Alpha-1 deficiency in severe asthma patients.

Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant condition, decreases protein concentration and activity at both serum and tissue levels. Few studies investigated whether the type of SERPINA1 gene phenotype in patients with severe asthma can influence symptoms and disease control during follow-up.To assess whether the presence of a non-MM genotype of SERPINA1 in patients with severe asthma is associated with disease control, systemic and airway inflammation, lung function and comorbidities prevalence compared to severe asthma patients with a homozygous genotype (MM).Asthmatic patients belonging to Global Initiative for Asthma (GINA) step 5 were retrospectively analysed in an Italian reference asthma clinic. We collected clinical, biological and functional variables at baseline and for the three following years.Out of 73 patients enrolled, 14 (19.18%) were non-MM and 59 (80.8%) were MM. Asthmatics with non-MM genotype had lower serum AAT concentration (P = 0.004) and higher emphysema prevalence than the MM group (P = 0.003) at baseline. During follow up, only MM patients showed a significant improvement of both ACQ-6 score (P < 0.0001) and eosinophilic systemic inflammation (P < 0.0001).Our findings emphasise the importance of a screening for AAT deficiency in severe asthma, as alleles mutation may influence patient's follow-up..

Minimal clinically important difference of the 6-min walking test in patients with asthma.

BACKGROUND: The 6-min walking test (6MWT) is responsive to physiological changes and pulmonary rehabilitation (PR) in patients with asthma. The minimal clinically important difference (MCID) has not been established yet.OBJECTIVE: To determine the MCID of 6MWT in patients with asthma.METHODS: Using the perceived change in walking ability and the modified Medical Research Council (mMRC) score as anchors, receiver operating characteristic curves and quantile regression, we evaluated 6MWT before and after PR in these patients. The St George Respiratory Questionnaire (SGRQ), the COPD assessment test (CAT) and other outcome measures were also assessed.RESULTS: Of 142 patients with asthma, 37 were enrolled. After PR, 6MWT increased from 453.4 m ± 88.8 to 493.0 m ± 97.2 (P = 0.0001); other outcome measures also increased. There was a slight correlation between baseline 6MWT and SGRQ, CAT and mMRC. No significant correlations were found between post-PR changes in 6MWT and in other outcome measures. Comparing different methods of assessment, the MCID ranged from 26 m to 27 m.CONCLUSION: The most conservative estimate of the MCID of 6MWT after PR was 26 m in patients with asthma. This estimate may be useful in clinical interpretation of data, particularly in response to intervention studies.

A standardized use of intraoperative anastomotic testing in colorectal surgery in the new millennium: is technology taking over? A systematic review and network meta-analysis.

BACKGROUND: Anastomotic leakage (AL) remains the most challenging complication following colorectal resection. There are several tests that can be used to test anastomotic integrity intraoperatively including air leak testing (ALT) and intraoperative colonoscopy (IOC). Indocyanine green (ICG) can be used to visualise blood supply to the bowel used in the anastomosis. However, there is no consensus internationally regarding routine use and which technique is superior. The aim of this study was to determine which intraoperative anastomotoic leak test (IALT) was most effective in reducing AL. METHODS: A systematic review and network meta-analysis were performed. An electronic systematic search was performed using Pubmed, CENTRAL, and Web of Science, of studies comparing ALT, IOC, and ICG. The inclusion criteria were as follows: (a) patients must have had colorectal surgery with formation of an anastomosis; (b) studies must have compared one or more IALTs; (c) and studies must have clear research methodology. RESULTS: Eleven articles totalling 3844 patients met the inclusion criteria and were included in this meta-analysis. Point estimation showed that the AL rate in the control group (no IALT) was significantly higher when compared to the ICG group (RR 0.44; Crl 0.14-0.87) and higher, but without reaching statistical significance, when compared to ALT (RR 0.53; Crl 0.21-1.30) and IOC (RR 0.49; Crl 0.10-1.80). Indirect comparison showed that the AL rate in the ICG group was lower, when compared to both ALT (RR 0.44; Crl 0.14-0.87) and IOC (RR 0.44; Crl 0.14-0.87). CONCLUSIONS: This study suggests that intraoperative testing for a good blood supply using ICG may reduce the AL rate following colorectal surgery.

