RESUMO
Primary mediastinal large B-cell lymphoma (PMBCL) is a rare, non-Hodgkin, B-cell lymphoma thought to originate from thymic B cells, which occurs primarily in young adults such as in the active duty population. Primary mediastinal large B-cell lymphoma (PMBCL) presents as a large mediastinal mass, posing risks to the cardiopulmonary safety of patients and challenging the routine approach to diagnosis. We describe a case of a 23-year-old male sailor who presented to sick call on his ship while in port with shortness of breath, night sweats, 50-pound weight loss, and pruritic punched-out lesions on all extremities. An initial chest X-ray showed a large consolidation. After being seen in the pulmonary medicine clinic 5 weeks after his initial presentation, the patient was admitted to the intensive care unit after computed tomography of his chest revealed a mediastinal mass, causing compression of both the right bronchus and superior vena cava with a large pericardial effusion. Empiric high-dose dexamethasone was initiated before a formal diagnosis due to his significant risk for cardiopulmonary compromise. Following diagnosis and two cycles of chemotherapy, the patient was transferred to a medical oncology facility in the continental USA. This case demonstrates the need to educate all military providers to recognize the presentation of mediastinal masses in active duty service members and the importance of urgently escalating these patients to higher levels of care in order to avoid life-threatening complications.
Assuntos
Linfoma de Células B , Neoplasias do Mediastino , Militares , Adulto Jovem , Humanos , Masculino , Adulto , Neoplasias do Mediastino/complicações , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Veia Cava Superior/patologia , Linfoma de Células B/complicações , PruridoRESUMO
GWAS and eQTL studies identified thousands of genetic variants associated with complex traits and gene expression. Despite the important role of environmental exposures in complex traits, only a limited number of environmental factors were measured in these studies. Measuring molecular phenotypes in tightly controlled cellular environments provides a more tractable setting to study gene-environment interactions in the absence of other confounding variables. We performed RNA-seq and ATAC-seq in endothelial cells exposed to retinoic acid, dexamethasone, caffeine, and selenium to model genetic and environmental effects on gene regulation in the vascular endothelium-a common site of pathology in cardiovascular disease. We found that genes near regions of differentially accessible chromatin were more likely to be differentially expressed [OR = (3.41, 6.52), [Formula: see text]]. Furthermore, we confirmed that environment-specific changes in transcription factor binding are a key mechanism for cellular response to environmental stimuli. Single nucleotide polymorphisms (SNPs) in these transcription response factor footprints for dexamethasone, caffeine, and retinoic acid were enriched in GTEx eQTLs from artery tissues, indicating that these environmental conditions are latently present in GTEx samples. Additionally, SNPs in footprints for response factors in caffeine are enriched in colocalized eQTLs for coronary artery disease (CAD), suggesting a role for caffeine in CAD risk. By combining GWAS, eQTLs, and response genes, we annotated environmental components that can increase or decrease disease risk through changes in gene expression in 43 genes. Interestingly, each treatment may amplify or buffer genetic risk for CAD, depending on the particular SNP or gene considered.
Assuntos
Doença da Artéria Coronariana/genética , Interação Gene-Ambiente , Predisposição Genética para Doença , Locos de Características Quantitativas/genética , Cafeína/farmacologia , Células Endoteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fenótipo , RNA-Seq , Fatores de Risco , Selênio/farmacologia , Tretinoína/farmacologiaRESUMO
BACKGROUND: Lidocaine is used to alleviate procedural pain but paradoxically increases pain during injection. Pain perception can be modulated by non-noxious stimuli such as temperature or touch according to the gate control theory of pain. We postulated that lidocaine dripped onto the skin prior to injection would cool or add the sensation of touch at the skin surface to reduce pain perception from the procedure. METHODS: A randomized clinical trial of patients referred to the procedure service from February 2011 through March 2015 was conducted. All patients received 1% subcutaneous lidocaine injection. Patients randomized to the intervention group had approximately 1 to 2 ml of lidocaine squirted onto the skin surface prior to subcutaneous lidocaine injection. Patients were blinded to the details of the intervention and were surveyed by a blinded investigator to document the primary outcome (severity of pain from the procedure) using a visual analog scale. RESULTS: A total of 481 patients provided consent and were randomized to treatment. There was a significant improvement in the primary outcome of procedural pain (control, 16.6 ± 24.8 mm vs 12.2 ± 19.4 mm; P = .03) with the intervention group as assessed by using the visual analog scale score. Pain scores were primarily improved for peripherally inserted central catheters (control, 18.8 ± 25.6 mm vs 12.2 ± 18.2 mm; P = .02) upon subgroup analysis. CONCLUSIONS: Bedside procedures are exceedingly common. Data regarding the severity of procedural pain and strategies to mitigate it are important for the informed consent process and patient satisfaction. Overall, pain reported from common bedside procedures is low, but pain can be further reduced with the addition of lidocaine onto the skin surface to modulate pain perception. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01330134; URL: www.clinicaltrials.gov.