Abstract. Aldolase A (ALDOA) has been reported to be negative survival marker of osteosarcoma (OS) and may be implicated in OS development and progression. In the present study, we assessed for the first time the functional role of ALDOA in OS cell invasion and survival in vitro and in vivo, using human OS cell lines and an orthotopic xenograft nude mouse model. Overexpression and knockdown of ALDOA were respectively performed in MG-63 and U-2 OS cells, which showed relatively low and high constitutive ALDOA expression levels, respectively. Overexpression of ALDOA in MG-63 cells significantly increased in vitro cell invasion, matrix metalloproteinase (MMP)-2 expression, and cell survival against cisplatin-induced apoptosis. On the other hand, knockdown of ALDOA in U-2 cells markedly decreased in vitro cell invasion, MMP-2 expression, and cell survival against cisplatin-induced apoptosis. In an orthotopic xenograft nude mouse model, intra-tibial injection of MG-63 cells overexpressing ALDOA led to significantly increased primary tumor volume and pulmonary metastasis as well as decreased cell apoptosis in the primary tumors, compared with the controls. In contrast, intra-tibial injection of U-2 cells with knockdown of ALDOA led to markedly decreased primary tumor volume and pulmonary metastasis as well as increased cell apoptosis in the primary tumors, compared with the controls. In conclusion, our in vitro data indicate that ALDOA promotes OS cell invasion and survival, and our in vivo data demonstrate an important role of ALDOA in promoting OS tumor growth and metastasis. The present study provides the first in vitro and in vivo evidence supporting a critical functional role of ALDOA in OS progression and metastasis, suggesting that ALDOA could serve as a novel therapeutic target in OS. Additionally, our results suggest that ALDOA is involved in the development of OS chemoresistance.

Purpose: Develop and validate simple risk scores based on initial clinical data and no or minimal laboratory testing to predict mortality in hospitalized adults with COVID-19.Methods: We gathered clinical and initial laboratory variables on consecutive inpatients with COVID-19 who had either died or been discharged alive at 6 US health centers. Logistic regression was used to develop a predictive model using no laboratory values (COVID-NoLab) and one adding tests available in many outpatient settings (COVID-SimpleLab). The models were converted to point scores and their accuracy evaluated in an internal validation group.Results: We identified 1340 adult inpatients with complete data for nonlaboratory parameters and 741 with complete data for white blood cell (WBC) count, differential, c-reactive protein (CRP), and serum creatinine. The COVID-NoLab risk score includes age, respiratory rate, and oxygen saturation and identified risk groups with 0.8%, 11.4%, and 40.4% mortality in the validation group (AUROCC = 0.803). The COVID-SimpleLab score includes age, respiratory rate, oxygen saturation, WBC, CRP, serum creatinine, and comorbid asthma and identified risk groups with 1.0%, 9.1%, and 29.3% mortality in the validation group (AUROCC = 0.833).Conclusions: Because they use simple, readily available predictors, developed risk scores have potential applicability in the outpatient setting but require prospective validation before use. ( J Am Board Fam Med 2021;34:S127-S135.

Background Biomarkers such as C‐reactive protein (CRP) and procalcitonin may help distinguish community‐acquired pneumonia (CAP) from other causes of lower respiratory tract infection. Methods We performed a systematic review of the literature to identify prospective studies evaluating the accuracy of a biomarker in patients with acute cough or suspected CAP. We performed parallel abstraction of data regarding study inclusion, characteristics, quality, and test accuracy. Study quality was evaluated using QUADAS‐2. Bivariate meta‐analysis was performed using the mada package in R, and summary receiver operating characteristic (ROC) curves were created. Results Fourteen studies met our inclusion and exclusion criteria; three were at low risk of bias and four at moderate risk of bias, largely due to failure to prespecify diagnostic thresholds. Considering all studies regardless of the cutoff used, CRP was most accurate (area under the ROC curve = 0.802), followed by leukocytosis (0.777) and procalcitonin (0.771). Lipopolysaccharide‐binding protein and fibrinogen are promising, but were only studied in a single report. For CRP and procalcitonin, the positive and negative likelihood ratios (LR+ and LR–, respectively) varied inversely based on the cutoff. For CRP, LR+ and LR− were 2.08 and 0.32 for a cutoff of 20 mg/L, 3.64 and 0.36 for a cutoff of 50 mg/L, and 5.89 and 0.47 for a cutoff of 100 mg/L. For procalcitonin, LR+ and LR− were 2.50 and 0.39 for a cutoff of 0.10 µg/L, 5.43 and 0.62 for a cutoff of 0.25 µg/L, and 8.25 and 0.76 for a cutoff of 0.50 µg/L. The combination of CRP >49.5 mg/L and procalcitonin >0.1 µg/L had LR+ of 2.24 and LR− of 0.44. Conclusions The best evidence supports CRP as the preferred biomarker for diagnosis of outpatient CAP given its accuracy, low cost, and point‐of‐care availability.

BackgroundCommunity‐acquired pneumonia (CAP) is an important source of morbidity and mortality. However, overtreatment of acute cough illness with antibiotics is an important problem, so improved diagnosis of CAP could help reduce inappropriate antibiotic use.MethodsThis was a meta‐analysis of prospective cohort studies of patients with clinically suspected pneumonia or acute cough that used imaging as the reference standard. All studies were reviewed in parallel by two researchers and quality was assessed using the QUADAS‐2 criteria. Summary measures of accuracy included sensitivity, specificity, likelihood ratios, the diagnostic odds ratio, and the area under the receiver operating characteristic curve (AUROCC) and were calculated using bivariate meta‐analysis.ResultsWe identified 17 studies, of which 12 were judged to be at low risk of bias and the remainder at moderate risk of bias. The prevalence of CAP was 10% in nine primary care studies and was 20% in seven emergency department studies. The probability of CAP is increased most by an abnormal overall clinical impression suggesting CAP (positive likelihood ratio [LR+] = 6.32, 95% CI = 3.58 to 10.5), egophony (LR+ = 6.17, 95% CI = 1.34 to 18.0), dullness to percussion (LR+ = 2.62, 95% CI = 1.14 to 5.30), and measured temperature (LR+ = 2.52, 95% CI = 2.02 to 3.20), while it is decreased most by the absence of abnormal vital signs (LR− = 0.25, 95% CI = 0.11 to 0.48). The overall clinical impression also had the highest AUROCC at 0.741.ConclusionsWhile most individual signs and symptoms were unhelpful, selected signs and symptoms are of value for diagnosing CAP. Teaching and performing these high value elements of the physical examination should be prioritized, with the goal of better targeting chest radiographs and ultimately antibiotics.

No abstract