Large-scale real-life analysis of survival and usage of therapies in multiple myeloma.

Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.

Impact of COVID-19 in patients with multiple myeloma based on a global data network.

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76-0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38-0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58-2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4-13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.

How to manage thromboembolic risk in patient with SARS-CoV-2-related disease in the Emergency Department: A case report of cardiogenic shock due to massive pulmonary embolism.

BACKGROUND: Although the most known feature of SARS-CoV-2 associated infection is a mild to severe pneumonia, increasing evidence suggests the existence of an infection-associated risk of both arterial and venous thromboembolism (VTE), but the exact magnitude of this phenomenon is still unknown.Given that, it is important for the Emergency Physician to remember that a SARS-CoV-2 associated respiratory failure can be caused not only by the pulmonary parenchymal inflammation that characterizes the pneumonia, but also by an associated pulmonary thromboembolism. CASE REPORT: A healthy 73-years old woman admitted to the ED for dyspnea, fever and thoracic pain. Cardiac ultrasound, electrocardiogram and clinical findings suggested a diagnosis of cardiogenic obstructive shock due to acute pulmonary embolism, successfully treated with thrombolysis. A CT angiography confirmed the pulmonary embolism (EP) diagnosis and showed bilateral pneumonia, caused by SARS-CoV-2 infection. CONCLUSION: Considering the high prevalence of thromboembolic events in COVID-19 patients it is mandatory for the emergency physician to systematically evaluate signs of pulmonary thromboembolism, in order to perform the most patient-tailored therapy as soon as possible.

ICD-10-CM extension with ICD-9 diagnosis codes to support integrated access to clinical legacy data.

INTRODUCTION: ICD is currently the most widely used terminology to code diagnosis and procedures. The transition from ICD-9-CM to ICD-10-CM became effective on October 1, 2015 in US and many other countries. Projects that use this codification for research purposes, requires advanced methods to exploit data with both versions of ICD. Although the General Equivalence Mappings (GEMs), provided by the Centers for Medicare and Medicaid Services, might help to overcome these challenges, their direct use as translation mappings is not possible, mostly due to the further specificity of ICD-10-CM concepts. OBJECTIVE: We propose a methodology to generate an extended version of ICD-10-CM with selected ICD-9-CM diagnosis codes. METHODS: The extension was generated using the GEMs relations between concepts of both terminologies and the hierarchical relations of ICD-10-CM. RESULTS: This extended ICD-10-CM, together with modifications to the mapping of ICD-9-CM concepts that were not inserted, allows the generation of an improved translation of legacy data, raising the number of 1-to-1 correspondences by +13.81%. CONCLUSION: The extended ICD-10-CM enables the accurate integration of ICD-9-CM and ICD-10-CM diagnosis data into a single terminology. With such analysis of data possible without having to specify both ICD-9-CM and ICD-10-CM separately for each query.

Glucose-6-phosphate dehydrogenase deficiency protects against coronary heart disease.

Previous studies suggest a reduction in cardiovascular risk among subjects expressing the glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) deficient phenotype. We aimed to test this hypothesis in male subjects expressing the G6PD-deficient phenotype vs wild type G6PD. In a case-control study we examined consecutive patients admitted for acute myocardial infarction or unstable angina, and controls admitted for diagnoses other than coronary heart disease (CHD). The G6PD phenotype was determined by measuring the enzyme activity in erythrocytes, as the absorbance rate change due to NADPH reduction. The CHD risk associated with the G6PD phenotype was assessed with unconditional logistic regression. G6PD-deficient subjects were less frequently represented among cases (11.8%) than among controls (18.6%, p=0.002). The genetic condition of G6PD deficiency conveyed a significant reduction in CHD risk (OR=0.6; 95% CI 0.4 to 0.9). We confirm the hypothesis that subjects with the G6PD-deficient phenotype are less prone to CHD. We suggest that such a protective effect may be ascribable to a reduced 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA R) activity, a statin-like effect, as well as to a downregulation in NADPH oxidase activity with a consequent reduction in oxygen-free radical production.

Non-invasive coronary flow reserve is correlated with microvascular integrity and myocardial viability after primary angioplasty in acute myocardial infarction.

