Recently methicillin resistant
Staphylococcus aureus (MRSA) was isolated from pigs and pig farmers in The Netherlands. In order to assess the dissemination of MRSA in the Dutch pig population, we ...screened 540 pigs in 9 slaughterhouses, where a representative portion of Dutch pigs (63%) was slaughtered in 2005. We found 209 (39%) of the pigs to carry MRSA in their nares. Forty-four of 54 groups of 10 consecutive pigs (81%), each group from a different farm, and all slaughterhouses were affected.
All MRSA isolates belonged to 1 clonal group, showing Multi-Locus Sequence Type 398 and closely related
spa types (mainly t011, t108 and t1254). Three types of the Staphylococcal Chromosome Cassette (SCC
mec) were found: III (3%), IVa (39%) and V (57%). All 44 tested isolates (1 isolate per group) were resistant to tetracycline, reflecting the high and predominant use of tetracyclines in pig husbandry. Twenty-three percent of the isolates were resistant to both erythromycin and clindamycin and 36% to kanamycin, gentamicin and tobramycin but only a single isolate was resistant to co-trimoxazole and none to ciprofloxacin and several other antibiotics.
The percentage of MRSA positive pigs was significantly different among slaughterhouses and among groups within slaughterhouses, indicating a high prevalence of MRSA in pigs delivered from the farms as well as cross contamination in the slaughterhouses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Highlights • The standardized incidence rate (ESR) of SGPA is 4.2–4.9 per 100,000 person years. • Women show a higher, increasing incidence and bimodal age distribution of SGPA. • The 20-year ...recurrence rate was 6.7%. Secondary malignant transformation 0.15%. • Positive or uncertain margins and lower age showed a higher odds of recurrence. • Tumors situated in the minor glands had a lower odds of recurrence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•PD-L1 ≥ 1% is expressed in 16% of stage IV LCNEC, 5% has expression ≥50%.•PD-L1 staining in LCNEC is comparable to values in SCLC, but lower than in NSCLC.•No difference in PD-L1 expression is found ...in RB1 mutated and RB1 wildtype subgroups.•Expression of PD-L1 (tumor cells) and CD8 (tumor infiltrating cells) is associated.•Overall survival is prolonged in patients with PD-L1+ and CD8+ LCNEC.
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare tumor with high mutational burden. Two subtypes of LCNEC are recognized, the co-mutated TP53 and RB1 group and the TP53 and STK11/KEAP1 group. We investigated PD-L1 and CD8 expression in a well characterized stage IV LCNEC cohort and compared expression in the two subtypes.
Immunohistochemical (IHC) analysis for PD-L1 and CD8 was performed on pathological reviewed pretreatment tumor samples for 148 stage IV LCNEC. Data about targeted next generation sequencing (TNGS) (TP53, RB1, STK11, KEAP1) and IHC for RB1 were available for most tumors. IHC staining for PD-L1 (DAKO 28-8) was performed and scored positive if tumors showed ≥1% membranous staining. CD8 was scored for intra-tumor T-cells and stromal cells.
PD-L1 IHC expression data could be generated in 98/148 confirmed LCNEC samples along with RB1 IHC (n = 97) of which 77 passed quality control for TNGS. PD-L1 expression was positive in 16/98 cases (16%); 5 (5%) with ≥50%. PD-L1 expression was equal in RB1 mutated and RB1 wildtype tumors. None of STK11 mutated tumors (n = 7) expressed PD-L1. PD-L1 expression was correlated with superior overall survival (OS), hazard ratio 0.55 ((95% Confidence Interval 0.31-0.96), p = 0.038). Intra-tumor CD8 was associated with PD-L1 expression (p = 0.021) and stromal and intra-tumor CD8 were correlated with improved OS (p = 0.037 and p = 0.026 respectively).
