Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

Cell-programmed nutrient partitioning in the tumour microenvironment.

Cancer cells characteristically consume glucose through Warburg metabolism1, a process that forms the basis of tumour imaging by positron emission tomography (PET). Tumour-infiltrating immune cells also rely on glucose, and impaired immune cell metabolism in the tumour microenvironment (TME) contributes to immune evasion by tumour cells2-4. However, whether the metabolism of immune cells is dysregulated in the TME by cell-intrinsic programs or by competition with cancer cells for limited nutrients remains unclear. Here we used PET tracers to measure the access to and uptake of glucose and glutamine by specific cell subsets in the TME. Notably, myeloid cells had the greatest capacity to take up intratumoral glucose, followed by T cells and cancer cells, across a range of cancer models. By contrast, cancer cells showed the highest uptake of glutamine. This distinct nutrient partitioning was programmed in a cell-intrinsic manner through mTORC1 signalling and the expression of genes related to the metabolism of glucose and glutamine. Inhibiting glutamine uptake enhanced glucose uptake across tumour-resident cell types, showing that glutamine metabolism suppresses glucose uptake without glucose being a limiting factor in the TME. Thus, cell-intrinsic programs drive the preferential acquisition of glucose and glutamine by immune and cancer cells, respectively. Cell-selective partitioning of these nutrients could be exploited to develop therapies and imaging strategies to enhance or monitor the metabolic programs and activities of specific cell populations in the TME.

Global warming impairs stock-recruitment dynamics of corals.

Changes in disturbance regimes due to climate change are increasingly challenging the capacity of ecosystems to absorb recurrent shocks and reassemble afterwards, escalating the risk of widespread ecological collapse of current ecosystems and the emergence of novel assemblages1-3. In marine systems, the production of larvae and recruitment of functionally important species are fundamental processes for rebuilding depleted adult populations, maintaining resilience and avoiding regime shifts in the face of rising environmental pressures4,5. Here we document a regional-scale shift in stock-recruitment relationships of corals along the Great Barrier Reef-the world's largest coral reef system-following unprecedented back-to-back mass bleaching events caused by global warming. As a consequence of mass mortality of adult brood stock in 2016 and 2017 owing to heat stress6, the amount of larval recruitment declined in 2018 by 89% compared to historical levels. For the first time, brooding pocilloporids replaced spawning acroporids as the dominant taxon in the depleted recruitment pool. The collapse in stock-recruitment relationships indicates that the low resistance of adult brood stocks to repeated episodes of coral bleaching is inexorably tied to an impaired capacity for recovery, which highlights the multifaceted processes that underlie the global decline of coral reefs. The extent to which the Great Barrier Reef will be able to recover from the collapse in stock-recruitment relationships remains uncertain, given the projected increased frequency of extreme climate events over the next two decades7.

Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products.

Time span in literature: 1985-early 2024Natural products play a key role in drug discovery, both as a direct source of drugs and as a starting point for the development of synthetic compounds. Most natural products are not suitable to be used as drugs without further modification due to insufficient activity or poor pharmacokinetic properties. Choosing what modifications to make requires an understanding of the compound's structure-activity relationships. Use of structure-activity relationships is commonplace and essential in medicinal chemistry campaigns applied to human-designed synthetic compounds. Structure-activity relationships have also been used to improve the properties of natural products, but several challenges still limit these efforts. Here, we review methods for studying the structure-activity relationships of natural products and their limitations. Specifically, we will discuss how synthesis, including total synthesis, late-stage derivatization, chemoenzymatic synthetic pathways, and engineering and genome mining of biosynthetic pathways can be used to produce natural product analogs and discuss the challenges of each of these approaches. Finally, we will discuss computational methods including machine learning methods for analyzing the relationship between biosynthetic genes and product activity, computer aided drug design techniques, and interpretable artificial intelligence approaches towards elucidating structure-activity relationships from models trained to predict bioactivity from chemical structure. Our focus will be on these latter topics as their applications for natural products have not been extensively reviewed. We suggest that these methods are all complementary to each other, and that only collaborative efforts using a combination of these techniques will result in a full understanding of the structure-activity relationships of natural products.

Social Determinants of Health Needs and Health-related Quality of Life Among Surgical Patients: A Retrospective Analysis of 8512 Patients.

