Chronic nodular prurigo: clinical profile and burden. A European cross-sectional study.

BACKGROUND: Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behaviour and the presence of pruriginous nodules. A comprehensive understanding of this condition, especially regarding its clinical characteristics and impact on quality of life is still lacking. OBJECTIVES: Aim of this pan-European multicentre cross-sectional study was to establish the clinical profile of CNPG, including its associated burden. METHODS: Fifteen centres from 12 European countries recruited CNPG patients presenting at the centre or using the centres' own databases. Patients were asked to complete a questionnaire in paper or electronic format. Demography, current co-morbidities, underlying disease, itch intensity, additional sensory symptoms, quality of life, highest burden and emotional experience of itch were assessed. RESULTS: A total of 509 patients (210 male, median age: 64 years [52; 72]) were enrolled. Of these, 406 reported itch and CNPG lesions in the previous 7 days and qualified to complete the whole questionnaire. We recorded moderate to severe worst itch intensity scores in the previous 24 h. Scores were higher in patients with lower educational levels and those coming from Eastern or Southern Europe. Most patients experience itch often or always (71%) and report that their everyday life is negatively affected (53%). Itch intensity was considered to be the most burdensome aspect of the disease by 49% of the patients, followed by the visibility of skin lesions (21%) and bleeding of lesions (21%). The majority of patients was unaware of an underlying condition contributing to CNPG (64%), while psychiatric diseases were the conditions most often mentioned in association with CNPG (19%). CONCLUSIONS: This multicentre cross-sectional study shows that itch is the dominant symptom in CNPG and reveals that the profile of the disease is similar throughout Europe.

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy.

Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues. Renal toxicity has been described in several ICI but not with atezolizumab, an IgG1 monoclonal antibody targeting PD-L1 (programmed death ligand 1), approved by FDA as a second-line therapy for advanced urothelial carcinoma. Here we present a patient with a single kidney and metastatic renal cell carcinoma treated with atezolizumab and bevacizumab combination, with biopsy-proven acute interstitial nephritis, who had a complete resolution of renal dysfunction after steroid therapy.

Vibrant Soundbridge® in preschool children with unilateral aural atresia: acceptance and benefit.

The aim of this pilot study was to determine the acceptance and benefit from the middle ear implant system Vibrant Soundbridge® (VSB, MED-EL Corporation, Austria) by means of a questionnaire, compared to a previously used conventional bone conducting hearing device, in preschool children with unilateral congenital aural atresia. Prospective cohort study. All nine children with unilateral congenital aural atresia used the VSB and had previous experience with a bone conducting hearing device. The benefit from the VSB was evaluated by questionnaires concerning acceptance of hearing aids, handling, listening effort, behavior, quality of life, and the duration of daily use and compared to the experience with the bone conducting hearing device. In addition, to quantify the benefit from the VSB use, audiological assessment (pure-tone audiometry via free field testing, speech audiometry, and localization test) was performed with and without VSB. The questionnaires and audiological test results were compared pairwise. According to all questionnaire areas, children benefited significantly more from the VSB compared to bone conducting hearing device (ps <.05). The most important finding was a significant increase in daily use from 2 h for the bone conducting hearing device to 10 h for the VSB. Children performed significantly better with the VSB than without it in the audiological assessment. Children with unilateral aural atresia benefited significantly more from the VSB compared to a conventional bone conducting hearing device according to the parents' questionnaires and yielded better results in the audiometry and localization test with the VSB than without it.

Treatment and outcome of 2904 CML patients from the EUTOS population-based registry.

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Effects of early contrast-enhanced computed tomography on clinical course and complications in patients with acute pancreatitis.

PURPOSE: To investigate the effect of an early contrast-enhanced computed tomography (CECT) on clinical course and complications of acute pancreatitis (AP). MATERIAL AND METHODS: 58 patients with AP who had at least one CECT examination were analyzed retrospectively. Laboratory as well as clinical data, and results from the assessment of disease severity (CT severity index (CTSI) and its modified (MCTSI) version) were analyzed. The primary endpoint was the development of severe complications, defined as death, respiratory failure, acute renal failure, and the need for invasive interventions. Patients were divided into two groups: an early group (CECT within the first 48 h after the onset of symptoms, n = 32) and a late group (CECT > 48 h after the onset of symptoms, n = 26). Multivariate regression analysis was performed to identify risk factors for severe complications. RESULTS: There were no statistically significant differences between both groups concerning baseline characteristics, CTSI, and MCTSI. Complications occurred more often in the early CECT group (p = 0.008). Multivariate logistic regression analysis identified an early CECT and a severe MCTSI as independent risk factors for the occurrence of severe complications (p = 0.02 and p = 0.002, respectively). CONCLUSION: CECT performed within the first 48 h after the onset of symptoms is associated with an unfavorable outcome in AP.

