From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies.

Cellular therapeutics and immunotherapies in wound healing - on the pulse of time?

Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.

Perceived Age and Gender Perception Using Facial Recognition Software Following Facial Feminization Surgery.

Measures of success for facial feminization surgery (FFS) have previously included improved rates of external gender perception as female and patient-reported outcome measures. In this study, we used artificial intelligence facial recognition software to objectively evaluate the effects of FFS on both perceived gender and age among male-to-female transgender patients, as well as their relationship with patient facial satisfaction. Standardized frontal preoperative and postoperative images of 27 transgender women undergoing FFS were analyzed by Amazon's AI facial recognition software to determine gender, femininity confidence score, and perceived age. Female gender-typing, improvement in gender-typing (preoperatively to postoperatively), and femininity confidence scores were analyzed. To assess patient satisfaction, FACE-Q modules were completed postoperatively. Preoperatively, FFS images were perceived as female 48.1% of the time, and postoperatively, this improved to 74.1% ( P =0.05). Femininity confidence scores improved from a mean score of 0.04 preoperatively to 0.39 postoperatively ( P =0.003). FFS was associated with a decrease in perceived age relative to the patient's true age (-2.4 y, P <0.001), with older patients experiencing greater reductions. Pearson correlation matrix found no significant relationship between improved female gender typing and patient facial satisfaction. Undergoing surgery at a younger age was associated with higher overall facial satisfaction ( r =-0.6, P =0.01). Transfeminine patients experienced improvements in satisfaction with facial appearance, perceived gender, and decreases in perceived age following FFS. Notably, patient satisfaction was not directly associated with improved AI-gender typing, suggesting that other factors may influence patient satisfaction.

Understanding the Drivers of Cost and Length of Stay in a Cohort of 21,875 Patients with Severe Burn.

Burn management has significantly advanced in the past 75 years, resulting in improved mortality rates. However, there are still over one million burn victims in the United States each year, with over 3,000 burn-related deaths annually. The impacts of individual patient, hospital, and regional demographics on length of stay (LOS) and total cost have yet to be fully explored in a large nationally representative cohort. Thus, this study aimed to examine various hospital and patient characteristics using a sample of over 20,000 patients. Inpatient data from the National Inpatient Sample from 2008 to 2015 were analyzed, and only patients with an ICD-9 code for second- or third-degree burns were included. In addition, a major operating room procedure must have been indicated on the discharge summary for patients to be included in the final dataset, ensuring that only severe burns requiring complex care were analyzed. Analysis of covariance models was used to evaluate the impact of various patient, hospital, and regional variables on both LOS and cost. The study found that skin grafts and fasciotomy significantly increased the cost of hospitalization. Having burns on the face, neck, and trunk significantly increased costs for patients with second-degree burns, while burns on the trunk resulted in the longest LOS for patients with third-degree burns. Infections in the hospital and additional procedures, such as flaps and skin grafts, also led to longer stays. The study also found that the prevalence of postoperative complications, such as electrolyte imbalance, was high among patients with burn surgery.

An update on long-term mental health in eight face transplant recipients - A single center experience.

OBJECTIVE: Face transplantation is a groundbreaking and complex surgical intervention offering profound physical and psychological benefits to patients with severe facial disfigurements. This report provides an update on the long-term psychosocial outcome of eight face transplant recipients. METHOD: All transplant recipients were initially transplanted at Brigham and Women´s Hospital (Boston, USA) between 2011 and 2020 and are seen as outpatient patients at Yale New Haven Hospital (New Haven, USA). A mixed-methods approach was used to assess the psychological well-being of these patients. The Short-Form 12, Brief-COPE, EQ-VAS and CES-D were administered between October 2022 and October 2023. RESULTS: Older age of face transplant recipients was significantly and positively associated with better mental health and increased use of both emotional and instrumental support (Brief-COPE). The initial enhancement in patients' self-reported quality of life, as assessed by the EQVAS, declined on the EQ-VAS score at the last follow-up period. Similarly, an increase in depression score was observed (CES-D score) up through the last follow-up assessment. Both of the latter results, however, did not reach statistical significance. CONCLUSIONS: These results underscore the importance of ongoing psychological support throughout the long-term journey of recovery for face transplant recipients. They emphasized the need for a comprehensive, patient-centered approach that also addresses the complex psychological dimensions and contributes to our understanding of the mental health dynamics involved in face transplantation, underscoring the need for guidelines and continued research in this evolving field.

