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Objective: This study analyzes indications and outcomes of premaxillary setback (PS) and presents an algorithm for its use in patients with bilateral cleft lip and/or palate (BCL ± P)., Design: Retrospective review., Setting: Children's Hospital Los Angeles., A retrospective review was conducted evaluating patients with BCL ± P undergoing lip repair from 2003-2023. Patients were categorized as undergoing repair with (BCL + PS) or without (BCL-PS) simultaneous PS. Presurgical nasoalveolar molding (NAM), indications for PS, timing of surgery, and complications were collected., Interventions: BCL with PS, BCL + PS., Main Outcome Measures(s): Primary outcomes included rates of postoperative complications and revision surgeries. Secondary outcome was the need for orthognathic surgery to correct midface hypoplasia in patients at least 14 years old at their most recent follow-up., Results: Of 1193 patients, 262 met inclusion criteria. One hundred forty-nine patients (56.9%) were referred for NAM. Fifty-one patients (19.5%) underwent PS during primary BCL repair. Patients who failed repositioning of the premaxilla following presurgical NAM (n = 12) were not candidates for NAM (n = 31) or presented late with a protruding premaxilla (n = 8, 12.977 ± 8.196 months) underwent PS. Median age at surgery was 4.29 months. Complications included wound dehiscence (n = 3) and abscess formation (n = 2). No premaxillary necrosis occurred. Overall revision rates were 9.9%. Of 41 patients over 14 years old, 53.6% needed orthognathic surgery. BCL + PS had comparable rates of wound dehiscence (2.0% vs 4.0%; P  = .790), lip revisions (7.8% vs 10.4%; P  = .770), and orthognathic surgery (50.0% vs 56.3%; P  > .999)., Conclusion: PS is a safe and effective method to facilitate BCL repair in patients who are not candidates for NAM., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Although blood loss in microsurgical reconstruction is rarely large enough to be life-threatening, preoperative anemia can be a particular issue in terms of postoperative morbidity, impaired wound healing, and compromised tissue viability. We seek to review the effect of preoperative hemoglobin (Hgb) levels on perioperative blood transfusion (PBT) requirements and complications to guide management of patients with preexisting anemia undergoing reconstruction., Methods: PubMed, Embase, and Scopus were queried for relevant articles. Inclusion criteria were as follows: original studies investigating outcomes and PBT requirements in flap-based reconstruction based on preoperative Hgb levels. Patient and study characteristics were analyzed using descriptive statistics. A meta-analysis was conducted to assess transfusion requirements across the included studies using Stata (version 18.0 Stata Corp, College Station, Texas, USA). The Fisher method was used to aggregate individual study p values into a single combined value to statistically assess the combined findings, where a p value of < 0.05 was set as statistically significant., Results: One thousand three hundred and eighty-nine studies were screened for title and abstract relevance, 14 of which met the inclusion criteria, including a total of 61,116 patients. Meta-analysis of the studies revealed a PBT requirement of 36.2% for anemic individuals, significantly higher than the 20.0% for those with normal preoperative Hgb levels (p < 0.001), with an average 4.9 versus 2.4 units of packed red blood cells being transfused (p < 0.001). The majority of studies concluded that preoperative anemia was associated with medical complications, such as myocardial infarction, stroke, and infection (p < 0.001). While six studies reported a significant relationship between low preoperative Hgb and flap morbidity (flap loss and partial flap necrosis), two studies found no correlation. The overall postoperative complication rate across the studies was 42.2% among patients with low preoperative Hgb levels, whereas the nonanemic group demonstrated a markedly lower rate of 13.9% (p < 0.001)., Conclusion: The existing evidence is strongly suggestive of increased PBT requirement in patients with anemia, highlighting the necessity for preoperative optimization of Hgb levels and intraoperative monitoring. While preliminary evidence demonstrates a relationship between anemia and medical complications, more research is warranted to characterize the specific association between preoperative Hgb levels and flap morbidity., (© 2024 Wiley Periodicals LLC.)

Self-inflicted burns (SIBs) represent a distinct entity in burn care often associated with an underlying psychiatric etiology. In this review, we summarize the existing evidence on SIBs in North America to inform targeted prevention and interventions for patients afflicted with SIBs. The following databases were queried to identify relevant articles used for literature review: PubMed, Embase, and Scopus. The main outcome measures were burn characteristics and risk factors of SIBs in the American population. A total of 14,189 patients were included across 13 included studies. The percent of total body surface area burned ranged from less than one to 100%, with a mean of 29.6 +/- 20.7%. Depressive disorders were the most reported overall; however, among mood disorders, bipolar disorder was also reported frequently, while anxiety was reported least. Motives for self-inflicting burn injury included premeditated self-injury as a coping mechanism, escape or response to delusions, impulsive self-injury, and most commonly, suicidal intention. The majority of the studies reported that pre-admission drug and alcohol abuse were associated with the occurrence of SIBs. Other identified risk factors for SIB injury included female sex, younger age, unemployment, and unmarried status. From this, it is imperative that targeted interventions are developed to address the complex interplay of psychiatric disorders, drug use, and other demographic risk factors among the American population. It is crucial for initiatives to emphasize early identification of individuals at-risk of self-harm, better access to mental health services, and stronger drug abuse programs to target SIB occurrence in the U.S.., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Secondary alveolar bone grafting (SABG) during mixed dentition is the standard of care for patients with complete cleft of lip and palate. Early SABG (E-SABG; 4 to 7 y) occurs before the eruption of lateral incisors, whereas late SABG (L-SABG; 8 to 12 y) occurs before the eruption of maxillary permanent canines. This study compares outcomes