Comparison of Pain Scores and Functional Outcomes of Patients Undergoing Arthroscopic Hip Labral Repair and Concomitant Capsular Repair or Plication Versus No Closure.

Background: The need for capsular closure during arthroscopic hip labral repair is debated. Purpose: To compare pain and functional outcomes in patients undergoing arthroscopic hip labral repair with concomitant repair or plication of the capsule versus no closure. Study Design: Cohort study. Methods: Outcomes were compared between patients undergoing arthroscopic hip labral repair with concomitant repair or plication of the capsule versus no closure at up to 2 years postoperatively and with stratification by age and sex. Patients with lateral center-edge angle <20°, a history of instability, a history of prior arthroscopic surgery in the ipsilateral hip, or a history of labral debridement only were excluded. Subanalysis was performed between patients undergoing no capsular closure who were propensity score matched 1:1 with patients undergoing repair or plication based on age, sex, and preoperative Modified Harris Hip Score (MHHS). We compared patients who underwent T-capsulotomy with concomitant capsular closure matched 1:5 with patients who underwent an interportal capsulotomy with concomitant capsular repair based on age, sex, and preoperative MHHS. Results: Patients undergoing capsular closure (n = 1069), compared with the no-closure group (n = 230), were more often female (68.6% vs 53.0%, respectively; P < .001), were younger (36.4 ± 13.3 vs 47.9 ± 14.7 years; P < .001), and had superior MHHS scores at 2 years postoperatively (85.8 ± 14.5 vs 81.8 ± 18.4, respectively; P = .020). In the matched analysis, no difference was found in outcome measures between patients in the capsular closure group (n = 215) and the no-closure group (n = 215) at any follow-up timepoint. No significant difference was seen between the 2 closure techniques at any follow-up timepoint. Patients with closure of the capsule achieved the minimal clinically important difference (MCID) and the patient acceptable symptom state (PASS) for the 1-year MHHS at a similar rate as those without closure (MCID, 50.3% vs 44.9%, P = .288; PASS, 56.8% vs 51.1%, P = .287, respectively). Patients with T-capsulotomy achieved the MCID and the PASS for the 1-year MHHS at a similar rate compared with those with interportal capsulotomy (MCID, 50.1% vs 44.9%, P = .531; PASS, 65.7% vs 61.2%, P = .518, respectively). Conclusion: When sex, age, and preoperative MHHS were controlled, capsular closure and no capsular closure after arthroscopic hip labral repair were associated with similar pain and functional outcomes for patients up to 2 years postoperatively.

Development of non-invasive flexible directional microwave ablation for central lung cancer: a simulation study.

Transbronchial microwave ablation (MWA) with flexible antennas has gradually become an attractive alternative to percutaneous MWA for lung cancer due to its characteristic of non-invasiveness. However, flexible antennas for the precision ablation of lung tumors that are adjacent to critical bronchial structures are still not available. In this study, a non-invasive flexible directional (FD) antenna for early stage central lung tumors surrounding the bronchia was proposed. A comprehensive numerical MWA model with the FD antenna was developed in a real human-sized left lung model. The structure of the antenna and the treatment protocol were optimized by a generic algorithm for the precision ablation of two cases of early stage central lung cancer (i.e. spherical-like and ellipsoidal tumors). The electromagnetic efficiency of the optimized antenna was also improved by implementing an optimizedπ-matching network for impedance matching. The results indicate that the electromagnetic energy of MWA can be restricted to a particular area for precision ablation of specific lung tumors using the FD antenna. This study contributes to the field of lung cancer management with MWA.

Mucosal immunization with dual influenza/COVID-19 single-replication virus vector protects hamsters from SARS-CoV-2 challenge.

