Adaptive adjustment of significance thresholds produces large gains in microbial gene annotations and metabolic insights.

Gene function annotations enable microbial ecologists to make inferences about metabolic potential from genomes and metagenomes. However, even tools that use the same database and general approach can differ markedly in the annotations they recover. We compare three popular methods for identifying KEGG Orthologs, applying them to genomes drawn from a range of bacterial families that occupy different host-associated and free-living biomes. Our results show that by adaptively tuning sequence similarity thresholds, sensitivity can be substantially improved while maintaining accuracy. We observe the largest improvements when few reference sequences exist for a given protein family, and when annotating genomes from non-model organisms (such as gut-dwelling Lachnospiraceae). Our results suggest that straightforward heuristic adjustments can broadly improve microbial metabolic predictions.

Association of Area Deprivation Index with Adherence to Proposed Regimen in Patients with Sarcoidosis in Detroit, Michigan.

BACKGROUND AND AIM: Social predictors affect severity of sarcoidosis, with Black patients, older individuals, those with lower income, and those without insurance having greater severity. This study aimed to explore potential disparities affecting access to care in sarcoidosis patients with a primary focus on metrics such as area deprivation index (ADI) and its association with adherence to the proposed regimen. METHODS: A retrospective chart review study of all patients seen in pulmonary clinics at a large urban tertiary care center over 2 years with sarcoidosis patients identified with International Classification of Diseases diagnosis code D86. Data collected included age, race, sex, ADI, insurance, online patient portal usage, chest x-rays, pulmonary function tests, missed visits, hospitalizations, positive biopsy, communication and visits around bronchoscopy. Categorical variables were described using frequency and percentage. Numerical variables were described using median, mean and standard deviation. Statistical analysis included chi-square test, two-sample T-test and Wilcoxon rank sum test. Multivariate logistic regression analysis was performed to model independent association with 12 month no-show occurrence as a metric of adherence to the proposed regimen. RESULTS: Among sarcoidosis patients (N = 788), univariate models showed the presence of active online patient portal use among younger patients (58.6 years with portal vs. 65.1 years without portal, p < 0.001), those with lower ADI (73 with portal vs. 92 without portal, p < 0.001) and with commercial insurance (48.5% with portal vs. 20.7% without portal, p < 0.001); more x-rays (45.6% with x-rays vs. 36.6% without x-rays, p = 0.018) and hospitalizations (50.3% with hospitalizations vs. 36.2% without hospitalizations, p < 0.001) in Medicare patients. Sarcoidosis patients with positive biopsies on file from 2013-2023 were more likely to be male (44.19% with positive biopsy vs. 33.91% without positive biopsy, p = 0.006), White (36.29% with positive biopsy vs. 22.9% without positive biopsy, p < 0.001) or other races (3.23% with positive biopsy vs. 2.25% without positive biopsy, p < 0.001), younger (55.8 years with positive biopsy vs. 61.7 years without positive biopsy, p < 0.001) and belonged to lower national ADI ranks (73 with positive biopsy vs. 80 without biopsy, p = 0.041). A multivariate analysis was done with those variables found to be significant in the univariate analyses, which revealed that higher ADI national was associated with failure to adhere to the proposed regimen. CONCLUSIONS: We identified intricate patterns of sociodemographic variables affecting access to care in sarcoidosis patients, especially higher ADI national associated with failure to adhere to the proposed regimen, raising concerns for potential healthcare barriers. Understanding these barriers is vital for equitable high-quality care, assisting in timely and efficient management of the patient's disease.

Framework for exploring the sensory repertoire of the human gut microbiota.

Bacteria sense changes in their environment and transduce signals to adjust their cellular functions accordingly. For this purpose, bacteria employ various sensors feeding into multiple signal transduction pathways. Signal recognition by bacterial sensors is studied mainly in a few model organisms, but advances in genome sequencing and analysis offer new ways of exploring the sensory repertoire of many understudied organisms. The human gut is a natural target of this line of study: it is a nutrient-rich and dynamic environment and is home to thousands of bacterial species whose activities impact human health. Many gut commensals are also poorly studied compared to model organisms and are mainly known through their genome sequences. To begin exploring the signals human gut commensals sense and respond to, we have designed a framework that enables the identification of sensory domains, prediction of signals that they recognize, and experimental verification of these predictions. We validate this framework's functionality by systematically identifying amino acid sensors in selected bacterial genomes and metagenomes, characterizing their amino acid binding properties, and demonstrating their signal transduction potential.IMPORTANCESignal transduction is a central process governing how bacteria sense and respond to their environment. The human gut is a complex environment with many living organisms and fluctuating streams of nutrients. One gut inhabitant, Escherichia coli, is a model organism for studying signal transduction. However, E. coli is not representative of most gut microbes, and signaling pathways in the thousands of other organisms comprising the human gut microbiota remain poorly understood. This work provides a foundation for how to explore signals recognized by these organisms.

Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

INTRODUCTION: Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. METHODS: A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. RESULTS: Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. CONCLUSION: The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Metastatic cutaneous squamous cell carcinoma accounts for nearly all squamous cell carcinomas of the parotid gland.

Primary squamous cell carcinoma of the parotid gland (pSCCP) has long been recognized as a separate entity and is included in the WHO classifications of salivary gland tumors. However, it is widely accepted among head and neck pathologists that pSCCP is exceptionally rare. Yet, there are many publications describing series of pSCCP and data from SEER and other cancer register databases indicate erroneously an increasing incidence of pSCCP. Importantly, pSCCP and metastatic (secondary) squamous cell carcinoma to the parotid gland (mSCCP) have nearly identical histological features, and the diagnosis of pSCCP should only be made after the exclusion of mSCCP. Moreover, all of the histological diagnostic criteria proposed to be in favor of pSCCP (such as, for example, dysplasia of ductal epithelium) can be encountered in unequivocal mSCCP, thereby representing secondary growth along preexistent ducts. Squamous cell differentiation has also been reported in rare genetically defined primary parotid carcinomas, either as unequivocal histological squamous features (e.g., NUT carcinoma, mucoepidermoid carcinoma), by immunohistochemistry (e.g., in NUT carcinoma, adamantinoma-like Ewing sarcoma, basal-type salivary duct carcinoma, mucoepidermoid carcinoma), or a combination of both. Another major issue in this context is that the International Classification of Diseases (ICD) coding system does not distinguish between primary or metastatic disease, resulting in a large number of patients with mSCCP being misclassified as pSCCP. Immunohistochemistry and new molecular biomarkers have significantly improved the accuracy of the diagnosis of many salivary gland neoplasms, but until recently there were no biomarkers that can accurately distinguish between mSCCP and pSCCP. However, recent genomic profiling studies have unequivocally demonstrated that almost all SCCP analyzed to date have an ultraviolet light (UV)-induced mutational signature typical of mSCCP of skin origin. Thus, mutational signature analysis can be a very useful tool in determining the cutaneous origin of these tumors. Additional molecular studies may shed new light on this old diagnostic and clinical problem. This review presents a critical view of head and neck experts on this topic.

Extranodal extension in head and neck squamous cell carcinoma: need for accurate pretherapeutic staging to select optimum treatment and minimize toxicity.

PURPOSE OF REVIEW: In 2017, the American Joint Committee on Cancer (AJCC) introduced the inclusion of extracapsular nodal extension (ENE) into the N staging of nonviral head and neck squamous cell carcinoma (HNSCC), while retaining the traditional N classification based on the number and sizes of metastatic nodes. The extent of ENE was further defined as microscopic ENE (ENEmi) and major ENE (ENEma) based on extent of disease beyond the nodal capsule (≤ or > 2 mm). This article reviews the evidence and progress made since these changes were introduced. RECENT FINDINGS: The 'gold standard' for evaluation ENE is histopathologic examination, the current preferred primary treatment of patients with HNSCC is by radiation-based therapy ±â€Šchemotherapy or biotherapy. The current pretreatment staging is by imaging, which needs improved reliability of radiologic rENE assessment with reporting needs to consider both sensitivity and specificity (currently computed tomography images have high-specificity but low-sensitivity). Adjuvant chemotherapy is indicated for patients with ENEma to enhance disease control, whereas for patients with ENEmi, there is a need to assess the benefit of adjuvant chemotherapy. Evidence that the presence of pENE in HPV-positive oropharyngeal carcinoma is an independent prognostic factor and should be considered for inclusion in future AJCC editions has recently emerged. SUMMARY: There remains a paucity of data on the reliability of imaging in the staging of rENE, more so the for the accurate assessment of ENEmi. Optimistic early results from use of artificial intelligence/deep learning demonstrate progress and may pave the way for better capabilities in tumor staging, treatment outcome prediction, resulting in improved survival outcomes.

