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1.
Circ Res ; 2024 Jun 11.
Article En | MEDLINE | ID: mdl-38860377

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163 macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase 3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

2.
Circ Heart Fail ; 17(6): e011057, 2024 Jun.
Article En | MEDLINE | ID: mdl-38847093

BACKGROUND: The immune systems and chronic inflammation are implicated in the pathogenesis of dilated cardiomyopathy (DCM) and heart failure. However, the significance of neutrophil extracellular traps (NETs) in heart failure remains to be elucidated. METHODS: We enrolled consecutive 62 patients with heart failure with idiopathic DCM who underwent endomyocardial biopsy. Biopsy specimens were subjected to fluorescent immunostaining to detect NETs, and clinical and outcome data were collected. Ex vivo and in vivo experiments were conducted. RESULTS: The numbers of NETs per myocardial tissue area and the proportion of NETs per neutrophil were significantly higher in patients with DCM compared with non-DCM control subjects without heart failure, and the numbers of NETs were negatively correlated with left ventricular ejection fraction. Patients with DCM with NETs (n=32) showed lower left ventricular ejection fraction and higher BNP (B-type natriuretic peptide) than those without NETs (n=30). In a multivariable Cox proportional hazard model, the presence of NETs was independently associated with an increased risk of adverse cardiac events in patients with DCM. To understand specific underlying mechanisms, extracellular flux analysis in ex vivo revealed that NETs-containing conditioned medium from wild-type neutrophils or purified NET components led to impaired mitochondrial oxygen consumption of cardiomyocytes, while these effects were abolished when PAD4 (peptidyl arginine deiminase 4) in neutrophils was genetically ablated. In a murine model of pressure overload, NETs in myocardial tissue were predominantly detected in the acute phase and persisted throughout the ongoing stress. Four weeks after transverse aortic constriction, left ventricular ejection fraction was reduced in wild-type mice, whereas PAD4-deficient mice displayed preserved left ventricular ejection fraction without inducing NET formation. CONCLUSIONS: NETs in myocardial tissue contribute to cardiac dysfunction and adverse outcomes in patients with heart failure with DCM, potentially through mitochondrial dysfunction of cardiomyocytes.


Cardiomyopathy, Dilated , Extracellular Traps , Heart Failure , Myocardium , Neutrophils , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/metabolism , Humans , Extracellular Traps/metabolism , Heart Failure/physiopathology , Male , Female , Middle Aged , Animals , Myocardium/pathology , Myocardium/metabolism , Neutrophils/metabolism , Stroke Volume/physiology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Ventricular Function, Left/physiology , Mice , Aged , Mitochondria, Heart/metabolism , Mitochondria, Heart/pathology , Mice, Inbred C57BL , Biopsy
3.
Eur Heart J Case Rep ; 8(6): ytae265, 2024 Jun.
Article En | MEDLINE | ID: mdl-38845807

Background: Several reports have shown that transcatheter aortic valves are comparable in durability to surgical aortic valves. However, early structural valve deterioration (SVD) is rarely reported to occur, especially in haemodialysis patients. Case summary: We present a case of rapidly progressive bioprosthetic aortic valve stenosis in a patient with end-stage renal disease secondary to diabetic nephropathy in an 83-year-old female admitted due to progressive dyspnoea and orthopnoea. A 23 mm sized SAPIEN3 bioprosthetic aortic valve showed normal function for the first year after transcatheter aortic valve implantation (TAVI), but then rapidly developed stenosis and required acute hospitalization for heart failure a year and a half after surgery. Emergent surgical aortic valve replacement with a 19 mm On-X valve (CryoLife, Kennesaw, GA, USA) was performed. Pathological examination of the explanted SAPIEN 3 valve demonstrated severely degenerated bioprosthetic pericardial leaflets with severe intrinsic and extrinsic nodular calcifications, which could limit the leaflet motion. Discussion: There is a lack of reports on the long-term procedural outcomes of TAVI in haemodialysis patients. The development of SVD in patients undergoing dialysis is multifactorial and has yet to be fully elucidated. In the presented case, the removed TAVI valve had severe extrinsic calcified nodules alongside a fibrin thrombus. Considering these pathological findings, antithrombotic therapy to prevent fibrin thrombus from adhering to the TAVI valve may be important to avoid early SVD.

