Construction of a prognostic model for radical esophagectomy based on immunohistochemical prognostic markers combined with clinicopathological factors.

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and lacks effective biomarkers to evaluate prognosis and treatment. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a protein highly expressed in ESCC tissues screened by isobaric tags for relative and absolute quantitation proteomics, which has significant prognostic value in a variety of malignant tumors, but its relationship with ESCC remains unclear. By immunohistochemical staining of 266 ESCC samples, we analyzed the relationship between GPNMB and ESCC. To explore how to improve the ability of ESCC prognostic assessment, we established a prognostic model of GPNMB and clinicopathological features. The results suggest that GPNMB expression is generally positive in ESCC tissues and is significantly associated with poorer differentiation, more advanced American Joint Council on Cancer (AJCC) stage, and higher tumor aggressiveness (P < .05). Multivariate Cox analysis indicated that GPNMB expression was an independent risk factor for ESCC patients. A total of 188 (70%) patients were randomly selected from the training cohort and the four variables were automatically screened by stepwise regression based on the AIC principle: GPNMB expression, nation, AJCC stage and nerve invasion. Through the weighted term, we calculate the risk score of each patient, and by drawing the receiver operating characteristic curve, we show that the model has good prognostic evaluation performance. The stability of the model was verified by test cohort. Conclusion: GPNMB is a prognostic marker consistent with the characteristics of tumor therapeutic targets. For the first time, we constructed a prognostic model combining immunohistochemical prognostic markers and clinicopathological features in ESCC, which showed higher prognostic efficacy than AJCC staging system in predicting the prognosis of ESCC patients in this region.

Presentation of the septic patient to the emergency department with respect to age and sex - a retrospective cross-sectional study.

OBJECTIVE: It is challenging to identify sepsis in the emergency department, in part due to the non-specific presentation of septic patients. Current clinical sepsis screening tools rely on vital signs but many patients present with near normal vital signs and are therefore not identified as septic. This suggests that variables, e.g. signs and symptoms, need to be included to improve sepsis detection in the emergency department. Our hypothesis was that the presentation of sepsis differs based age and sex. The potential differences in presentation could be used to apply to future sepsis screening tools. The aim was to analyze the prevalence of keywords reflecting the presentation of septic patients in the emergency department in relation to age and sex. METHOD: Retrospective cross-sectional study. Keywords reflecting sepsis presentation to the emergency department were quantified and compared between age categories and the sex. 479 patients admitted to the emergency department of Södersjukhuset, Stockholm during 2013 and discharged with an ICD-10 code consistent with sepsis were included. We adjusted for multiple comparisons by applying Bonferroni-adjusted significance levels for all comparisons. RESULT: "Pain" and "risk factors for sepsis" were significantly more common among patients younger than 65 years as compared with those 75 years and older: (n = 87/137; 63.5% vs n = 99/240; 41.3%, P-value < 0.000) and (n = 74/137; 54.0% vs 55/240; 22.9%, P-value < 0.000) respectively. "Risk factors for sepsis" was also significantly more common among patients between 65 and 74 years as compared with those 75 years and older: (n = 43/102; 42.2% vs 55/240; 22.9%, P-value < 0.000). "Pain" and "gastrointestinal symptoms" were significantly more common among women as compared with men: (n = 128/224; 57.1% vs n = 102/255; 40.0%, P-value < 0.000) and (n = 82/244; 36.6% vs n = 55/255; 21.6%, P-value < 0.000) respectively. CONCLUSION: The keywords "pain" and "risk factors for sepsis" were more common among younger patients and "pain" and "gastrointestinal symptoms" were more common among women. However, most keywords had a similar prevalence irrespective of age and sex. The results could potentially be used to augment sepsis screening tools or clinical decision tools.

Prognostic Value of GPNMB, EGFR, p-PI3K, and Ki-67 in Patients with Esophageal Squamous Cell Carcinoma.

