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1.
Colorectal Dis ; 26(4): 669-674, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38372024

RESUMO

AIM: Same day discharge (SDD) for colorectal surgery shows increasing promise in the era of enhanced recovery after surgery protocols and minimally invasive surgery. It has become increasingly relevant due to the constraints posed by the COVID-19 pandemic. The aim of this study was to compare SDD and postoperative day 1 (POD1) discharge to understand the clinical outcomes and financial impact on factors such as cost, charge, revenue, contribution margin and readmission. METHOD: A retrospective review of colectomies was performed at a single institution over a 2-year period (n = 143). Two populations were identified: SDD (n = 51) and POD1 (n = 92). Patients were selected by International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10) and Diagnosis Related Grouper (DRG) codes. RESULTS: There was a statistically significant difference favouring SDD in total hospital cost (p < 0.0001), average direct costs (p < 0.0001) and average charges (p < 0.0016). SDD average hospital costs were $8699 (values in USD throughout) compared with $11 652 for POD 1 (p < 0.0001), and average SDD hospital charges were $85 506 compared with $97 008 for POD1 (p < 0.0016). The net revenue for SDD was $22 319 while for POD1 it was $26 173 (p = 0.14). Upon comparison of contribution margins (SDD $13 620 vs. POD1 $14 522), the difference was not statistically significant (p = 0.73). There were no identified statistically significant differences in operating room time, robotic console time, readmission rates or surgical complications. CONCLUSIONS: Amidst the pandemic-related constraints, we found that SDD was associated with lower hospital costs and comparable contribution margins compared with POD1. Additionally, the study was unable to identify any significant difference between operating time, readmissions, and surgical complications when performing SDD.


Assuntos
COVID-19 , Colectomia , Custos Hospitalares , Alta do Paciente , Readmissão do Paciente , Humanos , Estudos Retrospectivos , Alta do Paciente/estatística & dados numéricos , Alta do Paciente/economia , Feminino , Masculino , Readmissão do Paciente/estatística & dados numéricos , Readmissão do Paciente/economia , Pessoa de Meia-Idade , Colectomia/economia , Colectomia/métodos , COVID-19/economia , COVID-19/epidemiologia , Idoso , Custos Hospitalares/estatística & dados numéricos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Preços Hospitalares/estatística & dados numéricos , Procedimentos Cirúrgicos Ambulatórios/economia , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , SARS-CoV-2 , Recuperação Pós-Cirúrgica Melhorada , Adulto
2.
J Immunol ; 199(12): 4056-4065, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29109121

RESUMO

The decision between T cell activation and tolerance is governed by the spatial and temporal integration of diverse molecular signals and events occurring downstream of TCR and costimulatory or coinhibitory receptor engagement. The PI3K-protein kinase B (PKB; also known as Akt) signaling pathway is a central axis in mediating proximal signaling events of TCR and CD28 engagement in T cells. Perturbation of the PI3K-PKB pathway, or the loss of negative regulators of T cell activation, such as the E3 ubiquitin ligase Cbl-b, have been reported to lead to increased susceptibility to autoimmunity. In this study, we further examined the molecular pathway linking PKB and Cbl-b in murine models. Our data show that the protein kinase GSK-3, one of the first targets identified for PKB, catalyzes two previously unreported phosphorylation events at Ser476 and Ser480 of Cbl-b. GSK-3 inactivation by PKB abrogates phosphorylation of Cbl-b at these two sites and results in reduced Cbl-b protein levels. We further show that constitutive activation of PKB in vivo results in a loss of tolerance that is mediated through the downregulation of Cbl-b. Altogether, these data indicate that the PI3K-PKB-GSK-3 pathway is a novel regulatory axis that is important for controlling the decision between T cell activation and tolerance via Cbl-b.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Quinase 3 da Glicogênio Sintase/fisiologia , Tolerância Imunológica/fisiologia , Ativação Linfocitária/fisiologia , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Subpopulações de Linfócitos T/enzimologia , Sequência de Aminoácidos , Animais , Autoimunidade/fisiologia , Ativação Enzimática , Regulação da Expressão Gênica/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Fosfatidilinositol 3-Quinases/fisiologia , Fosforilação , Fosfosserina/metabolismo , Isoformas de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Proto-Oncogênicas c-akt/fisiologia , Alinhamento de Sequência , Transdução de Sinais/fisiologia , Especificidade da Espécie , Organismos Livres de Patógenos Específicos , Subpopulações de Linfócitos T/imunologia
3.
Mil Med ; 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36458912

