Association between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index.

Background/Aims: Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI. Methods: The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses. Results: Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055-2.410, p=0.027) and 1.579 (1.072-2.324, p=0.021), respectively. Conclusions: In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.

Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSION: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Evolutionary Spread of Distinct O-methyltransferases Guides the Discovery of Unique Isoaspartate-Containing Peptides, Pamtides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a structurally diverse class of natural products with a distinct biosynthetic logic, the enzymatic modification of genetically encoded precursor peptides. Although their structural and biosynthetic diversity remains largely underexplored, the identification of novel subclasses with unique structural motifs and biosynthetic pathways is challenging. Here, it is reported that peptide/protein L-aspartyl O-methyltransferases (PAMTs) present in several RiPP subclasses are highly homologous. Importantly, it is discovered that the apparent evolutionary transmission of the PAMT gene to unrelated RiPP subclasses can serve as a basis to identify a novel RiPP subclass. Biochemical and structural analyses suggest that homologous PAMTs convert aspartate to isoaspartate via aspartyl-O-methyl ester and aspartimide intermediates, and often require cyclic or hairpin-like structures for modification. By conducting homology-based bioinformatic analysis of PAMTs, over 2,800 biosynthetic gene clusters (BGCs) are identified for known RiPP subclasses in which PAMTs install a secondary modification, and over 1,500 BGCs where PAMTs function as a primary modification enzyme, thereby defining a new RiPP subclass, named pamtides. The results suggest that the genome mining of proteins with secondary biosynthetic roles can be an effective strategy for discovering novel biosynthetic pathways of RiPPs through the principle of "guilt by association".

Treatment of Sagittal Fracture of the Zygomatic Arch Root.

A sagittal fracture at the temporal root of the zygomatic arch (ZAR) often occurs as a component of zygomaticomaxillary complex (ZMC) fractures. However, this area is difficult to access, and anchorage is limited due to the unstable structure around it. Therefore, a preauricular approach using single-screw fixation is proposed, and this study reports its results and usefulness. Forty-four patients with sagittal fractures of ZAR occurring with ZMC fractures were evaluated from 2012 to 2021. Open reduction and internal fixation were performed on all patients with ZMC fractures. Closed reduction using Dingman incision and external finger pressure in group A (indirect approach; 30 patients) and single-screw fixation using a preauricular approach in group B (direct approach; 14 patients) were performed to address sagittal fractures in ZAR. For single-screw fixation, the additional mean operation time was 11.34±3.25 minutes. On postoperative 3-dimensional computed tomography and plain radiographs, group B showed more accurate reduction and less deformity and trismus ( P <0.05). Moreover, a normal diet was initiated more quickly in group B than in group A ( P <0.05). Some cases in group A showed nonunion or malunion. This study revealed that a direct approach (group B) toward sagittal fractures of ZAR is recommended due to more accurate results and fewer complications than those observed with the indirect approach (group A). Moreover, the total operation time and complications may be lesser than those with the bicoronal approach.

Establishment of a humanized mouse model of keloid diseases following the migration of patient immune cells to the lesion: Patient-derived keloid xenograft (PDKX) model.

Keloid disorder is an abnormal fibroproliferative reaction that can occur on any area of skin, and it can impair the quality of life of affected individuals. To investigate the pathogenesis and develop a treatment strategy, a preclinical animal model of keloid disorder is needed. However, keloid disorder is unique to humans, and the development of an animal model of keloid disorder is highly problematic. We developed the patient-derived keloid xenograft (PDKX), which is a humanized mouse model, and compared it to the traditional mouse xenograft model (transplantation of only keloid lesions). To establish the PDKX model, peripheral mononuclear cells (PBMCs) from ten keloid patients or five healthy control subjects were injected into NOD/SCID/IL-2Rγnull mice, and their keloid lesions were grafted onto the back after the engraftment of immune cells (transplantation of keloid lesions and KP PBMCs or HC PBMCs). Four weeks after surgery, the grafted keloid lesion was subjected to histologic evaluation. Compared to the traditional model, neotissue formed along the margin of the grafted skin, and lymphocyte infiltration and collagen synthesis were significantly elevated in the PDKX model. The neotissue sites resembled the margin areas of keloids in several respects. In detail, the levels of human Th17 cells, IL-17, HIF-1a, and chemokines were significantly elevated in the neotissue of the PDKX model. Furthermore, the weight of the keloid lesion was increased significantly in the PDKX model, which was due to the proinflammatory microenvironment of the keloid lesion. We confirmed that our patient-derived keloid xenograft (PDKX) model mimicked keloid disorder by recapitulating the in vivo microenvironment. This model will contribute to the investigation of cellular mechanisms and therapeutic treatments for keloid disorders.

