Unbiased transcriptome analysis of human cleft palate reveals evolutionally conserved molecular signatures of development: experimental study.

BACKGROUND: The development of the secondary palate, an essential process for hard palate formation, involves intricate cellular processes. Here, we examined the expression patterns of palatal fusion-associated genes in postdevelopmental human palatal tissues. METHODS: Mucosal samples collected from the anterior fused (control; n=5) and posterior unfused regions (study; n=5) of cleft palate patients were subjected to RNA sequencing. Gene Set Enrichment Analysis (GSEA) was conducted to identify consistent changes in molecular signaling pathways using hallmark (h) gene set collections from the Molecular Signature Database v7.4. The results of RNA sequencing were validated by epithelial-mesenchymal transition (EMT) assays with suppression of target genes, including lrp6, shh, Tgfß-3 (Bioneer, Daejeon, Korea), and negative control siRNA in a human fibroblast cell line (hs68). RESULTS: Transcriptome profiling of the cleft mucosa demonstrated that the fully fused anterior mucosa exhibited globally upregulated EMT, Wnt ß-catenin, Hedgehog, and TGF-ß signaling pathways in gene set enrichment. This strongly indicates the evolutionary conserved similarities in pathways implicated in palatogenesis, as previously shown in murine models. In EMT assays with suppression of Lrp6, Shh, and TGF-ß3 in human fibroblast cell lines, suppression of Lrp6 exhibited consistent suppression effects on EMT markers. This indicates a closer association with EMT compared to the other two signals. CONCLUSION: Our study highlights evolutionarily conserved molecular signatures and provides insights into the importance of the EMT pathway in palatal fusion in humans. Furthermore, intraindividual comparative analysis showed the spatial regulation of gene expression within the same organism. Further research and animal models are needed to explore the complexities of EMT-related palatal fusion.

Long-Term Comparison of Esthetic Outcomes Between Hatchet and Transposition Flaps in Facial-Defect Reconstruction.

BACKGROUND: Transposition flaps are commonly used for facial-defect repair after wide excision of skin cancers. However, such repair often causes excessive tension at the donor site that can result in distortion of the adjacent area. The hatchet flap, a rotation-advancement flap, can prevent distortion by redistributing the donor site tension evenly to the recipient site. This study aims to compare the esthetic outcomes of the hatchet flap and transposition flap in facial-defect reconstruction. METHODS: We retrospectively included 50 patients who underwent facial reconstruction with the hatchet flap or transposition flap after excision of skin cancer. They were followed up for more than 6 months. At the last follow-up visit, the esthetic outcome was evaluated by subjective and objective assessments using the patients and observer scar assessment scale and Manchester scar scale. RESULTS: Thirty patients and 20 patients underwent reconstruction using the hatchet flap and the transposition flap, respectively. The total score from the patient and observer scar assessment scale was significantly lower in the hatchet flap group compared with the transposition flap group (p = 0.009). The Manchester scar scale showed a total score of 7.67 ± 2.2 for the hatchet flap and 9.95 ± 1.99 for the transposition flap: in the color (p < 0.001), distortion (p < 0.001), and texture (p < 0.02) categories, the hatchet flap yielded significantly better outcomes than the transposition flap. CONCLUSIONS: The hatchet flap had good esthetic outcome for facial reconstruction and could be a valuable option for reconstructing facial defects. 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 Table of Contents or online Instructions to Authors www.springer.com/00266.

Complete Preservation of Orbital Fat by Restoration of Attenuated Orbital Septa Using an Acellular Dermal Matrix in Lower Blepharoplasty.

