BACKGROUND: Nitroglycerin (NTG) increases tumor blood flow and oxygenation by inhibiting hypoxia-inducible-factor (HIF)-1. A randomized phase II study has shown improved outcome when NTG patches were added to vinorelbine/cispla-tin in patients with advanced nonsmall-cell lung cancer (NSCLC). In addition, there is evidence that the combination of bevacizumab and HIF-1 inhibitors increases antitumor activity. PATIENTS AND METHODS: In this randomized phase II trial, chemo-naive patients with stage IV nonsquamous NSCLC were randomized to four cycles of carboplatin (area under the curve 6)-paclitaxel (200 mg/m(2))-bevacizumab 15 mg/kg on day 1 every 3 weeks with or without NTG patches 15 mg (day -2 to +2) followed by bevacizumab with or without NTG until progression. Response was assessed every two cycles. Primary end point was progression-free survival (PFS). The study was powered (80%) to detect a decrease in the hazard of tumor progression of 33% at κ = 0.05 with a two-sided log-rank test when 222 patients were enrolled and followed until 195 events were observed. RESULTS: Between 1 January 2011 and 1 January 2013, a total of 223 patients were randomized;
112 control arm and 111 experimental arm; response rate was 54% in control arm and 38% in experimental arm. Median [95% confidence interval (CI)] PFS in control arm was 6.8 months (5.6-7.3) and 5.1 months (4.2-5.8) in experimental arm, hazard ratio (HR) 1.27 (95% CI 0.96-1.67). Overall survival (OS) was 11.6 months (8.8-13.6) in control arm and 9.4 months (7.8-11.3) in experimental arm, HR 1.02 (95% CI 0.71-1.46). In the experimental arm, no additional toxicity was observed except headache (6% versus 52% in patients treated with NTG). CONCLUSION: Adding NTG to first-line carboplatin-paclitaxel-bevacizumab did not improve PFS and OS in patients with stage IV nonsquamous NSCLC. TRIAL REGISTRATION:
ClinicalTrials.gov NCT01171170.
PMID: 26364993
Ammerdorffer A, Stappers MH, Oosting M, Schoffelen T, Hagenaars JC, Bleeker-Rovers CP, Wegdam-Blans MC, Wever PC, Roest HJ, van de Vosse E, Netea MG, Sprong T, Joosten LA. Genetic variation in TLR10 is not associated with chronic Q fever, despite the inhibitory effect of TLR10 on Coxiella burnetii-induced cytokines in vitro. Cytokine. 2016 Jan;77:196-202. doi: 10.1016/j.cyto.2015.09.005.
Coxiella burnetii, the causative agent of Q fever, is recognized by TLR2. TLR10 can act as an inhibitory receptor on TLR2-derived immune responses. Therefore, we investigated the role of TLR10 on C. burnetii-induced cytokine production and assessed whether genetic polymorphisms in TLR10 influences the development of chronic Q fever. HEK293 cells, transfected with TLR2, TLR10 or TLR2/TLR10, and human peripheral blood mononuclear cells (PBMCs) in the presence of anti-TLR10, were stimulated with C. burnetii. In both assays, the absence of TLR10 resulted in increased cytokine responses after C. burnetii stimulation. In addition, the effect of single nucleotide polymorphisms (SNPs) in TLR10 was examined in healthy volunteers whose PBMCs were stimulated with C. burnetii Nine Mile or the Dutch outbreak isolate C. burnetii 3262.
Individuals bearing SNPs in TLR10 displayed increased cytokine production upon C. burnetii 3262 stimulation. Further-more, 139 chronic Q fever patients and 220 controls were genotyped for TLR10 N241H, I775V and I369L. None of these polymorphisms were associated with increased susceptibility to chronic Q fever. In conclusion, TLR10 has an inhibitory effect on in vitro cytokine production by C. burnetii, but the presence of TLR10 polymorphisms does not lead to an increased risk of developing chronic Q fever.
