Testing Clinical Scores to Diagnose Incident Deep Vein Thrombosis in Patients Hospitalized in a Department of Medicine: Can Biomarkers Improve Accuracy?

Shifting the context from the emergency department to the department of medicine, we compared different scores to diagnose deep vein thrombosis (DVT) in patients with several comorbidities, hospitalized in a department of internal medicine. We prospectively recruited 178 consecutive hospitalized patients in whom clinical suspicion of DVT was assessed by Wells modified score for DVT, Hamilton, Kahn, and St Andrè Hospital scores. Deep vein thrombosis was confirmed in 85 (48%) patients by both echocolor Doppler and angiocomputed tomography scan. The use of risk scores based on symptoms and clinical signs was weakly useful (area under the curve [AUC]: 0.69, positive predictive value: 59%, and negative predictive value: 74%). Patients with DVT had significantly (P < .0001) lower serum albumin and protein S levels compared to those without DVT. Moreover, serum protein S (AUC: 0.82) and albumin in percentage (AUC: 0.80) showed a better accuracy than clinical scores (P < .001) in assessing the diagnosis of DVT. Therefore, serum albumin and protein S improved the accuracy of clinical scores for the diagnosis of incident DVT in patients hospitalized in a department of medicine.

Comparison of Wells and Revised Geneva Rule to Assess Pretest Probability of Pulmonary Embolism in High-Risk Hospitalized Elderly Adults.

OBJECTIVES: To assess and compare the diagnostic power for pulmonary embolism (PE) of Wells and revised Geneva scores in two independent cohorts (training and validation groups) of elderly adults hospitalized in a non-emergency department. DESIGN: Prospective clinical study, January 2011 to January 2013. SETTING: Unit of Internal Medicine inpatients, University of Catania, Italy. PARTICIPANTS: Elderly adults (mean age 76 ± 12), presenting with dyspnea or chest pain and with high clinical probability of PE or D-dimer values greater than 500 ng/mL (N = 203), were enrolled and consecutively assigned to a training (n = 101) or a validation (n = 102) group. The clinical probability of PE was assessed using Wells and revised Geneva scores. MEASUREMENTS: Clinical examination, D-dimer test, and multidetector computed angiotomography were performed in all participants. The accuracy of the scores was assessed using receiver operating characteristic analyses. RESULTS: PE was confirmed in 46 participants (23%) (24 training group, 22 validation group). In the training group, the area under the receiver operating characteristic curve was 0.91 (95% confidence interval (CI) = 0.85-0.98) for the Wells score and 0.69 (95% CI = 0.56-0.82) for the revised Geneva score (P < .001). These results were confirmed in the validation group (P < .05). The positive (LR+) and negative likelihood ratios (LR-) (two indices combining sensitivity and specificity) of the Wells score were superior to those of the revised Geneva score in the training (LR+, 7.90 vs 1.34; LR-, 0.23 vs 0.66) and validation (LR+, 13.5 vs 1.46; LR-, 0.47 vs 0.54) groups. CONCLUSION: In high-risk elderly hospitalized adults, the Wells score is more accurate than the revised Geneva score for diagnosing PE.

Inhibition of Cdk2 kinase activity selectively targets the CD44⁺/CD24⁻/Low stem-like subpopulation and restores chemosensitivity of SUM149PT triple-negative breast cancer cells.

Inflammatory breast cancer (IBC) is an angioinvasive and most aggressive type of advanced breast cancer characterized by rapid proliferation, chemoresistance, early metastatic development and poor prognosis. IBC tumors display a triple-negative breast cancer (TNBC) phenotype characterized by centrosome amplification, high grade of chromosomal instability (CIN) and low levels of expression of estrogen receptor α (ERα), progesterone receptor (PR) and HER-2 tyrosine kinase receptor. Since the TNBC cells lack these receptors necessary to promote tumor growth, common treatments such as endocrine therapy and molecular targeting of HER-2 receptor are ineffective for this subtype of breast cancer. To date, not a single targeted therapy has been approved for non-inflammatory and inflammatory TNBC tumors and combination of conventional cytotoxic chemotherapeutic agents remains the standard therapy. IBC tumors generally display activation of epithelial to mesenchymal transition (EMT) that is functionally linked to a CD44+/CD24-/Low stem-like phenotype. Development of EMT and consequent activation of stemness programming is responsible for invasion, tumor self-renewal and drug resistance leading to breast cancer progression, distant metastases and poor prognosis. In this study, we employed the luminal ER+ MCF-7 and the IBC SUM149PT breast cancer cell lines to establish the extent to which high grade of CIN and chemoresistance were mechanistically linked to the enrichment of CD44+/CD24low/- CSCs. Here, we demonstrate that SUM149PT cells displayed higher CIN than MCF-7 cells characterized by higher percentage of structural and numerical chromosomal aberrations. Moreover, centrosome amplification, cyclin E overexpression and phosphorylation of retinoblastoma (Rb) were restricted to the stem-like CD44+/CD24-/Low subpopulation isolated from SUM149PT cells. Significantly, CD44+/CD24-/Low CSCs displayed resistance to conventional chemotherapy but higher sensitivity to SU9516, a specific cyclin-dependent kinase 2 (Cdk2) inhibitor, demonstrating that aberrant activation of cyclin E/Cdk2 oncogenic signaling is essential for the maintenance and expansion of CD44+/CD24-/Low CSC subpopulation in IBC. In conclusion, our findings propose a novel therapeutic approach to restore chemosensitivity and delay recurrence of IBC tumors based on the combination of conventional chemotherapy with small molecule inhibitors of the Cdk2 cell cycle kinase.