BACKGROUND: We hypothesized that application of acellular dermal matrix (ADM) over the orbital septum overlying the herniated orbital fat to tighten and strengthen the attenuated orbital septum in lower blepharoplasty would allow successful repositioning of the herniated orbital fat within the bony orbit. METHODS: The author prospectively compared the cosmetic outcomes of lower blepharoplasty using ADM with standard blepharoplasty. We evaluated recurrence of eyelid bulging and tear trough deformity, volume of the lower periorbital region, and enophthalmos and eyelid droop 1 year after surgery. RESULTS: Twenty-two of the 24 enrolled patients completed the study. There was no significant difference in recurrence of eyelid bulging and tear trough deformity between standard blepharoplasty and blepharoplasty with ADM graft groups. In the standard blepharoplasty group, the volume of the lower periorbital region decreased significantly after surgery. In the blepharoplasty with ADM graft group, there was no significant change in the volume of the lower periorbital region after surgery. In the standard blepharoplasty group, there was no significant change in eyelid droop on either side after surgery. In the blepharoplasty with ADM graft group, the eyelid droop decreased significantly after surgery on the right side but showed no significant change on the left side. There was no significant change in enophthalmos after surgery for either group. CONCLUSIONS: This study demonstrated that ADM graft provided effective support for maintaining the replaced orbital fat in lower blepharoplasty. In the long-term, blepharoplasty with ADM graft might be effective in slowing development of age-related enophthalmos. 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 .

Fat graft survival requires metabolic reprogramming toward the glycolytic pathway.

BACKGROUND: Fat grafts are widely used as natural fillers in reconstructive and cosmetic surgery. However, the mechanisms underlying fat graft survival are poorly understood. Here, we performed an unbiased transcriptomic analysis in a mouse fat graft model to determine the molecular mechanism underlying free fat graft survival. METHODS: We conducted RNA-sequencing (RNA-seq) analysis in a mouse free subcutaneous fat graft model on days 3 and 7 following grafting (n = 5). High-throughput sequencing was performed on paired-end reads using NovaSeq6000. The calculated transcripts per million (TPM) values were processed for principal component analysis (PCA), unsupervised hierarchically clustered heatmap generation, and gene set enrichment analysis. RESULTS: PCA and heatmap data revealed global differences in the transcriptomes of the fat graft model and the non-grafted control. The top meaningful upregulated gene sets in the fat graft model were related to the epithelial-mesenchymal transition, hypoxia on day 3, and angiogenesis on day 7. Mechanistically, the glycolytic pathway was upregulated in the fat graft model at days 3 (FDR q = 0.012) and 7 (FDR q = 0.084). In subsequent experiments, pharmacological inhibition of the glycolytic pathway in mouse fat grafts with 2-deoxy-D-glucose (2-DG) significantly suppressed fat graft retention rates, both grossly and microscopically (n = 5). CONCLUSIONS: Free adipose tissue grafts undergo metabolic reprogramming toward the glycolytic pathway. Future studies should examine whether targeting this pathway can enhance the graft survival rate.

A High-Fat Diet in the Absence of Obesity Increases Lymphangiogenesis by Inducing VEGF-C in a Murine Lymphedema Model.

BACKGROUND: Many researchers have attempted to induce lymphangiogenesis for the treatment of lymphedema. However, most previous studies had limited clinical usefulness. A high-fat diet (HFD) increases serum ß-hydroxybutyrate (ß-OHB) levels, which can stimulate lymphangiogenesis. The authors hypothesized that an HFD will ameliorate lymphedema through enhanced lymphangiogenesis. METHODS: The effects of ß-OHB on the lymphangiogenic process in human dermal lymphatic endothelial cells were analyzed. A mouse tail lymphedema model was used to evaluate the effects of an HFD on lymphedema. Experimental mice were fed an HFD (45% kcal as fat, 20% as protein, and 35% as carbohydrates) for 4 weeks. Tail volume was measured using the truncated cone formula. Biopsy specimens were taken 6 weeks after surgical induction of lymphedema. RESULTS: In human dermal lymphatic endothelial cells, treatment with 20 mM of ß-OHB increased cell viability ( P = 0.008), cell migration ( P = 0.011), tube formation ( P = 0.005), and VEGF-C mRNA and protein expression ( P < 0.001) compared with controls. HFD feeding decreased tail volume by 14.3% and fibrosis by 15.8% ( P = 0.027), and increased the lymphatic vessel density ( P = 0.022) and VEGF-C protein expression ( P = 0.005) compared with those of operated, standard chow diet-fed mice. CONCLUSIONS: The authors' findings demonstrated that ß-OHB promoted lymphatic endothelial cell function and increased VEGF-C mRNA and protein expression. When mice with tail lymphedema were fed an HFD, volume and fibrosis of the tail decreased. Therefore, the authors' findings suggest that an HFD can be a successful novel dietary approach to treating lymphedema. CLINICAL RELEVANCE STATEMENT: Lymphatic regeneration after vascularized lymph node transfer can be augmented when a high-fat diet is used in conjunction with vascularized lymph node transfer.

