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Microsurgical methods, such as free vascularized lymph node transfer (VLNT) and lymphatico-venous anastomosis (LVA), have been increasingly used in the last two decades to treat lymphedema patients. The aim of our study was to evaluate the effectiveness of VLNT in the management of upper and lower limb secondary lymphedema in a long-term follow-up period. During a period of 8 years, 782 patients were examined in our lymphedema clinic with primary or secondary upper or lower limb lymphedema. From a total of 137 surgically managed patients, 92 underwent a VLNT. Their mean age was 48.3 years and mean BMI 28.4. The values concerning the volume of the affected limbs, the infection rates, the feeling of pain and heaviness and the overall function, were measured at the induction of patients in the study and at the last follow-up appointment. Follow-up ranged from 28 to 120 months. Postoperative lymphoscintigraphy of the operated patients showed positive findings in 78,9% of our cases. The mean volume of the affected limb was decreased by 55.2% at the last follow-up examination, the infection episodes were significantly reduced, and all patients reported significant reduction of pain and feeling of heaviness of the affected extremity with an overall functional improvement. The vascularized lymph node transfer represents an effective microsurgical procedure in volume reduction, decrease of infections, and functional improvement of secondary upper and lower limb lymphedema patients. [ABSTRACT FROM AUTHOR]

Microneedle (MN) patches are gaining increasing attention as a cost-effective technology for delivering drugs directly into the skin. In the present study, two different 3D printing processes were utilized to produce coated MNs, namely, digital light processing (DLP) and semisolid extrusion (SSE). Donepezil (DN), a cholinesterase inhibitor administered for the treatment of Alzheimer's disease, was incorporated into the coating material. Physiochemical characterization of the coated MNs confirmed the successful incorporation of donepezil as well as the stability and suitability of the materials for transdermal delivery. Optical microscopy and SEM studies validated the uniform weight distribution and precise dimensions of the MN arrays, while mechanical testing ensured the MNs' robustness, ensuring efficient skin penetration. In vitro studies were conducted to evaluate the produced transdermal patches, indicating their potential use in clinical treatment. Permeation studies revealed a significant increase in DN permeation compared to plain coating material, affirming the effectiveness of the MNs in enhancing transdermal drug delivery. Confocal laser scanning microscopy (CLSM) elucidated the distribution of the API, within skin layers, demonstrating sustained drug release and transcellular transport pathways. Finally, cell studies were also conducted on NIH3T3 fibroblasts to evaluate the biocompatibility and safety of the printed objects for transdermal applications.

Background: The use of sentinel lymph node biopsy (SLNB) for high-risk cutaneous squamous cell carcinoma (CSCC) is not yet clearly documented, especially for the head and neck area, due to its rich and cross-branching lymphatic system. We present the first prospective randomized study on the use of SLNB in high-risk CSCCs of the head and neck., Methods: Seventy-six patients with high-risk CSCCs of the head and neck were randomly divided into two groups: A (n = 38) and B (n = 38). In group A, SLNB was performed additionally to the excision of squamous cell carcinoma, whereas in group B, only excision of the lesion was performed. The patients were followed up for 5 years postoperatively, and local recurrences, regional metastases (regional lymph nodes), and mortality were documented., Results: One patient of group A, who never attended any follow-up, was excluded. Both groups had similar characteristics regarding Breslow thickness, perineurial invasion, peripheral limits, differentiation, size, previous incomplete excision, age, sex, education, sun exposure, Fitzpatrick score, previous incomplete excision, previous skin cancer, and smoking. Two patients had a positive sentinel lymph node and were submitted to regional lymphadenectomy. We documented deaths (three in group A and two in group B; P = 0.674), local recurrence (seven in group A and six in group B; P = 0.768), and regional metastasis (zero in group A and two in group B; P = 0.159)., Conclusion: There is no clear benefit on the use of SLNB in high-risk CSCCs of the head and neck regarding metastasis, mortality, or local recurrence control., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Keloids are complex fibroproliferative disorders with diverse clinical presentations. Spontaneous keloids (SKs) represent a rare subtype that emerges without any known preceding traumatic event. This report presents a case of familial spontaneous keloids appearing on the thoracic region in two brothers with no prior history of trauma or keloid occurrence in other family members. The lesions exhibited progressive growth over several years but responded to cycles of triamcinolone treatment. This case underscores an unusual spontaneous occurrence of keloids in the thoracic region of two siblings, highlighting the potential genetic predisposition in the aetiology of these lesions. Additionally, this instance reinforces the concept that keloids can develop spontaneously without any apparent trauma in the affected area., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kyriazidis et al.)

