04-1.24] P < 0.01). On subset analysis, AC was associated with improved OS for patients with ≥2 APFs (log-rank P=<0.001), and decreased mortality when adjusted for covariates (HR 0.81 [0.69-0.95] P=<0.01). The most significant predictor of mortality was old age (HR 3.78 [3.67, 3.89] p ≤ 0.01), followed by higher Charlson Comorbidity Index (HR 1.73 [1.69, 1.76] (p ≤ 0.01), and higher APF score (HR 1.46 [1.42, 15.2] p ≤ 0.01). CONCLUSION: AC was associated with decreased survival in the total cohort of stage 1 colon cancer patients, but was associated with improved survival for patients with multiple APFs.

Association of robotic surgery with early discharge, readmission, and complications in elective colectomy: an analysis of NSQIP data from 2012 to 2021.

Background Early discharge (ED) after colectomy has become a target outcome for multiple reasons, but the factors associated with ED are not well characterized. This study investigated the factors associated with ED and evaluated the impact of ED on overall outcome. Methods Data from ACS-NSQIP were used to identify patients who underwent non-emergent colectomy from 2012 to 2021. ED was defined as length of stay ≤ 2 days. Unpaired t-tests, chi-square tests and adjusted multivariate logistic regression modeling were used to estimate associated factors for ED. Bounceback readmission was defined as readmission within 7 days of discharge. Results In this cohort of 282,490 patients, 43,137 (15.3%) met the criteria for ED. Robotic colectomy (OR 14.35; 95% CI [13.63-15.12]) was more strongly associated with ED than any other patient characteristic, including laparoscopic colectomy (6.82 [6.51-7.14], ref open colectomy). ED vs. non-ED patients had lower rates of 30-day (5.84 vs. 10.37%, p < 0.01) and bounceback (3.56 vs. 5.75%, p < 0.01) readmissions, overall complications (5.65 vs. 18.63%, p < 0.01) and post-discharge complications (4.21 vs. 7.49%, p < 0.01). Conclusions Robotic surgery was the variable most strongly associated with ED, with greater odds of ED compared to both laparoscopic and open colectomy. Patients who had ED after robotic surgery had lower rates of complications and readmission compared to non-ED patients.

Mesenchymal Stem Cell Culture within Perfusion Bioreactors Incorporating 3D-Printed Scaffolds Enables Improved Extracellular Vesicle Yield with Preserved Bioactivity.

Extracellular vesicles (EVs) are implicated as promising therapeutics and drug delivery vehicles in various diseases. However, successful clinical translation will depend on the development of scalable biomanufacturing approaches, especially due to the documented low levels of intrinsic EV-associated cargo that may necessitate repeated doses to achieve clinical benefit in certain applications. Thus, here the effects of a 3D-printed scaffold-perfusion bioreactor system are assessed on the production and bioactivity of EVs secreted from bone marrow-derived mesenchymal stem cells (MSCs), a cell type widely implicated in generating EVs with therapeutic potential. The results indicate that perfusion bioreactor culture induces an ≈40-80-fold increase (depending on measurement method) in MSC EV production compared to conventional cell culture. Additionally, MSC EVs generated using the perfusion bioreactor system significantly improve wound healing in a diabetic mouse model, with increased CD31+ staining in wound bed tissue compared to animals treated with flask cell culture-generated MSC EVs. Overall, this study establishes a promising solution to a major EV translational bottleneck, with the capacity for tunability for specific applications and general improvement alongside advancements in 3D-printing technologies.

Cutting the fat: Utilizing LEAN methodology to improve rounding efficiency of surgical residents.

BACKGROUND: LEAN was developed by Toyota to provide a systematic way to eliminate waste and standardize processes. We sought to introduce LEAN methodology to surgical residents with the goal of increasing rounding efficiency. METHODS: A Kaizen event was used as a rounding efficiency improvement strategy. A multidisciplinary healthcare team participated in the event; first to identify the current state of rounds, second to create the ideal state. Value-stream maps were created and improved efficiency was seen by increased ratio of productive time to lead time. RESULTS: Two interventions were prioritized. The first introduced table rounds before walk rounds and the second changed the sign-out tool from Baton to Microsoft Word with file encryption. The ratio of productive time to lead time during morning rounds was higher after implementing these interventions (3.73 vs. 2.03). CONCLUSIONS: This Kaizen event introduced surgical trainees to LEAN and resulted in improved efficiency of morning rounds.

HOTAIR-Loaded Mesenchymal Stem/Stromal Cell Extracellular Vesicles Enhance Angiogenesis and Wound Healing.

Chronic wounds remain a substantial source of morbidity worldwide. An emergent approach that may be well-suited to induce the complex, multicellular processes such as angiogenesis that are required for wound repair is the use of extracellular vesicles (EVs). EVs contain a wide variety of proteins and nucleic acids that enable multifactorial signaling. Here, the capability of EVs is leveraged to be engineered via producer cell modification to investigate the therapeutic potential of EVs from mesenchymal stem/stromal cells (MSCs) transfected to overexpress long non-coding RNA HOX transcript antisense RNA (HOTAIR). HOTAIR is previously shown by the authors' group to be critical in mediating angiogenic effects of endothelial cell EVs, and MSCs are chosen as EV producer cells for this study due to their widely reported intrinsic angiogenic properties. The results indicate that MSCs overexpressing HOTAIR (HOTAIR-MSCs) produce EVs with increased HOTAIR content that promote angiogenesis and wound healing in diabetic (db/db) mice. Further, endothelial cells exposed to HOTAIR-MSC EVs exhibit increased HOTAIR content correlated with upregulation of the angiogenic protein vascular endothelial growth factor. Thus, this study supports EV-mediated HOTAIR delivery as a strategy for further exploration toward healing of chronic wounds.

Experiences and attitudes toward aesthetic procedures in East Asia: a cross-sectional survey of five geographical regions.

BACKGROUND: The demand for aesthetic procedures continues to grow globally, particularly in East Asian countries. The popularity of specific aesthetic procedures varies, however, depending on the particular East Asian geographical region being studied. This study aimed to evaluate the experiences of and attitudes toward aesthetic procedures in five East Asian countries/regions, including China, Japan, South Korea, Hong Kong, and Taiwan. METHODS: To recruit participants, an online questionnaire was designed and distributed on social media networks between May 2015 and March 2016. The statistical analysis was conducted using SPSS software, version 22.0. RESULTS: A total of 3,088 people responded (approximately 600 in each country/region). Of these, 940 participants (47.8%) responded that they had experienced at least one aesthetic procedure in the past. Taiwan had the highest number of participants who had experienced at least one procedure (264/940, 41%), with primarily non-surgical experiences. Only in South Korea did surgical cosmetic experiences exceed non-surgical cosmetic experiences (55.9% vs. 44.1%). The popularity of particular procedures and the motivation for undergoing aesthetic procedures varied by country. CONCLUSIONS: The popularity of aesthetic procedures continues to evolve. Similar trends were observed across the East Asian regions; however, each country had its unique demands and preferences. The information provided by this study can help aesthetic plastic surgeons further understand the patients in their corresponding region, customize their practice, and develop the requisite skills.

Factors associated with disease severity and mortality among patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. METHODS: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. RESULTS: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23-1.71), dyspnea (RR 2.55, 95%CI 1.88-2.46), diabetes (RR 1.59, 95%CI 1.41-1.78), hypertension (RR 1.90, 95%CI 1.69-2.15). Congestive heart failure (OR 4.76, 95%CI 1.34-16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57-27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19-7.39) and reticular pattern (OR 5.54, 95%CI 1.24-24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. CONCLUSION: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.