Relationship Between the Lipidome Profile and Disease Activity in Patients with Rheumatoid Arthritis.

Lipid mediators have been suggested to play important roles in the pathogenesis of rheumatoid arthritis (RA). Lipidomics has recently allowed for the comprehensive analysis of lipids and has revealed the potential of lipids as biomarkers for the early diagnosis of RA and prediction of therapeutic responses. However, the relationship between disease activity and the lipid profile in RA remains unclear. In the present study, we performed a plasma lipidomic analysis of 278 patients with RA during treatment and examined relationships with disease activity using the Disease Activity Score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR). In all patients, five lipids positively correlated and seven lipids negatively correlated with DAS28-ESR. Stearic acid [FA(18:0)] (r = -0.45) and palmitic acid [FA(16:0)] (r = -0.38) showed strong negative correlations. After adjustments for age, body mass index (BMI), and medications, stearic acid, palmitic acid, bilirubin, and lysophosphatidylcholines negatively correlated with disease activity. Stearic acid inhibited osteoclast differentiation from peripheral blood monocytes in in vitro experiments, suggesting its contribution to RA disease activity by affecting bone metabolism. These results indicate that the lipid profile correlates with the disease activity of RA and also that some lipids may be involved in the pathogenesis of RA.

Kudoa tanakai n. sp. (Myxozoa: Myxosporea: Multivalvulida), a new kudoid species with spheroid myxospores from the scalpel sawtail (Actinopterygii: Prionurus scalparum) from western Japan.

We describe a new kudoid species, Kudoa tanakai n. sp., in the scalpel sawfish, Prionurus scalprum (Actinopterygii: Acanthuriformes: Acanthuridae), from the natural water around western Japan. The plasmodia were filamentous, localized in pseudocysts in the myofibers of the trunk muscles. The occurrence of plasmodia in the trunk muscle showed no site preference. Its myxospores were spheroid, measuring 6.6-7.6 (7.0) µm by 5.8-6.9 (6.3) µm in apical view (width) and 5.7-6.6 (6.2) in length (n = 30), with four shell valves and a corresponding number of spheroid polar capsules. Shell valves lacked apical protrusions, but scanning electron microscopy revealed that one of the four shell valves had two semi-lunar flaps at its apical terminus. Nucleotide sequencing of the small and large subunit ribosomal RNA genes of the present isolate showed phylogenetic affinities to kudoid species characterized by spheroid myxospores, such as K. musculoliquefaciens, K. hemiscylli, and K. carcharhini, but was molecularly and morphometrically distinct from these and other kudoid species. For direct comparison, Kudoa hemiscylli was collected from the Pacific spadenose shark, Scoliodon macrorhynchos (Elasmobranchii: Carcharhiniformes: Carcharhinidae), in the South China Sea off Guangdong Province, China, and the myxospore surface of the species was observed using scanning electron microscopy. Our study describes the new host and distribution record of this kudoid species originally described from a variety of elasmobranchs in the Australian Coral Sea.

The Prognostic Impact of In-Hospital Major Bleeding and Recurrence of Myocardial Infarction during Acute Phase after Percutaneous Coronary Intervention for Acute Myocardial Infarction.