of E-SABG versus L-SABG among patients with unilateral cleft of lip and palate (UCLP). A prospective cohort study was conducted evaluating nonsyndromic patients with UCLP who underwent SABG from April 2018 to January 2020, 48 consecutive patients with UCLP were included. Preoperative and 6 to 10-month postoperative cone beam computed tomography imaging were obtained to assess graft and periodontal outcomes. Among 48 patients with UCLP, of which 21 were in the E-SABG group (6.9 ± 1.1 y), and 28 were in the L-SABG cohort (10.4 ± 1.6 y). The initial alveolar cleft width is significantly smaller in the E-SABG cohort compared with the L-SABG cohort (5.1 ± 1.5 versus 6.5 ± 2.0 mm, P = 0.008). Compared with the L-SABG cohort, the E-SABG cohort had higher rates of bony bridge formation (77.3% versus 65.4%, P= 0.367), thicker bony bridges (5.7 ± 2.1 versus 3.9 ± 1.5 mm, P= 0.004), lower Bergland scores [1.5 (interquartile range: 1 to 2) versus 2.25 (interquartile range: 1.5 to 3.5), P= 0.026], and greater alveolar bone coverage (79.8 ± 16.7% versus 67.9 ± 18.1%, 0.024). The authors' findings suggest that patients who undergo E-SABG at ∼7 years may have better graft outcomes and benefits to the periodontal bone support on cleft-adjacent incisor compared with L-SABG at 11 years., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Glucagon-like peptide-1 (GLP-1) agonists mimic the action of GLP-1, a hormone that regulates blood glucose levels via stimulation of insulin release and inhibition of glucagon secretion. After burn, the current literature suggests that the use of GLP-1 agonists results in less insulin dependence with similar glucose control and hypoglycemic events to patients receiving a basal-bolus insulin regimen. GLP-1 agonists may also promote wound healing through various mechanisms including angiogenesis and improved keratinocyte migration. Despite the potential benefits, GLP-1 agonists reduce gastrointestinal motility which impacts their widespread adoption in burn care. This dysmotility can result in inadequate nutrition delivery, unintentional weight loss, and is a potential aspiration risk. The net impact of these medications on burn patients is unclear. Given their potential to demonstrate the safety, efficacy, and optimal dosing of various GLP-1 agonists in acute burn management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Timely admission to the burn unit is crucial. Ideal burn care requires prompt interventions such as wound and body temperature management, infection control, and fluid resuscitation to prevent complications like burn progression and infection. In this study, we identify specific factors and outcomes associated with delayed admission to a regional burn center., Methods: Patients admitted to a large urban burn center from January 2015 to December 2023 were retrospectively queried, with subsequent collection of demographic and outcome variables from chart review. Descriptive statistics, Welch's t-tests of unequal variances, and Chi-square analysis were performed. Multiple logistic regression was performed to explore the association between delayed admission and ICU stay, ventilator requirements, and mortality., Results: A total of 3137 patients were included in the study. Approximately 63.4 % of patients were admitted within 24 h, while 36.6 % had a significant delay in care of over 24 h after injury. Male patients were likely to experience delayed admission (39.0 vs. 31.8 %, p < 0.001). There was no significant difference in age between the two cohorts (38.6 vs. 39.7 years, p = 0.199). There was no significant difference in time to admission by racial background (p = 0.061). Total body surface area burned (TBSA) varied between the delayed and control cohorts (15.5±18.7 % vs. 8.2±12.9 %, p < 0.001). Patients who were single (p < 0.001) and lived alone (p = 0.011) were more likely to experience a delay in burn unit admission. Homelessness (p < 0.001), substance abuse disorder (p < 0.001), and uninsured status (p < 0.001) were also associated with delayed admission. In regression analysis when controlling for TBSA, delay in care was significantly associated with a greater requirement for ICU stay (p < 0.001) and mechanical ventilation (p = 0.021) but was not associated with increased mortality (p = 0.232)., Conclusion: Sociodemographic variables such as homelessness, lack of social support, and substance abuse are associated with delayed burn unit admission. Knowledge of these factors can inform future interventions to improve outcomes for vulnerable patients, promoting better recovery and long-term outcomes after burn injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Soft tissue procedures are often crucial for normalizing the long-term facial appearance in patients with syndromic craniosynostosis, yet they are underrepresented in the literature and existing treatment algorithms. This study evaluated secondary soft tissue surgeries in relation to skeletal operations in patients with syndromic craniosynostosis., Methods: A retrospective review evaluated patients with syndromic craniosynostosis treated at a tertiary children's hospital from 2003 to 2023. Craniofacial skeletal and soft tissue procedures were assessed for timing and frequency. Skeletal surgeries included redo fronto-orbital advancements, monobloc advancement/distraction ± facial bipartition, and LeFort III or III/I advancement/distraction. Soft tissue surgeries encompassed oculoplastic procedures, scalp reconstruction, fat grafting, and septorhinoplasty., Results: Of 106 patients with syndromic craniosynostosis, 57 (57.8%) underwent ≥1 secondary skeletal operation, and 101 (95.3%) underwent ≥1 soft tissue procedures, averaging 3.7 ± 3.3 soft tissue procedures per patient. Patients who underwent secondary forehead advancement had significantly higher rates of subsequent lateral canthopexy (71.4% vs 25.6, P < 0.001), ptosis reconstruction (17.9% vs 7.7%, P = 0.025), and frontotemporal fat grafting (50.0% vs 15.4%, P < 0.001) than those who did not. Patients who underwent midface advancement surgery had significantly higher rates of subsequent lateral canthopexy (65.4% vs 11.1%, P < 0.001), medial canthopexy (7.7% vs 0.0%, P = 0.038), scalp reconstruction (36.5% vs 16.7%, P = 0.020), frontotemporal fat grafting (34.6% vs 14.8%, P = 0.018), malar fat grafting (11.5% vs 0.0%, P = 0.010), and septorhinoplasty (26.9% vs 1.9%, P < 0.001) than those who did not. Specifically, LeFort III or III/I advancement/distractions were significantly associated with higher rates of subsequent septorhinoplasties (33.3% vs 1.6%, P < 0.001). The mean