A novel lower eyelid reconstruction using a skin-tarsoligamentous sling to prevent postoperative drooping deformity: Quantitative analyses using drooping index and angular difference in canthal tilt.

Lower eyelid reconstruction using skin flaps sometimes results in undesirable deformities due to postoperative flap drooping. We aimed to examine the effectiveness of a novel procedure for reconstructing the skin-tarsoligamentous sling of the lower eyelid. We included 37 patients who underwent anterior lamellar reconstruction with a cheek rotation flap for full-thickness lower eyelid defect. They were divided into two groups: Group A included 19 patients who underwent tarsoligamentous sling reconstruction with a fascia lata strip and buccal mucosa grafting, and Group B comprised 18 patients who underwent skin-tarsoligamentous sling reconstruction using an additional combination of a periosteal flap and de-epithelialized triangular flap at the lateral canthal region, representing our novel approach. To evaluate the severity of postoperative deformities, we used the drooping index, the ratio of drooping compared to the healthy side, along with the angular difference in canthal tilt, obtained between the reconstructed and healthy sides, using photographs taken ≥6 months post-reconstruction. Group B demonstrated superior outcomes, with mean drooping indices of 1.13 compared to 1.33 in Group A (P = 0.031) and mean angular differences in canthal tilt of -0.73° compared to -2.45° in Group A (P = 0.021). Patient satisfaction was significantly higher in Group B than in Group A (P = 0.042). Furthermore, patients with drooping index <1.2 and an angular difference in canthal tilt ≥-1.0° exhibited higher satisfaction scores. Our novel approach to lower eyelid reconstruction using a skin-tarsoligamentous sling yielded improved aesthetic outcomes, fewer complications, and higher patient satisfaction.

Functional outcomes of reconstructive flap surgery for soft tissue sarcoma: Long-term outcomes of functional restoration using innervated muscle transplantation.

Functional outcomes associated with prognostic factors and innervated muscle transplantation after wide soft tissue sarcoma resection remain unclear. We retrospectively examined the functional outcomes of reconstructive flap surgery for soft tissue sarcoma. Twenty patients underwent innervated muscle transplantation with pedicled or free flaps for functional reconstruction of resected muscles. Thirteen latissimus dorsi muscles and one vastus lateralis muscle combined with an anterolateral thigh flap were transferred as free flaps using the epi-perineural suture technique. Six latissimus dorsi muscles were transferred as pedicled flaps with neural continuity. Postoperative functional outcomes were assessed using the Musculoskeletal Tumor Society (MSTS) scores for the upper and lower extremities of 22 and 24 patients, respectively. The mean MSTS score for all patients was 82.3 at 12 months postoperatively. The mean scores for patients who underwent reconstruction with pedicled and free flaps were 89.2 and 77.1, respectively. The MSTS scores for the lower extremity, tumor size ≥5 cm, and free flap reconstruction were significantly lower than those for the upper extremity, tumor size <5 cm, and pedicled flap reconstruction (P = 0.02, 0.37, and 0.008, respectively). The postoperative MSTS score for innervated muscle transplantation was 76.7 at 12 months and was significantly higher (83.7) at 24 months (P = 0.003). Functional outcomes were significantly associated with tumor location, tumor size, and reconstructive flap type based on the MSTS scores. Innervated muscle transplantation improved functional outcomes at 24 months postoperatively via sufficient recovery of the innervated muscle, not the compensatory recovery of the remaining muscle.

"KAIZEN" method realizing implementation of deep-learning models for COVID-19 CT diagnosis in real world hospitals.

Numerous COVID-19 diagnostic imaging Artificial Intelligence (AI) studies exist. However, none of their models were of potential clinical use, primarily owing to methodological defects and the lack of implementation considerations for inference. In this study, all development processes of the deep-learning models are performed based on strict criteria of the "KAIZEN checklist", which is proposed based on previous AI development guidelines to overcome the deficiencies mentioned above. We develop and evaluate two binary-classification deep-learning models to triage COVID-19: a slice model examining a Computed Tomography (CT) slice to find COVID-19 lesions; a series model examining a series of CT images to find an infected patient. We collected 2,400,200 CT slices from twelve emergency centers in Japan. Area Under Curve (AUC) and accuracy were calculated for classification performance. The inference time of the system that includes these two models were measured. For validation data, the slice and series models recognized COVID-19 with AUCs and accuracies of 0.989 and 0.982, 95.9% and 93.0% respectively. For test data, the models' AUCs and accuracies were 0.958 and 0.953, 90.0% and 91.4% respectively. The average inference time per case was 2.83 s. Our deep-learning system realizes accuracy and inference speed high enough for practical use. The systems have already been implemented in four hospitals and eight are under progression. We released an application software and implementation code for free in a highly usable state to allow its use in Japan and globally.

