Kikuchi-Fujimoto Disease and COVID-19 vaccination: pharmacovigilance approach.

Summary: Background. Kikuchi-Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitys is a rare disorder characterized by subacute necrotizing regional lymphadenopathy. It is usually presented as painful cervical nodes and associated with fever, headache, night sweats, nausea, vomiting and sore throat. Etiology of KFD is still unclear, two theories have been proposed: infections and autoimmune origin. Due to recent reports of KFD related to COVID-19 vaccination, the novelty of the mechanism of these vaccines and the immunomodulated role of both matters, a literature and adverse event databases review was carried out in order to shed light on the relationship between these two matters. Methods. A search in the Spanish and the European adverse events databases (FEDRA and Eudravigilance) was performed. Search criteria were any drug and the diagnosis "Histiocytic necrotizing lymphadenitis" according to the Medical Dictionary for Medical Activities version 25.0. All adverse events registered as June 2, 2022, were included. Results. FEDRA encompassed two KFD reports, one related to a mRNA COVID-19 vaccine. Eudravigilance included a total of 62 KFD cases, 14 of them associated to COVID-19 vaccines and eight to other vaccines. Conclusions. Pharmacovigilance is of utter importance in detecting adverse events caused by new vaccines. More research is needed to establish a final connection between KFD and COVD-19 vaccines, but due to the physiopathology of the condition, how vaccines stimulate the immune system and the high number of reported KFD cases with vaccines given its rare incidence, it is plausible to think that both entities are related.

Structural and functional findings in patients with moderate diabetic retinopathy.

PURPOSE: To evaluate structural and functional ocular changes in patients with type 2 diabetes mellitus (DM2) and moderate diabetic retinopathy (DR) without apparent diabetic macular edema (DME) assessed by optical coherence tomography (OCT) and microperimetry. METHODS: This was a single-center cross-sectional descriptive study for which 75 healthy controls and 48 DM2 patients with moderate DR were included after applying exclusion criteria (one eye per patient was included). All eyes underwent a complete ophthalmic examination (axial length, macular imaging with swept-source OCT, and MAIA microperimetry). Macular thicknesses, ganglion cell complex (GCC) thicknesses, and central retinal sensitivity were compared between groups, and the relationships between the OCT and microperimetry parameters were evaluated. RESULTS: Macular thickness was similar in both groups (242.17 ± 35.0 in the DM2 group vs 260.64 ± 73.9 in the control group). There was a diminution in the parafoveal area thickness in the DM2 group in the GCC complex. Retinal sensitivity was reduced in all sectors in the DM2 group. The central global value was 24.01 ± 5.7 in the DM2 group and 27.31 ± 2.7 in the control group (p < 0.001). Macular integrity was 80.89 ± 26.4 vs 64.70 ± 28.3 (p < 0.001) and total mean threshold was 23.90 ± 4.9 vs 26.48 ± 2.6 (p < 0.001) in the DM2 and control group, respectively. Moderate correlations were detected between the central sector of MAIA microperimetry and retina total central thickness (- 0.347; p = 0.0035). Age, visual acuity, and hemoglobin A1c levels also correlated with retinal sensitivity. CONCLUSION: Macular GCC thickness and central retinal sensitivity were reduced in patients with moderate DR without DME, suggesting the presence of macular neurodegeneration.

[Blinatumomab as a bridge to trasplantation in refractory Philadelphia chromosome negative b-cell acute lymphoblastic leukemia: a case report]. / Blinatumomab como puente al transplante en leucemia linfoblástica aguda refractaria con cromosoma Filadelfia negativo: a propósito de un caso.

Blinatumomab is a first class bispecific T-cell engager that has been shown to achieve negative minimal residual disease in patients with relapsed or refractory pre-B acute lymphoblastic leukemia after conventional chemotherapy. Nevertheless, there is little evidence about its role as an off label enhancer of cytological remission prior to stem cell transplantation (SCT). We describe the case of a patient with an excellent performance status who was allowed to undergo alogenic SCT after a single blinatumomab cycle, as well as the management of adverse events and the observed results.

Context-dependent effects of fire and browsing on woody alien invasion in mountain ecosystems.

