Evolution of Metastases in Space and Time under Immune Selection.

We examined how the immune microenvironment molds tumor evolution at different metastatic organs in a longitudinal dataset of colorectal cancer. Through multiplexed analyses, we showed that clonal evolution patterns during metastatic progression depend on the immune contexture at the metastatic site. Genetic evidence of neoantigen depletion was observed in the sites with high Immunoscore and spatial proximity between Ki67+ tumor cells and CD3+ cells. The immunoedited tumor clones were eliminated and did not recur, while progressing clones were immune privileged, despite the presence of tumor-infiltrating lymphocytes. Characterization of immune-privileged metastases revealed tumor-intrinsic and tumor-extrinsic mechanisms of escape. The lowest recurrence risk was associated with high Immunoscore, occurrence of immunoediting, and low tumor burden. We propose a parallel selection model of metastatic progression, where branched evolution could be traced back to immune-escaping clones. The findings could inform the understanding of cancer dissemination and the development of immunotherapeutics.

Germline genetic contribution to the immune landscape of cancer.

Understanding the contribution of the host's genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling. Common variants of IFIH1, TMEM173 (STING1), and TMEM108 were associated with differential interferon signaling and variants mapping to RBL1 correlated with T cell subset abundance. Pathogenic or likely pathogenic variants in BRCA1 and in genes involved in telomere stabilization and Wnt-ß-catenin also acted as immune modulators. Our findings provide evidence for the impact of germline genetics on the composition and functional orientation of the tumor immune microenvironment. The curated datasets, variants, and genes identified provide a resource toward further understanding of tumor-immune interactions.

IL-1ß+ macrophages fuel pathogenic inflammation in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies1. Inflammatory and immunomodulatory signals co-exist in the pancreatic tumour microenvironment, leading to dysregulated repair and cytotoxic responses. Tumour-associated macrophages (TAMs) have key roles in PDAC2, but their diversity has prevented therapeutic exploitation. Here we combined single-cell and spatial genomics with functional experiments to unravel macrophage functions in pancreatic cancer. We uncovered an inflammatory loop between tumour cells and interleukin-1ß (IL-1ß)-expressing TAMs, a subset of macrophages elicited by a local synergy between prostaglandin E2 (PGE2) and tumour necrosis factor (TNF). Physical proximity with IL-1ß+ TAMs was associated with inflammatory reprogramming and acquisition of pathogenic properties by a subset of PDAC cells. This occurrence was an early event in pancreatic tumorigenesis and led to persistent transcriptional changes associated with disease progression and poor outcomes for patients. Blocking PGE2 or IL-1ß activity elicited TAM reprogramming and antagonized tumour cell-intrinsic and -extrinsic inflammation, leading to PDAC control in vivo. Targeting the PGE2-IL-1ß axis may enable preventive or therapeutic strategies for reprogramming of immune dynamics in pancreatic cancer.

DNA synthesis is required for reprogramming mediated by stem cell fusion.

Embryonic stem cells (ESCs) can instruct the conversion of differentiated cells toward pluripotency following cell-to-cell fusion by a mechanism that is rapid but poorly understood. Here, we used centrifugal elutriation to enrich for mouse ESCs at sequential stages of the cell cycle and showed that ESCs in S/G2 phases have an enhanced capacity to dominantly reprogram lymphocytes and fibroblasts in heterokaryon and hybrid assays. Reprogramming success was associated with an ability to induce precocious nucleotide incorporation within the somatic partner nuclei in heterokaryons. BrdU pulse-labeling experiments revealed that virtually all successfully reprogrammed somatic nuclei, identified on the basis of Oct4 re-expression, had undergone DNA synthesis within 24 hr of fusion with ESCs. This was essential for successful reprogramming because drugs that inhibited DNA polymerase activity effectively blocked pluripotent conversion. These data indicate that nucleotide incorporation is an early and critical event in the epigenetic reprogramming of somatic cells in experimental ESC-heterokaryons.

Penetrant-induced plasticization in microporous polymer membranes.

