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Abstract Background Very large chest wall resections can lead to acute thoracic insufficiency syndrome due to the interdependence of lung expansion and thoracic volume. Chest wall tumor surgeries often encounter complications, with the size of the chest wall defect being a significant predictor. Several methods for large chest wall reconstruction have been described, aiming to provide stability, prevent flail chest, and ensure airtight closure. However, no single method fulfills all requirements. Composite chest wall reconstruction using titanium plates and Gore-Tex patches has shown the potential to minimize physiologic abnormalities caused by extensive defects. Case presentation A 42-year-old man with myxofibrosarcoma underwent multiple surgeries, chemotherapies, and radiation therapies due to repeated local recurrences. After right arm amputation and resection of the right third to fifth ribs, a local recurrence was detected. A 30 × 40 cm chest wall defect was resected en bloc, and a titanium plate was used for three-dimensional formability, preventing flail chest and volume loss. The Gore-Tex patch was then reconstructed into an arch shape, allowing lateral thoracic mobility. The patient recovered well and did not experience respiratory dysfunction or local recurrence but later succumbed to distant metastasis. Conclusions In this case, the combination of a titanium plate and a Gore-Tex patch proved effective for reconstructing massive lateral chest wall defects. The approach provided stability, preserved thoracic volume, and allowed for lateral mobility. While the patient achieved a successful outcome in terms of local recurrence and respiratory function, distant metastasis remained a challenge for myxofibrosarcoma patients, and its impact on long-term prognosis requires further investigation. Nevertheless, the described procedure offers promise for managing extensive chest wall defects.

Chronic kidney disease (CKD) is a common late complication associated with increased mortality after lung transplantation. Given the increased risk of infection in dialysis patients, late living-donor kidney transplantation (LDKT) provides excellent long-term survival in patients on dialysis after lung transplantation. However, recipients of living-donor lobar lung transplantation (LDLLT) might have scarce opportunity to receive LDKT due to the limited availability of living donors (LDs) for the second transplantation. We describe a successful case of late LDKT from the same donor after LDLLT. A 23-year-old woman with lymphangioleiomyomatosis underwent bilateral LDLLT of the right lower lobe from her brother and left lower lobe from her mother. Twelve years after LDLLT, she required hemodialysis for severe CKD. At the age of 37, she underwent LDKT from her mother, who was also an LD for the LDLLT. The postoperative courses of both the recipient and donor were uneventful, and the recipient remains in good physical condition (at the time of writing) despite developing recurrent lymphangioleiomyomatosis 23 years after the LDLLT, that is, 9 years after the LDKT. Her mother, the dual-organ LD, was able to return to her previous lifestyle. Late LDKT even from the same donor might be a viable option for patients developing severe CKD after LDLLT.

PurposeThe purpose of this study is to characterize and discuss the difference between software-detected non-invasive tear break-up time (NIBUT) and the traditional clinical method of fluorescein break-up time (FBUT).MethodsTear interferometry with the KOWA DR-1α (Kowa, Japan) and a standardized comprehensive ocular surface/tear evaluation were performed in 307 eyes. Software-detected NIBUT in the KOWA DR-1α images and the investigator-detected FBUT were compared.ResultsSoftware-detected NIBUT was significantly shorter than investigator-measured FBUT. NIBUT was 3.1 ± 2.5 s (mean ± SD), whereas FBUT was 4.8 ± 3.0 s. This difference was due to three different patterns or conditions: a spot break immediately after eyelid opening, moderate to severe keratitis sicca, and epithelial basement membrane corneal dystrophy (EBMD). In these cases, rapid tear film disruption was not captured by FBUT. A spot break immediately after eye opening that rapidly disappears was observed with conjunctivochalasis. This type of break-up may be difficult to detect using fluorescein because the human eye cannot catch such rapid blinks or post-blink events. In the second group with severe corneal epithelial disease, break-up may occur over the entire corneal surface upon eye opening, and distinct fluorescein tear break-up may not be identified because of poor dye dilution or spread over the corneal surface, whereas the non-invasive break-up is not solution-dependent, and the software can detect a distinct appearance. In the third group with EBMD, it is possible that focal break-up in the fluorescein pattern over the epithelial elevations, which might be missed visually, can be detected by software in video images.ConclusionWe found that software-detected NIBUT is more sensitive in detecting tear break-up, can identify certain tear film disruptions that are missed by traditional FBUT, and may be more useful in distinguishing certain tear disorders.