4.
Sci Rep ; 14(1): 13969, 2024 06 17.
Article En | MEDLINE | ID: mdl-38886503

Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of periodontitis on kidney transplantation (KT) outcomes, particularly allograft rejection, remains unclear. This study investigated the effect of periodontitis on transplant immunity, specifically examining Porphyromonas gingivalis-derived lipopolysaccharide (LPS-PG). In vitro experiments revealed that LPS-PG increased regulatory T cells (Tregs) in Lewis rat spleen cells. In a mixed lymphocyte reaction assay, concentrations of interferon-γ, indicative of alloreactivity, were lower than in controls when LPS-PG was added to the culture and when LPS-PG-administered Lewis rat spleen cells were used as responders. In a rat KT model, LPS-PG administration to recipients promoted mild tubulitis and low serum creatinine and blood urea nitrogen levels 5 days post-KT compared with PBS-administered controls. Furthermore, LPS-PG-administered recipients had an elevated Treg proportion in their peripheral blood and spleen cells, and increased infiltrating Tregs in kidney allografts, compared with controls. The elevated Treg proportion in peripheral blood and spleen cells had a significant negative correlation with serum creatinine, suggesting elevated Tregs modulated allograft rejection. These findings suggest that periodontitis might modulate alloimmune reactivity through LPS-PG and Tregs, offering insights to refine immunosuppressive strategies for KT recipients.


Graft Rejection , Kidney Transplantation , Lipopolysaccharides , Porphyromonas gingivalis , Rats, Inbred Lew , T-Lymphocytes, Regulatory , Animals , Porphyromonas gingivalis/immunology , Kidney Transplantation/adverse effects , Rats , T-Lymphocytes, Regulatory/immunology , Male , Graft Rejection/immunology , Allografts , Periodontitis/immunology , Periodontitis/microbiology , Disease Models, Animal , Spleen/immunology
5.
Can J Cardiol ; 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38692430

BACKGROUND: Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. METHODS: A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and chronic thromboembolic pulmonary hypertension (CTEPH) patients (n = 64) before the first and after the final balloon pulmonary angioplasty. RESULTS: CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was co-localized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human pulmonary arterial hypertension (P = 0.006) and CTEPH patients (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), and right ventricular fractional area change (R = -0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. CONCLUSIONS: CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

6.
Article En | MEDLINE | ID: mdl-38769726

BACKGROUND: During the transition from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), previous studies have raised concerns about a rebound effect. We compared platelet and inflammatory cell adhesion on different types of stents in the setting of clopidogrel presence and withdrawal. METHODS: In Experiment 1, three pigs were administered with DAPT, that is, clopidogrel and acetylsalicylic acid (ASA), for 7 days. Each animal underwent an extracorporeal carotid arteriovenous shunt model implanted with fluoropolymer-coated everolimus-eluting stent (FP-EES), biodegradable-polymer sirolimus-eluting stent (BP-SES), and biodegradable-polymer everolimus-eluting stents (BP-EES). In Experiment 2, two pigs were administered DAPT, clopidogrel was then withdrawn at day 7, and SAPT with ASA was continued for next 21 days. Then flow-loop experiments with the drawn blood from each time point were performed for FP-EES, BioLinx-polymer zotarolimus-eluting stents (BL-ZES), and BP-EES. The rebound effect was defined as the statistical increase of inflammation and platelet adhesion assessed with immunohistochemistry on the stent-strut level basis from baseline to day-14 or 28. RESULTS: Both experiments showed platelet adhesion value was highest in BP-EES, while the least in FP-EES during DAPT therapy. There was no increase in platelet or inflammatory cell adhesion above baseline values (i.e., no therapy) due to the cessation of clopidogrel on the stent-strut level. Monocyte adhesion was the least for FP-EES with the same trend observed for neutrophil adhesion. CONCLUSIONS: No evidence of rebound effect was seen after the transition from DAPT to SAPT. FP-EES demonstrated the most favorable antithrombotic and anti-inflammatory profile regardless of the different experimental designs.

