The long-term intercorrelation between post-burn pain, anxiety, and depression: a post hoc analysis of the "RE-ENERGIZE" double-blind, randomized, multicenter placebo-controlled trial.

BACKGROUND: Despite the growing prevalence of burn survivors, a gap persists in our understanding of the correlation between acute burn trauma and the long-term impact on psychosocial health. This study set out to investigate the prevalence of long-term pain and symptoms of anxiety and depression in survivors of extensive burns, comparing this to the general population, and identify injury and demographic-related factors predisposing individuals to psychosocial compromise. METHODS: RE-ENERGIZE was an international, double-blinded, randomized-controlled trial that enrolled 1200 patients with partial- or full-thickness burns that required surgical treatment. For the post hoc analysis, we excluded participants who did not complete the Short Form Health Survey (SF-36) questionnaire. Normative data were taken from the 2021 National Health Interview Survey dataset. Propensity score matching was performed using the nearest-neighbor 1-to-1 method, and the two cohorts were compared in terms of chronic pain, and symptoms of anxiety and depression. A multivariable analysis was performed on the burns cohort to identify factors predicting post-discharge pain and symptoms of anxiety and depression. RESULTS: A total of 600 burn patients and 26,666 general population adults were included in this study. Following propensity score matching, both groups comprised 478 participants each, who were predominately male, white, overweight and between 20 and 60 years old. Compared to the general population, burn patients were significantly more likely to report the presence of moderate and a lot of pain (p = 0.002). Symptoms of anxiety were significantly higher in the burn population in two of four levels (most of the time; some of the time; p < 0.0001 for both). Responders in the burn population were significantly less likely to report the absence of depressive symptoms (p < 0.0001). Burn patients were also significantly more likely to report that their mental health affects their social life. TBSA, history of depression, and female sex were identified as independently associated factors for pain, anxiety, and depressive symptoms. The presence of chronic pain and anxiety symptoms independently predicted for symptoms of depression. CONCLUSIONS: Analyzing the largest multicenter cohort of patients with extensive burns, we find that burn injury is associated with chronic pain, and symptoms of anxiety and depression. In addition, TBSA-burned and history of depression directly correlate with the prevalence of chronic pain, and symptoms of anxiety and depression. Finally, pain, and symptoms of anxiety and depression are interrelated and may have interactive effects on the process of recovery following burn injury. Burn patients would, therefore, benefit from a multidisciplinary team approach with early mobilization of pain and mental health experts, in order to promptly prevent the development of psychosocial challenges and their consequences.

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.

The Three-Dimensional Structure of Porcine Bladder Scaffolds Alters the Biology of Murine Diabetic Wound Healing.

OBJECTIVE: To determine if the various three-dimensional structures of bioscaffolds affect wound healing by investigating the efficacy of different porcine-derived urinary bladder matrix (UBM) structures in treating murine diabetic wound healing. METHODS: The authors studied three different UBM structures: particulate (pUBM), one-layer freeze-dried sheet (fdUBM), and three-layer laminated sheet (lmUBM). Scanning electron microscopy images of the structures were used to calculate a wound-exposed surface-area-to-volume ratio. A 1.0 × 1.0-cm full-thickness dorsal wound was excised on 90 db/db mice. Mice were either untreated (blank, n = 15), treated with one UBM structure (pUBM, n = 15; fdUBM, n = 15; lmUBM, n = 15), or treated with a combination of either the one- or three-layer sheet over the particulate matrix (fdUBM + pUBM, n = 15; lmUBM + pUBM, n = 15). The authors obtained macroscopic images of the wounds and harvested tissues for analyses at multiple time points. RESULTS: The surface area available to interact with the wound was highest in the pUBM group and lowest in the lmUBM group. Greater wound bed thickness was noted in the fdUBM, fdUBM + pUBM, and lmUBM groups compared with the blank group. Cellular proliferation was significantly higher in the fdUBM and fdUBM + pUBM groups than in the blank group. The lmUBM + pUBM group had the highest collagen deposition. The pUBM group induced significantly higher leukocyte infiltration compared with the lmUBM, lmUBM + pUBM, and blank groups. Microvessel density was highest in the fdUBM + pUBM group. Significant differences in the wound closure rate were noted between the blank group and the fdUBM and fdUBM + pUBM groups. CONCLUSIONS: Assessment of the three UBM bioscaffold structures highlighted differences in the wound-exposed surface area. Variations in wound healing effects, including collagen deposition, cellular proliferation, and angiogenesis, were identified, with combinations of the structures displaying synergistic effects. This study serves as a platform for future scaffold design and offers promising evidence of the benefits of combining various structures of scaffolds.

