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ABSTRACT Aims/Introduction Chronic kidney disease (CKD) is a very important issue globally because of the risk of its progressing to end‐stage renal disease. We aimed to identify factors contributing to long‐term estimated glomerular filtration rate (eGFR) decline to determine an early diagnosis and prevent CKD progression. Materials and Methods From January 2003 to December 2006, 5,507 individuals underwent health checkups at our hospital's Preventive Medicine Research Center. We ultimately enrolled 2,175 individuals. The eGFR was ≥60 mL/min/1.73 m2 at the start of observation period, which was 20 years. The event onset time was the day that the eGFR became

Abstract Background Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p

Abstract Aim The number of elderly patients with liver cancer is increasing with the aging society. The Geriatric Prognostic Scoring System is useful in predicting the postoperative prognosis for elderly patients with gastrointestinal cancer. The aim of the present study was to assess the predictive ability of the geriatric prognostic scoring system for postoperative survival in elderly patients with liver cancer. Methods Eighty‐eight patients aged ≥75 years who were treated for primary liver cancer and metastatic liver tumor were retrospectively analyzed. The Geriatric Prognostic Score (GPS) was created by several clinical parameters such as age, sex, type of cancer, stage, performance status, body mass index, and comprehensive geriatric assessment. Each patient was divided into two groups of high‐risk to low‐risk according to their GPS: ≧30 high‐risk group and

Background: Nonepisodic angioedema with eosinophilia (NEAE) is a condition marked by angioedema and significant eosinophilia and often linked with atopic dermatitis. It predominantly affects young Asian women and occurs more frequently in the autumn and winter. Despite over 100 reported cases, its etiology and pathogenesis remain unclear. Case presentation: A 23-year-old Japanese female florist presented with acute arm swelling following rose-thorn pricks to her hands and fingers in spring. One week later, she developed progressive symmetrical non-pitting edema in her lower legs and a 3 kg weight gain without any rash. She had a history of oral allergy syndrome to apples and pears for which allergen-specific IgE were previously detected. Blood tests showed significant eosinophilia (14,930 cells/μL) and elevated thymus and activation-regulated chemokine (TARC) levels (12,864 pg/mL). Thyroid disease, autoimmune disorders, and hematologic malignancies were ruled out. Normal cardiac markers and a whole-body computed tomography excluded visceral organ involvement. She was diagnosed with NEAE and treated with oral prednisolone, which resolved the edema within 10 days. Prednisolone was tapered gradually on an outpatient basis without recurrence. Conclusion: A review of the literature indicates that NEAE triggered by subcutaneous antigen exposure may not follow the typical age or seasonal patterns. Direct subcutaneous antigen exposure, including rose-thorn pricks, can trigger NEAE. Clinicians should consider NEAE in atypical presentations and thoroughly investigate preceding episodes.

Abstract Background and Aim Increased liver fibrosis scores (LFS), such as fibrosis‐4 index (FIB‐4) or non‐alcoholic fatty liver disease fibrosis score (NFS), and fatty liver are known risk factors for severe coronavirus disease 2019 (COVID‐19). The purpose of this study was to identify the best scores, which predict the prognosis of COVID‐19. Methods Participants comprised consecutive Japanese COVID‐19 patients admitted to our hospital between February 14, 2020, and April 14, 2021. Multivariate logistic regression analysis was performed to evaluate the relationships between LFS (FIB‐4, NFS, aspartate aminotransferase‐to‐platelet ratio index [APRI], BARD score, and hepatic steatosis index [HSI]) or fatty liver on computed tomography (CT), and severity of COVID‐19. Results Of the 415 patients (mean age, 59 years), 177 patients (42.7%) needed oxygen therapy, 90 patients (21.7%) worsened to severe COVID‐19, and 45 patients (10.8%) died during admission. Multivariate logistic regression analysis showed that increased FIB‐4 and NFS were risk factors for death, severe COVID‐19, and oxygen demand; that increased BARD was a risk factor for severe COVID‐19 and oxygen demand; and that increased APRI and HSI were not risk factors for any status of COVID‐19. Furthermore, increased NFS or BARD and fatty liver were independent risk factors for severe COVID‐19 and oxygen demand. Conclusions This study showed that FIB‐4 and NFS were the best liver fibrosis scores that predicted worse prognosis for COVID‐19, and that increased NFS or BARD and fatty liver evident on CT represented independent risk factors for severe COVID‐19 and oxygen demand.

Background: Our investigation focused whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before or after receiving the mRNA COVID-19 vaccine can increase immune protection. And we also investigated relationship of infection acquired. Methods: Three shots of the mRNA coronavirus disease 2019 (COVID-19) vaccine BNT162b2 were administered to 736 healthcare workers at Tokyo Shinagawa Hospital. Serum samples were collected before the first shot (P1), at one month (P2), and at six months (P3) after the second shot and at one month after the third shot (P4). The presence of infection was assessed using IgG against the nucleocapsid (IgG (N) and RBD in the spike protein of SARS-CoV-2. We defined infection before P2 as natural infection (NI) and infection between P2 and P3 as breakthrough infection (BI) and compared susceptibility to further infection between the NI (−) and NI (+) groups and between BI (−) and BI (+) groups. Events in 485 participants who had a complete dataset of IgG (N) and IgG (RBD) from P1 to P4 were analyzed. Results: The presence of SARS-CoV-2 infection before P2 were examined by examining the titers of IgG (N)P1, IgG (N) P2, and IgG (RBD) P1 that exceeded the cutoff values. Consequently, 35 participants (7.22 %) were categorized into the NI (+) group, whereas 450 (92.8 %) were categorized into the NI (−) group. Between P2 and P3, the NI (−) group showed a higher rate of SARS-CoV-2 infection than the NI (+) group; however, there was no significant difference in the infection rate between P3 and P4. The infection rate was significantly lower in the BI (+) group than in the BI (−) group. Pre-primary vaccination infection significantly increased IgG (RBD) levels between P1 and P3. Post-primary vaccination infection significantly increased IgG (RBD) levels between P3 and P4. Conclusions: Infection with SARS-CoV-2 before or after receiving the mRNA COVID-19 vaccine can increase immune protection; however, the duration of this effect may be limited.

Abstract The huge carbon stock of tropical peat swamp forest (PSF) in Southeast Asia has been threatened by environmental disturbances due to quasi-periodic El Niño-Southern Oscillation (ENSO) droughts, biomass and peat burning, smoke haze, drainage, and deforestation. Carbon dioxide (CO2) emissions from such disturbances have not been well quantified because of insufficient field data. Therefore, we quantified the ecosystem-scale CO2 balance and examine the disturbance effects from a long-term field experiment for 12–15 years at three PSF sites with different degrees of degradation in Indonesia. Here, we show a drastic change of an undrained PSF from a CO2 sink to a source owing to the transient groundwater lowering by the droughts, a significant decrease in ecosystem photosynthesis due to the radiation attenuation by smoke haze in drought years, and long-lasting CO2 emissions through enhanced peat decomposition by drainage. The impact on CO2 emissions was greater from drainage than drought-induced disturbances.