AIM: Both recurrent myocardial infarction (ReMI) and bleeding events after acute myocardial infarction (AMI) were reportedly associated with increased mortality. To date, the prognostic impact of these events on subsequent outcomes in East Asians is still unclear. In this study, we aimed to investigate the impact of bleeding or thrombotic events during acute phase on subsequent mortality and time-dependent change of the impact in patients with AMI undergoing percutaneous coronary intervention (PCI). METHOD: We conducted a prospective, multicenter, observational study of patients with AMI (n=12,093). The patients who did not undergo emergent PCI were excluded. In addition, the patients registered before 2003 were excluded because the data of bleeding severity was not obtained. Eligible patients were divided into two groups based on the occurrence of major bleeding within 7 days of PCI, and the same approach was performed for ReMI within 7 days of PCI. The endpoint of this study was all-cause death. We assessed the impact of major bleeding and ReMI, which occurred within 7 days of index PCI, on the subsequent clinical outcomes up to 5 years. RESULTS: A total of 6,769 patients were found to be eligible. All-cause death occurred in 898 (13.3%) patients during a median follow-up period of 1,726 [511-1,840] days. After adjustment for multiple confounders, major bleeding in 7 days from index PCI was independently associated with higher 30-day and 30-day to 1-year mortality (odds ratio [OR]: 2.06 [1.45-2.92] p＜0.001, OR: 2.03 [1.28-3.15] p=0.002), whereas ReMI was not (OR: 1.93 [0.92-3.80] p=0.07, OR: 0.81 [0.24-2.03] p=0.68). Major bleeding and ReMI did not affect mortality between 1 and 5 years (hazard ratio [HR]: 1.32 [0.77-2.26] p=0.31, HR: 0.48 [0.12-1.94] p=0.30). CONCLUSION: Major bleeding in 7 days from admission was independently associated with higher 30-day and 1-year mortality but not during 1-5 years. ReMI did not affect mortality in all phases. We should be more concerned about bleeding event during acute phase after PCI.

Remnant gastritis in gastric cancer patients causes loss of muscle mass 6 months after gastrectomy: a retrospective cohort study of Helicobacter pylori infection.

PURPOSE: In this study, we assessed the relationship between remnant gastritis and muscle mass loss and then investigated the potential relationship between Helicobacter pylori (HP) infection and remnant gastritis and muscle loss. METHODS: We reviewed the medical records of 463 patients who underwent distal gastrectomy between January 2017 and March 2020. Of these patients, 100 with pStage I after laparoscopic surgery were included in this analysis. RESULTS: A multivariate analysis showed that the total Residue, Gastritis, Bile (RGB) classification score, which indicates the degree of gastritis, was significantly associated with the rate of change (rate of decrease) in the psoas muscle area (PMA) during the first 6 months after surgery (p = 0.014). Propensity score matching was performed according to HP infection, and the rate of change in the PMA and the degree of remnant gastritis in 56 patients were compared. Neither was significantly associated with HP infection. CONCLUSIONS: Remnant gastritis did contribute to psoas muscle mass loss during the initial 6 months after gastrectomy, and HP infection was not significantly associated with either remnant gastritis or psoas muscle mass loss. Nevertheless, the potential for HP eradication to prevent muscle loss and improve the survival prognosis for gastrectomy patients merits further research.

[ESSENSE Concept and Perioperative Management in Esophageal Cancer Treatment].

The actual operation based on the philosophy of ESsential Strategy for Early Normalization after Surgery with patient's Excellent satisfaction (ESSENSE) in radical thoracic esophageal cancer surgery is described. ESSENSE, which is proposed by the Japanese Society of Surgical Metabolism and Nutrition to promote postoperative recovery, consists of four principles:reduction of invasive reactions, early independence of physical activity, early independence of nutrition intake, and perioperative anxiety reduction and motivation for recovery. Here, we describe the actual operation based on the ESSENSE philosophy in radical thoracic esophageal cancer surgery, which is classified as one of the highly invasive esophageal cancer surgeries. We have been performing perioperative management using the above protocol since April 2012. The outcomes of 334 patients up to April 2020 are described. Preoperative chemotherapy was administered in 74% of patients, 70% underwent thoracoscopic surgery, 50% had Clavien- DindoⅡ or higher postoperative complications, and 14% had postoperative pneumonia. The mean postoperative bed rest was 1.6 days. This contributed to a shorter hospital stay and fewer pulmonary complications compared with previous management. The four principles of ESSENSE are useful for early recovery programs in Japan. The ESSENSE should be implemented from this perspective according to the disease, medical facility, community, and family situation.

TRPV4-mediated Ca2+ deregulation causes mitochondrial dysfunction via the AKT/α-synuclein pathway in dopaminergic neurons.

Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca2+ permeable nonselective cation channel, cause TRPV4-related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4-mediated Ca2+ deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain-of-function TRPV4 mutation, c.1855C > T (p.L619F). The mutation was repaired using CRISPR/Cas9 to generate corrected isogenic stem cells. These stem cells were differentiated into dopaminergic neurons and the pharmacological effects of folic acid were examined. In mutant neurons, constitutively elevated cytosolic Ca2+ augmented AKT-mediated α-synuclein (α-syn) induction, resulting in mitochondrial Ca2+ accumulation and dysfunction. The TRPV4 antagonist, AKT inhibitor, or α-syn knockdown, normalizes the mitochondrial Ca2+ levels in mutant neurons, suggesting the importance of mutant TRPV4/Ca2+/AKT-induced α-syn in mitochondrial Ca2+ accumulation. Folic acid was effective in normalizing mitochondrial Ca2+ levels via the transcriptional repression of α-syn and improving mitochondrial reactive oxygen species levels, adenosine triphosphate synthesis, and neurite outgrowth of mutant neurons. This study provides new insights into the neuropathological mechanisms underlying TRPV4-related disorders and related therapeutic strategies.

Eimerian and capillariid infection in farmed ring-necked pheasants (Phasianus colchicus karpowi) in Ehime, Japan, with special reference to their phylogenetic relationships with congeners.

We performed a parasitological examination of the gastrointestinal tract of farmed ring-necked pheasants (Phasianus colchicus karpowi) on two farms in Ehime, Japan. Fecal examination through flotation and sedimentation methods (43, 103, and 50 samples in three consecutive years from 2020, respectively) detected coccidian oocysts (5-58%), or capillarid (40-56%) and heterakid eggs (45-72%). Following artificial sporology, most sporulated coccidian oocysts were ellipsoidal without micropyle nor residuum, but with 1-3 polar refractile granules, morphologically reminiscent of Eimeria phasiani (Apicomplexa: Eucoccidiorida: Eimeriidae). Intensive sequencing of mitochondrial cytochrome c oxidase subunit I gene (cox-1) using pan-eimerian primers and multiple oocyst samples from different pheasants indicated a single species. We characterized, for the first time, the cox-1 sequence of E. phasiani, known to be prevalent in wild and captive ring-necked pheasants worldwide. Worm recovery under a dissection microscope revealed two capillariid and one heterakid nematode species: Eucoleus perforans (Nematoda: Trichocephalida: Capillariidae) in the esophageal epithelium (prevalence, 8-73%), Capillaria phasianina (Capillariidae) in the cecal mucosa (10-87%), and Heterakis gallinarum (Nematoda: Ascaridida: Heterakidae) in the cecal lumen (69-88%). The small subunit ribosomal RNA gene (SSU rDNA) of E. perforans was perfectly identical to that in a previous isolate from farmed Japanese green pheasants (Phasianus colchicus versicolor) at a distant locality in Japan. The SSU rDNA of C. phasianina was characterized, for the first time, demonstrating a sister relationship with Capillaria anatis, parasites found in the ceca of domestic ducks, geese, and various wild anatid birds.

Effects of melatonin on dopaminergic neuron development via IP3-mediated mitochondrial Ca2+ regulation in autism spectrum disorder.

Melatonin entrainment of suprachiasmatic nucleus-regulating circadian rhythms is mediated by MT1 and MT2 receptors. Melatonin also has neuroprotective and mitochondrial activating effects, suggesting it may affect neurodevelopment. We studied melatonin's pharmacological effects on autism spectrum disorder (ASD) neuropathology. Deciduous tooth-derived stem cells from children with ASD were used to model neurodevelopmental defects and differentiated into dopaminergic neurons (ASD-DNs) with or without melatonin. Without melatonin, ASD-DNs had reduced neurite outgrowth, mitochondrial dysfunction, lower mitochondrial Ca2+ levels, and Ca2+ accumulation in the endoplasmic reticulum (ER) compared to control DNs from typically developing children-derived stem cells. Melatonin enhanced IP3-dependent Ca2+ release from ER to mitochondria, improving mitochondrial function and neurite outgrowth in ASD-DNs. Luzindole, an MT1/MT2 antagonist, blocked these effects. Thus, melatonin supplementation may improve dopaminergic system development in ASD by modulating mitochondrial Ca2+ homeostasis via MT1/MT2 receptors.