OBJECTIVE: To assess associations between social determinants of health (SDOH) needs and health-related quality of life (HRQOL) among surgical patients. BACKGROUND: Despite the profound impact of SDOH on health outcomes, studies examining the effect of SDOH needs on HRQOL among surgical patients are limited. METHODS: A retrospective study was conducted using responses from the SDOH needs assessment and the Patient-Reported Outcomes Measurement Information Systems Global Health instrument of adults seen in surgical clinics at a single institution. Patient characteristics including socioeconomic status (insurance type, education level, and employment status) were extracted. Stepwise multivariable logistic regression analyses were performed to identify independent predictors of global health scores. RESULTS: A total of 8512 surgical patients (mean age: 55.6±15.8 years) were included. 25.2% of patients reported one or more SDOH needs. The likelihood of reporting at least one SDOH need varied by patient characteristics and socioeconomic status variables. In fully adjusted regression models, food insecurity [odds ratio (OR), 1.53; 95% CI, 1.38-1.70 and OR, 1.49; 95% CI, 1.22-1.81, respectively], housing instability (OR, 1.27; 95% CI, 1.12-1.43 and OR, 1.39; 95% CI, 1.13-1.70, respectively) lack of transportation (OR, 1.46; 95% CI, 1.27-1.68 and OR, 1.25; 95% CI, 1.00-1.57, respectively), and unmet medication needs (OR, 1.31; 95% CI, 1.13-1.52 and OR, 1.61; 95% CI, 1.28-2.03, respectively) were independent predictors of poor physical and mental health. CONCLUSIONS: SDOH needs are independent predictors of poor patient-reported physical and mental health among surgical patients. Assessing and addressing SDOH needs should be prioritized in health care settings and by policymakers to improve HRQOL.

Targeted use of postoperative discharge phone calls to reduce early readmission rates.

OBJECTIVES: Postoperative readmissions are common and costly. Office-initiated phone calls to patients shortly after discharge may identify concerns and allow for early intervention to prevent readmission. We sought to evaluate our 30-day readmission rate after the implementation of a standardized postoperative discharge phone call (PODPC) intervention, compared with a historical aggregated cohort. METHODS: From July 2020 to 21, postoperative patients were prospectively identified at 48 hour after discharge. Medical assistants performed PODPCs, administering a survey designed to identify medical/surgical issues that could signify a complication and warrant escalation to a nurse practitioner (NP) for further management. Demographics, comorbidities, and procedure type were obtained retrospectively. Descriptive statistics were used to evaluate PODPC responses, frequency of escalation, readmission, and reasons. The electronic medical record identified a historical aggregated cohort (July 2018 to 2019) and the 30-day readmission rate. A χ2 analysis was used to compare readmission rates between the preintervention historical and PODPC intervention groups. Predictors of 30-day readmission were modeled with multivariable logistic regression. RESULTS: Of 411 PODPCs conducted, 106 patients (26%) reported not feeling well; having concerns. Eighty-four PODPCs (20%) triggered escalation to a NP; of these, 60 patients (71%) were counseled over the phone by an NP, 16 (19%) were brought into clinic, 6 (7%) were sent to the emergency department, and 2 (2%) did not answer the NP call. Of 411 patients, 17% (n = 68) were readmitted within 30 days. Comparatively, the historical aggregated cohort readmission rate was significantly higher at 28% (n = 346; P < .001). On multivariable analysis, chronic obstructive pulmonary disease (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.01-3.65; P = .046), and feeling run down; having difficulty with movement; needing assistance for most activities (OR, 3.94; 95% CI, 2.09-7.43; P < .0001) were predictive of 30-day readmission when controlling for procedure type. CONCLUSIONS: Although readmissions remained common (>15%), being in the intervention cohort was associated with a significantly lower readmission rate compared with the historical aggregated cohort. One-fifth of PODPCs identified a concern; however, >90% of these could be managed by an NP by phone or in clinic. This PODPC intervention holds promise as a viable mechanism for decreasing readmissions.

Patterns of Social Needs Predict Quality-of-Life and Healthcare Utilization Outcomes in Patients from a Large Hospital System.