RESUMO

INTRODUCTION: With increasing global unrest and military physician shortages potentially leading to a surgeon draft, we sought to evaluate the readiness of graduating general surgery residents to care for casualties of war. MATERIALS AND METHODS: We evaluated the National Data Reports of Surgery Case Logs for general surgery residents from 2009 to 2018 to quantify experience with key procedures that provide critical skills required for wartime surgery. Reported cases from the Accreditation Council for Graduate Medical Education for graduating residents from civilian and military residency programs were analyzed for 28 individual procedures determined to be critical for the care of combat casualties. These included central and peripheral vascular procedures, as well as neck, thoracic, abdominal, and peripheral interventions. RESULTS: From 2009 to 2018, there has been a significant decrease in wartime-relevant cases by graduating residents. Notably, these include aorto-iliac/femoral bypasses (50% reduction; 7.1%/year; P < .001), femoral-popliteal bypasses (60% reduction; 6.9%/year; P < .001), femoral-femoral bypasses (30% reduction; 2.6%/year; P < .001), upper extremity amputations (50% reduction; 6.4%/year; P = .016), fasciotomies for trauma (50% reduction; 4.5%/year; P = .013), open repair of ruptured infrarenal aorto-iliac aneurysms (70% reduction; 5.8%/year; P < .001), repair of traumatic aorta or vena cava injuries (70% reduction; 7%/year; P = .007), carotid endarterectomies (40% reduction; 4%/year; P < .001), lung resections (40% reduction; 3.7%/year; P = .001), trauma splenectomies/splenorrhaphy (30% reduction; 2.9%/year; P < .001), and repair of traumatic liver lacerations (30% reduction; 2.5%/year; P = .036). CONCLUSIONS: Graduating general surgery residents has limited exposure to wartime critical skills due to a significant reduction in open vascular, head and neck, thoracic, and operative trauma cases. As the threat of global war persists and new graduates continue to deploy worldwide, residency training must be augmented to ensure adequate preparation in case a surgeon draft is required to fulfill demand for military surgeons.

4.
J Trauma Acute Care Surg ; 92(4): 631-639, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34840271

RESUMO

BACKGROUND: Minimally invasive resuscitative endovascular balloon occlusion of the aorta (REBOA) following noncompressible hemorrhage results in significant ischemia reperfusion injury (IRI). Adverse outcomes from IRI include organ dysfunction and can result in profound hemodynamic and molecular compromise. We hypothesized that adenosine, lidocaine, and magnesium (ALM) attenuates organ injury and inflammation responses following REBOA IRI in a porcine model of hemorrhage. METHODS: Animals underwent a 20% controlled hemorrhage followed by 45 minutes of supraceliac balloon occlusion. They were randomized into two groups: control (n = 9) and ALM intervention (n = 9) to include a posthemorrhage, pre-REBOA bolus (200 mL of 3% NaCl ALM) followed by a continuous drip (2 mL/kg per hour of 0.9% NaCl ALM) during the 4-hour resuscitative period. Primary outcomes included hemodynamic parameters, gene expression of inflammatory signaling molecules, and plasma concentrations of select cytokines and chemokines. RESULTS: The ALM cohort demonstrated a significant reduction in cardiac output and cardiac index. Plasma concentrations of interleukin 2 and interleukin 10 were significantly lower 3 hours post-REBOA in animals treated with ALM versus vehicle. Interleukin 4 levels in plasma were also lower with ALM at 3 and 4 hours post-REBOA (p < 0.05). Liver expression of IL1RN, MTOR, and LAMP3 messenger RNA was significantly lower with ALM as compared with the vehicle. No significant difference in large bowel gene expression was observed between treatments. CONCLUSION: In a porcine model of hemorrhage, ALM treatment mitigated inflammatory responses early during post-REBOA resuscitation. Our findings suggest that ALM use with trauma may reduce inflammatory injury and improve outcomes related to REBOA utilization.


