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Pyoderma gangrenosum (PG) is a rare chronic skin disease characterised by painful skin ulcers. There are no treatment guidelines for PG, but systemic treatments including biologics are often used. Recently, adalimumab (ADA), a fully human monoclonal antibody against tumour necrosis factor, was approved for refractory PG treatment in Japan. Herein, we report a case of rheumatoid arthritis with refractory PG 2 months after orthopaedic surgery of the foot during treatment with low-dose etanercept and methotrexate. Although adding a moderate dose of glucocorticoid did not improve her PG, the patient showed a remarkable response after switching from etanercept to ADA in a higher dose than that used to treat rheumatoid arthritis. This higher dose of ADA may be effective for the treatment of refractory PG after the failure of other tumour necrosis factor inhibitors.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small to medium-vessel necrotizing vasculitis and eosinophilic inflammation. Mepolizumab, an anti-interleukin-5 (IL-5) monoclonal antibody, has been approved in Japan since 2018 for refractory EGPA treatment. Benralizumab, an anti-IL-5 receptor monoclonal antibody, also has been reported to reduce the glucocorticoid dose in patients with refractory EGPA. On the other hand, several investigators have demonstrated new-onset EGPA under biologics, and it is unclear whether this treatment for severe allergic diseases can prevent the development of EGPA. Herein, we report a case of new-onset EGPA under benralizumab treatment. The patient had fever, weight loss, muscle pain, and paraesthesia, the serum eosinophil count was 0/μL, and the biopsy showed necrotizing vasculitis without eosinophilic infiltration. She was diagnosed as having EGPA and treated with high-dose glucocorticoid and intravenous cyclophosphamide, with a good response. Our case report indicates that anti-IL-5 agents may mask the development of EGPA and clinicians should be aware of the development of EGPA during anti-IL-5 agents.

OBJECTIVES To demonstrate the differences in clinical outcomes between lobectomy and segmentectomy for non-small cell lung cancer using propensity score matching. METHODS A single-centre, retrospective, matched cohort study was conducted in clinical T1N0M0 non-small cell lung cancer patients treated by surgery between 2012 and 2019. Differences in freedom from recurrence, overall survival, postoperative complications, chest drainage and preservation of pulmonary function between lobectomy and segmentectomy were evaluated using the propensity score model. Matched variables of patients were age, sex, comorbidity index and pulmonary function. Matched variables of tumours were tumour size, T-stage, fluorodeoxyglucose uptake on positron emission tomography, histopathology, lobe site and tumour distance ratio from the hilum. RESULTS Of the 112 patients treated by lobectomy and 233 patients treated by segmentectomy, 93 patients each from both groups were selected after the matching. The median tumour distance ratio from hilum was 0.7 in lobectomy and 0.8 in segmentectomy group (P = 0.59), i.e. almost outer third tumour location. There were no significant differences in freedom from recurrence (P = 0.38), overall survival (P = 0.51), postoperative complications (P = 0.94), drainage period (P = 0.53) and prolonged air leakage (P = 0.82) between the two. Median preservation of pulmonary function was 93.2% after segmentectomy, which was significantly higher than 85.9% after lobectomy (P, Pulmonary segmentectomy is expected to change the surgical treatment of clinical (c) T1N0M0 non-small cell lung cancer (NSCLC).

