Παρασκευή 27 Νοεμβρίου 2015
CT cystography for evaluation of augmented bladder perforation: be safe and know the limitations
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Tyrosine kinase inhibitors in renal cell cancer: Losing an empire and yet to find a role
Trastuzumab for HER2+ metastatic breast cancer in clinical practice: Cardiotoxicity and overall survival
Publication date: January 2016
Source:European Journal of Cancer, Volume 52
Author(s): Marta Rossi, Greta Carioli, Martina Bonifazi, Alberto Zambelli, Matteo Franchi, Lorenzo Moja, Antonella Zambon, Giovanni Corrao, Carlo La Vecchia, Carlo Zocchetti, Eva Negri
The evidence on efficacy and safety of trastuzumab in metastatic breast cancers (MBC) mainly derives from randomized clinical trials. We assessed short- and long-term overall survival (OS) and cardiotoxicity in a large cohort of women with MBC treated with trastuzumab in clinical settings.Using healthcare administrative data of Lombardy (10 millions inhabitants), we identified a cohort of women receiving trastuzumab for MBC between 2006 and 2009. The cumulative risk of severe cardiac events and the OS from the first trastuzumab administration were estimated using the Kaplan–Meier method. Their predictors were assessed using Cox regression models.We found 681 trastuzumab MBC users. Thirty two (4.7%) women experienced severe cardiac adverse events. The cumulative risk increased sharply, reaching a value of 2.4% and 4.3% during the first and second year; thereafter it increased of about 1% per year. Age was a strong predictor of cardiotoxicity. The OS was 81.8%, 64.0%, 50.2%, 41.1% and 37.2% at 1, 2, 3, 4 and 5 years, respectively. Independent predictors of worse OS were: age, brain liver or lung metastasis compared to other metastasis, use of taxanes and other chemotherapies, a cardiac adverse event after trastuzumab use, and a higher time between metastasis and BC diagnoses.The incidence of cardiotoxicity among women treated with trastuzumab for HER2-positive MBC appeared higher than that reported in RCTs, particularly in elder patients. In spite of this, median survival, was, if anything, better.
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18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients
Publication date: November 2015
Source:European Journal of Cancer, Volume 51, Issue 17
Author(s): Elena Elimova, Xuemei Wang, Elba Etchebehere, Hironori Shiozaki, Yusuke Shimodaira, Roopma Wadhwa, Venkatram Planjery, Nikolaos Charalampakis, Mariela A. Blum, Wayne Hofstetter, Jeff H. Lee, Brian R. Weston, Manoop S. Bhutani, Jane E. Rogers, Dipen Maru, Heath D. Skinner, Homer A. Macapinlac, Jaffer A. Ajani
IntroductionThe purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS).Materials and methodsThirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12±2days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS.ResultsAmong the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1months (95% confidence interval (CI): 19.9–NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p=0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG (p=0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p=0.01 and 0.03, respectively).ConclusionNone of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS.
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The prognostic value of biological markers in paediatric Hodgkin lymphoma
Publication date: January 2016
Source:European Journal of Cancer, Volume 52
Author(s): Piero Farruggia, Giuseppe Puccio, Alessandra Sala, Alessandra Todesco, Salvatore Buffardi, Alberto Garaventa, Gaetano Bottigliero, Maurizio Bianchi, Marco Zecca, Franco Locatelli, Andrea Pession, Marta Pillon, Claudio Favre, Salvatore D'Amico, Massimo Provenzi, Angela Trizzino, Giulio Andrea Zanazzo, Antonella Sau, Nicola Santoro, Giulio Murgia, Tommaso Casini, Maurizio Mascarin, Roberta Burnelli
BackgroundMany biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children.Patients and methodsBy using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, procarbazine, doxorubicin, bleomycin and vinblastine) regimens.ResultsOn multivariate analysis with categorical forms, the 5-year freedom from progression survival was significantly lower in patients with stage IV or elevated value of platelets, eosinophils and ferritin at diagnosis. Furthermore, stage IV and eosinophils seem to maintain their predictive value independently of interim (after IV cycles of chemotherapy) positron emission tomography.ConclusionUsing the combination of four simple markers such as stage IV and elevated levels of platelets, ferritin and eosinophils, it is possible to classify the patients into subgroups with very different outcomes.
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Survival in familial and non-familial breast cancer by age and stage at diagnosis
Publication date: January 2016
Source:European Journal of Cancer, Volume 52
Author(s): Elham Kharazmi, Asta Försti, Kristina Sundquist, Kari Hemminki
We aimed to compare the survival in familial and sporadic breast cancer (BC) patients who were diagnosed at an identical age and TNM stage. The Nationwide Swedish Family-Cancer Database including all Swedes born after 1931 and their biological parents, totalling >14.7 million individuals, was used. Hazard ratios (HRs) were calculated for women with BC in a first-degree relative (FDR) versus BC patients without positive family history. There was no difference in survival of familial BC patients who were diagnosed at higher TNM status or older age (>40) compared to sporadic BC cases diagnosed at the same late TNM stage. Young BC patients (age <40) in early stages had the worst survival when their FDR was diagnosed with single (HR: 2.0–3.7) or multiple (HR: 2.4–7.1) BC at any age. We concluded that there is no difference in survival of familial and non-familial BC patients who are diagnosed at higher TNM status or older ages (>40). Young familial BC patients (age <40), diagnosed at early stage, have the poorer survival compared to sporadic cases. Our results urge the need for identifying the underling genetic component for such a difference in survival of familial BC.
