Employer-Sponsored Medicare Advantage Plans and the 2018 Therapy Cap Repeal: Reduced Overall Spending Does Not Constrain Out-of-Pocket Costs.

BACKGROUND: Policy impacting traditional Medicare beneficiaries may have unintended effects for privately insured patients. After the repeal of a longstanding $1500 outpatient therapy cap in 2018, we aimed to evaluate if this policy change was associated with differences in use of cost of postoperative therapy after common hand surgeries, including carpal tunnel release, trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture open reduction/internal fixation or percutaneous pinning. METHODS: The Medicare Supplement and Coordination of Benefits files from Marketscan were used. Frequency of therapy appointments, overall costs, and out-of-pocket costs were obtained. A segmented interrupted time series with Poisson and log-transformed linear regression was performed. RESULTS: No significant monthly change in odds of therapy use was found in the postpolicy period for patients who underwent trigger finger release, carpal tunnel release, Ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, or distal radius fracture, pinning, or open reduction/internal fixation. Overall cost decreased in the postpolicy period by 2% for comprehensive plans (95% confidence interval [CI]: -0.03 to -0.01, P < 0.001), by 7% for those with exclusive provider organizations (95% CI: -0.10 to -0.04, P < 0.001), by 1% for HMOs (95% CI: -0.01 to 0.002, P = 0.01), and by 3% for preferred provider organizations (95% CI: -0.03 to -0.02, P < 0.001). In the postpolicy period, no monthly change in out-of-pocket cost was observed for patients with comprehensive, exclusive provider organization, health maintenance organization, preferred provider organization, or point of service with capitation insurance plans. CONCLUSIONS: Patients with employer-sponsored Medicare Advantage plans experienced increased out-of-pocket costs for therapy despite lower net costs. These data highlight an urgent need for policy ensuring that patients benefit when overall costs of care decrease.

Postoperative hand therapy and the 2018 Medicare therapy cap repeal: Appraising cost and use changes.

BACKGROUND: Therapy use is common following carpal tunnel release (CTR), trigger finger release, ganglion cyst excision, De Quervain tenosynovitis release, carpometacarpal arthroplasty, and distal radius fracture, open reduction internal fixation or percutaneous pinning (DRF). Policy that improves coverage influences the cost and use of health care services. PURPOSE: This study aims to evaluate changes to the cost and use of postoperative hand therapy by race and procedure following the repeal of a longstanding annual Medicare outpatient therapy cap. STUDY DESIGN: Retrospective cohort study. METHODS: This is a longitudinal retrospective cohort study using a quasi-experimental interrupted time series design, including patients who underwent common hand surgeries from January 1, 2016-December 31, 2019. RESULTS: This study included 203,672 patients with a mean age of 71.4 years. Neither White (1.00, 95% confidence interval [CI]: 0.999-1.007, p = 0.45) nor non-White (1.00, 95% CI: 1.00-1.01, p = 0.06) patients experienced monthly changes in therapy use before policy implementation. Therapy frequency increased following CTR (odds ratio [OR] 1.12, 95% CI: 1.11-1.14, p < 0.001), trigger finger release (OR 1.09, 95% CI: 1.07-1.10, p < 0.001), and DRF (OR 1.05, 95% CI: 1.03-1.06, p < 0.001) following implementation. CONCLUSIONS: This study found that improved coverage was associated with increased postoperative therapy use among some subsets, including CTR and DRF, suggesting the need to optimize coverage by means such as prior authorization or bundled payments, rather than only increasing coverage benefits.

Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction.

We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust SB366791-sensitive dilation in WT coronary microvessels; however, this response was attenuated in vessels from db/db and V1KO mice, suggesting H2O2-induced vasodilation occurs, in part, via TRPV1. Acute H2O2 exposure potentiated capsaicin-induced CBF responses and capsaicin-mediated vasodilation in WT mice, whereas prolonged luminal H2O2 exposure blunted capsaicin-induced vasodilation. Electrophysiology studies re-confirms acute H2O2 exposure activated TRPV1 in HEK293A and bovine aortic endothelial cells while establishing that H2O2 potentiate capsaicin-activated TRPV1 currents, whereas prolonged H2O2 exposure attenuated TRPV1 currents. Verification of H2O2-mediated activation of intrinsic TRPV1 specific currents were found in isolated mouse coronary endothelial cells from WT mice and decreased in endothelial cells from V1KO mice. These data suggest prolonged H2O2 exposure impairs TRPV1-dependent coronary vascular signaling. This may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.