BACKGROUND: Unmet social needs (SNs) often coexist in distinct patterns within specific population subgroups, yet these patterns are understudied. OBJECTIVE: To identify patterns of social needs (PSNs) and characterize their associations with health-related quality-of-life (HRQoL) and healthcare utilization (HCU). DESIGN: Observational study using data on SNs screening, HRQoL (i.e., low mental and physical health), and 90-day HCU (i.e., emergency visits and hospital admission). Among patients with any SNs, latent class analysis was conducted to identify unique PSNs. For all patients and by race and age subgroups, compared with no SNs, we calculated the risks of poor HRQoL and time to first HCU following SNs screening for each PSN. PATIENTS: Adult patients undergoing SNs screening at the Mass General Brigham healthcare system in Massachusetts, United States, between March 2018 and January 2023. MAIN MEASURES: SNs included: education, employment, family care, food, housing, medication, transportation, and ability to pay for household utilities. HRQoL was assessed using the Patient-Reported Outcomes Measurement Information System Global-10. KEY RESULTS: Six unique PSNs were identified: "high number of social needs," "food and utility access," "employment needs," "interested in education," "housing instability," and "transportation barriers." In 14,230 patients with HRQoL data, PSNs increased the risks of poor mental health, with risk ratios ranging from 1.07(95%CI:1.01-1.13) to 1.80(95%CI:1.74-1.86). Analysis of poor physical health yielded similar findings, except that the "interested in education" showed a mild protective effect (0.97[95%CI:0.94-1.00]). In 105,110 patients, PSNs increased the risk of 90-day HCU, with hazard ratios ranging from 1.09(95%CI:0.99-1.21) to 1.70(95%CI:1.52-1.90). Findings were generally consistent in subgroup analyses by race and age. CONCLUSIONS: Certain SNs coexist in distinct patterns and result in poorer HRQoL and more HCU. Understanding PSNs allows policymakers, public health practitioners, and social workers to identify at-risk patients and implement integrated, system-wide, and community-based interventions.

Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

BACKGROUND: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care. METHODS: A multidisciplinary working group was formed. An electronic note comprised of (1) topics of discussion, (2) PV, and (3) advance care planning (ACP), was created and embedded into existing note templates for Gynecologic Surgical Oncology. Surgeons and advanced practice providers (APPs) were educated to conduct and document these conversations in preoperative clinic for patients undergoing cancer surgery for a pilot period. Data were collected regarding usage of the template. Focus groups with surgeons, APPs, and patients were conducted. Qualitative analysis was performed on transcripts. RESULTS: During the pilot, 7 surgeon/APP teams utilized the template on a total of 55 notes. Average number of notes completed per surgeon was 7.8 (SD 8.5). Forty-six notes (84%) included topics of discussion, 15 (27%) included PV, 4 (7%) included ACP. Qualitative analysis of focus group transcripts revealed that clinicians and patients perceived the initiative to be useful and important, although implementation barriers were identified. CONCLUSION: Creating a surgery-specific GOC template is feasible. Iterative revisions are needed to increase utility in clinic workflows.

Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period: A retrospective cohort study.

BACKGROUND: Calciphylaxis patients historically have experienced diagnostic challenges and high morbidity; however limited data is available examining these characteristics over time. OBJECTIVE: The primary goals were to a) investigate factors associated with diagnostic delay of calciphylaxis and b) assess morbidity outcomes. The secondary goal was to provide updated mortality rates. METHODS: A retrospective review of 302 adult patients diagnosed with calciphylaxis between January 1, 2006 and December 31, 2022 was conducted. Univariate and multivariate statistical analyses were performed. RESULTS: Nonnephrogenic calciphylaxis (P = .0004) and involvement of the fingers (P = .0001) were significantly associated with an increased diagnostic delay, whereas involvement of the arms (P = .01) and genitalia (P = .022) resulted in fewer days to diagnosis. Almost all patients with genitalia, finger, or toe involvement had nephrogenic disease. The number of complications per patient decreased with time, especially for wound infections (P = .028), increase in lesion number (P = .012), and recurrent hospitalizations (P = .020). Updated 1-year mortality rates were 36.70% and 30.77% for nephrogenic and nonnephrogenic calciphylaxis, respectively. LIMITATIONS: Limitations include the retrospective nature and data from a single institution. CONCLUSION: Diagnostic delay, particularly in nonnephrogenic calciphylaxis, and complications per patient decreased with time, highlighting the importance of continued awareness to expedite diagnosis. Mortality rates have continued to improve in recent years.