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Aggregated adverse-events outcomes in oncology phase III reports: A systematic review
Publication date: January 2016
Source:European Journal of Cancer, Volume 52
Author(s): Denis Maillet, Hui K. Gan, Jean-Yves Blay, Benoit You, Julien Péron
BackgroundRandomised controlled trials (RCTs) represent a major source of information on treatment-related adverse events (AEs). In this study, we reviewed the use and the reporting methods of aggregated-AEs (A-AEs) outcomes in RCTs reports published in oncology and compared that to the expectations of European Organisation for Research and Treatment of Cancer (EORTC) membership.MethodsRCTs reports published between 2007 and 2011 were reviewed regarding the reporting of A-AEs-outcomes. A-AEs were defined as summary outcome combining several related AEs, usually grouped by organ system e.g. cardiac-AEs, dermatologic-AEs. Trial characteristics associated with the use of A-AEs outcomes were investigated. The expectation of EORTC members concerning A-AEs utilisation was queried through a survey.ResultsAmong 325 RCTs published between 2007 and 2011, 94 (29%) included one or more A-AE outcomes. A clear description of the nature of AEs included in such aggregations was provided in 19 articles (20%). No description of A-AEs was conversely provided in the other 75 articles (80%). The most commonly used A-AEs-outcomes were dermatologic-AEs (45%) and cardiac-AEs (33%). In multivariate analysis, the use of A-AEs outcomes was more frequent when trials were conducted in Europe (p = 0.038) and in trials performed on colon/rectal cancers (p = 0.016). Finally, there is no consensus of EORTC members regarding the utilisation of A-AEs but a majority of them (88%) felt that a clear description of A-AEs should systematically be reported.ConclusionsThe use of A-AEs is infrequent in oncology RCT manuscripts although their use is accepted by most clinicians. However, a clear definition of A-AEs is strongly recommended if they are to be used in order to avoid a loss of important details about drug toxicities that is useful to clinicians.
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Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up
Publication date: November 2015
Source:European Journal of Cancer, Volume 51, Issue 17
Author(s): Meng-Xia Zhang, Jing Li, Guo-Ping Shen, Xiong Zou, Jun-Jie Xu, Rou Jiang, Rui You, Yi-Jun Hua, Ying Sun, Jun Ma, Ming-Huang Hong, Ming-Yuan Chen
BackgroundTo evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up.MethodsWe retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011.ResultsOf the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p<0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p=0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p=0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS.ConclusionsIMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used.
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Hypertension (HTN) as a potential biomarker of efficacy in pazopanib-treated patients with advanced non-adipocytic soft tissue sarcoma. A retrospective study based on European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 trials
Publication date: November 2015
Source:European Journal of Cancer, Volume 51, Issue 17
Author(s): F. Duffaud, S. Sleijfer, S. Litière, I. Ray-Coquard, A. Le Cesne, Z. Papai, I. Judson, P. Schöffski, S.P. Chawla, R. Dewji, S. Marreaud, J. Verweij, W.T. van der Graaf
BackgroundReliable biomarkers of pazopanib's efficacy in soft tissue sarcoma (STS) are lacking. Hypertension (HTN) is an on-target effect of vascular endothelial growth factor (VEGF)-receptor inhibitors such as pazopanib. We evaluated the association of pazopanib-induced HTN with antitumour efficacy in patients with metastatic non-adipocytic STS.MethodsAssociations between pazopanib-induced-HTN and antitumour efficacy were retrospectively assessed across 2 prospective studies (European Organisation for Research and Treatment of Cancer (EORTC) study 62043 and 62072) in metastatic STS patients who received pazopanib 800mg daily. Only patients with baseline blood pressure (BP)<150/90mmHg, were included. BP was measured monthly. HTN was reported according to National Cancer Institute-Common Toxicity Criteria Adverse Events (NCI-CTC AE) grading (v3.0), and as absolute differences compared to baseline. The effect of HTN developing in patients without baseline anti-hypertensive medication was assessed on progression-free (PFS) and overall survival (OS) using a landmark analysis stratified by study; univariately using the Kaplan–Meier method and a log-rank test, and in a multivariate Cox regression model after adjustment for important prognostic factors.ResultsOf the 337 patients eligible for this analysis, 21.7% received anti-hypertensive medication at baseline and had a similar PFS and OS compared to those who did not. In patients without baseline anti-hypertensive medication, 38.6% developed HTN. As the majority of patients developing HTN did so within 5weeks after initiation of pazopanib (68.6%), this time point was used as landmark. Univariately, there was no effect on PFS or OS from occurrence of HTN within 5weeks of treatment expressed either in NCI-CTC AE criteria or as maximal differences from baseline in systolic and diastolic BP. Also in multivariate analysis, after adjusting for important prognostic factors, the occurrence of HTN expressed in the different parameters was not associated with PFS and OS.ConclusionsIn this retrospective analysis, pazopanib-induced HTN did not correlate with outcome in pazopanib-treated STS patients. The occurrence of HTN cannot serve as biomarker in this setting.
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Recurrent antibiotic exposure may promote cancer formation – Another step in understanding the role of the human microbiota?