follow-up was 10.2 ± 7.0 years., Conclusions: This study revealed an intricate interplay between skeletal and soft tissue surgery in patients with syndromic craniosynostosis. Exploring techniques to reduce the need for further corrective surgery and anticipating necessary secondary interventions may improve patient counseling and outcomes., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Lower extremity (LE) reconstruction in the elderly population presents a multifaceted challenge, primarily due to age-related degenerative changes, comorbidities, and functional decline. Elderly individuals often encounter conditions such as osteoarthritis, osteoporosis, and cardiovascular and peripheral artery disease (PAD), which can severely compromise the structural integrity and function of the lower limbs. As such, we aim to assess postoperative complications and functional recovery following LE reconstruction in elderly patients., Methods: Patients ≥ 18 years who underwent post-traumatic LE reconstruction with flap reconstruction at a Level 1 trauma center between 2007 and 2022 were included. Patient demographics, flap/wound characteristics, complications, and ambulation for the elderly (≥ 60 years old) and the control (< 60 years old) cohorts were recorded. The primary outcome was final ambulation status, modeled with logistic regression. Secondary outcomes included postoperative complications., Results: The mean ages of the control (n = 374) and elderly (n = 49) groups were 37.4 ± 12.6 and 65.8 ± 5.1 years, respectively. Elderly patients more frequently required amputation after flap surgery (p = 0.002). There was no significant difference between the two cohorts in preoperative ambulation status (p = 0.053). Postoperatively, 22.4% of elderly patients were independently ambulatory at final follow-up, compared to 49.5% of patients < 60. Of the elderly, 14.3% could ambulate with an assistance device (cane, walker, etc.), compared to 26.5% in the control group. A wheelchair was required for 46.9% of elderly patients, significantly higher than the 22.7% of those < 60 years of age (p < 0.001). Multivariate regression confirmed an association between older age and nonambulatory final status (p = 0.033)., Conclusion: LE reconstruction can likely be performed safely in patients 60 years of age or older. However, older age is independently associated with significantly worse postoperative ambulation. Preoperative assessment, including gait and muscle strength, and early initiation of postoperative rehabilitation can potentially improve ambulation in elderly individuals undergoing LE reconstruction., (© 2024 Wiley Periodicals LLC.)

The pathogenesis of craniosynostosis, characterized by the premature fusion of calvarial sutures, is multifaceted and often the result of an amalgamation of contributing factors. The current study seeks examine the possible contributors to craniosynostosis development and its surgical trends over time. A multicenter/national retrospective cohort study was conducted of patients who underwent surgical repair of craniosynostosis (n=11,279) between 2012 and 2021 identified in the American College of Surgeons National Surgical Quality Improvement Program Pediatric Data File. Main outcome measures included risk factors and trends relating to surgical repair of craniosynostosis. Nationwide reports of craniosynostosis in the NSQIP-P database have increased between 2012 and 2021 by 195%. The prevalence of craniosynostosis per overall cases has remained between 1.0% and 1.3%. There were predominantly more White male patients in the craniosynostosis cohort ( P <0.001). Craniosynostosis patients had significantly greater birth weights, gestational ages, and were less likely to be premature ( P <0.05). Linear regression demonstrated that operative time, anesthesia time, and length of stay significantly decreased over the study period ( P <0.001). This national data analysis highlights trends in craniosynostosis repair indicating potential improvements in safety and patient outcomes over time. While these findings offer insights for health care professionals, caution is warranted in extrapolating beyond the data's scope. Future research should focus on diverse patient populations, compare outcomes across institutions, and employ prospective study designs to enhance the evidence base for craniosynostosis management. These efforts will help refine diagnostic and treatment strategies, potentially leading to better outcomes for patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background:  Scalp reconstruction in plastic and reconstructive surgery often necessitates the transfer of soft-tissue flaps to restore form and function. The critical decision lies in choosing between muscle-containing (MC) and fasciocutaneous (FC) flaps for scalp reconstruction, and while both variants have their merits, flap composition remains a subject of ongoing debate. This scientific discussion aims to explore this contentious issue through a comprehensive meta-analysis, shedding light on the rationale behind the choice of these flaps and the potential impact on clinical outcomes., Methods:  A comprehensive systematic review was conducted following PRISMA-P guidelines, encompassing six prominent databases up to the year 2023. Data were collected from studies assessing outcomes of MC and FC flaps for scalp reconstruction. Quality evaluation was performed using ASPS criteria and the ROBINS-I tool. Statistical analysis included descriptive statistics, meta-analysis, sensitivity analysis, and assessment of bias using STATA software., Results:  The meta-analysis included 28 nonrandomized studies, totaling 594 flaps (MC: 380, FC: 214). MC flaps were significantly larger than FC flaps. There were no significant differences in flap loss, flap necrosis, or wound dehiscence between the two flap types. However, the incidence of venous congestion was significantly higher in FC flaps. Sensitivity analysis confirmed the robustness of results, and publication bias assessment showed no significant evidence of bias., Conclusion:  While both MC and FC flaps offer viable options for scalp reconstruction, the choice should be tailored to individual patient characteristics and defect size. FC flaps may provide advantages such as shorter operative times and reduced morbidity, whereas MC flaps could be preferred for addressing larger defects. Future research should focus on prospective studies and strategies to mitigate venous congestion in FC flaps, enhancing their safety and efficacy in scalp reconstruction., Competing Interests: None declared., (Thieme. All rights reserved.)

