Periodontal disease and its association to endothelial dysfunction and clinical changes in limited systemic sclerosis: A case-control study.

OBJECTIVES: Periodontal disease occurs frequently in patients with limited cutaneous systemic sclerosis (lcSSc) while data about underlying pathways contributing to periodontal changes are scarce. The aim of this study was to evaluate periodontal disease and to investigate its association with endothelial dysfunction and clinical changes in patients with lcSSc. METHODS: In 38 lcSSc patients and 38 controls, periodontal status was evaluated by disease-specific questionnaire, dental examination including bleeding on probing (BOP), pocket depth, and plaque index, and dental panoramic radiograph. Periodontopathogen bacteria were collected subgingivally using paper points and interleukin-1 (IL-1) gene polymorphisms were evaluated using buccal swabs. Endothelial dysfunction was measured by flow-mediated dilatation, pulse-wave velocity and biochemical analysis, including arginine metabolites and endothelial microparticles. Additionally, lcSSc-specific clinical changes and parameters were recorded. RESULTS: Periodontitis was present in 31 patients with lcSSc (81.6%) and in 27 controls (71.1%) (p = .280). LcSSc patients had a lower teeth number (p = .039) and Eikenella corrodens was to a higher degree detectable in patients with lcSSc (p = .041) while the remaining periodontal parameters revealed no differences between both cohorts. Significant correlations between parameters of arterial stiffness, EUSTAR index, number of teeth and BOP were observed (all p < .05). Detection of Prevotella intermedia was associated with selected IL-1 gene polymorphisms (p = .032) and Porphyromonas gingivalis was associated with severe periodontitis (p = .041). CONCLUSION: Periodontal disease may occur frequently in patients with lcSSc and may be associated with arterial stiffness and with SSc activity.

Evaluation of endothelial dysfunction and clinical events in patients with early-stage vasculopathy in limited systemic sclerosis.

OBJECTIVES: Limited cutaneous systemic sclerosis (lcSSc) is characterised by vasculopathy contributing to vascular apoptosis, structural and functional changes. The aim of this study was to investigate parameters of endothelial dysfunction and their association to clinical events in lcSSc patients with early-stage vasculopathy. METHODS: Patients with lcSSc and early-stage vasculopathy defined as absent pre-existing pulmonary arterial hypertension (PAH), digital ulcers, and symptomatic cardiovascular diseases were recruited together with age-, race- and sex-matched controls with primary Raynaud's phenomenon. All subjects underwent measurements of flow-mediated (FMD) and nitroglycerine-mediated dilation (NMD), pulse-wave analysis, and biochemical analysis, including arginine, homoarginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and endothelial microparticles (EMP). Clinical events, including EUSTAR index, sicca symptoms, microvascular, skin, renal, gastrointestinal, and pulmonary involvement, were recorded by medical history, physical examination, laboratory parameters, disease-specific questionnaire, electrocardiogram, diagnostic imaging and spirometry. RESULTS: 38 patients with lcSSc and 38 controls were included after screening for eligibility. There was no difference in FMD (p=0.775), NMD (p=0.303), aortic pulse-wave velocity (p=0.662) or in augmentation index (p=0.600) between patients with lcSSc and controls. Higher values of ADMA (p=0.030), SDMA (p=0.025) and borderline significantly higher values for CD31+/CD42b- EMP (p=0.062) were observed in lcSSc patients, also with positive correlations between those parameters. ADMA, SDMA and CD31+/CD42b- were correlated with subclinical PAH, nephropathy and capillary changes. CONCLUSIONS: Selected parameters of endothelial dysfunction contribute to clinical events in lcSSc patients with early-stage vasculopathy and endothelial dysfunction seems to be primarily present in microvasculature, while its impact on macrovascular changes in lcSSc is still indistinct.

Successful Two-Stage Exchange Arthroplasty for Periprosthetic Infection Following Total Knee Arthroplasty: The Impact of Timing on Eradication of Infection.