The COVID-19 pandemic has highlighted the need for mucosal vaccines as breakthrough infections, short-lived immune responses and emergence of new variants have challenged the efficacy provided by the first generation of vaccines against SARS-CoV-2 viruses. M2SR SARS-CoV-2, an M2-deleted single-replication influenza virus vector modified to encode the SARS-CoV-2 receptor binding domain, was evaluated following intranasal delivery in a hamster challenge model for protection against Wuhan SARS-CoV-2. An adjuvanted inactivated SARS-CoV-2 whole virus vaccine administered intramuscularly was also evaluated. The intranasal M2SR SARS-CoV-2 was more effective than the intramuscular adjuvanted inactivated whole virus vaccine in providing protection against SARS-CoV-2 challenge. M2SR SARS-CoV-2 elicited neutralizing serum antibodies against Wuhan and Omicron SARS-CoV-2 viruses in addition to cross-reactive mucosal antibodies. Furthermore, M2SR SARS-CoV-2 generated serum HAI and mucosal antibody responses against influenza similar to an H3N2 M2SR influenza vaccine. The intranasal dual influenza/COVID M2SR SARS-CoV-2 vaccine has the potential to provide protection against both influenza and COVID.

The COVID-19 lockdown as a model of detraining in division 1 college softball players.

BACKGROUND: The COVID-19 pandemic interrupted the organized training of softball players, similar to the abrupt cessation of sports participation that can happen after an injury. Thus, the COVID-19 pandemic offers a unique model to study how sudden detraining influences softball players. METHODS: We recruited a sample of convenience of National Collegiate Athletic Association Division 1 softball players. They participated in three data collections: pre-lockdown (Jan 2020, T1), post-lockdown (Sept 2020, T2), and before the 2021 season (Jan 2021, T3). Between T1 and T2, players received an at-home conditioning and throwing program, but compliance was not strictly monitored. Between T2-T3, players resumed formal fall training (team-organized workouts, on-field practice, and within-team scrimmage games). At each time point, we collected bilaterally: 1) shoulder internal rotation (IR) and external rotation (ER) range of motion (ROM); 2) shoulder IR and ER strength; 3) hip IR and ER ROM; and 4) hip abduction and extension strength. We used four independent (2 Sides × 3 Timepoints) MANOVA with repeated measures; we followed up significant MANOVA main effect of time with Sidak posthoc tests for pairwise comparisons between time points. RESULTS: Fifteen players participated in this study. We found a significant MANOVA main effect of time for shoulder and hip ROM (p < 0.01). Between T1-T2, dominant shoulder ER ROM decreased 6.5°, dominant shoulder IR ROM increased 4.3°, and lead hip IR ROM increased 4.4°. Between T2-T3, dominant shoulder ER ROM increased 6.3° and trail hip ER ROM increased 5.9°. We found a significant MANOVA main effect of time for shoulder strength (p = 0.03) but not for hip strength (p = 0.18). Between T2-T3, non-dominant shoulder IR and ER increased 1.8 kg and 1.5 kg, respectively. CONCLUSION: A sudden and prolonged cessation of organized training generated changes in shoulder and hip ROM but affected strength to a lesser extent. The loss of shoulder ER and increased lead hip IR ROM are maladaptive as they are associated with injury in overhead athletes. Resuming team-organized training and scrimmage reversed some (shoulder ER), but not all of these changes. Practitioners should monitor clinical variables regularly and be aware of potential changes due to unexpected and prolonged interruptions in training, such as when players suffer sports-related injuries.

CYTOP® 366: A Tertiary Phosphine Inaccessible by Most Traditional Hydrophosphination Methods.

Homogenous catalysis is an essential tool within the commercial manufacture of bulk and fine chemicals. Within this, phosphine ligands, such as tricyclohexylphosphine, otherwise known as CYTOP® 366, are a crucial component. When designing a pathway to your ligand of choice, some key considerations include safety, yield and quality, but at commercial volumes we must also balance cost and consider the technologies readily available. Herein, we report the synthetic route that was chosen to manufacture tricyclohexylphosphine at commercial scale. We also consider, with the use of computational calculations, why traditional hydrophosphination methods failed, where the selected pathway succeeded.

Preseason lower extremity range of motion, flexibility, and strength in relation to in-season injuries in NCAA division I gymnasts.

