Docosahexaenoic acid (DHA) promotes recovery from postoperative ileus and the repair of the injured intestinal barrier through mast cell-nerve crosstalk.

The objective of this study was to investigate the neuroimmune mechanisms implicated in the enhancement of gastrointestinal function through the administration of oral DHA. Mast cell-deficient mice (KitW-sh) and C57BL/6 mice were used to establish postoperative ileus (POI) models. To further validate our findings, we conducted noncontact coculture experiments involving dorsal root ganglion (DRG) cells, bone marrow-derived mast cells (BMMCs) and T84 cells. Furthermore, the results obtained from investigations conducted on animals and cells were subsequently validated through clinical trials. The administration of oral DHA had ameliorative effects on intestinal barrier injury and postoperative ileus. In a mechanistic manner, the anti-inflammatory effect of DHA was achieved through the activation of transient receptor potential ankyrin 1 (TRPA1) on DRG cells, resulting in the stabilization of mast cells and increasing interleukin 10 (IL-10) secretion in mast cells. Furthermore, the activation of the pro-repair WNT1-inducible signaling protein 1 (WISP-1) signaling pathways by mast cell-derived IL-10 resulted in an enhancement of the intestinal barrier integrity. The current study demonstrated that the neuroimmune interaction between mast cells and nerves played a crucial role in the process of oral DHA improving the intestinal barrier integrity of POI, which further triggered the activation of CREB/WISP-1 signaling in intestinal mucosal cells.

The impact of laparoscopic radical gastrectomy on the inflammatory response and immune function of patients with gastric cancer.

The currest study aimed to measure the effects of laparoscopic radical gastrectomy on inflammatory response along with immune function in gastric cancer (GC) patients. Seventy patients with GC in our hospital were retrospectively chosen to be the study objects and separated into control group (CG, 35 cases) and observation group (OG, 35 cases). Patients in the OG received radical laparotomy. Patients in the OG received laparoscopic radical gastrectomy. The surgical indicators, postoperative recovery indicators, inflammatory factors, immune function, incidence of adverse reactions along with quality of life of patients in both groups were compared. In contrast to the CG, the operation time of the OG presented as shorter (P<0.05), and the amount of intraoperative blood loss together with postoperative VAS score in the OG presented lower (P<0.05), but the number of lymph nodes dissection presented not statistically significant between 2 groups (P>0.05). The postoperative exhaust time, feeding time as well as hospital stay in the OG presented shorter relative to the CG (P<0.05). The serum levels of CRP, and IL-6 together with TNF-α presented elevated in both groups after surgery, and those in the OG presented lower when compared with the CG (P<0.05). The serum levels of IgA, and IgG together with IgM presented declined in both groups after surgery, and those in the OG presented higher when compared with the CG (P<0.05). The incidence of postoperative complications in the OG presented reduction relative to the CG (P<0.05). The GLQI scores of the OG presented significantly higher relative to the CG at discharge (P<0.05). Compared with radical gastrectomy, laparoscopic radical gastrectomy is more suitable for the treatment of GC, which can reduce the inflammatory response and promote the immune function of GC patients.

Association between oral nutrition and inflammation after intestinal transplantation.

Intestinal transplantation (Itx) can be a life-saving treatment for certain patient populations, including those patients with intestinal failure (IF) who develop life-threatening complications due to the use of parenteral nutrition (PN). Most patients who have undergone Itx are eventually able to tolerate a full oral diet. However, little guidance or consensus exists regarding optimizing the specific components of an oral diet for Itx patients, including macronutrients, micronutrients and dietary patterns. While oral dietary prescriptions have moved to the forefront of primary and preventive care, this movement has yet to occur across the field of organ transplantation. Evidence to date points to the role of systemic chronic inflammation (SCI) in a wide variety of chronic diseases as well as post-transplant graft dysfunction. This review will discuss current trends in oral nutrition for Itx patients and also offer novel insights into nutritional management techniques that may help to decrease SCI and chronic disease risk as well as optimize graft function.