Monitoring suPAR levels in post-kidney transplant focal segmental glomerulosclerosis treated with therapeutic plasma exchange and rituximab.

BACKGROUND: Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. suPAR has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease. This study was targeted to evaluate the application of monitoring suPAR in TPE treated rFSGS. METHODS: A retrospective (n = 19) and a prospective (n = 15) cohort of post transplant FSGS patients treated with TPE and rituximab were enrolled. We measured serum suPAR levels before and after the combined therapies, and assessed the role of suPAR changes on proteinuria reduction and podocyte ß3- integrin activity. RESULTS: Treatment with TPE and rituximab resulted in significant decrease in proteinuria and suPAR levels. Among the variables including baseline suPAR, serum creatinine, proteinuria, eGFR, age at diagnosis, age at transplantation, transplantation numbers, time to recurrence, and TPE course numbers, only the reduction in suPAR levels and baseline proteinuria significantly correlated with the changes in proteinuria after treatment, with the former performed better in predicting proteinuria alteration. Additionally, the mean podocyte ß3 integrin activity significantly decreased after TPE and rituximab treatment (1.10 ± 0.08) as compared to before treatment (1.34 ± 0.08), p < 0.05. Only the reduction in suPAR predicted the response to therapies with an odds ratio of 1.43, 95% CI (1.02, 2.00), p < 0.05. CONCLUSIONS: Serum suPAR levels reduced significantly after TPE and rituximab treatment in post transplant FSGS patients. The reduction in suPAR levels may be utilized to assess the changes in proteinuria and monitor the response to the therapies. Larger, multi-centered prospective studies monitoring serum suPAR levels in TPE managed post transplant FSGS are warranted.

Novel unbiased assay for circulating podocyte-toxic factors associated with recurrent focal segmental glomerulosclerosis.

Focal segmental glomerular sclerosis (FSGS) is an irreversible renal pathology characterized by podocyte detachment from the glomerular basement membrane, hyalinosis, and sclerosis. Clinically, it manifests with proteinuria and progressive loss of glomerular filtration. Primary idiopathic FSGS can occur in isolation and frequently progresses to end-stage renal disease, requiring dialysis or kidney transplantation. In 30-50% of these patients, proteinuria and FSGS recur in the renal allograft, suggesting the presence of a podocyte-toxic factor(s) in the recipient's serum. Currently, there is no reliable way to quantify the serum activity or predict the subset of FSGS patients at risk for recurrence after transplantation. We describe a novel in vitro method that measures the podocyte-toxic activity of sera from FSGS patients using cultured human podocytes; we compare this with the effect of compounds such as adriamycin. Using immunofluorescence microscopy followed by computerized image-processing analysis, we show that incubation of human podocytes with adriamycin leads to a dose-dependent disassembly of focal adhesion complexes (FACs). We then demonstrate that sera from patients with posttransplant recurrent or idiopathic FSGS cause a similar FAC disturbance. In contrast, sera from nonrecurrent FSGS patients do not affect FACs. In some FSGS patients, toxic effects of serum can be prevented by blockade of the tumor necrosis factor-α pathway. We propose that this method may be useful as a diagnostic tool to identify FSGS patients with serum podocyte-toxic activity that presumably places them at increased risk for recurrence in the renal allograft.

Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis.

BACKGROUND: Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion. METHODS: One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 levels were measured by ELISA. Glomeruli were stained for CD80. RESULTS: After abatacept therapy, urinary CD80 became undetectable with a concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in the one patient with primary FSGS and in two of the three patients with recurrent FSGS despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. The third patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before the initiation of abatacept therapy; after abatacept therapy, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion. CONCLUSION: These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since the urinary CD80 of our three patients with recurrent FSGS was only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.