Publication date: November 2015
Source:European Journal of Cancer, Volume 51, Issue 17
Author(s): Ben Boursi, Ronac Mamtani, Kevin Haynes, Yu-Xiao Yang
BackgroundBacterial dysbiosis was previously described in human malignancies. In a recent animal model, tumour susceptibility was transmitted using faecal transplantation. Our aim was to evaluate possible association between antibiotic exposure and cancer risk.MethodsWe conducted nested case–control studies for 15 common malignancies using a large population-based electronic medical record database. Cases were defined as those with any medical code for the specific malignancy. Individuals with familial cancer syndromes were excluded. For every case, four eligible controls matched on age, sex, practice site and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1year before index-date. Adjusted odds-ratios (AORs) and 95% confidence intervals (CIs) were estimated for each antibiotic type using conditional logistic regression.Results125,441 cases and 490,510 matched controls were analysed. For gastro-intestinal malignancies, the use of penicillin was associated with an elevated risk of oesophageal, gastric and pancreatic cancers. The association increased with the number of antibiotic courses and reached 1.4 for gastric cancers associated with >5 courses of penicillin (95% CI 1.2–1.8). Lung cancer risk increased with the use of penicillin, cephalosporins, or macrolides (AOR for >5 courses of penicillin: 1.4 95% CI 1.3–1.6). The risk of prostate cancer increased modestly with the use of penicillin, quinolones, sulphonamides and tetracyclines. The risk of breast cancer was modestly associated with exposure to sulphonamides. There was no association between the use of anti-virals and anti-fungals and cancer risk.ConclusionRecurrent exposure to certain antibiotics may be associated with cancer risk in specific organ sites.
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Single organ metastatic disease and local disease status, prognostic factors for overall survival in stage IV non-small cell lung cancer: Results from a population-based study
Publication date: November 2015
Source:European Journal of Cancer, Volume 51, Issue 17
Author(s): L.E. Hendriks, J.L. Derks, P.E. Postmus, R.A. Damhuis, R.M.A. Houben, E.G.C. Troost, M.M. Hochstenbag, E.F. Smit, A.-M.C. Dingemans
PurposeTo analyse the prognostic impact on overall survival (OS) of single versus multiple organ metastases, organ affected, and local disease status in a population based stage IV non-small cell lung cancer (NSCLC) cohort.MethodsIn this observational study, data were analysed of all histologically confirmed stage IV NSCLC patients diagnosed between 1 January 2006 and 31 December 2012 registered in the Netherlands Cancer Registry. Location of metastases before treatment was registered. Multivariable survival analyses [age, gender, histology, M-status, local disease status, number of involved organs, actual organ affected] were performed for all patients and for an 18fluorodeoxyglucose-positron emission tomography (18FDG-PET)-staged subgroup.Results11,094 patients were selected: 60% male, mean age 65years, 73% adenocarcinoma. Median OS for 1 (N=5676), 2 (N=3280), and ⩾3 (N=2138) metastatically affected organs was 6.7, 4.3, 2.8months, respectively (p<0.001). Hazard ratio (HR) for 2 versus 1 organ(s) was 1.33 (p<0.001), for ⩾3 versus 1 organ(s) 1.91 (p<0.001). Results were confirmed in the 18FDG-PET-staged cohort (N=1517): patients with single organ versus 2 and ⩾3 organ metastases had higher OS (8.6, 5.7, 3.8months, HR 1.40 and 2.17, respectively, p<0.001). In single organ metastases, OS for low versus high TN-status was 8.5 versus 6.5months [HR 1.40 (p<0.001)]. 18FDG-PET-staged single organ metastases patients with low TN-status had a superior OS than those with high TN-status (11.6 versus 8.2months, HR 1.62, p<0.001).ConclusionPatients with single organ metastases stage IV NSCLC have a favourable prognosis, especially in combination with low TN status. They have to be regarded as a separate subgroup of stage IV disease.
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Induction chemotherapy prior to surgery with or without postoperative radiotherapy for oral cavity cancer patients: Systematic review and meta-analysis
Publication date: November 2015
Source:European Journal of Cancer, Volume 51, Issue 17
Author(s): Gustavo N. Marta, Rachel Riera, Paolo Bossi, Lai-ping Zhong, Lisa Licitra, Cristiane R. Macedo, Gilberto de Castro, André L. Carvalho, William N. William, Luis Paulo Kowalski
BackgroundLocoregionally advanced oral cavity cancers are aggressive tumours with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients.Material and methodsOnly prospective phase III randomised studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias.ResultsTwo studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n=226) versus Control Group (n=225). Most patients had tumours at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favour of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favour of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes.ConclusionsBased on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancer patients. Clinically assessed N2 patients might benefit from induction chemotherapy.
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TITF1 and TITF2 loci variants indicate significant associations with thyroid cancer
Abstract
A number of studies have investigated the influence of TITF1 and TITF2 genetic variants on thyroid carcinogenesis, but their associations remain unclear due to the controversial results. The objective of this study was to test the hypothesis that TITF1 and TITF2 variants modulate thyroid cancer susceptibility. Eligible studies were identified through online searches supplemented by manual search. Either the DerSimonian and Laird method or the Mantel–Haenszel method was used to estimate the risk of thyroid cancer (ORs and 95 % CIs). The pooled ORs were calculated assuming the allele model. We identified a total of 10 publications concerning the topic of interest. Overall, meta-analysis of rs944289 showed 1.11-fold increased risk of thyroid cancer related to the risk T allele (T vs. C: OR 1.11, 95 % CI 1.05–1.17). For rs965513, individuals carrying the risk A allele, compared to individuals with the G allele, had 31 % higher risk of thyroid cancer (A vs. G: OR 1.31, 95 % CI 1.17–1.46). Analyses in total samples for rs1867277, rs1443434, and rs907580 yielded similar associations (A vs. G: OR 1.22, 95 % CI 1.06–1.39; G vs. T: OR 1.26, 95 % CI 1.09–1.45; T vs. C: OR 1.42, 95 % CI 1.21–1.66, respectively). The significant association persisted among Caucasians in subgroup analyses for rs944289 and rs965513. The genetic susceptibility of thyroid cancer seems likely to be associated with the risk allele at rs944289 in the TITF1 gene and at rs1867277, rs965513, rs1443434, and rs907580 in the TITF2 gene.