Background. Living donor lobar lung transplantation is a life-saving procedure for critically ill patients. This requires 2 healthy donors exposed to risks and without medical benefit. Therefore, the donor’s safety and minimal postoperative complications are crucial. This study aimed to investigate the short-term outcomes and identify the risk factors affecting these outcomes. Methods. The data of 175 living donors enrolled between 1998 and 2022 were analyzed. Donors were divided into era 1 (1998–2009) and era 2 (2010–2022). Results. The overall incidence of postoperative complications was 39%, of which 7% were major complications. Donors who underwent surgery on the right side had a higher incidence of delayed pulmonary fistulae (P = 0.01) and elevated liver enzyme levels (P = 0.028). Living donor surgery on the right side (P = 0.01), era 2 (P = 0.01), and the need for plasty (P = 0.04) were predictors of postoperative complications. Conclusions. Updated data on complications and their correlation with postoperative quality of life from this study could aid in the selection of potential donors and facilitate informed consent.

Abstract To characterize and compare macular vessel density in central retinal artery occlusion (CRAO) eyes with retinal arterial cannulation and CRAO eyes with standard treatment. This study was Cross-sectional, observational study. Twenty-two eyes with nonarteric CRAO which underwent retinal arterial cannulation and 19 eyes with nonarteric CRAO with standard treatment were included. Optical coherent tomography angiography (OCTA)-based macular vessel density and visual acuity were examined. The dynamic ranged-based normalized rates of vessel density was compared within each group at the first visit to the clinic and 7 days after the onset. Macular vessel density in cannulation group was significantly better at 7 days after the onset than that at the first visit (3.73 ± 3.02 mm−1 vs. 7.89 ± 1.02 mm−1, P = 0.0001), while there wasn’t significant improvement of macular vessel density in standard treatment group at 7 days after the onset (2.13 ± 1.62 mm−1 vs. 2.89 ± 0.22 mm−1, P = 0.067). At one month after the onset, mean LogMAR visual acuity in CRAO eyes with cannulation significantly improved compared with that at the first visit after the onset (1.678 vs. 0.979, P = 0.00012). Macular vessel density loss in CRAO eyes was improved by retinal arterial cannulation. Early intervention of retinal arterial cannulation is useful for minimizing visual impairment in CRAO eyes.

Abstract Background The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation is an uncommon strategy in Japan owing to the severe donor shortage and absence of urgent allocation policy. Moreover, the use of veno-venous (VV) ECMO for immunosuppressed patients is controversial; thus, applying ECMO to patients who await lung re-transplantation is challenging. Case presentation A 16-year-old lung transplant recipient with grade 3 bronchiolitis obliterans syndrome was waitlisted for lung re-transplantation. Eleven months later, he fell into severe respiratory acidosis with hypercapnia, which were not resolved with mechanical ventilation. VV ECMO was introduced to minimize lung stress and strain. Tracheostomy was additionally performed on day 5 after the start of ECMO, and respiratory condition swiftly improved; hence, the weaning process from VV ECMO began on day 9. Rehabilitation became implementable, and bilateral re-lung transplantation was successfully performed 6 months after the ECMO treatment. No critical complication related to the precedent use of ECMO was noted. Conclusions VV ECMO can be a feasible treatment option even for lung transplant candidates awaiting re-transplantation for a prolonged period. Introduction of ECMO and tracheostomy in the early deterioration stage may be crucial to successful subsequent patient management.

Abstract Renal dysfunction is a long-term complication associated with an increased mortality after lung transplantation (LT). We investigated the association of single-nucleotide polymorphisms (SNPs) with the development of renal dysfunction after LT using a Japanese-specific SNP array. First, eligible samples of 34 LT recipients were genotyped using the SNP array and divided into two groups, according to the presence of homozygous and heterozygous combinations of mutant alleles of the 126 renal-related SNPs. To identify candidate SNPs, the renal function tests were compared between the two groups for each SNP. Next, we investigated the association between the candidate SNPs and the time course of changes of the estimated glomerular filtration rate (eGFR) in the 99 recipients until 10 years after the LT. ΔeGFR was defined as the difference between the postoperative and preoperative eGFR values. Eight SNPs were identified as the candidate SNPs in the 34 recipients. Validation analysis of these 8 candidate SNPs in all the 99 recipients showed that three SNPs, namely, rs10277115, rs4690095, and rs792064, were associated with significant changes of the ΔeGFR. Pre-transplant identification of high-risk patients for the development of renal dysfunction after LT based on the presence of these SNPs might contribute to providing personalized medicine.