Anthropogenic activities have increased disturbances and alien woody invasion in mountain ecosystems worldwide. Whether disturbances promote or counteract upward movement of woody aliens is poorly understood. We assessed if the most successful woody invader of low mountains of central Argentina (Gleditsia triacanthos) might expand its elevational distribution in response to the principal disturbances of these ecosystems (fire and livestock browsing) across increasing climatic severity. We assessed seedling emergence, growth and mycorrhizal colonization on sown plots distributed in burned and unburned sites, with and without browsing at the lower and upper elevation belts (i.e. 1000 and 2400 m a.s.l.). Additionally, several abiotic variables were measured to relate their influence on the seedling establishment. Disturbances reduced seedling emergence at both elevations. Burned conditions increased seedling growth and arbuscular colonization only in the lower belt. Seedling success (total seedling biomass per plot) was not modified by disturbances at the upper elevation, but was reduced by browsing and enhanced by fire in the lower elevation. The overall reduction in seedling emergence and growth in the upper elevation despite the higher soil nutrient content places climate as the strongest regulator of G. triacanthos seedling establishment. Accordingly, climate rather than disturbances would be the main limiting factor of upward expansion of this woody alien. Our findings differ from general patterns described for mountain invasion by herbaceous species, highlighting that mountain invasibility is highly growth-form dependent, and that upper range expansion by woody aliens interacting with multiple disturbances should be assessed worldwide.

Diagnostic ability of Humphrey perimetry, Octopus perimetry, and optical coherence tomography for glaucomatous optic neuropathy.

PurposeTo evaluate and compare the diagnostic accuracy of the Humphrey Field Analyzer (HFA), Octopus perimetry, and Cirrus OCT for glaucomatous optic neuropathy.MethodsEighty-eight healthy individuals and 150 open-angle glaucoma patients were consecutive and prospectively selected. Eligibility criteria for the glaucoma group were intraocular pressure ≥21 mm Hg and glaucomatous optic nerve head morphology. All subjects underwent a reliable standard automated perimetry with the HFA and Octopus perimeter, and were imaged with the Cirrus OCT. Receiver-operating characteristic (ROC) curves were plotted for the threshold values and main indices of the HFA and Octopus, the peripapillary retinal nerve fiber layer thicknesses, and the optic nerve head parameters. Sensitivities at 85 and 95% fixed-specificities were also calculated. The best areas under the ROC curves (AUCs) were compared using the DeLong method.ResultsIn the glaucoma group, mean deviation (MD) was -5.42±4.6 dB for HFA and 3.90±3.6 dB for Octopus. The MD of the HFA (0.966; P<0.001), mean sensitivity of the Octopus (0.941; P<0.001), and average cup-to-disc (C/D) ratio measured by the Cirrus OCT (0.958; P<0.001) had the largest AUCs for each test studied. There were no significant differences among them. Sensitivities at 95% fixed-specificity were 82% for pattern standard deviation of the HFA, 81.3% for average C/D ratio of OCT, and 80% for the MD of the Octopus.ConclusionsHFA, Octopus, and Cirrus OCT demonstrated similar diagnostic accuracies for glaucomatous optic neuropathy. Visual field and OCT provide supplementary information and thus these tests are not interchangeable.

Retinal Sensitivity in Patients with Type I Diabetes without Retinopathy or with Minor Retinal Changes.

Objective: To evaluate the ability of short-wavelength automated perimetry (SWAP) for the detection of visual impairment in patients with type I diabetes without retinopathy or with minor retinal vascular changes. Design: Comparative cross-sectional study. Participants: 30 eyes of 30 healthy subjects and 73 eyes of 73 patients with type I diabetes mellitus were studied. Methods: Ophthalmic examination of diabetic patients showed no retinopathy or minimal changes (less than 5 microaneurisms in each eye) with no previous laser treatment. All patients were examined by means of the SWAP 24-2 strategy. Mean Deviation (MD) and Pattern Standard Deviation (PSD) were compared between both groups. Results: There were differences in the clusters of altered points between both groups (p=0.004). SWAP MD was lower in the diabetic group than in the controls (-2.89 dB vs. -0.20 dB, p<0.001). SWAP PSD also differed between both groups (2.50 dB in control group, 3.12 dB in the diabetic group, p=0.003). In the diabetic group, mean period from the onset of diabetes was 12.6±6.7 years and minimal vascular changes were observed in the retina of 18 eyes (24.7%), while 55 had no lesions (75.3%). No differences in SWAP changes were found between patients without and with minimal diabetic retinopathy. Conclusions: Retinal sensitivity assessed by SWAP is depressed in patients with type I diabetes regardless of the presence of retinal vascular changes.

