Telehealth Follow-Up After Inguinal Hernia Repair in Veterans.

INTRODUCTION: Telehealth has been increasingly utilized with a renewed interest by surgical specialties given the COIVD-19 pandemic. Limited data exists evaluating the safety of routine postoperative telehealth follow-up in patients undergoing inguinal hernia repair, especially those who present urgent/emergently. Our study sought to evaluate the safety and efficacy of postoperative telehealth follow-up in veterans undergoing inguinal hernia repair. METHODS: Retrospective review of all Veterans who underwent inguinal hernia repair at a tertiary Veterans Affairs Medical Center over a 2-year period (9/2019-9/2021). Outcome measures included postoperative complications, emergency department (ED) utilization, 30-day readmission, and missed adverse events (ED utilization or readmission occurring after routine postoperative follow-up). Patients undergoing additional procedure(s) requiring intraoperative drains and/or nonabsorbable sutures were excluded. RESULTS: Of 338 patients who underwent qualifying procedures, 156 (50.6%) were followed-up by telehealth and 152 (49.4%) followed-up in-person. There were no differences in age, sex, BMI, race, urgency, laterality nor admission status. Patients with higher American Society of Anesthesiologists (ASA) classification [ASA class III 92 (60.5%) versus class II 48 (31.6%), P = 0.019] and open repair [93 (61.2%) versus 67 (42.9%), P = 0.003] were more likely to follow-up in-person. There was no difference in complications, [telehealth 13 (8.3%) versus 20 (13.2%), P = 0.17], ED visits, [telehealth 15 (10%) versus 18 (12%), P = 0.53], 30-day readmission [telehealth 3 (2%) versus 0 (0%), P = 0.09], nor missed adverse events [telehealth 6 (33.3%) versus 5 (27.8%), P = 0.72]. CONCLUSIONS: There were no differences in postoperative complications, ED utilization, 30-day readmission, or missed adverse events for those who followed-up in person versus telehealth after elective or urgent/emergent inguinal hernia repair. Veterans with a higher ASA class and who underwent open repair were more likely to be seen in person. Telehealth follow-up after inguinal hernia repair is safe and effective.

Telehealth follow-up after cholecystectomy is safe in veterans.

BACKGROUND: The COVID-19 pandemic has brought many challenges including barriers to delivering high-quality surgical care and follow-up while minimizing the risk of infection. Telehealth has been increasingly utilized for post-operative visits, yet little data exists to guide surgeons in its use. We sought to determine safety and efficacy of telehealth follow-up in patients undergoing cholecystectomy during the global pandemic at a VA Medical Center (VAMC). METHODS: This was a retrospective review of patients undergoing cholecystectomy at a level 1A VAMC over a 2-year period from August 2019 to August 2021. Baseline demographics, post-operative complications, readmissions, emergency department (ED) visits and need for additional procedures were reviewed. Patients who experienced a complication prior to discharge, underwent a concomitant procedure, had non-absorbable skin closure, had new diagnosis of malignancy or were discharged home with drain(s) were ineligible for telehealth follow-up and excluded. RESULTS: Over the study period, 179 patients underwent cholecystectomy; 30 (17%) were excluded as above. 20 (13%) missed their follow-up, 52 (35%) were seen via telehealth and 77 (52%) followed-up in person. There was no difference between the two groups regarding baseline demographics or intra-operative variables. There was no significant difference in post-operative complications [4 (8%) vs 6 (8%), p > 0.99], ED utilization [5 (10%) vs 7 (9%), p = 0.78], 30-day readmission [3 (6%) vs 6 (8%), p = 0.74] or need for additional procedures [2 (4%) vs 4 (5%), p = 0.41] between telehealth and in-person follow-up. CONCLUSION: Telehealth follow-up after cholecystectomy is safe and effective in Veterans. There were no differences in outcomes between patients that followed up in-person vs those that were seen via phone or video. Routine telehealth follow-up after uncomplicated cholecystectomy should be considered for all patients.

Cadmium modulates steatosis, fibrosis, and oncogenic signaling in liver cancer cells by activating notch and AKT/mTOR pathways.

