Posterior tibial slope angle in contact versus non-contact anterior cruciate ligament injuries.

BACKGROUND: Increased Posterior Tibial Slope (PTS) angle has been reported to be a risk factor for primary anterior cruciate ligament (ACL) tears. However, it is unknown whether increased PTS has an associated increased risk for non-contact versus contact ACL injury. PURPOSE: The purpose of this study is to determine whether patients with non-contact ACL injury have a higher PTS angle than those with contact ACL injury. METHODS: A total of 1700 patients who underwent primary ACL reconstruction between January 2011 and June 2023 at a single academic institution were initially included. Electronic medical records were reviewed for demographic information as well as evidence that the patient sustained a contact or non-contact ACL injury. Patients in the contact cohort were propensity score matched to patients in the non-contact cohort by age, sex and BMI. Additionally, patients in the contact cohort were then propensity score matched to a control group of patients with intact ACLs also by age, sex and BMI. RESULTS: One hundred and two patients with contact injury were initially identified and 1598 patients with non-contact injuries were identified. Of the 102, 67 had knee X-rays that were suitable for measurement. These 67 contact injury patients were propensity score matched to 67 noncontact patient and 67 patients with intact ACLs based on age, sex and BMI. There were no significant differences between contact and non-contact cohorts in age (28.7±6.3 vs. 27.1±6.5, p = 0.147), sex (Female: 36.0% vs. 34.3%, p = 0.858), or BMI (26.7±5.6 vs 26.1±3.4, p = 0.475). There was no significant difference in PTS angle between contact versus non-contact ACL injury patients (11.6±3.0 vs.11.6±2.8, p = 0.894). There was a significant difference in PTS between the contact ACL injury and the intact cohort (11.6±3.0 vs. 10.0±3.9, p = 0.010) and the non-contact ACL injury and the intact cohort (11.6±2.8 vs. 10.0±3.9, p = 0.010). CONCLUSION: There was no significant difference in the degree of PTS between patients who sustained contact versus non-contact ACL injuries. Additionally, there was a significantly increased PTS in both the contact and non-contact ACL injury cohorts compared to patients with intact ACLs.

Significant systematic bias of alpha angles measured on MRI compared to various radiographic views in patients with femoroacetabular impingement syndrome.

PURPOSE: The aim of this study was to assess the inter-rater reproducibility and inter-method comparability of hip alpha angle measurements on magnetic resonance imaging (MRI)/magnetic resonance arthrography (MRA) and plain radiographs in patients with femoroacetabular impingement syndrome (FAIS). METHODS: A cross-sectional study of patients who were diagnosed with symptomatic FAIS underwent preoperative MRI/MRA with axial oblique and/or radial plane imaging and had preoperative radiographs with anterior-posterior (AP), 45° Dunn and 90° Dunn views. Alpha angle measurements were performed independently by two musculoskeletal radiologists. Inter-rater reproducibility and inter-method comparability between MRI/MRA images and radiographic views were assessed using the intraclass correlation coefficient (ICC) with 95% confidence interval (CI). RESULTS: Ninety-seven patients were included of whom 93 (95.8%) received axial oblique plane images and 54 (55.6%) had radial plane MRI/MRA images. Inter-rater reproducibility was excellent (ICC > 0.9) for all planes on MRI/MRA and radiographs. MRI/MRA axial oblique images had poor (ICC 0.39, 95% CI [0.09, 0.59]), moderate (ICC 0.57, 95% CI [0.18, 0.75]) and moderate (ICC 0.64, 95% CI [0.20, 0.81]) comparability with AP, 45° Dunn and 90° Dunn, respectively. MRI/MRA radial plane images had equivocal (0 included in all CIs) comparability with AP (ICC 0.66), 45° Dunn (ICC 0.35) and 90° Dunn (ICC 0.14) radiographs. On average, alpha angle measurements were significantly higher with radial images and lower with axial oblique images, when compared to all radiographic views (p < 0.05), except axial oblique versus 45° Dunn views, where angles measured on axial oblique were significantly larger. CONCLUSION: Alpha angle measurements taken on axial oblique MRI/MRA images show moderate comparability to radiographic 45° Dunn and 90° Dunn views despite negative bias to measurements taken on radiographic AP and 45° Dunn view. Larger alpha angles were appreciated on MRI/MRA radial and axial oblique views compared to radiographic views supporting the inclusion of MRI/MRA alpha angle measurements to properly identify deformity. LEVEL OF EVIDENCE: Level II.

