Increased interferon signalling in vaginal tissue of patients with primary Sjögren's syndrome.

OBJECTIVE: Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren's syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from pSS patients compared to non-pSS controls. However, the molecular pathways that drive this inflammation remain unclear. Therefore, the aim of this study was to investigate inflammatory pathway activity in pSS patients' vaginal tissue. METHODS: Vaginal biopsies of eight premenopausal pSS patients with vaginal dryness complaints and seven age-matched non-pSS controls were included. Expression of genes involved in inflammation and tissue homeostasis was measured using Nanostring technology and validated using TaqMan Real-Time PCR. Vaginal tissue sections were stained by immunohistochemistry for Myxovirus resistance protein 1 (MxA) and CD123 (plasmacytoid dendritic cells (pDCs)). RESULTS: The most enriched pathway in vaginal biopsies from pSS patients compared to non-pSS controls was the IFN signalling pathway (p=0.01). Pathway scores for JAK-STAT and Notch signalling were also higher (p=0.01, both pathways). Conversely, TGFß-signalling and angiogenesis pathway scores were lower in pSS (p=0.02 and p=0.04, respectively). Differences in IFN signalling between pSS patients and non-pSS controls were confirmed by PCR and MxA tissue staining. No CD123+ pDCs were detected in vaginal biopsies. Interferon-stimulated gene expression levels correlated positively with CD45+ cell numbers in vaginal biopsies and serum anti-SSA/Ro positivity. CONCLUSION: Upregulation of IFN signalling in vaginal tissue of women with pSS, along with its association with tissue pathology, suggests that IFNs contribute to inflammation of the vaginal wall and potentially also to clinical symptomatology i.e. vaginal dryness.

The neo-open reading frame peptides that comprise the tumor framome are a rich source of neoantigens for cancer immunotherapy.

Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate cancer whole genome and long-read transcript sequencing to identify the collection of novel open reading frame peptides (NOPs) expressed in tumors, termed the framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe an uncharacterized class of hidden NOPs, which derive from structural genomic variants involving an upstream protein coding gene driving expression and translation of non-coding regions of the genome downstream of a rearrangement breakpoint. NOPs represent a vast amount of possible neoantigens particularly in tumors with many (complex) structural genomic variants and a low number of missense mutations. We show that NOPs are immunogenic and epitopes derived from NOPs can bind to MHC class I molecules. Finally, we provide evidence for the presence of memory T-cells specific for hidden NOPs in lung cancer patient peripheral blood.

Pain is what hurts: An exploration of perception and management of pain in peripheral blood stem cell donors.

BACKGROUND: Pain is a side effect of Granulocyte-Colony Stimulating Factor (G-CSF) administration. This prospective study investigates various aspects including pain perception occurring in Peripheral Blood Stem Cell (PBSC) donors. MATERIALS AND METHODS: Related and unrelated PBSC donors were prospectively studied. Donors recorded pain symptoms during the four-day period of G-CSF administration using the McGill Pain Questionnaire, a Visual Analog Scale and a pain diary. RESULTS: There were 208 donors included, 102 (49%) related and 106 (51%) unrelated donors. Ninety-two percent of all reported the occurrence of pain. Moderate or severe pain was reported by 52%. No differences were found between related and unrelated donors. Pain occurred more often in females (p = 0.035). Relatively young donors (age 16-30 years) more frequently showed to have pain in comparison to older donors (>50 years) (p = 0.006). Musculoskeletal pain was most frequently distributed in the gluteal and lower back region (65-71%). Irrespective of the pain location, pain was most often described as nagging, annoying, however tolerable. Donors experiencing pain most on days of G-CSF administration, most frequently occurring during relaxation or at night. Sleep-mode was often affected. The use of paracetamol (acetaminophen) was sufficient for all but one donor. CONCLUSION: This is the first study to describe different aspects of pain associated with G-CSF administration in donors. Although the observed pain was tolerable, it should never be neglected. Knowledge derived from this study is of use for staff members involved in donor information and care management.