Background: Periprosthetic joint infection (PJI) represents a serious complication following total knee arthroplasty. In the setting of chronic infections, the two-staged approach has traditionally been the preferred treatment method. The aim of this study was to determine the optimal period of rest between the first and second stage. Furthermore, we analyzed potentially outcome-relevant parameters, such as general and local conditions and the presence of difficult-to-treat or unidentified microorganisms, with regard to their impact on successful treatment of PJI. Patients and Methods: We performed a retrospective analysis of prospectively collected data for all patients treated for PJI at our institution. Seventy-seven patients who had undergone two-stage revision arthroplasty for PJI of the knee were included into the study. Antibiotic-loaded cement spacers were used for all patients. Results: After a median follow-up time of 24.5 months, infection had reoccurred in 14 (18.7%) patients. A prolonged spacer-retention period of more than 83 days was related to a significantly higher proportion of reinfections. Furthermore, significant compromising local conditions of the prosthetic tissue and surrounding skin, as well as repeated spacer-exchanges between first- and second-stage surgery, negatively influenced the outcome. Neither the patients' age nor gender exerted a significant influence on the outcome regarding reinfection rates for patients' age or gender. Conclusions: We observed the best outcome regarding infection control in patients who had undergone second-stage surgery within 12 weeks after first-stage surgery. Nearly 90% of these patients stayed free from infection until the final follow-up. An increased number of performed spacer-exchanges and a bad local extremity grade also had a negative impact on the outcome.

Extracts of different pollen species and their effect on human tear fluid and an epithelial cell line.

PURPOSE: Hazelnut and birch pollen are known to destroy tear film components and attack ocular surface cells. We investigated further pollen species from different plant families, whether they show similar effects on human tear fluid and an epithelial cell line in vitro, to provide a broad basis for further research on pollen reactions affecting the tear film and ocular surface. MATERIALS AND METHODS: Regional pollen species from different plant families (Adoxaceae, Betulaceae, Fagaceae, Juglandaceae, Malvaceae, Oleaceae, Pinaceae, Plantaginaceae, Poaceae, Salicaceae, Sapindaceae) were collected. Their proteolytic activity was evaluated by Zymography. Human tear fluid and cells of an epithelial cell line were incubated with pollen extracts. Tear fluid was analyzed by Polyacrylamide gel electrophoresis (PAGE). Cytomorphology was assessed microscopically and cell viability by proliferation (MTS), water-soluble tetrazolium (WST-1) assay and the impedance-based xCELLigence real-time analysis (RTCA). RESULTS: Zymography revealed significant protease activity and PAGE showed the degradation of tear proteins by different pollen species. Cells incubated with pollen extracts presented dose- and time-dependent cytomorphological changes. MTS, WST-1, and RTCA revealed cytostatic as well as cytotoxic effects of pollen extracts. CONCLUSIONS: Pollen species from different plant families exert proteolytic activity and degrade human tear fluid as well as epithelial cells, which may play a crucial role in the pathogenesis of allergic and non-allergic reactions affecting the ocular surface.

Superficial Vancomycin Coating of Bone Cement in Orthopedic Revision Surgery: A Safe Technique to Enhance Local Antibiotic Concentrations.

BACKGROUND: The use of antibiotic-loaded cement has become a well-accepted method to develop high local antibiotic concentrations in revision surgery of infected arthroplasty. A new surgical technique has been established to further increase the local antibiotic concentration and thereby minimizes the risk of reinfection. Our study aim was to investigate the safety of additional superficial vancomycin coating (SVC) by analyzing postoperative joint and serum vancomycin concentrations, as well as the creatinine levels of patients with orthopedic revision surgery. METHODS: A longitudinal case series was performed by reviewing collected data of patients who were treated by SVC during revision surgery (1- or 2-stage exchange) because of prosthetic joint infections. Vancomycin levels were obtained, local from drains and systemic from blood samples, on postoperative days 1 to 5. Furthermore, preoperative and postoperative serum creatinine levels were analyzed. RESULTS: Highest median local vancomycin levels were documented on postoperative day 1 with 546.8 µg/mL (range, 44.4-1485 µg/mL) in the reimplantation group and 408.7 µg/mL (range, 24.7-1650 µg/mL) in the spacer group. Median serum vancomycin level was 4.4 µg/mL (range, <2.0-11.7 µg/mL) on the first postoperative day in the reimplantation group and <2.0 µg/mL (range, <2.0-3.9 µg/mL) in the spacer group, and lower than 2.0 µg/mL (range, <2.0-7.5 µg/mL) from postoperative day 2 to 5 in both groups. Neither an anaphylactic reaction nor other side effects to SVC were observed. CONCLUSION: Our data showed that SVC of bone cement is an effective technique to enhance local concentrations of vancomycin without leading to systemic side effects.