Evaluation of Agreement between HRT III and iVue OCT in Glaucoma and Ocular Hypertension Patients.

Purpose. To determine the agreement between Moorfields Regression Analysis (MRA), Glaucoma Probability Score (GPS) of Heidelberg retinal tomograph (HRT III), and peripapillary nerve fibers thickness by iVue Optical Coherence Tomography (OCT). Methods. 72 eyes with ocular hypertension or primary open angle glaucoma (POAG) were included in the study: 54 eyes had normal visual fields (VF) and 18 had VF damage. All subjects performed achromatic 30° VF by Octopus Program G1X dynamic strategy and were imaged with HRT III and iVue OCT. Sectorial and global MRA, GPS, and OCT parameters were used for the analysis. Kappa statistic was used to assess the agreement between methods. Results. A significant agreement between iVue OCT and GPS for the inferotemporal quadrant (κ: 0.555) was found in patients with abnormal VF. A good overall agreement between GPS and MRA was found in all the eyes tested (κ: 0.511). A good agreement between iVue OCT and MRA was shown in the superonasal (κ: 0.656) and nasal (κ: 0.627) quadrants followed by the superotemporal (κ: 0.602) and inferotemporal (κ: 0.586) sectors in all the studied eyes. Conclusion. The highest percentages of agreement were found per quadrant of the MRA and the iVue OCT confirming that in glaucoma damage starts from the temporal hemiretina.

[Presence of Nuclear Medicine in the Spanish journals of Internal Medicine and other specialties (2000-2009)]. / Presencia de la Medicina Nuclear en revistas españolas de Medicina Interna y de otras especialidades (2000-2009).

OBJECTIVE: This article aims to provide a quantitative and qualitative description of the publications on Nuclear Medicine (NM) in journals from other disciplines, between 2000 and 2009. MATERIAL AND METHODS: A retrospective descriptive study was carried out including the years 2000-2009 in three internal medicine journals (IM) and in three related specialty journals (RS). The criteria used are that some of the authors were located professionally in a Service, Unit or Central MN and/or that the title of the article or at least its content made a reference to some specific aspect of NM. Date of publication, the magazine section, thematic, data of the authors, province and referral hospital were collected. RESULTS: A total of 186 articles were found, 81 in IM journals and 105 in RS. The IM journal articles came from 43 different hospitals. Vall d'Hebron (Barcelona, Spain) was the hospital with the largest volume. Twenty-four provinces were identified, Barcelona and Madrid standing out among them with 20 and 17 articles, respectively. In the RS journals, 59 hospitals/centers had participated, Vall d'Hebron standing out with 51 articles. There were 9 foreign articles. The articles were distributed into 19 provinces, Barcelona and Madrid standing out with 32 papers and 20 papers, respectively. CONCLUSIONS: There are at least twice as many articles in the RS Journals than in the IM ones. «Original¼ articles are the most frequent. The Clinical and Translational Oncology journal in RS and Medicina Clínica in IM stand out with the highest number of articles. No specific topic prevailed.

[Finding of retinal nerve fiber layer hypertrophy in ataxia of Charlevoix-Saguenay patients]. / Hallazgo de hipertrofia de la capa de fibras nerviosas de la retina en pacientes con ataxia de Charlevoix-Saguenay.

