Highly Concentrated Stabilized Hybrid Complexes of Hyaluronic Acid: Rheological and Biological Assessment of Compatibility with Adipose Tissue and Derived Stromal Cells towards Regenerative Medicine.

Cells and extracts derived from adipose tissue are gaining increasing attention not only in plastic surgery and for aesthetic purposes but also in regenerative medicine. The ability of hyaluronan (HA) to support human adipose stromal cell (hASC) viability and differentiation has been investigated. However, the compatibility of adipose tissue with HA-based formulation in terms of biophysical and rheological properties has not been fully addressed, although it is a key feature for tissue integration and in vivo performance. In this study, the biophysical and biochemical properties of highly concentrated (45 mg/mL) high/low-molecular-weight HA hybrid cooperative complex were assessed with a further focus on the potential application in adipose tissue augmentation/regeneration. Specifically, HA hybrid complex rheological behavior was observed in combination with different adipose tissue ratios, and hyaluronidase-catalyzed degradation was compared to that of a high-molecular-weight HA (HHA). Moreover, the HA hybrid complex's ability to induce in vitro hASCs differentiation towards adipose phenotype was evaluated in comparison to HHA, performing Oil Red O staining and analyzing gene/protein expression of PPAR-γ, adiponectin, and leptin. Both treatments supported hASCs differentiation, with the HA hybrid complex showing better results. These outcomes may open new frontiers in regenerative medicine, supporting the injection of highly concentrated hybrid formulations in fat compartments, eventually enhancing residing staminal cell differentiation and improving cell/growth factor persistence towards tissue regeneration districts.

Comparative Analysis of Nipple Reconstruction Techniques: Five Flap vs. C-V Flap.

Background: Nipple-areola complex reconstruction represents the final phase in the comprehensive post-mastectomy treatment regimen. Despite the diversity of approaches available, there is currently no universally accepted benchmark technique for this critical aspect of breast reconstruction. In this study, we conducted a comparative assessment of two prominent techniques, the five Flap and C-V Flap. Materials and Methods: Between November 2016 and April 2023, we recruited 100 female patients who had undergone unilateral post-oncological mastectomy and divided them into two groups: Group A comprising 50 patients who underwent the 5-Flap technique, whereas Group B comprising the remaining 50 underwent the C-V Flap technique. Over a 6-month observation period, we assessed nipple projection loss and evaluated overall satisfaction through self-reporting by patients and independent assessments by a medical observer. Results: In our study, none of the reconstructed nipples in Group A (5 Flap) experienced either total or partial necrosis, contrasting with Group B (C-V Flap) which encountered a 10% incidence of partial necrosis and 4% incidence of total necrosis. Furthermore, the average nipple projection loss in Group B was substantial, measuring a 30% reduction from the initial projection at the 1-year mark, whereas Group A demonstrated a significantly lower 13% reduction. Notably, despite these variations in outcomes, both groups reported an equal and high level of satisfaction, with patients and external observers providing an average satisfaction score of 8.0 and 9.0, respectively. Conclusion: The five-flap technique represents a safe and effective approach for patients undergoing nipple reconstruction.

Extremely rare case of unilateral gigantomastia after hormonal stimulation treated with a modified wise pattern technique: A case report.

INTRODUCTION: Gigantomastia, characterized by excessive breast size (usually heavier than 2.5 kg), can result from various causes and significantly affect patients' lives. Surgical intervention is often required, and over time, several techniques have been developed for its treatment. These techniques aim to address the functional and aesthetic concerns associated with gigantomastia, providing relief to patients and improving their quality of life. PRESENTATION OF THE CASE: A 40-year-old primiparous housewife developed unilateral gigantomastia as a consequence of hormone therapy. To address this, a modified reduction mammoplasty procedure was undertaken, incorporating NAC (Nipple-Areola Complex) grafting. The reduction involved removing 3450 g of tissue, resulting in restored breast symmetry and enabling the patient to reintegrate into normal daily life. DISCUSSION: Compared to the traditional technique, the introduction of some modifications in the design allowed for the absence of complications such as dehiscence of the scar at the intersection of the T, the failure of the nipple graft attachment, and the maintenance of a conical shape over time, enabling complete symmetrization of the two breasts. CONCLUSION: The use of a modified version of the Thorek technique allowed for optimal functional and aesthetic restoration even in the case of a significantly disproportionate breast compared to the contralateral one, with no complications.

