Addressing the Rhino in the Room: ChatGPT Creates "Novel" Patent Ideas for Rhinoplasty.

Background: OpenAI's ChatGPT can generate novel ideas for a number of applications. The aim of this study was to prompt the chatbot to generate possible innovations in aesthetic surgery relating to rhinoplasty. Methods: ChatGPT was prompted to develop rhinoplasty patents. The resulting outputs were tabulated and categorized based on technology domain and anatomic location. A Google Patents search was conducted to find uses of the term "rhinoplasty" between 2021 and 2023. Patents not pertaining to rhinoplasty were excluded. Filed patents were compared with those generated by ChatGPT to determine predictive power. Results: A total of 40 patents resulted from ChatGPT and 42 Google Patents from 2021 to 2023 were included. Patents generated without a detailed description command were related to preoperative planning (35%), intraoperative tools (30%), functional evaluation (15%), and 3D printing and implants (10%). Patents with a detailed description command resulted in the majority being postoperative tools (40%), followed by intraoperative tools (30%), 3D printing and implants (10%), and nonsurgical (10%) categories. The anatomic locations included the airway, dorsum, septum, and nasal tip. ChatGPT's predictive power yielded 45% for the detailed prompting, which was higher than the prompt without the detail command. Conclusions: ChatGPT has reasonable potential to generate ideas for innovations in plastic surgery with the assistance of an experienced surgeon-innovator. With new artificial intelligence generations and updates, chatbots will continue to improve. Determining whether these technologies can assist in the later portions of the patent process beyond idea generation will be crucial.

Development of Hsp90 C-terminal inhibitors with noviomimetics that manifest anti-proliferative activities.

Inhibition of the Hsp90 C-terminal domain offers a promising opportunity to treat numerous diseases/indications. Furthermore, the development of Hsp90 C-terminal inhibitors (CTIs) is advantageous over N-terminal inhibitors because it avoids the detriments associated with induction of the heat shock response (HSR). However, the lack of co-crystal structures of small molecules bound to the C-terminus have hindered their development. Therefore, structure-activity relationship (SAR) studies have been pursued to optimize such inhibitors. Noviose sugar surrogates, also known as noviomimetics have been prepared to investigate the size and nature of the C-terminal domain binding pocket. Herein, we report the synthesis and anti-proliferative activity manifested by this new series of Hsp90 C-terminal inhibitors.

Carpal Joint Malalignment With Distal Radius Malunion and Factors in Correction After Distal Radius Osteotomy.

Purpose: There is a paucity of data regarding recommendations on when to correct for distal radius malunions and if the initial severity of the radiographic outcomes is correlated with the ability to correct to baseline. We evaluated the effects of distal radius corrective osteotomy on preoperative carpal joint malalignment resulting from distal radius malunions, correlated injury severity and osteotomy timing to radiographic outcomes, and developed a straightforward classification system for predicting radiocarpal and midcarpal maladaptive patterns. Methods: A retrospective review included 26 patients (27 wrists) who reported initial closed treatment for a distal radius fracture and who subsequently underwent a corrective osteotomy for malunion. Data included patient demographics, range of motion, preoperative fracture deformity, fracture deformity correction, and preoperative and postoperative radiographic measurements of the radiocarpal and midcarpal alignment patterns. Results: Of 27 dorsally angulated malunions, 16 were classified as type 1 midcarpal adaptation and 11 as type 2 radiocarpal adaptation. The midcarpal group showed significant improvements in distal radius and carpal alignment parameters after surgery, except for the ulnar variance. The radiocarpal group showed significant improvements in distal radius and carpal alignment parameters, except for the radiolunate angle, radioscaphoid angle, and capitolunate angle. The radiocarpal group exhibited an overall decrease in range of motion compared with that of the midcarpal group. Severity of the fracture and time taken from injury to corrective osteotomy correlated with the ability to correct carpal radiographic parameters in dorsally angulated malunions of the distal radius, especially beyond 40 weeks. Conclusions: The severity of the initial fracture and time taken from injury to corrective osteotomy correlate with the ability to correct radiographic parameters in dorsally angulated malunions of the distal radius. Early correction of distal radius malunions is recommended, especially in radiocarpal malalignment patterns. A useful analysis for predicting midcarpal and radiocarpal adaptation patterns is the direct measurement of the distal articular surface of the radius to the lunate, termed the relative-radiolunate angle. Type of study/level of evidence: Therapeutic IV.

