A preliminary analysis of patient reported outcomes following posterolateral mandible reconstruction: The role of flap type.

BACKGROUND: The choice of tissue type for free flap reconstruction of posterolateral mandible resections is dependent on patient and defect characteristics. We compared clinical and patient-reported outcomes following reconstruction of these defects with a soft tissue or bony free flap. METHODS: A retrospective review was performed on patients who underwent posterolateral segmental mandibulectomy with immediate free flap reconstruction at MSKCC from 2006 to 2021. Outcomes of interest were patient-reported outcome measures (PROMs) assessed by FACE-Q surveys and complications at the flap recipient site. RESULTS: Ninety patients received a bony flap and 24 patients received a soft tissue flap. Patients reconstructed with soft tissue flaps had greater rates of composite soft tissue defects (p < 0.0001), condyle resection (p = 0.001), and peripheral vascular disease (p = 0.035). Complication rates were similar between the cohorts (p > 0.05). Bony flaps scored higher on multiple FACE-Q scales: Facial Appearance (p = 0.023) Eating/Drinking (p = 0.029), Smiling (p = 0.012), Speaking (p < 0.001), Swallowing (p = 0.012), Smiling Distress (p = 0.037), and Speaking Distress (p = 0.001). CONCLUSION: Reconstruction of posterolateral mandibular defects has a similar complication profile when utilizing a bony or soft tissue free flap. Bony flaps may perform better with respect to PROMs. Reconstructive surgeons should consider using bony flap reconstruction to achieve higher patient satisfaction and quality of life.

First Safety and Performance Evaluation of T45K, a Self-Assembling Peptide Barrier Hemostatic Device, After Skin Lesion Excision.

BACKGROUND: The self-assembling peptide barrier T45K (SAPB-T45K) is an oligopeptide that rapidly forms a biocompatible hemostatic barrier when applied to wounds. OBJECTIVE: Evaluate safety and performance of SAPB-T45K in cutaneous surgery. MATERIALS AND METHODS: In this single-blind study, after sequential shave excision of 2 lesions, wounds were randomized (intrapatient) to SAPB-T45K or control treatment. Safety was assessed at treatment, Day 7, and Day 30. Performance was evaluated using time to hemostasis (TTH) and ASEPSIS wound scores, with a subgroup analysis for patients with or without antiplatelet therapy. RESULTS: Each of 46 patients (10 [22%] with antiplatelet therapy) received randomized SAPB-T45K or control treatment for 2 wounds. Safety assessments were similar, and ASEPSIS scores reflected normal healing in both wound groups. SAPB-T45K demonstrated significantly faster median TTH (24.5 [range, 7-165] seconds) compared with control (44 [10-387] seconds), for a 41% median TTH reduction (18 [95% confidence interval, 7-35] seconds, p < .001). SAPB-T45K provided an identical median TTH of 24 seconds, regardless of antiplatelet therapy. Control median TTH was 90 and 40 seconds for patients taking or not taking antiplatelet therapy, respectively. CONCLUSIONS: SAPB-T45K provided significantly faster median TTH versus control, especially with antiplatelet therapy, and safety profiles were similar.

Closed Traumatic Avulsion of Both Flexor Digitorum Tendons: An Addition to the Leddy and Packer Classification and Review of the Literature.

Objective: We encountered the case of a patient who presented with an avulsion of both flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendons from their respective insertion in the ring finger. We aim to discuss the novel treatment of this injury pattern in the context of all previously encountered cases in the literature. Materials and Methods: We examined the case of our patient with avulsion of both flexor tendons in the same finger and discuss the novel method of treatment in our case. Additionally, we performed a literature review of all previous reported cases and discuss the treatment modalities and outcomes associated with each. Results: We have shown a novel and successful treatment technique for avulsion of both the FDP and FDS tendons. We identified twelve other cases of this injury pattern and have compared all outcomes documented. Conclusion: Closed tendon avulsion of both flexor tendons in the same finger is rare. We described a case and additionally propose a modification to the flexor tendon avulsion classification to incorporate this injury pattern and aid its management.

A rare case of rhabdomyosarcoma identified in a VRAM flap after lower extremity reconstruction.

Spindle cell sclerosing rhabdomyosarcoma (sc-RMS) is an extremely rare soft tissue tumor. We report an unusual case of sc-RMS in a 36-year-old patient whose tumor arose in a rectus abdominis muscle free flap that had been used for lower extremity reconstruction 18 years previously. After surgical excision of the tumor and immediate reconstruction, the patient has remained in remission and has full function of his lower extremity six months after diagnosis and treatment.

