Developing the Active Communities Tool to Implement the Community Guide's Built Environment Recommendation for Increasing Physical Activity.

Physical activity is higher in communities that include supportive features for walking and bicycling. In 2016, the Community Preventive Services Task Force released a systematic review of built environment approaches to increase physical activity. The results of the review recommended approaches that combine interventions to improve pedestrian and bicycle transportation systems with land use and environmental design strategies. Because the recommendation was multifaceted, the Centers for Disease Control and Prevention determined that communities could benefit from an assessment tool to address the breadth of the Task Force recommendations. The purpose of this article is to describe the systematic approach used to develop the Active Communities Tool. First, we created and refined a logic model and community theory of change for tool development. Second, we reviewed existing community-based tools and abstracted key elements (item domains, advantages, disadvantages, updates, costs, permissions to use, and psychometrics) from 42 tools. The review indicated that no tool encompassed the breadth of the Community Guide recommendations for communities. Third, we developed a new tool and pilot tested its use with 9 diverse teams with public health and planning expertise. Final revisions followed from pilot team and expert input. The Active Communities Tool comprises 6 modules addressing all 8 interventions recommended by the Task Force. The tool is designed to help cross-sector teams create an action plan for improving community built environments that promote physical activity and may help to monitor progress toward achieving community conditions known to promote physical activity.

Pathways to Program Success: A Qualitative Comparative Analysis (QCA) of Communities Putting Prevention to Work Case Study Programs.

OBJECTIVE: To examine the elements of capacity, a measure of organizational resources supporting program implementation that result in successful completion of public health program objectives in a public health initiative serving 50 communities. DESIGN: We used crisp set Qualitative Comparative Analysis (QCA) to analyze case study and quantitative data collected during the evaluation of the Communities Putting Prevention to Work (CPPW) program. SETTING: CPPW awardee program staff and partners implemented evidence-based public health improvements in counties, cities, and organizations (eg, worksites, schools). PARTICIPANTS: Data came from case studies of 22 CPPW awardee programs that implemented evidence-based, community- and organizational-level public health improvements. INTERVENTION: Program staff implemented a range of evidence-based public health improvements related to tobacco control and obesity prevention. MAIN OUTCOME MEASURE: The outcome measure was completion of approximately 60% of work plan objectives. RESULTS: Analysis of the capacity conditions revealed 2 combinations for completing most work plan objectives: (1) having experience implementing public health improvements in combination with having a history of collaboration with partners; and (2) not having experience implementing public health improvements in combination with having leadership support. CONCLUSION: Awardees have varying levels of capacity. The combinations identified in this analysis provide important insights into how awardees with different combinations of elements of capacity achieved most of their work plan objectives. Even when awardees lack some elements of capacity, they can build it through strategies such as hiring staff and engaging new partners with expertise. In some instances, lacking 1 or more elements of capacity did not prevent an awardee from successfully completing objectives. These findings can help funders and practitioners recognize and assemble different aspects of capacity to achieve more successful programs; awardees can draw on extant organizational strengths to compensate when other aspects of capacity are absent.

Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1.

Cortical development requires the precise timing of neural precursor cell (NPC) terminal mitosis. Although cell cycle proteins regulate terminal mitosis, the factors that influence the cell cycle machinery are incompletely understood. Here we show in mice that myeloid cell leukemia 1 (Mcl1), an anti-apoptotic Bcl-2 protein required for the survival of NPCs, also regulates their terminal differentiation through the cell cycle regulator p27(Kip1). A BrdU-Ki67 cell profiling assay revealed that in utero electroporation of Mcl1 into NPCs in the embryonic neocortex increased NPC cell cycle exit (the leaving fraction). This was further supported by a decrease in proliferating NPCs (Pax6(+) radial glial cells and Tbr2(+) neural progenitors) and an increase in differentiating cells (Dcx(+) neuroblasts and Tbr1(+) neurons). Similarly, BrdU birth dating demonstrated that Mcl1 promotes premature NPC terminal mitosis giving rise to neurons of the deeper cortical layers, confirming their earlier birthdate. Changes in Mcl1 expression within NPCs caused concomitant changes in the levels of p27(Kip1) protein, a key regulator of NPC differentiation. Furthermore, in the absence of p27(Kip1), Mcl1 failed to induce NPC cell cycle exit, demonstrating that p27(Kip1) is required for Mcl1-mediated NPC terminal mitosis. In summary, we have identified a novel physiological role for anti-apoptotic Mcl1 in regulating NPC terminal differentiation.