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Netupitant/Palonosetron: A Review in the Prevention of Chemotherapy-Induced Nausea and Vomiting
Abstract
An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo®) is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Netupitant is a highly selective neurokinin-1 receptor antagonist and palonosetron is a serotonin 5-HT3 receptor antagonist with a distinct pharmacological profile. Complete response rates during the delayed, acute and overall phases were significantly higher with single-dose netupitant 300 mg plus palonosetron 0.5 mg than with single-dose palonosetron 0.5 mg in cycle 1 of cisplatin-based highly emetogenic chemotherapy (HEC) in a phase II trial and with single-dose netupitant/palonosetron 300/0.5 mg than with single-dose palonosetron 0.5 mg in cycle 1 of anthracycline–cyclophosphamide (AC) moderately emetogenic chemotherapy (MEC) in a phase III trial; the greater efficacy of netupitant/palonosetron was maintained over repeated cycles of AC MEC in the phase III trial. In another phase III trial, netupitant/palonosetron 300/0.5 mg was effective over repeated cycles of non-AC MEC or HEC. Netupitant/palonosetron was well tolerated, with no cardiac safety concerns. The convenience of administering netupitant/palonosetron as a single dose in a fixed combination has the potential to improve adherence to CINV prevention guidelines. In conclusion, netupitant/palonosetron is an important option to consider in the prevention of acute and delayed CINV in patients receiving MEC or HEC.
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Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of circulating CD34 + CXCR4 + cells in patients with type 2 diabetes
Abstract
We investigated the effects of sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, on the number of circulating CD34+CXCR4+cells, a candidate for endothelial progenitor cells (EPCs), plasma levels of stromal cell-derived factor (SDF)-1α, a ligand for CXCR4 receptor and a substrate for DPP-4, and plasma levels of interferon-inducible protein (IP)-10, for a substrate for DPP-4, in patients with type 2 diabetes. We studied 30 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin and/or sulfonylurea. Thirty diabetic patients were randomized in a 2:1 ratio into a sitagliptin (50 mg/day) treatment group or an active placebo group (glimepiride 1 mg/day) for 12 weeks. Both groups showed similar improvements in glycemic control. The number of circulating CD34+CXCR4+ cells was increased from 30.5 (20.0, 47.0)/106 cells at baseline to 55.5 (31.5, 80.5)/106 cells at 12 weeks of treatment with 50 mg/day sitagliptin (P = 0.0014), while showing no significant changes in patients treated with glimepiride. Plasma levels of SDF-1α and IP-10, both physiological substrates of endogenous DPP-4 and chemokines, were significantly decreased at 12 weeks of sitagliptin treatment. In conclusion, treatment with sitagliptin increased the number of circulating CD34+CXCR4+ cells by approximately 2-fold in patients with type 2 diabetes.
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Microcystins do not necessarily lower the sensitivity of Microcystis aeruginosa to tannic acid
Different phytoplankton strains have been shown to possess varying sensitivities towards macrophyte allelochemicals, yet the reasons for this are largely unknown. To test whether microcystin (MC) is responsible for strain-specific sensitivities of Microcystis aeruginosa to macrophyte allelochemicals, we compared the sensitivity of 12 MC- and non-MC-producing M. aeruginosa strains, including an MC-deficient mutant and its wild-type, to the polyphenolic allelochemical tannic acid (TA). Non-MC-producing strains showed a significantly higher sensitivity to TA than MC-producing strains, both in Chlorophyll a concentrations and quantum yields of photosystem II. In contrast, an MC-deficient mutant displayed a higher fitness against TA compared to its wild-type. These results suggest that the resistance of M. aeruginosa to polyphenolic allelochemicals is not primarily related to MCs per se, but to other yet unknown protective mechanisms related to MCs.
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Management of mandibular angle fractures using a 1.7mm 3-dimensional strut plate
Publication date: Available online 27 November 2015
Source:Journal of Oral Biology and Craniofacial Research
Author(s): Varnika Pandey, Ongkila Bhutia, Shakil Ahmed Nagori, Ashu Seith, Ajoy Roychoudhury
AimWe report our experience with the use of 1.7mm 3-dimentional (3D) strut plate for the management of mandibular angle fractures.MethodsThis prospective study enrolled 15 patients in whom mandibular angle fractures were treated with 1.7mm 3D plate using trans-buccal trochar. Patients were evaluated at 72h, 2 weeks, 6 weeks and 12 weeks for fracture stability, occlusion, soft-tissue swelling, infection and post-operative inferior alveolar nerve damage. Other complications like wound dehiscence, non-union, mal-union and hardware failure were also assessed.ResultsIn the immediate post-operative period, fracture instability was seen in 1 (6.7%) patient which resolved by 2 weeks. Mild occlusal discrepancy was also noted in 1 (6.7%) patient. Wound dehiscence was seen in 5 (33.3%) patients and all resolved by local measures. 1 (6.7%) patient developed post-operative nerve paraesthesia. Immediate post-operative radiographic evaluation demonstrated optimal reduction in all cases with no inferior border gaping. No case of infection, hardware failure, non-union and mal-union was noted.ConclusionWithin the limitations of the study, 1.7mm 3D strut plate was found to be effective for management of non-communited mandibular angle fractures.