Introduction: Total nose reconstruction is demanding as it is a 3-dimensional structure that needs lining, support and external coverage. Usually, several stages are needed to achieve a satisfactory result. The authors present 2 cases of prelaminated radial forearm and 2 prelaminated forehead nose reconstructions and compare both methods. According to our review of the literature, this is the first report of prelaminated forehead for total nose reconstruction., Materials and Methods: The last 5 years the authors have treated 4 patients with prelaminated flaps for total nose reconstruction. The age ranged from 50 to 75 years. There were 3 male patients and one female. Three patients underwent total nose amputation due to squamous cell carcinoma and one due to melanoma., Results: Two patients were treated with prelaminated radial forearm reconstruction and 2 with prelaminated forehead reconstruction. Both patients that were treated with prelaminated radial forearm reconstruction had the collapse of the nasal pyramid and had salvage procedures with replacement of the cartilaginous framework with iliac bone graft framework., Conclusions: Prelaminated nose reconstruction with either the radial forearm or forehead flap needs several stages. There is the possibility of infection-collapse of the cartilage framework, therefore, the authors recommend reconstruction of the nasal skeleton with an iliac bone graft. The flaps are stiff and difficult to handle. The authors don't think that prelaminated nose reconstruction with the radial forearm flap has advantage compared with the classic several stages nose reconstruction with radial forearm flap. Possibly, prelaminated forehead reconstruction can be applied for aged patients who cannot undergo microsurgical reconstruction., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Hand injuries typically present with localized symptoms. However, we report an unusual case of a 32-year-old female who experienced a transient complete loss of sensation and motor function in her entire left nondominant hand after sustaining a minor 1 cm stab wound between the third and fourth metacarpals. Wound exploration under local anesthesia revealed no tendon, vascular, neural, or bony injury. Remarkably, she spontaneously regained full hand sensation and function within 120 minutes of the injury. Extensive neurological evaluation, including magnetic resonance imaging (MRI), electromyography (EMG), nerve conduction studies (NCS), and somatosensory evoked potentials (SSEPs), ruled out organic pathology and supported a diagnosis of functional neurological disorder (FND), specifically functional movement disorder (FMD). Close collaboration between hand surgeons, neurologists, and occupational therapists is essential for accurate diagnosis and appropriate multidisciplinary management. Further research is needed to elucidate the mechanisms underlying FND and optimize evidence-based treatment for FND in the context of hand trauma. The increased awareness of this condition across specialties involved in hand injury management is crucial to facilitate timely diagnosis and avoid unnecessary interventions., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kyriazidis et al.)

In the current study, coated microneedle arrays were fabricated by means of digital light processing (DLP) printing. Three different shapes were designed, printed, and coated with PLGA particles containing two different actives. Rivastigmine (RIV) and N-acetyl-cysteine (NAC) were coformulated via electrohydrodynamic atomization (EHDA), and they were incorporated into the PLGA particles. The two actives are administered as a combined therapy for Alzheimer's disease. The printed arrays were evaluated regarding their ability to penetrate skin and their mechanical properties. Optical microscopy and scanning electron microscopy (SEM) were employed to further characterize the microneedle structure. Confocal laser microscopy studies were conducted to construct 3D imaging of the coating and to simulate the diffusion of the particles through artificial skin samples. Permeation studies were performed to investigate the transport of the drugs across human skin ex vivo . Subsequently, a series of tape strippings were performed in an attempt to examine the deposition of the APIs on and within the skin. Light microscopy and histological studies revealed no drastic effects on the membrane integrity of the stratum corneum. Finally, the cytocompatibility of the microneedles and their precursors was evaluated by measuring cell viability (MTT assay and live/dead staining) and membrane damages followed by LDH release.

Background: Indocyanine green (ICG) lymphography, a key diagnostic tool for lymphedema, is influenced by the dilution process of ICG dye, impacting patient experience. Methods and Results: In our study, we assessed three different ICG diluents-water for injection (WFI), normal saline (NS), and Dextrose ® plus human albumin-in five healthy volunteer individuals undergoing superficial lymphography of the upper limb over 3 weeks. Results indicated that NS, as a diluent for ICG, caused the least discomfort during injection, in contrast to WFI, which led to the highest levels of discomfort. Transport time of ICG from the injection site to the axillary lymph nodes was notably shorter in intradermal injections than in subdermal injections. Conclusion: Our findings advocate for using NS as the optimal and cost-effective diluent for ICG, enhancing patient experience.

