Evaluating the Biomechanical Integrity of Various Constructs Utilized for First Metatarsophalangeal Joint Arthrodesis: A Systematic Review.

The first metatarsophalangeal (MTP) joint is a frequently loaded joint, handling loads up to 90% of bodyweight. First MTP arthrodesis is a frequently performed procedure designed to improve pain in patients with degenerative MTP joint disease. There are a wide variety of fixation constructs for this procedure without consensus on the most effective method. The purpose of this study was to compare the biomechanical integrity of various constructs utilized for first MTP arthrodesis. A systematic review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, CINAHL, MEDLINE, and Web of Science databases were searched from inception to 18 June 2023. Articles discussing the biomechanics of first MTP arthrodesis constructs were included. A total of 168 articles were retrieved. A total of 20 articles involving 446 cadaveric and synthetic bone constructs were included in the final review. Of the six articles comparing dorsal plating with compression screws to crossed interfragmentary screws, five found that dorsal plating had significantly higher stiffness. All three studies assessing shape-memory staples found them to be significantly less stable than crossed screws or dorsal plates alone. Both studies evaluating fully threaded screws found them to be stronger than crossed cancellous screws. Wedge resections have been shown to be 10 times stronger than standard planar or conical excision. Dorsal plating with compression screws is the gold standard for MTP arthrodesis. However, more research into newer methods such as fully threaded screws and wedge resections with an increased focus on translation to clinical outcomes is needed.

Mesh and layered electrospun fiber architectures as vehicles for Lactobacillus acidophilus and Lactobacillus crispatus intended for vaginal delivery.

Bacterial vaginosis (BV) is a recurrent condition that affects millions of women worldwide. The use of probiotics is a promising alternative or an adjunct to traditional antibiotics for BV prevention and treatment. However, current administration regimens often require daily administration, thus contributing to low user adherence and recurrence. Here, electrospun fibers were designed to separately incorporate and sustain two lactic acid producing model organisms, Lactobacillus crispatus (L. crispatus) and Lactobacillus acidophilus (L. acidophilus). Fibers were made of polyethylene oxide and polylactic-co-glycolic acid in two different architectures, one with distinct layers and the other with co-spun components. Degradation of mesh and layered fibers was evaluated via mass loss and scanning electron microscopy. The results show that after 48 h and 6 days, cultures of mesh and layered fibers yielded as much as 108 and 109 CFU probiotic/mg fiber in total, respectively, with corresponding daily recovery on the order of 108 CFU/(mg·day). In addition, cultures of the fibers yielded lactic acid and caused a significant reduction in pH, indicating a high level of metabolic activity. The formulations did not affect vaginal keratinocyte viability or cell membrane integrity in vitro. Finally, mesh and layered probiotic fiber dosage forms demonstrated inhibition of Gardnerella, one of the most prevalent and abundant bacteria associated with BV, respectively resulting in 8- and 6.5-log decreases in Gardnerella viability in vitro after 24 h. This study provides initial proof of concept that mesh and layered electrospun fiber architectures developed as dissolving films may offer a viable alternative to daily probiotic administration.

Metal Hypersensitivity Following Total Ankle Arthroplasty: Case Series and Literature Review.

Metal hypersensitivity following total ankle arthroplasty (TAA) is an underreported complication that can manifest as dermal, systematic, and orthopaedic-specific symptoms. It is critical to recognize that metal hypersensitivity is a diagnosis of exclusion; only after all other potential sources of failure, such as loosening or infection are ruled out, can this diagnosis be considered. Aside from imaging and common laboratory analysis, skin patch testing, leukocyte migration inhibition test (LMIT), and lymphocyte transformation test (LTT) are the testing options available for metal allergy. With regards to management of metal hypersensitivity, nonoperative modalities involving topical dermatological management are generally preferred. Severe cases of metal allergy may necessitate operative management consisting of explantation of the implant and either revision TAA with a custom hypoallergenic implant or conversion to an ankle fusion. We present 3 cases of presumed metal hypersensitivity following TAA. In all 3 cases, other forms of TAA failure were carefully ruled out. One patient underwent explantation and conversion to hypoallergenic implant, 1 patient underwent explantation and ankle arthrodesis with hypoallergenic hardware, and 1 patient elected for conservative care. In patients who underwent explantation and conversion to hypoallergenic hardware, no further symptoms associated with metal allergy were noted. Additional research is necessary to improve diagnostic accuracy of metal allergy and make treatment options more effective and accessible.Level of Evidence: Retrospective case series, IV.