Levels of Synovial Fluid Inflammatory Biomarkers on Day of Arthroscopic Partial Meniscectomy Predict Long-Term Outcomes and Conversion to TKA: A 10-Year Mean Follow-up Study.

BACKGROUND: The purpose of the present study was to evaluate the relationships of the concentrations of pro- and anti-inflammatory biomarkers in the knee synovial fluid at the time of arthroscopic partial meniscectomy (APM) to long-term patient-reported outcomes (PROs) and conversion to total knee arthroplasty (TKA). METHODS: A database of patients who underwent APM for isolated meniscal injury was analyzed. Synovial fluid had been aspirated from the operatively treated knee prior to the surgical incision, and concentrations of pro- and anti-inflammatory biomarkers (RANTES, IL-6, MCP-1, MIP-1ß, VEGF, TIMP-1, TIMP-2, IL-1RA, MMP-3, and bFGF) were quantified. Prior to surgery and again at the time of final follow-up, patients were asked to complete a survey that included a visual analog scale (VAS) for pain and Lysholm, Tegner, and Knee injury and Osteoarthritis Outcome Score-Physical Function Short Form (KOOS-PS) questionnaires. Clustering analysis of the 10 biomarkers of interest was carried out with the k-means algorithm. RESULTS: Of the 82 patients who met the inclusion criteria for the study, 59 had not undergone subsequent ipsilateral TKA or APM, and 43 (73%) of the 59 completed PRO questionnaires at long-term follow-up. The mean follow-up time was 10.6 ± 1.3 years (range, 8.7 to 12.4 years). Higher concentrations of individual pro-inflammatory biomarkers including MCP-1 (ß = 13.672, p = 0.017) and MIP-1ß (ß = -0.385, p = 0.012) were associated with worse VAS pain and Tegner scores, respectively. K-means clustering analysis separated the cohort of 82 patients into 2 groups, one with exclusively higher levels of pro-inflammatory biomarkers than the second group. The "pro-inflammatory phenotype" cohort had a significantly higher VAS pain score (p = 0.024) and significantly lower Lysholm (p = 0.022), KOOS-PS (p = 0.047), and Tegner (p = 0.009) scores at the time of final follow-up compared with the "anti-inflammatory phenotype" cohort. The rate of conversion to TKA was higher in the pro-inflammatory cohort (29.4% versus 12.2%, p = 0.064). Logistic regression analysis demonstrated that the pro-inflammatory phenotype was significantly correlated with conversion to TKA (odds ratio = 7.220, 95% confidence interval = 1.028 to 50.720, p = 0.047). CONCLUSIONS: The concentrations of synovial fluid biomarkers on the day of APM can be used to cluster patients into pro- and anti-inflammatory cohorts that are predictive of PROs and conversion to TKA at long-term follow-up. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Structural insights into CXCR4 modulation and oligomerization.

Activation of the chemokine receptor CXCR4 by its chemokine ligand CXCL12 regulates diverse cellular processes. Previously reported crystal structures of CXCR4 revealed the architecture of an inactive, homodimeric receptor. However, many structural aspects of CXCR4 remain poorly understood. Here, we use cryo-electron microscopy to investigate various modes of human CXCR4 regulation. CXCL12 activates CXCR4 by inserting its N terminus deep into the CXCR4 orthosteric pocket. The binding of US Food and Drug Administration-approved antagonist AMD3100 is stabilized by electrostatic interactions with acidic residues in the seven-transmembrane-helix bundle. A potent antibody blocker, REGN7663, binds across the extracellular face of CXCR4 and inserts its complementarity-determining region H3 loop into the orthosteric pocket. Trimeric and tetrameric structures of CXCR4 reveal modes of G-protein-coupled receptor oligomerization. We show that CXCR4 adopts distinct subunit conformations in trimeric and tetrameric assemblies, highlighting how oligomerization could allosterically regulate chemokine receptor function.