Anxiety, depression and suicidal ideation in Lebanese patients undergoing hemodialysis.

Anxiety, depression and suicidal thoughts are highly prevalent comorbidities of end-stage-renal-disease (ESRD). There are no studies in Lebanon on the prevalence of these symptoms in Lebanese end-stage-renal-disease patients. Moreover, the association between ESRD on one hand, and anxiety, depression and suicidal ideation on the other has never been established in Lebanon. Groups of patients at a high-risk of development of these symptoms are not determined. The Hospital Anxiety and Depression Score and M.I.N.I (module C) were used to measure the prevalence of anxiety, depression and suicidal ideation in 51 patients from the dialysis center of Hotel-Dieu de France Hospital in Lebanon. In our sample, 45% of included patients suffered from symptoms of anxiety and 50% presented symptoms of depression.The prevalence of suicidal ideation as detected by the M.I.N.I. is at 37%. No patients presented with a high risk of suicide. There was a statistically significant correlation between the existence of organic comorbidities and the presence of symptoms of depression and suicidal ideation. As for anxiety, the association was marginally significant. The results obtained by our study are consistent with those found in studies performed in other societies. The profile of depression- and suicidal ideation-prone patients has been determined. It consists of patients with at least one medical comorbidity to the ESRD. This, in turn, should lead to increased awareness and better treatment of these psychiatric ailments, considering their impact on morbidity and mortality in ESRD.

Racial disparities in surgical outcomes after mastectomy in 223 000 female breast cancer patients: a retrospective cohort study.

BACKGROUND: Breast cancer mortality and treatment differ across racial groups. It remains unclear whether such disparities are also reflected in perioperative outcomes of breast cancer patients undergoing mastectomy. STUDY DESIGN: The authors reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2008-2021) to identify female patients who underwent mastectomy for oncological purposes. The outcomes were stratified by five racial groups (white, Black/African American, Asian, American Indian/Alaska Native, and Native Hawaiian/Pacific Islander) and included 30-day mortality, reoperation, readmission, surgical and medical complications, and non-home discharge. RESULTS: The study population included 222 947 patients, 68% ( n =151 522) of whom were white, 11% ( n =23 987) Black/African American, 5% ( n =11 217) Asian, 0.5% ( n =1198) American Indian/Alaska Native, and 0.5% ( n =1018) Native Hawaiian/Pacific Islander. While 136 690 (61%) patients underwent partial mastectomy, 54 490 (24%) and 31 767 (14%) women received simple and radical mastectomy, respectively. Overall, adverse events occurred in 17 222 (7.7%) patients, the largest portion of which were surgical complications ( n =7246; 3.3%). Multivariable analysis revealed that being of Asian race was protective against perioperative complications [odds ratio (OR)=0.71; P <0.001], whereas American Indian/Alaska Native women were most vulnerable to the complication occurrence (OR=1.41; P <0.001). Black/African American patients had a significantly lower risk of medical (OR=0.59; P <0.001) and surgical complications (OR=0.60; P <0.001) after partial and radical mastectomy, respectively, their likelihood of readmission (OR=1.14; P =0.045) following partial mastectomy was significantly increased. CONCLUSION: The authors identified American Indian/Alaska Native women as particularly vulnerable to complications following mastectomy. Asian patients experienced the lowest rate of complications in the perioperative period. The authors' analyses revealed comparable confounder-adjusted outcomes following partial and complete mastectomy between Black and white races. Their findings call for care equalization in the field of breast cancer surgery.

Skin Inflammation with a Focus on Wound Healing.

