Identification and Characterization of Multiple Paneth Cell Types in the Mouse Small Intestine.

The small intestinal crypts harbor secretory Paneth cells (PCs) which express bactericidal peptides that are crucial for maintaining intestinal homeostasis. Considering the diverse environmental conditions throughout the course of the small intestine, multiple subtypes of PCs are expected to exist. We applied single-cell RNA-sequencing of PCs combined with deep bulk RNA-sequencing on PC populations of different small intestinal locations and discovered several expression-based PC clusters. Some of these are discrete and resemble tuft cell-like PCs, goblet cell (GC)-like PCs, PCs expressing stem cell markers, and atypical PCs. Other clusters are less discrete but appear to be derived from different locations along the intestinal tract and have environment-dictated functions such as food digestion and antimicrobial peptide production. A comprehensive spatial analysis using Resolve Bioscience was conducted, leading to the identification of different PC's transcriptomic identities along the different compartments of the intestine, but not between PCs in the crypts themselves.

Paneth cell TNF signaling induces gut bacterial translocation and sepsis.

The cytokine tumor necrosis factor (TNF) plays important roles in limiting infection but is also linked to sepsis. The mechanisms underlying these paradoxical roles are unclear. Here, we show that TNF limits the antimicrobial activity of Paneth cells (PCs), causing bacterial translocation from the gut to various organs. This TNF-induced lethality does not occur in mice with a PC-specific deletion in the TNF receptor, P55. In PCs, TNF stimulates the IFN pathway and ablates the steady-state unfolded protein response (UPR), effects not observed in mice lacking P55 or IFNAR1. TNF triggers the transcriptional downregulation of IRE1 key genes Ern1 and Ern2, which are key mediators of the UPR. This UPR deficiency causes a significant reduction in antimicrobial peptide production and PC antimicrobial activity, causing bacterial translocation to organs and subsequent polymicrobial sepsis, organ failure, and death. This study highlights the roles of PCs in bacterial control and therapeutic targets for sepsis.

Development and Psychometric Analysis of a Patient-Reported Measure of Diagnostic Excellence for Emergency and Urgent Care Settings.

BACKGROUND: Emergency and urgent care settings face challenges with routinely obtaining performance feedback related to diagnostic care. Patients and their care partners provide an important perspective on the diagnostic process and outcome of care in these settings. We sought to develop and test psychometric properties of Patient-Report to IMprove Diagnostic Excellence in Emergency Department settings (PRIME-ED), a measure of patient-reported diagnostic excellence in these care settings. METHODS: We developed PRIME-ED based on literature review, expert feedback, and cognitive testing. To assess psychometric properties, we surveyed AmeriSpeak, a probability-based panel that provides sample coverage of approximately 97% of the U.S. household population, in February 2022 to adult patients, or their care partners, who had presented to an emergency department or urgent care facility within the last 30 days. Respondents rated their agreement on a 5-point Likert scale with each of 17 statements across multiple domains of patient-reported diagnostic excellence. Demographics, visit characteristics, and a subset of the Emergency Department Consumer Assessment of Healthcare Providers & Systems were also collected. We conducted psychometric testing for reliability and validity. RESULTS: Over a thousand (n = 1116) national panelists completed the PRIME-ED survey, of which 58.7% were patients and 40.9% were care partners; 49.6% received care at an emergency department and 49.9% at an urgent care facility. Responses had high internal consistency within 3 patient-reported diagnostic excellence domain groupings: diagnostic process (Cronbach's alpha 0.94), accuracy of diagnosis (0.93), and communication of diagnosis (0.94). Domain groupings were significantly correlated with concurrent Emergency Department Consumer Assessment of Healthcare Providers & Systems items. Factor analyses substantiated 3 domain groupings. CONCLUSIONS: PRIME-ED has potential as a tool for capturing patient-reported diagnostic excellence in emergency and urgent care.

Offshore wind and wave energy can reduce total installed capacity required in zero-emissions grids.