Background: GPNMB is a newly discovered tumour-promoting factor that may promote tumour cell progression by activating the PI3K/AKT pathway by EGFR. However, there are insufficient studies about GPNMB in ESCC. This study investigated the relationship between GPNMB and EGFR/PI3K pathway genes in ESCC. Methods: The expression levels of GPNMB, EGFR, p-PI3K, and Ki-67 were examined using immunohistochemistry. Statistical analysis was done by SPSS 22.0 and R. Results: GPNMB mRNA expression is higher in ESCC compared with paracancerous tissues. The expression of EGFR, PIK3CA, PIK3CB, and AKT1 was increased in GPNMB upregulated samples. GPNMB expression was positively correlated with EGFR, p-PI3K, and Ki-67 expression. GPNMB was expressed higher in the AJCC III stage, lymph node metastasis, and moderately poorly differentiated patients. EGFR was higher expressed in patients with vascular invasion; p-PI3K expression in Kazak was higher than that in Han; Ki-67 expression was higher in tumour size ≥ 3 cm. Patients with high expression of GPNMB, p-PI3K, and Ki-67 had worse OS. p-PI3K, Ki-67, nerve invasion, and lymphatic metastasis were independent risk factors, and postoperative adjuvant therapy was a protective factor in ESCC. Conclusion: As a tumour-promoting factor, GPNMB is expected to be a potential target for ESCC.

Keywords reflecting sepsis presentation based on mode of emergency department arrival: a retrospective cross-sectional study.

BACKGROUND: Current sepsis screening tools are predominantly based on vital signs. However, patients with serious infections frequently present with normal vital signs and there has been an increased interest to include other variables such as symptoms in screening tools to detect sepsis. The majority of patients with sepsis arrive to the emergency department by emergency medical services. Our hypothesis was that the presentation of sepsis, including symptoms, may differ between patients arriving to the emergency department by emergency medical services and patients arriving by other means. This information is of interest to adapt future sepsis screening tools to the population in which they will be implemented. The aim of the current study was to compare the prevalence of keywords reflecting the clinical presentation of sepsis based on mode of arrival among septic patients presenting to the emergency department. METHODS: Retrospective cross-sectional study of 479 adult septic patients. Keywords reflecting sepsis presentation upon emergency department arrival were quantified and analyzed based on mode of arrival, i.e., by emergency medical services or by other means. We adjusted for multiple comparisons by applying Bonferroni-adjusted significance levels for all comparisons. Adjustments for age, gender, and sepsis severity were performed by stratification. All patients were admitted to the emergency department of Södersjukhuset, Stockholm, and discharged with an ICD-10 code compatible with sepsis between January 1, and December 31, 2013. RESULTS: "Abnormal breathing" (51.8% vs 20.5%, p value < 0.001), "abnormal circulation" (38.4% vs 21.3%, p value < 0.001), "acute altered mental status" (31.1% vs 13.1%, p value < 0.001), and "decreased mobility" (26.1% vs 10.7%, p value < 0.001) were more common among patients arriving by emergency medical services, while "pain" (71.3% vs 40.1%, p value < 0.001) and "risk factors for sepsis" (50.8% vs 30.8%, p value < 0.001) were more common among patients arriving by other means. CONCLUSIONS: The distribution of most keywords related to sepsis presentation was similar irrespective of mode of arrival; however, some differences were present. This information may be useful in clinical decision tools or sepsis screening tools.

Clinical Application of the FICE Technique for Biopsy of Bronchial Mucosal Lesions.

OBJECTIVE: To determine the diagnostic accuracy of flexile spectral imaging color enhancement (FICE) of abnormal morphologic changes in bronchial mucosal lesions. STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Department of endoscopy, the 10th People's Hospital of Shenyang, China, from January 2015 to April 2016. METHODOLOGY: Patients aged 17-71 years, who presented with abnormal lesions of lung and bronchus, were included. Patients with severe heart disease, arrhythmias, aneurysm of aorta, blood pressure >160/100 mmHg, allergic to anaesthetic drugs, and unwilling to undergo endoscopy were excluded. The bronchoscopic FICE technique was used to observe abnormal bronchial mucosa in 85 patients. Targeted brushings, lavage, and tissue biopsies were performed under the FICE mode. RESULTS: With routine pathological results under white light as a reference, high definition electronic bronchoscopy combined with FICE biopsy yielded a positive rate for bronchial mucosal lesions and bronchial tumors in up to (73 87%) of cases. CONCLUSION: The FICE technique showed significant enhancement of bronchial mucosal lesion diagnosis, which can help endoscopists in the early and accurate diagnosis. Key Words: FICE, Bronchial mucosal lesions, Biopsy, Diagnostic accuracy.

