An atlas of human vector-borne microbe interactions reveals pathogenicity mechanisms.

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.

Risk factors and health behaviors associated with loneliness among cancer survivors during the COVID-19 pandemic.

Loneliness may exacerbate poor health outcomes particularly among cancer survivors during the COVID-19 pandemic. Little is known about the risk factors of loneliness among cancer survivors. We evaluated the risk factors of loneliness in the context of COVID-19 pandemic-related prevention behaviors and lifestyle/psychosocial factors among cancer survivors. Cancer survivors (n = 1471) seen at Huntsman Cancer Institute completed a survey between August-September 2020 evaluating health behaviors, medical care, and psychosocial factors including loneliness during COVID-19 pandemic. Participants were classified into two groups: 'lonely' (sometimes, usually, or always felt lonely in past month) and 'non-lonely' (never or rarely felt lonely in past month). 33% of cancer survivors reported feeling lonely in the past month. Multivariable logistic regression showed female sex, not living with a spouse/partner, poor health status, COVID-19 pandemic-associated lifestyle factors including increased alcohol consumption and marijuana/CBD oil use, and psychosocial stressors such as disruptions in daily life, less social interaction, and higher perceived stress and financial stress were associated with feeling lonely as compared to being non-lonely (all p < 0.05). A significant proportion of participants reported loneliness, which is a serious health risk among vulnerable populations, particularly cancer survivors. Modifiable risk factors such as unhealthy lifestyle behaviors and psychosocial stress were associated with loneliness. These results highlight the need to screen for unhealthy lifestyle factors and psychosocial stressors to identify cancer survivors at increased risk of loneliness and to develop effective management strategies.

The association between adverse childhood experiences and treatment response for adults with alcohol and other drug use disorders.

BACKGROUND AND OBJECTIVES: Adverse events during childhood increase the risk for the development of substance use disorders (SUDs). This study examined the association between adverse childhood experiences (ACEs) and SUD treatment response. METHODS: This cohort analysis included data from longitudinal clinical assessments extracted from the records of 438 consenting individuals undergoing SUD treatment (63% male; 88.8% White). Mixed effects models evaluated the relationship between scores on the ACE questionnaire and indicators of treatment response (i.e., alcohol and drug abstinence self-efficacy; symptoms of depression, anxiety, and posttraumatic stress disorder) for individuals with alcohol-related (n = 332) and other drug-related (n = 275) diagnoses, with some participants included in both groups. RESULTS: Treatment response varied as a function of ACEs, with the magnitude of differences varying across time in treatment. Relative to those with no ACE history, those who experienced ≥2 ACEs reported worse depression, anxiety, PTSD symptoms, and alcohol/drug abstinence self-efficacy at baseline, with many differences remaining at the 30-day assessment. All differences abated by discharge, with the exception of PTSD symptoms among those in the drug use group with a history of ≥4 ACEs. Male gender and older age were generally associated with lower symptomology and higher abstinence self-efficacy. DISCUSSION AND CONCLUSIONS: Assessing ACE history early in SUD treatment may improve treatment planning and prognosis. Future studies should evaluate the role of trauma-informed programming and individual interventions to improve treatment response. SCIENTIFIC SIGNIFICANCE: This study demonstrates the association between adverse childhood experiences and symptom severity among patients across participation in SUD treatment.

Functional Characterization of Non-Ankyrin Repeat Domains of Orientia tsutsugamushi Ank Effectors Reveals Their Importance for Molecular Pathogenesis.

Orientia tsutsugamushi is a genetically intractable obligate intracellular bacterium, causes scrub typhus, and has one of the largest known armamentariums of ankyrin repeat-containing effectors (Anks). Most have a C-terminal F-box presumed to interact with the SCF ubiquitin ligase complex primarily based on their ability to bind overexpressed Skp1. Whether all F-box-containing Anks bind endogenous SCF components and the F-box residues essential for such interactions has gone unexplored. Many O. tsutsugamushi Ank F-boxes occur as part of a PRANC (pox protein repeats of ankyrin-C-terminal) domain. Roles of the non-F-box portion of the PRANC and intervening sequence region (ISR) that links the ankyrin repeat and F-box/PRANC domains are unknown. The functional relevance of these effectors' non-ankyrin repeat domains was investigated. The F-box was necessary for Flag-tagged versions of most F-box-containing Anks to precipitate endogenous Skp1, Cul1, and/or Rbx1, while the ISR and PRANC were dispensable. Ank toxicity in yeast was predominantly F-box dependent. Interrogations of Ank1, Ank5, and Ank6 established that L1, P2, E4, I9, and D17 of the F-box consensus are key for binding native SCF components and for Ank1 and Ank6 to inhibit NF-κB. The ISR is also essential for Ank1 and Ank6 to impair NF-κB. Ectopically expressed Ank1 and Ank6 lacking the ISR or having a mutagenized F-box incapable of binding SCF components performed as dominant-negative inhibitors to block O. tsutsugamushi NF-κB modulation. This study advances knowledge of O. tsutsugamushi Ank functional domains and offers an approach for validating their roles in infection.

Factors associated with changes in exercise behaviors during the COVID-19 pandemic.

PURPOSE: There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined changes in exercise behaviors since the pandemic and identified characteristics associated with these changes among cancer patients. METHODS: Cancer patients (n = 1,210) completed a survey from August to September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into three groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups. RESULTS: One-third of the patients reported a decreased amount of regular exercise, while 10% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired and have poor health status and psychosocial stressors such as disruptions in daily life while less likely to be former smokers (all p < 0.05). In contrast, patients who exercised more were younger, had stage IV diagnosis, and also reported disruptions in daily life (all p < 0.05). Patients who were living in rural areas were also more likely not to experience changes in exercise habits (all p < 0.05), although rural-urban status was not identified as a strong predictor. CONCLUSION: A significant proportion of cancer patients experienced changes in exercise habits, especially exercising less, during the first 6 months of the COVID-19 pandemic. Age, employment status, tumor stage, health status, smoking status, and psychosocial factors were associated with changes in exercise behaviors. Our results highlight the importance of promoting physical activity guidelines for cancer survivorship during the COVID-19 pandemic and may help improve the identification of cancer patients susceptible to exercising less.

Mutation based approaches to the treatment of anaplastic thyroid cancer.

OBJECTIVE: The treatment of anaplastic thyroid cancer (ATC) has continued to rapidly evolve over time. Increased utilization of novel, personalized therapies based upon the tumour's somatic mutation status has recently been integrated. The aim of this case series is to describe a series of patients that underwent rapid genomic testing upon their diagnosis of ATC, allowing for the early integration of novel therapies. DESIGN: A fast track pathway for genomic tumour analysis of patients with ATC was implemented at a single academic cancer hospital in January of 2020. PATIENTS: All patients were evaluated by head and neck surgery, endocrinology, and medical oncology upon diagnosis of ATC. MEASUREMENTS: Genetic work-up was completed, which prompted a recommendation for dual BRAF/MEK inhibition with dabrafenib and trametinib for tumours with BRAF V600E mutation. For patients whose tumours were BRAF V600E wild-type, pembrolizumab with lenvatinib was offered. RESULTS: A total of four patients were included in this series. Two patients (50%) had tumours that were BRAF V600E positive. Among patients that were BRAF V600E positive, both patients initiated urgent dabrafenib and trametinib dual tyrosine kinase inhibitor (TKI) therapy; with one patient demonstrating near-complete clinical response allowing for posttreatment surgery, while the other demonstrated decreased tumour burden. Among patients who were BRAF V600E wild-type, lenvatinib and pembrolizumab were recommended off-label; one patient demonstrated decreased tumour burden, but developed severe pure red cell aplasia, while the other patient is demonstrating an early clinical response. CONCLUSIONS: The integration of early genomic analysis and personalized neoadjuvant TKI therapy into the treatment of ATC can greatly benefit patient care outcomes and optimize tumour control.

Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

MOLECULAR PROFILE AND CLINICAL OUTCOMES IN DIFFERENTIATED THYROID CANCER PATIENTS PRESENTING WITH BONE METASTASIS.

Objective: Differentiated thyroid cancer patients uncommonly present with bone metastasis as the initial manifestation. Their molecular profile is largely unknown. The aim of this study was to evaluate the histopathology, molecular profiles, and response to radioactive iodine therapy in these patients. Methods: Eight patients presented with symptomatic bone metastasis from an unknown primary tumor. We identified these patients by performing a retrospective chart review. Pathology slides were reviewed and the molecular analysis of 112 thyroid cancer-related genes was performed on bone metastasis specimens using targeted next-generation sequencing. Results: These patients presented with long bone fractures, spinal cord compression, or intractable bone pain. Histopathologic analysis of the bone and thyroid tumor specimens revealed follicular variant of papillary carcinoma in 7 patients and tall cell variant papillary carcinoma in 1 patient. Primary tumor size ranged from 0.4 to 7.5 cm. All patients received high dose radioiodine therapy following thyroidectomy. Molecular analysis revealed telomerase reverse transcriptase (TERT) mutations in 7 (88%) tumors, 4 (50%) contained co-occurring TERT and RAS GTPase gene (RAS) mutations, 2 had isolated TERT mutations, and 1 had TERT and proto-oncogene B-Raf (BRAF) V600E mutations, respectively. Tumors carrying RAS, TERT, or a combination of these mutations were radioiodine-avid, with predictable tumor response and reduction in serum thyroglobulin levels. One patient with radioiodine-refractory disease harbored BRAF and TERT mutations. Conclusion: These results demonstrate that differentiated thyroid cancers presenting with bone metastasis independent of the primary tumor size have a high prevalence of TERT mutations, frequently coexisting with RAS mutations. This molecular signature may predict a favorable response to radioiodine therapy. Abbreviations: BRAF = proto-oncogene B-Raf; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; FV = follicular variant; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; RAS = Ras GTPase gene; TERT = telomerase reverse transcriptase; TG = thyroglobulin.

Modeling reproduction of whitetail deer and its applications.

Many environmental factors, such as annual precipitation, temperature variations, and the embedded stochasticity of natural systems, affect resource availability from one region to the next, such that animal survival and reproduction rates differ by region. For species exhibiting phenotypic plasticity, embedding phenotypes in a model of population dynamics becomes important, as region-driven plastic responses play a significant role when estimating parameters values. In this paper, we discuss how to include observable characteristics and climate patterns in estimates of reproduction rates of whitetail deer (Odocoileus virginianus). Using many studies already available in the literature, we establish a strong correlation between reproduction rate and both body weight and USDA plant hardiness zone. We demonstrate the accuracy of the estimated whitetail deer fecundity rates for various geographical regions in North America and show that Bergmann's rule is necessary to maintain similar biological fitness between various spatial distributions of deer populations. We demonstrate that the standard deviation of the weight distribution has almost no effect on reproduction rate estimates for adult deer populations. However, statistical analysis reveals sensitivity of fawn reproduction rates to environmental stochasticity. We incorporate the reproduction function in a stage- and gender-based model and prove the existence of a stable solution. Finally, we demonstrate a possible application of the model using harvested deer weights, without collecting reproduction data directly.

NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018.

The NCCN Guidelines for Thyroid Carcinoma provide recommendations for the management of different types of thyroid carcinoma, including papillary, follicular, Hürthle cell, medullary, and anaplastic carcinomas. These NCCN Guidelines Insights summarize the panel discussion behind recent updates to the guidelines, including the expanding role of molecular testing for differentiated thyroid carcinoma, implications of the new pathologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and the addition of a new targeted therapy option for BRAF V600E-mutated anaplastic thyroid carcinoma.

Orbital invasion routes of non-melanoma skin cancers and survival outcomes.

PURPOSE/OBJECTIVES: Overall non-melanoma head and neck skin cancer has a good prognosis; however, rarely patients have an aggressive variant which results in orbital invasion via perineural spread or direct extension. Despite these consequences, there are limited published studies defining this clinical entity. The main objectives of the current study are to describe orbital invasion patterns of non-melanoma head and neck skin cancers and their impact on survival. METHODS: Retrospective case series from a tertiary-care, academic institution performed between 2004 and 2014. Demographic and tumour characteristics are reported as well as patterns of orbital invasion, types of treatments received, and survival outcomes. RESULTS: There were 17 consecutive patients with non-melanoma skin cancer and orbital invasion who met inclusion criteria. Average age at orbital invasion diagnosis was 70.8 years old. 76% were male. Mean follow-up time was 28.5 months. Of these patients, 71% had squamous cell carcinoma and 29% had basal cell carcinoma. Brow (41%) was the most common primary sub-site followed by cheek (23%) and temple (12%). 76% of patients had a history of prior treatment. The lateral orbital wall (41%) was the most common site of invasion, followed by the medial orbital wall (29%) and antero-superior invasion (23%). Age, histology, and location of orbital invasion were associated with disease-specific and overall survival. CONCLUSION: Orbital invasion for non-melanoma head and neck skin cancers creates a treatment dilemma and the patterns of invasion are described. In addition, the location of orbital invasion is associated with survival outcomes.

Role of the nuclease of nontypeable Haemophilus influenzae in dispersal of organisms from biofilms.

Nontypeable Haemophilus influenzae (NTHI) forms biofilms in the middle ear during human infection. The biofilm matrix of NTHI contains extracellular DNA. We show that NTHI possesses a potent nuclease, which is a homolog of the thermonuclease of Staphylococcus aureus. Using a biofilm dispersal assay, studies showed a biofilm dispersal pattern in the parent strain, no evidence of dispersal in the nuclease mutant, and a partial return of dispersion in the complemented mutant. Quantitative PCR of mRNA from biofilms from a 24-h continuous flow system demonstrated a significantly increased expression of the nuclease from planktonic organisms compared to those in the biofilm phase of growth (P < 0.042). Microscopic analysis of biofilms grown in vitro showed that in the nuclease mutant the nucleic acid matrix was increased compared to the wild-type and complemented strains. Organisms were typically found in large aggregates, unlike the wild-type and complement biofilms in which the organisms were evenly dispersed throughout the biofilm. At 48 h, the majority of the organisms in the mutant biofilm were dead. The nuclease mutant formed a biofilm in the chinchilla model of otitis media and demonstrated a propensity to also form similar large aggregates of organisms. These studies indicate that NTHI nuclease is involved in biofilm remodeling and organism dispersal.

Anaplastic Thyroid Carcinoma, Version 2.2015.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Thyroid Carcinoma focuses on anaplastic carcinoma because substantial changes were made to the systemic therapy recommendations for the 2015 update. Dosages and frequency of administration are now provided, docetaxel/doxorubicin regimens were added, and single-agent cisplatin was deleted because it is not recommended for patients with advanced or metastatic anaplastic thyroid cancer.

Thyroid carcinoma, version 2.2014.

These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.

Uterine glycogen metabolism in mink during estrus, embryonic diapause and pregnancy.