As the world races to decarbonize power systems to mitigate climate change, the body of research analyzing paths to zero emissions electricity grids has substantially grown. Although studies typically include commercially available technologies, few of them consider offshore wind and wave energy as contenders in future zero-emissions grids. Here, we model with high geographic resolution both offshore wind and wave energy as independent technologies with the possibility of collocation in a power system capacity expansion model of the Western Interconnection with zero emissions by 2050. In this work, we identify cost targets for offshore wind and wave energy to become cost effective, calculate a 17% reduction in total installed capacity by 2050 when offshore wind and wave energy are fully deployed, and show how curtailment, generation, and transmission change as offshore wind and wave energy deployment increase.

Limited Awareness of Long COVID Despite Common Experience of Symptoms Among African American/Black, Hispanic/Latino, and Indigenous Adults in Arizona.

OBJECTIVES: Communities of color might disproportionately experience long-term consequences of COVID-19, known as Long COVID. We sought to understand the awareness of and experiences with Long COVID among African American/Black (AA/B), Hispanic/Latino (H/L), and Indigenous (Native) adults (18 + years of age) in Arizona who previously tested positive for COVID-19. METHODS: Between December 2022 and April 2023, the Arizona Community Engagement Alliance (AZCEAL) conducted 12 focus groups and surveys with 65 AA/B, H/L and Native community members. Data from focus groups were analyzed using thematic analysis to identify emerging issues. Survey data provided demographic information about participants and quantitative assessments of Long COVID experiences were used to augment focus group data. RESULTS: Study participants across all three racial/ethnic groups had limited to no awareness of the term Long COVID, yet many described experiencing or witnessing friends and family endure physical symptoms consistent with Long COVID (e.g., brain fog, loss of memory, fatigue) as well as associated mental health issues (e.g., anxiety, worry, post-traumatic stress disorder). Participants identified a need for Long COVID mental health and other health resources, as well as increased access to Long COVID information. CONCLUSION: To prevent Long COVID health inequities among AA/B, H/L, and Native adults living in AZ, health-related organizations and providers should increase access to culturally relevant, community-based Long COVID-specific information, mental health services, and other health resources aimed at serving these populations.

Investigating the modulation of the endocannabinoid system by probiotic Lactiplantibacillus plantarum IMC513 in a zebrafish model of di-n-hexyl phthalate exposure.

Environmental pollutants used as plasticizers in food packaging and in thousands of everyday products have become harmful for their impact on human health. Among them, phthalates, recognized as emerging endocrine disruptors (EDs) can induce toxic effects leading to different health disorders. Only few studies evaluated the effects of di-n-hexyl phthalate (DnHP) in in vivo models and no studies have been conducted to investigate the effect of DnHP on the endocannabinoid system (ECS), one of the majors signaling pathways involved in the microbiota-gut-brain axis. Due to the current relevance of probiotic bacteria as beneficial dietary interventions, the present study was aimed at evaluating the potential neuroprotective impact of daily administration of Lactiplantibacillus (Lpb.) plantarum IMC513 on zebrafish adults exposed to DnHP, with a focus on ECS modulation. Gene expression analysis revealed a promising protective role of probiotic through the restoration of ECS genes expression to the control level, in the brain of zebrafish daily exposed to DnHP. In addition, the levels of main endocannabinoids were also modulated. These findings confirm the potential ability of probiotics to interact at central level by modulating the ECS, suggesting the use of probiotics as innovative dietary strategy to counteract alterations by EDs exposure.

Peri-Implant Microbial Signature Shifts in Titanium, Zirconia and Ceria-Stabilized Zirconia Reinforced with Alumina Sites Subjected to Experimental Peri-Implantitis: A Preclinical Study in Dogs.