"Photochemical Surgery" of 1D Metal-Organic Frameworks with a Site-Selective Solubilization/Crystallization Strategy.

One-dimensional (1D) hybrid MOFs are attractive if they consist of different MOF blocks with interconnected channels. However, the precision synthesis of such 1D multiblock MOFs with the desired block lengths and sequences remains a formidable challenge. Herein we propose the "photochemical surgery" method, which combines top-down and bottom-up approaches to enable the site-selective solubilization (removal)/crystallization (reconstruction) of 1D MOFs. We employed photoreactive MOFs, which were prepared by complexing either Cd2+ or Zn2+ with a mixture containing a photochromic bispyridyl ligand (PyDTEopen or PyDTZEopen) and an isophthalate (5-nitroisophthalate (nip2-) or 5-bromoisophthalate (bip2-)). These MOFs were obtained as high-aspect-ratio, needlelike, colorless crystals that bore 1D channels oriented parallel to the long needle axis. When photoreactive DTECdMOFNO2 ([Cd(nip)(PyDTEopen)(H2O)]n), for example, was immobilized at both ends with a metal alloy on a glass substrate and exposed to UV light through a photomask for 60 min in N,N-dimethylformamide/methanol (DMF/MeOH), the unmasked part was removed via solubilization to produce a 50 µm gap. The resulting specimen was immersed for 24 h at 25 °C in DMF/MeOH containing the necessary components for the construction of DTZECdMOFNO2 ([Cd(nip)(PyDTZEopen)(H2O)]n). Eventually, the gap was filled with DTZECdMOFNO2 to produce a triblock hybrid MOF (DTECdMOFNO2-DTZECdMOFNO2-DTECdMOFNO2). The result of a guest diffusion experiment confirmed that the newly formed DTZECdMOFNO2 block shared its 1D channels with the host DTECdMOFNO2 blocks. "Photochemical surgery" can be applied to synthesize 1D hybrid MOFs bearing unconventional sequences and morphologies, e.g., honeycomb- and inverted-honeycomb-patterned hybrids.

Renal pathology in adult and paediatric population of Japan: review of the Japan renal biopsy registry database from 2007 to 2017.

BACKGROUND: The Japan Renal Biopsy Registry (J-RBR), a nationwide, web-based, registry system, started in 2007. This study aimed to summarise the epidemiology of biopsy-diagnosed kidney disease in Japan over 10 years. METHODS: We analysed the J-RBR database, from 2007 to 2017. Patients' clinical data collected at the time of biopsy and histopathological diagnoses were used for epidemiological and clinicopathologic analyses. RESULTS: The predominant renal biopsy diagnoses were immunoglobulin A nephropathy (39.2%), lupus nephritis (6.5%) and minimal change disease (6.0%) in younger adults (19-64 years), and membranous nephropathy (17.4%), antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis (13.0%), and immunoglobulin A nephropathy (12.5%) in older adults (≥ 65 years). The percentages of patients diagnosed with membranoproliferative glomerulonephritis and immunoglobulin A nephropathy decreased, whereas those with immunoglobulin A vasculitis and diabetic nephropathy increased over the decade. In paediatric patients (< 19 years), immunoglobulin A nephropathy (36.1%), minimal change disease (17.6%), and immunoglobulin A vasculitis (8.6%) were the predominant diagnoses. The percentage of patients diagnosed with immunoglobulin A vasculitis increased over the decade. Based on the sex distribution, minimal change disease and membranous nephropathy were predominant in men aged < 20 and > 40 years, respectively, whereas immunoglobulin A vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis or anti-glomerular basement membrane glomerulonephritis were predominant in women in their 20s and 30s and aged < 50 years, respectively. Immunoglobulin A nephropathy was predominant in men at most ages and in women in their 20s to 40s. CONCLUSIONS: This study describes the distribution and changes in kidney biopsy diagnoses over 10 years in Japan and paves the way for future research on kidney diseases in adults and children.