National implementation of advanced training in the safety planning intervention in the Department of Veterans Affairs health care system.

The Safety Planning Intervention (SPI) is an evidence-based therapeutic intervention designed to mitigate suicide risk by providing a suicidal individual with a written, personalized safety plan. The Department of Veterans Affairs (VA) has implemented safety planning, but research found variability in the quality of safety plans. To improve quality, the VA developed an Advanced Training in the Safety Planning Intervention (ASPI) that went beyond previous didactic training efforts by emphasizing experiential learning. The aim of this article is to describe the procedures and initial results of VA's competency-based ASPI Training Program. Before training, providers participating in this program uploaded a written, deidentified safety plan completed with a Veteran. Providers then completed four training components, including evaluation of fidelity of written safety plans and competency in SPI during live, standardized roleplays at the conclusion of training, and at a 3-month follow-up evaluation. Of the 409 providers who initiated training, 367 (90%) completed training, 26 (6%) dropped out of training, and 16 (4%) did not meet the competency requirements for training completion. Relative to pretraining, there was a medium to large increase in the effect size of the quality of written Safety Plans at the end of training that was maintained at the 3-month follow-up. Using a standardized, observational measure of SPI competency, 383 of 391 (98%) providers met competency criteria following the training, and 367 of 375 (98%) providers met competency at 3-month follow-up. Findings suggest that ASPI training is effective in helping providers achieve and maintain fidelity in safety planning. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predicting outcomes in head and neck surgery with modified frailty index and surgical apgar scores.

OBJECTIVE: To compare the efficacy of the Modified Frailty Index and Modified Surgical Apgar scores in predicting postoperative outcomes in head and neck cancer patients. METHODS: We retrospectively reviewed patients who underwent major head and neck surgery between 2012 and 2015. Modified Surgical Apgar, and Frailty Index, scores were calculated on 723 patients. The primary outcome was 30-day complication and/or mortality. RESULTS: The mean Modified Frailty Index was 0.11 ± 0.12, and mean Modified Surgical Apgar score was 6.15 ± 1.67. Both scores were significantly associated with 30-day complication (P<0.05). The Modified Surgical Apgar score was superior to the Modified Frailty Index in predicting complications (Area Under the Curve (AUC) = 0.76; 95 % Confidence Interval (CI), 0.722-0.793; and AUC=0.59; 95 % CI, 0.548-0.633, respectively). Concurrent use of both scoring systems (AUC=0.77) was not superior to individual use. An increase in the mFI from 0.27 to 0.36 was associated with an increase in the risk of complication postoperatively (Odds Ratio (OR) = 3.67; 95 % CI, 1.30-10.34, P=.014). A reduction in the mSAS from 7 to 6 increased the risk of complication following surgery (OR=2.64; 95 % CI, 1.45-4.80; P=.002). CONCLUSION: Both scores are useful in risk stratifying head and neck cancer patients. The Modified Surgical Apgar score was superior at predicting complications; concurrent use of both scores added minimal benefit.

Using a concept map as a tool for strategic planning: The Healthy Brain Initiative.