OBJECTIVES: To determine if preseason lower extremity ROM, flexibility, and strength differ in collegiate gymnasts (NCAA Division 1) who do or do not sustain an injury during the competitive season. METHODS: Over four seasons, a total of 15 female gymnasts (age = 20.5 ± 1.0 years) underwent preseason screening (30 gymnast-season). We tested joint ROM (hip: flexion, internal and external rotation; ankle: weightbearing dorsiflexion), muscle flexibility (passive straight leg raise, Thomas,' Ober's, Ely's tests) and strength (hip extensors, abductors, and flexors isometric strength via a handheld dynamometer; knee: quadriceps and hamstring isokinetic strength at 60°/sec). The team athletic trainer tracked overuse lower extremity injuries (restricted gymnasts from full participation, occurred as from participation in organized practice or competition, and required medical attention) during each season. For athletes that tested multiple seasons, each encounter was considered independent, and each preseason assessment was linked to overuse injuries sustained during the same competitive season. Gymnasts were dichotomized into injured and non-injured groups. An independent t-test was used to measure differences in preseason outcomes between injured and non-injured groups. RESULTS: During four years, we recorded 23 overuse lower extremity injuries. Gymnasts that sustained an in-season overuse injury demonstrated significantly lower hip flexion ROM (mean difference: -10.6°; 95% confidence interval: -16.5, -4.6; p < 0.01) and lower hip abduction strength (mean difference: -4.7% of body weight; 95% confidence interval: -9.2, -0.3; p = 0.04). CONCLUSION: Gymnasts who sustain an in-season overuse lower extremity injury have significant preseason deficit of hip flexion ROM and weakness in the hip abductors. These findings indicate potential impairments in the kinematic & kinetic chains responsible for skill performance and energy absorption during landing.

Protective Effect of Subcutaneous Drains on Wound Infections in Kidney Transplantation.

BACKGROUND: Wound infections following kidney transplantation are common, with a reported incidence of 5%-19%. In the first few days after surgery, these patients receive extremely high doses of immunosuppression and high volumes of intravenous fluids, and they represent a specific subgroup of surgical patients that may benefit from using prophylactic subcutaneous drains. METHODS: We analyzed a nonrandomized series of 112 consecutive kidney transplants between January 2017 and December 2019: those who received a subcutaneous drain in addition to the standard retroperitoneal drain (SQ drain group) vs those with a retroperitoneal drain alone (standard group). RESULTS: The SQ drain group had a significantly higher median BMI (31.2 vs 25.8, P < .0001) and a trend towards more patients having diabetes and receiving thymoglobulin on induction. Nonetheless, 1/36 (3%) of patients in the SQ drain group had a documented wound infection requiring packing compared to the standard group 13/73 (17%) (P = .032). When multivariate regression analysis accounted for the potential confounders BMI, thymoglobulin use, and diabetes, the protective effect of the SQ drain was more significant (P = .001). CONCLUSIONS: An SQ drain may be a simple and inexpensive method to reduce the rate of wound complications in kidney transplant recipients; prospective studies are warranted.

Optimal design of aperiodic tri-slot antennas for the conformal ablation of liver tumors using an experimentally validated MWA computer model.

OBJECTIVE: This study aims to demonstrate that the conformal microwave ablation (MWA) of liver tumors could be attained by optimizing the structure of an aperiodic tri-slot coaxial antenna, its insertion depth, and input power. METHODS: A computational MWA model with an aperiodic tri-slot coaxial antenna operating at the frequency of 2.45 GHz was built and validated by both an ex vivo and a pilot in vivo experiment with porcine healthy livers. The validated in vivo computational MWA model implemented with a liver tumor was then used as a testbed to investigate the conformal ablation of liver tumors. Five liver tumors in different sizes and shapes were investigated. A genetic algorithm optimization method (NSGA-II) was used to optimize the structure of antenna, insertion depth of antenna, and microwave antenna input power for the conformal ablation of liver tumors. RESULTS: The validation results showed that a good agreement in both the spatiotemporal temperature distribution and ablation zone was found between the computer model and the ex vivo experiments at both 45 W, 5 min and 60 W, 3 min treatments and the in vivo experiment at 45 W, 5 min treatment. The optimized simulation results confirmed that five cases of liver tumors in different sizes and shapes can be conformally ablated by optimizing the aperiodic tri-slot coaxial antenna, antenna insertion depth, and microwave antenna input power. CONCLUSION: This paper demonstrates that the aperiodic tri-slot coaxial antenna can be optimized with the insertion depth and input power for the conformal ablation of liver tumors, regardless the size and shape of liver tumors.