Polledness in Argentinean Creole cattle, five centuries surviving.

Polledness has been shown to have autosomal Mendelian inheritance, with the polled locus being dominant to the horned locus. This trait was mapped to the BTA1 centromeric end in several breeds. One of the distinctive attributes of Creole cattle, such as the Argentinean Creole, is the presence of long, lyre-shaped horns. However, polled native animals were reported before the introduction of modern selected European breeds. Here, we studied the origin of the polled mutation, either independent or introgressed, in a Creole line from the Creole cattle founder group at the IIACS-INTA Leales Experimental Station (northwest Argentina). The study sample (65 animals: 26 horned and 39 polled) was genotyped using high-density SNP microarrays and three previously reported genetic markers (P202 ID , P80kb ID and PG ). A genome-wide association study, selection signatures, linkage disequilibrium analysis and copy number variations were used to detect the responsible region and the segregating haplotypes/alleles. The interval mapped in the Leales herd (1.23-2.13 Mb) overlapped with the region previously reported in several European cattle breeds, suggesting that the same locus could be segregating in this population. The previously reported variants PF and PG were not detected, thus dismissing the Holstein-Friesian and Nellore origins of the polled phenotype in this native breed. Conversely, the presence of the Celtic variant PC suggests an almost complete co-segregation. The cluster analysis rejected the hypothesis of recent introgression, which is compatible with the historical record of polled Creole cattle in northwest Argentina.

Unenhanced CT for clinical triage of elderly patients presenting to the emergency department with acute abdominal pain.

PURPOSE: The purpose of this study was to compare the diagnostic accuracy and inter-reader agreement of unenhanced computed tomography (CT) to those of contrast-enhanced CT for triage of patients older than 75years admitted to emergency department (ED) with acute abdominal pain (AAP). PATIENTS AND METHODS: Two hundred and eight consecutive patients presenting with AAP to the ED who underwent CT with unenhanced and contrast-enhanced images were retrospectively included. There were 90 men and 118 women with a mean age of 85.4±4.9 (SD) (range: 75-101.4years). Three readers reviewed unenhanced CT images first, and then unenhanced and contrast-enhanced CT images as a single set. Diagnostic accuracy was compared to the standard of reference defined as the final diagnosis obtained after complete clinico-biological and radiological evaluation. Correctness of the working diagnosis proposed by the ED physician was evaluated. Intra- and inter-reader agreements were calculated using the kappa test and interclass correlation. Subgroup analyses were performed for patients requiring only conservative management and for those requiring intervention. RESULTS: Diagnostic accuracy ranged from 64% (95% CI: 62-66%) to 68% (95% CI: 66-70%) for unenhanced CT, and from 68% (95% CI: 66-70%) to 71% (95% CI: 69-73%) for both unenhanced and contrast-enhanced CT. Contrast-enhanced CT did not significantly improve the diagnostic accuracy (P=0.973-0.979). CT corrected the working diagnosis proposed by the ED physician in 59.1% (range: 58.1-60.0%) and 61.2% (range: 57.6-65.5%) of patients before and after contrast injection (P>0.05). Intra-observer agreement was moderate to substantial (k=0.513-0.711). Inter-reader agreement was substantial for unenhanced (kappa=0.745-0.789) and combined unenhanced and contrast-enhanced CT (kappa=0.745-0.799). Results were similar in subgroup analyses. CONCLUSION: Unenhanced CT alone is accurate and associated with high degrees of inter-reader agreement for clinical triage of patients older than 75years with AAP in the emergency setting.

Towards evidence-based follow-up intervals for breast cancer survivors: Estimates of the preclinical detectable phase of contralateral second breast cancer.

