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Purpose: To assess if pes anserinus tenotomy (PAT) during definitive open reduction and internal fixation (ORIF) of tibial plateau fractures is associated with a decreased risk of surgical site infection (SSI) and other postoperative complications., Methods: A retrospective review of all adults who underwent ORIF for tibial plateau fractures from April 2005 to February 2022 at single level 1 trauma center was performed. Patients who had a medial approach to the plateau with minimum three-month follow-up were required for inclusion. All patients with fasciotomy for compartment syndrome or with traumatically avulsed or damaged pes anserinus prior to ORIF were excluded. Two groups were created: those who received a pes anserinus tenotomy with repair (PAT group) and those whose pes anserinus were spared and left intact (control group). Patient demographics, injury and operative characteristics, and surgical outcomes were compared. The primary outcomes were rates of deep and superficial SSI., Results: The PAT group had significantly lower rates of deep SSI (9.2% vs. 19.7%, P = 0.009), superficial SSI (14.2% vs. 26.5%), P = 0.007), and any SSI (15.8% vs. 28.9%, P = 0.005). Multiple logistic regression showed that heart failure (aOR = 7.215, 95% CI 2.291-22.719, P < 0.001), and presence of open fracture (aOR = 4.046, 95% CI 2.074-7.895, P < 0.001) were independently associated with increased odds of deep SSI, while PAT was associated with a decreased odds of deep SSI (aOR = 0.481, 95% CI 0.231-0.992, P = 0.048). PAT had significantly lower rates of unplanned return to the operating room (20.8% vs. 33.7%, P = 0.010) and implant removal (10.0% vs. 18.0%, P = 0.042)., Conclusion: While these data do not allow for discussion of functional recovery or strength, pes anserinus tenotomy was independently associated with significantly lower rates of infection, unplanned operation, and implant removal., Level of Evidence: Level III., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Objectives: To determine potential factors influencing female medical students' interest and subsequent application to orthopedics, and to evaluate female and male medical students' perceptions of women in the field of orthopedics., Methods: An institutional review board-approved survey was distributed in March 2020 and subsequently in April 2022 to medical students in the classes of 2023 and 2024 at the University of Alabama at Birmingham Heersink School of Medicine. Study data were collected and managed using REDCap electronic data capture. An e-mail link to the REDCap survey was sent to students across the southeast region of the United States, followed by three reminder e-mails. All 25 allopathic medical schools in the southeastern United States with an Orthopedics Interest Group listed on their institution's Web site were invited to participate in the study. Nine Orthopedics Interest Group leaders interested in participating were asked to provide the researchers with a list of fourth-year medical students who attended an event hosted by that group (215). A total of 39 respondents who completed the survey were included in this study., Results: Overall, the majority of students (n = 35, 90%) believed that women faced more barriers to a career in orthopedics than did men. The most significant barriers to women entering the field of orthopedics were the perceived expectations of an orthopedic surgeon (n = 34, 87%), difficulty balancing career and family (n = 28, 72%), and demanding schedule (n = 13, 33%)., Conclusions: This study demonstrates that both male and female medical students believe there are significant additional barriers to success for women in the field. Study participants report that expectations set by physicians, other healthcare professionals, and patients contribute to creating greater barriers that deter medical students interested in orthopedics from ultimately applying to the specialty.

Objective: To determine whether premedical programming can address the interest level and perception of barriers to women in orthopaedics held by female high school and medical students., Design: A thirteen-question paper-based survey was distributed among the high school and medical school participants prior to the January 2020 Perry Outreach Program and Medical Student Outreach Program. After a day of participation in mock procedures and speaker sessions, participants subsequently completed another survey of seven-questions., Setting: The Perry Outreach Program and Medical Student Outreach Program were conducted at the University of Alabama at Birmingham campus., Participants: Participants consisted of high school and medical school women hailing from the Birmingham metropolitan area, who had signed up for the Perry programs via email, outreach to local high schools, and social media interest pages. Participant sampling was stratified by race and level of education (high school vs. medical school)., Results: A total of 36 women, 18 high school and 18 medical school, attended the Perry Initiative events and responded to the pre-event and post-event surveys. Before the Perry Initiative programs, all participants felt women faced more barriers than men in pursuing a career in orthopaedics. Participation in the Perry Initiative event increased average interest in orthopaedics by 28% among high school and 11% among medical school students., Conclusions: Prior to the Perry Initiative, 31% percent of the total attendees reported knowing a female orthopaedist. The Perry Initiative improved perceptions of both high school and medical students regarding the ability of women to have a work/life balance, family life, and children during orthopaedics residency. Medical student participation in the events led to a decreased belief in barriers regarding schedule, family life, perceptions of an orthopaedic surgeon, and perceptions of peers within healthcare setting., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase-contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P <0.001) and pulsatility and distensibility increased (15.9%±5.3% to 22.1%±7.9%, P <0.001; and 0.28%±0.10%/mm Hg to 0.40%±0.14%/mm Hg, P <0.001, respectively) following 6 months of spironolactone. Conclusions Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

