Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease : Cutoff Values and Diagnostic Accuracy of Quantitative [O]H2O PET Imaging

Background

Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD.

Objectives

The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [¹⁵O]H₂O positron emission tomography (PET).

Methods

A total of 330 patients underwent both quantitative [¹⁵O]H₂O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve ≤0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive.

Results

Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 ± 0.25 and 0.92 ± 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 ± 1.04 ml/min/g and 1.73 ± 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET.

Conclusions

Quantitative MBF measurements with the use of [¹⁵O]H₂O PET provided high diagnostic performance, but both sex and age should be taken into account.     

Comparison of extracapsular pseudotumors seen in magnetic resonance imaging and in revision surgery of 167 failed metal-on-metal hip replacements

Background and purpose

Magnetic resonance imaging (MRI) is important for detecting extracapsular pseudotumors, but there is little information on the accuracy of MRI and appropriate intervals for repeated imaging. We evaluated the sensitivity and specificity of MRI for detecting pseudotumors in 155 patients (167 hips) with metal-on-metal (MoM) hip arthroplasties that failed due to adverse reactions to metal debris (ARMD).

Methods

Preoperative MRIs were performed with two 1.5 T MRI scanners and graded by a senior musculoskeletal radiologist using a previously described MRI pseudotumor grading system. Revision findings were retrieved from surgical notes, and pseudotumors were retrospectively graded as fluid-filled, mixed-type, or solid.

Results

The sensitivity of MRI was 71% and the specificity was 87% for detecting extracapsular pseudotumors. The sensitivity was 88% (95% CI: 70–96) when MRI was performed less than 3 months before the revision surgery. Interestingly, when the time that elapsed between MRI and revision was more than 1 year, the sensitivity calculated was only 29% (95% CI: 14–56). Comparison between MRI and revision classifications gave moderate agreement (Cohen’s kappa = 0.4).

Interpretation

A recent MRI predicts the presence of a pseudotumor well, but there is more discrepancy when the MRI examination is over a year old, most likely due to the formation of new pseudotumors. 1 year could be a justifiable limit for considering a new MRI if development of ARMD is suspected. MRI images over a year old should not be used in decision making or in planning of revision surgery for MoM hips.Metal-on-metal (MoM) hip replacements have been widely used for the treatment of hip osteoarthritis, particularly in young and active patients (Bozic et al. 2009). During the last few years, an increased risk of developing soft tissue reactions linked to increased wear of MoM articulation has been reported (Pandit et al. 2008, Kwon et al. 2010, Langton et al. 2011). An umbrella term “adverse reaction to metal debris” (ARMD) has been used to describe these tissue reactions, which include metallosis, aseptic lymphocytic vasculitis-associated lesions, and the fluid-filled or solid extracapsular lesions often referred to as pseudotumors (Langton et al. 2011). Most patients have high blood metal ions and many experience pain in the groin and thigh region, but ARMD may also be found in patients presenting with no clinical symptoms and normal whole-blood metal ion levels (Hart et al. 2011, Wynn-Jones et al. 2011). Asymptomatic extracapsular pseudotumors have been reported to increase and decrease in size with occasional remission of small masses, and they may involve the abductor and iliopsoas muscles (Almousa et al. 2013). Revision surgeries because of pseudotumors have been reported to have significantly poorer outcome than hip revisions for other reasons (Grammatopolous et al. 2009). Imaging is therefore needed to identify these patients for closer follow-up or revision surgery. Preoperative magnetic resonance imaging (MRI) is also of importance for surgeons to visualize the location and dimensions of the pseudotumor for optimal resection (Liddle et al. 2013).MRI and ultrasonography are the main imaging modalities for assessment of ARMD lesions. Modern MRI techniques allow good visibility in the hip region, even though intracapsular lesions cannot be reliably assessed in some cases due to metal artifacts. To our knowledge, only 1 study has compared pseudotumors seen in MRI with those actually found in revision surgery (Liddle et al. 2013).The main aim of this study was to evaluate the ability of preoperative MRI to detect extracapsular pseudotumors encountered in revision surgery and to assess appropriate intervals for repeated imaging, when development/progression of soft tissue pathologies is suspected. A secondary aim was to ascertain whether pseudotumors fall into the same categories in both MRI and revision surgery classifications.     

