Search

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.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.Analysis of genes and microRNAs differentially regulated in50% 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.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.

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.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.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.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.Prognostic II.

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.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.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.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.

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.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.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.Traction tenolysis is an alternative to traditional open tenolysis surgery in selected patients.Therapeutic IV.

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.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.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.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.

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.