OBJECTIVE: To test whether preserved coronary flow reserve (CFR) two days after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction (" no-reflow" phenomenon) and is predictive of myocardial viability. DESIGN: 24 patients with anterior AMI underwent CFR assessment in the left anterior descending coronary artery (LAD) with transthoracic echocardiography and myocardial contrast echocardiography (MCE) 48 h after primary angioplasty in the LAD (mean 4 (SD 2) and 3 (1) days, respectively). Low-dose dobutamine echocardiography was performed 6 (3) days after AMI and follow-up echocardiography at three months. RESULTS: No-reflow extent was greater in patients with impaired CFR (< 2.5) than in those with preserved CFR (> 2.5) (55 (35)% v 11 (25)%, p < 0.001). MCE reflow was more common in patients with preserved CFR (8/12) than in those with reduced CFR (1/12, p < 0.05). Wall motion score index in the LAD territory (A-WMSI) was similar at the first echocardiography (2.14 (0.39) v 2.32 (0.47), NS), although it was better in patients with preserved CFR at dobutamine (1.38 (0.45) v 1.97 (0.67), p < 0.05) and follow-up echocardiography (1.36 (0.40) v 1.97 (0.64), p < 0.05). An inverse correlation was found between CFR and A-WMSI at dobutamine and follow-up echocardiography (r = -0.49, p = 0.016 and r = -0.55, p = 0.005) and between MCE and A-WMSI at dobutamine and follow-up echocardiography (r = -0.75, p < 0.001 and r = -0.75, p < 0.001). By multivariate analysis MCE reflow remained the only predictor of recovery at both dobutamine and follow-up echocardiography (odds ratio 1.06, 95% CI 1 to 1.1, p = 0.009). CONCLUSION: CFR is inversely correlated with the extent of microvascular dysfunction at MCE two days after reperfused AMI. CFR and MCE reflow early after AMI are correlated with myocardial viability at follow up.

Quantification of left ventricular function with contrast-enhanced harmonic colour Doppler and a semiautomated boundary detection algorithm in technically difficult patients: feasibility, accuracy, and inter-observer variability.

AIMS: Patients with poor quality echocardiograms impede the application of available automatic boundary detection technologies. Tissue harmonic imaging and contrast media can allow optimal differentiation of left ventricular blood pool and tissue, making it possible to utilize automatic boundary detection software for automatic non-operator-dependent computation of left ventricular volumes. We integrated contrast-enhanced harmonic colour Doppler with a semiautomated boundary detection algorithm to explore the feasibility, accuracy and inter-observer variability for left ventricular volume assessment in technically difficult patients. METHODS AND RESULTS: Twenty-six patients with more than two segments not clearly visualized in tissue harmonic imaging were studied with contrast-enhanced harmonic colour Doppler using Levovist. Twenty patients (77%) achieved full left ventricular contrast filling without apparent blooming artefacts. Contrast-enhanced harmonic colour Doppler-automatic boundary detection was successfully implemented in these 20 patients, despite three (15%) in which it was not possible to acquire more than three cardiac cycles' values. Contrast-enhanced harmonic colour Doppler-automatic boundary detection measurements agreed closely with the manually drawn data. Among the three independent readers in the three techniques, the best correlation, lowest SEE, smallest limits of agreement and inter-observer variability were obtained in contrast-enhanced harmonic colour Doppler-automatic boundary detection. CONCLUSION: Contrast-enhanced harmonic colour Doppler-automatic boundary detection was feasible and accurate in estimation of left ventricular volume and function in patients with poor acoustic windows. This technique significantly reduced inter-observer variability, thus improving reliability and confidence of investigators in left ventricular function assessment. Contrast-enhanced harmonic colour Doppler-automatic boundary detection may have great potential in clinical evaluation of left ventricular volume and function, especially when on-line software is available.

Contrast-enhanced harmonic color Doppler for left ventricular opacification: improved endocardial border definition compared to tissue harmonic imaging and optimization of methodologyin patients with suboptimal echocardiograms.

OBJECTIVES: This study compared the efficacy of contrast-enhanced harmonic color Doppler (C-HCD) and tissue harmonic imaging (THI) for left ventricular endocardial border delineation and explored the optimal methodology of C-HCD in patients with suboptimal echocardiograms. BACKGROUND: The value of C-HCD in improving endocardium remains unknown. Effects of harmonic velocity-encoded color Doppler (HVD) and harmonic power Doppler (HPD) as well as contrast administration and image acquisition modalities on left ventricular opacification (LVO) have not been established. METHODS: One hundred (50 HVD, 50 HPD) patients with suboptimal echocardiograms during conventional fundamental echocardiography were studied with THI and C-HCD using Levovist. Each patient underwent different random contrast administration and image acquisition modalities. Endocardial border definition score index (EBDI), blooming artifacts, contrast destruction, and salvage of suboptimal echocardiograms were calculated in each patient after contrast enhancement. RESULTS: EBDI improved from 2.05 +/- 0.61 in THI to 2.73 +/- 0.48 in HVD, and 1.98 +/- 0.73 in THI to 2.69 +/- 0.51 in HPD (both P < 0.001). The conversion of a nondiagnostic image from fundamental echocardiography to an optimal diagnostic image was 33 (33%) patients in THI compared to 77 (77%) patients in C-HCD (P < 0.001). Blooming artifacts were seen more commonly in HVD than HPD, intermittent than continuous image acquisition, and bolus than infusion administration (all P < 0.001). There was less contrast destruction in intermittent compared with continuous image acquisition (P < 0.001). Contrast destruction was similar in HVD and HPD, bolus and infusion injection of contrast. The highest salvage rate of a nondiagnostic image from THI to an optimal diagnostic image was 45.5% and 42.4% in HPD mode, with intermittent image acquisition during bolus and infusion contrast administrations. CONCLUSIONS: C-HCD seems more effective in demonstrating improved endocardial border definition compared to THI. HPD has less blooming artifacts compared with HCD. The optimal method for LVO was to use HPD with intermittent image acquisition during bolus or infusion administration of Levovist.