A retrospective study of isolated fractures of the alveolar process in the permanent dentition.

BACKGROUND/AIM: There is a lack of studies of fractures of the alveolar process (FAP). Only five were published in the last 50 years. The aim of this study was to analyze the risk of pulp necrosis and infection (PN), pulp canal obliteration (PCO), infection-related root resorption (IRR), ankylosis-related resorption (ARR), marginal bone loss (MBL), and tooth loss (TL) as well as to identify the possible risk factors for teeth involved in an isolated alveolar process fracture. In the second part, any late complications of the involved teeth were reported in patients who responded to a follow-up examination. MATERIAL AND METHOD: This study was a retrospective analysis of 126 patients with 329 traumatized permanent teeth treated in a regional dental trauma clinic. Follow-up examination was performed on 31 (24.6%) patients with 75 (22.8%) teeth. The risks of PN, PCO, RR, MBL, and TL were analyzed using the Kaplan-Meier method. Possible risk factors for PN (stage of root development, fracture position in relation to the root apex, concomitant injury, treatment delay, and antibiotics) were analyzed using univariate and multivariate Cox regression and generalized estimating equation. The level of significance was 5%. RESULTS: Pulp necrosis was observed in 43% of the teeth, and it was significantly associated with the presence of a concomitant injury and complete root formation. PCO was recorded in 2.8%, root resorption (RR, IRR, and ARR) in 4%, MBL in 8%, and TL in 0.6% of the teeth. Thirty-four percent of the teeth were assumed to have normal pulps, but they did not respond to pulp sensibility testing. At the follow-up examination, PN was found in 49%, PCO in 28%, RR (IRR and ARR) in 4%, MBL in 17%, and TL in 5%. Estimated risk after a 5-years follow up was as follows: PN: 48.2% (95% confidence interval (CI): 42.0-54.5), IRR: 7.2 (95% CI: 3.5-10.9), ARR: 33.0% (95% CI: 22.4-43.6), BL: 16.7% (95% CI: 9.6-23.8), TL: 4.0% (95% CI: 0.0-8.5). The following factors significantly increased the risk of PN: mature root development (hazard ratio [HR]: 7.50 [95% CI: 1.84-30.64], P=.005) and concomitant injury (HR: 2.68 [95% CI: 1.76-4.09], P<.001). In a logistic regression model, teeth with mature roots had a threefold risk of becoming non-responsive to pulp testing. CONCLUSION: Teeth involved in an isolated alveolar process fracture and managed with a conservative treatment approach appear to have a good prognosis. The most common complication was PN which did not negatively affect the survival of the teeth after root canal treatment.

Higher psychological and psychovegetative strain in adolescents with atypical pigment naevi.

An observational, exploratory, cross-sectional study was performed to assess whether the presence of atypical naevi (AN) in adolescents is associated with psychological and psychovegetative stress parameters. Fifty-one students of a secondary school in Graz, Austria, completed a defined test procedure consisting of an initial period of rest, a standardised mental stress task, another period rest and a questionnaire, the change-sensitive symptom list (ASS-SYM). Electrocardiogram and blood pressure were recorded continuously. The study population was divided in two groups: probands without AN (NAN, n = 33), and probands with at least one AN (n = 18). We found higher values for the AN group in all scales of ASS-SYM, reaching statistical significance in the dimensions "nervousness and mental tension" (p = 0.025), "psychophysiological dysregulation" (p = 0.020), burden of pain" (p = 0.023) and "general symptoms and problems" (p = 0.031). Regarding physiological parameters, the AN group showed higher vegetative strain reflected in heart rate and heart rate varibility during the periods of rest as well as a reduced baroreceptor sensitivity. On the basis of our results, the presence of AN in adolescents seems to be associated with a higher vegetative arousal. Additionally, participants with AN complained significantly more often about stress-associated general psychological symptoms and problems.

Two-stage revision of prosthetic hip joint infections using antibiotic-loaded cement spacers: When is the best time to perform the second stage?