Comprehensive studies on the incidence, risk factors, and prophylactic measures related to venous thromboembolism (VTE) are lacking in burn care. This study characterizes VTE risk and existing prevention measures to improve and inform overall patient care in the field of burn care on a national scale. The US National Trauma Data Bank (NTDB) was queried from 2007 to 2021 to identify burn-injured patients. Descriptive statistics and multivariate regression analyses were used to explore the association between demographic/clinical characteristics and VTE risk as well as compare various VTE chemoprophylaxis types. There were 326,614 burn-injured patients included for analysis; 5,642 (1.7%) experienced a VTE event during their hospitalization. Patients with VTE were significantly older, had greater BMIs and %TBSA, and were more likely to be male (p<0.001). History of smoking, hypertension or myocardial infarction, and/or substance use disorder were significant predictors of VTE (p<0.001). Patients who received low molecular weight heparin (LMWH) were less likely to have VTE compared to patients treated with heparin when controlling for other VTE risk factors (OR: .564 95% CI .523-.607, p<0.001). Longer time to VTE chemoprophylaxis (>6 hours) initiation was significantly associated with VTE (OR=1.04 95% CI 1.03=1.07, p<0.001). This study sheds light on risk factors and chemoprophylaxis in VTE to help guide clinical practice when implementing prevention strategies in burn patients. This knowledge can be leveraged to refine risk stratification models, inform evidence-based prevention strategies, and ultimately enhance the quality of care for burn patients at risk of VTE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background:  Autoimmune diseases are associated with characteristic chronic inflammation, aberrations in tissue perfusion, and hypercoagulability, and thus have considerable implications for local and free-flap reconstruction. We seek to summarize the current evidence on outcomes of flap-based reconstruction in patients with pre-existing autoimmune disease and present our experience with autologous breast reconstruction in this population., Methods:  PubMed, Embase, Scopus, Cochrane, and Web of Science were searched for relevant articles, and pertinent data were presented qualitatively. Institutional data were queried for patients who underwent autologous breast reconstruction with deep inferior epigastric perforator (DIEP) flaps between 2015 and 2024. A retrospective review was conducted to identify DIEP patients with a history of autoimmune disease. Data on patient demographics, medication history, flap outcomes, and perioperative complications were collected., Results:  The majority of existing studies found no increased independent risk of flap complications. However, other complications, predominantly wound dehiscence, were independently associated with autoimmune disease. Regarding immunosuppressant therapy, the literature demonstrated that perioperative glucocorticoid use was consistently associated with all complications, including seroma, infection, wound disruption, and partial flap loss.Our 13-patient institutional experience identified no cases of total flap loss or microvascular thrombotic complications. There was one case of partial flap necrosis further complicated by abdominal site cellulitis, and one case of recipient-site dehiscence managed with local wound care. No patients required re-operation for flap or donor-site complications., Conclusion:  The literature suggests that flap reconstruction can be performed safely in patients with autoimmune conditions, which was also supported by our institutional experience. While there is likely minimal risk of microsurgical complications in the context of free tissue transfer, donor-site morbidity and wound dehiscence remain major concerns for patients with a history of autoimmune disease. Limiting the use of immunosuppressive agents, especially corticosteroids, may potentially improve outcomes of flap reconstruction., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Glucagon-like peptide-1 (GLP-1) agonists, such as exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide, effectively manage type 2 diabetes by promoting insulin release, suppressing glucagon secretion, and enhancing glucose metabolism. They also aid weight reduction and cardiovascular health, potentially broadening their therapeutic scope. In plastic surgery, they hold promise for perioperative weight management and glycemic control, potentially impacting surgical outcomes., Methods: A comprehensive review was conducted to assess GLP-1 agonists' utilization in plastic surgery. We analyzed relevant studies, meta-analyses, and trials to evaluate their benefits and limitations across surgical contexts, focusing on weight reduction, glycemic control, cardiovascular risk factors, and potential complications., Results: Studies demonstrate GLP-1 agonists' versatility, spanning weight management, cardiovascular health, neurological disorders, and metabolic dysfunction-associated liver diseases. Comparative analyses highlight variations in glycemic control, weight loss, and cardiometabolic risk. Meta-analyses reveal significant reductions in hemoglobin A1C levels, especially with high-dose semaglutide (2 mg) and tirzepatide (15 mg). However, increased dosing may lead to gastrointestinal side effects and serious complications like pancreatitis and bowel obstruction. Notably, GLP-1 agonists' efficacy in weight reduction and glycemic control may impact perioperative management in plastic surgery, potentially expanding surgical candidacy for procedures like autologous flap-based breast reconstruction and influencing outcomes related to lymphedema. Concerns persist regarding venous thromboembolism and delayed gastric emptying, necessitating further investigation into bleeding and aspiration risk with anesthesia., Conclusions: GLP-1 agonists offer advantages in perioperative weight management and glycemic control in plastic surgery patients. They may broaden surgical candidacy and mitigate lymphedema risk but require careful consideration of complications, particularly perioperative aspiration risk. Future research should focus on their specific impacts on surgical outcomes to optimize their integration into perioperative protocols effectively. Despite challenges, GLP-1 agonists promise to enhance surgical outcomes and patient care in plastic surgery., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Elevated body mass index (BMI) is a known perioperative risk factor for complications such as delayed wound healing and infection. However, there is a gap in understanding how elevated BMI impacts outcomes after posttraumatic lower extremity (LE) microvascular reconstruction., Methods: A retrospective review was performed at a level 1 trauma center between 2007 and 2022 of patients who underwent posttraumatic microvascular LE reconstruction. Demographics, flap/wound details, complications, and outcomes were recorded. Patients were stratified into BMI Center for Disease Control categories., Results: A total of 398 patients were included with an average BMI of 28.2 ± 5.8. Nearly half (45%) of LE defects were located in the distal third of the leg, 27.5% in the middle third, and 34.4% in the proximal third. Most reconstructions utilized muscle-containing flaps (74.4%) compared with fasciocutaneous flaps (16.8%). Surgical approaches included free flaps (47.6%) and local flaps (52.5%). Class III obese patients were significantly more likely to be nonambulatory than nonobese patients (OR: 4.10, 95% CI 1.10-15.2, p = 0.035). At final follow-up, 30.1% of patients with Class III obesity were ambulatory, requiring either wheelchairs (42.3%) or assistance devices (26.9%). There were no significant differences in complication rates based on obesity status (0.704). The average follow-up time for the entire cohort was 5.8 years., Conclusions: BMI is critical for patient care and surgical decision-making in LE reconstruction. Further research is warranted to optimize outcomes for higher BMI patients, thereby potentially reducing the burden of postoperative complications and enhancing overall patient recovery., (© 2024 Wiley Periodicals LLC.)