PURPOSE: Follow-up schemes in breast cancer survivors are predominantly consensus-based. To determine evidence-based follow-up intervals, estimates of sensitivity of the screening test(s) and duration of the preclinical detectable phase (PCDP) are key. We estimated the sensitivity and the duration of the PCDP of clinical breast examination (CBE) and mammography for the detection of contralateral second breast cancers (CBC) in breast cancer survivors. METHODS: Women with a CBC (N = 589) diagnosed in Florence between 1980 and 2005 were included. Test sensitivity and the duration of PCDP were estimated using a simple exponential model of PCDP duration. Analyses were stratified by follow-up period (0-5 vs. >5 years after primary diagnosis) and age at CBC diagnosis (<50 vs. ≥50 years). RESULTS: For CBE, test sensitivity was 55% and the duration of the PCDP 16 months. Mammography sensitivity was 91% and duration of the PCDP 35 months. Stratified analyses showed a higher test sensitivity for CBE for women aged <50 (70% vs. 51%). No difference in the duration of PCDP of CBE was found. For mammography, test sensitivity and the duration of the PCDP were higher for women with longer follow-up and in older women. CONCLUSIONS: Poor test sensitivity for CBE with a shorter duration of the PCDP compared with mammography were observed. Mammography had high test sensitivity and the potential to detect CBCs early. The estimated duration of the PCDP (35 months) was considerably longer than the recommended follow-up interval (12 months). Future studies are needed to determine whether a longer follow-up interval is appropriate.

Adalimumab for patients with Crohn's disease complicated by intra-abdominal abscess: a multicentre, prospective, observational cohort study.

doi:10.1093/ecco-jcc/jjy222 Abstract P528 from the 'Poster presentations' section of the main abstract book has been withdrawn and re-inserted as DOP63 in the 'Late-breaking abstracts' section.

Non-invasive evaluation of portal hypertension using shear-wave elastography: analysis of two algorithms combining liver and spleen stiffness in 191 patients with cirrhosis.

BACKGROUND: Two algorithms based on sequential measurements of liver and spleen stiffness using two-dimensional shearwave elastography (2D-SWE) have been recently proposed to estimate clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] ≥10 mm Hg) in patients with cirrhosis, with excellent diagnostic accuracy. AIM: To validate externally these algorithms in a large cohort of patients with cirrhosis. METHODS: One hundred and ninety-one patients with stable cirrhosis (Child-Pugh class A 39%, B 29% and C 31%) who underwent liver and spleen stiffness measurements using 2D-SWE at the time of HVPG measurement were included. Diagnostic accuracy of the 2 algorithms was assessed by calculating sensitivity, specificity, positive and negative predictive values. RESULTS: The first algorithm, using liver stiffness <16.0 kilopascals (kPa) and then spleen stiffness <26.6 kPa, was used to rule-out HVPG ≥10 mm Hg. In our population, its sensitivity and negative predictive value were 95% and 63% respectively. The second algorithm, using liver stiffness >38.0 kPa, or liver stiffness ≤38.0 kPa but spleen stiffness >27.9 kPa, was used to rule-in HVPG ≥10 mm Hg. In our population, its specificity and positive predictive value were 52% and 83% respectively. Restricting the analyses to the 74 patients without any history of decompensation of cirrhosis or to the 65 patients with highly reliable liver stiffness measurement did not improve the results. CONCLUSION: In our population, diagnostic accuracies of non-invasive algorithms based on sequential measurements of liver and spleen stiffness using 2D-SWE were acceptable, but not good enough to replace HVPG measurement or to base clinical decisions.

Nonsynonymous changes of equine lentivirus receptor-1 (ELR1) gene in amino acids involved in the interaction with equine infectious anemia virus (EIAV).