Penetrant-induced plasticization has prevented the industrial deployment of many polymers for membrane-based gas separations. With the advent of microporous polymers, new structural design features and unprecedented property sets are now accessible under controlled laboratory conditions, but property sets can often deteriorate due to plasticization. Therefore, a critical understanding of the origins of plasticization in microporous polymers and the development of strategies to mitigate this effect are needed to advance this area of research. Herein, an integrative discussion is provided on seminal plasticization theory and gas transport models, and these theories and models are compared to an exhaustive database of plasticization characteristics of microporous polymers. Correlations between specific polymer properties and plasticization behavior are presented, including analyses of plasticization pressures from pure-gas permeation tests and mixed-gas permeation tests for pure polymers and composite films. Finally, an evaluation of common and current state-of-the-art strategies to mitigate plasticization is provided along with suggestions for future directions of fundamental and applied research on the topic.

An in vitro model for osteoarthritis using long-cultured inflammatory human macrophages repeatedly stimulated with TLR agonists.

Osteoarthritis (OA) is characterized by an abundance of inflammatory M1-like macrophages damaging local tissues. The search for new potential drugs for OA suffers from the lack of appropriate methods of long-lasting inflammation. Here we developed and characterized an in vitro protocol of long-lasting culture of primary human monocyte-derived macrophages differentiated with a combination of M-CSF+GM-CSF that optimally supported long-cultured macrophages (LC-Mϕs) for up to 15 days, unlike their single use. Macrophages repeatedly stimulated for 15 days with the TLR2 ligand Pam3CSK4 (LCS-Mϕs), showed sustained levels over time of IL-6, CCL2, and CXCL8, inflammatory mediators that were also detected in the synovial fluids of OA patients. Furthermore, macrophages isolated from the synovia of two OA patients showed an expression profile of inflammation-related genes similar to that of LCS-Mϕs, validating our protocol as a model of chronically activated inflammatory macrophages. Next, to confirm that these LCS-Mϕs could be modulated by anti-inflammatory compounds, we employed dexamethasone and/or celecoxib, two drugs widely used in OA treatment, that significantly inhibited the production of inflammatory mediators. This easy-to-use in vitro protocol of long-lasting inflammation with primary human macrophages could be useful for the screening of new compounds to improve the therapy of inflammatory disorders.

Shifting the paradigm: engaging multicellular networks for cancer therapy.

Most anti-cancer modalities are designed to directly kill cancer cells deploying mechanisms of action (MOAs) centered on the presence of a precise target on cancer cells. The efficacy of these approaches is limited because the rapidly evolving genetics of neoplasia swiftly circumvents the MOA generating therapy-resistant cancer cell clones. Other modalities engage endogenous anti-cancer mechanisms by activating the multi-cellular network (MCN) surrounding neoplastic cells in the tumor microenvironment (TME). These modalities hold a better chance of success because they activate numerous types of immune effector cells that deploy distinct cytotoxic MOAs. This in turn decreases the chance of developing treatment-resistance. Engagement of the MCN can be attained through activation of immune effector cells that in turn kill cancer cells or when direct cancer killing is complemented by the production of proinflammatory factors that secondarily recruit and activate immune effector cells. For instance, adoptive cell therapy (ACT) supplements cancer cell killing with the release of homeostatic and pro-inflammatory cytokines by the immune cells and damage associated molecular patterns (DAMPs) by dying cancer cells. The latter phenomenon, referred to as immunogenic cell death (ICD), results in an exponential escalation of anti-cancer MOAs at the tumor site. Other approaches can also induce exponential cancer killing by engaging the MCN of the TME through the release of DAMPs and additional pro-inflammatory factors by dying cancer cells. In this commentary, we will review the basic principles that support emerging paradigms likely to significantly improve the efficacy of anti-cancer therapy.

Clinical implications of the family history in patients with lung cancer: a systematic review of the literature and a new cross-sectional/prospective study design (FAHIC: lung).