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Sponsoring Organizations and Liaisons
FDG PET/CT for assessing the resectability of NSCLC patients with N2 disease after neoadjuvant therapy
Abstract
Objective
Neoadjuvant chemoradiotherapy (CMRT) is the most effective treatment of stage III non-small-cell lung cancer (NSCLC). The present study aimed at assessing FDG PET/CT for defining the response of N2 disease to neoadjuvant CMRT, as surgical resection after such therapy significantly improves 5-year survival in responding N2 disease.
Methods
Forty-five patients with locally advanced NSCLC underwent both pre-neoadjuvant therapy FDG PET/CT and post-neoadjuvant therapy FDG PET/CT followed by anatomical resection of lung and ipsilateral mediastinal lymph nodes (LN). Seventeen of these patients who had PET/CT studies in our institution and were operated after CMRT were retrospectively included in the study group (12 males, ages 43–78 years; stage IIIA: 14 patients, stage IIIB: 3 patients). PET/CT response in N2 was visually scored per-lymph node station and per patient. Quantitative N2 response was evaluated by SUVmax and total lesion glycolysis (TLG) measurements after therapy alone and in comparison with pre-therapy values. PET/CT N2 response was confirmed at surgery.
Results
Seventeen NSCLC patients with 29 metastatic N2 lymph nodes (LN) were assessed. Histopathology confirmed 14 responders and 3 non-responders, and was available in 20/29 metastatic LN, showing complete response in 17 and residual disease in 3 LN. LN-based visual analysis of N2 response on PET/CT defined 3 TP, 16 TN and 1 FP, for sensitivity, specificity, accuracy, negative and positive predictive values (NPV and PPV) of 100, 94, 95, 100 and 75 %, respectively. Patient-based visual analysis defined 3 TP, 13 TN and 1 FP study, for sensitivity, specificity, accuracy, NPV and PPV of 100, 93, 94, 100 and 75 %, respectively. Nodal-based quantitative analysis of FDG uptake in N2 nodes revealed a significant difference between responding and non-responding LN only of SUVmax post-therapy (2.5 ± 1.21 vs. 3.5 ± 2.36, P = 0.04).
Conclusion
FDG PET/CT after neoadjuvant therapy accurately defined response in metastatic N2 nodes of NSCLC patients, presenting very high sensitivity and NPV for detecting responding nodes. PET/CT may enable selection of candidates for curative resection of stage III NSCLC. Mediastinoscopy may not be mandatory in patients with a negative PET/CT after neoadjuvant therapy.
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The association between sleep-disordered breathing and aortic stiffness in a community cohort
• Sleep-disordered breathing in the community is linked to increased aortic stiffness.• Aortic stiffness is a strong predictor of cardiovascular risk.• The association persisted after adjustment for multiple potential cofounders.
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Effects of phase-locked acoustic stimulation during a nap on EEG spectra and declarative memory consolidation
• Participants were studied during an afternoon nap under two conditions: STIM and SHAM.• In the STIM condition, acoustic stimulation was applied in Stage 2 and 3 sleep.• Stimulation was phase-locked to the up-phase of slow wave activity.• Acoustic stimulation increased slow wave, theta and fast spindle activity.• Concurrently, memory improvement in the form of reduced forgetting was demonstrated.
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Microcystins do not necessarily lower the sensitivity of Microcystis aeruginosa to tannic acid
Different phytoplankton strains have been shown to possess varying sensitivities towards macrophyte allelochemicals, yet the reasons for this are largely unknown. To test whether microcystin (MC) is responsible for strain-specific sensitivities of Microcystis aeruginosa to macrophyte allelochemicals, we compared the sensitivity of 12 MC- and non-MC-producing M. aeruginosa strains, including an MC-deficient mutant and its wild-type, to the polyphenolic allelochemical tannic acid (TA). Non-MC-producing strains showed a significantly higher sensitivity to TA than MC-producing strains, both in Chlorophyll a concentrations and quantum yields of photosystem II. In contrast, an MC-deficient mutant displayed a higher fitness against TA compared to its wild-type. These results suggest that the resistance of M. aeruginosa to polyphenolic allelochemicals is not primarily related to MCs per se, but to other yet unknown protective mechanisms related to MCs.
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Giant inguinoscrotal hernia containing intestinal segments and urinary bladder successfully repaired by simple hernioplasty technique: a case report
IntroductionGiant inguinoscrotal hernias are extremely rare nowadays, but they may still be encountered after years or even decades of neglect. Such hernias containing both bowel loops and urinary bladder have not been reported in the medical literature to date, to the best of our knowledge.Case presentationWe report a case of a 65-year-old Moroccan man who presented with giant right-sided and long-standing inguinoscrotal hernia with compromised quality of life due to walking difficulties and sexual discomfort. Computed tomography revealed a voluminous hernia sac containing small and large bowel loops, greater omentum, and urinary bladder. Surgical repair was done through the classical inguinal incision using the Lichtenstein tension-free hernioplasty technique. No debulking or abdominal enlargement procedure had to be performed, apart from a partial omentectomy. Conclusions: Giant inguinoscrotal hernia containing intestinal segments and urinary bladder is a challenging surgical disease. A Lichtenstein tension-free technique seems to be the best surgical procedure for both the patient and the operating surgeon. It should be used whenever possible in such cases.
