Risk factors for catheter-related bloodstream infections in patients with intestinal failure undergoing home parenteral nutrition: a single-center study.

PURPOSE: The incidence and risk factors of catheter-related bloodstream infections (CRBSI) in patients with intestinal failure (IF) have not been established, partly because catheter management methods vary from different facilities. This study aimed to identify the risk factors and incidence rate of CRBSIs in patients with IF who were given prophylactic treatment. METHODS: Sixteen patients with IF who required home parenteral nutrition were enrolled in this study. Prophylactic management of CRBSI included monthly ethanol lock therapy and standardized infection prevention education. The outcomes included the incidence and risk factors of CRBSI. RESULTS: The median incidence rate of CRBSI was 1.2 per 1000 catheter days. Univariate analysis showed that the risk of developing CRBSI was significantly associated with short bowel syndrome (< 30 cm) (p = 0.016). Other relevant findings included a significant negative correlation between serum albumin and CRBSI rate (r = - 0.505, p = 0.046), and past history of mixed bacterial infections was significantly associated with increased CRBSI rate (p = 0.013). CONCLUSION: CRBSIs can still develop despite undergoing prophylactic management. Risk factors for CRBSI include the residual intestinal length, nutritional status, and susceptibility to certain microorganisms.

Postoperative complications and long-term outcomes in Currarino syndrome.

PURPOSE: This study aimed to present ten cases of Currarino syndrome, study their postoperative complications and prognosis, and analyze whether patient background and clinical factors influenced outcomes. METHODS: Ten patients with Currarino syndrome who were followed up at our institution between 2004 and 2020 were enrolled. Patient records were retrospectively reviewed for clinical details, postoperative complications, and long-term outcomes. RESULTS: The incidence of early postoperative complications was 80%, most of which were transient dysuria. The dysuria significantly developed in the higher normal sacral vertebra (p = 0.024) and the complete type of Currarino syndrome (p = 0.033). Later, intractable constipation requiring rectal irrigation and intractable dysuria requiring clean intermittent catheterization occurred in 40% and 30% of the patients, respectively. There was a tendency for tethered cord syndrome (p = 0.076), and the height of the normal sacral vertebra (p = 0.071) was related to intractable constipation. The height of the normal sacral vertebra (p = 0.05) and the tumor size on the image (p = 0.012) were significantly higher and larger, respectively, in the group with intractable dysuria than in the group without intractable dysuria. CONCLUSION: Postoperative complications, especially early ones, occur at a high rate. Long-term intractable constipation and dysuria may be influenced by the degree of sacral dysplasia.

Predictive factors for the development of postoperative Hirschsprung-associated enterocolitis in children operated during infancy.

PURPOSE: The risk factors for postoperative Hirschsprung-associated enterocolitis (HAEC) are still incompletely understood, especially age at which surgery is performed. Therefore, the aim of this study was to identify the risk factors for the development of postoperative HAEC in children operated during infancy. METHODS: Thirty-five children who had undergone radical surgery for Hirschsprung disease (HD) during infancy were included in the study. They were divided into two groups; those who developed postoperative HAEC (HAEC, 14 patients) and those who did not (no HAEC, 21 patients). Their medical records were retrospectively reviewed for clinical details. RESULTS: Developing postoperative HAEC was significantly associated with long-segment HD (p = 0.020) and the age at radical surgery (p = 0.0241). No other factors had a significant association with postoperative HAEC. In the patients who developed postoperative HAEC (n = 14), those with Trisomy 21 had significantly longer hospitalizations than those without. Patients with long-segment HD had a higher hospitalization rate than those with short-segment HD. CONCLUSION: This study clearly showed that long-segment HD and older age at radical surgery are risk factors for developing postoperative HAEC.

GITR controls intestinal inflammation by suppressing IL-15-dependent NK cell activity.