The role of collaboration and mentorship in the publication of surgical resident research.

Background: Research is an integral part of surgical training and a mandated competency by national accreditation bodies. Most residents engage in research, but the conversion of this research into peer-reviewed publications is unknown. The objectives of this study were to assess the conversion rate of resident research into published manuscripts and determine what variables predict publication. Methods: Through a retrospective design, 99 resident research abstracts were identified from the Surgery Research Day at the University of Saskatchewan 2008-2018. Publication status was verified using Google Scholar and PubMed. Variables associated with resident-specific, mentor-specific, and project-specific variables were assessed for their role in predicting publication. Results: Fifty-two (53%) of the 99 abstracts were published in a peer-reviewed journal, and 43 (43%) were presented at a national conference. Logistic regression analysis revealed multidisciplinary research (OR 4.46, CI 1.8-11.4, p = 0.002), projects involving multiple resident researchers (OR 2.56, CI 1.02-6.43, p = 0.045), and faculty supervisor having > 25 publications (OR 2.46, CI 1.03-5.88, p = 0.042) as significant predictors of publication. Conclusions: Our study identifies three variables related to collaboration and mentorship that can serve as potential starting points to increase research productivity amongst medical trainees.

Contexte: La recherche fait partie intégrante de la formation en chirurgie et elle est définie comme une compétence obligatoire par les organismes d'agrément nationaux. La plupart des résidents font de la recherche, mais la portion de ces travaux qui donne lieu à des publications évaluées par les pairs demeure inconnue. Les objectifs de cette étude étaient d'évaluer le taux de conversion en publications des travaux de recherche des résidents et de déterminer les variables permettant de prédire la publication. Méthodes: Aux fins de cette étude rétrospective, nous avons repéré 99 résumés de recherche présentés par des résidents dans le cadre de la Journée de la recherche en chirurgie à l'Université de Saskatchewan entre 2008 et 2018. Le statut de publication a été vérifié en utilisant Google Scholar et PubMed. Des variables liées au résident, au mentor et au projet ont été évaluées pour déterminer leur rôle dans la prédiction d'une publication. Résultats: Cinquante-deux (53 %) des 99 résumés ont été publiés dans une revue évaluée par les pairs, et 43 (43 %) ont été présentés à une conférence nationale. L'analyse de régression logistique a révélé que la recherche multidisciplinaire (OR 4,46, CI 1,8-11,4, p=0,002), les projets regroupant plusieurs chercheurs résidents (OR 2,56, CI 1,02-6,43, p=0,045) et ceux supervisés par un membre du corps professoral ayant > 25 publications (OR 2,46, CI 1,03-5,88, p=0,042) étaient des prédicteurs significatifs d'une publication. Conclusions: Notre étude fait ressortir trois variables liées à la collaboration et au mentorat qui peuvent servir de points de départ pour accroître la productivité en recherche des médecins résidents.

Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2 Variants.

Current SARS-CoV-2 vaccines provide protection for COVID-19-associated hospitalization and death, but remain inefficient at inhibiting initial infection and transmission. Despite updated booster formulations, breakthrough infections and reinfections from emerging SARS-CoV-2 variants are common. Intranasal vaccination to elicit mucosal immunity at the site of infection can improve the performance of respiratory virus vaccines. We developed SARS-CoV-2 M2SR, a dual SARS-CoV-2 and influenza vaccine candidate, employing our live intranasal M2-deficient single replication (M2SR) influenza vector expressing the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein of the prototype strain, first reported in January 2020. The intranasal vaccination of mice with this dual vaccine elicits both high serum IgG and mucosal IgA titers to RBD. Sera from inoculated mice show that vaccinated mice develop neutralizing SARS-CoV-2 antibody titers against the prototype and Delta virus strains, which are considered to be sufficient to protect against viral infection. Moreover, SARS-CoV-2 M2SR elicited cross-reactive serum and mucosal antibodies to the Omicron BA.4/BA.5 variant. The SARS-CoV-2 M2SR vaccine also maintained strong immune responses to influenza A with high titers of anti H3 serum IgG and hemagglutination inhibition (HAI) antibody titers corresponding to those seen from the control M2SR vector alone. With a proven safety record and robust immunological profile in humans that includes mucosal immunity, the M2SR influenza viral vector expressing key SARS-CoV-2 antigens could provide more efficient protection against influenza and SARS-CoV-2 variants.

