Feasibility and Impact of Embedding an Extended DNA and RNA Tissue-Based Sequencing Panel for the Routine Care of Patients with Advanced Melanoma in Spain.

Targeted NGS allows a fast and efficient multi-gene analysis and the detection of key gene aberrations in melanoma. In this study, we aim to describe the genetic alterations in a series of 87 melanoma cases using the oncomine focus assay (OFA), relate these results with the clinicopathological features of the patients, and compare them with our previous study results in which we used a smaller panel, the oncomine solid tumor (OST) DNA kit. Patients diagnosed with advanced melanoma at our center from 2020 to 2022 were included and DNA and RNA were extracted for sequencing. Common mutated genes were BRAF (29%), NRAS (28%), ALK, KIT, and MAP2K1 (5% each). Co-occurring mutations were detected in 29% of the samples, including BRAF with KIT, CTNNB1, EGFR, ALK, HRAS, or MAP2K1. Amplifications and rearrangements were detected in 5% of cases. Only BRAF mutation showed a significant statistical association with sun exposure. For patients with a given genetic profile, the melanoma survival and recurrence-free survival rates were equivalent, but not for stage and LDH values. This expanded knowledge of molecular alterations has helped to more comprehensively characterize our patients and has provided relevant information for deciding the best treatment strategy.

Tips, quips and pearls: Ultrasound-guided distal metatarsal minimal invasive osteotomy (US-DMMO).

Metatarsalgia is a frequent cause of forefoot pain. Surgical treatment is based on the performance of osteotomies at the level of the minor radii to restore a normal distribution of pressure within the forefoot and improve the biomechanics during gait. In recent years, percutaneous surgery of the foot, and specifically distal metatarsal minimal invasive osteotomy, have proven to be a valid technique, providing satisfactory clinical results, similar to open osteotomy with less soft tissue aggression, but it requires intraoperative fluoroscopy to be performed. This article will present a modification to guide the procedure by ultrasound providing a new option that eliminates radiation and provides greater portability and accessibility.

The MarrowMiner: A Novel Minimally Invasive and Effective Device for the Harvest of Bone Marrow.

Bone marrow (BM) is a rich source of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), and other important stem/progenitor cells. It is the traditional source of cells used in hematopoietic cell transplantation, which is a proven curative treatment for many blood and immune diseases. BM-derived cells have also been shown to have other diverse clinical uses and are increasingly being used in orthopedic medicine, regenerative medicine, and gene therapy applications. Traditional methods for harvesting BM are crude, tedious, time-consuming, and expensive, requiring multiple bone punctures under general anesthesia with serial small-volume aspirates often diluted with peripheral blood. The MarrowMiner (MM) is a novel device designed for rapid and minimally invasive BM harvest. Here we show the safety and efficacy of the MM in both preclinical and clinical settings. In a large-animal porcine model, the MM enabled effective BM collection with similar total nucleated cell collection and increased colony formation compared with standard methods. The MM was subsequently evaluated in a clinical study showing effective and complication-free anterior and posterior BM collection of 20 patients under only local anesthesia or light sedation. Increased total nucleated and mononucleated cell collection was achieved with the MM compared with standard methods in the same patients. Importantly, stem cell content was high with trends toward increased HSC, MSC, and endothelial progenitor cells with similar T cell content. Given the MM is a novel device approved by the US Food and Drug Administration, enabling safe, effective, and minimally invasive harvest of BM, we anticipate rapid adoption for various applications.

The Effect of Retinal Illuminance on the Subjective Amplitude of Accommodation.

SIGNIFICANCE: We show that the amplitude of accommodation decreases with retinal illumination even under photopic reading conditions and a constant pupil size. This result provides a basis for clinical approaches that are not based on an optical explanation. PURPOSE: We investigated the effect of retinal illuminance on the amplitude of accommodation while the pupil of the eye remained constant. METHODS: The amplitudes of accommodation of 10 young subjects (from 20 to 38 years of age) and that of 10 presbyopic subjects (from 45 to 54 years of age) were measured subjectively through an artificial pupil of 5 mm using a Badal optometer and for four values of retinal illuminance: 222, 821, 2138, and 5074 trolands. Phenylephrine was instilled to all the subjects to ensure that their natural pupil was greater than the artificial one in all experimental runs. Linear mixed-effects model for repeated measures with age and log luminance as covariates were used to check whether changes in amplitude of accommodation with retinal illumination were statistically significant. RESULTS: In the range of illuminances tested, the amplitude of accommodation decreased on average from 6.34 to 4.35 D in the young subjects and from 1.69 to 1.04 D in the presbyopic subjects. Illuminance was associated with the amplitude of accommodation in both young and presbyopic groups, with P < .01. CONCLUSIONS: The reduction in the amplitude of accommodation with target illumination (a phenomenon named night presbyopia) under photopic light conditions is not only due to a reduction in the depth of focus as a consequence of pupil dilation; it is strongly affected by the decrease of retinal illumination.

