Copper-deficiency anemia after esophagectomy: A pitfall of postoperative enteral nutrition through jejunostomy

AbstractINTRODUCTIONCopper deficiency leads to functional disorders of hematopoiesis and neurological system. There have been some reports of copper deficiency occurring to the patients on enteral nutrition through a jejunostomy in long-term-care hospitals. However, it is extremely rare to find patients with copper deficiency several months after esophagectomy, regardless of enteral nutrition through the jejunostomy. To the best of our knowledge, this is the first case report of a patient who experienced copper-deficiency anemia after esophagectomy and subsequent enteral nutrition through the jejunostomy.PRESENTATION OF CASEA 73-year-old man presented with pulmonary failure after esophagectomy for esophageal cancer with video-assisted thoracoscopic surgery, and needed long-term artificial ventilator support. Nutritional management included enteral nutrition through a jejunostomy from the early postoperative period. Copper-deficiency anemia was detected 3 months postoperatively; therefore, copper supplementation with cocoa powder was performed, and both serum copper and hemoglobin levels subsequently recovered.DISCUSSIONCopper-deficiency anemia has already been reported to occur in patients receiving enteral nutrition in long-term care hospitals. However, this is the first case report of copper deficiency after esophagectomy despite administration of standard enteral nutrition through the jejunostomy for several months.CONCLUSIONIt is extremely rare to find copper-deficiency anemia several months after esophagectomy followed by enteral nutrition through the jejunostomy. However, if anemia of unknown origin occurs in such patients, copper-deficiency anemia must be considered among the differential diagnoses

Urinary ACE2 in pediatric IgA nephropathy

Background : Our previous studies demonstrated that the intrarenal renin-angiotensin system (RAS) status was activated in pediatric patients with chronic glomerulonephritis. In the present study, we tested the hypothesis that angiotensin-converting enzyme 2 (ACE2) expression in the kidney is associated with the development of pediatric IgA nephropathy. Methods : We analyzed urinary ACE2 levels and ACE2 expression in the kidney tissues of pediatric patients with IgA nephropathy treated with RAS blockade. Paired tests were used to analyze changes from the first to the second biopsy. Results : Urinary ACE2 levels were significantly decreased after RAS blockade treatment, accompanied by decreased ACE2 expression levels in kidney tissues, urinary protein levels and mesangial hypercellularity scores. Urinary ACE2 levels at the first biopsy were positively correlated with the ACE2 expression levels. Conclusions : These data suggest that urinary ACE2 is associated with ACE2 expression in the diseased kidney, which correlates with the pathogenesis of IgA nephropathy in pediatric patients

NADPH oxidase and ROS in kidney growth

Ureteric bud branching and nephrogenesis are performed through large-scale proliferation and apoptosis events during renal development. Reactive oxygen species (ROS), produced by NADPH oxidase, may contribute to cell behaviors, including proliferation and apoptosis. We investigated the role of NADPH oxidase expression and ROS production in developing kidneys. Immunohistochemistry revealed that NADPH oxidase components were expressed on epithelial cells in ureteric bud branches, as well as on immature glomerular cells and epithelial cells in nephrogenic zones. ROS production, detected by dihydroethidium assay, was strongly observed in ureteric bud branches and nephrogenic zones, corresponding with NADPH oxidase localization. Organ culture of E14 kidneys revealed that the inhibition of NADPH oxidase significantly reduced the number of ureteric bud branches and tips, consistent with reduced ROS production. This was associated with reduced expression of phosphorylated ERK1/2 and increased expression of cleaved caspase-3. Organ culture of E18 kidneys showed that the inhibition of NADPH oxidase reduced nephrogenic zone size, accompanied by reduced ROS production, fewer proliferating cell nuclear antigen-positive cells, lower p-ERK1/2 expression, and increased expression of cleaved caspase-3. These results demonstrate that ROS produced by NADPH oxidase might play an important role in ureteric bud branching and nephrogenesis by regulating proliferation and apoptosis