Cadmium (Cd) is an environmental pollutant that increases hepatotoxicity and the risk of liver diseases. In the current study, we investigated the effect of a physiologically relevant, low concentration of Cd on the regulation of liver cancer cell proliferation, steatosis, and fibrogenic/oncogenic signaling. Exposure to low concentrations of Cd increased endogenous reactive oxygen species (ROS) production and enhanced cell proliferation in a human bipotent progenitor cell line HepaRG and hepatocellular carcinoma (HCC) cell lines. Acute exposure of Cd increased Jagged-1 expression and activated Notch signaling in HepaRG and HCC cells HepG2 and SK-Hep1. Cd activated AKT/mTOR signaling by increasing phosphorylation of AKT-S473 and mTOR-S-4448 residues. Moreover, a low concentration of Cd also promoted cell steatosis and induced fibrogenic signaling in HCC cells. Chronic exposure to low concentrations of Cd-activated Notch and AKT/mTOR signaling induced the expression of pro-inflammatory cytokines tumor necrosis factor-alpha (TNFα) and its downstream target TNF-α-Induced Protein 8 (TNFAIP8). RNA-Seq data revealed that chronic exposure to low concentrations of Cd modulated the expression of several fatty liver disease-related genes involved in cell steatosis/fibrosis in HepaRG and HepG2 cells. Collectively, our data suggest that low concentrations of Cd modulate steatosis along with fibrogenic and oncogenic signaling in HCC cells by activating Notch and AKT/mTOR pathways.

A dedicated feeding tube clinic reduces emergency department utilization for gastrostomy tube complications.

INTRODUCTION: Enteral access is required for a variety of reasons from neuromuscular disorders to dysphagia. Gastrostomy tubes (GTs) can be placed endoscopically, surgically, or radiographically and complications include infection, bleeding, leakage and unintentional removal. Routine post-procedural follow-up is limited by inconsistent guidelines and management by different specialty teams. We established a dedicated GT clinic to provide continuity of care and prophylactic GT exchange. We hypothesized that patients followed in the GT clinic would have reduced Emergency Department (ED) utilization. METHODS: A retrospective review of patients who underwent GT placement from January 2010 to January 2020 was conducted. Baseline demographics, indications for GT placement, number and reason for ED visits and utilization of a multidisciplinary GT clinic were studied. RESULTS: A total of 97 patients were included. The most common indication for placement was dysphagia (88, 91%) and the most common primary diagnosis was head and neck malignancy (51, 51%). The GT clinic is a multidisciplinary clinic staffed by surgeons and residents, dieticians, and wound care specialists and cared for 16 patients in this study. Three patients (19%) in the GT clinic group required ED visits compared to 44 (54%) in the standard of care (SOC) group (p < 0.05). There was an average of 0.9 ED visits per patient (range 0-7) in the GT clinic group vs 1.6 ED visits per patient (range 0-20) in the SOC group (p = 0.34). Feeding tubes were prophylactically exchanged an average of 7 times per patient in the GT clinic group vs 3 times per patient in the SOC group (p < 0.05). CONCLUSION: A multidisciplinary clinic dedicated to GT care limits ED visits for associated complications by more than 50%. Follow-up in a dedicated clinic with prophylactic tube exchange decreases ED visits and should be considered at facilities that care for patients with GTs.

Monopolar stray energy in robotic surgery.

