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Polyfluorinated aromatic reagents readily react with thiolates via nucleophilic aromatic substitution (SNAr) and provide excellent scaffolds for peptide cyclisation. Here we report a robust and versatile platform for peptide stapling and multicyclisation templated by 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, opening the door to the next generation of functional scaffolds for 3D peptide architectures. We demonstrate that stapling and multicyclisation occurs with a range of non-protected peptides under peptide-compatible conditions, exhibiting chemoselectivity and wide-applicability. Peptides containing two cysteine residues are readily stapled, and the remaining perfluoroaryl groups permit the introduction of a second peptide in a modular fashion to access bicyclic peptides. Similarly, peptides with more than two cysteine residues can afford multicyclic products containing up to three peptide ‘loops’. Finally, we demonstrate that a porphyrin-templated stapled peptide containing the Skin Penetrating and Cell Entering (SPACE) peptide affords a skin cell penetrating conjugate with intrinsic fluorescence.

Background: The objective of this study was to assess whether resident involvement in distal radius fracture open reduction internal fixation (ORIF) affect 30-day postoperative complication, hospital readmission, reoperation and operative time. Methods: A retrospective study was performed using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database by querying the Current Procedural Terminology (CPT) codes for distal radius fracture ORIF from 1 January 2011 to 31 December 2014. A final cohort of 5,693 adult patients who underwent distal radius fracture ORIF during the study period were included. Baseline patient demographics and comorbidities, intraoperative factors, including operative time and 30-day postoperative outcomes, including complications, readmission and reoperations, were collected. Bivariate statistical analyses were performed to identify variable associated with complication, readmission, reoperation and operative time. The significance level was adjusted using a Bonferroni correction as multiple comparisons were performed. Results: In this study of 5,693 patients who underwent distal radius fracture ORIF, 66 patients had a complication, 85 patients were readmitted and 61 patients underwent reoperation within 30 days of surgery. Resident involvement in the surgery was not associated with 30-day postoperative complication, readmission or reoperation, but was associated with longer operative time. Moreover, 30-day postoperative complication was associated with older age, American Society of Anesthesiologists (ASA) classification, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), hypertension and bleeding disorder. Thirty-day readmission was associated with older age, ASA classification, diabetes mellitus, COPD, hypertension, bleeding disorder and functional status. Thirty-day reoperation was associated with higher body mass index (BMI). Longer operative time was associated with younger age, male sex and the absence of bleeding disorder. Conclusions: Resident involvement in distal radius fracture ORIF is associated with longer operative time, but no difference in rates of episode-of-care adverse events. Patients may be reassured that resident involvement in distal radius fracture ORIF does not negatively impact short-term outcomes. Level of Evidence: Level IV (Therapeutic)

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is a rare but serious complication of total shoulder arthroplasty (TSA). Owing to limited evidence, Clinical Practice Guideline recommendations for VTE chemoprophylaxis after TSA rely heavily on the risk stratification of individual patients. The objectives of this study were to identify the prevalence and risk factors independently associated with VTE, PE, and DVT in the 30-day postoperative period after TSA.A retrospective case-control study was conducted using the American College of Surgeons National Surgical Quality Improvement Program database by querying the Current Procedural Terminology code for total shoulder arthroplasty from 2011 to 2020. The initial query resulted in 33,089 patients. After applying exclusion criteria for age younger than 50 years, emergency surgery, and open wound or infection, a final cohort of 31,918 patients who underwent TSA were included. The primary outcome was venous thromboembolism, and secondary outcome variables were PE and DVT. A bivariate screen was done for explanatory variables associated with our outcome variables, and variables with P0.1 in the bivariate screen were included in a multivariable logistic regression model.Of the 31,918 patients in our cohort, 183 patients (0.573%) developed VTE, 92 patients (0.29%) developed PE, and 104 patients (0.326%) developed DVT during the 30-day postoperative period. Multivariable logistic regression analysis showed that older age, higher body mass index, longer surgical time, and longer hospital length of stay were associated with VTE and PE and that hypertension and shorter hospital length of stay were associated with DVT.The prevalence of VTE after TSA is low. Older patients, patients with higher body mass index, and patients with longer surgical durations are at higher risk for VTE after TSA. Our findings are relevant for preoperative risk stratification and the decision for chemoprophylaxis.Level III Prognostic.