PURPOSE/METHODS: To present the neuro-ophthalmology examination in 5 spastic ataxia of Charlevoix-Saguenay (ARSACS) patients showing significant increases in retinal nerve fiber layer (RNFL) thickness. RESULTS/CONCLUSIONS: All patients showed abnormal visual fields, normal optic discs with increased visibility of RNFL in color stereo-photographs, normal examination with Heidelberg Retina Tomography instrument, and moderate to markedly increased RNFL thickness in Cirrus Optical Coherence Tomography evaluation (average thickness: 119 to 220 microns). We found evidence that RNFL hypertrophy may be an alternative funduscopic finding to the hypermyelinated retinal fibers in previous reports. A revision of ARSACS diagnostic criteria, particularly with regard to retinal alterations, is necessary.

Three-dimensional geometries representing the retinal nerve fiber layer in multiple sclerosis, optic neuritis, and healthy eyes.

BACKGROUND: To represent and interpret the three-dimensional (3D) geometry and the distribution of the axonal damage to the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS) compared with healthy subjects. To analyze alterations in RNFL morphology in eyes of MS patients with or without previous episodes of optic neuritis (ON). METHODS: MS patients (n = 122) and age-matched healthy subjects (n = 108) were enrolled. The Spectralis optical coherence tomography system was used to determine the circumpapillary RNFL thickness. The 768 RNFL thickness measurements were used to evaluate thickness measurements in patients with or without antecedent ON and to design a 3D reconstruction of the RNFL thickness representing the mechanobiologic tissue response to neurodegeneration caused by MS and ON episodes. RESULTS: RNFL thickness was decreased in MS patients, and was higher in the MS group with previous ON. Statistical analysis and 3D RNFL reconstruction revealed greater damage to the ganglionar cells in the superonasal RNFL area (101.77 µm in MS vs. 125.47 µm in healthy subjects) and in the inferotemporal RNFL (119.05 µm in MS eyes and 149.26 µm in healthy eyes). CONCLUSIONS: The 3D representation of RNFL thickness based on measurements allows physicians to better observe damage in the temporal areas, especially in patients with previous ON.

[Functional relationship between retinal sensitivity threshold values assessed by standard automated perimetry in glaucoma]. / Relación funcional entre los puntos de sensibilidad retiniana de la perimetría automatizada en el glaucoma.

OBJECTIVE: To study the correlation between the sensitivity threshold values of the different points assessed by the Humphrey visual field analyzer (24-2 Swedish interactive threshold algorithm [SITA] standard strategy) in glaucoma patients. SUBJECTS, MATERIAL AND METHODS: Prospective cross-sectorial study. One-hundred and four eyes of 104 glaucoma patients, defined by the appearance of the optic nerve head, were evaluated. Retinal threshold sensitivity points of standard automated perimetry (SA) with SITA standard 24-2 program were obtained. The upper and the lower hemifields were studied separately. Pearson correlation coefficients were calculated between the mean threshold sensitivity value at each point of the visual hemifield and the rest of the threshold points in the same hemifield. RESULTS: Perimetric correlation maps between retinal threshold sensitivity values in the same hemifield were obtained. Most of the points showed moderate to high correlations (r≥0.65. P<0.001) with neighboring points and distant points in the same hemifield. CONCLUSIONS: There is a functional relationship between neighboring and distant points in Humphrey Visual Field Analyzer (SITA Standard 24-2) in glaucoma patients. This correlation is related to the anatomical arrangement of ganglion cell axons. This fact enables perimetric patterns of glaucoma defects to be obtained.

Short-term changes in the optic nerve head and visual field after trabeculectomy.

UNLABELLED: AIMS OR PURPOSE: To evaluate short-term changes in optic nerve head topography and visual field induced by surgical reduction of intraocular pressure. METHODS: A prospective study was performed on 56 eyes of 56 patients with uncontrolled primary open-angle glaucoma despite maximum medical therapy, which underwent trabeculectomy. Optic nerve head evaluations by means of Heidelberg Retina Tomograph, and visual field tests were performed pre-operatively, and at 3 and 6 months after surgery. Differences in intraocular pressure, visual field indices, and Heidelberg Retina Tomograph parameters were evaluated with the t-test for paired data. A linear regression model was calculated to analyze the relationship between intraocular pressure reduction and visual field changes, and optic nerve head changes. RESULTS: Mean intraocular pressure decreased from 24.4 ± 5.0 mm Hg to 12.1 ± 3.1 mm Hg (month 3, P<0.001), and 10.6 ± 2.8 mm Hg (month 6, P<0.001) after trabeculectomy. Mean retinal nerve fiber layer thickness (baseline, 0.19 ± 0.034; month 3, 0.24 ± 0.039, P=0.05; month 6, 0.21 ± 0.037, P=0.05) showed a statistical significant change compared with baseline values. CONCLUSIONS: In this 6-months study, a significant increase in retinal nerve fiber layer thickness was detected after glaucoma filtration surgery.