Gut microbial stability in older Japanese populations: insights from the Mykinso cohort.

Gut microbiota imbalance plays an important role in the pathogenesis of various diseases. Here, we determined microbe-microbe interactions and gut microbiome stability in a Japanese population with varying body mass indices (BMIs) and enterotypes. Using 16S ribosomal RNA gene sequencing, we analyzed gut microbial data from fecal samples obtained from 3,365 older Japanese individuals. The individuals were divided into lean, normal, and obese groups based on their BMIs. They were further categorized according to their gut microbiota enterotypes: Bacteroides (enterotype B), Prevotella (enterotype P), and Ruminococcus (enterotype R). We obtained data on different host factors, such as age, BMI, and disease status, using a survey questionnaire evaluated by the Mykinso gut microbiome testing service. Subsequently, we evaluated the co-occurrence network. Individual differences in BMI were associated with differences in co-occurrence networks. By exploring the network topology based on BMI status, we observed that the network density was lower in the lean group than that in the normal group. Furthermore, a simulation-based stability analysis revealed a lower resistance index in the lean group than those in the other two groups. Our results provide insights into various microbe-microbe interactions and gut microbial stability and could aid in developing appropriate therapeutic strategies targeting gut microbiota modulation to manage frailty.

Effect of joint limitation and balance control on gait changes in diabetic peripheral neuropathy.

Aims: This study analyzed the gait patterns of diabetic peripheral neuropathy (DPN) patients and changes in the center of mass sway to prevent the formation and recurrence of foot ulcers. Methods: Forty-two subjects were divided into the diabetes mellitus (DM), DPN, and diabetic foot ulcer (DFU) groups. We measured the range of motion (ROM) of the lower limb joints in the resting position and the center of mass sway in the standing position. Joint angles, ROM during walking, and distance factors were evaluated. Results: In the DFU group, ROM limitation during walking was detected at the knee joint, and functional and ROM limitations were found at the ankle joint. The step length ratio and step width in the DFU group were significantly lower and higher than those in the DM group, respectively. The sway distances in the DFU group were greater than those in the DM and DPN groups. Conclusions: Functional joint limitations and gait changes due to the decreased ability to maintain the center of gravity were observed in the DFU group. As DPN progressed, the patients' gait became small, wide, and shuffled. Thus, supporting joint movement during walking may help reduce the incidence and recurrence of foot ulcers. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00647-9.

Protective effect of ebselen on bleomycin-induced lung fibrosis: analysis of the molecular mechanism of lung fibrosis mediated by oxidized diacylglycerol.

The molecular mechanisms underlying the development of pulmonary fibrosis remain unknown, and effective treatments have not yet been developed. It has been shown that oxidative stress is involved in lung fibrosis. Oxidized diacylglycerol (DAG) produced by oxidative stress is thought to play an important role in lung fibrosis. This study assessed the effect of oxidized DAG in an animal model of pulmonary fibrosis induced by aspiration of bleomycin (BLM) into the lungs. The inhibitory effect of ebselen on pulmonary fibrosis was also investigated. In lung fibrotic tissue induced by BLM, an increase in lipid peroxides and collagen accumulation was observed. Moreover, the levels of oxidized DAG, which has strong protein kinase C (PKC) activation activity, were significantly increased over time following the administration of BLM. Western blotting showed that phosphorylation of PKCα and δ isoforms was increased by BLM. Oral administration of ebselen significantly suppressed the increase in oxidized DAG induced by BLM and improved lung fibrosis. PKCα and δ phosphorylation were also significantly inhibited. The mRNA expression of α-smooth muscle actin and collagen I (marker molecules for fibrosis), as well as the production of transforming growth factor-ß and tumor necrosis factor-α(a potentially important factor in the fibrotic process), were increased by BLM and significantly decreased by ebselen. The administration of BLM may induce lipid peroxidation in lung tissue, while the oxidized DAG produced by BLM may induce overactivation of PKCα and δ, resulting in the induction of lung fibrosis.

Possible Glutathione Peroxidase 4-Independent Reduction of Phosphatidylcholine Hydroperoxide: Its Relevance to Ferroptosis.