Volume changes in the reconstructed breast over two years after free abdominal tissue transfer: Comparison of unipedicled versus bipedicled flaps.

BACKGROUND: Volume changes in reconstructed flaps, particularly regarding symmetry, are an important consideration to improve long-term esthetic results in patients who undergo breast reconstruction. Asian patients with thin abdominal tissues tend to require bipedicled flaps, which provide a greater volume of abdominal tissue. We investigated volume changes in free abdominal flaps and the factors that may affect flap volume, particularly the number of pedicles. METHODS: The study included all consecutive patients who underwent immediate unilateral breast reconstruction using free abdominal flaps between January 2016 and December 2018. The initial flap volume was calculated intraoperatively, and the postoperative flap volume was calculated using computed tomography or magnetic resonance imaging based on the Cavalieri principle. RESULTS: The study included 131 of 249 patients. Compared with the initial inset volume, the mean flap volumes at 1 and 2 years postoperatively decreased to 80.11% and 73.80%, respectively. The multivariable analysis of factors that affect flap volume showed a significant association with the flap inset ratio, radiation (P = .019,.040, respectively). Stratification based on the number of pedicles showed that the flap inset ratio was significantly negatively correlated with the postoperative flap volume change in unipedicled (P < .05) but not in bipedicled flaps. CONCLUSIONS: The flap volume decreased over time, and its change had a negative correlation with the flap inset ratio in the unipedicled group. Therefore, prediction of postoperative volume changes in various clinical situations is important before breast reconstruction.

Effect of Topical Tranexamic Acid on Seroma Formation in a Rat Mastectomy Model.

BACKGROUND: Seroma is the most common complication after mastectomy and reconstruction surgery. Therefore, this study aimed to determine whether the topical application of tranexamic acid would be useful to reduce seromas in a rat mastectomy model. METHODS: Forty-eight Sprague-Dawley rats were divided into four groups. After mastectomy and axillary lymph node dissection, 0.4 mL of normal saline was administered to group A in the dead space. In group B, 0.4 mL of a triamcinolone mixed solution was administered. In group C, 0.4 mL of a tranexamic acid (10 mg/kg) mixed solution was administered. In group D, 0.4 mL of a tranexamic acid (50 mg/kg) mixed solution was administered. Gross examination, assessment with micro-computed tomography (CT), quantitative analysis via aspiration, and histopathologic assessment were implemented 7 and 14 days postoperatively. RESULTS: No other complications such as wound infection and skin necrosis were observed. At postoperative week 1, groups B and C showed significantly lower seroma volume values on micro-CT (P < 0.001 and P < 0.05, respectively) and seroma volume values at aspiration (P < 0.01 and P < 0.001, respectively) than group A. According to histopathologic analysis, inflammation was observed more frequently in groups A and D than in the other groups, and angiogenesis was more active in groups B and C than in the other groups. CONCLUSIONS: Topical application of tranexamic acid was as effective as topical application of triamcinolone to prevent seroma formation. The stability of tranexamic acid was confirmed when the high dose of tranexamic acid was used. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hyaluronate-Black Phosphorus-Upconversion Nanoparticle Complex for Non-invasive Theranosis of Skin Cancer.