Feasibility and Clinical Utility of Prediction Models for Breast Cancer-Related Lymphedema Incorporating Racial Differences in Disease Incidence.

Importance: Breast cancer-related lymphedema (BCRL) is a common complication of axillary lymph node dissection (ALND) but can also develop after sentinel lymph node biopsy (SLNB). Several models have been developed to predict the risk of disease development before and after surgery; however, these models have shortcomings that include the omission of race, inclusion of variables that are not readily available to patients, low sensitivity or specificity, and lack of risk assessment for patients treated with SLNB. Objective: To create simple and accurate prediction models for BCRL that can be used to estimate preoperative or postoperative risk. Design, Setting, and Participants: In this prognostic study, women with breast cancer who underwent ALND or SLNB from 1999 to 2020 at Memorial Sloan Kettering Cancer Center and the Mayo Clinic were included. Data were analyzed from September to December 2022. Main Outcomes and Measures: Diagnosis of lymphedema based on measurements. Two predictive models were formulated via logistic regression: a preoperative model (model 1) and a postoperative model (model 2). Model 1 was externally validated using a cohort of 34 438 patients with an International Classification of Diseases diagnosis of breast cancer. Results: Of 1882 included patients, all were female, and the mean (SD) age was 55.6 (12.2) years; 80 patients (4.3%) were Asian, 190 (10.1%) were Black, 1558 (82.8%) were White, and 54 (2.9%) were another race (including American Indian and Alaska Native, other race, patient refused to disclose, or unknown). A total of 218 patients (11.6%) were diagnosed with BCRL at a mean (SD) follow-up of 3.9 (1.8) years. The BCRL rate was significantly higher among Black women (42 of 190 [22.1%]) compared with all other races (Asian, 10 of 80 [12.5%]; White, 158 of 1558 [10.1%]; other race, 8 of 54 [14.8%]; P < .001). Model 1 included age, weight, height, race, ALND/SLNB status, any radiation therapy, and any chemotherapy. Model 2 included age, weight, race, ALND/SLNB status, any chemotherapy, and patient-reported arm swelling. Accuracy was 73.0% for model 1 (sensitivity, 76.6%; specificity, 72.5%; area under the receiver operating characteristic curve [AUC], 0.78; 95% CI, 0.75-0.81) at a cutoff of 0.18, and accuracy was 81.1% for model 2 (sensitivity, 78.0%; specificity, 81.5%; AUC, 0.86; 95% CI, 0.83-0.88) at a cutoff of 0.10. Both models demonstrated high AUCs on external (model 1: 0.75; 95% CI, 0.74-0.76) or internal (model 2: 0.82; 95% CI, 0.79-0.85) validation. Conclusions and Relevance: In this study, preoperative and postoperative prediction models for BCRL were highly accurate and clinically relevant tools comprised of accessible inputs and underscored the effects of racial differences on BCRL risk. The preoperative model identified high-risk patients who require close monitoring or preventative measures. The postoperative model can be used for screening of high-risk patients, thus decreasing the need for frequent clinic visits and arm volume measurements.

Everyday emotional functioning in COVID-19 lockdowns.

Throughout the COVID-19 pandemic, policy makers have tried to balance the effectiveness of lockdowns (i.e., stay-at-home orders) with their potential mental health costs. Yet, several years into the pandemic, policy makers lack solid evidence about the toll of lockdowns on daily emotional functioning. Using data from two intensive longitudinal studies conducted in Australia in 2021, we compared the intensity, persistence, and regulation of emotions on days in and out of lockdown. Participants (N = 441, observations = 14,511) completed a 7-day study either entirely in lockdown, entirely out of lockdown, or both in and out of lockdown. We assessed emotions in general (Dataset 1) and in the context of social interactions (Dataset 2). Lockdowns took an emotional toll, but this toll was relatively mild: In lockdown, people experienced slightly more negative and less positive emotion; returned to a mildly negative emotional state more quickly; and used low-effort emotion-regulation strategies (i.e., distraction). There are three interpretations for our findings, which are not mutually exclusive. First, people may be relatively resilient to the emotional challenges posed by repeated lockdowns. Second, lockdowns may not compound the emotional challenges of the pandemic. Third, because we found effects even in a mostly childless and well-educated sample, lockdowns may take a greater emotional toll in samples with less pandemic privilege. Indeed, the high level of pandemic privilege of our sample limits the generalizability of our findings (e.g., to people with caregiving roles). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Qualitative Evaluation of a Caring Letters Suicide Prevention Intervention for the Veterans Crisis Line.