Introduction Associations of sleep duration with health outcomes could differ depending on whether sleep is restorative. Age-related changes in the relationship between sleep need and sleep opportunity could also influence these associations. Methods Using data from 5804 participants of the Sleep Heart Health Study, a multicenter population-based prospective cohort study, we examined the longitudinal association of feeling rested after sleep combined with in-home polysomnographymeasured total sleep time (TST) or time in bed (TIB) with allcause mortality. Results A total of 223 (7.1%) and 991 (37.0%) deaths were reported in 3128 middle-aged (40–64 years) and 2676 older adults (≥ 65 years) with a mean (standard deviation) age of 54.5 (6.6) and 73.3 (5.7) years at baseline over a median (interquartile range) follow-up time of 12.3 (11.3–13.5) and 11.3 (8.2–12.2) years, respectively. Among middleaged adults, compared with the interquartile TST range (331 to < 414 min) with feeling rested, the lowest TST quartile (< 331 min) with feeling unrested was associated with higher mortality (adjusted hazard ratio [aHR], 1.54; 95% confidence interval [CI] 1.01–2.33); the highest TST quartile (≥ 414 min) with feeling rested was associated with lower mortality, independently from health and sleep covariates (aHR, 0.55; 95% CI 0.32–0.97). Among older adults, TIB, but not TST, was consistently associated with mortality. Compared with the interquartile TIB range (404 to < 482 min) with feeling rested, the highest TIB quartile (≥ 482 min) with feeling unrested was associated with higher mortality (aHR, 1.57; 95% CI 1.23–2.01). Conclusion The results suggest the role of restorative sleep in differentiating the effects of sleep duration on mortality outcomes for middle-aged and older adults. Our findings further suggest that there is a need to change the way to optimize sleep hygiene according to age groups: in middle-aged adults maintaining a substantial amount of sleep is more critical, whereas in older adults optimizing sleep opportunity is more critical to determine the sleep–mortality relationship. Support (if any) This work was supported by the Ministry of Health, Labor and Welfare, Government of Japan (Grant numbers #19FA1009 and #21FA1002).

To elucidate the effect of Pleistocene climatic fluctuations on the historical distribution and geographical genetic structure of temperate Japanese species, we performed phylogeographical and demographic analyses using mitochondrial gene sequences obtained from the stonefly species Kamimuria tibialis, sampled from four main islands of the Japanese Archipelago (i.e. Hokkaido, Honshu, Shikoku and Kyushu) and Tsushima Island. We detected three main clades with distinct geographical distributions, including the Tsushima, Kyushu and Hokkaido–Honshu–Shikoku phylogroups. These groups were estimated to have diverged from one another 0.54–2.02 Mya, suggesting they have undergone several glacial cycles in different refugia. Our results showed that during the glacial epochs and with a fall in sea-level, gene flow was limited among Tsushima and Kyushu, and among Hokkaido and Honshu, probably because the straits between these islands are deep. The population in Kyushu and Shikoku, the southernmost islands, exhibited high genetic diversity, with two distinct haplotype lineages occurring sympatrically. These results suggest that the population division into multiple refugia and the existence of stable southern refugia have contributed to the high genetic diversity of the species in this region.

In the Tohoku Medical Megabank project, genome and omics analyses of participants in two cohort studies were performed. A part of the data is available at the Japanese Multi Omics Reference Panel (jMorp; https://jmorp.megabank.tohoku.ac.jp) as a web-based database, as reported in our previous manuscript published in Nucleic Acid Research in 2018. At that time, jMorp mainly consisted of metabolome data; however, now genome, methylome, and transcriptome data have been integrated in addition to the enhancement of the number of samples for the metabolome data. For genomic data, jMorp provides a Japanese reference sequence obtained using de novo assembly of sequences from three Japanese individuals and allele frequencies obtained using whole-genome sequencing of 8,380 Japanese individuals. In addition, the omics data include methylome and transcriptome data from ∼300 samples and distribution of concentrations of more than 755 metabolites obtained using high-throughput nuclear magnetic resonance and high-sensitivity mass spectrometry. In summary, jMorp now provides four different kinds of omics data (genome, methylome, transcriptome, and metabolome), with a user-friendly web interface. This will be a useful scientific data resource on the general population for the discovery of disease biomarkers and personalized disease prevention and early diagnosis.