Significance: The skin is the crucial first-line barrier against foreign pathogens. Compromise of this barrier presents in the context of inflammatory skin conditions and in chronic wounds. Skin conditions arising from dysfunctional inflammatory pathways severely compromise the quality of life of patients and have a high economic impact on the U.S. health care system. The development of a thorough understanding of the mechanisms that can disrupt skin inflammation is imperative to successfully modulate this inflammation with therapies. Recent Advances: Many advances in the understanding of skin inflammation have occurred during the past decade, including the development of multiple new pharmaceuticals. Mechanical force application has been greatly advanced clinically. Bioscaffolds also promote healing, while reducing scarring. Critical Issues: Various skin inflammatory conditions provide a framework for analysis of our understanding of the phases of successful wound healing. The large burden of chronic wounds on our society continues to focus attention on the chronic inflammatory state induced in many of these skin conditions. Future Directions: Better preclinical models of disease states such as chronic wounds, coupled with enhanced diagnostic abilities of human skin, will allow a better understanding of the mechanism of action. This will lead to improved treatments with biologics and other modalities such as the strategic application of mechanical forces and scaffolds, which ultimately results in better outcomes for our patients.

Characteristics and Outcomes of Patients Undergoing Surgical Management of Hidradenitis Suppurativa: An ACS-NSQIP Data Analysis.

Objective: Hidradenitis suppurativa (HS) is a painful inflammatory skin disease. Management is largely medical, with surgery reserved for severe refractory cases. In this study, we sought to conduct a retrospective analysis of a multi-institutional surgical database to investigate the surgical management of patients with HS and identify trends in the postoperative outcomes. Approach: The 2011-2019 American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was reviewed to identify patients who underwent surgery for management of HS. Postoperative outcomes were assessed, including surgical and medical complications, length of hospital stay, reoperation, readmission, and nonhome discharge. This article was reported according to the STROBE criteria. Results: We identified 1,030 patients, of which 62% were female and 50% were black. The most common comorbidity was obesity (61%). Surgery was mainly performed by general surgeons (62%) and plastic surgeons (31%). Complications were overall low, with readmission being the most common (7.1%, unplanned 6.0%), followed by reoperation (5.8%). The most common surgical complication was superficial incisional infection (5.1%) and most common medical complication was sepsis (3.8%). Obesity is seen to affect surgical complication rates, with patients with obesity having higher rates of dehiscence (obese: 3.1% and nonobese: 1.0%; p = 0.03) but lower rates of organ space infection (obese: 0.5% and nonobese: 2.0%; p = 0.03) and transfusion (obese: 2.5% and nonobese: 5.2%; p = 0.04). A focus on complications in patients undergoing flap reconstruction (n = 293; 23%), identified higher rates of surgical complications, with superficial incisional infection being the most common (flap reconstruction: 7.5% and incision and drainage, debridement, skin graft: 4.1%; p = 0.04). Innovation: The surgical management of HS is analyzed at the national level, with postoperative complications seen to depend on race and obesity-status. Conclusions: Surgical management for HS is associated with low postoperative complications, making surgery a viable treatment option for this debilitating disease.

Human Amniotic Membrane Promotes Angiogenesis in an Oxidative Stress Chronic Diabetic Murine Wound Model.

Objective: The development of animal models, which adequately replicate the pathophysiology of chronic wounds, has been challenging. In this study, we utilized an oxidative stress (OS) murine model, which was previously developed by our group, to study the effect of a human amniotic membrane (AM) on chronic wound healing. Approach: Forty-five diabetic (genetically obese leptin receptor-deficient mice [db/db]) mice were separated into three groups. Thirty mice received an OS regimen and a 1 - × 1 cm2 full-thickness excisional dorsal wound. The wounds were either covered with AM and occlusive dressing (db/dbOS-AM) or occlusive dressing only (db/dbOS). Fifteen mice did not receive the OS regimen, and were covered with AM and occlusive dressing (db/db-AM). The wounds were photographed, and tissue was harvested at various time points. Results: Vascular density was higher in the AM-treated groups (db/dbOS-AM: 34 ± 12; db/db-AM: 37 ± 14; vs. db/dbOS: 19 ± 9 cluster of differentiation 31 [CD31+]/high power field [HPF] photograph; p = 0.04 and p = 0.003). Vessel maturity was lowest in the db/dbOS group (21% ± 4%; vs. db/dbOS-AM: 38% ± 10%, p = 0.004; db/db-AM: 40% ± 11%, p = 0.0005). Leukocyte infiltration was higher in the AM groups (db/dbOS-AM: 15 ± 4; db/db-AM: 16 ± 4 vs. db/dbOS: 8 ± 3 lymphocyte common antigen [CD45+]/HPF; p = 0.005 and p = 0.06). AM upregulated various proangiogenic factors, including vascular endothelial growth factor (VEGF), and downregulated genes involved in chronicity, such as osteopontin, as visualized through proteome analysis and western blotting. Cell death was lower in the AM groups (db/dbOS-AM: 28 ± 10, db/db-AM: 7 ± 5 vs. db/dbOS: 17% ± 9% Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling [TUNEL+]; p = 0.03 and p < 0.0001). Innovation: This study offers new insight on the mechanisms of action of human AM in chronic wound healing. Conclusion: AM treatment promoted healing in mice with complex chronic wounds. The AM stimulated angiogenesis through upregulation of proangiogenic factors, improving the wound milieu by increasing leukocyte and growth factor delivery and decreasing cell death.

