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Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% (p = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% (p < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% (p < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% (p < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms.

Background/Objectives: We intended to investigate choroidal blood flow (CBF) and choroidal thickness (CT) alternations in treatment-naive eyes with non-ischemic branch retinal vein occlusion (BRVO) following intravitreal aflibercept injection (IVA). Methods: Twenty eyes of 20 patients with treatment-naive non-ischemic BRVO, treated with IVA 1+ pro re nata, were included in this study. In the BRVO eyes, CBF and CT were measured in the occlusive region, subfovea, as well as the non-occlusive region, via laser speckle flowgraphy (LSFG) and enhanced depth-imaging optical coherence tomography over a 6-month follow-up period. CBF was analyzed via the mean blur rate using LSFG analysis software (version 3.10.0). Results: CT showed significant reductions in both the occlusive and subfoveal region at 1 week and 1 month after treatment (both p < 0.05). CBF was significantly decreased in the subfovea and the non-occlusive region at 1 week and 1 month from baseline, respectively (both p < 0.05). The mean number of IVA injections during the 6-month period was 1.95 ± 0.6. Conclusions: Aflibercept treatment reduced CBF and CT in addition to a decrease in retinal thickness. These changes at each region might be associated with the improvement of macular edema in BRVO eyes.

Background/Objectives: To evaluate the roles of choroidal blood flow (CBF) and choroidal thickness (CT) as predictors of macular edema recurrence in patients with treatment-naive non-ischemic branch retinal vein occlusion (BRVO) after intravitreal ranibizumab (IVR) injection. Methods: Sixteen eyes from sixteen patients with treatment-naive non-ischemic BRVO treated with IVR, once initially and then as needed, were included in the study. CBF and CT in the subfovea, occlusive, and non-occlusive regions were measured via laser speckle flowgraphy and enhanced depth imaging optical coherence tomography over 12 months. Results: Baseline CT was significantly greater in the occlusive region (335 ± 72.1 µm) than in the non-occlusive region (274 ± 36.7 µm, p = 0.028). CT in the occlusive region was reduced significantly after 1 week (p = 0.008), but CBF did not change significantly after IVR throughout the follow-up period (p > 0.05). The occlusive/non-occlusive region CBF ratio at baseline was significantly associated with the number of IVR injections over 12 months (mean 2.63) in patients with BRVO (p = 0.048). Conclusions: Baseline CBF imbalance in eyes with treatment-naive BRVO may indicate the recurrence of macular edema after ranibizumab therapy.

Abstract Background Extrapulmonary tuberculosis commonly affects the lymphatic system, nervous system, and gastrointestinal system. Tuberculous infection in the muscle is very rare. Moreover, tuberculous infection in the diaphragm is extremely rare. We herein report a case of tuberculomas in the diaphragm and posterior mediastinum that were successfully diagnosed and treated. Case presentation We encountered a 62-year-old woman with a tuberculoma in the diaphragm. The patient presented with mild dyspnea. Computed tomography showed a mass in the left diaphragm, focal thickening of the posterior mediastinum, and multiple nodules in the lungs. Positron emission tomography–computed tomography showed increased uptake in the left diaphragm mass and thickening of the posterior mediastinum; therefore, we considered the masses to be malignant and planned surgical resection. However, the patient was diagnosed with tuberculosis from a sputum culture, and she was treated with anti-tuberculous therapy. The masses in the diaphragm and posterior mediastinum had become enlarged after 6 months of anti-tuberculous therapy; therefore, the patient underwent resection of both masses. Tuberculous infection was histologically confirmed in each lesion. She was pathologically diagnosed with tuberculous abscesses in the diaphragm and posterior mediastinum and began treatment with anti-tuberculosis drugs. Conclusions Preoperative diagnosis of a tuberculoma in the diaphragm is usually difficult, and surgical intervention is important for both diagnosis and treatment.

Abstract Background Preoperative maximum standardized uptake value (SUVmax) of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography and serum carcinoembryonic antigen (CEA) have been reported as prognostic factors for lung adenocarcinoma. However, the significance of combined SUVmax and CEA in early‐stage lung adenocarcinoma is not well known. Methods We retrospectively evaluated the relationship between the combination of SUVmax and CEA and the prognosis of 410 patients with clinical stage IA lung adenocarcinoma who underwent resection. The cutoff values for SUVmax and CEA were determined by receiver operating characteristic curve analysis, and patients were categorized into high SC (SUVmax and CEA) group (SUVmax ≥2.96 and CEA ≥5.3), moderate SC group (either SUVmax