P-Value Reporting and Reliability in Plastic and Reconstructive Surgery: A Primer for Readers and Investigators.

The p-value is ubiquitous in research. However, misuse and misinterpretation are common. This special topics article aims to demystify the p-value for researchers, students, physicians, and experienced investigators alike. To accomplish this aim, the origins of the p-value, what they represent, and principles of application are described through use of examples from real datasets. Developing understanding of the true meaning of this statistical measure has the power to improve and inform clinical research.

The effect of Medicaid expansion on rates of carpal tunnel release: an interrupted time series analysis.

BACKGROUND: Medicaid expansion through the Affordable Care Act (ACA) has been associated with greater access and utilization of surgical services in underserved populations. However, its impact on use of hand surgical care is less understood. The purpose of this study was to evaluate the association between New York State adoption of the ACA and carpal tunnel release (CTR) procedural volume in Medicaid beneficiaries. METHODS: We conducted a pooled cross-sectional analysis of patients who underwent CTR using the Healthcare Cost and Utilization Project New York State all-payer database (2010-2018). An interrupted time series (ITS) analysis using an autoregressive integrated moving average model estimated the immediate and long-term impact of Medicaid expansion in January 2014 on CTR procedural volume in Medicaid beneficiaries and uninsured individuals. RESULTS: A total of 112,569 patients were included in the sample. After expansion, we observed an absolute increase of 6% in the share of CTR procedures provided to Medicaid beneficiaries. Policy implementation was associated with an immediate 1.81% increase (95% CI=0.0085, 0.0277; p<0.001) in the probability of Medicaid as the primary payer and an annual increase of 1.68% (95% CI=0.0134, 0.0202; p<0.001) after reform. ITS analysis found this resulted in 4,190 additional CTR procedures in Medicaid beneficiaries than predicted without expansion. CONCLUSIONS: Study results suggest New York's adoption of the ACA was associated with an immediate and steady increase in use of outpatient CTR in Medicaid beneficiaries. Most of this increase represented newly treated patients rather than those who were previously uninsured.

Impact of Regional Surgeon Competition on Use, Cost, and Outcomes of Breast Reconstruction in the United States.

BACKGROUND: Breast reconstruction following mastectomy is underused in the United States. Evidence suggests that more competitive hospital markets offer increased access to procedural care across specialties. This study aims to determine the impact of regional plastic surgeon competition on use, outcomes, and cost of breast reconstruction following mastectomy for breast cancer. METHODS: We conducted a retrospective cross-sectional analysis using Marketscan claims data from 2009 to 2020. The Herfindahl-Hirschman Index (HHI), a measure of market concentration, was calculated using the sum-of-squares of the proportion of breast reconstruction cases performed by each surgeon in a metropolitan statistical area (MSA). Multivariable logistic regression was used to identify differences in rates, outcomes, and costs of reconstruction by HHI. RESULTS: Odds of receiving breast reconstruction within two years of mastectomy were higher for those in moderately competitive (OR: 1.51 [95% CI: 1.37 to 1.66]; p<0.001) or competitive (OR: 1.71 [95% CI: 1.58 to 1.86]; p<0.001) = regions compared to noncompetitive regions. Patient out-of-pocket costs decreased when comparing moderately competitive regions to noncompetitive regions (-$67.38, [95% CI: -$88.65 to -$46.11]; p=0.007), and further decreased when comparing competitive to non-competitive regions (-$113.06, [95% CI: -$137.00 to -$89.12]; p=0.02). No linear association between total, surgeon, or facility cost and market competition strata was identified. CONCLUSION: Greater competition among surgeons is associated with improved access to reconstructive surgery, but no difference in cost. Application of this evidence may include system-level strategies to bolster care coordination, while targeting drivers of cost, such as hospitals and hospital systems, through policy.