Comparison of Different Techniques for the Assessment of Sentinel Lymph Node Biopsy in Melanoma: A Systematic Review.

Background: The gold standard for sentinel lymph node staging in melanoma is the use of the combined technique of radioisotope plus blue dye. New techniques and alternative methods have been proposed, with the promise of achieving comparable efficacy. We then carried out a literature search. Methods: We conducted a literature search using the "sentinel lymph node biopsy" and "melanoma" keywords, then selected the case-control studies (the quality of which was assessed using the STROBE criteria). Results: Twelve studies of 13,017 were selected, concerning the identification rate of indocyanine green fluorescence and indocyanine green-99mtc-nanocolloid techniques. We have found a comparable identification rate between the various techniques, even if given the small population present for some techniques, the results did not reach statistical significance. Conclusions: The use of new techniques in sentinel lymph node detection promises results comparable to the gold standard techniques, but further studies are needed to validate these methods in the context of melanoma surgery.

Squamous Carcinoma of the Oral Cavity in Patient with Fanconi Anemia: A Challenging Reconstruction with Double-barrel Free Fibula Flap Case Report.

Fanconi anemia (FA) is a very rare form of aplastic anemia. Patients with FA have a higher risk of developing solid tumors such as head and neck squamous cell carcinoma, higher risk of local recurrence, and impaired resistance to chemotherapy and radiotherapy treatments than the normal population. In this article, we describe the challenging clinical case of a patient with FA who underwent surgery for the removal of a large squamous cell carcinoma in the oral cavity. Mandibular reconstruction was performed using a biaxial double-barrel fibular flap, with excellent functional aesthetic outcomes.

ß2-AR inhibition enhances EGFR antibody efficacy hampering the oxidative stress response machinery.

The ß2-Adrenergic receptor (ß2-ARs) is a cell membrane-spanning G protein-coupled receptors (GPCRs) physiologically involved in stress-related response. In many cancers, the ß2-ARs signaling drives the tumor development and transformation, also promoting the resistance to the treatments. In HNSCC cell lines, the ß2-AR selective inhibition synergistically amplifies the cytotoxic effect of the MEK 1/2 by affecting the p38/NF-kB oncogenic pathway and contemporary reducing the NRF-2 mediated antioxidant cell response. In this study, we aimed to validate the anti-tumor effect of ß2-AR blockade and the synergism with MEK/ERK and EGFR pathway inhibition in a pre-clinical orthotopic mouse model of HNSCC. Interestingly, we found a strong ß2-ARs expression in the tumors that were significantly reduced after prolonged treatment with ß2-Ars inhibitor (ICI) and EGFR mAb Cetuximab (CTX) in combination. The ß2-ARs down-regulation correlated in mice with a significant tumor growth delay, together with the MAPK signaling switch-off caused by the blockade of the MEK/ERK phosphorylation. We also demonstrated that the administration of ICI and CTX in combination unbalanced the cell ROS homeostasis by blocking the NRF-2 nuclear translocation with the relative down-regulation of the antioxidant enzyme expression. Our findings highlighted for the first time, in a pre-clinical in vivo model, the efficacy of the ß2-ARs inhibition in the treatment of the HNSCC, remarkably in combination with CTX, which is the standard of care for unresectable HNSCC.

Telemonitoring Wound Recovery with Smartphone: An Italian Experience during Pandemic Period.

An important problem of plastic surgeons is monitoring wound healing, loss of substance, and postsurgical scar in different pathologies of the skin. Face to face monitoring is expensive and cannot be performed in periods of social crisis such as the recent COVID-19 pandemic. The use of telemedicine techniques is rising in this field of healthcare, promising the same results as the standard follow-up with more flexibility and savings. The purpose of this case study was to evaluate the effectiveness of remote monitoring and treatment through remote follow-up using digital applications. We followed up 25 patients with postoperative or diabetic ulcers for a period of 6 months (ranging from 2 to 6 months). We have performed clinical assessments using the Scar Cosmesis Assessment and Rating scale, and we have measured patient satisfaction using questionnaires. We chose to use the application for smartphone, describing the types of ulcers, number and average consultations, and the type of recovery, whether partial or complete. Monitoring wound recovery was very easy, and the patients found the experience very satisfactory. The total number of consultations was 255 with a significant reduction in outpatient visits during the pandemic period. Telemedicine is a useful tool in wound management and can be used to provide an optimal health care service with no inferior results to standard care.