Concept mapping is a tool to assist in strategic planning that allows planners to work through a sequence of phases to produce a conceptual framework. Although several studies describe how concept mapping is applied to various public health problems, the flexibility of the methods used in each phase of the process is often overlooked. If practitioners were more aware of the flexibility, more public health endeavors could benefit from using concept mapping as a tool for strategic planning. The objective of this article is to describe how the 6 concept-mapping phases originally outlined by William Trochim guided our strategic planning process and how we adjusted the specific methods in the first 2 phases to meet the specialized needs and requirements to create The Healthy Brain Initiative: A National Public Health Road Map to Maintaining Cognitive Health. In the first stage (phases 1 and 2 of concept mapping), we formed a steering committee, convened 4 work groups over a period of 3 months, and generated an initial set of 42 action items grounded in science. In the second stage (phases 3 and 4), we engaged stakeholders in sorting and rating the action items and constructed a series of concept maps. In the third and final stage (phases 5 and 6), we examined and refined the action items and generated a final concept map consisting of 44 action items. We then selected the top 10 action items, and in 2007, we published The Healthy Brain Initiative: A National Public Health Road Map to Maintaining Cognitive Health, which represents the strategic plan for The Healthy Brain Initiative.

An Evaluation of the Effectiveness of Evidence-Based Psychotherapies for Depression to Reduce Suicidal Ideation among Male and Female Veterans.

BACKGROUND: Although most suicide-related deaths occur among male veterans, women veterans are dying by suicide in increasing numbers. Identifying and increasing access to effective treatments is imperative for Department of Veterans Affairs suicide prevention efforts. We examined the impact of evidence-based psychotherapies for depression on suicidal ideation and the role of gender and treatment type in patients' responses to treatment. METHODS: Clinicians receiving case consultation in interpersonal psychotherapy, cognitive-behavioral therapy for depression, and acceptance and commitment therapy for depression submitted data on depressive symptoms and suicidal ideation while treating veterans with depression. RESULTS: Suicidal ideation was reduced across time in all three treatments. A main effect for wave was associated with statistically significant decreases in severity of suicidal ideation, χ2 (2) = 224.01, p = .0001, and a subsequent test of the Gender × Wave interaction was associated with differentially larger decreases in ideation among women veterans, χ2 (2) = 9.26, p = .001. Within gender-stratified subsamples, a statistically significant Treatment × Time interaction was found for male veterans, χ2 (4) = 16.82, p = .002, with levels of ideation significantly decreased at waves 2 and 3 in interpersonal psychotherapy and cognitive-behavioral therapy for depression relative to acceptance and commitment therapy for depression; the Treatment × Wave interaction within the female subsample was not statistically significant, χ2 (4) = 3.41, p = .492. CONCLUSIONS: This analysis demonstrates the efficacy of each of the three tested evidence-based psychotherapies for depression as a means of decreasing suicidal ideation, especially in women veterans. For male veterans, decreases in suicidal ideation were significantly greater in interpersonal psychotherapy and cognitive-behavioral therapy for depression relative to acceptance and commitment therapy for depression.

Adaptation of POCT for pharmacies to reduce risk and optimize access to care in HIV, the APPROACH study protocol: examining acceptability and feasibility.

BACKGROUND: Approximately 1 in 5 Canadians with HIV are unaware of their status. In many provinces and especially rural communities, barriers to HIV testing include lack of access, privacy concerns, and stigma. The availability of HIV point-of-care testing (POCT) is limited across Canada. Pharmacists are well positioned to address barriers by offering rapid HIV POCT and facilitating linkage to care. METHODS: We will use a type-2 hybrid implementation-effectiveness design to assess a pilot HIV POCT model in one urban and one rural pharmacy in each of two Canadian provinces over 6 months. In this feasibility trial the research aims include developing and assisting pharmacies in implementing the model, evaluating processes/determinants of program implementation, evaluating the model's effects on client outcomes, preferences, and testing satisfaction. Using a community-based research approach, the research team will engage community stakeholders in each province including individuals with lived experience to inform the development of the pharmacy-based HIV testing model and support the research team throughout the study. A multipronged promotion campaign will be used to promote the study and facilitate recruitment. The pharmacy-based testing model will include pre/post-test counseling and linkage to care plans in addition to pharmacist-administered HIV POCT. Pharmacists will complete a comprehensive training program prior to implementing the testing model. Client demographics and satisfaction will be assessed by surveys and interviews. Pharmacists will document time required for testing and participate in a post-study focus group to discuss barriers/enablers. Implementation will be assessed qualitatively and quantitatively. The process of developing and implementing the model will be described using qualitative data and a logic model. Acceptability and barriers/enablers will be examined qualitatively based on survey responses. A preliminary costing assessment will consider the client, pharmacy, and government perspectives. DISCUSSION: The results of this pilot will inform modifications to the HIV POCT model to optimize effectiveness and increase scalability. The study has national importance, providing valuable information on improving access to HIV testing. Future applications of this research may expand the role of pharmacists in offering POCT for other sexually transmitted/bloodborne infections as tests become available in Canada. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03210701.

Utility of the Surgical Apgar Score in Head and Neck Squamous Cell Carcinoma.

Objectives To recognize the utility of the surgical Apgar score (SAS) in a noncutaneous head and neck squamous cell carcinoma (HNSCC) population. Study Design Retrospective case series with chart review. Setting Academic tertiary medical center. Subjects and Methods Patients (n = 563) undergoing noncutaneous HNSCC resection between April 2012 and March 2015 were included. Demographics, medical history, intraoperative data, and postoperative hospital summaries were collected. SASs were calculated following the published schema. The primary outcome was 30-day postoperative morbidity. A 2-sample t test, analysis of variance, and χ2 (or Fisher exact) test were used for statistical comparisons. A multivariable logistic regression analysis was conducted to identify independent predictors of 30-day morbidity. Results Mean SAS was 6.2 ± 1.5. SAS groups did not differ in age, sex, or race. Sixty-five patients (11.6%) had a SAS between 0 and 4, with 40 incidences of morbidity (61.5%), while 31 (5.5%) patients with SAS from 9 to 10 had 3 morbidity occurrences (9.7%). Results show that 30-day postoperative morbidity is inversely related to increasing SAS ( P < .0001). Furthermore, lower SAS was associated with significantly increased operative time (SAS 0-4: 9.3 ± 2.6 hours vs SAS 9-10: 3.0 ± 1.1 hours) and lengths of stay (SAS 0-4: 10.0 ± 7.3 days vs SAS 9-10: 1.6 ± 1.0 days), P < .0001. SAS remained highly significant after adjusting for potential confounding variables in the multivariable analysis ( P < .0001). Conclusions An increasing SAS is associated with significantly lower rates of 30-day postoperative morbidities in a noncutaneous HNSCC patient population.

Utility of the Modified Surgical Apgar Score in a Head and Neck Cancer Population.

Objective The Surgical Apgar Score (SAS) is a validated postoperative complication prediction model. The purpose of this study was to investigate the utility of the SAS in a diverse head and neck cancer population and to compare it with a recently developed modified SAS (mSAS) that accounts for intraoperative transfusion. Study Design Case series with chart review. Setting Academic tertiary care medical center. Subjects and Methods This study comprised 713 patients undergoing surgery for head and neck cancer from April 2012 to March 2015. SAS values were calculated according to intraoperative data obtained from anesthesia records. The mSAS was computed by assigning an estimated blood loss score of zero for patients receiving intraoperative transfusions. Primary outcome was 30-day postoperative morbidity. Results Mean SAS and mSAS were 6.3 ± 1.5 and 6.2 ± 1.7, respectively. SAS and mSAS were significantly associated with 30-day postoperative morbidity, length of stay, operative time, American Society of Anesthesiologists status, race, and body mass index ( P < .05); however, no significant association was detected for age, sex, and smoking status. Multivariable analysis identified SAS and mSAS as independent predictors of postoperative morbidity, with the mSAS ( P = .03) being a more robust predictor than the SAS ( P = .15). Strong inverse relationships were demonstrated for the SAS and mSAS with length of stay and operative time ( P < .0001). Conclusion The SAS serves as a useful metric for risk stratification of patients with head and neck cancer. With the inclusion of intraoperative transfusion, the mSAS demonstrates superior utility in predicting those at risk for postoperative complications.

Parotid gland metastasis in Merkel cell carcinoma of the head and neck: A series of 14 cases.

Merkel cell carcinoma (MCC) is a rare cutaneous cancer of neuroendocrine cell origin that occurs frequently on the head and neck. With a high incidence of local recurrence and regional and distant metastasis, it carries a poor prognosis. We performed a retrospective study to determine the prognostic implications of parotid gland metastasis in MCC of the head and neck. Our study population was made up of 14 patients-13 men and 1 woman, aged 62 to 87 years (mean: 75.9)-who underwent a parotidectomy for the diagnosis of MCC over a period of 10 years and 9 months. Ten patients had a primary skin lesion of the head and neck and 4 presented with a parotid mass and an unknown primary. In all, 13 of the 14 patients were found to have parotid involvement-either a direct extension of MCC into the gland or a positive intraparotid lymph node; some patients had both. All patients underwent tumor excision, and 10 underwent neck dissection. Eleven patients received adjuvant radiotherapy; none received adjuvant chemotherapy. Of the 10 patients who underwent a neck dissection, 6 were found to have a cervical lymph node metastasis on pathologic examination. Follow-up ranged from 1.3 to 39.2 months (mean: 12.4). Three patients were lost to follow-up shortly after surgery, although some information was available on 2 of them. At the final follow-up, mortality data were available on 12 patients; of these, 11 had died. The lone survivor was the patient without a parotid metastasis. Among those known to have died, survival ranged from 1.6 to 49.2 months (mean: 16.0). We conclude that parotid metastasis in patients with MCC of the head and neck is associated with a dismal survival rate that is even worse than the poor survival associated with cervical node involvement.

Early surgical intervention in type I laryngeal cleft.

OBJECTIVE: Diagnosis and treatment of type 1 laryngeal clefts remains a challenge. The purpose of this study is to determine if early surgical intervention in type I laryngeal clefts improves outcomes. METHODS: A retrospective case series was conducted at an academic tertiary care children's hospital. 18 children undergoing early (≤3 months from diagnosis) surgical intervention for type I laryngeal cleft repair between August of 2012 and December 2014. Data was compiled through a manual chart review. RESULTS: 18 children who underwent early surgical intervention for type I laryngeal cleft repair were identified for review. 14 (78%) were male and 4 (22%) were female and the average age at time of repair was 1.6 years. Most frequent presenting symptoms included dysphagia (61%) and recurrent respiratory issues (22%). Successful swallowing outcomes, defined as subjective improvement (i.e. absence of previous symptoms) per parental report in follow-up visits, +/- normal post-operative MBS (modified barium swallow) findings, was seen in 11 patients (61%). 9 patients required hospitalization for respiratory issues prior to surgical repair. Post-operatively, 4 patients still incurred an admission for respiratory reasons. CONCLUSIONS: Our series shows a success rate of 61% with early surgical intervention (≤3 months from diagnosis). A decrease in post-operative hospitalizations is appreciated.

Time-dependent pretreatment with bevacuzimab increases tumor specific uptake of cetuximab in preclinical oral cavity cancer studies.

Inadequate delivery of therapeutics into tumors has been suggested as a reason for poor response. We hypothesize that bevacizumab, an antibody to vascular endothelial growth factor (VEGF), can improve cetuximab uptake in squamous cell carcinoma tumors. Athymic nude mice were implanted with OSC19 and SCC1 human cancer lines in a subcutaneous flank model. Mice were imaged daily for 14 days after intravenous tail vein injections of the following groups: IgG-IRDye800 (Control), cetuximab-IRDye800 (CTX800 Only), bevacizumab-IRDye800 (BVZ800 Only), cetuximab-IRDye800 + bevacuzimuab-IRDye800 (Simultaneous), and unlabeled bevacizumab followed by cetuximab-IRDye800 3 days later (Neoadjuvant). Within single-agent groups, the CTX800 Only tumor-specific uptake (TSU) was significantly higher than BVZ800 Only at Day 13 (TSU 8.6 vs 2.8, P < 0.001). The Simultaneous treatment with BVZ800 and CTX800 demonstrated no increase in antibody delivery. However, administration of unlabeled bevacizumab 3 days prior to CTX800 (Neoadjuvant group) resulted in significantly higher tumor specific delivery than administration of both antibodies at the same time (11.8 vs Simultaneous 5.0, P < 0.001). This difference can be attributed to a slower decline in tumor fluorescence intensity (-6.8% vs. Simultaneous -11.5% per day, respectively). Structural changes in pericyte coverage and functional vessel changes demonstrating decreased proliferation and tumor growth corroborate these fluorescence results. Although simultaneous administration of bevacizumab with cetuximab failed to increase antibody delivery to the tumor, pretreatment with bevacizumab improved TSU reflecting an increase in tumor-specific uptake of cetuximab as a result of vessel normalization.

Head and neck cutaneous squamous cell carcinoma requiring parotidectomy: prognostic indicators and treatment selection.

OBJECTIVE: Evaluate characteristics and risk factors for patients with advanced cutaneous squamous cell carcinoma (cSCC). STUDY DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS AND METHODS: Chart review of patients with cSCC undergoing a parotidectomy (2003-2012). RESULTS: Of 218 patients identified, 49% presented with a new primary lesion (n = 107) and 51% with a recurrence (n = 111). Parotid lymph nodes were positive in 52% of patients; 81% had a concurrent neck dissection, and 28% had cervical lymph node metastases. In 18% of patients, both parotid and cervical nodes were positive, while 44% were both parotid and cervical node negative; 33% had positive parotid and negative cervical nodes, and only 5% had negative parotid and positive cervical nodes. The overall 2- and 5-year survival rates were 0.71 and 0.58. Overall 5-year survival was lower for patients presenting with recurrent (0.49) versus new primary disease (0.69; P = .04). In addition, decreased overall 5-year survival rates were associated with cervical lymph node involvement (0.47 vs. 0.62; P = .01). There was no difference in overall survival when stratified by parotid lymph node involvement (P = .85), margin status (P = .67), perineural invasion (P = .42), facial nerve sacrifice (P = .92), or type of parotid operation performed (P = .51). CONCLUSIONS: In this study, cervical, but not parotid, lymph node involvement was associated with poor outcomes in patients with advanced cSCC requiring a parotidectomy. In patients without evidence of cervical or parotid lymph node involvement, a neck dissection may be spared, given there is a 5% chance of occult disease.

Pathology quiz case: Plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that possesses a heterogenous clinical and immunophenotypic presentation. The current case report describes an interesting and unique presentation of BPDCN as a primary paranasal sinus tumor without evidence of cutaneous or systemic involvement. As such, the report further contributes to the ongoing debate regarding the true putative origin of the neoplasm, as well as highlights the optimal diagnostic modalities, paramount importance of early diagnosis, and vast heterogeneity exhibited by this fascinating malignancy. The atypical presentation described here indicates the manifestations of BPDCN are more heterogenous than previously documented and thus can not be definitively ruled out in the absence of bone marrow, peripheral blood, or cutaneous involvement. Furthermore, atypical neoplastic presentations mandate flow cytometry and adjunctive immunohistochemistry for the definitive diagnosis of BPDCN, and early diagnosis of such neoplasms are critical for rapid initiation of treatment and improved outcomes.

Predictors of clinical outcome after tracheotomy in critically ill obese patients.

OBJECTIVES/HYPOTHESIS: To identify patient factors associated with outcomes in critically ill obese patients requiring tracheotomy. STUDY DESIGN: Single-institution, retrospective cohort study. METHODS: Charts were reviewed for inpatients admitted to an intensive care unit from 2007 to 2010 with International Classification of Diseases, 9th Revision codes of obesity or morbid obesity and tracheotomy. Variables collected in the dataset include subject age, ethnicity, gender, body mass index, tracheotomy type, patient outcome, chief diagnosis, and medical comorbid conditions. The primary outcomes of interest were tracheotomy type and patient outcome at the time of hospital discharge. Logistic regression models were developed for the probability of each patient outcome using univariate and multivariate models. RESULTS: One hundred two patients met inclusion criteria. The most common outcome was tracheostomy dependence (49%). Increased mortality was independently significantly associated with pulmonary hypertension (P = .019) and African American ethnicity (P = .045). Increased tracheostomy dependence was significantly associated with obstructive sleep apnea (P = .030). Increased decannulation was significantly associated with percutaneous tracheotomy (P = .016) and Caucasian ethnicity (P < .001). CONCLUSIONS: Obese patients in the intensive care unit who undergo tracheotomy have a high likelihood of remaining tracheostomy dependent at the time of discharge from the hospital. The factors most commonly found to be significantly associated with poor outcomes were open tracheotomy, African American ethnicity, obstructive sleep apnea, and pulmonary hypertension.

Hardware removal after osseous free flap reconstruction.

OBJECTIVE: Identifying risk factors for hardware removal in patients undergoing mandibular reconstruction with vascularized osseous free flaps remains a challenge. The purpose of this study is to identify potential risk factors, including osteocutaneous radial forearm versus fibular flap, for need for removal and to describe the fate of implanted hardware. STUDY DESIGN: Case series with chart review Setting Academic tertiary care medical center. SUBJECTS AND METHODS: Two hundred thirteen patients undergoing 227 vascularized osseous mandibular reconstructions between the years 2004 and 2012. Data were compiled through a manual chart review, and patients incurring hardware removals were identified. RESULTS: Thirty-four of 213 evaluable vascularized osseous free flaps (16%) underwent surgical removal of hardware. The average length of time to removal was 16.2 months (median 10 months), with the majority of removals occurring within the first year. Osteocutaneous radial forearm free flaps (OCRFFF) incurred a slightly higher percentage of hardware removals (9.9%) compared to fibula flaps (6.1%). Partial removal was performed in 8 of 34 cases, and approximately 38% of these required additional surgery for removal. CONCLUSION: Hardware removal was associated with continued tobacco use after mandibular reconstruction (P = .03). Removal of the supporting hardware most commonly occurs from infection or exposure in the first year. In the majority of cases the bone is well healed and the problem resolves with removal.

Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma.

PURPOSE: Though various targets have been proposed and evaluated, no agent has yet been investigated in a clinical setting for head and neck cancer. The present study aimed to compare two fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibodies for detection of head and neck squamous cell carcinoma (HNSCC). PROCEDURES: Antigen specificities and in vitro imaging of the fluorescently labeled anti-EGFR antibodies were performed. Next, immunodeficient mice (n = 22) bearing HNSCC (OSC-19 and SCC-1) tongue tumors received systemic injections of cetuximab-IRDye800CW, panitumumab-IRDye800CW, or IgG-IRDye800CW (a nonspecific control). Tumors were imaged and resected using two near-infrared imaging systems, SPY and Pearl. Fluorescent lymph nodes were also identified, and all resected tissues were sent for pathology. RESULTS: Panitumumab-IRDye800CW and cetuximab-IRDye800CW had specific and high affinity binding for EGFR (K D = 0.12 and 0.31 nM, respectively). Panitumumab-IRDye800CW demonstrated a 2-fold increase in fluorescence intensity compared to cetuximab-IRDye800CW in vitro. In vivo, both fluorescently labeled antibodies produced higher tumor-to-background ratios compared to IgG-IRDye800CW. However, there was no significant difference between the two in either cell line or imaging modality (OSC-19: p = 0.08 SPY, p = 0.48 Pearl; SCC-1: p = 0.77 SPY, p = 0.59 Pearl; paired t tests). CONCLUSIONS: There was no significant difference between the two fluorescently labeled anti-EGFR monoclonal antibodies in murine models of HNSCC. Both cetuximab and panitumumab can be considered suitable targeting agents for fluorescent intraoperative detection of HNSCC.

Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma.

Intraoperative, real-time fluorescence imaging may significantly improve tumor visualization and resection and postoperatively, in pathological assessment. To this end, we sought to determine the optimal FDA approved therapeutic monoclonal antibody for optical imaging of human cutaneous squamous cell carcinoma (cSCC). A near-infrared (NIR) fluorescent probe (IRDye800) was covalently linked to bevacizumab, panitumumab or tocilizumab and injected systemically into immunodeficient mice bearing either cutaneous tumor cell lines (SCC13) or cutaneous human tumor explants. Tumors were then imaged and resected under fluorescent guidance with the SPY, an FDA-approved intraoperative imaging system, and the Pearl Impulse small animal imaging system. All fluorescently labeled antibodies delineated normal tissue from tumor in SCC13 xenografts based on tumor-to-background (TBR) ratios. The conjugated antibodies produced TBRs of 1.2-2 using SPY and 1.6-3.6 using Pearl; in comparison, isotype control antibody IgG-IRDye produced TBRs of 1.0 (SPY) and 0.98 (Pearl). Comparison between antibodies revealed them to be roughly equivalent for imaging purposes with both the SPY and Pearl (p = 0.89 SPY, p = 0.99 Pearl; one way ANOVA). Human tumor explants were also imaged and tumor detection was highest with panitumumab-IRDye800 when using the SPY (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC.

Use of panitumumab-IRDye800 to image cutaneous head and neck cancer in mice.

OBJECTIVE: To assess the feasibility of panitumumab in real-time fluorescent imaging and histologic processing of cutaneous squamous cell carcinoma (cSCC) in mice. DESIGN: A near-infrared (NIR) fluorescent probe (IRDye800CW) was covalently linked to a monoclonal antibody-targeting epidermal growth factor receptor (panitumumab) or nonspecific IgG and injected into mice bearing flank xenografts from a cSCC cell line (SCC-13 or SRB-12; n = 7), human split-thickness skin grafts (STSGs; n = 3), or a human tumor explant (n = 1). The tumor and lymph nodes were imaged and dissected using fluorescence guidance with the SPY imaging system and verified with a charge-coupled NIR system. An NIR scanning device (Odyssey) was used to measure fluorescence intensity in histological sections. SUBJECTS: Immunodeficient mice. SETTING: In vivo and in vitro imaging lab. RESULTS: Tumor tissue could be delineated from the human STSG with tumor-to-background ratios of 4.5 (Pearl) and 3.4 (SPY). Tumor detection was substantially improved with panitumumab-IRDye800 compared with IgG-IRDye800. Biopsies positive for fluorescence were assessed by histology and immunohistochemistry (n = 18/18) to confirm the presence of tumor, yielding a 100% sensitivity. Biopsies of nonfluorescent tissue negative for malignancy (n = 18/18) yielded a specificity of 100%. Furthermore, the SPY system was able to detect residual disease as small as 200 µm in diameter. In addition, the Odyssey confirmed fluorescence of microscopic disease (in tumor samples of frozen and paraffin-embedded histologic specimens) but not in adjacent noncancerous tissue. CONCLUSIONS: These data suggest panitumumab-IRDye800 may have clinical utility in detection and removal of subclinical cSCC using Food and Drug Administration-approved imaging hardware.