Electroacupuncture treatment improves postoperative ileus by inhibiting the Th1 cell-mediated inflammatory response through the vagus nerve.

BACKGROUND: Electroacupuncture (EA) has been reported to improve intestinal motility in mice with postoperative ileus (POI). Previous studies, however, have yielded heterogeneous results regarding the effect of EA on POI. METHODS: Herein, a POI mouse model was constructed by intestinal manipulation. To evaluate the effect of EA treatment on colonic transit, the levels of inflammatory markers (macrophage inflammatory protein (MIP)-1α, interleukin (IL)-1ß, IL-6, monocyte chemotactic protein (MCP)-1 and intercellular adhesion molecule (ICAM)-1) were detected by enzyme-linked immunosorbent assay (ELISA); immune cell infiltration was detected by immunohistochemical staining of myeloperoxidase (MPO), ectodysplasin (ED)-1 and ED-2, and the percentage of CD4+ interferon (IFN)-γ+ Th1 cells and IFN-γ secretion levels were determined. Activated Th1 cells and pentoxifylline, a cell differentiation inhibitor, were used to assess the role of Th1 cells in EA treatment of POI. Neostigmine administration and unilateral vagotomy were performed to confirm whether the effects of EA treatment on Th1 cells were mediated by the vagus nerve (VN). RESULTS: The results revealed that EA treatment at ST36 improved POI, as indicated by a decreased level of inflammatory-related markers and immune cell infiltration and shortened colonic transit time. The activated Th1 cells abolished the effects of EA treatment on POI. The effects of EA treatment on POI were enhanced by stimulation of the VN along with a decreased level of Th1 cells, but these effects were abolished by vagotomy along with an increased percentage of Th1 cells; this result indicates that the VN mediates the role of Th1 cells in the effects of EA treatment of POI. CONCLUSION: Our findings showed that the effects of EA treatment of POI were mainly mediated by Th1 cells through the stimulation of the VN and inhibition of the inflammatory response.

[Impact of the ratio between graft and host corneal size on immune rejection, re-bubbling rate and postoperative endothelial cell loss in 457 eyes after Descemet membrane endothelial keratoplasty (DMEK)]. / Einfluss des Verhältnisses von Transplantatgröße zu Hornhautgröße auf Immunreaktion, Re-Bubbling-Rate und postoperativen Endothelzellverlust bei 457 Augen nach Descemet-Membrane-Endothelial-Keratoplastik (DMEK).

BACKGROUND: The aim of this study was to assess the impact of the ratio between the graft and host corneal size (RGH) on postoperative complications, such as immune reactions, re-bubbling rate and endothelial cell loss (ECL) after Descemet membrane endothelial keratoplasty (DMEK). PATIENTS AND METHODS: Retrospectively, 457 patient eyes were included which had undergone surgery between 2016 and 2019 in the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar using DMEK or triple DMEK, diagnosed as Fuchs' endothelial dystrophy (n = 431), pseudophakic bullous keratopathy (n = 9) and others (n = 17). The follow-up period extended until the end of 2020. Main outcome measures included immune reaction (IR), re-bubbling rate and the postoperative endothelial cell loss (ECL) at 6 weeks, 6 months and 12 months and whether these measures depended on the RGH. RESULTS: The RGH in this study ranged from 0.35 to 0.62 (0.46 ± 0.04). There were 33 (7.2%) postoperative IRs (DMEK n = 25; triple DMEK n = 8). The average RGH without IR (0.46 ± 0.04) was significantly (p = 0.038) smaller than in the group with IR (0.47 ± 0.05). Re-bubbling was necessary in 159 of 457 (34.8%) patient eyes. The RGH in patient eyes with re-bubbling (0.47 ± 0.04) was significantly (p = 0.014) higher than that in eyes without re-bubbling (0.45 ± 0.04). The mean preoperative endothelial cell count (ECD) was 2603 ± 251 cells/mm2 (min: 2161, max: 3500 cells/mm2). It was shown that a larger RGH had no positive influence on endothelial cell loss (r = 0.001; p = 0.974). CONCLUSION: Our results suggest that a larger graft diameter compared to host corneal size is associated with an increased rate of immune reactions and a higher re-bubbling rate after DMEK. Otherwise, a larger RGH had no positive influence on endothelial cell loss after DMEK. Accordingly, the graft size for DMEK should not be unnecessarily large, especially in eyes with Fuchs' endothelial dystrophy.

