Safety and Effectiveness of Aortic Occlusion for Those Undergoing Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA): A Retrospective Single-Center Study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporarily control bleeding and maintain the cerebral and coronary blood flow in cases in which it is difficult to control hemorrhagic shock. However, the safety and effectiveness of REBOA remains uncertain. OBJECTIVES: This study aimed to estimate the safety and effectiveness of aortic occlusion in patients who undergo REBOA catheter placement. METHODS: We conducted a retrospective study of patients who underwent REBOA catheter placement at Fukuyama City Hospital Emergency Medical Center from August 1, 2008 to March 31, 2020. A propensity score-matching analysis was used to compare 30-day survival between patients who undergo REBOA catheter placement with and without aortic occlusion. RESULTS: Overall, 122 of the 147 who underwent REBOA catheter placement at Fukuyama City Hospital were eligible for inclusion. Thirty-five patients in the Occlusion group and 35 patients in the Nonocclusion group were selected by propensity score matching. According to the 30-day survival rate, the difference between the two groups was not statistically significant (p = 0.288 log-rank test). Moreover, the required treatment, the types and incidence of complications, and other outcomes did not differ according to the presence or absence of aortic occlusion in patients who underwent REBOA catheter placement. CONCLUSION: According to the results of this study, in trauma patients who undergo REBOA catheter placement, the presence of aortic occlusion was not significantly associated with 30-day mortality. Furthermore, the performance of aortic occlusion was not associated with a significant increase in complications.

Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin.

The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2-/- mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2-/- lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2-/- and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2-/- fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2-/- mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF.

Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.

MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1(-/-) mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1(-/-) mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1(-/-) mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1(-/-) mice. Transplantation of MCP-1(-/-) bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1(-/-) mice increased lung metastasis. The primary tumors of MCP-1(-/-) mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment.

Characterization of epidemic diarrhea outbreaks associated with bovine torovirus in adult cows.

Bovine torovirus (BToV) is recognized as an enteric pathogen of calves, but its etiological role in diarrhea and epidemiological characterization in adult cows remain unclear. In 2007-2008, three outbreaks of epidemic diarrhea occurred in adult cows at three dairy farms in Niigata Prefecture, Japan. BToV was the only enteric pathogen detected in these outbreaks, as determined by electron microscopy, reverse transcription-PCR, bacteria and parasite tests of fecal samples, and antibody tests with paired sera. The epidemiological features of the three outbreaks were similar to those of bovine coronavirus infection, except for the absence of bloody diarrhea, with diarrhea spreading among most adult cows, but not in calves, within several days and diarrhea lasting for 3-5 days with anorexia. Decreased milk production and mild respiratory symptoms were also observed in two of the outbreaks. Nucleotide sequence analysis of the BToV nucleocapsid, spike, and hemagglutinin-esterase (HE) genes revealed a close relatedness among the detected BToV strains from each outbreak and those of Japanese BToV strain Aichi/2004. Furthermore, we isolated a BToV strain, designated Niigata (TC), from a fecal sample using a human rectal tumor cell line. Sequence analysis of this isolate and Aichi/2004 indicated that both strains have truncated HE genes with deletions in the 3' region that occurred through cell culture-adaptation. The short projections that are believed to be formed by the HE protein on virus particles were not observed in these cultured strains by electron microscopy. Taken together, these results suggest that BToV causes epidemic diarrhea in adult cows and should be included in the differential diagnosis of diarrhea in adult cows. In addition, our findings indicate that the HE protein of BToV may not be necessary for viral replication.

Reduction of air leaks in a canine model of pulmonary resection with a new staple-line buttress.

OBJECTIVE: Recently, linear staplers have been used frequently in thoracic surgery; however, air leakage from the staple line is still unresolved. Various buttress materials have been developed to prevent air leakage, but performance is still not satisfactory. We are therefore developing a new material, consisting of calcium alginate nonwoven fabric covered with sodium alginate sponge. METHODS: Thirty-three beagle dogs were divided into 7 groups, and each underwent thoracotomy. Right middle lobe incision was performed with a linear stapler and 1 of the following buttress methods: group A, no buttress; group B, polyglycolic acid nonwoven fabric; group C, fibrin glue alone; group D, polyglycolic acid nonwoven fabric with fibrin glue; group E, polyglycomer sheet; group F, new alginate material; and group G, polyglycolic acid nonwoven fabric plus new alginate material. Burst pressures were measured under mechanical ventilation management. RESULTS: Burst pressures were 12.0 ± 6.8 cm H(2)O in group A, 31.3 ± 6.6 cm H(2)O in group B, 13.9 ± 3.8 cm H(2)O in group C, 26.9 ± 2.8 cm H(2)O in group D, 24.8 ± 1.8 cm H(2)O in group E, 48.5 ± 4.9 cm H(2)O in group F, and 54.2 ± 12.4 cm H(2)O in group G. F and G group pressures reached the target of 40 to 50 cm H(2)O and were significantly higher than those of the 5 conventional groups (P < .0005) CONCLUSIONS: This alginate buttress should be effective for preventing air leakage during operations because it has both sealant and bolster effects working in conjunction.