Outcomes in patients with sarcoidosis and COVID-19.

BACKGROUND AND AIM: The effect of COVID-19 in patients with sarcoidosis has not been fully explored. The aim was to conduct a retrospective cohort study investigating outcomes in patients with sarcoidosis who were hospitalized with COVID-19. METHODS: We included patients who had diagnoses of sarcoidosis and COVID-19 between January 1, 2020, and February 28, 2021. Primary outcomes included development of critical COVID-19; need for supplemental oxygen, noninvasive ventilation, and invasive ventilation; and death. Association of comorbidities and immunosuppression therapy with outcomes were analyzed. Multiple logistic regression analysis was used to assess risk factors associated with critical COVID-19. RESULTS: Of 1198 patients with COVID-19, 169 had sarcoidosis (14.1%) and 1029 (85.9%) did not (control group). Of the 169 patients with sarcoidosis and COVID-19, 84 (49.7%) were hospitalized (study group: mean age 62.4 years; 61.9% women; and 56.0% Black). The study group required supplemental oxygen (81% vs 62%; p = 0.001) and noninvasive ventilation (33.3% vs 6.4%; p < 0.001) more often and had lower mortality (15.5% vs. 30.4%; p = 0.004) than the control group. In patients hospitalized with COVID-19, sarcoidosis was not associated with critical COVID-19 (odds ratio, 0.77; 95% CI, 0.46-1.29; p = 0.317), but having sarcoidosis while taking immunosuppression therapy was associated with decreased risk of critical COVID-19 (odds ratio, 0.45; 95% CI, 0.31-0.65; p < 0.001). CONCLUSIONS: Patients with sarcoidosis may not be at increased risk of critical illness or death from COVID-19, and immunosuppression therapy in these patients may reduce the risk of critical COVID-19.

CD36/Lyn kinase interactions within macrophages promotes pulmonary fibrosis in response to oxidized phospholipid.

Recent data from human studies and animal models have established roles for type II alveolar epithelial cell (AEC2) injury/apoptosis and monocyte/macrophage accumulation and activation in progressive lung fibrosis. Although the link between these processes is not well defined, we have previously shown that CD36-mediated uptake of apoptotic AEC2s by lung macrophages is sufficient to drive fibrosis. Importantly, apoptotic AEC2s are rich in oxidized phospholipids (oxPL), and amongst its multiple functions, CD36 serves as a scavenger receptor for oxPL. Recent studies have established a role for oxPLs in alveolar scarring, and we hypothesized that uptake and accrual of oxPL by CD36 would cause a macrophage phenotypic change that promotes fibrosis. To test this hypothesis, we treated wild-type and CD36-null mice with the oxPL derivative oxidized phosphocholine (POVPC) and found that CD36-null mice were protected from oxPL-induced scarring. Compared to WT mice, fewer macrophages accumulated in the lungs of CD36-null animals, and the macrophages exhibited a decreased accumulation of intracellular oxidized lipid. Importantly, the attenuated accrual of oxPL in CD36-null macrophages was associated with diminished expression of the profibrotic mediator, TGFß. Finally, the pathway linking oxPL uptake and TGFß expression was found to require CD36-mediated activation of Lyn kinase. Together, these observations elucidate a causal pathway that connects AEC2 injury with lung macrophage activation via CD36-mediated uptake of oxPL and suggest several potential therapeutic targets.

Treatment of recurrent acute tonsillitis-a systematic review and clinical practice recommendations.