Meta-Analyses of Two Treatment Regimens for Retinal Vein Occlusion.

BACKGROUND AND OBJECTIVES: To pool available data on the change in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and number of injections as reported by treat and extend (T&E) and pro re nata (PRN) regimens for retinal vein occlusion (RVO). MATERIALS AND METHODS: After PubMed was queried, separate random effect models were fitted to the data extracted and the Wald test was used to compare the estimates of the two independent meta-analyses. RESULTS: Fourteen T&E and 29 PRN studies were included in two independent meta-analyses. No significant difference was observed in BCVA (+14.74 [+11.52, +17.96] in T&E vs +15.90 [+14.24, + 17.56] in PRN, P = 0.530) or CRT improvements (-259.56 [-189.02, -330.09] in T&E vs -256.58 [-226.57, -286.48] in PRN, P = 0.939). More injections over 12 months were observed in T&E regimens (7.48 [6.32, 8.65] vs 5.13 [4.20, 6.06] in PRN, P = 0.002). CONCLUSION: Although more injections may be required, T&E achieves similar functional and anatomic benefits as compared to PRN regimens. [Ophthalmic Surg Lasers Imaging Retina 2023;54:244-250.].

Baseline factors and reason for cancellation of elective ophthalmic surgery.

OBJECTIVES: To determine the baseline risk factors for elective ophthalmic surgery cancellations and characterise the reasons for cancellation. METHODS: This is a retrospective, non-randomised study performed at a large tertiary ophthalmic centre. It included a consecutive sample of patients above the age of 18 who had an ophthalmic surgery scheduled at Cole Eye Institute, Cleveland Clinic, OH between January 2012 and December 2019. An automated search pull identified 75,908 scheduled surgeries (63,987 completed and 11,921 cancelled surgeries). Statistical analysis was performed using R (version 3.5.1). Main outcome measures were baseline factors that impact risk for surgery cancellation and reasons for surgery cancellation. RESULTS: Analysis was performed on 69,963 scheduled surgeries (57.37% Female, 42.63% Male; Mean age of 62.72 years; 59,959 completed and 10,004 cancelled surgeries). Of the 2384 cancelled surgeries with reasons provided, the most common causes of cancellation were patient refusal (38.42%), patient health condition (18.79%), and rescheduling of surgery (15.27%). Female sex, black race, patient age less than 50 years, non-cataract surgeries, regional mean household income greater than $82,900, Medicare insurance, and geographical distance of less than 10 miles from home to the surgery site were each associated with a significantly increased risk of surgery cancellation (p < 0.01). CONCLUSIONS: This study successfully identified several baseline factors predicting elective ophthalmic surgery cancellation. The clinical insights gained from these lines of enquiry may be used to construct models that not only identify patients at greater risk for cancellation but also highlight which interventions have greatest efficacy in preventing ophthalmic surgery cancellations.

Does surgery change pelvic tilt? : an investigation in patients with osteoarthritis of the hip, dysplasia, and femoroacetabular impingement.