Quantifying Facial Feminization Surgery's Impact: Focus on Patient Facial Satisfaction.

Background: Facial feminization surgery (FFS) has been associated with improving gender dysphoria in transgender patients. This study aimed to quantify the impact of surgery on patient facial satisfaction, using the FACE-Q and a quality-of-life (QoL) survey. Methods: Transgender female patients were recruited to complete the FACE-Q and the World Health Organization's QoL Scale-Short Form (WHOQOL-BREF) if they were planning to or had undergone FFS at our institution. FACE-Q modules completed included "Satisfaction with Facial Appearance Overall," individual facial attributes (forehead/eyebrows, nose, cheeks, cheekbone, chin, jawline, and neck), and the WHOQOL-BREF, which assesses patient QoL through four domains (physical, psychological, social relations, and environment). Both matched and unmatched analyses of preoperative versus postoperative cohorts were performed. Results: Overall, 48 patients participated in our study and completed 31 FACE-Q surveys preoperatively and 37 postoperatively. On average, patients were 37.2 ± 12.5 years old. FACE-Q scores increased significantly for all facial attributes and for Satisfaction with Facial Appearance Overall between cohorts (P < 0.05). The facial attribute with the greatest increase in satisfaction was the jawline, followed by the nose. The WHOQOL-BREF's psychological and physical domains both improved significantly (P < 0.05). Wait time for surgery of less than 6 months (b = 22.42, P = 0.02) was associated with higher overall facial satisfaction, whereas age at surgery (b = -1.04, P < 0.01) was associated with lower overall facial satisfaction. Conclusions: Transgender female patients experienced significant improvements in facial satisfaction and QoL after FFS. Undergoing surgery at a younger age and shorter wait times for surgery were associated with increased overall facial satisfaction.

Ear Molding Therapy of Congenital Ear Anomalies: Long-Term Aesthetic Outcomes and Caretaker Satisfaction.

INTRODUCTION: Ear molding is a safe, non-surgical approach to treat newborns with congenital ear anomalies. In this study, we aimed to investigate long-term aesthetic outcomes and caretaker satisfaction from ear molding therapy. METHODS: A retrospective chart review from 2018 to 2020 was conducted for infants who underwent ear molding treatment at our institution. Patient demographics and treatment related variables were collected. Caretakers were surveyed regarding their experience, expectations, and aesthetic outcome at 1 year (short-term) and 3 years (long-term) from treatment. Independent physicians evaluated treatment efficacy. Responses were converted to a Likert scale (1-5), with 5 representing most desirable. RESULTS: Overall, 38 of 42 patients participated in our long-term study (90%) for a total of 62 ears. Average follow-up was 3.31 ± 0.50 years after completion of treatment. Mean age at treatment was 23.2 ± 19.7 days with a mean treatment duration of 21.7 ± 7.7 days. Caretakers' satisfaction regarding auricular appearance remained high (short-term: 4.18 vs. long-term: 4.17, p = 0.54) and anticipated social distress decreased over time. Physician aesthetic evaluations were favorable between "somewhat effective" and "very effective" and remained consistent over time (short term: 3.46 vs. long-term: 3.31, p = 0.31). Furthermore, physician evaluations were higher for deformations than malformations (p = 0.04) and in children who began treatment by 30 days old (p = 0.04). CONCLUSION: Caretaker satisfaction from ear molding therapy remained high after long-term follow up, and social distress from the perception of their child's ears decreased with time. Physician aesthetic ratings confirmed efficacy, with better outcomes seen in deformations than in malformations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

National Trends in Microtia Repair Cost and Hospital Length of Stay.

Microtia can have deleterious impacts on the functional, psychological, and aesthetic outcomes of affected young children. Reconstructive procedures can alleviate these negative outcomes and significantly improve the quality of life for patients; however, the cost and length of hospital stay (LOS) for such procedures and the factors that impact them have not been well-characterized. This study seeks to understand the hospital-level (institution type, size, and geographic region) and patient-level factors (race, age, and insurance status) that impact cost and LOS in patients who undergo microtia reconstructive surgery. A retrospective data analysis was conducted utilizing the National Inpatient Sample (NIS) database for the years 2008 to 2015. Inclusion criteria included patients who had an International Classification of Diseases, Ninth Revision (ICD-9) diagnostic code for microtia (744.23) as well as a procedure for microtia correction (186×/187×). A total of 714 microtia repair cases met the inclusion criteria and were sampled from the NIS database. Microtia repair cost was significantly increased on the West Coast compared with the Northeast ($34,947 versus $29,222, P =0.020), increased with patient age ($614/y, P =0.012), and gradually increased from 2008 to 2015 ($25,897-$48,985, P <0.001). Microtia LOS was significantly increased with government-controlled hospitals compared with private hospitals (1.93 versus 1.39 d, P =0.005), increased with patients on Medicaid compared with private insurance (2.33 versus 2.00 d, P =0.036), and overall decreased with patient age (-0.07 d/y, P =0.001). The results not only identify the multifactorial impacts that drive cost and LOS in microtia repair but provide insights into the financial and medical considerations patients and their families must navigate.

