Ageing-related bone and immunity changes: insights into the complex interplay between the skeleton and the immune system.

Ageing as a natural irreversible process inherently results in the functional deterioration of numerous organ systems and tissues, including the skeletal and immune systems. Recent studies have elucidated the intricate bidirectional interactions between these two systems. In this review, we provide a comprehensive synthesis of molecular mechanisms of cell ageing. We further discuss how age-related skeletal changes influence the immune system and the consequent impact of immune system alterations on the skeletal system. Finally, we highlight the clinical implications of these findings and propose potential strategies to promote healthy ageing and reduce pathologic deterioration of both the skeletal and immune systems.

A novel surgical risk predictor combining frailty and hypoalbuminemia - A cohort study of 9.8m patients from the ACS-NSQIP database.

INTRODUCTION: The functional decline seen in frail patients is associated with significant morbidity and mortality. The modified frailty index 5 (mFI-5) score is an accepted risk predictor score in surgery. Hypoalbuminemia has been correlated with poor postoperative outcomes.There exists, however, a gap in the literature regarding the combined assessment of frailty and hypoalbuminemia and the predictive power of this combined assessment. This retrospective cohort study aimed to investigate the association of preoperative albumin and frailty, as assessed with the mFI-5 score, and its ability to predict surgical outcomes. METHODS: We queried the ACS-NSQIP database (2008-2021) to identify all surgical patients. Perioperative data, including demographics and preoperative laboratory values, including albumin, were collected. The predictive power of the mFI-5 and hypoalbuminemia (Alb) independently, and in combination (mFI-5+Alb), was assessed using multivariable linear and logistic regression models 30-day outcomes were assessed including mortality, length of hospital stay, reoperation, medical and surgical complications, and discharge destination. RESULTS: A total of 9,782,973 patients were identified of whom 4,927,520 (50.4%) were non-frail (mFI=0), 3,266,636 had a frailty score of 1 (33.4%), 1,373,968 a score of 2 (14.0%), 188,821 a score of 3 (1.9%) and 26,006 a score greater or equal to 4 (0.3%). Albumin levels were available for 4,570,473 patients (46.7%), of whom 848,315 (18.6%) had hypoalbuminemia. The combined assessment (mFI-5+Alb) was found to be a more accurate risk predictor than each factor independently for all outcomes. A weak negative correlation between serum albumin levels and mFI scores was established (Spearman R: -0.2; <0.0001). CONCLUSIONS: Combined assessment of frailty and albumin was the strongest risk predictor. Therefore, for patients undergoing surgery, we recommend consideration of both serum albumin and frailty in order to optimally determine perioperative planning, including multi-disciplinary care mobilization and pre- and posthabilitation.

The free vastus lateralis-And conjoined vastus lateralis anterolateral thigh/tensor fascia lata flap for oncological chest wall reconstruction.

INTRODUCTION: A reconstructive option for extensive chest wall reconstruction is the free myocutaneous vastus lateralis muscle (VL) flap which can be performed in isolation or in conjunction with a fasciocutaneus anterolateral thigh (cVLALT) and/or myofasciocutaneous tensor fascia lata flap (cVLTFL). We aimed to directly compare the outcomes of these reconstructive options. METHODS: Patients who underwent oncological chest wall reconstruction with a free VL, cVLALT, or cVLTFL flap between February 2010 and 2022 were included in this retrospective study. Patient demographics, surgical characteristics, as well as medical and reconstructive outcomes, were evaluated. The operative outcomes between myocutaneous VL, cVLALT, and cVLTFL flap reconstructions were compared. RESULTS: A total of 41 patients underwent chest wall reconstruction with a free myocutaneous VL (n = 25; 61%), cVLALT (n = 14; 34%), or cVLTFL Three acute flap thromboses occurred in the entire cohort (3/41, 7%), with one myocutaneous VL flap failing because of recurrent venous thrombosis during the salvage procedure. Total flap necrosis was seen in two cases (5%; VL flap: n = 1; cVLALT flap: n = 1), and partial flap necrosis in one VL flap (1/25, 4%) and in the distal ALT portion of three cVLALT flaps (3/14, 21%). No significant difference was seen between isolated VL and conjoined VL flaps regarding the partial (p = .28) or total flap necrosis rate (p = .9). CONCLUSION: The free (conjoined) VL flap provides reliable outcomes for obliterating dead space achieving durable reconstruction of complex chest wall defects.

