Fellow-Eye Comparison Of Monocular Visual Outcomes Following Monofocal EDOF And Trifocal EDOF IOL Implantation.

PURPOSE: To compare intraindividual monocular visual performance of a monofocal EDOF and a trifocal EDOF IOL following bilateral cataract surgery. DESIGN: Single-center, prospective, fellow-eye comparison clinical trial. METHODS: All patients received uneventful bilateral cataract surgery with implantation of the monofocal EDOF Isopure IOL in the dominant eye and the trifocal EDOF FineVision Triumf IOL in the non-dominant eye. Intraindividual monocular comparison included visual acuity at various distances, defocus curves, internal total higher-order aberration (HOA), spherical aberration (SA) Z(4.0), IOL decentration and tilt. Additionally, subjective outcomes were evaluated using Halo and Glare simulation and the VF-7 questionnaire. RESULTS: In total, 25 patients (50 eyes) were included. Intraindividual monocular BCDVA, DCIVA, and BCNVA were comparable (p> .05). However, monocular contrast acuity (p= .019), DCNVA (p< .001) and defocus curves at defocus levels of 0.0D (p= .005) and between -1.5 and -4.0D (p< .001) differed significantly. At 5mm, internal HOA and SA Z(4.0) were significantly different (p< .001) and comparable at 3mm pupil diameter, as were IOL tilt and decentration (p> .05). CONCLUSION: In this combined fellow-eye comparison, near vision was significantly better with the trifocal EDOF IOL. The monofocal EDOF IOL demonstrated similar distance and intermediate visual performance as the trifocal EDOF IOL. Overall, low values of photic phenomena and visual impairment was observed.

Reverse pupillary block, in contemporary scleral intraocular lens procedures.

BACKGROUND: To evaluate the frequency and anterior segment optical coherence tomography parameters of patients with scleral fixated intraocular lenses (IOL) and reverse pupillary block (RPB). METHODS: Retrospective analysis at a tertiary care centre (Department for Ophthalmology and Optometry, Medical University of Vienna, Austria). We researched our records for patients who underwent scleral fixated IOL implantation from January 2018 till February 2023. Patients were included only if there was at least one adequate post-operative scan of anterior segment optical coherence tomography (AS-OCT) available. Initially, AS-OCT scans were assessed for IOL tilt and decentration employing a 3D scan and then later for anterior chamber angle (ACA), aqueous anterior chamber depth (AQD), pupil diameter and iris-IOL distance using the 2D scan at a 0° angle. Both an iris-IOL distance of 0 or less and an ACA of more than 70° were required to define an RPB. RESULTS: A total of 110 patients met the inclusion criteria, 41 were treated using the Carlevale, 33 the four flanged, 24 the Yamane and 12 the Scharioth technique, respectively. RPB was found in 32 patients (29%). Twenty patients with RPB were treated using YAG peripheral iridotomy, mean ACA decreased from 91.91° ± 13.77 to 61.02° ± 8.52, (p < 0.001), mean AQD decreased from 4.67 mm ± 0.47 to 4.31 ± 0.36 mm (p < 0.001) and mean iris-IOL distance increased from -0.09 ± 0.04 to 0.33 ± 0.30 (p < 0.001). CONCLUSIONS: RPB is found in a third of eyes who have undergone scleral fixated IOL implantation without iridectomy. YAG peripheral iridotomy is a potent option to treat RPB, and subsequently reduce the risk of iris chafing and secondary inflammation or glaucoma.

Intraindividual Comparison of an Enhanced Monofocal and an Aspheric Monofocal Intraocular Lens of the Same Platform.