AIMS: Pelvic tilt is believed to affect the symptomology of osteoarthritis (OA) of the hip by alterations in joint movement, dysplasia of the hip by modification of acetabular cover, and femoroacetabular impingement by influencing the impingement-free range of motion. While the apparent role of pelvic tilt in hip pathology has been reported, the exact effects of many forms of treatment on pelvic tilt are unknown. The primary aim of this study was to investigate the effects of surgery on pelvic tilt in these three groups of patients. METHODS: The demographic, radiological, and outcome data for all patients operated on by the senior author between October 2016 and January 2020 were identified from a prospective registry, and all those who underwent surgery with a primary diagnosis of OA, dysplasia, or femoroacetabular impingement were considered for inclusion. Pelvic tilt was assessed on anteroposterior (AP) standing radiographs using the pre- and postoperative pubic symphysis to sacroiliac joint (PS-SI) distance, and the outcomes were assessed with the Hip Outcome Score (HOS), International Hip Outcome Tool (iHOT-12), and Harris Hip Score (HHS). RESULTS: The linear regression model revealed a significant negative predictive association between the standing pre- and postoperative PS-SI distances for all three groups of patients (all p < 0.001). There was a significant improvement in all three outcome measures between the pre- and postoperative values (p < 0.05). CONCLUSION: There is a statistically significant decrease in pelvic tilt after surgery in patients with OA of the hip, dysplasia, and femoroacetabular impingement. These results confirm that surgery significantly alters the pelvic orientation. Pelvic tilt significantly decreased after total hip arthroplasty, periacetabular osteotomy, and arthroscopy/surgical hip dislocation. The impact of surgery on pelvic tilt should be considered within the therapeutic plan in order to optimize pelvic orientation in these patients.Cite this article: Bone Joint J 2022;104-B(9):1025-1031.

Free Flap Reconstruction of the Anterior Skull Base: A Systematic Review.

Objectives Given the limitations in the available literature, the precise indications, techniques, and outcomes of anterior skull base free flap reconstruction remain uncertain. The objective of this study was to perform a systematic review of published literature and evaluate indications, methods, and complications for anterior skull base free flap reconstruction. Methods A systematic review of the literature was performed using a set of search criteria to identify patients who underwent free flap reconstruction of the anterior skull base. Articles were reviewed for inclusion based on relevance, with the primary outcome being surgical complications. Results After a comprehensive search, 406 articles were obtained and 16 articles were ultimately found to be relevant to this review-79 patients undergoing free flap reconstruction were identified. Overall complication rates were 17.7% (95% confidence interval [CI]: 16.6-33.1%) for major complications and 19.0% (95% CI: 17.8-35.5%) for minor complications. Conclusion Microvascular reconstruction of the anterior skull base is feasible with high reliability reported in the literature.

The role of Meteorin-like in skeletal development and bone fracture healing.

Meteorin-like protein (Metrnl), homologous to the initially identified neurotrophic factor Meteorin, is a secreted, multifunctional protein. Here we used mouse models to investigate Metrnl's role in skeletal development and bone fracture healing. During development Metrnl was expressed in the perichondrium and primary ossification center. In neonates, single cell RNA-seq of diaphyseal bone demonstrated strongest expression of Metrnl transcript by osteoblasts. In vitro, Metrnl was osteoinductive, increasing osteoblast differentiation and mineralization in tissue culture models. In vivo, loss of Metrnl expression resulted in no change in skeletal metrics in utero, at birth, or during postnatal growth. Six-week-old Metrnl-null mice displayed similar body length, body weight, tibial length, femoral length, BV/TV, trabecular number, trabecular thickness, and cortical thickness as littermate controls. In 4-month-old mice, lack of Metrnl expression did not change structural stiffness, ultimate force, or energy to fracture of femora under 3-point-bending. Last, we investigated the role of Metrnl in bone fracture healing. Metrnl expression increased in response to tibial injury, however, loss of Metrnl expression did not affect the amount of bone deposited within the healing tissue nor did it change the structural parameters of healing tissue. This work identifies Metrnl as a dispensable molecule for skeletal development. However, the osteoinductive capabilities of Metrnl may be utilized to modulate osteoblast differentiation in cell-based orthopedic therapies.

Opsoclonus in Uremia With Resolution After Hemodialysis.

ABSTRACT: A 78-year-old man was evaluated for altered mentation in the setting of significant uremia. On examination, he was found to be encephalopathic with generalized myoclonus and spontaneous opsoclonus. He had no known risk factors for the development of opsoclonus and upon undergoing hemodialysis, experienced near resolution of his eye movement abnormalities, thus highlighting a possible link between the uremic state and opsoclonus.

Intraoperative removal of third molars does not affect the postoperative infections after BSSO - Randomized controlled trial.