INTRODUCTION: Stray energy transfer from monopolar radiofrequency energy during laparoscopy can be potentially catastrophic. Robotic surgery is increasing in popularity; however, the risk of stray energy transfer during robotic surgery is unknown. The purpose of this study was to (1) quantify stray energy transfer using robotic instrumentation, (2) determine strategies to minimize the transfer of energy, and (3) compare robotic stray energy transfer to laparoscopy. METHODS: In a laparoscopic trainer, a monopolar instrument (L-hook) was activated with DaVinci Si (Intuitive, Sunnyvale, CA) robotic instruments. A camera and assistant grasper were inserted to mimic a minimally invasive cholecystectomy. During activation of the L-hook, the non-electric tips of the camera and grasper were placed adjacent to simulated tissue (saline-soaked sponge). The primary outcome was change in temperature from baseline (°C) measured nearest the tip of the non-electric instrument. RESULTS: Simulated tissue nearest the robotic grasper increased an average of 18.3 ± 5.8 °C; p < 0.001 from baseline. Tissue nearest the robotic camera tip increased (9.0 ± 2.1 °C; p < 0.001). Decreasing the power from 30 to 15 W (18.3 ± 5.8 vs. 2.6 ± 2.7 °C, p < 0.001) or using low-voltage cut mode (18.3 ± 5.8 vs. 3.1 ± 2.1 °C, p < 0.001) reduced stray energy transfer to the robotic grasper. Desiccating tissue, in contrast to open air activation, also significantly reduced stray energy transfer for the grasper (18.3 ± 5.8 vs. 0.15 ± 0.21 °C, p < 0.001) and camera (9.0 ± 2.1 vs. 0.24 ± 0.34 °C, p < 0.001). CONCLUSIONS: Stray energy transfer occurs during robotic surgery. The assistant grasper carries the highest risk for thermal injury. Similar to laparoscopy, stray energy transfer can be reduced by lowering the power setting, utilizing a low-voltage cut mode instead of coagulation mode and avoiding open air activation. These practical findings can aid surgeons performing robotic surgery to reduce injuries from stray energy.

Stray energy transfer in single-incision robotic surgery.

INTRODUCTION: Stray energy transfer from surgical monopolar radiofrequency energy instruments can cause unintended thermal injuries during laparoscopic surgery. Single-incision laparoscopic surgery transfers more stray energy than traditional laparoscopic surgery. There is paucity of published data concerning stray energy during single-incision robotic surgery. The purpose of this study was to quantify stray energy transfer during traditional, multiport robotic surgery (TRS) compared to single-incision robotic surgery (SIRS). METHODS: An in vivo porcine model was used to simulate a multiport or single-incision robotic cholecystectomy (DaVinci Si, Intuitive Surgical, Sunnyvale, CA). A 5 s, open air activation of the monopolar scissors was done on 30 W and 60 W coag mode (ForceTriad, Covidien-Medtronic, Boulder, CO) and Swift Coag effect 3, max power 180 W (VIO 300D, ERBE USA, Marietta, GA). Temperature of the tissue (°C) adjacent to the tip of the assistant grasper or the camera was measured with a thermal camera (E95, FLIR Systems, Wilsonville, OR) to quantify stray energy transfer. RESULTS: Stray energy transfer was greater in the SIRS setup compared to TRS setup at the assistant grasper (11.6 ± 3.3 °C vs. 8.4 ± 1.6 °C, p = 0.013). Reducing power from 60 to 30 W significantly reduced stray energy transfer in SIRS (15.3 ± 3.4 °C vs. 11.6 ± 3.3 °C, p = 0.023), but not significantly for TRS (9.4 ± 2.5 °C vs. 8.4 ± 1.6 °C, p = 0.278). The use of a constant voltage regulating generator also minimized stray energy transfer for both SIRS (0.7 ± 0.4 °C, p < 0.001) and TRS (0.7 ± 0.4 °C, p < 0.001). CONCLUSIONS: More stray energy transfer occurs during single-incision robotic surgery than multiport robotic surgery. Utilizing a constant voltage regulating generator minimized stray energy transfer for both setups. These data can be used to guide robotic surgeons in their use of safe, surgical energy.

Acoustofluidic-mediated molecular delivery to human T cells with a three-dimensional-printed flow chamber.