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Severe connective tissue laxity including aortic dilatation in Sotos syndrome
Massive hemoptysis in Loeys–Dietz syndrome
We describe four unrelated individuals with Loeys–Dietz syndrome (LDS) who presented with massive hemoptysis of unknown etiology. LDS is an autosomal dominant connective-tissue disorder characterized by altered cardiovascular, craniofacial, and skeletal development that is attributed to mutations in the TGFBR1, TGFBR2, SMAD3, or TGFB2 genes. Massive hemoptysis (MH) is a rare and often fatal pulmonary medical emergency. This is the first report of MH in individuals with LDS and establishes it as part of the LDS spectrum. It compels providers to educate their LDS patients on MH, although much investigation needs to be done to determine etiology and appropriate treatment for this newly described LDS feature. © 2015 Wiley Periodicals, Inc.
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Table of Contents
The Essentials
Editorial Review Board
Annual review of selected scientific literature: Report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry
Publication date: December 2015
Source:The Journal of Prosthetic Dentistry, Volume 114, Issue 6
Author(s): Terence E. Donovan, Riccardo Marzola, William Becker, David R. Cagna, Frederick Eichmiller, James R. McKee, James E. Metz, Jean-Pierre Albouy
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Sponsoring Organization Directory December 2015
News and Notes
Expression of dermcidin in sebocytes supports a role for sebum in the constitutive innate defense of human skin
Sebaceous glands (SGs) are epidermal appendages normally found in association with a hair follicle, forming the pilosebaceous unit. Numerous functions have been attributed to SGs, including roles in epidermal barrier, hair follicle integrity, as well as antioxidant and antimicrobial properties. Furthermore, altered SG activity is an important component of several skin diseases such as acne and cicatricial alopecia. Sebocytes, the secretory cells within SGs, synthesize and accumulate large amounts of lipids, and eventually release their product (sebum) into the hair canal by holocrine secretion [1].
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Placas alopécicas en una cocinera
Publication date: Available online 27 November 2015
Source:Actas Dermo-Sifiliográficas
Author(s): Z. Ézsöl-Lendvai, L. Iñiguez-de Onzoño, L. Pérez-García
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Red cabbage yield, heavy metal content, water use and soil chemical characteristics under wastewater irrigation
Abstract
The objective of this 2-year field study was to evaluate the effects of drip irrigation with urban wastewaters reclaimed using primary (filtration) and secondary (filtration and aeration) processes on red cabbage growth and fresh yield, heavy metal content, water use and efficiency and soil chemical properties. Filtered wastewater (WW1), filtered and aerated wastewater (WW2), freshwater and filtered wastewater mix (1:1 by volume) (WW3) and freshwater (FW) were investigated as irrigation water treatments. Crop evapotranspiration decreased significantly, while water use efficiency increased under wastewater treatments compared to FW. WW1 treatment had the lowest value (474.2 mm), while FW treatments had the highest value (556.7 mm). The highest water use efficiency was found in the WW1 treatment as 8.41 kg m−3, and there was a twofold increase with regard to the FW. Wastewater irrigation increased soil fertility and therefore red cabbage yield. WW2 treatment produced the highest total fresh yield (40.02 Mg ha−1). However, wastewater irrigation increased the heavy metal content in crops and soil. Cd content in red cabbage heads was above the safe limit, and WW1 treatment had the highest value (0.168 mg kg−1). WW3 treatment among wastewater treatments is less risky in terms of soil and crop heavy metal pollution and faecal coliform contamination. Therefore, WW3 wastewater irrigation for red cabbage could be recommended for higher yield and water efficiency with regard to freshwater irrigation.
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Prediction models for transfer of arsenic from soil to corn grain ( Zea mays L.)
Abstract
In this study, the transfer of arsenic (As) from soil to corn grain was investigated in 18 soils collected from throughout China. The soils were treated with three concentrations of As and the transfer characteristics were investigated in the corn grain cultivar Zhengdan 958 in a greenhouse experiment. Through stepwise multiple-linear regression analysis, prediction models were developed combining the As bioconcentration factor (BCF) of Zhengdan 958 and soil pH, organic matter (OM) content, and cation exchange capacity (CEC). The possibility of applying the Zhengdan 958 model to other cultivars was tested through a cross-cultivar extrapolation approach. The results showed that the As concentration in corn grain was positively correlated with soil pH. When the prediction model was applied to non-model cultivars, the ratio ranges between the predicted and measured BCF values were within a twofold interval between predicted and measured values. The ratios were close to a 1:1 relationship between predicted and measured values. It was also found that the prediction model (Log [BCF]=0.064 pH-2.297) could effectively reduce the measured BCF variability for all non-model corn cultivars. The novel model is firstly developed for As concentration in crop grain from soil, which will be very useful for understanding the As risk in soil environment.