Early dynamic changes to monocytes following major surgery are associated with subsequent infections.

Background: Post-operative infections are a common cause of morbidity following major surgery. Little is understood about how major surgery perturbs immune function leading to heightened risk of subsequent infection. Through analysis of paired blood samples obtained immediately before and 24 h following surgery, we evaluated changes in circulating immune cell phenotype and function across the first 24 h, to identify early immune changes associated with subsequent infection. Methods: We conducted a prospective observational study of adult patients undergoing major elective gastrointestinal, gynecological, or maxillofacial surgery requiring planned admission to the post-anesthetic care unit. Patients were followed up to hospital discharge or death. Outcome data collected included mortality, length of stay, unplanned intensive care unit admission, and post-operative infections (using the standardized endpoints in perioperative medicine-core outcome measures for perioperative and anesthetic care criteria). Peripheral blood mononuclear cells were isolated prior to and 24 h following surgery from which cellular immune traits including activation and functional status were assessed by multi-parameter flow cytometry and serum immune analytes compared by enzyme-linked immunosorbent assay (ELISA). Results: Forty-eight patients were recruited, 26 (54%) of whom developed a post-operative infection. We observed reduced baseline pre- and post-operative monocyte CXCR4 and CD80 expression (chemokine receptors and co-stimulation markers, respectively) in patients who subsequently developed an infection as well as a profound and selective post-operative increase in CD4+ lymphocyte IL-7 receptor expression in the infection group only. Higher post-operative monocyte count was significantly associated with the development of post-operative infection (false discovery rate < 1%; adjusted p-value = 0.001) with an area under the receiver operating characteristic curve of 0.84 (p < 0.0001). Conclusion: Lower monocyte chemotaxis markers, higher post-operative circulating monocyte counts, and reduced co-stimulatory signals are associated with subsequent post-operative infections. Identifying the underlying mechanisms and therapeutics to reverse defects in immune cell function requires further exploration.

Dysregulated inflammatory response to urogynecologic meshes in women with diabetes and its implications.

BACKGROUND: Diabetes is an independent risk factor for mesh complications in women undergoing mesh-augmented surgical repairs of stress urinary incontinence and/or pelvic organ prolapse. The underlying mechanism remains unclear. OBJECTIVE: This study aimed to define the diabetes-associated alterations in the host inflammatory response to mesh and correlate them with perioperative glucose management. STUDY DESIGN: Deidentified demographics and medical records of patients who underwent mesh removal and participated in a mesh biorepository study were reviewed (n=200). In patients with diagnosed diabetes (n=25), blood glucose management before initial mesh implantation and before and after mesh removal was assessed by blood glucose and hemoglobin A1c levels. Age- and body mass index-matched tissue samples excised from patients with and without diabetes were examined. Transcriptomic profiles of immune cell markers, immune mediators, key inflammatory regulators, cell senescence, and epigenetic enzymes were determined by multiplex transcriptomic assays (NanoString). Ratios of apoptotic cells to CD68+ macrophages were examined with immunofluorescence. Protein profiles of 12 molecules involved in apoptotic cell clearance were examined with a multiplex protein assay (Luminex). RESULTS: Demographic and clinical characteristics, including duration between mesh implantation and removal, reason for removal, and type of mesh, etc., were comparable between patients with and without diabetes, except for 11.6% higher body mass index in the former (P=.005). In patients with diabetes, suboptimal management of blood glucose following mesh implantation was observed, with 59% of the patients having loosely or poorly controlled glucose before and after the mesh removal. Ongoing chronic inflammatory response was observed in the excised mesh-tissue complexes in both groups, whereas markers for M2 macrophages (Mrc1 [mannose receptor C-type 1]) and helper T cells (Cd4 [CD4 molecule]) were increasingly expressed in the diabetic vs nondiabetic group (P=.023 and .047, respectively). Furthermore, the gene expressions of proinflammatory Ccl24 (C-C motif chemokine ligand 24) and Ccl13 (C-C motif chemokine ligand 13) were upregulated by 1.5- and 1.8-fold (P=.035 and .027, respectively), whereas that of Il1a (interleukin 1 alpha) was paradoxically downregulated by 2.2-fold (P=.037) in the diabetic vs nondiabetic group. Interestingly, strong positive correlations were found between the expression of Ccl13, Setdb2 (SET domain bifurcated histone lysine methyltransferase 2), and M2 macrophage markers, and between the expression of Il1a, Fosl1 (activator protein-1 transcription factor subunit), and dendritic cell markers, suggesting the involvement of macrophages and dendritic cells in the diabetes-dysregulated proinflammatory response. Supportively, apoptotic cell clearance, which is an important function of macrophages, appeared to be impaired in the diabetic group, with a significantly increased protein level of CALR (calreticulin), an "eat-me" signal on the surface of apoptotic cells (P=.031), along with an increase of AXL (AXL receptor tyrosine kinase) (P=.030), which mediates apoptotic cell clearance. CONCLUSION: Diabetes was associated with altered long-term inflammatory response in complicated mesh implantation, particularly involving innate immune cell dysfunction. Suboptimal blood glycemic control following mesh implantation may contribute to this immune dysregulation, necessitating further mechanistic studies.