Measurements of serum cystatin C concentrations underestimate renal dysfunction in pediatric patients with chronic kidney disease.

BACKGROUND: In our clinical experience, cystatin C (CysC) concentrations are not as high as expected in patients with chronic kidney disease (CKD) and high-stage renal dysfunction. We therefore investigated whether measurements of serum CysC result in an underestimation of renal dysfunction in pediatric patients with CKD. METHODS: Glomerular filtration rate (GFR) was estimated from serum creatinine (Cr) concentration, using the equation Cr-GFR (%) = [0.30 × body length (m)/serum Cr] × 100; and from serum CysC concentration, using the equation Cys-GFR (%) = (0.70/serum CysC) × 100. We investigated the relationship between GFR estimated by these 2 equations. Patients aged 2-12 years were assorted into 5 groups, based on GFR-Cr categories of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75%, and GFR-CysC/GFR-Cr ratios were compared in these 5 groups. RESULTS: The median GFR-CysC/GFR-Cr ratio in groups of patients with GFR-Cr of <12.5, ≥12.5 to <25, ≥25 to <50, ≥50 to <75, and ≥75% were 2.28, 1.48, 1.22, 1.18 and 0.98, respectively, with statistically significant differences between any two groups (p < 0.001). CONCLUSION: Measurements of serum CysC concentrations lead to underestimation of renal dysfunction in pediatric patients with CKD.

Reference serum cystatin C levels in Japanese children.

BACKGROUND: Single measurements of serum cystatin C (cysC) concentration have generally been used to determine glomerular filtration rate (GFR) in adults. Since GFR varies to some extent among children, we attempted to determine reference serum cysC concentrations for Japanese children. METHODS: Serum cysC concentrations were determined by a latex particle-enhanced turbidimetric immunoassay in children who did not present with kidney disease or infectious disease, and the relationship between age and serum cysC level was assessed. RESULTS: We found that reference serum cysC levels gradually decreased during the first year after birth, thereafter becoming constant. Mean serum cysC concentration in children aged 1 year (0.76 ± 0.10 mg/L) was slightly higher than in children aged ≥2 years (0.70 ± 0.09 mg/L). CONCLUSION: Our reference values will be applicable for screening renal function in Japanese children.

Reference serum creatinine levels determined by an enzymatic method in Japanese children: relationship to body length.

BACKGROUND: It is necessary to set the standard serum creatinine (Cr) values for the medical care of pediatric chronic kidney disease patients. The estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) = kappa x body length (cm)/serum Cr value (mg/dl) determined by the Jaffe method devised by Schwartz has been used clinically. However, enzymatic methods have recently been used to measure Cr instead of the Jaffe method, making it necessary to reevaluate the coefficient kappa of the above equation. Following transformation of the above formula, the normal serum Cr level should be proportional to body length: normal serum Cr value (mg/dl) = k x body length (m). METHODS: Serum Cr values were measured by an enzymatic method in children who did not present with kidney disease or infectious disease, and the relationship between the body length and serum Cr level was determined by linear regression analysis. RESULTS: We found a regression equation capable of estimating the reference value of serum Cr from body length. In children aged 1-12 years, body length (m) x 0.30 yielded a value similar to the reference serum Cr level. CONCLUSION: There have been no previous reports of the determination of reference serum Cr levels by enzymatic methods in Japanese children. Our formula will be applicable for screening of renal function in Japanese children.

First isolation of cytopathogenic bovine torovirus in cell culture from a calf with diarrhea.

A cytopathogenic virus (designated the Aichi/2004 strain) was isolated in a human rectal adenocarcinoma cell line (HRT-18) from the ileum contents of a calf with diarrhea. Oval and elongated particles, approximately 100 to 170 nm in diameter, with club-shaped projections were seen in the infected culture supernatant, and torovirus-like (tubular and torus nucleocapsid) structures were seen in the infected cells by electron microscopy. An antiserum against bovine torovirus (BToV) reacted with the infected cells by immunofluorescence and neutralized the isolate. However, antisera against bovine coronavirus (BCV) failed to react with the infected cells by immunofluorescence or did not neutralize the isolate. Further, the isolate was positive for BToV by reverse transcription-PCR (RT-PCR) targeting fragments of the nucleocapsid (N), membrane (M), and spike (S) genes. Comparison of the nucleotide sequences of the PCR products with those of the published N, M, and S genes (476 to 497, 672, and 687 to 690 nucleotides, respectively) of toroviruses showed high sequence identities (up to 99.4%, 98.7%, and 94.9% for the N, M, and S genes, respectively) between the isolate and BToVs. In contrast, the isolate was negative for BCV by RT-PCR. In a serological survey of serum samples from 355 calves at 33 farms, 92% of calves were positive for neutralizing antibodies to the isolate. These results indicate that the isolate in this study was BToV and that BToV infection might be common in cattle in Japan. To our knowledge, this is the first isolation of BToV in tissue culture.