Cell-based therapies have garnered significant interest to treat cancer and other diseases. Acoustofluidic technologies are in development to improve cell therapy manufacturing by facilitating rapid molecular delivery across the plasma membrane via ultrasound and microbubbles (MBs). In this study, a three-dimensional (3D) printed acoustofluidic device was used to deliver a fluorescent molecule, calcein, to human T cells. Intracellular delivery of calcein was assessed after varying parameters such as MB face charge, MB concentration, flow channel geometry, ultrasound pressure, and delivery time point after ultrasound treatment. MBs with a cationic surface charge caused statistically significant increases in calcein delivery during acoustofluidic treatment compared to MBs with a neutral surface charge (p < 0.001). Calcein delivery was significantly higher with a concentric spiral channel geometry compared to a rectilinear channel geometry (p < 0.001). Additionally, calcein delivery was significantly enhanced at increased ultrasound pressures of 5.1 MPa compared to lower ultrasound pressures between 0-3.8 MPa (p < 0.001). These results demonstrate that a 3D-printed acoustofluidic device can significantly enhance intracellular delivery of biomolecules to T cells, which may be a viable approach to advance cell-based therapies.

Diseases with health disparities as drivers of COVID-19 outcome.

The COVID-19 pandemic has forced our society to come face to face with complex issues that were once theoretical but are now being played out in real time. As data from the pandemic accumulates, it is clear that COVID-19 is impacting some parts of society more than others. Unfortunately, there is an almost complete overlap between COVID-19 risk factors and conditions that are already represented as health disparities, such as hypertension, diabetes, heart disease, lung disease and immune disorders. In this review, we discuss our current understanding of the physiological and pathophysiological pathways that link these diseases to COVID-19 outcome. An increased awareness of the factors underlying this issue, both societal and medical, is needed to understand the long-term implications and possible solutions needed going forward.

Hepatic Ablation Promotes Colon Cancer Metastases in an Immunocompetent Murine Model.

OBJECTIVE: To determine the impact of radiofrequency (RF) and microwave (MW) energy compared to direct cautery on metatstatic colon cancer growth. BACKGROUND: Hepatic ablation with MW and RF energy creates a temperature gradient around a target site with temperatures known to create tissue injury and cell death. In contrast, direct heat application (cautery) vaporizes tissue with a higher site temperature but reduced heat gradient on surrounding tissue. We hypothesize that different energy devices create variable zones of sublethal injury that may promote tumor recurrence. To test this hypothesis we applied MW, RF, and cautery to normal murine liver with a concomitant metastatic colon cancer challenge. METHODS: C57/Bl6 mice received hepatic thermal injury with MW, RF, or cautery to create a superficial 3-mm lesion immediately after intrasplenic injection of 50K MC38 colon cancer cells. Thermal imaging recorded tissue temperature during ablation and for 10 seconds after energy cessation. Hepatic tumor location and volume was determined at day 7. RESULTS: Cautery demonstrated the highest maximum tissue temperatures (129°C) with more rapid return to baseline compared to MW or RF energy. All mice had metastasis at the ablation site. Mean tumor volume was significantly greater in the MW (95.3 mm; P = 0.007) and RF (55.7 mm; P = 0.015) than cautery (7.13 mm). There was no difference in volume between MW and RF energy (P = 0.2). CONCLUSIONS: Hepatic thermal ablation promotes colon cancer metastasis at the injury site. MV and RF energy result in greater metastatic volume than cautery. These data suggest that the method of energy delivery promotes local metastasis.

Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group.

In contrast to studies on class I histone deacetylase (HDAC) inhibitors, the elucidation of the molecular mechanisms and therapeutic potential of class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) is impaired by the lack of potent and selective chemical probes. Here we report the discovery of inhibitors that fill this void with an unprecedented metal-binding group, trifluoromethyloxadiazole (TFMO), which circumvents the selectivity and pharmacologic liabilities of hydroxamates. We confirm direct metal binding of the TFMO through crystallographic approaches and use chemoproteomics to demonstrate the superior selectivity of the TFMO series relative to a hydroxamate-substituted analog. We further apply these tool compounds to reveal gene regulation dependent on the catalytic active site of class IIa HDACs. The discovery of these inhibitors challenges the design process for targeting metalloenzymes through a chelating metal-binding group and suggests therapeutic potential for class IIa HDAC enzyme blockers distinct in mechanism and application compared to current HDAC inhibitors.

Feeding Tube Clinic Effect on Nutrition.

BACKGROUND: Optimizing nutrition is essential for recovery after major surgery or severe illness. Feeding tubes (FT) can be placed in patients limited by oral enteral nutrition. Given the myriad of locations in which these procedures are performed (radiology, intensive care unit, and endoscopy suite), routine follow-up is challenging. The purpose of this study was to evaluate the impact of an FT clinic on nutrition. We hypothesized that enrollment in the FT clinic would result in improved nutritional outcomes. METHODS: Retrospective review of Veteran Affairs Medical Center patients with FTs placed from January 2010 to January 2020. Demographics and body mass index (BMI) were recorded. Serum albumin recorded within 1 month of tube placement was compared to within 1 month of tube removal, death, or at the end of the study period. FT clinic participation required at least 2 visits. Indications for FT placement and duration were recorded. Patients were excluded when both BMI and albumin values were incomplete, and if FTs were placed for decompression. RESULTS: Ninety-three patients underwent FT placement during the study period; 5 (5%) were excluded. The average age was 64.8±9.7 years, with the majority being male, 85 patients (97%). Eighteen (20%) patients were seen in the FT clinic (FTC) and 70 (80%) were managed outside of FTC (nFTC). There were no differences in age, gender, or indication for FT. Mean albumin increased 0.42±0.85 g/dL in the FTC group versus -0.07±0.72 g/dL in the nFTC group ( P =0.037). The FTC group BMI increased, 0.38 kg/m 2 vs. -1.48 kg/m 2 in nFTC patients, P =0.041. The FTC patients maintained their tubes longer (36.5 vs. 7.0 mo, P =0.0014). CONCLUSIONS: Patients managed in a dedicated FT clinic experienced an improvement in their serum albumin values and increases in their BMI. In addition, they also maintained their FTs longer. To optimize nutrition and reduce weight loss, patients who require FTs should be enrolled in a dedicated FT clinic.

Telehealth for general surgery postoperative care.

BACKGROUND: Telehealth utilization rapidly increased following the pandemic. However, it is not widely used in the Veteran surgical population. We sought to evaluate postoperative telehealth in patients undergoing general surgery. METHODS: Retrospective review of Veterans undergoing general surgery at a level 1A VA Medical Center from June 2019 to September 2021. Exclusions were concomitant procedure(s), discharge with drains or non-absorbable sutures/staples, complication prior to discharge or pathology positive for malignancy. RESULTS: 1075 patients underwent qualifying procedures, 124 (12 â€‹%) were excluded and 162 (17 â€‹%) did not have follow-up. 443 (56 â€‹%) patients followed-up in-person (56 â€‹%) vs 346 (44 â€‹%) via telehealth. Telehealth patients had a lower rate of complications, 6 â€‹% vs 12 â€‹%, p â€‹= â€‹0.013. There were no significant differences in ED visits, 30-day readmission, postoperative procedures or missed adverse events. CONCLUSION: Telehealth follow-up after general surgical procedures is safe and effective. Postoperative telehealth care should be considered after low-risk general surgery procedures.

Comparison of Acoustofluidic and Static Systems for Ultrasound-Mediated Molecular Delivery to T Lymphocytes.

Continuous-flow acoustofluidic technologies can potentially improve processing of T lymphocytes for cell therapies by addressing the limitations with viral and non-viral delivery methods. The objective of this study was to assess the intracellular delivery efficiency with acoustofluidic treatment compared with that of static ultrasound treatment. Optimization of parameters in acoustofluidic and static configurations was performed by assessing intracellular delivery of a fluorescent compound (calcein) in viable human Jurkat T lymphocytes. Ultrasound pressure and the concentration of cationic phospholipid-coated microbubbles influenced calcein delivery in both systems. In the static system, a treatment time of 45 s increased molecular delivery compared with 0-30 s (p < 0.01). Refined parameters were used to assess molecular delivery of small and large compounds (0.6-kDa calcein and 150-kDa fluorescein isothiocyanate-dextran, respectively) after ultrasound treatment with the acoustofluidic or static systems. Molecular delivery was similar with refined parameters for acoustofluidic treatment and static treatment (p > 0.05), even though acoustofluidic treatment had lower microbubble concentration (24 µg/mL vs. 94 µg/mL) and shorter treatment time (∼2-3 s vs. 45 s). This study indicates that the acoustofluidic system can significantly enhance intracellular molecular delivery, which could potentially enable acoustofluidic cell transfection during continuous flow processing for manufacture of cell therapies or other applications.

Emerging Roles of Impaired Autophagy in Fatty Liver Disease and Hepatocellular Carcinoma.

Autophagy is a conserved catabolic process that eliminates dysfunctional cytosolic biomolecules through vacuole-mediated sequestration and lysosomal degradation. Although the molecular mechanisms that regulate autophagy are not fully understood, recent work indicates that dysfunctional/impaired autophagic functions are associated with the development and progression of nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), and hepatocellular carcinoma (HCC). Autophagy prevents NAFLD and AFLD progression through enhanced lipid catabolism and decreasing hepatic steatosis, which is characterized by the accumulation of triglycerides and increased inflammation. However, as both diseases progress, autophagy can become impaired leading to exacerbation of both pathological conditions and progression into HCC. Due to the significance of impaired autophagy in these diseases, there is increased interest in studying pathways and targets involved in maintaining efficient autophagic functions as potential therapeutic targets. In this review, we summarize how impaired autophagy affects liver function and contributes to NAFLD, AFLD, and HCC progression. We will also explore how recent discoveries could provide novel therapeutic opportunities to effectively treat these diseases.

Role of Autophagy in Cadmium-Induced Hepatotoxicity and Liver Diseases.

Cadmium (Cd) is a toxic pollutant that is associated with several severe human diseases. Cd can be easily absorbed in significant quantities from air contamination/industrial pollution, cigarette smoke, food, and water and primarily affects the liver, kidney, and lungs. Toxic effects of Cd include hepatotoxicity, nephrotoxicity, pulmonary toxicity, and the development of various human cancers. Cd is also involved in the development and progression of fatty liver diseases and hepatocellular carcinoma. Cd affects liver function via modulation of cell survival/proliferation, differentiation, and apoptosis. Moreover, Cd dysregulates hepatic autophagy, an endogenous catabolic process that detoxifies damaged cell organelles or dysfunctional cytosolic proteins through vacuole-mediated sequestration and lysosomal degradation. In this article, we review recent developments and findings regarding the role of Cd in the modulation of hepatotoxicity, autophagic function, and liver diseases at the molecular level.

A Multidisciplinary High-Risk Surgery Committee May Improve Perioperative Decision Making for Patients and Physicians.

Background: Surgeons must evaluate and communicate the risk associated with operative procedures for patients at high risk of poor postoperative outcomes. Multidisciplinary approaches to complex decision making are needed. Objective: To improve physician decision making for high-risk surgical patients. Design: This is a retrospective review of patients presented to a multidisciplinary committee for three years. Setting/Subjects: Evaluation of patients was done in a single-center U.S. veterans affairs (VA) hospital. All patients who were considered for surgery had a VA Surgical Quality Improvement Program (VASQIP) risk calculator 30-day mortality >5%. Measurements: Thirty-day and one-year mortality were measured. Results: Seventy-six patients were reviewed with an average expected 30-day mortality of 14.2%. Forty-two patients (57%) had a recommended change in the care plan before surgery. Fifty-four patients (71%) proceeded with surgery and experienced a 30-day mortality of 7.4%. Conclusions and Relevance: Multidisciplinary discussion of high-risk surgical patients may help surgeons make perioperative recommendations for patients. Implementation of a multidisciplinary high-risk committee should be considered at facilities that manage high-risk surgical patients.

Assembly and Operation of an Acoustofluidic Device for Enhanced Delivery of Molecular Compounds to Cells.