Background: There is an ongoing debate on the indications for tonsil surgery in both children and adults with recurrent acute tonsillitis. The aim is to provide practical recommendations for diagnostics and treatment for recurrent acute tonsillitis including evidence-based decision making for tonsillectomy. Methods: A systematic literature search in PubMed, Embase, Web of Science, and ScienceDirect from 2014 until April 2023 resulted in 68 articles. These were the basis for the review and a comprehensive series of consensus statements on the most important diagnostics and indications for both non-surgical and surgical therapy. A consensus paper was circulated among the authors and members of the International Head and Neck Scientific Group until a final agreement was reached for all recommendations. Results: The differentiation between sore throat and tonsillitis patient episodes is mostly not feasible and hence is not relevant for diagnostic decision making. Diagnostics of a tonsillitis/sore throat episode should always include a classification with a scoring system (Centor, McIssac, FeverPAIN score) to estimate the probability of a bacterial tonsillitis, mainly due to group A streptococcus (GAS). In ambiguous cases, a point-of-care test GAS swab test is helpful. Consecutive counting of the tonsillitis/sore throat episodes is important. In addition, a specific quality of life score (Tonsillectomy Outcome Inventory 14 or Tonsil and Adenoid Health Status Instrument) should be used for each episode. Conservative treatment includes a combination of paracetamol and/or non-steroidal anti-inflammatory drugs. In case of high probability of bacterial tonsillitis, and only in such cases, especially in patients at risk, standard antibiotic treatment is initiated directly or by delayed prescription. Tonsillectomy is indicated and is highly effective if the patient has had ≥7 adequately treated episodes in the preceding year, ≥5 such episodes in each of the preceding 2 years, or ≥3 such episodes in each of the preceding 3 years. An essential part of surgery is standardized pain management because severe postoperative pain can be expected in most patients. Conclusion: It is necessary to follow a stringent treatment algorithm for an optimal and evidence-based treatment for patients with recurrent acute tonsillitis. This will help decrease worldwide treatment variability, antibiotic overuse, and avoid ineffective tonsillectomy.

Mental Health Impacts of Climate Change Among Vulnerable Populations Globally: An Integrative Review.

Background: Climate change has been shown to be directly linked to multiple physiological sequelae and to impact health consequences. However, the impact of climate change on mental health globally, particularly among vulnerable populations, is less well understood. Objective: To explore the mental health impacts of climate change in vulnerable populations globally. Methods: We performed an integrative literature review to identify published articles that addressed the research question: What are the mental health impacts of climate change among vulnerable populations globally? The Vulnerable Populations Conceptual Model served as a theoretical model during the review process and data synthesis. Findings/Results: One hundred and four articles were selected for inclusion in this review after a comprehensive review of 1828 manuscripts. Articles were diverse in scope and populations addressed. Land-vulnerable persons (either due to occupation or geographic location), Indigenous persons, children, older adults, and climate migrants were among the vulnerable populations whose mental health was most impacted by climate change. The most prevalent mental health responses to climate change included solastalgia, suicidality, depression, anxiety/eco-anxiety, PTSD, substance use, insomnia, and behavioral disturbance. Conclusions: Mental health professionals including physicians, nurses, physician assistants and other healthcare providers have the opportunity to mitigate the mental health impacts of climate change among vulnerable populations through assessment, preventative education and care. An inclusive and trauma-informed response to climate-related disasters, use of validated measures of mental health, and a long-term therapeutic relationship that extends beyond the immediate consequences of climate change-related events are approaches to successful mental health care in a climate-changing world.

Lymph Node Metastases from Non-Melanoma Skin Cancer of the Head and Neck.

Non-melanoma skin cancer (NMSC) represents the most common malignancy in the world, comprising exceedingly common lesions such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) and rare lesions such as Merkel cell carcinoma. Risk factors are widely recognized and include ultraviolet (UV) light exposure, radiation exposure, immunosuppression, and many others. As a whole, survival and functional outcomes are favorable, but each histopathological subtype of NMSC behaves differently. Treatment regimens for the primary site usually include wide surgical excision and neck dissection in cases of clinically involved metastatic lymph nodes. The elective management of draining nodal basins, however, is a contested topic. Nearly all subtypes, excluding BCC, have a significant risk of lymphatic metastases, and have been studied with regard to sentinel lymph node biopsy (SLNB) and elective neck dissection. To date, no studies have definitively established a true single standard of care, as exists for melanoma, for any of the NMSCs. As a result, the authors have sought to summarize the current literature and identify indications and management options for the management of the cervical lymphatics for each major subtype of NMSC. Further research remains critically necessary in order to develop complete treatment algorithms.

Measuring disparities in virtual healthcare and outcomes in chronic obstructive pulmonary disease patients during the COVID-19 pandemic.

