Detection of malignant bone marrow involvement with dynamic contrast-enhanced magnetic resonance imaging.

BACKGROUND: The purpose of this study was to evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (dMRI) in detecting bone marrow involvement in cancer patients. PATIENTS AND METHODS: We studied 50 consecutive patients with histologically confirmed malignant dissemination to the bone marrow, using dMRI of the lumbosacral spine. Time-signal intensity curves were generated from regions of interest (ROIs) obtained from areas of obvious bone marrow disease (group B). In 16 patients from group B with focal disease, ROIs were also placed on areas with apparently normal bone marrow on static magnetic resonance images (group C). Twenty-two patients with no history of malignancy were used as a control group (group A). Wash-in (WIN) and wash-out (WOUT) rates, time to peak (TTPK), time to maximum slope (TMSP) values and WIN/TMSP ratios were calculated for each patient. Mean values for the three groups were compared statistically. Six patients from group B had follow-up dMRI after chemotherapy: four patients achieved a clinical partial response and two had resistant disease. RESULTS: A significant difference was found between groups A and B for all values. Between groups A and C, in spite of the similar static MRI appearance, all values were significantly different. Between groups B and C, a significant difference was found for WIN, WOUT rates and WIN/TMSP ratio. Follow-up dMRI data analysis correlated well with clinical staging. CONCLUSIONS: dMRI can distinguish normal from malignant bone marrow. It may identify malignant bone marrow infiltration in patients with negative static MRI and serve as both a diagnostic and prognostic tool for patients with bone marrow malignancies.     

Curability of solitary bone plasmacytoma.

PURPOSE: The effects of involved-field radiotherapy were assessed in patients with a solitary plasmacytoma of bone (SBP). PATIENTS AND METHODS: Forty-five consecutive patients with an SBP received megavoltage irradiation of at least 3,000 cGy. The median age was 53 years, 67% of patients showed a myeloma protein, and uninvolved immunoglobulins (Igs) were preserved in 93% of patients. RESULTS: Permanent control of presenting disease was achieved in all but two patients, but 46% of patients developed multiple myeloma. When it occurred, progression of myeloma occurred within 3 years in two thirds of the patients, suggesting that the extent of disease was understaged at diagnosis. Myeloma protein disappeared in nine patients (30%) whose disease has not yet recurred. The median survival for all patients was 13 years and the myeloma-specific survival fraction at 10 years was 53%. CONCLUSION: In patients with an SBP, the disappearance of myeloma protein with involved-field radiotherapy predicted long-term disease-free survival and possible cure. Nonsecretory disease and persistent myeloma protein after treatment were adverse prognostic factors for which adjuvant therapy with interferon alfa should be considered.     

European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma

Multiple myeloma management has undergone profound changes in the past thanks to advances in our understanding of the disease biology and improvements in treatment and supportive care approaches. This article presents recommendations of the European Myeloma Network for newly diagnosed patients based on the GRADE system for level of evidence. All patients with symptomatic disease should undergo risk stratification to classify patients for International Staging System stage (level of evidence: 1A) and for cytogenetically defined high- versus standard-risk groups (2B). Novel-agent-based induction and up-front autologous stem cell transplantation in medically fit patients remains the standard of care (1A). Induction therapy should include a triple combination of bortezomib, with either adriamycin or thalidomide and dexamethasone (1A), or with cyclophosphamide and dexamethasone (2B). Currently, allogeneic stem cell transplantation may be considered for young patients with high-risk disease and preferably in the context of a clinical trial (2B). Thalidomide (1B) or lenalidomide (1A) maintenance increases progression-free survival and possibly overall survival (2B). Bortezomib-based regimens are a valuable consolidation option, especially for patients who failed excellent response after autologous stem cell transplantation (2A). Bortezomib-melphalan-prednisone or melphalan-prednisone-thalidomide are the standards of care for transplant-ineligible patients (1A). Melphalan-prednisone-lenalidomide with lenalidomide maintenance increases progression-free survival, but overall survival data are needed. New data from the phase III study (MM-020/IFM 07-01) of lenalidomide-low-dose dexamethasone reached its primary end point of a statistically significant improvement in progression-free survival as compared to melphalan-prednisone-thalidomide and provides further evidence for the efficacy of lenalidomide-low-dose dexamethasone in transplant-ineligible patients (2B).     

