ABSTRACT
The development of rapid, accurate, sensitive, and low-cost diagnostic methods for COVID-19 detection in real-time is the unique way to control infection sources and monitor illness progression. In this work, we propose an electrochemical biosensor for the rapid and accuracy diagnosis of COVID-19, through the determination of ORF1ab specific sequence. The biosensor is based on the immobilization of a thiolated sequence partially complementary (domain 1) to ORF1ab on gold screen-printed electrodes and the use of bifunctional Au@Pt/Au core@shell nanoparticles modified with a second thiolated sequence partially complementary to ORF1ab (domain 2) as electrochemical indicator of the hybridization of DNA sequences. The synthesized Au@Pt/Au nanoparticles consist of an Au core, a shell of Pt (Au@Pt NPs), that provides an excellent electrocatalytic activity toward the oxygen reduction reaction (ORR) even after formation of hybrid biomaterials by modification, through the Au protuberances growth on the NPs surface, with an oligonucleotide with recognition ability. The ORR electrochemical activity, enhanced by the label element (Au@Pt/Au NPs), has been employed, for the first time, as indicator of the hybridization event. Based on this strategy, target sequences of the SARS-CoV-2 virus have been detected with a detection limit of 32 pM. The selectivity of the biosensor was confirmed by analysing ORF1ab sequence in the presence of DNA sequences from other viruses. The biosensor has been successfully applied to the direct detection of the virus in non-amplified samples of nasopharyngeal swabs from infected and non-infected patients. Results compare well with those obtained through RT-qPCR but our method is more rapid since does not need any amplification process.
ABSTRACT
CONTEXT: Exercise reduces adiposity, but its influence on bone marrow fat fraction (BMFF) is unknown; nor is it known whether a reduction in liver fat content mediates this reduction. OBJECTIVES: (i) To determine whether incorporating exercise into a lifestyle program reduces the lumbar spine (LS)-BMFF, and (ii), to investigate whether changes in liver fat mediate any such effect. DESIGN: Ancillary analysis of a two-arm, parallel, non-randomized clinical trial. SETTING: Primary care centres in Vitoria-Gasteiz (Spain). PARTICIPANTS: A total of 116 children with overweight/obesity were assigned to a 22-week family-based lifestyle program (control group [n=57]) or the same program plus an exercise intervention (exercise group [n=59]. INTERVENTIONS: The compared interventions consisted of a family-based lifestyle program (two 90-minute sessions/month) and the same program plus supervised exercise (three 90-minute sessions/week). MAIN OUTCOMES AND MEASURES: The primary outcome examined was the change in LS-BMFF between baseline and 22 weeks, as estimated by MRI. The effect of changes in hepatic fat on LS-BMFF were also recorded. RESULTS: Mean weight loss difference between groups was 1.4±0.5 kg favour of the exercise group. Only the children in the exercise group experienced a reduction in LS-BMFF (effect size [Cohen d] -0.42, CI: -0.86, -0.01). Importantly, 40.9% of the reductions in LS-BMFF were mediated by changes in percentage hepatic fat (indirect effect: ß=-0.104, 95%CI=-0.213, -0.019). The impact of changes in hepatic fat on LS-BMFF was independent of weight loss. CONCLUSIONS AND RELEVANCE: The addition of exercise to a family-based lifestyle program designed to reduce cardiometabolic risk improves bone health by reducing LS-BMFF in children with overweight or obesity. This beneficial effect on bone marrow appears to be mediated by reductions in liver fat.
ABSTRACT
The process of natural or spontaneous mummification has been observed for more than a hundred years in various Mexican pantheons. The construction materials used in the niches of the pantheons generate particular microenvironmental conditions that promote the preservation of organic materials. The construction materials (mining adobe, brick and stone material) that make up the three series of the municipal pantheon of Santa Paula were studied and analyzed using X-ray Diffraction, X-ray Fluorescence and petrographic analysis techniques. At the same time, the mechanical and physical properties of the materials were determined, as well as the relative humidity and temperature within the niches. The results indicate that the geochemistry, distribution and percentage of said materials inside of the niches created exceptional microclimatic conditions that favored the conservation of the bodies. With this contribution we intend to advance the understanding of the influence that construction materials had on the process of natural mummification.
