A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.

The cool brown dwarf Gliese 229 B is a close binary.

Owing to their similarities with giant exoplanets, brown dwarf companions of stars provide insights into the fundamental processes of planet formation and evolution. From their orbits, several brown dwarf companions are found to be more massive than theoretical predictions given their luminosities and the ages of their host stars1-3. Either the theory is incomplete or these objects are not single entities. For example, they could be two brown dwarfs each with a lower mass and intrinsic luminosity1,4. The most problematic example is Gliese 229 B (refs. 5,6), which is at least 2-6 times less luminous than model predictions given its dynamical mass of 71.4 ± 0.6 Jupiter masses (MJup) (ref. 1). We observed Gliese 229 B with the GRAVITY interferometer and, separately, the CRIRES+ spectrograph at the Very Large Telescope. Both sets of observations independently resolve Gliese 229 B into two components, Gliese 229 Ba and Bb, settling the conflict between theory and observations. The two objects have a flux ratio of 0.47 ± 0.03 at a wavelength of 2 µm and masses of 38.1 ± 1.0 and 34.4 ± 1.5 MJup, respectively. They orbit each other every 12.1 days with a semimajor axis of 0.042 astronomical units (AU). The discovery of Gliese 229 BaBb, each only a few times more massive than the most massive planets, and separated by 16 times the Earth-moon distance, raises new questions about the formation and prevalence of tight binary brown dwarfs around stars.

Circulating galectin-1 delineates response to bevacizumab in melanoma patients and reprograms endothelial cell biology.

Blockade of vascular endothelial growth factor (VEGF) signaling with bevacizumab, a humanized anti-VEGF monoclonal antibody (mAb), or with receptor tyrosine kinase inhibitors, has improved progression-free survival and, in some indications, overall survival across several types of cancers by interrupting tumor angiogenesis. However, the clinical benefit conferred by these therapies is variable, and tumors from treated patients eventually reinitiate growth. Previously we demonstrated, in mouse tumor models, that galectin-1 (Gal1), an endogenous glycan-binding protein, preserves angiogenesis in anti-VEGF-resistant tumors by co-opting the VEGF receptor (VEGFR)2 signaling pathway in the absence of VEGF. However, the relevance of these findings in clinical settings is uncertain. Here, we explored, in a cohort of melanoma patients from AVAST-M, a multicenter, open-label, randomized controlled phase 3 trial of adjuvant bevacizumab versus standard surveillance, the role of circulating plasma Gal1 as part of a compensatory mechanism that orchestrates endothelial cell programs in bevacizumab-treated melanoma patients. We found that increasing Gal1 levels over time in patients in the bevacizumab arm, but not in the observation arm, significantly increased their risks of recurrence and death. Remarkably, plasma Gal1 was functionally active as it was able to reprogram endothelial cell biology, promoting migration, tubulogenesis, and VEGFR2 phosphorylation. These effects were prevented by blockade of Gal1 using a newly developed fully human anti-Gal1 neutralizing mAb. Thus, using samples from a large-scale clinical trial from stage II and III melanoma patients, we validated the clinical relevance of Gal1 as a potential mechanism of resistance to bevacizumab treatment.

Clinical validation of a capnodynamic method for measuring end-expiratory lung volume in critically ill patients.

RATIONALE: End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ventilation induced lung injury. Clinical measurement of EELV however, remains difficult. OBJECTIVE: Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO2) kinetics for measuring EELV in mechanically ventilated critically-ill patients. METHODS: Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO2 values, the latter accounting for the amount of CO2 dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO2 was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO2 were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO2 tended to overestimate EELVCT with a correlation r2 0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO2 to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO2 with functional EELVCT with a r2 of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients. CONCLUSION: In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO2 for extra-alveolar CO2 content when compared with CT estimated volume. If confirmed in further validations EELVCO2 may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients. TRIAL REGISTRATION: clinicaltrials.gov (NCT04045262).

Genomic analysis of inbreeding level, kinship and breed relationships in Creole cattle from South America.

