Isolated Medial Patellofemoral Ligament Reconstruction Results in Lower Failure and Complication Rates than Isolated Trochleoplasty and Tibial Tubercle Osteotomy: A Systematic Review.

PURPOSE: To evaluate outcomes and complications of isolated medial patellofemoral ligament (MPFLR), tibial tubercle osteotomy (TTO), and trochleoplasty for management of patellar instability. METHODS: A query of Scopus, PubMed, Google Scholar, Cochrane CENTRAL Register of Controlled Trials, and the Cochrane Database of Systematic Reviews was performed in accordance with 2020 PRISMA guidelines. Included studies reported clinical outcome data after isolated MPFLR, TTO, or trochleoplasty for patellar instability with a minimum of 12 months of follow-up. Meta-analysis and data aggregation was not performed. RESULTS: Thirty-six studies (5 trochleoplasty, 14 TTO, and 18 MPFLR) consisting of 1,389 patients (114 trochleoplasty, 374 TTO, and 1,001 MPFLR) were included. Risk of bias was assessed with the Methodological Index for Non-Randomized Studies (MINORS) score which ranged from 11-12 in trochleoplasty, 10-18 in TTO, and 8-18 in MPFLR studies. Patient reported outcome measures including Lysholm Score (trochleoplasty: 51.1-71 to 71-95y; TTO: 57-63.3 to 84-98; MPFLR: 37.4-59.1 to 74-92.5), Kujala Score (trochleoplasty: 56-71 to 78-92; TTO: 48.6-68 to 78-92; MPFLR: 53.3-60 to 81.5-92), VAS Pain Scale (trochleoplasty: 52 to 25; TTO: 54-76 to 14-27; MPFLR: 29 to 17, out of 100), and Tegner Score (TTO: 3-4 to 3-4; MPFLR: 2.5-6 to 4.9-5) improved after all surgeries. Failure rates ranged from 0-33.3% after MPFLR, 0-30.8% after TTO, and 5.3-40% after trochleoplasty. Complication rates ranged from 0-14.7% after MPFLR, 1.6-58.3% after TTO, and 8-26.3% after trochleoplasty. CONCLUSIONS: Isolated MPFLR, TTO, or trochleoplasty may be effective treatment options for patellar stabilization. While failure rates were highest after isolated trochleoplasty and complication rates were highest after TTO, these procedures are not interchangeable as each addresses a specific pathology. LEVEL OF EVIDENCE: IV; Systematic Review of Level II-IV studies.

Editorial Commentary: The entry point-trochlear groove (EP-TG) angle measures lateralization of the proximal trochlear entry point in patients with patellar instability.

Patellar instability is a complex orthopedic condition, occurring at an incidence of 23.2 per 100,000 person-years, and resulting from a combination of osseous and soft tissue factors. Osseous abnormalities associated with patellar instability include trochlear dysplasia and a lateralized tibial tubercle. Evaluation of these factors includes dysplasia evaluation using the DeJour classification, and the tibial-tubercle-to-trochlear-groove distance (TT-TG) to evaluate relative lateralization of the tibial tubercle. Three-dimensional modeling has advanced the evaluation of complex trochlea geometry and patellar tracking. Evaluation of the TT-TG distance through flexion, dubbed the radial TT-TG (rTT-TG) distance, shows rTT-TG distances are notably larger than traditional TT-TG measurements, with increasing grade of dysplasia associated with a more pronounced difference between measurements. The entry point-trochlear groove (EP-TG) angle may help more accurately describe the morphology of the proximal trochlea and aid in planning or assessing osseous correction with a trochleoplasty. The EP-TG angle may also be of use as a variable to determine when an isolated medial patellofemoral ligament reconstruction (MPFLR) may fail and require osseous correction. A lateralized proximal trochlea entry point is associated with recurrent patellar instability.

Long-Term Clinical and Radiographic Outcomes of Meniscus Allograft Transplant.

PURPOSE OF REVIEW: To reduce pain, improve function and possibly mitigate the risk for development of osteoarthritis in patients with functionally deficient meniscus pathology, meniscal allograft transplantation (MAT) can be used to restore native joint biomechanics and increase knee joint longevity. This review explores the senior author's preferred bridge-in-slot technique and recently published long-term clinical and radiographic outcomes following MAT. RECENT FINDINGS: Recent literature demonstrates MAT to be a safe and largely successful procedure for patients with functional meniscus deficiency. A majority of patients reach established minimal clinically important difference (MCID) values. Graft survivorship is approximately 80% at 10 years, significantly delaying and in some cases, preventing the need for future joint reconstruction procedures in these young patients. Return to sport rates are over 70%, revealing meniscal allografts can withstand high impact activities. Cartilage damage at the time of MAT increases the risk for graft and clinical failure, though this may be mitigated with a concomitant cartilage restoration procedure. Meniscal allograft transplantation can provide a durable and effective long-term solution to meniscal deficiency in symptomatic patients who wish to decrease the risk of symptomatic progression and possibly further osteoarthritis and continue activities of daily life and sports with less pain and more function. By restoring more normal joint biomechanics, MAT can mitigate the potential need for future knee arthroplasty in this young active patient population.