Early Outcomes and Risk Factors in Orthognathic Surgery for Mandibular and Maxillary Hypo- and Hyperplasia: A 13-Year Analysis of a Multi-Institutional Database.

BACKGROUND: Orthognathic surgery (OS) is a frequently performed procedure for the correction of dentofacial deformities and malocclusion. Research on OS is mostly limited to single-surgeon experience or single-institutional reports. We, therefore, retrospectively analyzed a multi-institutional database to investigate outcomes of OS and identify risk factors for peri- and postoperative complications. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2008-2020) to identify patients who underwent OS for mandibular and maxillary hypo- and hyperplasia. The postoperative outcomes of interest included 30-day surgical and medical complications, reoperation, readmission, and mortality. We also evaluated risk factors for complications. RESULTS: The study population included 674 patients, 48% of whom underwent single jaw surgery, 40% double jaw surgery, and 5.5% triple jaw surgery. The average age was 29 ± 11 years, with an equal gender distribution (females: n = 336; 50%, males: n = 338; 50%). Adverse events were relatively rare, with a total of 29 (4.3%) complications reported. The most common surgical complication was superficial incisional infection (n = 14; 2.1%). While the multivariable analysis revealed isolated single lower jaw surgery (p = 0.03) to be independently associated with surgical complication occurrence, it also identified an association between the outpatient setting and the frequency of surgical complications (p = 0.03) and readmissions (p = 0.02). In addition, Asian ethnicity was identified as a risk factor for bleeding (p = 0.003) and readmission (p = 0.0009). CONCLUSION: Based on the information recorded by the ACS-NSQIP database, our analysis underscored the positive (short-term) safety profile of OS. We found OS of the mandible to be associated with higher complication rates. The calculated risk role of OS in the outpatient setting warrants further investigation. A significant correlation between Asian OS patients and postoperative adverse events was found. Implementation of these novel risk factors into the surgical workflow may help facial surgeons refine their patient selection and improve patient outcomes. Future studies are needed to investigate the causal relationships of the observed statistical correlations.

Modulation of Lymphangiogenesis in Incisional Murine Diabetic Wound Healing Using Negative Pressure Wound Therapy.

Objective: Despite the significant function of lymphatics in wound healing, and frequent clinical use of Negative Pressure Wound Therapy (NPWT), the effect of mechanical force application on lymphangiogenesis remains to be elucidated. We utilize a murine incisional wound healing model to assess the mechanisms of lymphangiogenesis following NPWT. Approach: Dorsal incisional skin wounds were created on diabetic mice (genetically obese leptin receptor-deficient mice [db/db]; n = 30) and covered with an occlusive dressing (Control, n = 15) or NPWT (-125 mmHg, continuous, 24 h for 7 days; NPWT, n = 15). The wounds were macroscopically assessed for 28 days. Tissue was harvested on day 10 for analysis. Qualitative functional analysis of lymphatic drainage was performed on day 28 using Evans Blue staining (n = 2). Results: NPWT increased lymphatic vessel density (40 ± 20 vs. 12 ± 6 podoplanin [PDPN]+ and 25 ± 9 vs. 14 ± 8 lymphatic vessel endothelial receptor 1 [LYVE-1]+) and vessel diameter (28 ± 9 vs. 12 ± 2 µm). Western blotting verified the upregulation of LYVE-1 with NPWT. Leukocyte presence was higher with NPWT (22% ± 3.7% vs. 9.1% ± 4.1% lymphocyte common antigen [CD45]+) and the leukocytes were predominately B cells clustered within vessels (8.8% ± 2.5% vs. 18% ± 3.6% B-lymphocyte antigen CD20 [CD20]+). Macrophage presence was lower in the NPWT group. Lymphatic drainage was increased in the NPWT group, which exhibited greater Evans Blue positivity. Innovation: The lymphangiogenic effects take place independent of macrophage infiltration, appearing to correlate with B cell presence. Conclusion: NPWT promotes lymphangiogenesis in incisional wounds, significantly increasing the lymph vessel density and diameter. This study highlights the potential of NPWT to stimulate lymphatic drainage and wound healing of surgical incisions.