GeneXpert MTB/RIF for rapid diagnosis and rifampin resistance detection of endobronchial tuberculosis.

BACKGROUND AND OBJECTIVE: Delayed diagnosis and treatment of tuberculosis (TB) contribute to poor outcomes, especially for endobronchial TB (EBTB), which typically leads to tracheobronchial stenosis. Finding rapid and accurate diagnostic tools for EBTB is crucial. GeneXpert Mycobacterium tuberculosis (MTB)/rifampin (RIF) was recommended by the World Health Organization (WHO) as a standard molecular biological diagnostic technique for MTB. The aim of this study was to evaluate the efficacy of GeneXpert MTB/RIF for diagnosing EBTB and for evaluating RIF resistance. METHODS: Biopsy tissue and bronchial brushings from EBTB patients were prospectively assessed with GeneXpert MTB/RIF. The diagnostic yields of auramine O-stained sputum smears and bronchial brush smears were obtained, and the results were compared with the cultures of sputum and biopsy tissues for MTB. RESULTS: In 61 confirmed cases of EBTB, the sensitivities of sputum smear, bronchial brush smear, sputum culture and tissue culture to diagnose EBTB were 13.1%, 32.8%, 36.1% and 68.9%, respectively. For bronchial brushings and biopsies, our data showed sensitivities of 57.4% and 63.9%, respectively, and a specificity of 100% for GeneXpert MTB/RIF, and these results were superior to those of sputum smears, bronchial brush smears and sputum culture. GeneXpert MTB/RIF for bronchial brushings and biopsies showed complementarity in its diagnostic performance. Resistance to RIF was identified in 17.4% (8/46) of GeneXpert MTB-positive cases. CONCLUSION: GeneXpert MTB/RIF may enable more rapid EBTB diagnosis and determination of RIF resistance, which are crucial for timely treatment.

Single centre experience: long term outcomes in spina bifida patients.

OBJECTIVE: To determine our single centre experience of long term renal function and mortality rates of our cohort of spina bifida patients born since 1970. MATERIALS AND METHODS: We collected a prospective database and included all patients born with spina bifida between 1970 and 2011 managed by our centre. Data we collected included the glomerular filtration rates, results of renal tract imaging, management strategies and mortalities. RESULTS: Of 160 patients identified, 120 were included for analysis with a mean age of 20 years. In our cohort 48% (58/120) had normal renal function and only 1.6% (2/120) had severe renal impairment or end stage renal failure. There was a mortality rate of 4.4% and there were no deaths from renal failure. CONCLUSION: Spina bifida patients have been reported to have high mortality rates and high morbidity secondary to renal failure. Historical data does not appear to reflect current advancements and we would therefore be more optimistic when counselling families about long term survival into adulthood.

Cultural bias in the AAP's 2012 Technical Report and Policy Statement on male circumcision.

The American Academy of Pediatrics recently released its new Technical Report and Policy Statement on male circumcision, concluding that current evidence indicates that the health benefits of newborn male circumcision outweigh the risks. The technical report is based on the scrutiny of a large number of complex scientific articles. Therefore, while striving for objectivity, the conclusions drawn by the 8 task force members reflect what these individual physicians perceived as trustworthy evidence. Seen from the outside, cultural bias reflecting the normality of nontherapeutic male circumcision in the United States seems obvious, and the report's conclusions are different from those reached by physicians in other parts of the Western world, including Europe, Canada, and Australia. In this commentary, a different view is presented by non-US-based physicians and representatives of general medical associations and societies for pediatrics, pediatric surgery, and pediatric urology in Northern Europe. To these authors, only 1 of the arguments put forward by the American Academy of Pediatrics has some theoretical relevance in relation to infant male circumcision; namely, the possible protection against urinary tract infections in infant boys, which can easily be treated with antibiotics without tissue loss. The other claimed health benefits, including protection against HIV/AIDS, genital herpes, genital warts, and penile cancer, are questionable, weak, and likely to have little public health relevance in a Western context, and they do not represent compelling reasons for surgery before boys are old enough to decide for themselves.

Ephedrine hydrochloride: novel use in the management of resistant non-neurogenic daytime urinary incontinence in children.