Altered Cortical Activity during a Finger Tap in People with Stroke.

This study describes electroencephalography (EEG) measurements during a simple finger movement in people with stroke to understand how temporal patterns of cortical activation and network connectivity align with prolonged muscle contraction at the end of a task. We investigated changes in the EEG temporal patterns in the beta band (13-26 Hz) of people with chronic stroke (N = 10, 7 F/3 M) and controls (N = 10, 7 F/3 M), during and after a cued movement of the index finger. We quantified the change in beta band EEG power relative to baseline as activation at each electrode and the change in task-based phase-locking value (tbPLV) and beta band task-based coherence (tbCoh) relative to baseline coherence as connectivity between EEG electrodes. Finger movements were associated with a decrease in beta power (event related desynchronization (ERD)) followed by an increase in beta power (event related resynchronization (ERS)). The ERS in the post task period was lower in the stroke group (7%), compared to controls (44%) (p < 0.001) and the transition from ERD to ERS was delayed in the stroke group (1.43 s) compared to controls (0.90 s) in the C3 electrode (p = 0.007). In the same post movement period, the stroke group maintained a heightened tbPLV (p = 0.030 for time to baseline of the C3:Fz electrode pair) and did not show the decrease in connectivity in electrode pair C3:Fz that was observed in controls (tbPLV: p = 0.006; tbCoh: p = 0.023). Our results suggest that delays in cortical deactivation patterns following movement coupled with changes in the time course of connectivity between the sensorimotor and frontal cortices in the stroke group might explain clinical observations of prolonged muscle activation in people with stroke. This prolonged activation might be attributed to the combination of cortical reorganization and changes to sensory feedback post-stroke.

Author Correction: Crowther et al. reply.

In this Brief Communications Arising Reply, the affiliation for author P. H. Templer was incorrectly listed as 'Department of Ecology & Evolutionary Biology, University of California Irvine, Irvine, California 92697, USA' instead of 'Department of Biology, Boston University, Boston, Massachusetts 02215, USA'. This has been corrected online.

Psychological Resilience: An Affect-Regulation Framework.

Exposure to adversity (e.g., poverty, bereavement) is a robust predictor of disruptions in psychological functioning. However, people vary greatly in their responses to adversity; some experience severe long-term disruptions, others experience minimal disruptions or even improvements. We refer to the latter outcomes-faring better than expected given adversity-as psychological resilience. Understanding what processes explain resilience has critical theoretical and practical implications. Yet, psychology's understanding of resilience is incomplete, for two reasons: (a) We lack conceptual clarity, and (b) two major approaches to resilience-the stress and coping approach and the emotion and emotion-regulation approach-have limitations and are relatively isolated from one another. To address these two obstacles,we first discuss conceptual questions about resilience. Next, we offer an integrative affect-regulation framework that capitalizes on complementary strengths of both approaches. This framework advances our understanding of resilience by integrating existing findings, highlighting gaps in knowledge, and guiding future research.

What influences trust in and understanding of clinical trials? An analysis of information and communication technology use and online health behavior from the Health Information National Trends Survey.

BACKGROUND: Using information and communication technologies to seek, discuss, and share health-related information influences people's trust and knowledge of several health practices. However, we know little about the associations between individuals' information and communication technology use and their perceptions of trust and knowledge of clinical trials. Examining these associations may lead to the identification of target audiences and channels for developing effective educational interventions and campaigns about clinical trials. METHODS: In this study, we analyzed Health Information National Trends Survey data to document perceptions of clinical trial-related knowledge and trust that were recently added as questions in this annual national survey of US adults. We also examined correlates of these clinical trial perceptions that included sociodemographic factors and individuals' use of information and communication technologies to seek health information, discuss such information with their healthcare providers, and share the information in their network. RESULTS: More than 90% of participants had no or limited perceived knowledge about clinical trials. Knowledge was higher among those who seek or discuss health-related information online. Differences in perceived knowledge and trust emerged for some racial/ethnic subgroups and other demographic factors. Providers were considered the most trusted source of information (73.6%), followed by health organizations (19.4%) and social support (7.1%). Trust in health organizations compared to health providers was higher among those who used online resources to share health information online with others. Trust in social support was significantly higher among those who used information and communication technologies to communicate about health. CONCLUSION: Based on these findings, we recommend developing online resources about clinical trials to be distributed through social media. These resources should facilitate a dialogue and be targeted to several groups considering their information and communication technologies' use.