Traumatic brain injury and the pathways to cerebral tau accumulation.

Tau is a protein that has received national mainstream recognition for its potential negative impact to the brain. This review succinctly provides information on the structure of tau and its normal physiological functions, including in hibernation and changes throughout the estrus cycle. There are many pathways involved in phosphorylating tau including diabetes, stroke, Alzheimer's disease (AD), brain injury, aging, and drug use. The common mechanisms for these processes are put into context with changes observed in mild and repetitive mild traumatic brain injury (TBI). The phosphorylation of tau is a part of the progression to pathology, but the ability for tau to aggregate and propagate is also addressed. Summarizing both the functional and dysfunctional roles of tau can help advance our understanding of this complex protein, improve our care for individuals with a history of TBI, and lead to development of therapeutic interventions to prevent or reverse tau-mediated neurodegeneration.

Pediatric Facial Burns and Consumer Products: A Nationwide Analysis.

Pediatric facial burns pose significant challenges in terms of physical, psychological, and social impacts on children. Understanding the causes of these burns is crucial for prevention and appropriate care. This study aims to provide a comprehensive analysis of causes and preventive measures related to pediatric facial burns caused by consumer products. Using data from the National Electronic Injury Surveillance System (NEISS) from 2012 to 2021, we analyzed 130,461 cases of pediatric facial burns. Common causes included household items such as cleaning supplies, hot water, kitchen appliances, and health and beauty products. Differences in burn causes were observed between genders, with boys more prone to burns from welding equipment, gasoline, and grills, while girls were more susceptible to burns from hair curling equipment, candles, and health and beauty products. The mean age of children burned by different items varied, highlighting the need for age-appropriate preventive measures. The authors discuss the importance of caregiver education, safe storage practices, supervision, and clear communication in preventing pediatric facial burns. By raising awareness of potential burn sources and implementing preventive strategies, the incidence of pediatric facial burns can be significantly reduced.

Tranexamic Acid in Facial Feminization Surgery: Quantifying a High-risk Setting With Exogenous Estrogen Supplementation.

Tranexamic acid (TXA) has been increasingly utilized in orthognathic surgery, aesthetic surgery, and craniofacial surgery. However, the risk of increasing venous thromboembolic events (VTE) must be carefully considered as TXA is a prothrombotic agent. Our study aimed to investigate the safety of TXA in the setting of facial feminization surgery. These patients are at an elevated risk for VTE at baseline given their uniform history of exogenous estrogen supplementation. A retrospective review of all patients that underwent facial feminization surgery at our medical center between December 2015 and September of 2022 was performed. Demographic information, procedure type, Caprini scores, hematoma rate, VTE rate, estimated blood loss, and operative time were all studied. Unpaired t tests were used to compare patients that received TXA and those who did not. In total, there were 79 surgeries performed during our study period. There were 33 surgeries (41.77%) that used TXA intraoperatively. Ten patients (12.65%) received anticoagulation postoperatively, 5 of whom received TXA intraoperatively. Of the 33 patients who received TXA, 30 patients remained on estrogen therapy. There was no statistically significant difference in VTE rates in patients who received TXA (n=33, 41.77%) and those who did not (n=46, 58.23%). Bleeding events, Caprini scores, estimated blood loss, and operative time were also not found to be significantly different between the 2 cohorts. The authors found no significant increase in VTE in facial feminization patients undergoing estrogen supplementation when intraoperative TXA was utilized. This is the first known report investigating the safety of TXA in this higher risk patient population.

Acute disseminated encephalomyelitis (ADEM) following COVID-19 vaccination: A systematic review.