A prospective observational study of recall of discomfort on tracheal extubation after general anaesthesia.

Background: Tracheal extubation is a critical stage in the management of general anaesthesia during which serious complications may occur. Immediately before extubation, patients often exhibit signs that suggest that they are awake and experiencing discomfort. There is concern that patients may retain such memories of the extubation process. However, previous studies have not examined patient recall of extubation in detail. We therefore investigated the frequency of recall of discomfort during extubation, as well as first orientation to place, and other recollections upon emerging from general anaesthesia. Methods: In a prospective observational study, 818 patients were interviewed during routine post-anaesthesia rounds on the day after general anaesthesia. The primary outcome was the proportion of patients recalling discomfort during extubation. The secondary outcome was the location of orientation to place upon emerging from general anaesthesia. Results: Recall of discomfort during extubation was uncommon, at 1.1% (n=9; 95% confidence interval [CI]: 0.5-2.1%). Only 3.1% of patients recalled the extubation process at all (n=25; 95% CI: 2.0-4.5%). The first orientation to place was most commonly in transit to a ward, in 41% of cases (n=337; 95% CI: 38-45%). Conclusions: Recall of discomfort during extubation appears to be rare, and the great majority of patients may not retain any memory of the extubation process. This information may be used to reassure patients and guide extubation practices for anaesthetists. Clinical trial registration: UMIN Clinical Trials Registry (UMIN000046136).

Efficacy and safety of patient-controlled thoracic epidural analgesia alone versus patient-controlled intravenous analgesia with acetaminophen after laparoscopic distal gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: Laparoscopic gastrectomy is a common procedure for early gastric cancer treatment. Improving postoperative pain control enhances patient recovery after surgery. The use of multimodal analgesia can potentially enhance the analgesic effect, minimize side effects, and change the postoperative management. The purpose of this study was to evaluate and compare the efficacies of the use of patient-controlled intravenous analgesia with regular acetaminophen (PCIA + Ace) and patient-controlled thoracic epidural analgesia (PCEA) for postoperative pain control. METHODS: We retrospectively collected the data of 226 patients who underwent laparoscopic distal gastrectomy (LDG) with delta-shaped anastomosis between 2016 and 2019. After 1:1 propensity-score matching, we compared 83 patients who used PCEA alone (PCEA group) with 83 patients who used PCIA + Ace (PCIA + Ace group). Postoperative pain was assessed using a numeric rating scale (NRS) with scores ranging from 0 to 10. An NRS score ≥ 4 was considered the threshold for additional intravenous rescue medication administration. RESULTS: Although NRS scores at rest were comparable between the PCEA and PCIA + Ace groups, NRS scores of patients in the PCIA + Ace group during coughing or movement were significantly better than those of patients in the PCEA group on postoperative days 2 and 3. The frequency of additional rescue analgesic use was significantly lower in the PCIA + Ace group than in the PCEA group (1.1 vs. 2.7, respectively, p < 0.001). The rate of reduction or interruption of the patient-controlled analgesic dose was higher in the PCEA group than in the PCIA + Ace group (74.6% vs. 95.1%, respectively, p = 0.0002), mainly due to hypotension occurrence in the PCEA group. Physical recovery time, postoperative complication occurrence, and liver enzyme elevation incidence were not significantly different between groups. CONCLUSIONS: PCIA + Ace can be safely applied without an increase in complications or deterioration in gastrointestinal function; moreover, PCIA + Ace use may provide better pain control than PCEA use in patients following LDG.