PMID: 26365665
Broos PP, Hagenaars JC, Kampschreur LM, Wever PC, Bleeker-Rovers CP, Koning OH, Teijink JA, Wegdam-Blans MC. Vascular complications and surgical interventions after world’s largest Q fever outbreak. J Vasc Surg. 2015 Nov;62(5):1273-80. doi: 10.1016/j.jvs.2015.06.217. Epub 2015 Sep 10
OBJECTIVE: Since chronic Q fever often develops insidiously, and symptoms are not always recognized at an early stage, complications are often present at the time of diagnosis. We describe complications associated with vascular chronic Q fever as found in the largest cohort of chronic Q fever patients so far. METHODS: Patients with proven or probable chronic Q fever with a focus of infection in an aortic aneurysm or vascular graft were included in this study, using the Dutch national chronic Q fever database. RESULTS: A total of 122 patients were diagnosed with vascular chronic Q fever between April 2008 and June 2012. The infection affected a vascular graft in 62 patients (50.8%) and an aneurysm in 53 patients (43.7%). Seven patients (5.7%) had a different vascular focus. Thirty-six patients (29.5%) presented with acute complications, and 35 of these patients (97.2%) underwent surgery. Following diagnosis and start of antibiotic treatment, 26 patients (21.3%) presen-ted with a variety of complications requiring surgical treatment during a mean follow-up of 14.1 ± 9.1 months. The overall mortality rate was 23.7%. Among these patients, mortality was associated with chronic Q fever in 18 patients (62.1%).
CONCLUSIONS: The management of vascular infections with C. burnetii tends to be complicated. Diagnosis is often difficult due to asymptomatic presentation. Patients undergo challenging surgical corrections and long-term antibiotic treatment.
Complication rates and mortality are high in this patient cohort.
PMID: 26381746
Van der Steen M, Leenstra T, Kluytmans JA, van der Bij AK; ISIS-AR study group (Renders NH). Trends in Expanded-Spectrum Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae among Dutch Clinical Isolates, from 2008 to 2012. PLoS One. 2015 Sep 18;10(9):e0138088. doi: 10.1371/journal.pone.0138088.
eCollection 2015.
171 BIJLAGE WETENSCHAPPELIJKE PUBLICATIES 2013-2014 OPGENOMEN IN PUBMED
We investigated time trends in extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae iso-lates from different patient settings in The Netherlands from 2008-2012. E. coli and K. pneumoniae isoiso-lates from blood and urine samples of patients > = 18 years were selected from the Dutch Infectious Disease Surveillance System-Antimicrobial Resistance (ISIS-AR) database. We used multivariable Poisson regression to study the rate per year of blood stream infec-tions by susceptible and resistant isolates, and generalized estimating equation (GEE) log-binomial regression for trends in the proportion of extended-spectrum cephalosporin-resistant isolates. Susceptibility data of 197,513 E. coli and 38,244 K.
pneumoniae isolates were included. The proportion of extended-spectrum cephalosporin-resistant E. coli and K. pneumo-niae isolates from urine and blood samples increased in all patient settings, except for K. pneumopneumo-niae isolates from patients admitted to intensive care units. For K. pneumoniae, there was a different time trend between various patient groups (p<0.01), with a significantly higher increase in extended-spectrum cephalosporin-resistant isolates from patients attending a general practitioner than in isolates from hospitalized patients. For E. coli, the increasing time trends did not differ among different patient groups. This nationwide study shows a general increase in extended-spectrum cephalosporin-resistant E.
coli and K. pneumoniae isolates. However, differences in trends between E. coli en K. pneumoniae underline the importance of E. coli as a community-pathogen and its subsequent influence on hospital resistance level, while for K. pneumoniae the level of resistance within the hospital seems less influenced by the resistance trends in the community.
PMID: 26384483
Slok EN, Dijkstra F, de Vries E, Rietveld A, Wong A, Notermans DW, van Steenbergen JE. Estimation of acute and chronic Q fever incidence in children during a three-year outbreak in the Netherlands and a comparison with international literature. BMC Res Notes. 2015 Sep 18;8(1):456. doi: 10.1186/s13104-015-1389-0.
BACKGROUND: In the Dutch 2007-2009 Q fever outbreak Coxiella burnetii was transmitted aerogenically from dairy goat farms to those living in the surrounding areas. Relatively few children were reported. The true number of pediatric infections is unknown. In this study, we estimate the expected number of acute and chronic childhood infections. METHODS:
As Coxiella was transmitted aerogenic to those living near infected dairy goat farms, we could use adult seroprevalence data to estimate infection risk for inhabitants, children and adults alike. Using Statistics Netherlands data we estimated the number of children at (high) risk for developing chronic Q fever. Literature was reviewed for childhood (0-15 years) Q fever reports and disease rates. We compared this with Dutch reported and our estimated data for 2007-2009. RESULTS: In The Netherlands epidemic, 44 children were reported (1.2 % of total notifications). The childhood incidence was 0.15 compared to 2.6 per 10,000 inhabitants for adults. No complications were reported. Based on the expected similarity in childhood and adult exposure we assume that 9.8 % of children in the high-risk area had Q fever infection, resulting in 1562 acute infections during the Q fever epidemic interval. Based on the prevalence of congenital heart disease, at least 13 children are at high risk for developing chronic Q fever. In medical literature, 42 case reports described 140 childhood Q fever cases with a serious outcome (four deaths). In chronic Q fever, cardiac infections were predominant. Four outbreaks were reported involving children, describing 11 childhood cases. 36 National and/or regional studies reported seroprevalences varying between 0 and 70 %. CONCLUSION: In the 3-year Dutch epidemic, few childhood cases were reported, with pulmonary symptoms leading, and none with a serious presentation. With an estimated 13 high-risk children for chronic infection in the high exposure area, and probably forty in the whole country, we may expect several chronic Q fever complications in the coming years in paediatric practice.