Compared to other malignancies, few studies have investigated the role of family history of cancer (FHC) in patients with lung cancer, yielding largely heterogeneous results. We performed a systematic literature review in accordance with PRISMA guidelines, searching the PubMed and Scopus databases from their inception to November 25, 2023, to identify studies reporting on the role of FHC in patients with lung cancer. A total of 53 articles were included, most with a retrospective design and encompassing a variety of geographical areas and ethnicities.Thirty studies (56.6%) assessed patients with non-small cell lung cancer (NSCLC), while 17 studies (32.1%) assessed patients with mixed histologies. Overall, the rates of FHC ranged from 8.3 to 68.9%, and the rates of family history of lung cancer ranged from 2 to 46.8%. Twenty-seven studies investigated FHC as a potential risk factor for lung cancer, with more than half reporting an increased risk for subjects with FHC. Five studies reported on the potential role of FHC in determining clinical outcomes, and twelve studies examined the relationship between FHC and germline mutations. Notably, only one study reported a significantly increased rate of germline mutations, including ATM, BRCA2, and TP53, for patients with a family history of lung cancer compared to those without, but both groups had a low prevalence of mutations (< 1%).The FAHIC-Lung (NCT06196424) is the first cross-sectional/prospective study specifically developed to identify FHC patterns and within-family clusters of other risk factors, including smoking, to guide patients with NSCLC to systematic genetic counseling. Acknowledging the largely heterogeneous results of our systematic review and considering the clinical implications of detecting pathogenic germline variants (PGVs), the FAHIC-lung study aims to identify patients potentially enriched with PGVs/likely PGVs to direct them to germline screening outside of the research setting.

Histological analysis and etiology of a pathological iguanodontian femur from England.

Derived ornithopods, such as hadrosaurids, show a high occurrence of fossilized lesions and diseases. However, paleopathologies in iguanodontians seem to be less common, considering the rich fossil record of these taxa in Europe, in particular in Belgium, Britain and Spain. Here, we describe an iguanodontian femur discovered in England that exhibits a large overgrowth of its lateral aspect, not previously recognized in any other similar remains. The specimen was scanned with micro-computed tomography (microCT) and later sectioned in three sites of the overgrowth for histological analysis. The femur belongs to an early adult Iguanodontia indet., based on the presence of a woven parallel fibered complex in the outer cortex and three to four lines of arrested growth. Internal analysis of the dome-like overgrowth suggests it can be diagnosed as a fracture callus. The injury might have negatively impacted upon the animal's locomotion as the trauma had occurred in the region above the knee, a crucial spot for hindlimb musculature. Finally, a cancellous medullary bone-like tissue was recognized in the medullary cavity next to the pathological overgrowth. An attempt was made to determine the precise nature of this tissue, as medullary bone is linked with the ovulation period in (avian) dinosaurs, whereas other types of endosteal, medullary bone-like tissue have previously been recognized in pathological bones.

Olfactory Neuron Prokineticin-2 as a Potential Target in Parkinson's Disease.

OBJECTIVE: The objective of this study was to outline the dynamics of prokineticin-2 pathway in relation to clinical-pathological features of Parkinson's disease by examining olfactory neurons of patients. METHODS: Thirty-eight patients (26 de novo, newly diagnosed) and 31 sex/age-matched healthy controls underwent noninvasive mucosa brushing for olfactory neurons collection, and standard clinical assessment. Gene expression levels of prokineticin-2, prokineticin-2 receptors type 1 and 2, and prokineticin-2-long peptide were measured in olfactory neurons by real-time polymerase chain reaction (PCR); moreover, the prokineticin-2 protein and α-synuclein species (total and oligomeric) were quantified by immunofluorescence staining. RESULTS: Prokineticin-2 expression was significantly increased in Parkinson's disease. De novo patients had higher prokineticin-2 levels, directly correlated with Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III motor score. In addition, oligomeric α-synuclein was higher in Parkinson's disease and directly correlated with prokineticin-2 protein levels. Total α-synuclein did not differ between patients and controls. INTERPRETATION: Prokineticin-2 is a chemokine showing neuroprotective effects in experimental models of Parkinson's disease, but translational proof of its role in patients is still lacking. Here, we used olfactory neurons as the ideal tissue to analyze molecular stages of neurodegeneration in vivo, providing unprecedented evidence that the prokineticin-2 pathway is activated in patients with Parkinson's disease. Specifically, prokineticin-2 expression in olfactory neurons was higher at early disease stages, proportional to motor severity, and associated with oligomeric α-synuclein accumulation. These data, consistently with preclinical findings, support prokineticin-2 as a candidate target in Parkinson's disease, and validate reliability of olfactory neurons to reflect pathological changes of the disease. ANN NEUROL 2023;93:196-204.