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Nanoscale zerovalent iron-mediated degradation of DDT in soil
Abstract
Nanoscale zerovalent iron (nZVI)-mediated degradation of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) was investigated in a spiked soil under different conditions (iron sources, iron dosage, soil moisture, temperature, and soil types) and DDT-contaminated field. The degradation efficiency of p,p′-DDT by nZVI and nZVI coated with sodium oleate (SO-nZVI) was much higher than that by nZVI coated with polyimide (PI-nZVI). The rapid degradation of p,p′-DDT by nZVI only occurred in flooded soil. The degradation half-life of p,p′-DDT decreased significantly from 58.3 to 27.6 h with nZVI dosage from 0.5 to 2.0 % and from 46.5 to 32.0 h with temperature from 15 to 35 °C. The degradation efficiency of p,p′-DDT by nZVI differed in Jinhua (JH), Jiaxing (JX), Xiaoshan (XS), Huajiachi (HJC), and Heilongjiang (HLJ) soils. A good correlation was found between the degradation half-life of p,p′-DDT and multiple soil properties. The probable nZVI-mediated degradation pathway of p,p′-DDT in soil was proposed as DDT → DDD/DDE → DDNS → DDOH based on the metabolites identified by GC-MS. The in situ degradation efficiency of residual DDTs in a contaminated field was profoundly enhanced by the addition of nZVI as compared to the control. It is concluded that nZVI might be an efficient agent for the remediation of DDT-contaminated soil under anaerobic environment.
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48-year-old patient with a 20-year histo...
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Behçet disease presenting with movement disorders and anti basal ganglia antibodies
Publication date: Available online 27 November 2015
Source:Autoimmunity Reviews
Author(s): Giovanni Rizzo, Laura Licchetta, Cesa Scaglione, Maura Buttiglione, Sabina Capellari, Paolo Martinelli, Davide Martino
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Survival and Prognostic Factors of Systemic Lupus Erythematosus-Associated Pulmonary Arterial Hypertension: A PRISMA-Compliant Systematic Review and Meta-Analysis
Publication date: Available online 27 November 2015
Source:Autoimmunity Reviews
Author(s): Junyan Qian, Yanhong Wang, Can Huang, Xiaoxi Yang, Jiu Liang Zhao, Qian Wang, Zhuang Tian, Mengtao Li, Xiaofeng Zeng
Objective: This study aims to evaluate the survival of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) by a systematic review and meta-analysis.Methods: Studies were searched from MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trial and Scopus databases and selected according to the inclusion and exclusion criteria. Two independent reviewers extracted data from selected studies. Quality assessments were also performed using the Newcastle-Ottawa Scale. All pooled analyses were conducted both for random-effects model and fixed-effects model. Subgroup analysis and sensitivity analysis were conducted to investigate the origins of heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger's test.Results: Six studies encompassing 323 patients with SLE-associated PAH were included in the meta-analysis. The pooled 1, 3 and 5-year survival rates were 88% (95% CI 0.80-0.93), 81% (95% CI 0.67-0.90) and 68% (95% CI 0.52-0.80) respectively. No significant publication bias was shown. WHO Functional class (Fc) III/IV was found to be an independent prognostic factor of mortality. Higher mean pulmonary arterial pressure (mPAP), higher pulmonary vascular resistance (PVR), lower six minutes walking distance (6MWD), higher brain natriuretic peptide (BNP) and higher N-terminal proBNP (NT-proBNP) level were also related to poor survival.Conclusion: The long-term survival of patients with SLE-associated PAH is poor, which is worth paying greater clinical and academic attention. This study suggested that early diagnosis and management are recommended in patients with SLE-associated PAH for a better outcome of survival.
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Reply to the Letter to the Editor: “The need for differentiating between exercise, physical activity, and training.” Budde et al. Autoimmun Rev (2015)
Publication date: Available online 27 November 2015
Source:Autoimmunity Reviews
Author(s): Pascale Duché, Emmanuelle Rochette, Etienne Merlin
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Kawasaki disease in adults: observations in France and literature review Short title: Kawasaki disease in adults in France
Publication date: Available online 26 November 2015
Source:Autoimmunity Reviews
Author(s): Jean-Baptiste Fraison, Pascal Sève, Claire Dauphin, Alfred Mahr, Emeline Gomard-Mennesson, Loig Varron, Gregory Pugnet, Cédric Landron, Pascal Roblot, Eric Oziol, Gihane Chalhoub, Jean-Marc Galempoix, Sébastien Humbert, Philippe Humbert, Emilie Sbidian, Florent Grange, Olivier Bayrou, Pascal Cathebras, Philippe Morlat, Olivier Epaulard, Patricia Pavese, Thi Huong Du Boutin, Abdelkader Zoulim, Katia Stankovic, Hervé Bachelez, Amar Smail, C. Bachmeyer, Brigitte Granel, Jacques Serratrice, Graziella Brinchault, Arsène Mekinian, Nathalie Costedoat-Chalumeau, Anne Bourgarit-Durand, Xavier Puéchal, Loïc Guillevin, Maryam Piram, Isabelle Koné-Paut, Olivier Fain
ObjectiveKawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France.MethodsWe collected retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature.ResultsWe included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18–68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8–21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1–117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p=0.01).ConclusionGiven the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcome.
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Adaptive immune regulation in autoimmune diabetes
Publication date: Available online 26 November 2015
Source:Autoimmunity Reviews
Author(s): Concetta Ferretti, Antonio La Cava
Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing pancreatic β cells. The pathogenesis of T1D is complex and multifactorial and involves a genetic susceptibility that predisposes to abnormal immune responses in the presence of ill-defined environmental insults to the pancreatic islets. This review discusses how adaptive immunoregulatory T cells contribute to the modulation of the development and evolution of T1D, together with potential approaches that target these cells for new therapies in the disease.