Outcomes of Biceps Tenodesis Variations With Concomitant Rotator Cuff Repair: A Multicenter Database Analysis.

Background: Studies to date comparing biceps tenodesis methods in the setting of concomitant rotator cuff repair (RCR) have demonstrated relatively equivalent pain and functional outcomes. Purpose: To compare biceps tenodesis constructs, locations, and techniques in patients who underwent RCR using a large multicenter database. Study Design: Cohort study; Level of evidence, 3. Methods: A global outcome database was queried for patients with medium- and large-sized tears who underwent biceps tenodesis with RCR between 2015 and 2021. Patients ≥18 years of age with a minimum follow-up of 1 year were included. The American Shoulder and Elbow Surgeons, Single Assessment Numeric Evaluation, visual analog scale for pain, and Veterans RAND 12-Item Health Survey (VR-12) scores were compared at 1 and 2 years of follow-up based on construct (anchor, screw, or suture), location (subpectoral, suprapectoral, or top of groove), and technique (inlay or onlay). Nonparametric hypothesis testing was used to compare continuous outcomes at each time point. The proportion of patients achieving the minimal clinically important difference (MCID) at the 1- and 2-year follow-ups were compared between groups using chi-square tests. Results: A total of 1903 unique shoulder entries were analyzed. Improvement in VR-12 Mental score favored anchor and suture fixations at 1 year of follow-up (P = .042) and the onlay tenodesis technique at 2 years of follow-up (P = .029). No additional tenodesis comparisons demonstrated statistical significance. The proportion of patients with improvement exceeding the MCID did not differ based on tenodesis methods for any outcome score assessed at the 1- or 2-year follow-up. Conclusion: Biceps tenodesis with concomitant RCR led to improved outcomes regardless of tenodesis fixation construct, location, or technique. A clear optimal tenodesis method with RCR remains to be determined. Surgeon preference and experience with various tenodesis methods as well as patient clinical presentation should continue to guide surgical decision-making.

Quadrivalent Formulation of Intranasal Influenza Vaccine M2SR (M2-Deficient Single Replication) Protects against Drifted Influenza A and B Virus Challenge.

Current influenza vaccines demonstrate low vaccine efficacy, especially when the predominantly circulating strain and vaccine are mismatched. The novel influenza vaccine platform M2- or BM2-deficient single replication (M2SR and BM2SR) has been shown to safely induce strong systemic and mucosal antibody responses and provide protection against significantly drifted influenza strains. In this study, we demonstrate that both monovalent and quadrivalent (Quad) formulations of M2SR are non-pathogenic in mouse and ferret models, eliciting robust neutralizing and non-neutralizing serum antibody responses to all strains within the formulation. Following challenge with wildtype influenza strains, vaccinated mice and ferrets demonstrated reduced weight loss, decreased viral replication in the upper and lower airways, and enhanced survival as compared to mock control groups. Mice vaccinated with H1N1 M2SR were completely protected from heterosubtypic H3N2 challenge, and BM2SR vaccines provided sterilizing immunity to mice challenged with a cross-lineage influenza B virus. Heterosubtypic cross-protection was also seen in the ferret model, with M2SR vaccinated animals exhibiting decreased viral titers in nasal washes and lungs following the challenge. BM2SR-vaccinated ferrets elicited robust neutralizing antibodies toward significantly drifted past and future influenza B strains. Mice and ferrets that received quadrivalent M2SR were able to mount immune responses equivalent to those seen with each of the four monovalent vaccines, demonstrating the absence of strain interference in the commercially relevant quadrivalent formulation.