GSK1322322 is the first in a new class of antibiotics that inhibit peptide deformylase, necessary for bacterial protein maturation. Previously, low absolute bioavailability was observed for the 1500-mg oral tablet formulation, resulting in a less than dose-proportional increase from the 1000-mg dose. Furthermore, high variability of pharmacokinetic (PK) parameters within cohorts was suggested to be associated with differences in body weight. This open-label, randomized, 4-period, crossover, single-dose phase I study in healthy individuals compared the PK, safety, and tolerability of free base oral tablets under fasted or fed conditions with intravenous and oral mesylate salt solution of GSK1322322 under fasted conditions. Absolute bioavailability of GSK1322322 1500-mg free base tablets under fasted conditions, fed conditions, and oral mesylate salt solution was 57%, 77%, and 92%, respectively. Moderate-fat/calorie food intake increased area under the concentration-time curve (AUC 0-∞ ) by 36%, maintained maximum observed concentration (C max ), and delayed time to C max . It appeared that AUC 0-∞ decreased with body weight, whereas clearance increased. GSK1322322 administration resulted in only mild-to-moderate adverse events. These results support future clinical investigations of the free base oral tablet formulation of GSK1322322 1500 mg after intake of a moderate-fat/calorie meal, including further investigation of a potential weight-based dosage change.

The purpose of this research was to develop a stable fixed dose combination tablet for a model DPP-IV inhibitor and metformin hydrochloride. The dipeptidyl peptidase IV (DPP-IV) inhibitor was particularly challenging to formulate due to its significant chemical instability and moisture sensitivity. Various formulation strategies were investigated and placed on accelerated stability to determine the lead approach and critical quality attributes. The lead formulation investigated was a drug layered pellet containing the DPP-IV inhibitor, which was further coated with various seal coats and moisture barriers, then compressed into a tablet with compression aids and granulated metformin hydrochloride. The investigations revealed that the drug layered pellets compressed into a fixed dose combination tablet yielded a unique stability enhancement. The stability was highly dependent on the final tablet water content and could be further improved by the addition of moisture barrier coatings. A fundamental understanding of the key critical quality attributes for the fixed dose combination product containing a DPP-IV inhibitor and metformin hydrochloride as an oral solid dosage form were established. This research identified a formulation approach to enable a successful commercial product to be developed.

Purpose: To develop a robust radiolabeling technique to enable evaluation of difficult to radiolabel gastric retentive formulations using gamma scintigraphy. The use of a successful radiolabel will allow accurate assessment of the gastric residence time of the formulations., Materials and Methods: The retention of two radionuclides, indium ((111)In) and samarium ((153)Sm), with and without further processing to improve radiolabel performance were evaluated in simulated gastric pH in vitro. The most successful formulation from the in vitro screening was further evaluated in preclinical and clinical studies., Results: In vitro evaluation revealed significant radionuclide leakage at pH 1.5 for most radiolabeling attempts. Radionuclide leakage at pH 4.5 was less pronounced. The most successful radiolabel was formulated by adsorbing indium chloride onto activated charcoal, followed by entrapment in a cellulose acetate polymer melt. This provided the best radiolabel retention under both pH conditions in vitro. The radiolabel also proved to be successful during preclinical and clinical evaluations, allowing evaluation of gastric retention performance as well as complete gastrointestinal transit., Conclusion: A simple, yet robust radiolabel was developed for gastric retentive formulations to be evaluated pre-clinically or in a clinical setting by entrapping the radionuclide in an insoluble polymer through a simple polymer melt process.

The accelerating effect of polyethylene glycol 400 on small intestinal transit has been previously reported. The aim of this study was to investigate the influence of other solubility-enhancing excipient, propylene glycol, D-alpha-tocopheryl-polyethylene glycol-1,000 succinate (VitE-TPGS) and Capmul MCM, on human intestinal transit. A 5-g dose of each excipient was administered to seven healthy male subjects. Propylene glycol and VitE-TPGS were administered dissolved in 150 mL water. Capmul MCM was administered in the form of four 000 hard gelatin capsules to mask its taste and then given with 150 mL water. On a separate occasion, 150 mL water was administered as the control. Each formulation was radiolabelled with technetium-99 m to follow its transit using a gamma camera. The mean small intestinal transit times were 234, 207, 241 and 209 min for the control, propylene glycol, VitE-TPGS and Capmul MCM treatments, respectively. Although there were differences in the small intestinal transit times for the excipients investigated compared with the control, none of the results were statistically significant. Unlike polyethylene glycol 400 at the same dose of 5 g, the excipients tested (propylene glycol, VitE-TPGS and Capmul MCM) had little or no impact on small intestinal transit.

Previous work has shown that polyethylene glycol 400 (PEG 400) has an accelerating effect on gastrointestinal transit and a modulating influence on drug absorption in humans. The aim of this study was to assess the impact of various excipients, PEG 400, propylene glycol, d-alpha-tocopheryl-polyethylene glycol-1000 succinate (TPGS) and Labrasol on gastrointestinal transit and drug absorption in four beagle dogs using scintigraphy. Each dog received, on five separate occasions, water (control) or a dose of excipient equivalent to 1 g PEG 400, 2 g propylene glycol, 1 g TPGS or 2 g Labrasol dissolved in water and administered in the form of two capsules. The model drugs ampicillin (200mg) and antipyrine (100mg) were co-administered in the capsules. The capsule solutions were radiolabelled with technetium-99m to follow their transit using a dual-headed gamma camera, and blood samples were collected to determine drug pharmacokinetics. On a separate occasion, the drugs were dissolved in saline and given intravenously. The capsules rapidly disintegrated in the stomach liberating their liquid contents. The mean small intestinal transit times for the different treatments (control, PEG 400, propylene glycol, TPGS and Labarasol) were 183, 179, 195, 168 and 154 min, respectively. The corresponding mean absolute oral bioavailability figures were 36, 32, 39, 42 and 32% for ampicillin and 76, 74, 85, 73 and 74% for antipyrine, respectively. The transit and bioavailability data for the excipient treatments were not significantly different from the control. In summary, these excipients, at the doses administered, have limited influence on gastrointestinal transit and drug in beagle dogs.

Purpose: The aim of the study was to investigate the effect of different concentrations of polyethylene glycol 400 (PEG 400) on liquid transit through, and ranitidine absorption from, the gastrointestinal tract., Methods: Six healthy male volunteers received, on four separate occasions, 150 mL water containing 150 mg ranitidine and either 0 (control), 1,2.5, or 5 g PEG 400. The solutions were radiolabeled with technetium-99m to allow their gastrointestinal transit to be followed using a gamma camera. Urine samples were collected over a 24-h period to assess the amount of ranitidine excreted and hence absorbed., Results: No significant differences in gastric emptying were noted between the four solutions. In contrast, the presence of 1, 2.5, and 5 g PEG 400 reduced the mean small intestinal transit times of the solutions by 9, 20, and 23%, respectively, against the control. In terms of drug absorption, the mean cumulative amount of ranitidine excreted was reduced by 38% in the presence of both 2.5 and 5 g PEG 400, although it was significantly increased by 41% in the presence of 1 g PEG 400., Conclusions: The results show that low concentrations of PEG 400 enhance the absorption of ranitidine possibly via modulation of intestinal permeability, while high concentrations have a detrimental effect on ranitidine absorption presumably via a reduction in the small intestinal transit time.

Pseudolatexes of the biodegradable polyesters poly(D,L-lactide) (PLA) and poly(epsilon-caprolactone) (PCL) have been developed as potential aqueous coatings for sustained release. Since PLA and PCL are known to hydrolyze, the influence of the surfactant system, temperature, pH, and particle size on the chemical stability of the polymers as aqueous colloidal dispersions was investigated. Pseudolatexes of PLA and PCL formulated with a nonionic surfactant system were the most stable. When these dispersions were stored in unbuffered media for 350 days at 5 degrees C, only small changes in the weight-average molecular weights (Mw) of the polymers were observed. At 37 degrees C there was rapid degradation of both polymers in the dispersions. Arrhenius plots for the degradation of PLA and PCL resulted in a linear relationship for PCL. The nonlinear relationship for PLA was attributed to the polymer being in two different physical states within the 5 to 37 degrees C range which was used for the Arrhenius plots. PCL was in the rubbery state at all temperatures studied. Storage of the pseudolatexes in pH 1.65 buffer at 37 degrees C catalyzed the rates of degradation of both PLA and PCL. However, refrigeration of the pseudolatexes stabilized the polymers even at pH 1.65 for up to 4 months. Particle size had an insignificant effect on PLA and PCL stability in pseudolatexes prepared with either a nonionic or an anionic surfactant system.