Identification of Cutibacterium modestum in Spondylitis by Metagenomics Analysis.

BACKGROUND/AIM: Identifying pathogens with culture-negative pyogenic spondylitis is difficult. Shotgun metagenomic sequencing is an unbiased and culture-free approach in the diagnosis of infectious diseases. There are, however, a variety of contaminating factors that can confound the precision of metagenomic sequencing. CASE REPORT: In a 65-year-old man suffering from culture-negative L3-5 spondylitis, metagenomics was applied to facilitate the diagnosis. The patient underwent percutaneous endoscopic lumbar discectomy. We applied metagenomic sequencing with a robust contamination-free protocol to the bone biopsy. By comparing the abundance for each taxon between the replicates and negative controls, we reliably identified Cutibacterium modestum as having a statistically higher abundance in all replicates. The patient's antibiotic therapy was switched to penicillin and doxycycline based upon the resistome analysis; the patient fully recovered. CONCLUSION: This application of next-generation sequencing provides a new perspective in the clinical approach to spinal osteomyelitis and illustrates the potential of this technique in rapid etiological diagnosis.

Transthoracic echocardiography monitoring during ASD closure using an artificial hand system.

AIM: Continuous real-time echocardiographic monitoring is essential for guidance during ASD closure. However, transthoracic echocardiography (TTE) can only be implemented intermittently during fluoroscopy. We evaluate a novel approach to provide real-time imaging during the entire procedure. FINDING: We developed a custom-made TTE monitoring apparatus using artificial hand (AH-TTE) that enables real-time TTE images during atrial septal defect (ASD) closure. Thirty-two patients underwent successful device implantation using AH-TTE monitoring without complications. The median duration for real-time AH-TTE monitoring was 22 min and the median fluoroscopy time was 7.2 min. One case of pericardial effusion and one of transient bradycardia event due to air embolism was detected. All patients had uneventful recoveries. CONCLUSIONS: Our simple and novel monitoring technique with AH-TTE provides TEE-like monitoring and may be a new alternative method for ASD closure. It gives real-time stable TTE images and minimizes radiation exposure for the interventional team during fluoroscopy.

Does Resveratrol Play a Role in Decreasing the Inflammation Associated with Contrast Induced Nephropathy in Rat Model?

Contrast is widely used in invasive image examinations such as computed tomography (CT) and angiography; however, the risk of contrast-induced nephropathy (CIN) is high. The aim of this study was to investigate the protective effect of resveratrol in a rat model of CIN. Sprague-Dawley rats were divided into four groups: the control group (0.9% saline infusion only); resveratrol group (RSV, resveratrol, 30 mg/kg); contrast media group (CIN); and resveratrol + contrast media group (RCIN, resveratrol 30 mg/kg 60 min before CIN). CIN was induced via an intravenous injection of a single dose of indomethacin (10 mg/kg), one dose of N-nitro-L-arginine methyl ester (10 mg/kg), and a single dose of contrast medium iopromide (2 g/kg). Blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) were higher in the CIN group compared to the other groups. Histopathological tubule injury scores were also higher in the CIN group compared to the other groups (p < 0.01). NLPR3 in kidney tissue were higher in the CIN group compared to the other groups; however, these results were improved by resveratrol in the RCIN group compared with the CIN group. The expressions of IL-1ß and the percentage of apoptotic cells were higher in the CIN group than in the control and RSV groups, but they were lower in the RCIN group than in the CIN group. The expression of cleaved caspase-3 was higher in the CIN group than in the control and RSV groups, but lower in the RCIN group than in the CIN group. Resveratrol treatment attenuated both injury processes and apoptosis and inhibited the inflammasome pathway in this rat CIN model.

Initial experience of transcatheter closure of subarterial VSD with the Amplatzer duct occluder.

BACKGROUND: The traditional treatment of subarterial ventricular septal defect (VSD) is open heart surgery. This study aimed to evaluate the feasibility, safety and outcome of transcatheter closure with the Amplatzer duct occluder (ADO). METHODS: Between March 2012 and June 2015, a total of 16 patients (8 male and 8 female) with subarterial VSD who underwent transcatheter closure with the ADO were enrolled retrospectively. Their age ranged from 3.0 to 65.6 years, with the median of 35.6 years; their body weights ranged from 14 to 92 kg with the median of 60 kg. All patients had prolapse of the right coronary cusp without subaortic rim. Mild aortic regurgitation was noted in 11 (69%) patients. RESULTS: Left ventriculogram showed VSD size ranged from 1.3 to 9.3 mm with the median of 3.5 mm. The device was successfully implanted in 88% (14/16) of the patients. Although one patient had mild skin allergy to contrast medium, no other complication was noted. Complete closure rate was 64%, 86%, 86% and 86% at 1-day, 1-month, 6-month and 12-month follow-up, respectively. Two patients developed new or worsening aortic regurgitation during follow-up. CONCLUSION: Transcatheter closure of subarterial VSD with ADO is technically feasible and safe in patients older than 7 years of age. However, development or worsening of aortic regurgitation requires long-term follow-up.

