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A 54-year-old woman presented with an anterior neck subcutaneous tumor that had appeared one month prior. Mild tenderness was noted. As a diagnosis was difficult to make based on physical examination and ultrasonography, a magnetic resonance imaging (MRI) scan was performed. Both examinations revealed a 1-cm subcutaneous mass with well-defined margins; the MRI scan was hypointense on T1-weighted images and slightly hyperintense with low point foci on T2-weighted images. Subsequently, an excisional biopsy was performed, and the pathologic diagnosis of glomus tumor was obtained. Glomus tumors usually present as a painful subcutaneous mass beneath the nail bed but may be painless or occur in areas other than the fingers. Because glomus tumors in the neck resemble a variety of diseases, their diagnosis may be delayed. This case highlights the importance of considering glomus tumors as a potential cause of neck subcutaneous tumors.

Abstract Background Platelet-rich plasma (PRP), which is prepared by concentrating platelets in autologous blood, shows efficacy in chronic skin wounds via multiple growth factors. However, it exhibits heterogeneity across patients, leading to unstable therapeutic efficacy. Human induced pluripotent stem cell (iPSC)-derived megakaryocytes and platelets (iMPs) are capable of providing a stable supply, holding promise as materials for novel platelet concentrate-based therapies. In this context, we evaluated the effect of iMPs on wound healing and validated lyophilization for clinical applications. Methods The growth factors released by activated iMPs were measured. The effect of the administration of iMPs on human fibroblasts and human umbilical vein endothelial cells (HUVECs) was investigated in vitro. iMPs were applied to dorsal skin defects of diabetic mice to assess the wound closure rate and quantify collagen deposition and angiogenesis. Following the storage of freeze-dried iMPs (FD-iMPs) for three months, the stability of growth factors and their efficacy in animal models were determined. Result Multiple growth factors that promote wound healing were detected in activated iMPs. iMPs specifically released FGF2 and exhibited a superior enhancement of HUVEC proliferation compared to PRP. Moreover, an RNA-seq analysis revealed that iMPs induce polarization to stalk cells and enhance ANGPTL4 gene expression in HUVECs. Animal studies demonstrated that iMPs promoted wound closure and angiogenesis in chronic wounds caused by diabetes. We also confirmed the long-term stability of growth factors in FD-iMPs and their comparable effects to those of original iMPs in the animal model. Conclusion Our study demonstrates that iMPs promote angiogenesis and wound healing through the activation of vascular endothelial cells. iMPs exhibited more effectiveness than PRP, an effect attributed to the exclusive presence of specific factors including FGF2. Lyophilization enabled the long-term maintenance of the composition of the growth factors and efficacy of the iMPs, therefore contributing to stable supply for clinical application. These findings suggest that iMPs provide a novel treatment for chronic wounds.

Objectives: Submucous cleft palate is a congenital disorder resulting in velopharyngeal insufficiency. Nasal regurgitation is one of the symptoms of submucous cleft palate. This study aims to investigate a relationship between submucous cleft palate and a history of nasal regurgitation in patients during infancy. Methods: This retrospective study includes patients diagnosed with submucous cleft palate at our hospital for 20 years, from 1998 to 2017. Based on the clinical records of these patients, we investigated sex, age at referral to our facility, age at surgery, presence of nasal regurgitation, method of surgery, association of syndromes and mental retardation, and transition of velopharyngeal function. Results: There were fifty-seven patients referred to our facility. Patients with episodes of nasal regurgitation were referred to clinics later than those without nasal regurgitation. The timing of surgery was also the same. The velopharyngeal function of patients with nasal regurgitation was worse than that of those without nasal regurgitation. Conclusions: A history of nasal regurgitation cannot predict submucous cleft palate. However, patients with submucous cleft palate with nasal regurgitation had worse velopharyngeal function than those without nasal regurgitation. An increased understanding of the relationship between submucous cleft palate and nasal regurgitation and further study will predict submucous cleft palate and determine a good timing for surgical interventions.