Patient Perspectives on Telemedicine During the COVID-19 Pandemic.

BACKGROUND: Patients received care over telemedicine during the COVID-19 pandemic, and their perspective is useful for hand surgeons. METHODS: Online surveys were sent October-November 2020 to 497 patients who received telemedicine care. Questions were free-response and multi-item Likert scales asking about telehealth in general, limitations, benefits, comparisons to in-person visits, and opinions on future use. RESULTS: The response rate was 26% (n = 130). Prior to the pandemic, 55% had not used telemedicine for hand surgery consultation. Patients liked their telemedicine visit and felt their provider spent enough time with them (means = 9/10). In all, 48% would have preferred in-person visits despite the pandemic, and 69% would prefer in-person visits once the pandemic concludes. While 43% had no concerns with telemedicine, 36% had difficulties explaining their symptoms. Telemedicine was easy to access and navigate (M = 9/10). However, 23% saw telemedicine of limited value due to the need for an in-person visit soon afterward. Of these patients, 46% needed an in-person visit due to inadequate physical examination. Factors that make telemedicine more favorable to patients included convenience, lack of travel, scheduling ease, and time saved. Factors making telemedicine less favorable included need for in-person examination or procedure, pain assessment, and poor connectivity. There was no specific appointment time the cohort preferred. Patient recommendations to improve telemedicine included decreasing wait times and showing patient queue, wait time, or physician status online. CONCLUSIONS: Telemedicine was strongly liked by patients during the COVID-19 pandemic. However, nearly 70% of patients still preferred in-person visits for the future.

Return to Sport Following Distal Triceps Repair.

PURPOSE: The purpose of this investigation was to examine the timeline of return-to-sport following distal triceps repair; evaluate the degree of participation and function upon returning to sport; and identify risk factors for failure to return to sport. METHODS: Patients who underwent distal triceps repair with a minimum of 1 year of follow-up were retrospectively reviewed. Patients completed a subjective sports questionnaire and were scored on a visual analog scale for pain; the Mayo Elbow Performance Index; the Quick Disabilities of the Arm, Shoulder, and Hand; and the Single Assessment Numerical Evaluation. RESULTS: Out of 113 eligible patients who had a distal triceps repair, 81 patients (71.7%) were contacted. Sixty-eight patients (84.0%) who participated in sports prior to surgery were included at 6.0 ± 4.0 years after surgery, and the average age was 46.6 ± 11.5 years. Sixty-one patients (89.7%) resumed playing at least 1 sport by 5.9 ± 4.4 months following distal triceps repair. However, 18 patients (29.5%) returned to a lower level of activity intensity. The average postoperative Quick Disabilities of the Arm, Shoulder, and Hand; Mayo Elbow Performance; visual analog scale for pain; and Single Assessment Numerical Evaluation scores were 8.2 ± 14.0, 89.5 ± 13.4, 2.0 ± 1.7, and 82.2 ± 24.3, respectively. No patients underwent revision surgery at the time of final follow-up. CONCLUSIONS: Distal triceps repair enables 89.7% of patients to return to sport by 5.9 ± 4.4 months following surgery. However, 29.5% of patients were unable to return to their preinjury level of activity. It is imperative that patients are appropriately educated to manage postoperative expectations regarding sport participation following distal triceps repair. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Multi-genomic analysis of 260 adrenocortical cancer patient tumors identifies novel network BIRC5-hsa-miR-335-5p-PAX8-AS1 strongly associated with poor survival.