Therapeutic Effects of Amnion-Conjugated Chitosan-Alginate Membranes on Diabetic Wounds in an Induced Diabetic Swine Model: An In Vitro and In Vivo Study.

Background Chitosan (CS) is a well-known antimicrobial dressing material. Moreover, widely used amniotic membranes contain growth factors beneficial for wound healing. Herein, we created a novel amnion-conjugated CS-alginate membrane dressing and tested its wound healing potency in a diabetic swine model. Methods The bovine amniotic powder growth factor contents were evaluated by protein assay, and the powder's wound healing effects were assessed in vitro by HaCaT cell scratch closure. In vivo, two minipigs developed streptozotocin-induced diabetes. Serial serum glucose measurements and intravenous glucose tolerance tests were performed to confirm their diabetic status. Twelve square-shaped wounds created on each pig's back were randomly divided into control ( n = 4), CS ( n = 4), and amnion-CS (AC; n = 4) groups and treated accordingly with different dressings. Wound healing in each group was assessed by measuring wound contraction over time, capturing wound perfusion with indocyanine green (ICG) angiography, and histologically analyzing inflammatory markers. Results Amniotic powder elution promoted HaCaT cell migration in the scratch wound model, suggesting its beneficial in vitro wound healing effects. In vivo, the CS and AC groups showed earlier wound contraction initiation and reepithelialization and earlier wound perfusion improvement by ICG angiography than the control group. Additionally, the wound size of the AC group at week 3 was significantly smaller than those in the control group. There was no significant difference in the numbers of acute and chronic inflammatory cells between the groups. Conclusion The amnion-conjugated CS-alginate membrane, as well as CS dressing alone, could be a favorable dressing option for diabetic wounds.

Comparative Study of En Bloc Excision and Dermal Shaving in Treating Axillary Osmidrosis.

BACKGROUND: Axillary osmidrosis is a distressing problem caused by hyperactivity of apocrine glands. There have been numerous studies on various surgical treatment methods. In this study, we evaluated the effectiveness of en bloc excision in comparison with dermal shaving. METHODS: The electronic records of 146 patients (286 axillae) who underwent surgery at our center for axillary osmidrosis between January 2009 and December 2020 were reviewed. Twenty-five patients (49 axillae) underwent en bloc excision and 121 (237 axillae) underwent dermal shaving. Patients in the en bloc excision group underwent Minor test preoperatively to detect sweating areas. Severity of osmidrosis was graded using a 4-point scale (0-3). A satisfaction questionnaire was used to evaluate patient experiences in the 2 types. RESULTS: Mean operation time was significantly shorter in the en bloc excision group than in dermal shaving group. Most en bloc excisions were performed on an outpatient basis under local anesthesia. Both groups showed an improvement in osmidrosis score at 6 months after surgery. A satisfaction questionnaire revealed better perioperative experiences in the en bloc excision group. Various surgical complications such as hematoma, wound dehiscence, and flap necrosis occurred in the dermal shaving group, and the en bloc excision group experienced significantly fewer complications that required intervention. CONCLUSIONS: En bloc excision combined with Minor test effectively reduces malodor without causing severe complications. In addition, perioperative patient satisfaction was better in the en bloc excision group than in the dermal shaving group as en bloc excision provided more rapid returns to normality and simplified communications with patients.