MCP-1 in synovial fluid as a predictor of inferior clinical outcomes after meniscectomy.

PURPOSE: To evaluate knee intra-articular cytokine concentrations in patients undergoing isolated meniscectomy and determine if these concentrations are associated with clinical outcomes. METHODS: Concentrations of ten biomarkers were quantified in synovial fluid aspirated from the operative knees of patients who underwent isolated meniscectomy from 10/2011-12/2019. Patients completed a survey at final follow-upincluding VAS, Lysholm, Tegner, and KOOS Physical Function Short Form (KOOS-PS). Failure was defined as subsequent TKA or non-achievement of the Patient Acceptable Symptom State (PASS) for knee pain defined as VAS > 27/100. Regression analysis investigating the relationship between cytokine concentrations and failure was performed. RESULTS: The study consisted of 100 patients, including 50 males (50.0%) with a mean age of 51.1 ± 11.7 years, a median BMI of 28.9 kg/m2 [25.5, 32.4], and a mean follow-up of 8.0 ± 2.2 years. There were no demographic or clinical differences between failures (n = 41) and non-failures (n = 59) at baseline. Monocyte Chemotactic Protein 1 (MCP-1) concentration was significantly higher in failures than in non-failures (344.3 pg/ml vs. 268.6 pg/ml, p = 0.016). In a regression analysis controlling for age, sex, BMI, symptom duration, length of follow-up, and ICRS grade, increased MCP-1 was associated with increased odds of failure (p = 0.002). CONCLUSIONS: The concentration of MCP-1 on the day of arthroscopic meniscectomy was predictive of failure as defined by an unacceptable pain level at intermediate- to long-term follow-up. This finding may help identify patients at high risk for poor postoperative outcomes following isolated meniscectomy and serve as a target for future postoperative immunomodulation research.

Outcomes of sciatic neurolysis in chronic hamstring tears: a retrospective case series.

PURPOSE: Proximal hamstring tears may present with neurological dysfunction due to compression or stretching of the sciatic nerve. The purpose of this study was to evaluate the effectiveness of hamstring repair with concurrent sciatic nerve neurolysis for clinical outcomes and patient symptoms. METHODS: A retrospective chart review of patients who were diagnosed with hamstring injury at a large tertiary care institution was conducted. Patients with chronic tears (> 6 weeks from injury to surgery) who underwent hamstring repair were reviewed for demographics, clinical variables including symptoms of sciatic neuritis, sciatic nerve abnormalities on MRI, and postoperative outcomes. Chi-square tests were used for categorical variables, t test for continuous variables. Pairwise t tests were used to compare average pre- and postoperative strength for patients with and without symptoms of sciatic neuritis. RESULTS: Thirty-two patients with chronic hamstring tears were included in the analysis. Patients were 59.4% female with an average age of 51.4 years (SD 13.1). Preoperatively, 27 patients (84.4%) were noted to have symptoms of sciatic neuritis. These patients did not differ in age (p = .677) or sex (p = .374) from patients without preoperative symptoms. Sciatic nerve abnormalities were noted on MRI report in 7 patients who had sciatic nerve symptoms and 0 patients who did not have sciatic nerve symptoms. Symptomatic improvement was seen in 21/26 (81%) of patients who had preoperative neurological symptoms, and in 6/7 (86%) of patients with MRI findings. All patients had equivalent or improved strength postoperatively. CONCLUSION: A sciatic nerve neurolysis is a safe and effective procedure to perform on patients with preoperative sciatic nerve symptoms and chronic hamstring tears that leads to improvement in neurological symptoms and strength. In neurologically asymptomatic patients with chronic hamstring injuries and MRI findings indicating possible nerve damage, a discussion should be held about the risks and benefits of performing a sciatic nerve neurolysis.

Epigenetic therapy potentiates transposable element transcription to create tumor-enriched antigens in glioblastoma cells.