Despite the wide investigation on black phosphorus (BP) for biophotonic applications, the finite depth of light penetration has limited further development of BP-based photomedicines. Here, we developed a hyaluronate-BP-upconversion nanoparticle (HA-BP-UCNP) complex for near-infrared (NIR) light-mediated multimodal theranosis of skin cancer with photoacoustic (PA) bioimaging, photodynamic therapy (PDT), and photothermal therapy (PTT). In contrast to the conventional BP-based skin cancer theranosis, the HA-BP-UCNP complex could be non-invasively delivered into the tumor tissue to induce the cancer cell apoptosis upon NIR light irradiation. The PA imaging of BP successfully visualized the non-invasive transdermal delivery of the HA-BP-UCNP complex into the mice skin. HA in the complex facilitated the transdermal delivery of BP into the tumor tissue under the skin. Upon 980 nm NIR light irradiation, the UCNP converted the light to UV-blue light to generate reactive oxygen species by sensitizing BP in the HA-BP-UCNP complex for PDT. Remarkably, 808 nm NIR irradiation with PTT triggered the apoptosis of tumor cells. Taken together, we could confirm the feasibility of the HA-BP-UCNP complex for NIR light-mediated multimodal theranosis of skin cancers.

Brain Region and Sex-specific Changes in Mitochondrial Biogenesis Induced by Acute Trimethyltin Exposure.

Objective: In this study, we investigated sex- and region-specific effects of acute trimethyltin (TMT) exposure on mitochondrial biogenesis. Methods: We treated TMT to primary neuronal cultures and 4-week-old male and female mice. We measured the mitochondrial DNA copy numbers using the quantitative polymerase chain reaction method. We also measured mitochondrial biogenesis related genes (sirtuin-1, estrogen-related receptor alpha, cytochrome C oxidase subunit IV) by western blotting. Results: The mitochondrial DNA copy number increased in the primary hippocampal neuron; however, it decreased in the primary cortical neuron. The mitochondrial copy number increased in the hippocampus and decreased in the cortex in the TMT treated female mice, though the mitochondrial copy number increased in both cortex and hippocampus in the TMT treated male mice. TMT treatment increased sirtuin-1 expression in the male hippocampus but did not in the female brain. In the female brain, estrogen-related receptor alpha expression decreased in the cortex though there is no significant change in the male brain. The protein level of mitochondrial protein, cytochrome C oxidase subunit IV, increased in both cortex and hippocampus after TMT injection in male mice brain, but not in female mice brain. Conclusion: Our data suggest that acute TMT exposure induces distinct sex-specific metabolic characteristics in the brain before significant sexual maturation.

Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model.

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.

Correction of a Secondary Bilateral Cleft Lip Nasal Deformity in Adults Using Repositioning of Both Lower Lateral Cartilages and Nasal Tip Plasty Through an Open Bilateral Reverse-U Incision.

BACKGROUND: Correcting a secondary bilateral cleft lip nasal deformity is very complex with many challenges due to its complexity. This study presents the surgical results after correcting a secondary bilateral cleft lip nasal deformity using isolation and repositioning of the lower lateral cartilages, the columellar strut, and an onlay graft on the nasal tip. METHOD: Eighteen patients who had bilateral cleft lip nasal deformities and who had surgery performed between September 2013 and December 2019 were included in this study. The age of the patients ranged between 19 and 52 years. Open rhinoplasty with bilateral reverse-U incision was performed. The lower lateral cartilages were isolated and repositioned. Nasal tip support is provided using a columellar strut with a septal cartilage or Medpor strut. In the vertical component of the nasal tip, a conchal cartilage graft was used. The mean follow-up period was 2 years (ranging from 1 to 6 years). RESULTS: Fourteen of the 18 patients underwent photogrammetric evaluation. After surgery, the projection of the nasal tip and angle increased, but nasal bridge length decreased. The columella-labial angle significantly increased by 10.1% after surgery which was statistically significant (P < 0.05). The angle between the nostril axes significantly decreased by 46.2% postoperatively and also reached statistical significance (P < 0.05), indicating that the displaced alar base and lower nostril sill improved and the major axis of the nostril changed more vertically oblique. All patients were pleased with their surgical results. CONCLUSION: The proposed technique was highly effective in correcting secondary bilateral cleft lip nasal deformities in adults.

Big data analysis of the risk factors and rates of perioperative transfusion in immediate autologous breast reconstruction.