Dll4 Inhibition Promotes Graft Retention in Fat Grafting Enriched with Adipose-Derived Stem Cells.

Autologous fat grafting is among the safest and most effective treatments for soft-tissue restoration and augmentation, and many efforts have been made to improve its efficiency, including adipose-derived stem cell (ASC) supplementation. Here, we investigated the role of Notch ligand Delta-like ligand 4 (Dll4) in angiogenesis within grafted fat and its effect on graft retention, as well as the effect of Dll4 inhibition on ASC supplementation. Using a murine fat graft model, we investigated the expression of Dll4 in fat grafts and assessed the graft volume, vascularity, and perfusion within the graft, and ASC differentiation patterns depending on the blockade of Dll4. The underlying mechanism of Dll4 inhibition on ASC supplemented fat grafts was investigated using transcriptome analysis. Dll4 was highly expressed in vascular endothelial cells (ECs) within grafted fat, where Dll4-blocking antibody treatment-induced angiogenesis, promoting fat graft retention. In addition, its effect on fat graft retention was synergistically improved when ASCs were concomitantly supplemented. The expression of junctional proteins was increased in ECs, and inflammatory processes were downregulated in grafted fat upon ASC supplementation and Dll4 inhibition. Dll4 inhibition induced vascularization within the grafted fat, thereby promoting graft retention and exhibiting synergistic effects with concomitant ASC supplementation. This study serves as a basis for developing new potential therapeutic approaches targeting Dll4 to improve graft retention after cell-assisted transfer.

Estrogen-Related Receptor γ Maintains Pancreatic Acinar Cell Function and Identity by Regulating Cellular Metabolism.

BACKGROUND & AIMS: Mitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production. METHODS: Two models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histologic and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in 2 distinct human pancreatitis cohorts. RESULTS: Blocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss of ERRγ in primary acini abrogates messenger RNA expression and protein levels of mitochondrial oxidative phosphorylation complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, endoplasmic reticulum stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics, indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared with normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants for ERRγ that are associated with chronic pancreatitis. CONCLUSIONS: Collectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.

Thyroid Hormone Ameliorates Lymphedema by Suppressing Adipogenesis in a Murine Lymphedema Model.

Background: Exogenous supplementation of thyroid hormone could inhibit excessive fat deposition in lymphedema tissue by suppressing adipogenesis. Methods and Results: Cell viability, adipogenic differentiation, and mRNA expression were measured in 3T3-L1 preadipocytes treated with L-thyroxine. Twelve mice were divided into control and L-thyroxine groups. Two weeks after lymphedema was surgically induced, the experimental mice were fed L-thyroxine for 4 weeks. Tail volume and body weight were measured, and 6 weeks after the surgery, tail skin and subcutaneous tissue were harvested for histopathologic examination and protein isolation. In 3T3-L1 cells, treatment with 10-500 µM L-thyroxine did not affect cell viability. Eight days after induction of adipogenic differentiation, lipid accumulation decreased significantly in the 50 and 100 µM L-thyroxine groups (p < 0.001). mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and fatty acid-binding protein 4 (FABP4) decreased significantly in the 100 µM L-thyroxine group compared with the control group (p = 0.017). Lymphedema tails treated with L-thyroxine exhibited decreased volume (p = 0.028) and thickness of dermal and subcutaneous tissue (p = 0.01) and increased vascular endothelial growth factor-C protein expression (p = 0.017) compared with the control. Conclusion: Thyroid hormone therapy inhibits the adipogenesis of 3T3-L1 cells in vitro and decreases the volume of murine lymphedema tail in vivo. These findings suggest that thyroid hormone therapy could be used to treat lymphedema.