Summary:. Acrodysostosis, a rare congenital syndrome, is characterized by peripheral dysostosis, nasal hypoplasia, mental retardation, and other skeletal deformities. Although severe saddle nose associated with midfacial hypoplasia causes great distress to patients, no studies have reported conducting rhinoplasty. In our experience, we suspected a boy with a significant saddle nose as having acrodysostosis and conducted genetic testing on the boy and his parents. Genetic analyses revealed that the patient had a deleterious mutation in the PDE4D gene that was not seen in either of his parents. Thus, the patient was diagnosed with de novo acrodysostosis. Rhinoplasty of the saddle nose using autogenous costal cartilage was planned; however, a major concern in using costal cartilage is the distortion caused by warping. To prevent this problem, a counterbalancing technique was used. After the surgery, no warping was observed during follow-up, and the patient and his family were satisfied with the outcomes. To our knowledge, we present the first case of surgical treatment of a patient with a saddle nose caused by acrodysostosis.

Summary:. “COVID toe,” one of the extrapulmonary disorders of coronavirus disease 2019 (COVID-19), may result in toe necrosis. In this case, we successfully reconstructed a severe COVID-19-induced defect in the great toe by using an innervated hemi-pulp V-Y advancement flap. A 48-year-old woman was diagnosed with fulminant myocarditis due to COVID-19 and received intensive care. Even after the acute phase, a skin defect measuring 10 mm × 7 mm was noted, exposing the underlying bone on her right great toe tip. Because of ulceration, she was unable to start walking training. To continue rehabilitation, we reconstructed it with the innerved hemi-pulp V-Y advancement flap. The pain improved quickly, and rehabilitation was resumed. During the 6-month follow-up period, no cosmetic or functional complications were observed. Plantar pressure measurements demonstrated favorable loading on the great toe, and it was a favorable outcome in walking function. This flap is a valuable option as one of the innervated flaps for toe-end necrosis with preserved blood flow, which helps in implementing prompt gait rehabilitation.

Abstract Lower extremity lymphedema (LEL) is a common complication after gynecological cancer treatment, which significantly reduces the quality of life. While early diagnosis and intervention can prevent severe complications, there is currently no consensus on the optimal screening strategy for postoperative LEL. In this study, we developed a computer-aided diagnosis (CAD) software for LEL screening in pelvic computed tomography (CT) images using deep learning. A total of 431 pelvic CT scans from 154 gynecological cancer patients were used for this study. We employed ResNet-18, ResNet-34, and ResNet-50 models as the convolutional neural network (CNN) architecture. The input image for the CNN model used a single CT image at the greater trochanter level. Fat-enhanced images were created and used as input to improve classification performance. Receiver operating characteristic analysis was used to evaluate our method. The ResNet-34 model with fat-enhanced images achieved the highest area under the curve of 0.967 and an accuracy of 92.9%. Our CAD software enables LEL diagnosis from a single CT image, demonstrating the feasibility of LEL screening only on CT images after gynecologic cancer treatment. To increase the usefulness of our CAD software, we plan to validate it using external datasets.

A human tail complicated by Crouzon syndrome is extremely rare, with only eight reported cases of human tails associated with Crouzon syndrome. A human tail is defined as a true human tail or a pseudo-human tail according to the presence or absence of the bone tissue. A 4-year-old boy had a true caudal sacral protrusion from birth and was also diagnosed with Crouzon syndrome. There were no neurological symptoms or vesico-rectal disturbances. The patient underwent a human tail resection at 4 years and 7 months. The postoperative course was uneventful, and there was no recurrence at 6 months postoperatively. Some reports suggested that Crouzon syndrome and the human tail are associated with FGFR2 gene mutation, but the details are currently unknown. Further genetic searches for cases of the combined human tail and Crouzon syndrome in the future are likely to reveal further associations.

Summary:. A 59-year-old man with right maxillary cancer presented with a right buccal fistula and an ectropion of the lower eyelid after multidisciplinary treatment. With no suitable vessels in the right face or neck for anastomosis, we planned reconstruction with a free thinned deep inferior epigastric artery perforator flap using the contralateral left facial artery and vein as the recipient. To simulate the length of the vascular pedicle, we used our original software and determined to use the route passing through the nasal cavity. The vascular pedicle was passed through a tunnel from the medial wall of the right maxillary sinus, through the nasal septum and the medial-frontal wall of the left maxillary sinus, to the left facial artery and vein. The flap survived completely, and facial deformity was corrected. At 1 year postoperatively, there had been concerns about the fragility of the vascular pedicle in the nasal cavity and the possibility of easy bleeding. Endoscopic examination revealed that the vascular pedicle in the nasal cavity was covered by fibrous tissue and multirow lineage epithelium, and an excisional biopsy indicated a low possibility of hemorrhage. Cutting off the vascular pedicle to prevent bleeding may not be necessary because the vascular pedicle through the nasal cavity becomes fibrotic and epithelialized in the surrounding area in the long term.