Inhibiting epigenetic modulators can transcriptionally reactivate transposable elements (TEs). These TE transcripts often generate unique peptides that can serve as immunogenic antigens for immunotherapy. Here, we ask whether TEs activated by epigenetic therapy could appreciably increase the antigen repertoire in glioblastoma, an aggressive brain cancer with low mutation and neoantigen burden. We treated patient-derived primary glioblastoma stem cell lines, an astrocyte cell line and primary fibroblast cell lines with epigenetic drugs, and identified treatment-induced, TE-derived transcripts that are preferentially expressed in cancer cells. We verified that these transcripts could produce human leukocyte antigen class I-presented antigens using liquid chromatography with tandem mass spectrometry pulldown experiments. Importantly, many TEs were also transcribed, even in proliferating nontumor cell lines, after epigenetic therapy, which suggests that targeted strategies like CRISPR-mediated activation could minimize potential side effects of activating unwanted genomic regions. The results highlight both the need for caution and the promise of future translational efforts in harnessing treatment-induced TE-derived antigens for targeted immunotherapy.

Self-management interventions for chronic widespread pain including fibromyalgia: a systematic review and qualitative evidence synthesis.

ABSTRACT: Supporting behavioural self-management is increasingly important in the care for chronic widespread pain (CWP), including fibromyalgia. Understanding peoples' experiences of these interventions may elucidate processes and mechanisms that lead to or hinder their intended impact. We conducted a systematic review and thematic synthesis of qualitative studies exploring peoples' experiences of self-management interventions for CWP, including fibromyalgia. MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science were searched. Primary qualitative or mixed-methods studies were included if they explored people's self-management intervention experiences for their CWP, including fibromyalgia. Screening, data extraction, and critical appraisal were conducted by 2 reviewers. Data analysis was conducted through thematic synthesis. Twenty-three studies were included, mostly were rated as high or moderate quality. We developed 4 analytic themes: A multifaceted experience of the intervention, potential for transformative experience of group cohesion, a new outlook, and striving for change after the loss of support. Broadly, personalisation was perceived as beneficial and people experienced a range of emotional experiences. These appeared to support positive behavioural and cognitive changes. For most, group activities promoted acceptance and support, fostering new perspectives and improved self-management, although some found aspects of group contexts challenging. Lack of on-going support after interventions led to challenges in applying behavioural strategies, and some struggled without social support from the group. The experiences of self-management interventions for CWP reflect a complex, multifaceted process. Although many reported positive experiences, addressing issues with integration of physical activity, group dynamics and postintervention support may improve effectiveness for a broader range of people.

Characterization of bone marrow edema patterns among patients with Segond fracture in the setting of acute anterior cruciate ligament injury: A comparative MRI study.

PURPOSE: The purpose of this study is to investigate the anatomic distribution of bone marrow edema on MRI among patients who sustained a Segond fracture compared to those with an isolated ACL tear. METHODS: A retrospective cohort study was performed of patients aged 18-40 years old who presented with an acute isolated ACL tear between January 2012 and May 2022. Two blinded readers reviewed all knee MRIs to assess bone marrow edema using the Whole-Organ Magnetic Resonance Imaging Score and the area of each sub-compartment was scored. RESULTS: There were 522 patients in the final analysis, of which 28 patients (5.4%) were identified to have a Segond fracture. The Segond group demonstrated significantly greater rates of WORMS grades 2 and 3 in the central lateral femoral condyle, as well as the anterior, central, and posterior lateral tibial plateau. Furthermore, the Segond group demonstrated significantly greater rates of WORMS grades 2 and 3 in the central medial femoral condyle and the anterior medial tibial plateau. Bone edema at the central lateral femoral condyle (R = 0.034, p = 0.019) and central tibial plateau (R = 0.093, p = 0.033) were significantly correlated with lateral meniscus tears, while the edema in the posterior medial femoral condyle was correlated with medial meniscus tears (R = 0.127, p = 0.004). CONCLUSION: Patients who present with ACL tear and a concomitant Segond fracture demonstrate significantly more extensive bone marrow edema in both the medial and lateral compartments of the knee compared to patients with an isolated ACL tear.

Medicaid Reimbursement for Total Hip and Knee Arthroplasty: A State-by-State Analysis Compared With Medicare.