AIM: Managing periprosthetic joint infections remains a challenging task, and adequate treatment strategies seem to be mandatory to avoid irreversible damage of the affected joint and/or systemic complications. Two-stage revision arthroplasty includes removing all implants and subsequent implantation of an antibiotic-loaded cement spacer, followed by revision arthroplasty as the second stage. Although this procedure is well described in the literature, results remain unpredictable due to various clinical findings and the absence of prospective randomised trials. We analysed (1) mortality and (2) reinfection rates in a series of patients who underwent two-stage revision surgery for periprosthetic hip joint infections with antibiotic-augmented joint spacers. We maintained a special focus on the spacer retention period and its influence on outcome in order to determine the best time for second-stage surgery. PATIENTS AND METHODS: A consecutive series of 76 patients with native and periprosthetic hip joint infections and who underwent two-stage revision surgery with antibiotic-loaded cement spacers were studied between 2005 and 2010. The second-stage operation was performed when it was assumed that infection was eradicated. The further operative procedure depended upon intra-operative findings (frozen section, local status). RESULTS: Mean implant-free period with the antibiotic-loaded spacer in situ was 12.6 weeks. Spacer re-implantation was necessary in 13 cases due to positive signs of acute infection in the frozen section and suspect intra-operative findings. Eight patients were not operated for a second time in the investigated time period due to poor general condition. In 40 patients, the spacer retention period was four to 11 weeks: 11 weeks for 23. We observed a significantly higher proportion of women free from reinfection in the four to 11-week group than in patients with the shorter or longer period. CONCLUSION: According to our findings, the optimal timing for second-stage surgery as a second-stage procedure is between four and 11 weeks. A significantly optimal reinfection rate was seen in patients undergoing revision arthroplasty within that time frame, and 90% of those patients remained infection free until final follow-up.

Short-term intravenous fish-oil emulsions in pediatric oncologic patients--effect on liver parameters.

Pediatric oncologic patients often need parenteral nutrition (PN) during chemotherapy. Long-term use of soybean-based lipid emulsions is associated with progressive liver disease and cholestasis, whereas fish-oil based emulsions have anticholestatic effects. We studied the potentially hepato-protective effects of short-term use of SMOF lipids in children undergoing chemotherapy. Fifteen pediatric oncologic patients treated with SMOF lipids were retrospectively analyzed in respect to bilirubin and liver parameters and compared to matched-controls who had received soybean-based fat emulsions. For statistics the time-points baseline, Day 14 of PN (PN14), and post (Day+7) were chosen. None of the study patients developed cholestasis. Within the SMOF-lipid group there were no differences in the laboratory parameters between baseline, PN14, and post. In the control group, gamma glutamyltransferase (γGT) levels increased during PN (baseline vs. PN14, 26.43 vs. 63.00 U/l, P < 0.05). Lactate dehydrogenase (LDH) levels showed a significantly different behavior in the 2 groups: In the SMOF lipids group, LDH decreased whereas it increased in the controls (-32.75 U/l vs. + 29.57 U/l, P < 0.05). An advantage of fish oil-based fat emulsions can be shown even after short-term PN. In children undergoing chemotherapy the use of soybean-based fat emulsions but not SMOF lipids led to increased γGT levels.

Prosthetic joint infection following total hip replacement: results of one-stage versus two-stage exchange.

PURPOSE: Prosthetic hip joint infection remains a challenging socio-economic problem. Curative treatment is usually a one- or two-stage revision surgery, but neither of these options has yet emerged as the treatment of choice. The aim of this study was to evaluate which of these methods produced superior outcomes. METHODS: A retrospective study was performed including 92 patients with deep infections after implantation of primary total hip arthroplasty (THA) who had undergone either one-stage or two-stage revision surgery at a single centre. Infections were classified according to McPherson and we evaluated the rate of persisting infection or reinfection after surgical intervention. RESULTS: The two-stage revision surgery revealed superior outcomes for the analysed infection categories compared to the one-stage procedure except for the least serious category of infections (i.e. McPherson Stage I/A/1, early postoperative infection, no systemic comorbidities, local status uncompromised). Eradication of prosthetic infection was achieved in 94.5 % (n = 52) within the group of two-stage exchange, and 56.8 % (n = 21) of patients treated with a one-stage procedure. Outcome of patients following a one-stage or a two-stage exchange was overall significantly different with p < 0.001. Further deviations between the described two procedures were noted in the subgroups following the classification described by McPherson. CONCLUSIONS: Our results indicate superiority of two-stage revision surgery in case of serious infections. The authors believe that decisions on the surgical approach for the treatment of deep prosthesis infections should be made on the basis of standardized staging systems.

Application frequency - key indicator for the efficiency of severe dry eye disease treatment - evidence for the importance of molecular weight of hyaluronan in lubricating agents.