Summary:. It is believed that skin flaps should not be used to reconstruct large scrotal defects because thick flaps increase testicular temperature and decrease fertility, and those skin grafts should be used to reconstruct large scrotal defects. We report a case of extensive scrotal defect reconstructed with bilateral superficial circumflex iliac perforator (SCIP) flaps in which spermatogenesis improved postoperatively over time. A 44-year-old man underwent reconstruction of an extensive scrotal defect caused by Fournier gangrene, and bilateral SCIP flaps were used for the reconstruction. In the third postoperative month, his semen volume and sperm count after centrifugation were 1.5 mL and eight, respectively. Based on these semen findings, fertility specialists diagnosed the patient with extremely low fertility. In the ninth postoperative month, the semen volume was 2.2 mL, sperm density was 2.7 × 106/mL, sperm motility was 64%, and normal sperm morphology was 54%, indicating significant improvement. Based on the sperm findings, fertility specialists considered the patient capable of causing pregnancy. There have been no reports of preservation of spermatogenesis after scrotal reconstruction with a thinned perforator flap. In the postoperative period, we observed improvement of spermatogenesis, which suggests that scrotal reconstruction with an SCIP flap may be effective for improving both cosmetic appearance and fertility.

Background: Familial lecithin: cholesterol acyltransferase (LCAT) deficiency (FLD) is a severe inherited disease without effective treatment. Patients with FLD develop severe low HDL, corneal opacity, hemolytic anemia, and renal injury. Objective: We developed genetically modified adipocytes (GMAC) secreting LCAT (LCAT-GMAC) for ex vivo gene therapy. GMACs were prepared from the patient’s adipocytes to express LCAT by retroviral gene transduction to secrete functional enzymes. This study aimed to evaluate the safety and efficacy of LCAT-GMAC implantation in an FLD patient. Methods: Proliferative preadipocytes were obtained from a patient using a ceiling culture and retrovirally transduced with LCAT. After obtaining enough cells by expansion culture of the transduced cells, the resulting LCAT-GMACs were implanted into a patient with FLD. To evaluate the safety and efficacy, we analyzed the outcome of the autologous implantation for 24 weeks of observation and subsequent 240 weeks of the follow-up periods. Results: This first-in-human autologous implantation of LCAT-GMACs was shown to be safe by evaluating adverse events. The LCAT-GMAC implantation increased serum LCAT activity by approximately 50% of the baseline and sustained over three years. Consistent with increased LCAT activity, intermediate-density lipoprotein (IDL) and free cholesterol levels of the small and very small HDL fractions decreased. We found the hemoglobin/haptoglobin complex in the hemolyzed pre-implantation sera of the patient. After one week of the implantation, the hemoglobin/haptoglobin complex almost disappeared. Immediately after the implantation, the patient's proteinuria decreased temporarily to mild levels and gradually increased to the baseline. At 48 weeks after implantation, the patient's proteinuria deteriorated with the development of mild hypertension. By the treatment with antihypertensives, the patient's blood pressure normalized. With the normalization of blood pressure, the proteinuria rapidly decreased to mild proteinuria levels. Conclusions: LCAT-GMAC implantation in a patient with FLD is shown to be safe and appears to be effective, in part, for treating anemia and proteinuria in FLD.

Backgrounds: Despite the absolute need for life-long treatment of inherited and genetic diseases, there has been little effort to develop such treatments for most of these conditions due to their rarity. Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is recognized as one such orphan disease. We have been developing an adipocyte-based ex vivo gene therapy/regenerative medicine, a novel methodology that differs from the adeno-associated virus-mediated in vivo gene therapy or ex vivo gene-transduced hematopoietic cell therapy, to treat familial LCAT deficiency. Recently, a first-in-human (FIH) clinical study was conducted under the Act on Securement of Safety of Regenerative Medicine, wherein a patient with familial LCAT deficiency was treated. To obtain approval to put this treatment into practical use, a clinical trial has been designed with reference to the FIH clinical study. Methods: An interventional, open-label, unblinded dose-escalation trial was planned, referring to previous FIH clinical study. The trial aims to evaluate the safety of the investigational product in relation to the characteristics of the investigational product (ex vivo gene/cell therapy product by retroviral vector-mediated LCAT gene transduction) using two doses, and the efficacy of the treatment will be evaluated exploratively. A total of three patients will be enrolled sequentially and followed for 24 weeks after administration. This study is designed as a multicenter trial, with Chiba University Hospital administering and evaluating the safety/efficacy of the investigational products at the prescribed visit. Conclusion: This clinical trial is expected to facilitate the provision of lifelong treatment to many patients with LCAT deficiency. Trial registration number: Japan Registry of Clinical Trials (jRCT2033200096).