OBJECTIVE: To determine whether the adrenoceptor agonist, ephedrine hydrochloride, is an effective treatment for resistant non-neurogenic daytime urinary incontinence in children. METHODS: From 2000 to 2010, eighteen children with resistant non-neurogenic daytime urinary incontinence were treated with oral ephedrine hydrochloride at our institution. Sixteen were female and two were male. Median age at treatment was 12 years (range 5-15 years). Two children had spina bifida occulta. There were no other co-morbidities. Multiple anticholinergics were prescribed and dose maximized to support a bladder and bowel training programme, without achieving continence in this resistant group of children. Pre-treatment urodynamics were normal in 10, but revealed an open bladder neck in 8 patients. None showed detrusor over-activity. Oral ephedrine hydrochloride was started at 7.5 mg or 15 mg twice daily and titrated up to a maximum of 30 mg four times daily according to response. RESULTS: Median follow-up was 7 years (range 6-8 years). Seventeen children (94%) reported improvement in symptoms and six (33%) achieved complete urinary continence. All patients maintained compliant bladders on post-treatment urodynamics. Seven of the 8 previously open bladder necks were closed. No patients reported any significant side effects. Patients with open bladder necks on pre-treatment urodynamics were more likely to show a full response to ephedrine (odds ratio 15; 95% CI 1.2-185.2). CONCLUSIONS: Oral ephedrine hydrochloride is an effective treatment for carefully selected children with resistant non-neurogenic daytime urinary incontinence.

VANG-1 and PRKL-1 cooperate to negatively regulate neurite formation in Caenorhabditis elegans.

Neuritogenesis is a critical early step in the development and maturation of neurons and neuronal circuits. While extracellular directional cues are known to specify the site and orientation of nascent neurite formation in vivo, little is known about the genetic pathways that block inappropriate neurite emergence in order to maintain proper neuronal polarity. Here we report that the Caenorhabditis elegans orthologues of Van Gogh (vang-1), Prickle (prkl-1), and Dishevelled (dsh-1), core components of planar cell polarity (PCP) signaling, are required in a subset of peripheral motor neurons to restrict neurite emergence to a specific organ axis. In loss-of-function mutants, neurons display supernumerary neurites that extend inappropriately along the orthogonal anteroposterior (A/P) body axis. We show that autonomous and non-autonomous gene activities are required early and persistently to inhibit the formation or consolidation of growth cone protrusions directed away from organ precursor cells. Furthermore, prkl-1 overexpression is sufficient to suppress neurite formation and reorient neuronal polarity in a vang-1- and dsh-1-dependent manner. Our findings suggest a novel role for a PCP-like pathway in maintaining polarized neuronal morphology by inhibiting neuronal responses to extrinsic or intrinsic cues that would otherwise promote extraneous neurite formation.

Indications and relative renal function for paediatric nephrectomy over a 20-year period.

BACKGROUND: The indications for partial or total nephrectomy for urological reasons are not clearly documented in the paediatric surgical literature and there are only a limited number of publications on this subject. PURPOSE: In order to clarify the situation in our centre, we reviewed our own indications for nephrectomy over a 20-year period. METHODS: Medical records of patients who underwent nephrectomy for urological and oncological causes between May 1990 and October 2010 at our centre were retrospectively reviewed. Indications for nephrectomy were noted. Renal function was noted for urological cases. RESULTS: A total of 357 nephrectomies were undertaken; out of these, 241 cases were for urological causes and 116 for oncological reasons. The majority of total nephrectomies were performed for multicystic dysplastic kidneys, reflux nephropathy, pelvi-ureteric junction obstruction and dysplasia. Eighty-seven patients exhibited no function at the time of nephrectomy. Of the remainder, 17 had <5% function, 18 had 5-10% function, 5 had 10-15% function and 2 patients had 15-20% function. CONCLUSIONS: This is the largest series of nephrectomies in the paediatric surgery literature to date. The majority of nephrectomies were undertaken for urological conditions with relative renal function of <10% and could not have been usefully preserved in situ. We suggest that kidneys with >10% function should not be routinely removed.

The N-glycanase png-1 acts to limit axon branching during organ formation in Caenorhabditis elegans.