The goal of this study was to evaluate the incidence of postoperative wound infection and timing of mandibular third molar removal in bilateral sagittal split osteotomy (BSSO). This wis a prospective, single-blinded, randomized, split-mouth clinical trial. All patients were divided into two groups: Group I, where pre-operative removal of the third molars were done 6 months prior to BSSO and Group II, where intra-operative removal of contralateral third molars were done for the same patients during the osteotomy. The primary outcome variable studied was postoperative infection rate and the secondary outcome variable was bad split during BSSO. Among the seventy five patients (150 sites), one site in group II developed infection whereas none of the sites in group I developed infection (p = 1.000). No sites had bad split in both the groups. The results from the present study show that there is no difference between the presence or absence of mandibular third molars on post-operative wound infection following bilateral sagittal split osteotomy, and the authors hence suggest removing third molars during BSSO for patient comfort.

Patient Satisfaction in the Era of COVID-19: Virtual Visit versus In-person Visit Satisfaction.

SIGNIFICANCE: Teleophthalmology became widely used during the coronavirus 2019 pandemic; however, the quality of this care remains to be understood. PURPOSE: This study aimed to compare patient satisfaction levels from virtual and in-person visits based on post-visit surveys, as well as investigate demographic characteristics that may predict patient satisfaction with virtual visits. METHODS: Virtual (n = 2943) and in-person (n = 56,175) visits from March 19, 2020, to July 31, 2020, were identified using the electronic health record system. For in-person visits, a random subset of 3000 visits was acquired using a random number generator. Of these, 2266 virtual and 2590 in-person visits met the inclusion criteria. Patients who completed the Telemedicine for Medical Practice Survey and Medical Practice Survey were analyzed in this report. Nonparametric Mann-Whitney test was used to compare scores between groups. RESULTS: Two hundred eleven virtual patients (9.31%; 82 phone, 115 video, 14 hybrid) and 307 in-person patients (11.85%) completed the Telemedicine for Medical Practice Survey and Medical Practice Survey, respectively. Satisfaction scores were similar and high in both groups-virtual visit satisfaction scores averaged 4.82, whereas in-person visit satisfaction averaged 4.85 (P = .80, θ = 0.501 [0.493 to 0.509]). Only one question yielded significantly different satisfaction scores, and no demographic variables were significant predictors of satisfaction scores. CONCLUSIONS: Patient satisfaction is comparable between virtual and in-person visits, validating the continued usage of telemedicine for eye care visits.

Examining the Necessity of Postoperative Day-1 Review After Pars Plana Vitrectomy: A Meta-Analysis.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the necessity of the postoperative day-1 (POD1) review after pars plana vitrectomy. PATIENTS AND METHODS: The analysis included available literature that documented medical and surgical interventions performed on POD1 review after pars plana vitrectomy. A meta-analysis of proportions was conducted using a binomial-normal model to analyze three data sets consisting of all interventions, medical interventions, and surgical interventions. Heterogeneity and publication bias analyses were performed. RESULTS: POD1 reviews of 2,262 patients across 14 studies were examined to yield a total POD1 intervention rate estimate of 4.7% (95% confidence interval [CI], 3.0-13.9). When stratified by medical or surgical intervention, the intervention rate estimates were 4.1% (95% CI, 1.4-11.6) and 0.7% (95% CI, 0.3-1.3), respectively. The most common complication requiring postoperative intervention was elevated intraocular pressure. CONCLUSION: Given the wide confidence intervals of the estimated intervention rates, variability in postoperative practices, and range of interventions performed, the POD1 review cannot be discarded in its entirety. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:513-518.].

Should We Stop Treating Patients With Eplerenone for Chronic CSCR? Commentary on the VICI Trial.