BACKGROUND: Medicare (MCR) reimbursement for arthroplasty procedures has been declining, but little has been reported on Medicaid (MCD) reimbursement. We sought to determine MCD reimbursement rates using state MCD data for nine arthroplasty procedure codes and compare them to MCR rates. METHODS: The Centers for Medicare & Medicaid Services physician fee schedule was used to collect MCR reimbursement rates, and state MCD fee schedules were accessed to collect MCD rates for nine procedures encompassing primary and revision hip and knee arthroplasty surgery. State MCR and MCD rates were compared to determine the mean dollar difference and dollar difference per relative value unit. A cost of living adjustment was performed using the Medicare Wage Index for each state. Coefficients of variation were calculated for each state to determine overall variability between the two systems. RESULTS: The mean reimbursement rates for MCD were lower for eight of the nine codes used in the study. Medicaid reimbursed physicians an average of 11.3% less overall and 23.1% less when adjusted for cost of living. The amount of variability in the MCR rates was low with a consistent coefficient of variation of 0.06, but was higher in the MCD rates with a range of 0.26 to 0.29 in the unadjusted rates and 0.34 to 0.37 in the adjusted rates. There was a mean $6.73 decreased reimbursement per relative value unit for MCD procedures. CONCLUSIONS: For the most common arthroplasty procedures, MCD reimbursed physicians less than MCR on average. MCD also demonstrated increased variability when compared to MCR rates between states.

Peer support for patients with opioid use disorder in the emergency department: A narrative review.

Faced with a growing opioid overdose crisis, emergency departments (EDs) are increasingly hiring peers-people with lived experiences of addiction and recovery-to work with patients in the ED who have opioid use disorders (OUDs) or who have experienced an opioid overdose. Despite a clear need for more support for patients with OUD and rapid expansion in grant funding for peer programs, there are limited data on how these programs affect clinical outcomes and how they are best implemented within the ED. In this narrative review, we synthesize the existing evidence on how to develop and implement peer programs for OUD in the ED setting. We describe the key activities peers can undertake in the ED, outline requirements of the peer role and best practices for peer supervision and hiring, detail how ED administrators have built financial and political support for peer programs, and summarize the limited evidence on clinical and care linkage outcomes of peer programs. We highlight key resources that ED clinicians and administrators can use to develop peer programs and key areas where additional research is needed.

Nutritional convergence in plants growing on gypsum soils in two distinct climatic regions.

BACKGROUND AND AIMS: Soil endemics have long fascinated botanists due to the insights they can provide about plant ecology and evolution. Often, these species have unique foliar nutrient composition patterns that reflect potential physiological adaptations to these harsh soil types. However, understanding global nutritional patterns to unique soil types can be complicated by the influence of recent and ancient evolutionary events. Our goal was to understand whether plant specialization to unique soils is a stronger determinant of plant nutrient composition than climate or evolutionary constraints. METHODS: We worked on gypsum soils. We analyzed whole-plant nutrient composition (leaves, stems, coarse roots and fine roots) of 36 native species of gypsophilous lineages from the Chihuahuan Desert (North America) and the Iberian Peninsula (Europe) regions, including widely distributed gypsum endemics, as specialists, and narrowly distributed endemics and non-endemics, as non-specialists. We evaluated the impact of evolutionary events and soil composition on the whole-plant composition, comparing the three categories of gypsum plants. KEY RESULTS: Our findings reveal nutritional convergence of widely distributed gypsum endemics. These taxa displayed higher foliar Sulfur and higher whole-plant Magnesium than their non-endemic relatives, irrespective of geographic location or phylogenetic history. Sulfur and Magnesium concentrations were mainly explained by non-phylogenetic variation among species related to gypsum specialization. Other nutrient concentrations were determined by more ancient evolutionary events. For example, Caryophyllales usually displayed high foliar Calcium, whereas Poaceae did not. In contrast, plant concentrations of Phosphorus was mainly explained by species-specific physiology not related to gypsum specialization or evolutionary constraints. CONCLUSIONS: Plant specialization to a unique soil may strongly influence plant nutritional strategies, as we described for gypsophilous lineages. Taking a whole-plant perspective (all organs) within a phylogenetic framework has enabled us to gain a better understanding of plant adaptation to unique soils when studying taxa from distinct regions.

Strategies used to improve vaccine uptake among healthcare providers: A systematic review.