Impact of sarcopenia on outcomes in surgical patients: a systematic review and meta-analysis.

BACKGROUND: Surgeons have historically used age as a preoperative predictor of postoperative outcomes. Sarcopenia, the loss of skeletal muscle mass due to disease or biological age, has been proposed as a more accurate risk predictor. The prognostic value of sarcopenia assessment in surgical patients remains poorly understood. Therefore, the authors aimed to synthesize the available literature and investigate the impact of sarcopenia on perioperative and postoperative outcomes across all surgical specialties. METHODS: The authors systematically assessed the prognostic value of sarcopenia on postoperative outcomes by conducting a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching the PubMed/MEDLINE and EMBASE databases from inception to 1st October 2022. Their primary outcomes were complication occurrence, mortality, length of operation and hospital stay, discharge to home, and postdischarge survival rate at 1, 3, and 5 years. Subgroup analysis was performed by stratifying complications according to the Clavien-Dindo classification system. Sensitivity analysis was performed by focusing on studies with an oncological, cardiovascular, emergency, or transplant surgery population and on those of higher quality or prospective study design. RESULTS: A total of 294 studies comprising 97 643 patients, of which 33 070 had sarcopenia, were included in our analysis. Sarcopenia was associated with significantly poorer postoperative outcomes, including greater mortality, complication occurrence, length of hospital stay, and lower rates of discharge to home (all P <0.00001). A significantly lower survival rate in patients with sarcopenia was noted at 1, 3, and 5 years (all P <0.00001) after surgery. Subgroup analysis confirmed higher rates of complications and mortality in oncological (both P <0.00001), cardiovascular (both P <0.00001), and emergency ( P =0.03 and P =0.04, respectively) patients with sarcopenia. In the transplant surgery cohort, mortality was significantly higher in patients with sarcopenia ( P <0.00001). Among all patients undergoing surgery for inflammatory bowel disease, the frequency of complications was significantly increased among sarcopenic patients ( P =0.007). Sensitivity analysis based on higher quality studies and prospective studies showed that sarcopenia remained a significant predictor of mortality and complication occurrence (all P <0.00001). CONCLUSION: Sarcopenia is a significant predictor of poorer outcomes in surgical patients. Preoperative assessment of sarcopenia can help surgeons identify patients at risk, critically balance eligibility, and refine perioperative management. Large-scale studies are required to further validate the importance of sarcopenia as a prognostic indicator of perioperative risk, especially in surgical subspecialties.

Artificial intelligence-enabled simulation of gluteal augmentation: A helpful tool in preoperative outcome simulation?

BACKGROUND: While the buttock region is considered an esthetic hallmark, the Brazilian butt lift (BBL) remains controversially discussed in the plastic surgery community. This is due to its contentious safety profile. Thus, informed consent and patient education play a key role in preoperative planning. To this end, we aimed to program an easy-to-use, widely accessible, and low-budget algorithm that produces reliable outcome simulations. METHODS: The conditional generative adversarial network (GAN) was trained using pre- and postoperative images from 1628 BBL patients. To validate outcome simulation, 25 GAN-generated images were assessed deploying 67 Amazon Mechanical Turk Workers (Mturks). RESULTS: Mturks could not differentiate between GAN-generated and real patient images in approximately 49.4% of all trials. CONCLUSION: This study presents a free-to-use, widely accessible, and reliable algorithm to visualize potential surgical outcomes that could potentially be applied in other fields of plastic surgery.