Shunt overdrainage syndrome: review of the literature.

Shunt overdrainage in patients with hydrocephalus still represents a challenge for neurosurgeons, in part due to the lack of agreement or uniformity concerning the entity. Important problems exist relating to the real incidence of the entity, its definition, classification, and the pathophysiological theories behind the various treatment strategies proposed. Recent reports have suggested that the evidence about overdrainage and its consequences is not so robust as presumed. Consequently, the topic requires more detailed examination. In this review, we comment on all the main facets related with shunt overdrainage.

Non-invasive measurements of the dynamic changes in the ciliary muscle, crystalline lens morphology, and anterior chamber during accommodation with a high-resolution OCT.

PURPOSE: The purpose of the study was to assess non-invasively the changes in the anterior chamber eye, crystalline lens morphology, and ciliary muscle during accommodation by means of an anterior chamber optical coherence tomographer (OCT), and correlate them with vergence. METHODS: Twenty-five eyes of twenty-five healthy subjects, whose mean age was 29.9±7.1 years, were included and measured with an anterior chamber OCT. The central corneal thickness (CCT), anterior chamber depth (ACD), anterior crystalline lens radius of curvature (ALRC), crystalline lens thickness (CLT), and ciliary muscle area (CMA) were measured for each participant at 0, -1, -2, and -3 D of target vergence. A linear model was used to assess the correlation of each eye parameter with the vergence demand. RESULTS: The mean CCT showed no change for all the accommodative stimuli. The mean ACD and ALRC decreased with the vergence, about 4.5 and 30 % at -3 D, respectively. On the contrary, the CLT and CMA showed an opposite tendency, where the mean CLT was increased by 4.0 % and the mean CMA was done by 26% at -3 D. Statistical significant differences (p < 0.001) were obtained among all vergences for each eye metric, except for the CCT (p = 0.76). CONCLUSION: The ACD and ALRC decreased about 2 and 10 % per dioptre of accommodation, respectively; whereas the CLT and CMA increased about 2 and 9 %, respectively. These results add knowledge regarding the understanding of accommodation and give new perspectives for biomechanics and biometry.

Human eyes do not need monochromatic aberrations for dynamic accommodation.

PURPOSE: To determine if human accommodation uses the eye's own monochromatic aberrations to track dynamic accommodative stimuli. METHODS: Wavefront aberrations were measured while subjects monocularly viewed a monochromatic Maltese cross moving sinusoidally around 2D of accommodative demand with 1D amplitude at 0.2 Hz. The amplitude and phase (delay) of the accommodation response were compared to the actual vergence of the stimulus to obtain gain and temporal phase, calculated from wavefront aberrations recorded over time during experimental trials. The tested conditions were as follows: Correction of all the subject's aberrations except defocus (C); Correction of all the subject's aberrations except defocus and habitual second-order astigmatism (AS); Correction of all the subject's aberrations except defocus and odd higher-order aberrations (HOAs); Correction of all the subject's aberrations except defocus and even HOAs (E); Natural aberrations of the subject's eye, i.e., the adaptive-optics system only corrected the optical system's aberrations (N); Correction of all the subject's aberrations except defocus and fourth-order spherical aberration (SA). The correction was performed at 20 Hz and each condition was repeated six times in randomised order. RESULTS: Average gain (±2 standard errors of the mean) varied little across conditions; between 0.55 ± 0.06 (SA), and 0.62 ± 0.06 (AS). Average phase (±2 standard errors of the mean) also varied little; between 0.41 ± 0.02 s (E), and 0.47 ± 0.02 s (O). After Bonferroni correction, no statistically significant differences in gain or phase were found in the presence of specific monochromatic aberrations or in their absence. CONCLUSIONS: These results show that the eye's monochromatic aberrations are not necessary for accommodation to track dynamic accommodative stimuli.

The effect of aberrations on objectively assessed image quality and depth of focus.