Background: Vaccination is one of the most effective available public health tools, preventing infectious diseases to safeguard public health and save millions of lives annually. However, in recent years vaccine hesitancy has increased among all populations, including healthcare workers. Healthcare providers are central to vaccination efforts due to their increased exposure to disease and vulnerable patients, and their role in patient confidence and decision-making. These decreasing uptake rates highlight a critical need to address specific barriers within this target group. This systematic review aims to explore the strategies used to improve vaccine uptake among healthcare providers. Methods: A literature search was conducted in PubMed, EMBASE, and MEDLINE databases, alongside a grey literature search, to identify studies describing interventions to improve vaccine uptake among healthcare providers. This was followed by de-duplication and double-blinded screening processes using Rayyan. Data extraction and thematic analysis focused on categorising interventions and identifying frequencies of use, to develop recommendations for further interventions tailored to target regions. Results: 60 studies were identified, predominantly concerning influenza vaccination. Interventions included educational initiatives, reminders, incentives, access solutions, feedback, and policy implementation. Key strategies included targeted educational lectures, posters, and pamphlets; mobile vaccination units; extended vaccination hours; and leadership engagement. The findings underscore the importance of a multifaceted approach combining educational efforts, enhanced accessibility, and motivational incentives to improve vaccination rates within the healthcare providers, especially where mandatory vaccination is controversial. Conclusions: This review evaluates tailored strategies to enhance vaccine confidence and uptake among healthcare providers, advocating for a holistic approach that includes educational initiatives, reminder systems, incentives, improved access, feedback mechanisms, and policy enactment to effectively address hesitancy and promote public health.

Airway decision making in major head and neck surgery: Irish multicenter, multidisciplinary recommendations.

Major head and neck surgery poses a threat to perioperative airway patency. Adverse airway events are associated with significant morbidity, potentially leading to hypoxic brain injury and even death. Following a review of the literature, recommendations regarding airway management in head and neck surgery were developed with multicenter, multidisciplinary agreement among all Irish head and neck units. Immediate extubation is appropriate in many cases where there is a low risk of adverse airway events. Where a prolonged definitive airway is required, elective tracheostomy provides increased airway security postoperatively while delayed extubation may be appropriate in select cases to reduce postoperative morbidity. Local institutional protocols should be developed to care for a tracheostomy once inserted. We provide guidance on decision making surrounding airway management at time of head and neck surgery. All decisions should be agreed between the operating, anesthetic, and critical care teams.

Nasal sprays and behavioural interventions compared with usual care for acute respiratory illness in primary care: a randomised, controlled, open-label, parallel-group trial.