The conservation of animal genetic resources refers to measures taken to prevent the loss of genetic diversity in livestock populations, including the protection of breeds from extinction. Creole cattle populations have suffered a drastic reduction in recent decades owing to absorbent crosses or replacement with commercial breeds of European or Indian origin. Genetic characterization can serve as a source of information for conservation strategies to maintain genetic variation. The objective of this work was to evaluate the levels of inbreeding and kinship through the use of genomic information. A total of 903 DNAs from 13 cattle populations from Argentina, Bolivia and Uruguay were genotyped using an SNP panel of 48 K. Also, a dataset of 76 K SNPs from Peruvian Creole was included. Two inbreeding indices (FROH and Fhat2) and kinship relationships were calculated. In addition, effective population size (Ne), linkage disequilibrium, population composition and phylogenetic relationships were estimated. In Creole cattle, FROH ranged from 0.14 to 0.03, and Fhat2 was close to zero. The inferred Ne trends exhibited a decline toward the present for all populations, whereas Creole cattle presented a lower magnitude of Ne than foreign breeds. Cluster analysis clearly differentiated the taurine and Zebu components (K2) and showed that Bolivian Creole cattle presented Zebu gene introgression. Despite the population reduction, Creole populations did not present extreme values of consanguinity and kinship and maintain high levels of genetic diversity. The information obtained in this work may be useful for planning conservation programmes for these valuable local animal genetic resources.

Allergic contact dermatitis in adults with and without atopic dermatitis: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC).

BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. OBJECTIVES: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. METHODS: We analysed two groups (AD and non-AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. RESULTS: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non-AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age-adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61-0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non-AD individuals. CONCLUSIONS: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non-AD population, except for a negative relationship between AD and sensitisation to nickel sulphate.

Malignant transformation of oral lichen planus: where are we now?

BACKGROUND: Oral lichen planus (OLP) is a very prevalent disease whose main clinical feature is the appearance of white hyperkeratotic reticular lesions, which may or may not be accompanied by erosive and/or atrophic lesions, among others. One of the most relevant aspects of the process is its current consideration as an oral potentially malignant disorder (OPMD), although this is currently the subject of considerable controversy. MATERIAL AND METHODS: A review of the literature was carried out in order to critically analyze the controversies surrounding the consideration of OLP as an OPMD, where they originate from and the available evidence that has led to the conclusion that OLP patients are at risk of developing oral cancer. RESULTS: The controversies over the definitive acceptance of OLP as an OPMD were classified as controversies related to the lack of widely accepted diagnostic criteria for OLP; controversies related to histopathological aspects of OLP and the presence of epithelial dysplasia as a diagnostic exclusion criterion; and controversies related to clinical aspects of OLP (which in turn were subclassified into: controversies on how to interpret reticular lesions in OLP, on the nature of the white plaques that appear in OLP; on the changing character of reticular lesions in OLP; and on the criteria for accepting a case as a true malignant OLP). Furthermore, evidence to justify the acceptance of OLP as an OPMD was in depth reviewed, including the molecular evidence, evidence from research studies with the highest evidence design -systematic reviews and meta-analyses-, and evidence from case series reporting strong results. CONCLUSIONS: This paper presents the reasons for the controversies as well as the evidence that allows us to accept that OLP behaves as an OPMD.

Implications of p53 protein upregulation in oral lichen planus: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis qualitatively and quantitatively analyzes the current evidence on the implications of p53 upregulation in oral lichen planus (OLP) assessed by immunohistochemical techniques, in order to identify molecular mechanisms involved in the behavior of OLP as an oral potentially malignant disorder. MATERIAL AND METHODS: We searched MEDLINE/PubMed, Embase, Web of Science and Scopus for studies published before February-2024. We critically assessed the methodological quality of primary-level studies and performed meta-analyses. RESULTS: Twenty-four individual studies met the inclusion criteria, comprising 721 OLP samples, in which the expression of p53 was analyzed through immunohistochemistry. Most OLP displayed p53 protein upregulation (pooled proportion [PP]= 66.76%, 95%CI=54.84-77.76). Regarding the magnitude of association analysis, oral squamous cell carcinoma (OSCC) cases showed a significantly higher frequency according to p53 expression in comparison to OLP (OR=2.79, 95%CI=1.84-4.24; p<0.001); while, OLP exhibited a significantly higher frequency for p53 expression in comparison to healthy controls (OR=5.70, 95%CI=2.90-11.19; p<0.001). CONCLUSIONS: In conclusion, the present study demonstrates the frequent p53 protein upregulation in patients with OLP, which is probably indicating an antitumor response in an epithelium whose cells are under cellular stress and at risk of cancer.

Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends. / Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias.

BACKGROUND: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. OBJECTIVES: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. METHODS: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). RESULTS: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. CONCLUSIONS: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study. / Condicionantes de acceso a nuevos medicamentos dermatológicos en España: resultados del proyecto EQUIDAD.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

Genes with 5' terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein.

Viruses rely on the host translation machinery to synthesize their own proteins. Consequently, they have evolved varied mechanisms to co-opt host translation for their survival. SARS-CoV-2 relies on a nonstructural protein, Nsp1, for shutting down host translation. However, it is currently unknown how viral proteins and host factors critical for viral replication can escape a global shutdown of host translation. Here, using a novel FACS-based assay called MeTAFlow, we report a dose-dependent reduction in both nascent protein synthesis and mRNA abundance in cells expressing Nsp1. We perform RNA-seq and matched ribosome profiling experiments to identify gene-specific changes both at the mRNA expression and translation levels. We discover that a functionally coherent subset of human genes is preferentially translated in the context of Nsp1 expression. These genes include the translation machinery components, RNA binding proteins, and others important for viral pathogenicity. Importantly, we uncovered a remarkable enrichment of 5' terminal oligo-pyrimidine (TOP) tracts among preferentially translated genes. Using reporter assays, we validated that 5' UTRs from TOP transcripts can drive preferential expression in the presence of Nsp1. Finally, we found that LARP1, a key effector protein in the mTOR pathway, may contribute to preferential translation of TOP transcripts in response to Nsp1 expression. Collectively, our study suggests fine-tuning of host gene expression and translation by Nsp1 despite its global repressive effect on host protein synthesis.

Performance assessment of an equine metabolomics model for screening a range of anabolic agents.

INTRODUCTION: Despite their ban, Anabolic Androgenic Steroids (AAS) are considered as the most important threat for equine doping purposes. In the context of controlling such practices in horse racing, metabolomics has emerged as a promising alternative strategy to study the effect of a substance on metabolism and to discover new relevant biomarkers of effect. Based on the monitoring of 4 metabolomics derived candidate biomarkers in urine, a prediction model to screen for testosterone esters abuse was previously developed. The present work focuses on assessing the robustness of the associated method and define its scope of application. MATERIALS AND METHODS: Several hundred urine samples were selected from 14 different horses of ethically approved administration studies involving various doping agents' (AAS, SARMS, ß-agonists, SAID, NSAID) (328 urine samples). In addition, 553 urine samples from untreated horses of doping control population were included in the study. Samples were characterized with the previously described LC-HRMS/MS method, with the objective of assessing both its biological and analytical robustness. RESULTS: The study concluded that the measurement of the 4 biomarkers involved in the model was fit for purpose. Further, the classification model confirmed its effectiveness in screening for testosterone esters use; and it demonstrated its ability to screen for the misuse of other anabolic agents, allowing the development of a global screening tool dedicated to this class of substances. Finally, the results were compared to a direct screening method targeting anabolic agents demonstrating complementary performances of traditional and omics approaches in the screening of anabolic agents in horses.

Real-world effectiveness and safety of stereotactic body radiotherapy for liver metastases with different respiratory motion management techniques.