OBJECTIVE: Suicide is a leading cause of death in the United States. This has prompted the U.S. surgeon general to issue a report describing actionable items to reduce suicide rates, including a recommendation to increase the use of the caring letters intervention. This intervention involves mailing brief, nondemanding messages of care. As part of the Department of Veterans Affairs' (VA's) efforts to reduce suicide rates among veterans, a caring letters project was developed for veterans who contact the Veterans Crisis Line (VCL). This article describes the results of qualitative interviews conducted to better understand the experiences of veterans who received caring letters. METHODS: Beginning in 2020, all identifiable veterans who used Veterans Health Administration services and contacted the VCL received nine letters over 1 year, along with a list of mental health resources. Semistructured interviews (N=23) were conducted, and content analysis was used to identify veterans' perspectives and suggestions for improving the intervention. RESULTS: Sixteen men and seven women participated (mean age=53 years). Feedback varied, with most participants reporting that receiving caring letters had a positive impact and others noting aspects that could be improved to enhance the intervention's caring intent. Some also reported that the letters helped them engage with community resources and made them more likely to seek VA care. CONCLUSIONS: The caring letters intervention, received after contact with the VCL, was well received by participants. They described feeling appreciated, cared for, encouraged, and connected. The results of this study will inform future evaluation examining veteran outcomes.

Analysis of Outcomes of Pharyngo-laryngo-esophagectomy and Reconstruction with Longitudinal Comparison in a Single Institution.

Advanced hypopharyngeal tumours present complex clinical challenges, and where resection is attempted, there is a requirement for major reconstruction. Despite advances in surgical technique, outcomes remain poor for this patient group, and optimum treatment has yet to be established. We aimed to assess the treatment and outcomes of patients in our institution in the context of previous studies. All patients from 2008 to 2018 who underwent surgical management for hypopharyngeal tumours with pharyngo-laryngo-esophagectomy and flap-based reconstruction were included in the study. Demographic and outcome data were collected, and patient-reported outcomes were solicited from surviving patients using the EORTC QLQ H&N 43 questionnaire. Thirty patients were assessed, in which 12 had gastric pull-ups, 16 had free jejunum flaps, and 2 had free anterolateral thigh flaps. There was a 38% five-year survival rate. Overall, the rates of stricture (10.7%) and fistula (7.1%) were low. The majority of patients (53.6%) returned to a normal diet within three months with a soft or puree diet in 35.7% of patients. Some form of speech was possible in 92.9% of patients. The average questionnaire score for surviving patients was 87.3, with good outcomes related to eating and swallowing, but poorer outcomes for speech and communication. This study showed that outcomes for patients receiving complex reconstruction following hypopharyngeal tumour resection are improving over time. There is still scope for improvement of patient outcomes and refinement of optimum surgical management strategies.

Implementation strategy to increase clinicians' use of the caring letters suicide prevention intervention.

Caring Letters is recommended in multiple best practice guidelines; however, the Caring Letters intervention has not been widely implemented. The process of tracking, scheduling, and mailing letters for multiple patients over many months may represent a significant barrier for busy clinicians. This evaluation examined whether the use of centralized administrative support (Centralized Caring Letters; CCL) was associated with increased utilization of the intervention. These procedures were tested in the Department of Veterans Affairs (VA) Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH VET) program. In REACH VET, VA clinicians are routinely asked to consider Caring Letters as one option for veterans identified as at-risk. In this evaluation, clinicians at two VA facilities were offered assistance in the tracking, preparation, mailing, and documentation of Caring Letters for veterans they chose to enroll in CCL. The utilization of Caring Letters increased more than 14-fold after CCL was implemented. In the year that preceded CCL, 3% of REACH VET veterans were sent Caring Letters at the two sites; this increased to 43% of cases after the implementation of CCL (45% at Site 1 and 41% at Site 2). In qualitative interviews with providers, clinicians described Caring Letters as beneficial and stated that the centralized features of the program were helpful. Caring Letters were discontinued for 30% of enrolled veterans, often because of a bad address (9% of enrolled) or relocation (8% of enrolled). Although there are barriers for the use of Caring Letters, CCL was associated with a very large increase in the use of Caring Letters. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Development of the Veterans Crisis Line Caring Letters Suicide Prevention Intervention.