Bridging frailty and burns: Defining acute burn injury as a cause of long-term frailty.

Although our understanding of frailty has evolved and multiple indices have been developed, the impact of burn injuries on long-term health has been overlooked. With over 11 million annual cases globally, burns affect all demographics, although socioeconomic disparities are evident. With survival rates improved, morbidity among survivors is becoming more evident, and shows similarity to predictors of frailty. Some of the chronic effects of burns, including mental health issues and increased risks of disease, mirror frailty markers. Studies show burn survivors have lower life expectancy, independent of burn severity. Integrating burn history into frailty assessments and establishing specialized long-term care can mitigate this frailty risk. Improved interdisciplinary follow-up and research are vital for enhancing burn survivors' quality of life and longevity.

Robot-assisted Microsurgery: Lessons Learned from 50 Consecutive Cases.

Background: The potential of robot-assisted surgery in plastic and reconstructive surgery remains to be established, especially in free tissue transfer. This prospective study aimed to present our experience and findings from the first 50 consecutive cases of robot-assisted microsurgery using the Symani surgical system. Methods: A prospective database was maintained, recording patient demographics and surgical details for all cases of robot-assisted microsurgery in a large academic institution. All surgeons underwent an intensive training program with the Symani surgical system. Results: A total of 50 patients who underwent robot-assisted microsurgical reconstruction were identified. Free microsurgical tissue transfer was performed in 45 cases, targeted muscle reinnervation in four cases, and lymphovenous anastomoses in a single case. A total of 94 robot-assisted anastomoses and coaptations were performed, (46 venous and 30 arterial anastomoses, 16 nerve coaptations, two lymphovenous anastomoses). Six cases involved perforator-to-perforator anastomoses. Ninety-eight percent of attempted anastomoses were completed using the robot. Size-mismatch anastomoses, seen in 37.8% of cases, took significantly longer. Minor complications occurred in three cases and major in six cases. There were three cases of microvascular compromise requiring revision. One partial flap loss and no complete flap loss occurred. Conclusions: Our study highlights the immense potential of robot-assisted microsurgery, and a feasible and effective modality for various microsurgical procedures, with outcomes comparable to those of conventional microsurgery. Despite challenges, such as increased operating times and higher costs, the technology offers significant advantages, such as enhanced precision and motion scaling. We identify a slow learning curve and a necessity for higher caseloads.

A nomogram for predicting outcomes following pedicled flap reconstruction of the lower extremity.

INTRODUCTION: Lower extremity reconstructions with soft tissue flaps account for a significant proportion of reconstructive surgery. Pedicled flaps are a procedure of choice, particularly in multimorbid patients and those with small to medium-sized defects. Complication rates are high and should not be underestimated, with accurate preoperative risk factor assessment being imperative. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program Database (2008-2021), we analyzed all patients who underwent pedicled flap reconstruction of the lower extremity. Demographic data, comorbidities, and perioperative data were extracted. We identified risk factors of major surgical complications within 30 days of surgery through uni- and multivariate regression analyses. On this basis, a nomogram for predicting the risk of complications was developed to allow for feasible point-of-care risk assessment. RESULTS: A total of 6475 adult patients were identified. The most common comorbidities were hypertension (n = 3363, 51.9%) and obesity (n = 2306, 35.6%) and most common American Society of Anesthesiologists (ASA) class was class 3 (n = 3703, 57.2%). The most common complication was bleeding/transfusion (n = 1293, 19.9%). Multivariate regression revealed longer procedures, inpatient setting, higher ASA scores, hypertension, and procedures performed by orthopedic and vascular surgeons as predictors for higher risk of post-operative complications. CONCLUSION: Leveraging a risk- and case-mix-adjusted multi-institutional database, a nomogram for post-operative surgical complications within 30 days after pedicled flap reconstruction in the lower extremity was developed. This broadly applicable risk prediction tool can aid in decision-making when assessing patient eligibility.