Incidence and survival of cancers among 1,054 hemophilia patients: A nationwide and 14-year cohort study.

As life expectancy increases in persons with hemophilia (PWH), more age-related diseases such as cancer emerge among this patient group. The aim of this study was to investigate incidence and survival of cancers among PWH in Taiwan. We analyzed data of 1,054 PWH retrieved from Taiwan's National Health Insurance Research Database between 1997 and 2010, by comparing variables to 10540 age- and gender-matched healthy individuals from the general population. There were 43 PWH and 178 individuals of general population with newly diagnosed cancer (RR 2.42, 95% CI 1.74-3.35). The cumulative incidences of cancer in PWH and the general population were 4.7 and 1.9%, respectively. Hepatocellular carcinoma (HCC) was the major type of cancer (17 cases) in PWH; cancer rate was still increased when HCC and HIV-related cancers were excluded (RR 1.66, 95% CI 1.06-2.59). There was no significant difference observed in lung, colorectal, or prostate cancer occurrence. Compared to the general population, PWH were younger at the time of cancer diagnosis (45.1 vs. 57.2 years old, P value < 0.001), and had fewer co-morbidities. Nineteen PWH with cancers died during the study period, and no bleeding-related death was recorded among these patients. The survival rate was not different between PWH and the general population, P = 0.86. In conclusion, the cumulative incidence of cancer among PWH was higher than the general population. PWH with cancer were younger and had fewer comorbidities, but the survival rates were similar in the two groups.

Gab1 is essential for membrane translocation, activity and integrity of mTORCs after EGF stimulation in urothelial cell carcinoma.

Urothelial carcinoma is the most common type of malignancy in long-term dialysis patients and kidney transplant recipients in Taiwan. mTORCs (mammalian target of rapamycin complexes) and EGF are important in urothelial carcinoma. To identify the regulation of mTORCs upon EGF stimulation is necessary. mTOR integrates signals from growth factors via mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). The mechanism of mTORC1 action has been widely studied; however, the regulation of mTORC2 has not been well studied. Here, we demonstrate that Gab1 is an important upstream regulator in EGF-mediated activation of mTORCs. In our study, we confirm that mTORCs translocate from the cytoplasm to the plasma membrane via the PH domain of Gab1 upon EGF stimulation. Moreover, Gab1 associates with mTORCs. This association stabilizes the integrity of mTORCs and induces mTORC activity. Compared to normal bladder tissue, the expression of Gab1 and activity of mTORCs are elevated in urothelial carcinoma. Collectively, our results suggest that Gab1 is an essential regulator of the EGF-mediated mTORC pathways and may potentially be used as a biomarker for urothelial carcinoma to predict diagnosis and drug response.

Successful percutaneous transluminal coronary angioplasty for acute myocardial infarction in a 12-year-old boy with fibromuscular dysplasia: a case report.

Acute myocardial infarction is rarely reported in children. Most of the cases are secondary to congenital anomalies or Kawasaki disease. Coronary artery total occlusion caused by fibromuscular dysplasia has never been reported in young children. Here we report a case of a 12-year-old boy with fibromuscular dysplasia, who underwent successful coronary intervention for acute myocardial infarction.

An increase in CD3+CD4+CD25+ regulatory T cells after administration of umbilical cord-derived mesenchymal stem cells during sepsis.