2020 CMS prior authorization for hospital outpatient departments: Associated surgical volume impact.

BACKGROUND: Prior authorization is common for privately administered Medicare Advantage plans but is rarely used for surgical care when considering publicly administered plans. A 2020 Centers for Medicare and Medicaid services (CMS) policy, CMS-1717-FC, requires prior authorization for Medicare Fee-for-Service beneficiaries undergoing select procedures (blepharoplasty, abdominoplasty, botulinum toxin injection, rhinoplasty, and vein ablation) in hospital outpatient departments. The impact of this policy on surgical volume at hospital outpatient departments and shifts in care to ambulatory surgery centers is unknown. METHODS: This study used a segmented interrupted time series and pre-post logistic regression model. This study was a retrospective cohort study using data from the Healthcare Cost and Utilization Project state ambulatory surgery database and state inpatient database. RESULTS: From 2016 through 2021, a total of 272,879 patients underwent the affected procedures. Pre-CMS-1717-FC, a trend of decreasing hospital outpatient department utilization was found for Medicare Fee-for-Service beneficiaries (-10.82, 95% confidence interval: -18.32 to -3.33, P = .01). In the post-implementation period, no change in the rate of decreasing hospital outpatient department utilization was found for Medicare Fee-for-Service beneficiaries (-3.45, 95% confidence interval: -36.15 to 29.25, P = .83). In the pre-policy period, Medicare Fee-for-Service beneficiaries were 46% less likely to use freestanding ambulatory surgery centers but 27% less likely to use hospital-owned ambulatory surgery centers. CONCLUSION: CMS-1717-FC was not associated with significant changes in hospital outpatient department volume beyond baseline trends. Policy aiming to right-size prior authorization for these procedures and considering site-of-service will balance the need to ensure medical necessity while constraining costs.

REPORTED PRICES FOR HIGH VOLUME HAND SURGERY IN THE ERA OF PRICE TRANSPARENCY: IMPLICATIONS FOR FUTURE POLICY ITERATIONS.

BACKGROUND: In 2021, the United States enacted a law requiring hospitals to report prices for healthcare services. Across several healthcare services, poor compliance and wide variation in pricing was found. This study aims to investigate variation in reporting and listed prices by hospital features for high-volume hand surgeries including Carpal Tunnel release, Trigger Finger Release, De Quervain Tenosynovitis Release, and Carpometacarpal Arthroplasty. METHODS: The Turquoise Health price transparency database was used to obtain listed prices and linked to hospital characteristics from the 2021 Annual American Hospital Association Survey. This study used descriptive statistics and generalized linear regression. RESULTS: The analytic cohort included 2,652 hospitals from across the US. The highest rate of price reporting was in the Midwest (52%, n=836) and lowest in the South (39%, n=925). Compared to commercial insurers, ($3,609, 95% CI: $3,414 to $3,805) public insurance rates were significantly lower (Medicare: $1,588, 95% CI: $1,484 to $1,693, adjusted difference = -$2,021, p<0.001, Medicaid: $1,403, (95% CI: $1,194 to $1,612, adjusted difference = -$2,206, p<0.001). Listed rates for self-pay patients were not statistically different from commercial rates. CONCLUSIONS: Although pricing for high volume elective hand surgeries is frequently reported, a high proportion of hospitals do not report prices. These data highlight the need for future transparency policy to include pricing for high-volume hand surgery to give patients the ability to make financially informed choices. These results are a valuable aid for surgeons and patients to promote financially conscious decisions.

Post-Bariatric Panniculectomy: Postoperative Complications by Weight Loss Surgery Type.

BACKGROUND: Over 250,000 patients undergo bariatric surgery each year in the United States. Approximately 21% will undergo subsequent body contouring after massive weight loss. Patients with prior bariatric surgery are at a greater risk for complications relative to the general population. However, it is unknown if bariatric surgery type is associated with differential complication risk after panniculectomy. METHODS: A retrospective chart review of post-bariatric who underwent abdominal panniculectomy at a single large quaternary care center was performed. Postoperative complications were graded according to the Clavien-Dindo classification. Descriptive statistics, multivariable logistic regression, and power calculations were performed. RESULTS: In total, 216 patients were included. Restrictive bariatric surgery accounted for 48.6% while 51.3% had a history of malabsorptive bariatric surgery. The overall rate of complications was 34.3% (restrictive: 36.2%; malabsorptive: 32.8%, p=0.66). Wound complications were observed in 25.5% (n=55) of patients. Systemic complications occurred in 11.1% of patients overall, with statistically similar rates between restrictive and malabsorptive groups. After adjusting for both patient and operative factors, no significant difference in total complications (OR=1.15, 95% CI: 0.47 to 2.85, p=0.76), systemic complications (OR=0.26, 95% CI: 0.05 to 1.28, p=0.10), or wound complications (OR=2.31, 95% CI: 0.83 to 6.41, p=0.11) was observed. CONCLUSIONS: Complications following panniculectomy in bariatric surgery patients is high and predominantly related to wound healing. No significant difference between type of bariatric surgery and complication risk was found.