Precision medicine in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that has diverse clinical manifestations, ranging from restricted cutaneous involvement to life-threatening systemic organ involvement. The heterogeneity of pathomechanisms that lead to SLE contributes to between-patient variation in clinical phenotype and treatment response. Ongoing efforts to dissect cellular and molecular heterogeneity in SLE could facilitate the future development of stratified treatment recommendations and precision medicine, which is a considerable challenge for SLE. In particular, some genes involved in the clinical heterogeneity of SLE and some phenotype-related loci (STAT4, IRF5, PDGF genes, HAS2, ITGAM and SLC5A11) have an association with clinical features of the disease. An important part is also played by epigenetic varation (in DNA methylation, histone modifications and microRNAs) that influences gene expression and affects cell function without modifying the genome sequence. Immune profiling can help to identify an individual's specific response to a therapy and can potentially predict outcomes, using techniques such as flow cytometry, mass cytometry, transcriptomics, microarray analysis and single-cell RNA sequencing. Furthermore, the identification of novel serum and urinary biomarkers would enable the stratification of patients according to predictions of long-term outcomes and assessments of potential response to therapy.

SGLT2 breast expression could affect the cardiovascular performance in pre-menopausal women with fatty vs. non fatty breast via over-inflammation and sirtuins' down regulation.

OBJECTIVES: To evaluate the expression of sodium-glucose transporter 2 (SGLT2), inflammatory cytokines, and sirtuins in breast fat tissue at baseline, and serum cytokines of fatty vs. non-fatty pre-menopausal women at baseline, and at 12 months of follow-up. To correlate SGLT2/cytokines/sirtuins expression to clinical variables, and their changes (Δ) at follow-up, as intima-media wall thickness (IMT), left ventricle mass (LVM), left ventricle ejection fraction (LVEF), and myocardial performance index (MPI), and its normalization. BACKGROUND: Pre-menopausal women with the lowest breast fat density (fatty breast) vs. higher breast fat density (non-fatty breast) are a high-risk population for cardiovascular diseases and worse prognosis. METHODS: We analyzed SGLT2/cytokines/sirtuins of excised fatty breasts of fatty vs. non-fatty pre-menopausal women. We correlated SGLT2/cytokines/sirtuins to Δ IMT, Δ LVM, Δ LVEF, and Δ MPI, and normal cardiac performance (NCP) at 1 year of follow-up. RESULTS: fatty vs. non-fatty breast over-expressed SGLT2/inflammatory cytokines, with lowest values of sirtuins (p<0.05). We found a direct correlation between SGLT2 (R2 0.745), TNFα (R2 0.262), and ΔMPI (p<0.05), and an inverse correlation between breast density (R2 -0.198), SIRT-3 (R2-0.181), and ΔMPI (p<0.05). Fatty breast (0.761, CI 95% [0.101-0.915]), SGLT2 (0.812, CI 95% [0.674-0.978]) and SIRT-3 (1.945, CI 95% [1.201-3.148]) predicted NCP at 1 year of follow-up. CONCLUSIONS: fatty vs. non-fatty breast women over-expressed SGLT2/inflammatory cytokines, and down-regulated breast sirtuins. SGLT2/inflammatory cytokines expression and inversely the tissue sirtuin 3 (tSIRT3) and breast percentage density linked to ΔMPI at 1 year of follow-up. Fatty breast and SGLT2 inversely predicted NCP; SIRT-3 increased the probability of NCP at 1 year of follow-up.

Late relapse after CAR-T cell therapy for adult patients with hematologic malignancies: A definite evidence from systematic review and meta-analysis on individual data.

Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy - tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene - is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%-78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%-42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.

How organoids can improve personalized treatment in patients with gastro-esophageal tumors.