Glucocorticoid-induced TNFR family related gene (GITR) is a member of the TNFR superfamily that is expressed on cells of the immune system. Although the protective and pathogenic roles of GITR in T cell immunity are well characterized, the role of GITR in innate immunity in the intestinal tissues has not been well clarified. In this study, using a dextran sulfate sodium (DSS)-induced colitis model in mice, we found that GITR-deficiency rendered mice more susceptible to acute intestinal inflammation and that a significantly higher number of activated natural killer (NK) cells was accumulated in the colonic lamina propria of Gitr-/- mice as compared to wild-type mice. Additionally, Rag2-/- Gitr-/- mice, which lack T cells but have NK cells, also displayed more severe colonic inflammation than Rag2-/- mice. In contrast, an anti-GITR agonistic antibody significantly alleviated colitis in Rag2-/- mice. Engagement of GITR inhibited IL-15-mediated activating signaling events in NK cells, which include cell activation and proliferation, and production of cytokines and cytotoxic granules. Taken together, our results provide the first evidence that GITR negatively controls intestinal inflammation through NK cell functions.

TRAF5 Deficiency Ameliorates the Severity of Dextran Sulfate Sodium Colitis by Decreasing TRAF2 Expression in Nonhematopoietic Cells.

TNFR-associated factor 5 (TRAF5) is a cytosolic adaptor protein and functions as an inflammatory regulator. However, the in vivo function of TRAF5 remains unclear, and how TRAF5 controls inflammatory responses in the intestine is not well understood. In this study, we found that intestinal epithelial cells from Traf5-/- mice expressed a significantly lower level of NF-κB-regulated proinflammatory genes, such as Tnf, Il6, and Cxcl1, as early as day 3 after dextran sulfate sodium (DSS) exposure when compared with wild-type mice. The intestinal barrier integrity of DSS-treated Traf5-/- mice remained intact at this early time point, and Traf5-/- mice showed decreased body weight loss and longer colon length at later time points. Surprisingly, the protein level of TRAF2, but not TRAF3, was reduced in colon tissues of Traf5-/- mice after DSS, indicating the requirement of TRAF5 for TRAF2 protein stability in the inflamed colon. Experiments with bone marrow chimeras confirmed that TRAF5 deficiency in nonhematopoietic cells caused the attenuated colitis. Our in vitro experiments demonstrated that proinflammatory cytokines significantly promoted the degradation of TRAF2 protein in Traf5-/- nonhematopoietic cells in a proteasome-dependent manner. Collectively, our data suggest a novel regulatory function of TRAF5 in supporting the proinflammatory function of TRAF2 in nonhematopoietic cells, which may be important for acute inflammatory responses in the intestine.

Simultaneous computed tomographic angiography of the coronary and radial arteries.

Our aim was to assess a method of simultaneous computed tomographic (CT) angiography of the coronary and radial arteries without increasing contrast medium usage. Radial access is a standard approach in coronary interventions. However, radial artery puncture is difficult due to the small size of the radial artery and potential unexpected anomaly. If we can obtain anatomical information on the radial artery beforehand, the success rate of radial artery puncture may increase. Simultaneous CT angiography of the coronary and radial arteries without increasing contrast medium usage was planned. Contrast medium was injected in the right elbow vein. Time to peak concentration of contrast medium in the aorta (TPA) and time to peak concentration of contrast medium in the radial artery (TPR) were obtained by the test scan in each patient based on the time-density curve. The main scan was performed using 265 mg iodine/kg of contrast medium. The start time was decided according to TPA and TPR, respectively. This study included 192 cases [age, mean ± standard deviation (SD),72.0 ± 9.9 years]. Mean TPA and TPR were 19.0 ± 2.3(SD) seconds and 34.0 ± 10.0 s, respectively. Clear images of radial arteries were obtained in 89.6% (right) and 84.9% (left). Radiation exposure during cardiac CT angiography (CCTA) and radial artery CT angiography (RCTA) was 269.9 ± 155.6 mGy cm and 31.1 ± 12.3 mGy cm as dose length product, respectively. RCTA immediately following CCTA was safely performed with minimal increase in radiation exposure and no additional contrast medium. These images can help in radial access as well as distal radial access in coronary interventions.

IQ motif-containing GTPase-activating protein 1 is essential for the optimal maintenance of lung ILC2s.