ABSTRACT
BACKGROUND: We assessed the effects of a 20-week combined (aerobic and resistance) exercise training programme on the inflammatory profile of prepubertal children with overweight or obesity. METHODS: Totally 109 participants (10.1 ± 1.1 years, 41% girls) were randomly allocated to an exercise or control group. Adiponectin, C-reactive protein, epidermal growth factor, insulin-like growth factor-1, interleukin (IL)-1ß, IL-6, leptin, tumour necrosis factor-α and vascular endothelial growth factor A (VEGFA) were analysed in plasma. Total white blood cell (WBC) count and immune subpopulations (eosinophils, basophils, neutrophils, lymphocytes and monocytes) were also determined. RESULTS: No intervention effect was found for any of the analysed biomarkers (all p ≥ 0.05). We observed a significant sex by intervention interaction for IL-1ß (p = 0.03). When stratifying the sample by sex, the exercise programme induced a significant effect on IL-1ß levels (mean Z-score difference, 0.66 [95% confidence interval 0.32-1.01]) in girls, but not in boys. A lower number of girls in the exercise group showed a meaningful reduction in IL-1ß (i.e., ≥0.2 standard deviations) than in the control group (15% vs. 85%, p = 0.01). CONCLUSIONS: This exercise programme failed to improve the inflammatory profile in prepubertal children with overweight/obesity. Future studies should explore the effect of longer exercise interventions and in combination with diet.
ABSTRACT
The presence of comorbidities and complex drug regimens makes palliative care patients more susceptible to opioid medication errors. Most of the studies conducted so far have mainly focused on patients admitted to hospitals or hospice facilities. During this study, we examined the frequency of medication errors with opioids and the causes and consequences for patients, followed by home palliative care teams. Errors occurred in 39% of patients (n = 378) and 27% of all prescribed opioids (n = 708). Of the 148 (39%) patients with error/s in the opioid/s prescribed, in 55% the patient and/or the caregiver were involved in the error; in 26% the health care providers were involved. An association was found between the presence of error in the prescribed opioid and the level of patient education, p = .038, and with the number of days of follow-up, p < .001. Considering their formulation, the prescribed opioids were associated with medication error, type of error, and cause of the error. The study demonstrated an association between the route of administration and error p < .004, and type of error p < .001.
ABSTRACT
A simple IgG-speciï¬c ELISA for Leptospira spp. was compared with the microscopic agglutination test (MAT) to detect IgG antibody responses to a commercial vaccine in cattle. We used an enzyme-linked immunosorbent assay (ELISA) with sonicated Leptospira interrogans serovar copenhageni M 20. After initial vaccination, specific antibodies against Leptospira spp. were detected in 90â¯% of the animals by IgG-ELISA and 60â¯% by MAT, while after booster, antibodies were detected in 100â¯% and 80â¯% of the animals by IgG-ELISA and MAT, respectively. Both serological MAT and ELISA tests revealed interferences of vaccine antibodies. Disease diagnosis with ELISA and MAT methods should be made two and a half months and four months, respectively, after vaccination to avoid interference of vaccine antibodies. On the other hand, our results suggest that IgG-ELISA may be a useful method to assess the development of IgG antibodies induced by Leptospira vaccine.
Subject(s)
Agglutination Tests , Antibodies, Bacterial , Bacterial Vaccines , Cattle Diseases , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Leptospirosis , Animals , Leptospirosis/veterinary , Leptospirosis/diagnosis , Leptospirosis/immunology , Cattle , Cattle Diseases/microbiology , Cattle Diseases/diagnosis , Cattle Diseases/immunology , Cattle Diseases/blood , Enzyme-Linked Immunosorbent Assay/veterinary , Antibodies, Bacterial/blood , Bacterial Vaccines/immunology , Immunoglobulin G/blood , Agglutination Tests/veterinary , Leptospira interrogans/immunology , Leptospira/immunology , Vaccination/veterinary , Serologic Tests/veterinaryABSTRACT
Lentigo maligna (LM), a form of melanoma in situ, and LM melanoma (LMM), its invasive counterpart, exhibit distinctive epidemiology, risk factors, and clinical features compared to other melanoma subtypes. Notably, LM occurs on chronically sun-damaged skin presenting as a slow-growing, ill-defined patch which makes it difficult to diagnose and to treat. Additionally, while LM generally presents a favourable prognosis, it can also lead to dermal invasion and behave similarly to other melanomas with the same Breslow thickness. Hence, surgery continues to be the cornerstone treatment. Wide excisions are often necessary, but challenges arise when these lesions manifest in cosmetically sensitive regions, limiting the feasibility and desirability of large excisions. Specialized approaches, including margin-controlled surgery and image-guided treatment with reflectance confocal microscopy, have been developed to address these issues. Other non-surgical treatments such as cryosurgery, imiquimod, radiotherapy, or photodynamic therapy, may also be used but commonly present with recurrent/persistent disease. Herein we comprehensively review the existing literature on the management of LM/LMM, and discus the potential new advances on managing this challenging skin cancer.