Fate of melatonin orally administered in preterm newborns: Antioxidant performance and basis for neuroprotection.

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age ≤ 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns.

Comparison of split thickness skin graft versus full thickness skin graft for radial forearm flap donor site closure: A systematic review and Meta-analysis.

BACKGROUND: The radial forearm flap (RFF) is one of the most commonly used flaps in reconstructive surgery. Split-thickness skin grafting (STSG) has traditionally been used for closure of the forearm. However, full-thickness skin grafting (FTSG) has gained in popularity to achieve more satisfactory results. The aim of the study is to identify the best RFF donor site closure technique by comparing the functional and aesthetic outcomes of STSG and FTSG. METHODS: PubMed and EMBASE databases were queried. Only studies comparing complications rate, functional and aesthetic outcomes between STSG and FTSG were included. The primary outcome was graft failure rate. Secondary outcomes included the aesthetic result and functionality of the forearm/wrist. RESULTS: A total of 13 studies were included in this review, accounting for a total of 712 patients with mean age of 60.7 years. Overall, 348 patients underwent FTSG and 377 underwent STSG. The mean follow-up was 14.7 months. The rate of graft failure in FTSG was significantly higher compared to STSG (OR: 2.79, 95 % CI 1.38-5.65, p = 0.004). There was no significant difference in rate of tendon exposure (OR: 0.83, p = 0.65) and infection (OR: 1.37, p = 0.42). Regarding the aesthetic outcome, no significant difference between FTSG and STSG based on observer (SMD = -0.37, p = 0.17) and patient (SMD = -0.016, p = 0.93) assessment, respectively. Overall postoperative functional assessment showed a not severely impaired hand and arm function in both groups. Subjective evaluation of pain was similar between groups. CONCLUSION: FTSG is associated with higher risk of graft failure than STSG in RFF donor site closure, without significant improvement in aesthetic results.

Are We Speaking the Same "Language" Regarding Underrepresented Groups in Plastic Surgery and Increasing Diversity Within Our Field?

BACKGROUND: Plastic Surgery is one of the fields that lags behind the rest when it comes to surgeons from backgrounds underrepresented in medicine (URiM). Extensive research has shown that diversity in health care not only fosters inclusivity but also saves lives. The study aim is to quantify how many integrated plastic surgery residency programs have outlined criteria defining diversity goals and/or groups of people they consider to be URiM. METHODS: All American Council for Graduate Medical Education-accredited integrated plastic surgery program Web sites were reviewed for diversity missions/statements and explicit mentions of the racial and ethnic groups. Web sites were deemed "up-to-date" if they were last updated within 6 months before the initial data collection period. The data collection period was from November 20 to 29, 2022. RESULTS: A total of 86 program were reviewed. Only 8 programs (9%) had clear URiM criteria listed on their Web sites, whereas 26 (30%) relied on institution/department-wide criteria, 1 (1%) listed that they were adhering to American Association of Medical Colleges definition of URiM, and 51 programs (60%) had no form of definition for what is considered URiM. When looking at the programs that have some form of criteria for URiM (n = 35 [40%]), all programs (100%) considered African American/Black, Native American/Alaskan Native, Hispanic/Latinx, and Pacific Islander/Native Hawaiian as groups URiM. Assessing the same subset of programs that have a form of criteria listed (n = 35 [40%]), 19 (58%) had listed other groups outside of race/ethnicity considered to be URiM for their program, and 14 (42%) programs did not. Fourteen programs (74%) considered LGBTQIA+ as a URiM group. CONCLUSION AND SIGNIFICANCE: There still is a great deal of heterogeneity among residency programs when it comes to identifying which medical students are URiM. Numerous plastic surgery organizations have placed diversity and inclusive excellence at the forefront of their agendas; however, it is critical that residency programs also actively align their efforts in an equitable and intentional way. This study serves to encourage residency programs to evaluate their mission toward diversity, equity, and inclusion and to spark discussion toward creating a clearer URiM definition to be consistent among all programs.