Group 2 innate lymphoid cells (ILC2s) play critical roles in type 2 immunity and are crucial for pathogenesis of various types of inflammatory disease. IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein that is involved in multiple cellular functions such as cell survival and trafficking. While the roles for IQGAP1 in T and B lymphocytes have been uncovered, the physiological significance of IQGAP1 in innate lymphocytes remains to be elucidated. In the current study, we demonstrate that using bone marrow chimeras, the deficiency of IQGAP1 caused an impaired survival of lung ILC2s in a cell-intrinsic manner and that Iqgap1-/- mice displayed decreased accumulation of ILC2s after administration of papain and thereby reduced the pathology of the disease. Moreover, Iqgap1-/- ILC2s showed a significantly enhanced apoptosis as compared to wild-type ILC2s under both steady-state and inflammatory conditions. Together these results identify for the first time that IQGAP1 is essential for homeostasis of ILC2s in the lung.

TNF Receptor-Associated Factor 5 Limits Function of Plasmacytoid Dendritic Cells by Controlling IFN Regulatory Factor 5 Expression.

The physiological functions of TNF receptor-associated factor 5 (TRAF5) in the skin inflammation and wound healing process are not well characterized. We found that Traf5 -/- mice exhibited an accelerated skin wound healing as compared with wild-type counterparts. The augmented wound closure in Traf5 -/- mice was associated with a massive accumulation of plasmacytoid dendritic cells (pDCs) into skin wounds and an enhanced expression of genes related to wound repair at skin sites. In accordance with this result, adoptive transfer of Traf5 -/- pDCs, but not wild-type pDCs, into the injured skin area in wild-type recipient mice significantly promoted skin wound healing. The expression of skin-tropic chemokine receptor CXCR3 was significantly upregulated in Traf5-/- pDCs, and treatment with a CXCR3 inhibitor cancelled the promoted wound healing in Traf5-/- mice, suggesting a pivotal role of CXCR3 in pDC-dependent wound healing. Traf5 -/- pDCs displayed significantly higher expression of IFN regulatory factor 5 (IRF5), which correlated with greater induction of proinflammatory cytokine genes and CXCR3 protein after stimulation with TLR ligands. Consistently, transduction of exogeneous TRAF5 in Traf5-/- pDCs normalized the levels of abnormally elevated proinflammatory molecules, including IRF5 and CXCR3. Furthermore, knockdown of IRF5 also rescued the abnormal phenotypes of Traf5-/- pDCs. Therefore, the higher expression and induction of IRF5 in Traf5-/- pDCs causes proinflammatory and skin-tropic characteristics of the pDCs, which may accelerate skin wound healing responses. Collectively, our results uncover a novel role of TRAF5 in skin wound healing that is mediated by IRF5-dependent function of pDCs.

Analysis of the prognostic factors of long-term native liver survival in survivors of biliary atresia.

PURPOSE: Long-term survivors of biliary atresia (BA) sometimes experience liver dysfunction. We evaluated the prognostic factors for long-term native liver survival (NLS) in BA patients after the Kasai procedure. METHODS: This study included 67 patients with jaundice disappearance after the Kasai procedure performed between 1972 and 1995, and NLS for over 10 years. We retrospectively evaluated the clinical parameters, including the type of BA, age at the Kasai procedure, medical conditions, and treatments. The adjusted odds ratios (aOR) were obtained for 20-year NLS using logistic regression analysis. RESULTS: The median age of the patients at the Kasai procedure was 63 days. Of the 67 study patients, 62 patients (92.5 %) had jaundice-free NLS at the age of 20 years, 4 patients died before the age of 20 years from liver failure, and 1 patient underwent living related liver transplantation. The presence of gastro-esophageal varices requiring endoscopic injection sclerotherapy was a significant factor (aOR 33.8; p = 0.0033), while hypersplenism and cholangitis were not identified as significant factors. CONCLUSIONS: The existence of symptomatic portal hypertension would influence long-term NLS in BA patients after the Kasai procedure. In such patients, accurate evaluation of hepatic function and adequate treatment for sequelae are needed.