The effects of aberrations on image quality and the objectively assessed depth of focus (DoF) were studied. Aberrometry data from 80 young subjects with a range of refractive errors was used for computing the visual Strehl ratio based on the optical transfer function (VSOTF), and then, through-focus simulations were performed in order to calculate the objective DoF (using two different relative thresholds of 50% and 80%; and two different pupil diameters) and the image quality (the peak VSOTF). Both lower order astigmatism and higher order aberration (HOA) terms up to the fifth radial order were considered. The results revealed that, of the HOAs, the comatic terms (third and fifth order) explained most of the variations of the DoF and the image quality in this population of subjects. Furthermore, computer simulations demonstrated that the removal of these terms also had a significant impact on both DoF and the peak VSOTF. Knowledge about the relationship between aberrations, DoF, image quality, and their interactions is essential in optical designs aiming to produce large values of DoF while maintaining an acceptable level of image quality. Comatic aberration terms appear to contribute strongly towards the configuration of both of these visually important parameters.

Factors related to shunt survival in paediatric hydrocephalus. Could failure be avoided?

BACKGROUND: Improved shunt survival and a better understanding of factors related to failure in paediatric hydrocephalus still pose a challenge for neurosurgeons, in order to avoid morbidity and mortality, as well as the economic impact of repeated revision surgeries. For these reasons, an analysis is performed on the factors related to the first shunt failure in the long-term follow-up of a series in a single centre. METHODS: A retrospective review was conducted on 166 hydrocephalic paediatric patients shunted for the first time between 2000 and 2014. An analysis was made of the statistical relationships between first shunt failure and the demographic, aetiological, surgical and clinical variables. RESULTS: Of the 166 shunts implanted in our centre during the study period, 111 required revision over a mean follow-up period of 93 months. Factors significantly related to failure were post-haemorrhagic and post-infectious hydrocephalus, meningitis episode, posterior burr hole, differential pressure valve, standard catheter in first surgery, and symptomatic over-drainage. Multivariable analysis showed that previous meningitis and symptomatic over-drainage were risk factors for shunt failure, whereas frontal burr hole location and antibiotic-impregnated catheters were protective factors. Cox regression determined that independent factors significantly related to a worse shunt survival, were shunt infection and symptomatic over-drainage. CONCLUSIONS: Meningitis, symptomatic over-drainage, frontal burr hole, and antibiotic impregnated catheters are significant prognostic factors for shunt survival. Shunt infection and symptomatic over-drainage are independent factors significantly related to a shorter shunt survival. Prospective, randomised, controlled trials are required to validate these results.

In vitro optical quality comparison between the Mini WELL Ready progressive multifocal and the TECNIS Symfony.

PURPOSE: To compare the optical quality between two intraocular lenses (IOLs): the Mini WELL Ready progressive multifocal (SIFI Medtech, Catania, Italy), and the TECNIS Symfony (Abbott Laboratories, Illinois, USA), which both provide a continuous range of vision from far to near positions. METHODS: The in vitro optical quality of each lens was assessed with an instrument conceived for measuring the modulation transfer function (MTF). The optical quality of each lens was described in terms of MTF, through-focus MTF, defocus tolerance, pupil dependence, and Strehl ratio MTF. These metrics were assessed for the best lens far focus, and at four vergences (from -1.5 to -3.0 D in 0.5-D steps), at 3.0 and 4.5 mm apertures. RESULTS: The through-focus curves of each lens showed two main areas: one corresponding to far-distance vision, and another to intermediate- and near-distance vision. Both lenses showed similar MTF curves and Strehl ratio values at both apertures. The optical quality of both lenses slightly decreased with the aperture for all vergences. Nevertheless, the quality of the progressive multifocal lens increased with the aperture at far-distance vision. This lens also showed the largest defocus tolerance at near-distance vision for both apertures. CONCLUSIONS: The results obtained in the present study suggest that both designs might enlarge the depth of focus. Whereas, the Mini WELL Ready showed better optical quality than the TECNIS Symfony at far vision with 4.5 mm aperture, and larger defocus tolerance than the diffractive lens at near-distance vision.

Surgical outcome of the shunt: 15-year experience in a single institution.