Sepsis remains an important cause of death worldwide, and vigorous immune responses during sepsis could be beneficial for bacterial clearance but at the price of collateral damage to self tissues. Mesenchymal stem cells (MSCs) have been found to modulate the immune system and attenuate sepsis. In the present study, MSCs derived from bone marrow and umbilical cord were used and compared. With a cecal ligation and puncture (CLP) model, the mechanisms of MSC-mediated immunoregulation during sepsis were studied by determining the changes of circulating inflammation-associated cytokine profiles and peripheral blood mononuclear cells 18 hours after CLP-induced sepsis. In vitro, bone marrow-derived MSCs (BMMSCs) and umbilical cord-derived MSCs (UCMSCs) showed a similar morphology and surface marker expression. UCMSCs had stronger potential for osteogenesis but lower for adipogenesis than BMMSCs. Compared with rats receiving PBS only after CLP, the percentage of circulating CD3+CD4+CD25+ regulatory T (Treg) cells and the ratio of Treg cells/T cells were elevated significantly in rats receiving MSCs. Further experiment regarding Treg cell function demonstrated that the immunosuppressive capacity of Treg cells from rats with CLP-induced sepsis was decreased, but could be restored by administration of MSCs. Compared with rats receiving PBS only after CLP, serum levels of interleukin-6 and tumor necrosis factor-α were significantly lower in rats receiving MSCs after CLP. There were no differences between BMMSCs and UCMSCs. In summary, this work provides the first in vivo evidence that administering BMMSCs or UCMSCs to rats with CLP-induced sepsis could increase circulating CD3+CD4+CD25+ Treg cells and Treg cells/T cells ratio, enhance Treg cell suppressive function, and decrease serum levels of interleukin-6 and tumor necrosis factor-α, suggesting the immunomodulatory association of Treg cells and MSCs during sepsis.

Multi-detector row computed tomographic evaluation of a rare type of complete vascular ring: double aortic arch with atretic left arch distal to the origin of left subclavian artery.

Double aortic arch with an atretic left arch distal to the origin of left subclavian artery was diagnosed with multi-detector row computed tomography (MDCT) in two children with dysphagia. This rare type of complete vascular ring is clinically important because it may be confused with right aortic arch in mirror imaging. Anatomic details of this rare type of complete vascular ring demonstrated on MDCT facilitated appropriate surgical treatment.

Hydronephrotic urine in the obstructed kidney promotes urothelial carcinoma cell proliferation, migration, invasion through the activation of mTORC2-AKT and ERK signaling pathways.

Obstructive nephropathy is the most common presentation of urothelial carcinoma. The role of the urine in the obstructed kidney namely "hydronephrotic urine" in urothelial carcinoma has not been extensively explored. This study aims to evaluate whether hydronephrotic urine in the obstructed kidney could promote urothelial carcinoma. The hydronephrotic urine was collected from the obstructed kidneys of Sprague-Dawley rats induced by different periods of unilateral ureteral obstruction (UUO). By the inhibition of LY294002 and PD184352, we confirm that hydronephrotic urine promotes urothelial carcinoma cell (T24) and immortalized normal urothelial cells (E6) proliferation, migration and invasion in a dose-dependent manner through the activation of the mTORC2-AKT and ERK signaling pathways. Hydronephrotic urine also increases the expression of cyclin-D2, cyclin-B and CDK2. It also decreases the expression of p27 and p21 in both urothelial carcinoma cells and normal urothelial cells. By the protein array study, we demonstrate that many growth factors which promote tumor cell survival and metastasis are over-expressed in a time-dependent manner in the hydronephrotic urine, including beta-FGF, IFN-γ, PDGF-BB, PIGF, TGF-ß, VEGF-A, VEGF-D and EGF. These results suggest that hydronephrotic urine promotes normal and malignant urothelial cells proliferation, migration and invasion, through the activation of the mTORC2-AKT and ERK signaling pathways. Further investigation using live animal models of tumor growth may be needed to clarify aspects of these statements.

Plasma globotriaosylsphingosine (lysoGb3) could be a biomarker for Fabry disease with a Chinese hotspot late-onset mutation (IVS4+919G>A).

BACKGROUND: Previous studies revealed a high incidence of late-onset Fabry disease mutation, IVS4+919G>A, in Taiwan. However, the natural course is largely unclear and suitable biomarkers for monitoring disease progress are unavailable. METHODS AND RESULTS: Patients carrying IVS4+919G>A or classical Fabry mutations were enrolled in this study. The subjects ranged from newborn to eighty year old adults. Plasma globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) were measured by LC-MS/MS in subjects to evaluate the sensitivity of these two biomarkers. All adult males and symptomatic females could be distinguished from healthy controls by an elevated plasma lysoGb3 level. The lysoGb3 level was also related to the left ventricular mass considering gender and age (p<0.01). Moreover, approximately 70% of male and 45% of female newborns already had an elevated plasma lysoGb3 level which increased gradually as the subjects got older (p<0.01). CONCLUSIONS: Plasma lysoGb3 is a more sensitive and reliable biomarker than plasma Gb3. LysoGb3 also correlated with age and left ventricular mass index in Fabry patients with IVS4+919G>A mutation. Because lots of infants with the IVS4+919G>A mutation already had elevated lysoGb3 levels at birth, that indicates that the development of hypertrophic cardiomyopathy may require a long and insidious course after lysoGb3 accumulation.