Prognosis of long-term survival considering disease-specific death in patients with chronic myeloid leukemia.

In patients with chronic myeloid leukemia (CML), first-line imatinib treatment leads to 8-year overall survival (OS) probabilities above 80%. Many patients die of reasons unrelated to CML. This work tackled the reassessment of prognosis under particular consideration of the probabilities of dying of CML. Analyses were based on 2290 patients with chronic phase CML treated with imatinib in six clinical trials. 'Death due to CML' was defined by death after disease progression. At 8 years, OS was 89%. Of 208 deceased patients, 44% died of CML. Higher age, more peripheral blasts, bigger spleen and low platelet counts were significantly associated with increased probabilities of dying of CML and determined a new long-term survival score with three prognostic groups. Compared with the low-risk group, the patients of the intermediate- and the high-risk group had significantly higher probabilities of dying of CML. The score was successfully validated in an independent sample of 1120 patients. In both samples, the new score differentiated probabilities of dying of CML better than the Sokal, Euro and the European Treatment and Outcome Study (EUTOS) score. The new score identified 61% low-risk patients with excellent long-term outcome and 12% high-risk patients. The new score supports the prospective assessment of long-term antileukemic efficacy and risk-adapted treatment.

[Palsy of CVI caused by ecchordosis physaliphora]. / N.-VI-Parese durch Ecchordosis physaliphora.

We report a case of symptomatic ecchordosis physaliphora (EP) in a 34-year-old woman who presented with progressive diplopia due to palsy of the left sixth cranial nerve. Repeated magnetic resonance imaging (MRI) disclosed typical characteristics of a congenital EP lesion with compression of the left abducens nerve presumably because of a secondary herniation of the arachnoid mater. We performed an augmenting combined recess resect procedure on the left eye. No progression of the lesion was observed over a period of 5 years. For differential diagnostics an EP has to be distinguished from skull base tumors, such as chordoma and chondrosarcoma.

Pro-Active Fall-Risk Management is Mandatory to Sustain in Hospital-Fall Prevention in Older Patients--Validation of the LUCAS Fall-Risk Screening in 2,337 Patients.

OBJECTIVES: Prevention of in-hospital falls contributes to improvement of patient safety. However, the identification of high-risk patients remains a challenge despite knowledge of fall-risk factors. Hence, objective was to prospectively validate the performance of the LUCAS (Longitudinal Urban Cohort Ageing Study) fall-risk screening, based on routine data (fall history, mobility, mental status) and applied by nurses. DESIGN: Observational study comparing two groups of patients who underwent different fall-risk screenings; the LUCAS screening (2010 - 2011) and the STRATIFY (St. Thomas's Risk Assessment Tool In Falling Elderly Inpatients) (2004 - 2006). SETTING: Urban teaching hospital. PARTICIPANTS: Consecutively hospitalized patients (≥ 65 years old) were screened on admission; LUCAS n = 2,337, STRATIFY n = 4,735. MEASUREMENTS: The proportions of fallers were compared between the STRATIFY and the LUCAS time periods. The number of fallers expected was compared to that observed in the LUCAS time period. Standardized fall-incidence recording included case-note checks for unreported falls. Plausibility checks of fall-risk factors and logistic regression analysis for variable fall-risk factors were performed. RESULTS: The proportions of fallers during the two time periods were LUCAS n = 291/2,337 (12.5%) vs. STRATIFY n = 508/4,735 (10.7%). After adjustment for risk-factor prevalence, the proportion of fallers expected was 14.5% (334/2,337), the proportion observed was 12.5% (291/2,337) (p = 0.038). CONCLUSIONS: In-hospital fall prevention including systematic use of the LUCAS fall-risk screening reduced the proportion of fallers compared to that expected from the patients' fall-risk profile. Raw proportions of fallers are not suitable to evaluate fall prevention in hospital because of variable prevalence of patients' fall-risk factors over time. Continuous communication, education and training is needed to sustain in-hospital falls prevention.