PURPOSE: Surgical outcome after shunt insertion in pediatric hydrocephalus can vary greatly. Although first shunt survival rates and complications have been studied by several teams, much less is known about survival and complications of subsequent systems. The goals of this study were to evaluate the surgical outcome in a series of pediatric patients followed for a long time and establish the differences between first and subsequent extracranial shunt survival and complications. METHODS: We undertook a retrospective study in pediatric patients treated with ventriculoperitoneal shunts between 2000 and 2015 at our institution. Surgical outcome was assessed, and different shunt survival curves were studied with Kaplan-Meier. Complications related to each shunt failure were examined and compared. RESULTS: A total of 166 patients underwent 425 procedures, with a mean follow-up period of 93 months. The median number of shunt revision surgeries was 2. Shunt survival rates were better with the first shunt compared to those with the subsequent shunts. The main complication necessitating system revision surgery was overdrainage, the frequency of proximal and distal dysfunctions was similar in all the shunt failures, and isolated ventricle and infection were more frequent in younger patients. Shunt-related infections accounted for 7 % of the procedures, and the shunt independence rate was 10 %. CONCLUSIONS: The frequency of complications related to shunt failure in pediatric patients changes during follow-up. A strict protocol of overdrainage detection and active treatment could explain the need for repeat surgeries and the progressively shorter shunt survival time in our series.

Opto-mechanical artificial eye with accommodative ability.

The purpose of this study was to describe the design and characterization of a new opto-mechanical artificial eye (OMAE) with accommodative ability. The OMAE design is based on a second-pass configuration where a small source of light is used at the artificial retina plane. A lens whose focal length can be changed electronically was used to add the accommodation capability. The changes in the OMAE's aberrations with the lens focal length, which effectively changes the accommodative state of the OMAE, were measured with a commercial aberrometer. Changes in power and aberrations with room temperature were also measured. The OMAE's higher-order aberrations (HOAs) were similar to the ones of the human eye, including the rate at which fourth-order spherical aberration decreased with accommodation. The OMAE design proposed here is simple, and it can be implemented in an optical system to mimic the optics of the human eye.

Melanoma on congenital melanocytic nevi.

Among nevus-associated melanomas, which overall account for 20%-30% of all melanomas, those arising specifically in congenital melanocytic nevi are infrequent, but can be disproportionately frequent in childhood and adolescence. Congenital melanocytic nevi (CMNi) are common benign melanocytic tumors that are present at birth or become apparent in early childhood. They are classified based on the projected adult size. Small and medium-sized CMNi are frequent, whereas large/giant CMNi (over 20 cm in diameter) are rare, but can be associated with high morbidity due to marked aesthetic impairment and the risk of neurocutaneous syndrome or melanoma development. In this setting, melanomas can appear in early childhood and are very aggressive, while the risk of small-medium CMNi of developing melanoma is low and similar to non-congenital melanocytic nevi. Histologically, most melanomas on CMNi initiate their growth at the epidermal-dermal junction, but in large/giant CMNi they can develop entirely in the dermis, in deeper tissues, or in extracutaneous sites (especially in the central nervous system). Most CMNi harbour an NRAS mutation, but other genes are rarely involved, and gene translocations have recently been described. However, no prognostic implications have been associated with the CMN genotype. Melanomas developed on CMNi harbour additional molecular alterations to which the aggressive clinical course of these tumors has been attributed. This review covers the distinctive clinical and pathological aspects of melanomas on CMNi, and includes the epidemiology, etiopathogenesis, clinical and dermoscopic presentation, histological and molecular characteristics, as well as tumour behaviour.

Optical and clinical simulated performance of a new refractive extended depth of focus intraocular lens.

OBJECTIVES: The purpose of this study is to evaluate the optical and expected clinical performance of a new refractive Extended Depth of Focus (EDF) intraocular lens (IOL) designed to maintain a monofocal-like dysphotopsia profile. METHODS: Simulated visual acuity (sVA) with varying defocus was calculated using the area under the Modulation Transfer Function measured in an average eye model and from computer simulations in eye models with corneal higher-order aberrations. Tolerance to defocus was evaluated using computer simulations of the uncorrected distance sVA under defocus. To evaluate the dysphotopsia profile, halo pictures obtained using an IOL-telescope, as well as simulated images in a realistic eye model under defocus were assessed. The results of the refractive EDF were compared to those of a diffractive EDF of the same platform. RESULTS: The refractive EDF IOL provides similar range of vision to the diffractive EDF IOL with the same distance, and similar intermediate and near sVA. The refractive EDF IOL provides the same tolerance to hyperopia as the diffractive EDF but more tolerance to myopia. Halo pictures and simulations showed that the refractive EDF provides comparable dysphotopsia profile to the monofocal IOL and better than the diffractive EDF. CONCLUSIONS: The results of this preclinical study in clinically relevant conditions show that the new refractive EDF IOL is expected to provide similar range of vision to the diffractive IOL of the same platform and higher tolerance to refractive errors. The refractive EDF provides a dysphotopsia profile that is better than the diffractive EDF and comparable to that of the monofocal IOL, also in the presence of residual refractive errors.