OBJECTIVE: To describe the design, implementation, and plans to evaluate the Veterans Crisis Line (VCL) Caring Letters intervention. DATA SOURCES: Veterans with VCL contact and VHA service utilization. STUDY DESIGN: Caring Letters is an evidence-based post-acute care suicide prevention intervention in which brief messages are mailed to individuals at high risk of suicide repeatedly over time to communicate that people care about them and are concerned for their well-being. An effectiveness-implementation hybrid type 1 trial using the RE-AIM evaluation framework is underway to examine the use of Caring Letters with veterans who contact the VCL. A team of suicide prevention subject matter experts, researchers, and operational partners from the VCL will evaluate the effects of Caring Letters on clinical outcomes and Department of Veterans Affairs - Veterans Health Administration (VHA) clinical utilization rates and examine facilitators and barriers to implementing the Caring Letters campaign. DATA COLLECTION METHODS: Veterans who contact the VCL are linked with national administrative VHA data. Semi-structured interviews were conducted as part of a qualitative formative evaluation. PRINCIPAL FINDINGS: In the first 12 months of the intervention, Caring Letters have been sent to over 100,000 veterans with VCL contact (over 500,000 letters mailed). A formative qualitative evaluation early in implementation revealed a variety of positive veteran perspectives on the intervention. CONCLUSIONS: Partnered program design and evaluation with a high level of stakeholder engagement and participant feedback can result in a rigorous and feasible evaluation plan that improves implementation processes and produces actionable results. The initial results of this evaluation will be used to better inform care in the VHA and, specifically, the VCL.

Posterior interosseous neuropathy: distinguishing from a proximal radial neuropathy.

The posterior interosseous nerve is the terminal motor branch of the radial nerve that innervates the extensor carpi ulnaris and the extensors of the thumb and fingers. We describe a case of a posterior interosseous neuropathy presenting with the typical 'finger drop' and partial 'wrist drop'. We focus on the clinical signs that distinguish it from a more proximal radial neuropathy, clarified by nerve conduction studies and needle electromyography. Multimodal imaging of the forearm did not identify a compressive lesion. Persistent symptoms prompted surgical exploration 5 years after initial onset. It identified compression of the posterior interosseous nerve in the region of the arcade of Frohse and leash of Henry. The sites were decompressed and concurrent salvage secondary reconstructive tendon transfers were required in view of the severe axonal loss with minimal chance of functional reinnervation.

Adapting Caring Contacts for Veterans in a Department of Veterans Affairs Emergency Department: Results From a Type 2 Hybrid Effectiveness-Implementation Pilot Study.

Transitions in care, such as discharge from an emergency department (ED), are periods of increased risk for suicide and effective interventions that target these periods are needed. Caring Contacts is an evidence-based suicide prevention intervention that targets transitions, yet it has not been widely implemented. This pilot study adapted Caring Contacts for a Department of Veterans Affairs (VA) ED setting and population, created an implementation toolkit, and piloted implementation and evaluation of effectiveness. To inform adaptation, qualitative interviews were conducted with stakeholders. Data were used by an advisory board comprised of stakeholders, experts, and veterans to make adaptations and develop an implementation planning guide to delineate steps needed to implement. Key decisions about how to adapt Caring Contacts included recipients, author, content, and the schedule for sending. Pilot implementation occurred at one VA ED. Caring Contacts involved sending patients at risk of suicide brief, non-demanding expressions of care. Program evaluation of the pilot used a type 2 hybrid effectiveness-implementation design to both pilot an implementation strategy and evaluate effectiveness of Caring Contacts. Evaluation included qualitative interviews with veteran patients during implementation. VA electronic health records were used to evaluate VA service utilization in the 6-month periods immediately before and after veterans were delivered their first Caring Contact. Hundred and seventy-five veterans were mailed Caring Contacts and the facility continued adoption after the pilot. Participants were positive about the intervention and reported feeling cared about and connected to VA as a result of receiving Caring Contacts. This project developed an implementation planning process that successfully implemented Caring Contacts at one site. This can be used to further implement Caring Contacts at additional VA or community EDs.

The cell cycle hypothesis of Alzheimer's disease: suggestions for drug development.

The cell cycle of hypothesis of neural dysfunction in chronic neurodegenerative conditions such as Alzheimer's disease (AD) offers a unified approach to understanding both existing and novel strategies for drug development. At the present time, a ligand based approach is a pragmatic solution for identifying new chemical leads on which to base future discovery and optimisation. We have pursued a ligand based approach on the basis of public domain data to identify existing compounds capable of abrogating the cell cycle at the G0-G1 interface. Selected on this basis, irrespective of the tissue under study, we identified several classes of compounds as potential chemical leads. Of these compounds, at least ten have already been shown to be neuroprotective in animal models of acute neurodegeneration. Such compounds could form the basis of a screening exercise after development of suitable screening tools. Progressing of chemical leads through such an approach will be more efficient if future leads display relevant "drug-like" properties. Further, drug development in this arena should take account of the special concerns raised by targeting an elderly population. This will involve accounting for frequent polypharmacy in the aging population, and age-related alterations in physiology.