Moderate and Severe Chronic Kidney Disease Predict Greater 5-Year Mortality following Major Lower-Extremity Amputation.

BACKGROUND: Severe chronic kidney disease (CKD) predicts greater mortality after major lower-extremity amputation (LEA), but it remains poorly understood whether patients with earlier stages of CKD share similar risk. METHODS: We assessed long-term postoperative outcomes for patients with CKD in a retrospective chart review of 565 patients who underwent atraumatic major LEA at a large tertiary referral center from 2015 to 2021. We stratified patients by renal function and compared outcomes including survival. RESULTS: Preoperative CKD diagnosis was related to many patient characteristics, co-occurred with many comorbidities, and was associated with less follow-up and survival. Kaplan-Meier and Cox Regression analyses showed significantly worse 5-year survival for major LEA patients with mild, moderate, or severe CKD compared to major LEA patients with no history of CKD at the time of amputation (P < 0.001). Severe CKD independently predicted worse mortality at 1-year (odds ratio [OR] 2.91; P = 0.003) and 5-years (OR 3.08; P < 0.001). Moderate CKD independently predicted worse 5-year mortality (OR 2.66; P = 0.029). CONCLUSIONS: This study demonstrates that moderate and severe CKD predict greater long-term mortality following major LEA when controlling for numerous potential confounders. This finding raises questions about the underlying mechanism if causal and highlights an opportunity to improve outcomes with earlier recognition and optimization CKD preoperatively.

Sex differences in laterality of motor unit firing behavior of the first dorsal interosseous muscle in strength-matched healthy young males and females.

PURPOSE: The purpose of this study was to compare laterality in motor unit firing behavior between females and males. METHODS: Twenty-seven subjects (14 females) were recruited for this study. The participants performed ramp up and hold isometric index finger abduction at 10, 30, and 60% of their maximum voluntary contraction (MVC). High-density surface electromyography (HD-sEMG) signals were recorded in the first dorsal interosseous (FDI) muscle and decomposed into individual motor unit (MU) firing behavior using a convolution blind source separation method. RESULTS: In total, 769 MUs were detected (females, n = 318 and males, n = 451). Females had a significantly higher discharge rate than males at each relative torque level (10%: male dominant hand, 13.4 ± 2.7 pps vs. female dominant hand, 16.3 ± 3.4 pps; 30%: male dominant hand, 16.1 ± 3.9 pps vs. female dominant hand, 20.0 ± 5.0 pps; and 60%: male dominant hand, 19.3 ± 3.8 vs. female dominant hand, 25.3 ± 4.8 pps; p < 0.0001). The recruitment threshold was also significantly higher in females than in males at 30 and 60% MVC. Furthermore, males exhibited asymmetrical discharge rates at 30 and 60% MVC and recruitment thresholds at 30 and 60% MVC, whereas no asymmetry was observed in females. CONCLUSION: In the FDI muscle, compared to males, females exhibited different neuromuscular strategies with higher discharge rates and recruitment thresholds and no asymmetrical MU firing behavior. Notably, the findings that sex differences in neuromuscular activity also occur in healthy individuals provide important information for understanding the pathogenesis of various diseases.

Immediate effect of local vibration on motor unit firing behavior and muscle strength in healthy young adult males.