Patients undergoing autologous breast reconstruction (ABR) are more likely to require perioperative transfusions due to the increased intraoperative bleeding. In addition to the mastectomy site, further incisions and muscle dissection are performed at the donor sites, including the back or abdomen, increasing the possibility of transfusion. The purpose of this study was to evaluate perioperative transfusion rates and risk factors according to the type of ABR through analysis of big data. Patients who underwent total mastectomy for breast cancer between 2014 and 2019 were identified. The patients were divided into mastectomy only and immediate ABR groups. The transfusion rate was 14-fold higher in the immediate ABR group (16.1%) compared to the mastectomy only group (1.2%). The transfusion rate was highest with the pedicled transverse rectus abdominis myocutaneous flap (24.2%). Performance of the operation in medical institutions located in the provinces and coronary artery disease (CAD) were significant risk factors for the need for transfusion. The perioperative transfusion risk among patients undergoing immediate ABR was related to the flap type, location of medical institution, and CAD. Based on the higher transfusion rate in this study (16.1%) compared to previous studies, the risk factors for the need for transfusion should be determined and evidence-based guidelines should be developed to reduce the transfusion rates.

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model.

Steroids are currently being used in sepsis, particularly in septic shock. However, clinical trials to date have shown contradictory results. This could be attributed to the different patient endotypes and steroid doses, which have also contributed to the inconclusive results. We investigated the effects of glucocorticoid therapy on sepsis in a polymicrobial sepsis model in a variety of settings, such as steroid dose, severity, and sepsis phase. We used a rat model of fecal slurry polymicrobial sepsis. First, we investigated the optimum dose of steroids in a sepsis model. We administered different doses of dexamethasone after sepsis induction (0.1DEX; 0.1 mg/kg, 0.2DEX; 0.2 mg/kg, 5DEX; 5 mg/kg). Second, we used two different severities of the fecal slurry polymicrobial sepsis rat model to examine the effects of the steroids. A moderate or severe model was defined as a survival rate of approximately 70% and 30%, respectively. Third, we administered steroids in an early (1 h after sepsis induction) or late phase (25 h after sepsis). In all the experiments, we investigated the survival rates. In the determined optimal model and settings, we measured serum lactate, alanine transferase (ALT), creatinine, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and arterial blood gas. We evaluated the bacterial burden in the blood and spleen. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was also investigated to determine the level of immune suppression 24 h after sepsis by measuring TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. Early treatment of 0.2 mg/kg dexamethasone in a severe sepsis model showed the best beneficial effects. In moderate- or late-phase sepsis, there was no survival gain with steroid treatment. DEX0.2 group showed less acute kidney injury manifested by serum creatinine and blood urea nitrogen. DEX decreased the levels of cytokines, including IL-6, IL-10, and TNF-α. Colony-forming units were significantly decreased in the blood when administered with dexamethasone. Endotoxin tolerance was not significantly different between the DEX0.2 and control groups. In conclusion, early treatment of 0.2 mg/kg dexamethasone improved the outcomes of rats in a severe sepsis model.

Analysis of 461 Consecutive Patients' Donor Site Morbidity following Abdominal Tissue-Based Breast Reconstruction without Fascia Reinforcement Graft.

Despite the popularity of breast reconstruction with abdominal flap, the integrity of the abdominal wall gets compromised after the operation. To decrease donor site morbidity, researchers have developed various inlay or onlay graft materials. However, the indications of use are unclear and dependent on the subjective decision of the surgeons. In this study, we have investigated donor site morbidities in breast reconstruction with free abdominal flap surgery in which graft materials were not used. We reviewed 461 consecutive cases for the preoperative characteristics of patients, intraoperative details, and postoperative donor site complications from May 2013 to March 2019. While 386 patients underwent deep inferior epigastric perforators (83.7%), muscle sparing type 2 transverse rectus abdominis musculocutaneous flaps were performed in 75 patients (16.3%). Bilateral dissection of the pedicle was performed in 162 patients, compared to unilateral dissection in 299 patients. The mean follow-up duration was 22.7 months. The overall complication rate in the donor site was 7.2%. The flap height was significantly associated with the overall complication. While majority of them were delayed wound healing (n = 28, 6.1%), there were four cases of hematoma (0.9%). There were two cases of bulging (0.4%), which occurred in patients receiving bipedicle dissection; however, there was no case of hernia. Conclusions. Breast reconstruction with an abdominal free flap can be safely performed without fascia reinforcement graft even with bilateral dissection of the pedicle. With complete preservation of fascia and zigzag fascial incision, a low incidence of abdominal bulging can be obtained even with bilateral harvesting of the flap.