PMID: 26391102
van la Parra RF, de Wilt JH, Mol SJ, Mulder AH, de Roos WK, Bosscha K. Is SLN Biopsy Alone Safe in SLN Positive Breast Cancer Patients? Breast J. 2015 Nov-Dec;21(6):621-6. doi: 10.1111/tbj.12496. Epub 2015 Sep 22.
The Z0011 trial demonstrated no difference in overall survival (OS) and locoregional recurrence in breast cancer patients
with a positive sentinel lymph node (SLN) randomized to axillary lymph node dissection (ALND) or no further surgery.
The aim of this study was to evaluate locoregional recurrence in a nonrandomized group of SLN positive patients, in whom cALND was not performed, that were retrospectively categorized by the Z0011 eligibility criteria. From two hospital breast cancer databases consisting of 656 consecutive SLN positive breast cancer patients, 88 patients, who did not undergo cALND, were identified. This population was categorized by the Z0011 inclusion criteria (e.g., eligible versus ineligible) and the groups were compared. Thirty-four patients (38.6%) were retrospectively eligible for omitting cALND according to the Z0011 criteria and 54 (61.4%) were not. The median number of SLNs removed in both groups was 1 (range 1-5). The number of positive SLNs did not differ between the groups. Tumor size was slightly larger in the ine-ligible group (21 mm versus 19 mm) and 76% of patients in the ineine-ligible group underwent a mastectomy. At a median follow-up of 26 months (range 1-84 months), one axillary recurrence was observed in the ineligible group versus 0 in the eligible group. Axillary recurrence was low, even in patients who did not meet the Z0011 inclusion criteria. Future trials that randomize Z0011 ineligible patients are needed to investigate long-term results.
PMID: 26395089
Ranschaert ER, van Ooijen PM, Lee S, Ratib O, Parizel PM. Social media for radiologists: an introduction.
Insights Imaging. 2015 Dec;6(6):741-752. Epub 2015 Sep 22.
Social media, which can be defined as dynamic and interactive online communication forums, are becoming increasingly popular, not only for the general public but also for radiologists. In addition to assisting radiologists in finding useful pro-fession-related information and interactive educational material in all kinds of formats, they can also contribute towards improving communication with peers, clinicians, and patients. The growing use of social networking in healthcare also has an impact on the visibility and engagement of radiologists in the online virtual community. Although many radiolo-gists are already using social media, a large number of our colleagues are still unaware of the wide spectrum of useful information and interaction available via social media and of the added value these platforms can bring to daily practice.
For many, the risk of mixing professional and private data by using social media creates a feeling of insecurity, which still keeps radiologists from using them. In this overview we aim to provide information on the potential benefits, challenges, and inherent risks of social media for radiologists. We will provide a summary of the different types of social media that can be of value for radiologists, including useful tips on how to use them safely and efficiently. MAIN MESSAGES: • Online social networking enhances communication and collaboration between peers • Social media facilitate access to educati-onal and scientific information • Recommendations and guidelines from policymakers and professieducati-onal organisations are needed • Applications are desired for efficient and secure exchange of medical images in social media.
PMID: 26395570
Hopstaken RM, van Balen JA, Kusters R. Point-of-care-testing in general practice. Ned Tijdschr Geneeskd.
2015;159:A9475. Dutch.
Point-of-care testing (POCT) is being used increasingly in general practice and other healthcare contexts outside the hospital. Recommendations for correct and safe use of POCT in Dutch general practice have been laid down in the guide-line ‘Point-of-care testing in general practice’. The recommendations in this guideguide-line are based on existing regulations and guidelines, both national and international, and respect the different roles and responsibilities within the healthcare chain.