Intrinsic Water Transport in Moisture-Capturing Hydrogels.

Moisture-capturing hydrogels have emerged as attractive sorbent materials capable of converting ambient humidity into liquid water. Recent works have demonstrated exceptional water capture capabilities of hydrogels while simultaneously exploring different strategies to accelerate water capture and release. However, on the material level, an understanding of the intrinsic transport properties of moisture-capturing hydrogels is currently missing, which hinders their rational design. In this work, we combine absorption and desorption experiments of macroscopic hydrogel samples in pure vapor with models of water diffusion in the hydrogels to demonstrate the first measurements of the intrinsic water diffusion coefficient in hydrogel-salt composites. Based on these insights, we pattern hydrogels with micropores to significantly decrease the required absorption and desorption times by 19% and 72%, respectively, while reducing the total water capacity of the hydrogel by only 4%. Thereby, we provide an effective strategy toward hydrogel material optimization, with a particular significance in pure-vapor environments.

External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.

BACKGROUND: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands). METHODS: Aliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18-21, and KRAS exon 2-3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance. RESULTS: A broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of >0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately. CONCLUSIONS: Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine.

Identification of direct connections between the dura and the brain.

The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance1,2. How the arachnoid barrier balances separation and communication is poorly understood. Here, using transcriptomic data, we developed transgenic mice to examine specific anatomical structures that function as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, magnetic resonance imaging tracers transit along bridging veins in a similar manner to access the subarachnoid space. Notably, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also enable cellular trafficking, representing a route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that link the central nervous system with the dura and its immunological diversity and waste clearance systems.

A 2D ferroelectric vortex pattern in twisted BaTiO3 freestanding layers.

The wealth of complex polar topologies1-10 recently found in nanoscale ferroelectrics results from a delicate balance between the intrinsic tendency of the materials to develop a homogeneous polarization and the electric and mechanical boundary conditions imposed on them. Ferroelectric-dielectric interfaces are model systems in which polarization curling originates from open circuit-like electric boundary conditions, to avoid the build-up of polarization charges through the formation of flux-closure11-14 domains that evolve into vortex-like structures at the nanoscale15-17 level. Although ferroelectricity is known to couple strongly with strain (both homogeneous18 and inhomogeneous19,20), the effect of mechanical constraints21 on thin-film nanoscale ferroelectrics has been comparatively less explored because of the relative paucity of strain patterns that can be implemented experimentally. Here we show that the stacking of freestanding ferroelectric perovskite layers with controlled twist angles provides an opportunity to tailor these topological nanostructures in a way determined by the lateral strain modulation associated with the twisting. Furthermore, we find that a peculiar pattern of polarization vortices and antivortices emerges from the flexoelectric coupling of polarization to strain gradients. This finding provides opportunities to create two-dimensional high-density vortex crystals that would enable us to explore previously unknown physical effects and functionalities.

From imaging to precision: low cost and accurate determination of stereotactic coordinates for brain surgery Sapajus apella using MRI.

The capuchin monkey (Sapajus apella), a New World monkey species, exhibits prominent characteristics that make it an ideal model for neuroscience research. These characteristics include its phylogenetic traits, telencephalization coefficient, anatomical structures and pathways, genetic profile, immune responses, cognitive abilities, and complex behavioral repertoires. Traditionally, methodologies for stereotactic neurosurgery in research models have relied on the use of brain atlases. However, this approach can lead to errors due to the considerable variation in brain size and shape among individual monkeys. To address this issue, we developed a protocol for deriving individual coordinates for each monkey using a straightforward and relatively inexpensive method involving MRI imaging. Our protocol utilizes a specially designed, 3D-printed stereotactic head-holder that is safe to use with an MR magnet, non-invasive placement of fiducial markers, and post-processing with open-source software. This approach enhances MRI data visualization, improves anatomical targeting, and refines the design of neurosurgical experiments. Our technique could also prove beneficial in other areas of neuroscience research that require accurate calculation of stereotaxic coordinates. Furthermore, it could be useful for other nonhuman primate species for which brain atlases are typically unavailable.

