RESUMO
INTRODUCTION: The use of non-narcotic modalities for postoperative analgesia may decrease exposure to opioids, thereby limiting their deleterious effects. The objective of this study was to determine the effectiveness of a liposomal bupivacaine transverse abdominis plane (TAP) block prior to laparoscopic sleeve gastrectomy (LSG) and laparoscopic gastric bypass (LRYGB). The primary outcome was total postoperative morphine equivalents. METHODS: A single-surgeon, IRB-approved retrospective chart review was performed on consecutive patients who underwent LRYGB or LSG from 2010 to 2016. Patients were grouped according to those who received TAP blocks immediately preoperatively with rescue opioids (TAP group) and those who received PCA only (PCA group). Total parenteral morphine equivalents (PME) were calculated. Numerical pain scores were collected immediately following surgery, 12 h postoperatively, and on the day of discharge. Median length of stay (LOS) and 30-day readmissions were also calculated. RESULTS: There were 440 patients who met inclusion criteria. The TAP group had significantly less opioid use (total PME) than the PCA, irrespective of surgical approach (70.4 ± 2.7 PCA LRYGB and 26.5 ± 1.5 TAP block LRYGB, p value ≤ 0.0001; 60.0 ± 3.5 PCA LSG vs. and 24.1 ± 2.0 TAP block LSG, p value < 0.0001). Median LOS was 2.0 days for both PCA groups, whereas LOS decreased to 1.0 day for both groups of patients receiving TAP blocks (p < 0.0001). Pain scores immediately following and 12 h after surgery were significantly elevated in the TAP LRYGB versus PCA LRYGB (p < 0.05) and immediately following surgery for PCA versus TAP block for LSG (p = 0.0109). CONCLUSIONS: TAP blocks with liposomal bupivacaine lead to significantly less use of parenteral morphine equivalents and decreased LOS compared to PCA alone. Pain scores were higher in the TAP LRYGB group compared to the LRYGB PCA group, with no differences in pain scores noted in the LSG groups.
Assuntos
Analgésicos não Narcóticos/administração & dosagem , Bupivacaína/administração & dosagem , Gastrectomia , Derivação Gástrica , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Músculos Abdominais/inervação , Adulto , Analgesia Controlada pelo Paciente , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Bupivacaína/uso terapêutico , Feminino , Gastrectomia/métodos , Derivação Gástrica/métodos , Humanos , Laparoscopia , Tempo de Internação/estatística & dados numéricos , Lipossomos , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Medição da Dor , Dor Pós-Operatória/diagnóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: Opioid-related adverse drug events continue to occur. This study aimed to characterize the patient population receiving naloxone to inform future intervention efforts. DESIGN: We describe a case series of patients who received naloxone in the hospital during a 16-week time frame in 2016. Data were collected on other administered medications, reason for admission to the hospital, pre-existing diagnoses, comorbidities, and demographics. SETTING: Twelve hospitals within a large healthcare system. PATIENTS: 46,952 patients were admitted during the study period. 31.01 percent (n = 14,558) of patients received opioids, of which 158 received naloxone. INTERVENTION: Administration of naloxone. Main outcome of interest: Sedation assessment via Pasero Opioid-Induced Sedation Scale (POSS), administration of sedating medications. RESULTS: POSS score was documented prior to opioid administration in 93 (58.9 percent) patients. Less than half of patients had a POSS documented prior to naloxone administration with 36.8 percent documented 4 hours prior. 58.2 percent of patients received multimodal pain therapy with other nonopioid medications. Most patients received more than one sedating medication concurrently (n = 142, 89.9 percent). CONCLUSIONS: Our findings highlight areas for intervention to prevent opioid oversedation. Investing in electronic clinical decision support mechanisms, such as sedation assessment, could detect patients at risk for oversedation and ultimately prevent the need for naloxone. Coordinated order sets for pain management can reduce the percentage of patients receiving multiple sedating medications and promote the use of multimodal pain management in efforts to reduce opioid reliance while optimizing pain control.
Assuntos
Analgésicos Opioides , Naloxona , Humanos , Analgésicos Opioides/uso terapêutico , Fluxo de Trabalho , Estudos Retrospectivos , Dor/tratamento farmacológico , Antagonistas de EntorpecentesRESUMO
A common integration site, cloned from MoMuLV-induced rat T cell lymphomas, was mapped immediately upstream of Not dead yet-1 (Ndy1)/KDM2B, a gene expressed primarily in testis, spleen, and thymus, that is also known as FBXL10 or JHDM1B. Ndy1 encodes a nuclear, chromatin-associated protein that harbors Jumonji C (JmjC), CXXC, PHD, proline-rich, F-box, and leucine-rich repeat domains. Ndy1 and its homolog Ndy2/KDM2A (FBXL11 or JHDM1A), which is also a target of provirus integration in retrovirus-induced lymphomas, encode proteins that were recently shown to possess Jumonji C-dependent histone H3 K36 dimethyl-demethylase or histone H3 K4 trimethyl-demethylase activities. Here, we show that mouse embryo fibroblasts engineered to express Ndy1 or Ndy2 undergo immortalization in the absence of replicative senescence via a JmjC domain-dependent process that targets the Rb and p53 pathways. Knockdown of endogenous Ndy1 or expression of JmjC domain mutants of Ndy1 promote senescence, suggesting that Ndy1 is a physiological inhibitor of senescence in dividing cells and that inhibition of senescence depends on histone H3 demethylation.