Quality of life and satisfaction after breast augmentation: A systematic review and meta-analysis of Breast-Q patient-reported outcomes.

BACKGROUND: Breast augmentation ranks among the most popular plastic surgery procedures. Yet, reports on post-operative patient-reported quality of life (QoL) and satisfaction remain conflicting. METHODS: A systematic review was conducted following the PRISMA guidelines. Three databases were searched for eligible studies that reported pre-and/or post-operative Breast-Q™ augmentation scores for patient QoL (psychosocial, sexual, and physical well-being) and/or satisfaction. RESULTS: A total of 39 studies (53 patient cohorts and 18,322 patients) were included in the quantitative synthesis. The pairwise meta-analysis revealed significant improvements in patient-reported psychosocial (MD: +38.10) and sexual well-being (MD: +40.20) as well as satisfaction with breast (MD: +47.88) (all p < 0.00001). Physical well-being improved slightly after breast augmentation (MD: +6.97; p = 0.42). The single-arm meta-analysis yielded comparable results, with Breast-Q™ scores in psychosocial and sexual well-being as well as satisfaction with breast increasing from 37.2, 31.1, and 26.3 to 75.0, 70.6, and 72.7, respectively (all p < 0.00001). Physical well-being improved by 8.1 (75.8 pre-operatively to 83.9 post-operatively; p = 0.17). Subgroup analyses highlighted higher QoL and satisfaction following breast augmentation for purely esthetic purposes and alloplastic mammaplasty. Although patient-reported physical and sexual well-being increased in the long term, psychosocial well-being was the highest in the short term. CONCLUSION: Patient satisfaction with breast, psychosocial, and sexual well-being increased significantly after breast augmentation. In contrast, patient-reported physical well-being yielded ambivalent results, varying by mammaplasty technique and post-operative follow-up time. Plastic surgeons should be sensitized about our findings to refine eligibility criteria and gain a deeper understanding of the patients' perceived surgical experience. PROSPERO TRIAL REGISTRATION NO: CRD42023409605.

The Epidemiology and Outcomes of Perineal and Genital Burn Injury in Low- and Middle- Income Countries: A Global Burn Registry Study.

INTRODUCTION: The epidemiology, care, and outcomes of perineal and genital burns (PG) in high-income countries have been previously described, but an analysis of this topic in LMICs has yet to be performed. We use the World Health Organization's Global Burn Registry to fill this gap. METHODS: The GBR was searched from inception to November 2023 to identify all burn patients, excluding cases from high-income countries. Demographics and mechanism of injury were retrieved. Primary outcomes were length of hospital stay (LOHS), surgical intervention, discharge with physical impairment, and mortality. A multivariate regression analysis was performed controlling for burnt total body surface area (TBSA), age, sex, inhalation injury, mechanism of burn and care center characteristics. RESULTS: Of 9041 patients identified, 1213 (13.4 %) had PG burns with 136 (1.6 %) isolated to the PG region. PG patients had higher TBSA (p < 0.001) and more inhalation injury (p < 0.001). They had better access to rehabilitation and lower access to theater space for burns (p < 0.001). Multivariable analysis showed that PG patients had longer LOHS (p = 0.001), greater mortality (p < 0.001), were less likely to undergo surgery (p = 0.01) or be discharged home with physical impairment (p = 0.03). CONCLUSION: Similarities and differences exist between high- and low/middle-income countries in terms of the patterns of injury, care, and recovery in patients with PG burns. The longer LOHS and higher mortality among PG patients, previously reported in high-income countries, are verified. This highlights the importance of greater vigilance when caring for such patients.

A new surgical concept for the efficient treatment of large and deep burns.