Efficient intracellular delivery of biomolecules is required for a broad range of biomedical research and cell-based therapeutic applications. Ultrasound-mediated sonoporation is an emerging technique for rapid intracellular delivery of biomolecules. Sonoporation occurs when cavitation of gas-filled microbubbles forms transient pores in nearby cell membranes, which enables rapid uptake of biomolecules from the surrounding fluid. Current techniques for in vitro sonoporation of cells in suspension are limited by slow throughput, variability in the ultrasound exposure conditions for each cell, and high cost. To address these limitations, a low-cost acoustofluidic device has been developed which integrates an ultrasound transducer in a PDMS-based fluidic device to induce consistent sonoporation of cells as they flow through the channels in combination with ultrasound contrast agents. The device is fabricated using standard photolithography techniques to produce the PDMS-based fluidic chip. An ultrasound piezo disk transducer is attached to the device and driven by a microcontroller. The assembly can be integrated inside a 3D-printed case for added protection. Cells and microbubbles are pushed through the device using a syringe pump or a peristaltic pump connected to PVC tubing. Enhanced delivery of biomolecules to human T cells and lung cancer cells is demonstrated with this acoustofluidic system. Compared to bulk treatment approaches, this acoustofluidic system increases throughput and reduces variability, which can improve cell processing methods for biomedical research applications and manufacturing of cell-based therapeutics.

Perioperative Care Strategy for Older Adults.

Geriatric patients are not just older adult patients. Aging brings about unique physiologic, psychological, and sociologic changes within individuals. Recognition of these unique characteristics and measuring for their impact; instituting mitigating strategies; using age-specific anesthetic measures; and performing a systematic, algorithmic care model in the postoperative period overseen by a multidisciplinary team brings about enhanced outcomes and improved quality of care for this expanding group of patients.

The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells.

Exosomes are membrane-bound extracellular vesicles (EVs) that transport bioactive materials between cells and organs. The cargo delivered by exosomes can alter a wide range of cellular responses in recipient cells and play an important pathophysiological role in human cancers. In hepatocellular carcinoma (HCC), for example, adipocyte- and tumor-secreted factors contained in exosomes contribute to the creation of a chronic inflammatory state, which contributes to disease progression. The exosome-mediated crosstalk between adipocytes and liver cancer cells is a key aspect of a dynamic tumor microenvironment. In this review, we summarize the role of increased adiposity and the role of adipocyte-derived exosomes (AdExos) and HCC-derived exosomes (HCCExos) in the modulation of HCC progression. We also discuss recent advances regarding how malignant cells interact with the surrounding adipose tissue and employ exosomes to promote a more aggressive phenotype.

Ultrasound-induced molecular delivery to erythrocytes using a microfluidic system.

Preservation of erythrocytes in a desiccated state for storage at ambient temperature could simplify blood transfusions in austere environments, such as rural clinics, far-forward military operations, and during space travel. Currently, storage of erythrocytes is limited by a short shelf-life of 42 days at 4 °C, and long-term preservation requires a complex process that involves the addition and removal of glycerol from erythrocytes before and after storage at -80 °C, respectively. Natural compounds, such as trehalose, can protect cells in a desiccated state if they are present at sufficient levels inside the cell, but mammalian cell membranes lack transporters for this compound. To facilitate compound loading across the plasma membrane via ultrasound and microbubbles (sonoporation), a polydimethylsiloxane-based microfluidic device was developed. Delivery of fluorescein into erythrocytes was tested at various conditions to assess the effects of parameters such as ultrasound pressure, ultrasound pulse interval, microbubble dose, and flow rate. Changes in ultrasound pressure and mean flow rate caused statistically significant increases in fluorescein delivery of up to 73 ± 37% (p < 0.05) and 44 ± 33% (p < 0.01), respectively, compared to control groups, but no statistically significant differences were detected with changes in ultrasound pulse intervals. Following freeze-drying and rehydration, recovery of viable erythrocytes increased by up to 128 ± 32% after ultrasound-mediated loading of trehalose compared to control groups (p < 0.05). These results suggest that ultrasound-mediated molecular delivery in microfluidic channels may be a viable approach to process erythrocytes for long-term storage in a desiccated state at ambient temperatures.