Equine lentivirus receptor-1 (ELR1) has been characterized as the specific functional receptor that mediates equine infectious anemia virus (EIAV) entrance to horse macrophages. This receptor is tumor necrosis factor receptor superfamily member 14 (TNFRSF14). The aim of this study was to investigate the occurrence of allelic variants in the coding sequence of equine TNFRSF14 gene by screening for single-nucleotide polymorphisms (SNPs) in different equine populations. Forty seven horse samples were randomly selected from a reservoir of EIAV-seropositive and seronegative samples collected from different outbreaks and regions of Argentina. DNA samples were scanned via PCR and direct sequencing of exon 3 and exon 5 of TNFRSF14 gene. A total of 21 SNPs were identified, of which 11 were located in coding sequences. Within exon 5, four SNPs caused nonsynonymous substitutions, while two other SNPs caused synonymous substitutions in crucial residues (Ser112 and Thr114) implicated in the interaction with EIAV. Despite some of exon 5 variants occurred exclusively in EIAV-positive or EIAV-negative horses, critical residues for the function of the mature protein were conserved, accounting for selective pressures in favor of preserving the specific function of TNFRSF members and the host immune response. To our knowledge, this is the first report of the existence of allelic variations involving some crucial amino acid residues in horse ELR1. Further, it could be an initial step to test the possible functional relevance and relationship of these variants with EIAV infection and disease progression as well as to develop preventive strategies.

Is abdominal CT useful for the management of patients with severe acute colitis complicating inflammatory bowel disease? A study in 54 consecutive patients.

AIM: To evaluate the contribution of CT for the management of patients with severe acute exacerbation of colitis (SAC) complicating inflammatory bowel disease (IBD); in particular, its contribution to surgical decision making. METHOD: All patients who were admitted to our institution for SAC complicating IBD were divided into two groups: group A (those who received surgical treatment); and group B (those who received medical treatment). Admission CT results were compared between groups. RESULTS: From 2006 to 2015, 54 patients [26 male; median age 39 (17-71) years] presenting with SAC were placed in either group A (n = 41; 76%) or group B (n = 13; 24%). Surgical patients in group A more frequently had altered general status (50 vs 17%; P = 0.01). Physical examination, Lichtiger score, endoscopic findings and laboratory results were similar between the groups. There was no significant difference in CT data between the groups with respect to extent of the colitis (pan-colitis in 54 and 69%, respectively, P = 0.35), median colonic thickness [10 (4-16) vs 8 (6-11) mm, P = 0.15], target enhancement (88 vs 77%, P = 0.38) and occurrence of toxic megacolon (2 vs 0%). CONCLUSION: Admission CT is not helpful in surgical decision making in SAC.

The first joint ESGAR/ ESPR consensus statement on the technical performance of cross-sectional small bowel and colonic imaging.

OBJECTIVES: To develop guidelines describing a standardised approach to patient preparation and acquisition protocols for magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) of the small bowel and colon, with an emphasis on imaging inflammatory bowel disease. METHODS: An expert consensus committee of 13 members from the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) and European Society of Paediatric Radiology (ESPR) undertook a six-stage modified Delphi process, including a detailed literature review, to create a series of consensus statements concerning patient preparation, imaging hardware and image acquisition protocols. RESULTS: One hundred and fifty-seven statements were scored for agreement by the panel of which 129 statements (82 %) achieved immediate consensus with a further 19 (12 %) achieving consensus after appropriate modification. Nine (6 %) statements were rejected as consensus could not be reached. CONCLUSIONS: These expert consensus recommendations can be used to help guide cross-sectional radiological practice for imaging the small bowel and colon. KEY POINTS: • Cross-sectional imaging is increasingly used to evaluate the bowel • Image quality is paramount to achieving high diagnostic accuracy • Guidelines concerning patient preparation and image acquisition protocols are provided.

Effectiveness of HPV vaccination in women reaching screening age in Italy.

BACKGROUND AND OBJECTIVES: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. STUDY DESIGN: During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. RESULTS: Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. CONCLUSIONS: Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.

Is it time to rethink the rule of total mesorectal excision? A prospective radiological and pathological study in 49 consecutive patients with mid-rectal cancer.