Clinical significance of blood pressure ratios in hypertensive crisis in children.

OBJECTIVES: Hypertensive crisis is categorised into hypertensive urgency and hypertensive emergency. The present work aimed to determine the effect of different gradings of blood pressure (BP) ratios in predicting the severity of paediatric hypertensive crisis. METHODS: This was a retrospective case series, based in the paediatric emergency departments of the Changhua Christian Hospital and the Tzu-Chi General Hospital, Taiwan. From 1995 to 2010, the correlation between the severity of hypertension (HTN) and the difference in elevated systolic BP and 99th percentile plus 5 mm Hg (dSBP), the difference in elevated diastolic BP and 99th percentile plus 5 mm Hg (dDBP), dSBP ratio (dSBP/99th percentile plus 5 mm Hg) and dDBP ratio were analysed. A total of 110 children with a first attack of hypertensive crisis were recruited. RESULTS: Patients with hypertensive crisis caused by essential HTN had lower dDBP ratios than the other causes (p=0.033), while those with an oncological aetiology had the highest dSBP and dDBP ratios among all the aetiologies. For clinical presentations, patients with nausea/vomiting and visual impairment presented with higher dSBP ratios than those without the symptoms (both p<0.05), but patients with altered consciousness had higher dSBP and dDBP ratios than those who had clear consciousness (p<0.05). Children with hypertensive urgency had lower dSBP and dDBP ratios than those with hypertensive emergency (both p<0.05). CONCLUSIONS: dDBP and dSBP ratios may serve as BP parameters in predicting the severity of paediatric hypertensive crisis. A dSBP ratio greater than 20% may indicate a critical point for severe hypertensive crisis in children.

Diagnosing appendicitis at different time points in children with right lower quadrant pain: comparison between Pediatric Appendicitis Score and the Alvarado score.

BACKGROUND: Acute appendicitis is the most common abdominal emergency in clinical surgery. This study was designed to compare the diagnostic value of the Pediatric Appendicitis Score (PAS) with that of the Alvarado score based on different time points in children with right lower quadrant (RLQ) abdominal pain. METHODS: This prospective cohort study comprised 1,395 children (aged 3-18 years) with RLQ abdominal pain between 2005 and 2009. The patients were scored by the pediatric emergency physicians. Receiver operating characteristic (ROC) curves were used to determine the appropriate cutoff scores of the Alvarado and PAS systems. The sensitivity and specificity, and area under ROC curve were calculated for both systems. RESULTS: The AUCs of the Alvarado system were all higher than those of the PAS system (day 1: 0.09 vs. 0.87; day 2: 0.87 vs. 0.84; day 3: 0.88 vs. 0.82). The best appropriate cutoff scores were seven (days 1 and 2) and six (day 3) on the PAS and six (days 1 and 2) and seven (day 3) on the Alvarado system. CONCLUSIONS: The preliminary data show that the best cutoff score of Alvarado and PAS systems vary with the different time points of RLQ pain presentation. It may provide helpful information for primary or emergency physicians to determine whether the patient should undergo surgical consultation.

Transcatheter device closure of muscular ventricular septal defect.

Traditional treatment of muscular ventricular septal defect (VSD) is surgical closure, but it carries considerable morbidity and mortality. The Amplatzer muscular VSD occluder (AGA Medical Corporation, Plymouth, MN, USA) was approved by the United States Food and Drug Administration in September 2007 and by the Taiwan Department of Health in September 2009. It is a self-expandable double-disc device made from a nitinol wire mesh. Dacron polyester patches are sewn into each disc and the connecting waist to increase the thrombogenicity of the device. Many reports have shown that transcatheter device closure of muscular VSDs is effective and safe. It has no scar, less pain, shorter hospital stay, and less cost compared to the traditional open heart surgery.

Effect of exercise on asymptomatic children with an isolated aberrant subclavian artery.

