Background. Triazole resistance is an increasing problem in invasive aspergillosis (IA). Small case series show mortality rates of 50%-100% in patients infected with a triazole-resistant Aspergillus fumigatus, but a direct comparison with triazole-susceptible IA is lacking.Methods. A 5-year retrospective cohort study (2011)(2012)(2013)(2014)(2015) was conducted to compare mortality in patients with voriconazole-susceptible and voriconazole-resistant IA. Aspergillus fumigatus culture-positive patients were investigated to identify patients with proven, probable, and putative IA. Clinical characteristics, day 42 and day 90 mortality, triazole-resistance profiles, and antifungal treatments were investigated.Results. Of 196 patients with IA, 37 (19%) harbored a voriconazole-resistant infection. Hematological malignancy was the underlying disease in 103 (53%) patients, and 154 (79%) patients were started on voriconazole. Compared with voriconazole-susceptible cases, voriconazole resistance was associated with an increase in overall mortality of 21% on day 42 (49% vs 28%; P = .017) and 25% on day 90 (62% vs 37%; P = .0038). In non-intensive care unit patients, a 19% lower survival rate was observed in voriconazole-resistant cases at day 42 (P = .045). The mortality in patients who received appropriate initial voriconazole therapy was 24% compared with 47% in those who received inappropriate therapy (P = .016), despite switching to appropriate antifungal therapy after a median of 10 days.Conclusions. Voriconazole resistance was associated with an excess overall mortality of 21% at day 42 and 25% at day 90 in patients with IA. A delay in the initiation of appropriate antifungal therapy was associated with increased overall mortality.

Colonic fermentation of dietary carbohydrates and fiber might produce a protective effect against the development of large bowel cancer. Resistant starch, ie, starch that escapes small bowel digestion, is a candidate fermentable substrate that has been hitherto little studied. We supplemented 19 healthy volunteers with 15 g native amylomaize (Hylon-VII) three times a day, containing 28 g type II resistant starch, or with dextrins as a placebo for 7 d in a crossover design. Pre-experimentally, 11 subjects regularly produced breath methane and 8 did not. Resistant starch increased 24-h integrated excretion of breath hydrogen. The mean rise relative to placebo was 35% (P = 0.03) for all subjects and 60% for eight subjects not producing methane (P = 0.02). The 11 methane producers showed a 93% increase in breath-methane excretion on resistant starch (P = 0.03). Continued consumption of 28 g type II resistant starch/d is well tolerated and increases colonic fermentation in healthy volunteers.

Primary mucinous ovarian carcinomas (MOC) are notoriously difficult to distinguish from mucinous carcinomas metastatic to the ovary (mMC). Studies performed on small cohorts reported algorithms based on tumor size and laterality to aid in distinguishing MOC from mMC. We evaluated and improved these by performing a large-scale, nationwide search in the Dutch Pathology Registry. All registered pathology reports fulfilling our search criteria concerning MOC in the Netherlands from 2000 to 2011 were collected. Age, histology, laterality, and size were extracted. An existing database covering the same timeline containing tumors metastatic to the ovary was used, extracting all mMC, age, size, laterality, and primary tumor location. Existing algorithms were applied to our cohort. Subsequently, an algorithm based on tumor histology, laterality, and a nomogram based on age and size was created for differentiating MOC and mMC. We identified 735 MOC and 1018 mMC. Patients with MOC were significantly younger and MOC were significantly larger and more often unilateral than mMC. Signet ring cell carcinomas were rarely primary. Our algorithm used signet ring cell histology, bilaterality, and a nomogram integrating patient age and tumor size to diagnose mMC. Sensitivity and specificity for mMC was 90.1% and 59.0%, respectively. Applying existing algorithms on our cohort yielded a far lower sensitivity. The algorithm described here using tumor histology, laterality, size, and patient age has higher sensitivity but lower specificity compared to earlier algorithms and aids in indicating tumor origin, but for conclusive diagnosis, careful integration of morphology, immunohistochemistry, and clinical and imaging data is recommended. Electronic supplementary material The online version of this article (10.1007/s00428-018-2504-0) contains supplementary material, which is available to authorized users.

Approximately half of the colorectal cancer (CRC) patients develop metastatic disease. Fluoropyrimidine-based chemotherapy forms the backbone of treatment in these patients. However, the response to this therapy varies between individuals. Therefore, an important challenge in CRC research is to identify biomarkers that are predictive of this response. In this study, we explored the potential of miRNAs, and the miRNA producing protein Dicer, as biomarkers that can predict chemo-sensitivity to fluoropyrimidine chemotherapy in patients with metastatic colorectal cancer (mCRC). We analyzed the levels of 22 miRNAs and the Dicer protein in primary tumors from patients with mCRC who were treated with first-line capecitabine monotherapy within the CAIRO trial of the Dutch Colorectal Cancer Group. Correlation between the expression status of miRNAs or Dicer in primary tumors and the progression free survival (PFS) were investigated. Patients with low expression of miR-143 in their primary tumor had increased median PFS compared to those with high expression of miR-143. Furthermore, FXYD3, an ion transport regulator and a putative target of miR-143, also showed an association with PFS. These findings warrant further studies to investigate the relationship between miR-143, FXYD3 and fluoropyrimidines, and the clinical utility of miR-143 as biomarker.

An ischemic forearm test with simultaneous measurement of both lactate and ammonia can be used as a screening method for myoadenylate deaminase deficiency (MADD) and for various glyco(geno)lytic defects. A standardized and a nonstandardized test have been compared in a group of 186 patients with exertional myalgia. Standardization of the ischemic forearm test has led to greater yields of both lactate and ammonia in venous return blood of patients and controls. The sensitivity of the proposed test procedure in detecting MADD patients was 100%, whereas the specificity amounted to 98.8% among exertional myalgia patients.