This study evaluates the dynamic shift in the microbiota at the peri-implant site of titanium (Ti) and zirconia (Zr) implants subjected to experimental peri-implantitis (PI) and, for the first time, of implants made of ceria-stabilized alumina-reinforced zirconia (Ce-TZP/Al), a revolutionary zirconia that is set to play a key role in modern implant dentistry. One- and two-piece (TP) implants, including Ce-TZP/AL TP/G3 glass, were placed bilaterally (six implants/side) in five beagle dogs to mimic a natural vs. ligature-induced PI following a split-mouth design. The experiment spanned 30 weeks from tooth extraction. Both PI models promoted plaque deposition at peri-implant sites. Comparatively, the PI induced by ligatures favored the deposition of anaerobes (p = 0.047 vs. natural). Regardless of the model, the plaque deposition pattern was entirely dependent on the implanted material. Ligated Ti and Zr implant sites accumulated up to 2.14 log CFU/mL unit anaerobic load (p ≤ 0.033 vs. non-ligated implant sites), predominantly comprising obligate anaerobes. Naturally occurring PI induced the deposition of co-occurring networks of obligate anaerobes and less oxygen-dependent bacteria. PI induction favored the enrichment of Ti and Zr sites with bacterial taxa belonging to the orange and red complexes (up to 28% increase naturally and up to 71% in the ligated hemiarch). Anaerobic deposition was significantly lower in ligated Ce-TZP/Al implant sites (p ≤ 0.014 vs. TI and Zr) and independent of the induction model (0.63-1 log units of increase). Facultative bacteria prevailed at Ce-TZP/AL sites. The abundance was lower in the Ce-TZP/AL TP implant. Unlike Ti and Zr sites, taxa from the orange and red complexes were negligible. Biofilms configured at the Ti and Zr sites after ligation-induced PI resemble those found in severe IP. We hypothesize that, although surface properties (surface energy and surface roughness) and physicochemical properties of the substrate play an important role in bacterial adhesion and subsequent plaque formation, Ce-TZP/Al modulates several biological activities that preserve the integrity of the gingival seal by limiting PI progression. In conclusion, biofilm progression differs in peri-implant sites according to the specific properties of the material. Ce-TZP/A, unlike titanium or zirconia, prevents dysbiosis in sites subjected to experimental PI and preserves the microbial signature of emergent obligate anaerobes related to PI development.

Dynamic BTB-domain filaments promote clustering of ZBTB proteins.

The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution. In cells, the BTB-domain filamentation supports clustering of full-length human ZBTB8A and ZBTB18 into dynamic nuclear foci and contributes to the ZBTB18-mediated repression of a reporter gene. The BTB domains of up to 21 human ZBTB family members and two related proteins, NACC1 and NACC2, are predicted to behave in a similar manner. Our results suggest that filamentation is a more common feature of transcription factors than is currently appreciated.

Clinical Reasoning: A 60-Year-Old Woman With Rapidly Progressive Muscle Weakness and Ophthalmoparesis.

The clinical assessment of patients with proximal muscle weakness represents a frequent yet intricate challenge. We present the case of a 60-year-old woman who experienced a progressive, symmetrical weakness in proximal limbs and bulbar muscles over 6 months. Notable clinical findings included bilateral ophthalmoparesis; widespread muscle atrophy; and pronounced weakness in craniobulbar, cervical, and proximal muscles, more severe than in distal ones. We elucidate a methodical diagnostic approach, focusing on constructing a comprehensive differential diagnosis and identifying potential causes of proximal muscle weakness. Special emphasis is placed on exploring the etiologies in cases presenting with both progressive muscle weakness and ophthalmoparesis. We further describe the role of muscle biopsy results and their integration with genetic testing outcomes.

A Light-Responsive Neural Circuit Suppresses Feeding.

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb→5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light-responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.

A pan-genomic assessment: Delving into the genome of the marine epiphyte Bacillus altitudinis strain 19_A and other very close Bacillus strains from multiple environments.

Marine macroalgae are the habitat of epiphytic bacteria and provide several conditions for a beneficial biological interaction to thrive. Although Bacillus is one of the most abundant epiphytic genera, genomic information on marine macroalgae-associated Bacillus species remains scarce. In this study, we further investigated our previously published genome of the epiphytic strain Bacillus altitudinis 19_A to find features that could be translated to potential metabolites produced by this microorganism, as well as genes that play a role in its interaction with its macroalgal host. To achieve this goal, we performed a pan-genome analysis of Bacillus sp. and a codon bias assessment, including the genome of the strain Bacillus altitudinis 19_A and 29 complete genome sequences of closely related Bacillus strains isolated from soil, marine environments, plants, extreme environments, air, and food. This genomic analysis revealed that Bacillus altitudinis 19_A possessed unique genes encoding proteins involved in horizontal gene transfer, DNA repair, transcriptional regulation, and bacteriocin biosynthesis. In this comparative analysis, codon bias was not associated with the habitat of the strains studied. Some accessory genes were identified in the Bacillus altitudinis 19_A genome that could be related to its epiphytic lifestyle, as well as gene clusters for the biosynthesis of a sporulation-killing factor and a bacteriocin, showing their potential as a source of antimicrobial peptides. Our results provide a comprehensive view of the Bacillus altitudinis 19_A genome to understand its adaptation to the marine environment and its potential as a producer of bioactive compounds.