Ferroptosis is mainly caused by iron-mediated peroxidation of phospholipids and has recently attracted attention due to its involvement in various diseases. At the center of it is supposedly the inability of glutathione peroxidase 4 (GPX4) to reduce excess peroxidized phospholipids (e.g., phosphatidylcholine hydroperoxide (PCOOH)) that trigger ferroptosis. However, the involvement of enzymes other than GPX4 in ferroptosis is scarcely known. To elucidate this matter, we evaluated the uptake of PCOOH in a GPX4 knockout (KO) human hepatoma cell line HepG2 generated using CRISPR-Cas9. After confirming that GPX4 expression in the KO cells was below the detection limit, we cultured both wild-type (WT) and GPX4 KO HepG2 cells in a medium containing 50 µM PCOOH for 1-8 hours. By analyzing the level of PCOOH and its reduction product (phosphatidylcholine hydroxide, PCOH) in cells using liquid chromatography-tandem mass spectrometry, we detected the cellular uptake of PCOOH. On top of this, we detected a large amount of PCOH not only in WT HepG2 but also in GPX4 KO HepG2, thus indicating the notable involvement of enzymes other than GPX4 (e.g., other GPX family, glutathione S-transferase, thioredoxin, or peroxiredoxin) in reducing PCOOH. Further corroboration of these findings hopefully leads to the development of novel methods to prevent ferroptosis-related diseases by targeting enzymes other than GPX4.

Relationship between fluctuations in skin perfusion pressure values and wound healing in patients with chronic limb-threatening ischemia undergoing hemodialysis.

Background : Patients with chronic limb-threatening ischemia are often on hemodialysis. It is unclear which skin perfusion pressure (SPP) values, i.e., those measured immediately after hemodialysis on a hemodialysis day or those measured on a non-hemodialysis day, reflect the actual wound healing course in chronic limb-threatening ischemia. Methods : Eighteen patients undergoing hemodialysis (49 measurements) who were treated for leg ulcers due to critical limb ischemia were included in the study. The SPP values were divided into two groups : those measured immediately after hemodialysis (HD day group) and those measured on non-hemodialysis days (non-HD day group). The wound healing outcomes were investigated. The cutoff SPP value for predicting wound healing was set to ≥ 35 mmHg. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SPP in each group were measured. The relationship between SPP and blood pressure was analyzed by regression analysis. Results : Significant differences were observed in the positive predictive value (HD day : 100%, non-HD day : 50% ; P = 0.002), The correlation coefficient was 0.698 in the HD day group and 0.292 in the non-HD day group. Diastolic blood pressure had a significant effect on SPP (P = 0.039). Conclusions : The measurements are best taken immediately after hemodialysis for more accuracy. J. Med. Invest. 69 : 294-298, August, 2022.

Radiographic Study Evaluating Perforator Vessels in the Ischiorectal Fossa for Safe Elevation of Island Flaps.

Perforator flaps based on the ischiorectal fossa (IRF) (ie, internal pudendal artery perforator flaps) are useful for perineal reconstruction. The three-dimensional characterization of perforator arteries in the IRF remains unclear, as the IRF contains thick adipose tissue as well as organs, such as the rectum, vagina, and urethra. This study aimed to evaluate perforators in the IRF to guide the safe elevation of skin flaps designed based on the IRF. Methods: IRF vessels were examined in 200 bilateral computed tomography angiography scans performed in 100 patients. We examined branching patterns arising from the internal iliac artery and the origins of the skin perforators in the IRF. Results: The branching patterns of the internal iliac artery were divided into three groups: perforators derived exclusively from the internal pudendal artery (78%), perforators derived from the internal pudendal artery and the inferior gluteal artery (18%), and perforators derived exclusively from the inferior gluteal artery (4%). The average number of perforators in the IRF was 1.5 ± 0.7. The number of perforators was significantly higher in women than in men. The perforator arteries were found exclusively around the medial and dorsal sides of the ischial tuberosity. Conclusions: We found that perforators in the IRF were stable. All cases had more than one skin perforator, which was mainly derived from the internal pudendal artery. Although perforators cannot be identified during flap elevation because the fatty tissue in the IRF is very thick, physicians must focus on preserving the perforator-containing fatty tissue around the ischial tuberosity.

Average gut flora in healthy Japanese subjects stratified by age and body mass index.