Introduction There is evidence for a mismatch between subjective and objective sleep durations not only in individuals with insomnia but also in healthy individuals . However, it is unclear how such discrepancy impacts long-term health outcomes. This study investigated whether and how the discrepancy between subjective and objective sleep duration affected all-cause mortality in a sample of community-dwelling older adult men, aged ≥ 65 years. Methods We conducted a secondary analysis of data obtained via the Osteoporotic Fractures in Men Sleep Study, a community-based, longitudinal, observational, and multicenter study. We included data from 2,674 individuals who underwent an in-home polysomnography, completed morning surveys to assess subjective sleep duration during the polysomnography, and for whom survival or death data were available. We assessed the longitudinal association between misperception index (MI), calculated as MI = (objective sleep duration – subjective sleep duration) / objective sleep duration, and all-cause mortality. MI was treated as both a continuous and categorical predictor: the lowest (≤ -0.19; the overestimation of sleep duration) and highest MI quartiles (> 0.08; the underestimation of sleep duration) were compared to the interquartile range of MI (-0.19 Results During the follow-up with a mean (standard deviation) of 10.8 (4.2) years, 1,596 deaths (59.7%) were observed. As a continuous variable, MI showed a negative association with all-cause mortality after adjusting for multiple covariates, including polysomnography-measured objective sleep duration (fully adjusted hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.56–0.84). As a categorical variable, the lowest MI quartile (vs. the interquartile MI range) was associated with increased mortality (fully adjusted HR, 1.28; 95% CI, 1.12–1.46), whereas the highest MI quartile was not associated with mortality (fully adjusted HR, 0.97; 95% CI, 0.85–1.11). Conclusion The subjective overestimation (“reverse” misperception) of sleep duration, may be a risk factor for all-cause mortality in older men. Further investigations are needed to examine physiological mechanisms through which subjective overestimation of sleep duration leads to negative long-term health outcomes. Support (if any) This work was supported by the Ministry of Health, Labor and Welfare, Government of Japan (Grant numbers #19FA1009 and #21FA1002).

Resection of malignant tumors in the posterior pelvis requires multidirectional approaches for the resection and the subsequent spine-pelvic fixation. The multifidus muscle can be scarified during the operation. This is a case report of a 44-year-old male with a secondary chondrosarcoma arising from an osteochondroma in the sacral ala. Recurrence occurred 11 months after the initial operation, and the resected tissue from the recurrence was diagnosed as a chondrosarcoma. In both operations, the multifidus muscle was elevated from its distal attachment to provide an adequate view of the tumor resection and insertion of spine-pelvic instrumentation. An adequate view by elevation of the multifidus muscle is useful for a safe operation. A preserved multifidus muscle covering the instrumentation may reduce the risk of infection. The elevation and preservation of the multifidus muscle is an easy and simple method that contributes to successful resection of a malignant tumor of the pelvis.

Background The optimal coronary revascularization strategy for the patients on hemodialysis is yet to be determined. In the real-world practice, we sometimes encounter the rapid deterioration after percutaneous coronary intervention (PCI) to angiographically intermediate but functionally significant stenosis. According to the fractional flow reserve (FFR) based revascularization strategy, the clinical outcome of the deferred lesions is reported to be almost equivalent to that of the lesions received PCI. However, whether the relationship also applies to hemodialysis patients is unclear. Purpose To assess the clinical outcome of the lesions for which revascularization strategy was determined by FFR in patients with hemodialysis. Methods Consecutive 147 vessels in 120 patients with hemodialysis whose revascularization strategy was decided according to the FFR were enrolled in this study. We compared the clinical outcomes of the deferred group (FFR ≥0.80, 87 vessels, 78 patients) with the PCI group (FFR Results The median follow-up period was 2.3 years (interquartile range, 1.5–4.0 years). The beseline characteristics of the lesions and patients were well balanced between the 2 treatment groups except for the distribution of target vessels and FFR value. The cumulative TVF rate was not significantly different between the deferred group and PCI group (2-year event rate 26.7% vs. 17.7%; Log-rank p=0.23). The risk of MACE was also not significantly different between two groups (2-year event rate 35% vs. 30%; Log-rank p=0.48). Conclusion The clinical outcome of the lesions/patients for which received revascularization based on FFR was equivalent to the deferred lesions/patients even in the patients on hemodialysis (2,129/3,000). Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Introduction Lumbar spinal canal stenosis (LSCS) is not always correlated with spinal stenosis and severity of clinical symptoms. Although, it is important for trunk muscle function to enhance the dynamic stability of the lumbar spine, however few studies have reported on this. We hypothesized that trunk muscle function and gait ability of LSCS patients are related. This study aimed to clarify the association between trunk muscle function, using Side Bridge test (SB), and gait ability of LSCS patients. Methods The subjects were 42 patients with LSCS: 17 supported the trunk by the foot (F-group), and 25 supported the trunk by the knee (K-group) in the SB test. The SB test was performed to determine the posture holding time. Gait ability was evaluated by measuring the time of 10-m walk test (10MWT) preoperatively and 2 weeks postoperatively. The 2 weeks postoperative 10MWT was divided by the preoperative 10MWT to calculate the 10MWT change rate. The contents of this study were the relation between SB test and preoperative 10MWT, SB test and 10MWT change rate in each group. Moreover, the median value of SB test was calculated for both groups; based on these values, the patients were categorized into high-value and low-value groups. Differences between the 10MWT and 10MWT change rates of both groups were examined using Mann-Whitney U-test. Results There was a significant correlation between SB test and 10MWT (F-group: r=-0.63, p=0.004; K-group: r=-0.59, p = 0.002), 10 MWT change rate (F-group: r=-0.59, p=0.01; K-group: r=-0.41, p=0.04). With respect to the 10MWT, the high-value group was significantly faster than the low-value group (F-group: p=0.02, K-group: p=0.03), and with respect to the 10MWT change rate, the high-value group was significantly better than the low-value group (F-group: p=0.02, K-group: p=0.01). Conclusion Trunk muscle function is associated with gait ability of LSCS patients.