PURPOSE: To compare intraindividual differences in visual performance of a monofocal and enhanced monofocal intraocular lens (IOL) of the same platform. DESIGN: Prospective, interventional, fellow-eye comparison clinical study. METHODS: In total, 55 patients (110 eyes) with bilateral age-related cataract were enrolled. All patients received a monofocal ZCB00 IOL in the dominant and an enhanced monofocal Eyhance ICB00 IOL in the nondominant eye. After 2 to 4 months, monocular best-corrected distant visual acuity (BCDVA), distance-corrected intermediate visual acuity (DCIVA), distance-corrected near visual acuity (DCNVA), contrast visual acuity, monocular defocus curves, internal higher-order aberrations (HOAs) and spherical aberrations (SA), decentration, and tilt were compared. RESULTS: The monocular mean BCDVA, DCIVA at 80 cm and 66 cm, and DCNVA were -0.03 ± 0.07, 0.24 ± 0.12, 0.32 ± 0.13, and 0.50 ± 0.13 logarithm of the minimum angle of resolution for the enhanced ICB00 and -0.06 ± 0.06 (P = .014), 0.30 ± 0.11 (P = .005), 0.38 ± 0.12 (P = .004), and 0.55 ± 0.14 (P = .034) logarithm of the minimum angle of resolution for the ZCB00, respectively. Internal HOAs (P = .001) and negative SA (P < .001) were increased with the ICB00 at 3 mm and comparable at 5 mm (P > .05). Contrast acuity, tilt, and decentration were similar (P > .05). CONCLUSIONS: Significantly increased monocular DCIVA at 80 cm and 66 cm and DCNVA at 40 cm were observed with the enhanced ICB00 IOL, and the ZCB00 IOL demonstrated better BCDVA. This would result in a mean gain of 2 to 3 Early Treatment of Diabetic Retinopathy Study letters at near and intermediate distance. Monocular defocus curves displayed highest differences of 5 Early Treatment of Diabetic Retinopathy Study letters at -1.25 diopters (D) and -1.50 D levels of defocus and a depth of focus of 1.23 D for the ICB00 IOL and 0.94 D for the ZCB00 IOL. Decentration, tilt, and HOAs were generally low.

Initial antibiotic therapy for postoperative moderate or severe diabetic foot infections: Broad versus narrow spectrum, empirical versus targeted.

AIM: To retrospectively evaluate clinical and microbiological outcomes after combined surgical and medical therapy for diabetic foot infections (DFIs), stratifying between the empirical versus the targeted nature, and between an empirical broad versus a narrow-spectrum, antibiotic therapy. METHODS: We retrospectively assessed the rate of ultimate therapeutic failures for each of three types of initial postoperative antibiotic therapy: adequate empirical therapy; culture-guided therapy; and empirical inadequate therapy with a switch to targeted treatment based on available microbiological results. RESULTS: We included data from 332 patients who underwent 716 DFI episodes of surgical debridement, including partial amputations. Clinical failure occurred in 40 of 194 (20.6%) episodes where adequate empirical therapy was given, in 77 of 291 (26.5%) episodes using culture-guided (and correct) therapy from the start, and in 73 of 231 (31.6%) episodes with switching from empirical inadequate therapy to culture-targeted therapy. Equally, a broad-spectrum antibiotic choice could not alter this failure risk. Group comparisons, Kaplan-Meier curves and Cox regression analyses failed to show either statistical superiority or inferiority of any of the initial antibiotic strategies. CONCLUSIONS: In this study, the microbiological adequacy of the initial antibiotic regimen after (surgical) debridement for DFI did not alter therapeutic outcomes. We recommend that clinicians follow the stewardship approach of avoiding antibiotic de-escalation and start with a narrow-spectrum regimen based on the local epidemiology.

Temporal association between COVID-19 vaccination and Raynaud's phenomenon: A case series.

COVID-19 vaccine-related adverse events are mostly minor to moderate, and serious events are rare. Single cases of Raynaud's phenomenon (RP) in temporal proximity to COVID-19 vaccination have been reported. Demographic data, medical history, and detailed information regarding vaccination status and RP characteristics were obtained from patients with confirmed RP after COVID-19 vaccination. Fifteen participants reported the initial manifestation of RP, which occurred in 40% after the first, in 33% after the second, and in 27% after the third vaccination. RP development and occurrence of episodes were not linked to any specific vaccine type. New onset of disease was observed in 40% of the vaccinees after BNT162b2, in 33% after mRNA-1273, and in 27% after ChAdOx1 vaccination. Three out of four participants with preexisting RP prior to COVID-19 vaccination reported aggravation in frequency and intensity after immunization. Although COVID-19 vaccination is pivotal in controlling the pandemic, the observed temporal association between vaccine administration and RP occurrence warrants global activities to support pharmacovigilance for the detection of adverse reactions, one of which may include RP.

Performance evaluation of the Elecsys PIVKA-II and Elecsys AFP assays for hepatocellular carcinoma diagnosis.