173 BIJLAGE WETENSCHAPPELIJKE PUBLICATIES 2013-2014 OPGENOMEN IN PUBMED
PMID: 26407752
Derikx LA, Nissen LH, Smits LJ, Shen B, Hoentjen F. Risk of Neoplasia After Colectomy in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2016 Jun;14(6):798-806.e20. doi: 10.1016/j.cgh.2015.08.042. Epub 2015 Sep 25.
BACKGROUND & AIMS: Colorectal neoplasia can still develop after colectomy for inflammatory bowel disease. However, data on this risk are scare, and there have been few conclusive findings, so no evidence-based recommendations have been made for postoperative surveillance. We conducted a systematic review and meta-analysis to determine the prevalence and incidence of and risk factors for neoplasia in patients with inflammatory bowel disease who have undergone colectomy, including the permanent-end ileostomy and rectal stump, ileorectal anastomosis (IRA), and ileal pouch-anal anastomosis (IPAA) procedures. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library through May 2014 to identify studies that reported prevalence or incidence of colorectal neoplasia after colec-tomy or specifically assessed risk factors for neoplasia development. Studies were selected, quality was assessed, and data were extracted by 2 independent researchers. RESULTS: We calculated colorectal cancer (CRC) prevalence values from 13 studies of patients who underwent rectal stump surgery, 35 studies of IRA, and 33 studies of IPAA. Signifi-cantly higher proportions of patients in the rectal stump group (2.1%; 95% confidence interval [CI], 1.3%-3.0%) and in the IRA group (2.4%; 95% CI, 1.7%-3.0%) developed CRC than in the IPAA group (0.5%; 95% CI, 0.3%-0.6%); the odds ratio (OR) for CRC in the rectal stump or IRA groups compared with the IPAA group was 6.4 (95% CI, 4.3-9.5). A history of CRC was the most important risk factor for development of CRC after colectomy (OR for patients receiving IRA, 12.8;
95% CI, 3.31-49.2 and OR for patients receiving IPAA, 15.0; 95% CI, 6.6-34.5). CONCLUSIONS: In a meta-analysis of published studies, we found the prevalence and incidence of CRC after colectomy to be less than 3%; in patients receiving IPAA it was less than 1%. Factors that increased risk of cancer development after colectomy included the presence of a residual rectum and a history of CRC. These findings could aid in development of individualized strategies for post-surgery surveillance.
PMID: 26438336
Nieuwesteeg AM, Hartman EE, Aanstoot HJ, van Bakel HJ, Emons WH, van Mil E, Pouwer F. The relationship between parenting stress and parent-child interaction with health outcomes in the youngest patients with type 1 diabetes (0-7 years). Eur J Pediatr. 2016 Mar;175(3):329-38. doi: 10.1007/s00431-015-2631-4.
To test whether parenting stress and the quality of parent-child interaction were associated with glycemic control and quality of life (QoL) in young children (0-7 years) with type 1 diabetes (T1DM), we videotaped 77 families with a young child with T1DM during mealtime (including glucose monitoring and insulin administration). Parent-child interactions were scored with a specifically designed instrument. Questionnaires assessed general and disease-related parenting stress and (diabetes-specific (DS)) QoL. HbA(1c) (glycemic control) was extracted from the medical records. Both general and disease-related parenting stress were associated with a lower (DS)QoL (r ranged from -0.39 to -0.70, p < 0.05), but not with HbA(1c) levels. Furthermore, with regard to the parent-child interaction, emotional involvement of parents (r = 0.23, p < 0.05) and expressed discomfort of the child (r = 0.23, p < 0.05) were related to suboptimal HbA(1c) levels. There was no clear pattern in the correlations between parent-child interaction and (DS)QoL. CONCLU-SION: The results support the notion that diabetes does not only affect the child with T1DM: T1DM is a family disease, as parenting factors (like stress and parent-child interactions) are associated with important child outcomes. Therefore, it is important for health-care providers to not only focus on the child with T1DM, but also on the family system.
PMID: 26447542
Derikx LA, Nissen LH, Drenth JP, van Herpen CM, Kievit W, Verhoeven RH, Mulders PF, Hulsbergen-van de Kaa CA, Boers-Sonderen MJ, van den Heuvel TR, Pierik M, Nagtegaal ID, Hoentjen F; Dutch Initiative on Crohn and Colitis; PALGA Group. Better survival of renal cell carcinoma in patients with inflammatory bowel disease. Oncotarget. 2015 Nov 10;6(35):38336-47. doi: 10.18632/oncotarget.5186.