Assessment of Aflatoxin and Fumonisin Contamination of Maize in Western Kenya.

We conducted a survey of aflatoxin and fumonisin in maize in western Kenya. In a regional survey of aflatoxin conducted in 2009 across three agroecological zones within three administrative regions, milled maize samples were collected from 985 patrons of 26 hammer mills. Aflatoxin contamination was detected in 49% of samples and was above the regulatory (10 ppb) in 15% of the samples overall; 65% of samples from a drought-prone area were over the limit. In a detailed survey in Bungoma County, we investigated aflatoxin and fumonisin contamination in four popular maize varieties at harvest and after 2 and 4 months of storage. We collected whole-grain samples from farmers' storage sheds and milled samples from patrons of local mills. Mean aflatoxin contamination was identical for storage sheds and mills at 2.3 ppb. In all, 41% of the samples from mills had detectable aflatoxin, with 4% over the regulatory limit, whereas 87% had detectable fumonisin, with 50% over the regulatory limit (1 ppm). Mean contamination levels did not change during storage. Maize varieties differed in fumonisin contamination, with the most popular varieties vulnerable to both mycotoxins and weevils, which are potential factors in exacerbating mycotoxin contamination. Mycotoxin surveillance is important not just in areas known previously for aflatoxin contamination and acute poisoning but also is needed in all maize-producing regions.

Reflectance confocal microscopy for monitoring the density of Demodex mites in patients with rosacea before and after treatment.

BACKGROUND: Demodex mites seem to serve as a pathogenic trigger in many Demodex-associated diseases such as rosacea. In facial skin of patients with rosacea significantly higher numbers of Demodex mites have been shown compared with healthy controls. Reflectance confocal microscopy (RCM) allows the detection and quantification of Demodex mites in vivo noninvasively. It is hypothesized that a reduction of Demodex mites under rosacea therapy can be monitored by RCM. OBJECTIVES: To use RCM to monitor the density of Demodex mites in patients with rosacea before and after treatment. METHODS: In 25 patients with facial rosacea RCM was performed before and after therapy. Mosaics of 5 × 5 mm(2) and 8 × 8 mm(2) were scanned, and the total numbers of mites per follicle and per area were counted, along with the number of follicles per area. RESULTS: In all patients Demodex folliculorum could be detected and quantified using RCM. RCM showed significant differences pre- and post-treatment (P = 0.0053 for 5 × 5 mm(2) and P < 0.001 for 8 × 8 mm(2)). The mean numbers of mites per follicle were 0.63 (range 0.16-2.28) per 8 × 8 mm(2) area and 0.70 (range 0.11-2.20) per 5 × 5 mm(2) area before treatment, and 0.41 (range 0.074-1.75) and 0.51 (range 0.094-1.70), respectively, after treatment. The corresponding mean numbers of mites were 155 (range 45-446) and 86.2 (range 12-286), respectively, before treatment and 96.2 (range 18-363) and 58.5 (range 12-230), respectively, after treatment. CONCLUSIONS: By RCM, a reduction in the density of Demodex mites in facial skin of patients with rosacea under therapy, correlating to clinical improvement, can be quantified and monitored noninvasively. Possible reasons for this therapeutic effect are discussed.

The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries.

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

Clinical management of chronic hepatitis B infection: results from a registry at a German tertiary referral center.

PURPOSE: We studied a cohort of adult patients with chronic hepatitis B (CHB) infection, followed at a tertiary referral liver center in Germany over 12.5 years to analyze the clinical features and impact of management on disease progression and survival of CHB patients in general and of those with CHB and HCC in particular. METHODS: We retrospectively evaluated the medical records of 242 adult (age ≥ 18 years) patients. CHB was defined as positive hepatitis B surface antigen (HBsAg) and/or HBV-DNA levels >10 IU/mL for at least 6 months. Patient demographics, HBV markers, antiviral treatment, laboratory parameters, liver imaging and histology were recorded for each visit. HCC patients were divided into two groups and separately analyzed (group 1: n = 24, HCC at first visit and group 2: n = 11, HCC during surveillance). RESULTS: The mean age was 44 years in CHB patients without HCC (63% male) and about 59 years in patients with HCC (77% male). Antiviral therapy was given to 59% of patients without HCC compared to only 25% in group 1 and 18% in group 2 with comparable median HBV DNA levels of approximately 36,000 IU/mL. There was no statistically significant difference concerning the HCC stages (Milan, UCSF, BCLC) at first diagnosis. Five-year survival was 19% in group 1 vs. 64% in group 2 (p = 0.019), with LTx performed in 12 vs. 45%, respectively. CONCLUSION: Surveillance of CHB patients did not result in early stage detection of HCC but in a higher likelihood to receive potentially curative treatments.