Abstract This single-center retrospective cohort study analyzed the 1-year real-world treatment outcomes of 63 consecutive eyes (of 60 patients) with neovascular age-related macular degeneration (nAMD) that were switched from intravitreal brolucizumab (IVBr) to intravitreal faricimab (IVF) and managed on a treat-and-extend regimen with discontinuation criteria. After the switch, patients opted to continue IVF, to switch back to IVBr, or receive photodynamic therapy (PDT). Thirty-eight patients continued IVF, 16 patients were switched back to IVBr, 2 patients received PDT, and 4 patients paused treatment. Best-corrected visual acuity (BCVA), central subfield thickness (CST), subfoveal choroidal thickness (sf-CT), and injection intervals were compared immediately before and 1 year after the initial IVF. Whereas there was no change in BCVA and CST; 0 [− 0.0969 to 0.125, P = 0.58], − 1.5 [− 27.8 to 13.5, P = 0.11] µm, respectively, sf-CT decreased significantly; − 19.5 [− 45.5 to 7.75, P = 0.015] µm. The patients switched back showed no significant change in sf-CT. The injection interval extended significantly in the IVF continuation and the switch-back group (2.0 and 3.0 weeks, respectively; [P = 0.0007 and 0.0078]) in eyes with a pre-switching interval of less than 12 weeks. Faricimab shows promise as a safe and effective alternative to brolucizumab for treating nAMD.

Abstract Background In pancreatic ductal adenocarcinoma (PDAC), invasion of connective tissues surrounding major arteries is a crucial prognostic factor after radical resection. However, why the connective tissues invasion is associated with poor prognosis is not well understood. Materials and methods From 2018 to 2020, 25 patients receiving radical surgery for PDAC in our institute were enrolled. HyperEye Medical System (HEMS) was used to examine lymphatic flow from the connective tissues surrounding SMA and SpA and which lymph nodes ICG accumulated in was examined. Results HEMS imaging revealed ICG was transported down to the paraaortic area of the abdominal aorta along SMA. In pancreatic head cancer, 9 paraaortic lymph nodes among 14 (64.3%) were ICG positive, higher positivity than LN#15 (25.0%) or LN#18 (50.0%), indicating lymphatic flow around the SMA was leading directly to the paraaortic lymph nodes. Similarly, in pancreatic body and tail cancer, the percentage of ICG-positive LN #16a2 was very high, as was that of #8a, although that of #7 was only 42.9%. Conclusions Our preliminary result indicated that the lymphatic flow along the connective tissues surrounding major arteries could be helpful in understanding metastasis and improving prognosis in BR-A pancreatic cancer.

Abstract Aim The aim of this study was to evaluate the intra‐abdominal status related to postoperative pancreatic fistula by combining postoperative fluid collection and drain amylase levels. Methods We retrospectively reviewed the data of 203 patients who underwent distal pancreatectomy and classified their postoperative abdominal status into four groups based on postoperative fluid collection size and drain amylase levels. We also evaluated the incidence of clinically relevant postoperative pancreatic fistula in each group according to C‐reactive protein values. Results The incidence of clinically relevant postoperative pancreatic fistula in the entire cohort (n = 203) was 28.1%. Multivariate analysis revealed that postoperative fluid collection, drain amylase levels, and C‐reactive protein levels are considerable risk factors for clinically relevant postoperative pancreatic fistula. In the subgroup with large postoperative fluid collection and high drain amylase levels, 65.9% of patients developed clinically relevant postoperative pancreatic fistula. However, no significant difference was observed in C‐reactive protein levels between patients with clinically relevant postoperative pancreatic fistula and those without it. In contrast, in the subgroup with a large postoperative fluid collection size or a high amylase level alone, a significant difference was observed in C‐reactive protein values between the patients with clinically relevant postoperative pancreatic fistula and those without it. Conclusion Postoperative fluid collection status and the C‐reactive protein value provide a more precise assessment of intra=abdominal status related to postoperative pancreatic fistula after distal pancreatectomy. This detailed analysis may be a clinically reasonable approach to individual drain management.

Abstract Background This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections. Case presentation Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon’s capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. Case 2. An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn’t due to progression of nAMD. Conclusions Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.

Objectives: Pharyngeal follicles similar to those seen in influenza have been observed in patients with coronavirus disease 2019 (COVID-19), suggesting their potential as early-stage diagnostic markers. In this study, we examined the diagnostic potential of pharyngeal follicles for COVID-19, particularly the Omicron variant and its subtypes, to obtain basic data for AI-based diagnostic imaging tools. Methods: A cross-sectional study was conducted from July 21, 2022, to March 31, 2023, at the Tokyo Shinagawa Hospital's fever clinic. Participants aged ≥15 years who underwent real-time polymerase chain reaction testing for COVID-19 and pharyngeal examinations were included. Demographic details, symptom onset, throat pain, and vaccination status were also recorded. Pharyngeal structures were categorized into four groups: follicles, buds, mixed, or absent. Results: Of the 1223 participants, 829 (67.8%) tested positive for COVID-19. Among those who tested positive, 73.6% (95% CI: 70.6%-76.6%) had follicular structures, compared to 52.8% (95% CI: 47.9%-57.7%) of those who tested negative (P = 1.0 × 10−12). Overall, 818 participants exhibited follicular structures (439 with follicles, 281 with buds, and 98 with mixed structures), while 405 lacked any follicular structures. Regression analysis identified throat pain and follicular structures as significant COVID-19 predictors (95% confidence intervals: 2.49-4.85 and 1.43-2.59, respectively). Mixed follicles were identified as a potentially characteristic feature of COVID-19. Conclusion: Pharyngeal follicular structures demonstrated high sensitivity for early COVID-19 diagnosis.

Chronic inflammation of the pancreas is considered to be one of the causes of pancreatic cancer. However, the diagnosis of chronic pancreatitis (CP) is very difficult in the pancreas, where biopsies are difficult to perform. The prevalence of CP is estimated to be many times more common than in patients with actual symptomatic CP. In recent years, abnormal cleavage of certain proteins has attracted attention as a biomarker for CP other than pancreatic enzymes. Connective tissue growth factor (CTGF) is one of the growth factors involved in tissue repair and other processes and is increased by stimulation of transforming growth factor-β, suggesting a relationship of CTGF with fibrosis. In this study, we measured the total length of CTGF in blood and N-terminal fragment CTGF in 48 cases of chronic pancreatitis, 64 cases of pancreatic cancer and 45 healthy volunteers (HV). Interestingly, we found that blood N-terminal fragment CTGF level was significantly increased in CP and pancreatic cancer patients. Multiple logistic regression analysis showed serum levels of N-terminal fragment CTGF, CRP and amylase were significant and independent variables for the differential diagnosis of CP from HV. Receiver operating characteristic analysis showed that area under the curve (AUC) value of serum N-terminal fragment CTGF level was 0.933, which can differentiate between CP and HV. Several factors would be involved in the increase in serum N-terminal fragment CTGF level. In conclusion, serum N-terminal fragment CTGF level is a promising new biomarker for CP.