Randomised controlled trial of cultural-adapted and programme-adopted cognitive behavioural therapy for children and adolescents' anxiety in Japan: protocol for a Multi-, Inter-, and Cross-cultural Clinical Child Study (MIXCS).

INTRODUCTION: The primary objective of the Multi-, Inter-, and Cross-cultural Clinical Child Study (MIXCS) is to evaluate the hypothesis that the effects of cultural-adapted cognitive behavioural therapy (CA-CBT) and programme-adopted cognitive behavioural therapy (PA-CBT) for children and adolescents' anxiety are both superior to a psychological control (moral education control: MEC) for reducing child and adolescent anxiety disorders and symptoms as well as related constructs. The secondary objective is to explore commonalities and differences in therapy factors between CA-CBT and PA-CBT. METHOD AND ANALYSIS: The study has been designed as a randomised, controlled and assessor masked multicentre superiority trial with three groups: CA-CBT, PA-CBT and MEC. Primary outcome is remission of primary anxiety disorders evaluated by independent evaluators. Secondary outcomes are clinician's severity ratings, child self-reported anxiety symptoms, depressive symptoms, cognitive errors and family accommodation, as well as parent-reported anxiety symptoms, and family accommodation. Competence and adherence of treatment, therapy factors in treatment sessions are also measured based on behavioural observation. Finally, satisfaction and comprehension are collected. We aim to recruit at least 99 families for the analysis. Treatment will be delivered weekly for 10 sessions and assessment will be conducted 2 weeks before the treatment (pre), 3 months after the base date when the treatment starts (post), 6 months (six months follow-up) and 12 months (12 months follow-up) after the postassessment. ETHICS AND DISSEMINATION: The MIXCS study was approved by Doshisha University Research Ethics Review Committee, Kwansei Gakuin University Institutional Review Board for Medical and Biological Research Involving Human Subjects and Shinshu University Certified Review Board of Clinical Research. Regardless of the results, the primary outcome will be published in a journal, and if the efficacy and effectiveness of CA-CBT and/or PA-CBT are empirically supported, the authors will encourage dissemination of the programmes including the assessment system through key stakeholders in education, health, and welfare areas. TRIAL REGISTRATION NUMBER: UMIN000038128.

Polar vasculosis is associated with better kidney outcome in type 2 diabetes with biopsy-proven diabetic kidney disease: A multicenter cohort study.

AIMS/INTRODUCTION: This multicenter cohort study retrospectively assessed the association between polar vasculosis and the progression of diabetic kidney disease (DKD) in type 2 diabetes. MATERIALS AND METHODS: We enrolled 811 patients with type 2 diabetes, biopsy-proven DKD, and proteinuria (≥0.15 g/g creatinine [g/day]). The association between polar vasculosis and other kidney lesions was explored. The outcome was DKD progression defined as a composite of renal replacement therapy initiation or 50% decline in estimated glomerular filtration rate (eGFR) from baseline. RESULTS: Of the 811 cases, 677 (83.5%) had polar vasculosis. In multivariate logistic regression analysis, subendothelial widening of the glomerular basement membrane, glomerulomegaly, glomerular class in the Renal Pathology Society classification ≥IIb, vascular lesions, age, eGFR, and hemoglobin A1c were positively associated with polar vasculosis, whereas interstitial fibrosis and tubular atrophy (IFTA) was negatively associated with polar vasculosis. During a median follow-up of 5.2 years, progression of DKD occurred in 322 of 677 (7.4 events/100 person-years) and 79 of 134 (11.4 events/100 person-years) cases with and without polar vasculosis, respectively. Kaplan-Meier analysis showed that polar vasculosis was associated with lower cumulative incidences of DKD progression. Multivariate Cox regression analyses showed that polar vasculosis was associated with a lower risk of DKD progression, regardless of eGFR or proteinuria subgroups. These associations between polar vasculosis and better kidney outcome were unchanged considering all-cause mortality before DKD progression as a competing event. CONCLUSIONS: This study showed that polar vasculosis of DKD was associated with less advanced IFTA and a better kidney outcome in type 2 diabetes with proteinuria.