Outcomes of young active patients with displaced clavicle fractures treated with Rockwood pin.

PURPOSE: Various fixation techniques have been described for midshaft clavicle fractures in the literature. We hypothesized that use of the Rockwood pin for fixation of displaced midshaft clavicle fractures would result in favorable outcomes in a young active cohort. METHODS: Patients aged 10-35 years who underwent Rockwood clavicle pin fixation at a single institution were identified. Preoperative and postoperative radiographs were reviewed and assessed for fracture characteristics, postoperative alignment, and radiographic union. Postoperative outcome scores were obtained. RESULTS: A total of 39 patients (age 17.3 ± 3.9 years) with clavicle fracture treated with Rockwood pin were identified. Radiographic review demonstrated that 88% of fractures were 100%, or more, displaced, and surgery achieved near-anatomic reduction in 92% of cases. Average time to radiographic union was 2.3 ± 0.8 months, and average time to clinical union was 2.5 ± 0.3 months. One patient required revision for nonunion (3%). Complete outcome responses were obtained for 24 patients, with an average 40 ± 27.7 months of follow-up. Mean Total Clavicle Functional score was 2.75 ± 3.6 for minor patients. For adult patients, Nottingham Clavicle score was 90.7 ± 10.7, mean American Shoulder and Elbow Society score was 92.4 ± 11.2, and mean Single Assessment Numerical Evaluation score was 88.8 ± 21.5. 77% of adults reported no long-term functional limitation; 54% reported a bump at the prior fracture site, but 100% reported satisfaction with shoulder appearance. CONCLUSIONS: In our cohort of young active patients, treatment with Rockwood pin allowed for anatomic reduction, healing with a low nonunion rate, and favorable patient reported outcomes.

Syngeneic model of carcinogen-induced tumor mimics basal/squamous, stromal-rich, and neuroendocrine molecular and immunological features of muscle-invasive bladder cancer.

Introduction: Bladder cancer is a heterogenous disease and the emerging knowledge on molecular classification of bladder tumors may impact treatment decisions based on molecular subtype. Pre-clinical models representing each subtype are needed to test novel therapies. Carcinogen-induced bladder cancer models represent heterogeneous, immune-competent, pre-clinical testing options with many features found in the human disease. Methods: Invasive bladder tumors were induced in C57BL/6 mice when continuously exposed to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Tumors were excised and serially passed by subcutaneous implantation into sex-matched syngeneic C57BL/6 hosts. Eight lines were named BBN-induced Urothelium Roswell Park (BURP) tumor lines. BURP lines were characterized by applying consensus molecular classification to RNA expression, histopathology, and immune profiles by CIBERSORT. Two lines were further characterized for cisplatin response. Results: Eight BURP tumor lines were established with 3 male and 3 female BURP tumor lines, having the basal/squamous (BaSq) molecular phenotype and morphology. BURP-16SR was established from a male mouse and has a stromal-rich (SR) molecular phenotype and a sarcomatoid carcinoma morphology. BURP-19NE was established from a male mouse and has a neuroendocrine (NE)-like molecular phenotype and poorly differentiated morphology. The established BURP tumor lines have unique immune profiles with fewer immune infiltrates compared to their originating BBN-induced tumors. The immune profiles of the BURP tumor lines capture some of the features observed in the molecular classifications of human bladder cancer. BURP-16SR growth was inhibited by cisplatin treatment, while BURP-24BaSq did not respond to cisplatin. Discussion: The BURP lines represent several molecular classifications, including basal/squamous, stroma-rich, and NE-like. The stroma-rich (BURP-16SR) and NE-like (BURP-19NE) represent unique immunocompetent models that can be used to test novel treatments in these less common bladder cancer subtypes. Six basal/squamous tumor lines were established from both male and female mice. Overall, the BURP tumor lines have less heterogeneity than the carcinogen-induced tumors and can be used to evaluate treatment response without the confounding mixed response often observed in heterogeneous tumors. Additionally, basal/squamous tumor lines were established and maintained in both male and female mice, thereby allowing these tumor lines to be used to compare differential treatment responses between sexes.