Abstract A new anti-vascular endothelial growth factor agent, brolucizumab, was approved by the United States Food and Drug Administration in 2019. We evaluated whether brolucizumab reduces the treatment burden of neovascular age-related macular degeneration (nAMD) after switching by examining 1-year treatment outcomes in a real-world setting. This retrospective single-institution study included 107 consecutive eyes with nAMD treated with brolucizumab. Among these eyes, 30 with treatment-naïve nAMD and 77 treated with other anti-VEGF agents for more than a year were included. All eyes were managed using a treat and extend (TAE) or modified TAE regimen. The last injection intervals at 52 weeks were 12.9 and 12.1 weeks in the treatment-naïve and switch therapy groups, respectively. Among switch therapy group patients whose pre-switch injection intervals were shorter than 120 days (n = 62 eyes), the injection interval was significantly longer after the switch than before, with a mean difference of 2.7 weeks (P

Nickel (Ni) -base alloy 82 weld material is widely used for the primary reactor components of boiling water reactor (BWR). Although alloy 82 has shown excellent service performance for BWR application in terms of material reliability, several experiences have recently been reported regarding stress corrosion cracking (SCC) in welds associated with alloy 82. The present study aimed at enhancing the SCC resistance of the weld material by developing and evaluating alloy 82 with increased chromium (Cr) content of 30%, 33% and 36%. Weld joint specimens were prepared by tungsten inert gas (TIG) welding with the prototyped wires of alloy 82 with increased Cr content. The mechanical properties and weldability were investigated using the weld joint specimens. For comparison, conventional alloy 82 and alloy 52M were also tested. The mechanical properties of alloy 82 with increased Cr content were equal to or better than those of the conventional alloy 82. The varestraint test and bending test were carried out to determine the weldability. In the varestraint test, the susceptibility to solidification cracking and ductility-dip cracking was evaluated. The temperature ranges of the ductility-dip cracking of the alloy 82 with increased Cr content was about the same as that of the conventional alloy 82. As a result of these tests, it was confirmed that the alloy 82 with increased Cr content has the same weldability as that of the conventional alloy 82 and was applicable for BWR components.

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.

Abstract Introduction The aim of this study was to investigate the safety and efficacy of a single injection of intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) who had a prior treatment history. Methods A retrospective analysis was conducted on a consecutive cohort of 80 eyes of 75 patients with nAMD who had a prior history of treatment with an injection of anti-vascular endothelial growth factor. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and central choroidal thickness (CCT) were compared before the initial IVF injection and after a treatment interval matching the previous duration. Results Central choroidal thickness decreased significantly following the IVF injection, but there was no significant change in BCVA or CST. Mean (± standard deviation) BCVA changed from 0.34 ± 0.37 to 0.36 ± 0.40 (P = 0.29), CST changed from 242 ± 72 to 242 ± 82 µm (P = 0.99), and CCT changed from 189 ± 98 to 179 ± 97 µm (P

Abstract Background After orthotopic liver transplantation (OLT), complications such as hepatic artery stenosis, thrombosis, and bleeding are possible. Hepatic artery pseudoaneurysms (HAP) are prone to rupture, rupture hemorrhage, and increased mortality risk. Endovascular treatment of HAP may result in recurrence, even after successful embolization with thrombin. Formation of a HAP in the common hepatic artery (CHA) is challenging because the CHA is the only artery in the liver graft after OLT. Therefore, CHA embolization in HAP is not an initial option. We report a case of HAP at the CHA after OLT that was treated with endovascular therapy, resulting in the occlusion of the CHA with coil embolization, achieving a radical cure. Case presentation A 59-year-old man with decompensated hepatitis C virus cirrhosis underwent deceased donor whole-liver transplantation after graft failure of a living donor liver transplantation. After the second transplantation, the patient developed infectious narrow-necked HAP at the CHA associated with postoperative pancreatic fistula. Repeated transcatheter arterial embolization with thrombin and n-butyl-2-cyanoacrylate was unsuccessful, as confirmed by postprocedure angiography, which revealed recanalization and regrowth of the HAP. Eight months after the first transcatheter arterial embolization, the patient presented with a chief complaint of abdominal pain due to an enlarged HAP. Angiography of the superior mesenteric artery (SMA) revealed a collateral bypass around the bile duct from the SMA to the liver graft. Coil embolization of the HAP in the CHA completely occluded the HAP without complications. More than 2 years after coil embolization, the liver graft function test results remained within normal limits without HAP recurrence. Conclusions HAP at the CHA after liver transplantation can be fatal if ruptured. Because the liver is a highly angiogenic organ, even if initial treatment is not successful, radical treatment to occlude the CHA with HAP is possible if sufficient collateral vessels are developed.

Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1α (SDF-1α)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: “indirect effects” mediated by angiogenesis and “direct effects” of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.

The estimation of central choroidal thickness from colour fundus images can improve disease detection. We developed a deep learning method to estimate central choroidal thickness from colour fundus images at a single institution, using independent datasets from other institutions for validation. A total of 2,548 images from patients who underwent same-day optical coherence tomography examination and colour fundus imaging at the outpatient clinic of Jichi Medical University Hospital were retrospectively analysed. For validation, 393 images from three institutions were used. Patients with signs of subretinal haemorrhage, central serous detachment, retinal pigment epithelial detachment, and/or macular oedema were excluded. All other fundus photographs with a visible pigment epithelium were included. The main outcome measure was the standard deviation of 10-fold cross-validation. Validation was performed using the original algorithm and the algorithm after learning based on images from all institutions. The standard deviation of 10-fold cross-validation was 73 μm. The standard deviation for other institutions was reduced by re-learning. We describe the first application and validation of a deep learning approach for the estimation of central choroidal thickness from fundus images. This algorithm is expected to help graders judge choroidal thickening and thinning.

Abstract In general, it is known that extreme climatic conditions such as El Niño and positive Indian Ocean Dipole (IOD+) cause prolonged drought in Indonesia's tropical peatlands so that groundwater levels (GWL) drop and peat is prone to fire. However, 27 years of GWL measurements in Central Kalimantan peat forests show the opposite condition, where the lowest GWL occurs several weeks before El Niño and after IOD+ reaches its peaks. We show that the dropped sea surface temperature anomaly induced by anomalously easterly winds along the southern Java-Sumatra occurs several weeks before the GWL drop to the lowest value. Local rainfall decreased, and GWL dropped sharply by 1.0 to 1.5 m, during the super El Niño events in 1997/98 and 2015, as well as remarkable events of IOD+ in 2019. It is suggested that the tropical peatland ecohydrological system (represented by the GWL), El Niño Southern Oscillation (ENSO), and IOD+ are teleconnected. Hence, monitoring GWL variability of peatland over the IMC is a possibility an alert for extreme climate events associated with El Niño and/or moderate IOD+.

Abstract Background Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19–9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT). Methods This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured. Results Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03–4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039). Conclusion Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis.