PURPOSE: Stereotactic body radiotherapy (SBRT) has been firmly established as a treatment choice for patients with oligometastases, as it has demonstrated both safety and efficacy by consistently achieving high rates of local control. Moreover, it offers potential survival benefits for carefully selected patients in real-world clinical settings. METHODS: Between January 2008 and May 2020, a total of 149 patients (with 414 liver metastases) received treatment. The Active Breathing Coordinator device was used for 68 patients, while respiratory gating was used for 65 and abdominal compression was used for 16 patients. The most common histological finding was colorectal adenocarcinoma, with 37.6% of patients having three or more metastases, and 18% having two metastases. The prescribed dose ranged from 36 to 60 Gy, delivered in 3-5 fractions. RESULTS: Local control rates at 2 and 3 years were 76.1% and 61.2%, respectively, with no instances of local recurrence after 3 years. Factors negatively impacting local control included colorectal histology, lower prescribed dose, and the occurrence of new liver metastases. The median overall survival from SBRT was 32 months, with the presence of metastases outside the liver and the development of new liver metastases after SBRT affecting survival. The median disease-free survival was 10 months. No substantial differences in both local control and survival were observed between the respiratory motion control techniques employed. Treatment tolerance was excellent, with only one patient experiencing acute grade IV thrombocytopenia and two patients suffering from ≥ grade II chronic toxicity. CONCLUSION: For radical management of single or multiple liver metastases, SBRT is an effective and well-tolerated treatment option. Regardless of the technology employed, experienced physicians can achieve similarly positive outcomes. However, additional studies are required to elucidate prognostic factors that can facilitate improved patient selection.

Dynamics of Nucleation in Solids: A Self-Consistent Phase Field Approach.

We derive a phase field method for computing rigorously the nucleation rate and the incubation time from the sole knowledge of the free energy of the system in the metastable regime. Our theoretical results are assessed against experimental data relative to demixing of an iron-chromium alloy. Our work clarifies the notions of nucleation rate and incubation time extensively used in classical nucleation theory (CNT) processes in solids. Our work thus emerges as an alternative to CNT but of more general applicability, and enables us to model the nucleation process across the whole range of condition encountered in first order phase transitions, an aspect in which CNT fails.

Cavity Optomechanics with Anderson-Localized Optical Modes.

Confining photons in cavities enhances the interaction between light and matter. In cavity optomechanics, this enables a wealth of phenomena ranging from optomechanically induced transparency to macroscopic objects cooled to their motional ground state. Previous work in cavity optomechanics employed devices where ubiquitous structural disorder played no role beyond perturbing resonance frequencies and quality factors. More generally, the interplay between disorder, which must be described by statistical physics, and optomechanical effects has thus far been unexplored. Here, we demonstrate how sidewall roughness in air-slot photonic-crystal waveguides can induce sufficiently strong backscattering of slot-guided light to create Anderson-localized modes with quality factors as high as half a million and mode volumes estimated to be below the diffraction limit. We observe how the interaction between these disorder-induced optical modes and in-plane mechanical modes of the slotted membrane is governed by a distribution of coupling rates, which can exceed g_{o}/2π∼200 kHz, leading to mechanical amplification up to self sustained oscillations via optomechanical backaction. Our Letter constitutes the first steps towards understanding optomechanics in the multiple-scattering regime and opens new perspectives for exploring complex systems with a multitude of mutually coupled degrees of freedom.

Metallothionein expression in the central nervous system in response to chronic heavy metal exposure: possible neuroprotective mechanism.

It has been reported that volcanoes release several tonnes of mercury per year among other heavy metals through eruptions, fumaroles, or diffuse soil degassing. Since a high percentage of the world's population lives in the vicinity of an active volcano, the aim of this study is to evaluate the accumulation of these metals in the central nervous system and the presence of cellular mechanisms of heavy metal detoxification such as metallothioneins. To carry out this study, wild mice (Mus musculus) chronically exposed to an active volcanic environment were captured in Furnas village (Azores, Portugal) and compared with those trapped in a reference area (Rabo de Peixe, Azores, Portugal). On the one hand, the heavy metal load has been evaluated by analyzing brain and cerebellum using ICP-MS and a mercury analyzer and on the other hand, the presence of metallothionein 2A has been studied by immunofluorescence assays. Our results show a higher load of metals such as mercury, cadmium and lead in the central nervous system of exposed mice compared to non-exposed individuals and, in addition, a higher immunoreactivity for metallothionein 2A in different areas of the cerebrum and cerebellum indicating a possible neuroprotection process.

First wave of COVID-19 impact on emergency general surgery in a Spanish tertiary hospital. A cohort study.