Background and Aims: Prothrombin induced by vitamin K absence-II (PIVKA-II) is a serum biomarker linked to hepatocellular carcinoma (HCC), showing superiority to alpha-fetoprotein (AFP) for early disease detection. We aimed to assess the clinical and analytical performance of the Elecsys® PIVKA-II immunoassay in diagnosing HCC and evaluate PIVKA-II's technical performance. Methods: Serum samples from adult cases (i.e. patients with a first-time HCC diagnosis; n = 168) and disease controls (i.e. patients without HCC with an at-risk condition; n = 208) were assessed. An AFP cut-off of 20 ng/mL was used to differentiate between HCC cases and disease controls. Clinical performance of the Elecsys PIVKA-II assay was compared with that of comparator assays (Lumipulse G PIVKA-II, µTASWako DCP, ARCHITECT PIVKA-II) using receiver operating characteristic curve analysis to determine the area under the curve (AUC) values. Results: The Elecsys PIVKA-II assay compared favorably with comparator assays. Using a 28.4 ng/mL cut-off, the Elecsys PIVKA-II assay detected HCC with 86.9% sensitivity and 83.7% specificity. Clinical performance of the Elecsys PIVKA-II assay (AUC: 90.8%) was equivalent to that of comparator assays (AUC: 88.3-89.6%). Relatively high PIVKA-II concentrations were observed for cholangiocarcinoma and pancreatic cancer with the Elecsys assay in specificity panel analyses, indicating that high PIVKA-II concentrations should not be used alone in the absence of other clinical data. Conclusions: The Elecsys PIVKA-II assay showed good analytical performance under routine laboratory conditions, comparing favorably with comparator assays. These findings support the suitability of the Elecsys PIVKA-II assay as an aid in HCC diagnosis.

The impact of the length of total and intravenous systemic antibiotic therapy for the remission of diabetic foot infections.

OBJECTIVE: We investigated the impact of the total length of systemic antibiotic therapy (ABT) and its initial intravenous (IV) part on clinical failure (CF) and microbiological failure (MF) in diabetic foot infections (DFIs). METHODS: In this single-center, retrospective, unmatched case-control study, we included DFI episodes treated with a combined surgical-antibiotic approach. RESULTS: We included 721 DFI episodes, 537 with osteomyelitis (DFO). CF occurred in 191 (26.5%) and MF in 42 (5.8%) episodes. Multivariate Cox regression analysis showed that a short ABT of 8-21 days (hazard ratio [HR] 0.4; 95% CI 0.2-0.7) was inversely associated with CF. This was also applicable for IV ABT with relatively short durations of 2-7 days (HR 0.5; 95% CI 0.3-0.8) or 8-14 days (HR 0.6; 95% CI 0.4-0.9). We failed to detect a minimal threshold of total or IV ABT predictive for CF or MF. CONCLUSIONS: Compared with total ABT of more than 84 days and IV therapy of more than 14 days, shorter total and IV ABT yielded no enhanced risk of CF or MF. Considering the "bias by indication" that is inherent to retrospective DFI studies, the best study design concerning the duration of ABT would be a stratified, prospective randomized trial, which is currently under way in our medical center.

Quality and readability of online resources on chronic ankle instability.

BACKGROUND: Online resources on medical conditions often provide misleading or outdated information for patients. The aim of this study was to evaluate the quality of online patient information on ankle instability. METHODS: The terms "ankle instability", "ankle instability treatment" and "ankle laxity" were entered into the three largest internet search engines. The quality, accuracy and readability were evaluated using the EQIP36, a custom 25-item list and the Flesch-Kincaid-Score. RESULTS: The mean 25-item score of 102 included websites reached 10 ± 5, the mean EQIP36 score was 41 ± 11 and 96% of evaluated websites exceeded the recommended 8th-grade reading level for patient information. The quality was significantly higher with reading levels of college graduates (P < 0.001). CONCLUSIONS: Online resources on ankle instability are often inaccurate or at inappropriately high reading level. The quality and accuracy depend on the reading levels, with high reading levels providing more in-depth information. Foot and ankle surgeons should be aware of available online resources to direct patients to adequate websites. LEVEL OF EVIDENCE: Level V.

Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China.