Online patient education materials (PEMs) on lymphedema surgery were assessed for quality, readability, and content. A total of 37 PEMs were identified, primarily authored by academic/medical organizations. Readability scores indicated materials were difficult to read, with an average Flesch-Kincaid Grade Level of 10.4. PEM Assessment Tools showed acceptable understandability (72.3%) but poor actionability (28.5%). PEMs often lacked information on surgical risks, postoperative care, and long-term follow-up. Simplifying language and adding visual aids could improve PEM effectiveness., (© 2024 Wiley Periodicals LLC.)

Background: Cyanide poisoning poses a significant threat to burn patients exposed to smoke in residential or workplace fires, leading to central nervous system dysfunction, hemodynamic instability, cardiovascular collapse, and death. Prompt administration of an effective antidote is critical. Hydroxocobalamin, a form of vitamin B12, is the gold standard treatment for cyanide toxicity, by binding to cyanide molecules and converting them into non-toxic cyanocobalamin that is eliminated by the kidneys. This mechanism is distinct from previous cyanide antidotes, which induce the formation of methemoglobin to bind to cyanide. Recent case studies have reported elevated methemoglobin levels after hydroxocobalamin administration, raising concerns regarding its safety. The current study investigates smoke inhalation patients treated with hydroxocobalamin at a single institution Burn Unit in hopes of enhancing our understanding of the complexities surrounding cyanide antidote therapy., Methods: After Institutional Board Approval, a retrospective cohort study was conducted. Our sample comprised burn patients with inhalation injury admitted to a single institution from 2013 to 2023 and treated with hydroxocobalamin for suspected cyanide toxicity. We also analyzed a matched control cohort of similar patients with inhalation injury not treated with hydroxocobalamin. We analyzed changes and peaks in methemoglobin levels, lactate levels, blood urea nitrogen (BUN) and creatinine, ventilator days, % total body surface area (TBSA), various types of medications and dressings, and mortality. Statistical analyses included t-tests, chi-square, linear and logistic regressions, and correlation analysis., Results: In the study, 36 patients with suspected inhalation injury were treated with hydroxocobalamin at the Los Angeles General (LAG) Burn Unit from 2013 to 2023, who were matched to 32 control patients with inhalation injury who were not treated with hydroxocobalamin. Demographic and baseline characteristics showed no statistically significant differences between the groups, including age, gender, BMI, and %TBSA. No significant differences were found in initial, final, peak, or change in methemoglobin levels. The study also revealed no significant disparities in initial lactate levels, mortality, kidney function tests, ventilator days, surgeries, or use of medications/treatments (e.g., Silvadene dressings, Vitamin C) between the two groups. When controlling for covariates, multiple linear regression analysis (age, gender, and %TBSA) indicated that hydroxocobalamin administration was not significantly associated with changes in methemoglobin or mortality. Increased %TBSA, however, was linked to elevated lactate levels., Conclusions: Our investigation sought to assess the potential risks associated with hydroxocobalamin administration in burn patients with concomitant inhalation injury. Contrary to our initial hypothesis, we found no statistically significant differences in methemoglobinemia, lactate levels, mortality, or kidney function. The influence of other factors, such as methemoglobinemia-inducing drugs or hydroxocobalamin's interference with co-oximetry, adds complexity. Although elevated methemoglobin levels were observed in some cases, their clinical significance was limited. However, this study's limitations, particularly the rarity of inhalation injury cases with concern for cyanide toxicity, warrant consideration. Further research is required to comprehensively elucidate the impact of hydroxocobalamin administration on burn patients' outcomes., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest or financial disclosures related to this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Despite the growing recognition of self-harm as a pressing public health issue, demographic risk factors of self-inflicted burn (SIB) injuries in the U.S. have not been extensively described. In this retrospective study, we seek to identify demographic risk factors and patterns associated with SIB injuries at an urban burn center. Charts were reviewed of patients admitted to a single American Burn Association (ABA)-verified burn unit between 2015 and 2023 with a history of SIB injury, identified with ICD10 code X76.XXXA. Descriptive statistics, Welch's t-test of unequal variances, and Chi-Squared-analysis were performed. A total of 3,212 patients were admitted to our institution for management of acute burn injury, with 94 (2.9%) patients who presented with SIB injury. SIB patients were more likely than the control cohort to be male (p = 0.035), single (p=0.008), unhoused (p < 0.001), live alone (p < 0.001), and have documented psychiatric diagnoses (72.3% vs. 2.1%, p < 0.001). They had larger %TBSA affected (p < 0.001) and higher rates of inhalation injury (p < 0.001). The SIB cohort also showed significantly higher rates of positive urine toxicology results, primarily for stimulants and opiates (p < 0.001). Patients with SIBs had longer hospital stays (21.7 ± 2.6 days vs. 12.0 ± 22.1 days, p = 0.006), higher rates of ICU admission (p < 0.001), and mechanical ventilation requirement (p < 0.001). Mental health support services, substance abuse rehabilitation programs, and community outreach need to be prioritized, especially targeting vulnerable populations such as the unhoused., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The timing of primary repair in nonsyndromic cleft palate remains controversial. Recent evidence suggests earlier repair is associated with a lower incidence of velopharyngeal insufficiency (VPI). The authors aim to evaluate these findings in a large cohort study using causal inference., Methods: All nonsyndromic cleft palate repairs in California were extracted between 2000 and 2021 from the California Health Care Access and Information (HCAI) database. Cases were linked with VPI surgery following cleft palate repair based on unique identifiers. The main outcome measure was incidence of VPI surgery evaluated with propensity score matching. Early cleft palate repair was defined as <7 months of age versus traditional cleft palate repair at >11 months of age. Standardized mean differences (SMD) were measured before and after matching for potential confounders including sex, race, payer, and distance from patient home to hospital., Results: In all, 52,007 cleft palate repairs were included, of which 12,169 (23.3%) were repaired early and 39,838 (76.7%) were repaired traditionally. Early cleft palate repairs underwent VPI surgery in 1.2% (13/1,000) of cases, compared with 6.1% (61/1000) in the traditional repair cohort. Post-matching, the average treatment effect of early repair was a 6.3% reduction in VPI surgery (P<0.001, 95% CI -6.3, -5.4%). All covariate SMDs were <|0.1| after matching., Conclusion: Our cohort study demonstrates a significantly reduced incidence of VPI surgery in children with primary cleft palate repair <7 months of age. Craniofacial centers should consider early cleft palate repair in appropriate patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Surgical