OBJECTIVE: An aberrant subclavian artery (aSCA) is the most common congenital anomaly of the aortic arch. Most cases are asymptomatic and found incidentally.This study was conducted to estimate the occult exercise-induced oesophago-tracheal compression (EIETC) in children with isolated aSCA found by screening echocardiography. METHODS: A total of 42 asymptomatic children with isolated aSCA, aged from 6.8 to 16 years, were studied in 2007. Barium oesophagography, echocardiography and magnetic resonance angiography or computed tomography were used to confirm this anomaly. In order to estimate the occult EIETC, we conducted a protocol of pulmonary function tests (PFTs), a feeding test and a treadmill exercise test (TET) on the patients. RESULTS: All of the children could be diagnosed by both barium oesophagography and echocardiography. Six (14%) patients had a globus sensation before testing. None had a history of inspiratory stridor, failure to thrive or dysphagia. No complications developed in this study.An additional patient had a globus sensation after TET, but none had dysphagia, chest pain, dizziness or dyspnoea. Response to exercise was normal, feeding tests were normal and there were no significant changes in the results of PFTs or the grade of respiratory impairment after exercise. CONCLUSIONS: Based on the function tests used, there is no evidence of EIETC and cardiopulmonary deficits in the patients with isolated aSCA. These findings support the known concept not to operate asymptomatic patients with an isolated aSCA found incidentally by screening echocardiography and that there is no increased risk of cardiopulmonary decompensation under defined exercise.

Application with repeated serum biomarkers in pediatric appendicitis in clinical surgery.

PURPOSE: To apply the repeated serum laboratory tests in diagnosing acute appendicitis in children with suspected appendicitis. METHODS: From 2005 to 2007, we prospectively collected 217 pediatric patients with clinically suspected appendicitis. The repeated serum laboratory tests were measured 6 h later and the changes in serum inflammatory biomarkers analyzed. Significant changes in serum parameters between primary and repeated examinations were selected as the discriminating variables. The receiver operating characteristic (ROC) curves were used to determine the cutoff values of the changes between two examinations in predicting appendicitis. RESULTS: Based on the ROC analysis, the change in the serum parameters could include simple appendicitis when the change in neutrophils (delta neutrophils) was >23.5% and delta C-reactive protein (CRP) was >118 mg/L; but for the exclusion of simple appendicitis, delta neutrophils was -44% or under and delta CRP was -10.0 mg/L or under. For perforated appendicitis, delta white blood cell counts, delta neutrophils, delta bands and delta CRP were all significant discriminators. However, based on analysis of the area under the ROC curve (AUC), only delta CRP had the greatest AUCs in predicting both simple and perforated appendicitis. The cutoff point of delta CRP was taken as 4.80 mg/L in distinguishing simple appendicitis from other acute abdominal diseases, and taken as 9.45 mg/L in predicting perforated appendicitis. CONCLUSIONS: Significant change between primary and repeated serum laboratory tests may serve as a helpful method in predicting acute appendicitis in children with suspected appendicitis.

Application with repeated serum biomarkers in pediatric appendicitis in clinical surgery.

PURPOSE: To apply the repeated serum laboratory tests in diagnosing acute appendicitis in children with suspected appendicitis. METHODS: From 2005 to 2007, we prospectively collected 217 pediatric patients with clinically suspected appendicitis. The repeated serum laboratory tests were measured 6 h later and the changes in serum inflammatory biomarkers analyzed. Significant changes in serum parameters between primary and repeated examinations were selected as the discriminating variables. The receiver operating characteristic (ROC) curves were used to determine the cutoff values of the changes between two examinations in predicting appendicitis. RESULTS: Based on the ROC analysis, the change in the serum parameters could include simple appendicitis when the change in neutrophils (delta neutrophils) was >23.5% and delta C-reactive protein (CRP) was >118 mg/L; but for the exclusion of simple appendicitis, delta neutrophils was -44% or under and delta CRP was -10.0 mg/L or under. For perforated appendicitis, delta white blood cell counts, delta neutrophils, delta bands and delta CRP were all significant discriminators. However, based on analysis of the area under the ROC curve (AUC), only delta CRP had the greatest AUCs in predicting both simple and perforated appendicitis. The cutoff point of delta CRP was taken as 4.80 mg/L in distinguishing simple appendicitis from other acute abdominal diseases, and taken as 9.45 mg/L in predicting perforated appendicitis. CONCLUSIONS: Significant change between primary and repeated serum laboratory tests may serve as a helpful method in predicting acute appendicitis in children with suspected appendicitis.