Background:  The aim of our study was to evaluate a new propeller vascularized lymphatic tissue flap (pVLNT) combined with aligned nanofibrillar collagen scaffolds (CS) (BioBridge) in reducing lymphedema in the rat lymphedema model., Methods:  Unilateral left hindlimb lymphedema was created in 15 female Sprague-Dawley rats following inguinal and popliteal lymph nodes (LN) resection and radiation. An inguinal pVLNT was elevated from the contralateral groin and transferred through a skin tunnel to the affected groin. Four collagen threads were attached to the flap and inserted in the hindlimb at the subcutaneous level in a fan shape. The three study groups consisted of group A (control), group B (pVLNT), and group C (pVLNT + CS). Volumetric analysis of both hindlimbs was performed using micro-computed tomography imaging before the surgery (at initial time point) and then at 1 and 4 months, postoperatively, and the relative volume difference (excess volume) was measured for each animal. Lymphatic drainage was assessed by indocyanine green (ICG) fluoroscopy for number and morphology of new collectors and the time required for ICG to move from injection point to the midline., Results:  Four months after the induction of lymphedema, an increased relative volume difference remained in group A (5.32 ± 4.74%), while there was a significant relative volume reduction in group B (-13.39 ± 8.55%) and an even greater reduction in group C (-14.56 ± 5.04%). ICG fluoroscopy proved the functional restoration of lymphatic vessels and viability of pVLNT in both B and C groups. Notably, only group C demonstrated statistically significant improvements in lymphatic pattern/morphology and in the number of lymphatic collectors as compared with the control group A., Conclusion:  The pedicle lymphatic tissue flap combined with SC is an effective procedure for the treatment of lymphedema in rats. It can be easily translated into treatment of humans' lower and upper limb lymphedema and further clinical studies are warranted., Competing Interests: None declared., (Thieme. All rights reserved.)

The combined use of a deep inferior epigastric perforator (DIEP) flap coupled with vascularized inguinal lymph nodes (VILNs) for simultaneous breast and lymphedema reconstruction has already been well established, and promising results have been reported. However, a standardized approach for the planning and shaping of this combined flap is still lacking. We aimed to propose a comprehensive algorithmic approach for delayed unilateral breast and lymphedema reconstruction using a predesigned abdominal flap associated with inguinal lymph node transfer. We present in detail the preoperative measurements and surgical technique of the chimeric flap, which combines a predesigned DIEP template and a preselected inguinal lymph node flap, based on the preoperative computed tomography angiography and SPEC-CT findings, respectively; four different flap types are described according to the location of the pedicles of the two flap components. Our results of a series of 34 consecutive female patients with unilateral mastectomy and arm lymphedema, who underwent this combined predesigned reconstructive procedure, are retrospectively analyzed and reported. We recorded a high survival rate of the chimeric flaps in our series, with only one case of partial ischemic loss of a DIEP skin island. In the majority of our patients, the pedicles of the combined flaps were located in opposite positions. After a mean 35-month follow-up, we recorded a 47% mean volume difference reduction of the lymphedematous compared to the unaffected arm; no donor-site lymphedema was documented. Self-evaluation questionnaires showed high patient satisfaction rates regarding breast reconstruction. This algorithmic approach provides standardized guidance for accurate design and transfer of the DIEP-VILN chimeric flap while achieving highly satisfactory outcomes for both breast and lymphedema reconstruction., Competing Interests: None., (© 2024 The Authors.)

Competing Interests: None declared.