Effective burn surgery is based on two fundamental principles: prompt excision of necrotic tissue and definitive coverage preserving functional dermis and body contour. There is often compromise, either prioritizing the urgency of excision or opting for patient stability and optimal conditions prior to autografting. We propose a surgical concept that addresses this critical treatment gap. In 2022 we implemented a new three-phase protocol, EDM: (Excision phase, E) Immediate excision of the burn wound preserving body contour; (Dermis phase, D) definitive temporization of the wound bed, using Biodegradable Temporizing Matrix (BTM), to prepare it for successful grafting. (Meek phase, M): Upon complete dermal temporization, full autologous coverage in a single micrografting procedure. We performed a retrospective single-center cohort study to characterize the EDM protocol compared to the prior standard of care (>40%TBSA, n=5 in EDM vs. n=10 matched controls). Primary outcomes were total surgeries required, total surgeries to achieve>90% healing, uninterrupted recovery time without surgery, and time on mechanical ventilation. The EDM group required fewer surgeries in total (5 vs. 9.5 ; p=0.01) and to achieve>90% healing (3 vs. 6.5; p=0.001). EDM patients experienced longer uninterrupted recovery (24 vs. 14 days, p=0.001). Additionally, EDM patients spent less time on mechanical ventilation (210 vs. 1136 hours, p=0.005). The EDM protocol could improve surgical efficiency, ultimately having the potential to expedite rehabilitation in severely burned patients. The study underscores the potential of combining fundamentals of burn surgery, with innovative surgical techniques and materials, in order to bridge the gap between excision and grafting.

The Application of a Synthetic Biodegradable Temporizing Matrix in Extensive Burn Injury: A Unicenter Experience of 175 Cases.

Objectives: Addressing extensive and deep burn wounds poses considerable challenges for both patients and surgeons. The NovoSorb® Biodegradable Temporizing Matrix (BTM) emerged as a novel dermal substitute and has been subjected to evaluation in large burn wound cases, with a specific focus on identifying risk factors associated with suboptimal take rates. Methods: All patients with burn wounds greater than 10% body surface that underwent BTM treatment between March 2020 and November 2023 were eligible for inclusion. Univariate analyses and linear regression models were employed to discern risk factors and predictors influencing the take rates of both the BTM and split-thickness skin grafts (STSGs). Results: A total of 175 patients (mean age 56.2 ± 19.8 years, 70.3% male) were evaluated. The mean take rates of the BTM and STSGs were 82.0 ± 24.7% and 87.3 ± 19.0%, respectively. There were significant negative correlations between BTM take and the number of surgeries before BTM application (r = -0.19, p = 0.01), %TBSA and STSG take (r = -0.36, p = <0.001) and significant positive correlations between BTM and STSG take (r = 0.41, p ≤ 0.001) in addition to NPWT and STSG take (r = 0.21, p = 0.01). Multivariate regression analyses showed that a larger number of surgeries prior to BTM application (OR -3.41, 95% CI -6.82, -0.03, p = 0.04) was associated with poorer BTM take. Allograft treatment before BTM application (OR -14.7, 95% CI -23.0, -6.43,p = 0.01) and failed treatment with STSG before BTM application (OR -20.8, 95% CI -36.3, -5.23, p ≤ 0.01) were associated with poorer STSG take, whereas higher BTM take rates were associated with overall higher STSG take (OR -0.15, 95% 0.05, 0.26, p = 0.01). The Meek technique was used in 24 patients and showed similar take rates (BTM: 76.3 ± 28.0%, p = 0.22; STSG: 80.7 ± 21.1, p = 0.07). Conclusions: This study summarizes our findings on the application of a BTM in the context of large burn wounds. The results demonstrate that successful treatment can be achieved even in patients with extensive burns, resulting in satisfying take rates for both the BTM and STSG. The data underscore the importance of promptly applying a BTM to debrided wounds and indicate good results when using Meek.

Turn Your Vision into Reality-AI-Powered Pre-operative Outcome Simulation in Rhinoplasty Surgery.