Abstract Background Rendu–Osler–Weber disease (Osler disease) is a genetic disease with an autosomal dominant inheritance pattern. It is characterized by widespread telangiectasia in multiple organs. Liver involvement of FNH is relatively common, but liver cancer is very rare, and there are few reports on hepatectomy or postoperative complications. We report a very rare case in which hepatectomy was performed for a patient with Osler disease. Case presentation The patient was a 39-year-old man with Osler disease who had been previously diagnosed with multiple FNH and who had been followed for 8 years. During follow-up, the diameter of an S6 lesion gradually increased from 30 to 50 mm; no other lesions increased in size. We decided to perform partial liver resection as total biopsy for the growing tumor, due to the possibility that the growing tumor lesion included malignant components. The pathological examination revealed no obvious malignancy, which was finally diagnosed FNH. The postoperative course was uneventful and he was discharged on the 14th day after surgery. In the second month after discharge, he was transferred to our hospital with sudden abdominal pain in the right hypochondrium with severe tenderness. CT showed extravasation of contrast medium from the hepatic dissection surface in S6, and the hematoma extended to the pelvic floor. Emergency IVR was performed and revealed leakage of the contrast medium from the A6 branch. We embolized the A6 with Lipiodol. After embolization, there were no major problems, and the patient was discharged on the 9th day after the treatment. Conclusions Postoperative hemorrhage often occurs within 24 h after surgery, and 2 months after surgery is considered to be the late stage of the wound healing process, and postoperative hemorrhage at this timepoint is considered rare. This unexpected delayed postoperative hemorrhage may have been related to the etiology and pathology of Osler disease, nevertheless, case reports of hepatectomy for patients with Osler disease are limited. We, therefore, report the present case with a review of the relevant literature.

Abstract Aims/Introduction The increase in the number of patients with type 2 diabetes mellitus is an important concern worldwide. The goal of this study was to investigate factors involved in the onset of type 2 diabetes mellitus, and sex differences in long‐term follow up of people with normal glucose tolerance. Materials and Methods Of 1,309 individuals who underwent screening at our facility in 2004, 748 individuals without diabetes were enrolled. Correlations of metabolic markers including serum adiponectin (APN) with onset of type 2 diabetes mellitus were examined over 15 years in these individuals. Results The Kaplan–Meier curve for onset of type 2 diabetes mellitus for 15 years in the decreased APN group was examined. Hazard ratios for the APN concentration for onset of diabetes were 1.78 (95% confidence interval [CI] 1.20–2.63, P = 0.004) in all participants, 1.48 (95% CI 0.96–2.29, P = 0.078) for men and 3.01 (95% CI 1.37–6.59, P = 0.006) for women. During the follow‐up period of 15 years, body mass index, estimated glomerular filtration rate, fatty liver, C‐reactive protein and alanine aminotransferase in men were significant in univariate analysis, but only estimated glomerular filtration rate and fatty liver were significantly related to onset of type 2 diabetes mellitus in multivariate analysis. In women, body mass index, systolic blood pressure, triglyceride, fatty liver and APN were significant in univariate analysis, and APN was the only significant risk factor in multivariate analysis (P

Mass spectrometry is a powerful approach for untargeted lipidomics, however, the unambiguous determination of double bond positions remains challenging. Here, the authors present an approach for double bond position-resolved untargeted lipidomics using a combination of oxygen attachment dissociation and computational mass spectrometry to accurately annotate the biologically relevant lipidome.

Abstract We herein propose a PraNet-based deep-learning model for estimating the size of non-perfusion area (NPA) in pseudo-color fundus photos from an ultra-wide-field (UWF) image. We trained the model with focal loss and weighted binary cross-entropy loss to deal with the class-imbalanced dataset, and optimized hyperparameters in order to minimize validation loss. As expected, the resultant PraNet-based deep-learning model outperformed previously published methods. For verification, we used UWF fundus images with NPA and used Bland–Altman plots to compare estimated NPA with the ground truth in FA, which demonstrated that bias between the eNPA and ground truth was smaller than 10% of the confidence limits zone and that the number of outliers was less than 10% of observed paired images. The accuracy of the model was also tested on an external dataset from another institution, which confirmed the generalization of the model. For validation, we employed a contingency table for ROC analysis to judge the sensitivity and specificity of the estimated-NPA (eNPA). The results demonstrated that the sensitivity and specificity ranged from 83.3–87.0% and 79.3–85.7%, respectively. In conclusion, we developed an AI model capable of estimating NPA size from only an UWF image without angiography using PraNet-based deep learning. This is a potentially useful tool in monitoring eyes with ischemic retinal diseases.

Abstract In cases after pancreas transplantation (PTx), the pancreas graft might be lost for various reasons, including a pancreatoduodenal graft-related complication or patient death with a functioning graft. Although the causes seem to have distinct characteristics, the causes of pancreas graft loss have not been characterized. This study aimed to characterize the causes of pancreas graft loss by analyzing data from a Japanese nationwide registry. This study included 391 patients who received simultaneous pancreas-kidney transplantation among 461 patients with PTx during the study period in approved institutions in Japan. We characterized each cause in terms of the timing of the cause-specific graft loss and preoperative factors associated with graft loss based on nationwide data from a Japanese nationwide registry. Among the 391 cases, 113 lost the pancreas graft due to patient death with a functioning graft (DWFG; n = 34, 44.2%), graft thrombus (n = 22, 28.6%), or chronic rejection (CR; n = 7, 9.1%). Average (± standard deviation) time from PTx to graft loss due to DWFG, graft thrombus, and CR was 3.70 ± 4.36, 0.02 ± 0.01, and 2.37 ± 2.08 years, respectively. Duration of type 1 diabetes mellitus and donor body mass index were significantly associated with pancreas graft loss due to DWFG and graft thrombus, respectively. This characterization showed that the timing and preoperative factors associated with pancreas graft loss were significantly different for different causes of graft loss. These results may inform PTx follow-up protocols to ensure that appropriate care is based on the cause of graft loss.

Abstract Background SMAD4 is a key mediator of TGFβ signaling and one of the mutated genes in extrahepatic bile duct cancer (eBDC). It has been also reported that SMAD4 has dual functions, in carcinogenesis via silencing and in tumor invasion/metastasis via signaling, depending on tumor stage. We previously visualized more nuclear transitioning functional SMAD4 at the tumor invasion front than the central lesion. So, we investigated the localization of functional SMAD4 (e.g., invasion area or metastasis lesion) and its association with chemotherapy and chemo-radiation therapy. Methods We performed SMAD4 immunostaining on 98 resected eBDC specimens and evaluated the presence of the functional form of nuclear SMAD4 at the central lesion, invasion front, and metastatic lymph node. We also examined the influence on chemotherapy after recurrence (n = 33) and neoadjuvant chemo-radiation therapy (NAC-RT, n = 21) and the prognostic value of using retrospective data. Results In 73 patients without NAC-RT, 8.2% had loss of SMAD4 expression and 23.3% had heterogeneous expression. Patients without SMAD4 expression at any site had significantly poorer overall survival (OS) than other patients (P = 0.014). Expression of SMAD4 at the invasion front was related to better survival (recurrence-free survival [RFS] P = 0.033; OS P = 0.047), and no SMAD4 expression at the metastatic lymph node was related to poorer OS (P = 0.011). The patients who had high SMAD4 expression had poorer prognosis after recurrence (RFS P = 0.011; OS P = 0.056). At the residual cancer in the resected specimen, SMAD4 was highly expressed after NAC-RT (P = 0.039). Conclusions Loss of SMAD4 protein expression was a poor prognostic factor in eBDC at resectable stage. However, the intensity of functional SMAD4 in eBDC is a marker of resistance to chemo-radiotherapy and malignant potential at advanced stages.