PURPOSE: Lubricant eye drops are the main therapeutic resource for dry eye disease (DED), with each drop representing the equivalent of ocular surface disease treatment. Thus, any reduction in the frequency of eye drop application reflects a degree of therapeutic success. Considering also the socioeconomic burden of DED, we investigated eye drop application frequency (DF) as a parameter to potentially track the success of therapy in severe DED. Hyaluronan (HA)-containing eye drops have become the first choice for tear substitution in many countries, and recent data indicate that the average molecular weight (Mw) of HA determines the therapeutic efficacy of such eye drops. This post-hoc subgroup analysis of a previously published multicentre prospective randomized open-label study, HYLAN M, is set out to compare the effects of very high Mw HA (hylan A) eye drops to comparator eye drops, containing lower Mw HA (control). METHODS: Patients with severe DED (n = 47), recruited as part of the larger HYLAN M prospective, multicentre, open-label study, were randomized into two groups: hylan A and control group. In the hylan A group, 24 patients replaced their HA-containing eye drops with eye drops containing 0.15% hylan A, whereas the 23 control patients continued to use comparator HA eye drops. The DF was recorded daily by all participants over 8 weeks, and other subjective and objective parameters of DED were assessed at the time of inclusion (baseline), as well as at week 4 and 8. RESULTS: There was a significant decrease in DF in the hylan A users between the baseline and week 4 (p = 0.004), remaining stable until week 8. Indeed, in contrast to the baseline, the hylan A group had a significantly lower DF than the control group at weeks 4 (p = 0.018) and 8 (p = 0.008). Likewise, the ocular surface disease index (OSDI) improved significantly between the time of inclusion and week 4 (p < 0.001) in hylan A users, remaining stable until week 8. The OSDI was similar in both groups at the baseline but it was significantly lower in the hylan A group than in the control group at week 4 (p = 0.002), remaining lower at week 8. Such a decrease in the DF and OSDI was not witnessed in the control group at any time point. The objective parameters assessed did not differ significantly within or between the two groups. CONCLUSION: When treating severe DED, the DF can be significantly reduced by using very high Mw HA (3 MDa) lubricant eye drops, which better alleviate DED symptoms and decrease the OSDI scores. These drops not only provide an attractive and comfortable alternative for patients with severe DED but also offer the possibility of reducing the disease's socioeconomic burden, both for affected individuals and society as a whole.

The systemic impact of different COVID-19 vaccines in 2-[18F] FDG-PET/CT.

Austria started its COVID-19-vaccination program in December 2020 with three different vaccines. As the vaccination program continues, we encountered increased 2-[18F] FDG-activity not only in axillary lymph nodes ipsilateral to the injection site but also in other organs. The aim of this retrospective study is to present results of the metabolic activity of ipsilateral axillary lymph nodes, liver, blood pool, spleen, and bone marrow after three different vaccines. To our knowledge, this is the first study to examine systemic response changes in relation to time after COVID-19 vaccination using three different vaccines. The collected data of 220 eligible vaccinated patients (127 with BioNTech/Pfizer BNT162b2, 61 with Moderna, and 32 with AstraZeneca) examined with 2-[18F] FDG-PET/CT were enrolled. The PET/CT examinations were evaluated from day 1 to day 135 (SD: 23.2, median: 26) after different vaccinations. Seventy-one out of these 220 patients underwent a pre-vaccination 2-[18F] FDG -PET/CT. SUVmax of axillary node(s), and blood pool, liver, spleen, and bone marrow as reference organs were calculated. The ratio of SUVmax activity of axillary lymph node to reference organs was also compared in all patients. The tracer activity dynamics were investigated in three different vaccines. After BioNTech/Pfizer vaccination 2-[18F] FDG activity in axillary lymph nodes shows a steady decrease in all patients. Ten days after vaccination the 2-[18F] FDG uptake was at its highest activity. Seventy days after vaccination, tracer activity is not different from the background activity of 2-[18F] FDG in the axillary region. This result also applies to other two vaccines; however, in the 4th week after Moderna vaccination SUVmax in lymph nodes showed the highest peak of tracer activity. With AstraZeneca the highest activity was at the earlier days. There was no significant statistical difference of SUVmax of lymph nodes or its ratios to other reference organs between three groups of vaccines. SUVmax in lymph nodes was statistically significant lower than SUVmax in the liver, spleen, and bone marrow with p-values of < 0.001, 0.044, and 0.001, respectively. In the group of 71 patients with a pre-vaccination PET/CT examination, the median SUVmax of lymph nodes increased significantly after vaccination from 0.82 (IQR 0.59-1.38) to 1.80 (IQR 1.07-3.89)(p < 0.001). In contrast median tracer activity in the liver decreased from 3.37 (IQR 2.83-3.91) to 3.11 (2.56-3.70) (p = 0.032). There was no significant change of tracer activity after vaccination in other reference regions (mediastinum, spleen, and bone marrow). In this group of 71 patients, there was also no significant difference in tracer activity in different types of vaccines. Local site and ipsilateral axillary lymph node activity in 2-[18F] FDG PET/CT after COVID19-vaccination is suggested in many studies. The main challenge is recognizing the changes in lymph nodes during time after vaccination to minimize false interpretation, foremost in patients with oncological diagnoses. Moreover, different vaccines cause different system metabolic changes. The knowledge of vaccine type, the time interval between vaccination and PET/CT scan is essential, especially in therapy evaluation.