Usefulness of Incisional Negative Pressure Wound Therapy for Decreasing Wound Complication Rates and Seroma Formation Following Prepectoral Breast Reconstruction.

BACKGROUND: Seroma is a common complication in prepectoral breast reconstruction. PICOTM dressing, a type of incisional negative pressure wound therapy (iNPWT), was used to reduce complications postoperatively. METHODS: This study was a retrospective cohort study that included patients who underwent prepectoral breast reconstruction between February 2017 and July 2019. There were two groups: one that received PICOTM dressing and a control group. The frequencies of overall complications, major seromas, and reoperations were analyzed. The durations and total amounts of seromas were also analyzed. RESULT: Sixty patients were included in this study (PICOTM : 37 and non-PICOTM patients: 23). The overall incidence of complications, major seromas, and frequency of reoperations were lower in the PICO group compared to the non-PICOTM group (18.9% vs. 52.2%, p = 0.007; 16.2% vs. 43.5%, p = 0.020; 2.7% vs. 26.1%, p = 0.006, respectively). Univariate analysis was used to analyze the risk factors for complications due to the application of PICOTM dressing and showed statistically significant results for any complication. When univariate analysis was performed on risk factors for seroma, the duration of seroma showed statistical significance in association with PICOTM dressing status and mastectomy volume. The total number of patients who developed seroma was statistically correlated with age, PICOTM dressing status, and mastectomy volume. CONCLUSIONS: PICOTM dressing after prepectoral breast reconstruction could be a useful tool for reducing the frequency of complications and major seroma, as well as the duration and total incidences of seroma. 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 .

Influence of Irradiation on Capsules of Silicone Implants Covered with Acellular Dermal Matrix in Mice.

BACKGROUND: In advanced breast cancer, radiotherapy is recommended as adjuvant therapy following breast reconstructive surgery. This inevitably led to growing concerns over possible complications of radiotherapy on implants. In this experimental animal study, we investigated the utility of acellular dermal matrix (ADM) wraps around implants as preventive management for radiotherapy complications. METHODS: Black mice (C57NL6; n = 32) were assigned to groups that either received radiation or did not: groups A and B underwent surgery using implants without radiotherapy; while groups C and D underwent surgery using implants with radiotherapy for one and three months, respectively. The hemispheric silicone implants with an 0.8-cm-diameter were inserted on the left back of each mouse, and implants wrapped by ADM were inserted on the right back. The Clinic 23EX LINAC model was used for irradiation at 10 Gy. The samples were evaluated by gross assessment, histological analysis, immunohistochemical analysis, and the Western blotting test. RESULTS: The H&E staining analysis showed that membrane thickness is smallest in group A, followed by groups C, D, and B. In a Masson trichrome histological analysis, collagen fibers became less dense and more widespread over time in the groups that received an ADM. Immunohistochemistry findings were similarly constant. However, the expression of TGF-ß1 was increased in the irradiated groups, whereas it was decreased in the non-irradiated groups as observed over time. CONCLUSIONS: Radiotherapy was shown to increase risk factors for capsular contracture, including inflammatory response, pseudoepithelium, thinning of membrane, and TGF-ß1 expression over time; however, the accompanying framework using an ADM as a barrier between implant and tissue was shown to be effective in alleviating these risks. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Flavonoid Baicalein Negatively Regulates Progesterone Target Genes in the Uterus in Vivo.