BACKGROUND: Adrenocortical carcinoma is a rare endocrine cancer with poor overall survival. Linking survival outcomes to a common target across multiple genomic datasets incorporating microRNA-long non-coding RNA dysregulation have not been well described. We hypothesized that a multi-database analysis of microRNA-long noncoding RNA-messenger RNA regulatory networks associated with survival will identify novel biomarkers. METHODS: Significantly dysregulated genes or microRNA in adrenocortical carcinoma compared to normal adrenal was identified from sequencing data for 260 human adrenocortical carcinomas using GEO2R. The miRnet identified hub microRNA and genes and long noncoding RNA and microRNA associated with survival genes. The R2 generated Kaplan-Meier curves. The database miRTarBase linked genes associated with poor survival and dysregulated microRNA. RESULTS: Analysis of genes and microRNAs differentially regulated in >50% of datasets revealed 75 genes and 12 microRNAs were upregulated, and 167 genes and 12 microRNAs were downregulated (bonf. P < .05). Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed cell cycle, P53 signaling, arachidonic acid and innate immune response, and PI3/Akt are altered in adrenocortical carcinoma. A microRNA-target interaction network of differentially regulated microRNAs identified upregulated miRNA107, 103a-3p and 27a-3p, 16-5p, and downregulated 335-5p to have the highest degree of interaction with upregulated (ie, TPX2, CDK1, BIRC5, PRC1, CCNB1, GINS1) and downregulated (ie, RSPO3, NR2F1, TLR4, HOXA5, USP53, SLC16A9) hub genes as well as hub long noncoding RNAs XIST, NEAT1, KCNQ1OT1, and PAX8-AS1. Survival analysis revealed that the hub genes are associated with poor overall survival (P < .05) of adrenocortical carcinoma in the Cancer Genome Atlas data. CONCLUSION: A messenger RNA-microRNA-long noncoding RNA network analysis identified the BIRC5-miR335-5p-PAX8-AS1 network as one that was associated with poor overall survival in adrenocortical carcinoma, warranting further validation as a potential therapeutic target.

Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma.

Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) from Physalis longifolia as a lead compound for targeting HNSCC. We hypothesized that combining WGA-TA with cisplatin may allow for lower, less toxic cisplatin doses. HNSCC cell lines were treated with WGA-TA and cisplatin. After treatment with the drugs, the cell viability was determined by MTS assay. The combination index was calculated using CompuSyn. The expression of proteins involved in the targeting of translational initiation complex, epithelial to mesenchymal transition (EMT), and apoptosis were measured by western blot. Invasion and migration were measured using the Boyden-chamber assay. Treatment of MDA-1986 and UMSCC-22B cell lines with either WGA-TA or cisplatin alone for 72 h resulted in a dose dependent decrease in cell viability. Cisplatin in combination with WGA-TA resulted in significant synergistic cell death starting from 1.25 µM cisplatin. Combination treatment with WGA-TA resulted in lower cisplatin dosing while maintaining the downregulation of translational initiation complex proteins, the induction of apoptosis, and the blockade of migration, invasion, and EMT transition. These results suggest that combining a low concentration of cisplatin with WGA-TA may provide a safer, more effective therapeutic option for HNSCC that warrants translational validation.

Recovery from open osteocapsular débridement for primary elbow osteoarthritis is rapid and does not depend on preoperative motion.

Background and Hypothesis: Osteocapsular débridement is a surgical treatment for functionally limiting primary elbow osteoarthritis (PEOA). We hypothesized that postoperative improvement in range of motion (ROM) following elbow osteocapsular débridement could be grouped into predictable patterns. We also hypothesized that significant improvements in ROM frequently take place for up to 6 months after surgery. Methods: A retrospective chart review of patients who underwent open elbow débridement for PEOA was performed. Demographic information and surgical approach were recorded. ROM data were also collected at preoperative, intraoperative, and postoperative intervals of 2 weeks, 6 weeks, 3 months, and 6 months. Growth mixture modeling and latent class growth analysis were performed to identify groups of motion recovery trajectories, while Student's t-tests were performed to compare ROM data between intervals. Results: Our study included 76 patients who underwent open elbow débridement (9 with a lateral approach, 55 medial, and 12 both) for PEOA. The mean preoperative arc of motion was 95° ± 22°. This improved to a mean final motion arc of 127° ± 11 at final follow-up, which was 92% of the mean intraoperative arc. The mean time to achieve final motion was 3 months, with 79% of patients achieving their final ROM arc by this point. Patients achieved an average of 85% of their final arc of motion by the 2-week postoperative visit (92% of final flexion and 61% of final extension). Growth mixture modeling and latent class growth analysis did not identify any statistically significant groupings for postoperative ROM progression trajectories. Arc of motion preoperatively, intraoperatively, and at 2 weeks postoperatively did not correlate with the final arc of motion. There were no characteristics or thresholds of motion which conferred a higher likelihood of achieving a better result postoperatively. Conclusions: ROM recovery after osteocapsular débridement for PEOA is not dependent on preoperative, intraoperative, or 2-week postoperative arcs of motion. Most of the ROM recovery occurs in the early postoperative period, with flexion restored preferentially faster than extension. The final arc of motion can be expected by 3 months postoperatively. This knowledge has potential benefit in affecting patients' personal time commitment to rehabilitation and the overall cost for therapy and splinting beyond the 3-month time point.

Relationship Between Preoperative and Postoperative Motion After Four-Corner Wrist Fusion for Osteoarthritis: Clustering and Regression Analyses.

PURPOSE: Four-corner fusion (4CF) is a surgical option for refractory scapholunate advanced collapse and scaphoid nonunion advanced collapse wrist arthritis. Preoperative range of motion (ROM) predicts outcomes in many orthopedic procedures. This study investigates ROM in a cohort of 4CF patients to examine the relationship between preoperative and postoperative motion and identifies different clinical patterns. METHODS: We performed a retrospective review of 4CF patients. Patients with a history of inflammatory arthritis and radiographic characteristics of inflammation were excluded. Demographics, prior wrist surgery history, and ROM data were collected at preoperative and postoperative intervals after cast removal at 8 weeks, 3 months, and 8 months. Regression analysis compared the motion before and after 4CF. Subsequent cluster analysis to reduce confounding compared postoperative motion differences in the top 20% to the bottom 20% of patients by preoperative motion. RESULTS: We included 148 patients; 27 had prior surgery on the ipsilateral wrist. Preoperative arc averaged 86° ± 28° (flexion 46° ± 17°, extension 40° ± 15°); 8-week arc 43° ± 19° (flexion 19° ± 12°, extension 24° ± 12°); 3-month arc 62° ± 17° (flexion 30° ± 12°, extension 32° ± 11°); and 8-month arc 74° ± 17° (flexion 36° ± 11°, extension 37° ± 12°). Preoperative and final arcs were (r = 0.39). Clustering by the preoperative arc, the top 20% (mean 124° ± 15°) achieved a mean final arc of 81° ± 16°, while the bottom 20% (mean 47° ± 16°) achieved a mean final arc of 65° ± 19°. Intercluster differences were statistically significant. The bottom 20% gained motion postoperatively. Most patients in the middle 60% did not differ significantly in postoperative motion. CONCLUSIONS: Although wrist motion following 4CF correlates positively with preoperative motion, most patients do not differ significantly in postoperative motion. Patients with substantial preoperative motion deficits gain motion after 4CF. This information is important when counseling patients, determining the timing of surgical intervention, and managing expectations related to motion outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Traction Tenolysis for Flexor Tendon Adhesions: Outcomes in 97 Patients.

PURPOSE: Traction tenolysis is an alternative, less invasive way of performing flexor tendon tenolysis by winding affected tendons around a surgical instrument. This study assessed outcomes and complications in a cohort of patients who underwent traction tenolysis to determine its effectiveness. METHODS: We retrospectively reviewed 97 patients who underwent traction tenolysis performed by 4 fellowship-trained hand surgeons from 2010 to 2019. We collected data on preoperative and postoperative ranges of motion, the number and type of prior ipsilateral hand surgeries, and the duration of therapy and follow-up. Cases of traditional open tenosynovectomy tenolysis were excluded. RESULTS: Approximately two-thirds of the patients achieved more than 75% of the normal total active motion, and 80% achieved at least 50% of the normal total active motion. The mean total active flexion increased significantly by 42° and passive flexion by 25°. The differences in active and passive flexion significantly decreased from 28° before the surgery to 9° after the surgery. The active and passive flexion of the distal interphalangeal and proximal interphalangeal joints improved similarly, at approximately 20° and 10°, respectively. The average duration of follow-up was 11 ± 8 weeks. The complication rate was 5%: 1 case of intraoperative flexor digitorum superficialis tendon rupture, 1 case of postoperative infection, and 3 reoperations because of failure to progress. CONCLUSIONS: Traction tenolysis is an alternative to traditional open tenolysis surgery in selected patients. LEVEL OF EVIDENCE: Therapeutic IV.

Telemedicine Use during the COVID-19 Pandemic: Results of an International Survey.