Subject(s)
Hutchinson's Melanotic Freckle , Skin Neoplasms , Humans , Hutchinson's Melanotic Freckle/therapy , Hutchinson's Melanotic Freckle/diagnosis , Skin Neoplasms/therapy , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Photochemotherapy , Imiquimod/therapeutic useABSTRACT
We present the case of a 52-year-old woman diagnosed with stage IV clear cell renal cell carcinoma who received combination of surgery and systemic therapy with nivolumab (anti-PD1) and ipilimumab (anti-CTLA-4). During treatment, patient presented oral intolerance, vomiting and abdominal pain. Computed tomography (CT) and gastroscopy (EGD) were performed, identifying findings suggestive of severe gastro-duodenitis with friability and diffuse oedema of the mucosa and deep ulcers. A gastrointestinal immunotherapy-induced toxicity was suspected so patient was managed with proton pump inhibitors (PPIs) and intravenous corticosteroids 1mg/Kg. Three weeks later, corticosteroid treatment failed. EGD was repeated and gastric biopsies were taken for histological and microbiological tests. Gastric biopsies revealed the presence of cytomegalovirus (CMV) inclusion bodies by immunohistochemistry (IHC). CMV viral load by quantitative PCR in plasma was 2,000 IU/mL so intravenous ganciclovir was prescribed. Then, the patient presented poor clinical course with persistent vomiting due to a failure of first-line corticosteroid and antiviral treatment. Another EGD was performed. Last IHC reveals a low CMV viral load. Second-line treatment with Anti-TNF was performed using a single-dose regimen of intravenous infliximab 5 mg/Kg. Finally, the patient presented a clinical and endoscopic response and a negative CMV DNA test in the blood after completing the antiviral treatment.
ABSTRACT
BACKGROUND: Individuals with type 1 diabetes mellitus (T1DM) face impaired cardiorespiratory fitness and glycemic control, increasing the risk of cardiovascular complications. High-intensity interval training (HIIT) has emerged as a promising exercise modality with potential benefits for both aspects in this population. OBJECTIVES: The primary aim was to investigate the effects of HIIT on cardiorespiratory fitness and glycemic parameters in patients with T1DM. The secondary aim was to examine the most effective HIIT protocol for cardiorespiratory fitness and glycemic parameters in patients with T1DM. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Two major electronic databases (Web of Science and PubMed) were searched up to February 2024. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized and non-randomized trials involving adult patients with T1DM, free of complications and other diseases examining the effects of HIIT (HIIT pre vs. post; HIIT vs. control group or HIIT vs. moderate-intensity continuous training (MICT)) on cardiorespiratory fitness and glycemic parameters were included. RESULTS: A total of ten studies met the inclusion criteria. The meta-analysis revealed a significant improvement in cardiorespiratory fitness following HIIT interventions (pre vs. post) in patients with T1DM (standardized mean difference (SMD) = 0.59, 95% confidence interval (CI) = 0.16 to 1, p = 0.01). Furthermore, HIIT (pre vs. post) was associated with significant improvements in 24-h mean glucose control (SMD = - 0.44, 95% CI = - 0.81 to - 0.06, p = 0.02), but the results (pre vs. post) failed to identify significant improvements in fasting glucose (SMD = - 0.26, 95% CI = - 0.78 to 0.24, p = 0.3) and glycated hemoglobin (HbA1C) values (SMD = - 0.28, 95% CI = - 0.61 to 0.05, p = 0.1). However, in comparison with a control group, HIIT showed significantly favorable effects on HbA1C (SMD = - 0.74, 95% CI = - 1.35 to - 0.14, p = 0.02). Finally, the meta-regression analysis did not find any moderating effect of any HIIT characteristics (i.e., intervention duration, session duration, work time, rest time, number of bouts, and intensity) on cardiorespiratory fitness and glycemic parameters. CONCLUSION: Our systematic review and meta-analysis show that T1DM patients who performed a HIIT intervention significantly improved cardiorespiratory fitness and reduced their 24-h mean glucose levels, but not their HbA1C and fasting glucose. These findings support the application of HIIT interventions in T1DM patients. However, the guidelines for the most effective protocol remain unclear; hence, future studies are needed.
ABSTRACT
The main objective of this work is to investigate the relationship between the Mediterranean diet (MD) and metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary objective is to analyze sex differences. METHODS: A cross-sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, and a total of 3417 subjects with a mean age ± SD of 60.14 ± 9.14 years (57% men) were included. We followed the five criteria established in the National Cholesterol Education Program III to define MetS. The MD was assessed with the 14-item Mediterranean diet adherence screener (MEDAS) used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. RESULTS: The mean ± SD value of the MEDAS questionnaire was 5.83 ± 2.04 (men 5.66 ± 2.06 and women 6.04 ± 1.99; p < 0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p < 0.001). MetS was observed in 41.6% (39.0% men and 45.2% women; p < 0.001). In the multiple regression analysis, after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (ß = -0.336), and with the different components of MetS: systolic blood pressure (ß = -0.011), diastolic blood pressure (ß = -0.029), glycemia (ß = -0.009), triglycerides (ß = -0.004), and waist circumference (ß = -0.026), except with the HDL-cholesterol value which showed a positive association (ß = 0.021); p < 0.001 in all cases. In the logistic regression analysis performed, we found that an increase in MD adherence was associated with a decrease in the probability of MetS (OR = 0.56) and its components: blood pressure levels ≥ 130/85 mmHg (OR = 0.63), fasting plasma glucose ≥ 100 mg/dL (OR = 0.62), triglyceride levels ≥ 150 mg/dL (OR = 0.65), waist circumference levels ≥ 88 cm in women and ≥102 cm in men (OR = 0.74), and increased high-density lipoprotein cholesterol < 40 mg/dL in men and <50 mg/dL in women (OR = 1.70); p < 0.001 in all cases. The results by sex were similar, both in multiple regression and logistic regression. CONCLUSIONS: The results found in our work indicate that the greater the adherence to the MD, the lower the probability of presenting MetS. This result is repeated in the study by sex. More studies are needed to clarify that these results can be extended to the rest of the Mediterranean countries, and to other countries outside the Mediterranean basin.
Subject(s)
Diet, Mediterranean , Metabolic Syndrome , White People , Humans , Diet, Mediterranean/statistics & numerical data , Metabolic Syndrome/epidemiology , Male , Female , Cross-Sectional Studies , Middle Aged , Aged , Adult , Sex Factors , Waist Circumference , Surveys and Questionnaires , Blood Pressure , Triglycerides/blood , Blood Glucose/metabolismABSTRACT
As cancer progresses, patients may experience physical decline, which can impair their ability to carry out essential daily tasks. The aim of this study was to analyze the levels of physical activity in patients with advanced cancer undergoing systemic treatment and its relationship with sociodemographic, clinical, and psychological factors. A prospective, cross-sectional, multicenter study was carried out in 15 oncology departments in Spain. Patients with locally advanced, unresectable, or metastatic cancer who were candidates for systemic treatment were included. Participants completed demographic information and psychological scales. In total, 508 patients were included in the study, the majority of whom were male, over the age of 65, and diagnosed with bronchopulmonary tumors (36%) and metastatic disease. Based on their physical activity levels, participants were categorized as sedentary (20%, n = 190), engaging in light physical activity (43%, n = 412), or demonstrating moderate physical activity (37%, n = 351). Patients who were over 65 years old; had a worse baseline status (ECOG ≥ 1); lacked a partner; had a lower educational level; or were retired or unemployed were found to have lower levels of physical activity. Those with sedentary physical activity reported higher levels of psychological distress, anxiety, depression, somatization, and physical symptoms, as well as worse functional status, global health status, and well-being. Understanding the complex interplay between physical activity and sociodemographic, clinical, and psychological factors can help neuroscientists develop tailored exercise interventions that address the unique needs of advanced cancer patients.