Assessing vaccine-induced immunity against pneumococcus, hepatitis A and B over a 9-year follow-up in pediatric liver transplant recipients: A nationwide retrospective study.

Pediatric liver transplant recipients are particularly at risk of infections. The most cost-effective way to prevent infectious complications is through vaccination, which can potentially prevent infections due to hepatitis B (HBV) virus, hepatitis A virus (HAV), and invasive pneumococcal diseases. Here, we performed a retrospective analysis of HBV, HAV, and pneumococcal immunity in pediatric liver transplant recipients between January 1, 2009, and December 31, 2020, to collect data on immunization and vaccine serology. A total of 94% (58/62) patients had available vaccination records. At transplant, 90% (45/50) were seroprotected against HBV, 63% (19/30) against HAV, and 78% (18/23) had pneumococcal immunity, but immunity against these 3 pathogens remained suboptimal during the 9-year follow-up. A booster vaccine was administered to only 20% to 40% of patients. Children who had received >4 doses of HBV vaccine and > 2 doses of HAV vaccine pretransplant displayed a higher overall seroprotection over time post-solid organ transplant. Our findings suggest that a serology-based approach should be accompanied by a more systematic follow-up of vaccination, with special attention paid to patients with an incomplete vaccination status at time of transplant.

Combination of early Interleukin-6 and -18 levels predicts postoperative nosocomial infection.

Background: The inflammatory response plays a critical role in postoperative nosocomial infections, which are the most common postoperative complications causing adverse events and poor postoperative outcomes. This study aimed to explore the ability of early inflammation-related factor levels to predict the occurrence of nosocomial infections after abdominal surgery. Methods: The study included 146 patients with open abdominal surgery (a nosocomial infection group (NI group, n=42) and a no-nosocomial infection group (NNI group, n=104)). After 1:1 matching, the patients were divided into a matching nosocomial infection group (M-NI group, n=25) and a matching no-nosocomial infection group (M-NNI group, n=25). Serum levels of interleukin (IL)-6, IL-8, IL-10, IL-12, IL-18, macrophage migration inhibitory factor (MIF), and monocyte chemotactic protein (MCP-1) were tested at three time points (pre-operation, 0-hour post-operation (POD1) and 24-hour post-operation (POD2)). The area under the receiver operating characteristic curve (AUC-ROC) was used to test the predictive abilities. Results: There were significant differences in the levels of IL-6, IL-12, and IL-18 between the M-NI and M-NNI groups (p < 0.05), but not in the levels of other inflammatory factors. MIF, IL-8, and MCP-1 levels were higher in the M-NI group than in the M-NNI group at POD2 (p < 0.05). In the ROC analysis, the AUC for prediction of nosocomial infection using a combination of IL-6 and IL-18 at POD1 was 0.9616, while the AUCs for IL-6 alone and IL-12 alone were 0.8584 and 0.8256, respectively. Conclusions: The combination of the levels of inflammatory factors, IL-6 and IL-18, at the 0-hour postoperative time point, significantly improved the predictive ability to the development of postoperative infection during perioperative period. Our study suggests the importance of monitoring postoperative inflammatory markers.