Objective The aim of the study is to survey hand surgeons' perspectives on telemedicine during the coronavirus disease 2019 (COVID-19) pandemic and intended applications after the pandemic. Methods Online surveys were sent to 285 Canadian and American surgeons in late April and early May 2020. Results Response rate was 63% (180)-84% (152) American and 16% (28) Canadian. Forty-three percent (76) of respondents were in private practice, 36% (64) academics, 13% (24) privademics, and 6% (12) hospital employed. The most common telemedicine platform was Zoom. During the pandemic, 42% of patient visits were conducted via telemedicine; however, 37% required a subsequent in-person office visit. The most common complaint by surgeons was the inability to provide routine in-office procedures. The most beneficial feature was ease of use, and the most frustrating feature was connectivity difficulty. Time spent was similar to in-person visits, and surgeons were likely to recommend their platforms. Surgeons were neutral about using telehealth in the future and were most likely to use it for follow-up visits. New patient visits for traumatic injuries or fractures were of limited value. Canadians used telemedicine for a greater proportion than Americans (50 vs. 40%, p <0.05) and spent more time than in-person visits (7/10 vs. 5/10, p <0.05). Americans were more likely to use telemedicine for postoperative follow-up visits (6/10 vs. 4/10, p <0.05) and in mornings before clinic opens (4/10 vs. 2/10, p <0.05). Private practices were more likely to use telemedicine for future allied health provider visits than all other practice types ( p <0.05). Conclusion Telemedicine comprised nearly half of patient encounters during the COVID-19 pandemic, but limitations remain.

Extended Reality International Grand Rounds: An Innovative Approach to Medical Education in the Pandemic Era.

PROBLEM: While bedside training has always presented its own unique challenges, the COVID-19 pandemic era has intensified barriers to suitable provider and trainee experiences for both patient care and medical education. APPROACH: This project introduced an innovative solution with the Extended Reality International Grand Rounds, a collaboration between the University of Michigan Center for Medical and Surgical Extended Reality and Imperial College London. Three complex cases were presented to trainees through a wireless, extended reality (XR) headset and augmented by holographic visual aids and expert commentary. This pilot rounding experience was performed through the first-person view of one clinician at the bedside. OUTCOMES: In 2020, 140 attendees participated in XR International Grand Rounds, and 82 (59%) and 61 (44%) completed pre- and postsurveys, respectively. Survey analysis showed that the majority of respondents (65, 79.3%) had very little to no baseline experience with XR technologies and nearly all (75, 91.5%) agreed that the development and implementation of XR curricula are important in medical training, indicating an unmet need. Nearly all respondents (59, 96.7%) found value in the ability to visualize patients' clinical findings in the XR rounding experience and 60 (98.4%) found value in the ability to visualize patient-specific imaging and test findings in an XR format. Limiting exposure to high-risk patients and care team members with this innovative format was believed to be important to 79 (96.3%) respondents at baseline and that perception was unchanged following the event. NEXT STEPS: This solution to a long-standing dilemma, newly stressed by a unique era in medicine, was a successful collaboration using state-of-the-art XR technology. Next steps will include introducing more advanced physical exam visualization and detection and comprehensive evaluation of the patient experience, as well as expanding the international experience in a format that is scalable to other interested institutions.

Progression patterns of range of motion progression after open release for post-traumatic elbow stiffness.

Background & Hypothesis: Post-traumatic stiffness of the elbow may be treated surgically with open osteocapsular release. This study investigated postoperative range of motion (ROM) improvements after this procedure. We hypothesized that there would be predictable recovery patterns and significant progress up to 6 months after surgery. Methods: A retrospective chart review of patients who underwent open elbow release for post-traumatic stiffness (PTS) was performed. Demographic information and surgical approach were recorded. Patients with ipsilateral primary elbow osteoarthritis were excluded. Range of motion (ROM) data were collected at preoperative, intraoperative, and postoperative intervals of 2 weeks, 6 weeks, 3 months, and 6 months. Growth mixture modeling (GMM) and latent class growth analysis (LCGA) were performed to identify motion recovery trajectory groups, and Student's t-tests were performed to compare ROM data between intervals. Results: One hundred and eighty-seven patients who underwent open elbow release for PTS were included (112 with a medial approach, 50 lateral, and 25 both). The mean preoperative arc was 84° ± 31, and the arc of motion at final follow-up was 119° ± 19 (P < .05). The mean time to the final follow-up arc of motion was 16 weeks, with 56% of patients achieving their final arc by their 3-month follow-up visit. The largest improvement was seen with extension between 6 weeks and 3 months, where 26% of the extension at final follow-up was gained. Most of the recovery occurred within the first 3 months postoperatively, with small improvements thereafter. GMM and LCGA did not identify statistically significant groups for postoperative ROM progression trajectories. Arc of motion preoperatively, intraoperatively, and at 2 weeks postoperatively did not correlate with the final arc of motion. There were no demographic or historical characteristics, or thresholds of motion, which conferred a higher likelihood of achieving a better result postoperatively. Conclusions: ROM recovery after surgical release for post-traumatic elbow stiffness did not depend on the preoperative, intraoperative, or 2-week postoperative arcs of motion. Most ROM recovery occurs early after surgery, and maximal arc of motion can be expected by approximately 16 weeks postoperatively. This knowledge may inform patients about their expected rehabilitation and splinting time and reduce the total costs of therapy.