[Ability of Heidelberg Retina Tomograph III to predict progression in patients with early glaucoma or suspected primary open-angle glaucoma]. / Valor predictivo del Heidelberg Retina Tomograph III en pacientes con glaucoma incipiente o sospecha de glaucoma.

PURPOSE: To study the ability of Heidelberg Retina Tomography III (HRT 3) measurements to predict perimetry changes in patients with early glaucoma or suspected primary open-angle glaucoma. MATERIAL AND METHODS: One hundred and thirty two eyes with early glaucoma or suspected glaucoma with no changes in basal perimetry were prospectively selected and periodically evaluated over five years. The eyes were divided in two groups depending on the presence or absence of progression (changes in glaucoma perimetry). The association between morphometric parameters and baseline HRT 3 indices, glaucoma probability score (GPS) and Moorefield's Regression Analysis (MRA), and perimetry progression were studied using Cox multivariate regression analyses. Kaplan-Meier curves were used to illustrate the results. RESULTS: Forty-eight eyes (36.36%) showed perimetry progression. Perimetry progression showed higher correlations with the disc area (p = 0.001), the cup area (p = 0.002) and the vertical cup disc area (p = 0.001). Multivariate regression analyses showed that eyes with baseline MRA or baseline GPA changes were at a higher risk of having perimetry abnormalities and a faster progression. CONCLUSIONS: MRA and GPA indices are useful to predict perimetry progression in patients with early primary open-angle glaucoma or suspected glaucoma. These indices can be used as risk markers of functional progression in glaucoma.

[Relationship between standard automated perimetry and retinal nerve fiber layer parameters measured with laser polarimetry]. / Relación entre la perimetría automatizada convencional y los parámetros de la capa de fibras nerviosas de la retina obtenidos con la polarimetría láser.

PURPOSE: To determine the relationship between the structural parameters of the retinal nerve fiber layer (RNFL) obtained by using the scanning laser polarimetry with variable corneal compensation (GDx VCC) and the results of standard automated perimetry (SAP), in normal, ocular hypertensive, preperimetric glaucomas and glaucoma subjects. METHODS: A total of 423 eyes of 423 consecutive subjects were prospectively included in the study and classified depending on the basal intraocular pressure, optic nerve head appearance and SAP results into four groups: 87 normal eyes, 192 ocular hypertensive eyes, 70 preperimetric glaucomas and 74 glaucomatous eyes. Pearson's correlation coefficients, between mean deviation (MD), pattern standard deviation, number of points altered in each quadrant, and number of points altered at different probability levels of SAP and structural parameters of RNFL obtained by using GDx VCC, were calculated in the different diagnostic groups. In the glaucoma group correlations between the 52 points tested by 24- 2 SITA standard and GDx parameters were also calculated. Regression curves were plotted for the strongest correlations. RESULTS: Weak or non-significant correlations were found in the normal, ocular hypertensive and preperimetric glaucoma groups. However, the glaucoma group presented weak to moderate correlations between several GDx VCC parameters and the SAP variables analysed. The strongest correlation was observed between the standard deviation TSNIT and the MD (0.460). CONCLUSIONS: RNFL parameters measured with the GDx VCC presented weak to moderate correlations with the visual field indices and the number of altered points in the glaucoma group.

Diagnostic ability of a linear discriminant function for optic nerve head parameters measured with optical coherence tomography for perimetric glaucoma.