ABSTRACT
Multiple sclerosis (MS) is an autoimmune demyelinating disease affecting the central nervous system (CNS). T helper (Th) 17 cells are involved in the pathogenesis of MS and its animal model of experimental autoimmune encephalomyelitis (EAE) by infiltrating the CNS and producing effector molecules that engage resident glial cells. Among these glial cells, astrocytes have a central role in coordinating inflammatory processes by responding to cytokines and chemokines released by Th17 cells. In this study, we examined the impact of pathogenic Th17 cells on astrocytes in vitro and in vivo. We identified that Th17 cells reprogram astrocytes by driving transcriptomic changes partly through a Janus Kinase (JAK)1-dependent mechanism, which included increased chemokines, interferon-inducible genes, and cytokine receptors. In vivo, we observed a region-specific heterogeneity in the expression of cell surface cytokine receptors on astrocytes, including those for IFN-γ, IL-1, TNF-α, IL-17, TGFß, and IL-10. Additionally, these receptors were dynamically regulated during EAE induced by adoptive transfer of myelin-reactive Th17 cells. This study overall provides evidence of Th17 cell reprogramming of astrocytes, which may drive changes in the astrocytic responsiveness to cytokines during autoimmune neuroinflammation.
Subject(s)
Astrocytes , Encephalomyelitis, Autoimmune, Experimental , Janus Kinase 1 , Myelin-Oligodendrocyte Glycoprotein , Receptors, Cytokine , Th17 Cells , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Animals , Astrocytes/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Mice , Receptors, Cytokine/metabolism , Receptors, Cytokine/genetics , Janus Kinase 1/metabolism , Mice, Inbred C57BL , Cytokines/metabolism , Cellular Reprogramming , Female , Cells, CulturedABSTRACT
BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and nonrecovery in ACLF. APPROACH AND RESULTS: Here, we mapped the single-cell transcriptome of circulating immune cells from patients with ACLF and acute decompensated (AD) cirrhosis and healthy individuals. We further interrogate how these findings, as well as immunometabolic and functional profiles, associate with ACLF-recovery (ACLF-R) or nonrecovery (ACLF-NR). Our analysis unveiled 2 distinct states of classical monocytes (cMons). Hereto, ACLF-R cMons were characterized by transcripts associated with immune and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1 . Additional metabolomic and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program, and blunted activation among lymphoid populations in patients with ACLF-R. Conversely, ACLF-NR cMon featured elevated expression of inflammatory and stress response genes such as VIM , LGALS2 , and TREM1 , along with blunted metabolic activity and increased functionality. CONCLUSIONS: This study identifies distinct immunometabolic cellular states that contribute to disease outcomes in patients with ACLF. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or nonrecovery phenotypes, which may be harnessed as potential therapeutic targets in the future.
ABSTRACT
BACKGROUND AND OBJECTIVES: Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). METHODS: This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. RESULTS: Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). DISCUSSION: Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.
Subject(s)
Aquaporin 4 , Brain , Magnetic Resonance Imaging , Multiple Sclerosis , Myelin-Oligodendrocyte Glycoprotein , Neuromyelitis Optica , Humans , Female , Male , Myelin-Oligodendrocyte Glycoprotein/immunology , Adolescent , Child , Retrospective Studies , Brain/diagnostic imaging , Brain/pathology , Multiple Sclerosis/diagnostic imaging , Aquaporin 4/immunology , Neuromyelitis Optica/diagnostic imaging , Neuromyelitis Optica/immunology , Young Adult , Autoantibodies/blood , Adult , Disease ProgressionABSTRACT
Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks.Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed.Results: This analysis included 901 patients. Within 1-2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p <.05). Improvements increased through weeks 4-8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%-77.7% with upadacitinib 15 mg + TCS and 71.3%-83.6% with upadacitinib 30 mg + TCS.Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.
Subject(s)
Dermatitis, Atopic , Drug Therapy, Combination , Heterocyclic Compounds, 3-Ring , Pruritus , Quality of Life , Humans , Dermatitis, Atopic/drug therapy , Pruritus/drug therapy , Pruritus/etiology , Female , Male , Adolescent , Adult , Heterocyclic Compounds, 3-Ring/administration & dosage , Treatment Outcome , Patient Reported Outcome Measures , Young Adult , Middle Aged , Severity of Illness Index , Double-Blind Method , Adrenal Cortex Hormones/administration & dosage , Administration, CutaneousABSTRACT
OBJECTIVES: To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional, observational, non-randomised study was conducted in JIA patients younger than 18 years. All patients underwent anterior segment (AS-OCT) and macular OCT. RESULTS: A total of 300 eyes of 150 patients diagnosed with JIA were included; 74% were females, and mean age was 11.12 ± 3.51 years old (range 4.13-18.60). In the slit-lamp examination, anterior uveitis was diagnosed in 16 eyes. In the AS-OCT, anterior uveitis was suspected in 27 eyes; cells were detected in 27 eyes and retrokeratic precipitates in 5 eyes. Sensitivity was 0.94 and specificity was 0.96, positive predictive value was 0.59 and negative predictive value was 0.99, and Kappa-Cohen index was 0.71. CONCLUSIONS: AS-OCT could be considered for the screening of anterior segment uveitis in children diagnosed with JIA.
Subject(s)
Arthritis, Juvenile , Tomography, Optical Coherence , Uveitis, Anterior , Humans , Arthritis, Juvenile/diagnostic imaging , Arthritis, Juvenile/complications , Child , Female , Male , Cross-Sectional Studies , Adolescent , Uveitis, Anterior/diagnostic imaging , Child, Preschool , Predictive Value of Tests , Anterior Chamber/diagnostic imaging , Anterior Chamber/pathology , Reproducibility of ResultsABSTRACT
OBJECTIVES: To examine the relationship between sleep and subcortical brain structures using a shape analysis approach. METHODS: A total of 98 children with overweight/obesity (10.0 ± 1.1 y, 59 boys) were included in the cross-sectional analyses. Sleep behaviors (i.e., wake time, sleep onset time, total time in bed, total sleep time, sleep efficiency, and wakening after sleep onset) were estimated with wrist-worn accelerometers. The shape of the subcortical brain structures was acquired by magnetic resonance imaging. A partial correlation permutation approach was used to examine the relationship between sleep behaviors and brain shapes. RESULTS: Among all the sleep variables studied, only total time in bed was significantly related to pallidum and putamen structure, such that those children who spent more time in bed had greater expansions in the right and left pallidum (211-751 voxels, all p's <0.04) and right putamen (1783 voxels, p = 0.03). CONCLUSIONS: These findings suggest that more time in bed was related to expansions on two subcortical brain regions in children with overweight/obesity.
ABSTRACT
Purpose: To examine whether image processing of non-mydriatic DRI Triton SS-OCT (Topcon Corporation, Tokyo, Japan) using the red free filter could assess the presence of choroidal nodules and thus include their detection as a diagnostic criterion in neurofibromatosis type 1 (NF1). Material and methods: We included 417 eyes from 210 patients, 377 - from 190 patients diagnosed with NF1 according to the criteria established by the National Institutes of Health Consensus Development Conference (NIH) and 40 from 20 healthy patients as a control group. The mean age was 9.4 years (range 2 years-18 years). All patients had their visual acuity measured by a test according to age, were examined for the presence of lisch nodules and an Optical Coherence Tomography (OCT) of the macular area was performed. All the OCT images were analysed to check if visible nodules could be identified. Results: Ages 14 (95% CI=(9.7,18.3)) and 12 years (95% CI=(9.1,14)) are the cut-off points that best separate those with choroidal nodules with Triton OCT and lisch with slit lamp, respectively, from those without. lisch nodules were detected in 50% of cases of NF1 patients. The presence of choroidal nodules did not present a statistically significant correlation with the occurrence of optic pathway glioma (p = 0.96) nor with the patient's visual worsening (p = 0.072). A statistically significant correlation was observed between the presence of choroidal nodules and the presence of lisch nodules (p < 0.05). Conclusion: The Topcon Triton OCT red free tool would not be a good tool to detect choroidal nodules in patients with NF1 because of its low sensitivity. If the presence of choroidal nodules were to be included in the diagnostic criteria for NF1, it would be convenient to use a device with red and infrared radiations.