BACKGROUND: Although global vaccination against COVID-19 infection has its excellence, potential side effects are yet of concern. Several lines of evidence have proposed ADEM occurrence after SARS-CoV-2 infection. Moreover, a large number of case reports and case series have also suggested the casual association between ADEM and COVID-19 vaccination. To better understand the development of ADEM following COVID-19 vaccination and its potential association, we aimed to systematically review ADEM cases reported after COVID-19 vaccination. METHODS: We conducted a comprehensive systematic search using three databases including PubMed, Scopus, and Web of Science. Studies that reported ADEM after COVID-19 vaccination were eligible to include in our study. Observational studies, case reports, and case series which reported cases of ADEM with sufficient detail to confirm clinical diagnosis following COVID-19 vaccination were eligible to enter our study. RESULTS: Twenty studies were included in our systematic review after the abstract and full-text screening with a total of 54 cases. Among included patients, 45 (85.1 %) developed ADEM after the first dose of the COVID-19 vaccine, and seven (12.9 %) cases experienced ADEM after the second dose. The median time interval between vaccination and neurological symptoms was 14 days which ranged from 12 h to 63 days. Twelve (22.2 %) patients experienced symptoms of muscle weakness, ten (18.5 %) presented unconsciousness, nine (16.6 %) patients had urinary complaints, nine (16.6 %) had visual impairments, and five (9.2 %) experienced a seizure. After treatments, four (13.8 %) patients died. Forty-six patients had clinical improvement (85.1 %), also improvement in brain MRI was observed among 44 (81.4 %) patients. CONCLUSION: In conclusion, it is not clear that ADEM could be a potential complication of COVID-19 vaccination based on the current evidence and further studies are needed. However, this rare condition should not trigger stopping the mass vaccination programs since the only way to eradicate the current pandemic of COVID-19 is to extend the number of immunized people.

Serum neurofilament light chain in LRRK2 related Parkinson's disease: A five years follow-up.

BACKGROUND: Studies revealed that serum neurofilament light chain (NFL) levels not only increase considerably over time in Parkinson's disease (PD) but also have a significant association with disease progression. However, there is no evidence of the level of serum NFL in PD patients with leucine-rich repeat kinase 2 (LRRK2) mutation (LRRK2-PD) which is the most common mutation that causes familial and sporadic PD. AIM: Here we aimed to investigate the difference and longitudinal alteration of the serum level of NFL in LRRK2-PD and idiopathic PD (iPD) patients. METHODS: We entered 228 iPD and 103 LRRK2-PD patients and 176 healthy controls (HCs) from PPMI. We compared the level of serum NFL at baseline, six months, one year, two years, three years, and five years visits. Also, we used linear mixed models to assess longitudinal changes of serum NFL over six months, one year, two years, three years, and five years within groups. RESULTS: We found a significant difference in the level of serum NFL between three groups at baseline, two years, three years, and five years time points. Also, our analysis showed that LRRK2-PD patients had significantly lower serum NFL compared to iPD subjects at baseline. In the longitudinal analysis, there was no significant change in the HCs group over five years. The level of serum NFL was significantly increased after two, three, and five years from baseline in LRRK2-PD patients. Also, we found similar results for iPD subjects after three and five years from baseline. CONCLUSION: We can conclude that the overall neurodegeneration might be similar in LRRK2-PD and healthy subjects and lower than the idiopathic form of PD at the early stages, which may disappear in the later stages. Moreover, our findings suggest that the serum NFL might be a more accurate biomarker to distinguish iPD from healthy subjects rather than all PD patients or LRRK2-PD from healthy subjects at the early stages.

Ultrasonic Vitrectomy Performance Assessment Using Micro-Extensional Rheology.

Purpose: The purpose of this study was to assess the performance of ultrasonic (US) vitrectomy devices by quantifying and comparing its impact on extracted vitreous properties to conventional pneumatic blade (PB) cutters using micro-extensional rheology. US vitrectomy is a new technology that offers an alternative to PB cutters used in vitreo-retinal surgeries. Methods: Thirty-six porcine vitreous samples were extracted using US and PB cutters. Each sample was kept at 4°C and tested within 24 hours postmortem and 4 hours post-vitrectomy. A recently developed micro-extensional rheology technique is used to infer the relative protein fragment size of extracted vitreous by quantifying the extensional relaxation time. Results: US-extracted vitreous exhibited extensional relaxation times orders of magnitude lower than PB-extracted vitreous (0.37 ms and 27.25 ms, respectively). Relaxation time is directly correlated to the fragment size of the collagen fibers in the vitreous. The formation of beads-on-a-string droplets within the PB samples indicates the presence of larger collagen fragments. These droplets were not seen on US samples. Conclusions: This new micro-extensional rheology technique can identify significant differences in physical properties of extracted vitreous. Long relaxation times and beads-on-a-string droplets within the PB vitreous samples indicate larger protein fragments compared to the US samples. Translational Relevance: Higher fragmentation of vitreous and lower extensional relaxation times may improve retina safety due to a reduction in vitreo-retinal traction resulting from the continuous shear action and aspiration applied by ultrasonic vitrectomy technology.