Gastro-esophageal tumors constitute a big health problem. Treatment options still mainly rely on chemotherapy, and apart from human epidermal growth factor receptor 2 positive and microsatellite instable/Epstein-Barr Virus disease, there are no molecularly guided options. Therefore, despite the large number of identified molecular alterations, precision medicine is still far from the clinic. In this context, the recently developed technology of patient-derived organoids (PDOs) could offer the chance to accelerate drug development and biomarker discovery. Indeed, PDOs are 3D primary cultures that were shown to reproduce patient's tumor characteristics. Moreover, several reports indicated that PDOs can replicate patient's response to a given drug; therefore, they are one of the most promising tools for functional precision medicine.

Tuberous Breast Management: A Review of Literature and Novel Technique Refinements.

The tuberous breast is a rare malformation that can affect psychosocial well-being in young women. Its management represents a great challenge to plastic surgeons. Many surgical procedures have been described to correct different grades of tuberous breast deformity (TBD). The authors describe their one-stage technique for correcting grade 2 TBD. Methods: Sixteen women affected by grade 2 TBD treated with glandular flaps, silicone gel prosthesis, and only an hemiperiareolar incision between January 2018 and January 2019 were reviewed. The age range was 19-27 years (mean age was 25). Follow-up average was 25 months (range 16-33 months). To evaluate the results, we used two analogic scales with values from 1 to 3, where the lower value was the worst result. First, an independent medical team of three plastic surgeons evaluated two parameters: correction of deformity and symmetry. Then, patients were asked to judge the result obtained. Results: The resulting breast has a normal-shaped areola without bulging, a natural shape, a volume matching the contralateral breast, and no evidence of "double-bubble" deformity or irregularities of the lower pole shape. Conclusion: We propose this one-stage approach with hemiperiareolar incision, to minimize time interval to obtain final results in TBD correction, with reduced scar dimensions to avoid all the possible complications related to the round block suture.

Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy.

Type 1 diabetes (T1D) is an autoimmune disease with immune cells' islet infiltration (called "insulitis"), which leads to beta cell loss. Despite being the critical element of T1D occurrence and pathogenesis, insulitis is often present in a limited percentage of islets, also at diagnosis. Therefore, it is needed to define reproducible methods to detect insulitis and beta-cell decline, to allow accurate and early diagnosis and to monitor therapy. However, this goal is still far due to the morphological aspect of islet microvasculature, which is rather dense and rich, and is considerably rearranged during insulitis. More studies on microvasculature are required to understand if contrast-enhanced ultrasound sonography measurements of pancreatic blood-flow dynamics may provide a clinically deployable predictive marker to predict disease progression and therapeutic reversal in pre-symptomatic T1D patients. Therefore, it is needed to clarify the relation between insulitis and the dynamics of ß cell loss and with coexisting mechanisms of dysfunction, according to clinical stage, as well as the micro vessels' dynamics and microvasculature reorganization. Moreover, the ideal cell-based therapy of T1D should start from an early diagnosis allowing a sufficient isolation of specific Procr+ progenitors, followed by the generation and expansion of islet organoids, which could be transplanted coupled to an immune-regulatory therapy which will permit the maintenance of pancreatic islets and an effective and long-lasting insulitis reversal.

Nonsurgical Reshaping of the Lower Jaw With Hyaluronic Acid Fillers: A Retrospective Case Series.

Introduction: Nonsurgical aesthetic treatments of the lower face are increasing in demand. In particular, they aim to restore facial youth following the changes due to progressive resorption of facial skeleton and atrophy of facial fat compartments which give the perception of a descent face. Objectives: The aim of this research is to describe the nonsurgical reshaping of the aged lower jaw by means of hyaluronic acid fillers. Methods: A retrospective analysis of data from adult female patients undergoing treatment with hyaluronic acid injections in the lower third of the face was performed. Injection techniques, relevant anatomy of the anatomical area and rheological properties of the fillers to be used are highlighted. Results: Thirty-six consecutive patients were enrolled (100% female; mean age: 45.7 years). A minimum of 4 up to 7 vials of hyaluronic acid filler was injected to achieve the desired results. The visual analogue scale was used to assess patient satisfaction. Thirty-two patients (88.8%) rated their appearance post-treatment with a satisfaction score ranging between 85% and 100%. A total absence of ecchymosis and/or swelling in the early postoperative days has been highlighted. There were no cases of infection, paresthesia, hematoma or necrosis. Conclusions: For those patients not willing to undergo surgery, the jawline remodelling with hyaluronic acid fillers seems to be a viable option for ameliorating the definition of the lower third of the face. Nonetheless, it is mandatory to perform multilayer injections using fillers with different rheological properties.