Characterization of patient population receiving bioactive glass bone graft substitute as intraoperative treatment for orthopaedic trauma fractures.

Background: Bioactive glass synthetic bone grafts are used to treat osseous defects in orthopaedic surgery. Characterization of the clinical scenarios associated with bioactive glass use in the context of orthopaedic trauma, are not well established. This study aims to characterize population demographics, operative variables, as well as postoperative variables, for patients who required bone grafting for treatment of traumatic orthopaedic injuries and received a bioactive glass bone substitute intraoperatively. Methods: The electronic medical record at a large Level I trauma center was queried for fracture patients between January 1st, 2019, and April 30th, 2022. Our retrospective cohort included fracture patients who received Fibergraft Matrix or Fibergraft Putty intraoperatively, and their respective control groups. This study ascertained patient demographic variables, operative variables, and postoperative variables. Differences in categorical variables were tested with Fischer's Exact Tests, while differences in continuous variables were tested with ANOVA. Statistical significance was determined as P < 0.05. If the overall Group model was significant for a given variable, post-hoc Fischer's Exact or Tukey HSD tests were used to assess pairwise significance between individual Group pairs. Results: A total of four categories across our analysis of demographic, operative, and postoperative variables displayed significant differences amongst subject Groups (P ≤ 0.03). Individual groups were compared such that significant differences between subject groups could be appreciated for a specific variable. FM subjects had greater length of surgery, billable costs, and vitamin D supplementation at the time of surgery compared to FM controls. Similarly, FP subjects had greater length of surgery, billable cost, and implants used intraoperatively compared to FP controls. Conclusion: This analysis revealed Fibergraft patients to have greater length of surgery and billable cost, with respect to their matched controls. These data suggest that Fibergraft patients had more severe orthopaedic fractures compared to matched controls.

Understanding the Alkylation of a Phenol by 1-(3-Chloropropyl)pyrrolidine: Evidence for the Intermediacy of an Azetidinium Ion.

The final synthetic step in the synthesis of cediranib, AZD2171, 1, is the alkylation of a phenol with an alkyl halide to generate an ether. Our need to understand and control the formation of synthetic impurities generated in this step of the synthesis led us to investigate the kinetics and mechanism of the alkylation of indolphenol, 2, 4-[(4-fluoro-2-methyl-1 H-indol-5-yl)oxy]-6-methoxyquinazolin-7-ol, by chloropyrrolidine, 3, 1-(3-chloropropyl)pyrrolidine. Studies in 1-methyl-2-pyrrolidinone (NMP) established that the active alkylating agent is the azetidinium ion, 4, 4-azoniaspiro[3.4]octane, formed via a slow intramolecular cyclization reaction of chloropyrrolidine, 3. The azetidinium ion was isolated as its tetraphenylborate salt from water by heating 3 in the presence of aqueous potassium tetraphenyl borate, and its competence as an intermediate was demonstrated by its fast reaction with 2 to yield cediranib, 1.

Suppression of 13C satellites in 1H DOSY spectra.

Diffusion-ordered spectroscopy (DOSY) is a valuable tool for the analysis of intact mixtures, since it can separate the signals of components according to their apparent diffusion coefficients. However, DOSY experiments are acutely sensitive to spectral quality, and especially to signal overlap, which can lead to misleading apparent diffusion coefficients. Here, we introduce a new NMR experiment to reduce signal overlap in mixtures with a wide range of concentrations, by removing one-bond 13C satellites. In such high dynamic range mixtures, 13C isotopomer signals from major components can overlap with signals from minor components, causing problematic distortions in the diffusion domain of a DOSY spectrum. The new method, Oneshot-iDISPEL, is a combination of the Oneshot and DISPEL experiments, and its performance has been demonstrated on a Greek alcoholic beverage, ouzo, which contains small amounts of anise flavour components and sucrose. Ethanol is a major component, and the suppression of its 13C satellites reduces signal overlap with minor components, offering significant improvement in DOSY spectra.

FESTA: An Efficient Nuclear Magnetic Resonance Approach for the Structural Analysis of Mixtures Containing Fluorinated Species.

In complex mixtures, proton nuclear magnetic resonance (NMR) spectra are often very crowded, making spectral analysis complicated or even impossible, particularly when detailed structural information about the mixture components is needed. A new 1D NMR method (fluorine-edited selective TOCSY acquisition, FESTA) is introduced that facilitates the structural analysis of mixtures of species that contain fluorine. It allows simplified 1H spectra to be obtained that show only those protons that are in a spin system coupled to fluorine of interest. The new method is illustrated by factorizing a complex 1H spectrum into subspectra for individual spin systems involving different 19F sites.

13C Satellite-Free 1H NMR Spectra.

A new NMR experiment (Destruction of Interfering Satellites by Perfect Echo Low-pass filtration, DISPEL) is introduced that facilitates the analysis of low-level components in high dynamic range mixtures by suppressing one-bond 13C satellite signals in 1H spectra. Since the natural abundance of 13C is around 1.1%, these satellites appear at 0.54% of the intensity of a parent peak, mimicking and often masking impurity signals. The new experiment suppresses one-bond 13C satellite signals, with high efficiency, at negligible cost in signal-to-noise ratio, and over a wide range of one-bond coupling constants, without the need for broadband 13C decoupling.

Ultraclean pure shift NMR.

"Pure shift" methods can greatly improve the resolution of proton NMR spectra. However, current pure shift spectra show small periodic artefacts that prevent their use for studying dilute mixture components. A new technique, compatible with all current pure shift methods, is presented that suppresses such sidebands to arbitrary order, allowing ultraclean spectra to be obtained.

Clearing the undergrowth: detection and quantification of low level impurities using 19F NMR.

A new method for the analysis of low level impurities in sparsely fluorinated species allows measurement of clean high dynamic range 19F spectra, fully decoupled and free of interfering signals from 13C isotopomers.

Very broadband diffusion-ordered NMR spectroscopy: (19)F DOSY.

A new pulse sequence, CHORUS Oneshot, allows measurements of diffusion-ordered spectroscopy (DOSY) spectra over the full chemical shift range of (19)F for the first time. Swept-frequency pulses are used to give very broadband excitation; the sequence is a prototype for a large family of very broadband liquid state NMR methods.

Investigating the Dissolution Performance of Amorphous Solid Dispersions Using Magnetic Resonance Imaging and Proton NMR.

We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state-of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64.

Proton NMR: a new tool for understanding dissolution.

We present the use of (1)H NMR as a new measurement approach for improving understanding of the dissolution of pharmaceutical tablets. NMR has benefits over the conventional UV measurement approach in respect to much greater analyte selectivity and the ability to detect non-UV-absorbing species such as sugars. We used an in-line flow cell and water suppression experiments to determine the release profiles of three drug substances and lactose from the same tablet. Dissolution was performed in a pharmacopieal dissolution system with a standard protic buffer. NMR was shown to give high selectivity with each analyte having a well-resolved signal and sufficient sensitivity to determine the full release profile of even a compound present at only 5 mg in the tablet. The in-line flow cell gives excellent quality NMR spectra having little impact on peak shape. Dissolution of all the drug substances and lactose were determined to proceed at the same relative rates.

Oral bioavailability of cinnarizine in dogs: relation to SNEDDS droplet size, drug solubility and in vitro precipitation.

The in vivo performance of self-nanoemulsifying drug delivery systems (SNEDDSs) with different in vitro physicochemical properties were determined with the purpose of elucidating the parameters determining the in vivo performance of SNEDDSs. The in vitro characterisation included the use of pulsed field gradient NMR and the dynamic lipolysis model. In vivo characterisation was carried out in dogs with elevated gastric pH. Four SNEDDSs containing cinnarizine were dosed orally, and the obtained PK profiles were related to in vitro characterisation data. The SNEDDSs with the lowest solubility of cinnarizine in the preconcentrates and the smallest droplet size had the highest AUC values after oral administration. No difference in C(max) and t(max) was observed between the SNEDDSs. Despite of precipitation occurring during in vitro lipolysis of one of the SNEDDS this SNEDDS performed as well in vivo as another SNEDDS that did not show any precipitation. The area under the colloidal dispersion curves as well as under the lipolysis curves could be used to rank order the in vivo performance of the SNEDDSs. Selection of in vitro optimisation parameters for SNEDDSs should be done carefully. It may not always be best to aim for the highest solubility in the preconcentrate and to avoid precipitation during in vitro lipolysis.

The measurement of high enantiomeric excesses in chiral liquid crystals using 19F NMR and exchangeable protons in 2H NMR.

It is shown that the 19F spectrum and the 2H NMR spectrum of deuterated protons in a chiral liquid crystal medium can be used to measure high enantiomeric excesses.