Fourteen-Year Experience in Burn Eyelid Reconstruction and Complications Recurrence: A Retrospective Cohort Study.

BACKGROUND: Loss of vision and other ocular defects are a concern with eyelid burn sequelae. This most commonly progresses from eyelid contracture to cicatricial ectropion and lagophthalmos. When left untreated, these may lead to exposure keratitis, ulceration, infection, perforation, and loss of vision. In the case of full-thickness eyelid burns, release and grafting are required. However, there is a paucity of studies on outcomes in eyelid burn surgery treatment, despite concern for permanent ocular damage or loss of vision. The aim of the study is to describe the complication rates in burn eyelid reconstruction at a single center for 14 years. METHODS: A retrospective cohort study was performed of all patients who had sustained eyelid burns and required reconstruction between April 2009 and February 2023. Medical records were obtained from patients' charts. Collected data include demographics, medical history, type of injury, indication for surgery, procedure performed, and complications. RESULTS: A total of 14 patients and 25 eyelids underwent eyelid reconstruction of the 901 total patients with burn-related injuries requiring plastic surgery reconstruction. These patients underwent 54 eyelid surgeries with a mean follow-up time of 13.1 ± 17.1 months. Patients were 71% men and 29% women, with a mean age of 45.1 ± 15.6 years. In 53.7% (n = 29) of the cases, the simultaneous reconstruction of both the upper and lower eyelids was necessary. The reconstruction of the upper and lower eyelid alone represented a smaller percentage (25.9% and 20.4%, respectively). On average, the patients received 3.9 ± 3.5 eyelid surgeries. The overall complication rate was 53.7% (n = 29). The most common complication was ectropion (42.6%, n = 23). Other complications included eye injury (25.9%, n = 14), lagophthalmos (24.1%, n = 13), local infection (7.4%, n = 4), and graft loss (5.6%, n = 3). CONCLUSION: Periorbital burns represent a major challenge that may require complex surgical intervention. Full-thickness skin graft remains the standard of care for patients with eyelid burns. However, there is a high incidence of ectropion that may require reoperation. Further studies examining the conditions of successful eyelid burn procedures may provide guidance on when patients may benefit from eyelid reconstruction during their burn treatment.

The Development and Management of Neck Burn Scar Contracture Recurrence: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Burn neck contractures pose a great challenge for reconstructive surgeons. A paucity of literature exist regarding long-term outcomes based on different surgical management strategies. The aim of this study was to evaluate the long-term outcomes of the treatment of neck burn scar contractures and evaluate surgical strategies according to their long-term effectiveness and associated complications. METHODS: A retrospective cohort study was conducted to review outcomes of neck contractures release after burn injury. All patients operated on between January 2009 and February 2023 at a single institution were included. RESULTS: A total of 20 patients developed neck burn scar contracture and were included in this study. The mean age was 32.9 ± 20.3 years. The burn injuries were most commonly thermal (n = 19, 95%). All burn injuries were full-thickness burns, with an average neck defect size of 130.5 ± 106.0 cm2. Overall, 45 surgical scar release procedures were performed on the 20 patients who developed a neck contracture. Patients underwent 1.65 ± 1.04 surgeries on average to address neck contracture. Although 25% of patients only received 1 surgery to treat neck contracture, some patients underwent as many as 8 surgeries. Contracture recurrence (CR) was the most common complication and occurred in 28.9% of the cases. The mean percentage total body surface area did not significantly differ in CR patients (26.7% ± 14.9%) and no-CR patients (44.5% ± 30.2%). However, there was a significant difference (P = 0.01) in the average neck defect size between CR patients (198.5 ± 108.3 cm2) and no-CR patients (81.1 ± 75.1 cm2). CONCLUSIONS: This study showed that risk factors for initial burn scar contractures may differ from those associated with CR, highlighting the importance of neck defect size as a predictor. The study also examines various surgical approaches, with Z-plasty showing promise for managing CR. However, the absence of data on neck range of motion is a limitation. This research underscores the complexity of managing CR and emphasizes the need for ongoing postoperative monitoring.