Assuntos
Oclusão com Balão , Procedimentos Endovasculares , Traumatismo por Reperfusão , Choque Hemorrágico , Animais , Adenosina/uso terapêutico , Aorta/cirurgia , Oclusão com Balão/métodos , Modelos Animais de Doenças , Procedimentos Endovasculares/métodos , Hemorragia/terapia , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Magnésio/farmacologia , Magnésio/uso terapêutico , Traumatismo por Reperfusão/terapia , Choque Hemorrágico/etiologia , Choque Hemorrágico/terapia , Suínos
5.
Expert Opin Investig Drugs ; 14(4): 411-21, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15882117

RESUMO

Research into new methods of controlling acid secretion is driven by existing medical needs in gastro-oesophageal reflux disease treatment. Histamine receptor subtype 3 agonists offer one approach for acid inhibition but no agent is yet undergoing clinical testing. Other, as yet unrealized strategies include preventing the fusion of the tubulovesicular elements that contain H+/K+-ATPase with the parietal cell membrane, or blocking channels that recycle K+ in the parietal cell. Of more promise are gastrin (cholecystokinin) receptor antagonists and potassium-competitive acid blockers; examples of both are in clinical development. It is probable that gastrin receptor antagonists would be used adjunctively with proton pump inhibitors, possibly for meal-induced reflux. The potassium-competitive acid blockers have attributes that may facilitate use as monotherapy for the treatment of gastro-oesophageal reflux disease. The early promise of gastrin receptor antagonists and potassium-competitive acid blockers remains to be defined in large-scale trials.


Assuntos
Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Refluxo Gastroesofágico/tratamento farmacológico , Fármacos Gastrointestinais/farmacologia , Animais , Ensaios Clínicos como Assunto , Mucosa Gástrica/metabolismo , Refluxo Gastroesofágico/metabolismo , Fármacos Gastrointestinais/uso terapêutico , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Agonistas dos Receptores Histamínicos/farmacologia , Agonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Células Parietais Gástricas/efeitos dos fármacos , Células Parietais Gástricas/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Bloqueadores dos Canais de Potássio/uso terapêutico , Inibidores da Bomba de Prótons , Bombas de Próton/metabolismo , Receptor de Colecistocinina B/antagonistas & inibidores , Receptor de Colecistocinina B/metabolismo , Receptores Histamínicos H3/efeitos dos fármacos , Receptores Histamínicos H3/metabolismo
6.
J Immunol ; 175(6): 3790-9, 2005 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16148125

RESUMO

Protein kinase B (PKBalpha/Akt1) a PI3K-dependent serine-threonine kinase, promotes T cell viability in response to many stimuli and regulates homeostasis and autoimmune disease in vivo. To dissect the mechanisms by which PKB inhibits apoptosis, we have examined the pathways downstream of PKB that promote survival after cytokine withdrawal vs Fas-mediated death. Our studies show that PKB-mediated survival after cytokine withdrawal is independent of protein synthesis and the induction of NF-kappaB. In contrast, PKB requires de novo gene transcription by NF-kappaB to block apoptosis triggered by the Fas death receptor. Using gene-deficient and transgenic mouse models, we establish that NF-kappaB1, and not c-Rel, is the critical signaling molecule downstream of the PI3K-PTEN-PKB signaling axis that regulates lymphocyte homeostasis.


Assuntos
Homeostase , Linfócitos/fisiologia , NF-kappa B/fisiologia , Transdução de Sinais , Animais , Apoptose , Sobrevivência Celular , Citocinas , Linfócitos/citologia , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Transcrição Gênica , Receptor fas
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