Genetic mechanisms influencing COVID-19 susceptibility are not well understood. Here, the authors analyzed whole blood RNA-seq data of 465 Japanese individuals with COVID-19, highlighting thousands of fine-mapped variants affecting expression and splicing of genes, as well as the presence of COVID-19 severity-interaction eQTLs.

We studied the optical variability of 241 BL Lacertae (BL Lacs) and 83 flat-spectrum radio quasars (FSRQs) from the 4LAC catalog using data from the Tomo-e Gozen Northern Sky Transient Survey, with ∼50 epochs per blazar on average. We excluded blazars whose optical variability may be underestimated due to the influence of their host galaxy based on their optical luminosity ( L _O ). FSRQs with γ -ray photon index greater than 2.6 exhibit very low optical variability, and their distribution of standard deviation of repeated photometry is significantly different from that of the other FSRQs (Kolmogorov–Smirnov test p -value equal to 5 × 10 ^−6 ). Among a sample of blazars at any particular cosmological epoch, those with lower γ -ray luminosity ( L _γ ) tend to have lower optical variability, and those FSRQs with a γ -ray photon index greater than 2.6 tend to have low L _γ . We also measured the structure function of optical variability and found that the amplitude of the structure function for FSRQs is higher than previously measured and higher than that of BL Lacs at multiple time lags. Additionally, the amplitude of the structure function of FSRQs with high γ -ray photon index is significantly lower than that of FSRQs with low γ -ray photon index. The structure function of FSRQs of high γ -ray photon index shows a characteristic timescale of more than 10 days, which may be the variability timescale of the accretion disk. In summary, we infer that the optical component of FSRQs with high γ -ray photon index may be dominated by the accretion disk.

We present a multiple emission line study of ∼1300 H α emitters (HAEs) at z ∼ 2.3 in the ZFOURGE survey. In contrast to the traditional spectroscopic method, our sample is selected based on the flux excess in the ZFOURGE K _s broadband data relative to the best-fit stellar continuum. Using the same method, we also extract the strong diagnostic emission lines for these individual HAEs: [O iii ] λ λ 4959, 5007 and [O ii ] λ λ 3726, 3729. Our measurements demonstrate good consistency with those obtained from spectroscopic surveys. We investigate the relationship between the equivalent widths (EWs) of these emission lines and various galaxy properties, including stellar mass, stellar age, star formation rate, specific star formation rate, and ionization state (O32). We have identified a discrepancy between HAEs at z ∼ 2.3 and typical local star-forming galaxies observed in the Sloan Digital Sky Survey, suggesting the evolution of lower gas-phase metallicity ( Z ) and higher ionization parameters ( U ) with redshift. Notably, we have observed a significant number of low-mass HAEs exhibiting exceptionally high EW _[O _iii _] . Their galaxy properties are comparable to those of extreme objects, such as extreme O3 emitters and Ly α emitters at z ≃ 2–3. Considering that these characteristics may indicate potential strong Lyman continuum leakage, higher-redshift analogs of the low-mass HAEs could be significant contributors to the cosmic reionization. Further investigations of this particular population are required to gain a clearer understanding of galaxy evolution and cosmic reionization.

Abstract Objectives Perihilar cholangiocarcinoma (PCC) is a complex disorder involving the hepatic hilum. Multiple endoscopic retrograde cholangiopancreatography sessions are necessary for diagnosis and treatment with underlying cholangitis risk. Our aim is to clarify the initial‐drainage‐related prognostic factors of PCC. Methods This study was a single‐center retrospective study. A total of 104 consecutive patients diagnosed with PCC from January 2010 to February 2020 were enrolled. We defined the diagnostic period as the time between the first biliary drainage attempt and the final drainage when treatment, including surgery or chemotherapy, was started. We focused on this initial period and analyzed the endoscopy‐related factors that affected mortality. Results Overall survival of all PCC patients was 599 days. Overall survival of surgically treated patients and unresectable patients were 893 days and 512 days, respectively. In 48 surgically treated patients, drainage‐related cholangitis within the diagnostic period, defined as new cholangitis that occurred after the first biliary drainage attempt, worsened overall survival from 1460 days to 607 days. Endoscopic sphincterotomy, the first drainage method other than endoscopic nasobiliary drainage, and four or more endoscopic retrograde cholangiopancreatography sessions were risk factors for drainage‐related cholangitis. Drainage‐related cholangitis increased pathological lymph node metastasis. Percutaneous transhepatic biliary drainage as final drainage was the only prognostic factor in unresectable chemotherapy‐treated patients. Conclusions Drainage‐related cholangitis worsened the prognosis in PCC patients who underwent surgery. Appropriate endoscopic retrograde cholangiopancreatography strategies, especially during the diagnostic period, are of great importance in PCC.

Abstract Urinary free-glycans are promising markers of disease. In this study, we attempted to identify novel tumor markers by focusing on neutral free-glycans in urine. Free-glycans extracted from the urine of normal subjects and cancer patients with gastric, colorectal, pancreatic and bile duct were fluorescently labeled with 2-aminopyridine. Profiles of these neutral free-glycans constructed using multidimensional high performance liquid chromatography separation were compared between normal controls and cancer patients. The analysis identified one glycan in the urine of cancer patients with a unique structure, which included a pentose residue. To reveal the glycan structure, the linkage fashion, monosaccharide species and enantiomer of the pentose were analyzed by high performance liquid chromatography and mass spectrometry combined with several chemical treatments. The backbone of the glycan was a monoantennary complex-type free-N-glycan containing β1,4-branch. The pentose residue was attached to the antennal GlcNAc and released by α1,3/4-l-fucosidase. Intriguingly, the pentose residue was consistent with d-arabinose. Collectively, this glycan structure was determined to be Galβ1-4(d-Araβ1-3)GlcNAcβ1-4Manα1-3Manβ1-4GlcNAc-PA. Elevation of d-arabinose-containing free-glycans in the urine of cancer patients was confirmed by selected reaction monitoring. This is the first study to unequivocally show the occurrence of a d-arabinose-containing oligosaccharide in human together with its detailed structure.