Peptide:N-glycanases (PNGases) are cytoplasmic de-N-glycosylation enzymes that have been shown in cultured cells to facilitate the degradation of misfolded glycoproteins during endoplasmic reticulum-associated degradation and in the processing of major histocompatibility complex class I antigens for proper cell-surface presentation. The gene encoding PNGase activity was initially described in budding yeast (Png1p) and shown to be highly conserved from yeast to humans, but physiological roles in higher organisms have not been elucidated. Here we describe peripheral nervous system defects associated with the first loss-of-function mutations in an animal PNGase. Mutations in png-1, the Caenorhabditis elegans PNGase ortholog, result in an increase in axon branching during morphogenesis of the vulval egg-laying organ and egg-laying behavior changes. Neuronal defects include an increase in the branched morphology of the VC4 and VC5 egg-laying neurons as well as inappropriate branches from axons that run adjacent to the vulva but would normally remain unbranched. We show that png-1 is widely expressed and can act from both neurons and epithelial cells to restrict axon branching. A deletion allele of the DNA repair gene rad-23, orthologs of which are known to physically interact with PNGases in yeast and mammals, displays similar axon branching defects and genetic interactions with png-1. In summary, our analysis reveals a novel developmental role for a PNGase and Rad-23 in the regulation of neuronal branching during organ innervation.

Coming face to face with the stenotic MACE-combined Maceoscopy and colonoscopy (the rendez-vous procedure): a preliminary report.

OBJECTIVE: The aim of our study was to review the management of stomal stenosis after the Malone antegrade continence enema (MACE) procedure at our center, and to describe and assess the early outcomes of 2 novel procedures used in the management of conduit stenosis: Maceoscopy and the rendez-vous. SUBJECTS/PATIENTS AND METHODS: We retrospectively reviewed 45 consecutive MACE cases performed by 1 surgeon at St George's hospital over a 13-year period. RESULTS: Until April 2002, 5 cases presented with difficulty catheterizing their MACE. This was attributed to stenosis without further investigation, and the MACE revised surgically. Of 13 cases presenting with suspected stenosis since May 2002, 8 channels turned out to be patent when assessed and catheterized endoscopically via Maceoscopy. Two truly stenotic MACEs were revised; patency of the other 3 was reestablished by means of a new double-endoscopic procedure we have termed the rendez-vous.

Are prophylactic antibiotics necessary with clean intermittent catheterization? A randomized controlled trial.

BACKGROUND/PURPOSE: Clean intermittent catheterization has been an established practice for more than 3 decades. The validity of antibiotic prophylaxis has been questioned although not tested. METHODS: Eighty-five patients were recruited into a randomized controlled trial. The randomization involved the placement into 1 of 2 groups: (A) continuing antibiotics or (B) discontinuing antibiotics. The trial would last 4 months with the outcome being a confirmed urinary tract infection. All groups were matched for age, sex, and pathology. RESULTS: The incidence of urinary tract infections was significantly increased in the group who continued to use antibiotics (n = 20) when compared with the group who discontinued prophylaxis (n = 3). The common infecting organism was Escherichia coli. CONCLUSIONS: The use of prophylactic antibiotics for children who intermittently catheterize may not be necessary. The use of prophylactic antibiotics may result in increased rates of infection because of the development of resistant organisms.

Attenuation of glucocorticoid signaling through targeted degradation of p300 via the 26S proteasome pathway.

The effects of acetylation on gene expression are complex, with changes in chromatin accessibility intermingled with direct effects on transcriptional regulators. For the nuclear receptors, both positive and negative effects of acetylation on specific gene transcription have been observed. We report that p300 and steroid receptor coactivator 1 interact transiently with the glucocorticoid receptor and that the acetyltransferase activity of p300 makes an important contribution to glucocorticoid receptor-mediated transcription. Treatment of cells with the deacetylase inhibitor, sodium butyrate, inhibited steroid-induced transcription and altered the transient association of glucocorticoid receptor with p300 and steroid receptor coactivator 1. Additionally, sustained sodium butyrate treatment induced the degradation of p300 through the 26S proteasome pathway. Treatment with the proteasome inhibitor MG132 restored both the level of p300 protein and the transcriptional response to steroid over 20 h of treatment. These results reveal new levels for the regulatory control of gene expression by acetylation and suggest feedback control on p300 activity.