Quasi-Experimental Design for Health Policy Research: A Methodology Overview.

SUMMARY: Health policy impacts all aspects of the authors' field. Research on this topic informs future policy direction and serves as an impactful means to advocate for their patients. The present work aims to promote policy research in plastic surgery. To accomplish this goal, the authors discuss quasi-experimental research design. The authors include in-depth discussion regarding study techniques that are well suited to health policy, including interrupted time series, difference-in-differences analysis, regression discontinuity design, and instrumental variable design. For each study design, the authors discuss examples and potential limitations.

Regional Implicit Racial Bias and Rates of Breast Reconstruction, Complications, and Cost Among US Patients With Breast Cancer.

Importance: Racial disparities influencing breast reconstruction have been well-researched; however, the role of implicit racial bias remains unknown. An analysis of the disparities in care for patients with breast cancer may serve as a policy target to increase the access and quality of care for underserved populations. Objective: To identify whether variations in implicit racial bias by region are associated with the differences in rates of immediate breast reconstruction, complications, and cost for White patients and patients from minoritized racial and ethnic groups. Design, Setting, and Participants: This cohort study used data from the National Inpatient Sample (NIS) from 2009 to 2019. Adult female patients with a diagnosis of or genetic predisposition for breast cancer receiving immediate breast reconstruction at the time of mastectomy were included. Patients receiving both autologous free flap and implant-based reconstruction were included in this analysis. US Census Bureau data were extracted to compare rates of reconstruction proportionately. The Implicit Association Test (IAT) was used to classify whether implicit bias was associated with the primary outcome variables. Data were analyzed from April to November 2022. Exposure: IAT score by US Census Bureau geographic region. Main Outcomes and Measures: Variables of interest included demographic data, rate of reconstruction, complications (reconstruction-specific and systemic), inpatient cost, and IAT score by region. Spearman correlation was used to determine associations between implicit racial bias and the reconstruction utilization rate for White patients and patients from minoritized racial and ethnic groups. Two-sample t tests were used to analyze differences in utilization, complications, and cost between the 2 groups. Results: A total of 52 115 patients were included in our sample: 38 487 were identified as White (mean [SD] age, 52.0 [0.7] years) and 13 628 were identified as minoritized race and ethnicity (American Indian, Asian, Black, and Hispanic patients and patients with another race or ethnicity; mean [SD] age, 49.7 [10.5] years). Implicit bias was not associated with disparities in breast reconstruction rates, complications, or cost. Nonetheless, the White-to-minoritized race and ethnicity utilization ratio differed among the regions studied. Specifically, the reconstruction ratio for White patients to patients with minoritized race and ethnicity was highest for the East South Central Division, which includes Alabama, Kentucky, Mississippi, and Tennessee (2.17), and lowest for the West South Central Division, which includes Arkansas, Louisiana, Oklahoma, and Texas (0.75). Conclusions and Relevance: In this cohort study of patients with breast cancer, regional variation of implicit bias was not associated with differences in breast reconstruction utilization, complications, or cost. Regional disparities in utilization among racial and ethnic groups suggest that collaboration from individual institutions and national organizations is needed to develop robust data collection systems. Such systems could provide surgeons with a comparative view of their care. Additionally, collaboration with high-volume breast centers may help patients in low-resource settings receive the desired reconstruction for their breast cancer care, helping improve the utilization rate and quality of care.

Medicare Eligibility and Racial and Ethnic Disparities in Operative Fixation for Distal Radius Fracture.