Abstract Background Although the RECOVERY trial showed that dexamethasone was efficacious for the treatment of coronavirus disease 2019 (COVID-19), its impact on the risk of pulmonary embolism (PE) and other serious procoagulant events was not assessed. Case presentation Here we report the case of a previously healthy 83-year-old woman with COVID-19, without any genetic predisposition to thrombosis. She developed moderate respiratory distress 12 days after symptom onset and a 10-day course of dexamethasone therapy was initiated. Her clinical condition and imaging findings improved initially; however, they deteriorated after the completion of dexamethasone therapy, despite the improvement in her pneumonia and viral clearance. Laboratory tests showed markedly raised serum D-dimer, ferritin, and sIL-2R levels, and contrast-enhanced computed tomography showed deep vein thrombosis (DVT) in the left iliac vein and PE of the right pulmonary artery. The DVT and PE were successfully treated using intravenous heparin administration. Conclusions This case illustrates the potential risk of rebound inflammation and procoagulant events following dexamethasone withdrawal. We believe that COVID-19-induced DVT and PE can be affected by dexamethasone therapy. Although dexamethasone reduces procoagulant factors, increases anticoagulant factors, and modulates cytokines, which can suppress/delay thrombus formation during treatment, it confers the risk for rebound cytokine production after treatment completion, triggering cytokine and coagulation cascades that can lead to thromboembolic diseases. In this critical clinical period, the patient’s deteriorating condition may be overlooked because of the masking effects of dexamethasone treatment on fever and other clinical conditions and laboratory changes. Clinicians should follow-up coagulation markers carefully and contrast-enhanced computed tomography is useful for detecting coagulation; and, if PE occurs, therapeutic heparin administration is essential because emboli can also generate cytokines.

Abstract We modeled the vertical deformation detected from a leveling survey in Jigokudani valley, Tateyama volcano, central Japan. In Jigokudani valley, uplift of 4 cm/year was previously detected during the period from 2007 to 2010 by interferometric synthetic aperture radar (InSAR). To confirm whether this inflation has continued to present day, we have conducted leveling surveys in Jigokudani valley since 2015. Most bench marks showed a subsidence of up to 5.6 cm during the 4-year period from October 2016 to September 2020, while a bench mark located at the center of the leveling route uniquely showed an uplift of 1.6 cm. We applied a dislocation source model to the deformation using a grid search method. A crack with a length of 650 m, a width of 425 m, a strike of N18° E and a dip of 67° is located at a depth of 50 m near the center of Jigokudani valley (Koya jigoku and the new fumarolic area) where higher activity has been observed recently. Closing of the crack of 59 cm yields a volume decrease of 163,000 m3. The closing direction of the crack is parallel to the line of old explosion craters (Mikurigaike and Midorigaike ponds) and corresponds to the current maximum compressive stress field in the region of the Hida Mountains, including Tateyama volcano. The deformation source of the previous period from 2007 to 2010 detected from InSAR was estimated to be at a depth of 50 m and a gas chamber was correspondingly found in an audio-frequency magnetotelluric (AMT) survey. The AMT survey also revealed that thermal fluid is accumulating from a magma chamber and the location of our crack is similar to uppermost part of the thermal fluid path. During the period from 2015 to 2016, the crack opened and the inflation stopped during the next 1 year period from 2016 to 2017. During the period from 2017 to 2020, the crack began closing, probably because of the increase in emissions of volcanic fluid or gas with the formation of a new crater at the western side of Jigokudani valley during the period from 2017 to 2018. Graphical Abstract

Abstract Background Gastric cancer with portal vein tumor thrombus (PVTT) is poor prognosis, and the treatment remains challenging. Regarding surgery, there are only reports of highly invasive laparotomy. We report some techniques of the completely robotic total gastrectomy with thrombectomy and portal vein reconstruction for the patient with gastric cancer and PVTT for the first time. Case presentation A 79-year-old man was diagnosed with a 5-cm gastric cancer on the side of the lesser curvature from the middle of the gastric body to the cardia. Computed tomography revealed a massive PVTT extending from the left gastric vein to the portal trunk (28 x 16 mm). There were no other distant metastases. After 3 cycles of the chemotherapy, the PVTT shrank to 19 x 12 mm. After obtaining informed consent from the patient, robotic total gastrectomy with regional lymphadenectomy and thrombectomy were performed. We used the da Vinci Xi Surgical System. A 3-cm incision was made at the umbilicus, and a wound retractor was placed. Five additional ports were placed. The right side suprapancreatic lymph nodes were performed at the time of the thrombectomy. It was important to identify the precise extent of the PVTT with intraoperative ultrasonography before the thrombectomy. After PVTT identification, the portal trunk was clamped above and below the tumor thrombus with vascular clips. The membrane on the anterior wall of the portal trunk around the PVTT was carefully incised with da Vinci Scissors. The tumor thrombus was completely enucleated without separation. The incised part of the portal trunk was reconstructed with continuous 5-0 synthetic monofilament nonabsorbable polypropylene sutures. After removing the vascular clamps, we made sure there was no leakage from the portal vein and no tumor thrombus remnants with intraoperative ultrasonography. Robotic total gastrectomy with lymphadenectomy and Roux-en-Y reconstruction were performed. The patient was discharged without complications. The patient has remained alive for 30 months after surgery. Conclusions Robotic total gastrectomy with thrombectomy and portal vein reconstruction is a safe, minimally invasive, and precise surgery. It may contribute to improved prognosis of gastric cancer with PVTT when combined with chemotherapy.

Abstract Purpose Pathological extramural venous invasion (EMVI) is defined as the active invasion of malignant cells into veins beyond the muscularis propria in colorectal cancer. It is associated with poor prognosis and increases the risk of disease recurrence. Specific findings on MRI (termed MRI-EMVI) are reportedly associated with pathological EMVI. In this study, we aimed to identify risk factors for lateral lymph node (LLN) metastasis related to rectal cancer and to evaluate whether MRI-EMVI could be a new and useful imaging biomarker to help LLN metastasis diagnosis besides LLN size. Methods We investigated 67 patients who underwent rectal resection and LLN dissection for rectal cancer. We evaluated MRI-EMVI grading score and examined the relationship between MRI-EMVI and LLN metastasis. Results Pathological LLN metastasis was detected in 18 cases (26.9%), and MRI-EMVI was observed in 32 cases (47.8%). Patients were divided into two cohorts, according to LLN metastasis. Multivariate analyses demonstrated that higher risk of LLN metastasis was significantly associated with MRI-EMVI (P = 0.0112) and a short lateral lymph node axis (≥ 5 mm) (P = 0.0002). The positive likelihood ratios of MRI-EMVI alone, LLN size alone, and the combination of both factors were 2.12, 4.84, and 16.33, respectively. Patients negative for both showed better 2-year relapse-free survival compared to other patients (84.4% vs. 62.1%, P = 0.0374). Conclusions MRI-EMVI was a useful imaging biomarker for identifying LLN metastasis in patients with rectal cancer. The combination of MRI-EMVI and LLN size can improve diagnostic accuracy.