treatment of pediatric maxillary and mandibular tumors can cause significant postresection disfigurement, mastication, and speech dysfunction. The need to restore form and function without compromising growth at the recipient and donor sites poses a particular reconstructive dilemma. This study evaluates outcomes of the custom endoprosthesis (CE) compared with noncustom reconstruction (NCR) and introduces an algorithm using CE to optimize available soft tissue reconstructive options. An Institutional Review Board-approved retrospective review of all patients undergoing maxillary or mandibular reconstruction between 2016 and 2022 was completed. The independent variable of interest was CE utilization. Primary outcomes of interest included hardware failure/removal or exposure, major complications, and revision surgeries. Covariates of interest included patient demographics, medical comorbidities, tumor size, and pathologic diagnosis. Statistical analyses including independent t test, χ2 analyses, and univariate/multivariate logistic regression were performed using RStudio version 4.2.1. Fifty-one patients (37 mandible and 14 maxilla) underwent CE or NCR. Of patients, 37% (n = 19) received CE. Of patients who underwent mandibular reconstruction, there were significantly lower rates of hardware exposure (14.3% versus 47.8%, P = 0.018), failure (7.1% versus 43.5%, P = 0.048), major complications (28.6% versus 78.2%, P = 0.008), and revisions (11.1% versus 50.0%, P = 0.002) in the CE cohort compared with the NCR cohort. The rates of hardware failure, exposure, major complications, and revisions did not significantly differ in maxillary reconstructions, however, CE successfully reconstructed significantly larger defects (179.5 versus 74.6 cm3, P = 0.020) than NCRs. Deviating from NCR, the authors propose an algorithm considering anatomical location, extent of resection, and patient age for soft tissue selection. This algorithm yielded improved mandibular reconstructive outcomes and no increase in complications rate in maxillary reconstruction despite larger resection defects. Furthermore, the authors' initial findings demonstrate that CE is a safe option for pediatric maxillary and mandibular reconstruction that may, in addition, facilitate improved form and function., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background:  Historically, the use of intraoperative vasopressors during free flap lower extremity (LE) reconstruction has been proposed to adversely affect flap survival due to concerns about compromising flap perfusion. This study aims to analyze the impact of intraoperative vasopressor use and fluid administration on postoperative outcomes in patients undergoing traumatic LE reconstruction., Methods:  Patients who underwent LE free flap reconstruction between 2015 and 2023 at a Level I Trauma Center were retrospectively reviewed. Statistical analysis was conducted to evaluate the association between vasopressor use and intraoperative fluids with partial/complete flap necrosis, as well as the differential effect of vasopressor use on flap outcomes based on varying fluid levels., Results:  A total of 105 LE flaps were performed over 8 years. Vasopressors were administered intraoperatively to 19 (18.0%) cases. Overall flap survival and limb salvage rates were 97.1 and 93.3%, respectively. Intraoperative vasopressor use decreased the overall risk of postoperative flap necrosis (OR 0.00005, 95% CI [9.11 × 10 -9 -0.285], p  = 0.025), while a lower net fluid balance increased the risk of this outcome (OR 0.9985, 95% CI [0.9975-0.9996], p  = 0.007). Further interaction analysis revealed that vasopressor use increased the risk of flap necrosis in settings with a higher net fluid balance (OR 1.0032, 95% CI [1.0008-1.0056], p -interaction =0.010)., Conclusion:  This study demonstrated that intraoperative vasopressor use and adequate fluid status may be beneficial in improving flap outcomes in LE reconstruction. Vasopressor use with adequate fluid management can optimize hemodynamic stability when necessary during traumatic LE microvascular reconstruction without concern for increased risk of flap ischemia., Competing Interests: None declared., (Thieme. All rights reserved.)

Discharge to acute rehabilitation following major burn injury is crucial for patient recovery and quality of life. However, barriers to acute rehabilitation, including race and payor type impede access. The effect of burn center organizational structure on discharge disparities remains unknown. This study aims to investigate associations between patient demographics, burn center factors, and discharge to acute rehabilitation on a population level. Using the California Healthcare Access and Information Database, 2009-2019, all inpatient encounters at verified and non-verified burn centers were extracted. The primary outcome was the proportion of patients discharged to acute rehabilitation. Key covariates included age, race, burn center safety net status, diagnosis related group, American Burn Association (ABA) verification status, and American College of Surgeons (ACS) Level 1 trauma center designation. Logistic regression and mixed-effects modeling were performed, with Bonferroni adjustment for multiple testing. Among 27,496 encounters, 0.8% (228) were discharged to inpatient rehabilitation. By race/ethnicity, the proportion admitted to inpatient rehabilitation was 0.9% for White, 0.6% for Black, 0.7% for Hispanic, and 1% for Asian. After adjusting for burn severity and age, notable predictors for discharge to inpatient rehabilitation included Medicare as payor (OR 0.30-0.88, p=0.015) compared to commercial insurance, trauma center status (OR 1.45-3.43, p<.001), ABA verification status (OR 1.16-2.74, p=0.008), and safety-net facility status (OR 1.09-1.97, p=0.013). Discharge to inpatient rehabilitation varies by race, payor status, and individual burn center. Verified and safety-net burn centers had more patients discharge to inpatient rehabilitation adjusted for burn severity and demographics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To increase awareness and improve perioperative care of patients with cleft palate (CP) and coexisting cardiopulmonary anomalies., Design: Retrospective cohort., Setting: Multi-center., Patients/participants: Patients who underwent surgical repair of CP between 2012-2020 identified in the American College of Surgeons National Surgical Quality Improvement Program Pediatric Data File. Chi-squared analysis and Student's t-test were implemented to make associations between congenital heart disease (CHD) and congenital pulmonary disease (CPD) and postoperative complications. Multiple logistic regression was performed to identify associations between CP and CHD/CPD while controlling for age, gender, and ASA class. C2 values were used to assess the logistic regressions, with a significance level of 0.05 indicating statistical significance., Main Outcomes Measures: Length of stay (LOS), perioperative complications (readmission, reoperation, reintubation, wound dehiscence, cerebrovascular accidents, and mortality)., Results: 9 96 181 patients were identified in the database, 17 786 of whom were determined to have CP, of whom 16.0% had congenital heart defects (CHD) and 13.2% had congenital pulmonary defects (CPD). Patients with CHD and CPD were at a significantly greater risk of increased LOS and all but one operative complication rate (wound dehiscence) relative to patients with CP without a history of CHD and CPD., Conclusion: This study suggests that congenital cardiopulmonary disease is associated with increased adverse outcomes in the setting of CP repair. Thus, heightened clinical