7.
Front Microbiol ; 15: 1403903, 2024.
Article En | MEDLINE | ID: mdl-38756723

In natural microbiomes, microorganisms interact with each other and exhibit diverse functions. Microbiome engineering, which enables bacterial knockdown, is a promising method to elucidate the functions of targeted bacteria in microbiomes. However, few methods to selectively kill target microorganisms in the microbiome without affecting the growth of nontarget microorganisms are available. In this study, we focused on the host-specific lytic ability of virulent phages and validated their potency for precise microbiome engineering. In an artificial microbiome consisting of Escherichia coli, Pseudomonas putida, Bacillus subtilis, and Lactiplantibacillus plantarum, the addition of bacteriophages infecting their respective host strains specifically reduced the number of these bacteria more than 102 orders. Remarkably, the reduction in target bacteria did not affect the growth of nontarget bacteria, indicating that bacteriophages were effective tools for precise microbiome engineering. Moreover, a virulent derivative of the λ phage was synthesized from prophage DNA in the genome of λ lysogen by in vivo DNA assembly and phage-rebooting techniques, and E. coli-targeted microbiome engineering was achieved. These results propose a novel approach for precise microbiome engineering using bacteriophages, in which virulent phages are synthesized from prophage DNA in lysogenic strains without isolating phages from environmental samples.

8.
Angew Chem Int Ed Engl ; : e202403461, 2024 May 27.
Article En | MEDLINE | ID: mdl-38803130

Dearomative construction of multiply-fused 2D/3D frameworks, composed of aromatic two-dimensional (2D) rings and saturated three-dimensional (3D) rings, from readily available quinolines has greatly contributed to drug discovery. However, dearomative cycloadditions of quinolines in the presence of photocatalysts usually afford 5,6,7,8-tetrahydroquinoline (THQ)-based polycycles, and dearomative access to 1,2,3,4-THQ-based structures remains limited. Herein, we present a chemo-, regio-, diastereo-, and enantioselective dearomative transformation of quinolines into 1,2,3,4-THQ-based 6-6-4-membered rings without any catalyst, through a combination of nucleophilic addition and borate-mediated [2+2] photocycloaddition. Detailed mechanistic studies revealed that the photoexcited borate complex, generated from quinoline, organolithium, and HB(pin), accelerates the cycloaddition and suppresses the rearomatization that usually occurs in conventional photocycloaddition. Based on our mechanistic analysis, we also developed further photoinduced cycloadditions affording other types of 2D/3D frameworks from isoquinoline and phenanthrene.

9.
Microorganisms ; 12(4)2024 Mar 28.
Article En | MEDLINE | ID: mdl-38674625

Accretionary prisms are composed mainly of ancient marine sediment scraped from the subducting oceanic plate at convergent plate boundaries. Anoxic groundwater is stored in deep aquifers associated with accretionary prisms and can be collected via deep wells. We investigated how such groundwater pumping affects the microbial community in a deep aquifer. Groundwater samples were collected from a deep well drilled down to 1500 m every six months (five times in total) after completion of deep well construction and the start of groundwater pumping. Next-generation sequencing and clone-library analyses of 16S rRNA genes were used to describe the subterranean microbial communities in the samples. The archaea: the prokaryote ratio in groundwater increased significantly from 1 to 7% (0 and 7 months after initiating groundwater pumping) to 59 to 72% (13, 19, and 26 months after initiating groundwater pumping), and dominant prokaryotes changed from fermentative bacteria to sulfate-reducing archaea. The optimal growth temperature of the sulfate-reducing archaea, estimated based on the guanine-plus-cytosine contents of their 16S rRNA genes, was 48-52 °C, which agreed well with the groundwater temperature at the deep-well outflow. Our results indicated that, in deep aquifers, groundwater pumping enhances groundwater flow, and the supply of sulfate-containing seawater activates the metabolism of thermophilic sulfate-reducing archaea.

