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Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.
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Lesão Pulmonar , Síndrome do Desconforto Respiratório , Animais , Humanos , Hipóxia/etiologia , Inflamação/complicações , Pulmão , Lesão Pulmonar/complicações , CamundongosRESUMO
Objectives. To evaluate Chicas Creando Acceso a la Salud (Girls Creating Access to Health; ChiCAS), a Spanish-language, small-group intervention designed to increase preexposure prophylaxis (PrEP) use, consistent condom use, and medically supervised gender-affirming hormone therapy use among Spanish-speaking transgender Latinas who have sex with men. Methods. Participants were 144 HIV-negative Spanish-speaking transgender Latinas, aged 18 to 59 years, living in North and South Carolina. From July 2019 to July 2021, we screened, recruited, and randomized them to the 2-session ChiCAS intervention or the delayed-intervention waitlist control. Participants completed assessments at baseline and 6-month follow-up. Follow-up retention was 94.4%. Results. At follow-up, relative to control participants, ChiCAS participants reported increased PrEP use (adjusted odds ratio [AOR] = 4.64; 95% confidence interval [CI] = 1.57, 13.7; P < .006). However, ChiCAS participants did not report increased use of condoms or medically supervised gender-affirming hormone therapy. ChiCAS participants reported increases in knowledge of HIV (P < .001), sexually transmitted infections (P < .001), and gender-affirming hormone therapy (P = .01); PrEP awareness (P < .001), knowledge (P < .001), and readiness (P < .001); condom use skills (P < .001); and community attachment (P < .001). Conclusions. The ChiCAS intervention was efficacious in increasing PrEP use among Spanish-speaking, transgender Latinas in this trial. (Am J Public Health. 2024;114(1):68-78. https://doi.org/10.2105/AJPH.2023.307444).
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Infecções por HIV , Profilaxia Pré-Exposição , Infecções Sexualmente Transmissíveis , Pessoas Transgênero , Masculino , Humanos , Feminino , Infecções por HIV/prevenção & controle , South Carolina , Hormônios , Homossexualidade MasculinaRESUMO
BACKGROUND AND AIMS: Kelps are the primary foundation species in temperate subtidal rocky shores worldwide. However, global change is causing their decline with consequences for the organisms that rely on them. An accurate assessment of these consequences may depend on which attributes of the associated community are considered. This study shows that conventional α-diversity approaches may overlook some of these consequences compared to spatially explicit approaches such as with ß-diversity. METHODS: A 1-year seasonal study was conducted to compare the macroalgal understorey between healthy reefs with a Laminaria ochroleuca canopy and degraded reefs where the canopy collapsed years ago due to excessive fish herbivory. At each reef, the understorey seaweed assemblage was recorded in five replicate quadrats to estimate α-diversity (total richness, species density, Shannon index) and ß-diversity (intra- and inter-reef scale). KEY RESULTS: The understorey assemblage exhibited a distinct seasonal dynamic in both healthy and degraded reefs. α-Diversity attributes increased in spring and summer; turf-forming algae were particularly dominant in degraded reefs during summer. ß-Diversity also showed seasonal variability, but mostly due to the changes in degraded reefs. None of the α-diversity estimates differed significantly between healthy and degraded reefs. In contrast, spatial ß-diversity was significantly lower in degraded reefs. CONCLUSIONS: Although the loss of the kelp canopy affected the composition of the macroalgal understorey, none of the conventional indicators of α-diversity detected significant differences between healthy and degraded reefs. In contrast, small-scale spatial ß-diversity decreased significantly as a result of deforestation, suggesting that the loss of kelp canopy may not significantly affect the number of species but still have an effect on their spatial arrangement. Our results suggest that small-scale ß-diversity may be a good proxy for a more comprehensive assessment of the consequences of kelp forest decline.