BACKGROUND/AIMS: To calculate and validate a linear discriminant function (LDF) for optical coherence tomography (OCT) to improve the diagnostic ability of isolated optic nerve head (ONH) parameters to discriminate between healthy individuals and glaucoma patients. METHODS: Two independent samples (teaching and validating sets) were prospectively selected. The teaching set (54 normal eyes and 73 glaucoma patients) was used to calculate the LDF. The validating set (70 healthy individuals and 67 glaucoma patients) was used to test the performance of the LDF in an independent population. Receiver operating characteristic (ROC) curves were plotted and compared with the ONH parameters measured using OCT. RESULTS: The optimized function was: LDF=8.204+(2.59xdisc area)-(9.25xhorizontal rim width). The largest areas under the ROC curve were 0.923 and 0.898 for our LDF and the vertical rim area in the validating population respectively. There were no significant differences between the areas. At 95% fixed specificity, the LDF (71.64%) and the vertical rim area (65.67%) yielded the highest sensitivity values. CONCLUSIONS: All ONH parameters obtained with OCT, except disc area, had a good ability to differentiate between healthy and glaucoma individuals. As judged by the area under the ROC curve, the LDF performed better than any single parameter, although statistics did not prove it better than vertical cup/disc ratio or vertical rim area with the number of subjects we studied.

Test-retest variability of intraocular pressure and ocular pulse amplitude for dynamic contour tonometry: a multicentre study.

AIMS: To assess the test-retest variability of intraocular pressure (IOP) and ocular pulse amplitude (OPA) measurements utilising dynamic contour tonometry (DCT) and to evaluate possible influential factors. METHODS: The study included 350 consecutive subjects (175 glaucoma, 175 control; one eye per subject) from seven European centres. IOP was measured once with a Goldmann applanation tonometer (GAT) and twice by DCT (DCT1, DCT2) in a randomised sequence. OPA was also recorded for both DCT measurements. Differences (DCT1-DCT2; OPA1-OPA2; GAT-DCT1; GAT-DCT2) were assessed using the t test. The intraclass coefficient of correlation (ICC) and coefficient of variation (CoV) for DCT and OPA were calculated. RESULTS: DCT1 was 0.6+/-1.6 mm Hg higher than DCT2 (p<0.001); OPA1 was 0.1+/-0.7 mm Hg higher than OPA2 (p=0.02). Results were not influenced by randomisation test order. In both glaucoma and normal subjects, DCT and OPA showed ICC>0.90 and >0.76, and CoV=4.8-5.0% and 10.3-10.5%, respectively. DCT1 and 2 were 2.4+/-2.6 and 1.8+/-2.6 mm Hg higher respectively than GAT (p<0.001). DISCUSSION: DCT test-retest variability was almost perfect for IOP and good for OPA. Tonometry measurements with DCT tended to be overestimated compared with GAT.

Performance of GDx and HRT in the Finnish Evidence-Based Guideline for Open-Angle Glaucoma.

AIM: To compare the performance of Heidelberg retina tomograph (HRT) and scanning laser polarimetry (GDx) with photographic evaluation of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) in the application of the Finnish Evidence-Based Guideline for Open-Angle Glaucoma. METHODS: A total of 41 control participants and 312 patients referred for glaucoma evaluation were included in the study. All the participants underwent ophthalmic evaluation, ONH stereophotography, monochromatic RNFL photography, HRT, optical coherence tomography, and GDx evaluation. Participants were classified on the basis of stereophotographic or imaging device results based by applying the Finnish Guideline. RESULTS: Agreement between the stereophotographic evaluation and that on the basis of the imaging devices was 52.9%. Classification of patients with similar management advice on the basis of these evaluations had 56.4% agreement. The specificity of the Finnish guideline for detecting normal patients was 78% (stereophotography) and 83% (imaging devices). Optic disc size interfered with the diagnosis in patients evaluated using the HRT3 glaucoma probability score. Structural changes were more frequently detected before functional changes. CONCLUSION: The Finnish Evidence-Based Guideline for Open-Angle Glaucoma is useful for classifying normal participants and patients with suspected glaucoma or glaucoma through either conventional stereophotographic evaluation of the neuroretinal structures or with the new imaging devices.