BACKGROUND: Immunosuppressive therapy may impact cancer risk in inflammatory bowel disease (IBD). Cancer specific data regarding risk and outcome are scarce and data for renal cell carcinoma (RCC) are lacking. We aimed(1) to identify risk factors for RCC development in IBD patients (2) to compare RCC characteristics, outcome and survival between IBD patients and the general population. METHODS: A PALGA (Dutch Pathology Registry) search was performed to establish a case group consisting of all IBD patients with incident RCC in The Netherlands (1991-2013).
Cases were compared with two separate control groups: (A) with a population-based IBD cohort for identification of risk factors (B) with a RCC cohort from the general population to compare RCC characteristics and outcomes.
RESULTS: 180 IBD patients with RCC were identified. Pancolitis (OR 1.8-2.5), penetrating Crohn’s disease (OR 2.8), IBD related surgery (OR 3.7-4.5), male gender (OR 3.2-5.0) and older age at IBD onset (OR 1.0-1.1) were identified as independent risk factors for RCC development. IBD patients had a significantly lower age at RCC diagnosis (p < 0.001), lower N-stage (p = 0.025), lower M-stage (p = 0.020) and underwent more frequently surgical treatment for RCC (p
< 0.001) compared to the general population. This translated into a better survival (p = 0.026; HR 0.7) independent of immunosuppression. CONCLUSIONS: IBD patients with a complex phenotype are at increased risk to develop RCC.
They are diagnosed with RCC at a younger age and at an earlier disease stage compared to the general population.
This translates into a better survival independent of immunosuppressive or anti-TNFκ therapy.
PMID: 26452336
Willemsen AE, Grutters JC, Gerritsen WR, van Erp NP, van Herpen CM, Tol J. mTOR inhibitor-induced interstitial lung disease in cancer patients: Comprehensive review and a practical management algorithm.
Int J Cancer. 2016 May 15;138(10):2312-21. doi: 10.1002/ijc.29887.
Mammalian target of rapamycin inhibitors (mTORi) have clinically significant activity against various malignancies, such as renal cell carcinoma and breast cancer, but their use can be complicated by several toxicities. Interstitial lung disease (ILD) is an adverse event of particular importance. Mostly, mTORi-induced ILD remains asymptomatic or mildly symp-tomatic, but it can also lead to severe morbidity and even mortality. Therefore, careful diagnosis and management of ILD is warranted. The reported incidence of mTORi-induced ILD varies widely because of a lack of uniform diagnostic criteria and active surveillance. Because of the nonspecific clinical features, a broad differential diagnosis that includes (opportunistic) infections should be considered in case of suspicion of mTORi-induced ILD. The exact mechanism or interplay of mechanisms leading to the development of ILD remains to be defined. Suggested mechanisms are either a direct toxic effect or immune-mediated mechanisms, considering mTOR inhibitors have several effects on the immune system. The clinical course of ILD varies widely and is difficult to predict. Consequently, the discrimination between when mTOR inhibitors can be continued safely and when discontinuation is indicated is challenging. In this review, we give a comprehensive review of the incidence, clinical presentation and pathophysiology of mTORi-induced ILD in cancer patients. We present newly developed diagnostic criteria for ILD, which include clinical symptoms as well as basic pulmonary function tests and radiological abnormalities. In conjunction with these diagnostic criteria, we provide a detailed and easily applicable clinical management algorithm.
175 BIJLAGE WETENSCHAPPELIJKE PUBLICATIES 2013-2014 OPGENOMEN IN PUBMED
PMID: 26466011
Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators (Biesma B.). First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 371; 2167-77, 2014. doi: 10.1056/
NEJMoa1408440. Erratum in: N Engl J Med. 2015 Oct 15;373(16):1582. doi: 10.1056/NEJMx150034.
PMID: 26475650
van Grinsven J, van Brunschot S, Bakker OJ, Bollen TL, Boermeester MA, Bruno MJ, Dejong CH, Dijkgraaf MG, van Eijck CH, Fockens P, van Goor H, Gooszen HG, Horvath KD, van Lienden KP, van Santvoort HC, Besselink MG; Dutch Pancreatitis Study Group (Cappendijk VC). Diagnostic strategy and timing of
intervention in infected necrotizing pancreatitis: an international expert survey and case vignette study. HPB (Oxford). 2015 Oct 17. doi: 10.1111/hpb.12491.
BACKGROUND: The optimal diagnostic strategy and timing of intervention in infected necrotizing pancreatitis are subject to debate. A survey was performed on these topics amongst a group of international expert pancreatologists.
METHODS: An online survey including case vignettes was sent to 118 international pancreatologists. The use and
METHODS: An online survey including case vignettes was sent to 118 international pancreatologists. The use and