Validation and recalibration of sex estimation methods using pubic nonmetric traits for the Chilean population.

Chile had a violent military coup (1973-1990) that resulted in 3,000 victims declared detained, missing or killed; many are still missing and unidentified. Currently, the Human Rights Unit of the Forensic Medical Service in Chile applies globally recognised forensic anthropological approaches, but many of these methods have not been validated in a Chilean sample. As current research has demonstrated population-specificity with extant methods, the present study aims to validate sex estimation methods in a Chilean population and thereafter establish population-specific equations. A sample of 265 os coxae of known age and sex of adult Chileans from the Santiago Subactual Osteology Collection were analysed. Visual assessment and scoring of the pelvic traits were performed in accordance with the Phenice (1969) and Klales et al. (2012) methods. The accuracy of Phenice (1969) in the Chilean sample was 96.98%, with a sex bias of 7.68%. Klales et al. (2012) achieved 87.17% accuracy with a sex bias of -15.39%. Although both methods showed acceptable classification accuracy, the associated sex bias values are unacceptable in forensic practice. Therefore, six univariate and eight multivariate predictive models were formulated for the Chilean population. The most accurate univariate model was the ventral arc at 96.6%, with a sex bias of 5.2%. Classification accuracy using all traits was 97.0%, with a sex bias of 7.7%. This study provides Chilean practitioners a population-specific morphoscopic standard with associated classification probabilities acceptable to accomplish legal admissibility requirements in human rights and criminal cases specific to the second half of the 20th century.

Gutless Helper-Dependent and First-Generation HAdV5 Vectors Have Similar Mechanical Properties and Common Transduction Mechanisms.

Delivering vectorized information into cells with the help of viruses has been of high interest to fundamental and applied science, and bears significant therapeutic promise. Human adenoviruses (HAdVs) have been at the forefront of gene delivery for many years, and the subject of intensive development resulting in several generations of agents, including replication-competent, -defective or retargeted vectors, and recently also helper-dependent (HD), so-called gutless vectors lacking any viral protein coding information. While it is possible to produce HD-AdVs in significant amounts, physical properties of these virus-like particles and their efficiency of transduction have not been addressed. Here, we used single-cell and single virus particle assays to probe the effect of genome length on HAdV-C5 vector transduction. Our results demonstrate that first-generation C5 vectors lacking the E1/E3 regions of the viral genome as well as HD-AdV-C5 particles with a wild type (wt) ∼36 kbp or an undersized double-strand DNA genome are similar to human adenovirus C5 (HAdV-C5) wt regarding attachment to human lung epithelial cells, endocytic uptake, endosome penetration and dependency on the E3 RING ubiquitin ligase Mind Bomb 1 for DNA uncoating at the nuclear pore complex. Atomic force microscopy measurements of single virus particles indicated that small changes in the genome length from 94% to 103% of HAdV-C5 have no major impact on physical and mechanical features of AdV vectors. In contrast, an HD-AdV-C5 with ∼30 kbp genome was slightly stiffer and less heat-resistant than the other particles, despite comparable entry and transduction efficiencies in tissue culture cell lines, including murine alveolar macrophage-like Max-Planck-Institute (MPI)-2 cells. Together, our in vitro studies reinforce the use of HD-AdV vectors for effective single round gene delivery. The results illustrate how physical properties and cell entry behavior of single virus particles can provide functional information for anticipated therapeutic vector applications.

Strengthening the relationship between intractable plantar keratosis and human papillomavirus.

