RESUMO
OBJECTIVES: To assess the impact of a discharge diagnosis of critical illness polyneuromyopathy on health-related outcomes in a large cohort of patients requiring ICU admission. DESIGN: Retrospective cohort with propensity score-matched analysis. SETTING: Analysis of a large multihospital database. PATIENTS: Adult ICU patients without preexisting neuromuscular abnormalities and a discharge diagnosis of critical illness polyneuropathy and/or myopathy along with adult ICU propensity-matched control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,567 ICU patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy, we matched 3,436 of these patients to 3,436 ICU patients who did not have a discharge diagnosis of critical illness polyneuropathy and/or myopathy. After propensity matching and adjusting for unbalanced covariates, we used conditional logistic regression and a repeated measures model to compare patient outcomes. Compared to patients without a discharge diagnosis of critical illness polyneuropathy and/or myopathy, patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy had fewer 28-day hospital-free days (6 [0.1] vs 7.4 [0.1] d; p < 0.0001), had fewer 28-day ventilator-free days (15.7 [0.2] vs 17.5 [0.2] d; p < 0.0001), had higher hospitalization charges (313,508 [4,853] vs 256,288 [4,470] dollars; p < 0.0001), and were less likely to be discharged home (15.3% vs 32.8%; p < 0.0001) but had lower in-hospital mortality (13.7% vs 18.3%; p < 0.0001). CONCLUSIONS: In a propensity-matched analysis of a large national database, a discharge diagnosis of critical illness polyneuropathy and/or myopathy is strongly associated with deleterious outcomes including fewer hospital-free days, fewer ventilator-free days, higher hospital charges, and reduced discharge home but also an unexpectedly lower in-hospital mortality. This study demonstrates the clinical importance of a discharge diagnosis of critical illness polyneuropathy and/or myopathy and the need for effective preventive interventions.
Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Polineuropatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Preços Hospitalares/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças Musculares/epidemiologia , Readmissão do Paciente/estatística & dados numéricos , Pontuação de Propensão , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Cognitive load theory asserts that learning and performance degrade when cognitive load exceeds working memory capacity. This is particularly relevant in the learning environment of ICU rounds, when multidisciplinary providers integrate complex decision-making and teaching in a noisy, high-stress environment prone to cognitive distractions. RESEARCH QUESTION: What features of ICU rounds correlate with high provider cognitive load? STUDY DESIGN AND METHODS: This was an observational, multisite study of multidisciplinary providers during ICU rounds. Investigators recorded rounding characteristics and hourly extraneous cognitive load events during rounds (defined as distractions, episodes of split-attention or repetition, and deviations from standard communication format). After rounds, investigators measured each provider's cognitive load using the provider task load (PTL), an instrument derived from the National Aeronautics and Space Administration Task Load Index survey that assesses perceived workload associated with complex tasks. Relationships between rounding characteristics, extraneous load, and PTL score were evaluated using mixed-effects modeling. RESULTS: A total of 76 providers were observed during 32 rounds from December 2020 to May 2021. The mean rounding census ± SD was 12.5 ± 2.9 patients. The mean rounding time ± SD was 2 h 17 min ± 49 min. The mean extraneous load ± SD was 20.5 ± 4.5 events per hour, or one event every 2 min 51 s. This included 8.6 ± 3.4 distractions, 8.2 ± 4.2 communication deviations, 1.9 ± 1.4 repetitions, and 1.8 ± 1.3 episodes of split-attention per hour. Controlling for covariates, the hourly extraneous load events, number of new patients, and number of higher acuity patients were each associated with increased PTL score (slope, 2.40; 95% CI, 0.76-4.04; slope, 5.23; 95% CI, 2.02-8.43; slope, 3.35; 95% CI, 1.34-5.35, respectively). INTERPRETATION: Increased extraneous load, new patients, and patient acuity were associated with higher cognitive load during ICU rounds. These results can help direct how the ICU rounding structure may be modified to reduce workload and optimize provider learning and performance.