Abstract Background Pressure sores are sometimes refractory to treatment, often due to malnutrition. Small intestinal bacterial overgrowth (SIBO) obstructs absorption in the digestive tract and causes malnutrition. However, little is known about the association between pressure sore wound healing and SIBO. Here, we report a case of a patient with a refractory sacral pressure sore and SIBO. Case presentation A 66-year-old woman who was spinal cord injured 14 years before visiting our hospital presented with the chief complaint of a sacral pressure sore, 10.0 × 6.5 cm in size, which was refractory to treatment. Physical examination showed abdominal distension and emaciation, with a body mass index of 15. Further examination revealed elevated serum alkaline phosphatase (1260 U/L), bilateral tibial fracture, multiple rib fracture, and osteoporosis. We diagnosed the patient with osteomalacia with vitamin D deficiency. Despite oral supplementation, serum levels of calcium, phosphorous, and vitamin D remained low. Also, despite concentrative wound therapy for the sacral pressure sore by plastic surgeons, no wound healing was achieved. Due to a suspicion of disturbances in nutrient absorption, we performed bacterial examination of collected gastric and duodenal fluid, which showed high numbers of bacteria in gastric content (104 E. coli, 105 Streptococcus species, and 105 Neisseria species) and duodenal content (106 E. coli, 104 Candida glabrata). Therefore, we diagnosed the patient with SIBO and started selective decontamination of the digestive tract using polymyxin B sulfate and amphotericin B. After starting treatment for SIBO, the sacral pressure sore began to heal and was nearly healed after 285 days. The patient’s serum levels of calcium, phosphorous, vitamin D, and other fat-soluble vitamins also gradually increased after starting treatment for SIBO. Conclusion We report a case of a patient with a refractory sacral pressure sore that healed after starting treatment for SIBO. We conclude that SIBO may be an overlooked cause of malnutrition and poor wound healing in patients with chronic pressure sores.

Background:. Although the functional and anatomical differences between the left and right eyelids are important in the evaluation of age-related changes in the eyelids, they have not been described clearly as indications for surgical treatments. This study aimed to investigate how laterality of the eyelids affects evaluation of age-related changes. Methods:. Photographs of either one or both eyelids of 100 people were evaluated in four stages by 10 plastic surgeons. To investigate the consistency of the results between evaluations, surgeons evaluated the single-eyelid photographs (group U) or two-eyelid photographs (group B). It was investigated whether the difference in margin reflex distance 1, height of the upper eyelid crease, height of eyebrow, and levator contractile function were associated with mismatched evaluations. Results:. The weighted kappa coefficient for groups B and U was 0.77 (substantial agreement). One-point difference in scores was observed in 23 cases. In the multiple logistic regression analysis, only the laterality the height of the eyelid crease was significantly different between patients whose evaluations were matched and those whose evaluations were mismatched (0.9 ± 0.1 mm versus 1.7 ± 0.2 mm; OR = 1.06, 95%CI: 1.01–1.10; P = 0.01). Conclusions:. Besides the structure and function of each eyelid, the laterality of the height of the eyelid crease was important in the evaluation of the age-related changes in the eyelids. This factor may be important in evaluating the aesthetic and visual impressions of age-related changes in the eyelids.

Summary:. Axiality of lymphatic flow is possibly an important consideration for stimulating recanalization of flow between the transferred flap and the recipient site during wound healing. Antegrade lymphatic flow reconstruction has previously been reported. Here we report the first case where lymph stasis following groin lymph nodes dissection could be recanalized in a pedicled anterolateral thigh flap in which the collecting lymphatics were arranged retrograde. A 78-year-old male patient presented with bilateral lower extremity lymphedema and bilateral inguinal skin ulcers with lymphorrhea. He had been treated for rectal cancer by low-anterior resection, lymph nodes dissection, colostomy, and subsequent heavy particle radiotherapy for a local recurrence involving pelvic lymph nodes. We planned a reconstruction using a pedicled anterolateral thigh flap that included retrograde collecting lymphatic vessels, with the flap rotated as a propeller flap. The flap successfully survived and clinical symptoms of edema in both lower limbs improved during the short postoperative course. Although the collecting lymphatic vessels within the flap were arranged retrograde to the direction of the anatomical lymphatic flow at the recipient site, linear lymphatic flow consistent with the transferred flap was confirmed by lymphoscintigraphy. This case shows that the lymphatic flow may recanalize after tissue transplantation, even if the collecting lymphatic vessels in the flap are arranged retrograde to the direction of lymphatic flow.