Abstract Pulmonary alveolar proteinosis (PAP) affecting transplanted lungs is not well recognized. Herein, we report two cases of PAP after lung transplantation (LTx). The first case was a 4‐year‐old boy with hereditary pulmonary fibrosis who underwent bilateral LTx and presented with respiratory distress on postoperative day (POD) 23. He was initially treated for acute rejection, died due to infection on POD 248, and was diagnosed with PAP at autopsy. The second case involved a 52‐year‐old man with idiopathic pulmonary fibrosis who underwent bilateral LTx. On POD 99, chest computed tomography revealed ground‐glass opacities. Bronchoalveolar lavage and transbronchial biopsy led to a diagnosis of PAP. Follow‐up with immunosuppression tapering resulted in clinical and radiological improvement. PAP after lung transplantation mimics common acute rejection; however, is potentially transient or resolved with tapering immunosuppression, as observed in the second case. Transplant physicians should be aware of this rare complication to avoid misconducting immunosuppressive management.

Abstract Antibodies to Ro52/tripartite motif-containing 21 (TRIM21), referred to as anti-Ro52, are found in patients diagnosed with diverse systemic autoimmune rheumatic disease and associated with interstitial lung diseases. However, little is known about the clinical characteristics of anti-Ro52 in patients with idiopathic interstitial pneumonias (IIPs). We aimed to analyze the prevalence, co-existent autoantibodies, and clinical characteristics of anti-Ro52 in patients with IIP. The study enrolled 288 patients diagnosed with IIP. Clinical, laboratory and radiographic findings of IIP patients were compared between anti-Ro52 positives and negatives. Anti-Ro52 (20/288; 6.9%), anti-ARS (18/288; 6.3%), and anti-Ro60/SS-A (16/288; 5.6%) were the most common autoantibodies detected in IIP patients. Among 20 IIP patients who had anti-Ro52, anti-ARS was present in 8 (40%) patients. The criteria for interstitial pneumonia with autoimmune features (IPAF) were significantly better fulfilled by patients with anti-Ro52 than those without (P = 0.001). Meeting serological domain (P

Abstract One-step nucleic acid amplification (OSNA) is a rapid intraoperative molecular detection technique for sentinel node assessment via the quantitative measurement of target cytokeratin 19 (CK19) mRNA to determine the presence of metastasis. It has been validated in breast cancer but its application in lung cancer has not been adequately investigated. 214 LNs from 105 patients with 100 primary lung cancers, 2 occult primary lung tumors, and 3 metastatic lung tumors, who underwent surgical lung resection with LN dissection between February 2018 and January 2020, were assessed. Resected LNs were divided into two parts: one was snap-frozen for OSNA and the other underwent rapidly frozen histological examination. Intraoperatively collected LNs were evaluated by OSNA using loop-mediated isothermal amplification and compared with intraoperative pathological diagnosis as a control. Among 214 LNs, 14 were detected as positive by OSNA, and 11 were positive by both OSNA and intraoperative pathological diagnosis. The sensitivity and specificity of OSNA was 84.6% and 98.5%, respectively. The results of 5 of 214 LNs were discordant, and the remainder all matched (11 positive and 198 negative) with a concordance rate of 97.7%. Although the analysis of public mRNA expression data from cBioPortal showed that CK19 expression varies greatly depending on the cancer type and histological subtype, the results of the five cases, except for primary lung cancer, were consistent. OSNA provides sufficient diagnostic accuracy and speed and can be applied to the intraoperative diagnosis of LN metastasis for non-small cell lung cancer.

Background: MicroRNAs (miRNAs) involved in the pathogenesis of pulmonary fibrosis have been shown to be associated with the development of chronic lung allograft dysfunction (CLAD) after lung transplantation (LT). We investigated the role of circulating miRNAs in the diagnosis of CLAD after bilateral LT, including cadaveric LT (CLT) and living-donor lobar LT (LDLLT). Methods: The subjects of this retrospective study were 37 recipients of bilateral CLT (n = 23) and LDLLT (n = 14), and they were divided into a non-CLAD group (n = 24) and a CLAD group (n = 13). The plasma miRNA levels of the two groups were compared, and correlations between their miRNAs levels and percent baseline forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) values were calculated from one year before to one year after the diagnosis of CLAD. Results: The plasma levels of both miR-21 and miR-155 at the time of the diagnosis of CLAD were significantly higher in the CLAD group than in the non-CLAD group (miR-21, P = 0.0013; miR-155, P = 0.042). The miR-21 levels were significantly correlated with the percent baseline FEV1, FVC, and TLC value of one year before and at the time of diagnosis of CLAD (P

Abstract Background Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. Methods This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. Results Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival. Conclusion Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.