Study question Can deep learning (DL) algorithms trained on time-lapse videos be used to detect and track the size and gender of pronuclei in developing human zygotes? Summary answer Our DL algorithm not only outperforms state-of-the-art models in detecting the pronuclei but can also accurately identify and track its gender and size over time. What is known already Recent researches have explored the use of DL to extract key morphological features of human embryos. Existing studies, however, focus either on blastocysts’ morphological measurements (Au et al. 2020) or on embryos’ general developmental stages classification (Gingold et al. 2018, Liu et al. 2019, Lau et al. 2019). So far, only one paper attempted to evaluate zygotes’ morphological components but stopped short of identifying the existence and location of their pronuclei (Leahy et al. 2020). We address this research gap by training a DL model that can detect, classify the gender, and quantify the size of zygotes’ pronuclei over time. Study design, size, duration A retrospective analysis using 91 fertilized oocytes from infertile patients undergoing IVF or ICSI treatment at Hanabusa Women’s Clinic between January 2011 and August 2019 was conducted. Each embryo was time-lapse monitored using Vitrolife which records an image every 15 minutes at 7 focal planes. For our study, we used videos of the first 1–2 days of the embryo from its 3 central focal planes, corresponding to 70–150 images per focal plane. Participants/materials, setting, methods All 273 timelapse videos were split into 30,387 grayscale still images at a 15-minute interval. Each image was checked and annotated by experienced embryologists where every pixel of the image was classified into 3 categories: male pronuclei, female pronuclei, and others. Images were converted into grayscale, resized into 500x500 pixels, and then fed into a neural network with the Mask R-CNN architecture and a ResNet101 backbone to produce a pronuclei instance segmentation model. Main results and the role of chance The 91 embryos were split into training (∼70% or 63 embryos) and validation (∼30% or 28 embryos). Our pronuclei model takes as input a single image and outputs a bounding box, mask, category, confidence score, and size measured in terms of pixel for each detected candidate. For prediction, we run the model on the 3 middle focal planes and merge candidates by using the one with the highest confidence score. We used the mean-average precision (mAP) score to evaluate our model’s ability to detect pronuclei and used the mean absolute percentage error (MAPE) between the actual size (as annotated by the embryologist) and the predicted one to check the model’s performance in tracking the pronuclei’s size. The mAP for detecting pronuclei, regardless of its gender, achieved by our model was 0.698, higher than the 0.680 value reported in the Leahy et al. paper (2020). Breakdown by gender, our model’s mAP for male and female pronuclei are 0.734 and 0.661 respectively. The overall MAPE for tracking pronuclei’s size is 21.8%. Breakdown by gender, our model’s MAPE for male and female pronuclei are 19.4% and 24.3% respectively. Limitations, reasons for caution Samples were collected from one clinic with videos recorded from one time-lapse system which can limit our results’ reproducibility. The accuracy of our DL model is also limited by the small number of embryos that we used. Wider implications of the findings: Even with a limited training dataset, our results indicate that we can accurately detect and track the gender and the size of zygotes’ pronuclei using time-lapse videos. In future models, we will increase our training dataset as well as include other time-lapse systems to improve our models’ accuracy and reproducibility. Trial registration number Not applicable