To ensure the structural integrity of advanced thin sheet metals in engineering applications, it is necessary to understand their ductile crack propagation behaviour. In this work, we clarified the governing factors for ductile crack propagation paths in sheet metals by the comprehensive investigation with experimental and numerical approaches. Using two types of sheet metals, a steel and an aluminium alloy, experiments with Arcan tests were performed, and the difference in the crack paths were observed and analysed. The strategy for simulating ductile fracture proposed by the authors was successfully validated with the experimental Arcan test results, and it was applied to a parametric study based on the numerical simulations for clarifying the governing factors for ductile crack propagation paths in sheet metals. The two factors, strain hardening ability and ductility diagram parameter, were confirmed to be dominant in controlling the ductile crack propagation. The findings in the parametric study explain the difference of the crack paths as observed in the experimental Arcan tests for the two materials, thus elucidating the inverse design philosophy that facilitates material design to achieve desired performance metrics in enhancing the integrity of engineering structures.

Purpose: We aimed to examine the changes in choroidal blood flow (CBF) and central choroidal thickness (CCT) in children with anisohypermetropic amblyopia using laser speckle flowgraphy (LSFG) and enhanced depth imaging optical coherence tomography (EDI-OCT). Observations: The patients were both 6-year-old Japanese male children with complaints of worsening right visual acuity and were diagnosed with anisohypermetropic amblyopia. The decimal best-corrected visual acuities (BCVAs) in cases 1 and 2 were both 0.5. In both cases, LSFG results demonstrated CBF impairment in amblyopic eyes compared with fellow eyes. EDI-OCT results also showed that the CCTs of amblyopic eyes were greater than those of fellow eyes at the initial visit. Several months after the first visit, the decimal BCVAs in both cases had improved to 1.0 because of treatment. Further, the CBF gradually increased along with a decrease in the CCT of the amblyopic eye. The axial lengths and spherical powers of the amblyopic eyes in the two cases were not different during follow-up. Conclusions and importance: We have determined the changes in CBF and CCT in two children with anisohypermetropic amblyopia for the first time. CBF impairments may be involved in the pathogenesis of anisohypermetropic amblyopia, and LSFG may be useful in examining CBF in pediatric anisohypermetropic amblyopia.

Purpose: To report the time course of choroidal blood flow (CBF) in a commotio retinae case using laser speckle flowgraphy (LSFG). Observations: A 58-year-old Japanese man with complaints of worsening left visual acuity after blunt eye trauma was diagnosed with commotio retinae. A funduscopic examination showed macular opacity, and LSFG results demonstrated CBF impairment in the affected eye. Optical coherence tomography also showed disruption of the photoreceptor outer segment. Seven months after the initial visit, CBF was significantly increased, along with improvement in the photoreceptor outer segment. Conclusion: and importance: We revealed CBF impairment in a case of commotio retinae for the first time. CBF impairment may be involved in the pathogenesis of commotio retinae, and LSFG may be useful for examining CBF in commotio retinae.

Background: Recently, significant inframalleolar disease seems to increase in chronic limb-threatening ischemia (CLTI) patients, making identifying sufficient outflow vessels in the foot challenging. In these difficult situations, free tissue transfer is a valuable tool to provide a low-resistance vascular bed to the affected part. However, there remains concern that free tissue transfer may impede adequate perfusion of the higher resistance diseased vascular bed., Methods: To improve perfusion of the affected area directly, the authors have developed a concept of a free bypass flap, adding bypass surgery to free tissue transfer. After anastomosis with the recipient vessels in a conventional manner for free tissue transfer, bypass surgery to the foot is performed by anastomosis of the branch of the flap pedicle with the diseased artery to the foot. A retrospective chart review of nine CLTI patients was performed to analyze the outcomes of free bypass flap transfer between 2018 and 2023., Results: The flap success rate was 100% (n = 9). Postoperative angiography or echo confirmed the patency of all but one bypass vessel (n = 8). There were six fatalities, however, due to causes other than foot lesions, with an average observation period of 16 months. The limb salvage rate was 89% (n = 8)., Conclusions: A free bypass flap enhances the overall blood circulation to the foot. Due to its high patency rate of bypass vessels, it is a valuable method for preserving the limbs of highly comorbid patients with CLTI., 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.)