Reply to: Letter on the Effect of Fat Grafting on Scars Hyperpigmentation: A Systematic Review and Meta-Analysis.

Our meta-analysis indicated favorable results in improving scar hyperpigmentation through fat grafting, but there remains a need for further investigation using objective measures to validate these clinical findings and elucidate the underlying mechanisms. Current evidence from animal studies showed that fat grafting may exert its beneficial effects on scar hyperpigmentation through complex cellular and molecular pathways involving the regulation of melanin synthesis and skin remodeling. However, interpretation can be influenced by various factors, highlighting the importance of integrating multiple lines of evidence to draw robust conclusions.Level of Evidence V 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 .

A Bibliometric Analysis of the 50 Most Cited Articles on Body Contouring Surgery After Massive Weight Loss.

BACKGROUND: Body contouring surgery after massive weight loss has emerged a safe and reliable option to improve self-esteem, social life, work ability, physical activity, and sexual activity, and it is considered as an essential step in the multidisciplinary approach to morbid obesity. In this study, we aim to provide a comprehensive overview of the current state of literature on body contouring after massive weight loss, identifying research trends and areas for future investigation. METHODS: The Web of Science Core Collection was used to identify the 50 most cited publications on post-massive weight loss surgery. Data collected from each article included: title, journal, publication year, total citations, average citations per year, authors, study type, study topic, country, and institution of origin. RESULTS: The top 50 most-cited articles include 44 original articles and 6 review articles. The most cited article, published by Lockwood in 1991, received a total of 224 citations. The research areas included surgical outcomes and complications (n=19, 38%), psychological aspects such as body image, quality of life and desire for body contouring procedures (n=18, 36%), surgical techniques (n=11, 22%), an anatomical study (n=1, 2%), and a classification system (n=1; 2%). Plastic and Reconstructive Surgery journal published most (44%) of the papers identified. The University of Pittsburgh was the single institution that contributed the most (n=11; 22%). CONCLUSION: This bibliometric analysis provides insights and research trends for clinicians interested in body contouring after massive weight loss, facilitating the understanding and evolution of post-bariatric surgery and elucidating the rationale behind current practice. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. 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 .

Consulting the Digital Doctor: Google Versus ChatGPT as Sources of Information on Breast Implant-Associated Anaplastic Large Cell Lymphoma and Breast Implant Illness.

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare complication associated with the use of breast implants. Breast implant illness (BII) is another potentially concerning issue related to breast implants. This study aims to assess the quality of ChatGPT as a potential source of patient education by comparing the answers to frequently asked questions on BIA-ALCL and BII provided by ChatGPT and Google. METHODS: The Google and ChatGPT answers to the 10 most frequently asked questions on the search terms "breast implant associated anaplastic large cell lymphoma" and "breast implant illness" were recorded. Five blinded breast plastic surgeons were then asked to grade the quality of the answers according to the Global Quality Score (GQS). A Wilcoxon paired t-test was performed to evaluate the difference in GQS ratings for Google and ChatGPT answers. The sources provided by Google and ChatGPT were also categorized and assessed. RESULTS: In a comparison of answers provided by Google and ChatGPT on BIA-ALCL and BII, ChatGPT significantly outperformed Google. For BIA-ALCL, Google's average score was 2.72 ± 1.44, whereas ChatGPT scored an average of 4.18 ± 1.04 (p < 0.01). For BII, Google's average score was 2.66 ± 1.24, while ChatGPT scored an average of 4.28 ± 0.97 (p < 0.01). The superiority of ChatGPT's responses was attributed to their comprehensive nature and recognition of existing knowledge gaps. However, some of ChatGPT's answers had inaccessible sources. CONCLUSION: ChatGPT outperforms Google in providing high-quality answers to commonly asked questions on BIA-ALCL and BII, highlighting the potential of AI technologies in patient education. LEVEL OF EVIDENCE: Level III, comparative study 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 .