Assuntos
Cognição , Unidades de Terapia Intensiva , Gravidade do Paciente , Visitas de Preceptoria , Carga de Trabalho , Humanos , Visitas de Preceptoria/métodos , Cognição/fisiologia , Masculino , FemininoRESUMO
Human Cripto-1 (CR-1) plays an important role in regulating embryonic development while also regulating various stages of tumor progression. However, mechanisms that regulate CR-1 expression during embryogenesis and tumorigenesis are still not well defined. In the present study, we investigated the effects of two nuclear receptors, liver receptor homolog (LRH)-1 and germ cell nuclear factor receptor (GCNF) and epigenetic modifications on CR-1 gene expression in NTERA-2 human embryonal carcinoma cells and in breast cancer cells. CR-1 expression in NTERA-2 cells was positively regulated by LRH-1 through direct binding to a DR0 element within the CR-1 promoter, while GCNF strongly suppressed CR-1 expression in these cells. In addition, the CR-1 promoter was unmethylated in NTERA-2 cells, while T47D, ZR75-1, and MCF7 breast cancer cells showed high levels of CR-1 promoter methylation and low CR-1 mRNA and protein expression. Treatment of breast cancer cells with a demethylating agent and histone deacetylase inhibitors reduced methylation of the CR-1 promoter and reactivated CR-1 mRNA and protein expression in these cells, promoting migration and invasion of breast cancer cells. Analysis of a breast cancer tissue array revealed that CR-1 was highly expressed in the majority of human breast tumors, suggesting that CR-1 expression in breast cancer cell lines might not be representative of in vivo expression. Collectively, these findings offer some insight into the transcriptional regulation of CR-1 gene expression and its critical role in the pathogenesis of human cancer.
Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Embrionário/metabolismo , Metilação de DNA , Proteínas Ligadas por GPI/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Neoplasias/metabolismo , Membro 1 do Grupo A da Subfamília 6 de Receptores Nucleares/metabolismo , Regiões Promotoras Genéticas , Receptores Citoplasmáticos e Nucleares/metabolismo , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Sítios de Ligação , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Carcinoma Embrionário/genética , Carcinoma Embrionário/patologia , Movimento Celular , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/metabolismo , Decitabina , Relação Dose-Resposta a Droga , Células-Tronco de Carcinoma Embrionário/metabolismo , Células-Tronco de Carcinoma Embrionário/patologia , Feminino , Proteínas Ligadas por GPI/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Luciferases/biossíntese , Luciferases/genética , Células MCF-7 , Invasividade Neoplásica , Proteínas de Neoplasias/genética , Membro 1 do Grupo A da Subfamília 6 de Receptores Nucleares/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Tempo , Análise Serial de Tecidos , Transcrição Gênica , Transfecção , Tretinoína/farmacologia , Ácido Valproico/farmacologiaRESUMO
PURPOSE: To generate an expert-derived list of recommendations for how medical schools should approach decisions about the placement of basic science topics within shortened preclinical curricula, which allow for early clinical immersion. METHOD: A modified Delphi process was used to develop consensus on recommendations (March-November 2021). The authors performed semistructured interviews with national undergraduate medical education (UME) experts from institutions that previously underwent curricular reforms involving shortened preclinical curricula to elicit perspectives on how decisions were made at their institutions. The authors condensed the findings into a preliminary list of recommendations and distributed this list in 2 survey rounds to a larger group of national UME experts (from institutions that previously underwent curricular reforms or held positions of authority within national UME organizations) to gauge their level of agreement with each recommendation. Recommendations were revised based on participant comments, and those with at least 70% somewhat or strong agreement after the second survey were included in the final comprehensive list of recommendations. RESULTS: Interviews were conducted with 9 participants and resulted in 31 preliminary recommendations that were then sent via survey to the 40 recruited participants. Seventeen/40 (42.5%) participants completed the first survey, after which 3 recommendations were removed, 5 were added, and 5 were revised based on comments-resulting in 33 recommendations. Twenty-two/38 (57.9%) participants responded to the second survey, after which all 33 recommendations met inclusion criteria. The authors removed 3 recommendations that did not directly address the curriculum reform process and consolidated the final 30 recommendations into 5 succinct, actionable takeaways. CONCLUSIONS: This study generated 30 recommendations (summarized by the authors in 5 succinct takeaways) for medical schools designing a shortened preclinical basic science curriculum. These recommendations reinforce the importance of vertically integrating basic science instruction with explicit clinical relevance into all curricular phases.
