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.

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.

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).

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.

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.

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.

Demodex Mite Infestation and its Associations with Tear Film and Ocular Surface Parameters in Patients with Ocular Discomfort.

PURPOSE: The presence of Demodex species can be associated with blepharitis. Their pathogenic potential in meibomian gland dysfunction is discussed herein. The purpose of this study was to determine the prevalence of Demodex mites in eyelashes of Austrian patients with ocular discomfort and to evaluate associated changes of the lid margins and meibomian glands. DESIGN: This is a case-control study. METHODS: Two hundred twenty-nine consecutive patients with ocular discomfort from an Austrian dry eye clinic were investigated for the presence of Demodex mites on sampled eyelashes. Associations of a mite infestation with individual dry eye and lid parameters were assessed. Lid margins were evaluated for scales, vascularization, Marx line, expressibility and quality of meibum, and drop-out of meibomian glands. RESULTS: Demodex mites were identified in 40.2% of patients suffering from ocular discomfort (mean mite count 3.3 ± 2.9 per patient). Infestation with mites was associated with the presence of significantly more cylindrical scales (sleeves), a higher Marx line score, and a lower quality of meibum compared with mite-free patients. There were no significant associations with the expressibility and the drop-out of meibomian glands. CONCLUSION: The prevalence of Demodex mites in patients with ocular discomfort is high. The mean mite count per patient in this Austrian dry eye unit population is lower compared with previously published data from Asian regions. The infestation of the eyelids with Demodex species is associated with changes of the anterior and posterior lid margin, suggesting a pathogenic role in blepharitis and meibomian gland dysfunction.

Limiting factors for wearing personal protective equipment (PPE) in a health care environment evaluated in a randomised study.

Pandemics and re-emerging diseases put pressure on the health care system to prepare for patient care and sample logistics requiring enhanced personnel protective equipment (PPE) for health care workers. We generated quantifiable data on ergonomics of PPE applicable in a health care setting by defining error rates and physically limiting factors due to PPE-induced restrictions. Nineteen study volunteers tested randomly allocated head- or full body-ventilated PPE suits equipped with powered-air-purifying-respirators and performed four different tasks (two laboratory tutorials, a timed test of selective attention and a test investigating reaction time, mobility, speed and physical exercise) during 6 working hours at 22°C on one day and 4 working hours at 28°C on another day. Error rates and physical parameters (fluid loss, body temperature, heart rate) were determined and ergonomic-related parameters were assessed hourly using assessment sheets. Depending on the PPE system the most restrictive factors, which however had no negative impact on performance (speed and error rate), were: reduced dexterity due to multiple glove layers, impaired visibility by flexible face shields and back pain related to the respirator of the fully ventilated suit. Heat stress and liquid loss were perceived as restrictive at a working temperature of 28°C but not 22°C.

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.

CXCL13 is an activity marker for systemic, but not cutaneous lupus erythematosus: a longitudinal cohort study.

Serum levels of the IFN-regulated cytokine CXCL13 have been found to correlate with SLEDAI and renal involvement in systemic lupus erythematosus. This study investigates whether CXCL13 can also be a marker of disease activity in patients with subacute cutaneous or chronic cutaneous lupus erythematosus (SCLE, CCLE). We analysed CXCL13 levels in 60 patients' sera (18 SLE, 19 SCLE, 23 CCLE) at five time points within 1 year and correlated these levels with disease activity scores and laboratory markers. Clinical scores with no/mild, moderate or high/severe disease activity were categorized by SLEDAI in SLE, by CLASI in SCLE/CCLE. CXCL13 levels were significantly higher in SLE (median 122.5, IQR 88.0-239.0 pg/ml) than in CCLE patients (median 69.0, IQR 60.0-102.0 pg/ml) (p = 0.006). CXCL13 levels were elevated in 59% (41/70) of SLE patient visits with mild or no disease activity, but in 90% (9/10) with high disease activity. CXCL13 levels correlated with ECLAM, dsDNA-antibodies, and inversely with complement factors C3 and C4 in SLE, and with IgA and ESR in SCLE. In CCLE CXCL13 did not correlate with CLASI or laboratory markers. One SCLE and two CCLE patients with CXCL13 levels > 500 pg/ml had conversion to SLE or an underlying autoimmune disease. CXCL13 seems to be a useful marker of disease activity in SLE, but not in SCLE and CCLE. Conversion from normal to elevated CXCL13 may indicate a flare of SLE. Whether high CXCL13 levels in cutaneous LE indicate the development of SLE should be further investigated.