Because lipofilling is often associated with various reconstructive procedures, especially breast reconstructions, improving fat-graft retention remains a major concern for plastic surgeons. We conducted an experimental protocol in a rat model simulating an autologous breast reconstruction method using the fat-augmented latissimus dorsi myocutaneous (LDM) flap. This study aimed to compare the survival rates of autologous adipocytes when injected subcutaneously and intramuscularly and to evaluate the role of recipient host tissue, volume of the injected fat, and postoperative radiation on fat-graft retention. Thirty rats were divided into five groups (A, B, C, D, and E), of six rats each. All animals underwent a pedicled LDM flap transfer to the anterior thoracic wall, and different volumes of autologous fat were injected into three recipient areas, namely, the pectoralis major and latissimus dorsi muscles and the subcutaneous tissue of the flap's skin island, as follows: 1 mL of fat was injected in total in group A, 2 mL in groups B and D, and 5 mL in group C. Group D animals received postoperative radiation (24 Gy), whereas group E animals (controls) did not undergo any fat grafting procedure. Eight weeks after surgery, adipocyte survival was assessed in all groups using histological and immunochemistry techniques. The results showed that the pectoralis major muscle was the substrate with the highest adipocyte survival rates, which were proportional to the amount of fat injected, followed by the latissimus dorsi muscle and the subcutaneous tissue. Increased volumes of transplanted fat into the subcutaneous tissue did not correspond to increased adipocyte survival. Irradiation of host tissues resulted in a statistically significant decrease in surviving adipocytes in all three recipient sites (p<0.001). Our study strongly suggests that muscle ensures optimal fat-graft retention, whereas postoperative radiation negatively affects adipocyte survival following fat transplantation., Competing Interests: None., (© 2023 The Author(s).)

Background: Lymphedema is a debilitating and progressive clinical entity characterized by abnormal accumulation of lymph and fluid in the extracellular space. Most of the cases in western population are related to cancer treatment. Research on cancer-related lymphedema (CRL) is mounting for potential risk factors associated to disease, treatment, or patient. However, only a few cancer survivors with the same risk factors will develop lymphedema, giving rise to the hypothesis that inherited genetic susceptibility may play a role in CRL pathophysiology. This systematic review aimed to identify, critically appraise, and summarize the results of individual studies that have examined the genetic predisposition to CRL. Methods and Results: A comprehensive literature search in MEDLINE, Cochrane, and Scopus was conducted from inception to February 2021. Screening of available studies and quality of the included studies were carried out by two reviewers independently. Eight studies fulfilled eligibility criteria, involving 573 women with breast-cancer related lymphedema (BCRL) among 1,481 participants. Associations between the development of CRL and genetic factors were observed for variations in 23 genes in patients with BCRL. Conclusions: The present systematic review is the first examining specifically the genetic predisposition in CRL. Statistically significant genetic variations were found in 23 genes in patients with BCRL. These preliminary findings highlight the importance of genetic susceptibility in the development of CRL, altering the traditional perception of its iatrogenic etiology. Additional well-designed research, aiming toward the confirmation of previously performed genetic analyses and functional assessment of the genetic variations, is required.

Background: In this experimental study, the authors investigated whether fat placement in the pocket during implant insertion affects capsule formation., Methods: Twenty albino Wistar rats, 400 g each, were used. The rats were divided into two groups, A and B, of 10 rats each. At the dorsum of each rat, four pockets (2 × 2 cm each) were dissected, two left and two right of the midline. In each pocket, a 1 × 1 × 1.5-cm silicone implant was inserted. In the two left pockets, only silicone implants were placed (control). In the two right pockets, 0.4 ml of fat was injected around the implant. Animals in group A were killed 2 months postoperatively, and those in group B were killed 4 months postoperatively. The implants were dissected with the capsule and sent for histopathologic examination., Results: The data of the fat transfer group was compared with control in groups A and B. Capsule thickness, neovascularization, myofibroblast layer thickness, and mast cell population demonstrated no statistically significant difference in either group A (p = 0.385, p = 0.862, p = 0.874, and p = 0.210, respectively) or group B (p = 0.338, p = 1.000, p = 0.288, and p = 0.344, respectively). Inflammation was statistically significantly less (p = 0.07) at 4 months (group B) in the fat transfer group compared to the control group. Likewise, cellularity was statistically significantly less (p = 0.019) at 4 months for the fat transfer group compared with the control group., Conclusion: Fat injection in the pocket during implant placement may reduce inflammation and cellularity of capsules and predispose to faster capsule maturation., Clinical Relevance Statement: Fat transfer around implants may positively affect implant-based breast reconstruction and/or breast augmentation., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Currently, there is a lack of models representing the skin dermal heterogeneity for relevant research and skin engineering applications. This is the first study reporting production of dermal equivalents reproducing features of papillary and reticular dermal compartments. Inspired from our current knowledge on the architecture and composition differences between the papillary and reticular dermis, we evaluated different collagen-based porous materials to serve as scaffolds for the three-dimensional expansion of freshly isolated papillary and/or reticular fibroblasts. The scaffolds, composed of either collagen I or collagen I and III mixtures, were prepared by lyophilization. Pore size and hydrolytic stability were controlled by crosslinking with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) or EDC/NHS with covalently bound heparin. The evaluation of the resultant "papillary" and "reticular" dermal equivalents was based on the analysis of characteristic features of each dermal compartment, such as cell density and deposition of newly synthetized extracellular matrix components in histological sections. Crosslinking supported cell growth during dermal tissue formation independent on the fibroblast subpopulation. The presence of collagen III seemed to have some positive but non-specific effect only on the maintenance of the mechanical strength of the scaffolds during dermal formation. Histological analyses demonstrated a significant and specific effect of heparin on generating dermal equivalents reproducing the respective higher papillary than reticular cell densities and supporting distinct extracellular matrix components deposition (three to five times more carbohydrate material deposited by papillary fibroblasts in all scaffolds containing heparin, while higher collagen production was observed only in the presence of heparin)., (© 2021 Wiley Periodicals LLC.)