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The presence of cadmium in the intertidal environments of a moderately impacted coastal lagoon in western Portugal (Óbidos Lagoon)—spatial and seasonal evaluations
Abstract
A seasonal environmental monitoring program was carried out (winter 2009 to summer 2010) to evaluate the spatial and seasonal cadmium concentrations in the intertidal environments of the Óbidos Lagoon (Portugal). Also, some environmental parameters were monitored at each sampling station. Both the water and the sediment samples were contaminated, although to different degrees. In general, cadmium contamination appears to be mostly focused on the inner areas of the lagoon, namely, in Barrosa's arm, which receives a small tributary contaminated by agro-industrial activities. Only cadmium concentration in sediment showed to be significantly influenced by seasons. Some environmental parameters presented spatial and temporal heterogeneity which influenced, to some extent, cadmium bioavailability. The results of this study allow a better understanding of the environmental quality of this ecosystem regarding cadmium contamination and may assist in the definition of future coastal management measures specifically targeted to trace metal contamination and pollution monitoring.
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Intraoperative herniation of an L5-S1 disc during microdiscectomy and transforaminal lumbar interbody fusion: a case report
IntroductionWe report the progression of an intraoperative L5-S1 lumbar disc herniation that occurred during a routine microdiscectomy and transforaminal lumbar interbody fusion, which, to the best of our knowledge, has never been previously reported in the literature. The objective of this report is to bring to light the possibility of a lumbar disc herniating intraoperatively, and to demonstrate that accompanying neurologic involvement can be detected and subsequently addressed with the aid of neurophysiologic monitoring.Case presentationA 36-year-old African American woman, who had previously undergone minimally invasive microdiscectomy for a right L5-S1 herniated nucleus pulposus with full recovery, presented with a large reherniation of the L5-S1 disc on the right side. During her operation, while a tap was followed into the L5 left pedicle, there was a sudden profound spasm of our patient's legs and back that lasted for the duration of 15 seconds, culminating in the loss of all somatosensory evoked potentials in our patient's lower extremities. Exploration of this previous microlaminotomy site revealed a massive disc extrusion protruding through the microlaminotomy. Immediate removal of this extruded disc material restored all somatosensory evoked potentials and our patient awoke with no neurologic deficits. Conclusions: An intraoperative disc herniation in the lumbar spine, though very rare, can occur and can result in neurologic compromise as evidenced by the loss of somatosensory evoked potentials. By identifying the event, it can be remedied by evaluating the disc visually, removing extruded fragments and decompressing nerve roots with recovery of somatosensory evoked potentials and normal neurologic function postoperatively. If neurophysiological monitoring shows there is a sudden loss of response, then consideration should be given to the possibility of an acute intraoperative herniation.
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Post-treatment of anaerobic reactor effluent using coagulation/oxidation followed by double filtration
Abstract
This study evaluates the efficacy of a sanitary sewage treatment system, proposing post-treatment of the effluent generated by the upflow anaerobic sludge blanket UASB reactor, through a Fenton coagulation/oxidation ((ferric chloride (FC) or ferrous sulfate (FS) and peracetic acid (PAA)), followed by a double filtration system, composed of a gravel ascending drainage filter and a sand descending filter. Following the assessment of treatability, the system efficiency was evaluated using physicochemical and microbiological parameters. In all treatments performed in the pilot unit, total suspended solids (TSS) were completely removed, leading to a decrease in turbidity greater than 90 % and close to 100 % removal of total phosphorous. In the FC and PAA combination, the effluent was oxygenated prior to filtration, enabling a more significant removal of biochemical oxygen demand (BOD), which characterizes aerobic degradation even in a quick sand filter. The treatments carried out in the presence of the PAA oxidizing agent showed a more significant bleaching of the effluent. Concerning the microbiological parameters, the simultaneous use of PAA and FC contributed to the partial inactivation of the assessed microorganisms. A 65 % recovery of the effluent was obtained with the proposed treatment system, considering the volume employed in filter backwashing.
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Regulating riparian forests for aquatic productivity in the Pacific Northwest, USA: addressing a paradox
Abstract
Forested riparian buffers isolate streams from the influence of harvesting operations that can lead to water temperature increases. Only forest cover between the sun and stream limits stream warming, but that cover also reduces in-stream photosynthesis, aquatic insect production, and fish productivity. Water temperature increases that occur as streams flow through canopy openings decrease rapidly downstream, in as little as 150 m. Limiting management options in riparian forests restricts maintenance and optimization of various buffer contributions to beneficial uses, including forest products, fish, and their food supply. Some riparian disturbance, especially along cold streams, appears to benefit fish productivity. Options for enhancing environmental investments in buffers should include flexibility in application of water quality standards to address the general biological needs of fish and temporary nature of clearing induced warming. Local prescriptions for optimizing riparian buffers and practices that address long-term habitat needs deserve attention. Options and incentives are needed to entice landowners to actively manage for desirable riparian forest conditions.
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 Purification and characterization of a new β-lactamase OXA-205 from Pseudomonas aeruginosa We have identified a novel class 1 integron (1503 bp), named In671 in a clinical Pseudomonas aeruginosa isolate. Integron sequence analysis revealed two gene cassettes, one coding for a new OXA-type β-lactamase d... Read More » | ||||
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