Baicalein is a flavonoid extracted from the root of Scutellaria baicalensis (Chinese skullcap) and is consumed as part of this botanical dietary supplement to reduce oxidative stress, pain, and inflammation. We previously reported that baicalein can also modify receptor signaling through the progesterone receptor (PR) and glucocorticoid receptor (GR) in vitro, which is interesting due to the well-established roles of both PR and GR in reducing inflammation. To understand the effects of baicalein on PR and GR signaling in vivo in the uterus, ovariectomized CD-1 mice were treated with DMSO, progesterone (P4), baicalein, P4 with baicalein, and P4 with RU486, a PR antagonist, for a week. The uteri were collected for histology and RNA sequencing. Our results showed that baicalein attenuated the antiproliferative effect of P4 on luminal epithelium as well as on the PR target genes HAND2 and ZBTB16. Baicalein did not change levels of PR or GR RNA or protein in the uterus. RNA sequencing data indicated that many transcripts significantly altered by baicalein were regulated in the opposite direction by P4. Similarly, a large portion of GO/KEGG terms and GSEA gene sets were altered in the opposite direction by baicalein as compared to P4 treatment. Treatment of baicalein did not change body weight, organ weight, or blood glucose level. In summary, baicalein functioned as a PR antagonist in vivo and therefore may oppose P4 action under certain conditions such as uterine hyperplasia, fibroids, and uterine cancers.

Simultaneous nipple reconstruction in autologous breast reconstruction.

BACKGROUND: Reconstruction of the nipple-areola complex is the final step in surgical restoration of the breast. Nipple-areola reconstruction was previously done after an interval of several months using variable techniques, often resulting in low projection and flattened breast mound over time. We present algorithm of simultaneous nipple reconstruction (SNR) that leaves adequate residual projection and naturally shaped breast mound. METHODS: Forty patients underwent a skin-sparing mastectomy and nipple excision between October 2016 and December 2020. In the control group, 21 patients underwent delayed nipple reconstruction for 6 months after breast reconstruction. The experimental group of 19 patients underwent nipple and breast reconstruction simultaneously. We collected relevant information and photographs of nipple profiles of both groups in the preoperative, postoperative 6-month, and postoperative 1-year time periods. We also examined the ratio between the reconstructed and contralateral nipples. RESULTS: Scores regarding patient satisfaction questionnaire averaged higher in experimental groups to every category. The control group's scores gradually declined over time and the experimental group showed lesser decline. At the 1-year postoperative follow-up, the mean projection of the immediately reconstructed nipple was approximately the same as the contralateral nipple at 91%, whereas the delayed reconstructed nipple resulted in a 77% ratio. CONCLUSIONS: Nipple reconstruction should no longer be considered as a secondary complement to immediate breast reconstruction. The nipple appears to be essential component of breast reconstruction for patient. SNR with immediate breast reconstruction is a simple and reliable technique, giving stable aesthetic results over time.

Tissue Expansion after Non-Skin-Sparing Mastectomy: A Comparative Study of Expansion Courses of Prepectoral and Subpectoral Tissue Expander Placement with Acellular Dermal Matrix.

Although skin- or nipple-sparing mastectomy has been popular in the treatment of breast cancer, the radical excision of breast tissue is unavoidable in certain circumstances. However, the ability of an acellular dermal matrix (ADM) to expand remains questionable, and this situation may further hinder tissue expansion. From October 2017 to January 2020, patients who underwent immediate breast reconstruction with tissue expander placement using ADM whose initial fill volume was less than 50 mL were retrospectively reviewed. The primary outcomes were the number of visits and number of days required to complete the expansion, and the secondary outcomes were the amount of postoperative expansions, expander fill ratio and expander volume. Between the prepectoral group (n = 26) and subpectoral group (n = 39), the mean number of days (81.46 days versus 88.64 days, p = 0.365) and mean number of visits (5.08 versus 5.69, p = 0.91) required to complete expansion exhibited no significant differences. Additionally, there were no significant differences in the mean amount of postoperative expansion (314.23 mL versus 315.38 mL, p = 0.950), the mean final volume (353.08 mL versus 339.62 mL, p = 0.481) or the mean final volume ratio (0.89 versus 0.86, p = 0.35) between the two groups. Therefore, we suggest that prepectoral tissue expander placement after conventional mastectomy can be a valid option.