PURPOSE: The aim of this study was to examine the effect of vibration on motor unit (MU) firing behavior and physical performance of antagonist muscles in healthy young adult males. METHODS: Fourteen males (age = 24.3 ± 3.6 years) were included in this study. There were two conditions, one in which participants received 80 Hz vibration in the distal tendon of the hamstring for 30 s and the control condition (no vibration). High-density surface electromyography (HD-SEMG) signals and maximal voluntary contraction (MVC) of knee extensor muscles were evaluated before and after the respective conditions and recorded from the vastus lateralis muscle during submaximal ramp-up and sustained contractions at 30% MVC. Convolution blind source separation was used to decompose the HD-SEMG signals into individual MU firing behaviors. RESULTS: In total, 739 MUs were detected (control; 360 MUs and vibration; 379 MUs), and a total of 312 matched MUs were identified across both submaximal contraction conditions (control: 150 MUs; vibration: 162 MUs). Vibration significantly increased the discharge rate (p = 0.047) and decreased the recruitment threshold before and after intervention (p = 0.001) but not in the control condition. Furthermore, the recruitment threshold is a factor that influences discharge rate. Significant correlations were observed between the recruitment threshold and both the ∆ discharge rate and the ∆ recruitment threshold under the vibration condition (p < 0.001). CONCLUSION: Vibration increased in the discharge rate and decreased the recruitment threshold of the antagonist muscle. These findings suggested that vibration contributes to immediate changes in the neural control of antagonist muscles.

Dural arteriovenous fistula in the setting of cerebral venous sinus thrombosis and COVID-19 infection.

OBJECTIVE: The aim of this study was to examine the presence of concurrent venous thrombosis and COVID-19 infections in patients with dural arteriovenous fistulas (dAVFs). METHODS: An analysis of all patients diagnosed with dAVF via cerebral angiography by the senior author was conducted, with special attention given to the presence of cerebral venous sinus thrombosis (CVST) and COVID-19 infection. General demographics, clinical presentation, presence of CVST, and COVID-19 infection status were reported. RESULTS: A total of 30 patients with dAVFs were included in this study. Three patients were diagnosed with COVID-19 (10%), with one of these patients developing CVST (33%) at 6 months postinfection. Of the 27 patients not infected with COVID-19, one was diagnosed with a likely chronic CVST at the time of presentation of dAVF (4%). A total of 11 case reports and 3 retrospective studies describing patients diagnosed with CVST at or after diagnosis of dAVFs have been reported in the literature. The incidence of dAVFs in patients with CVST has been reported as 2.4%, and the incidence of dAVF has reportedly increased five- to tenfold since the COVID-19 pandemic. CONCLUSIONS: COVID-19 infections may pose as an emerging risk factor for the development of CVST and subsequent dAVF development. To the authors' knowledge, this study presents the first cases in the literature describing a temporal relationship between COVID-19 and development of a dAVF with CVST. The effect of both COVID-19 and associated vaccines should be further assessed in future studies to examine its impact as an effect modifier on the association of dAVF and CVST.

Socioeconomic Disparities in Postoperative Outcomes of Osteocutaneous Fibula Free Flaps for Head and Neck Reconstruction.

BACKGROUND: Osteocutaneous fibula free flaps (FFFs) are a fundamental component of reconstructive surgery in the head and neck region, particularly after traumatic injuries or oncologic resections. Despite their utility, FFFs are associated with various postoperative complications, such as infection, flap failure, and donor site morbidity, impacting up to 54% of cases. This study aimed to investigate the influence of socioeconomic variables, with a particular focus on median household income (MHI), on the incidence of postoperative complications in FFF reconstruction for head and neck cancer. METHODS: A retrospective analysis of 80 patients who underwent FFF reconstruction for head and neck cancer at a single center from 2016 to 2022 was conducted. Demographic and patient characteristics, including race, MHI, insurance type, history of radiation therapy, and TNM (tumor, node, metastasis) cancer stage, were evaluated. Logistic regression, controlling for comorbidities, was used to assess the impact of MHI on 30-, 90-, and 180-day postoperative complications. RESULTS: The patient population was predominantly male (n = 51, 63.8%) and White (n = 63, 78.8%), with the majority falling within the $55,000 to $100,000 range of MHI (n = 51, 63.8%). Nearly half of the patients had received neoadjuvant radiation treatment (n = 39, 48.75%), and 36.25% (n = 29) presented with osteoradionecrosis. Logistic regression analysis revealed that the $55,000-$100,000 MHI group had significantly lower odds of developing complications in the 0- to 30-day postoperative period when compared with those in the <$55,000 group (odds ratio [OR], 0.440; 95% confidence interval [CI], 0.205-0.943; P = 0.035). This trend persisted in the 31- to 90-day period (OR, 0.136; 95% CI, 0.050-0.368; P < 0.001) and was also observed in the likelihood of flap takeback. In addition, the $100,000-$150,000 group had significantly lower odds of developing complications in the 31- to 90-day period (OR, 0.182; 95% CI, 0.035-0.940; P = 0.042). No significant difference was found in the >$150,000 group. CONCLUSIONS: Median household income is a significant determinant and potentially a more influential factor than neoadjuvant radiation in predicting postoperative complications after FFF reconstruction. Disparities in postoperative outcomes based on income highlight the need for substantial health care policy shifts and the development of targeted support strategies for patients with lower MHI.