Delayed melatonin circadian timing, lower melatonin output, and sleep disruptions in myopic, or short-sighted, children.

STUDY OBJECTIVES: This study investigated the differences in melatonin circadian timing and output, sleep characteristics, and cognitive function in myopic and non-myopic (or emmetropic) children, aged 8-15 years. METHODS: Twenty-six myopes (refractive error [mean ±â€…standard error mean] -2.06 ±â€…0.23 diopters) and 19 emmetropes (-0.06 ±â€…0.04 diopters), aged 11.74 ±â€…2.31 years were recruited. Circadian timing was assessed using salivary dim-light melatonin onset (DLMO), collected half-hourly for 7 hours, beginning 5 hours before and finishing 2 hours after individual average sleep onset in a sleep laboratory. Nocturnal melatonin output was assessed via aMT6s levels from urine voids collected from 05:30 pm to 8:00 am the following morning. Actigraphy-derived objective sleep timing were acquired for a week prior to the sleep laboratory visit. Cognitive assessments of sustained attention (using psychomotor vigilance task [PVT]) and working memory (using digit spans) were performed on the night of sleep laboratory. RESULTS: Myopic children (9:07 pm ±â€…14 minutes) exhibited a DLMO phase-delay of 1 hour 8 minutes compared to emmetropes (7:59 pm ±â€…13 minutes), p = 0.002. aMT6s melatonin levels were significantly lower among myopes (18.70 ±â€…2.38) than emmetropes (32.35 ±â€…6.93, p = 0.001). Myopes also exhibited significantly delayed sleep onset, delayed wake-up time, poor and reduced sleep, and more evening-type diurnal preference than emmetropes (all p < 0.05). Finally, myopes showed a slower reaction time in the PVT (p < 0.05), but not digit span tasks at night. CONCLUSIONS: These findings suggest a potential association between circadian rhythm dysfunction and myopia in children.

Phase-Driving Hole Spin Qubits.

The spin-orbit interaction in spin qubits enables spin-flip transitions, resulting in Rabi oscillations when an external microwave field is resonant with the qubit frequency. Here, we introduce an alternative driving mechanism mediated by the strong spin-orbit interactions in hole spin qubits, where a far-detuned oscillating field couples to the qubit phase. Phase-driving at radio frequencies, orders of magnitude slower than the microwave qubit frequency, induces highly nontrivial spin dynamics, violating the Rabi resonance condition. By using a qubit integrated in a silicon fin field-effect transistor, we demonstrate a controllable suppression of resonant Rabi oscillations and their revivals at tunable sidebands. These sidebands enable alternative qubit control schemes using global fields and local far-detuned pulses, facilitating the design of dense large-scale qubit architectures with local qubit addressability. Phase-driving also decouples Rabi oscillations from noise, an effect due to a gapped Floquet spectrum and can enable Floquet engineering high-fidelity gates in future quantum processors.

Skull bone marrow channels as immune gateways to the central nervous system.

Decades of research have characterized diverse immune cells surveilling the CNS. More recently, the discovery of osseous channels (so-called 'skull channels') connecting the meninges with the skull and vertebral bone marrow has revealed a new layer of complexity in our understanding of neuroimmune interactions. Here we discuss our current understanding of skull and vertebral bone marrow anatomy, its contribution of leukocytes to the meninges, and its surveillance of the CNS. We explore the role of this hematopoietic output on CNS health, focusing on the supply of immune cells during health and disease.

Effect of Fe-O ReaxFF on Liquid Iron Oxide Properties Derived from Reactive Molecular Dynamics.