Association of age with perioperative morbidity among patients undergoing surgical management of minor burns.

Introduction: Burn injuries are associated with significant morbidity, often necessitating surgical management. Older patients are more prone to burns and more vulnerable to complications following major burns. While the relationship between senescence and major burns has already been thoroughly investigated, the role of age in minor burns remains unclear. To better understand differences between elderly and younger patients with predominantly minor burns, we analyzed a multi-institutional database. Methods: We reviewed the 2008-2020 ACS-NSQIP database to identify patients who had suffered burns according to ICD coding and underwent initial burn surgery. Results: We found 460 patients, of which 283 (62%) were male and 177 (38%) were female. The mean age of the study cohort was 46 ± 17 years, with nearly one-fourth (n = 108; 23%) of all patients being aged ≥60 years. While the majority (n = 293; 64%) suffered from third-degree burns, 22% (n = 99) and 15% (n = 68) were diagnosed with second-degree burns and unspecified burns, respectively. An average operation time of 46 min, a low mortality rate of 0.2% (n = 1), a short mean length of hospital stay (1 day), and an equal distribution of in- and outpatient care (51%, n = 234 and 49%, n = 226, respectively) indicated that the vast majority of patients suffered from minor burns. Patients aged ≥60 years showed a significantly prolonged length of hospital stay (p<0.0001) and were significantly more prone to non-home discharge (p<0.0001). In univariate analysis, advanced age was found to be a predictor of surgical complications (p = 0.001) and medical complications (p = 0.0007). Elevated levels of blood urea nitrogen (p>0.0001), creatinine (p>0.0001), white blood cell count (p=0.02), partial thromboplastin time (p = 0.004), and lower levels of albumin (p = 0.0009) and hematocrit (p>0.0001) were identified as risk factors for the occurrence of any complication. Further, complications were more frequent among patients with lower body burns. Discussion: In conclusion, patients ≥60 years undergoing surgery for predominantly minor burns experienced significantly more complications. Minor lower body burns correlated with worse outcomes and a higher incidence of adverse events. Decreased levels of serum albumin and hematocrit and elevated values of blood urea nitrogen, creatinine, white blood count, and partial thromboplastin time were identified as predictive risk factors for complications.

The surgical patient of yesterday, today, and tomorrow-a time-trend analysis based on a cohort of 8.7 million surgical patients.

BACKGROUND: Global healthcare delivery is challenged by the aging population and the increase in obesity and type 2 diabetes. The extent to which such trends affect the cohort of patients the authors surgically operate on remains to be elucidated. Comprising of 8.7 million surgical patients, the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database can be analyzed to investigate the echo of general population dynamics and forecast future trends. MATERIAL AND METHODS: The authors reviewed the ACS-NSQIP database (2008-2020) in its entirety, extracting patient age, BMI, and diabetes prevalence. Based on these data, the authors forecasted future trends up to 2030 using a drift model. RESULTS: During the review period, median age increased by 3 years, and median BMI by 0.9 kg/m2. The proportion of patients with overweight, obesity class I, and class II rates increased. The prevalence of diabetes rose between 2008 (14.9%) and 2020 (15.3%). The authors forecast the median age in 2030 to reach 61.5 years and median BMI to climb to 29.8 kg/m2. Concerningly, in 2030, eight of ten surgical patients are projected to have a BMI above normal. Diabetes prevalence is projected to rise to 15.6% over the next decade. CONCLUSION: General population trends echo in the field of surgery, with the surgical cohort aging at an alarmingly rapid rate and increasingly suffering from obesity and diabetes. These trends show no sign of abating without dedicated efforts and call for urgent measures and fundamental re-structuring for improved future surgical care.