Twenty-year outcomes of free and I-composite radial artery grafts for coronary artery revascularization.

PURPOSE: To compare the 20-year outcomes of coronary artery grafting (CABG) using radial artery (RA) grafts (free and I-composite) and internal thoracic artery (ITA) grafts. METHODS: Long-term graft patency was evaluated in patients who underwent isolated CABG between August, 1996 and January, 2022. The long-term graft patency of free RA grafts, I-composite ITA-RA grafts, and saphenous vein (SV) grafts were compared. RESULTS: The RA was used as a coronary bypass conduit in 111 of the 246 patients enrolled in this study. The RA patency after 10 and 20 years was 94.2% and 76.6%, respectively. Landmark analysis showed that although graft patency for up to 10 years did not differ between the RA and ITA grafts (hazard ratio = 0.87; P = 0.8), patency of the ITA grafts was better from 10 to 20 years post-surgery (hazard ratio = 0.19; P = 0.013). The 20-year graft patency of the I-composite RA grafts was better than that of the free RA grafts (80.0% vs. 72.4%; P = 0.029), but not significantly different from that of the ITA grafts (80.0% vs. 90.7%; P = 0.24). CONCLUSIONS: The 20-year patency of the I-composite ITA-RA graft was better than that of the free RA graft; therefore, the I-composite graft may be an effective conduit for CABG.

Deficiency of G protein-coupled receptor Gpr111/Adgrf2 causes enamel hypomineralization in mice by alteration of the expression of kallikrein-related peptidase 4 (Klk4) during pH cycling process.

Enamel is formed by the repetitive secretion of a tooth-specific extracellular matrix and its decomposition. Calcification of the enamel matrix via hydroxyapatite (HAP) maturation requires pH cycling to be tightly regulated through the neutralization of protons released during HAP synthesis. We found that Gpr115, which responds to changes in extracellular pH, plays an important role in enamel formation. Gpr115-deficient mice show partial enamel hypomineralization, suggesting that other pH-responsive molecules may be involved. In this study, we focused on the role of Gpr111/Adgrf2, a duplicate gene of Gpr115, in tooth development. Gpr111 was highly expressed in mature ameloblasts. Gpr111-KO mice showed enamel hypomineralization. Dysplasia of enamel rods and high carbon content seen in Gpr111-deficient mice suggested the presence of residual enamel matrices in enamel. Depletion of Gpr111 in dental epithelial cells induced the expression of ameloblast-specific protease, kallikrein-related peptidase 4 (Klk4), suggesting that Gpr111 may act as a suppressor of Klk4 expression. Moreover, reduction of extracellular pH to 6.8 suppressed the expression of Gpr111, while the converse increased Klk4 expression. Such induction of Klk4 was synergistically enhanced by Gpr111 knockdown, suggesting that proper enamel mineralization may be linked to the modulation of Klk4 expression by Gpr111. Furthermore, our in vitro suppression of Gpr111 and Gpr115 expression indicated that their suppressive effect on calcification was additive. These results suggest that both Gpr111 and Gpr115 respond to extracellular pH, contribute to the expression of proteolytic enzymes, and regulate the pH cycle, thereby playing important roles in enamel formation.

Seasonal variations in renal biopsy numbers and primary glomerular disease features based on the Japan renal biopsy registry.