As iron powder nowadays attracts research attention as a carbon-free, circular energy carrier, molecular dynamics (MD) simulations can be used to better understand the mechanisms of liquid iron oxidation at elevated temperatures. However, prudence must be practiced in the selection of a reactive force field. This work investigates the influence of currently available reactive force fields (ReaxFFs) on a number of properties of the liquid iron-oxygen (Fe-O) system derived (or resulting) from MD simulations. Liquid Fe-O systems are considered over a range of oxidation degrees ZO, which represents the molar ratio of O/(O + Fe), with 0 < ZO < 0.6 and at a constant temperature of 2000 K, which is representative of the combustion temperature of micrometric iron particles burning in air. The investigated properties include the minimum energy path, system structure, (im)miscibility, transport properties, and the mass and thermal accommodation coefficients. The properties are compared to experimental values and thermodynamic calculation results if available. Results show that there are significant differences in the properties obtained with MD using the various ReaxFF parameter sets. Based on the available experimental data and equilibrium calculation results, an improved ReaxFF is required to better capture the properties of a liquid Fe-O system.

Advances in Folic Acid Biosensors and Their Significance in Maternal, Perinatal, and Paediatric Preventive Medicine.

Auxotrophic primates like human beings rely on exogenous dietary vitamin B9 supplementation to meet their metabolic demands. Folates play a crucial role in nucleotide synthesis and DNA methylation. Maternal folate deficiency causes several pregnancy-related complications, perinatal defects, and early childhood cognitive impairments. New evidence suggests excess FA is a potential risk factor resulting in unfavourable genomic and epigenomic alterations. Thus, it is essential to revisit the need to consistently monitor maternal folate levels during pregnancy. Yet, to date, no point-of-care folate-monitoring biosensor is commercially available. Here, we critically appraise the advances in folate biosensors to understand the translational gaps in biosensor design. Further, our review sheds light on the potential role of folate biosensors in strengthening maternal, perinatal, and child healthcare.

Detection and Monitoring of Tumor-Derived Mutations in Circulating Tumor DNA Using the UltraSEEK Lung Panel on the MassARRAY System in Metastatic Non-Small Cell Lung Cancer Patients.

Analysis of circulating tumor DNA (ctDNA) is a potential minimally invasive molecular tool to guide treatment decision-making and disease monitoring. A suitable diagnostic-grade platform is required for the detection of tumor-specific mutations with high sensitivity in the circulating cell-free DNA (ccfDNA) of cancer patients. In this multicenter study, the ccfDNA of 72 patients treated for advanced-stage non-small cell lung cancer (NSCLC) was evaluated using the UltraSEEK® Lung Panel on the MassARRAY® System, covering 73 hotspot mutations in EGFR, KRAS, BRAF, ERBB2, and PIK3CA against mutation-specific droplet digital PCR (ddPCR) and routine tumor tissue NGS. Variant detection accuracy at primary diagnosis and during disease progression, and ctDNA dynamics as a marker of treatment efficacy, were analyzed. A multicenter evaluation using reference material demonstrated an overall detection rate of over 90% for variant allele frequencies (VAFs) > 0.5%, irrespective of ccfDNA input. A comparison of UltraSEEK® and ddPCR analyses revealed a 90% concordance. An 80% concordance between therapeutically targetable mutations detected in tumor tissue NGS and ccfDNA UltraSEEK® analysis at baseline was observed. Nine of 84 (11%) tumor tissue mutations were not covered by UltraSEEK®. A decrease in ctDNA levels at 4-6 weeks after treatment initiation detected with UltraSEEK® correlated with prolonged median PFS (46 vs. 6 weeks; p < 0.05) and OS (145 vs. 30 weeks; p < 0.01). Using plasma-derived ccfDNA, the UltraSEEK® Lung Panel with a mid-density set of the most common predictive markers for NSCLC is an alternative tool to detect mutations both at diagnosis and during disease progression and to monitor treatment response.

Circadian aspects in the aetiology and pathophysiology of insomnia.