Aims The purpose of this study was to evaluate the effect of aggressive lipid-lowering therapy with pitavastatin and ezetimibe in patients with ST-segment elevation myocardial infarction (STEMI) as compared with those with other classification of an acute coronary syndrome (ACS) including non-STEMI (NSTEMI) and unstable angina pectoris (UA). Methods This is a post hoc sub-analysis of the HIJ-PROPER study. In the original study, ACS patients with dyslipidemia were randomized to either pitavastatin + ezetimibe therapy or pitavastatin monotherapy. In the present analysis, we divided HIJ-PROPER participants into the STEMI group (n=880) and NSTEMI + UA group (n=841). Cardiovascular events were analyzed between the two groups. The primary endpoint was a composite of major advanced cardiovascular events (MACE; all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, and ischemia-driven revascularization) Result During median follow-up period of 3.4 years, the cumulative incidence of the primary endpoint in STEMI group was 31.9% in the pitavastatin+ezetimibe therapy, compared with 39.7% in the pitavastatin-monotherapy (HR, 0.77; 95% CI, 0.62–0.97; p=0.02). However, there was no effect of pitavastatin+ezetimibe therapy on the primary endpoint in the NSTEMI + UA group. Concerning the individual components of the primary endpoint in STEMI group, the percentage of occurrence of all-cause death was significantly lower in the pitavastatin+ezetimibe therapy compared to pitavastatin mono-therapy (14 patients (3.2%) vs. 31 patients (6.9%), respectively; HR, 0.45; 95% CI, 0.23–1.84, p=0.01). Multivariate analysis revealed that use of ezetimibe and prevalence of diabetes mellitus at baseline were independent predictors of primary endpoints in STEMI group (HR, 0.79; 95% CI, 0.63–0.99; p=0.04 for use of ezetimibe, HR 1.54; 95% CI, 1.22–1.94, p=0.0003 for diabetes mellitus). Conclusion Patients with pitavastatin+ezetimibe therapy as compared with pitavastatin-monotherapy had lower cardiovascular event in patients with ST-segment elevation myocardial infarction. Kaplan-Meier curves for primary endpoint Funding Acknowledgement Type of funding source: None

Background This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events. Methods The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. For the present analysis, the entire cohort was divided into three groups according to HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, 43–53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and the incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups. Results The primary endpoint was reported in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively. The incidence of the primary endpoint was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19–1.9; p=0.001). Irrespective of the treatment regimen, Group 1 had a significantly higher rate of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12–2.22; p=0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05–1.98; p=0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles. Conclusions Lower levels of HDL-C at 3-month follow-up are associated with higher incidence of the cardiovascular events in patients with acute coronary syndrome receiving contemporary lipid-lowering therapy. HDL-C levels and Cardiovascular events Funding Acknowledgement Type of funding source: None