Purpose Arthroscopy is an efficacious and popular treatment modality in developed nations for a variety of musculoskeletal conditions. However, arthroscopy requires specialized training, complex infrastructure, and expensive equipment, occasionally causing barriers to use in developing countries. Consequently, the utilization of resources to perform and teach arthroscopy in low- and middle-income countries (LMICs) is controversial. Through this investigation, we assessed the current capacity and barriers to arthroscopy use and training in these settings. Methods Focused interviews were conducted with surgeons from Haiti (low-income) and Romania (middle-income) regarding their experience with arthroscopy. Based on responses, a multiple-choice survey was developed and administered to orthopaedic trainees and practicing orthopaedic surgeons during national orthopaedics conferences in each country. Results Fifty-eight orthopaedists in Haiti, and 29 in Romania completed the survey. Most (91% from Haiti; 79% from Romania) reported that learning arthroscopy is essential or important for orthopaedic training in their country. Yet only 17% from Haiti compared to 69% from Romania indicated their primary hospital has the equipment necessary for arthroscopy. In Haiti, equipment was the main barrier to use of arthroscopy, followed by training, while in Romania, the main barrier was training, followed by equipment. Simulations and telemedicine were ranked as top choices of effective methods for learning arthroscopy. Conclusions Regardless of their country’s resource limitations, most participants place high value on the practice of arthroscopy and arthroscopic training. The results from this study highlight a hierarchy of needs in developing nations. Furthermore, local providers report a strong belief in the need for arthroscopic treatment to benefit their patients, and a clear desire for further training and development of these techniques. By identifying similarities and differences by location, we may better tailor global orthopaedic training initiatives and partnerships in LMICs.

A method for measuring peptidylprolyl bond cis-trans conformational status in peptide models is described, using 4-fluorophenylalanine (4FPhe) as a distal reporter for 19F NMR. The %cis-Pro population was measured for peptides of the general structure Ac-X-Pro-Z-Ala-Ala-4FPhe (X and Z are proteinogenic amino acids) at pH 7.4, and provided conformational populations consistent with literature values obtained by more complex methods. This approach was applied to probe the prolyl bond status in pentapeptide models of the intrinsically disordered C-terminal region of α-synuclein, which mirrored the preferences in the Ac-X-Pro-Z-Ala-4FPhe models. Advantageously, the 19F reporter group does not need to be adjacent to or attached to proline to provide quantifiable signals and distal 4-fluorophenylalanines can be placed so as not to influence prolyl bond conformation. Finally, we demonstrated that the prolyl bond status is not significantly affected by pH when there are ionisable amino acid residues at the carboxyl side of proline, which makes 19F NMR an invaluable tool with which to study proline isomerism at a range of pHs and in different solvents and buffers.

Despite increased utilization, recent temporal trends in patient comorbidities and episode-of-care outcomes for distal radius fracture open reduction and internal fixation (ORIF) have not been studied. The objective of this study was to assess 10-year national trends in (1) patient characteristics and comorbidities and (2) 30-day postoperative adverse outcomes for patients who underwent distal radius fracture ORIF using a large patient database.A retrospective study was conducted using the National Surgical Quality Improvement Program database by querying the procedural codes for distal radius fracture ORIF from January 1, 2011, to December 31, 2020. A cohort of 28,616 adult patients who underwent distal radius fracture ORIF during the study period was included. Baseline patient characteristics and 30-day postoperative outcome data were collected for each year of the study. Temporal trends from 2011 to 2020 for all variables were assessed using the two-tailed Mann-Kendall trend test.Of the 28,616 patients in the study cohort, the mean age was 56.4 years and 73.1% were female. Demographically, there was a trend toward higher body mass index, higher American Society of Anesthesiologists classification, and lower proportions of active smokers; functionally dependent patients; and patients with hypertension, chronic obstructive pulmonary disease, and bleeding disorder. There was a trend toward worse sepsis physiology and wound classification on presentation. There was a trend toward fewer blood transfusions, hospital readmissions, and revision surgeries; however, there was an increasing trend for the development of a superficial surgical site infection.Ten-year national trends in distal radius fracture ORIF demonstrated improvements in several important patient comorbidities and the rates of readmission and revision surgery. However, overall patient comorbidities, sepsis physiology, and wound classification have worsened, and the rate of superficial surgical site infections has increased. Trends in patient comorbidities and episode-of-care outcomes should be considered when transitioning toward value-based care models.