Intramuscular Deep Inferior Epigastric Vessels Are Insulated by Perimysial Fibroadipose Tissue Network.

BACKGROUND: The difficulty of elevating a deep inferior epigastric perforator (DIEP) flap largely depends on the intramuscular course of the vessel and the perforator. Previous studies, however, have lacked histologic descriptions of the vessels and surrounding structures. The present study analyzed the histologic aspects of the deep inferior epigastric vessels and perforators, focusing on their perivascular relationships with muscle fibers. METHODS: The abdomen of a cadaver was histologically evaluated to identify intramuscular deep inferior epigastric vessels. Tissue samples were stained with hematoxylin and eosin and with Masson trichrome stain to visualize fibrous components. Twenty-one DIEPs from 12 patients were also evaluated to determine the histologic aspects of the perivascular structure. In the cross-section of each perforator and adjacent tissue, the perforator-to-muscle distance and trichrome-stained area were measured, and the correlation of the perforator size with the perforator-to-muscle distance and the percent collagenous portion of the distance were determined. RESULTS: Histologic analysis showed that the deep inferior epigastric vessels and perforators were encased by perimysial connective tissue and were not in direct contact with the muscle fibers. The smaller perimysia branched out from the larger perimysia, forming an interconnecting network structure. Correlation analysis showed that larger vessels had more collagenous portions in the perimysial structures (Spearman's ρ = 0.537, p = 0.012). CONCLUSION: The deep inferior epigastric vessels and perforators reside in a perimysial fibroadipose tissue network. This may provide surgeons with a microscopic perspective during DIEP dissections. Having an idea of the perforator anatomy in microscopic level can help us to perform safer perforator dissections.

Revision Rates of Left and Right Breast Reconstruction Differ With DIEP Flaps: Implications for Inexperienced Surgeons.

BACKGROUND: The internal mammary system provides the recipient vessel of choice in free autologous tissue breast reconstruction. However, left internal mammary veins (IMVs) are smaller than right IMVs, thus raising questions about their reliability. Here we analyzed right and left breast deep inferior epigastric perforator (DIEP) flap reconstruction performed by an experienced versus less experienced surgeon and hypothesized that less experienced surgeons might encounter difficulty in cases of smaller left IMVs. METHODS: We respectively reviewed the charts of 714 DIEP flap breast reconstructions performed by an experienced surgeon (>15 years' DIEP flap experience) and 231 performed by a relatively inexperienced surgeon (<4 years' DIEP flap experience). Reconstructions requiring microvascular revisions were compared with nonrevision controls, and left-side reconstructions were compared with right-side controls. RESULTS: Preoperative risk factors were not significantly different between the left and right cohorts for either surgeon. The experienced surgeon performed 17 microvascular revisions (2.4%), including 9 left (52.9%) and 8 right (47.1%). The less experienced surgeon performed 7 microvascular revisions (3.0%), all left. The left- and right-side revision rates were 2.4% and 2.3% for the experienced surgeon versus 6.1% and 0% for the less experienced surgeon, respectively, with a higher rate for the left side (P = 0.0299). CONCLUSIONS: The left-side microvascular revision rate was higher for the less experienced surgeon. Considering that left IMVs are smaller, less experienced surgeons should carefully perform left-side free flap breast reconstructions and be prepared to convert to thoracodorsal recipient vessel use.

A New Technique of Open Septal Reduction Using Polydioxanone Plates for Nasoseptal Fracture: Three-Dimensional Volumetric Analysis.