PD-L1 expression was positive in 16% of stage IV LCNEC tumors. This was independent of molecular subtype but associated with CD8 expression. In LCNEC patients with PD-L1 and/or CD8 expression superior OS was observed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Muscle Invasive Bladder Cancer (MIBC) has a poor prognosis. Whilst patients can achieve a 6% improvement in overall survival with Neo-Adjuvant Chemotherapy (NAC), many do not respond. Body fluid ...mutant DNA (mutDNA) may allow non-invasive identification of treatment failure. We collected 248 liquid biopsy samples including plasma, cell pellet (UCP) and supernatant (USN) from spun urine, from 17 patients undergoing NAC. We assessed single nucleotide variants and copy number alterations in mutDNA using Tagged-Amplicon- and shallow Whole Genome- Sequencing. MutDNA was detected in 35.3%, 47.1% and 52.9% of pre-NAC plasma, UCP and USN samples respectively, and urine samples contained higher levels of mutDNA (p = <0.001). Longitudinal mutDNA demonstrated tumour evolution under the selective pressure of NAC e.g. in one case, urine analysis tracked two distinct clones with contrasting treatment sensitivity. Of note, persistence of mutDNA detection during NAC predicted disease recurrence (p = 0.003), emphasising its potential as an early biomarker for chemotherapy response.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The rising demand for clean and safe water has increased the interest in advanced wastewater treatment and reuse. Reverse osmosis (RO) can provide reliable and high-quality water from treated ...wastewater. Biofouling inevitably occurs, certainly with wastewater effluents, resulting in RO performance decline and operational problems. Chlorination of feed water has been commonly applied to limit biological growth. However, chlorine use may lead to a loss of membrane integrity of RO systems. In this study the potential of monochloramine as an alternative for chlorine was studied by (i) evaluating the biological stability of a full-scale wastewater membrane bioreactor (MBR) effluent during transport over 13 km to a full-scale RO plant and (ii) assessing the biofouling control potential in membrane fouling simulator (MFS) and pilot-scale RO installation. Microbial water analysis was performed on samples taken at several locations in the full-scale water reuse system (MBR effluent, during transport, and at the RO inlet and outlet) using a suite of tools including heterotrophic plate counts (HPC), adenosine triphosphate (ATP), flow cytometry (FCM), and 16 S rRNA gene pyrosequencing. Growth potential tests were used to evaluate the effect of monochloramine presence and absence on bacterial growth. Results showed limited changes in the microbial water quality in the presence of monochloramine. MFS studies showed that membrane biofouling could be effectively repressed by monochloramine over prolonged time periods. The normalized salt passage in a pilot RO system with monochloramine dosage was constant over a one year period (data of last 130 days presented), demonstrating that no membrane damage occurred. From this study, it can be concluded that monochloramine dosage in wastewater applications is effective in controlling biofouling in RO systems and maintaining a monochloramine residual during water transport provides biologically stable water.
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•Impact of monochloramine dosage on biological stability and biofouling.•Stable microbial water quality in the presence of monochloramine.•Increase in microbial activity after monochloramine removal.•Monochloramine dosage did not impact salt passage.•Biofouling was restricted by residual monochloramine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Electroanatomic mapping systems have become an essential tool to guide the identification and ablation of arrhythmic substrate. Recently, a novel guiding system for electrophysiology procedures was ...introduced that uses dielectric sensing to perform high resolution anatomical imaging. Dielectric imaging systems use electrical fields to differentiate anatomic structures based on their conductivity and permittivity. This technique enables non‐fluoroscopic, noncontact mapping of anatomic structures, assessment of pulmonary vein occlusion state during cryoballoon ablation, and has the potential to assess for additional tissue characterization including tissue thickness and tissue type. This article elaborates on the functioning and potential of dielectric imaging systems and provides two cases to illustrate the clinical impact for electrophysiology procedures.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Purpose
Treatment schedules for antithrombotic therapy are complex, and there is a risk of inappropriate prescribing or continuation of antithrombotic therapy beyond the intended period of time. The ...primary aim of this study was to determine the frequency of unintentional guideline deviations in hospitalized patients. Secondary aims were to determine whether the frequency of unintentional guideline deviations decreased after intervention by a pharmacist, to determine the acceptance rate of the interventions and to determine the type of interventions.
Methods
We performed a non-controlled prospective intervention study in three teaching hospitals in the Netherlands. We examined whether hospitalized patients who used the combination of an anticoagulant plus at least one other antithrombotic agent had an unintentional guideline deviation. In these cases, the hospital pharmacist contacted the physician to assess whether this deviation was intentional. If the deviation was unintentional, a recommendation was provided how to adjust the antithrombotic regimen according to guideline recommendations.
Results
Of the 988 included patients, 407 patients had an unintentional guideline deviation (41.2%). After intervention, this was reduced to 22 patients (2.2%) (p < 0.001). The acceptance rate of the interventions was 96.6%. The most frequently performed interventions were discontinuation of an low molecular weight heparin in combination with a direct oral anticoagulant and discontinuation of an antiplatelet agent when there was no indication for the combination of an antiplatelet agent and an anticoagulant.
