Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: A systematic review

The accurate identification of peripheral artery disease (PAD) in patients with diabetes and foot ulceration is important, in order to inform timely management and to plan intervention including revascularisation. A variety of non‐invasive tests are available to diagnose PAD at the bedside, but there is no consensus as to the most useful test, or the accuracy of these bedside investigations when compared to reference imaging tests such as magnetic resonance angiography, computed tomography angiography, digital subtraction angiography or colour duplex ultrasound. Members of the International Working Group of the Diabetic Foot updated our previous systematic review, to include all eligible studies published between 1980 and 2018. Some 15 380 titles were screened, resulting in 15 eligible studies (comprising 1563 patients, of which >80% in each study had diabetes) that evaluated an index bedside test for PAD against a reference imaging test. The primary endpoints were positive likelihood ratio (PLR) and negative likelihood ratio (NLR). We found that the most commonly evaluated test parameter was ankle brachial index (ABI) <0.9, which may be useful to suggest the presence of PAD (PLR 6.5) but an ABI value between 0.9 and 1.3 does not rule out PAD (NLR 0.31). A toe brachial index >0.75 makes the diagnosis of PAD less likely (NLR 0.14‐0.24), whereas pulse oximetry may be used to suggest the presence of PAD (if toe saturation < 2% lower than finger saturation; PLR 17.23‐30) or render PAD less likely (NLR 0.2‐0.27). We found that the presence of triphasic tibial waveforms has the best performance value for excluding a diagnosis of PAD (NLR 0.09‐0.28), but was evaluated in only two studies. In addition, we found that beside clinical examination (including palpation of foot pulses) cannot reliably exclude PAD (NLR 0.75), as evaluated in one study. Overall, the quality of data is generally poor and there is insufficient evidence to recommend one bedside test over another. While there have been six additional publications in the last 4 years that met our inclusion criteria, more robust evidence is required to achieve consensus on the most useful non‐invasive bedside test to diagnose PAD.     

Blood pressure target for hypertension in chronic kidney disease: One size does not fit all

There is disagreement between the American and the European guidelines for hypertension management in regard to the optimal blood pressure target in patients with chronic kidney disease (CKD). Randomized clinical trials and meta‐analyses of individual patient data pooled from these trials do not clearly support an intensive blood pressure target for the entire population of CKD patients with hypertension. However, some evidence suggests that in CKD patients with proteinuria strict blood pressure control might confer benefit in terms of renal outcome. Tailored treatment strategy based on the individual’s proteinuric profile and tolerability along with standardization of blood pressure measurement methodology including out‐of‐office evaluation are of paramount importance in patients with CKD.     

The role of soluble P selectin in the diagnosis of venous thromboembolism

Introduction

Soluble P selectin (sPsel), a member of the selectin family of cell adhesion receptors, has been proposed as a key molecule in hemostasis and thrombosis mediating platelet rolling, generating procoagulant microparticles and enhancing fibrin deposition. The aim of this study was to examine the role of sPsel in the diagnosis of venous thromboembolism (VTE).

Materials and Methods

We performed a systematic review and we used meta-analysis to synthesize data from published studies reporting sPsel levels in patients with i) VTE (deep venous thrombosis; DVT or DVT and pulmonary embolism; PE) and ii) DVT only. Pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were appropriately calculated among patients and controls. Diagnostic performance of sPsel was tested with pooled sensitivity, specificity, Diagnostic Odds Ratio (DOR) and summary receiver operator characteristic (SROC) curve.

Results

Eleven studies, comprising of 586 VTE patients and 1,843 controls were deemed eligible. The sPsel was significantly increased after VTE (OR = 2.89, 95%CI = 2.31-3.61, p < 0.001), or DVT only (OR = 2.64, 95%CI = 1.95-3.56, p < 0.001). Subgroup analysis evidenced that sPsel was also increased after VTE when evaluating only studies with patients that had no prior medical history (OR = 2.88, 95%CI = 1.98-4.19, p < 0.001). Exclusion of studies including patients with solid organ tumor, HIV or lupus anticoagulants positive patients did not alter findings. Pooled sensitivity and specificity of sPsel was 0.57 (95%CI = 0.30-082, p < 0.001) and 0.73 (95%CI = 0.51-0.90, p < 0.001), respectively and DOR was 4.31 (95%CI = 2.22-8.37, p < 0.01). SROC curve yielded in significant accuracy of sPsel performance (AUC = 0.74, p = 0.05).