10.
J Surg Res ; 298: 149-159, 2024 Jun.
Article En | MEDLINE | ID: mdl-38608426

INTRODUCTION: Bench surgery for the preparation of deceased donor pancreatic grafts is labor-intensive and time-consuming. We hypothesized that energy devices could be used during bench surgery to decrease the bench surgery time. However, because bench surgery has two unique characteristics, wet conditions and no blood flow in the vessels, it is necessary to verify the safety and efficacy under such conditions. METHODS: In an animal tissue model, we validated both ultrasonic and bipolar energy devices: Harmonic Shears and the LigaSure (LS) vessel-sealing device by evaluating heat spread and pressure resistance under bench surgery conditions. In a clinical evaluation of the LS, we compared the outcomes of 22 patients in two different bench surgery groups: with and without the use of the LS. RESULTS: Clinically, the bench surgery time was significantly shorter in the LS group than that in the conventional group (P < 0.001). In the animal tissue experiments, the highest temperature in bench surgery conditions was 60.4°C after 1 s at a 5-mm distance in the LS group. Pressure resistance of ≥ 750 mmHg was achieved in almost all trials in both veins and arteries, with no difference between Harmonic Shears and LS. There was more surgical smoke visually in bench conditions versus in dry conditions and under half bite versus full bite conditions. CONCLUSIONS: The encouraging results of our exploratory clinical and animal studies of the energy devices suggest that they may be useful in the setting of bench surgery.


Pancreas Transplantation , Animals , Pancreas Transplantation/instrumentation , Pancreas Transplantation/methods , Pancreas Transplantation/adverse effects , Humans , Male , Female , Adult , Middle Aged , Models, Animal , Swine , Pancreas/surgery , Pancreas/blood supply
11.
Catheter Cardiovasc Interv ; 103(6): 972-981, 2024 May.
Article En | MEDLINE | ID: mdl-38606477

BACKGROUND: Ethylene diamine tetra-acetic acid (EDTA) is a chelating agent used to dissolve calcium deposits but evidence in decalcifying atherosclerotic lesions is limited. AIMS: We assessed the feasibility and efficacy of EDTA delivered via porous balloon to target calcified lesions in cadaveric below-the-knee (BTK) arteries. METHODS: Using porcine carotid arteries, EDTA concentration was measured in the arterial wall and outside the artery at the 0-, 0.5-, 4-, and 24-h circulation after the injection through a porous balloon. In cadaver BTK samples, the proximal and distal anterior tibial artery (ATA) and distal posterior tibial artery (PTA) were studied. EDTA-2Na/H2O or EDTA-3Na/H2O were administrated using a porous balloon, then circulated for 6 h for EDTA-3Na/H2O and 24 h for EDTA-2Na/H2O and EDTA-3Na/H2O. Micro-CT imaging of the artery segments before and after the circulation and cross-sectional analyses were performed to evaluate calcium burden. RESULTS: In the porcine carotid study, EDTA was delivered through a porous balloon present in the arterial wall and was retained there for 24 h. In BTK arteries, cross-sectional analyses of micro-CT revealed a significant decrease in the calcium area in the distal ATA segment under 24-h circulation with EDTA-2Na/H2O and in the distal ATA segment under 24-h circulation with EDTA-3Na/H2O. The proximal ATA segment under 6-h circulation with EDTA-3Na/H2O showed no significant change in any parameters of calcium CONCLUSION: EDTA-3Na/H2O or EDTA-2Na/H2O with longer circulation times resulted in greater calcium reduction in atherosclerotic lesion. EDTA may have a potential therapeutic option for the treatment of atherosclerotic calcified lesions.