Importance: Medicare provides near-universal health insurance to US residents aged 65 years or older. How eligibility for Medicare coverage affects racial and ethnic disparities in operative management after orthopedic trauma is poorly understood. Objective: To assess the association of Medicare eligibility with racial and ethnic disparities in open reduction and internal fixation (ORIF) after distal radius fracture (DRF). Design, Setting, and Participants: This retrospective cohort study with a regression discontinuity design obtained data from the Healthcare Cost and Utilization Project all-payer statewide databases for Florida, Maryland, and New York. These databases contain encounter-level data and unique patient identifiers for longitudinal follow-up across emergency departments, outpatient surgical centers, and hospitals. The cohort included patients aged 57 to 72 years who sustained DRFs between January 1, 2016, and November 30, 2019. Data analysis was performed between March 1 and October 15, 2023. Exposure: Eligibility for Medicare coverage at age 65 years. Main Outcomes and Measures: Type of management for DRF (closed treatment, external fixation, percutaneous pinning, and ORIF). Time to surgery was ascertained in patients undergoing ORIF. Multivariable logistic regression and regression discontinuity design were used to compare racial and ethnic disparities in patients who underwent ORIF before or after age 65 years. Results: A total of 26 874 patients with DRF were included (mean [SD] age, 64.6 [4.6] years; 22 359 were females [83.2%]). Of these patients, 2805 were Hispanic or Latino (10.4%; hereafter, Hispanic), 1492 were non-Hispanic Black (5.6%; hereafter, Black), and 20 548 were non-Hispanic White (76.5%; hereafter, White) and 2029 (7.6%) were individuals of other races and ethnicities (including Asian or Pacific Islander, Native American, and other races). Overall, 32.6% of patients received ORIF but significantly lower use was observed in Black (20.2% vs 35.4%; P < .001) and Hispanic (25.8% vs 35.4%; P < .001) patients compared with White individuals. After adjusting for potential confounders, multivariable logistic regression analysis confirmed the disparity in ORIF use in Black (odds ratio [OR], 0.60; 95% CI, 0.50-0.72) and Hispanic patients (OR, 0.82; 95% CI, 0.72-0.94) compared with White patients. No significant difference in ORIF use was found among racial and ethnic groups at age 65 years. The expected disparity in ORIF use between White and Black patients at age 65 years without Medicare coverage was 12.6 percentage points; however, the actual disparity was 22.0 percentage points, 9.4 percentage points (95% CI, 0.3-18.4 percentage points) greater than expected, a 75% increase (P = .04). In the absence of Medicare coverage, the expected disparity in ORIF use between White and Hispanic patients was 8.3 percentage points, and this result persisted without significant change in the presence of Medicare coverage. Conclusions and Relevance: Results of this study showed that surgical management for DRF was popular in adults aged 57 to 72 years, but there was lower ORIF use in racial or ethnic minority patients. Medicare eligibility at age 65 years did not attenuate race and ethnicity-based disparities in surgical management of DRFs.

Pancreatic neuroendocrine tumors: Surgical outcomes and survival analysis.

BACKGROUND: Pancreatic neuroendocrine tumors are rare, with rising incidence and limited clinicopathological studies. METHODS: Adult patients with pNET at a single tertiary care center were retrospectively evaluated. RESULTS: In total, 87 patients with histologically confirmed pNET who underwent resection were evaluated. 11% of patients had functioning pNETs: 9 insulinoma and 1 VIPoma. The majority (88.5%) were nonfunctioning. The most common surgical procedure performed was distal pancreatectomy with splenectomy (36.8%). 35.6% of cases were performed with minimally invasive surgery (MIS). MIS patients had fewer postoperative complications, shorter length of stay, and fewer ICU admissions.Disease-free survival (DFS) was unaffected by tumor size (p = 0.5) or lymph node status (p = 0.62). Patients with high-grade (G3) tumors experienced significantly shorter DFS (p = 0.02). CONCLUSIONS: This series demonstrates that survival in patients with pNET is driven mostly by tumor grade, though overall most have long-term survival after surgical resection. Additionally, an MIS approach is efficacious in appropriately selected cases.

Non-Hispanic Blacks undergoing distal pancreatectomy have higher risk-adjusted rates of morbidity and are more likely to be high-cost outliers.