Because the endogenous circadian pacemaker is a very strong determinant of alertness/sleep propensity across the 24 h period, its mistiming may contribute to symptoms of insomnia (e.g., difficulties initiating sleep and maintaining sleep) and to the development of insomnia disorder. Despite the separation of insomnia and circadian rhythm disorders in diagnostic nosology implying independent pathophysiology, there is considerable evidence of co-morbidity and interaction between them. Sleep onset insomnia is associated with later timed circadian rhythms and can be treated with morning bright light to shift rhythms to an earlier timing. It is also possible that the causal link may go in both directions and that having a delayed circadian rhythm can result in enough experiences of delayed sleep onset to lead to some conditioned insomnia or insomnia disorder further exacerbating a delayed circadian rhythm. Early morning awakening insomnia is associated with an advanced circadian phase (early timing) and can be treated with evening bright light resulting in a delay of rhythms and an improved ability to sleep later in the morning and to obtain more sleep. There is some evidence suggesting that sleep maintenance insomnia is associated with a blunted amplitude of circadian rhythm that may be treated with increased regularity of sleep and light exposure timing. However, this is an insomnia phenotype that requires considerably more circadian research as well as further insomnia clinical research with the other insomnia phenotypes incorporating circadian timing measures and treatments.

Radiomic signatures from T2W and DWI MRI are predictive of tumour hypoxia in colorectal liver metastases.

BACKGROUND: Tumour hypoxia is a negative predictive and prognostic biomarker in colorectal cancer typically assessed by invasive sampling methods, which suffer from many shortcomings. This retrospective proof-of-principle study explores the potential of MRI-derived imaging markers in predicting tumour hypoxia non-invasively in patients with colorectal liver metastases (CLM). METHODS: A single-centre cohort of 146 CLMs from 112 patients were segmented on preoperative T2-weighted (T2W) images and diffusion-weighted imaging (DWI). HIF-1 alpha immunohistochemical staining index (high/low) was used as a reference standard. Radiomic features were extracted, and machine learning approaches were implemented to predict the degree of histopathological tumour hypoxia. RESULTS: Radiomic signatures from DWI b200 (AUC = 0.79, 95% CI 0.61-0.93, p = 0.002) and ADC (AUC = 0.72, 95% CI 0.50-0.90, p = 0.019) were significantly predictive of tumour hypoxia. Morphological T2W TE75 (AUC = 0.64, 95% CI 0.42-0.82, p = 0.092) and functional DWI b0 (AUC = 0.66, 95% CI 0.46-0.84, p = 0.069) and b800 (AUC = 0.64, 95% CI 0.44-0.82, p = 0.071) images also provided predictive information. T2W TE300 (AUC = 0.57, 95% CI 0.33-0.78, p = 0.312) and b = 10 (AUC = 0.53, 95% CI 0.33-0.74, p = 0.415) images were not predictive of tumour hypoxia. CONCLUSIONS: T2W and DWI sequences encode information predictive of tumour hypoxia. Prospective multicentre studies could help develop and validate robust non-invasive hypoxia-detection algorithms. CRITICAL RELEVANCE STATEMENT: Hypoxia is a negative prognostic biomarker in colorectal cancer. Hypoxia is usually assessed by invasive sampling methods. This proof-of-principle retrospective study explores the role of AI-based MRI-derived imaging biomarkers in non-invasively predicting tumour hypoxia in patients with colorectal liver metastases (CLM).

Formalin-Fixed, Paraffin-Embedded-Targeted Locus Capture: A Next-Generation Sequencing Technology for Accurate DNA-Based Gene Fusion Detection in Bone and Soft Tissue Tumors.

Chromosomal rearrangements are important drivers in cancer, and their robust detection is essential for diagnosis, prognosis, and treatment selection, particularly for bone and soft tissue tumors. Current diagnostic methods are hindered by limitations, including difficulties with multiplexing targets and poor quality of RNA. A novel targeted DNA-based next-generation sequencing method, formalin-fixed, paraffin-embedded-targeted locus capture (FFPE-TLC), has shown advantages over current diagnostic methods when applied on FFPE lymphomas, including the ability to detect novel rearrangements. We evaluated the utility of FFPE-TLC in bone and soft tissue tumor diagnostics. FFPE-TLC sequencing was successfully applied on noncalcified and decalcified FFPE samples (n = 44) and control samples (n = 19). In total, 58 rearrangements were identified in 40 FFPE tumor samples, including three previously negative samples, and none was identified in the FFPE control samples. In all five discordant cases, FFPE-TLC could identify gene fusions where other methods had failed due to either detection limits or poor sample quality. FFPE-TLC achieved a high specificity and sensitivity (no false positives and negatives). These results indicate that FFPE-TLC is applicable in cancer diagnostics to simultaneously analyze many genes for their involvement in gene fusions. Similar to the observation in lymphomas, FFPE-TLC is a good DNA-based alternative to the conventional methods for detection of rearrangements in bone and soft tissue tumors.