Food Protein-Induced Enterocolitis Syndrome in Children with Down Syndrome: A Pilot Case-Control Study.

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobin E-mediated food hypersensitivity disorder. However, little is known about the clinical features of FPIES in patients with Down syndrome (DS). Medical records of children with DS diagnosed at our hospital between 2000 and 2019 were retrospectively reviewed. Among the 43 children with DS, five (11.6%) were diagnosed with FPIES; all cases were severe. In the FPIES group, the median age at onset and tolerance was 84 days and 37.5 months, respectively. Causative foods were cow's milk formula and wheat. The surgical history of colostomy was significantly higher in the FPIES group than in the non-FPIES group. A colostomy was performed in two children in the FPIES group, both of whom had the most severe symptoms of FPIES, including severe dehydration and metabolic acidosis. The surgical history of colostomy and postoperative nutrition of formula milk feeding may have led to the onset of FPIES. Therefore, an amino acid-based formula should be considered for children who undergo gastrointestinal surgeries, especially colostomy in neonates or early infants. When an acute gastrointestinal disease is suspected in children with DS, FPIES should be considered. This may prevent unnecessary tests and invasive treatments.

The effect of BKV reactivation on cytokines behavior in kidney transplanted patients.

BACKGROUND: BK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients. METHODS: EDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes. RESULTS: The results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load. CONCLUSIONS: Our findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients' groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.

Influence of inguinal hernia repair on sperm autoimmunity: The largest single center experience.

BACKGROUND: Studies on immunological infertility after inguinal hernia correction are few and not very representative. Anti-sperm antibodies have been shown to reduce male fertility. Although the extent of infertility due to anti-sperm antibodies alone is not very clear, data indicates that about 8%-10% of infertile patients have immunological infertility DESIGN: This retrospective study includes all infertile male patients (n = 2258) who underwent mixed antiglobulin reaction tests and urologic examination from 2000 to 2020. Sperm quality (assessed by the number of spermatozoa, their motility, vitality, and normal form) was also evaluated. Among these patients, 191 had previously undergone unilateral or bilateral inguinal hernia surgery repair. The aim of the study is to evaluate if there is a higher incidence of positive mixed antiglobulin reaction test among patients undergoing inguinal hernioplasty compared to the unselected infertile population. RESULTS: Anti-sperm antibodies would seem to increase in both patients who performed general andrological surgery and groin hernia correction, respectively 3.48 (95% Confidence Interval: 1.70-7.10; p < 0.001) and 2.45 (95% Confidence Interval: 1.01-5.99; p < 0.05) times more than the unselected infertile population. CONCLUSIONS: Mixed antiglobulin reaction test could be useful in patients undergone previous scrotal surgery or hernia correction men, to avoid false unexplained infertility diagnoses and to direct the couple to assisted reproductive technology procedures. Basal evaluation of spermatozoa does not actually consider andrological surgery as an indication to autoimmunity investigation.

Increased complications in patients who test COVID-19 positive after elective surgery and implications for pre and postoperative screening.