INTRODUCTION: The need to care for patients with emergency symptoms still continues during the COVID-19 pandemic. The number of emergency surgery procedures performed in Spanish hospitals decreased significantly during the first wave of COVID-19. PATIENTS AND METHODS: We performed a retrospective cohort study comparing the emergency surgery activity in a Spanish tertiary Hospital during the COVID-19 pandemic and emergency surgery activity registered in 2019 during the equivalent time period. RESULTS: A total of 1802 patients were included in control group (CG) versus 756 in pandemic group (PG). Mean number of patients who underwent emergency surgery during the control and pandemic periods was 3.42 patients per day, in contrast to 1.62 during the pandemic period, which represents a 52.6% decrease in emergency surgery activity. During the pandemic period, most of the patients consulted after more than 72 h of symptoms, representing a delay in presenting in the ER of 23.7% when compared to CG. Surgeries due to complications from previous elective procedures decreased (12% vs. 6.1%) in PG, probably because elective procedures are being postponed. We had a 13.1% COVID-19 positivity rate. Morbidity was higher during pandemic (52.5% vs. 35.2%). Mortality rates in patients undergoing emergency surgery was higher in PG (12.1% vs. 4.8%). CONCLUSIONS: The impact of the first wave of COVID-19 in emergency surgery activity has been profound. A significant reduction in emergency surgery was observed, along with longer time periods between patients' onset of symptoms and their arrival at the Emergency Department. Higher morbidity was also observed during the pandemic period.

Association of oral lichen planus with hepatic disorders and hepatocellular carcinoma: systematic review and meta-analysis.

BACKGROUND: Oral lichen planus (OLP) is a prevalent autoimmune chronic inflammatory disease of unknown etiology. The importance of the association between hepatic disease and OLP lies in the fact that many of these disorders (HC, HB, cirrhosis, hepatic steatosis) behave as risk factors for hepatocellular carcinoma. MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, and Scopus for studies published before January 2022. We evaluated the quality of studies (Joanna Briggs Institute tool). We performed meta-analyses, investigated the heterogeneity between studies, and we also carried out subgroups, meta-regression, and small-study effects analyses. 146 studies (21,187 patients) were included in this study. Our study aims to evaluate current evidence on the prevalence and magnitude of association between hepatic diseases (especially those with risk of malignancy), hepatocellular carcinoma and OLP. RESULTS: Our results suggest that patients with OLP present a significant tendency to the development of hepatitis B (OR=1.62, 95%CI=1.01-2.40, p=0.02), hepatitis C (OR=4.09, 95%CI=2.77-6.03, p<0.001), cirrhosis (OR=5.58, 95%CI=1.83-16.96, p=0.002), hepatic steatosis (OR=5.71, 95%CI=0.97-33.60, p=0.05) and hepatocellular carcinoma (OR=3.10,95%CI=1.14-8.43, p=0.03). CONCLUSIONS: Patients with OLP should be investigated to rule out the presence of hepatic disease, which can lead to hepatocellular carcinoma, allowing an early diagnosis that would help to a better approach to liver disease and a notable improvement in prognosis in terms of both progression and severity.

Contact Allergy to Shellac. Retrospective Cross-Sectional Study With Data From the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC).

INTRODUCTION: Shellac is a known allergen present mainly in cosmetics used on the eyelids and lips, although new sources of exposure have recently been described. Our objective was to assess the use of shellac as a contact allergen in Spain and the clinical profile of patients allergic to shellac. METHODS: This retrospective cross-sectional study included patients patch tested for shellac between 2018 and 2021 from the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC). RESULTS: A total of 980 patients were patch tested for shellac (20% in ethanol), and 37 (3.77%, 95% confidence interval [CI], 2.58-3.97%) showed positive results. Most of these patients were tested for shellac due to a suspicion of cosmetic contact dermatitis. Seven patients with present relevance were found, five with relation to cosmetics, and the other two with an occupational background of food handling. The reaction index for shellac was 0.51 and the positivity ratio was 67.56% (95% CI, 52.48-82.65%). CONCLUSIONS: Shellac appears to be a prevalent allergen in patients with suspected contact dermatitis related with cosmetics or foodstuff. However, further studies are needed to validate its use in other patients.