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Algas Comestíveis , Kelp , Laminaria , Alga Marinha , Animais , Florestas , Verduras , EcossistemaRESUMO
BACKGROUND: Emotional problems can be evaluated using categorical approaches to guide treatment choices focused on targeting specific disorders, or dimensional approaches to reduce symptom severity. Moreover, recent evidence points out the need to intervene in patients' quality of life (QoL), which often remains low even after the remission of emotional problems. Thus, assessment instruments are needed to provide information on diagnosis, symptom severity, and QoL. The present study aimed to provide diagnostic and QoL cutoffs for the Inventory of Depression and Anxiety Symptoms-II (IDAS-II). METHODS: 273 patients recruited from mental health services in Huelva (Spain) completed the IDAS-II, Mini International Neuropsychiatric Interview, and Short Form-36 Health Survey. Receiver operating characteristic curve analyses were used to establish cutoff values. Diagnostic, balanced, and screening cutoffs were provided for each IDAS-II scale to detect corresponding diagnoses and poor QoL. RESULTS: The specific IDAS-II scales Suicidality, Panic, Social Anxiety, Claustrophobia, and Traumatic Intrusions showed adequate discrimination values for their corresponding diagnoses (suicidal behavior disorder, panic disorder, social anxiety disorder, agoraphobia, and post-traumatic stress disorder, respectively). Both the General Depression and Dysphoria scales showed adequate ability to detect major depressive disorder. The IDAS-II scales showed a higher discrimination ability for Mental Health-related QoL, than for General Health-related QoL. CONCLUSIONS: The diagnostic and QoL cutoffs expand the clinical utility of the IDAS-II in clinical practice and research, making it a comprehensive, detailed, and versatile self-report tool. The IDAS-II allows for the assessment of emotional problems consistent with the dimensional, categorical, transdiagnostic, and QoL approaches.
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Psicometria , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Feminino , Masculino , Adulto , Espanha , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica/normas , Depressão/diagnóstico , Depressão/psicologia , Ansiedade/diagnóstico , Ansiedade/psicologia , Inquéritos e Questionários , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Reprodutibilidade dos TestesRESUMO
Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.
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Fator 2 Relacionado a NF-E2 , Doença Pulmonar Obstrutiva Crônica , Humanos , Macrófagos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Malato Desidrogenase/metabolismoRESUMO
Sexual dysfunction (SD) has been associated with worse quality of life and higher disease activity in patients with rheumatic diseases, yet it is still not regularly addressed during routine rheumatologic evaluations. This study aimed to determine the prevalence of sexual dysfunction in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and evaluate their perception of their sexual health. We performed a retrospective study in an outpatient rheumatology clinic to evaluate patients over 18 years old with a diagnosis of RA or SLE through the Spanish version of the Arizona Sexual Experiences Scale (ASEX) and the Sexual Health Perception Survey (SHEPS), a questionnaire of 6 items designed in our clinic. Additionally, we applied the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F version 4) and the Hospital Anxiety and Depression Scale (HADS). A total of 567 patients were evaluated with SHEPS, most of whom were women with a median age of 50 years (IQR: 34) and a median disease duration of 5 years (IQR: 9). Through the ASEX, we found that 67% of the patients with RA and 60% of the patients with SLE experienced SD. Patients reported the level of sex drive, arousal, and the ability to achieve orgasms as the areas with the most difficulties. Most patients did not know their disease could affect their sexuality and had never addressed these issues with their rheumatologists, but almost all of them were willing to. Our findings highlight the importance of addressing sexual health issues regularly during rheumatologic evaluations.
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A high-fat diet (HFD) can induce hyperglycemia and metabolic syndromes that, in turn, can trigger visual impairment. To evaluate the acute effects of HFD feeding on retinal degeneration, we assessed retinal function and morphology, inflammatory state, oxidative stress, and gut microbiome in dystrophic retinal degeneration 10 (rd10) mice, a model of retinitis pigmentosa, fed an HFD for 2 to 3 wk. Short-term HFD feeding impaired retinal responsiveness and visual acuity and enhanced photoreceptor degeneration, microglial cell activation, and Müller cell gliosis. HFD consumption also triggered the expression of inflammatory and oxidative markers in rd10 retinas. Finally, an HFD caused gut microbiome dysbiosis, increasing the abundance of potentially proinflammatory bacteria. Thus, HFD feeding drives the pathological processes of retinal degeneration by promoting oxidative stress and activating inflammatory-related pathways. Our findings suggest that consumption of an HFD could accelerate the progression of the disease in patients with retinal degenerative disorders.