suspicion for coexisting congenital anomalies in the presence of CP should prompt referring providers to perform a comprehensive and multidisciplinary evaluation to ensure cardiopulmonary optimization prior to surgical intervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To compare postoperative outcomes and costs between inpatient and outpatient ABG in the United States., Design: Retrospective cohort., Setting: Multi-institutional/national., Patients and Participants: Patients who underwent ABG (n = 6649) were identified in the National Surgical Quality Improvement Program Pediatric database from 2012-2021. Inpatient and outpatient cohorts were matched using coarsened exact matching., Main Outcomes Measure(s): Thirty-day readmission, reoperation, and complications. A modified Markov model was developed to estimate the cost difference between cohorts. One-way and probabilistic sensitivity analyses were performed., Results: After matching, 3718 patients were included, of which 1859 patients were in each hospital-setting cohort. The inpatient cohort had significantly higher rates of reoperations (0.6% vs. 0.2%; p = 0.032) and surgical site infections (0.8% vs. 0.2%; p = 0.018). The total cost of outpatient ABG was estimated to be $10,824 vs. $20,955 for inpatient ABG, resulting in $10,131 cost savings per patient. Probabilistic sensitivity analysis revealed that all 10,000 simulations resulted in consistent cost savings for the outpatient cohort that ranged from $8000 to $24,000., Conclusions: Outpatient ABG has become increasingly more popular over the past ten years, with a majority of cases being performed in the ambulatory setting. If deemed safe for the individual patient, outpatient ABG may confer a lower risk of nosocomial complications and offer significant cost savings to the healthcare economy., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background:  Free flaps are essential for limb salvage in patients with lower extremity (LE) trauma; however, significant donor-site morbidity could impact functional outcomes. This study compares postoperative ambulatory function between contralateral and ipsilateral free flap harvest in LE traumatic reconstruction., Methods:  A retrospective review was performed on patients who underwent LE reconstruction at a level 1 trauma center from 2009 to 2022. Flap characteristics, injury history, and ambulatory function were collected. Flap harvest laterality was determined in relation to the injured leg. The flaps were categorized as either fasciocutaneous or those that included a muscle component (muscle/myocutaneous). Chi-squared and Mann-Whitney tests were used for statistical analysis., Results:  Upon review, 173 LE free flaps were performed, of which 70 (65.4%) were harvested from the ipsilateral leg and 37 (34.6%) were from the contralateral leg. Among all LE free flaps, the limb salvage rate was 97.2%, and the flap survival rate was 94.4%. Full ambulation was achieved in 37 (52.9%) patients in the ipsilateral cohort and 18 (48.6%) in the contralateral cohort ( p  = 0.679). The average time to full ambulation did not vary between these cohorts ( p  = 0.071). However, upon subanalysis of the 61 muscle/myocutaneous flaps, the ipsilateral cohort had prolonged time to full ambulation (6.4 months, interquartile range [IQR]: 4.8-13.5) compared with the contralateral one (2.3 months, IQR: 2.3 [1.0-3.9]) p  = 0.007. There was no significant difference in time to full ambulation between flap harvest laterality cohorts among the fasciocutaneous flaps ( p  = 0.733)., Conclusion:  Among free flaps harvested from the ipsilateral leg, fasciocutaneous flaps were associated with faster recovery to full ambulation relative to muscle/myocutaneous flaps. Since harvesting muscle or myocutaneous flaps from the ipsilateral leg may be associated with a slower recovery of ambulation, surgeons may consider harvesting from a donor site on the contralateral leg if reconstruction requires a muscle component., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Delayed repair of cleft palate is associated with worse speech outcomes. Social determinants of health may influence the timing of surgery; however, there are no population health investigations to evaluate factors such as travel distance, language barriers, and payer. This study sought to identify factors that may interfere with timely cleft palate repair., Design: Retrospective cohort., Setting: National/multi-center., Patients/participants: All cleft palate repairs within California were extracted from 2000-2021., Main Outcomes Measures: The primary outcome was age at surgical repair, which was modeled with linear regression. Covariates included race, primary language, distance from patient home to hospital, socioeconomic status, primary payer, and managed care enrollment status., Results: 11 260 patients underwent surgical repair of a cleft palate. Black race was associated with delayed repair (22 additional days, P  = .004, 95% CI 67.00-37.7) along with Asian/Pacific-Islander race (11 additional days, P  = .006, 95% CI 3.26-18.9) compared to white race. Spanish-speaking patients had significantly later cleft palate repairs by 19 days, ( P  < .001, 95% CI 10.8-27.7) compared with English-speaking. Further distances from the hospital were significantly associated with later cleft surgeries with out-of-state patients undergoing surgery 52 days later ( P  < .001, 95% CI 11.3-24.3). Managed care plans and Medi-Cal were significantly associated with earlier surgical repair compared with private insurance., Conclusion: Black, Asian Pacific Islander, and Spanish-speaking patients and greater distance traveled to hospital were associated with delayed cleft palate repairs. These results underscore the importance of addressing structural and social barriers to care to improve outcomes and reduce health disparities for patients with cleft palate., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The aim of the current review is to summarize the current evidence on graft materials used in fusion procedures for spinal deformity corrections., Methods: PubMed, Embase, and Cochrane Library were searched for relevant published observational studies and clinical trials using osteobiologics and biomaterials in spinal deformity surgery., Results: The use of autograft in deformity correction surgeries has been reported in a limited number of studies, with the harvest sites including iliac crest, ribs, and local bone. Various allografts and biologics have been used in the treatment of spinal deformities including idiopathic and degenerative scoliosis, either as stand alone or in combination with autograft. Limited number of studies reported no differences in fusion rates or outcomes. Use of rh-BMP2 in anterior, posterior or front/back approaches showed higher fusion rates than other graft materials in patients with spinal deformities. Due to the limited number of quality studies included in the review, as well as alternative factors, such as costs, availability, and surgeon expertise/preference, no definitive conclusion or recommendations can be made as to the ideal graft choice in spinal deformity surgery., Conclusions: Most commonly used grafts included autograft, allograft and rh-BMP2, with new biologics and biomaterials constantly emerging in the market. Limited number of high-quality comparative studies and heterogeneity in study design prevented direct comparisons that can lead to meaningful recommendations. Further studies are needed to prove superiority of any single graft material and/or biologic that is also cost-effective and safe., (© 2022. The Author(s), under exclusive licence to Scoliosis Research Society.)