Abstract Purpose Postoperative pancreatic fistula is a serious complication of distal pancreatectomy. Although many studies have described the incidence and risk factors associated with postoperative pancreatic fistula (POPF), few have focused on the healing time. This study investigated the healing time and potential factors associated with the healing time of POPF after distal pancreatectomy (DP). Methods Among 114 patients that underwent DP in our hospital from January 2010 to December 2020, we included 88 that developed POPF. The healing time for a postoperative pancreatic fistula was defined as the interval between the completion of DP and the removal of all drains related to the treatment for POPF. Based on the definition, three cases who required additional treatment after removal of all drains were excluded from this study. Clinical factors associated with the fistula healing times were investigated in the 85 patients. Results The average POPF healing time was 11 ± 10 days (median: 6 days, range: 3‐57). We found that the neutrophil‐to‐lymphocyte ratio, a marker of inflammatory and nutritional status, was the only factor independently associated with the POPF healing time; the mean healing time was significantly shorter in patients with neutrophil‐to‐lymphocyte ratio ≤2.1 (8 ± 6 days) than in those with neutrophil‐to‐lymphocyte ratio >2.1 (13 ± 12 days; P = .0139). Conclusion We demonstrated that the neutrophil‐to‐lymphocyte ratio could independently predict the POPF healing time after DP. These findings suggested that improving the neutrophil‐to‐lymphocyte ratio might shorten the healing times for POPF after DP.

Abstract Background The chorioretinal inflammatory lesions occurring in punctate inner choroiditis evolve into punched-out atrophic scars. Typically, the progression is gradual. We report a case of highly myopic punctate inner choroiditis with rapid progression of chorioretinal atrophy. Case presentation A 48-year-old Japanese woman with high myopia presented with decreased visual acuity. Best-corrected visual acuity was 20/28 in the right eye and 20/16 in the left eye; axial length was 29.0 mm and 28.7 mm, respectively. Fundoscopy revealed an epiretinal membrane in the left eye. Three years later, the best-corrected visual acuity in the left eye had decreased to 20/33; at this time, the patient underwent vitrectomy with epiretinal membrane and internal limiting membrane peeling in this eye. Six months later, the best-corrected visual acuity in the left eye decreased suddenly to 20/100. Optical coherence tomography showed a nodule-like lesion in the outer retina with disruption of the retinal pigment epithelium and a focally thickened choroid, compatible with PIC. One month later, the choroidal thickness had decreased. The central chorioretinal atrophy expanded rapidly at a rate of 0.45 mm2/year over the next 3 years, and new areas of patchy focal chorioretinal atrophy developed in the perifovea. Conclusions Rapid progression of chorioretinal atrophy was observed in a patient with punctate inner choroiditis. Because punctate inner choroiditis is often associated with degenerative myopia, the retina is fragile and may be susceptible to mechanical damage. This case report alerts clinicians to the need for careful management of patients with punctate inner choroiditis, especially after vitrectomy.

Computer simulations using the combination of finite element method and modal analysis are now common methods for vibration prediction. However, when it comes to detailed models with large degrees-of-freedom, it is time consuming to evaluate and treat each characteristic mode one by one. Therefore, an efficient vibration analysis method is strongly desired. Macroscopically, characteristic modes of vehicle bodies, which mainly consist of frame structures and attached panels, are regarded as combinations of global and local deformations. Global deformation is attributable to frame structure which is defined as main component of the model, and local deformation is attributable to each panel component defined as sub component. As these deformations differ in priorities and countermeasures in design phase, it is essential to clarify the relation of global and local deformations, especially when they combine and compose coupled vibration. The purpose of this study is to present an analytical method to efficiently evaluate characteristic modes based on global and local deformations. In this paper, component mode decomposition is proposed to automatically decompose global and local deformation from characteristic modes of a frame-panel structure model. In this method, characteristic mode is first transformed into volume data and then three-dimensional wavelet transform is applied to separate global and local deformations. Then, from these separated deformations, component mode which consists of each single global and local deformation is derived using orthogonal transformation. By means of this orthogonal transformation, characteristic modes are effortlessly analyzed how much they contain each global and local deformation. In this paper, the proposed method is demonstrated on a simple frame-panel structure model.

Abstract Background Total mesorectal excision (TME) and lateral lymph node dissection (LLND) without radiotherapy (RT) are standard treatment for lower cT3/4 rectal cancers in Eastern countries. In comparative studies, both TME + LLND and RT + TME yield good local control. Although Japanese guidelines recommend LLND for locally advanced rectal cancers below the peritoneal reflection, LLND dissection of clinically negative lateral pelvic lymph nodes (LPLN) is controversial, and laparoscopic TME + LLND is technically challenging and time-consuming. New optical instruments for laparoscopy allow easy perioperative sentinel lymph node (SLN) identification using ICG. The SLN concept may facilitate accurate diagnosis of LPLN involvement, and thus reduce LLND in laparoscopic rectal cancer surgery. Here we investigated lateral pelvic SLN navigation surgery for SLN detection during laparoscopic rectal cancer surgery. Methods This study included 21 patients with clinical StageII/III lower rectal cancer without LPLN enlargement, who underwent curative laparoscopic surgery. All patients underwent TME, followed by lateral SLN identification and biopsy using ICG, and then laparoscopic LLND. ICG fluorescence imaging was conducted using the laparoscopic near-infrared camera system. Results Lateral SLNs were successfully identified in 16 (76.2%) of the 21 patients. Among the 15 patients without SLN tumor metastasis, the dissected lateral non-SLNs were all negative. Conclusions A lack of metastasis in the lateral pelvic SLN seems to reflect a lack of metastases to all lateral LNs. Our present results suggest that this laparoscopic ICG-guided SLN strategy may be a low-risk and time-saving method to prevent laparoscopic LLND in cases with negative lateral pelvic lymph nodes.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and multimodal strategies, such as surgery plus neoadjuvant chemotherapy (NAC)/adjuvant chemotherapy, have been attempted to improve survival in patients with localized PDAC. To date, there is one prospective study providing evidence for the superiority of a neoadjuvant strategy over upfront surgery for localized PDAC. However, which NAC regimen is optimal remains unclear. Methods A randomized, exploratory trial is performed to examine the clinical benefits of two chemotherapy regimens, gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GA), as NAC for patients with planned PDAC resection. Patients are enrolled after the diagnosis of resectable or borderline resectable PDAC. They are randomly assigned to either NAC regimen. Adjuvant chemotherapy after curative resection is highly recommended for 6 months in both arms. The primary endpoint is tumor progression-free survival time, and secondary endpoints include the rate of curative resection, the completion rate of protocol therapy, the recurrence type, the overall survival time, and safety. The target sample size is set as at least 100. Discussion This study is the first randomized phase II study comparing GS combination therapy with GA combination therapy as NAC for localized pancreatic cancer. Trial registration UMIN Clinical Trials Registry UMIN000021484 . This trial began in April 2016.