BACKGROUND: A small amount of evidence suggests that nasal sprays, or physical activity and stress management, could shorten the duration of respiratory infections. This study aimed to assess the effect of nasal sprays or a behavioural intervention promoting physical activity and stress management on respiratory illnesses, compared with usual care. METHODS: This randomised, controlled, open-label, parallel-group trial was done at 332 general practitioner practices in the UK. Eligible adults (aged ≥18 years) had at least one comorbidity or risk factor increasing their risk of adverse outcomes due to respiratory illness (eg, immune compromise due to serious illness or medication; heart disease; asthma or lung disease; diabetes; mild hepatic impairment; stroke or severe neurological problem; obesity [BMI ≥30 kg/m2]; or age ≥65 years) or at least three self-reported respiratory tract infections in a normal year (ie, any year before the COVID-19 pandemic). Participants were randomly assigned (1:1:1:1) using a computerised system to: usual care (brief advice about managing illness); gel-based spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); saline spray (two sprays per nostril at the first sign of an infection or after potential exposure to infection, up to 6 times per day); or a brief behavioural intervention in which participants were given access to a website promoting physical activity and stress management. The study was partially masked: neither investigators nor medical staff were aware of treatment allocation, and investigators who did the statistical analysis were unaware of treatment allocation. The sprays were relabelled to maintain participant masking. Outcomes were assessed using data from participants' completed monthly surveys and a survey at 6 months. The primary outcome was total number of days of illness due to self-reported respiratory tract illnesses (coughs, colds, sore throat, sinus or ear infections, influenza, or COVID-19) in the previous 6 months, assessed in the modified intention-to-treat population, which included all randomly assigned participants who had primary outcome data available. Key secondary outcomes were possible harms, including headache or facial pain, and antibiotic use, assessed in all randomly assigned participants. This trial was registered with ISRCTN, 17936080, and is closed to recruitment. FINDINGS: Between Dec 12, 2020, and April 7, 2023, of 19 475 individuals screened for eligibility, 13 799 participants were randomly assigned to usual care (n=3451), gel-based nasal spray (n=3448), saline nasal spray (n=3450), or the digital intervention promoting physical activity and stress management (n=3450). 11 612 participants had complete data for the primary outcome and were included in the primary outcome analysis (usual care group, n=2983; gel-based spray group, n=2935; saline spray group, n=2967; behavioural website group, n=2727). Compared with participants in the usual care group, who had a mean of 8·2 (SD 16·1) days of illness, the number of days of illness was significantly lower in the gel-based spray group (mean 6·5 days [SD 12·8]; adjusted incidence rate ratio [IRR] 0·82 [99% CI 0·76-0·90]; p<0·0001) and the saline spray group (6·4 days [12·4]; 0·81 [0·74-0·88]; p<0·0001), but not in the group allocated to the behavioural website (7·4 days [14·7]; 0·97 [0·89-1·06]; p=0·46). The most common adverse event was headache or sinus pain in the gel-based group: 123 (4·8%) of 2556 participants in the usual care group; 199 (7·8%) of 2498 participants in the gel-based group (risk ratio 1·61 [95% CI 1·30-1·99]; p<0·0001); 101 (4·5%) of 2377 participants in the saline group (0·81 [0·63-1·05]; p=0·11); and 101 (4·5%) of 2091 participants in the behavioural intervention group (0·95 [0·74-1·22]; p=0·69). Compared with usual care, antibiotic use was lower for all interventions: IRR 0·65 (95% CI 0·50-0·84; p=0·001) for the gel-based spray group; 0·69 (0·45-0·88; p=0·003) for the saline spray group; and 0·74 (0·57-0·94; p=0·02) for the behavioural website group. INTERPRETATION: Advice to use either nasal spray reduced illness duration and both sprays and the behavioural website reduced antibiotic use. Future research should aim to address the impact of the widespread implementation of these simple interventions. FUNDING: National Institute for Health and Care Research.

Long-term patient-reported outcomes of open subpectoral biceps tenodesis with cortical button fixation.

BACKGROUND: Open subpectoral biceps tenodesis (OSBT) with cortical button fixation has been shown to deliver acceptable results in the short and intermediate term for long head of the biceps (LHB) pathology with the benefit of smaller bone tunnel diameter and a reduced risk of postoperative humeral shaft fracture. The primary purpose of this study was to determine whether OSBT with cortical button fixation results in significant improvements in patient reported outcomes (PROs) from pre-operative to long-term final follow-up. METHODS: A retrospective analysis of patients who underwent OSBT with cortical button fixation at a single institution between the years of 2012 and 2014 was conducted and PROs were collected in the intermediate (> 2 years follow-up) and long term (> 9 years follow-up). PROs were measured pre-operatively, at intermediate follow-up, and at long-term follow-up using three validated questionnaires: American Shoulder and Elbow Surgeons (ASES) score, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and Oxford Shoulder Score (OSS). Patients were additionally asked at final follow-up if they would undergo the same procedure again if they needed it. RESULTS: Twenty-nine (29) patients with a mean age of 51.16 ± 9.06 years at the time of surgery were included in the study at final follow-up. Mean final follow-up time was 10.2 ± 0.5 years (range: 9.2-11.1 years). All PROs (ASES, OSS, and DASH) demonstrated statistically significant improvements from pre-operative to final follow-up with p < 0.01 for each. The proportions of patients exceeding established values for minimum clinically important difference (MCID) were 96.55%, 93.10%, and 75.86% for ASES, OSS, and DASH respectively. Only one patient had required re-operation as of final follow-up. None experienced humeral fractures post-operatively. A significant majority (89.66%; p < 0.01) of patients reported that they would undergo the same procedure again if they needed it. Fifty-three (53) patients were included in the study at intermediate follow-up with a mean follow-up time of 3.5 ± 1.4 years (range: 2-5.3 years). There were no statistically significant differences in any of the PRO measures from intermediate to long-term follow-up. CONCLUSION: This study reported a minimum 9-year follow-up of patients undergoing OSBT with cortical button fixation for the management of LHBT pathology in the setting of concomitant shoulder procedures. All patients had significantly improved functional outcomes assessed with ASES, OSS, and DASH and no obvious differences in median group scores were found between patients assessed at intermediate (mean 3.5 years) and final (mean 10.2 years) follow-up. No infections, fractures, or fixation failures were reported.