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Dieta Hiperlipídica/efeitos adversos , Degeneração Retiniana/etiologia , Retinose Pigmentar/etiologia , Animais , Morte Celular , Modelos Animais de Doenças , Eletrorretinografia , Feminino , Microbioma Gastrointestinal , Intolerância à Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Modelos Biológicos , Estresse Oxidativo , Células Fotorreceptoras de Vertebrados/patologia , Retina/metabolismo , Retina/patologia , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologiaRESUMO
Dyskeratosis congenita (DC) is a rare inherited bone marrow failure and cancer predisposition syndrome caused by mutations in telomerase or telomeric proteins. Here, we report that zebrafish telomerase RNA (terc) binds to specific DNA sequences of master myeloid genes and controls their expression by recruiting RNA Polymerase II (Pol II). Zebrafish terc harboring the CR4-CR5 domain mutation found in DC patients hardly interacted with Pol II and failed to regulate myeloid gene expression in vivo and to increase their transcription rates in vitro. Similarly, TERC regulated myeloid gene expression and Pol II promoter occupancy in human myeloid progenitor cells. Strikingly, induced pluripotent stem cells derived from DC patients with a TERC mutation in the CR4-CR5 domain showed impaired myelopoiesis, while those with mutated telomerase catalytic subunit differentiated normally. Our findings show that TERC acts as a transcription factor, revealing a target for therapeutic intervention in DC patients.
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Disceratose Congênita/genética , Mielopoese/fisiologia , RNA Polimerase II/genética , RNA/metabolismo , Telomerase/metabolismo , Animais , Animais Geneticamente Modificados , Sítios de Ligação , Células Cultivadas , Disceratose Congênita/patologia , Regulação da Expressão Gênica , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Larva/genética , Mutação , Mielopoese/genética , Regiões Promotoras Genéticas , Domínios Proteicos , RNA/genética , RNA Polimerase II/metabolismo , Telomerase/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genéticaRESUMO
OBJECTIVE: The aim of this work was to examine the profile and treatment outcomes of patients with dual pathology depending on whether the patients were attending addiction centers or are being treated in a coordinated model by mental health services. METHODS: Data from 7225 dual diagnosis patients were used, of whom 2417 (33.5%) received treatment in the mental health coordinated modality. Clinical information was taken from the patients' electronic health record. RESULTS: Differences were found in patients' sociodemographic and comorbidity profiles according to treatment modality. In general, coordinated care yielded favorable outcomes (higher attendance and lower dropout rates but no differences in retention). The logistic regression analysis identified predictors of patient profiles in coordinated care, emphasizing having a severe mental health disorder (OR = 3.878, 95% CI [3.443, 4.368]; p = .000), being referred by social/health services, or having retired status. Main differences were observed according to the comorbid diagnosis presented, particularly in cases in which the patient had impulse control, hyperkinetic, or cluster C personality disorder. CONCLUSIONS: While therapeutic outcomes are influenced by associated comorbidities, the disorders prognosis can be favorable with appropriate treatment. Furthermore, analysis of differences according to treatment modality allows for predicting the type of patient who will receive a particular service, which enables the development of tailored treatments.