Abstract The aim of this study was to compare aqueous humour (AqH) cytokine profiles before and after Descemet’s membrane endothelial keratoplasty (DMEK) in eyes with bullous keratopathy (BK) and age-matched normal eyes. A total of 49 participants (mean age 75.0 ± 13.5 years) were divided into three groups: (1) BK patients scheduled for DMEK (BK group); (2) patients after DMEK (DMEK group; average postoperative time 1,018 ± 460 days); and (3) control participants without corneal endothelial disease scheduled for cataract surgery (control group). AqH (0.2 mL) was collected from all participants, and the levels of various AqH cytokines were simultaneously measured using a multiplex bead immunoassay. The DMEK group exhibited significantly lower concentrations of several pro-inflammatory cytokines, such as IL-1β, IL-5, IL-6, IL-10, and IL-8, and granulocyte colony stimulating factor than the BK group. In addition, the levels of IL-1β and IL-5 were significantly lower in the DMEK group than in the control group. The AqH levels of several pro-inflammatory cytokines were significantly reduced after DMEK, indicating that regeneration of the endothelial pump owing to the transplantation of a healthy endothelium might have a positive effect on anterior chamber inflammation.

Summary: Single-cell RNA sequencing (scRNAseq) has been used to assess the intra-tumor heterogeneity and microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, previous knowledge is not fully universalized. Here, we built a single cell atlas of PDAC from six datasets containing over 70 samples and >130,000 cells, and demonstrated its application to the reanalysis of the previous bulk transcriptomic cohorts and inferring cell–cell communications. The cell decomposition of bulk transcriptomics using scRNAseq data showed the cellular heterogeneity of PDAC; moreover, high levels of tumor cells and fibroblasts were indicative of poor-prognosis. Refined tumor subtypes signature indicated the tumor cell dynamics in intra-tumor and their specific regulatory network. We further identified functionally distinct tumor clusters that had close interaction with fibroblast subtypes via different signaling pathways dependent on subtypes. Our analysis provided a reference dataset for PDAC and showed its utility in research on the microenvironment of intra-tumor heterogeneity.

In port and harbour areas, soft soils such as dredged soil can be solidified by mixing them with cement and other solidifiers in a pumping pipe. This method is known as pneumatic flow mixing. In this method, the soil and solidifiers are stirred and mixed using the turbulence effect of the plug flow generated in the pipe. The authors investigate the long-term durability of the treated soil on the artificial island where this method was first fully introduced. This paper summarises the results of five investigations on the island immediately after construction and 4, 10, 15, and 20 years after construction. No reduction in the unconfined compressive strength or needle penetration gradient was observed in the treated soil. Some degradation was observed at the top and bottom exposed surfaces of the treated soil, similar to that of soil subjected to other treatments. In addition to needle penetration and chemical tests, elemental mapping using an electron beam microanalysis was performed to determine the degree of degradation. The depth of degradation 20 years after construction was 18–25 mm. Although the amount of cement added in the pneumatic flow mixing method was relatively small, this value was within the range of degradation depths over time investigated in previous studies and did not represent a significant degradation.

Detection of early clinical keratoconus (KCN) is a challenging task, even for expert clinicians. In this study, we propose a deep learning (DL) model to address this challenge. We first used Xception and InceptionResNetV2 DL architectures to extract features from three different corneal maps collected from 1371 eyes examined in an eye clinic in Egypt. We then fused features using Xception and InceptionResNetV2 to detect subclinical forms of KCN more accurately and robustly. We obtained an area under the receiver operating characteristic curves (AUC) of 0.99 and an accuracy range of 97–100% to distinguish normal eyes from eyes with subclinical and established KCN. We further validated the model based on an independent dataset with 213 eyes examined in Iraq and obtained AUCs of 0.91–0.92 and an accuracy range of 88–92%. The proposed model is a step toward improving the detection of clinical and subclinical forms of KCN.

Abstract Aim The management of diabetes mellitus (DM) after pancreatic surgery is a long‐standing issue. We aimed to investigate DM concerning pancreatic surgery, including new onset diabetes mellitus (NODM), DM resolution, and the change in insulin excretion before/after pancreatic surgery. Methods We retrospectively investigated three different cohorts (total 403 patients) undergoing pancreatectomy. Of those, 275 patients without preoperative DM were investigated for the risk factors of NODM. Fifty‐four patients without preoperative DM of the other cohort were assessed for pre/postoperative 24‐hour urinary C‐peptide excretion (24‐hr CPR). To evaluate the influence of pancreatic surgery on DM treatment in patients with preoperative DM, 74 patients were investigated. In all those patients, the pancreatic volume in pre/postoperative images was assessed to estimate the resected pancreatic volume. Results NODM was observed in 60 patients (21%), and a lower ratio of remnant pancreatic volume (RRPV) was the only significant risk factor for NODM. Postoperative 24‐hr CPR was significantly associated with two factors, RRPV and preoperative 24‐hr CPR. Nine of 74 patients with preoperative DM achieved DM resolution after pancreatic surgery, and the presence of gastrointestinal anastomosis was a significant preferable factor for DM resolution. Conclusions Considering the management of DM after surgery, both predicting the postoperative pancreatic volume and the presence of gastrointestinal reconstruction are significant. We concluded that the combined assessment of the predicted remnant pancreatic volume and the preoperative 24‐hr CPR value is useful to predict the postoperative pancreatic function.

Objectives: Anastomotic leakage is one of the most severe complications of rectal cancer surgery. A diverting ileostomy was constructed for the purpose of reducing anastomotic failure risk. Outlet obstruction (OO) is one of the complications of diverting stoma that results in a lack of fecal discharge from the stoma. Detailed etiologies and preventive measures for outlet obstruction have not yet been identified. Methods: We studied 125 patients who underwent rectal resection, anastomosis, and elective ileostomy. We evaluated the incidence of outlet obstruction and looked for any relationship between perioperative factors and outlet obstruction. Results: Outlet obstruction was detected in 20 cases (16.0%). Outlet obstruction occurred 9 days after surgery in most cases. Inserting a decompressing tube improved obstructive symptoms in 4 days. Patients were divided into two cohorts according to the occurrence of outlet obstruction. Postoperative hospital stay was longer in the outlet obstruction group (19 vs. 15 days; p = 0.0003). A multivariate analysis identified that younger patients, a postoperative thicker rectus abdominis muscle at the stoma passage and high output syndrome were independent risk factors for outlet obstruction. Conclusions: Younger patients, a postoperative thicker rectus abdominis muscle at stoma passage and high output syndrome were independent risk factors for outlet obstruction.

Abstract JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504–0.937) in the low CCr group. Although the total number of incidences of all Grade 3–4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.

Abstract We report the cases of two patients with secondary hemophagocytic lymphohistiocytosis caused by immune checkpoint inhibitors, who were diagnosed using the recently developed HScore. The first patient presented with fever, cytopenia, and elevated liver enzyme levels at 46 days post‐pembrolizumab administration. The HScore was 175. The second patient developed an immune‐related adverse event at 30 days after the final pembrolizumab dose. The HScore was 185. Hemophagocytic lymphohistiocytosis was confirmed in both patients, and corticotherapy improved their condition. It is challenging to diagnose hemophagocytic lymphohistiocytosis, particularly after development at a late stage. Our patients developed hemophagocytic lymphohistiocytosis late after immune checkpoint inhibitor administration. However, the HScore enabled us to diagnose both cases precisely and in a timely manner.