Conclusion
A significant number of hospitalized patients who used an anticoagulant plus one other antithrombotic agent had an unintentional guideline deviation. Intervention by a pharmacist decreased unintentional guideline deviations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
BackgroundLiterature suggests that patients who display disruptive behaviours in the consulting room fuel negative emotions in doctors. These emotions, in turn, are said to cause diagnostic errors. ...Evidence substantiating this claim is however lacking. The purpose of the present experiment was to study the effect of such difficult patients’ behaviours on doctors’ diagnostic performance.MethodsWe created six vignettes in which patients were depicted as difficult (displaying distressing behaviours) or neutral. Three clinical cases were deemed to be diagnostically simple and three deemed diagnostically complex. Sixty-three family practice residents were asked to evaluate the vignettes and make the patient's diagnosis quickly and then through deliberate reflection. In addition, amount of time needed to arrive at a diagnosis was measured. Finally, the participants rated the patient's likability.ResultsMean diagnostic accuracy scores (range 0–1) were significantly lower for difficult than for neutral patients (0.54 vs 0.64; p=0.017). Overall diagnostic accuracy was higher for simple than for complex cases. Deliberate reflection upon the case improved initial diagnostic, regardless of case complexity and of patient behaviours (0.60 vs 0.68, p=0.002). Amount of time needed to diagnose the case was similar regardless of the patient's behaviour. Finally, average likability ratings were lower for difficult than for neutral-patient cases.ConclusionsDisruptive behaviours displayed by patients seem to induce doctors to make diagnostic errors. Interestingly, the confrontation with difficult patients does however not cause the doctor to spend less time on such case. Time can therefore not be considered an intermediary between the way the patient is perceived, his or her likability and diagnostic performance.
•DLL3 is expressed in 74% of stage IV LCNEC patients•The majority (80%) has cytoplasmic/membranous expression•DLL3 is expressed in both SCLC- and NSCLC-like LCNEC subtype•6/6 STK11mt, 10/11 KEAP1mt ...and 9/9 TP53wt tumors were DLL3 positive•DLL3 expression is associated with expression of ASCL1 and neuroendocrine markers
For stage IV pulmonary large cell neuroendocrine carcinoma (LCNEC), the only therapeutic option is palliative chemotherapy. DLL3 is a new therapeutic target, which seems to be often expressed in SCLC and LCNEC. It has recently been reported that DLL3 mRNA expression is particularly upregulated in the LCNEC subgroup with STK11/KEAP1 and TP53 co-mutations, in contrast to lower expression levels in RB1 and TP53 co-mutated LCNEC. Our aim was to investigate DLL3 protein expression in stage IV LCNEC and correlate data with mutational profiles (i.e.STK11/KEAP1/RB1), immunostaining results (pRb, NE markers) and clinical characteristics.
Immunohistochemical analysis for DLL3 (SC16.65) and ASCL1 (SC72.201) was performed on 94 and 51 FFPE tissue sections, respectively, of pathologically reviewed stage IV LCNEC. DLL3 and ASCL1 were scored positive if ≥1% of the tumor cells showed cytoplasmic/membranous or dotlike (DLL3) or nuclear (ASCL1) immunostaining. Data were correlated with available sequencing (TP53, RB1, STK11, KEAP1), immunostaining (pRb, NE markers) and clinical data.
DLL3 was expressed in 70/94 (74%) LCNEC, 56 (80%) of which showed cytoplasmic/membranous staining. Median H-score was 55 (interquartile range 0–160). DLL3 staining was not different in pRb immunohistochemistry negative and positive patients (DLL3+ in 53/70 (76%) vs. 14/21 (67%), p = 0.409) or RB1 mutated and wildtype patients (DLL3+ in 27/34 (79%) vs. 23/33 (70%), p = 0.361). Nevertheless, 6/6 (100%) STK11 mutated, 10/11 (91%) KEAP1 mutated and 9/9 (100%) TP53 wildtype tumors were DLL3+ . Furthermore, DLL3 expression was associated with expression of ASCL1 and at least 2 out of 3 neuroendocrine markers.
The high percentage (74%) of DLL3 expression in stage IV LCNEC denotes the potential of DLL3 targeted therapy in this patient group.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. Community-acquired pneumonia (CAP) remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard ...microbiological methods and, therefore, may improve the accuracy of microbiological diagnosis for patients with CAP. Methods. Conventional detection techniques and multiplex real-time PCR for atypical bacteria and respiratory viruses were performed on samples collected from 105 adults enrolled in a prospective study. An infiltrate was visible on each patient's chest radiograph, and a pneumonia severity index score was determined for each patient. Results. Microbiological diagnoses were determined for 52 (49.5%) of 105 patients by conventional techniques and for 80 (76%) of 105 patients by real-time PCR. The time to obtain the result of real-time PCR could be reduced to 6 h. PCR methodology was significantly more sensitive for the detection of atypical pathogens and viruses (P ⩽ .001). Respiratory viral infections and mixed infections were detected in 15 (14.2%) and 3 (2.8%) of 105 patients, respectively, by conventional methods, but were detected in 59 (56.2%) and 28 (26.5%) of 105, respectively, by real-time PCR. Presence of a mixed infection was significantly associated with severe pneumonia (P = .002). Human rhinoviruses and coronaviruses, OC43 and 229E, were frequently identified pathogens. Conclusions. The combined real-time PCR assay is more sensitive for diagnosis of the main viruses and atypical bacteria that cause CAP compared with conventional methods, and obtains results in a clinically relevant time period.
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