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Transtornos Mentais , Serviços de Saúde Mental , Transtornos Relacionados ao Uso de Substâncias , Humanos , Diagnóstico Duplo (Psiquiatria) , Feminino , Masculino , Adulto , Transtornos Mentais/terapia , Transtornos Mentais/epidemiologia , Transtornos Mentais/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Serviços de Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Resultado do Tratamento , Centros de Tratamento de Abuso de Substâncias , ComorbidadeRESUMO
In recent years, there has been growing interest in understanding the potential role of microbiota dysbiosis or alterations in the composition and function of human microbiota in the development of chronic rhinosinusitis with nasal polyposis (CRSwNP). This systematic review evaluated the literature on CRSwNP and host microbiota for the last ten years, including mainly nasal bacteria, viruses, and fungi, following the PRISMA guidelines and using the major scientific publication databases. Seventy original papers, mainly from Asia and Europe, met the inclusion criteria, providing a comprehensive overview of the microbiota composition in CRSwNP patients and its implications for inflammatory processes in nasal polyps. This review also explores the potential impact of microbiota-modulating therapies for the CRSwNP treatment. Despite variability in study populations and methodologies, findings suggest that fluctuations in specific taxa abundance and reduced bacterial diversity can be accepted as critical factors influencing the onset or severity of CRSwNP. These microbiota alterations appear to be implicated in triggering cell-mediated immune responses, cytokine cascade changes, and defects in the epithelial barrier. Although further human studies are required, microbiota-modulating strategies could become integral to future combined CRSwNP treatments, complementing current therapies that mainly target inflammatory mediators and potentially improving patient outcomes.
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Microbioma Gastrointestinal , Pólipos Nasais , Rinossinusite , Humanos , Doença Crônica , Disbiose/microbiologia , Microbiota , Pólipos Nasais/microbiologia , Rinossinusite/microbiologiaRESUMO
OBJECTIVE: To test whether labetalol improved cardiovascular function in anaesthetized dogs injected with dexmedetomidine. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A group of 20 healthy client-owned dogs undergoing ovariohysterectomy. METHODS: Each dog received dexmedetomidine (5 µg kg-1) and methadone (0.2 mg kg-1) intramuscularly. General anaesthesia was induced with propofol and maintained with isoflurane in oxygen. All dogs were mechanically ventilated, and epidural anaesthesia with lidocaine was performed. Standard anaesthetic monitoring, invasive blood pressure, oesophageal Doppler and near-infrared tissue perfusion/oxygenation were applied. Peak velocity (PV), mean acceleration and stroke distance (SD) from the oesophageal Doppler were recorded. Arterial elastance (Ea) was calculated. Tissue oxygenation (rStO2) was also recorded. Prior to surgery, animals received either 0.1 mg kg-1 of labetalol intravenously (IV) over 60 seconds or the equivalent volume of saline. Data were recorded for 20 minutes. Age, weight and propofol dose were compared with a Wilcoxon rank-sum test. The effects of time, treatment and their interaction with haemodynamic and perfusion variables were analysed with mixed-effect models and Tukey's post hoc tests. RESULTS: Significant effects of the interaction between treatment and time were observed whereby heart rate (HR) was higher in dogs given labetalol (p = 0.01), whereas arterial blood pressure and Ea were lower (p < 0.01). Similarly, PV, SD and rStO2 were higher in the labetalol group, and significant effects were detected for the interaction between treatment and time (p < 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Labetalol at a dose of 0.1 mg kg-1 IV in dogs under general anaesthesia and administered a pre-anaesthetic medication of dexmedetomidine produced mild vasodilation (reduction of Ea), resulting in an increase in HR and left ventricular outflow. Although labetalol could be an effective option to achieve haemodynamic optimization after dexmedetomidine-induced vasoconstriction, future studies are needed to assess long-term effects.