The Effect of Fat Grafting on Scars Hyperpigmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Hyperpigmented scars, particularly in exposed body areas, can be difficult to conceal and may evoke psychological distress. While the precise causes of scar dyschromia are not fully understood, alterations in melanogenic activity appear to hold more significance than changes in melanocyte quantity. Current treatments encompass laser interventions. However, it is essential to consider their costs and potential complications in relation to their limited proven effectiveness. Fat grafting has gained interest as a scar modulation technique due to its regenerative properties, and its efficacy in reducing scar hyperpigmentation is currently under investigation. METHODS: A systematic review and meta-analysis was reported according to PRISMA guidelines. PubMed, Embase, and Cochrane Library databases were accessed. PROSPERO registration number is CRD42023457778. The primary outcome was a change in scar pigmentation after fat grafting. Pigmentation changes after fat grafting were calculated using the standardized mean difference (SMD) between baseline and postoperative scores according to POSAS and VSS scales. Bias assessment was conducted according to the National Institute for Health and Clinical Excellence quality assessment tool. RESULTS: A total of 8 articles meeting inclusion and exclusion criteria were identified, involving 323 patients with hyperpigmented scars treated with fat grafting. A significant difference in scar pigmentation was noted after treatment with fat grafting according to observers' ratings, with a SMD of - 1.09 [95% CI: - 1.32; - 0.85], p<0.01. The SMD for patient-reported scar pigmentation after treatment with fat grafting was - 0.99 [96% CI: - 1.31; - 0.66], p<0.01. Four studies provided objective measurements of melanin changes after fat grafting and revealed inconsistent findings compared to subjective observations. CONCLUSIONS: Fat grafting shows promise in ameliorating hyperpigmented scars based on subjective assessments, but further corroborating evidence from objective measures is required. 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 .

Risks and Complications Rate in Liposuction: A Systematic Review and Meta-Analysis.

Liposuction is a surgical procedure used to remove localized excess adipose tissue. According to The Aesthetic Society's latest annual report, liposuction is the most commonly performed cosmetic procedure. Despite its popularity, the existing literature lacks a unified understanding of the risks associated with liposuction. The aim of this study was to measure complications of liposuction. A systematic review and meta-analysis was reported according to PRISMA guidelines and registered on the PROSPERO database (CRD42023471626). The primary outcome was overall complication rate. The absolute risk for individual complications was also assessed. From 2957 articles, 39 studies were selected for analysis. In total, 29,368 patients were included, with a mean age of 40.62 years and mean BMI of 26.36 kg/m2. Overall, the rate of any complication was 2.62 (95% CI, 1.78-3.84). The most common complication was contour deformity, with a prevalence of 2.35% (95% CI, 1.05%-5.16%). The prevalence of hyperpigmentation was 1.49% (95% CI, 1.12%-1.99%), seroma 0.65% (95% CI, 0.33%-1.24%), hematoma 0.27% (95% CI, 0.12%-0.60%), superficial burn 0.25% (95% CI, 0.17%-0.36%), allergic reaction 0.16% (95% CI, 0.050%-0.52%), skin necrosis 0.046% (95% CI, 0.013%-0.16%), generalized edema 0.041% (95% CI, 0.0051%-0.32%), infection 0.020% (95% CI, 0.010%-0.050%), venous thromboembolism 0.017% (95% CI, 0.0060%-0.053%), and local anesthesia toxicity 0.016% (95% CI, 0.0040%-0.064%). Liposuction is a safe procedure with low complications, of which contour deformity is the most common. Raising awareness of specific risks can enhance surgical outcomes and improve patient-physician understanding.