Pilot study on the acceptance of mobile teledermatology for the home monitoring of high-need patients with psoriasis.

BACKGROUND/OBJECTIVES: The willingness to be educated is one of the highest desires among patients with psoriasis. Therefore, a collaborative model of management would appear to be essential in enhancing patient satisfaction in this challenging condition. The present study aimed at examining the applicability of a mobile teledermatology service in this regard and assessing the association between patient acceptance and perceived health-related quality of life. METHODS: High-need patients with psoriasis performed visits over 12 weeks transmitting clinical images together with some relevant clinical information via mobile phones to teledermatologists, who provided treatment instructions. Ten patients and two teledermatologists completed 20-item patient (weeks 6 and 12) and 10-item physician (at week 12) acceptance questionnaires. In addition, patients answered the dermatology life quality index (DLQI) at weeks 0, 6 and 12. RESULTS: Both patients and teledermatologists were pleased with the service with high acceptance rates (patients: 81.0% at week 6 and 82.9% at week 12; teledermatologists: 74.0%). In addition, 80% of the patients considered the service an alternative to in-person consultation and 90% felt they were in good hands but had achieved a more flexible and empowered lifestyle. No significant correlations were found between patient acceptance and DLQI. Both teledermatologists found the service a convenient and reliable tool for patient monitoring. Neither patients nor teledermatologists thought further in-person consultations necessary. CONCLUSION: Mobile teledermatology is a valuable tool for the home monitoring of patients with psoriasis that makes a meaningful difference in their lives. It is well accepted by both patients and the physicians involved.

Design and development of a mobile computer application to reengineer workflows in the hospital and the methodology to evaluate its effectiveness.

This paper describes a new method of collecting additional data for the purpose of skin cancer research from the patients in the hospital using the system Mobile Computing in Medicine Graz (MoCoMed-Graz). This system departs from the traditional paper-based questionnaire data collection methods and implements a new composition of evaluation methods to demonstrate its effectiveness. The patients fill out a questionnaire on a Tablet-PC (or iPad Device) and the resulting medical data is integrated into the electronic patient record for display when the patient enters the doctor's examination room. Since the data is now part of the electronic patient record, the doctor can discuss the data together with the patient making corrections or completions where necessary, thus enhancing data quality and patient empowerment. A further advantage is that all questionnaires are in the system at the end of the day - and manual entry is no longer necessary - consequently raising data completeness. The front end was developed using a User Centered Design Process for touch tablet computers and transfers the data in XML to the SAP based enterprise hospital information system. The system was evaluated at the Graz University Hospital - where about 30 outpatients consult the pigmented lesion clinic each day - following Bronfenbrenner's three level perspective: The microlevel, the mesolevel and the macrolevel: On the microlevel, the questions answered by 194 outpatients, evaluated with the System Usability Scale (SUS) resulted in a median of 97.5 (min: 50, max: 100) which showed that it is easy to use. On the mesolevel, the time spent by medical doctors was measured before and after the implementation of the system; the medical task performance time of 20 doctors (age median 43 (min: 29; max: 50)) showed a reduction of 90%. On the macrolevel, a cost model was developed to show how much money can be saved by the hospital management. This showed that, for an average of 30 patients per day, on a 250 day basis per year in this single clinic, the hospital management can save up to 40,000 EUR per annum, proving that mobile computers can successfully contribute to workflow optimization.

