Objective Low tidal volume ventilation (LTVV) lowers mortality in the acute respiratory distress syndrome (ARDS). Previous studies reported poor LTVV implementation. We sought to determine the rate, quality, and predictors of LTVV use. Design Retrospective cross-sectional study. Setting One academic, three community hospitals in the Chicago region. Patients 362 adults meeting the Berlin Definition of ARDS consecutively admitted between June-December, 2013. Measurements and Main Results Seventy patients (19.3%) were treated with LTVV (tidal volume <6.5mL/kg predicted body weight [PBW]) at some time during mechanical ventilation. 22.2% of patients requiring a fraction of inspired oxygen (FIO2) >40% and 37.3% of patients with FIO2>40% and plateau pressure >30cm H2O received LTVV. The entire cohort received LTVV 11.4% of the time patients had ARDS. Among patients who received LTVV, the mean (SD) percentage of ARDS time it was used was 59.1% (38.2%), and 34% waited more than 72 hours prior to LTVV initiation. Women were less likely to receive LTVV, whereas sepsis and FIO2>40% were associated with increased odds of LTVV use. Four attending physicians (6.2%) initiated LTVV within one day of ARDS onset for ≥50% of their patients, whereas 34 physicians (52.3%) never initiated LTVV within one day of ARDS onset. 54.4% of patients received a tidal volume <8ml/kg PBW, and the mean tidal volume during the first 72 hours after ARDS onset was never less than 8mL/kg PBW. Conclusions More than 12 years after publication of the landmark LTVV study, use remains poor. Interventions that improve adoption of LTVV are needed.
Cell migration plays a central role in the invasion and metastasis of tumors. As cells leave the primary tumor, they undergo an epithelial to mesenchymal transition (EMT) and migrate as single cells. Epithelial tumor cells may also migrate in a highly directional manner as a collective group in some settings. We previously discovered that myoferlin (MYOF) is overexpressed in breast cancer cells and depletion of MYOF results in a mesenchymal to epithelial transition (MET) and reduced invasion through extracellular matrix (ECM). However, the biomechanical mechanisms governing cell motility during MYOF depletion are poorly understood. We first demonstrated that lentivirus-driven shRNA-induced MYOF loss in MDA-MB-231 breast cancer cells (MDA-231MYOF-KD) leads to an epithelial morphology compared to the mesenchymal morphology observed in control (MDA- 231LTVC) and wild-type cells. Knockdown of MYOF led to significant reductions in cell migration velocity and MDA- 231MYOF-KD cells migrated directionally and collectively, while MDA-231LTVC cells exhibited single cell migration. Decreased migration velocity and collective migration were accompanied by significant changes in cell mechanics. MDA-231MYOF-KD cells exhibited a 2-fold decrease in cell stiffness, a 2-fold increase in cell-substrate adhesion and a 1.5-fold decrease in traction force generation. In vivo studies demonstrated that when immunocompromised mice were implanted with MDA- 231MYOF-KD cells, tumors were smaller and demonstrated lower tumor burden. Moreover, MDA- 231MYOF-KD tumors were highly circularized and did not invade locally into the adventia in contrast to MDA- 231LTVC-injected animals. Thus MYOF loss is associated with a change in tumor formation in xenografts and leads to smaller, less invasive tumors. These data indicate that MYOF, a previously unrecognized protein in cancer, is involved in MDA-MB-231 cell migration and contributes to biomechanical alterations. Our results indicate that changes in biomechanical properties following loss of this protein may be an effective way to alter the invasive capacity of cancer cells.
Clinicians had positive attitudes toward low-Vt ventilation and perceived few barriers to using it, but attitudes and perceived process barriers were not correlated with actual low-Vt ventilation use, which was low. Implementation strategies should be focused on examining other issues, such as ARDS recognition and process solutions, to improve low-Vt ventilation use.
Objective The 2019 Coronavirus (COVID-19) results in a wide range of clinical severity and there remains a need for prognostic tools which identify patients at risk of rapid deterioration and who require critical care. Chest radiography (CXR) is routinely obtained at admission of COVID-19 patients. However, little is known regarding correlates between CXR severity and time to intubation. We hypothesize that the degree of opacification on CXR at time of admission independently predicts need and time to intubation. Methods In this retrospective cohort study, we reviewed COVID-19 patients who were admitted to an urban medical center during March 2020 that had a CXR performed on the day of admission. CXRs were divided into 12 lung zones and were assessed by two blinded thoracic radiologists. A COVID-19 opacification rating score (CORS) was generated by assigning one point for each lung zone in which an opacity was observed. Underlying comorbidities were abstracted and assessed for association. Results One hundred forty patients were included in this study and 47 (34%) patients required intubation during the admission. Patients with CORS ≥ 6 demonstrated significantly higher rates of early intubation within 48 h of admission and during the hospital stay (ORs 24 h, 19.8, p < 0.001; 48 h, 28.1, p < 0.001; intubation during hospital stay, 6.1, p < 0.0001). There was no significant correlation between CORS ≥ 6 and age, sex, BMI, or any underlying cardiac or pulmonary comorbidities. Conclusions CORS ≥ 6 at the time of admission predicts need for intubation, with significant increases in intubation at 24 and 48 h, independent of comorbidities. Key Points • Chest radiography at the time of admission independently predicts time to intubation within 48 h and during the hospital stay in COVID-19 patients. • More opacities on chest radiography are associated with several fold increases in early mechanical ventilation among COVID-19 patients. • Chest radiography is useful in identifying COVID-19 patients whom may rapidly deteriorate and help inform clinical management as well as hospital bed and ventilation allocation.
ImportanceDespite its efficacy, low tidal volume ventilation (LTVV) remains severely underutilized for patients with acute respiratory distress syndrome (ARDS). Physician under-recognition of ARDS is a significant barrier to LTVV use. We propose a computational method that addresses some of the limitations of the current approaches to automated measurement of whether ARDS is recognized by physicians.ObjectiveTo quantify patient and physician factors affecting physicians’ tidal volume selection and to build a computational model of physician recognition of ARDS that accounts for these factors.Design, setting, and participantsIn this cross-sectional study, electronic health record data were collected for 361 ARDS patients and 388 non-ARDS hypoxemic (control) patients in nine adult intensive care units at four hospitals between June 24 and December 31, 2013.MethodsStandardized tidal volumes (mL/kg predicted body weight) were chosen as a proxy for physician decision-making behavior. Using data-science approaches, we quantified the effect of eight factors (six severity of illness, two physician behaviors) on selected standardized tidal volumes in ARDS and control patients. Significant factors were incorporated in computational behavioral models of physician recognition of ARDS.ResultsHypoxemia severity and ARDS documentation in physicians’ notes were associated with lower standardized tidal volumes in the ARDS cohort. Greater patient height was associated with lower standardized tidal volumes (which is already normalized for height) in both ARDS and control patients. The recognition model yielded a mean (99% confidence interval) physician recognition of ARDS of 22% (9%-42%) for mild, 34% (19%-49%) for moderate, and 67% (41%-100%) for severe ARDS.Conclusions and relevanceIn this study, patient characteristics and physician behaviors were demonstrated to be associated with differences in ventilator management in both ARDS and control patients. Our model of physician ARDS recognition measurement accounts for these clinical variables, providing an electronic approach that moves beyond relying on chart documentation or resource intensive approaches.
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