The aim of the study was to determine the presence of human papillomavirus (HPV) in patients with intractable plantar keratosis (IPK) by comparing the histopathological findings of biopsies. A prospective, observational, and concordance study was carried out. Three different specimens were taken from each IPK. A first punch was sent for histopathological examination, and a second punch and a superficial skin scraping were both sent for HPV  polymerase chain reaction (PCR) and type determination. A total of 51 patients were included. From the histopathological examination, it was determined that 35 (68.6%) samples were diagnosed as warts and 16 (31.3%) as keratosis. However, the presence of HPV was confirmed by PCR in 49 (96.1%) and in 42 (82.4%) samples obtained by punch and superficial scraping, respectively. In the 49 PCR-positive samples, the most common HPV types were HPV1, HPV2, HPV27, HPV57, and HPV65, accounting for 81.6% of the samples. In conclusion, this study demonstrates that HPV infection and IPK lesions are very closely related. Although we cannot confirm that HPV is the cause of the development of IPK, the high prevalence of HPV observed in these lesions calls for a change to the procedures for managing IPK.

How do patients and care partners describe diagnostic uncertainty in an emergency department or urgent care setting?

OBJECTIVES: Little is known about how patients perceive diagnostic uncertainty. We sought to understand how patients and care partners perceive uncertainty in an emergency or urgent care setting, where making a final diagnosis is often not possible. METHODS: We administered a survey to a nationally representative panel on patient-reported diagnostic excellence in an emergency department or urgent care setting. The survey included items specific to perceived diagnostic excellence, visit characteristics, and demographics. We analyzed responses to two open-ended questions among those who reported uncertainty in the explanation they were given. Themes were identified using an inductive approach, and compared by whether respondents agreed or disagreed the explanation they were given was true. RESULTS: Of the 1,116 respondents, 106 (10 %) reported that the care team was not certain in the explanation of their health problem. Five themes were identified in the open-ended responses: poor communication (73 %), uncertainty made transparent (10 %), incorrect information provided (9 %), inadequate testing equipment (4 %), and unable to determine (4 %). Of the respondents who reported uncertainty, 21 % (n=22/106) reported the explanation of their problem given was not true. CONCLUSIONS: The findings of this analysis suggest that the majority of patients and their care partners do not equate uncertainty with a wrong explanation of their health problem, and that poor communication was the most commonly cited reason for perceived uncertainty.

Reparación percutánea de insuficiencia mitral primaria con técnica borde a borde: primer reporte de caso en Uruguay / Percutaneous edge-to-edge repair of primary mitral regurgitation: first case report in Uruguay / Correção percutânea de regurgitação mitral primária com técnica "edge-to-edge": primeiro caso reportado em Uruguai

La insuficiencia mitral (IM) es una enfermedad frecuente. La degeneración mixomatosa es la principal causa de IM primaria en los países desarrollados. Si no se corrige, conduce a la disfunción ventricular y a la insuficiencia cardíaca congestiva, con elevada morbimortalidad. La cirugía de reparación valvular es el tratamiento recomendado en la IM primaria severa y sintomática. En los pacientes con alto riesgo quirúrgico las opciones terapéuticas son limitadas. El surgimiento de la reparación percutánea borde a borde ha permitido ofrecer alternativas terapéuticas para estos pacientes, y se han demostrado buenos resultados. Se presenta el caso clínico de un paciente añoso con IM primaria severa. Por su elevado riesgo quirúrgico se optó por realizar reparación percutánea con técnica borde a borde, con excelentes resultados clínicos y ecocardiográficos. Se trata del primer reporte de caso de estas características en nuestro país.

Mitral regurgitation (MR) is a common disease. Myxomatous degeneration is the main cause of primary MR in developed countries. If not corrected, it leads to ventricular dysfunction and congestive heart failure, with high morbidity and mortality. Valve repair surgery is the recommended treatment for severe and symptomatic primary MR. In patients with high surgical risk, therapeutic options are limited. The emergence of edge-to-edge percutaneous repair has made it possible to offer therapeutic alternatives for these patients, and good results have been demonstrated. We present the clinical case of an elderly patient with severe primary MR. Due to his high surgical risk, it was decided to perform percutaneous repair with edge-to-edge technique, with excellent clinical and echocardiographic results. It is the first case report of these characteristics in our country.