The purpose of this study was to assess the impact of resident involvement on periprocedural outcomes and costs after common procedures performed at an academic hand surgical practice.A retrospective review was performed in all patients undergoing 7 common elective upper extremity procedures between January 2008 and December 2018: carpal tunnel release, distal radius open reduction and internal fixation (ORIF), trigger finger release, thumb carpometacarpal arthroplasty, phalanx closed reduction and percutaneous pinning, cubital tunnel release, and olecranon ORIF. The medical record was reviewed to determine the impact of surgical assistants (resident, fellow, or physician assistant) on periprocedural outcomes, periprocedural costs, and 1-year postoperative outcomes. The involvement of surgical trainees operating under direct supervision was compared with the entire operation performed by the attending surgeon with a physician assistant present.A total of 396 procedures met the inclusion criteria. Analysis of the whole study sample revealed low rates of intraoperative complications, wound complications, medical complications, readmissions, and mortality. Subgroup analysis of carpal tunnel releases revealed significantly greater tourniquet times for residents compared with physician assistants (7 ± 2 min, 6 ± 1 min), as well as longer overall operating room times for residents compared to fellows or physician assistants (17 ± 5 min, 13 ± 3 min, 12 ± 3 min). Operating room times for distal radius ORIF were significantly greater among residents compared to fellows or physician assistants (68 ± 19 min, 57 ± 17 min, 56 ± 14 min). There were no differences in any other perioperative metrics or periprocedural costs for the trigger finger release or cubital tunnel release cohorts.Resident involvement in select upper extremity procedures can lengthen operative times but does not have an impact on blood loss or operating room costs.Surgeons should be aware that having a resident assistant slightly increases operative times in elective hand surgery.

Background: We aimed to describe the demographic, injury-related, and treatment-related characteristics of patients who undergo fasciotomies for acute hand compartment syndrome. Methods: A cohort of 53 adult patients with acute hand compartment syndrome treated with fasciotomy at 2 tertiary care referral centers over a 10-year time period from January 1, 2006, to June 30, 2015, were retrospectively identified. We reviewed the electronic medical record for patient-related variables (eg, age, sex, smoking status, diabetes mellitus), injury-related variables (eg, mechanism of injury, presence of fractures), and treatment-related variables (eg, compartments released, number of operations, use of split-thickness skin grafts, and time from injury to surgery). Results: The mean age of our cohort was 45 years, and 33 patients (62%) were men. The mechanism of injury varied widely, but the most common causative mechanisms were crush injury (25%), prolonged decubitus (17%), and infection (11%). Associated hand fractures were present in 15 (28%) patients. The surgically released compartments varied; the dorsal interosseous compartments (83%), thenar compartment (75%), and hypothenar compartment (74%) were most frequently released, while the adductor pollicis compartment (43%) and Guyon canal (28%) were least frequently released. Conclusions: The demographics of acute hand compartment syndrome have evolved in the last 25 years compared with the prior literature, partly as a result of the opioid epidemic leading to a rise in “found down” compartment syndrome. Treating providers should recognize crush injury, prolonged decubitus, and infection as the most common causes of acute hand compartment syndrome.