Assuntos
Educação de Graduação em Medicina , Humanos , Inquéritos e Questionários , Currículo , Faculdades de Medicina , ConsensoRESUMO
Survivors of intensive care unit (ICU) admission face unique challenges after hospital discharge. In addition to an increased overall mortality and rates of hospital readmission, patients often experience difficulties in physical functioning, cognition, and mental health, which are collectively termed post-intensive care syndrome. To this date, there are no established strategies to address these deleterious outcomes. A number of studies have examined various unique methods to prevent and treat PICS symptoms, including early physical and occupational therapy, providing post-discharge education, or facilitating routine follow up in post-ICU clinics. These trials have yet to demonstrate any substantial or meaningful effect in post-ICU patients and collectively reinforce the need for further research to identify effective intervention for patients who survive critical illness.
RESUMO
BACKGROUND Hyperglycemic crises can cause severe neurologic impairment. One of the most dreaded consequences of hyperglycemic crises is cerebral edema, a rare complication seen during the treatment of hyperglycemic crises resulting from overly-aggressive fluid resuscitation and rapid correction of hyperglycemia and hyperosmolarity. CASE REPORT We present a case of profound hyperglycemic crisis with blood glucose greater than 2000 mg/dL, complicated by the development of new neurologic deficits after rapid correction of hyperglycemia. Brain imaging failed to reveal a diagnosis of cerebral edema or other acute intracranial process. However, the deficits did not resolve by the time of discharge, raising concern that the neurologic impairment may have been the consequence of overly-aggressive treatment of the hyperglycemic crisis. CONCLUSIONS Neurologic status must be monitored closely, with frequent re-examination, in patients who present with hyperglycemic crises. Care should be taken to prevent over-correction of hyperglycemia and hyperosmolarity following initial fluid resuscitation of these patients to prevent cerebral edema or other significant neurologic impairment.
Assuntos
Edema Encefálico/diagnóstico , Hiperglicemia/complicações , Hiperglicemia/terapia , Adulto , Cetoacidose Diabética/complicações , Hidratação/efeitos adversos , Humanos , Hipernatremia/sangue , MasculinoRESUMO
BACKGROUND Recognition and appropriate management of right ventricular (RV) infarction is essential, as RV injury increases mortality and substantially alters management during acute coronary syndrome. We report a case of RV infarction presenting with new right bundle branch block (RBBB), and therapeutic use of inhaled epoprostenol to reduce RV afterload and augment cardiac output during refractory cardiogenic shock. CASE REPORT A 53-year-old male presented to our institution in ventricular fibrillation with subsequent development of RBBB in the setting of proximal right coronary artery occlusion. Following percutaneous coronary intervention, the patient developed severe RV dysfunction with refractory cardiogenic shock. This was successfully managed with inhaled epoprostenol with normalization of right ventricular systolic function. CONCLUSIONS Although typically associated with anterior myocardial infarction, new RBBB should be recognized as a potential presenting sign of acute RV infarction. The use of inhaled epoprostenol in the setting of RV infarction has not been previously described, but it may augment right ventricular cardiac output via pulmonary vasodilatation.
Assuntos
Anti-Hipertensivos/administração & dosagem , Epoprostenol/administração & dosagem , Infarto do Miocárdio/complicações , Choque Cardiogênico/tratamento farmacológico , Disfunção Ventricular Direita/tratamento farmacológico , Administração por Inalação , Bloqueio de Ramo/etiologia , Bloqueio de Ramo/terapia , Oclusão Coronária/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Choque Cardiogênico/etiologia , Disfunção Ventricular Direita/etiologiaRESUMO
The gut hormone apelin is a major therapeutic focus for several diseases involving inflammation and aberrant cell growth. We investigated whether apelin-36 contained alternative bioactive peptides associated with normal physiology or disease. Amino acid sequence analysis of apelin-36 identified an amidation motif consistent with the formation of a secondary bioactive peptide (SCNH2). SCNH2 is proven to be mitogenic and chemotactic in normal/malignant cells and augments angiogenesis via a PTX-resistant/CT-X-sensitive G protein-coupled receptor (GPCR). Notably, SCNH2 is substantially more potent and sensitive than apelin-13 and vascular endothelial growth factor-A. Endogenous SCNH2 is highly expressed in human tumors and placenta and in mouse embryonic tissues. Our findings demonstrate that SCNH2 is a new apelinergic member with critical pluripotent roles in angiogenesis related diseases and embryogenesis via a non-APJ GPCR.