BACKGROUND: The increasing demand and changing trends in rhinoplasty surgery emphasize the need for effective doctor-patient communication, for which Artificial Intelligence (AI) could be a valuable tool in managing patient expectations during pre-operative consultations. OBJECTIVE: To develop an AI-based model to simulate realistic postoperative rhinoplasty outcomes. METHODS: We trained a Generative Adversarial Network (GAN) using 3,030 rhinoplasty patients' pre- and postoperative images. One-hundred-one study participants were presented with 30 pre-rhinoplasty patient photographs followed by an image set consisting of the real postoperative versus the GAN-generated image and asked to identify the GAN-generated image. RESULTS: The study sample (48 males, 53 females, mean age of 31.6 ± 9.0 years) correctly identified the GAN-generated images with an accuracy of 52.5 ± 14.3%. Male study participants were more likely to identify the AI-generated images compared with female study participants (55.4% versus 49.6%; p = 0.042). CONCLUSION: We presented a GAN-based simulator for rhinoplasty outcomes which used pre-operative patient images to predict accurate representations that were not perceived as different from real postoperative outcomes. LEVEL OF EVIDENCE III: 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 .

Recurrence and Complications of Peri-operative Steroid Injection of Keloids: A Systematic Review and Meta-analysis.

Keloid scars are a particularly challenging fibroproliferative wound healing disorder with a variety of proposed management approaches including concurrent surgery and intralesional steroid injection. We aimed to identify the optimum time for triamcinolone injection of keloids, by comparing the recurrence and complication occurrence in patients who received pre-, intra- or post-operative injection. Studies reporting on the rate of recurrence and complication occurrence following treatment of keloid scarring with concurrent surgical excision and intralesional steroid injection were identified from the PubMed, Web of science and Embase databases. The I-squared (I2) statistic was used to quantify the variability in study estimates due to heterogeneity and to determine whether the fixed or random effect models will be employed. Publication bias was visualized through funnel plots and tested with the Egger's test. We found that the recurrence rate was significantly lower with post-operative injection compared to intra-operative injection (p < 0.001) and pre-operative injection (p = 0.009). A significant difference between intra-operative and pre-operative injection was not found (p = 0.46). In conclusion, post-operative steroid injection after surgical excision results in lower keloid recurrence compared to pre- and intra-operative injection.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 ."

Neural Interconnections of Extracranial Nerves in Headache Surgery: Anatomical Landmarks and Clinical Implications - A Review of Literature.

Headache disorders (HD) remain a nationwide challenge for the US healthcare system affecting nearly 60% of the US population. Surgical deactivation of the peripheral trigger site, also referred to as headache surgery, represents an effective treatment for patients with refractory HD pain or non-response to pharmacological regimes. Research stemming from other surgical specialties has underlined the clinical relevance of neural interconnections in refining diagnostic algorithms, adapting surgical techniques, and improving overall patient outcomes. While different HD trigger points have been identified, there is a paucity of studies discussing these mostly sensory neural interconnections between these trigger points in a comprehensive fashion. Herein, we aim to provide an overview of the specific nerves involved in HD and synthesize the current literature on HD nerve interconnections to, ultimately, deduce clinical implications. Overall, this line of research may help refine the perioperative workflow and enhance HD patient care.

The Triple Adipose-Derived Stem Cell Exosome Technology as a Potential Tool for Treating Triple-Negative Breast Cancer.

BACKGROUND: Extracellular vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties and clinical and therapeutical applications. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates cancer's growth and spread. METHODS: The most significant PubMed literature about extracellular vesicles and Adipose-Derived Stem Cell Exosomes and breast cancer was selected in order to report their biological properties and potential applications, in particular in treating triple-negative breast cancer. RESULTS: Adipose-Derived Stem Cell Exosomes represent a potential tool in targeting triple-negative breast cancer cells at three main levels: the tumor core, the tumor microenvironment and surrounding tissues, including metastases. CONCLUSIONS: The possibility of impacting triple-negative breast cancer cells with engineered Adipose-Derived Stem Cell Exosomes is real. The opportunity to translate our current in vitro analyses into a future in vivo scenario is even more challenging.

Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves.

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential.

Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial.

Background: Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods: The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results: More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, p = 0.01). Conclusions: The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions.

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery.

Lymphadenopathy and lymph node rejection following facial vascularized composite allotransplantation.