BACKGROUND: Few studies evaluate racial disparities in costs and clinical outcomes for patients undergoing distal pancreatectomy (DP). METHODS: We queried the Healthcare Cost and Utilization Project State Inpatient Databases to identify patients undergoing DP. Multivariable regression (MVR) was used to evaluate the association between race and postoperative outcomes. RESULTS: 2,493 patients underwent DP; 265 (10%) were black, and 221 (8%) were of Hispanic ethnicity. On MVR, black and Hispanic patients were less likely than whites to undergo surgery in high volume centers (OR 0.53, 95% CI [0.40, 0.71]; OR 0.45, 95% CI [0.32, 0.62]). Black patients had a greater risk of postoperative complication (OR 1.40, 95% CI [1.07, 1.83]), 90-day readmission (OR 1.53, 95% CI [1.15, 2.02]), prolonged length of stay (OR 1.74, 95% CI [1.25-2.44]), and of being a high cost outliers (OR 1.40, 95% CI [1.02, 1.91]) compared to white patients. CONCLUSION: Black patients have increased risk of having a postoperative complication, prolonged hospitalization, and of being a high-cost outlier than non-Hispanic whites.

Association of obesity with postoperative outcomes after proctectomy.

BACKGROUND: Prior efforts evaluating obesity as a risk factor for postoperative complications following proctectomy have been limited by sample size and uniform outcome classification. METHODS: The ACS NSQIP was queried for patients with non-metastatic rectal adenocarcinoma who underwent elective proctectomy. After stratification by BMI classification, multivariable modeling was used to identify the effect of BMI class on adjusted risk of 30-day outcomes controlling for patient, procedure, and tumor factors. RESULTS: Of 2241 patients identified, 33.4% had a normal BMI, 33.5% were overweight, 21.1% were obese, and 12.0% were morbidly obese. Increased risk of superficial surgical site infection (SSI) was observed in obese (OR 2.42, 95%CI:[1.36-4.29]) and morbidly obese (OR 3.29, 95%CI:[1.77-6.11]) patients when compared to normal BMI. Morbid obesity was associated with increased risk of any complication (OR 1.44, 95%CI:[1.05-1.96]). BMI class was not associated with risk adjusted odds of anastomotic leak. CONCLUSIONS: Morbid obesity is independently associated with an increased composite odds risk of short-term morbidity following elective proctectomy for cancer primarily due to increased risk of superficial SSI.

Recurrent pseudoaneurysm after carotid endarterectomy.

Pseudoaneurysms and patch infections are known complications of carotid endarterectomy with patch angioplasty. Although they are rare occurrences, they carry high morbidity and almost uniformly require surgical intervention. Infectious pathogens are often gram-positive bacteria, most commonly Staphylococcus species, whereas gram-negative infections are less frequently observed. We present a case of recurrent pseudoaneurysm in a patient who had a carotid endarterectomy with bovine pericardial patch angioplasty complicated by Pasteurella multocida infection. This case demonstrates the need for recognition and consideration of a broad differential of pathogens in evaluating and treating vascular infections.

4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling.

We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including 4-Hydroxynonenal (4-HNE). 4-HNE is notorious for producing protein post-translation modification (PTM) via reactions with the amino acids: cysteine, histidine and lysine. Thus, we sought to determine if 4-HNE mediated post-translational modification of TRPV1 could account for dysfunctional TRPV1-mediated signaling observed in diabetes. Our initial studies demonstrate 4-HNE infusion decreases TRPV1-dependent coronary blood flow in C57BKS/J (WT) mice. Further, we found that TRPV1-dependent vasorelaxation was suppressed after 4-HNE treatment in isolated mouse coronary arterioles. Moreover, we demonstrate 4-HNE significantly inhibited TRPV1 currents and Ca2+ entry utilizing patch-clamp electrophysiology and calcium imaging respectively. Using molecular modeling, we identified potential pore cysteines residues that, when mutated, could restore TRPV1 function in the presence of 4-HNE. Specifically, complete rescue of capsaicin-mediated activation of TRPV1 was obtained following mutation of pore Cysteine 621. Finally, His tag pull-down of TRPV1 in HEK cells treated with 4-HNE demonstrated a significant increase in 4-HNE binding to TRPV1, which was reduced in the TRPV1 C621G mutant. Taken together these data suggest that 4-HNE decreases TRPV1-mediated responses, at both the in vivo and in vitro levels and this dysfunction can be rescued via mutation of the pore Cysteine 621. Our results show the first evidence of an amino acid specific modification of TRPV1 by 4-HNE suggesting this 4-HNE-dependent modification of TRPV1 may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.