Imbalance of the gut microbiota plays an important role in the pathogenesis of various diseases. Although many clinical studies have analyzed the gut microbiota, the definition of normal gut microbiota remains unclear. In this study, we aim to establish the average gut microbiota in the healthy Japanese population. Using 16S ribosomal RNA gene sequencing, we analyzed gut microbial data from fecal samples obtained from 6,101 healthy Japanese individuals. Based on their ages, the individuals were divided into three groups: young, middle-age, and old. Individuals were further categorized according to body mass index (BMI) into lean, normal, and obese groups. The α and ß diversities in the old group were significantly higher than those in the young and middle-age groups. The Firmicutes/Bacteroidetes ratio of subjects in the obese category was significantly lower compared with those of subjects in the lean and normal categories in the young and middle-age groups. Genus Bacteroides was the dominant gut microbiota across all the BMI categories in all the age groups. Among the top ten genera, the abundances of Bacteroides, Bifidobacterium, Anaerostipes, Blautia, Dorea, Fusicatenibacter, Lachnoclostridium, and Parabacteroides were significantly lower in the old group than in the young and middle-age groups. The correlation network at the genus level revealed different microbe-microbe interactions associated with age and BMI. We determined the average Japanese gut microbiota, and this information could be used as a reference. The gut microbiota greatly differs based on the life stage and metabolic status of the host, and this gives rise to a variety of host-gut microbe interactions that can lead to an increased susceptibility to disease.

Immunohistochemical features of canine ovarian papillary adenocarcinoma and utility of cell block technique for detecting neoplastic cells in body cavity effusions.

Dogs with ovarian papillary adenocarcinoma occasionally present with ascites and/or pleural effusion. These aspirated fluids often contain a large number of cells, and distinction between neoplastic cells and activated mesothelial cells can be difficult. In this study, 7 cases of canine ovarian papillary adenocarcinoma, including 3 with ascites and pleural effusion, were immunohistochemically examined. Ovarian tumor cells were positive for cytokeratin CAM5.2 (CAM5.2), Wilms' tumor 1 (WT-1) and progesterone receptor (PR) in all 7 cases. A metastatic lesion of the mediastinum in one case was also positive for CAM5.2, WT-1 and PR. Immunohistochemistry on cell blocks obtained from ascites and/or pleural effusion of 2 cases revealed the presence of PR-positive epithelial cells. Whereas, activated mesothelial cells in ascites or pleural effusion collected from dogs without neoplastic lesions were negative for PR. In addition, surface epithelium and subsurface epithelial structures (SES) of normal canine ovaries, that are considered to be the cell of origin for ovarian papillary adenocarcinoma, were also positive for CAM5.2, WT-1 and PR. These results indicate that, together with CAM5.2, WT-1 and PR is a useful diagnostic marker for canine ovarian papillary adenocarcinoma. Expression of PR may be associated with progesterone-dependent nature of canine ovarian papillary adenocarcinoma.

Major intraoperative bleeding and drastic change in circulatory dynamics in a pregnant patient with metastatic pheochromocytoma: a case report.

BACKGROUND: Metastatic pheochromocytoma in the spine is a very rare complication during pregnancy. We report anesthesia in a pregnant woman for resection of an undiagnosed spinal tumor, accompanied by remarkable hemodynamic changes and massive bleeding. CASE PRESENTATION: A 33-year-old woman at 17 weeks of gestation presented with the rapid progress of bilateral lower leg paralysis. A diagnosis of spinal tumor was made, and surgical resection was planned. Although the surgery was suspended because of remarkable hemodynamic changes and massive bleeding, fetal heart rate was stable. Postoperative examination revealed pheochromocytoma in the urinary bladder as a primary lesion with spinal metastasis. CONCLUSION: Although spinal pheochromocytoma is extremely rare in pregnant women, it should be suspected when abnormal hypertension is observed with accompanying neurological deficits. Preservation of maternal circulation and uteroplacental blood flow should be the first priority during anesthesia.

Lateral Nasal Artery Perforator Flap for Nasal Reconstruction: Clinical Applications and Risk Factors Associated With Nasal Deformities.

BACKGROUND: Nasal reconstruction is challenging because of the difficulty in balancing superior aesthetic outcomes and less invasive surgery. The use of the lateral nasal artery (LNA) perforator flap has been reported for nasal reconstruction. However, few reports have described appropriate applications of nasal reconstruction and assessments of nasal deformity. This study aimed to quantify the aesthetic outcomes on using this flap and reveal the risk factors associated with nasal deformities. METHODS: Twenty patients underwent nasal reconstruction using the LNA flap with a cranial perforator adjacent to the nasal defect. Postoperative protuberant deformities were scored by 2 independent plastic surgeons using a 5-point Likert scale and classified as excellent, good, or poor. The risk factors of deformities were identified using univariate analyses. A nasal alar deviation index was developed to analyze correlations with flap harvesting. The sensory function was assessed by the Semmes-Weinstein test. RESULTS: Flaps survived in 19 patients (95%), and 1 flap showed distal necrosis. All arterial perforators used remained within 5 mm lateral to the boundary between the cheek and nasal ala. The flaps were most often used to cover 2 subunits, including the nasal sidewall defects. Protuberant deformities in 6 (30%), 8 (40%), and 6 (30%) patients were classified as excellent, good, and poor, respectively. Nasal defects involving more than 3 subunits caused severe protuberant deformity. Only 2 patients (5%) in the good and fair groups underwent additional debulking surgery. Nasal alar deviation was not significantly correlated with flap harvesting, when the nasal alar deviation index before and after surgery were compared. Sensory function was retained in all patients. CONCLUSIONS: Aesthetic outcomes and sensory function were good on using the LNA perforator flap as a propeller flap having a wide arc of rotation. This flap is suitable for nasal reconstruction involving less than 2 nasal subunits without any severe nasal alar deviation deformity. In addition, this flap allows for better outcomes because it requires less invasive 1-stage surgery.