Summary:. Blepharoplasty for thyroid eye disease (TED) has been indicated for the purpose of improving upper and lower eyelid retraction caused by exophthalmos. Both aponeurotic blepharoptosis and aging lower eyelid are common conditions that require plastic surgeries and could be complicated with other disease conditions, such as TED. This is the first report of planned and staged treatment of the contradictory pathophysiologies of aging changes of upper and lower eyelids associated with TED. A 59-year-old woman suffered complicated bilateral asymmetric aponeurosis blepharoptosis of the lower and upper eyelids, caused by both advanced aging and TED. To achieve aesthetic improvement, three-stage surgical treatments were planned, as follows: (1) Orbital decompression for exophthalmos; (2) Extraocular muscle surgery, if necessary; (3) Blepharoplasty for functional and aesthetic abnormalities due to loosening of the upper and lower eyelids. After medial and lateral orbital floors were opened bilaterally, the patient did not need extraocular surgery. As the final step, levator aponeurosis advancement procedure was performed in the upper eyelids for bilateral asymmetrical aponeurotic blepharoptosis, and transitional lower blepharoplasty using a skin-muscle flap technique via a sub-ciliary incision was performed in the lower eyelids for age-related loosening. The typical face displayed by Graves’ disease disappeared, and the symptoms associated with loosening of the upper and lower eyelids improved substantially. Improvement of exophthalmos by orbital decompression revealed the severity of the blepharoptosis and the aging change of lower eyelid. Step-by-step planning from decompression surgery to upper and lower blepharoplasty could lead to sufficient improvement in the facial appearance in TED.

Abstract Background Shingles (localized zoster) and disseminated zoster are caused by the reactivation of latent varicella zoster virus (VZV). Reactivation of VZV is related to impaired cell-mediated immunity. Extensive burns affecting a patient result in burn-related immunosuppression and cytokine storm. Despite immunosuppression in burn patients, the reactivation of VZV is extremely rare, whereas eczema herpeticum, caused by reactivation of latent herpes simplex virus (HSV), is common. We have found only 1 published case of VZV reactivation during burn treatment in the literature. Case presentation A 51-year-old man was burned in a fire, which affected 60% of his total body surface area (TBSA), and also received inhalation injury (day 0). Despite fluid resuscitation, he showed persistent renal failure. Continuous hemodialysis and filtration (CHDF) combined with polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) therapy was used for cytokine modulation. Autologous and allogeneic skin grafting was performed. On day 15, multiple-drug-resistant Pseudomonas aeruginosa (MDRP) was detected from a blood specimen, and the patient developed multiple organ failure (MOF). On day 31, compact aggregations of small vesicles appeared on the intact skin of his left knee and left buttock. The vesicles were located within the 4th lumbar (L4) spinal dermatome. From day 32 to day 34, similar new vesicles arose on his intact skin and epithelializing skin-graft donor sites. We diagnosed disseminated zoster, based on the patient’s age, the characteristic occurrence of the initial vesicles within a limited area of intact skin in the left L4 dermatome, and a positive Tzank smear. Serologic testing on day 36 showed a high level of anti-VZV immunoglobulin (Ig)G with low levels of anti-VZV IgM, anti-HSV IgG, and anti-HSV IgM. The patient was isolated in a negative-pressure room to avoid air-borne spread of VZV. On day 52, the patient died. Conclusions To the best of our knowledge, our patient is the second case of reactivation of VZV during burn treatment. It is unclear why reactivation of VZV is rare in patients with burn-related immunosuppression, whereas HSV reactivation is common. Cytokine modulation throughout the treatment period using CHDF combined with PMX-DHP might have been related to the rare reactivation of VZV in our patient. Our case provides an additional information on the relationship between the immune status of a patient with extensive burns and reactivation of latent VZV or HSV.

Introduction: Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery. Methods and analysis: This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy—one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA. Ethics and dissemination: The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020. Trial registration number: jRCT2031190064; Pre-results.