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1.
Artículo en Inglés | MEDLINE | ID: mdl-39358543

RESUMEN

Post-COVID-19 cognitive deficits are common, persistent, and disabling. Evidence on effective treatments is limited. The goal of this study was to investigate the efficacy of a digital intervention to reduce cognitive and functional deficits in adults with persistent post-COVID-19 cognitive dysfunction. We used the remotely-delivered intervention in a randomized clinical trial conducted from July 13, 2021 to April 26, 2023. We hypothesized that participants in the intervention group would improve in measures of cognition and daily functioning. Participants were adults with cognitive deficits persisting >4 weeks following acute COVID-19 illness. Of 183 participants screened, 110 were enrolled; 98 participants (78.6% female; mean age = 48.1) completed at least one study visit. Participants were randomized 1:1 to the intervention (AKL-T01) or waitlist control. AKL-T01 is a digital therapeutic using a videogame interface to target attention and executive control. The intervention was delivered remotely for 6 weeks. The primary outcome was change in performance on a sustained attention measure (Digit Symbol Matching Task). The difference in the primary outcome between the intervention (n = 49) and controls (n = 49) was not statistically significant (F [3,261] = 0.12, p = 0.95). Secondary cognitive outcomes of task-switching (F[3,262] = 2.78, p = 0.04) and processing speed (F[3,267] = 4.57, p = 0.004) improved in the intervention relative to control. Secondary measures of functioning also improved in the intervention relative to control, including disability (F[1,82] = 4.02, p = 0.05) and quality of life (F[3,271] = 2.66, p = 0.05). Exploratory analyses showed a greater reduction in total fatigue (F[1,85] = 4.51, p = 0.04), cognitive fatigue (F[1,85] = 7.20, p = 0.009), and anxiety (F[1,87] = 7.42, p = 0.008) in the intervention relative to control. Despite the lack of improvement in sustained attention, select post-COVID-19 cognitive deficits may be ameliorated by targeted cognitive training with AKL-T01, with associated improvements in quality of life and fatigue. If replicated, the scalable nature of this digital intervention may help address substantial need for accessible, effective treatments among individuals with long COVID.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39227035

RESUMEN

BACKGROUND: Autism commonly co-occurs with attention-deficit/hyperactivity disorder (ADHD), but less is known regarding how ADHD symptoms impact the early presentation of autism. This study examined early behavioral characteristics of a community sample of toddlers later identified with autism diagnosis, ADHD symptoms, combined autism and ADHD symptoms, or neither condition. METHODS: Participants were 506 toddlers who were part of a longitudinal study of children's behavioral development. Parents completed questionnaires about their children's behavior at two time points. Four groups were identified based on study measures or medical record: autism diagnosis (n = 45), elevated ADHD symptoms (n = 70), autism and ADHD symptoms (n = 30), or neurotypical development (n = 361). Relationships between early parent report of autism- and ADHD-related behaviors, social-emotional and behavioral functioning, and caregiver experience and subsequent group designation were evaluated with adjusted linear regression models controlling for sex. RESULTS: Significant group differences were found in measures of autism-related behaviors, ADHD-related behaviors, externalizing and internalizing behaviors, and parent support needs (p < .0001). Pairwise comparisons indicated toddlers later identified with combined autism diagnosis and ADHD symptoms had higher levels of autism-related behaviors, externalizing and internalizing behaviors, and autism-related parent support needs compared to the other groups. Toddlers with subsequent elevated ADHD symptoms or combined autism diagnosis and ADHD symptoms exhibited similar levels of ADHD-related behaviors, while both groups displayed more ADHD-related behaviors than toddlers subsequently identified with autism or those with neither condition. CONCLUSIONS: In this community sample, toddlers for whom combined autism diagnosis and ADHD symptoms were subsequently identified showed a distinct presentation characterized by higher early autism-related behaviors, broader behavioral concerns, and higher parent support needs. Presence of ADHD symptoms (alone or in combination with autism) was associated with higher parent-reported ADHD-related behaviors during toddlerhood. Results indicate that ADHD-related behaviors are manifest by toddlerhood, supporting screening for both autism and ADHD during early childhood.

3.
bioRxiv ; 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39253496

RESUMEN

Astrocytes, a major glial cell type of the brain, regulate synapse numbers and function. However, whether astrocyte dysfunction can cause synaptic pathologies in neurological disorders such as Parkinson's Disease (PD) is unknown. Here, we investigated the impact of the most common PD-linked mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (G2019S) on the synaptic functions of astrocytes. We found that both in human and mouse cortex, the LRRK2 G2019S mutation causes astrocyte morphology deficits and enhances the phosphorylation of the ERM proteins (Ezrin, Radixin, and Moesin), which are important components of perisynaptic astrocyte processes. Reducing ERM phosphorylation in LRRK2 G2019S mouse astrocytes restored astrocyte morphology and corrected excitatory synaptic deficits. Using an in vivo BioID proteomic approach, we found Ezrin, the most abundant astrocytic ERM protein, interacts with the Autophagy-Related 7 (Atg7), a master regulator of catabolic processes. The Ezrin/Atg7 interaction is inhibited by Ezrin phosphorylation, thus diminished in the LRRK2 G2019S astrocytes. Importantly, Atg7 function is required to maintain proper astrocyte morphology. These studies reveal an astrocytic molecular mechanism that could serve as a therapeutic target in PD.

4.
Physiol Rep ; 12(18): e70059, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39289171

RESUMEN

Cannabidiol (CBD) is widely used in sports for recovery, pain management, and sleep improvement, yet its effects on muscle are not well understood. This study aimed to determine the transcriptional response of murine skeletal muscle myotubes to broad-spectrum CBD and synthetic CBD (sCBD). Differentiated C2C12 myotubes were treated with 10 µM CBD, sCBD, or vehicle control (DMSO) for 24 h before RNA extraction. Poly-A tail-enriched mRNA libraries were constructed and sequenced using 2 × 50 bp paired-end sequencing. CBD and sCBD treatment induced 4489 and 1979 differentially expressed genes (DEGs; p < 0.001, FDR step-up <0.05), respectively, with common upregulation of 857 genes and common downregulation of 648 genes. Common upregulated DEGs were associated with "response to unfolded protein," "cell redox homeostasis," "endoplasmic reticulum stress," "oxidative stress," and "cellular response to hypoxia." Common downregulated DEGs were linked to "sarcomere organization," "skeletal muscle tissue development," "regulation of muscle contraction," and "muscle contraction." CBD treatment induced unique DEGs compared to sCBD. The data indicate CBD may induce mild cellular stress, activating pathways associated with altered redox balance, unfolded protein response, and endoplasmic reticulum stress. We hypothesize that CBD interacts with muscle and may elicit a "mitohormetic" effect that warrants further investigation.


Asunto(s)
Cannabidiol , Fibras Musculares Esqueléticas , Transcriptoma , Cannabidiol/farmacología , Animales , Ratones , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Transcriptoma/efectos de los fármacos , Línea Celular
5.
PLOS Digit Health ; 3(9): e0000612, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39348377

RESUMEN

Immigrants and refugees seeking admission to the United States must first undergo an overseas medical exam, overseen by the US Centers for Disease Control and Prevention (CDC), during which all persons ≥15 years old receive a chest x-ray to look for signs of tuberculosis. Although individual screening sites often implement quality control (QC) programs to ensure radiographs are interpreted correctly, the CDC does not currently have a method for conducting similar QC reviews at scale. We obtained digitized chest radiographs collected as part of the overseas immigration medical exam. Using radiographs from applicants 15 years old and older, we trained deep learning models to perform three tasks: identifying abnormal radiographs; identifying abnormal radiographs suggestive of tuberculosis; and identifying the specific findings (e.g., cavities or infiltrates) in abnormal radiographs. We then evaluated the models on both internal and external testing datasets, focusing on two classes of performance metrics: individual-level metrics, like sensitivity and specificity, and sample-level metrics, like accuracy in predicting the prevalence of abnormal radiographs. A total of 152,012 images (one image per applicant; mean applicant age 39 years) were used for model training. On our internal test dataset, our models performed well both in identifying abnormalities suggestive of TB (area under the curve [AUC] of 0.97; 95% confidence interval [CI]: 0.95, 0.98) and in estimating sample-level counts of the same (-2% absolute percentage error; 95% CIC: -8%, 6%). On the external test datasets, our models performed similarly well in identifying both generic abnormalities (AUCs ranging from 0.89 to 0.92) and those suggestive of TB (AUCs from 0.94 to 0.99). This performance was consistent across metrics, including those based on thresholded class predictions, like sensitivity, specificity, and F1 score. Strong performance relative to high-quality radiological reference standards across a variety of datasets suggests our models may make reliable tools for supporting chest radiography QC activities at CDC.

6.
Dermatol Clin ; 42(4): 527-535, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39278706

RESUMEN

Atopic dermatitis (AD) and food allergies are 2 atopic conditions that tend to develop early in life. Their interrelationship has been a topic of controversy and many studies. The presence of atopic dermatitis in infancy and early childhood, particularly if severe, is a risk factor for the development of immunoglobulin E (IgE) -mediated food allergies. While it is common for children with AD to demonstrate extensive sensitization to foods, serum IgE testing is not always indicative of clinical allergy.


Asunto(s)
Dermatitis Atópica , Hipersensibilidad a los Alimentos , Inmunoglobulina E , Humanos , Dermatitis Atópica/inmunología , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/complicaciones , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Factores de Riesgo , Lactante
7.
Dermatol Clin ; 42(4): 591-600, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39278712

RESUMEN

Recommendations about allergy prevention through diet are rapidly changing. In just the past several years, multiple organizations have provided updated guidance and recommendations about infant feeding based on recent studies and meta-analyses. In addition to the increased number of studies supporting the benefit of early introduction of allergenic foods, in particular peanut and egg, recent studies demonstrate that infant and maternal diet diversity may also reduce risk of food allergy and atopy. Skin emollients have not been found to be helpful in prevention of food allergy, and more evidence is needed to determine if emollients play a role in prevention of atopic dermatitis.


Asunto(s)
Hipersensibilidad a los Alimentos , Humanos , Hipersensibilidad a los Alimentos/prevención & control , Lactante , Dermatitis Atópica/prevención & control , Alimentos Infantiles , Factores de Tiempo , Lactancia Materna , Dieta
8.
Artículo en Inglés | MEDLINE | ID: mdl-39293782

RESUMEN

In February 2024, omalizumab was approved by the Food and Drug Administration for the treatment of food allergy, based on data from the landmark Phase 3 clinical trial "Omalizumab as Monotherapy and as Adjunct Therapy in Children and Adults (OUtMATCH)." In this Rostrum, OUtMATCH investigators share their perspectives on the trial results, the implications for translation into daily practice, and on remaining gaps in the field. The study met its primary and key secondary endpoints, demonstrating a large effect size in multi-allergen desensitization compared to placebo; yet there were some participants who did not respond, and the percentage of responders tolerating all 3 food allergens was lower than that for single foods. . Clinicians are likely to have many questions about appropriate patient selection, monitoring for treatment responsiveness, and how to manage off-label considerations such as dietary incorporation or co-treatment with oral immunotherapy. Additional research is needed to answer these remaining questions and ensure that the translation of omalizumab in real-world practice leads to high-quality outcomes.

9.
BMC Psychiatry ; 24(1): 618, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285361

RESUMEN

BACKGROUND: The objectives of this study were to examine the association of psychiatric comorbidities and patient characteristics with treatment change and response as well as to assess the association between treatment change and healthcare resource utilization (HCRU) among adult patients with attention-deficit/hyperactivity disorder (ADHD) and psychiatric comorbidities. METHODS: De-identified electronic health records from the NeuroBlu Database (2002-2021) were used to select patients ≥ 18 years with ADHD who were prescribed ADHD-specific medication. The index date was set as the first prescription of ADHD medication. The outcomes were treatment change (discontinuation, switch, add-on, or drop) and HCRU (inpatient, outpatient, composite) within 12 months of follow-up. Cox proportional-hazard model was used to assess the association between clinical and demographic patient characteristics and treatment change, while generalized linear model with negative binomial distribution and log link function was used to assess the association between key risk factors linked to treatment change and HCRU rates. RESULTS: A total of 3,387 patients with ADHD were included (ADHD only: 1,261; ADHD + major depressive disorder (MDD): 755; ADHD + anxiety disorder: 467; ADHD + mood disorder: 164). Nearly half (44.8%) of the study cohort experienced a treatment change within the 12-month follow-up period. Treatment switch and add-on were more common in patients with ADHD and comorbid MDD and anxiety disorder (switch: 18.9%; add-on: 20.5%) compared to other cohorts (range for switch: 8.5-13.6%; range for add-on: 8.9-12.1%) Survival analysis demonstrated that the probability of treatment change within 12 months from treatment initiation in the study cohort was estimated to be 42.4%. Outpatient visit rates statistically significantly increased from baseline (mean [SD] 1.03 [1.84] visits/month) to 3 months post-index (mean [SD] 1.62 [1.91] visits/month; p < 0.001), followed by a gradual decline up to 12 months post-index. Being prescribed both a stimulant and a non-stimulant at index date was statistically significantly associated with increased risk of treatment change (adjusted hazard ratio: 1.64; 95% CI: 1.13, 2.38; p = 0.01). CONCLUSIONS: This real-world study found that treatment change was common among patients with ADHD and psychiatric comorbidities. These findings support the need for future studies to examine the unmet medical and treatment needs of this complex patient population.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Comorbilidad , Registros Electrónicos de Salud , Humanos , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Femenino , Masculino , Adulto , Estados Unidos/epidemiología , Bases de Datos Factuales , Persona de Mediana Edad , Adulto Joven , Aceptación de la Atención de Salud/estadística & datos numéricos , Trastornos Mentales/epidemiología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Modelos de Riesgos Proporcionales
10.
J Chromatogr A ; 1735: 465281, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39243589

RESUMEN

Therapeutic formats derived from the monoclonal antibody structure have been gaining significant traction in the biopharmaceutical market. Being structurally similar to mAbs, most Fc-containing therapeutics exhibit product-related impurities in the form of aggregates, charge variants, fragments, and glycoforms, which are inherently challenging to remove. In this work, we developed a workflow that employed rapid resin screening in conjunction with an in silico tool to identify and rank orthogonally selective processes for the removal of product-related impurities from a Fc-containing therapeutic product. Linear salt gradient screens were performed at various pH conditions on a set of ion-exchange, multimodal ion-exchange, and hydrophobic interaction resins. Select fractions from the screening experiments were analyzed by three different analytical techniques to characterize aggregates, charge variants, fragments, and glycoforms. The retention database generated by the resin screens and subsequent impurity characterization were then processed by an in silico tool that generated and ranked all possible two-step resin sequences for the removal of product-related impurities. A highly-ranked process was then evaluated and refined at the bench-scale to develop a completely flowthrough two-step polishing process which resulted in complete removal of the Man5 glycoform and aggregate impurities with a 73% overall yield. The successful implementation of the in silico mediated workflow suggests the possibility of a platformable workflow that could facilitate polishing process development for a wide variety of mAb-based therapeutics.


Asunto(s)
Anticuerpos Monoclonales , Simulación por Computador , Contaminación de Medicamentos , Fragmentos Fc de Inmunoglobulinas , Flujo de Trabajo , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/aislamiento & purificación , Fragmentos Fc de Inmunoglobulinas/química , Fragmentos Fc de Inmunoglobulinas/aislamiento & purificación , Cromatografía por Intercambio Iónico/métodos , Cricetulus , Interacciones Hidrofóbicas e Hidrofílicas , Células CHO , Animales
11.
Cancers (Basel) ; 16(18)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39335129

RESUMEN

Background: Synovial sarcoma is rare and may present as a small, slow-growing mass. These tumors are often mistaken as benign and are therefore prone to unplanned and/or non-oncologic excision. We sought to identify the rate of unplanned excision of synovial sarcoma and risk factors for recurrence and survival among this cohort. Methods: The medical records of 246 patients evaluated at a single institution for synovial sarcoma between 1997 and 2022 were retrospectively reviewed. Of these, 87 (35%) underwent unplanned, non-oncologic excision. The mean age of the cohort was 49 years. Primary tumors were located in the extremity (n = 63), abdomen (n = 6), thorax (n = 7), head/neck (n = 8), and paraspinal region (n = 3). The median maximum pre-treatment dimension of the primary tumor was 4.8 cm (IQR 7-2.4). Seventy-seven (86%) patients underwent re-excision of the tumor bed, 39 (45%) received chemotherapy, and 63 (72%) received radiation therapy. Results: Among patients who underwent unplanned excision, local recurrence-free survival (LRFS) was 98% at 1 year and 82% at 5 years. Metastasis-free survival (MFS) was 91% at 1 year and 72% at 5 years. Disease-specific survival (DSS) was 98% at 1 year and 72% at 5 years. When adjusting for tumor size, tumors which underwent unplanned excision did not have worse recurrence or survival compared to those which had planned excision (p > 0.10). Size > 5 cm, monophasic subtype, and axial location were associated with increased risk of disease recurrence. Forty-six patients had residual tumor following re-excision, which was associated with worse MFS (HR 8.17, 95% CI [1.89, 35.2], p < 0.01) and DSS (HR 7.66, 95% CI [1.76, 33.4], p < 0.01). Patients who received radiotherapy had improved MFS (HR 6.4, 95% CI [1.42, 29.0], p = 0.02) and DSS (HR 5.86, 95% CI [1.27, 26.9], p = 0.02). Conclusions: One-third of patients presenting with synovial sarcoma were diagnosed after unplanned, non-oncologic excision. Patients with large, axial tumors had worse survival. Approximately half of patients who underwent unplanned excision had no residual tumor after pre-operative radiation. The use of radiation was associated with decreased rates of recurrence and improved disease-specific survival. Our results suggest that margin-negative re-resection and radiotherapy should be considered when feasible following unplanned excision of synovial sarcoma.

12.
Cancers (Basel) ; 16(18)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39335204

RESUMEN

BACKGROUND: Myxoid liposarcoma predominantly affects young and middle-aged individuals, and little is known regarding treatment tolerability and outcomes in older patients. This study aims to better understand this older patient population. METHODS: This single institution retrospective study included patients aged 70 years and older with localized (non-metastatic) myxoid liposarcoma. RESULTS: Sixteen patients were included. The median age was 75 years, and 9 (56%) were female. Fourteen (88%) were extremity tumors and two (12%) were trunk. The median tumor size was 10.4 cm (range, 3.6 to 28 cm). Five (31%) tumors had a round cell component. All patients had surgery. Fourteen (88%) had perioperative radiation, and three (19%) had perioperative chemotherapy. One patient had postoperative infection, and one patient had neutropenic fever from preoperative chemotherapy. The median follow up from surgery was 6.3 years. Eight (50%) patients died from MLPS. The median relapse-free survival and overall survival were 34 months and 75 months, respectively. CONCLUSIONS: Most older patients with localized MLPS received perioperative radiation therapy with surgery, and few serious toxicities were reported. Even with treatment, half of the patients relapsed.

13.
Int J Mol Sci ; 25(18)2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39337350

RESUMEN

The basal cell maintains the airway's respiratory epithelium as the putative resident stem cell. Basal cells are known to self-renew and differentiate into airway ciliated and secretory cells. However, it is not clear if every basal cell functions as a stem cell. To address functional heterogeneity amongst the basal cell population, we developed a novel monoclonal antibody, HLO1-6H5, that identifies a subset of KRT5+ (cytokeratin 5) basal cells. We used HLO1-6H5 and other known basal cell-reactive reagents to isolate viable airway subsets from primary human airway epithelium by Fluorescence Activated Cell Sorting. Isolated primary cell subsets were assessed for the stem cell capabilities of self-renewal and differentiation in the bronchosphere assay, which revealed that bipotent stem cells were, at minimum 3-fold enriched in the HLO1-6H5+ cell subset. Crosslinking-mass spectrometry identified the HLO1-6H5 target as a glycosylated TFRC/CD71 (transferrin receptor) proteoform. The HLO1-6H5 antibody provides a valuable new tool for identifying and isolating a subset of primary human airway basal cells that are substantially enriched for bipotent stem/progenitor cells and reveals TFRC as a defining surface marker for this novel cell subset.


Asunto(s)
Diferenciación Celular , Células Epiteliales , Queratina-5 , Mucosa Respiratoria , Células Madre , Humanos , Células Madre/citología , Células Madre/metabolismo , Queratina-5/metabolismo , Células Epiteliales/citología , Células Epiteliales/metabolismo , Mucosa Respiratoria/citología , Mucosa Respiratoria/metabolismo , Receptores de Transferrina/metabolismo , Anticuerpos Monoclonales , Antígenos CD/metabolismo , Células Cultivadas , Citometría de Flujo/métodos , Biomarcadores/metabolismo , Separación Celular/métodos
14.
Curr Biol ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39332403

RESUMEN

A critical question in biology is how new traits evolve, but studying this in wild animals remains challenging. Here, we probe the genetic basis of trait gain in sea robin fish, which have evolved specialized leg-like appendages for locomotion and digging along the ocean floor. We use genome sequencing, transcriptional profiling, and interspecific hybrid analysis to explore the molecular and developmental basis of leg formation. We identified the ancient, conserved transcription factor tbx3a as a major determinant of sensory leg development. Genome editing confirms that tbx3a is required for normal leg formation in sea robins, and for formation of enlarged central nervous system lobes, sensory papillae, and adult digging behavior. Our study establishes sea robins as a model organism for studying the evolution of major trait gain and illustrates how ancient developmental control genes can underlie novel organ formation.

15.
Am Surg ; : 31348241265135, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39349054

RESUMEN

Background: The Stop the Bleed campaign gives bystanders an active role in prehospital hemorrhage control. Whether extending bystanders' role to private vehicle transport (PVT) for urban penetrating trauma improves survival is unknown, but past research has found benefit to police and PVT. We hypothesized that for penetrating trauma in an urban environment, where prehospital procedures have been proven harmful, PVT improves outcomes compared to any EMS or advanced life support (ALS) transport.Methods: Post-hoc analysis of an EAST multicenter trial was performed on adult patients with penetrating torso/proximal extremity trauma at 25 urban trauma centers from 5/2019-5/2020. Patients were allocated to PVT and any EMS or ALS transport using nearest neighbor propensity score matching. Univariate analyses included Wilcoxon signed rank or McNemar's Test and logistic regression.Results: Of 1999 penetrating trauma patients in urban settings, 397 (19.9%) had PVT, 1433 (71.7%) ALS transport, and 169 (8.5%) basic life support (BLS) transport. Propensity matching yielded 778 patients, distributed equally into balanced groups. PVT patients were primarily male (90.5%), Black (71.2%), and sustained gunshot wounds (68.9%). ALS transport had significantly higher ED mortality (3.9% vs 1.9%, P = 0.03). There was no difference in in-hospital mortality rate, hospital LOS, or complications for all EMS or ALS only transport patients.Conclusion: Compared to PVT, ALS, which provides more prehospital procedures than BLS, provided no survival benefit for penetrating trauma patients in urban settings. Bystander education incorporating PVT for early arrival of penetrating trauma patients in urban settings to definitive care merits further investigation.

16.
Eur Respir Rev ; 33(173)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39293854

RESUMEN

Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Mediadores de Inflamación , Pulmón , Terapia Molecular Dirigida , Neutrófilos , Humanos , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/enzimología , Neutrófilos/enzimología , Neutrófilos/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Animales , Mediadores de Inflamación/metabolismo , Pulmón/efectos de los fármacos , Pulmón/enzimología , Inhibidores de Serina Proteinasa/uso terapéutico , Serina Proteasas/metabolismo , Antiinflamatorios/uso terapéutico , Transducción de Señal , Bronquiectasia/tratamiento farmacológico , Bronquiectasia/enzimología
17.
Curr Oncol ; 31(9): 5384-5398, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39330026