Acute leukocyte,cytokine and adipocytokine responses to maximal and hypertrophic resistance exercise bouts

The purpose of this study was to examine the acute immune response (circulating levels of leukocytes, cytokines and adipocytokines) to maximal resistance (MAX, 15 × 1RM) and hypertrophic resistance (HYP, 5 × 10RM) exercise bouts. Twelve healthy men (age = 28.2 ± 3.5 years, weight = 78.6 ± 10.4 kg, height 178.8 ± 5.0 cm, fat percentage = 16.5 ± 3.5 %) participated in the study. Blood was sampled before, immediately after and 15 and 30 min after exercise. Leukocytes (WBC) significantly increased immediately after HYP (p < 0.01), whereas in MAX, increases in WBC became significant after 30 min (p < 0.05). Lymphocytes increased only after HYP (p < 0.001), while MAX induced lymphopenia during recovery (p < 0.01). Monocyte chemoattractant protein-1 (MCP-1) decreased (p < 0.05) and interleukin-1 receptor antagonist (IL-1ra) increased after HYP, which were not observed after MAX. Adipsin and resistin decreased after both exercise bouts (p < 0.05), which suggest that heavy resistance exercise is at least transiently beneficial for adipocytokine profile. Immediate mechanical stress seemed similar as no differences in myoglobin response were observed. The higher magnitude of metabolic demand reflected in higher lactate response in HYP could be the reason for the significantly high responses in WBC, IL-1ra and decrease in MCP-1.     

Evaluation of pure-tone audiometric protocols in vestibular schwannoma screening

The objective was to evaluate the pure-tone audiogram-based screening protocols in VS diagnostics. We retrospectively analyzed presenting symptoms, pure tone audiometry and MRI finding from 246 VS patients and 442 controls were collected to test screening protocols (AAO-HNS, AMCLASS-A/B, Charing Cross, Cueva, DOH, Nashville, Oxford, Rule3000, Schlauch, Seattle, Sunderland) for sensitivity and specificity. Results were pooled with data from five other studies, and analysis of sensitivity, specificity and positive likelihood ratio (LR+) for each protocol was performed. Our results show that protocols with significantly higher sensitivity (AMCLASS-A/B, Nashville) show also significantly lowest specificity, and tend to have low association (positive likelihood ratio, LR+) to the VS. The highest LR+ was found for protocols AAO-HNS, Rule3000 and Seattle. In conclusions, knowing their properties, screening protocols are simple decision-making tools in VS diagnostic. To use the advantage of the highest sensitivity, protocols AMCLASS-A + B or Nashville can be of choice. For more reasonable approach, applying the protocols with high LR+ (AAO-HNS, Rule3000, Seattle) may reduce the overall number of MRI scans at expense of only few primarily undiagnosed VS.     

Increased Heparanase Levels in Urine during Acute Puumala Orthohantavirus Infection Are Associated with Disease Severity

Old–world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus–caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS–associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus–infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus–infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.     

Labyrinthine malformation in the 22q11.2 deletion syndrome

Velocardiofacial syndrome and DiGeorge syndrome, integrating to form the 22q11.2 deletion syndrome, manifest frequently with hearing loss. Instead, a labyrinthine anomaly is only occasionally described in velocardiofacial syndrome/DiGeorge syndrome. We report a vestibular labyrinthine malformation demonstrated with computed tomographic scan in a patient with a palatal cleft and a 22q11.2 deletion presenting as velocardiofacial syndrome.     

Off-pump versus on-pump coronary artery bypass surgery in patients aged 80 years and older: institutional results and meta-analysis