Angioplasty, Balloon , Edetic Acid , Feasibility Studies , Vascular Calcification , Animals , Edetic Acid/pharmacology , Angioplasty, Balloon/instrumentation , Porosity , Vascular Calcification/diagnostic imaging , Vascular Calcification/therapy , Cadaver , Tibial Arteries/diagnostic imaging , Calcium Chelating Agents/pharmacology , Time Factors , X-Ray Microtomography , Humans , Vascular Access Devices , Equipment Design , Sus scrofa , Peripheral Arterial Disease/therapy , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/metabolism , Plaque, Atherosclerotic , Swine
12.
Article En | MEDLINE | ID: mdl-38451583

BACKGROUND: Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers. OBJECTIVE: To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them. METHODS: A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated. RESULTS: Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis. CONCLUSION: This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.

13.
EuroIntervention ; 20(6): e389-e398, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38506736

BACKGROUND: Drug-coated balloons (DCBs) are important treatment options for coronary artery disease; however, randomised controlled trials comparing various DCB technologies are sparse, and further investigations are needed. AIMS: This preclinical study aimed to histologically and biologically compare the drug effects and safety of a low-dose paclitaxel-coated DCB (PCB; AGENT), a regular-dose PCB (SeQuent Please NEO) and a sirolimus-coated DCB (SCB; MagicTouch). METHODS: The DCBs were inflated in the healthy iliac arteries of 18 rabbits, which were euthanised after 28 days. The treated iliac arteries and distal skeletal muscles were histopathologically evaluated, and drug concentrations were measured. RESULTS: In the histopathological evaluation, the medial smooth muscle cell loss score regarding depth, an indicator of drug efficacy, was significantly higher with AGENT and SeQuent Please NEO than with MagicTouch (4.0 [3.6-4.0] vs 3.7 [3.7-4.0] vs 2.2 [2.0-2.4]), with significant differences in comparisons between AGENT and MagicTouch (p<0.01) and between SeQuent Please NEO and MagicTouch (p<0.01). AGENT and SeQuent Please NEO showed comparable drug concentrations in the treated artery (p=0.61). In contrast, the drug concentrations in distal skeletal muscles were the highest for MagicTouch, followed by SeQuent Please NEO and AGENT (28.07 [13.19-52.46] ng/mg vs 0.66 [0.22-3.76] ng/mg vs 0.25 [0.04-3.23] ng/mg, respectively). CONCLUSIONS: This study demonstrated that PCBs might have higher efficacy and lower drug concentrations in distal skeletal muscles than the MagicTouch SCB. The efficacy of the AGENT low-dose PCB and the SeQuent Please NEO regular-dose PCB was comparable.


Coronary Artery Disease , Polychlorinated Biphenyls , Animals , Rabbits , Heart , Arteries , Paclitaxel/pharmacology , Sirolimus/therapeutic use
14.
Org Lett ; 26(11): 2180-2185, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38466232

We have developed visible-light-induced trans-hydroboration of diaryl alkynes via direct photoexcitation of in-situ-generated diboron complexes, affording previously elusive (E)-1,2-diaryl-vinylboronates with high stereoselectivity. Experimental, spectroscopic, and theoretical mechanistic studies revealed that the triplet-state borate complex facilitates B-B bond cleavage and the desired C-B bond formation. This methodology does not require any catalyst and is operationally simple. The highly borylated 1,2-diaryl alkenes [1-(2-borylphenyl)vinyl)boronates] are shown to be useful as building blocks.