The use of tranexamic acid in open elbow release surgery.

Background: Tranexamic acid (TXA) has been effective in reducing perioperative blood loss in hip, knee, and shoulder arthroplasty. Our purpose was to assess the effect of TXA on perioperative blood loss for open elbow release. Methods: Consecutive open elbow releases performed between October 2016 and March 2020 were identified. Patients were included if both anterior and posterior joint releases with a single medial approach was performed. From November 2018 onward, intravenous TXA and topical TXA infused through a deep hemovac drain were administered as part of the perioperative protocol. Drain output, intraoperative blood loss, postoperative aspiration rate, and postoperative transfusion frequency were assessed. Results: Fifty patients (25 TXA, 25 non-TXA) were included. Drain output was significantly lower in the TXA-treated group compared to the non-treated group (121 mL vs. 221 mL; p = 0.003). There was no significant difference in intraoperative blood loss and the incidence of postoperative aspiration between groups. None of the patients received a blood transfusion or had a documented thromboembolic event. Discussion: The use of tranexamic acid with open elbow release surgeries resulted in decreased drain output, with no thromboembolic events. Perioperative tranexamic acid can be a safe and effective modality in reducing perioperative blood loss for open elbow release surgery.

International Mixed Reality Immersive Experience: Approach via Surgical Grand Rounds.

BACKGROUND: Coronavirus disease 2019 created unintended but significant experiential barriers for surgical learners to interact at the bedside for teaching/case presentations. We hypothesized that an international grand rounds using the Microsoft HoloLens 2 extended reality (XR) headset would create an improved bedside-learning experience compared to traditional grand rounds formats. STUDY DESIGN: From December 2020 to March 2021, the world's first 2 international mixed reality grand rounds events using the HoloLens 2 headset were held, broadcasting transatlantically (between the University of Michigan and the Imperial College of London) bedside rounding experiences on 5 complex surgical patients to an international audience of 325 faculty, residents, and medical trainees. Participants completed pre- and post-event surveys to assess their experience. RESULTS: Of the 325 participants, 267 (80%) completed pre-surveys, and 95 (29%) completed both the pre- and post-surveys. Respondents (average age, 38 y; 44% women, 56% men; 211 US, 56 UK) included 92 (34%) medical students and residents and 175 faculty and staff. In the pre-event survey, 76% had little or no earlier experience with XR devices, and 94% thought implementation of XR into medical curricula was valuable. In the post-survey, 96% thought telerounding using XR technology was important for the current era, and 99% thought the ability to visualize the examination, imaging, and laboratory results at bedside via XR rounding was highly valuable and that this format was superior to traditional grand rounds. CONCLUSIONS: Almost all of the participants in the mixed reality international grand rounds felt the immersive XR experiences-allowing visualization of clinical findings, imaging, and laboratory results at the patient's bedside-were superior to a traditional grand rounds format, and that it could be a valuable tool for surgical teaching and telerounding.

Identification of novel lipid metabolic biomarkers associated with poor adrenocortical carcinoma prognosis using integrated bioinformatics.