Background: This retrospective study aimed to assess the impact of certain flap characteristics on long-term outcomes following microsurgical treatment in Breast Cancer-Related Lymphedema (BCRL) patients., Methods: Sixty-four out of 65 BCRL patients, guided by the "Selected Lymph Node" ("SeLyN") technique, underwent Vascularized Lymph Node Transfer (VLNT) between 2012 and 2018. According to their surface size, flaps were divided into small (<25 cm 2 , n = 32) and large (>25 cm 2 , n = 32). Twelve large and six small flaps were combined with free abdominally based breast reconstruction procedures. Lymphedema stage, flap size, vascular pedicle and number of lymph nodes (LNs) were analyzed in correlation with long-term Volume Differential Reduction (VDR)., Results: At 36-month follow-up, no major complication was recorded in 64 cases; one flap failure was excluded from the study. Mean flap size was 27.4 cm 2 , mean LNs/flap 3.3 and mean VDR 55.7%. Small and large flaps had 2.8 vs. 3.8 LNs/flap ( p = 0.001), resulting in 49.6% vs. 61.8% VDR ( p = 0.032), respectively. Lymphedema stage and vascular pedicle (SIEA or SCIA/SCIP) had no significant impact on VDR., Conclusion: In our series, larger flaps included a higher number of functional LNs, directly associated with better outcomes as quantified by improved VDR.

Purpose: The genomic status of non-malignant tissues from carriers of pathogenic germline BRCA1/2 (gBRCA1/2) variants may reveal information towards individualized prophylaxis. We performed spatiotemporal tissue genotype comparisons in a real-life cohort of gBRCA1/2 carriers of Greek origin, who underwent multiple risk-reducing/prophylactic surgeries at various time points., Methods: Fifty-three women (median age 36 years) within cancer families were observed for up to 37.5 years; 43 were cancer carriers and 10 were healthy carriers. Histology review and genotyping were performed for 187 paraffin tissues (average: 3.5 per carrier) including 46 carcinomas (40 breast) and 141 non-malignant breast and gynecological samples., Results: High allelic imbalance (AI) and somatic pathogenic TP53 variants were present in cancer carriers only (p values < 0.0001). High AI was associated with gBRCA1/2 indels (p < 0.0001) and gBRCA2 alterations (p = 0.0109). Somatic (pathogenic) variants were infrequently shared between non-malignant tissues and matched carcinomas. Aberrations of gBRCA1 variant heterozygosity were noticed in tissues from cancer carriers only (13/43, 30.2%). These pertained to classic LOH (neoplastic lesions in 9/43 carriers, 20.9%) and under-representation of the germline variants (5 samples, 4 non-malignant, all in the breast). Both aberrations coexisted in matched samples in one case. Over time, germline variant heterozygosity prevailed in non-malignant tissues; intra-carrier genomic alterations were aggravated (21.1%), ameliorated (26.3%) or remained stable., Conclusion: This real-life case study supports the need to address tissue genotypes from prophylactic surgeries in combination with polygenic scores towards personalized prophylaxis. To this end, knowing the traditionally classified pathogenic potential of a gBRCA1/2 variant may not be enough., (© 2021. The Japanese Breast Cancer Society.)