The prevalence of meibomian gland dysfunction, tear film and ocular surface parameters in an Austrian dry eye clinic population.

PURPOSE: The purpose of this study was to assess the prevalence of meibomian gland dysfunction (MGD) and its association with tear film and ocular surface parameters in an Austrian clinical population of dry eye patients. METHODS: The records of 1372 consecutive patients from a dry eye unit were analysed retrospectively. Symptoms and objective tear film and ocular surface parameters were evaluated. Patients were classified into pure MGD, pure aqueous tear deficiency (ATD), MGD combined with ATD, pure anterior blepharitis (AB), Sjogren's syndrome (SS) without MGD and SS together with MGD. RESULTS: Nine-hundred and sixty-five patients, that is 70.3% of the investigated population, mean age 55.4 ± 16.6 years, had signs of MGD. Of these, 684 (70.9%) were female. The intensity of symptoms did not differ between subgroups. Four hundred and ninety (50.8%) MGD patients had Schirmer test values ≤10 mm/5 min. The fluorescein break-up time and Schirmer test values were significantly higher in the pure AB and MGD group. The pure MGD group showed a significantly lower fluorescein staining of the cornea compared to the other groups, except for pure AB. Lissamine green staining of the ocular surface was present in all groups, but was at least pronounced in the pure MGD and AB group. CONCLUSION: Meibomian gland dysfunction is a major cause of ocular discomfort and could often be found in combination with a reduced aqueous tear secretion. Although the intensity of subjective complaints was similar to all other subgroups, pure MGD exhibited the lowest severity of signs of ocular surface damage and also affected younger people.

Depth of focus after implantation of spherical or aspheric intraocular lenses in hyperopic and emmetropic patients.

PURPOSE: To evaluate whether hyperopic patients with short axial length and high dioptric intraocular lens (IOL) power can achieve a higher depth of focus after implantation of a monofocal spherical or aspheric IOL than emmetropic patients. SETTING: Department of Ophthalmology, Medical University Graz, Graz, Austria. DESIGN: Prospective case series. METHODS: Patients presenting for cataract surgery were divided by calculated IOL power into a hyperopic (≥22.0 diopters [D]) or emmetropic (18.0 to 21.5 D) groups and received an aspheric (Tecnis ZA9003) or a spherical IOL (Sensar AR40e). Postoperative measurements included corrected (CDVA) and uncorrected (UDVA) distance visual acuities, distance-corrected intermediate (DCIVA) and near (DCNVA) visual acuities, root-mean-square values of corneal and total eye higher-order aberrations and spherical aberrations, and photopic and mesopic contrast sensitivity. RESULTS: Sixty-two eyes of 62 patients were enrolled in this study, 34 eyes (15 hyperopic, 19 emmetropic) in the aspheric IOL group and 28 eyes (14 hyperopic, 14 emmetropic) in the spherical IOL group. The UDVA, CDVA, and contrast sensitivity did not differ significantly between the 2 IOL groups, whereas the DCIVA and DCNVA were significantly better in the spherical IOL group (P = .004 and P = .001, respectively). No significant differences were found in DCIVA and DCNVA between hyperopic patients and emmetropic patients with aspheric or spherical IOLs. CONCLUSIONS: Implantation of a monofocal spherical IOL resulted in an increased depth of focus without significant degradation of distance visual acuity or contrast sensitivity. There were no differences in the depth of focus between hyperopic eyes and emmetropic eyes.