Background: There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction., Methods: This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence., Results: Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15., Conclusion: The authors' risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction., Clinical Question/level of Evidence: Risk, III., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Abstract: Langerhans cell histiocytosis (LCH) is a rare disease in which LCH cells derived from myeloid dendritic cells proliferate and invade single or multiple systems. We have encountered a case of short-term resorption of the grafted bone after split calvarial bone grafting for an occipital skull defect in a 6-year-old girl with multisystem LCH in remission who was referred to our department for reconstructive surgery. We performed cranioplasty using a split calvarial bone graft. Two months after surgery, computed tomography scans revealed that most of the grafted bone had been resorbed. To our knowledge, there have been no such reports previously. There are 2 possible explanations for the resorption of an autologous bone graft in this patient. The first possibility is that the recipient site contained an active lesion and the second is that the bone resorption occurred because the bone graft was placed on the periosteum., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Purpose: To evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD., Methods: Sixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters., Results: Of the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p<0.05). Multivariable analysis revealed that patients who showed non-compliance with the supplement intake were more likely to develop nAMD (p<0.05). No significant association was found between the patchy pattern and CNV development (p = 0.86)., Conclusion: The fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD., Competing Interests: Santen Pharmaceutical Co., Ltd. provided support in the form of honoraria for speaking and/or organizing at meetings [TY, RM, MS, AS, TS, Yuji Oshima, Yuichiro Ogura, TI, FG]. Mayumi Nakamura and Erika Kimura are employees of Santen Pharmaceutical Co., Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Nontraumatic atlantoaxial rotatory fixation after microtia reconstruction surgery is a rare complication. Intraoperative cervical hyperextension and/or excessive rotation and postoperative inflammation have been reported as causes of atlantoaxial rotatory fixation. We herein describe cases of atlantoaxial rotatory fixation after microtia reconstruction surgery., Methods: This was a retrospective study of 80 patients (165 surgeries) who underwent microtia reconstruction surgery in Dokkyo Medical University Hospital between April 2006 and December 2012. The patient- and operation-related variables were obtained from medical charts. Neck radiographs and computed tomography scans of patients with atlantoaxial rotatory fixation were evaluated to check for cervical spine abnormalities., Results: Five cases of atlantoaxial rotatory fixation after microtia reconstruction surgery were recorded. Three of these five cases were diagnosed with Klippel-Feil syndrome after the onset of atlantoaxial rotatory fixation. No significant difference was found in the operative duration and other variables between patients with atlantoaxial rotatory fixation and those without. All patients immediately underwent conservative treatment and showed complete recovery and no recurrences., Conclusions: Although atlantoaxial rotatory fixation is a rare complication, surgeons should consider it in patients with neck problems following microtia reconstruction surgery. A patient with microtia may have unrecognized Klippel-Feil syndrome. Patients with Klippel-Feil syndrome are more likely to develop atlantoaxial rotatory fixation, which may have severe consequences. Thus, it is crucial to preoperatively identify Klippel-Feil syndrome with neck radiography and to detect atlantoaxial rotatory fixation at the earliest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The primary goal of abdominal wall reconstruction is to prevent hernia recurrence through robust and durable repair. Synthetic mesh utilization can provide sound strength but is susceptible to extrusion, infection, and intestinal fistulization. The use of autologous fasciae latae to reinforce the primary fascial reapproximation has mostly been abandoned, presumably because synthetic patches are readily available. There is a specific demand for a sustainable, less-invasive, and ready-to-use repair method without mesh. The authors devised a herniorrhaphy lamination technique using local musculofascial flaps inspired by composite laminates. In this procedure, the primary fascial reapproximation is reinforced with 3 additional laminated musculofascial layers: (1) turnover hinge flaps of the anterior sheath of the rectus abdominis, (2) bilateral rectus abdominis, and (3) advancement flaps of newly generated edges of the fascia of the rectus sheath. Our technique's stability is essentially due to the mechanical superiority of the centralized pipe-like structure of musculofascia. Between February 2009 and November 2019, we used the lamination technique to repair midline incisional hernias in 10 patients. The operative procedure was successful in all patients, and there has been no evidence of recurrence. The follow-up period ranged from 12 to 69 months, with a mean follow-up of 35 months. The herniorrhaphy lamination technique to reinforce the primary repair can help prevent hernia recurrence. Although our technique is suitable for a small-sized defect, it is less invasive, and can be readily applied. Because it does not include any mesh, it is suitable for the contaminated abdominal wall reconstruction., Competing Interests: Disclosure: All the authors have no financial interest in relation to the content of this article., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Purpose: To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD)., Methods: Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. "Close" was defined as the portion within 1 degree from the border of any abnormal FAF, and "Distant" was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects., Results: We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF ("Distant": p<0.001, time2 from baseline: p<0.001, angle: p<0.001). The mean retinal sensitivity of the "Close" tended to deteriorate after the third year and eventually showed the similar sensitivity as the portion within the abnormal FAF., Conclusion: FAF patterns can change about half during the 5 years and the retinal sensitivity near abnormal FAF tends to deteriorate after the third year., Competing Interests: Santen Pharmaceutical Co., Ltd. provided support in the form of honoraria for speaking and/or organizing at meetings [TY, RM, MS, AS, TS, Yuji Oshima, TI, Yuichiro Ogura, TI, FG]. Mayumi Nakamura, Kiyoshi Matsuno, Noriyuki Kuno, and Erika Kimura are (were) employees of Santen Pharmaceutical Co., Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.