Valproic acid-induced hyperammonemia in neuropsychiatric disorders: a 2-year clinical survey.

INTRODUCTION: Valproic acid (VPA)-induced hyperammonemia (HA) is a rare adverse effect reported even at therapeutic VPA levels. The present study aimed to investigate the characteristics of VPA-induced HA and its association with the total dose, duration, and level of VPA. This study also investigated whether the use of VPA in combination with other medications has any effect on elevating serum ammonia levels. METHODS: A total of 316 patients with a history of VPA prescribed for underlying neuropsychiatric disorders were found eligible for the study. Data including demographic information, medical history and diagnosis, VPA dosage, VPA treatment duration, VPA level, and ammonia serum level were extracted and reviewed from our hospital records. The history of other neuropsychiatric medications was also included. RESULTS: Among 316 patients receiving VPA, HA was observed in 54 (17%) patients, and 15 patients were symptomatic among them. There was no significant difference in demographics between symptomatic and asymptomatic HA groups except for the number of co-administrated medications (p = 0.044). Besides, VPA duration and dose did not show a significant difference between the two groups. Additionally, the VPA level was significantly higher in patients who used risperidone in addition to VPA (p = 0.019). Eventually, VPA level showed a significant association with ammonia level (p = 0.025) and symptomatic HA (p = 0.033) after adjusting for possible confounders. CONCLUSION: VPA level showed a significant association with ammonia level and symptomatic HA. Moreover, co-administrated medications such as risperidone might have an impact on the serum level of VPA. Further studies are recommended to confirm these findings.

De novo testicular tissue generation from non-testicular cell lines, biologic and synthetic scaffolds: Current findings and future translational applications.

In recent decades, reproductive science has revolutionized the options for biological parenthood for the 20-50% of infertility cases affected by male factors. However, current solutions exclude those who are infertile due to absent testicular tissue. This includes anorchic 46, XY individuals due to trauma or congenital factors and transgender men with a 46, XX genotype. There is a clinical need for methods to restore testicular function independent of pre-existing testicular tissue. This mini-review analyzes studies that have applied non-testicular cell lines to generate germline and non-germline testicular parenchymal components. While only 46, XY cell lines have been evaluated in this context to date, the potential for future application of cell lines from 46, XX individuals is also included. Additionally, the role of varied culture methods, media supplementation, and biologic and synthetic scaffolds to further support testicular parenchyma generation are critiqued. De novo testicular tissue generation in this manner will require a focus on both cellular and environmental aspects of tissue engineering. Put together, these studies highlight the future potential for expanded clinical, reproductive, and endocrine management options for individuals who are currently excluded from aspects of biologic reproduction most consistent with their gender identity and reproductive preferences.

Effects of Collagenase Type II on Vitreous Humor-An In Situ Rheological Study.

The purpose of this study is to quantify the impact of enzyme activity on the vitreous humor structure over time to understand the mechanical characteristics of the vitreous humor gel. Changes in the mechanical behavior of the vitreous occur due to many reasons including aging, which may lead to many vitreoretinal diseases. The degeneration process of the vitreous has been studied; however, in situ experimental procedures to validate the existing hypotheses are limited. We examined thirty-eight porcine eyes using in situ rheological creep tests to measure the mechanical properties of the vitreous humor of the eyes prior to, 1 h and 24 h after the intravitreal injection. Eyes in one group were injected with collagenase type II solution and eyes in the control group were injected with phosphate buffered saline solution (PBS) with calcium and magnesium chloride. Prior to the injection, viscosity and creep compliance intercept values between both groups were not statistically different. At 1 h and 24 h after the injection, vitreous properties in the eyes from the first group showed a statistically significant increase in the J intercept values (representing the inverse of elasticity) compared to the control group. In addition, 1 h and 24 h after the injection, vitreous viscosity was lower in the eyes from the first group than in the eyes from the control group. These findings are a foundation for future studies on the effectiveness of intravitreal drugs that modify the mechanical properties of the vitreous humor.