BACKGROUND: The COVID-19 pandemic has necessitated the adoption of protocols to minimize risk of periprocedural complications associated with SARS-CoV-2 infection. This typically involves a preoperative symptom screen and nasal swab RT-PCR test for viral RNA. Asymptomatic patients with a negative COVID-19 test are cleared for surgery. However, little is known about the rate of postoperative COVID-19 positivity among elective surgical patients, risk factors for this group and rate of complications. METHODS: This prospective multicenter study included all patients undergoing elective surgery at 170 Veterans Health Administration (VA) hospitals across the United States. Patients were divided into groups based on first positive COVID-19 test within 30 days after surgery (COVID[-/+]), before surgery (COVID[+/-]) or negative throughout (COVID[-/-]). The cumulative incidence, risk factors for and complications of COVID[-/+], were estimated using univariate analysis, exact matching, and multivariable regression. RESULTS: Between March 1 and December 1, 2020 90,093 patients underwent elective surgery. Of these, 60,853 met inclusion criteria, of which 310 (0.5%) were in the COVID[-/+] group. Adjusted multivariable logistic regression identified female sex, end stage renal disease, chronic obstructive pulmonary disease, congestive heart failure, cancer, cirrhosis, and undergoing neurosurgical procedures as risk factors for being in the COVID[-/+] group. After matching on current procedural terminology code and month of procedure, multivariable Poisson regression estimated the complication rate ratio for the COVID[-/+] group vs. COVID[-/-] to be 8.4 (C.I. 4.9-14.4) for pulmonary complications, 3.0 (2.2, 4.1) for major complications, and 2.6 (1.9, 3.4) for any complication. DISCUSSION: Despite preoperative COVID-19 screening, there remains a risk of COVID infection within 30 days after elective surgery. This risk is increased for patients with a high comorbidity burden and those undergoing neurosurgical procedures. Higher intensity preoperative screening and closer postoperative monitoring is warranted in such patients because they have a significantly elevated risk of postoperative complications.

Restrictive allograft syndrome vs bronchiolitis obliterans syndrome: Immunological and molecular characterization of circulating exosomes.

BACKGROUND: Chronic lung allograft dysfunction in lung transplant recipients (LTxRs) has 2 phenotypes: obstructive bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Our goal was to define distinct immunologic markers of exosomes from LTxRs with BOS or RAS. METHODS: Plasma was collected from LTxRs with BOS (n = 18), RAS (n = 13), and from stable LTxRs (n = 5). Antibodies to lung self-antigens (SAgs) were determined by ELISA. Exosomes were isolated by ultracentrifugation. Donor specific antibodies to HLA were quantified using Luminex. Exosomes were characterized for lung SAgs, transcription factors, 20S proteasome, HLA class I and II, and polymeric immunoglobulin receptor protein using western blot. Exosome miRNA was analyzed using NanoString. The exosome-induced immune response was determined in mice. RESULTS: LTxRs with RAS, but not BOS, had donor specific antibodies at diagnosis. CIITA, NFkB, polymeric immunoglobulin receptor protein, 20S proteasome, HLA-DQ, and HLA-DR were significantly higher in RAS exosomes than in BOS exosomes. RAS plasma had high levels of proinflammatory cytokines and distinct exosomal miRNA. Immunization of C57BL/6 mice with RAS exosomes showed severe inflammation and peribronchial fibrosis, whereas BOS exosomes induced patchy inflammation and fibrosis. CONCLUSION: LTxRs with BOS or RAS had exosomes with distinct molecular and immunologic profiles. RAS samples had a higher concentration of proinflammatory factors, HLA class II, lung SAgs, and antibodies to HLA class II molecules, indicating severe allograft injury. Mice immunized with RAS exosomes developed lesions in airways, pleura, interlobular septum, and alveoli, whereas BOS exosomes induced mild to patchy inflammation with lung fibrosis.

Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation.