Cholecalciferol supplementation to improve the hepatitis B vaccination response in hemodialysis patients: A first randomized open label pilot study (DeVitaHep).

BACKGROUND: Patients with advanced chronic kidney disease should be vaccinated against hepatitis B. In observational studies vitamin D insufficiency is associated with a reduced seroconversion rate. The effect of cholecalciferol supplementation on hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency is unknown. METHODS: In this randomized open label pilot study 40 unvaccinated haemodialysis patients with 25(OH)D insufficiency (<30 ng/mL) were enrolled. In the supplementation group, we administered cholecalciferol orally in a dose of 28,000 IU weekly for a maximum of 12 weeks. Hepatitis B vaccination (HBvaxPRO 40 µg i.m. months 0, 1, 6) was performed after achieving a 25(OH)D level >30 ng/mL or after completing three months of supplementation despite failure to achieve the target level. In the control group, patients were vaccinated immediately after randomization. Anti-hepatitis B-antibody titer (anti-HBs) was measured eight weeks after completing the vaccination course. RESULTS: Thirty-seven (26 male, 11 female) patients aged 65 (13.5) years underwent randomization with 17 patients allocated to the control group and 20 patients included in the supplementation group. After 12 weeks of cholecalciferol supplementation, mean (SD) 25(OH)D concentration increased from 15.0 (8.0) to 31.0 (7.1) ng/mL, but remained unchanged in the control group (14.0 (7.1) to 11.6 (7.5) mg/mL). Neither the number of patients with seroconversion (anti-HBs titer ≥ 10 IU/L; n = 6 (35.3%) vs n = 3 (27.3%), p = 0.704), nor the number of patients with seroprotection (anti-HBs titer >100 IU/L; n = 4 (23.5%) vs n = 2 (18.2%) differed between treatment groups. Cholecalciferol supplementation was safe without treatment-related adverse events. CONCLUSION: In this small pilot study, high-dose oral cholecalciferol supplementation did not improve the hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency. This clinical trial was registered within EudraCT (EudraCT number 2011-004621-26).

Peripheral blood stem cell mobilization with pegfilgrastim compared to filgrastim in children and young adults with malignancies.

BACKGROUND: Pegfilgrastim, the long acting agent of rh-GCSF, has been shown to be as effective as Filgrastim in children undergoing cytotoxic chemotherapy by reducing the duration of neutropenia. Recent studies in adults have also shown that Pegfilgrastim is effective to mobilize CD34+ stem cells, resulting in earlier peripheral stem cell collections (PSCC). The aim of the study was to compare the efficacy of Pegfilgrastim with Filgrastim for CD34+ stem cell mobilization in children. PROCEDURE: Three groups of patients were compared: Group 1: six patients with Ewing Sarcoma stimulated with Filgrastim; Group 2: five patients with Ewing Sarcoma, Ependymoma, and Neuroblastoma; Group 3: four patients with relapsed neoplasm. Patients of Group 2 and 3 were stimulated with Pegfilgrastim followed by peripheral stem cell collection. Two patients in Group 3 needed further cytokine stimulation with Filgrastim combined with stem cell factor, Ancestim. RESULTS: In Groups 1-3, a median of 4, 3, and 3 PSCC between day 12-24, 6-13, and 8-30 were performed, yielding a median of 14.2, 24.0, and 10.3 x 10(6) CD34+ stem cells/kg BW, respectively. CONCLUSIONS: Group 2 data show that stem cell mobilization with Pegfilgrastim in children when performed during primary or without previous long lasting chemotherapy seems to produce earlier CD34+ peaks and better CD34+ yields than in Group 1. CD34+ cell mobilization with Pegfilgrastim in Group 3-patients with previous long lasting chemotherapy was possible.

Concordance of tumor infiltrating lymphocytes, PD-L1 and p16 expression in small biopsies, resection and lymph node metastases of oropharyngeal squamous cell carcinoma.