Surgical complications in immediate and delayed breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: Because of improved aesthetic results, immediate breast reconstruction has become the most widely used timing of reconstruction following mastectomy. Many studies report complication rates between immediate and delayed reconstructions at certain medical institutions, but no systematic reviews exist to summarize the literature. This systematic review was conducted to assess the outcomes in women who underwent immediate versus delayed breast reconstruction following mastectomy for breast cancer. METHODS: Cochrane, PubMed, and EMBASE electronic databases were screened, and data were extracted from included studies. The clinical outcomes assessed were surgical complications, length of postoperative hospital stay, and reoperation rate. RESULTS: A total of 30 studies met the inclusion criteria for the review and provided enough data to be included in the meta-analysis (14,034 patients). Women receiving immediate breast reconstruction were significantly more likely to experience surgical complications (OR 1.30, 95% CI 1.03, 1.65; p = 0.03). Sensitivity analysis showed that women receiving immediate reconstruction were also more likely to experience infection (OR 1.41, 95% 1.04, 1.92; p = 0.03) and hematoma/seroma (OR 2.01, 95% CI 1.27-3.17; p = 0.003). Furthermore, a separate sensitivity analysis showed no significant differences in reported outcomes when comparing studies whose patient cohorts received post-mastectomy radiation therapy (PMRT). CONCLUSIONS: This study provides evidence that immediate breast reconstruction generally increases the risk of complications in comparison with delayed reconstruction. Additional prospective and observational studies are needed to determine the role of PMRT and reconstruction surgical technique in the incidence of complications between immediate and delayed reconstructions.

A novel 'social contract' - An attempt to harmonize a sponsor's exploratory research with a clinical study participant's data rights.

BACKGROUND: Pharmaceutical drug development rarely addresses a study participant's control of their genomic data, how to return individual incidental findings, and how to make use of genomic data more efficiently for exploratory research purposes. Mutually beneficial solutions to these issues are needed, as whole genome sequencing (WGS) is increasingly adopted in human research and as access to such information could provide impactful health-related information for a participant. METHODS: In this paper, we offer a novel framework to align a trial sponsor's need for broad exploratory research of the human genome with the study participant's right to data access and access control. The Exploratory Genetic Research Project (EGRP) aims to gather WGS on all participants of a sponsor's clinical trials. It is set up as a separate umbrella protocol to facilitate the consenting process, as well as the delineation between clinical trial endpoints versus exploratory future research. CONCLUSION: This concept establishes a participant's autonomy regarding access to genomic data and the disclosure of actionable incidental findings. The feasibility of EGRP will be tested and reassessed as it is deployed over the next few years.

Xenogenic induction of adipose tissue and maintenance through pre- and post-conditioning using external volume expansion.

External volume expansion (EVE) has been shown to improve fat graft survival. In this study, we investigated the xenogenic implantation of human allograft adipose matrix (AAM) in non-immunocompromised mice in combination with pre- and post-conditioning with EVE to assess long-term adipose tissue survival. Sixty-eight recipient sites in thirty-four eight-week-old wild type (C57BL/6J) mice were separated into four groups. Thirty-four sites received no conditioning and either a subcutaneous injection of 300 µl saline (n= 17; PBS group) or AAM (n= 17; AAM group). Thirty-four sites received pre-conditioning with EVE (Day -7-3 pre-grafting) and 300 µl of AAM. Seventeen of these sites received immediate post-conditioning (Day 1-5 post-grafting) and 17 delayed post-conditioning (Day 28-32 post-grafting). Tissue was harvested at week 12 for analysis. At 12 weeks, immediate and delayed post-conditioning enabled higher volume retention (p= 0.02 andp< 0.0001, respectively). Adipose Stem Cells were greater in the AAM+Del-EVE group compared to the AAM (p= 0.01). Microvessel density was lower in the AAM group compared to the AAM+Imm-EVE (p= 0.04) and AAM+Del-EVE group (p= 0.02). Macrophage infiltration was lower in the AAM+Imm-EVE (p= 0.002) and AAM+Del-EVE (p= 0.003) groups compared to the AAM group. PCR analysis and Western blotting identified a significantly higher expression of PPAR-γ, LPL and VEGF with delayed-conditioning. Pre- and post-conditioning, particularly delayed-post-conditioning, of the recipient site optimized the microenvironment allowing significant adipogenesis and survival of neo-adipose tissue through robust angiogenesis. This study supports that xenogenic transplantation of adipose matrix allows adipose tissue formation and survival with EVE as an adjuvant.