Subacromial-Subdeltoid Bursitis With Rice Bodies After Rotator Cuff Repair With a Collagen Scaffold Implant: A Case Report.

CASE: We report the second-known case of subacromial-subdeltoid bursitis with rice bodies after rotator cuff repair with a Smith + Nephew REGENETEN bovine-derived bioinductive collagen scaffold implant. After the removal of rice bodies and a portion of implant that had not incorporated, the patient recovered well and made a full return to work and recreational activities. CONCLUSION: This case demonstrates that persistent pain, swelling, or decreased range of motion for several months after rotator cuff repair with the use of a collagen implant may warrant a relatively early magnetic resonance imaging to evaluate for underlying pathology. It also provides a framework for physicians who may see similar patients in the future.

Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering.

The multidisciplinary fields of tissue engineering and regenerative medicine have the potential to revolutionize the practise of medicine through the abilities to repair, regenerate, or replace tissues and organs with functional engineered constructs. To this end, tissue engineering combines scaffolding materials with cells and biologically active molecules into constructs with the appropriate structures and properties for tissue/organ regeneration, where scaffolding materials and biomolecules are the keys to mimic the native extracellular matrix (ECM). For this, one emerging way is to decellularize the native ECM into the materials suitable for, directly or in combination with other materials, creating functional constructs. Over the past decade, decellularized ECM (or dECM) has greatly facilitated the advance of tissue engineering and regenerative medicine, while being challenged in many ways. This article reviews the recent development of dECM for tissue engineering and regenerative medicine, with a focus on the preparation of dECM along with its influence on cell culture, the modification of dECM for use as a scaffolding material, and the novel techniques and emerging trends in processing dECM into functional constructs. We highlight the success of dECM and constructs in the in vitro, in vivo, and clinical applications and further identify the key issues and challenges involved, along with a discussion of future research directions.

Intranasal M2SR (M2-Deficient Single Replication) H3N2 Influenza Vaccine Provides Enhanced Mucosal and Serum Antibodies in Adults.

BACKGROUND: We previously demonstrated that an intranasal dose of 108 50% tissue culture infectious dose (TCID50) M2-deficient single replication (M2SR) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection. METHODS: Serosusceptible subjects aged 18-49 years were randomized to receive 2 doses (108-109 TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines. RESULTS: The vaccine was well tolerated at all dose levels. Against Belgium2015, ≥ 2-fold increases in MN antibodies were noted among 40% (95% confidence interval [CI], 24.9%-56.7%) of subjects following a single 108 TCID50 M2SR dose and among 80.6% (95% CI, 61.4%-92.3%) after 109 dose (P < .001). A single 109 TCID50 dose of M2SR generated ≥4-fold hemagglutination inhibition antibody seroconversion against the vaccine strain in 71% (95% CI, 52.0%-85.8%) of recipients. Mucosal and cellular immune responses were also induced. CONCLUSIONS: These results indicate that M2SR may provide substantial protection against infection with highly drifted strains of H3N2 influenza. CLINICAL TRIALS REGISTRATION: NCT03999554.

In recent years, influenza A H3N2 viruses have evolved into multiple cocirculating clades, resulting in low vaccine efficacy and highlighting the need for more effective influenza vaccines. In a previous challenge study, a single intranasal dose of the investigational vaccine M2SR demonstrated protection against a highly drifted H3N2 influenza challenge virus in a subset of vaccine recipients with a signature immune response. Increasing the dose of the M2SR vaccine in this phase1b study demonstrated a statistically significant increase in the proportion of subjects with the signature immune responses seen previously. The vaccine-induced antibodies were cross-reactive with a panel of drifted H3N2 viruses from 2007 to 2019. Additionally, M2SR generated a rise in serum hemagglutination inhibition antibody titer in 71% of subjects. In contrast, the H3N2 seroresponse rate for the licensed intranasal vaccine FluMist is 10% in seronegative adults. Moreover, M2SR elicited mucosal and cell-mediated immune responses. This study demonstrates that the intranasal M2SR generates a multifaceted immune response and has the potential to provide better efficacy against vaccine-matched strains and influenza drift variants reducing the need to update the vaccine on an annual basis. This is a noteworthy step in the development of a broadly protective influenza vaccine.