15.
Transplant Proc ; 56(3): 488-493, 2024 Apr.
Article En | MEDLINE | ID: mdl-38326204

BACKGROUND: This study aimed to examine the outcomes of kidney retransplantation in patients with allograft failure at Kyushu University. METHODS: We reviewed data from 1043 consecutive patients (including 1001 in a first kidney transplantation [KT] group and 42 in a second KT group) who had undergone KT alone at our institution between January 2008 and September 2022. We also studied immunologic risks and outcomes of patients who had undergone preoperative testing for KT at Kyushu University during the same period. RESULTS: No patient received more than 2 transplants. Donor-specific anti-HLA antibody (DSA) had been detected in a greater percentage of patients in the second KT group than in the first (31% vs 11%, respectively; P < .001). There were no significant differences in 5-year death-censored/overall graft survival rates, rates of surgical complications, or incidence of delayed graft function between the groups. During the study period, significantly more candidates for second than first KT were rejected for this procedure because of their high immunologic risk (20% vs 2%, P < 001). Seven of the 42 patients in the second KT group required the removal of the primary graft during the second transplantation. CONCLUSION: There is a higher percentage of patients whose DSA has been detected among patients undergoing retransplantation after allograft failure than among those receiving first KTs, which often leads to remaining on the waiting list in the former group. However, if the immunologic risk is within acceptable limits, the graft survival for retransplantation is not inferior to that of a first KT.


Graft Rejection , Graft Survival , Kidney Transplantation , Reoperation , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Male , Female , Middle Aged , Adult , Graft Rejection/immunology , Allografts , HLA Antigens/immunology
16.
Transplant Proc ; 56(3): 482-487, 2024 Apr.
Article En | MEDLINE | ID: mdl-38331594

BACKGROUND: At our institution, we switched from hand-assisted retroperitoneal laparoscopic donor nephrectomy (HRN) to hand-assisted transperitoneal laparoscopic donor nephrectomy (HTN); we later switched to standard retroperitoneal laparoscopic donor nephrectomy (SRN). This study was performed to evaluate outcomes and hospital costs among the 3 techniques. METHODS: This retrospective, observational, single-center, inverse probability of treatment weighting analysis study compared the outcomes among 551 cases of living donor kidney transplantation between 2014 and 2022. RESULTS: After the inverse probability of treatment weighting analysis, there were 114 cases in the HRN group, 204 cases in the HTN group, and 213 cases in the SRN group. Donor complication rates were lowest in the SRN group but did not differ between the HRN and HTN groups (1.1 vs 4.4 and 5.9%, P = .021). Donors in the SRN group had the lowest serum C-reactive protein concentrations on postoperative day 1 (4.3 vs 10.5 and 7.8 mg/dL, P < .001) and the shortest postoperative stay (4.3 vs 7.4 and 8.4 days, P < .001). Donors in the SRN group had the lowest total cost among the 3 groups (8868 vs 9709 and 10,592 USD, P < .0001). Donors in the SRN group also had the lowest costs in terms of "basic medical fees," "medication and injection fees," "Intraoperative drug and material costs," and "testing fees." Furthermore, the presence of complications was significantly correlated with higher total hospital costs (P < .001). CONCLUSION: SRN appeared to have the least invasive and complication, and a potential cost savings compared with the HRN and HTN.


Kidney Transplantation , Laparoscopy , Living Donors , Nephrectomy , Humans , Nephrectomy/economics , Nephrectomy/methods , Retrospective Studies , Male , Female , Laparoscopy/economics , Laparoscopy/methods , Kidney Transplantation/economics , Kidney Transplantation/methods , Adult , Middle Aged , Treatment Outcome , Hospital Costs , Postoperative Complications/economics , Tissue and Organ Harvesting/economics , Tissue and Organ Harvesting/methods , Length of Stay/economics
17.
Pancreatology ; 24(2): 223-231, 2024 Mar.
Article En | MEDLINE | ID: mdl-38320953

BACKGROUND: The impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years. METHODS: In this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor. RESULTS: Of 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07-13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04-7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005). CONCLUSIONS: Cessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.


Autoimmune Diseases , Autoimmune Pancreatitis , Humans , Autoimmune Pancreatitis/complications , Retrospective Studies , Autoimmune Diseases/drug therapy , Autoimmune Diseases/complications , Steroids/adverse effects , Chronic Disease , Recurrence
18.
J Gastroenterol Hepatol ; 39(5): 893-901, 2024 May.
Article En | MEDLINE | ID: mdl-38273469

BACKGROUND AND AIM: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. METHODS: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data. RESULTS: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). CONCLUSION: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression.