Optimizing Fat Grafting Using a Hydraulic System Technique for Fat Processing: A Time and Cost Analysis.

Background Many authors have researched ways to optimize fat grafting by looking for a technique that offers safe and long-term fat survival rate. To date, there is no standardized protocol. We designed a "hydraulic system technique" optimizing the relationship among the quantity of injected fat, operative time, and material cost to establish fat volume cutoffs for a single procedure. Methods Thirty-six patients underwent fat grafting surgery and were organized into three groups according to material used: standard, "1-track," and "2-tracks" systems. The amount of harvested and grafted fat as well as material used for each procedure was collected. Operating times were recorded and statistical analysis was performed to establish the relationship with the amount of treated fat. Results In 15 cases the standard system was used (mean treated fat 72 [30-100] mL, mean cost 4.23 ± 0.27 euros), in 11 cases the "1-track" system (mean treated fat 183.3 [120-280] mL, mean cost 7.63 ± 0.6 euros), and in 10 cases the "2-tracks" one (mean treated fat 311[220-550] mL, mean cost 12.47 ± 1 euros). The mean time difference between the standard system and the "1-track" system is statistically significant starting from three fat syringes (90 mL) in 17.66 versus 6.87 minutes. The difference between the "1-track" system and "2-tracks" system becomes statistically significant from 240 mL of fat in 15 minutes ("1-track") versus 9.3 minutes for the "2-tracks" system. Conclusion Data analysis would indicate the use of the standard system, "1-track," and "2-tracks" to treat an amount of fat < 90 mL of fat, 90 ÷ 240 mL of fat, and ≥ 240 mL of fat, respectively.

Polydatin Incorporated in Polycaprolactone Nanofibers Improves Osteogenic Differentiation.

Polycaprolactone nanofibers are used as scaffolds in the field of tissue engineering for tissue regeneration or drug delivery. Polycaprolactone (PCL) is a biodegradable hydrophobic polyester used to obtain implantable nanostructures, which are clinically applicable due to their biological safety. Polydatin (PD), a glycosidic precursor of resveratrol, is known for its antioxidant, antitumor, antiosteoporotic, and bone regeneration activities. We aimed to use the osteogenic capacity of polydatin to create a biomimetic innovative and patented scaffold consisting of PCL-PD for bone tissue engineering. Both osteosarcoma cells (Saos-2) and mesenchymal stem cells (MSCs) were used to test the in vitro cytocompatibility of the PD-PCL scaffold. Reverse-phase (RP) HPLC was used to evaluate the timing release of PD from the PCL-PD nanofibers and the MTT assay, scanning electron microscopy, and alkaline phosphatase (ALP) activity were used to evaluate the proliferation, adhesion, and cellular differentiation in both osteosarcoma and human mesenchymal stem cells (MSCs) seeded on PD-PCL nanofibers. The proliferation of osteosarcoma cells (Saos-2) on the PD-PCL scaffold decreased when compared to cells grown on PLC nanofibers, whereas the proliferation of MSCs was comparable in both PCL and PD-PCL nanofibers. Noteworthy, after 14 days, the ALP activity was higher in both Saos-2 cells and MSCs cultivated on PD-PCL than on empty scaffolds. Moreover, the same cells showed a spindle-shaped morphology after 14 days when grown on PD-PCL as shown by SEM. In conclusion, we provide evidence that nanofibers appropriately coated with PD support the adhesion and promote the osteogenic differentiation of both human osteosarcoma cells and MSCs.

The Impact of Direct Oral Anticoagulant Prophylaxis for Thromboembolism in Thrombophilic Patients Undergoing Abdominoplastic Surgery.