We have determined uterine glycogen content, metabolizing enzyme expression and activity in the mink, a species that exhibits obligatory embryonic diapause, resulting in delayed implantation. Gross uterine glycogen concentrations were highest in estrus, decreased 50% by diapause and 90% in pregnancy (P ≤ 0.05). Endometrial glycogen deposits, which localized primarily to glandular and luminal epithelia, decreased 99% between estrus and diapause (P ≤ 0.05) and were nearly undetectable in pregnancy. Glycogen synthase and phosphorylase proteins were most abundant in the glandular epithelia. Glycogen phosphorylase activity (total) in uterine homogenates was higher during estrus and diapause, than pregnancy. While glycogen phosphorylase protein was detected during estrus and diapause, glycogen synthase was almost undetectable after estrus, which probably contributed to a higher glycogenolysis/glycogenesis ratio during diapause. Uterine glucose-6-phosphatase 3 gene expression was greater during diapause, when compared to estrus (P ≤ 0.05) and supports the hypothesis that glucose-6-phosphate resulting from phosphorylase activity was dephosphorylated in preparation for export into the uterine lumen. The relatively high amount of hexokinase-1 protein detected in the luminal epithelia during estrus and diapause may have contributed to glucose trapping after endometrial glycogen reserves were depleted. Collectively, our findings suggest to us that endometrial glycogen reserves may be an important source of energy, supporting uterine and conceptus metabolism up to the diapausing blastocyst stage. As a result, the size of uterine glycogen reserves accumulated prior to mating may in part, determine the number of embryos that survive to the blastocyst stage, and ultimately litter size.

Analysis of nontypeable haemophilus influenzae phase-variable genes during experimental human nasopharyngeal colonization.

BACKGROUND: Studies of nontypeable Haemophilus influenzae (NTHi) have demonstrated that a number of genes associated with infectivity have long repeat regions associated with phase variation in expression of the respective gene. The purpose of this study was to determine the genes that underwent phase variation during a 6-day period of experimental human nasopharyngeal colonization. METHODS: Strain NTHi 2019Str(R)1 was used to colonize the nasopharynx of human subjects in a study of experimental colonization. Thirteen phase-variable genes were analyzed in NTHi 2019Str(R)1. Samples of NTHi 2019Str(R)1 were cultured from subjects during the 6-day colonization period. We used capillary electrophoresis and Roche 454 pyrosequencing to determine the number of repeats in each gene from each sample. RESULTS: A significant number of samples switched licA and igaB from phase off in the inoculated strain to phase on during the 4-day period of observation. lex2A also showed variability as compared to baseline, but the differences were not significant. The remaining genes showed no evidence of phase variation. CONCLUSIONS: Our studies suggest that the phase-on genotypes of licA and igaB are important for early human nasopharynx colonization. lex2A showed a trend from phase off to phase on, suggesting a potentially important role in the colonization process.

The Role of Temperature, Wind Speed, and Precipitation on the Abundance of Culex Species and West Nile Virus Infection Rate in Rural West-Central Illinois.

While most research on West Nile virus (WNV) and its main vector, the Culex mosquito, has been conducted in laboratory or urban settings, studies with field-caught mosquitoes in rural areas, such as west-central Illinois, are lacking. The objective of this research was to investigate key abiotic factors using macroclimate data, including temperature, precipitation, and wind speed, to determine their influence on field-caught mosquito abundance in 4 rural counties in Illinois from 2014 to 2016. Additionally, the relationship between minimum infection rate (MIR) and thermal time was examined. Using gravid traps at 15 sites, Culex mosquitoes were collected twice a week. A total of 5,255 adult female Culex mosquitoes (Cx. pipiens, Cx. quinquefasciatus, and Cx. restuans) were collected in 2014; 9,138 in 2015; and 5,702 in 2016. Regression models were developed based on outcomes of relationships between field-caught mosquitoes and abiotic factors. Precipitation and thermal time had the most significant relationship with mosquito abundance (r2 = 0.993 and r2 = 0.993, respectively), while wind speed was less (r2 = 0.714). The greatest number of Culex and the highest annual MIR were observed in 2015, which was also the driest of the 3 sampling seasons. Mosquito abundance was observed to increase with warmer degree days and MIR was found to increase with abundance in mosquitoes. These models can be used for other mosquito surveillance and monitoring studies in various climate types and environments.

Four-Dimensional Computed Tomography for Parathyroid Adenoma Localization: A Pre-Operative Imaging Protocol.