Breast DWI Analyzed Before and After Gadolinium Contrast Administration-An Intrapatient Analysis on 1.5 T and 3.0 T.

OBJECTIVES: Diffusion-weighted magnetic resonance imaging (MRI) is gaining popularity as an addition to standard dynamic contrast-enhanced breast MRI. Although adding diffusion-weighted imaging (DWI) to the standard protocol design would require increased scanning-time, implementation during the contrast-enhanced phase could offer a multiparametric MRI protocol without any additional scanning time. However, gadolinium within a region of interest (ROI) might affect assessments of DWI. This study aims to determine if acquiring DWI postcontrast, incorporated in an abbreviated MRI protocol, would statistically significantly affect lesion classification. In addition, the effect of postcontrast DWI on breast parenchyma was studied. MATERIALS AND METHODS: Screening or preoperative MRIs (1.5 T/3 T) were included for this study. Diffusion-weighted imaging was acquired with single-shot spin echo-echo planar imaging before and at approximately 2 minutes after gadoterate meglumine injection. Apparent diffusion coefficients (ADCs) based on 2-dimensional ROIs of fibroglandular tissue, as well as benign and malignant lesions at 1.5 T/3.0 T, were compared with a Wilcoxon signed rank test. Diffusivity levels were compared between precontrast and postcontrast DWI with weighted κ. An overall P ≤ 0.05 was considered statistically significant. RESULTS: No significant changes were observed in ADC mean after contrast administration in 21 patients with 37 ROI of healthy fibroglandular tissue and in the 93 patients with 93 (malignant and benign) lesions. This effect remained after stratification on B 0 . In 18% of all lesions, a diffusion level shift was observed, with an overall weighted κ of 0.75. CONCLUSIONS: This study supports incorporating DWI at 2 minutes postcontrast when ADC is calculated based on b150-b800 with 15 mL 0.5 M gadoterate meglumine in an abbreviated multiparametric MRI protocol without requiring extra scan time.

Papiledema como posible signo guía en el diagnóstico del síndrome periódico asociado a la criopirina: a propósito de un caso / Papilledema as a possible key sign for diagnosis of cryopyrin-associated periodic syndromes (CAPS): A case report

El síndrome periódico asociado a la criopirina es una enfermedad rara y probablemente infradiagnosticada. Se presenta con manifestaciones sistémicas, entre ellas oftalmológicas, muy diversas, por lo que su diagnóstico supone un reto para el clínico. Presentamos el caso de una niña de 4 años en la que la identificación de papiledema en el examen oftalmológico constituyó el signo guía para el diagnóstico de síndrome periódico asociado a la criopirina. Pretendemos así concienciar sobre esta enfermedad de graves implicaciones y cuyo diagnóstico precoz resulta esencial para los afectados, para que sea tenido en cuenta con mayor frecuencia como diagnóstico diferencial (AU)

Cryopyrin-associated periodic syndrome is a rare and probably underdiagnosed disease. It presents with various systemic manifestations, including ophthalmological, making its diagnosis a challenge for the clinician. We present the case of a 4-year-old girl for which the identification of papilledema in the ophthalmological examination was the key sign for the diagnosis of cryopyrin-associated periodic syndrome. Our aim is to raise awareness of this syndrome with serious implications for affected patients, so that it is taken into account more frequently as a differential diagnosis, allowing an early diagnosis (AU)