INTRODUCTION: The use of virtual healthcare increased with the COVID-19 pandemic, even among chronic obstructive pulmonary disease (COPD) patients. We measured disparities in virtual compared to traditional healthcare and outcomes in COPD patients during the pandemic. METHODS: This study retrospectively identified adult patients with virtual or in-person primary care encounters at a large, Midwestern hospital system between March 1, 2020, and June 30, 2020. Data regarding age, sex, race, smoking, area deprivation index (ADI), COPD diagnosis, visit type (office, telephone, video, E-visit, virtual, or hybrid of office and virtual), and time to hospital admission in the following 12 months were collected. Analysis was performed using chi-square, analysis of variance, Kruskal-Wallis rank sum, and Cox proportional modeling. RESULTS: This study identified 86,715 patients. Of those, 4702 had COPD and were more likely to be 65 years or older, White, have higher ADI, use telephone or hybrid visits compared to the rest of the study population and majority had smoking history. Office, telephone, and hybrid visits were used frequently, consistently seen across sex, race, ADI, and smoking categories. Increasing age was associated with increased use of office and telephone visits, and decreased use of video visits. Higher ADI was associated with telephone visits, and lower ADI was associated with video visits. There were no significant differences in overall, COPD, or COVID-19 hospital admission rates across visit types. DISCUSSION: Complex disparities in utilizing traditional healthcare are also reflected in virtual healthcare in COPD patients, and do not significantly affect hospital admissions.

Novel Imaging-Based Biomarkers for Identifying Carotid Plaque Vulnerability.

Carotid artery disease has traditionally been assessed based on the degree of luminal narrowing. However, this approach, which solely relies on carotid stenosis, is currently being questioned with regard to modern risk stratification approaches. Recent guidelines have introduced the concept of the "vulnerable plaque," emphasizing specific features such as thin fibrous caps, large lipid cores, intraplaque hemorrhage, plaque rupture, macrophage infiltration, and neovascularization. In this context, imaging-based biomarkers have emerged as valuable tools for identifying higher-risk patients. Non-invasive imaging modalities and intravascular techniques, including ultrasound, computed tomography, magnetic resonance imaging, intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have played pivotal roles in characterizing and detecting unstable carotid plaques. The aim of this review is to provide an overview of the evolving understanding of carotid artery disease and highlight the significance of imaging techniques in assessing plaque vulnerability and informing clinical decision-making.

Artificial Intelligence in Head and Neck Cancer: A Systematic Review of Systematic Reviews.

INTRODUCTION: Several studies have emphasized the potential of artificial intelligence (AI) and its subfields, such as machine learning (ML), as emerging and feasible approaches to optimize patient care in oncology. As a result, clinicians and decision-makers are faced with a plethora of reviews regarding the state of the art of applications of AI for head and neck cancer (HNC) management. This article provides an analysis of systematic reviews on the current status, and of the limitations of the application of AI/ML as adjunctive decision-making tools in HNC management. METHODS: Electronic databases (PubMed, Medline via Ovid, Scopus, and Web of Science) were searched from inception until November 30, 2022. The study selection, searching and screening processes, inclusion, and exclusion criteria followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A risk of bias assessment was conducted using a tailored and modified version of the Assessment of Systematic Review (AMSTAR-2) tool and quality assessment using the Risk of Bias in Systematic Reviews (ROBIS) guidelines. RESULTS: Of the 137 search hits retrieved, 17 fulfilled the inclusion criteria. This analysis of systematic reviews revealed that the application of AI/ML as a decision aid in HNC management can be thematized as follows: (1) detection of precancerous and cancerous lesions within histopathologic slides; (2) prediction of the histopathologic nature of a given lesion from various sources of medical imaging; (3) prognostication; (4) extraction of pathological findings from imaging; and (5) different applications in radiation oncology. In addition, the challenges in implementation of AI/ML models for clinical evaluations include the lack of standardized methodological guidelines for the collection of clinical images, development of these models, reporting of their performance, external validation procedures, and regulatory frameworks. CONCLUSION: At present, there is a paucity of evidence to suggest the adoption of these models in clinical practice due to the aforementioned limitations. Therefore, this manuscript highlights the need for development of standardized guidelines to facilitate the adoption and implementation of these models in the daily clinical practice. In addition, adequately powered, prospective, randomized controlled trials are urgently needed to further assess the potential of AI/ML models in real-world clinical settings for the management of HNC.

Four-part harmony between diet, drugs, microbes, and host.