Dose-Dependent association of cumulative tobacco consumption with the presence of carotid atherosclerosis in individuals with type 1 diabetes.

AIMS: Evaluate the association between cumulative tobacco consumption (CTC; packs-year) and atherosclerosis in type 1 diabetes (T1D), and study whether the inclusion of CTC in the Steno T1 Risk Engine (ST1RE) equation improves the identification of plaques. METHODS: Cross-sectional study in T1D patients without cardiovascular disease (CVD), with ≥ 1 of the following: ≥40 years-old, diabetic kidney disease, and/or T1D duration ≥ 10 years + cardiovascular risk factors.Preclinical atherosclerosis was evaluated by carotid ultrasonography. RESULTS: N = 584 patients were included (46.1 % women, age 48.7 ± 10.5 years, T1D duration 27.3 ± 10.8 years, 26.2 % active smokers). The overall plaque prevalence was 40.9 %. In models adjusted for age, sex, lipids, blood pressure, kidney function, statin use, microvascular complications and HbA1c, CTC was dose-dependently associated with the number of plaques (none, 1-2, ≥3) overall and in both active and former smokers (p < 0.001). This association remained after adjusting for ST1RE (OR 1.11 [1.02-1.19]). Although the inclusion of CTC in the ST1RE did not improve plaque identification overall (p = 0.180), it did so when analyzing active smokers separately (AUC 0.738 vs. 0.768; p < 0.01). CONCLUSIONS: In T1D patients, CTC is dose-dependently associated with atherosclerosis. Further prospective studies are needed to determine if CTC could identify T1D individuals more prone to accelerated atherosclerosis.

Predictors of outcomes after internal fixation of periprosthetic femoral hip fractures Subgroup analysis of the peri-implant and peri-prosthetic fractures Spanish registry (PIPPAS).

PURPOSE: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems. METHODS: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay). RESULTS: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization. CONCLUSION: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization.

Immediate changes in masticatory mechanosensitivity, mouth opening, and head posture after myofascial techniques in pain-free healthy participants: a randomized controlled trial.

OBJECTIVE: This study aimed to assess the immediate effects on masticatory muscle mechanosensitivity, maximal vertical mouth opening (VMO), and head posture in pain-free healthy participants after intervention with myofascial treatment in the temporalis and masseter muscles. METHODS: A randomized, double-blind study was conducted. The sample group included 48 participants (n=48), with a mean age of 21±2.47 years (18-29). Two subgroups were defined: an intervention group (n=24), who underwent a fascial induction protocol in the masseter and temporalis muscles, and a control group (n=24), who underwent a sham (placebo) intervention. The pressure pain threshold in 2 locations in the masseter (M1, M2) and temporalis (T1, T2) muscles, maximal VMO, and head posture, by means of the craniovertebral angle, were all measured. RESULTS: Significant improvements were observed in the intragroup comparison in the intervention group for the craniovertebral angle with the participant in seated (P<.001; F1,23=16.45, R2=0.41) and standing positions (P=.012, F1,23=7.49, R2=0.24) and for the pressure pain threshold in the masticatory muscles, except for M2 (P=.151; M1: P=.003; F1,23=11.34, R2=0.33; T1: P=.013, F1,23=7.25, R2=0.23; T2: P=.019, F1,23=6.41, R2=0.21). There were no intragroup differences for the VMO (P=.542). Nevertheless, no significant differences were observed in the intergroup analysis in any of the studied variables (P>.05). CONCLUSION: Myofascial induction techniques in the masseter and temporalis muscles show no significant differences in maximal VMO, in the mechanical sensitivity of the masticatory muscles, and in head posture in comparison with a placebo intervention in which the therapist's hands are placed in the temporomandibular joint region without exerting any therapeutic pressure.

Craniocervical posture and trigeminal nerve mechanosensitivity in subjects with a history of orthodontic use: a cross-sectional study.