AIM: Total mesorectal excision (TME) after neoadjuvant chemoradiotherapy is the standard treatment for T3-T4 and/or N+ mid-rectal tumours, regardless of the exact tumour level. This leads to optimal oncological results but possible impaired functional results. Reducing rectal excision could reduce the functional drawbacks. This study prospectively assessed the risk of N+ or other mesorectal tumour deposit (OTD) below the tumour level by magnetic resonance imaging (MRI) performed after chemoradiotherapy and pathological examination of the TME specimen. METHOD: Consecutive patients with mid-rectal cancer who underwent TME after chemoradiotherapy were included. A prospective evaluation by postchemoradiotherapy MRI and pathological examination was performed to assess the location of N+ nodes and/or OTDs. RESULTS: Of 49 consecutive patients, 27 (55%) presented with nodes on postchemoradiotherapy MRI. However, only 12 nodes (size 2-4 mm) in 9 patients (18%) were under the tumour level. On pathological examination, 717 total lymph nodes were found, with 37 N+ and 22 OTD. According to the tumour level: (i) above tumour level, 21/453 nodes were N+ and 6 OTD; (ii) at tumour level, 16/166 nodes were N+ and 15 OTD; (iii) below tumour level, 0/98 nodes (0%) was N+ and only 1 OTD (2%) was noted at 2 cm below tumour level. CONCLUSION: After chemoradiotherapy, N+ and/or OTD located under the level of the rectal cancer seems to be a very rare event. A postchemoradiotherapy MRI could help detect such patients. For others patients, conservation of the lower rectum with only a subtotal mesorectal excision could possibly improve function.

MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

First report of cerebellar abiotrophy in an Arabian foal from Argentina.

Evidence of cerebellar abiotrophy (CA) was found in a six-month-old Arabian filly with signs of incoordination, head tremor, wobbling, loss of balance and falling over, consistent with a cerebellar lesion. Normal hematology profile blood test and cerebrospinal fluid analysis excluded infectious encephalitis, and serological testing for Sarcocystis neurona was negative. The filly was euthanized. Postmortem X-ray radiography of the cervical cephalic region identified not abnormalities, discounting spinal trauma. The histopathological analysis of serial transverse cerebellar sections by electron microscopy revealed morphological characteristics of apoptotic cells with pyknotic nuclei and degenerate mitochondria, cytoplasmic condensation and areas with absence of Purkinje cells, matching with CA histopathological characteristics. The indirect DNA test for CA was positive in the filly, and DNA test confirmed the CA carrier state in the parents and the recessive inheritance of the disease. To our knowledge this is the first report of a CA case in Argentina.

Cost-effectiveness of prostate cancer screening: a simulation study based on ERSPC data.

BACKGROUND: The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. METHODS: Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. RESULTS: Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. CONCLUSION: Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis.

Can postoperative complications be predicted by a routine CT scan on day 5? A study of 78 laparoscopic colorectal resections.

BACKGROUND: Postoperative computed tomography (CT) scan patterns after colorectal resection are difficult to analyze for both clinicians and radiologists. This study aimed to assess the role of single CT scan on postoperative day 5 in predicting postoperative morbidity. METHODS: From October 2007 to August 2009, 78 patients undergoing laparoscopic colorectal resection were enrolled in a research study involving a routine contrast-enhanced multi-detector CT scan on postoperative day 5. Two groups were defined: patients with intra-abdominal postoperative morbidity requiring specific management, i.e., surgical or radiological procedure, and/or antibiotic therapy ("complications" group), and patients with uneventful postoperative outcome ("uneventful" group). CT findings were compared between the two groups with Fisher's exact test or chi-square test. RESULTS: Postoperative abdominal complications occurred in 16 patients (21 %). Of the CT findings on day 5, pneumonia, pulmonary embolism, portal or mesenteric thrombosis, operative area fat infiltration, peritoneal effusion, pneumoperitoneum, intra-abdominal collection, parietal inflammation or collection, and subcutaneous emphysema were observed in both groups without any significant difference. Only small bowel distension [25 % (4/16) in the "complications" group vs. 5 % (3/62) in the "uneventful" group; p = 0.029] and pleural effusion [81 % (13/16) vs. 48 % (30/62); p = 0.024, respectively] were observed significantly more often in the "complications" group. CONCLUSIONS: This study suggested that abdominal complications cannot be predicted by a CT scan on day 5 after laparoscopic colorectal resection. Thus, it cannot be recommended for routine use.