OBJECTIVE: Primary hyperparathyroidism (PHPT) affects approximately 0.86% of the population, with surgical resection as the treatment of choice. A 4D computed tomography (CT) is a highly effective tool in localizing parathyroid adenomas; however, there is currently no defined role for 4D CT when stratified against ultrasonography (USG) and nuclear medicine Technetium Sestamibi SPECT/CT (SES) imaging. STUDY DESIGN: Retrospective Study. SETTING: University Hospital. METHODS: All patients who underwent parathyroidectomy for PHPT between 2014 and 2019 at a single institution were reviewed. Patients who had a 4D CT were included. We compared outcomes of 4D CT as a second line imaging modality to those of USG and SES as first line modalities. An imaging algorithm was proposed based on these findings. RESULTS: There were 84 patients identified who had a 4D CT after unsuccessful first line imaging. A 4D CT localized parathyroid adenoma to the correct quadrant in 64% of cases, and to the correct laterality in 75% of cases. Obese patients had significantly lower rates of adenoma localization with USG (33.4%), compared to non-obese patients (67.5%; P = .006). In determining multigland disease the sensitivity of 4D CT was 86%, while the specificity was 87%. CONCLUSIONS: A 4D CT has impressive rates of accurate localization of parathyroid adenomas; however due to the radiation exposure involved, it should remain a second line imaging modality. PHPT patients should first be evaluated with USG, with 4D CT used if this is unsuccessful and patients are greater than 40 years old, have a high BMI, or are having revision surgery.

Pain Predicts Dropout From Substance Use Treatment.

OBJECTIVE: This project aimed to characterize the relationship between physical pain experienced at time of entry to residential treatment for substance use disorders (SUDs) and the frequency of treatment dropout. We hypothesized that both endorsement of recent pain and higher magnitude of endorsed pain intensity would be associated with higher dropout rates. We further hypothesized that these effects would be exacerbated among patients with opioid use disorder (OUD). METHOD: Participants included 1,095 individuals in residential treatment for SUD. Data were collected within 24 hours of treatment entry. Analyses were conducted using logistic regression with dropout as the dependent variable. Dropout was operationally defined as leaving treatment against medical advice or being discharged from treatment because of use of substances. Pain (including endorsement and intensity) was the primary independent variable in all analyses. Analyses included demographic and affective covariates and included both main effects of OUD and interaction terms between OUD and pain. RESULTS: Pain endorsement was associated with greater frequency of dropout (odds ratio [OR] = 1.49, p = .04). Higher levels of pain intensity predicted increased rates of dropout (OR = 1.13, p < .01). In contrast with our hypothesis, no interactions between OUD and pain were observed. CONCLUSIONS: These results underscore the import of integrating pain monitoring and pain interventions as core components of treatment for SUD. Our findings are highly consistent with a growing literature recognizing the impact of pain across a constellation of important treatment outcomes and provide novel data strongly suggesting that pain predicts early cessation of treatment.

Early ambulation after fibular free flap surgery is associated with reduced length of stay, increased mobility independence, and discharge to home.

BACKGROUND: Fibula free flaps (FFF) are one of the most common bony flaps utilized. This paper describes a quality improvement project aimed at increasing early ambulation. METHODS: A review of FFF patients at an academic hospital was completed (2014-2023). In 2018, an institutional change to encourage early ambulation without placement of a boot was made. Changes in hospital disposition and physical therapy outcomes were evaluated. RESULTS: A total of 168 patients underwent FFF reconstruction. There was a statistically significant lower length of stay in Group 2 (early ambulation, no boot) (8.1 vs. 9.4; p = 0.04). A higher rate of discharge to a skilled nursing facility was noted in Group 1 (delayed ambulation with boot) (21.3% vs. 11.9%; p = 0.009). A higher proportion of patients in Group 2 demonstrated independence during bed mobility, transfers, and gait (p < 0.05). CONCLUSIONS: Early ambulation without boot placement after FFF is associated with decreased length of hospital stay, improved disposition to home and physical therapy outcomes.