Conclusions

The sPsel was significantly elevated in patients with DVT, both uncomplicated and complicated with PE and presented with high levels of diagnostic performance. sPsel is a plasma biomarker that may help in the diagnosis of VTE.     

Melan-A/Mart-1- or HMB-45-positive melanocytes are not present in calcifying cystic odontogenic tumors (calcifying odontogenic cysts): a study in 13 Caucasian patients

Melanin pigment and melanocytes may be found in odontogenic cysts and tumors, particularly calcifying cystic odontogenic tumor (CCOT). In the present study we investigated the immunohistochemical expression of the Melan-A/Mart-1 and HMB-45 antigens in 13 Caucasians patients with CCOT. Melan-A/Mart-1- and HMB-45-positive melanocytes were not seen in any of the cases. Our findings are in agreement with the assumption that pigmentation in odontogenic lesions may be a racial phenomenon.     

Long-term impact of multifactorial treatment on new-onset diabetes and related cardiovascular events in metabolic syndrome: a post hoc ATTEMPT analysis

This post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study assesses the 3? year incidence of new-onset diabetes (NOD) and related cardiovascular disease (CVD) events in patients with metabolic syndrome (MetS), after multifactorial (lifestyle and drug, including atorvastatin) intervention. Patients were randomized to group A (low-density lipoprotein cholesterol [LDL-C] target < 100 mg/dL) and group B (< 130 mg/dL). The incidence of NOD during the 42-month follow-up was very low, 0.83 to 1.00/100 patient-years in patients with MetS and MetS with impaired fasting glucose, respectively. Older age, increased waist circumference, and persistent MetS were determinants of NOD. One CVD nonfatal event occurred in the 28 patients with NOD. Our findings suggest that treating the characteristics of MetS is achievable and beneficial. New-onset diabetes incidence and CVD events were negligible and not different from what is expected in the general population.     

Inflammatory markers and plaque morphology: an optical coherence tomography study

Background

OCT with its unique image resolution is the ideal method to detect culprit lesion characteristics in different clinical presentations. The identification of inflammatory markers related to plaque characteristics may be of clinical importance.

Methods

Thirty-two patients with acute coronary syndromes (ACS) and fourteen patients with stable angina pectoris (SAP) were enrolled in this study. Culprit lesion morphology was assessed by optical coherence tomography (OCT) in patients with ACS and SAP. The possible relations between serum levels of high sensitivity-C reactive protein (hs-CRP) and interleukin-18 (IL-18) with plaque characteristics were investigated in those patients.

Results

Plaque rupture and thin-cap fibroatheroma (TCFA) were detected more frequently in ACS patients compared with SAP patients, (78.6% vs. 14.3%, p < 0.001, 92.9% vs. 14.3%, p < 0.001, respectively). Higher levels of serum hs-CRP and IL-18 were found in patients with plaque rupture vs. those with no plaque rupture (median value: 19.2 mg/L vs. 1.6 mg/L, p < 0.001 and 219.5 pg/ml vs. 127.5 pg/ml, p = 0.001 respectively), and TCFA vs. those without TCFA (median value: 15.2 mg/L vs. 1.6 mg/L, p = 0.004 and 209.0 pg/ml vs.153.2 pg/ml, p = 0.03 respectively). Serum hs-CRP was the only independent predictor of plaque rupture (p = 0.02, odds ratio 1.1, 95% confidence interval 1.0 to 1.2). A cut-off value of hs-CRP > 4.5 mg/L could detect ruptured plaque with a sensitivity of 91.7% and a specificity of 77.8%.

Conclusions

OCT detected plaque rupture and TCFA more frequent in ACS patients compared with SAP. Elevated hs-CRP and IL-18 were positively related to plaque instability and rupture.