BACKGROUND: We performed a multicenter evaluation of the Elecsys® progastrin-releasing peptide (ProGRP) immunoassay in Europe and China. METHODS: The assay was evaluated at three European and two Chinese sites by imprecision, stability, method comparison and differentiation potential in lung cancer. RESULTS: Intermediate imprecision across five analyte concentrations ranged from 2.2% to 6.0% coefficient of variation. Good stability for plasma and serum samples was shown for various storage conditions. There was excellent correlation between the Elecsys® and ARCHITECT assays in plasma (slope 1.02, intercept -2.72pg/mL). The Elecsys® assay also showed good correlation between serum and plasma samples (slope 0.93, intercept 2.35pg/mL; correlation coefficient 0.97). ProGRP differentiated small-cell and non-small-cell lung cancer (NSCLC; area under the curve 0.90, 95% CI 0.87-0.93; 78.3% sensitivity, 95% specificity; at 84pg/mL), with no relevant effects of ethnicity, age, gender or smoking. Median ProGRP concentrations were low in benign diseases (38pg/mL), other malignancies (40pg/mL) or NSCLC (39pg/mL), except chronic kidney disease above stage 3 (>100pg/mL). CONCLUSIONS: Increased stability of the Elecsys® ProGRP assay in serum and plasma offers clear benefits over existing assays. This first evaluation of a ProGRP assay in China demonstrated comparable differentiation potential among different ethnicities.

High expression of 5-lipoxygenase in normal and malignant mantle zone B lymphocytes.

BACKGROUND: Human B lymphocytes can produce leukotriene B4 but the biological function of the 5-lipoxygenase (5-LO) pathway in B cells is unclear. In order to better understand and define the role of 5-LO in B cells, we investigated the expression of 5-LO mRNA and protein in subsets of B cells from human tonsils and different types of B cell lymphoma. RESULTS: Based on RT-PCR and western blot/immunohistochemical staining, with a polyclonal antibody raised against 5-LO, high expression of 5-LO was found in mantle zone B cells from tonsils. By contrast, only a weak expression of 5-LO was detected in germinal centre cells and no expression in plasma cells from tonsils. This pattern of 5-LO expression was preserved in malignant lymphoma with high expression in mantle B cell lymphoma (MCL) and weak or no expression in follicular lymphoma. Primary leukemized MCL, so called B-prolymphocytic leukaemia cells, and MCL cell lines also expressed 5-LO and readily produced LTB4 after activation. CONCLUSION: The present report demonstrates the expression of 5-LO mainly in normal and malignant mantle zone B cells while the expression is low or absent in germinal centre B cells and plasma cells, indicating a role of the 5-LO pathway in B cells before the cells finally differentiate to plasma cells.

In vivo near-infrared fluorescence imaging of carcinoembryonic antigen-expressing tumor cells in mice.

PURPOSE: To prospectively depict carcinoembryonic antigen (CEA)-expressing tumors in mice with a high-affinity probe consisting of a near-infrared (NIR) fluorochrome and the clinically used anti-CEA antibody fragment arcitumomab. MATERIALS AND METHODS: This study was approved by the regional animal committee. By coupling a NIR fluorescent (NIRF) cyanine dye (DY-676) to a specific antibody fragment directed against CEA (arcitumomab) and a nonspecific IgG Fab fragment, a bio-optical high-affinity fluorescent probe (anti-CEA-DY-676) and a low-affinity fluorescent probe (FabIgG-DY-676) were designed. The dye-to-protein ratios were determined, and both probes were tested for NIRF imaging in vitro on CEA-expressing LS-174T human colonic adenocarcinoma cells and CEA-nonexpressing A-375 human melanoma cells by using a bio-optical NIR small-animal imager. In vivo data of xenografted LS-174T and A-375 tumors in mice (n = 10) were recorded and statistically analyzed (Student t test). RESULTS: The dye-to-protein ratios were determined as 3.0-3.5 for both probes. In vitro experiments revealed the specific binding of the anti-CEA-DY-676 probe on CEA-expressing cells as compared with CEA-nonexpressing cells; the FabIgG-DY-676 probe showed a markedly lower binding affinity to cells. In vivo LS-174T tumors xenografted in all mice could be significantly distinguished from A-375 tumors with application of the anti-CEA-DY-676 but not with that of the FabIgG-DY-676 at different times (2-24 hours, P < .005) after intravenous injection of the probes. Semiquantitative analysis revealed maximal fluorescence signals of anti-CEA-DY-676 to CEA-expressing tumors about 8 hours after injection. CONCLUSION: Findings of this study indicate the potential use of the high-affinity probe anti-CEA-DY-676 for specific NIRF imaging in in vivo tumor diagnosis.

Fluorescent bacterial magnetic nanoparticles as bimodal contrast agents.