Outcomes of Biceps Tenotomy Versus Tenodesis During Arthroscopic Rotator Cuff Repair: An Analysis of Patients From a Large Multicenter Database.

Background: Studies to date evaluating biceps tenotomy versus tenodesis in the setting of concomitant rotator cuff repair (RCR) have demonstrated relatively equivalent pain and functional outcomes. Hypothesis: It was hypothesized that a significant difference could be demonstrated for pain and functional outcome scores comparing biceps tenotomy versus tenodesis in the setting of RCR if the study was adequately powered. Study Design: Cohort study; Level of evidence, 3. Methods: The Arthrex Surgical Outcomes System database was queried for patients who underwent arthroscopic biceps tenotomy or tenodesis and concomitant RCR between 2013 and 2021; included patients had a minimum of 2 years of follow-up. Outcomes between treatment types were assessed using the American Shoulder and Elbow Surgeons Shoulder (ASES), Single Assessment Numeric Evaluation (SANE), visual analog scale (VAS) for pain, and Veterans RAND 12-Item Health Survey (VR-12) scores preoperatively and at 3 months, 6 months, 1 year, and 2 years postoperatively. Results were stratified by age at surgery (3 groups: <55, 55-65, >65 years) and sex. Results: Overall, 1936 primary RCRs were included for analysis (1537 biceps tenodesis and 399 biceps tenotomy patients). Patients who underwent tenotomy were older and more likely to be female. A greater proportion of female patients aged <55 years and 55 to 65 years received a biceps tenotomy compared with tenodesis (P = .012 and .026, respectively). All scores were comparable between the treatment types preoperatively and at 3 months, 6 months, and 1 year postoperatively. At 2-year follow-up, patients who received a biceps tenodesis had statistically more favorable ASES, SANE, VAS pain, and VR-12 scores (P ≤ .031); however, the differences did not exceed the minimal clinically important difference (MCID) for these measures. Conclusion: Our findings indicate that surgeons are more likely to perform a biceps tenotomy in female and older patients. Biceps tenodesis provided improved pain and functional scores compared with tenotomy at 2-year follow-up; however, the benefit did not exceed previously reported MCID for the outcome scores. Both procedures provided improvement in outcomes; thus, the choice of procedure should be a shared decision between the surgeon and patient.

Radiofrequency ablation for liver tumors abutting complex blood vessel structures: treatment protocol optimization using response surface method and computer modeling.

OBJECTIVE: To achieve a result of a large tumor ablation volume with minimal thermal damage to the surrounding blood vessels by designing a few clinically-adjustable operating parameters in radiofrequency ablation (RFA) for liver tumors abutting complex vascular structures. METHODS: Response surface method (RSM) was employed to correlate the ablated tumor volume (Ra) and thermal damage to blood vessels (Dt) based on RFA operating parameters: ablation time, electrode position, and insertion angle. A coupled electric-thermal-fluid RFA computer model was created as the testbed for RSM to simulate RFA process. Then, an optimal RFA protocol for the two conflicting goals, namely (1) large tumor ablation and (2) small thermal damage to the surrounding blood vessels, has been achieved under a specific ablation environment. RESULTS: Linear regression analysis confirmed that the RFA protocol significantly affected Ra and Dt (the adjusted coefficient of determination Radj2 = 93.61% and 95.03%, respectively). For a proposed liver tumor scenario (liver tumor with a dimension of 4×3×2.9 cm3 abutting a complex vascular structure), an optimized RFA protocol was found based on the regression results in RSM. Compared with a reference RFA protocol, in which the electrode was centered in the tumor with a 12-min ablation time, the optimized RFA protocol has increased Ra  from 98.1% to 99.6% and decreased Dt from 4.1% to 0.4%, achieving nearly the complete ablation of proposed liver tumor and ignorable thermal damages to vessels. CONCLUSION: This work showed that it is possible to design a few clinically-adjustable operating parameters of RFA for achieving a large tumor ablation volume while minimizing thermal damage to the surrounding blood vessels.