Thrombophilia in Patients With Lower Limb Deep Veins Thrombosis (LDVT) Results of a Monocentric Survey on 103 Consecutive Outpatients.

A debate concerns the utility of large screening for acquired or inherited thrombophilia. The study concerns relationship between inherited thrombophilic status and lower limb deep vein thrombosis (LDVT) and highlights the possible use of extensive thrombophilia screening to determine an emerging risk of LDVT. From January 2010 to January 2012, 103 consecutive patients with LDVT were considered. In all, 57 (55.3%) patients with LDVT showed inherited thrombophilia. The most frequent trombophilic alterations were deficiency of protein S (33 patients, 32.0%), methylentethrafolate reductase (MTHFR) gene C677T variant (22 patients, 21.4%), protrombin gene G20210A alteration (50, 14.6%), and deficiency of protein C (12, 11.6%). Age and MTHFR variant were found related to LDVT and thrombophilia was related to distal LDVT. A high frequency of thrombophylic factor was found in patients with LDVT, but we believe that a generic genetic screening should not be suggested for these patients.

Patients with unrecognized peripheral arterial disease (PAD) assessed by ankle-brachial index (ABI) present a defined profile of proinflammatory markers compared to healthy subjects.

BACKGROUND: Many studies have postulated that atherosclerosis should be considered as an inflammatory disease. In addition, some studies have focused on the relationship between inflammation and peripheral arterial disease (PAD). OBJECTIVE: Define the plasma levels of soluble markers, including the proinflammatory cytokine interleukin-6 (IL-6), the anti-inflammatory cytokine transforming growth factor-ß1 (TGF-ß1), the endothelial-specific adhesion factor (E-selectin) and two proteinases involved in extracellular matrix degradation (matrix metalloproteinases-2 and -9, MMP-2, and MMP-9) in previously unrecognized patients with peripheral artery disease (PAD) and non-PAD controls. RESULTS: Significantly higher levels of IL-6, E-selectin and MMP-2/MMP-9 and significantly reduced levels of TGF-ß1 were found in PAD patients (ankle-brachial index, ABI⩽0.9) compared to non-PAD control subjects (1.4>ABI>0.9). CONCLUSION: The results demonstrated the subjects with unrecognized PAD (ABI⩽0.9) show a characteristic phlogistic pattern differently from healthy subjects and it strongly supports the pivotal role played by inflammatory and immunological mechanisms in the initiation and progression of the atherosclerotic process in peripheral arteries. These biomarkers could be helpful to screen the susceptibility for the diseases in peripheral arteries.

The prevalence of the cardiac origin of chest pain: the experience of a rural area of southeast Italy.

This study was designed to assess the application of diagnostic guidelines to the management of chest pain by an observational study carried out in a small town (Ragusa) of southeast Sicily. This study was an attempt to compare a Sicilian experience with the literature. In this observational study, we examined all the patients referred for chest pain to the Emergency Department (ED) of "Civile-M. P. Arezzo" Hospital during a period of 6 months (from January 1st 2008 to June 30th 2008). As much as 857 patients were studied. The results of our study show that musculoskeletal chest pain is the most common final diagnosis (49%), followed by cardiac chest pain (26.3%), gastrointestinal chest pain (13%), pulmonary chest pain (7%) and psychiatric chest pain (4%). The majority of patients (95%) never made contact with their primary care providers, and came straight to ED. These results emphasize the need for reworking a strategy to avoid the situation in which all cases of non-emergency chest pain, such as musculoskeletal ones, come to the hospital for evaluation, thereby overwhelming the ED, particularly in rural areas where the management of any emergency is centralized in a single hospital.

Pulse pressure is an independent predictor of aortic stiffness in patients with mild to moderate chronic kidney disease.

BACKGROUND: In patients with end-stage renal disease pulse wave velocity (PWV) has been widely assessed, but its behavior in mild to moderate chronic kidney disease (CKD) has been less investigated. We evaluated PWV in mild to moderate CKD. METHODS: We studied 31 patients with grade II-IV CKD. Aortic PWV (aPWV), aortic and upper limb augmentation index, creatinine clearance, C-reactive protein, serum fibrinogen, interleukin-1, interleukin-6, tumor necrosis factor, albumin, total and high-density lipoprotein cholesterol and blood pressure were evaluated. RESULTS: aPWV (7.95 +/- 0.64 m/s), but not augmentation index was significantly higher (p = 0.03) in CKD patients than age-matched healthy subjects (aPWV: 6.24 +/- 0.43 m/s; upper limb: 32.8 +/- 1.9; aortic: 27.7 +/- 1.9). At univariate regression analysis, aPWV was significantly correlated with age (r = 0.44; p = 0.013), interleukin-6 (r = 0.43; p = 0.027), pulse (r = 0.39; p = 0.029), systolic blood pressure (r = 0.37; p = 0.038) and tumor necrosis factor (r = 0.39; p = 0.029). At multivariate analysis, pulse pressure was the only significant independent determinant (beta = 0.37; p = 0.05) of aPWV. CONCLUSION: The results of this study confirm an aPWV increase in mild to moderate CKD and emphasize association between pulse pressure and PWV, independently of renal failure.