Background: Failed back surgery syndrome (FBSS) is a significant cause of lumbar disability and is associated with severe patient morbidity. As the etiology of FBSS is not completely elucidated, the risk factors and evaluation of patients with FBSS remains challenging. Our analysis of a wide variety of operation types, clinical setting, and their correlation to FBSS seeks to allow fellow clinicians to be aware of the potential risk factors that leads to this devastating diagnosis., Methods: Data were obtained for patients undergoing anterior lumbar fusion, posterior lumbar fusion, or decompression procedures from January 2010 to December 2017 from the Mariner insurance database. Rates of FBSS at six- and twelve-months post-surgery were determined for patients undergoing single/multilevel procedures according to place of service, and approach/procedure type., Results: From 2010 to 2017, 102,047 patients underwent lumbar fusion or decompression surgery (54% decompression procedures, 36% posterior fusions, and 8.9% anterior fusions).5.4% of patients were diagnosed with FBSS within six months of the index procedure, and 8.4% were diagnosed with FBSS within twelve months. FBSS was higher in the inpatient (6.0%) vs. outpatient (4.3%) cohort. Among the surgical techniques, multi-level procedures had significantly higher rates of FBSS than single-level procedures, the highest being 10% in multi-level inpatient decompression procedures (p < 0.05)., Conclusion: The highest rates of FBSS occurred in in the elderly (age group 70-74), for those patients whose index procedure was received in an inpatient setting, as well as for those receiving a multi-level surgery., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Significance: Secondary lymphedema is a debilitating disease caused by lymphatic dysfunction characterized by chronic swelling, dysregulated inflammation, disfigurement, and compromised wound healing. Since there is no effective cure, animal model systems that support basic science research into the mechanisms of secondary lymphedema are critical to advancing the field. Recent Advances: Over the last decade, lymphatic research has led to the improvement of existing animal lymphedema models and the establishment of new models. Although an ideal model does not exist, it is important to consider the strengths and limitations of currently available options. In a systematic review adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we present recent developments in the field of animal lymphedema models and provide a concise comparison of ease, cost, reliability, and clinical translatability. Critical Issues: The incidence of secondary lymphedema is increasing, and there is no gold standard of treatment or cure for secondary lymphedema. Future Directions: As we iterate and create animal models that more closely characterize human lymphedema, we can achieve a deeper understanding of the pathophysiology and potentially develop effective therapeutics for patients.

Background:  Living donor liver transplantation (LDLT) has expanded the availability of liver transplant but has been associated with early technical complications including the devastating complication of hepatic artery thrombosis (HAT), which has been reported to occur in 14% to 25% of LDLT using standard anastomotic techniques. Microvascular hepatic artery reconstruction (MHAR) has been implemented in an attempt to decrease rates of HAT. The purpose of this study was to review the available literature in LDLT, specifically related to MHAR to determine its impact on rates of posttransplant complications including HAT., Methods:  A systematic review was conducted using PubMed/Medline and Web of Science. Case series and reviews describing reports of microscope-assisted hepatic artery anastomosis in adult patients were considered for meta-analysis of factors contributing to HAT., Results:  In all, 462 abstracts were screened, resulting in 20 studies that were included in the meta-analysis. This analysis included 2,457 patients from eight countries. The pooled rate of HAT was 2.20% with an overall effect size of 0.00906., Conclusion:  Systematic literature review suggests that MHAR during LDLT reduces vascular complications and improves outcomes posttransplant. Microvascular surgeons and transplant surgeons should collaborate when technical challenges such as small vessel size, short donor pedicle, or dissection of the recipient vessel wall are present., Competing Interests: None declared., (Thieme. All rights reserved.)

The NLRP3 inflammasome senses diabetic metabolites and initiates inflammation implicated in diabetic complications and neurodegeneration. No studies have investigated NLRP3 in diabetic bladder dysfunction (DBD), despite a high clinical prevalence. In vitro, we found that numerous diabetic metabolites activate NLRP3 in primary urothelial cells. In vivo, we demonstrate NLRP3 is activated in urothelia from a genetic type 1 diabetic mouse (Akita) by week 15. We then bred an NLRP3 -/- genotype into these mice and found this blocked bladder inflammation and cystometric markers of DBD. Analysis of bladder innervation established an NLRP3-dependent decrease in overall nerve density and Aδ-fibers in the bladder wall along with an increase in C-fiber populations in the urothelia, which potentially explains the decreased sense of bladder fullness reported by patients and overactivity detected early in DBD. Together, the results demonstrate the role of NLRP3 in the genesis of DBD and suggest specific NLRP3-mediated neuronal changes can produce specific DBD symptoms., (© 2018 by the American Diabetes Association.)