Patients aged ≥80 years are at high risk of adverse events after coronary artery bypass grafting. This study was performed to evaluate whether off-pump coronary artery bypass surgery (OPCAB) is superior to conventional surgery (CCAB) in these high-risk patients. The outcome of 185 patients aged ≥80 years who underwent OPCAB or CCAB at our institution was reviewed and a meta-analysis on this issue was performed. Similar immediate postoperative results were observed after OPCAB and CCAB at our institution, despite significantly different operative risk (mean logistic EuroSCORE, OPCAB 20.3% vs CCAB 13.4%, P = 0.003). Among 56 propensity score matched pairs a trend toward lower postoperative stroke (0%, 95% CI 0–0 vs 3.6%, 95% CI 0–10.0, P = 0.50) was observed after OPCAB. No significant differences were observed in the other outcome end points. Five-year survival was 81.0% after OPCAB and 78.1% after CCAB (P = 0.239). Pooled analysis of eight studies including 3416 patients showed a significantly higher risk of postoperative stroke after CCAB (pooled rates: 4.2%, 95% confidence interval (95% CI) 2.4–7.1 vs 1.5%, 95% CI 0.9–2.5, risk ratio (RR) 2.15, 95% CI 1.17–3.96, P = 0.01). A trend toward higher immediate postoperative mortality was observed after CCAB (15 studies including 4409 patients, pooled rates: 6.5%, 95% CI 5.2–8.0 vs 5.6%, 95% CI 4.2–7.4, RR 1.29, 95% CI 0.86–1.93, P = 0.21). Generic inverse variance analysis showed similar intermediate survival after CCAB and OPCAB (RR 1.31, 95% CI 0.85–2.01, P = 0.22). At 2 years, survival was 82.8% (95% CI 76.4–89.2) after CCAB and 88.3% (95% CI 82.9–93.7) after OPCAB. Current results indicate that OPCAB compared with CCAB in patients aged ≥80 years is associated with significantly lower postoperative stroke and with a trend toward better early survival. However, suboptimal quality of the available studies, particularly the lack of comparability of the study groups, prevents conclusive results on this controversial issue.     

Long-term outcomes after ascending aortic replacement and aortic root replacement for type A aortic dissection

 Open in a separate windowOBJECTIVESWe investigated whether the selective use of supracoronary ascending aorta replacement achieves late outcomes comparable to those of aortic root replacement for acute Stanford type A aortic dissection (TAAD).METHODSPatients who underwent surgery for acute type A aortic dissection from 2005 to 2018 at the Helsinki University Hospital, Finland, were included in this analysis. Late mortality was evaluated with the Kaplan–Meier method and proximal aortic reoperation, i.e. operation on the aortic root or aortic valve, with the competing risk method.RESULTSOut of 309 patients, 216 underwent supracoronary ascending aortic replacement and 93 had aortic root replacement. At 10 years, mortality was 33.8% after aortic root replacement and 35.2% after ascending aortic replacement (P = 0.806, adjusted hazard ratio 1.25, 95% confidence interval, 0.77–2.02), and the cumulative incidence of proximal aortic reoperation was 6.0% in the aortic root replacement group and 6.2% in the ascending aortic replacement group (P = 0.65; adjusted subdistributional hazard ratio 0.53, 95% confidence interval 0.15–1.89). Among 71 propensity score matched pairs, 10-year survival was 34.4% after aortic root replacement and 36.2% after ascending aortic replacement surgery (P = 0.70). Cumulative incidence of proximal aortic reoperation was 7.0% after aortic root replacement and 13.0% after ascending aortic replacement surgery (P = 0.22). Among 102 patients with complete imaging data [mean follow-up, 4.7 (3.2) years], the estimated growth rate of the aortic root diameter was 0.22 mm/year, that of its area 7.19 mm²/year and that of its perimeter 0.43 mm/year.CONCLUSIONSWhen stringent selection criteria were used to determine the extent of proximal aortic reconstruction, aortic root replacement and ascending aortic replacement for type A aortic dissection achieved comparable clinical outcomes.     

SARS‐CoV‐2 and human milk: What is the evidence?

The novel coronavirus SARS‐CoV‐2 has emerged as one of the most compelling and concerning public health challenges of our time. To address the myriad issues generated by this pandemic, an interdisciplinary breadth of research, clinical and public health communities has rapidly engaged to collectively find answers and solutions. One area of active inquiry is understanding the mode(s) of SARS‐CoV‐2 transmission. Although respiratory droplets are a known mechanism of transmission, other mechanisms are likely. Of particular importance to global health is the possibility of vertical transmission from infected mothers to infants through breastfeeding or consumption of human milk. However, there is limited published literature related to vertical transmission of any human coronaviruses (including SARS‐CoV‐2) via human milk and/or breastfeeding. Results of the literature search reported here (finalized on 17 April 2020) revealed a single study providing some evidence of vertical transmission of human coronavirus 229E; a single study evaluating presence of SARS‐CoV in human milk (it was negative); and no published data on MERS‐CoV and human milk. We identified 13 studies reporting human milk tested for SARS‐CoV‐2; one study (a non‐peer‐reviewed preprint) detected the virus in one milk sample, and another study detected SARS‐CoV‐2 specific IgG in milk. Importantly, none of the studies on coronaviruses and human milk report validation of their collection and analytical methods for use in human milk. These reports are evaluated here, and their implications related to the possibility of vertical transmission of coronaviruses (in particular, SARS‐CoV‐2) during breastfeeding are discussed.