Effects of Polymorphisms in the Serotonin Transporter Promoter-Linked Polymorphic Region on Postthoracotomy Pain Severity.

PURPOSE: Serotonin (5-HT) is highly associated with pain modulation. The human 5-HT transporter (5-HTT) gene (SLC6A4) features several polymorphisms in its promoter region (5-HTTLPR) that affect the 5-HTT expression. The S allele of 5-HTTLPR induces low 5-HT tone, and it may influence the modulation of chronic pain. Meanwhile, pain occurs in 40-50% of patients after thoracic surgery, and its mechanism remains under investigation. This study assessed the role of 5-HTTLPR polymorphisms in postthoracotomy pain severity. PATIENTS AND METHODS: A total of 178 patients undergoing pneumonectomy were enrolled. The genotypes of 5-HTTLPR were divided into two groups: S/S group and S/L or L/L group. Linear mixed-effects models were used to assess the association between 5-HTTLPR genotypes and the numerical rating scale (NRS) score change over time. RESULTS: Among the participants, data were obtained for 162 patients. The genotype distribution was as follows: S/S, 67.3%; S/L or L/L, 32.7%. No significant difference in patient characteristics was found between the genotype groups. There was no significant interaction between the 5-HTTLPR genotypes and the NRS score change over time (p = 0.842). CONCLUSION: Polymorphisms in 5-HTTLPR were not associated with postthoracotomy pain severity.

Analysis of clinical factors and reasons that influence the disposition of cryopreserved embryos in Japanese patients with infertility treated in our clinic.

AIM: To investigate the clinical factors and factors that affect the decisions regarding storage of cryopreserved embryos obtained using assisted reproductive technology. METHODS: Clinical characteristics affecting the decisions regarding cryopreserved embryos were analyzed in 5724 Japanese couples who underwent in vitro fertilization (IVF) or intra-cytoplasmic sperm insemination (ICSI) and embryo transfer over 4 years since April 2015 at our clinic. Statistical analysis was carried out using JMP software. RESULTS: The number of oocytes retrievals and embryos stored, outcomes and number of children, and age of the female patients and male partners were related to the decision-making regarding cryopreserved embryos. Childbearing and no wish for another child were the major reasons for discontinuing embryo storage. The number of oocytes retrievals and embryos in storage, age of the female patients, and sex of the child were independently associated with this decision-making in 2682 patients with a single child. Women with male children were more likely to choose discontinuation of embryo storage than those with female children. CONCLUSION: Already having a child and not wishing for further treatment due to age along with the presence of a male child affect the decision to continue or discontinue embryo storage in Japanese patients with infertility.

Synovial sarcoma cell lines showed reduced DNA repair activity and sensitivity to a PARP inhibitor.

Synovial sarcoma is a soft-tissue sarcoma and a rare type of cancer. Unfortunately, effective chemotherapies for synovial sarcomas have not been established. In this report, we show that synovial sarcoma cell lines have reduced repair activity for DNA damage induced by ionizing radiation (IR) and a topoisomerase II inhibitor (etoposide). We also observed reduced recruitment of RAD51 homologue (S. cerevisiae; RAD51) at sites of double-strand breaks (DSBs) in synovial sarcoma cell lines that had been exposed to IR. These findings showed that synovial sarcoma cell lines are defective in homologous recombination (HR) repair. Furthermore, we found that a poly-(ADP-ribose) polymerase (PARP) inhibitor (AZD2281; olaparib) effectively reduced the growth of synovial sarcoma cell lines in the presence of an alkylating agent (temozolomide). Our findings offer evidence that treatment combining a PARP inhibitor and an alkylating agent could have therapeutic benefits in the treatment of synovial sarcoma.