AIM: Bacterial and fungal infections are serious, life-threatening conditions after kidney transplantation. The development of oral/oesophageal candidiasis after kidney transplantation is not a reported risk factor for subsequent severe infection. This study was performed to investigate the relationship between oral/oesophageal candidiasis after kidney transplantation and the development of subsequent infection requiring hospitalization. METHODS: This retrospective study included 522 consecutive patients who underwent kidney transplantation at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital from 1 January 2010 to 1 February 2019. Ninety-five percentage of patients were living donor transplant recipients. Visual examination was performed to detect oral candidiasis, beginning immediately after kidney transplantation; upper gastrointestinal endoscopy was performed 8-10 months after kidney transplantation. Twenty-five patients developed candidiasis (Candida-onset group) and 497 did not (non-Candida-onset group). The follow-up periods were 67 (37-86) months in the Candida-onset group and 55 (34-89) months in the non-Candida-onset group. Severe infection was defined as bacterial or fungal infection requiring hospitalization; viral infections were excluded. RESULTS: Severe infection developed in 9/25 (36%) patients in the Candida-onset group and in 77/497 (15%) patients in the non-Candida-onset group (p = .006). Binomial logistic analysis revealed that Candida infection (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.06-6.06; p = .037) and use of rituximab (OR 1.81, 95% CI 1.12-2.93; p = .016) were significant predictors of subsequent severe infection. CONCLUSION: Oral/oesophageal candidiasis is a risk factor for severe infection after kidney transplantation and suggests an over-immunosuppressive state, which should prompt evaluation of immunosuppression.

Impact of antibody induction on the outcomes of new onset diabetes after kidney transplantation: a registry analysis.

PURPOSE: We conducted this observational study to examine the impact of antibody inductions administered at kidney transplant (KT) on outcomes of 5 year exposure to post-transplant diabetes (PTDM) in adult deceased-donor kidney transplant recipients (DDKTRs). We also studied the risk of PTDM associated with antibody inductions. METHODS: Using 2000-2016 Organ Procurement Transplantation Network data, we employed multivariable Cox models to determine the adjusted hazard ratios (HR) of death, and overall and death-censored graft loss (OAGL, DCGL; respectively) at the 5 year landmark period in antibody induction cohorts with and without PTDM at the 1 year post-transplant index time point. We used multivariable logistic regression in determining the risk factors for PTDM. All multivariable analyses were adjusted for the potential confounding effects of maintenance immunosuppression, steroid regimens, and other relevant covariates. RESULTS: 48,031 adult DDKTRs were classified into cohorts based on antibody induction at transplant: (anti-thymocyte globulin) ATG (n = 26, 788); (alemtuzumab) ALM (n = 5916); and interleukin-2 receptor antagonist (IL-2RA) (n = 15,327). PTDM was a risk factor for 5 year OAGL and death, not DCGL [(HR = 1.25, CI = 1.16-1.36), (HR = 1.13, CI = 1.06-1.21), and (HR = 1.05, CI = 0.96-1.16); respectively]. Induction regimens were not risk factors for 5 year outcomes in DDKTRs with and without PTDM. Risk factors for PTDM included DDKTR obesity, age > / = 50 years, acute rejection, and ATG induction, among others. CONCLUSIONS: In adult DDKTRs, after controlling the confounding effects of clinically relevant variables including maintenance and steroid regimens, PTDM at 1 year post-transplant is associated with death and OAGL, not DCGL in the following 5 years: induction received at KT did not modify these associations.

Transcriptome sequencing analysis of primary fibroblasts: a new insight into postoperative abdominal adhesion.

PURPOSE: The specific genes or pathways in fibroblasts responsible for the pathogenesis of postoperative abdominal adhesion (PAA) remain to be elucidated. We aim to provide a new insight into disease mechanisms at the transcriptome level. METHODS: Male Sprague-Dawley rats were used to establish a PAA model. Primary fibroblasts were separated from normal peritoneal tissue (NF) and postoperative adhesion tissue (PF). RNA sequencing was used to analyze the transcriptome in NF and PF. RESULTS: One thousand two hundred thirty-five upregulated and 625 downregulated DEGs were identified through RNA-Seq. A pathway enrichment analysis identified distinct enriched biological processes, among which the most prominent was related to immune and inflammatory response and fibrosis. HE staining and Masson's trichrome staining histologically validated the RNA-Seq results. Six hub genes, ITGAM, IL-1ß, TNF, IGF1, CSF1R and EGFR were further verified by RT-PCR. CONCLUSIONS: Our study revealed the roles of the immune and inflammatory responses and fibrosis in the process of PAA. We also found six hub genes that may be potential therapeutic targets for PPA.