This study investigated the effects of millimeter wave (MMW) irradiation with a wide range of frequencies on the proliferation and activity of normal human skin fibroblast (NB1RBG) and human glioblastoma (A172) cells. Very few studies have focused on low-power, long-term irradiation of cells with a widely tunable source. Our research examined non-thermal effects on cells exposed to radiation at low power with tunable frequencies from 70 GHz to 300 GHz. A widely tunable MMW source was set within a cell culture incubator. To avoid the effect of heat generation due to irradiation, the intensity was maintained below 10 μW and the device was arranged such that the irradiation came from underneath the cells. Irradiation was performed by sweeping from 70 GHz to 300 GHz in 1.0 GHz steps. The MMW source was positioned 100 mm away from the container in which the cells were cultured. Cells were exposed to MMWs for either 3, 70 or 94 h. Measurements of cell proliferation were made using the alternating current measurement method. We found no difference in proliferation between cells exposed to MMWs and unexposed cells. A colorimetric method using novel tetrazolium compound: MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] was used for cell activity and cytotoxicity assays. We found no difference in cellular activity or toxicity between MMW-exposed cells and sham cells. Our study thus found no non-thermal effect as a result of exposure of cells to 70 GHz to 300 GHz of radiation.

Glutamine synthetase (GS) is an important enzyme for nitrogen assimilation, and GS2, encoded by GLN2, is the only plastid-type GS in Arabidopsis thaliana. A co-expression analysis suggested that the expression level of the gene encoding a uridylyltransferase-like protein, ACR11, is strongly correlated with GLN2 expression levels. Here we showed that the recombinant ACR11 protein increased GS2 activity in vitro by reducing the Km values of its substrate glutamine. A T-DNA insertion mutant of ACR11 exhibited a reduced GS activity under low nitrate conditions and reduced glutamine levels. Biochemical analyses revealed that ACR11 and GS2 interacted both in vitro and in vivo. These data demonstrate that ACR11 is an activator of GS2, giving it a mechanistic role in the nitrogen assimilation of A. thaliana.

A complete excision is the most reliable therapy for bronchogenic cysts (BC) but is often accompanied by technical difficulties due to severe adhesions. An 83-year-old-woman with poorly controlled diabetes noted worsening upper abdominal pain after meals and paroxysmal atrial fibrillation. Magnetic resonance imaging revealed a cystic mass in the subcarinal region, and she underwent a thoracoscopic prone position surgery. The cyst wall was found to have strictly adhered to the adjacent organs, and the lesion was not amenable to a complete excision. We performed a fenestration of the cyst wall with the aspiration of an yellowish mucus content. After opening the cavity wide enough, the remnant luminal epithelium was ablated by electrocautery. Her clinical symptoms disappeared immediately after the surgery without any surgical morbidity. A prone-position thoracoscopic palliative fenestration is a feasible option for a symptomatic subcarinal BC.

Background The role of circulating progenitor cells (CPCs) on vascular repair after everolimus-eluting stent (EES) implantation is largely unknown. Objectives The aim of the study was to investigate the quantitative and temporal variations of CPCs levels after EES implantation, and its relationship with the degree of peri-procedural vascular damage, stent healing and neointimal hyperplasia, as measured by optical coherence tomography (OCT). Methods In a consecutive series of patients with stable coronary artery disease undergoing stent implantation CPC subpopulations (CD34+/CD45low, CD133+/CD45low, CD34/KDR/CD45low, CD133/KDR/CD45low) were evaluated using a flow cytometry technique at baseline, 1 and 4 weeks. OCT evaluation was performed immediately after stent implantation to quantify stenting-related injury, and at 9-month follow-up to assess mid-term vascular response. Results Twenty patients (mean age 66±9 years; 80%male) with 24 stenoses treated with EES were included in the study. Vascular injury score was associated with the increase of CD133+/KDR/CD45 low at 1-week (β0.28 [95% CI0.15; 0.41], p Conclusion Long-term vascular healing after EES implantation is modulated by early changes in levels of CPC subpopulations. This systemic response is proportional to the extent of vessel wall injury. Early mobilization of CPCs influences mid-term strut coverage and the development of neointimal hyperplasia. Acknowledgement/Funding Dr Jimenez-Quevedo is a recipient of the ISCIII (Instituto de Salud Carlos III) grant “Fondo de Investigaciόn Sanitaria” (PI11/00299) to perform this