The VICI trial reported by Lotery et al. is a recent placebo-controlled, randomized trial that examined the efficacy of eplerenone treatment for chronic central serous chorioretinopathy (CSCR) in 104 patients. The study found no significant difference in best-corrected visual acuity (BCVA) between the eplerenone-treated and placebo groups, prompting the VICI investigators to conclude that eplerenone should not be prescribed to treat CSCR. Limitations of the study include the patients' high baseline BCVA, use of a functional outcome like BCVA as the primary endpoint instead of an anatomical outcome, failure to account for rebound effect, and measuring subretinal fluid (SRF) thickness instead of the more informative SRF volume. Based on these reasons and evidence from multiple case series and prospective studies over the past 7 years, it is the opinion of the authors of this editorial that the VICI investigators' conclusion to stop prescribing eplerenone for CSCR is too severe. Future clinical trials should continue to explore the potential for eplerenone as long-term maintenance treatment in chronic CSCR. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:308-310.].

Prevalence, Surgical Management, and Audiologic Impact of Sigmoid Sinus Dehiscence Causing Pulsatile Tinnitus.

OBJECTIVE: To evaluate the prevalence, surgical management, and audiologic impact of pulsatile tinnitus caused by sigmoid sinus dehiscence. STUDY DESIGN AND SETTING: Retrospective chart review at a tertiary care hospital. PATIENTS: Adults with unilateral pulsatile tinnitus attributable to sigmoid sinus dehiscence who underwent resurfacing between January 2010 and January 2020. INTERVENTIONS: Transmastoid sigmoid resurfacing. MAIN OUTCOME MEASURES: Resolution of pulsatile tinnitus; audiologic outcomes; complications; tinnitus etiologies. RESULTS: Nineteen patients (89.4% women) had surgery for suspected sigmoid sinus dehiscence. The mean dehiscence size was 6.1 mm (range, 1-10.7 mm). Eight patients had concurrent sigmoid sinus diverticulum and one patient also had jugular bulb dehiscence. Only two patients (10.5%) had the defect identified by radiology. Low-frequency pure-tone average, measured at frequencies of 250 and 500 Hz, showed a significant median improvement of 8.8 dB following resurfacing (18.8 dB versus 10.0 dB, p = 0.02). The majority of patients had complete resolution of pulsatile tinnitus (16/19, 84.2%). Of those without complete resolution, two patients had partial response and one patient had no improvement. There were no significant complications. Of 41 consecutively tracked patients with a pulsatile tinnitus chief complaint, sigmoid pathology represented 32% of cases. CONCLUSIONS: Sigmoid sinus dehiscence represents a common vascular cause of pulsatile tinnitus that, if properly assessed, may be amenable to surgical intervention. Sigmoid sinus resurfacing is safe, does not require decompression, and may improve low-frequency hearing. Radiographic findings of dehiscence are often overlooked without a high index of clinical suspicion. Its relationship with transverse sinus pathology and idiopathic intracranial hypertension remain unclear.

The Specificity of Downstream Signaling for A1 and A2AR Does Not Depend on the C-Terminus, Despite the Importance of This Domain in Downstream Signaling Strength.

Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the unstructured C-terminus, which has been utilized for all the adenosine receptor crystal structures obtained to date. Ligand binding for this truncated receptor has been shown to be similar to full-length receptor for A2AR. However, the C-terminus has been identified as a location for protein-protein interactions that may be critical for the physiological function of these important drug targets. We show that variants with A2AR C-terminal truncations lacked cAMP-linked signaling compared to the full-length receptor constructs transfected into mammalian cells (HEK-293). In addition, we show that in a humanized yeast system, the absence of the full-length C-terminus affected downstream signaling using a yeast MAPK response-based fluorescence assay, though full-length receptors showed native-like G-protein coupling. To further study the G protein coupling, we used this humanized yeast platform to explore coupling to human-yeast G-protein chimeras in a cellular context. Although the C-terminus was essential for Gα protein-associated signaling, chimeras of A1R with a C-terminus of A2AR coupled to the A1R-specific Gα (i.e., Gαi1 versus Gαs). This surprising result suggests that the C-terminus is important in the signaling strength, but not specificity, of the Gα protein interaction. This result has further implications in drug discovery, both in enabling the experimental use of chimeras for ligand design, and in the cautious interpretation of structure-based drug design using truncated receptors.

Functional Expression of Adenosine A3 Receptor in Yeast Utilizing a Chimera with the A2AR C-Terminus.