Transmural heterogeneity of myocardial contraction and ischemia. Diagnosis and clinical implications.

Myocardial contraction behaves heterogeneously, being greater in subendocardial than in subepicardial layers. Similarly, during acute myocardial ischemia or infarction, the subendocardium is the first myocardial layer to suffer. Conventional two-dimensional echocardiography cannot distinguish the transmural extension of myocardial ischemia or infarction, showing akinesia also when only the subendocardium is affected. Novel ultrasonographic techniques (like tissue characterization with integrated backscatter or Doppler tissue imaging) and nuclear magnetic resonance tagging can investigate myocardial contraction in different transmural layers and distinguish subendocardial from transmural ischemia or infarction. With the advent of thrombolysis and primary angioplasty in the acute phase of myocardial infarction a correct diagnosis of the extension of myocardial necrosis cannot ignore its transmural wavefront development. The salvage of the subepicardial layer does not give direct information on overall myocardial thickening but is one of the major determinants of overall left ventricular dysfunction and size. Although it is still necessary to investigate this phenomenon, new ultrasonographic techniques give us important information and more opportunities to appropriate diagnosis and future treatment of cardiac patients.

Validation of a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire.

OBJECTIVES: We tested the hypothesis that coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD) as assessed by a new noninvasive method (contrast-enhanced transthoracic second harmonic echo Doppler) is in agreement with CFR measurements assessed by intracoronary Doppler flow wire. BACKGROUND: Contrast-enhanced transthoracic second harmonic echo Doppler is a novel noninvasive method to detect blood flow velocity and reserve in the LAD. However, it has not yet been validated versus a gold-standard method. METHODS: Twenty-five patients undergoing CFR assessment in the LAD by Doppler flow wire were also evaluated by contrast-enhanced transthoracic Doppler to record blood flow in the distal LAD at rest and during hyperemia obtained by adenosine i.v. infusion. In five patients CFR was evaluated twice (before and after angioplasty). RESULTS: As a result of the combined use of i.v. contrast and second harmonic Doppler technology, feasibility in assessing coronary flow reserve equaled 100%. The agreement between the two methods was high. In fact, in all but five patients the maximum difference between the two CFR measurements was 0.38. Overall, the prediction (95%) interval of individual differences was -0.69 to +0.72. Reproducibility of CFR measurements was also high. The limits of the agreement (95%) between the two measurements were -0.32 to +0.32. CONCLUSIONS: Coronary flow reserve in the LAD as assessed by contrast-enhanced transthoracic echo Doppler along with harmonic mode concurs very closely with Doppler flow wire CFR measurements. This new noninvasive method allows feasible, reliable and reproducible assessment of CFR in the LAD.

Effects of acute myocardial ischemia on intramyocardial contraction heterogeneity: A study performed with ultrasound integrated backscatter during transesophageal atrial pacing.

BACKGROUND: [corrected] Subendocardial thickening is greater than subepicardial thickening and acute myocardial ischemia mainly impairs the former. Integrated backscatter cyclic variations (IBScv) reflect regional myocardial contractility and are blunted during myocardial ischemia. We hypothesized that stress-induced myocardial ischemia mainly affects subendocardial IBScv. METHODS AND RESULTS: Multiplane transesophageal echocardiography and simultaneous atrial pacing were performed in 12 patients without coronary artery disease (CAD) and in 25 with significant CAD. In a transgastric 2-chamber view, we calculated IBScv in subendocardium and subepicardium and a heterogeneity index, both at rest and at peak-pacing. In 27 myocardial segments of patients with normal coronary arteries, and in 16 myocardial segments supplied by coronary artery without significant stenosis in patients with CAD, there was a transmural gradient of IBScv at rest and the heterogeneity index did not change during all the protocol steps. In the 53 myocardial segments related to a significantly narrowed coronary artery, the transmural gradient of IBScv, present at rest, significantly decreased at peak-pacing because of subendocardial blunting, but promptly recovered 5 seconds after pacing interruption. Moreover, the myocardial thickening at rest and peak pacing correlated with the subendocardial IBScv behavior and not with the subepicardial one. CONCLUSIONS: IBScv are greater in the subendocardium than in the subepicardium. Atrial pacing stress test does not affect IBScv in segments supplied by nonstenotic coronary arteries, whereas it affects segments supplied by diseased coronary arteries, blunting exclusively subendocardial IBScv. Heterogeneity of IBScv intramyocardial changes caused by stress-induced ischemia must be taken into account when using IBScv for investigating myocardial ischemia.