OBJECTIVES: The purpose of this study was to assess whether fluorochrome-coupled bacterial magnetic nanoparticles can be used as bimodal contrast agent for both magnetic resonance imaging (MRI) and near-infrared fluorescence optical (NIRF) imaging of cultured macrophages. MATERIALS AND METHODS: Bacterial magnetic nanoparticles (magnetosomes, particle diameter: 42 nm) were harvested from Magnetospirillum gryphiswaldense and characterized by using MRI. After covalent coupling to the fluorescent dye DY-676 (lambdaabs./lambdaem.= 676 nm/701 nm, Dyomics, Jena, Germany), the fluorescent magnetosomes were analyzed by fluorescence-activated cell sorting. Subsequently, murine macrophages J774 were incubated with the bimodal contrast agent (3 hours) and examined by a whole-body near infrared small animal imaging system as well as by using a 1.5 T clinical MR system. Moreover, labeled cells were characterized using confocal laser scanning microscopy (CLSM) and ultrathin section transmission electron microscopy. RESULTS: Characterization of the nanoparticles by MRI revealed R1 and R2 relaxivities of 3.2 mMs and 526 mMs, respectively. Fluorochrome-coupled magnetosomes exhibited increased fluorescence intensities at wavelengths >670 nm. Macrophages that were incubated with the contrast agent showed a significant fluorescence emission in the near infrared range as imaged with a whole body NIR imaging system, FACS analysis and CLSM. Moreover, CLSM data showed the greatest fluorescence intensities within intracellular compartments and colocalized with the magnetosomes. With MRI, both T1 and T2 relaxation times were substantially shortened at concentrations greater than 600 cells/microL. DISCUSSION AND CONCLUSION: Macrophages could be labeled with fluorescent magnetosomes, and they were successfully imaged using both a 1.5 T MR scanner as well as with NIRF optical methods. The use of this bimodal contrast agent for diagnostic purposes may benefit from the excellent spatial resolution of the MRI and the high sensitivity of the fluorescence imaging.

MR imaging of Her-2/neu protein using magnetic nanoparticles.

The aim of this study was to assess whether Her-2/neu expressing tumour cells can be detected in vitro as well as in animal tumour models with magnetic resonance imaging at 1.5 T. Magnetic nanoparticles (with relaxivities R 1, R 2 of 3.7 ± 0.4 (mM s)(-1), 277 ± 32 (mM s)(-1) at 21 °C, respectively) coupled to anti-Her-2/neu antibodies or gamma globulin IgG (high or non-affinity probe, respectively) were used. After incubation of Her-2/neu expressing cells (SKBR3) with high or non-affinity probes (20 min), values of R 1 = 0.34 ± 0.02 (mM s)(-1) and R 2 = 63.02 ± 30 (mM s)(-1) were obtained. Electron microscopy and atomic absorption spectrometry examinations verified the presence of relatively high iron levels in cells incubated with the high affinity probe compared to controls. For in vivo MRI, high or non-affinity probes (≈1.7 mg Fe/animal) were injected into the tail vein of mice (n = 16) bearing SKBR3 tumours. A distinct decrease in the normalized MR signal ratio between tumour and reference area (approximately -17 ± 2%) after application of the high affinity probe was observed. In conclusion, in vivo detection of Her-2/neu expressing tumours is feasible in a clinical MR scanner by using immunoconjugated magnetic nanoparticles.

Diagnosis of peritonitis using near-infrared optical imaging of in vivo labeled monocytes-macrophages.

Peritonitis is an inflammatory process characterized by massive monocytes-macrophages infiltration. Since early diagnosis is important for a successful therapeutic outcome, the feasibility for a selective labeling and imaging of macrophages for highly sensitive optical imaging was assessed. After in vitro incubation of mouse macrophages J774A.1 with the far-red/near-infrared fluorochrome DY-676, distinct fluorescence intensities (1026+/-142 a.u.) were detected as compared to controls (552+/-54 a.u.) using a whole-body small animal near-infrared fluorescence (NIRF) imaging system. Macrophage labeling was confirmed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting, (FACS). The fluorochrome was also found to be predominantly distributed within compartments in the cytoplasm. Additionally, peritonitis was induced in mice by intraperitoneal injection of zymosanA. After intravenous injection of fluorochrome (55 nmol/kg) and using whole-body fluorescence imaging, higher fluorescence intensities (869+/-151 a.u.) were detected in the peritoneal area of diseased mice as compared to controls (188+/-41 a.u.). Furthermore, cells isolated from peritoneal lavage revealed the presence of labeled monocytes-macrophages. The results indicate that in vivo diagnosis of peritonitis by near-infrared optical imaging of labeled monocytes-macrophages is feasible. Possibly, early stages of other inflammatory diseases could also be detected by the proposed diagnostic method in the long term.