Factors affecting the formation of the radiation pre-peak at the operation of a Grimm-type source in pulsed DC mode.

The plasma emission pre-peaks of many atomic and ionic spectral lines of Cu and Ar were systematically investigated in a Grimm-type pulsed glow discharge (PGD). To register the pre-peaks with sufficient time resolution, a monochromator with photomultiplier detection was used. When the applied power exceeded a specific threshold, pre-peaks were found in all spectral lines investigated, and it was revealed that the electrical pre-peak was the cause of the atomic emission pre-peak. The form and intensity of the pre-peak radiation were, however, found to be different for different atomic emission lines. The excitation energy of the upper energy level of the atomic line transition, and factors related to recombination and self-absorption, were found to affect the emission pre-peak. Pre-peaks observed when using pulsed DC and pulsed radio-frequency power were compared. This investigation provides insight into best practice when selecting spectral lines most suitable for analytical spectrometry using PGD.

Extent and drivers of mycotoxin contamination: inferences from a survey of kenyan maize mills.

The prevalence of aflatoxin and fumonisin was investigated in maize intended for immediate human consumption in eastern Kenya at a time in 2010 when an aflatoxin outbreak was recognized. Samples were collected from people who brought their maize for processing at local commercial mills. Sites were selected using a geographical information system overlay of agroecological zones and Kenya's administrative districts. Interviews and collection of maize flour samples was conducted from 1,500 people who processed maize at 143 mills in 10 administrative districts. Mycotoxins were analyzed using enzyme-linked immunosorbent assays for aflatoxin and fumonisin, leading to detection at levels above the respective maximum tolerable limits in 39 and 37% of the samples, respectively. Samples with aflatoxin contamination above the legal limit ranged between 22 and 60% across the districts. A higher occurrence of aflatoxin was associated with smaller maize farms, lower grain yield, and monocropping systems, while a larger magnitude of the toxin was observed in the subhumid agroecological zone, in samples with more broken kernels, and, curiously, less maize ear damage at harvest. Analysis of paired grain samples (visually sorted and unsorted) showed that sorting reduced fumonisin by 65%, from above to below the legal limit of 1,000 ppb. Sorting did not, however, reduce aflatoxin levels. Although the aflatoxin problem is widely acknowledged, the high prevalence of fumonisin has not previously been reported. There is need for surveillance of the two mycotoxins and establishment of intervention strategies to reach vulnerable small-scale farmers.

The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib.

The introduction of tyrosine kinase inhibitors (TKI) in the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) has revolutionized the outcome, but the prognosis of the disease is still based on prognostic systems that were developed in the era of conventional chemotherapy and interferon (IFN)-alfa. A new prognostic score including only two variables, spleen size and basophils, was developed for the prediction of complete cytogenetic response (CCyR) and progression-free survival (PFS). The score was based on a large series of patients who were enrolled in prospective multicenter studies of first-line imatinib treatment. The prognostic value of the EUTOS (European Treatment and Outcome Study for CML) score has now been tested in an independent, multicenter, multinational series of 1288 patients who were treated first-line with imatinib outside prospective studies. It was found that also in these patients, the EUTOS prognostic score was predictive for CCyR, PFS and overall survival (OS). In addition, the prognostic value of the score was reported to be significant in seven of the eight other independent studies of almost 2000 patients that were performed in Europe, the Americas and Asia. The EUTOS risk score is a valid tool for the prediction of the therapeutic effects of TKI, particularly imatinib.

In-hospital fall-risk screening in 4,735 geriatric patients from the LUCAS project.