Histopathologic Features of Mucosal Head and Neck Cancer Cachexia.

Objective: Determine the histopathologic features that correlate with head and neck cancer (HNC) cachexia. Methods: A single-institution, retrospective study was performed on adults with HPV-negative, mucosal squamous cell carcinoma of the aerodigestive tract undergoing resection and free flap reconstruction from 2014 to 2019. Patients with distant metastases were excluded. Demographics, comorbidities, preoperative nutrition, and surgical pathology reports were collected. Comparisons of histopathologic features and cachexia severity were made. Results: The study included 222 predominantly male (64.9%) patients aged 61.3 ± 11.8 years. Cachexia was identified in 57.2% patients, and 18.5% were severe (≥15% weight loss). No differences in demographics were identified between the groups. Compared to control, patients with severe cachexia had lower serum hemoglobin (p=0.048) and albumin (p < 0.001), larger tumor diameter (p < 0.001), greater depth of invasion (p < 0.001), and elevated proportions of pT4 disease (p < 0.001), pN2-N3 disease (p=0.001), lymphovascular invasion (p=0.009), and extranodal extension (p=0.014). Multivariate logistic regression identified tumor size (OR [95% CI] = 1.36 [1.08-1.73]), oral cavity tumor (OR [95% CI] = 0.30 [0.11-0.84]), and nodal burden (OR [95% CI] = 1.16 [0.98-1.38]) as significant histopathologic contributors of cancer cachexia. Conclusions: Larger, more invasive tumors with nodal metastases and aggressive histologic features are associated with greater cachexia severity in mucosal HNC.

Immune Hypersensitivity Is Associated With Higher Graft Failure Rate After Osteochondral Allograft Transplantation of the Knee.

Purpose: To analyze the effects of 1 or more patient-reported allergies on clinical outcomes, in particular graft failure rate, and patient-reported outcomes (PROs) following osteochondral allograft transplantation (OCA) of the knee. Methods: Retrospective review of patients who underwent knee OCA from August 2010 to May 2021 with a minimum of 2-year follow-up. Patients were initially divided into 2 cohorts: those with at least 1 allergy and those without any allergies. Clinical outcomes assessed included graft failure, reoperation rates, deep vein thrombosis/pulmonary embolism, and manipulation under anesthesia/lysis of adhesions (MUA/LOA). PROs assessed, including the visual analog scale (VAS) for pain and satisfaction, the Knee injury and Osteoarthritis Outcome Score (KOOS), and return to sport rates, were compared. Results: In total, 285 patients were included with a mean clinical follow-up of 4.8 ± 2.0 years. The allergy cohort had a significantly higher rate of graft failure (P = .008). In a regression analysis controlling for confounding variables, graft failure remained significantly associated with the presence of medication allergies (odds ratio [OR], 3.631; 95% CI, 1.139-11.577; P = .029). Furthermore, an increasing number of allergies were associated with an increased rate of graft failure (OR, 1.644; 95% CI, 1.074-2.515; P = .022). There was no difference in rate of reoperation, complications, infection, and MUA/LOA. Of the 100 patients who completed PROs, there was no difference in VAS satisfaction, pain, and any of the KOOS outcome scores or return to sport. Conclusions: The presence of 1 or more patient-reported allergies was shown to be significantly associated with OCA graft failure. Furthermore, an increasing number of patient-reported allergies were associated with a higher rate of graft failure. However, there were no significant differences in VAS satisfaction or pain, KOOS symptom, quality of life, pain, or return to sport in patients with at least 1 patient-reported allergy and those without allergies. Level of Evidence: Level III, retrospective cohort study.