PurposeDry eye disease affects hundreds of millions of people worldwide and is one of the most common causes for visits to eye care practitioners. The fluorescein tear breakup time test is currently widely used to diagnose dry eye disease, but it is an invasive and subjective method, thus resulting in variability in diagnostic results. This study aimed to develop an objective method to detect tear breakup using the convolutional neural networks on the tear film images taken by the non-invasive device KOWA DR-1α.MethodsThe image classification models for detecting characteristics of tear film images were constructed using transfer learning of the pre-trained ResNet50 model. The models were trained using a total of 9,089 image patches extracted from video data of 350 eyes of 178 subjects taken by the KOWA DR-1α. The trained models were evaluated based on the classification results for each class and overall accuracy of the test data in the six-fold cross validation. The performance of the tear breakup detection method using the models was evaluated by calculating the area under curve (AUC) of receiver operating characteristic, sensitivity, and specificity using the detection results of 13,471 frame images with breakup presence/absence labels.ResultsThe performance of the trained models was 92.3%, 83.4%, and 95.2% for accuracy, sensitivity, and specificity, respectively in classifying the test data into the tear breakup or non-breakup group. Our method using the trained models achieved an AUC of 0.898, a sensitivity of 84.3%, and a specificity of 83.3% in detecting tear breakup for a frame image.ConclusionsWe were able to develop a method to detect tear breakup on images taken by the KOWA DR-1α. This method could be applied to the clinical use of non-invasive and objective tear breakup time test.

BackgroundNutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.MethodIn a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal (“MCI-stable,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.ResultsPlasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.ConclusionThe PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.Clinical trial registration[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].

Abstract Background Idiopathic multicentric Castleman disease (iMCD) is a rare polyclonal lymphoproliferative disease caused by the overrepresentation of interleukin-6 (IL-6). Tocilizumab (TCZ) is a humanized monoclonal antibody that binds to the IL-6 receptor and is approved for the treatment of iMCD. The efficacy and tolerability of TCZ in patients with iMCD undergoing lung transplantation (LTx) remain unknown. Case presentation We present the case of a 48-year-old iMCD patient with end-stage lung disease (ESLD) who was successfully treated with cadaveric single-LTx. Intravenous TCZ was used to stabilize the iMCD patient every 2 weeks, except for withdrawal immediately after LTx. At 32 month post-transplant, the patient remained asymptomatic without evidence of rejection, development of de novo donor-specific antibody (DSA), and recurrent iMCD in the native lung. Conclusions Single-LTx can be a feasible treatment option for ESLD caused by iMCD. TCZ can be used safely and may be beneficial in recipients with iMCD, and TCZ in combination with usual immunosuppression can be helpful in stabilizing iMCD patients pre- and post-LTx.

Anti-fibrillarin autoantibodies are useful for the diagnosis and prognosis of systemic sclerosis (SSc). Anti-fibrillarin produces a clumpy nucleolar pattern in indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA). Here we develop and validate a reliable cell-based anti-fibrillarin assay (Fibrillarin/CBA) for use in clinical diagnostic laboratories. A TransMembrane Signal was fused to the human fibrillarin gene (TMS-fibrillarin). HEp-2 cells overexpressing transgenic TMS-fibrillarin at the cytoplasmic membrane were used as IFA substrate in the Fibrillarin/CBA. Sixty-two serum samples with nucleolar pattern in the HEp-2 IFA (41 clumpy; 21 homogeneous/punctate) were tested for anti-fibrillarin using Fibrillarin/CBA, immunoprecipitation (IP), line-blot and ELISA. In addition, samples from 106 SSc-patients were evaluated with Fibrillarin/CBA and the results were correlated with disease phenotypes. Thirty-eight of 41 samples with the clumpy nucleolar pattern (92.7%) were positive in the Fibrillarin/CBA, while all 21 samples with other nucleolar patterns were negative. Fibrillarin/CBA results agreed 100% with IP results. Among the 38 Fibrillarin/CBA-positive samples, only 15 (39.5%) and 11 (29%) were positive for anti-fibrillarin in line-blot and ELISA, respectively. Higher frequency of diffuse cutaneous SSc (dcSSc) phenotype (72.7% vs 36.8%; p=0.022), cardiac involvement (36.4% vs 6.5%; p=0.001) and scleroderma renal crisis (18.2% vs 3.3% p = 0.028) was observed in SSc patients with positive compared to negative Fibrillarin/CBA result. Performance of Fibrillarin/CBA in the detection of anti-fibrillarin autoantibodies was comparable to the gold standard IP. Positive Fibrillarin/CBA results correlated with disease phenotypes known to be associated with anti-fibrillarin autoantibodies, underscoring the clinical validation of this novel assay.