Colitis, Ulcerative , Propensity Score , Humans , Male , Female , Middle Aged , Colitis, Ulcerative/pathology , Colitis, Ulcerative/complications , Colitis, Ulcerative/epidemiology , Aged , Japan/epidemiology , Crohn Disease/pathology , Crohn Disease/epidemiology , Crohn Disease/complications , Colitis-Associated Neoplasms/pathology , Colitis-Associated Neoplasms/etiology , Colitis-Associated Neoplasms/epidemiology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Adult , Adenocarcinoma/pathology , Adenocarcinoma/epidemiology , Adenocarcinoma/etiology , Neoplasm Staging , Neoplasm Grading , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/epidemiology , Adenocarcinoma, Mucinous/etiology , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/epidemiology , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/etiology , Diagnosis, Differential , Prevalence
19.
Int J Mol Sci ; 25(2)2024 Jan 12.
Article En | MEDLINE | ID: mdl-38256064

Flavonoids have garnered attention because of their beneficial bioactivities. However, some flavonoids reportedly interact with drugs via transporters and may induce adverse drug reactions. This study investigated the effects of food ingredients on organic anion-transporting polypeptide (OATP) 4C1, which handles uremic toxins and some drugs, to understand the safety profile of food ingredients in renal drug excretion. Twenty-eight food ingredients, including flavonoids, were screened. We used ascorbic acid (AA) to prevent curcumin oxidative degradation in our method. Twelve compounds, including apigenin, daidzein, fisetin, genistein, isorhamnetin, kaempferol, luteolin, morin, quercetin, curcumin, resveratrol, and ellagic acid, altered OATP4C1-mediated transport. Kaempferol and curcumin strongly inhibited OATP4C1, and the Ki values of kaempferol (AA(-)), curcumin (AA(-)), and curcumin (AA(+)) were 25.1, 52.2, and 23.5 µM, respectively. The kinetic analysis revealed that these compounds affected OATP4C1 transport in a competitive manner. Antioxidant supplementation was determined to benefit transporter interaction studies investigating the effects of curcumin because the concentration-dependent curve evidently shifted in the presence of AA. In this study, we elucidated the food-drug interaction via OATP4C1 and indicated the utility of antioxidant usage. Our findings will provide essential information regarding food-drug interactions for both clinical practice and the commercial development of supplements.


Curcumin , Food Ingredients , Antioxidants/pharmacology , Curcumin/pharmacology , Kaempferols , Kinetics , Ascorbic Acid , Flavonoids , Peptides , Anions
20.
Trop Med Health ; 52(1): 8, 2024 Jan 08.
Article En | MEDLINE | ID: mdl-38191472

BACKGROUND: Efforts to prevent malnutrition in children under five are crucial for both short-term and long-term impact, especially in resource-constrained low- and middle-income countries, where ensuring minimal food diversity remains an urgent challenge. Our organization implemented initiatives to improve dietary diversity among children under five in rural areas of Lao People's Democratic Republic (Lao PDR). METHODS: We carried out educational and awareness programs directed at caregivers of children aged 6-59 months. These programs were delivered by healthcare professionals and trained community volunteers in specific areas of Xaybouathong District, Khammouane Province. To evaluate the impact of our interventions, we conducted surveys both at the beginning and end of the project. We designated the Individual Dietary Diversity Score IDDS as the objective variable, serving as an indicator of child dietary diversity. Using sociodemographic and economic indicators as explanatory variables, we assessed the impact of the intervention through multivariate analysis with a generalized linear model as well as a bivariate analysis. RESULTS: The comparison between 210 children at baseline and 205 children at endline revealed a significant increase in IDDS among children aged 6-23 months (from 3.36 to 4.22) and children aged 24-59 months (from 3.29 to 3.83). Multivariate analysis indicated a significant association between the intervention effect (baseline vs. endline) and the village of residence. Furthermore, significant improvements were observed in each food group that constitute IDDS, including vegetables and fruits, eggs, and legumes and nuts. CONCLUSIONS: Even in resource-limited settings, such as rural areas of Lao PDR, it is possible to improve child dietary diversity through educational approaches that encourage the utilization of locally available foods.

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