The purpose of the study was to evaluate whether, in asymptomatic subjects, there are differences in: (i) head posture while sitting and standing still and (ii) trigeminal nerve mechanosensitivity, between those who have a history of using orthodontics and those who do not. The sample consisted of 72 subjects (21 +/- 2.14 years): one group who had used orthodontics in the past (n = 37), and another group who had not had previous orthodontic treatment (n = 35). The authors measured the CranioVertebral Angle (CVA) while the subject was sitting and standing still by means of lateral photographs, and the pressure pain threshold (PPT) of the trigeminal nerve. The orthodontics group showed a more upright position of the head when sitting compared to the non-orthodontics group, with the difference being statistically significant (ANOVA test; p < 0.001; F1,70 = 16.705; R2 = 0.19), but not for the standing position (p = 0.538). The values of the PPT in the trigeminal nerve (supraorbital-V1, infraorbital-V2 and mandibular-V3) were lower on both sides (dominant and nondominant) in the non-orthodontics group. The between-group comparison (ANOVA test) showed statistically significant differences for the trigeminal nerve PPT in its different branches (V1 p = 0.001; F1,70 = 13.012; R2 = 0.15) (V2 p = 0.004; F1,70 = 9.103; R2 = 0.11) (V3 p = 0.005; F1,70 = 8.228; R2 = 0.10). Based on these observations, it was concluded that subjects with a history of orthodontic use show a better sitting craniocervical posture and mechano-sensitivity of the trigeminal nerve branches compared to the group that had not used orthodontics in the past.

Influence of decentration and tilt of Tecnis ZCB00 on visual acuity and higher order aberrations.

BACKGROUND/OBJECTIVES: To determine the influence of decentration and tilt of a pseudophakic aspheric intraocular lens (IOL) on visual acuity (VA) and higher-order aberrations (HOAs), and to analyze the agreement between pupil center/axis and iridocorneal angles center/axis when assessing IOL decentration and tilt. SUBJECTS/METHODS: A prospective interventional case series study including thirty-three patients undergoing Tecnis ZCB00 (Abbott Medical Optics) implantation. IOL decentration and tilt with respect to two reference systems (pupil and iridocorneal angles centers/axes), in cartesian (X,Y) and polar (radius/tilt, polar angle/azimuth) coordinates, were assessed with optical coherence tomography. VA and internal and ocular HOAs were evaluated. Multiple linear regression models and intraclass correlation coefficient (ICC) were computed. RESULTS: IOL decentration only showed a significant effect on internal HOAs for [Formula: see text] (R2 = 0.20, P = 0.04). IOL decentration with respect to the pupil center showed a significant effect on ocular [Formula: see text] (R2 = 0.18, P = 0.05), [Formula: see text] (R2 = 0.36, P = 0.001) and [Formula: see text] (R2 = 0.24, P = 0.02); and with respect to the center of iridocorneal angles, on ocular [Formula: see text] (R2 = 0.21, P = 0.03), [Formula: see text] (R2 = 0.32, P = 0.003), primary coma (R2 = 0.41, P < 0.001), and coma-like (R2 = 0.40, P = 0.001). Poor agreement between both reference systems was found for IOL decentration measurements (ICC ≤ 0.41), except for the polar angle coordinate (ICC = 0.83). Tilt measurements showed good agreement (ICC ≥ 0.75). CONCLUSIONS: Tecnis ZCB00 decentration and tilt values after uneventful implantation appear not to have influence on VA, and their effect on HOAs are not high enough to clinically affect quality of vision. Pupil and iridocorneal angles used as reference systems may be interchangeable for IOL tilt measurements, but not for decentration.

Exploring the chemistry of epoxy amides for the synthesis of the 2''-epi-diazepanone core of liposidomycins and caprazamycins.

New synthetic strategies have been explored for the synthesis of the structural core of liposidomycins and caprazamycins, an intriguing class of complex nucleoside-type antibiotics. This structural core is comprised of a cyclic diazepanone system linked to an uridyl fragment. The various synthetic approaches have in common that they originate from an epoxy amide derived from uridine, obtained via reaction of uridyl aldehyde 19 with an amide-stabilized sulfur ylide. Two different strategies were shown to be efficient in constructing the diazepanone ring system: (a) a reductive amination of an epoxy aldehyde with N-methylamine with subsequent intramolecular oxirane ring opening and (b) a carbene insertion reaction of an acyclic diazoamine precursor.