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Anestésicos , Dexmedetomidina , Hemodinâmica , Labetalol , Animais , Cães , Feminino , Anestésicos/farmacologia , Dexmedetomidina/farmacologia , Hemodinâmica/efeitos dos fármacos , Isoflurano/farmacologia , Labetalol/farmacologia , Propofol , Estudos Prospectivos , Anestesia Geral/veterináriaRESUMO
High-quality clinical practice guidelines (CPGs) and consensus statements (CSs) are essential for evidence-based medicine. The purpose of this systematic review was to appraise the quality and reporting of colorectal cancer (CRC) screening CPGs and CSs. After prospective registration (Prospero no: CRD42021286156), a systematic review searched CRC guidances in duplicate without language restrictions in ten databases, 20 society websites, and grey literature from 2018 to 2021. We appraised quality with AGREE II (% of maximum score) and reporting with RIGHT (% of total 35 items) tools. Twenty-four CPGs and 5 CSs were analysed. The median overall quality and reporting were 54.0% (IQR 45.7-75.0) and 42.0% (IQR 31.4-68.6). The applicability had low quality (AGREE II score <50%) in 83% of guidances (24/29). Recommendations and conflict of interest were low-reported (RIGHT score <50%) in 62% guidances (18/29) and 69% (20/29). CPGs that deployed systematic reviews had better quality and reporting than CSs (AGREE: 68.5% vs. 35.5%; p = 0.001; RIGHT: 74.6% vs. 41.4%; p = 0.001). In summary, CRC screening CPGs and CSs achieved low quality and reporting. It is necessary a revision and an improvement of the current guidances. Their development should apply a robust methodology using proper guideline development tools to obtain high-quality evidence-based documents.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Estudos Prospectivos , Medicina Baseada em Evidências , ConsensoRESUMO
This study evaluates the safety of early oral ambulatory treatment of adult patients diagnosed with bacteremia after their discharge from the emergency department. A cohort of 206 febrile ambulatory patients was assessed. Bacteremic low-risk patients were recommended an oral treatment and were compared with matched febrile non-bacteremic outpatients. Rates of 14-day mortality and unplanned re-consultations were similar and below 5% in both cohorts, highlighting the safety of oral therapy of low-risk bacteremia, even from its onset.
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Bacteriemia , Alta do Paciente , Adulto , Humanos , Antibacterianos , Serviço Hospitalar de Emergência , Estudos RetrospectivosRESUMO
Marine viruses play a major role in the energy and nutrient cycle and affect the evolution of their hosts. Despite their importance, there is still little knowledge about RNA viruses. Here, we have explored the Atlantic Ocean, from surface to deep (4.296 m), and used viromics and quantitative methods to unveil the genomics, biogeography, and the mass contribution of RNA viruses to the total viroplankton. A total of 2481 putative RNA viral contigs (>500 bp) and 107 larger bona fide RNA viral genomes (>2.5 kb) were identified; 88 of them representing novel viruses belonging mostly to two clades: Yangshan assemblage (sister clade to the class Alsuviricetes) and Nodaviridae. These viruses were highly endemic and locally abundant, with little or no presence in other oceans since only ≈15% of them were found in at least one of the Tara sampling metatranscriptomes. Quantitative data indicated that the abundance of RNA viruses in the surface and deep chlorophyll maximum zone was within ≈106 VLP/mL representing a potential contribution of 5.2%-24.4% to the total viroplankton community (DNA and RNA viruses), with DNA viruses being the predominant members (≈107 VLP/mL). However, for the deep sample, the observed trend was the opposite, although as further discussed, several biases should be considered. Together these results contribute to our understanding of the diversity, abundance, and distribution of RNA viruses in the oceans and provide a basis for further investigation into their ecological roles and biogeography.