BACKGROUND: In this study, we designed a new technique for open septal reduction using a polydioxanone (PDS) plate and compared it with closed reduction (CR). METHODS: This study included 19 consecutive patients with nasoseptal fracture: 10 receiving open reduction with a PDS plate (PDS group) and 9 undergoing CR group. Open septal reduction was performed after CR for nasal bone fracture. A mucoperichondrial flap was unilaterally elevated, and the deviated septal cartilage was reduced. The PDS plate was inserted horizontally above the vomerine suture. Surgical outcome was analyzed with three-dimensional volumetry and with a quality-of-life scale for nasal obstruction (Nasal Obstruction Symptom Evaluation scale). RESULTS: Complications included 1 case of septal perforation in the CR group and 1 case of PDS exposure and septal hematoma in the PDS group. In the three-dimensional volumetric analysis of the PDS group, the median value of the nasal cavity change significantly differed between 1.14 mL (interquartile range; 0.46-2.4) at the preoperative computed tomography scan and 0.33 mL (interquartile range; -0.22 to 1.29) at the postoperative computed tomography scan (∗∗P = 0.0039). The Nasal Obstruction Symptom Evaluation scale revealed significant improvement in nasal obstruction postsurgically (median value, 42.5-7.5; ∗P = 0.0139) in the PDS group. CONCLUSIONS: Polydioxanone plates potentially present a new concept of open septal reduction in terms of septal reinforcement compared with the subtractive approach of open septal reduction.

The PAP Flap Breast Reconstruction: A Practical Option for Slim Patients.

BACKGROUND: The posterior thigh-based profunda artery perforator (PAP) flap has been an emerging option as a secondary choice in breast reconstructions. However, whether a PAP flap could consistently serve as the secondary option in slim patients has not been investigated. METHODS: Records of immediate unilateral breast reconstructions performed from May 2017 to June 2019 were reviewed. PAP flap breast reconstructions were compared with standard deep inferior epigastric perforator (DIEP) flap breast reconstructions, and were grouped into single or stacked PAP flaps for further analysis. RESULTS: Overall, 43 PAP flaps were performed to reconstruct 32 breasts. Eleven patients underwent stacked PAP flap reconstruction, while 17 patients underwent 21 single PAP flap reconstruction. The average body mass index (BMI) of the patients was 22.2 ± 0.5 kg/m2. The results were as follows: no total loss, one case of venous congestion (2.3%), two donor site wound dehiscence cases (4.7%), and one case of fat necrosis from partial flap loss (2.3%). When compared with 192 DIEP flap reconstructions, the final DIEP flap supplied 98.1 ± 1.7% of mastectomy weight, while the final PAP flap supplied 114.1 ± 6.2% of mastectomy weight (p < 0.005), demonstrating that PAP flaps can successfully supply final reconstruction volume. In a separate analysis, single PAP flaps successfully supplied 104.2% (84.2-144.4%) of mastectomy weights, while stacked PAP flaps supplied 103.7% (98.8-115.2%) of mastectomy weights. CONCLUSION: In our series of PAP flap reconstructions performed in low-to-normal BMI patients, we found that PAP flaps, as single or stacked flaps, provide sufficient volume to reconstruct mastectomy defects.

An Evaluation of Muscle Repair Techniques: Implications in Musculoskeletal Healing and Corollaries in Oral-Facial Clefting.