BACKGROUND: Adrenocortical carcinoma while rare, often presents with advanced metastatic disease carrying a 5-year survival of <15%. Despite adrenocortical carcinoma tumors having high avidity for cholesterol, the role of lipids in adrenocortical carcinoma has not been well described. Therefore, we performed an integrated bioinformatic analysis to identify novel lipid biomarkers correlating with poor survival that may help identify adrenocortical carcinoma tumor progression or therapy resistance. METHODS: A meta-analysis of collated adrenocortical carcinoma studies from the correlation engine identified lipid metabolism genes differentially expressed between adrenocortical carcinoma and the normal adrenal, which were then selected for enrichment analysis by the Database for Annotation, Visualization and Integrated Discovery database. A protein-protein interaction network of genes was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape. Top hub genes identified were validated using the Xena database. Survival analysis of hub genes was performed in the R2 genomic analysis platform using The Cancer Genome Atlas program data set. RESULTS: Examination of pathways by correlation engine identified a unique subset of lipid metabolism-related genes that are differentially regulated in adrenocortical carcinoma tumors versus normal tissues (P < .01). Enrichment pathway analysis in Database for Annotation, Visualization and Integrated Discovery indicated that genes involved in sphingolipid, steroid, and peroxisome proliferator-activated receptor-α metabolism is upregulated in adrenocortical carcinoma, whereas glycerol phospholipid, fatty acid, and phosphatidylinositol metabolism are downregulated. Survival analysis of differentially regulated genes indicated that upregulation of SGPL1, FDFT1, SQLE and downregulation of PIK3C2B, PIK3CD, SYNJ2, DGAT1, PLA2G16, PLD1, GPD1 are all significantly associated with poor overall survival (P < .05) in adrenocortical carcinoma patients. CONCLUSION: Upregulation of sphingolipid and steroid synthesis genes and downregulation of phosphatidylinositol and glycerol phospholipid metabolism are associated with worse survival in patients with adrenocortical carcinoma.

Re-Evaluation of Combinational Efficacy and Synergy of the Italian Protocol In Vitro: Are We Truly Optimizing Benefit or Permitting Unwanted Toxicity?

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy, with very poor prognosis as a majority of the patients have advanced disease at the time of diagnosis. Currently, adjuvant therapy for most patients consists of either mitotane (M) alone or in combination with multi-drug chemotherapeutics such as etoposide (E), doxorubicin (D), and cisplatin (P), known as the Italian protocol (IP; EDPM). This multi-drug treatment regimen, however, carries significant toxicity potential for patients. One way to improve toxicity profiles with these drugs in combination is to understand where their synergy occurs and over what dosing range so that lower dose regimens could be applied in combination with equal or improved efficacy. We hypothesize that a better understanding of the synergistic effects as well as the regulation of steroidogenic enzymes during combination therapy may provide more optimized combinational options with good potency and lower toxicity profiles. METHODS: Two human ACC cell lines, NCI-H295R (hormonally active) and SW13 (hormonally inactive), were grown in 2D culture in appropriate growth medium. The viability of the cells after treatment with varying concentrations of the drugs (E, D, and P) either alone or in combinations with M was determined using the CellTiter Glow assay after 72 h, and the combination index for each was calculated using Compusyn by the Chou-Talalay method. The expression levels of enzymes associated with steroidogenesis were evaluated by RT-PCR in NCI-H295R. RESULTS: When both cell lines were treated with M (ranging 25-50 µM), +E (ranging 18.75-75 µM), and +D (ranging 0.625-2.5 µM) we observed a synergistic effect (CI < 1) with potency equivalent to the full Italian protocol (IP), whereas combining M + P + D had an antagonistic effect (CI > 1) indicating the negative effect of adding cisplatin in the combination. Comparing the hormonally active and inactive cell lines, M + P + E was antagonistic in NCI-H295R and synergistic in SW13. Treatment of NCI-H295R cells with antagonistic combinations (M + P + D, M + P + E) resulted in a significant decrease in the levels of steroidogenic enzymes STAR, CYP11A1, and CYP21A2 compared to IP (p < 0.05) while M + E + D resulted in increased expression or no significant effect compared to IP across all genes tested. CONCLUSIONS: The synergistic effect for M + E + D was significant and equivalent in potency to the full IP in both cell lines and resulted in a steroidogenic gene expression profile similar to or better than that of full IP, warranting further evaluation. Future in vivo evaluation of the combination of M + E + D (with removal of P from the IP regimen) may lower toxicity while maintaining anticancer efficacy in ACC.