The role of cochlear and vestibular afferents in long-latency cervical vestibular evoked myogenic potentials.

OBJECTIVE: To examine the origin of cervical vestibular evoked myogenic potential (cVEMP) late waves (n34-p44) elicited with air-conducted click stimuli. DESIGN: Using a retrospective design, cVEMPs from normal volunteers were compared to those obtained from patients with vestibular and auditory pathologies. STUDY SAMPLE: (1) Normal volunteers (n = 56); (2) severe-to-profound sensorineural hearing loss (SNHL) with normal vestibular function (n = 21); (3) peripheral vestibular impairment with preserved hearing (n = 16); (4) total vestibulocochlear deficit (n = 23). RESULTS: All normal volunteers had ipsilateral-dominant early p13-n23 peaks. Late peaks were present bilaterally in 78%. The p13-n23 response was present in all patients with SNHL but normal vestibular function, and 43% had late waves. Statistical comparison of these patients to a subset of age-matched controls showed no significant difference in the frequencies, amplitudes or latencies of their ipsilateral early and late peaks. cVEMPs were absent in all patients with vestibular impairment. CONCLUSION: The presence of long-latency cVEMP waves was not dependent on the integrity of sensorineural hearing pathways, but instead correlated with intact vestibular function. This finding conflicts with the view that these late waves are cochlear in origin, and suggests that vestibular afferents may assume a more prominent role in their generation.

Symptomatic peripheral artery disease increases risk of perioperative mortality following open abdominal aortic aneurysm repair.

OBJECTIVE: Peripheral artery disease (PAD) is associated with worse survival following abdominal aortic aneurysm (AAA) repair. However, little is known about the impact of PAD and sex on outcomes following open infrarenal AAA repair (OAR). METHODS: All elective open infrarenal AAA cases were queried from the Society for Vascular Surgery Vascular Quality Initiative from 2003 to 2022. PAD was defined as history of non-cardiac arterial bypass, non-coronary percutaneous vascular intervention (PVI), or non-traumatic major amputation. Cohorts were stratified by sex and history of PAD. Multivariable logistic regression and Cox proportional hazards models were constructed to assess the primary endpoints: 30-day and 5-year mortality, respectively. RESULTS: Of 4910 patients who underwent elective OAR, 3421 (69.7%) were men without PAD, 298 (6.1%) were men with PAD, 1098 (22.4%) were women without PAD, and 93 (1.9%) were women with PAD. Men with PAD had prior bypass (45%), PVI (62%), and amputation (6.7%). Women with PAD had prior bypass (32%), PVI (76%), and amputation (5.4%). Thirty-day mortality was significantly higher in men with PAD compared with men without PAD (4.4% vs 1.7%; P = .001) and in women with PAD compared with women without PAD (7.5% vs 2.4%; P = .01). After risk adjustment, when compared with men without PAD, women with PAD had nearly four times the odds of 30-day mortality (odds ratio, 3.86; 95% confidence interval [CI], 1.55-9.64; P = .004) and men with PAD had almost three times the odds of 30-day mortality (odds ratio, 2.77; 95% CI, 1.42-5.40; P = .003). Five-year survival was 87.8% in men without PAD, 77.8% in men with PAD, 85% in women without PAD, and 76.2% in women with PAD (P < .001). After risk adjustment, only men with PAD had an increased hazard of death at 5 years (hazard ratio, 1.52; 95% CI, 1.07-2.17; P = .019) compared with men without PAD. CONCLUSIONS: PAD is a potent risk factor for increased perioperative mortality in both men and women following OAR. In women, this equates to nearly four times the odds of perioperative mortality compared with men without PAD. Future study evaluating risk/benefit is needed to determine if women with PAD reflect a high-risk cohort that may benefit from a more conservative OAR threshold for treatment.