OBJECTIVES: In-hospital falls in older patients are frequent, but the identification of patients at risk of falling is challenging. Aim of this study was to improve the identification of high-risk patients. Therefore, a simplified screening-tool was developed, validated, and compared to the STRATIFY predictive accuracy. DESIGN: Retrospective analysis of 4,735 patients; evaluation of predictive accuracy of STRATIFY and its single risk factors, as well as age, gender and psychotropic medication; splitting the dataset into a learning and a validation sample for modelling fall-risk screening and independent, temporal validation. SETTING: Geriatric clinic at an academic teaching hospital in Hamburg, Germany. PARTICIPANTS: 4,735 hospitalised patients ≥65 years. MEASUREMENTS: Sensitivity, specificity, positive and negative predictive value, Odds Ratios, Youden-Index and the rates of falls and fallers were calculated. RESULTS: There were 10.7% fallers, and the fall rate was 7.9/1,000 hospital days. In the learning sample, mental alteration (OR 2.9), fall history (OR 2.1), and insecure mobility (Barthel-Index items 'transfer' + 'walking' score = 5, 10 or 15) (OR 2.3) had the most strongest association to falls. The LUCAS Fall-Risk Screening uses these risk factors, and patients with ≥2 risk factors contributed to the high-risk group (30.9%). In the validation sample, STRATIFY SENS was 56.8, SPEC 59.6, PPV 13.5 and NPV 92.6 vs. LUCAS Fall-Risk Screening was SENS 46.0, SPEC 71.1, PPV 14.9 and NPV 92.3. CONCLUSIONS: Both the STRATIFY and the LUCAS Fall-Risk Screening showed comparable results in defining a high-risk group. Impaired mobility and cognitive status were closely associated to falls. The results do underscore the importance of functional status as essential fall-risk factor in older hospitalised patients.

Noninvasive in vivo detection and quantification of Demodex mites by confocal laser scanning microscopy.

BACKGROUND: In many Demodex-associated skin diseases Demodex mites are present in abundance and seem to be at least partially pathogenic. So far all diagnostic approaches such as scraping or standardized superficial skin biopsy are (semi-)invasive and may cause discomfort to the patient. OBJECTIVES: To see whether confocal laser scanning microscopy (CLSM) - a noninvasive method for the visualization of superficial skin layers - is able to detect and quantify D. folliculorum in facial skin of patients with rosacea. METHODS: Twenty-five patients (34-72 years of age) with facial rosacea and 25 age- and sex-matched normal controls were examined by CLSM. Mosaics of 8 × 8 mm and 5 × 5 mm were created by scanning horizontal layers of lesional skin and quantification of mites per follicle and per area as well as follicles per area was performed. RESULTS: In all patients D. folliculorum could be detected by CLSM and presented as roundish or lengthy cone-shaped structures. CLSM allowed the quantification of Demodex mites and revealed significant differences (P < 0·0001): the mean number of mites was 165·4 per 8 × 8 mm area and 94·2 per 5 × 5 mm area in the patients compared with 34·7 and 22·4, respectively, in the controls. The corresponding mean number of mites per follicle was 0·7 and 0·8, respectively, in the patients and 0·1 and 0·2, respectively, in the controls. CONCLUSIONS: With the help of CLSM it is possible to detect, image and quantify Demodex mites noninvasively in facial skin of patients with rosacea.

Enhancements in specimen preparation of Cu(In,Ga)(S,Se)2 thin films.

When producing slices from Cu(In,Ga)(S,Se)(2) thin films for solar cells by use of a focused ion beam (FIB), agglomerates form on the Cu(In,Ga)(S,Se)(2) surfaces, which deteriorate substantially the imaging and analysis in scanning electron microscopy. Similar problems are also experienced when depth-profiling Cu(In,Ga)(S,Se)(2) thin films by means of glow-discharge or secondary ion mass spectrometry. The present work shows that the agglomerates are composed of (mainly) Cu, and that their formation may be impeded considerably by either cooling of the sample or by use of reactive gases during the ion-beam sputtering. The introduction of XeF(2) during FIB slicing resulted in excellent images, in which the microstructures of most layers in the Cu(In,Ga)(S,Se)(2) thin film stack are visible, including the microstructure of the 20 nm thin MoSe(2) layer. Acquisition of high-quality two-dimensional and also three-dimensional electron backscatter diffraction data was possible. The present work gives a basis for enhanced SEM imaging and analysis not only in the case of Cu(In,Ga)(S,Se)(2) thin films but also when dealing with further material systems exhibiting similar formations of agglomerates.