BACKGROUND: Apart from the skin, little is known about the immunological processes in deeper tissues, which are typically not accessible to biopsy and inspection, of vascularized composite allografts (VCAs). Face transplant patients develop prominent adenopathy shortly after transplantation that resolves over time. The mechanisms underlying this process are not understood. MATERIALS AND METHODS: A retrospective cohort study was conducted on 9 patients who underwent 10 facial VCAs at the Brigham and Women's Hospital, Boston, MA, between April 2009 and July 2019. Clinical, radiological, and histological data related to lymphadenopathy of the head and neck were reviewed. RESULTS: Patients who received donor-derived lymph nodes (LNs) developed bilateral lymphadenopathy of the submental or submandibular superficial LNs. Median time of presentation was POD18 (range POD6-POM3). Notably, bilateral adenopathy of the neck was not observed in later stages of follow-up (mean follow-up, 115 months). Histology of 3 LNs showed increased histiocytes and apoptosis, with the features reminiscent of necrotizing histiocytic lymphadenitis, and B and T lymphocytes (mostly CD8 + T) admixed with CD163 + histiocytes and dendritic cells. Molecular chimerism analysis in one case showed the coexistence of donor (81%) and recipient (19%) derived lymphocytes. Granzyme B (GZMB) expression confirmed the presence of increased cytotoxic T cells in this LN sample. CONCLUSION: Our data suggested the involvement of an immunological process within the donor-derived LNs after facial allotransplantation between the recipient and donor cells. GZMB expression suggested LN rejection that can occurred independently of skin rejection. This finding supports the need to better define the role of donor-derived immune cells in the context of allograft rejection.

The combined risk predictive power of frailty and hypoalbuminemia in free tissue flap reconstruction: A cohort study of 34,571 patients from the NSQIP database.

INTRODUCTION: Significant morbidity and mortality are hallmarks of the functional decline seen in physically frail patients. The modified frailty index 5 (mFI-5) represents a risk predictor score that has been validated as a comorbidity-based scale in surgery. Serum albumin levels of <3.5 g/dL (hypoalbuminemia) have also been implicated with poor postoperative outcomes. However, the association between these two parameters remains to be investigated. We aimed to elucidate the interdependence of preoperative albumin levels and frailty, as evaluated by the mFI-5 score, and its reliability to prognosticate postoperative results in free flap reconstruction (FFR). METHODS: We conducted a multicenter, retrospective cohort study and accessed the ACS National Surgical Quality Improvement Program (ACS-NSQIP) from 2008 to 2021. We identified all adult patients (≥18 years of age) who underwent a FFR. We extracted perioperative data and lab values including albumin. Multivariable linear and logistic regression analyses were performed to identify independent risk predictors. Main outcomes involved mortality, length of hospital stay, reoperation, medical and surgical complications, and discharge destination within the 30-day postoperative period. RESULTS: A total of 34,571 patients were included in the study, with an average age of 53.9 years (standard deviation [SD] 12.2) and an average body mass index (BMI) of 28.8 (SD 6.1). Of these patients, 7484 were male (21.6%), whereas 22,363 (64.7%) had no frailty (mFI = 0). Additionally, 9466 patients had a frailty score of 1 (27.4%), 2505 had a score of 2 (7.2%), 226 had a score of 3 (0.7%), and 11 had a score of 4 or higher (0.0%). Albumin levels were available for 16,250 patients (47.0%), and among them, 1334 (8.2%) had hypoalbuminemia. Regression analyses showed that higher mFI scores were independent predictors of any, surgical, and medical complications, as well as increased rates of reoperations, unplanned readmissions, and prolonged hospital stays. Hypoalbuminemia independently predicted any, surgical, and medical complications, and higher mortality, reoperation, and longer hospital stay. When both frailty and albumin levels (mFI-5 and albumin) were considered together, this combined assessment was found to be a more accurate predictor of all major outcomes (any, medical and surgical complications, mortality, and reoperation). Further, our analysis identified a weak negative correlation between serum albumin levels and mFI scores (Spearman R: -.1; p < .0001). CONCLUSION: In conclusion, this cohort study highlights the association of hypoalbuminemia with adverse postoperative outcomes, including those not directly related to frailty. Simultaneously, higher mFI scores independently predicted outcomes not associated with hypoalbuminemia. Stemming from these findings, we recommend considering both serum albumin levels and frailty in patients receiving FFR. This perioperative algorithm may help provide more individualized planning including multidisciplinary care and pre and posthabilitation.