Role of ERK1/2 and ERK5 in glomerulonephritis

Aim: Extracellular signal regulated kinase (ERK)1/2 and ERK5 are key kinases of the signaling pathways involved in various cellular responses to kidney injury; however, the mechanistic links between those kinase and renin-angiotensin system (RAS) activation in glomerulonephritis (GN) have not been fully elucidated. In this study, we sought to clarify the potential roles of ERK1/2 and ERK5 via RAS activation in the pathogenesis of GN. Methods: A rat model of progressive GN was induced by anti-glomerular basement membrane (GBM) injection and the signal transduction pathway in angiotensin II (Ang II)-induced glomerular pathologic alterations were investigated in primary cultured mesangial cells (MCs). Results: Rats developed typical cellular crescents in glomeruli on day 7 that progressed to severe fibrocellular crescents and glomerulosclerosis on day 28. Strong expression of phospho-ERK1/2 was observed on day 7 and phospho-ERK5 expression was markedly increased on day 28 of GN. An angiotensin II type 1 receptor blocker (ARB) suppressed those augmentations. Moreover, ARB treatment attenuated the increases in macrophage infiltration and PCNA-positive cells observed on day 7 in GN rats, as well as the increase in collagen type 1 expression on day 28. Consistently, MCs stimulated by Ang II showed significant increases in proliferation and the expression of MCP-1 and collagen type 1. Interestingly, while the ERK1/2 inhibitor PD98059 abolished the elevations in MCP-1 expression and cell proliferation, the ERK5 inhibitor BIX02189 abrogated the elevation in collagen type 1 expression. Conclusion: Altogether, these data suggest that ERK1/2 regulates acute inflammatory reactions, while ERK5 promotes the development of RAS-induced chronic glomerular fibrosis activation in GN

Observation of the Pharynx to the Cervical Esophagus Using Transnasal Endoscopy with Blue Laser Imaging

Background In 2014, the new transnasal endoscopy with Blue laser Imaging (BLI) has been developed. Aim We present the usefulness of the observation of from the pharynx to the cervical esophagus using transnasal endoscopy with BLI. Patients and Methods This study was conducted between June 2014 and October 2014. During this period, 70 consecutive patients (60 men, 10 women; mean age 67.9 years old) with esophageal or head and neck cancer underwent endoscopic screening at the oropharynx and hypopharynx by transnasal endoscopy with BLI system We performed this endoscopic observation from oral cavity to pharynx before inserting into the cervical esophagus.The visibility of subsites of the hypopharynx and the orifice of the esophagus was evaluated. The extent of the view of hypopharyngeal opening was classified into 3 categories (excellent, good, poor). Then, the diagnostic accuracy of transnasal endoscopy with BLI system was estimated. Our screening is as follows. First, the patient is asked to bow their head deeply in the left lateral position. We put a hand on the back of the patient’s head and push it forward. The patient is then asked to lift the chin as far as possible. In order to inspect the oral cavity, we insert an endoscope without a mouthpiece. After observation of the oral cavity, the endoscope was inserted through the nose. When the tip of the endoscope reached caudal to the uvula, the patient opened his mouth wide, stuck his tongue forward as much as possible and made a vocal sound like “ayyy”. The endoscopist caused the endoscope to U-turn and observed the oropharynx, in particular the radix linguae (Intra-oropharyngeal U-turn method). For examination of the hypopharynx and the orifice of the esophagus, the patient is asked to blow hard and puff their cheeks while the mouth remains closed (Trumpet maneuver). Results 8 elderly cases were excluded because they could not perform the adequate ballooning. Finally, 62 cases were investigated. The ballooning the pyriform sinus and posterior wall not only allows accurate assessment of the stretched pharyngeal mucosa but also gives a view of postcricoid subsite and the orifice of the esophagus. The wide endoscopic view of the pharynx was obtained in a series of the procedures (excellent=53/62, 85.4%; good=7/52, 4.5%; and poor=2/62, 7.6%). Among 70 patients, 6 superficial lesions (8.6%) at the oropharynx(n=1) and hypopharynx (n=5) were discovered with BLI system. Mucosal redness, a pale thickened mucosa, white deposits or loss of a normal vascular pattern, well demarcated areas covered with scattered dots are important characteristics to diagnose superficial carcinoma. Conclusion The more progress achieved in transnasal endoscopy rapidly in the last few years, it can improve for observing the blind area using trans-oral endoscopy, therefore the trans-nasal endoscope will be a standard tool for the screening of the upper gastrointestinal tract in the near future

Activation of Src Mediates PDGF-Induced Smad1 Phosphorylation and Contributes to the Progression of Glomerulosclerosis in Glomerulonephritis

Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis

Emerging IL-12 family cytokines in the fight against fungal infections

Invasive fungal infections cause approximately 1.5 million deaths per year worldwide and are a growing threat to human health. Current anti-fungal therapies are often insufficient, therefore studies into host-pathogen interactions are critical for the development of novel therapies to improve mortality rates. Myeloid cells, such as macrophages and dendritic cells, express pattern recognition receptor (PRRs), which are important for fungal recognition. Engagement of these PRRs by fungal pathogens induces multiple cytokines, which in turn activate T effector responses. Interleukin (IL)-12 family members (IL-12p70, IL-23, IL-27 and IL-35) link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-12 and IL-23 have established roles during anti-fungal immunity, whereas emerging roles for IL-27 and IL-35 have recently been reported. Here, we discuss the IL-12 family, focusing on IL-27 and IL-35 during anti-fungal immune responses to pathogens such as Candida and Aspergillus

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered