Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.

Ultrasonographic and hemodynamic characteristics of patients with symptomatic carotid near-occlusion: results from a multicenter registry study.

PURPOSE: The ultrasonographic and hemodynamic features of patients with carotid near-occlusion (CNO) are still not well known. Our aim was to describe the ultrasonographic and hemodynamic characteristics of a cohort of patients with CNO. METHODS: A prospective, observational, nationwide, and multicenter study was conducted from January/2010 to May/2016. Patients with digital subtraction angiography (DSA)-confirmed CNO were included. We collected information on clinical and demographic characteristics, carotid and transcranial ultrasonography and DSA findings, presence of full-collapse, collateral circulation, and cerebrovascular reactivity (CVR). RESULTS: One hundred thirty-five patients were analyzed. Ultrasonographic and DSA diagnosis of CNO were concordant in only 44%. This disagreement was related to the presence/absence of full-collapse: 45% of patients with CNO with full-collapse were classified as a complete carotid occlusion, and 40% with a CNO without full-collapse were interpreted as severe stenosis (p < 0.001). Mean velocities (mV) and pulsatility indexes (PIs) were significantly lower in the ipsilateral middle cerebral artery compared with the contralateral (43 cm/s vs 58 cm/s, p < 0.001; 0.80 vs 1.00, p < 0.001). Collateral circulation was identified in 92% of patients, with the anterior communicating artery (73%) being the most frequent. CVR was decreased or exhausted in 66% of cases and was more frequent in patients with a poor or absent collateral network compared with patients with ≥ 2 collateral arteries (82% vs 56%, p = 0.051). CONCLUSION: The accuracy of carotid ultrasonography in the diagnosis of CNO seems to be limited, with significant discrepancies with DSA. Decreased ipsilateral mV, PI, and CVR suggest a hemodynamic compromise in patients with CNO.

Efficacy of an organically modified bentonite to adsorb 2,4-dichlorophenoxyacetic acid (2,4-D) and prevent its phytotoxicity.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used due to it selective action, and preferential control of dicotyledonous weeds affecting cereal crops. Physiological responses of sensitive dicotyledonous plants to 2,4-D include growth retardation, senescence, and cell death. Due to soil and water contamination by agricultural practices, 2,4-D constitutes a potential risk to non-target plant species. In this work, the potential advantage of using organic modified bentonite (Bent) to adsorb 2,4-D and therefore mitigate damage produced by this herbicide on sensitive not-target vegetable species was investigated. Dodecylamine (DDA) was used as an organic modifier to change the hydrophilic nature of Bent into an organophilic matrix. The adsorption performances of 2,4-D by Bent-DDA were analyzed. The maximum adsorptions of 2,4-D (22.1 mg/L) from aqueous solution containing 1.0 or 2.5 mg/mL Bent-DDA were 40 and 80 %, respectively. The physical interaction of Bent-DDA with 2,4-D was characterized by Wide Angle X-ray Scattering (WAXS) and thermogravimetric analysis (TGA). The biological functionality of Bent-DDA matrix as 2,4-D adsorbent was tested in a bioassay in the Arabidopsis thaliana plant model system. The primary root growth of Arabidopsis seedlings is strongly inhibited by low concentrations of 2,4-D. Arabidopsis seedlings submitted to Bent-DDA pre-treated herbicide aqueous solution showed similar root growth than 2,4-D non-treated seedlings. Finally, the ability of Bent-DDA to prevent 2,4-D phytotoxicity was exploratory investigated in lettuce plants. Lettuce plants pre-treated with 20 µg/mL Bent-DDA showed reduced sensitivity to 2,4-D including an increment on chlorophyll content and biomass compared with non-treated plants. Our findings revealed a promising scenario for the application of Bent-DDA as an effective adsorbent of 2,4-D at productive scale.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

First report of Escherichia coli O157:H7 in ready-to-eat sushi.

AIMS: The aim of this study was to evaluate the microbiological quality of commercially prepared ready-to-eat (RTE) sushi by enumerating aerobic mesophilic bacteria (AMB) and thermotolerant coliforms (TC) and detecting Escherichia coli and Salmonella ssp. An isolate was identified as E. coli O157:H7 which was evaluated for its virulence and antimicrobial resistance profiling as well as its ability to form biofilms on stainless steel. METHODS AND RESULTS: There were four sampling events in seven establishments, totalling 28 pools of sushi samples. Mean AMB counts ranged between 5·2 and 7·7 log CFU per gram. The enumeration of TC varied between 2·1 and 2·7 log MPN per gram. Salmonella ssp. were not detected, and one sample was positive for E. coli and was identified as E. coli O157:H7. To the best of our knowledge, this is the first report of E. coli O157:H7 in sushi samples in the world literature. This isolate presented virulence genes stx1, stx2, eae and hlyA. It was also susceptible to 14 antimicrobials tested and had the ability to form biofilms on stainless steel. CONCLUSIONS: There is a need to improve the good hygiene practices adopted in establishments selling sushi in the city of Pelotas, Brazil. In addition, the isolated E. coli O157:H7 carries a range of important virulence genes being a potential risk to consumer health, as sushi is a RTE food. This isolate also presents biofilm formation ability, therefore, may trigger a constant source of contamination in the production line of this food. SIGNIFICANCE AND IMPACT OF THE STUDY: The increase in the consumption of sushi worldwide attracts attention regarding the microbiological point of view, since it is a ready-to-eat food. To our knowledge, this was the first time that E. coli O157:H7 was identified in sushi samples.

Spiny keratoderma.

Spiny keratoderma is a rare entity characterized by filiform keratotic lesions on palms and soles. Although there are some inherited cases the majority are acquired. This last variant can be idiopathic or associated with neoplasms and chronic systemic diseases. We report a new case of spiny keratoderma associated with endometrial carcinoma.

The risk of recurrent stroke at 24 months in patients with symptomatic carotid near-occlusion: results from CAOS, a multicentre registry study.

BACKGROUND AND PURPOSE: The risk of recurrent stroke amongst patients with symptomatic carotid near-occlusion (SCNO) has not been clearly established, and its management remains controversial. The aim was to define the 24-month risk of recurrent stroke and to analyse the effect of the different treatment modalities (medical treatment and revascularization) in a population of patients with SCNO. METHODS: A multicentre, nationwide, prospective study from January 2010 to May 2016 was performed. Patients with angiography-confirmed SCNO were included. The primary end-point was ipsilateral ischaemic stroke including periprocedural events within 24 months following the presenting event. Revascularization results and periprocedural complications, ipsilateral transient ischaemic attack, disabling or fatal stroke, and mortality were also noted. RESULTS: The study population comprised 141 patients from 17 Spanish centres. Seventy patients (49.6%) were treated by revascularization (carotid stenting in 47, endarterectomy in 23). Complete revascularization was achieved in 58 patients (83%). Periprocedural stroke or death occurred in 5.7%. The 24-month cumulative incidence of the primary end-point was 11.1% (95% confidence interval 5.8-16.4; n = 15), 12% in the medical treatment group and 10.2% in the revascularization group, log-rank P = 0.817. The cumulative rates of ipsilateral ischaemic stroke or transient ischaemic attack, disabling or fatal stroke, and mortality, were 17%, 4.5% and 7.5%, respectively. CONCLUSIONS: The rate of ipsilateral ischaemic stroke in patients with SCNO seems to be lower than the known rate associated with severe carotid stenosis without near-occlusion. The potential benefit of revascularization in the prevention of stroke in patients with SCNO may be influenced by the effectiveness and safety of the procedure.

Characterization of minimal lesions related to the presence of visna/maedi virus in the mammary gland and milk of dairy sheep.

BACKGROUND: In order to characterize the complete range of lesions, especially minimal, affecting mammary gland and viral antigen distribution and target cells using immunohistochemistry in naturally Visna/maedi (VM) 84 infected sheep were studied, forty-four from flocks with clinical cases (A) and 35 randomly sampled from two abattoirs (B) together with five negative controls (C). An immunocytochemistry technique was developed and further milk samples (n = 39) were used to study viral excretion, carrier cells and the role of milk and colostrum in the transmission of the disease. RESULTS: All sheep from group C and three sheep from group B were negative to VM in tissue sections by histopathology, immunohistochemistry and PCR, and also in serum using ELISA. Several degrees of CD3 + lymphocytic interstitial mastitis were observed in groups A and B: minimal (+) n = 26 sheep; moderate (++), n = 32 and severe (+++), n = 12. No differences in lesion distribution were observed between groups A and B. Viral presence was confirmed by immunohistochemistry using two different antibodies and/or PCR in every tissue with lesions while serology was negative in six sheep with lesions. Two milk samples taken from milk tanks from two flocks from group A and fourteen milk samples from 29 infected sheep from group B were positive to VM (most of them from animals with moderate and severe lesions). Positivity was only found in macrophages, even in focal and minimal lesions, while no positivity was observed in epithelial or any other cells in either tissue and milk samples. CONCLUSIONS: This new observation of the minimal lesions described in this work increased the prevalence of VM lesions in mammary gland up to 90.9% and VM should be considered as a differential diagnosis when minimal interstitial lesions are detected. A high prevalence of VM was observed in intensive milk-producing sheep, ELISA serology did not detect as positivity all infected animals, while histology, IHC or PCR showed higher sensitivity. The cytological technique developed was very useful in milk-cell studies using hematoxylin and eosin and immunocytochemistry. Viral detection in milk samples (16/39) confirms a potential but limited role of milk/colostrum in viral transmission.

Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?

Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.

Skin temperature in youth soccer players with functional equinus and non-equinus condition after running.

OBJECTIVES: To check how a thermal IR camera can check skin temperature in gastrocnemius-soleus equinus condition and non-gastrocnemius-soleus condition in youth soccer players and thus detect association between the extensibility of the triceps surae (with gastrocnemius-soleus equinus and non-gastrocnemius-soleus equinus) and the muscle temperature pattern. DESIGN: A cross-sectional study secondary level of care. METHODS: Sample from an elite soccer academy in Madrid (Spain) 35 healthy male subjects (youth soccer players) age 12.82 ± 1.07 years, height 158.68 ± 10.79 cm, weight 49.19 ± 9.45 kg, body mass index 19.41 ± 2.25. The exclusion criteria were the presence of musculoskeletal and joint injuries, pelvic pain, ankle sprains, low back pain and use of drugs in the previous week, and scoliosis. RESULTS: Temperature value for gastrocnemius muscles and Achilles tendon were assessed in 35 youth soccer players from an academia before and after training in both 12 gastrocnemius-soleus equinus and 23 non-gastrocnemius-soleus equinus soccer players conditions. State absolute for gastrocnemius soleus condition obtained a 0.34 value (0.19-0.5); we found a significant increase in temperature among these conditions for the gastrocnemius (P = 0.028) and the Achilles tendon (P = 0.007) (confidence interval 95%). The temperature of gastrocnemius-soleus equinus for gastrocnemius and Achilles tendon was increased more than non-gastrocnemius-soleus equinus in youth soccer players. CONCLUSIONS: IR imaging captured temperature is associated with muscle pattern activation for lower limb. Based on our findings, we propose that infrared thermography evaluation of the gastrocnemius and Achilles tendon is suitable to differ gastrocnemius-soleus equinus and non-gastrocnemius-soleus equinus conditions in youth soccer players.

Impact of the mechanical hyperkeratotic lesions and its association with quality of life: An observational case-control study.

BACKGROUND: Mechanical hyperkeratotic lesions (MHL) are common condition amongst population of all ages. Such problems may be associated with pain, reduction in mobility, changes of gait and risk of falls and is believed to affect the quality of life (QoL), general health and optimal foot health. OBJECTIVE: The main aim of this study was to describe and compare both foot and general health-related QoL in two groups of participants: (i) with MHL and (ii) healthy controls. METHOD: A total sample of 150 patients, mean age 49.50 ± 36.50 years, was recruited from an outpatient clinic. Demographic data, medical history and clinical characteristics of overall health were determined, and the obtained values were compared by the Foot Health Status Questionnaire (FHSQ). RESULTS: The FHSQ scores of the sample with MHL showed lower scores than control subjects in sections one and two for footwear, general and foot health, foot pain, foot function and physical activity (P < 0.01), but not for social capacity and vigour (P > 0.01). CONCLUSIONS: People with MHL showed a decrease in QoL, based on FHSQ scores, regardless of gender.

Efficacy of Pseudomonas graminis CPA-7 against Salmonella spp. and Listeria monocytogenes on fresh-cut pear and setting up of the conditions for its commercial application.

Pseudomonas graminis CPA-7 has been reported to control foodborne pathogens on fresh-cut apple, peach and melon. The first aim of this study was to assess its antagonistic activity against Salmonella spp. and L. monocytogenes on fresh-cut pear. CPA-7 was able to control both pathogens on fresh-cut pear stored in air conditions at 5, 10 and 20 °C. However, when CPA-7 antagonistic effect was tested by simulating commercial application (with antioxidant solution and passive modified atmosphere packaging), its effect decreased and no reductions of foodborne pathogens were reported at 10 °C. Therefore, the second aim was to optimise the antioxidant solution and the packaging in order to retain its antagonistic capacity. The selected antioxidant solution was 2% ascorbic acid +2% sodium citrate +1% CaCl2 according to growth and effect of CPA-7. Film permeability, which affects gas composition inside fruit packages, influenced CPA-7 efficacy. If the biopreservative strain is used, film has to be sufficiently gas permeable to allow CPA-7 function and at the same time to maintain product quality.

Early referral and control of disease's flares prevent Orthopedic and Hand Surgery Indication (OHSI) in a dynamic cohort of Hispanic early rheumatoid arthritis patients.

BACKGROUND: Reconstructive joint surgery is an indicator of poor prognosis in rheumatoid arthritis (RA). Objectives of this study were to describe the incidence rate of orthopedic and hand surgery indication (OHSI) in an ongoing cohort of Hispanic early RA patients treated according to a T2T strategy and to investigate predictors. METHODS: Through February 2018, the cohort comprised 185 patients recruited from 2004 onwards, with variable follow-up, and rheumatic assessments at fixed intervals that included prospective determination of OHSI. Charts were reviewed by a single data abstractor. OHSI incidence rate was calculated. A case-control study nested within a cohort investigated the predictors; cases (OHSI patients) were paired with controls (1:4) according to age, sex and autoantibodies. A logistic regression model included baseline and cumulative (up to OHSI or equivalent) variables related to disease activity, treatment and to persistence with therapy. The IRB approved the study. RESULTS: Patients from the cohort were predominantly middle-aged (mean ± SD age: 38.5 ± 12.9 years) females (87.6%) with 5.4 ± 2.6 months of disease duration. The cohort contributed to 1538 patient-years of follow-up. Twelve patients received incidental OHSI at a follow-up of 85 ± 44.5 months. The OHSI incident global rate was 8/1000 patient-years. Longer symptom duration at cohort referral (OR: 1.313, 95%CI: 1.02-1.68, p = 0.032) and a higher number of flares/patient (OR: 1.608, 95%CI: 1.05-1.61, p = 0.015) predicted OHSI. OHSI patients had more severe flares than their counterparts, and the opposite figure was true for mild flares. CONCLUSION: Early referral for appropriate management and flare control may prevent OHSI in Hispanic recent-onset RA patients.

Antimicrobial susceptibility and molecular typing of toxigenic clinical isolates of Clostridium difficile causing infections in the south of Spain.

Antimicrobial susceptibility to 6 antimicrobial agents, PCR-ribotyping and molecular genetics of fluoroquinolone resistance was assessed in 70 toxigenic clinical isolates of C. difficile recovered from patients attended in a hospital in southern Spain with suspected Clostridium difficile infection. Moxifloxacin was the least active drug, mainly driven by the aminoacid substitution Thr82Ile in GyrA, while PCR-ribotype 078 was the most prevalent lineage identified and grouped several of the fluoroquinolone resistant isolates.

Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method.

Method-dependent Etest epidemiological cutoff values (ECVs) are not available for susceptibility testing of either Candida or Aspergillus species with amphotericin B or echinocandins. In addition, reference caspofungin MICs for Candida spp. are unreliable. Candida and Aspergillus species wild-type (WT) Etest MIC distributions (microorganisms in a species-drug combination with no detectable phenotypic resistance) were established for 4,341 Candida albicans, 113 C. dubliniensis, 1,683 C. glabrata species complex (SC), 709 C. krusei, 767 C. parapsilosis SC, 796 C. tropicalis, 1,637 Aspergillus fumigatus SC, 238 A. flavus SC, 321 A. niger SC, and 247 A. terreus SC isolates. Etest MICs from 15 laboratories (in Argentina, Europe, Mexico, South Africa, and the United States) were pooled to establish Etest ECVs. Anidulafungin, caspofungin, micafungin, and amphotericin B ECVs (in micrograms per milliliter) encompassing ≥97.5% of the statistically modeled population were 0.016, 0.5, 0.03, and 1 for C. albicans; 0.03, 1, 0.03, and 2 for C. glabrata SC; 0.06, 1, 0.25, and 4 for C. krusei; 8, 4, 2, and 2 for C. parapsilosis SC; and 0.03, 1, 0.12, and 2 for C. tropicalis The amphotericin B ECV was 0.25 µg/ml for C. dubliniensis and 2, 8, 2, and 16 µg/ml for the complexes of A. fumigatus, A. flavus, A. niger, and A. terreus, respectively. While anidulafungin Etest ECVs classified 92% of the Candida fks mutants evaluated as non-WT, the performance was lower for caspofungin (75%) and micafungin (84%) cutoffs. Finally, although anidulafungin (as an echinocandin surrogate susceptibility marker) and amphotericin B ECVs should identify Candida and Aspergillus isolates with reduced susceptibility to these agents using the Etest, these ECVs will not categorize a fungal isolate as susceptible or resistant, as breakpoints do.

Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients.

BACKGROUND: RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. PATIENTS AND METHODS: RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. RESULTS: Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. CONCLUSION: The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Prevalence and distribution of hepatitis C virus genotypes in Spain during the 2000-2015 period (the GEHEP 005 study).

We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000-2015), and we relate them with clinical, epidemiological and virological factors. Patients from 29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla-Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV-infected patients with the following characteristics: median age 51 years (IQR, 44-58), 67.9% male, 19.1% HIV-coinfected, 23.5% HBV-coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono-infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.