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Vírus de RNA , Vírus , Oceanos e Mares , Vírus de RNA/genética , Oceano Atlântico , RNA , Água do MarRESUMO
OBJECTIVES: Patients with COVID-19-associated acute respiratory distress syndrome (ARDS) have a high risk for developing acute kidney injury (AKI) which is associated with an increased risk of death and persistent renal failure. Early prediction of AKI is crucial in order to implement preventive strategies. The purpose of this study was to investigate the predictive performance of tissue inhibitor of metalloproteinases 2 and insulin like growth factor binding protein 7 (TIMP-2) × (IGFBP7) in critically ill patients with COVID-19-associated ARDS. DESIGN: Multicenter, prospective, observational study. SETTING: Twelve centers across Europe and United Kingdom. PATIENTS: Patients with moderate or severe COVID-19-associated ARDS were included and serial measurements of (TIMP-2) × (IGFBP7) were performed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the development of moderate or severe AKI according to the Kidney Disease: Improving Global Outcomes definition. Three hundred patients were available for the primary analysis, and 39 met the primary endpoint. At enrollment, urinary (TIMP-2) × (IGFBP7) had high predictive value for the primary endpoint with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.84-0.93). (TIMP-2) × (IGFBP7) was significantly higher in endpoint-positive patients at enrollment and at 12 hours. CONCLUSIONS: Urinary (TIMP-2) × (IGFBP7) predicts the occurrence of AKI in critically ill patients with COVID-19-associated ARDS.
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Injúria Renal Aguda , COVID-19 , Humanos , Inibidor Tecidual de Metaloproteinase-2 , Estudos Prospectivos , Estado Terminal , COVID-19/complicações , Biomarcadores , Pontos de Checagem do Ciclo Celular , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Proteínas de Ligação a Fator de Crescimento Semelhante a InsulinaRESUMO
A new procedure to measure the extinction coefficient k of film materials that are relatively transparent is presented. This procedure does not require the use of an optical-constant model or the knowledge of extra physical properties of the material, such as the specific heat capacity. It involves preparing a sample with two areas, at least one of them coated with the film, whereas the other may remain uncoated or may be coated with a different thickness of the same material. The differential transmittance between the two sample areas is shown to be proportional to k of the film material in the following measurement conditions: the incident light is p polarized and it impinges at the film material Brewster angle. The differential transmittance is obtained with a single measurement by making the light beam or the sample to oscillate with respect to one another and by using a lock-in amplifier; for normalization purposes, the transmittance in one of the sample areas is also measured. The proportionality factor between the normalized differential transmittance and k only involves the wavelength, the film thickness, and the Brewster angle. The knowledge of the film Brewster angle requires that the film refractive index (n) is measured beforehand; this can be performed with standard procedures, such as ellipsometry, since such techniques are efficient at measuring n of a transparent material, but are inefficient at measuring a small k. The procedure is exemplified with the calculation of k in the far ultraviolet of AlF3 films deposited by evaporation. The dependence of the uncertainty of k obtained with this procedure is analyzed in terms of the uncertainty of the film n, of wavelength, and of the degree of polarization of the incident beam. The selection of a substrate with similar n to the film material is also discussed. The uncertainties involved with the present procedure were analyzed for a specific example and an uncertainty of 2 × 10-5 in k calculation is considered feasible.
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Locally advanced breast cancer (LABC) is a subset of breast cancer with locoregional progression without distant metastasis. The multimodality treatment (surgery, chemotherapy, radiotherapy, hormonal and targeted therapy if required) could significantly improve results in this specific group of patients. The complex and multiple options of treatment with similar mortality rates but different outcomes depending on the patient's desires, preferences and social environment require aid to facilitate the individual patient's decisions (e.g. Decision Aids (DAs) targeting patients considering primary or adjuvant treatment in LABC). In this context, DAs have been proven fundamental to help patients and clinicians share and agree on the best value option. The current systematic review aimed to evaluate the existing DAs related to these patients with LABC and identify current status and possible improvement areas (possible scarcity and heterogeneity of instruments, the status of their development, explanation of their purpose, ). No previous systematic reviews have been published on this topic. Following Prospero registration no: CRD42021286173, studies about LABC DAs were identified, without data or language restrictions, through a systematic search of bibliographic databases in December 2021. Quality was assessed using Qualsyst criteria (range 0.0-1.0). The quality of the 17 selected studies ranged from 0.46 to 0.95. Of them, 14/17 (82%) were DAs about treatment, only one (6%) about diagnosis, and 2/17 (12%) about the employment of DAs. No screening or follow-up DAs were retrieved. Twelve (70.6%) DAs were online tools. They varied broadly regarding their characteristics and purposes. Most of the studies focused on developing and testing different DAs (5/17; 29.4%) and their impact (7/17; 41.2%). Only 4/17 (23.5%) analysed their implementation and cost. These instruments have proven to improve patient's knowledge and decision-making, decrease patient anxiety, and patients tend to undergo treatment. However, nowadays, there is still a need for further research and consensus on methodology to develop practical DAs.