In this issue of Cell Host & Microbe, Zeng et al. show that a specific gut microbe causes diet-dependent attenuation of acetaminophen toxicity in mice. This link between gut microbes and toxicity is mechanistically detailed, yet intriguingly indirect, mediated by the transformation of ingested phytochemicals as opposed to the drug itself.

Auto-segmentation of the tibia and femur from knee MR images via deep learning and its application to cartilage strain and recovery.

The ability to efficiently and reproducibly generate subject-specific 3D models of bone and soft tissue is important to many areas of musculoskeletal research. However, methodologies requiring such models have largely been limited by lengthy manual segmentation times. Recently, machine learning, and more specifically, convolutional neural networks, have shown potential to alleviate this bottleneck in research throughput. Thus, the purpose of this work was to develop a modified version of the convolutional neural network architecture U-Net to automate segmentation of the tibia and femur from double echo steady state knee magnetic resonance (MR) images. Our model was trained on a dataset of over 4,000 MR images from 34 subjects, segmented by three experienced researchers, and reviewed by a musculoskeletal radiologist. For our validation and testing sets, we achieved dice coefficients of 0.985 and 0.984, respectively. As further testing, we applied our trained model to a prior study of tibial cartilage strain and recovery. In this analysis, across all subjects, there were no statistically significant differences in cartilage strain between the machine learning and ground truth bone models, with a mean difference of 0.2 ± 0.7 % (mean ± 95 % confidence interval). This difference is within the measurement resolution of previous cartilage strain studies from our lab using manual segmentation. In summary, we successfully trained, validated, and tested a machine learning model capable of segmenting MR images of the knee, achieving results that are comparable to trained human segmenters.

Peristomal recurrence following primary total laryngectomy: the enigma of the central compartment neck lymph nodes.

PURPOSE OF REVIEW: The practice of primary total laryngectomy (TL) for advanced laryngo-hypopharyngeal cancer has significantly declined in the developed countries. The treatment options most frequently adopted have changed from open surgery to transoral laser or robotic approaches or nonsurgical (bio-chemo-) radiotherapy. Primary TL remains the treatment of choice in the developing world where healthcare resources are limited, especially for the treatment of cancer. RECENT FINDINGS: Peristomal recurrence (PSR) is quite a serious complication, with an incidence of 6.6% from the published literature (mainly concerning the developed world), most diagnosed within 2 years, and associated with >80% mortality. The major risk factors include pretreatment tracheostomy, specific primary tumor subsites, positive surgical margins, and presence of nodal metastasis. The treatment options are limited and most success has been observed with surgery, especially when PSR is diagnosed at an early-stage, which is uncommon. Treatment of advanced-stage disease is usually palliative. Reduction and/or prevention of the known risk factors for PSR remain the goal when performing TL. In particular, central compartment (para- and pretracheal) lymph nodes dissection in case of large tumors with extra-laryngeal and/or subglottic extension or pretreatment tracheotomy plays a paramount role in PSR prevention. SUMMARY: Research is required to conclude the formulation of guidelines for proper dissection of the central compartment (level VI) lymph nodes as indicated either prophylactically or therapeutically during TL for preventing PSR.

Elevated In Vivo ACL Strain Is Associated With a Straight Knee in Both the Sagittal and the Coronal Planes.

BACKGROUND: Noncontact anterior cruciate ligament (ACL) injuries typically occur during deceleration movements such as landing or cutting. However, conflicting data have left the kinematic mechanisms leading to these injuries unclear. Quantifying the influence of sagittal and coronal plane knee kinematics on in vivo ACL strain may help to elucidate noncontact ACL injury mechanisms. PURPOSE/HYPOTHESIS: The purpose of this study was to measure in vivo sagittal and coronal plane knee kinematics and ACL strain during a single-leg jump. We hypothesized that ACL strain would be modulated primarily by motion in the sagittal plane and that limited coronal plane motion would be measured during this activity. STUDY DESIGN: Descriptive laboratory study. METHODS: Seventeen healthy participants (8 male/9 female) underwent magnetic resonance imaging (MRI) followed by high-speed biplanar radiography, obtained as participants performed a single-leg jump. Three-dimensional models of the femur, tibia, and associated ACL attachment site footprints were created from the MRIs and registered to the radiographs to reproduce the position of the knee during the jump. ACL strain, knee flexion/extension angles, and varus/valgus angles were measured throughout the jump. Spearman rank correlations were used to assess relationships between mean ACL strain and kinematic variables. RESULTS: Mean ACL strain increased with decreasing knee flexion angle (ρ = -0.3; P = .002), and local maxima in ACL strain occurred with the knee in a straight position in both the sagittal and the coronal planes. In addition, limited coronal plane motion (varus/valgus angle) was measured during this activity (mean ± SD, -0.5°± 0.3°). Furthermore, we did not detect a statistically significant relationship between ACL strain and varus/valgus angle (ρ = -0.01; P = .9). CONCLUSION: ACL strain was maximized when the knee was in a straight position in both the sagittal and coronal planes. Participants remained in <1° of varus/valgus position on average throughout the jump. As a ligament under elevated strain is more vulnerable to injury, landing on a straight knee may be an important risk factor for ACL rupture. CLINICAL RELEVANCE: These data may improve understanding of risk factors for noncontact ACL injury, which may be useful in designing ACL injury prevention programs.

Efficacy of Larynx Preservation Surgery and Multimodal Adjuvant Therapy for Hypopharyngeal Cancer: A Case Series Study.

Background: Larynx preservation surgery (LPS) combined with multimodal adjuvant therapy (MAT) is re-emerging as treatment option for hypopharyngeal cancer (HPC). This study aims to explore the survival and functional outcome of this combined approach. Methods: This is a retrospective cohort study. Selected patients with primary HPC treated by LPS and MAT at two large Beijing medical centers between 2005 and 2019 were included. In addition to LPS, patients received one or more of the following treatments: preoperative induction chemotherapy, postoperative intensity-modulated radiotherapy, chemotherapy, or targeted therapy. Results: In total, 64 patients were included (62 were men, and median age was 57.5 years). The disease in most patients was in stage III (28.1%) or IV (56.3%), or in stage T2 (34.4%) or T3 (45.3%), based on the TNM scale. Across all patients, the rate of overall survival (OS) was 60.7% at 3 yr and 47.3% at 5 yr. OS was significantly higher for patients with stage I or II disease than for those with stage III or IV disease (HR 8.64, 95% CI 3.69-20.2, log-rank P = .010). Decannulation was successful in 55 patients (85.9%), and swallowing function was satisfactory (stage 0-III, on Functional Outcome Swallowing Scale) for 50 (78.1%). Median Voice Handicap Index-10 score on voice performance was 19 (range 4-40), and median Functional Assessment of Cancer Therapy-General Questionnaire score for QoL was 75 (range 16-105). Conclusions: LPS and MAT can provide satisfactory oncologic control and good functional outcomes for selected patients with HPC, especially those with stage I or II disease.

Feasibility and outcomes of a real-world regional lung cancer prehabilitation programme in the UK.

BACKGROUND: Prehabilitation, or multimodality patient optimisation before major treatment, has demonstrated meaningful improvements in patients' outcomes. In the setting of lung cancer surgery, postoperative complications and length of hospital stay are reduced, but there is currently limited access to prehabilitation. Prehab4Cancer (P4C) is an innovative regional programme serving all areas of Greater Manchester (GM). METHODS: The lung cancer P4C service commenced in 2019 as a collaboration between the GM Cancer alliance and 12 leisure and community organisations. Patients planning surgical resection could be referred to receive exercise, nutrition, and well-being assessment and interventions before surgery. We evaluated the programme's feasibility, uptake, and outcomes during the 11 months before COVID-19 restrictions. RESULTS: In total, 377 patients were referred to the lung cancer P4C service from all 11 hospitals in GM. Of the patients reached by telephone, 80.0% (n=280/348) attended initial P4C assessment, which occurred a median of 8 days (inter-quartile range [IQR]: 4-14) after referral. In addition, 74.3% (n=280/377) attended for baseline assessment and 47.7% (n=180/377) completed prehabilitation, attending a median of six sessions (IQR: 4-9). Statistically significant improvements in all objective physiological and subjective functional assessments were observed preoperatively, including a mean increase in the incremental shuttle walk test of 50 m (95% confidence interval: 25-74; P<0.001). CONCLUSIONS: The P4C programme demonstrated feasibility at scale, high uptake, and promising impact on the status of patients with lung cancer before surgery. P4C is the first regional prehabilitation service internationally, and this evaluation provides a framework for implementing similar services in other regions.