Neuroticism personality trait is associated with Quality of Life in patients with Chronic Heart Failure

AIM: To evaluate Quality of life(QoL) in chronic heart failure(CHF) in relation to Neuroticism personality trait and CHF severity.METHODS: Thirty six consecutive, outpatients with Chronic Heart Failure(6 females and 30 males, mean age: 54 ± 12 years), with a left ventricular ejection fraction ≤ 45% at optimal medical treatment at the time of inclusion, were asked to answer the Kansas City Cardiomyopathy Questionnaire(KCCQ) for Quality ofLife assessment and the NEO Five-Factor Personality Inventory for personality assessment. All patients un-derwent a symptom limited cardiopulmonary exercise testing on a cycle-ergometer, in order to access CHF severity. A multivariate linear regression analysis us-ing simultaneous entry of predictors was performed to examine which of the CHF variables and of the person-ality variables were correlated independently to QoL scores in the two summary scales of the KCCQ, namely the Overall Summary Scale and the Clinical Summary Scale.RESULTS: The Neuroticism personality trait score had a significant inverse correlation with the Clinical Sum-mary Score and Overall Summary Score of the KCCQ(r =-0.621, P 0.05 and r =-0.543, P 0.001, respec-tively). KCCQ summary scales did not show significant correlations with the personality traits of Extraversion, Openness, Conscientiousness and Agreeableness. Mul-tivariate linear regression analysis using simultaneous entry of predictors was also conducted to determine the best linear combination of statistically significant univari-ate predictors such as Neuroticism, VE/VCO2 slope and VO2 peak, for predicting KCCQ Clinical Summary Score. The results show Neuroticism(β =-0.37, P 0.05), VE/VCO2 slope(β =-0.31, P 0.05) and VO2 peak(β = 0.37, P 0.05) to be independent predictors of QoL. In multivariate regression analysis Neuroticism(b =-0.37, P 0.05), the slope of ventilatory equivalent for carbon dioxide output during exercise,(VE/VCO2 slope)(b =-0.31, P 0.05) and peak oxygen uptake(VO2 peak),(b = 0.37, P 0.05) were independent predictors of QoL(adjusted R2 = 0.64; F = 18.89, P 0.001).CONCLUSION: Neuroticism is independently associat-ed with QoL in CHF. QoL in CHF is not only determined by disease severity but also by the Neuroticism person-ality trait.     

Mitochondrial UCP4 and bcl-2 expression in imprints of breast carcinomas: relationship with DNA ploidy and classical prognostic factors

Mitochondria are the bioenergetic and metabolic centers of cells and play an important role in the regulation of cell death. The mitochondrial apoptosis pathway is controlled by the bcl-2 protein family. Overexpression of mitochondrial uncoupling protein 4 (UCP4) can promote proliferation and inhibit apoptosis and differentiation. Imprint smears obtained from 124 tumors were studied immunocytochemically, and results were correlated with prognostic markers. There were 112 ductal and 12 lobular carcinomas. The positivity of UCP4 was correlated with lymph node metastases (p = 0.005), positive ER and PR expression (p < 0.0001 for both), as well as positivity for p53 (p < 0.0001) and Ki-67 (p < 0.0001). Decreased expression of bcl-2 correlated with increased expression of UCP4 (p = 0.001). Regarding DNA ploidy, UCP4 positivity was correlated with aneuploid tumors (p = 0.002). Negative expression of bcl-2 was correlated with poorly differentiated carcinomas (p < 0.0001), as well as with positive expression of p53 (p < 0.0001) and Ki-67 (p < 0.0001). Logistic regression revealed that ploidy and p53 expression had an impact on UCP4. These findings encourage future investigations regarding the potential role of UCPs not only into mechanisms underlying breast cancer, but also as a novel candidate to the design and development of more effective therapeutic strategies.     

Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID-19 pandemic

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID-19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID-19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID-19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.     

Long‐term outcomes of primary systemic light chain (AL) amyloidosis in patients treated upfront with bortezomib or lenalidomide and the importance of risk adapted strategies

Bortezomib and lenalidomide are increasingly used in patients with AL amyloidosis, but long term data on their use as primary therapy in AL amyloidosis are lacking while early mortality remains significant. Thus, we analyzed the long term outcomes of 85 consecutive unselected patients, which received primary therapy with bortezomib or lenalidomide and we prospectively evaluated a risk adapted strategy based on bortezomib/dexamethasone to reduce early mortality. Twenty‐six patients received full‐dose bortezomib/dexamethasone, 36 patients lenalidomide with oral cyclophosphamide and low‐dose dexamethasone and 23 patients received bortezomib/dexamethasone at a dose and schedule adjusted to the risk of early death. On intent to treat, 67% of patients achieved a hematologic response (24% hemCRs) and 34% an organ response; both were more frequent with bortezomib. An early death occurred in 20%: in 36% of those treated with full‐dose bortezomib/dexamethasone, in 22% of lenalidomide‐treated patients but only in 4.5% of patients treated with risk‐adapted bortezomib/dexamethasone. Activity of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs. weekly administration of bortezomib also had similar activity. After a median follow up of 57 months, median survival is 47 months and is similar for patients treated with bortezomib vs. lenalidomide‐based regimens. However, risk adjusted‐bortezomib/dexamethasone was associated with improved 1‐year survival vs. full‐dose bortezomib/dexamethasone or lenalidomide‐based therapy (81% vs. 56% vs. 53%, respectively). In conclusion, risk‐adapted bortezomib/dexamethasone may reduce early mortality and preserve activity while long term follow up indicates that remissions obtained with lenalidomide or bortezomib may be durable, even without consolidation with alkylators.Am. J. Hematol. 90:E60–E65, 2015. © 2015 Wiley Periodicals, Inc.     

Overall survival of relapsed and refractory multiple myeloma patients after adjusting for crossover in the MM‐003 trial for pomalidomide plus low‐dose dexamethasone

In the phase III MM‐003 trial, pomalidomide plus low‐dose dexamethasone (POM+LoDEX) improved overall survival (OS) versus high‐dose dexamethasone (HiDEX) in 455 patients with relapsed and refractory multiple myeloma (RRMM) after treatment with bortezomib and lenalidomide. Here, a two‐stage Weibull method was used to adjust for the crossover of patients in the HiDEX arm to pomalidomide‐based therapy. The adjusted difference in median OS between patients in the POM+LoDEX and HiDEX arms was 7·0 months (12·7 vs. 5·7 months, respectively). These findings provide important evidence for understanding the clinical efficacy of pomalidomide on OS benefits seen in RRMM patients.     

Isolated right ventricular infarction during percutaneous coronary intervention

Isolated right ventricular infarction (RVI) is an increasingly recognized cause of precordial ST-segment elevation (STE). A patient is described who developed STE in leads V1?CV5 secondary to occlusion of the right ventricular branch during stent angioplasty to the right coronary artery. The pattern of precordial STE was thought to be suggestive of anteroseptal myocardial infarction because of progressive STE toward lead V3. Repeat angiography disclosed a patent left anterior descending artery. Subsequent scrutiny of the electrocardiogram (ECG) revealed that leads V2 and V3 were switched and ECG interpretation considering this technical error revealed STE in V2>V3, which favored RVI. Furthermore, the mean spatial ST vector was approximately +120° in the frontal plane producing ST-segment depression in lead?I which argued against anteroseptal myocardial infarction and indicated right ventricular epicardial injury. This report highlights that analysis of the ECG using vector concepts is a useful adjunct to pattern recognition for the diagnosis of RVI.