Loss of chromosome 1p/19q in oligodendroglial tumors: refinement of chromosomal critical regions and evaluation of internexin immunostaining as a surrogate marker.

Loss of chromosome 1p/19q in oligodendrogliomas represents a powerful predictor of good prognosis. Expression of internexin (INA), a neuronal specific intermediate filament protein, has recently been proposed as a surrogate marker for 1p/19q deletion based on the high degree of correlation between both parameters in oligodendrogliomas. The aim of this study was to assess further the diagnostic utility of INA expression in a set of genetically well-characterized oligodendrogliomas. On the basis of a conservative approach for copy number determination, using both comparative genomic hybridization and fluorescent in situ hybridization, INA expression as a surrogate marker for 1p/19q loss had both reduced specificity (80%) and sensitivity (79%) compared with respective values of 86% and 96% reported in the previous report. The histologic interpretation and diagnostic value of INA expression in oligodendrogliomas should therefore be assessed with greater caution when compared with 1p/19q DNA copy number analysis. In addition, DNA copy number aberrations of chromosomes 10, 16, and 17 were detected exclusively in 1p/19q codeleted samples, suggesting that other regions of the genome may contribute to the 1p/19q-deleted tumor phenotype inthese samples.

Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease.

BACKGROUND: Chronic neurodegeneration results in microglial activation, but the contribution of inflammation to the progress of neurodegeneration remains unclear. We have shown that microglia express low levels of proinflammatory cytokines during chronic neurodegeneration but are "primed" to produce a more proinflammatory profile after systemic challenge with bacterial endotoxin (lipopolysaccharide [LPS]). METHODS: Here, we investigated whether intraperitoneal (IP) challenge with LPS, to mimic systemic infection, in the early stages of prion disease can 1) produce exaggerated acute behavioral (n = 9) and central nervous system (CNS) inflammatory (n = 4) responses in diseased animals compared with control animals, and 2) whether a single LPS challenge can accelerate disease progression (n = 34-35). RESULTS: Injection of LPS (100 microg/kg), at 12 weeks postinoculation (PI), resulted in heightened CNS interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-beta (IFN-beta) transcription and microglial IL-1beta translation in prion-diseased animals relative to control animals. This inflammation caused exaggerated impairments in burrowing and locomotor activity, and induced hypothermia and cognitive changes in prion-diseased animals that were absent in LPS-treated control animals. At 15 weeks PI, LPS (500 microg/kg) acutely impaired motor coordination and muscle strength in prion-diseased but not in control animals. After recovery, these animals also showed earlier onset of disease-associated impairments on these parameters. CONCLUSIONS: These data demonstrate that transient systemic inflammation superimposed on neurodegenerative disease acutely exacerbates cognitive and motor symptoms of disease and accelerates disease progression. These deleterious effects of systemic inflammation have implications for the treatment of chronic neurodegeneration and associated delirium.

Effects of inbreeding on coastal Douglas fir growth and yield in operational plantations: a model-based approach.

In advanced generation seed orchards, tradeoffs exist between genetic gain obtained by selecting the best related individuals for seed orchard populations, and potential losses due to subsequent inbreeding between these individuals. Although inbreeding depression for growth rate is strong in most forest tree species at the individual tree level, the effect of a small proportion of inbreds in seed lots on final stand yield may be less important. The effects of inbreeding on wood production of mature stands cannot be assessed empirically in the short term, thus such effects were simulated for coastal Douglas fir [ Pseudotsuga menziesii var. menziesii (Mirb.) Franco] using an individual-tree growth and yield model TASS (Tree and Stand Simulator). The simulations were based on seed set, nursery culling rates, and 10-year-old field test performance for trees resulting from crosses between unrelated individuals and for inbred trees produced through mating between half-sibs, full-sibs, parents and offspring and self-pollination. Results indicate that inclusion of a small proportion of related clones in seed orchards will have relatively low impacts on stand yields due to low probability of related individuals mating, lower probability of producing acceptable seedlings from related matings than from unrelated matings, and a greater probability of competition-induced mortality for slower growing inbred individuals than for outcrossed trees. Thus, competition reduces the losses expected due to inbreeding depression at harvest, particularly on better sites with higher planting densities and longer rotations. Slightly higher breeding values for related clones than unrelated clones would offset or exceed the effects of inbreeding resulting from related matings. Concerns regarding the maintenance of genetic diversity are more likely to limit inclusion of related clones in orchards than inbreeding depression for final stand yield.