A regurgitação mitral (RM) é uma doença frequente. A degeneração mixomatosa é a principal causa de RM primária em países desenvolvidos. Se não for corrigido, leva à disfunção ventricular e insuficiência cardíaca congestiva, com alta morbimortalidade. A cirurgia de reparo valvular é o tratamento recomendado na RM primária grave. Em pacientes com alto risco cirúrgico, as opções terapêuticas são limitadas. O surgimento do reparo percutâneo com plicatura dos segmentos é uma opção terapêutica alternativa, com bons resultados demonstrados. Apresentamos o caso clínico de um paciente doente por RM primária grave. Devido ao seu alto risco cirúrgico, optou-se pela correção percutânea com técnica "edge-to-edge", com excelentes resultados clínicos e ecocardiográficos. Este é o primeiro caso publicado com a técnica em Uruguai.

Patient Reasoning: Patients' and Care Partners' Perceptions of Diagnostic Accuracy in Emergency Care.

OBJECTIVES: In the context of validating a measure of patient report specific to diagnostic accuracy in emergency department or urgent care, this study investigates patients' and care partners' perceptions of diagnoses as accurate and explores variations in how they reason while they assess accuracy. METHODS: In February 2022, we surveyed a national panel of adults who had an emergency department or urgent care visit in the past month to test a patient-reported measure. As part of the survey validation, we asked for free-text responses about why the respondents indicated their (dis)agreement with 2 statements comprising patient-reported diagnostic accuracy: 1) the explanation they received of the health problem was true and 2) the explanation described what to expect of the health problem. Those paired free-text responses were qualitatively analyzed according to themes created inductively. RESULTS: A total of 1,116 patients and care partners provided 982 responses coded into 10 themes, which were further grouped into 3 reasoning types. Almost one-third (32%) of respondents used only corroborative reasoning in assessing the accuracy of the health problem explanation (alignment of the explanation with either test results, patients' subsequent health trajectory, their medical knowledge, symptoms, or another doctor's opinion), 26% used only perception-based reasoning (perceptions of diagnostic process, uncertainty around the explanation received, or clinical team's attitudes), and 27% used both types of reasoning. The remaining 15% used general beliefs or nonexplicated logic (used only about accurate diagnoses) and combinations of general reasoning with perception-based and corroborative. CONCLUSIONS: Patients and care partners used multifaceted reasoning in their assessment of diagnostic accuracy. IMPLICATIONS: As health care shifts toward meaningful diagnostic co-production and shared decision making, in-depth understanding of variations in patient reasoning and mental models informs use in clinical practice. HIGHLIGHTS: An analysis of 982 responses examined how patients and care partners reason about the accuracy of diagnoses they received in emergency or urgent care.In reasoning, people used their perception of the process and whether the diagnosis matched other factual information they have.We introduce "patient reasoning" in the diagnostic measurement context as an area of further research to inform diagnostic shared decision making and co-production of health.

Predictive Value of Antithrombin III and d -Dimer in the Development of Moderate-To-Severe Acute Pancreatitis : A Prospective, Observational Study (AT-PROPANC).

OBJECTIVES: To analyze if antithrombin III (AT-III) and d -dimer levels at admission and at 24 hours can predict acute pancreatitis (AP) progression to moderately severe AP (MSAP) to severe AP (SAP) and to determine their predictive value on the development of necrosis, infected necrosis, organ failure, and mortality. METHODS: Prospective observational study conducted in patients with mild AP in 2 tertiary hospitals (2015-2017). RESULTS: Three hundred forty-six patients with mild AP were included. Forty-four patients (12.7%) evolved to MSAP/SAP. Necrosis was detected in 36 patients (10.4%); in 10 (2.9%), infection was confirmed. Organ failure was recorded in 9 patients (2.6%), all of whom died. Those who progressed to MSAP/SAP showed lower AT-III levels; d -dimer and C-reactive protein (CRP) levels increased. The best individual marker for MSAP/SAP at 24 hours is CRP (area under the curve [AUC], 0.839). Antithrombin III (AUC, 0.641), d -dimer (AUC, 0.783), and creatinine added no benefit compared with CRP alone. Similar results were observed for patients who progressed to necrosis, infected necrosis, and organ failure/death. CONCLUSION: Low AT-III and high d -dimer plasma levels at 24 hours after admission were significantly associated with MSAP/SAP, although their predictive ability was low. C-reactive protein was the best marker tested. CLINICAL STUDY IDENTIFIER: ClinicalTrials.gov NCT02373293.

Oral squamous cell carcinomas and oral potentially malignant disorders: A Latin American study.

OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.