We analyzed the seasonal variations in the number of renal biopsies and clinical characteristics of primary glomerular disease in Japan using the Japan Renal Biopsy Registry (J-RBR). We retrospectively collected clinical and pathological data of patients with primary glomerular disease who were registered in the J-RBR between 2007 and 2018. Immunoglobulin A nephropathy (IgAN), minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), and postinfectious acute glomerulonephritis (PIAGN) constituted the four major glomerular disorders included in this study (total, 13,989; IgAN, 9121; MCNS, 2298; MN, 2447; and PIAGN, 123). The number of patients with IgAN or MCNS was higher during summer. However, no overt seasonal variations were observed in patients with MN or PIAGN. Subgroup analyses suggested that in the patients with IgAN, more renal biopsies of severe cases were performed during winter, probably owing to age and blood pressure. Furthermore, more renal biopsies of severe cases were performed during spring and winter in patients with MCNS even after adjusting for the abovementioned host factors. This study suggests that seasonal factors influence the decision to perform renal biopsy as well as the pathogenesis of primary glomerular disease. Thus, our findings may provide important insights regarding the pathophysiology of primary glomerular disease.

Surgical outcomes of reconstruction using the gastric tube and free jejunum for cervical esophageal cancer: analysis using the National Clinical Database of Japan.

BACKGROUND: Cervical esophageal cancer accounts for a small proportion of all esophageal cancers. Therefore, studies examining this cancer include a small patient cohort. Most patients with cervical esophageal cancer undergo reconstruction using a gastric tube or free jejunum after esophagectomy. We examined the current status of postoperative morbidity and mortality of cervical esophageal cancer based on big data. METHODS: Based on the Japan National Clinical Database, 807 surgically treated patients with cervical esophageal cancer were enrolled between January 1, 2016, and December 31, 2019. Surgical outcomes were retrospectively reviewed for each reconstructed organ using gastric tubes and free jejunum. RESULTS: The incidence of postoperative complications related to reconstructed organs was higher in the gastric tube reconstruction (17.9%) than in the free jejunum (6.7%) for anastomotic leakage (p < 0.01), but not significantly different for reconstructed organ necrosis (0.4% and 0.3%, respectively). The incidence rates of overall morbidity, pneumonia, 30-day reoperation, tracheal necrosis, and 30-day mortality using these reconstruction methods were 64.7% and 59.7%, 16.7% and 11.1%, 9.3% and 11.4%, 2.2% and 1.6%, and 1.2% and 0.0%, respectively. Only pneumonia was more common in the gastric tube reconstruction group (p = 0.03), but was not significantly different for any other complication. CONCLUSIONS: The incidence of overall morbidities and reoperation, especially anastomotic leakage after gastric tube reconstruction, suggested a necessity for further improvement. However, the incidence of fatal complications, such as tracheal necrosis or reconstructed organ necrosis, was low for both reconstruction methods, and the mortality rate was acceptable as a means of radical treatment.

Temperature analysis of aortic repair with hypothermic circulatory arrest to quantify the injury by cooling.

OBJECTIVES: We analyzed the temperature in proximal aortic repair with moderate hypothermic circulatory arrest (HCA) and evaluated the effect of the cooling status on postoperative outcomes. METHODS: A total of 340 patients who underwent elective ascending aortic replacement or total arch replacement with moderate HCA from December 2006 to January 2021 were studied. The change in body temperature trends recorded during surgery was shown graphically. Several parameters, such as the nadir temperature, cooling speed and the degree of cooling (cooling area), which was the area under curve of inverted temperature trends from cooling to rewarming as calculated by the integral method, were analyzed. The relationships between these variables and a major adverse outcome (MAO) postoperatively defined as prolonged ventilation (>72 h), acute renal failure, stroke, reoperation for bleeding, deep sternal wound infection or in-hospital death were evaluated. RESULTS: An MAO was observed in 68 patients (20%). The cooling area was larger in the MAO group than in the non-MAO group (1668.7 vs 1383.2°C min; P < 0.0001). A multivariate logistic model showed that old myocardial infarction, peripheral vascular disease, chronic renal dysfunction, cardiopulmonary bypass time and the cooling area were independent risk factors for an MAO (odds ratio = 1.1 per 100°C min; P < 0.001). CONCLUSIONS: The cooling area, which indicates the degree of cooling, shows a significant relationship with an MAO after aortic repair. This finding indicates that the cooling status with HCA can affect clinical outcomes.