Small airway function before and after cold dry air challenge in pediatric asthma patients during remission.

BACKGROUND: We wanted to compare cold dry air challenge (CACh) induced changes in spirometric parameters with changes in nitrogen multiple breath washout (N2 MBW) parameters in pediatric asthma patients during clinical remission over the past year (ie, with "inactive asthma"). As N2 MBW assesses ventilation heterogeneity we expected to gain detailed information about peripheral airways contribution. METHODS: In subjects with normal spirometry N2 MBW, spirometry and body plethysmography were performed at baseline, after CACh, and after salbutamol inhalation. An initial measurement of the fraction of exhaled nitric oxide (FeNO) was conducted. RESULTS: Forty-three (20 female) subjects, mean age 13.7 years (range 6.5-18.6) performed reproducible N2 MBW measurements. Ten were tested hyperresponsive (23.3%) and 33 normoresponsive (76.7%). Baseline spirometry and body plethysmography as well as FRC (N2 MBW) were similar in both groups. Scond (0.031 vs 0.022), Sacin (0.057 vs 0.067), and FeNO (92.0 vs 28.5 ppb) were not statistically different between hyperresponsive and nomoresponsive subjects at baseline. Subjects with airway hyperresponsiveness (AHR) showed significant increases in lung clearance index (LCI, P = 0.011) and Scond (P = 0.008) after CACh, and significant decreases after salbutamol (LCI: P = 0.005; Scond: P = 0.005). In contrast, normoresponsive subjects showed no relevant changes after CACh, and only a decrease of Scond after salbutamol (P = 0.007). There were significant correlations between the CACh induced changes in FEV1 and changes in LCI (r = -0.45, P = 0.003), Scond (r = -0.30, P = 0.047), and Sacin (r = -0.47, P = 0.008), respectively. CONCLUSION: Our study provides evidence of small airway involvement in children and adolescents with inactive asthma and airway hyperresponsiveness.

Istaroxime, a potential anticancer drug in prostate cancer, exerts beneficial functional effects in healthy and diseased human myocardium.

The current gold standard for prostate cancer treatment is androgen deprivation therapy and antiandrogenic agents. However, adverse cardiovascular events including heart failure can limit therapeutic use. Istaroxime, which combines Na+-K+-ATPase (NKA) inhibition with sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) stimulation, has recently shown promising anti-neoplastic effects in prostate cancer (PC) models and may also improve cardiac function. Considering the promising anticancer effects of istaroxime, we aimed to assess its functional effects on human myocardium. RESULTS: Istaroxime and strophanthidin elicited dose-dependent positive inotropic effects with a decline in developed force at supraphysiological concentrations in human atrial, nonfailing, and failing ventricular (ToF) myocardium. Diastolic force and RT50% did not change after exposure to both drugs. The maximal developed force in our in-vitro model of heart failure (ToF) was significantly higher after istaroxime administration. Such a difference did not occur in atrial or nonfailing ventricular trabeculae and was not applicable to the diastolic force. MATERIALS AND METHODS: Human atrial and ventricular trabeculae were isolated from nonfailing hearts and hearts of infants with tetralogy of Fallot (ToF), which were used as an in-vitro model of heart failure. The samples were electrically stimulated and treated with increasing concentrations of istaroxime and strophanthidin (10 nM-1 µM). Systolic and diastolic force development and relaxation parameters (RT50%) were analyzed. CONCLUSIONS: Combined NKA inhibition/SERCA2a stimulation increases contractility in atrial, nonfailing, and failing myocardium. Considering that heart failure is a potential side effect of current PC treatments, especially in elderly patients, istaroxime might combine beneficial cardiac and anti-cancer properties.

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.

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.