Background The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.Methods We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)tau and AT(N)NfL). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.Results We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)tau and AT(N)NfL classifications. When we used t-tau as the N marker (AT(N)tau), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)NfL). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)tau and AT(N)NfL classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)tau classification, but not in the AT(N)NfL classification.Conclusions AT(N)tau and AT(N)NfL in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.

Purpose: To evaluate an outbreak of endophthalmitis caused by Fusarium oxysporum after cataract surgery. Methods: In the present study, we conducted a retrospective review of the medical records of cases of endophthalmitis that developed after cataract surgery. All eyes underwent phacoemulsification and intraocular lens implantation (PEA + IOL) at a single eye clinic on the same date. Symptoms of endophthalmitis occurred 21.5 ± 3.4 days after the cataract surgery. Results: Nine eyes of 9 patients with fungal endophthalmitis (5 males and 4 females) were enrolled in the current study. The mean age of the patients was 63.4 ± 8.5 years. Soon after the diagnosis of endophthalmitis, pars plana vitrectomy (PPV) had been performed in all the eyes. However, because there was no response to the first PPV plus antibacterial drug therapy, we performed repeat PPV for all the eyes, combined with IOL removal and antifungal therapy (natamycin eye drops plus oral voriconazole or fosfluconazole). After the antifungal drug therapy, no recurrence of endophthalmitis was observed in any of the operated eyes, and good visual outcomes were obtained. Fusarium oxysporum was identified by culture and sequencing analysis. Conclusion: Early diagnosis and appropriate, adequate treatment are needed for successful management of fungal endophthalmitis.

The purpose of this study is to compare visual versus software detection of non-invasive tear break-up with the KOWA DR-1α tear interferometer and investigate the relationship between non-invasive tear break-up time (NIBUT) and dry eye clinical severity. Tear interferometry with the KOWA DR-1α, together with a standardized comprehensive ocular surface/tear evaluation, was performed on 348 consecutive eyes. Investigator visually detected or software detected non-invasive tear break-up and NIBUT were measured and compared on a subset of these examinations. The relationship between software-detected NIBUT and categorical dry eye severity based on irritation symptoms and corneal and conjunctival dye staining scores was determined. The sensitivity of visual (frame-by-frame) or software detected non-invasive tear break-up in eyes with tear instability (FBUT < 10) was similar (range 63–69%). NIBUT, measured visually or by software, had a correlation coefficient of 0.87. NIBUT was significantly lower in severity levels 2 and 3 compared to levels 0 + 1, and level 3 was significantly lower than level 2. In conclusion, there is a good correlation between investigator visually detected and software-detected tear break-up and tear break-up time in the KOWA DR-1α interferometric fringe images. Software-detected NIBUT is a clinically relevant measure of dry eye clinical severity.

(1) Background: Lung ischemia–reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury.

PurposeTo examine the usefulness of red channel fundus imaging to detect the ischemic status in eyes with central retinal vein occlusion (CRVO).MethodsUltra-widefield (UWF) fundus images were obtained from 42 eyes with CRVO. Twenty-one eyes were ischemic, and 21 eyes were non-ischemic. Rubeosis was found in 11 ischemic eyes. UWF images were split into red and green channels using ImageJ software. Both the color and red channel images were used to predict the presence or absence of ischemia when examined by masked graders. The sensitivity and specificity of UWF imagings for the detection of ischemia were calculated in Group A (total 42 eyes), Group B (32 eyes excluding non-rubeotic ischemic CRVO) and Group C (31 eyes excluding rubeotic ischemic CRVO), respectively. Moreover, a linear mixed model was conducted to investigate the relationship between the type of images and the accuracy of prediction in each group.ResultsNo significant difference in the sensitivity of color fundus imaging was seen between Group A and Group B. By contrast, a significant difference in the sensitivity of red channel imaging was seen between Group A and Group B (p = 0.031). The accuracies of the predictions were not associated with the type of image in Group A and Group B, but were significantly associated in Group C (p = 0.026).ConclusionsUWF red channel imaging enabled more accurate detection of the ischemic status, compared with color fundus images, especially in non-rubeotic CRVO eyes.