We performed an animal study to identify the techniques associated with the best muscle healing outcomes in cleft lip/palate surgery. The right triceps of thirty adult male Sprague-Dawley rats were cut and repaired by three different suture techniques: simple (n = 10), overlapping (n = 10), and splitting sutures (n = 10). Muscle tissues were isolated from 5 rats per group 1 and 8 weeks postoperation. The inflammatory response and muscle fiber healing were evaluated by hematoxylin and eosin (H&E) staining, Western blotting, immunohistochemistry for TNF-α and IL-1ß, and immunofluorescence for laminin and MyoD. Grip strength (N/100 g) and spatial gait symmetry were evaluated before surgery and 1, 2, 4 and 8 weeks postoperation. Eight weeks postoperation, grip force per weight was significantly higher in the simple suture (median, 3.49; IQR, 3.28-3.66) and overlapping groups (median, 3.3; IQR, 3.17-3.47) than the splitting group (median, 2.91; IQR, 2.76-3.05). There was no significant difference in range of motion between groups. The simple group exhibited significant remission of inflammation by H&E staining and lower expression of TNF-α and IL-1ß than the other groups by Western blotting and immunohistochemistry. Immunofluorescence revealed stronger expression of MyoD and weaker expression of laminin in the splitting group than in the other groups at week 8, indicating prolonged inflammation and healing followed by poor muscle fiber remodeling. Simple and overlapping sutures demonstrated similar functional healing, although greater inflammation and failure to maintain a thicker muscle belly were observed in the overlapping suture group compared with the simple suture group. Therefore, reconstruction of the philtral column with overlapping sutures alone may result in limited long-term fullness, and additional procedures may be needed.

Reconstruction of a pathologic fracture following osteomyelitis of the mandible using a fibula osteocutaneous flap.

The use of a fibula osteocutaneous flap is currently the mainstay of segmental mandibular reconstruction. This type of flap is used to treat tumors, trauma, or osteoradionecrosis of the mandible. However, a fibula osteocutaneous flap may also be a good option for reconstructing the mandible to preserve oropharyngeal function and facial appearance in cases of pathological fracture requiring extensive segmental bone resection. Chronic osteomyelitis is one of the various causes of subsequent pathologic mandibular fractures; however, it is rare, and there have been few reports using free flaps in osteomyelitis of the mandible. We share our experience with a 76-year-old patient who presented with a pathologic fracture following osteomyelitis of the mandible that was reconstructed using a fibula osteocutaneous flap after wide segmental resection.

Immediate breast reconstruction after salvage mastectomy: Case control outcome comparisons of DIEP flap and DTI reconstruction.

BACKGROUND: Cancer recurrence after breast-conserving therapy is most often managed by salvage mastectomy. Successful breast reconstruction immediately after salvage mastectomy, however, remains challenging because the reconstruction is performed on previously irradiated breast tissue. METHODS: Records of patients who underwent breast reconstruction from June 2010 to June 2019 were reviewed, including their demographic characteristics, methods of breast reconstruction, and early and late outcomes. Deep inferior epigastric perforator (DIEP) flaps and direct-to-implant (DTI) reconstructions following salvage mastectomies were compared with reconstructions following completion or primary mastectomies. Patients who underwent reconstruction followed by postmastectomy radiotherapy (PMRT) and patients followed up for less than 6 months were excluded. RESULTS: DIEP flaps in 27 breasts that underwent salvage mastectomy were compared with DIEP flaps in 32 breasts that underwent completion and 564 that underwent primary mastectomy. Rates of early complications, including microsurgical revision and total flap loss, and of late complications (>6 months after surgery), including fat necrosis and flap volume loss, did not differ significantly. DTI reconstruction in 20 breasts that underwent salvage mastectomy was compared with DTI reconstruction in 12 breasts that underwent completion and 351 that underwent primary mastectomy. Wound healing problems, including wound dehiscence and delayed wound healing (15% vs. 2.6%, P = 0.0022), and capsular contracture (30% vs. 5.4%, P = 0.0000), were significantly more frequent in breasts that underwent salvage than primary mastectomy. CONCLUSIONS: DIEP flap is a successful reconstruction option after salvage mastectomy. DTI reconstruction is associated with higher rates of wound healing problems and capsular contracture after salvage than after primary mastectomy.

Outcome of distal lower leg reconstruction with the propeller perforator flap in diabetic patients.