Congenital or acquired thrombophilia is observed in 10-15% of the general population; therefore, careful screening is carried out in patients at higher risk of venous thrombo-embolism (VTE). High risk of VTE is a contraindication in patients undergoing abdominoplasty. We evaluated rivaroxaban, an oral Xa inhibitor, with enoxaparin, a subcutaneously low molecular weight heparin (LMWH), in 48 female patients with documented thrombophilia, undergoing thrombo-prophylaxis after abdominoplasty. Patients were stratified into two groups according to thrombo-prophylaxis procedure: enoxaparin Group (n = 28) and rivaroxaban Group (n = 20). Hematologic outcomes were evaluated including VTE and hematoma. No episodes of VTE occurred in both groups; two patients during their course of enoxaparin presented severe hematoma for drainage and hemostasis revision. This study suggests that abdominoplasty, in patients with thrombophilia, in combination with thrombo-prophylaxis can be performed safely. Rivaroxaban was as effective as LMWH for preventing VTE, with only a moderate risk of clinically relevant bleeding. More research is needed to determine the optimal timing and duration of prophylaxis in patients undergoing plastic surgery.

Current and future therapeutic perspective in chronic heart failure.

The incidence of heart failure is primarily flat or declining for a presumably reflecting better management of cardiovascular diseases, but that of heart failure with preserved ejection fraction (HFpEF) is probably increasing for the lack of an established effective treatment. Moreover, there is no specific pharmacological treatment for patients with heart failure with mildly reduced ejection fraction (HFmrEF) since no substantial prospective randomized clinical trial has been performed exclusively in such population. According to the recent 2021 European Society of Cardiology (ESC) guidelines, the triad composed of an Angiotensin Converting Enzyme inhibitor or Angiotensin Receptor-Neprilysin Inhibitor (ARNI), a beta-blocker, and a Mineralcorticoid Receptor Antagonist is the cornerstone therapy for all patients with heart failure with reduced ejection fraction (HFrEF) but a substantial gap exists for patients with HFpEF/HFmrEF. Despite the important role of the Renin-Angiotensin-Aldosterone System (RAAS) in heart failure pathophysiology, RAAS blockers were found ineffective for HFpEF patients. Indeed, even the new drug class of ARNI was found effective only in HFrEF patients. In this regard, a therapeutic alternative may be represented by drug stimulating the non-classic RAAS (ACE2 and A1-7) as well as other emerging drug classes (such as SGLT2 inhibitors). Reflecting on this global health burden and the gap in treatments among heart failure phenotypes, we summarize the leading players of heart failure pathophysiology, the available pharmacological treatments for each heart failure phenotype, and that in future development.

Clinical epigenetics and restoring of metabolic health in severely obese patients undergoing batriatric and metabolic surgery.

Epigenetic-sensitive mechanisms, mainly DNA methylation, mirror the relationship between environmental and genetic risk factors able to affect the sensitiveness to development of obesity and its comorbidities. Bariatric and metabolic surgery may reduce obesity-related cardiovascular risk through tissue-specific DNA methylation changes. Among the most robust results, differential promoter methylation of ACACA, CETP, CTGF, S100A8, and S100A9 genes correlated significantly with the levels of mRNA before and after gastric bypass surgery (RYGB) in obese women. Additionally, promoter hypermethylation of NFKB1 gene was significantly associated with reduced blood pressure in obese patients after RYGB suggesting useful non-invasive biomarkers. Of note, sperm-related DNA methylation signatures of genes regulating the central control of appetite, such as MC4R, BDNF, NPY, and CR1, and other genes including FTO, CHST8, and SH2B1 were different in obese patients as compared to non-obese subjects and patients who lost weight after RYGB surgery. Importantly, transgenerational studies provided relevant evidence of the potential effect of bariatric and metabolic surgery on DNA methylation. For example, peripheral blood biospecimens isolated from siblings born from obese mothers before bariatric surgery showed different methylation signatures in the insulin receptor and leptin signaling axis as compared to siblings born from post-obese mothers who underwent surgery. This evidence suggests that bariatric and metabolic surgery of mothers may affect the epigenetic profiles of the offspring with potential implication for primary prevention of severe obesity. We update on tissue-specific epigenetic signatures as potential mechanisms underlying the restoration of metabolic health after surgery suggesting useful predictive biomarkers.