Assuntos
Transformação Celular Neoplásica , Embrião de Mamíferos/química , Proteínas Oncogênicas/fisiologia , Sequência de Aminoácidos , Animais , Animais Recém-Nascidos , Northern Blotting , Western Blotting , Transformação Celular Viral , Fibroblastos/citologia , Linfoma de Células T/patologia , Linfoma de Células T/virologia , Camundongos , Dados de Sequência Molecular , Vírus da Leucemia Murina de Moloney/fisiologia , Ratos , Ratos Endogâmicos F344 , Proteína do Retinoblastoma/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
The implementaion of the Comprehensive Care for Joint Replacement (CJR) model has necessitated value-focused care for a 90-day period. Pain management in joint arthroplasty therefore represents a focused opportunity to achieve lasting change in the delivery of care. To be successful, orthopedic surgeons must integrate approaches that take into account administration route and therapy duration, and various combinations thereof, to achieve improved longer term outcomes for joint arthroplasty patients. In addition, pain management choices must be based on value and not on simple costs, as patient satisfaction scores affect CJR repayments. While the postdischarge time period poses the highest risk, improved collaboration with post-acute care providers, such as hospitalists, pharmacists, and rehabilitation facilities will be crucial to addressing patient comorbidities and ensuring optimal outcomes post-surgery. Furthermore, multimodal pain management strategies associated with optimal pain control and shorter hospital stays are valuable in achieving improved outcome and financial metrics.
Assuntos
Artroplastia de Quadril/economia , Artroplastia do Joelho/economia , Assistência Integral à Saúde/economia , Manejo da Dor/economia , Dor Pós-Operatória/economia , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Humanos , Tempo de Internação/economia , Dor Pós-Operatória/tratamento farmacológicoRESUMO
Reprogramming of somatic cells to induced pluripotent stem cells (iPSC) provides an important cell source to derive patient-specific cells for potential therapeutic applications. However, it is not yet clear whether reprogramming through pluripotency allows the production of differentiated cells with improved functional properties that may be beneficial in regenerative therapies. To address this, we compared the production and assembly of extracellular matrix (ECM) by iPSC-derived fibroblasts to that of the parental, dermal fibroblasts (BJ), from which these iPSC were initially reprogrammed, and to fibroblasts differentiated from human embryonic stem cells (hESC). iPSC- and hESC-derived fibroblasts demonstrated stable expression of surface markers characteristic of stromal fibroblasts during prolonged culture and showed an elevated growth potential when compared to the parental BJ fibroblasts. We found that in the presence of L: -ascorbic acid-2-phosphate, iPSC- and hESC-derived fibroblasts increased their expression of collagen genes, secretion of soluble collagen, and extracellular deposition of type I collagen to a significantly greater degree than that seen in the parental BJ fibroblasts. Under culture conditions that enabled the self-assembly of a 3D stromal tissue, iPSC- and hESC-derived fibroblasts generated a well organized, ECM that was enriched in type III collagen. By characterizing the functional properties of iPSC-derived fibroblasts compared to their parental fibroblasts, we demonstrate that these cells represent a promising, alternative source of fibroblasts to advance future regenerative therapies.
Assuntos
Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/farmacologia , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Células Cultivadas , Colágeno/biossíntese , Células-Tronco Embrionárias/citologia , Matriz Extracelular/metabolismo , Fibroblastos/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologiaRESUMO
Pre-TCR signals regulate the transition of the double-negative (DN) 3 thymocytes to the DN4, and subsequently to the double-positive (DP) stage. In this study, we show that pre-TCR signals activate Akt and that pharmacological inhibition of the PI3K/Akt pathway, or combined ablation of Akt1 and Akt2, and to a lesser extent Akt1 and Akt3, interfere with the differentiation of DN3 and the accumulation of DP thymocytes. Combined ablation of Akt1 and Akt2 inhibits the proliferation of DN4 cells, while combined ablation of all Akt isoforms also inhibits the survival of all the DN thymocytes. Finally, the combined ablation of Akt1 and Akt2 inhibits the survival of DP thymocytes. Constitutively active Lck-Akt1 transgenes had the opposite effects. We conclude that, following their activation by pre-TCR signals, Akt1, Akt2, and, to a lesser extent, Akt3 promote the transition of DN thymocytes to the DP stage, in part by enhancing the proliferation and survival of cells undergoing beta-selection. Akt1 and Akt2 also contribute to the differentiation process by promoting the survival of the DP thymocytes.
Assuntos
Proteínas Proto-Oncogênicas c-akt/fisiologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Timo/imunologia , Animais , Proliferação de Células , Sobrevivência Celular , Expressão Gênica , Ativação Linfocitária/genética , Camundongos , Camundongos Knockout , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/fisiologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Timo/citologia , TransgenesRESUMO
T cell differentiation in the thymus is dependent upon signaling through the TCR and is characterized by the resulting changes in expression patterns of CD4 and CD8 surface coreceptor molecules. Although recent studies have characterized the effects of proximal TCR signaling on T cell differentiation, the downstream integration of these signals remains largely unknown. The growth factor independence-1 (GFI1) and GFI1B transcriptional repressors may regulate cytokine signaling pathways to affect lymphocyte growth and survival. In this study, we show that Gfi1 expression is induced upon induction of the T cell program. Gfi1B expression is low and dynamic during T cell development, but is terminated in mature thymocytes. Transgenic expression of GFI1 and GFI1B in T cells allowed us to determine the functional consequences of constitutive expression. GFI1 potentiates response to TCR stimulation and IL-2, whereas GFI1B-transgenic T cells are defective in T cell activation. Moreover, GFI1B-transgenic thymocytes display reduced expression of the late-activation marker IL-7R alpha, and a decrease in CD4(-)8(+) single-positive T cells that can be mitigated by transgenic expression of BCL2 or GFI1. These data show that GFI1 and GFI1B are functionally unique, and implicate a role for GFI1 in the integration of activation and survival signals.