The adenosine A3 receptor (A3R) is the only adenosine receptor subtype to be overexpressed in inflammatory and cancer cells and therefore is considered a novel and promising therapeutic target for inflammatory diseases and cancer. Heterologous expression of A3R at levels to allow biophysical characterization is a major bottleneck in structure-guided drug discovery efforts. Here, we apply protein engineering using chimeric receptors to improve expression and activity in yeast. Previously we had reported improved expression and trafficking of the chimeric A1R variant using a similar approach. In this report, we constructed chimeric A3/A2AR comprising the N-terminus and transmembrane domains from A3R (residues 1-284) and the cytoplasmic C-terminus of the A2AR (residues 291-412). The chimeric receptor showed approximately 2-fold improved expression with a 2-fold decreased unfolded protein response when compared to wild type A3R. Moreover, by varying culture conditions such as initial cell density and induction temperature a further 1.7-fold increase in total receptor yields was obtained. We observed native-like coupling of the chimeric receptor to Gai-Gpa1 in engineered yeast strains, activating the downstream, modified MAPK pathway. This strategy of utilizing chimeric receptor variants in yeast thus provides an exciting opportunity to improve expression and activity of "difficult-to-express" receptors, expanding the opportunity for utilizing yeast in drug discovery.

Lower concentrations of curcumin inhibit Her2-Akt pathway components in human breast cancer cells, and other dietary botanicals potentiate this and lapatinib inhibition.

Her2-dependent breast cancer is treated with pharmacological drugs (eg, Herceptin, lapatinib) that target Her2 signaling. Curcumin has emerged as a potential co-treatment for this and other cancers, but prior studies have focused on non-attainable concentrations. Here we test the hypothesis that attainable in vivo levels of dietary curcumin can reduce Her2 signaling. Consistent with previous studies, higher dose curcumin (18 µmol/L) inhibits Her2-Akt pathway signaling (pHer2, total Her2 and pAkt levels) and cell growth using AU565 human breast cancer cells. We then examined lower, more physiologically relevant concentrations of curcumin, alone and in combination with other dietary botanicals (quercetin and OptiBerry fruit extract). At 4 µmol/L, curcumin reduced Her2 signaling, and even more when combined with quercetin or OptiBerry. At 1.5 µmol/L curcumin, pHer2 and Her2 (but not pAkt) were reduced, with all three pathway markers reduced more in the presence of quercetin. We also found that 1.5 µmol/L curcumin strongly potentiated lapatinib inhibition of Her2-Akt pathway signaling, and more so for pAkt, when combined with quercetin plus OptiBerry (CQO). Parallel analyses revealed cell growth inhibition at 18 and 4 µmol/L but not 1.5 µmol/L curcumin, and potentiation of 1.5 µmol/L curcumin growth arrest with other botanicals +/- lapatinib. These studies demonstrate that a physiological attainable level of curcumin (1.5 µmol/L) can reduce some components of the critical Her2-Akt pathway; that even more complete inhibition can be achieved by combination with other dietary botanicals; and that curcumin and other botanicals can potentiate the action of the Her2-cancer metastatic drug lapatinib, in turn suggesting the potential anti-cancer clinical use of these botanicals.

Management of Elevated Intracranial Pressure: a Review.

PURPOSE OF REVIEW: Principles of intracranial pressure (ICP) management continue to be an essential part of the neurointensivist's skillset as appropriate treatment decisions can prevent secondary injury to the central nervous system. This review of the literature aims to: discuss commonly encountered pathologies associated with increased ICP, summarize diagnostic approaches used in evaluating ICP, and present evidence-based treatment paradigms that drive clinical care in intensive care units. RECENT FINDINGS: Recent topics of discussion include invasive and non-invasive modalities of diagnosis and monitoring, recent developments in hypothermia, hyperosmolar therapy, pharmacological interventions, and surgical therapies. The authors also present an example of an algorithm used within our system of hospitals for managing patients with elevated ICP. Recent advances have shown the mortality benefits in appropriately recognizing and treating increased ICP. Multiple modalities of treatment have been explored, and evidence has shown benefit in some. Further work continues to provide clarity in the appropriate management of intracranial hypertension.