Nutritional epidemiology has shown the importance of protein intake for maintaining brain function in the elderly population. Mild cognitive impairment (MCI) may be associated with malnutrition, especially protein intake. We explored blood-based biomarkers linking protein nutritional status with MCI in a multicenter study. In total, 219 individuals with MCI (79.5 ± 5.7 year) from 10 institutions and 220 individuals who were cognitively normal (CN, 76.3 ± 6.6 year) in four different cities in Japan were recruited. They were divided into the training (120 MCI and 120 CN) and validation (99 MCI and 100 CN) groups. A model involving concentrations of PFAAs and albumin to discriminate MCI from CN individuals was constructed by multivariate logistic regression analysis in the training dataset, and the performance was evaluated in the validation dataset. The concentrations of some essential amino acids and albumin were significantly lower in MCI group than CN group. An index incorporating albumin and PFAA discriminated MCI from CN participants with the AUC of 0.705 (95% CI: 0.632–0.778), and the sensitivities at specificities of 90% and 60% were 25.3% and 76.8%, respectively. No significant association with BMI or APOE status was observed. This cross-sectional study suggests that the biomarker changes in MCI group may be associated with protein nutrition.

Abstract Background Interstitial lung disease (ILD) is a prognostic indicator of poor outcome in myositis. Although the pathogenesis of myositis-associated ILD is not well understood, neutrophils are thought to play a pivotal role. Neutrophils store azurophil granules that contain defensins, which are antimicrobial peptides that regulate the inflammatory response. Here, we evaluated levels of the human neutrophil peptides (HNPs) α-defensin 1 through 3 in patients with myositis-associated ILD to determine whether HNPs represent disease markers and play a role in the pathogenesis of myositis-associated ILD. Methods HNP levels were measured in the plasma and bronchoalveolar lavage fluid (BALF) of 56 patients with myositis-associated ILD and 24 healthy controls by enzyme-linked immunosorbent assay. Results Analysis revealed significantly higher HNP levels in plasma and BALF samples from patients with myositis-associated ILD as compared to those of healthy controls; however, plasma HNPs were significantly correlated with total cell counts in BALF. Additionally, BALF HNP levels were positively correlated with serum surfactant protein-A and the percentage of neutrophils in BALF, and BALF HNP levels correlated with the percentage of reticular opacities in high-resolution computed tomography results for patients with anti-aminoacyl-tRNA synthetase (ARS) antibody positive myositis-associated ILD. Survival did not differ between patients with higher and lower levels of plasma and BALF HNPs. Conclusions Plasma and BALF HNPs might reflect the disease activities of myositis-associated ILD, especially in patients with anti-ARS antibody positive myositis-associated ILD. However further studies are necessary to clarify whether HNPs represent disease markers and play roles in disease pathogenesis.

Purpose: To report the clinical and genetic findings of a male toddler who presented bilateral bullous retinoschisis with a novel RS1 mutation. Observations: This is an observational case report of a patient referred to our hospital with esotropia. A comprehensive ophthalmic examination was performed with the boy (age, 1 year 4 months) under general anesthesia that included fundus examinations, fluorescein angiography (FA), swept-source optical coherence tomography (SS-OCT), and full-field electroretinography (FF-ERG). Genetic analysis of the coding region in the RS1 gene was performed by Sanger sequencing for the patient and mother. There was a family history of X-linked retinoschisis (XLRS). Fundus examinations and FA showed bullous retinoschisis bilaterally in the inferior retina. The SS-OCT images showed two kinds of schisis in the inner nuclear layer (INL) and more proximally. In general, the inner plexiform layer, ganglion cell layer, and retinal nerve fiber layer are in the proximal INL; however, in this case there was hyperreflective tissue with a rough surface instead of normal retinal layers. In addition, in the schisis cavity between the hyperreflective tissue and separated retina, a number of hyperreflective fiber-like strands arose from the hyperreflective tissue and extended to the schisis cavity. During the follow-up period, the bullous retinoschisis collapsed spontaneously in the right eye. FF-ERG showed a reduced b-wave and relatively preserved a-wave in all components. Genetic analysis showed a novel RS1 mutation (c.185_186insT, p.E62DfsX24 in exon 4) in the patient and mother. Conclusions and importance: We report the detailed retinal structure in a genetically identified case of bullous retinoschisis. The notable finding was that the cavity of bullous retinoschisis contained a number of fiber-like strands as observed in the cavity of typical retinoschisis.