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We retrospectively studied 97 acute myeloid leukemia patients with trisomy 19 (median age at diagnosis 57 years; range, 17- 83 years) treated between 2001 and 2019 within two multicenter study groups. Trisomy 19 occurred alone in ten (10.5%) patients, with additional abnormalities being present in non-complex karyotypes in eight (8%) patients and in complex karyotypes in 79 (82%) patients. Altogether, karyotypes characterized by trisomies only were present in 27 (28%) patients. Data on response and outcome of intensively treated patients were available for 92 cases. The median follow-up was 6.4 years (95% confidence interval [95% CI]: 2.9-9.0 years). The complete remission (CR) rate after induction therapy was 52% (48 patients); the early death rate was 10% (n=9). Notably, patients with trisomy 19 as the sole abnormality had a CR rate of 89%. Allogeneic hematopoietic stem cell transplantation (allo-HCT) was performed in 34 (35%) patients (CR, n=19; active disease, n=15). Five-year relapse-free and overall survival rates were 26% (95% CI: 16-43%) and 20% (95% CI: 13-31%), respectively. Overall survival rates were significantly higher in patients with trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only (P=0.05). An Andersen-Gill model including allo-HCT as a time-dependent covariable on overall survival revealed that trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only was a favorable factor (hazard ratio [HR]=0.47; P=0.021); higher age at diagnosis had an adverse impact (10 years difference; HR=1.29; P=0.002), whereas allo-HCT did not have a beneficial impact (odds ratio=1.45; P=0.21). In our cohort, patients with trisomy 19 as the sole abnormality or within karyotypes characterized by trisomies only had a high CR rate and better clinical outcome.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Pessoa de Meia-Idade , Criança , Trissomia/genética , Estudos Retrospectivos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Indução de Remissão , Cariótipo AnormalRESUMO
AIMS: Same-day discharge (SDD) is feasible after pulmonary vein isolation (PVI). We aim to compare prospectively cryoballoon (CRYO) vs. radiofrequency (RF) ablation in a systematic SDD programme. METHODS AND RESULTS: We prospectively analysed the 617 scheduled PVI performed consecutively at our institution (n = 377 CRYO, n = 240 RF) from 1 April 2019 to 31 December 2022 within a systematic programme of SDD. The feasibility of SDD, the 10-day incidence of urgent/unplanned medical care after discharge (UUC-10), and the cost per procedure due to hospital resource use were studied. The 100 procedures performed during the previous year, in which patients were systematically hospitalized, were used as a control group. Same-day discharge was achieved in 585/617 (95%) procedures, with a significant trend towards a higher monthly SDD rate from 2019 to 2022 (P = 0.03). The frequency of SDD was similar in CRYO (356/377; 94%) vs. RF (229/240; 95%). After SDD, the UUC-10 was 66/585 (11.3%), being similar for CRYO (41/356; 11.5%) and RF (25/229; 10.9%); P = 0.8 (log-rank test). Of these, 10 patients were re-hospitalized, with an identical rate in CRYO-treated (6/356; 1.7%) and RF-treated (4/229; 1.7%) patients and owing to similar causes (4 haematomas, 4 pericarditis, and 2 symptomatic sinus node dysfunction). Same-day discharge was associated with an average savings per procedure of 63% (P < 0.001), but no differences were found between the CRYO and RF (P = 0.8). CONCLUSION: In a systematic SDD programme, feasibility (95%, increasing over time), safety (11% UUC-10, 1.7% re-hospitalizations), and savings (63% per procedure) were similar for CRYO and RF ablation procedures.