OBJECTIVE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC), especially human papillomavirus (HPV)-associated, is increasing worldwide. Immunotherapy become available for patients with carcinomas in the head and neck region, however without ideal biomarker. Markers like PD-L1 vary in the clone of the antibody used, and the method of evaluation. Adequate and reliable immune cells characterization and evaluation is still not found. Furthermore, studies analyzing representativeness of different tissue samples are scarce. We analyzed small biopsy, lymph node (LN) metastasis and resected OPSCC, in regards of tumor infiltrating lymphocyte (TIL) density, PD-L1 and p16 expression. MATERIAL AND METHODS: Patients with OPSCC diagnosed from 2000 to 2016, with small biopsy, resection specimen and LN metastasis samples were selected. We analyzed TILs on hematoxylin-eosin stain, and PD-L1 and p16 expression in tumor cells. Concordance between different tumor locations was evaluated. RESULTS: 93 patients, with 65 small biopsies, 72 resection specimens, and 70 LN metastases were included. TILs, p16 and PD-L1 demonstrated very high concordance. Additionally, PD-L1 expression in the small biopsies was more representative of the PD-L1 expression in the resection specimens, than the LN samples. CONCLUSION: TILs density can be reliably assessed using hematoxylin-eosin stain with high concordance between the small biopsy, resection specimen and LN metastasis. Evaluation of concordance of p16 expression is very high, nevertheless some cases might be misdiagnosed on a small biopsy or lymph node metastasis. Evaluation of PD-L1 expression is very reliable on the biopsy specimen. Different PD-L1 clones and methods of evaluation still remain to be addressed.

Adult patients' wellbeing and disturbances during early recovery in the post anaesthesia care unit. A cross-sectional study.

OBJECTIVES: Assessment of patients' wellbeing in the post anaesthesia care unit and how much each disturbance influences it. Furthermore, assessment of the incidence of the correlated disturbances and whether there are gender-specific aspects. DESIGN/SETTING: Observational anonymised survey with a validated questionnaire in a university hospital in central Europe. MAIN OUTCOME MEASURES: Incidence rates of wellbeing and disturbances in the post anaesthesia care unit. RESULTS: The patients' most frequently reported early postsurgical disturbances (n = 349) were i) dry mouth (35.4%), ii) pain in the surgical area (12.7%) and iii) hunger (12.2%). Every other disturbance was below 10% (e.g. nausea). Subjective wellbeing was reported by 57.2% of our patients. There were weak correlations between wellbeing and physical discomfort, pain in the surgical area, sleepiness and nausea. The strongest correlation was with physical discomfort. Female patients showed more feelings of cold, nausea and headache. CONCLUSION: Even in hospitals repeatedly certified in pain management, a high percentage of patients still claim early postoperative discomfort. We see the necessity for an increased focus on this topic and the need for investigations regarding patients' perception. The most frequent claims were related to pain in the surgical area and a dry mouth.

Combination of different noninvasive measuring techniques: a new approach to increase accuracy of peripheral near infrared spectroscopy.

One of the problems of near-infrared-spectroscopy (NIRS) measurements is low reproducibility. The aim of the present study was to introduce quality criteria to increase reproducibility of peripheral NIRS measurements. In a prospective cohort study in 40 neonates, repeated NIRS measurements were performed on the calf. During five "reapplication" periods (of NIRS optodes), five "measurements" (venous occlusions) were performed. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO2), fractional oxygen extraction (FOE), hemoglobin flow (Hbflow), oxygen delivery (DO2), and oxygen consumption (VO2) were assessed. Measurements with linear changes during venous occlusions were included for further analysis (first quality criterion: R(2)>0.95). The second quality criterion was the equation 0 < or = TOI-SvO2 < or = (SaO2-SvO2)x0.2. Variance components and mean standard deviations were analyzed after introduction of the quality criteria. Variance components of reapplication and measurement decreased after introduction of the second quality criterion (TOI: 46.6-35.0%, SvO2: 76.8-38.2%, FOE: 73.1-37.5%, Hbflow: 70.3-51.9%, DO2: 71.5-52.7%, and VO2: 70.9-63.8%). Mean standard deviations of TOI (6.6+/-3.0 to 4.7+/-3.2%), SvO2 (11.1+/-4.8 to 5.7+/-3.9%), FOE (11.3+/-4.8 to 5.9+/-4.0%), Hbflow (4.3+/-2.0 to 2.9+/-1.6 micromol100 mLmin), and DO2 (17.8+/-7.6 to 11.4+/-6.2 micromol100 mLmin) decreased significantly, too. Only 12% of measurements fulfilled both quality criteria. With the introduction of two quality criteria, test-retest variability of peripheral NIRS measurements decreased significantly and reproducibility increased significantly.