RESUMEN

BACKGROUND: Liposarcoma, one of the most prevalent sarcoma histologies, is recognized for its tendency for extra-pulmonary metastases. While oligometastatic cardiac disease is rarely reported, it poses a unique challenge as oligometastatic sarcomas are often managed with surgical resection. CASE REPORT: We present a case of a 62-year-old man diagnosed with an oligometastatic myxoid liposarcoma (MLPS) to the heart 19 years after the primary tumor resection from the lower limb. The metastatic mass, situated in the pericardium adjacent and infiltrating the left ventricle, was not managed surgically but with a combination of chemotherapy and radiotherapy. The patient's disease remains stable to date, for more than 10 years. LITERATURE REVIEW: We conducted a review of the literature to determine the preferred management approach for solitary cardiac metastases of sarcomas. We also conducted an in-depth analysis focusing on reported cases of MLPS metastasizing to the heart, aiming to extract pertinent data regarding the patient characteristics and the corresponding management strategies. CONCLUSIONS: Although clinical diagnoses of solitary or oligometastatic cardiac metastases from sarcomas are infrequent, this case underscores the significance of aggressive management employing chemotherapy and radiotherapy for chemosensitive and radiosensitive sarcomas, especially when surgical removal is high-risk. Furthermore, it challenges the notion that surgery is the exclusive therapeutic option leading to long-term clinical benefit in patients with recurrent sarcomas.


Asunto(s)
Neoplasias Cardíacas , Liposarcoma Mixoide , Humanos , Masculino , Liposarcoma Mixoide/tratamiento farmacológico , Liposarcoma Mixoide/terapia , Liposarcoma Mixoide/patología , Neoplasias Cardíacas/secundario , Neoplasias Cardíacas/terapia , Neoplasias Cardíacas/tratamiento farmacológico , Persona de Mediana Edad
18.
Vet Sci ; 11(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39330780

RESUMEN

Medical procedures necessary for routine care can induce stress in both the veterinary and human clinical situations. In the research environment, nonhuman primates undergo procedures like physical examination, blood sampling, and intravenous drug or fluid administration either as a part of routine veterinary care or during the modeling of clinical disease and interventions under study. Behavioral management techniques, such as training for cooperation, allow caregivers to train primates to voluntarily engage in various medical procedures. This approach reduces stress and anxiety associated with necessary procedures, thereby enhancing efficiency and minimizing the invasiveness of medical care. Consequently, veterinary evaluation and care can be provided without compromise, resulting in enhanced clinical outcomes and overall better health. In this study, we explored the impact of the behavioral management program implemented at our center on a subset of animals undergoing routine veterinary care, focusing on the overall experience, including animal welfare, scientific rigor, and efficiency in terms of economics and time. We investigated its impact on key factors, such as the total procedure and recovery time, incidence of side effects, and welfare indicators, revealing a significant positive influence on animal care. Furthermore, through case studies, we illustrate how behavioral management facilitates timely medical care and monitoring, effectively mitigating stressors that could otherwise impair health and welfare, enabling the provision of care that would have otherwise been unachievable. A thoughtfully designed primate behavioral management program, integrating cooperation and participation with veterinary care, forms the cornerstone of superior animal welfare, enhanced clinical care, and more accurate scientific outcomes.

19.
Retin Cases Brief Rep ; 18(5): 585-588, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39288228

RESUMEN

PURPOSE: Postoperative endophthalmitis is a relatively uncommon, but potentially visually devastating, complication associated with cataract surgery. Specific microbial causes of endophthalmitis are characteristically associated with particular disease time courses. Although Cutibacterium acnes is typically associated with an indolent course of inflammation, we report a case of C. acnes endophthalmitis with onset on postoperative day (POD) 1 and a positive culture from POD 2. METHODS: This is a case report. RESULTS: A 56-year-old man underwent cataract extraction and posterior chamber intraocular lens placement in his left eye. On POD 1, he presented with severe discomfort, reduced visual acuity, and significant inflammation. On POD 2, his anterior chamber was tapped and injected with broad-spectrum antibiotics and steroids. The inflammation ultimately resolved, and his visual acuity improved to 20/20. CONCLUSION: C. acnes is a rare cause of hyperacute-onset postoperative endophthalmitis. Maintaining a high clinical suspicion and initiating prompt treatment can help to optimize long-term visual outcomes.


Asunto(s)
Extracción de Catarata , Endoftalmitis , Infecciones Bacterianas del Ojo , Humanos , Endoftalmitis/microbiología , Endoftalmitis/diagnóstico , Masculino , Persona de Mediana Edad , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/diagnóstico , Extracción de Catarata/efectos adversos , Complicaciones Posoperatorias/microbiología , Propionibacteriaceae/aislamiento & purificación , Antibacterianos/uso terapéutico , Enfermedad Aguda , Agudeza Visual , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/microbiología
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