In diabetic foot patients, wound coverage options are quite limited due to vascular abnormalities. However, even though significant atherosclerotic changes are found in major vessels of the lower leg in diabetic foot patients, perforating vessels, which are used as the vascular pedicle of propeller perforator flaps, are often spared from atherosclerosis. Therefore, the propeller perforator flap could be an alternative option for diabetic foot patients. The purpose of this study was to compare the outcome of the propeller perforator flap between diabetic and nondiabetic patients in reconstruction of the distal lower leg. We retrospectively included all patients who underwent reconstruction of the distal lower leg with a propeller flap between 2014 and 2018. Thirty-five propeller perforator flaps in 20 diabetic patients and 15 nondiabetic patients were included. Of the 35 patients, 21 showed complete healing, and 14 showed flap complications. The rate of complications in diabetic patients was approximately 85.7%. Sex (p = .002), diabetes (p = .007), chronic renal failure (p < .001), and diabetic neuropathy (p = .011) were associated with flap complications. Crude regression analysis showed that the female sex (p = .002), diabetes (p = .01), and diabetic neuropathy (p = .012) were significant risk factors for the occurrence of any complications, but the significance of diabetes and diabetic neuropathy was not maintained in the adjusted models. Therefore, the propeller perforator flap might not be effective for reconstructing diabetic foot ulcers.

Comparison of transverse upper gracilis and profunda femoris artery perforator flaps for breast reconstruction: A systematic review.

BACKGROUND: Thigh-based flaps are generally considered a secondary option for breast reconstruction, with inner thigh-based transverse upper gracilis (TUG) flaps being the preferred choice for many surgeons; however, its well-established drawbacks include short pedicle length, lack of volume, and donor morbidity. The posterior thigh-based profunda femoris artery perforator (PAP) flap was introduced as an alternative approach, but these flaps were not comparatively analyzed with TUG flaps on a large scale. We aimed to systematically review TUG- and PAP-flap breast reconstruction to determine the better secondary option. METHODS: We performed a systematic review of the literature using the PubMed database. Our selected series for systematic analyses included 613 TUG flaps in 432 patients and 475 PAP flaps in 329 patients. Elementary data on the flaps and complications were collected and analyzed. Pooled estimates of proportions of flaps with recipient complications and donor site morbidity were compared using random effect single arm meta-analysis. RESULTS: The basic patient demographics were comparable between the flap types. The mean operation time was comparable. The PAP flap had longer pedicle length and higher flap weight. The total loss (p = .6579), partial loss rate (p = .3247), and fat necrosis rate (p = .0771) were comparable between flap types. Regarding donor morbidity, the PAP flap group had less wound dehiscence (p < .0001) and lower rate of sensory disturbance (p < .0001). CONCLUSIONS: The study findings indicate that the PAP flap, when compared with the TUG flap, could be a better secondary option for breast reconstructions.

Risk of necrosis in the adjacent toe after one-toe fillet flap in diabetic foot: Retrospective study of 107 cases over 5 years.

PURPOSE: Fillet flap is a "spare part" concept. This technique allows the defect to be covered without donor site morbidity. Over the past 5 years, there were 107 diabetic foot cases of one-toe fillet flap in our hospital. After the operation, in some patients, there was necrosis of the adjacent toe that required additional amputation. The aim of our study was to determine the cause of necrosis of the adjacent toe after fillet flap. METHODS: The patients were divided into two groups. One group had no necrosis of the adjacent toe (group A) after the operation, and the other group had necrosis of the adjacent toe that required additional amputation after the operation (group B). Then, to confirm the cause of the additional necrosis of the adjacent toe, χ2 tests, Fisher's tests, and logistic regression tests were performed. RESULTS: A total of 107 patients were included, and 48 patients needed additional amputation. The logistic regression test revealed that a fillet flap at the metatarsophalangeal joint (MTPJ), horizontal sutures, and a fillet flap at the second toe were significant risk factors for developing necrosis. CONCLUSIONS: If a fillet flap with a second toe, fillet flap on MTPJ level and horizontal closure after fillet flap is needed, the chance of developing necrosis of the adjacent toe and additional revisional surgery must be communicated preoperatively.