Introduction Transcatheter aortic valve implantation (TAVI) theoretically increases renal blood flow through increasing cardiac output by relieving aortic valvular obstruction of blood flow from left ventricle, resulting in a renal functional recovery in patients with severe aortic valve stenosis (AS). However, procedural steps of TAVI including contrast use potentially damages renal medulla and may deteriorate renal function. Purpose The aim of this study was to investigate renal functional change and clarify preoperative predictors for renal functional improvement after TAVI in chronic kidney disease (CKD) patients with severe AS. Methods A total of 88 consecutive severe AS patients with CKD (grade >3) who underwent TAVI from 2015 to 2018 was enrolled in this observational study. They were divided into two groups depending on their renal functional improvement after TAVI that was defined as more than 10% increase in estimated glomerular filtration rate (eGFR) at discharge from their preoperative level. Results Among the whole candidates, 49 patients (55.7%) were improved their renal function. Patients with the lowest preoperative eGFR achieved the highest increase in eGFR after TAVI (CKD grade >4: +22.7±23.7%, Figure). Patients in the Improved group had lower hemoglobin level, higher mean transaortic pressure gradient (TAPG), and higher aortic valve gradient before TAVI, compared to those in the Non-improved group. However, contrast volume during the procedure was not significantly different between the groups. Multivariate logistic regression analysis revealed that high mean TAPG and low left ventricular ejection fraction (LVEF) before TAVI were independent predictors for the improvement of renal function (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.00–1.08; OR: 0.94, 95% CI: 0.89–0.99, respectively), even after the adjustment of baseline eGFR level and hemoglobin level that were statistically significant on univariate logistic regression analysis. Receiver Operating Characteristic (ROC) curve showed the cut-off level of preoperative mean TAPG in renal functional improvement after TAVI as 47.0 mmHg (Sensitivity: 47.9%, Specificity: 79.5%, area under the curve: 0.62). Correlation between CKDgrade and ΔeGFR Conclusions Preoperative high mean TAPG may predict renal functional improvement after TAVI in patients with deteriorated renal function. This non-invasive predictor may help clinicians to consider to perform TAVI in a challenging case with severe CKD.

Objectives To achieve the growth of right-sided heart structures, our choice of the first palliation for patients with pulmonary atresia and intact ventricular septum (PA-IVS) includes a modified Blalock-Taussig shunt (BTS) with pulmonary valvotomy. We sought to analyse the impact of the first palliation on the growth of right-sided heart structures and factors associated with a choice of definitive surgical procedure. Methods Fifty patients with PA-IVS who underwent a staged surgical approach from 1991 to 2012 were retrospectively reviewed. Results Right ventricular (RV)-coronary artery fistulas were seen in 42% of patients at the time of birth. All 50 patients had a modified BTS with pulmonary valvotomy. Six patients died after the first palliation or inter-stage. Thirty patients achieved a biventricular repair (BVR group), 6 patients had a 1 + 1/2 ventricular repair (1 + 1/2V group) and 5 patients had a Fontan completion (Fontan group). After modified BTS with pulmonary valvotomy, tricuspid valve z-score did not increase in any of the group (BVR: pre -2.79 vs post -2.24, 1 + 1/2V: pre -5.25 vs post -6.69, Fontan: pre -6.82 vs post -7.94). Normalized RV end-diastolic volume increased only in BVR group after modified BTS with pulmonary valvotomy (BVR: pre 32% vs post 64%, 1 + 1/2V: pre 43% vs post 42%, Fontan: pre 29% vs post 32%). Major RV-coronary artery fistula was a strong factor with proceeding single-ventricle palliation [BVR: 4/30 (13%) patients, 1 + 1/2V: 1/6 (17%) and Fontan: 4/5 (80%)]. Conclusions Tricuspid valve growth was not obtained by modified BTS with pulmonary valvotomy; therefore, tricuspid valve size at birth appeared to be a predictor for achieving BVR. Proportionate RV growth was seen only in patients who achieved BVR. However, RV growth was not seen in patients having 1 + 1/2 ventricular repair. Major RV-coronary artery fistula was a strong predictor for proceeding single-ventricle palliation.