Dissecting Ubiquitylation and DNA Damage Response Pathways in the Yeast Saccharomyces cerevisiae Using a Proteome-Wide Approach.

In response to genotoxic stress, cells evolved with a complex signaling network referred to as the DNA damage response (DDR). It is now well established that the DDR depends upon various posttranslational modifications; among them, ubiquitylation plays a key regulatory role. Here, we profiled ubiquitylation in response to the DNA alkylating agent methyl methanesulfonate (MMS) in the budding yeast Saccharomyces cerevisiae using quantitative proteomics. To discover new proteins ubiquitylated upon DNA replication stress, we used stable isotope labeling by amino acids in cell culture, followed by an enrichment of ubiquitylated peptides and LC-MS/MS. In total, we identified 1853 ubiquitylated proteins, including 473 proteins that appeared upregulated more than 2-fold in response to MMS treatment. This enabled us to localize 519 ubiquitylation sites potentially regulated upon MMS in 435 proteins. We demonstrated that the overexpression of some of these proteins renders the cells sensitive to MMS. We also assayed the abundance change upon MMS treatment of a selection of yeast nuclear proteins. Several of them were differentially regulated upon MMS treatment. These findings corroborate the important role of ubiquitin-proteasome-mediated degradation in regulating the DDR.

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.

Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony.

Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

Wound Complications Following Olecranon Fracture Fixation: Implant and Soft Tissue Considerations.

BACKGROUND: The aim of this multicenter, retrospective, case-control series was to investigate patient- and treatment-specific factors associated with wound breakdown following olecranon fracture fixation.  Methods: We identified patients at our two participating academic centers who were operatively treated for olecranon fractures and those who subsequently underwent a re-operation secondary to postoperative wound breakdown. Demographic and historical information was collected, including BMI and Charlson comorbidity index (CCI) scores. The primary outcome measure was the standardized radiographic measurement of plate prominence and soft tissue thickness posterior to the plate tip.  Results: We identified 32 patients who underwent internal fixation and subsequent wound breakdown. This was compared to a cohort of 35 matched controls that did not have wound issues. Cases with wound breakdown were of higher energy, nine being open cases compared to two in the control group (p<0.05). No differences were identified in plate prominence, soft tissue thickness, and plate type.  Conclusions: Wound breakdown following olecranon fracture fixation is more commonly seen in high-energy open injuries. Plate prominence, soft tissue thickness, and patient-specific factors do not correlate with wound breakdown. Further investigation into the factors influencing plate placement and how they may contribute to wound complications is needed.

A Soft-Tissue Landmark to Assess Humeral Component Rotation in Total Elbow Arthroplasty.

HYPOTHESIS: Assessing the rotational alignment of the humeral component during total elbow arthroplasty is dependent upon bony landmarks that can be absent or altered in cases of distal humerus fractures, revision arthroplasty, severe bone loss, or deformity. We hypothesize that the intermuscular septum can be used as a reliable soft-tissue landmark to set the rotation of the humeral component intra-operatively when previously described bony landmarks are not reliable or present. MATERIALS AND METHODS: Forty-eight unpaired cadaveric human subjects (mean age and standard deviation 63 ± 12 years; 24 males, 24 females) underwent computed tomography (CT) scans. The geometric centers of the trochlea and capitellum were assessed, and the line through these two points was set as the flexion-extension axis (FEA) of the elbow. The intermuscular septum axis (IMSA) was drawn proximal to the olecranon fossa and at least 4 cm proximal to the most distal point of the articular surface, where the posterior humeral cortex was flat. The angles between the FEA and IMSA were calculated and compared using a two-tailed t-test. Regression analysis was used to assess the inter- and intra-observer reliability of the IMSA. RESULTS: The IMSA was externally rotated 10.3° ± 2.8 compared to the FEA (p < 0.001 and confidence interval (CI) of 2.8 with α set to 0.01). The inter- and intra-observer reliability of the IMSA was high, with an R-value of 0.91 and 0.97, respectively. CONCLUSIONS: The intermuscular septum can be used as a soft-tissue landmark to set humeral component rotation and is 10.3° externally rotated with respect to the FEA of the ulnohumeral joint.

ISW1a modulates cohesin distribution in centromeric and pericentromeric regions.

Cohesin is a highly conserved, multiprotein complex whose canonical function is to hold sister chromatids together to ensure accurate chromosome segregation. Cohesin association with chromatin relies on the Scc2-Scc4 cohesin loading complex that enables cohesin ring opening and topological entrapment of sister DNAs. To better understand how sister chromatid cohesion is regulated, we performed a proteomic screen in budding yeast that identified the Isw1 chromatin remodeler as a cohesin binding partner. In addition, we found that Isw1 also interacts with Scc2-Scc4. Lack of Isw1 protein, the Ioc3 subunit of ISW1a or Isw1 chromatin remodeling activity resulted in increased accumulation of cohesin at centromeres and pericentromeres, suggesting that ISW1a may promote efficient translocation of cohesin from the centromeric site of loading to neighboring regions. Consistent with the role of ISW1a in the chromatin organization of centromeric regions, Isw1 was found to be recruited to centromeres. In its absence we observed changes in the nucleosomal landscape at centromeres and pericentromeres. Finally, we discovered that upon loss of RSC functionality, ISW1a activity leads to reduced cohesin binding and cohesion defect. Taken together, our results support the notion of a key role of chromatin remodelers in the regulation of cohesin distribution on chromosomes.

Identification of amino acid substitutions that toggle substrate selectivity of the yeast arsenite transporter Acr3.

The Acr3 protein family plays a crucial role in metalloid detoxification and includes members from bacteria to higher plants. Most of the Acr3 transporters studied so far are specific for arsenite, whereas Acr3 from budding yeast also shows some capacity to transport antimonite. However, the molecular basis of Acr3 substrate specificity remains poorly understood. By analyzing randomly generated and rationally designed yeast Acr3 variants, critical residues determining substrate specificity were identified for the first time. Replacement of Val173 with Ala abolished antimonite transport without affecting arsenite extrusion. In contrast, substitution of Glu353 with Asp resulted in a loss of arsenite transport activity and a concomitant increase in antimonite translocation capacity. Importantly, Val173 is located close to the hypothetical substrate binding site, whereas Glu353 has been proposed to participate in substrate binding. Identification of key residues conferring substrate selectivity provides a valuable starting point for further studies of the Acr3 family and may have implications for the development of biotechnological applications in metalloid remediation. Moreover, our data contribute to understanding why members of the Acr3 family evolved as arsenite-specific transporters in an environment of ubiquitously present arsenic and trace amounts of antimony.

Role of ubiquitination in arsenic tolerance in plants.

Arsenic (As) is harmful to all living organisms, including humans and plants. To limit As uptake and avoid its toxicity, plants employ systems that regulate the uptake of As from the soil and its translocation from roots to grains. Ubiquitination, a highly conserved post-translational modification (PTM) in all eukaryotes, plays crucial roles in modulating As detoxification mechanisms in budding yeast (Saccharomyces cerevisiae), but little is known about its roles in As tolerance and transport in plants. In this opinion article we review recent findings and suggest that ubiquitination plays a crucial role in regulating As transport in plants. We also propose ideas for future research to explore the importance of ubiquitination for enhancing As tolerance in crops.

Bridge Plating of a First Proximal Phalanx Intra-articular Base Fracture-Benefits Over External Fixation.

A 62-year-old right-handed man presented with an intra-articular fracture of the proximal phalanx base of the right thumb after a motor vehicle accident. Computed tomography revealed severe comminution, apex volar angulation, and minimal bone stock at the proximal phalanx base. The patient consented to open reduction internal fixation with a locking plate to bridge the fracture and cancellous bone grafting of the distal radius. The hardware was removed at 8 weeks, without complications. The patient began therapy, and at 19 weeks following the surgery, the patient's thumb metacarpophalangeal joint motion was 10° to 30° and the interphalangeal motion was 30° to 50°. Radiographs showed fracture union and proper alignment, with modest shortening. The patient was satisfied with this result. Bridge plating may be an alternative to external fixation for certain thumb fractures, with the potential to maintain alignment and articular congruity while permitting earlier return to activities of daily living and avoiding the risk of pin-track infections.

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.

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.

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.

Spontaneous Diabetic Myonecrosis Presenting as Acute Carpal Tunnel Syndrome.

A 57-year-old man with diabetes mellitus presented with a 4-day history of left palm pain out of proportion, with swelling, erythema, and dense median and ulnar nerve distribution sensory changes. Magnetic resonance imaging with and without contrast revealed diffuse hand edema and myonecrosis. The patient was treated surgically because the examination was concerning for acute carpal tunnel syndrome and ulnar nerve compression. Spontaneous diabetic myonecrosis is a complication of diabetes mellitus that can be confused with several other conditions. It presents as acute-onset painful swelling in any muscle, and in the hand, may cause compressive neuropathies that necessitate surgical intervention.

Timing of Complications following Hand Surgery.

Introduction Our purposes were to (1) characterize the timeline of eight postoperative complications following hand surgery, (2) assess complication timing for the procedures that account for the majority of adverse events, and (3) determine any differences in complication timing between outpatient and inpatient procedures. Materials and Methods Patients undergoing hand, wrist, and forearm procedures from 2005 to 2016 were identified in the National Surgical Quality Improvement Program database. Timing of eight adverse events was characterized. Cox proportional hazards modeling was used to compare adverse event timing between inpatient and outpatient procedures. Results A total of 59,040 patients were included. The median postoperative day of diagnosis for each adverse event was as follows: myocardial infarction 1, pulmonary embolism 2, acute kidney injury 3, pneumonia 8, deep vein thrombosis 9, sepsis 13, urinary tract infection 15, and surgical site infection 16. Amputations, fasciotomies, and distal radius open reduction internal fixation accounted for the majority of adverse events. Complication timing was significantly earlier in inpatients compared with outpatients for myocardial infarction. Conclusion This study characterizes postoperative adverse event timing following hand surgery. Surgeons should have the lowest threshold for testing for each complication during the time period of greatest risk. Level of Evidence This is a therapeutic, Level III study.

Etp1 confers arsenite resistance by affecting ACR3 expression.

In a high-throughput yeast two-hybrid screen of predicted coiled-coil motif interactions in the Saccharomyces cerevisiae proteome, the protein Etp1 was found to interact with the yeast AP-1-like transcription factors Yap8, Yap1 and Yap6. Yap8 plays a crucial role during arsenic stress since it regulates expression of the resistance genes ACR2 and ACR3. The function of Etp1 is not well understood but the protein has been implicated in transcription and protein turnover during ethanol stress, and the etp1∆ mutant is sensitive to ethanol. In this current study, we investigated whether Etp1 is implicated in Yap8-dependent functions. We show that Etp1 is required for optimal growth in the presence of trivalent arsenite and for optimal expression of the arsenite export protein encoded by ACR3. Since Yap8 is the only known transcription factor that regulates ACR3 expression, we investigated whether Etp1 regulates Yap8. Yap8 ubiquitination, stability, nuclear localization and ACR3 promoter association were unaffected in etp1∆ cells, indicating that Etp1 affects ACR3 expression independently of Yap8. Thus, Etp1 impacts gene expression under arsenic and other stress conditions but the mechanistic details remain to be elucidated.

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.